Jaimey M. Pauli, MD

Attributed to the ancient Greek philosopher Heraclitus, and often quoted in contemporary times, is the expression “the only constant is change.” This sentiment rings true for the field of obstetrics this past year, as several bread-and-butter guidelines for managing common obstetric conditions were either challenged or altered.

The publication of the PROLONG trial called into question the use of intramuscular progesterone for the prevention of preterm birth. Prophylaxis guidelines for group B streptococcal disease were updated, including several significant clinical practice changes. Finally, there was a comprehensive overhaul of the guidelines for hypertensive disorders of pregnancy, which replaced a landmark Task Force document from the American College of Obstetricians and Gynecologists (ACOG) that was published only a few years ago.

Change is constant, and in obstetrics it is vital to keep up with the changing guidelines that result as new data become available for digestion and implementation into everyday clinical practice.

Results from the PROLONG trial may shake up treatment options for recurrent preterm birth 

Blackwell SC, Gyamfi-Bannerman C, Biggio JR Jr, et al. 17-OHPC to prevent recurrent preterm birth in singleton gestations (PROLONG study): a multicenter, international, randomized double-blind trial. Am J Perinatol. 2019. doi: 10.1055/s-0039-3400227. 

The drug 17 α-hydroxyprogesterone caproate (17-OHPC, or 17P; Makena) was approved by the US Food and Drug Administration (FDA) in 2011 for the prevention of spontaneous preterm birth (PTB) in women with a singleton pregnancy and a history of singleton spontaneous PTB. The results of the trial by Meis and colleagues of 17-OHPC played a major role in achieving that approval, as it demonstrated a 34% reduction in recurrent PTB and a reduction in some neonatal morbidities.¹ Following the drug's approval, both ACOG and the Society for Maternal-Fetal Medicine (SMFM) published guidelines recommending progesterone therapy, including 17-OHPC, for the prevention of recurrent spontaneous PTB.²   

The FDA approval of 17-OHPC was granted under an accelerated conditional pathway that required a confirmatory trial evaluating efficacy, safety, and long-term infant follow-up to be performed by the sponsor. That trial, Progestin's Role in Optimizing Neonatal Gestation (PROLONG), was started in 2009, and its results were published on October 25, 2019.³ 

Continue to: Design of the trial...

Design of the trial 

PROLONG was a multicenter (93 sites), randomized, placebo-controlled, double-blind study conducted in 9 countries (23% of participants were in the United States, 60% were in Russia and Ukraine). The co-primary outcome was PTB < 35 weeks and a composite neonatal morbidity and mortality index. The primary safety outcome was fetal/early infant death. 

The study was designed to have 98% power to detect a 30% reduction in PTB < 35 weeks, and 90% power to detect a 35% reduction in the neonatal composite index. It included 1,708 participants (1,130 were treated with 17-OHPC, and 578 received placebo). 

Trial outcomes. There was no difference in PTB < 35 weeks between the 17-OHPC and the placebo groups (11.0% vs 11.5%; relative risk [RR], 0.95; 95% confidence interval [CI], 0.71-1.26). There was no difference in PTB < 32 or < 37 weeks. 

The study revealed also that there was no difference between groups in the neonatal composite index (5.6% for 17-OHPC vs 5.0% for placebo; RR, 1.12; 95% CI, 0.68-1.61). In addition, there was no difference in fetal/early infant death between the 17-OHPC and placebo groups (1.7% vs 1.9%; RR, 0.87; 95% CI, 0.4-1.81). 

Conclusions. The trial investigators concluded that 17-OHPC did not demonstrate a reduction in recurrent PTB and did not decrease neonatal morbidity. 

Study limitations included underpowering and selection bias 

The investigators noted that the PTB rate in PROLONG was unexpectedly almost 50% lower than that in the Meis trial, and that therefore the PROLONG trial was underpowered to assess the primary outcomes. 

Further, the study populations of the 2 trials were very different: The Meis trial included women at higher baseline risk for PTB (> 1 prior PTB and at least 1 other risk factor for PTB). Additionally, while the PROLONG trial included mostly white (90%), married (90%), nonsmoking women (8% smoked), the Meis trial population was 59% black and 50% married, and 20% were smokers.  

The availability and common use of 17-OHPC in the United States likely led to a selection bias for the PROLONG trial population, as the highest-risk patients were most likely already receiving treatment and were therefore excluded from the PROLONG trial. 

Society, and FDA, responses to the new data 

The results of the PROLONG trial call into question what has become standard practice for patients with a history of spontaneous PTB in the United States. While the safety profile of 17-OHPC has not been cited as a concern, whether or not the drug should be used at all has—as has its current FDA-approved status. 

In response to the publication of the PROLONG trial results, ACOG released a Practice Advisory that acknowledged the study's findings but did not alter the current recommendations to continue to offer progesterone for the prevention of preterm birth, upholding ACOG's current Practice Bulletin guidance.^2,4 Additional considerations for offering 17-OHPC use include the patients' preferences, available resources, and the setting for the intervention.  

SMFM's response was more specific, stating that it is reasonable to continue to use 17-OHPC in high-risk patient populations consistent with those in the Meis trial.⁵ In the rest of the general population at risk for recurrent PTB, SMFM recommends that, due to uncertain benefit with 17-OHPC, the high cost, patient discomfort, and increased visits should be taken into account.  

Four days after the publication of the PROLONG study, the FDA Bone, Reproductive, and Urologic Drugs Advisory Committee voted 9-7 to withdraw approval for 17-OHPC.⁶ In response, SMFM released a statement supporting continued access to 17-OHPC.⁷ The FDA's final decision on the status of the drug is expected within the next several months from this writing. 

Continue to: ACOG updates guidance on preventing early-onset GBS disease...

ACOG updates guidance on preventing early-onset GBS disease 

American College of Obstetricians and Gynecologists—Committee on Obstetric Practice. ACOG committee opinion no. 782: prevention of early-onset group B streptococcal disease in newborns. Obstet Gynecol. 2019;134:e19-e40. 

Group B streptococcus (GBS) is the leading cause of newborn infection and is associated with maternal infections as well as preterm labor and stillbirth. Early-onset GBS disease occurs within 7 days of birth and is linked to vertical transmission via maternal colonization of the genitourinary or gastrointestinal tract and fetal/neonatal aspiration at birth.  

Preventing early-onset GBS disease with maternal screening and intrapartum prophylaxis according to the Centers for Disease Control and Prevention (CDC) guidelines has reduced early-onset disease by 80% since the 1990s. By contrast, late-onset GBS infection, which occurs 7 days to 3 months after birth, usually is associated with horizontal maternal transmission or hospital or community infections, and it is not prevented by intrapartum treatment. 

In 2018, the CDC transferred responsibility for GBS prophylaxis guidelines to ACOG and the American Academy of Pediatrics (AAP). In July 2019, ACOG released its Committee Opinion on preventing early-onset GBS disease in newborns.⁸ This guidance replaces and updates the previous guidelines, with 3 notable changes.  

The screening timing has changed 

In the CDC's 2010 guidelines, GBS screening was recommended to start at 35 weeks' gestation. The new guidelines recommend universal vaginal-rectal screening at 36 to 37 6/7 weeks' gestation. The new timing of culture will shift the expected 5-week window in which GBS cultures are considered valid up to at least 41 weeks' gestation. The rationale  for this change is that any GBS-unknown patient who previously would have been cultured under 37 weeks' would be an automatic candidate for empiric therapy and the lower rate of birth in the 35th versus the 41st week of gestation. 

Identifying candidates for intrapartum treatment 

The usual indications for intrapartum antibiotic prophylaxis include a GBS-positive culture at 36 weeks or beyond, GBS bacteriuria at any point in pregnancy, a prior GBS-affected child, or unknown GBS status with any of the following: < 37 weeks, rupture of membranes ≥ 18 hours or temperature ≥ 100.4°F (38°C), and a positive rapid GBS culture in labor. In addition, antibiotics now should be considered for patients at term with unknown GBS status but with a history of GBS colonization in a prior pregnancy.  

This represents a major practice change for women at ≥ 37 weeks with unknown GBS status and no other traditional risk factors. The rationale for this recommendation is that women who have been positive for GBS in a prior pregnancy have a 50% chance of being colonized in the current pregnancy, and their newborns are therefore at higher risk for early-onset GBS disease.  

Managing patients with penicillin allergy 

Intravenous penicillin (or ampicillin) remains the antibiotic of choice for intrapartum prophylaxis against GBS due to its efficacy and specific, narrow coverage of gram-positive organisms. The updated recommendations emphasize that it is important to carefully evaluate patients with reported penicillin allergies for several reasons: determining risk of anaphylaxis and clindamycin susceptibility testing in GBS evaluations are often overlooked by obstetric providers, the need for antibiotic stewardship to reduce the development of antibiotic resistance, and clarification of allergy status for future health care needs. 

Three recommendations are made: 

• Laboratory requisitions for cultures should specifically note a penicillin allergy so that clindamycin susceptibility testing can be performed. 
• Penicillin allergy skin testing should be considered for patients at unknown or low risk for anaphylaxis, as it is considered safe in pregnancy and most patients (80%-90%) who report a penicillin allergy are actually penicillin tolerant. 
• For patients at high risk for anaphylaxis to penicillin, the recommended vancomycin dosing has been changed from 1 g IV every 12 hours to 20 mg/kg IV every 8 hours (maximum single dose, 2 g). Renal function should be assessed prior to dosing. This weight- and renal function-based dosing increased neonatal therapeutic levels in several studies of different doses.

Continue to: Managing hypertension in pregnancy: New recommendations...

Managing hypertension in pregnancy: New recommendations  

American College of Obstetricians and Gynecologists. ACOG practice bulletin no. 202. Gestational hypertension and preeclampsia. Obstet Gynecol. 2019;133:e1-e25. 

In 2013, ACOG released "Hypertension in pregnancy," a 99-page comprehensive document developed by their Task Force on Hypertension in Pregnancy, to summarize knowledge on the subject, provide guidelines for management, and identify needed areas of research.⁹ I summarized key points from that document in the 2014 "Update on Obstetrics" (OBG Manag. 2013;26[1]:28-36). Now, ACOG has released 2 Practice Bulletins—"Gestational hypertension and preeclampsia" and "Chronic hypertension in pregnancy"—that replace the 2013 document.^10,11 These Practice Bulletins are quite comprehensive and warrant a thorough read. Several noteworthy changes relevant to the practicing obstetrician are summarized below. 

Highlights of revised guidance 

Expectant management vs early delivery in preeclampsia with fetal growth restriction. Fetal growth restriction, which was removed from the definition of preeclampsia with severe features in 2013, is no longer an indication for delivery in preeclampsia with severe features (previously, if the estimated fetal weight was < 5th percentile for gestational age, delivery after steroid administration was recommended). Rather, expectant management is reasonable if fetal antenatal testing, amniotic fluid, and Doppler ultrasound studies are reassuring. Abnormal umbilical artery Doppler studies continue to be an indication for earlier delivery. 

Postpartum NSAID use in hypertension. The 2013 document cautioned against nonsteroidal anti-inflammatory drug (NSAID) use postpartum in women with hypertensive disorders of pregnancy because of concern for exacerbating hypertension. The updated Practice Bulletins recommend NSAIDs as the preferred choice over opioid analgesics as data have not shown these drugs to increase blood pressure, antihypertensive requirements, or other adverse events in postpartum patients with blood pressure issues. 

More women will be diagnosed with chronic hypertension. Recently, the American College of Cardiology and the American Heart Association changed the definition of hypertension. Stage 1 hypertension is now defined as a systolic blood pressure of 130-139 mm Hg or a diastolic blood pressure of 80-89 mm Hg. Treatment of stage 1 hypertension is recommended for nonpregnant adults with risk factors for current or future cardiovascular disease. The potential impact is that more women will enter pregnancy with a diagnosis of chronic hypertension, and more may be on prepregnancy antihypertensive therapy that will need to be addressed during the pregnancy.  

Blood pressure goals. The target blood pressure range for pregnant women with chronic hypertension is recommended to be ≥ 120/80 mm Hg and < 160/110 mm Hg (this represents a slight change, as previously diastolic blood pressure was to be < 105 mm Hg). Postpartum blood pressure goals of < 150/100 mm Hg remain the same. 

Managing acute hypertensive emergencies. Both Practice Bulletins emphasize the importance of aggressive management of acute hypertensive emergency, with options for 3 protocols: labetalol, nifedipine, and hydralazine. The goal is to administer antihypertensive therapy within 30 to 60 minutes, but administration as soon as feasibly possible after diagnosis of severe hypertension is ideal. 

Timing of delivery. Recommended delivery timing in patients with chronic hypertension was slightly altered (previous recommendations included a range of 37 to 39 6/7 weeks). The lower limit of gestational age for recommended delivery timing in chronic hypertension has not changed—it remains not before 38 weeks if no antihypertensive therapy and stable, and not before 37 weeks if antihypertensive therapy and stable.  

The upper limit of 39 6/7 weeks is challenged, however, because data support that induction of labor at either 38 or 39 weeks reduces the risk of severe hypertensive complications (such as superimposed preeclampsia and eclampsia) without increasing the risk of cesarean delivery. Therefore, for patients with chronic hypertension, expectant management beyond 39 weeks is cautioned, to be done only with careful consideration of risks and with close surveillance. 

Attributed to the ancient Greek philosopher Heraclitus, and often quoted in contemporary times, is the expression “the only constant is change.” This sentiment rings true for the field of obstetrics this past year, as several bread-and-butter guidelines for managing common obstetric conditions were either challenged or altered.

The publication of the PROLONG trial called into question the use of intramuscular progesterone for the prevention of preterm birth. Prophylaxis guidelines for group B streptococcal disease were updated, including several significant clinical practice changes. Finally, there was a comprehensive overhaul of the guidelines for hypertensive disorders of pregnancy, which replaced a landmark Task Force document from the American College of Obstetricians and Gynecologists (ACOG) that was published only a few years ago.

Change is constant, and in obstetrics it is vital to keep up with the changing guidelines that result as new data become available for digestion and implementation into everyday clinical practice.

Results from the PROLONG trial may shake up treatment options for recurrent preterm birth 

Blackwell SC, Gyamfi-Bannerman C, Biggio JR Jr, et al. 17-OHPC to prevent recurrent preterm birth in singleton gestations (PROLONG study): a multicenter, international, randomized double-blind trial. Am J Perinatol. 2019. doi: 10.1055/s-0039-3400227. 

The drug 17 α-hydroxyprogesterone caproate (17-OHPC, or 17P; Makena) was approved by the US Food and Drug Administration (FDA) in 2011 for the prevention of spontaneous preterm birth (PTB) in women with a singleton pregnancy and a history of singleton spontaneous PTB. The results of the trial by Meis and colleagues of 17-OHPC played a major role in achieving that approval, as it demonstrated a 34% reduction in recurrent PTB and a reduction in some neonatal morbidities.¹ Following the drug's approval, both ACOG and the Society for Maternal-Fetal Medicine (SMFM) published guidelines recommending progesterone therapy, including 17-OHPC, for the prevention of recurrent spontaneous PTB.²   

The FDA approval of 17-OHPC was granted under an accelerated conditional pathway that required a confirmatory trial evaluating efficacy, safety, and long-term infant follow-up to be performed by the sponsor. That trial, Progestin's Role in Optimizing Neonatal Gestation (PROLONG), was started in 2009, and its results were published on October 25, 2019.³ 

Continue to: Design of the trial...

Design of the trial 

PROLONG was a multicenter (93 sites), randomized, placebo-controlled, double-blind study conducted in 9 countries (23% of participants were in the United States, 60% were in Russia and Ukraine). The co-primary outcome was PTB < 35 weeks and a composite neonatal morbidity and mortality index. The primary safety outcome was fetal/early infant death. 

The study was designed to have 98% power to detect a 30% reduction in PTB < 35 weeks, and 90% power to detect a 35% reduction in the neonatal composite index. It included 1,708 participants (1,130 were treated with 17-OHPC, and 578 received placebo). 

Trial outcomes. There was no difference in PTB < 35 weeks between the 17-OHPC and the placebo groups (11.0% vs 11.5%; relative risk [RR], 0.95; 95% confidence interval [CI], 0.71-1.26). There was no difference in PTB < 32 or < 37 weeks. 

The study revealed also that there was no difference between groups in the neonatal composite index (5.6% for 17-OHPC vs 5.0% for placebo; RR, 1.12; 95% CI, 0.68-1.61). In addition, there was no difference in fetal/early infant death between the 17-OHPC and placebo groups (1.7% vs 1.9%; RR, 0.87; 95% CI, 0.4-1.81). 

Conclusions. The trial investigators concluded that 17-OHPC did not demonstrate a reduction in recurrent PTB and did not decrease neonatal morbidity. 

Study limitations included underpowering and selection bias 

The investigators noted that the PTB rate in PROLONG was unexpectedly almost 50% lower than that in the Meis trial, and that therefore the PROLONG trial was underpowered to assess the primary outcomes. 

Further, the study populations of the 2 trials were very different: The Meis trial included women at higher baseline risk for PTB (> 1 prior PTB and at least 1 other risk factor for PTB). Additionally, while the PROLONG trial included mostly white (90%), married (90%), nonsmoking women (8% smoked), the Meis trial population was 59% black and 50% married, and 20% were smokers.  

The availability and common use of 17-OHPC in the United States likely led to a selection bias for the PROLONG trial population, as the highest-risk patients were most likely already receiving treatment and were therefore excluded from the PROLONG trial. 

Society, and FDA, responses to the new data 

The results of the PROLONG trial call into question what has become standard practice for patients with a history of spontaneous PTB in the United States. While the safety profile of 17-OHPC has not been cited as a concern, whether or not the drug should be used at all has—as has its current FDA-approved status. 

In response to the publication of the PROLONG trial results, ACOG released a Practice Advisory that acknowledged the study's findings but did not alter the current recommendations to continue to offer progesterone for the prevention of preterm birth, upholding ACOG's current Practice Bulletin guidance.^2,4 Additional considerations for offering 17-OHPC use include the patients' preferences, available resources, and the setting for the intervention.  

SMFM's response was more specific, stating that it is reasonable to continue to use 17-OHPC in high-risk patient populations consistent with those in the Meis trial.⁵ In the rest of the general population at risk for recurrent PTB, SMFM recommends that, due to uncertain benefit with 17-OHPC, the high cost, patient discomfort, and increased visits should be taken into account.  

Four days after the publication of the PROLONG study, the FDA Bone, Reproductive, and Urologic Drugs Advisory Committee voted 9-7 to withdraw approval for 17-OHPC.⁶ In response, SMFM released a statement supporting continued access to 17-OHPC.⁷ The FDA's final decision on the status of the drug is expected within the next several months from this writing. 

Continue to: ACOG updates guidance on preventing early-onset GBS disease...

ACOG updates guidance on preventing early-onset GBS disease 

American College of Obstetricians and Gynecologists—Committee on Obstetric Practice. ACOG committee opinion no. 782: prevention of early-onset group B streptococcal disease in newborns. Obstet Gynecol. 2019;134:e19-e40. 

Group B streptococcus (GBS) is the leading cause of newborn infection and is associated with maternal infections as well as preterm labor and stillbirth. Early-onset GBS disease occurs within 7 days of birth and is linked to vertical transmission via maternal colonization of the genitourinary or gastrointestinal tract and fetal/neonatal aspiration at birth.  

Preventing early-onset GBS disease with maternal screening and intrapartum prophylaxis according to the Centers for Disease Control and Prevention (CDC) guidelines has reduced early-onset disease by 80% since the 1990s. By contrast, late-onset GBS infection, which occurs 7 days to 3 months after birth, usually is associated with horizontal maternal transmission or hospital or community infections, and it is not prevented by intrapartum treatment. 

In 2018, the CDC transferred responsibility for GBS prophylaxis guidelines to ACOG and the American Academy of Pediatrics (AAP). In July 2019, ACOG released its Committee Opinion on preventing early-onset GBS disease in newborns.⁸ This guidance replaces and updates the previous guidelines, with 3 notable changes.  

The screening timing has changed 

In the CDC's 2010 guidelines, GBS screening was recommended to start at 35 weeks' gestation. The new guidelines recommend universal vaginal-rectal screening at 36 to 37 6/7 weeks' gestation. The new timing of culture will shift the expected 5-week window in which GBS cultures are considered valid up to at least 41 weeks' gestation. The rationale  for this change is that any GBS-unknown patient who previously would have been cultured under 37 weeks' would be an automatic candidate for empiric therapy and the lower rate of birth in the 35th versus the 41st week of gestation. 

Identifying candidates for intrapartum treatment 

The usual indications for intrapartum antibiotic prophylaxis include a GBS-positive culture at 36 weeks or beyond, GBS bacteriuria at any point in pregnancy, a prior GBS-affected child, or unknown GBS status with any of the following: < 37 weeks, rupture of membranes ≥ 18 hours or temperature ≥ 100.4°F (38°C), and a positive rapid GBS culture in labor. In addition, antibiotics now should be considered for patients at term with unknown GBS status but with a history of GBS colonization in a prior pregnancy.  

This represents a major practice change for women at ≥ 37 weeks with unknown GBS status and no other traditional risk factors. The rationale for this recommendation is that women who have been positive for GBS in a prior pregnancy have a 50% chance of being colonized in the current pregnancy, and their newborns are therefore at higher risk for early-onset GBS disease.  

Managing patients with penicillin allergy 

Intravenous penicillin (or ampicillin) remains the antibiotic of choice for intrapartum prophylaxis against GBS due to its efficacy and specific, narrow coverage of gram-positive organisms. The updated recommendations emphasize that it is important to carefully evaluate patients with reported penicillin allergies for several reasons: determining risk of anaphylaxis and clindamycin susceptibility testing in GBS evaluations are often overlooked by obstetric providers, the need for antibiotic stewardship to reduce the development of antibiotic resistance, and clarification of allergy status for future health care needs. 

Three recommendations are made: 

• Laboratory requisitions for cultures should specifically note a penicillin allergy so that clindamycin susceptibility testing can be performed. 
• Penicillin allergy skin testing should be considered for patients at unknown or low risk for anaphylaxis, as it is considered safe in pregnancy and most patients (80%-90%) who report a penicillin allergy are actually penicillin tolerant. 
• For patients at high risk for anaphylaxis to penicillin, the recommended vancomycin dosing has been changed from 1 g IV every 12 hours to 20 mg/kg IV every 8 hours (maximum single dose, 2 g). Renal function should be assessed prior to dosing. This weight- and renal function-based dosing increased neonatal therapeutic levels in several studies of different doses.

Continue to: Managing hypertension in pregnancy: New recommendations...

Managing hypertension in pregnancy: New recommendations  

American College of Obstetricians and Gynecologists. ACOG practice bulletin no. 202. Gestational hypertension and preeclampsia. Obstet Gynecol. 2019;133:e1-e25. 

In 2013, ACOG released "Hypertension in pregnancy," a 99-page comprehensive document developed by their Task Force on Hypertension in Pregnancy, to summarize knowledge on the subject, provide guidelines for management, and identify needed areas of research.⁹ I summarized key points from that document in the 2014 "Update on Obstetrics" (OBG Manag. 2013;26[1]:28-36). Now, ACOG has released 2 Practice Bulletins—"Gestational hypertension and preeclampsia" and "Chronic hypertension in pregnancy"—that replace the 2013 document.^10,11 These Practice Bulletins are quite comprehensive and warrant a thorough read. Several noteworthy changes relevant to the practicing obstetrician are summarized below. 

Highlights of revised guidance 

Expectant management vs early delivery in preeclampsia with fetal growth restriction. Fetal growth restriction, which was removed from the definition of preeclampsia with severe features in 2013, is no longer an indication for delivery in preeclampsia with severe features (previously, if the estimated fetal weight was < 5th percentile for gestational age, delivery after steroid administration was recommended). Rather, expectant management is reasonable if fetal antenatal testing, amniotic fluid, and Doppler ultrasound studies are reassuring. Abnormal umbilical artery Doppler studies continue to be an indication for earlier delivery. 

Postpartum NSAID use in hypertension. The 2013 document cautioned against nonsteroidal anti-inflammatory drug (NSAID) use postpartum in women with hypertensive disorders of pregnancy because of concern for exacerbating hypertension. The updated Practice Bulletins recommend NSAIDs as the preferred choice over opioid analgesics as data have not shown these drugs to increase blood pressure, antihypertensive requirements, or other adverse events in postpartum patients with blood pressure issues. 

More women will be diagnosed with chronic hypertension. Recently, the American College of Cardiology and the American Heart Association changed the definition of hypertension. Stage 1 hypertension is now defined as a systolic blood pressure of 130-139 mm Hg or a diastolic blood pressure of 80-89 mm Hg. Treatment of stage 1 hypertension is recommended for nonpregnant adults with risk factors for current or future cardiovascular disease. The potential impact is that more women will enter pregnancy with a diagnosis of chronic hypertension, and more may be on prepregnancy antihypertensive therapy that will need to be addressed during the pregnancy.  

Blood pressure goals. The target blood pressure range for pregnant women with chronic hypertension is recommended to be ≥ 120/80 mm Hg and < 160/110 mm Hg (this represents a slight change, as previously diastolic blood pressure was to be < 105 mm Hg). Postpartum blood pressure goals of < 150/100 mm Hg remain the same. 

Managing acute hypertensive emergencies. Both Practice Bulletins emphasize the importance of aggressive management of acute hypertensive emergency, with options for 3 protocols: labetalol, nifedipine, and hydralazine. The goal is to administer antihypertensive therapy within 30 to 60 minutes, but administration as soon as feasibly possible after diagnosis of severe hypertension is ideal. 

Timing of delivery. Recommended delivery timing in patients with chronic hypertension was slightly altered (previous recommendations included a range of 37 to 39 6/7 weeks). The lower limit of gestational age for recommended delivery timing in chronic hypertension has not changed—it remains not before 38 weeks if no antihypertensive therapy and stable, and not before 37 weeks if antihypertensive therapy and stable.  

The upper limit of 39 6/7 weeks is challenged, however, because data support that induction of labor at either 38 or 39 weeks reduces the risk of severe hypertensive complications (such as superimposed preeclampsia and eclampsia) without increasing the risk of cesarean delivery. Therefore, for patients with chronic hypertension, expectant management beyond 39 weeks is cautioned, to be done only with careful consideration of risks and with close surveillance. 

Attributed to the ancient Greek philosopher Heraclitus, and often quoted in contemporary times, is the expression “the only constant is change.” This sentiment rings true for the field of obstetrics this past year, as several bread-and-butter guidelines for managing common obstetric conditions were either challenged or altered.

The publication of the PROLONG trial called into question the use of intramuscular progesterone for the prevention of preterm birth. Prophylaxis guidelines for group B streptococcal disease were updated, including several significant clinical practice changes. Finally, there was a comprehensive overhaul of the guidelines for hypertensive disorders of pregnancy, which replaced a landmark Task Force document from the American College of Obstetricians and Gynecologists (ACOG) that was published only a few years ago.

Change is constant, and in obstetrics it is vital to keep up with the changing guidelines that result as new data become available for digestion and implementation into everyday clinical practice.

Results from the PROLONG trial may shake up treatment options for recurrent preterm birth 

Blackwell SC, Gyamfi-Bannerman C, Biggio JR Jr, et al. 17-OHPC to prevent recurrent preterm birth in singleton gestations (PROLONG study): a multicenter, international, randomized double-blind trial. Am J Perinatol. 2019. doi: 10.1055/s-0039-3400227. 

The drug 17 α-hydroxyprogesterone caproate (17-OHPC, or 17P; Makena) was approved by the US Food and Drug Administration (FDA) in 2011 for the prevention of spontaneous preterm birth (PTB) in women with a singleton pregnancy and a history of singleton spontaneous PTB. The results of the trial by Meis and colleagues of 17-OHPC played a major role in achieving that approval, as it demonstrated a 34% reduction in recurrent PTB and a reduction in some neonatal morbidities.¹ Following the drug's approval, both ACOG and the Society for Maternal-Fetal Medicine (SMFM) published guidelines recommending progesterone therapy, including 17-OHPC, for the prevention of recurrent spontaneous PTB.²   

The FDA approval of 17-OHPC was granted under an accelerated conditional pathway that required a confirmatory trial evaluating efficacy, safety, and long-term infant follow-up to be performed by the sponsor. That trial, Progestin's Role in Optimizing Neonatal Gestation (PROLONG), was started in 2009, and its results were published on October 25, 2019.³ 

Continue to: Design of the trial...

Design of the trial 

PROLONG was a multicenter (93 sites), randomized, placebo-controlled, double-blind study conducted in 9 countries (23% of participants were in the United States, 60% were in Russia and Ukraine). The co-primary outcome was PTB < 35 weeks and a composite neonatal morbidity and mortality index. The primary safety outcome was fetal/early infant death. 

The study was designed to have 98% power to detect a 30% reduction in PTB < 35 weeks, and 90% power to detect a 35% reduction in the neonatal composite index. It included 1,708 participants (1,130 were treated with 17-OHPC, and 578 received placebo). 

Trial outcomes. There was no difference in PTB < 35 weeks between the 17-OHPC and the placebo groups (11.0% vs 11.5%; relative risk [RR], 0.95; 95% confidence interval [CI], 0.71-1.26). There was no difference in PTB < 32 or < 37 weeks. 

The study revealed also that there was no difference between groups in the neonatal composite index (5.6% for 17-OHPC vs 5.0% for placebo; RR, 1.12; 95% CI, 0.68-1.61). In addition, there was no difference in fetal/early infant death between the 17-OHPC and placebo groups (1.7% vs 1.9%; RR, 0.87; 95% CI, 0.4-1.81). 

Conclusions. The trial investigators concluded that 17-OHPC did not demonstrate a reduction in recurrent PTB and did not decrease neonatal morbidity. 

Study limitations included underpowering and selection bias 

The investigators noted that the PTB rate in PROLONG was unexpectedly almost 50% lower than that in the Meis trial, and that therefore the PROLONG trial was underpowered to assess the primary outcomes. 

Further, the study populations of the 2 trials were very different: The Meis trial included women at higher baseline risk for PTB (> 1 prior PTB and at least 1 other risk factor for PTB). Additionally, while the PROLONG trial included mostly white (90%), married (90%), nonsmoking women (8% smoked), the Meis trial population was 59% black and 50% married, and 20% were smokers.  

The availability and common use of 17-OHPC in the United States likely led to a selection bias for the PROLONG trial population, as the highest-risk patients were most likely already receiving treatment and were therefore excluded from the PROLONG trial. 

Society, and FDA, responses to the new data 

The results of the PROLONG trial call into question what has become standard practice for patients with a history of spontaneous PTB in the United States. While the safety profile of 17-OHPC has not been cited as a concern, whether or not the drug should be used at all has—as has its current FDA-approved status. 

In response to the publication of the PROLONG trial results, ACOG released a Practice Advisory that acknowledged the study's findings but did not alter the current recommendations to continue to offer progesterone for the prevention of preterm birth, upholding ACOG's current Practice Bulletin guidance.^2,4 Additional considerations for offering 17-OHPC use include the patients' preferences, available resources, and the setting for the intervention.  

SMFM's response was more specific, stating that it is reasonable to continue to use 17-OHPC in high-risk patient populations consistent with those in the Meis trial.⁵ In the rest of the general population at risk for recurrent PTB, SMFM recommends that, due to uncertain benefit with 17-OHPC, the high cost, patient discomfort, and increased visits should be taken into account.  

Four days after the publication of the PROLONG study, the FDA Bone, Reproductive, and Urologic Drugs Advisory Committee voted 9-7 to withdraw approval for 17-OHPC.⁶ In response, SMFM released a statement supporting continued access to 17-OHPC.⁷ The FDA's final decision on the status of the drug is expected within the next several months from this writing. 

Continue to: ACOG updates guidance on preventing early-onset GBS disease...

ACOG updates guidance on preventing early-onset GBS disease 

American College of Obstetricians and Gynecologists—Committee on Obstetric Practice. ACOG committee opinion no. 782: prevention of early-onset group B streptococcal disease in newborns. Obstet Gynecol. 2019;134:e19-e40. 

Group B streptococcus (GBS) is the leading cause of newborn infection and is associated with maternal infections as well as preterm labor and stillbirth. Early-onset GBS disease occurs within 7 days of birth and is linked to vertical transmission via maternal colonization of the genitourinary or gastrointestinal tract and fetal/neonatal aspiration at birth.  

Preventing early-onset GBS disease with maternal screening and intrapartum prophylaxis according to the Centers for Disease Control and Prevention (CDC) guidelines has reduced early-onset disease by 80% since the 1990s. By contrast, late-onset GBS infection, which occurs 7 days to 3 months after birth, usually is associated with horizontal maternal transmission or hospital or community infections, and it is not prevented by intrapartum treatment. 

In 2018, the CDC transferred responsibility for GBS prophylaxis guidelines to ACOG and the American Academy of Pediatrics (AAP). In July 2019, ACOG released its Committee Opinion on preventing early-onset GBS disease in newborns.⁸ This guidance replaces and updates the previous guidelines, with 3 notable changes.  

The screening timing has changed 

In the CDC's 2010 guidelines, GBS screening was recommended to start at 35 weeks' gestation. The new guidelines recommend universal vaginal-rectal screening at 36 to 37 6/7 weeks' gestation. The new timing of culture will shift the expected 5-week window in which GBS cultures are considered valid up to at least 41 weeks' gestation. The rationale  for this change is that any GBS-unknown patient who previously would have been cultured under 37 weeks' would be an automatic candidate for empiric therapy and the lower rate of birth in the 35th versus the 41st week of gestation. 

Identifying candidates for intrapartum treatment 

The usual indications for intrapartum antibiotic prophylaxis include a GBS-positive culture at 36 weeks or beyond, GBS bacteriuria at any point in pregnancy, a prior GBS-affected child, or unknown GBS status with any of the following: < 37 weeks, rupture of membranes ≥ 18 hours or temperature ≥ 100.4°F (38°C), and a positive rapid GBS culture in labor. In addition, antibiotics now should be considered for patients at term with unknown GBS status but with a history of GBS colonization in a prior pregnancy.  

This represents a major practice change for women at ≥ 37 weeks with unknown GBS status and no other traditional risk factors. The rationale for this recommendation is that women who have been positive for GBS in a prior pregnancy have a 50% chance of being colonized in the current pregnancy, and their newborns are therefore at higher risk for early-onset GBS disease.  

Managing patients with penicillin allergy 

Intravenous penicillin (or ampicillin) remains the antibiotic of choice for intrapartum prophylaxis against GBS due to its efficacy and specific, narrow coverage of gram-positive organisms. The updated recommendations emphasize that it is important to carefully evaluate patients with reported penicillin allergies for several reasons: determining risk of anaphylaxis and clindamycin susceptibility testing in GBS evaluations are often overlooked by obstetric providers, the need for antibiotic stewardship to reduce the development of antibiotic resistance, and clarification of allergy status for future health care needs. 

Three recommendations are made: 

• Laboratory requisitions for cultures should specifically note a penicillin allergy so that clindamycin susceptibility testing can be performed. 
• Penicillin allergy skin testing should be considered for patients at unknown or low risk for anaphylaxis, as it is considered safe in pregnancy and most patients (80%-90%) who report a penicillin allergy are actually penicillin tolerant. 
• For patients at high risk for anaphylaxis to penicillin, the recommended vancomycin dosing has been changed from 1 g IV every 12 hours to 20 mg/kg IV every 8 hours (maximum single dose, 2 g). Renal function should be assessed prior to dosing. This weight- and renal function-based dosing increased neonatal therapeutic levels in several studies of different doses.

Continue to: Managing hypertension in pregnancy: New recommendations...

Managing hypertension in pregnancy: New recommendations  

American College of Obstetricians and Gynecologists. ACOG practice bulletin no. 202. Gestational hypertension and preeclampsia. Obstet Gynecol. 2019;133:e1-e25. 

In 2013, ACOG released "Hypertension in pregnancy," a 99-page comprehensive document developed by their Task Force on Hypertension in Pregnancy, to summarize knowledge on the subject, provide guidelines for management, and identify needed areas of research.⁹ I summarized key points from that document in the 2014 "Update on Obstetrics" (OBG Manag. 2013;26[1]:28-36). Now, ACOG has released 2 Practice Bulletins—"Gestational hypertension and preeclampsia" and "Chronic hypertension in pregnancy"—that replace the 2013 document.^10,11 These Practice Bulletins are quite comprehensive and warrant a thorough read. Several noteworthy changes relevant to the practicing obstetrician are summarized below. 

Highlights of revised guidance 

Expectant management vs early delivery in preeclampsia with fetal growth restriction. Fetal growth restriction, which was removed from the definition of preeclampsia with severe features in 2013, is no longer an indication for delivery in preeclampsia with severe features (previously, if the estimated fetal weight was < 5th percentile for gestational age, delivery after steroid administration was recommended). Rather, expectant management is reasonable if fetal antenatal testing, amniotic fluid, and Doppler ultrasound studies are reassuring. Abnormal umbilical artery Doppler studies continue to be an indication for earlier delivery. 

Postpartum NSAID use in hypertension. The 2013 document cautioned against nonsteroidal anti-inflammatory drug (NSAID) use postpartum in women with hypertensive disorders of pregnancy because of concern for exacerbating hypertension. The updated Practice Bulletins recommend NSAIDs as the preferred choice over opioid analgesics as data have not shown these drugs to increase blood pressure, antihypertensive requirements, or other adverse events in postpartum patients with blood pressure issues. 

More women will be diagnosed with chronic hypertension. Recently, the American College of Cardiology and the American Heart Association changed the definition of hypertension. Stage 1 hypertension is now defined as a systolic blood pressure of 130-139 mm Hg or a diastolic blood pressure of 80-89 mm Hg. Treatment of stage 1 hypertension is recommended for nonpregnant adults with risk factors for current or future cardiovascular disease. The potential impact is that more women will enter pregnancy with a diagnosis of chronic hypertension, and more may be on prepregnancy antihypertensive therapy that will need to be addressed during the pregnancy.  

Blood pressure goals. The target blood pressure range for pregnant women with chronic hypertension is recommended to be ≥ 120/80 mm Hg and < 160/110 mm Hg (this represents a slight change, as previously diastolic blood pressure was to be < 105 mm Hg). Postpartum blood pressure goals of < 150/100 mm Hg remain the same. 

Managing acute hypertensive emergencies. Both Practice Bulletins emphasize the importance of aggressive management of acute hypertensive emergency, with options for 3 protocols: labetalol, nifedipine, and hydralazine. The goal is to administer antihypertensive therapy within 30 to 60 minutes, but administration as soon as feasibly possible after diagnosis of severe hypertension is ideal. 

Timing of delivery. Recommended delivery timing in patients with chronic hypertension was slightly altered (previous recommendations included a range of 37 to 39 6/7 weeks). The lower limit of gestational age for recommended delivery timing in chronic hypertension has not changed—it remains not before 38 weeks if no antihypertensive therapy and stable, and not before 37 weeks if antihypertensive therapy and stable.  

The upper limit of 39 6/7 weeks is challenged, however, because data support that induction of labor at either 38 or 39 weeks reduces the risk of severe hypertensive complications (such as superimposed preeclampsia and eclampsia) without increasing the risk of cesarean delivery. Therefore, for patients with chronic hypertension, expectant management beyond 39 weeks is cautioned, to be done only with careful consideration of risks and with close surveillance. 

The past year was an exciting one in obstetrics. The landmark ARRIVE trial presented at the Society for Maternal-Fetal Medicine’s (SMFM) annual meeting and subsequently published in the New England Journal of Medicine contradicted a long-held belief about the safety of elective labor induction. In a large randomized trial, Cahill and colleagues took a controversial but practical clinical question about second-stage labor management and answered it for the practicing obstetrician in the trenches. Finally, the American College of Obstetricians and Gynecologists (ACOG) placed new emphasis on the oft overlooked but increasingly more complicated postpartum period, offering guidance to support improving care for women in this transitional period.

Ultimately, this was the year of the patient, as research, clinical guidelines, and education focused on how to achieve the best in safety and quality of care for delivery planning, the delivery itself, and the so-called fourth trimester.

ARRIVE: Labor induction at 39 weeks reduces CD rate with no difference in perinatal death or serious outcomes 

Grobman WA, Rice MM, Reddy UM, et al; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Labor induction versus expectant management in low-risk nulliparous women. N Engl J Med. 2018;379:513-523.

The term "elective induction of labor" has long had a negative connotation because of its association with increased CD rates and adverse perinatal outcomes. This view was based on results from older observational studies that compared outcomes for labor induction with those of spontaneous labor. In more recent observational studies that more appropriately compared labor induction with expectant management, however, elective induction of labor appears to be associated with similar CD rates and perinatal outcomes. 
To test the hypothesis that elective induction would have a lower risk for perinatal death or severe neonatal complications than expectant management in low-risk nulliparous women, Grobman and colleagues conducted A Randomized Trial of Induction Versus Expectant Management (ARRIVE).1 

Study population, timing of delivery, and trial outcomes 

This randomized controlled trial included 6,106 women at 41 US centers in the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Study participants were low-risk nulliparous women with a singleton vertex fetus who were randomly assigned to induction of labor at 39 to 39 4/7 weeks (n = 3,062) or expectant management (n = 3,044) until 40 5/7 to 42 2/7 weeks. 

"Low risk" was defined as having no maternal or fetal indication for delivery prior to 40 5/7 weeks. Reliable gestational dating was required.  

While no specific protocol for induction of labor management was required, there were 2 requests: 1) Cervical ripening was requested for an unfavorable cervix (63% of participants had a modified Bishop score <5), and 2) a duration of at least 12 hours after cervical ripening, rupture of membranes, and use of uterine stimulant was requested before performing a CD for "failed induction" (if medically appropriate). 

The primary outcome was a composite of perinatal death or serious neonatal complications. The main secondary outcome was CD. 

Potentially game-changing findings 

The investigators found that there was no statistically significant difference between the elective induction and expectant management groups for the primary composite perinatal outcome (4.3% vs 5.4%; P = .049, with P<.046 prespecified for significance). In addition, the rate of CD was significantly lower in the labor induction group than in the expectant management group (18.6% vs 22.2%; P<.001). 
Other significant findings in secondary outcomes included the following: 

• Hypertensive disorders of pregnancy were significantly lower in the labor induction group compared with the expectant management group (9.1% vs 14.1%; P<.001). 
• The labor induction group had a longer length of stay in the labor and delivery unit but a shorter postpartum hospital stay. 
• The labor induction group reported less pain and more control during labor. 

Results refute negative notion of elective labor induction 

The authors concluded that in a low-risk nulliparous patient population, elective induction of labor at 39 weeks does not increase the risk for adverse perinatal outcomes and decreases the rate of CD and hypertensive disorders of pregnancy. Additionally, they noted that induction at 39 weeks should not be avoided with the goal of preventing CD, as even women with an unfavorable cervix had a lower rate of CD in the induction group compared with the expectant management group.

Continue to: Immediate pushing in second stage...

Immediate pushing in second stage offers benefits and is preferable to delayed pushing 

Cahill AG, Srinivas SK, Tita AT, et al. Effect of immediate vs delayed pushing on rates of spontaneous vaginal delivery among nulliparous women receiving neuraxial analgesia: a randomized clinical trial. JAMA. 2018;320:1444-1454. 

In a randomized trial of 2,414 women, Cahill and colleagues sought to answer a seemingly simple question: What is the best timing for pushing during the second stage of labor--immediate or delayed? 

Practical management of the second stage of labor (defined as complete cervical dilation to the delivery of the infant) varies by provider and setting, and previous data on pushing efforts are conflicting. Delayed pushing, or "laboring down," has been suggested to allow passive fetal rotation and to conserve maternal energy for pushing. Older studies have shown that delayed pushing decreases the rate of operative delivery. More recent study data have not demonstrated a difference between immediate and delayed pushing techniques on vaginal delivery rates and have noted that increased maternal and neonatal morbidities are associated with a longer second stage of labor. 

The recent trial by Cahill and colleagues was designed to determine the effect of these 2 techniques on spontaneous vaginal delivery rates and on maternal and neonatal morbidities.⁴ 

Large study population 

This randomized pragmatic trial was conducted at 6 centers in the United States. Study participants (2,404 women completed the study) were nulliparous women at 37 or more weeks' gestation with neuraxial anesthesia who were randomly assigned at complete cervical dilation either to immediate pushing (n = 1,200) or to delayed pushing, that is, instructed to wait 60 minutes before starting to push (n = 1,204). The obstetric provider determined the rest of the labor management. 

The primary outcome was the rate of spontaneous vaginal delivery. Secondary outcomes included duration of the second stage of labor, duration of active pushing, operative vaginal delivery, CD, and several maternal assessments (postpartum hemorrhage, chorioamnionitis, endometritis, and perineal lacerations). 

Both groups had similar vaginal delivery rates, differences in some measures 

There was no difference in the primary outcome between the 2 groups: The spontaneous vaginal delivery rate was 85.9% (n = 1,031) in the immediate pushing group and 86.5% (n = 1,041) in the delayed pushing group (P = .67).  
Analysis of secondary outcomes revealed several significant differences: 

• decreased total time for the second stage of labor in the immediate pushing group compared with the delayed pushing group (102.4 vs 134.2 minutes) but longer active pushing time (83.7 vs 74.5 minutes) 
• a lower rate of postpartum hemorrhage, chorioamnionitis in the second stage, neonatal acidemia, and suspected neonatal sepsis in the immediate pushing group 
• a higher rate of third-degree perineal lacerations in the immediate pushing group. 

 No difference was found between groups in rates of operative vaginal deliveries, CDs, endometritis, overall perineal lacerations, or spontaneous vaginal delivery by fetal station or occiput position. 

Authors' takeaway 

The authors concluded that since delayed pushing does not increase spontaneous vaginal delivery rates and increases the duration of the second stage of labor and both maternal and neonatal morbidity, immediate pushing may be preferred in this patient population. 

ACOG aims to optimize postpartum care 

American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 736. Optimizing postpartum care. Obstet Gynecol. 2018;131:e140-e150. 

In May 2018, ACOG released "Optimizing postpartum care," a committee opinion that proposes a new model of comprehensive postpartum care focused on improving both short- and long-term health outcomes for women and infants. (This replaces the June 2016 committee opinion No. 666.) Described as "the fourth trimester," the postpartum period is a critical transitional period in which both pregnancy-related and pre-existing conditions may affect maternal, neonatal, and family status; half of pregnancy-related maternal deaths occur during the postpartum period.⁶ 

The postpartum visit: Often a lost opportunity 

ACOG cites that up to 40% of women in the United States do not attend their postpartum visit.6 Many aspects of the postpartum visit, including follow-up for chronic diseases, mental health screening, and contraceptive counseling, provide opportunities for acute intervention as well as establishment of healthy behaviors. Some studies have shown that postpartum depression, breastfeeding, and patient satisfaction outcomes improve as a result of postpartum engagement. 

Continue to: ACOG's recommendations...

ACOG's recommendations 

Ongoing process. ACOG's first proposed change concerns the structure of the postpartum visit itself, which traditionally has been a single visit with a provider at approximately 6 weeks postpartum. Postpartum care plans actually should be started before birth, during regular prenatal care, and adjusted in the hospital as needed so that the provider can educate patients about the issues they may face and resources they may need during this time. This prenatal preparation hopefully will encourage more patients to attend their postpartum visits. 

Increased provider contact. Another proposed change is that after delivery, the patient should have contact with a provider within the first 3 weeks postpartum. For high-risk patients, this may involve an in-person clinic visit as soon as 3 to 10 days postpartum (for hypertensive disorders of pregnancy) or at 1 to 2 weeks (for postpartum depression screening, incision checks, and lactation issues). For lower-risk patients, a phone call may be appropriate and/or preferred. Ongoing follow-up for all patients before the final postpartum visit should be individualized. 

Postpartum visit and care transition. ACOG recommends a comprehensive postpartum visit at 4 to 12 weeks to fully evaluate the woman's physical, social, and psychologic well-being and to serve as a transition from pregnancy care to well-woman care. This is a large order and includes evaluation of the following: 

• mood and emotional well-being 
• infant care and feeding 
• sexuality, contraception, and birth spacing 
• sleep and fatigue 
• physical recovery from birth 
• chronic disease management and transition to primary care provider 
• health maintenance 
• review of labor and delivery course if needed 
• review of risks and recommendations for future pregnancies. 

After these components are addressed, it is expected that the patient will be transitioned to a primary care provider (who may continue to be the ObGyn, as appropriate) to coordinate her future care in the primary medical home.  

Useful resource for adopting new paradigm 

ACOG's recommendations are somewhat daunting, and these changes will require education and resources, a significant increase in obstetric provider time and effort, and consideration of policy change regarding such issues as parental leave and postpartum care reimbursement. As a start, ACOG has developed an online aid for health care providers called "Postpartum toolkit" (https://www.acog.org/About-ACOG/ACOG-Departments/Toolkits-for-Health-Care-Providers/Postpartum-Toolkit), which provides education and resources for all steps in the process and can be individualized for each practice and patient.⁷  
 

The past year was an exciting one in obstetrics. The landmark ARRIVE trial presented at the Society for Maternal-Fetal Medicine’s (SMFM) annual meeting and subsequently published in the New England Journal of Medicine contradicted a long-held belief about the safety of elective labor induction. In a large randomized trial, Cahill and colleagues took a controversial but practical clinical question about second-stage labor management and answered it for the practicing obstetrician in the trenches. Finally, the American College of Obstetricians and Gynecologists (ACOG) placed new emphasis on the oft overlooked but increasingly more complicated postpartum period, offering guidance to support improving care for women in this transitional period.

Ultimately, this was the year of the patient, as research, clinical guidelines, and education focused on how to achieve the best in safety and quality of care for delivery planning, the delivery itself, and the so-called fourth trimester.

ARRIVE: Labor induction at 39 weeks reduces CD rate with no difference in perinatal death or serious outcomes 

Grobman WA, Rice MM, Reddy UM, et al; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Labor induction versus expectant management in low-risk nulliparous women. N Engl J Med. 2018;379:513-523.

The term "elective induction of labor" has long had a negative connotation because of its association with increased CD rates and adverse perinatal outcomes. This view was based on results from older observational studies that compared outcomes for labor induction with those of spontaneous labor. In more recent observational studies that more appropriately compared labor induction with expectant management, however, elective induction of labor appears to be associated with similar CD rates and perinatal outcomes. 
To test the hypothesis that elective induction would have a lower risk for perinatal death or severe neonatal complications than expectant management in low-risk nulliparous women, Grobman and colleagues conducted A Randomized Trial of Induction Versus Expectant Management (ARRIVE).1 

Study population, timing of delivery, and trial outcomes 

This randomized controlled trial included 6,106 women at 41 US centers in the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Study participants were low-risk nulliparous women with a singleton vertex fetus who were randomly assigned to induction of labor at 39 to 39 4/7 weeks (n = 3,062) or expectant management (n = 3,044) until 40 5/7 to 42 2/7 weeks. 

"Low risk" was defined as having no maternal or fetal indication for delivery prior to 40 5/7 weeks. Reliable gestational dating was required.  

While no specific protocol for induction of labor management was required, there were 2 requests: 1) Cervical ripening was requested for an unfavorable cervix (63% of participants had a modified Bishop score <5), and 2) a duration of at least 12 hours after cervical ripening, rupture of membranes, and use of uterine stimulant was requested before performing a CD for "failed induction" (if medically appropriate). 

The primary outcome was a composite of perinatal death or serious neonatal complications. The main secondary outcome was CD. 

Potentially game-changing findings 

The investigators found that there was no statistically significant difference between the elective induction and expectant management groups for the primary composite perinatal outcome (4.3% vs 5.4%; P = .049, with P<.046 prespecified for significance). In addition, the rate of CD was significantly lower in the labor induction group than in the expectant management group (18.6% vs 22.2%; P<.001). 
Other significant findings in secondary outcomes included the following: 

• Hypertensive disorders of pregnancy were significantly lower in the labor induction group compared with the expectant management group (9.1% vs 14.1%; P<.001). 
• The labor induction group had a longer length of stay in the labor and delivery unit but a shorter postpartum hospital stay. 
• The labor induction group reported less pain and more control during labor. 

Results refute negative notion of elective labor induction 

The authors concluded that in a low-risk nulliparous patient population, elective induction of labor at 39 weeks does not increase the risk for adverse perinatal outcomes and decreases the rate of CD and hypertensive disorders of pregnancy. Additionally, they noted that induction at 39 weeks should not be avoided with the goal of preventing CD, as even women with an unfavorable cervix had a lower rate of CD in the induction group compared with the expectant management group.

Continue to: Immediate pushing in second stage...

Immediate pushing in second stage offers benefits and is preferable to delayed pushing 

Cahill AG, Srinivas SK, Tita AT, et al. Effect of immediate vs delayed pushing on rates of spontaneous vaginal delivery among nulliparous women receiving neuraxial analgesia: a randomized clinical trial. JAMA. 2018;320:1444-1454. 

In a randomized trial of 2,414 women, Cahill and colleagues sought to answer a seemingly simple question: What is the best timing for pushing during the second stage of labor--immediate or delayed? 

Practical management of the second stage of labor (defined as complete cervical dilation to the delivery of the infant) varies by provider and setting, and previous data on pushing efforts are conflicting. Delayed pushing, or "laboring down," has been suggested to allow passive fetal rotation and to conserve maternal energy for pushing. Older studies have shown that delayed pushing decreases the rate of operative delivery. More recent study data have not demonstrated a difference between immediate and delayed pushing techniques on vaginal delivery rates and have noted that increased maternal and neonatal morbidities are associated with a longer second stage of labor. 

The recent trial by Cahill and colleagues was designed to determine the effect of these 2 techniques on spontaneous vaginal delivery rates and on maternal and neonatal morbidities.⁴ 

Large study population 

This randomized pragmatic trial was conducted at 6 centers in the United States. Study participants (2,404 women completed the study) were nulliparous women at 37 or more weeks' gestation with neuraxial anesthesia who were randomly assigned at complete cervical dilation either to immediate pushing (n = 1,200) or to delayed pushing, that is, instructed to wait 60 minutes before starting to push (n = 1,204). The obstetric provider determined the rest of the labor management. 

The primary outcome was the rate of spontaneous vaginal delivery. Secondary outcomes included duration of the second stage of labor, duration of active pushing, operative vaginal delivery, CD, and several maternal assessments (postpartum hemorrhage, chorioamnionitis, endometritis, and perineal lacerations). 

Both groups had similar vaginal delivery rates, differences in some measures 

There was no difference in the primary outcome between the 2 groups: The spontaneous vaginal delivery rate was 85.9% (n = 1,031) in the immediate pushing group and 86.5% (n = 1,041) in the delayed pushing group (P = .67).  
Analysis of secondary outcomes revealed several significant differences: 

• decreased total time for the second stage of labor in the immediate pushing group compared with the delayed pushing group (102.4 vs 134.2 minutes) but longer active pushing time (83.7 vs 74.5 minutes) 
• a lower rate of postpartum hemorrhage, chorioamnionitis in the second stage, neonatal acidemia, and suspected neonatal sepsis in the immediate pushing group 
• a higher rate of third-degree perineal lacerations in the immediate pushing group. 

 No difference was found between groups in rates of operative vaginal deliveries, CDs, endometritis, overall perineal lacerations, or spontaneous vaginal delivery by fetal station or occiput position. 

Authors' takeaway 

The authors concluded that since delayed pushing does not increase spontaneous vaginal delivery rates and increases the duration of the second stage of labor and both maternal and neonatal morbidity, immediate pushing may be preferred in this patient population. 

ACOG aims to optimize postpartum care 

American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 736. Optimizing postpartum care. Obstet Gynecol. 2018;131:e140-e150. 

In May 2018, ACOG released "Optimizing postpartum care," a committee opinion that proposes a new model of comprehensive postpartum care focused on improving both short- and long-term health outcomes for women and infants. (This replaces the June 2016 committee opinion No. 666.) Described as "the fourth trimester," the postpartum period is a critical transitional period in which both pregnancy-related and pre-existing conditions may affect maternal, neonatal, and family status; half of pregnancy-related maternal deaths occur during the postpartum period.⁶ 

The postpartum visit: Often a lost opportunity 

ACOG cites that up to 40% of women in the United States do not attend their postpartum visit.6 Many aspects of the postpartum visit, including follow-up for chronic diseases, mental health screening, and contraceptive counseling, provide opportunities for acute intervention as well as establishment of healthy behaviors. Some studies have shown that postpartum depression, breastfeeding, and patient satisfaction outcomes improve as a result of postpartum engagement. 

Continue to: ACOG's recommendations...

ACOG's recommendations 

Ongoing process. ACOG's first proposed change concerns the structure of the postpartum visit itself, which traditionally has been a single visit with a provider at approximately 6 weeks postpartum. Postpartum care plans actually should be started before birth, during regular prenatal care, and adjusted in the hospital as needed so that the provider can educate patients about the issues they may face and resources they may need during this time. This prenatal preparation hopefully will encourage more patients to attend their postpartum visits. 

Increased provider contact. Another proposed change is that after delivery, the patient should have contact with a provider within the first 3 weeks postpartum. For high-risk patients, this may involve an in-person clinic visit as soon as 3 to 10 days postpartum (for hypertensive disorders of pregnancy) or at 1 to 2 weeks (for postpartum depression screening, incision checks, and lactation issues). For lower-risk patients, a phone call may be appropriate and/or preferred. Ongoing follow-up for all patients before the final postpartum visit should be individualized. 

Postpartum visit and care transition. ACOG recommends a comprehensive postpartum visit at 4 to 12 weeks to fully evaluate the woman's physical, social, and psychologic well-being and to serve as a transition from pregnancy care to well-woman care. This is a large order and includes evaluation of the following: 

• mood and emotional well-being 
• infant care and feeding 
• sexuality, contraception, and birth spacing 
• sleep and fatigue 
• physical recovery from birth 
• chronic disease management and transition to primary care provider 
• health maintenance 
• review of labor and delivery course if needed 
• review of risks and recommendations for future pregnancies. 

After these components are addressed, it is expected that the patient will be transitioned to a primary care provider (who may continue to be the ObGyn, as appropriate) to coordinate her future care in the primary medical home.  

Useful resource for adopting new paradigm 

ACOG's recommendations are somewhat daunting, and these changes will require education and resources, a significant increase in obstetric provider time and effort, and consideration of policy change regarding such issues as parental leave and postpartum care reimbursement. As a start, ACOG has developed an online aid for health care providers called "Postpartum toolkit" (https://www.acog.org/About-ACOG/ACOG-Departments/Toolkits-for-Health-Care-Providers/Postpartum-Toolkit), which provides education and resources for all steps in the process and can be individualized for each practice and patient.⁷  
 

The past year was an exciting one in obstetrics. The landmark ARRIVE trial presented at the Society for Maternal-Fetal Medicine’s (SMFM) annual meeting and subsequently published in the New England Journal of Medicine contradicted a long-held belief about the safety of elective labor induction. In a large randomized trial, Cahill and colleagues took a controversial but practical clinical question about second-stage labor management and answered it for the practicing obstetrician in the trenches. Finally, the American College of Obstetricians and Gynecologists (ACOG) placed new emphasis on the oft overlooked but increasingly more complicated postpartum period, offering guidance to support improving care for women in this transitional period.

Ultimately, this was the year of the patient, as research, clinical guidelines, and education focused on how to achieve the best in safety and quality of care for delivery planning, the delivery itself, and the so-called fourth trimester.

ARRIVE: Labor induction at 39 weeks reduces CD rate with no difference in perinatal death or serious outcomes 

Grobman WA, Rice MM, Reddy UM, et al; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Labor induction versus expectant management in low-risk nulliparous women. N Engl J Med. 2018;379:513-523.

The term "elective induction of labor" has long had a negative connotation because of its association with increased CD rates and adverse perinatal outcomes. This view was based on results from older observational studies that compared outcomes for labor induction with those of spontaneous labor. In more recent observational studies that more appropriately compared labor induction with expectant management, however, elective induction of labor appears to be associated with similar CD rates and perinatal outcomes. 
To test the hypothesis that elective induction would have a lower risk for perinatal death or severe neonatal complications than expectant management in low-risk nulliparous women, Grobman and colleagues conducted A Randomized Trial of Induction Versus Expectant Management (ARRIVE).1 

Study population, timing of delivery, and trial outcomes 

This randomized controlled trial included 6,106 women at 41 US centers in the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Study participants were low-risk nulliparous women with a singleton vertex fetus who were randomly assigned to induction of labor at 39 to 39 4/7 weeks (n = 3,062) or expectant management (n = 3,044) until 40 5/7 to 42 2/7 weeks. 

"Low risk" was defined as having no maternal or fetal indication for delivery prior to 40 5/7 weeks. Reliable gestational dating was required.  

While no specific protocol for induction of labor management was required, there were 2 requests: 1) Cervical ripening was requested for an unfavorable cervix (63% of participants had a modified Bishop score <5), and 2) a duration of at least 12 hours after cervical ripening, rupture of membranes, and use of uterine stimulant was requested before performing a CD for "failed induction" (if medically appropriate). 

The primary outcome was a composite of perinatal death or serious neonatal complications. The main secondary outcome was CD. 

Potentially game-changing findings 

The investigators found that there was no statistically significant difference between the elective induction and expectant management groups for the primary composite perinatal outcome (4.3% vs 5.4%; P = .049, with P<.046 prespecified for significance). In addition, the rate of CD was significantly lower in the labor induction group than in the expectant management group (18.6% vs 22.2%; P<.001). 
Other significant findings in secondary outcomes included the following: 

• Hypertensive disorders of pregnancy were significantly lower in the labor induction group compared with the expectant management group (9.1% vs 14.1%; P<.001). 
• The labor induction group had a longer length of stay in the labor and delivery unit but a shorter postpartum hospital stay. 
• The labor induction group reported less pain and more control during labor. 

Results refute negative notion of elective labor induction 

The authors concluded that in a low-risk nulliparous patient population, elective induction of labor at 39 weeks does not increase the risk for adverse perinatal outcomes and decreases the rate of CD and hypertensive disorders of pregnancy. Additionally, they noted that induction at 39 weeks should not be avoided with the goal of preventing CD, as even women with an unfavorable cervix had a lower rate of CD in the induction group compared with the expectant management group.

Continue to: Immediate pushing in second stage...

Immediate pushing in second stage offers benefits and is preferable to delayed pushing 

Cahill AG, Srinivas SK, Tita AT, et al. Effect of immediate vs delayed pushing on rates of spontaneous vaginal delivery among nulliparous women receiving neuraxial analgesia: a randomized clinical trial. JAMA. 2018;320:1444-1454. 

In a randomized trial of 2,414 women, Cahill and colleagues sought to answer a seemingly simple question: What is the best timing for pushing during the second stage of labor--immediate or delayed? 

Practical management of the second stage of labor (defined as complete cervical dilation to the delivery of the infant) varies by provider and setting, and previous data on pushing efforts are conflicting. Delayed pushing, or "laboring down," has been suggested to allow passive fetal rotation and to conserve maternal energy for pushing. Older studies have shown that delayed pushing decreases the rate of operative delivery. More recent study data have not demonstrated a difference between immediate and delayed pushing techniques on vaginal delivery rates and have noted that increased maternal and neonatal morbidities are associated with a longer second stage of labor. 

The recent trial by Cahill and colleagues was designed to determine the effect of these 2 techniques on spontaneous vaginal delivery rates and on maternal and neonatal morbidities.⁴ 

Large study population 

This randomized pragmatic trial was conducted at 6 centers in the United States. Study participants (2,404 women completed the study) were nulliparous women at 37 or more weeks' gestation with neuraxial anesthesia who were randomly assigned at complete cervical dilation either to immediate pushing (n = 1,200) or to delayed pushing, that is, instructed to wait 60 minutes before starting to push (n = 1,204). The obstetric provider determined the rest of the labor management. 

The primary outcome was the rate of spontaneous vaginal delivery. Secondary outcomes included duration of the second stage of labor, duration of active pushing, operative vaginal delivery, CD, and several maternal assessments (postpartum hemorrhage, chorioamnionitis, endometritis, and perineal lacerations). 

Both groups had similar vaginal delivery rates, differences in some measures 

There was no difference in the primary outcome between the 2 groups: The spontaneous vaginal delivery rate was 85.9% (n = 1,031) in the immediate pushing group and 86.5% (n = 1,041) in the delayed pushing group (P = .67).  
Analysis of secondary outcomes revealed several significant differences: 

• decreased total time for the second stage of labor in the immediate pushing group compared with the delayed pushing group (102.4 vs 134.2 minutes) but longer active pushing time (83.7 vs 74.5 minutes) 
• a lower rate of postpartum hemorrhage, chorioamnionitis in the second stage, neonatal acidemia, and suspected neonatal sepsis in the immediate pushing group 
• a higher rate of third-degree perineal lacerations in the immediate pushing group. 

 No difference was found between groups in rates of operative vaginal deliveries, CDs, endometritis, overall perineal lacerations, or spontaneous vaginal delivery by fetal station or occiput position. 

Authors' takeaway 

The authors concluded that since delayed pushing does not increase spontaneous vaginal delivery rates and increases the duration of the second stage of labor and both maternal and neonatal morbidity, immediate pushing may be preferred in this patient population. 

ACOG aims to optimize postpartum care 

American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 736. Optimizing postpartum care. Obstet Gynecol. 2018;131:e140-e150. 

In May 2018, ACOG released "Optimizing postpartum care," a committee opinion that proposes a new model of comprehensive postpartum care focused on improving both short- and long-term health outcomes for women and infants. (This replaces the June 2016 committee opinion No. 666.) Described as "the fourth trimester," the postpartum period is a critical transitional period in which both pregnancy-related and pre-existing conditions may affect maternal, neonatal, and family status; half of pregnancy-related maternal deaths occur during the postpartum period.⁶ 

The postpartum visit: Often a lost opportunity 

ACOG cites that up to 40% of women in the United States do not attend their postpartum visit.6 Many aspects of the postpartum visit, including follow-up for chronic diseases, mental health screening, and contraceptive counseling, provide opportunities for acute intervention as well as establishment of healthy behaviors. Some studies have shown that postpartum depression, breastfeeding, and patient satisfaction outcomes improve as a result of postpartum engagement. 

Continue to: ACOG's recommendations...

ACOG's recommendations 

Ongoing process. ACOG's first proposed change concerns the structure of the postpartum visit itself, which traditionally has been a single visit with a provider at approximately 6 weeks postpartum. Postpartum care plans actually should be started before birth, during regular prenatal care, and adjusted in the hospital as needed so that the provider can educate patients about the issues they may face and resources they may need during this time. This prenatal preparation hopefully will encourage more patients to attend their postpartum visits. 

Increased provider contact. Another proposed change is that after delivery, the patient should have contact with a provider within the first 3 weeks postpartum. For high-risk patients, this may involve an in-person clinic visit as soon as 3 to 10 days postpartum (for hypertensive disorders of pregnancy) or at 1 to 2 weeks (for postpartum depression screening, incision checks, and lactation issues). For lower-risk patients, a phone call may be appropriate and/or preferred. Ongoing follow-up for all patients before the final postpartum visit should be individualized. 

Postpartum visit and care transition. ACOG recommends a comprehensive postpartum visit at 4 to 12 weeks to fully evaluate the woman's physical, social, and psychologic well-being and to serve as a transition from pregnancy care to well-woman care. This is a large order and includes evaluation of the following: 

• mood and emotional well-being 
• infant care and feeding 
• sexuality, contraception, and birth spacing 
• sleep and fatigue 
• physical recovery from birth 
• chronic disease management and transition to primary care provider 
• health maintenance 
• review of labor and delivery course if needed 
• review of risks and recommendations for future pregnancies. 

After these components are addressed, it is expected that the patient will be transitioned to a primary care provider (who may continue to be the ObGyn, as appropriate) to coordinate her future care in the primary medical home.  

Useful resource for adopting new paradigm 

ACOG's recommendations are somewhat daunting, and these changes will require education and resources, a significant increase in obstetric provider time and effort, and consideration of policy change regarding such issues as parental leave and postpartum care reimbursement. As a start, ACOG has developed an online aid for health care providers called "Postpartum toolkit" (https://www.acog.org/About-ACOG/ACOG-Departments/Toolkits-for-Health-Care-Providers/Postpartum-Toolkit), which provides education and resources for all steps in the process and can be individualized for each practice and patient.⁷  
 

The past year brought new information and guidance from the American College of Obstetricians and Gynecologists (ACOG) on many relevant obstetric topics, making it difficult to choose just a few for this Update. Opioid use in pregnancy was an obvious choice given the national media attention and the potential opportunity for intervention in pregnancy for both the mother and the fetus/newborn. Postpartum hemorrhage, an “oldie but goodie,” was chosen for several reasons: It got a new definition, a new focus on multidisciplinary care, and an exciting novel tool for the treatment toolbox. Finally, given the rapidly changing technology, new screening recommendations, and the complexity of counseling, carrier screening was chosen as a genetic hot topic for this year.

Opioids, obstetrics, and opportunities

Reddy UM, Davis JM, Ren Z, Greene MF; Opioid Use in Pregnancy, Neonatal Abstinence Syndrome, and Childhood Outcomes Workshop Invited Speakers. Opioid use in pregnancy, neonatal abstinence syndrome, and childhood outcomes: Executive summary of a joint workshop. Obstet Gynecol. 2017;130(1):10-28.

ACOG Committee on Obstetric Practice. ACOG committee opinion No. 711: Opioid use and opioid use disorder in pregnancy. Obstet Gynecol. 2017;130(2):e81-e94.

The term "opioid epidemic" is omnipresent in both the lay media and the medical literature. In the past decade, the United States has had a huge increase in the number of opioid prescriptions, the rate of admissions and deaths due to prescription opioid misuse and abuse, and an increased rate of heroin use attributed to prior prescription opioid use.

Obstetrics is unique in that opioid use and abuse disorders affect 2 patients simultaneously (the mother and fetus), and the treatment options are somewhat at odds in that they need to balance a stable maternal status and intrauterine environment with the risk of neonatal abstinence syndrome (NAS). Additionally, pregnancy is an opportunity for a woman with opioid use disorder to have access to medical care (possibly for the first time) leading to the diagnosis and treatment of her disease. As the clinicians on the front line, obstetricians therefore require education and guidance on best practice for management of opioid use in pregnancy.

In 2017, Reddy and colleagues, as part of a joint workshop on opioid use in pregnancy, and a committee opinion from ACOG provided the following recommendations.

Screening

Universally screen for substance use, starting at the first prenatal visit; this is recommended over risk factor-based screening.

Use a validated screening tool. A tool such as a questionnaire is recommended as the first-line screening test (for example, the 4Ps screen, the National Institute on Drug Abuse Quick Screen, and the CRAFFT Screening Interview).

Do not universally screen urine and hair for drugs. This type of screening has many limitations, such as the limited number of substances tested, false-positive results, and inaccurate determination of the frequency or timing of drug use. Information regarding the consequences of the test must be provided, and patient consent must be obtained prior to performing the test.

Treatment

Use medication-assisted treatment with buprenorphine or methadone, which is preferred to medically supervised withdrawal. Medication-assisted treatment prevents withdrawal symptoms and cravings, decreases the risk of relapse, improves compliance with prenatal care and addiction treatment programs, and leads to better obstetric outcomes (higher birth weight, lower rate of preterm birth, lower perinatal mortality).

Know that buprenorphine has several advantages over methadone, including the convenience of an outpatient prescription, a lower risk of overdose, and improved neonatal outcomes (higher birth weight, lower doses of morphine to treat NAS, shorter treatment duration).

Prioritize methadone as the preferred option for pregnant women who are already receiving methadone treatment (changing to buprenorphine may precipitate withdrawal), those with a long-standing history of or multi-substance abuse, and those who have failed other treatment programs.

Prenatal care

Screen for comorbid conditions such as sexually transmitted infections, other medications or substance use, social conditions, and mental health disorders.

Perform ultrasonography serially to monitor fetal growth because of the increased risk of fetal growth restriction.

Consult with anesthesiology for pain control recommendations for labor and delivery and with neonatalogy/pediatrics for NAS counseling.

Intrapartum/postpartum care

Recognize heightened pain. Women with opioid use disorder have increased sensitivity to painful stimuli.

Continue the maintenance dose of methadone or buprenorphine throughout hospitalization, with short-acting opioids added for a brief period for postoperative pain.

Prioritize regional anesthesia for pain control in labor or for cesarean delivery.

Consider alternative therapies such as regional blocks, nonopioid medications (nonsteroidal anti-inflammatory drugs, acetaminophen), or relaxation/mindfulness training.

Avoid mixed antagonist and agonist narcotics (butorphanol, nalbuphine, pentazocine) as they may cause acute withdrawal.

Encourage breastfeeding to decrease the severity of NAS and maternal stress and increase maternal-child bonding and maternal confidence.

Offer contraceptive counseling and services immediately postpartum in the hospital, with strong consideration for long-acting reversible contraception.

Opioid prescribing practices

Opioids are prescribed in excess post–cesarean delivery. Several recent studies have demonstrated that most women are prescribed opioids post–cesarean delivery in excess of the amount they use (median 30–40 tablets prescribed, median 20 tablets used).^1,2 The leftover opioid medication usually is not discarded and therefore is at risk for diversion or misuse. A small subset of patients will use all the opioids prescribed and feel as though they have not received enough medication.

Prescribe post–cesarean delivery opioids more appropriately by considering individual inpatient opioid requirements or a shared decision-making model.³

Prioritize acetaminophen and ibuprofen during breastfeeding. In a recent editorial in OBG Management, Robert L. Barbieri, MD, recommended that whenever possible, acetaminophen and ibuprofen should be the first-line treatment for breastfeeding women, and narcotics that are metabolized by CYP2D6 should be avoided to reduce the risk to the newborn.⁴

Read about new strategies for postpartum hemorrhage.

Postpartum hemorrhage: New definitions and new strategies for stemming the flow

ACOG Committee on Practice Bulletins—Obstetrics. ACOG practice bulletin No. 183: Postpartum hemorrhage. Obstet Gynecol. 2017;130(4):e168-e186.

From the very first sentence of the new ACOG practice bulletin, postpartum hemorrhage (PPH) is redefined as "cumulative blood loss greater than or equal to 1,000 mL or blood loss accompanied by signs or symptoms of hypovolemia within 24 hours after the birth process (includes intrapartum loss) regardless of route of delivery." Although this does not seem to be a huge change from the traditional teaching of a 500-mL blood loss at vaginal delivery and a 1,000-mL loss at cesarean delivery, it reflects a shift in focus from simply responding to a certain amount of bleeding to using a multidisciplinary action plan for treating this leading cause of maternal mortality worldwide.

Focus on developing a PPH action plan

As part of the shift toward a multidisciplinary action plan for PPH, all obstetric team members should be aware of the following:  

• For most postpartum women, by the time they begin to show signs of hemodynamic compromise, the amount of blood loss approaches 25% of their total blood volume (1,500 mL). Lactic acidosis, systemic inflammation, and a consumptive coagulopathy result.  
• Risk stratification prior to delivery, recognition and identification of the source of bleeding, and aggressive early resuscitation to prevent hypovolemia are paramount. Experience gleaned from trauma massive transfusion protocols suggests that judicious transfusion of packed red blood cells, fresh frozen plasma, and platelets in a 1:1:1 ratio is appropriate for obstetric patients. Additionally, patients with low fibrinogen levels should be treated with cryoprecipitate.  
• The use of fixed transfusion ratios and standardized protocols for recognition and management of PPH has been demonstrated to increase earlier intervention and resolution of hemorrhage at an earlier stage, although the maternal outcomes results have been mixed.  
• Multidisciplinary team drills and simulation exercises also should be considered to help solidify training of an institution's teams responsible for PPH response.

Novel management option: Tranexamic acid

In addition to these strategies, there is a new recommendation for managing refractory PPH: tranexamic acid, which works by binding to lysine receptors on plasminogen and plasmin, inhibiting plasmin-mediated fibrin degradation.5 Previously, tranexamic acid was known to be effective in trauma, heart surgery, and in patients with thrombophilias. Pacheco and colleagues recently demonstrated reduced mortality from obstetric bleeding if tranexamic acid was given within 3 hours of delivery, without increased thrombotic complications.⁵ ACOG recommends its use if initial medical therapy fails, while the World Health Organization strongly recommends that tranexamic acid be part of a standard PPH package for all cases of PPH (TABLE).⁶

Read about new ACOG guidance on prepregnancy and prenatal screening.

ACOG Committee on Genetics. Committee opinion No. 690: Carrier screening in the age of genomic medicine. Obstet Gynecol. 2017;129(3):e35-e40.

ACOG Committee on Genetics. Committee opinion No. 691: Carrier screening for genetic conditions. Obstet Gynecol. 2017;129(3):e41-e55.

Ideally, carrier screening should be offered prior to pregnancy to fully inform couples of their reproductive risks and options for pregnancy. If not performed in the preconception period, carrier screening should be offered to all pregnant women. If a patient chooses screening and screens positive for a particular disorder, her reproductive partner should then be offered screening so that the risk of having an affected child can be determined.

New ACOG guidance on prepregnancy and prenatal screening

Carrier screening recommendations have evolved as the technology available has expanded. All 3 of the following strategies now are considered "acceptable" according to 2 recently published ACOG committee opinions.

Traditional ethnic-specific carrier screening, previously ACOG's sole recommendation, involves offering specific genetic screening to patients from populations with a high prevalence for certain conditions. One such example is Tay-Sachs disease screening in Ashkenazi Jewish patients.

Panethnic screening, which takes into account mixed or uncertain backgrounds, involves screening for a certain panel of disorders and is available to all patients regardless of their background (for example, cystic fibrosis screening offered to all pregnant patients).

Expanded carrier screening is when a large number of disorders can be screened for simultaneously for a lower cost than previous testing strategies. Expanded carrier screening panels vary in number and which conditions are tested by the laboratory. An ideal expanded carrier screening panel has been debated in the literature but not agreed on.⁷

ObGyns and practices therefore are encouraged to develop a standard counseling and screening protocol to offer to all their patients while being flexible to make available any patient-requested screening that is outside their protocol. Pretest and posttest counseling, including a thorough family history, is essential (as with any genetic testing) and should include residual risk after testing, potential need for specific familial mutation testing instead of general carrier screening, and issues with consanguinity.

Three essential screens

Regardless of the screening strategy chosen from the above options, 3 screening tests should be offered to all pregnant women or couples considering pregnancy (either individually or in the context of an expanded screening panel):

• Cystic fibrosis. At the least, a panel of the 23 most common mutations should be used. More expanded panels, which include hundreds of mutations, increase detection in non-Caucasian populations and for milder forms of the disease or infertility-related mutations.
• Hemoglobinopathies (sickle cell, α- and β-thalassemia). Complete blood count and red blood indices are recommended for all, with hemoglobin electrophoresis recommended for patients of African, Middle Eastern, Mediterranean, or West Indian descent or if mean corpuscular volume is low.
• Spinal muscular atrophy (SMA). The most recent addition to ACOG's recommendations for general carrier screening due to the relatively high carrier frequency (1-in-40 to 1-in-60) and the severity of the disease, SMA causes degeneration of the spinal cord neurons, skeletal muscular atrophy, and overall weakness. Screening is via polymerase chain reaction for SMN1 copy number: 2 copies are normal, and 1 copy indicates a carrier of the SMN1 deletion. About 3% to 4% of patients will screen negative but still will be "carriers" due to having 2 copies of the SMN1 gene on 1 chromosome and no copies on the other chromosome.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

The past year brought new information and guidance from the American College of Obstetricians and Gynecologists (ACOG) on many relevant obstetric topics, making it difficult to choose just a few for this Update. Opioid use in pregnancy was an obvious choice given the national media attention and the potential opportunity for intervention in pregnancy for both the mother and the fetus/newborn. Postpartum hemorrhage, an “oldie but goodie,” was chosen for several reasons: It got a new definition, a new focus on multidisciplinary care, and an exciting novel tool for the treatment toolbox. Finally, given the rapidly changing technology, new screening recommendations, and the complexity of counseling, carrier screening was chosen as a genetic hot topic for this year.

Opioids, obstetrics, and opportunities

Reddy UM, Davis JM, Ren Z, Greene MF; Opioid Use in Pregnancy, Neonatal Abstinence Syndrome, and Childhood Outcomes Workshop Invited Speakers. Opioid use in pregnancy, neonatal abstinence syndrome, and childhood outcomes: Executive summary of a joint workshop. Obstet Gynecol. 2017;130(1):10-28.

ACOG Committee on Obstetric Practice. ACOG committee opinion No. 711: Opioid use and opioid use disorder in pregnancy. Obstet Gynecol. 2017;130(2):e81-e94.

The term "opioid epidemic" is omnipresent in both the lay media and the medical literature. In the past decade, the United States has had a huge increase in the number of opioid prescriptions, the rate of admissions and deaths due to prescription opioid misuse and abuse, and an increased rate of heroin use attributed to prior prescription opioid use.

Obstetrics is unique in that opioid use and abuse disorders affect 2 patients simultaneously (the mother and fetus), and the treatment options are somewhat at odds in that they need to balance a stable maternal status and intrauterine environment with the risk of neonatal abstinence syndrome (NAS). Additionally, pregnancy is an opportunity for a woman with opioid use disorder to have access to medical care (possibly for the first time) leading to the diagnosis and treatment of her disease. As the clinicians on the front line, obstetricians therefore require education and guidance on best practice for management of opioid use in pregnancy.

In 2017, Reddy and colleagues, as part of a joint workshop on opioid use in pregnancy, and a committee opinion from ACOG provided the following recommendations.

Screening

Universally screen for substance use, starting at the first prenatal visit; this is recommended over risk factor-based screening.

Use a validated screening tool. A tool such as a questionnaire is recommended as the first-line screening test (for example, the 4Ps screen, the National Institute on Drug Abuse Quick Screen, and the CRAFFT Screening Interview).

Do not universally screen urine and hair for drugs. This type of screening has many limitations, such as the limited number of substances tested, false-positive results, and inaccurate determination of the frequency or timing of drug use. Information regarding the consequences of the test must be provided, and patient consent must be obtained prior to performing the test.

Treatment

Use medication-assisted treatment with buprenorphine or methadone, which is preferred to medically supervised withdrawal. Medication-assisted treatment prevents withdrawal symptoms and cravings, decreases the risk of relapse, improves compliance with prenatal care and addiction treatment programs, and leads to better obstetric outcomes (higher birth weight, lower rate of preterm birth, lower perinatal mortality).

Know that buprenorphine has several advantages over methadone, including the convenience of an outpatient prescription, a lower risk of overdose, and improved neonatal outcomes (higher birth weight, lower doses of morphine to treat NAS, shorter treatment duration).

Prioritize methadone as the preferred option for pregnant women who are already receiving methadone treatment (changing to buprenorphine may precipitate withdrawal), those with a long-standing history of or multi-substance abuse, and those who have failed other treatment programs.

Prenatal care

Screen for comorbid conditions such as sexually transmitted infections, other medications or substance use, social conditions, and mental health disorders.

Perform ultrasonography serially to monitor fetal growth because of the increased risk of fetal growth restriction.

Consult with anesthesiology for pain control recommendations for labor and delivery and with neonatalogy/pediatrics for NAS counseling.

Intrapartum/postpartum care

Recognize heightened pain. Women with opioid use disorder have increased sensitivity to painful stimuli.

Continue the maintenance dose of methadone or buprenorphine throughout hospitalization, with short-acting opioids added for a brief period for postoperative pain.

Prioritize regional anesthesia for pain control in labor or for cesarean delivery.

Consider alternative therapies such as regional blocks, nonopioid medications (nonsteroidal anti-inflammatory drugs, acetaminophen), or relaxation/mindfulness training.

Avoid mixed antagonist and agonist narcotics (butorphanol, nalbuphine, pentazocine) as they may cause acute withdrawal.

Encourage breastfeeding to decrease the severity of NAS and maternal stress and increase maternal-child bonding and maternal confidence.

Offer contraceptive counseling and services immediately postpartum in the hospital, with strong consideration for long-acting reversible contraception.

Opioid prescribing practices

Opioids are prescribed in excess post–cesarean delivery. Several recent studies have demonstrated that most women are prescribed opioids post–cesarean delivery in excess of the amount they use (median 30–40 tablets prescribed, median 20 tablets used).^1,2 The leftover opioid medication usually is not discarded and therefore is at risk for diversion or misuse. A small subset of patients will use all the opioids prescribed and feel as though they have not received enough medication.

Prescribe post–cesarean delivery opioids more appropriately by considering individual inpatient opioid requirements or a shared decision-making model.³

Prioritize acetaminophen and ibuprofen during breastfeeding. In a recent editorial in OBG Management, Robert L. Barbieri, MD, recommended that whenever possible, acetaminophen and ibuprofen should be the first-line treatment for breastfeeding women, and narcotics that are metabolized by CYP2D6 should be avoided to reduce the risk to the newborn.⁴

Read about new strategies for postpartum hemorrhage.

Postpartum hemorrhage: New definitions and new strategies for stemming the flow

ACOG Committee on Practice Bulletins—Obstetrics. ACOG practice bulletin No. 183: Postpartum hemorrhage. Obstet Gynecol. 2017;130(4):e168-e186.

From the very first sentence of the new ACOG practice bulletin, postpartum hemorrhage (PPH) is redefined as "cumulative blood loss greater than or equal to 1,000 mL or blood loss accompanied by signs or symptoms of hypovolemia within 24 hours after the birth process (includes intrapartum loss) regardless of route of delivery." Although this does not seem to be a huge change from the traditional teaching of a 500-mL blood loss at vaginal delivery and a 1,000-mL loss at cesarean delivery, it reflects a shift in focus from simply responding to a certain amount of bleeding to using a multidisciplinary action plan for treating this leading cause of maternal mortality worldwide.

Focus on developing a PPH action plan

As part of the shift toward a multidisciplinary action plan for PPH, all obstetric team members should be aware of the following:  

• For most postpartum women, by the time they begin to show signs of hemodynamic compromise, the amount of blood loss approaches 25% of their total blood volume (1,500 mL). Lactic acidosis, systemic inflammation, and a consumptive coagulopathy result.  
• Risk stratification prior to delivery, recognition and identification of the source of bleeding, and aggressive early resuscitation to prevent hypovolemia are paramount. Experience gleaned from trauma massive transfusion protocols suggests that judicious transfusion of packed red blood cells, fresh frozen plasma, and platelets in a 1:1:1 ratio is appropriate for obstetric patients. Additionally, patients with low fibrinogen levels should be treated with cryoprecipitate.  
• The use of fixed transfusion ratios and standardized protocols for recognition and management of PPH has been demonstrated to increase earlier intervention and resolution of hemorrhage at an earlier stage, although the maternal outcomes results have been mixed.  
• Multidisciplinary team drills and simulation exercises also should be considered to help solidify training of an institution's teams responsible for PPH response.

Novel management option: Tranexamic acid

In addition to these strategies, there is a new recommendation for managing refractory PPH: tranexamic acid, which works by binding to lysine receptors on plasminogen and plasmin, inhibiting plasmin-mediated fibrin degradation.5 Previously, tranexamic acid was known to be effective in trauma, heart surgery, and in patients with thrombophilias. Pacheco and colleagues recently demonstrated reduced mortality from obstetric bleeding if tranexamic acid was given within 3 hours of delivery, without increased thrombotic complications.⁵ ACOG recommends its use if initial medical therapy fails, while the World Health Organization strongly recommends that tranexamic acid be part of a standard PPH package for all cases of PPH (TABLE).⁶

Read about new ACOG guidance on prepregnancy and prenatal screening.

ACOG Committee on Genetics. Committee opinion No. 690: Carrier screening in the age of genomic medicine. Obstet Gynecol. 2017;129(3):e35-e40.

ACOG Committee on Genetics. Committee opinion No. 691: Carrier screening for genetic conditions. Obstet Gynecol. 2017;129(3):e41-e55.

Ideally, carrier screening should be offered prior to pregnancy to fully inform couples of their reproductive risks and options for pregnancy. If not performed in the preconception period, carrier screening should be offered to all pregnant women. If a patient chooses screening and screens positive for a particular disorder, her reproductive partner should then be offered screening so that the risk of having an affected child can be determined.

New ACOG guidance on prepregnancy and prenatal screening

Carrier screening recommendations have evolved as the technology available has expanded. All 3 of the following strategies now are considered "acceptable" according to 2 recently published ACOG committee opinions.

Traditional ethnic-specific carrier screening, previously ACOG's sole recommendation, involves offering specific genetic screening to patients from populations with a high prevalence for certain conditions. One such example is Tay-Sachs disease screening in Ashkenazi Jewish patients.

Panethnic screening, which takes into account mixed or uncertain backgrounds, involves screening for a certain panel of disorders and is available to all patients regardless of their background (for example, cystic fibrosis screening offered to all pregnant patients).

Expanded carrier screening is when a large number of disorders can be screened for simultaneously for a lower cost than previous testing strategies. Expanded carrier screening panels vary in number and which conditions are tested by the laboratory. An ideal expanded carrier screening panel has been debated in the literature but not agreed on.⁷

ObGyns and practices therefore are encouraged to develop a standard counseling and screening protocol to offer to all their patients while being flexible to make available any patient-requested screening that is outside their protocol. Pretest and posttest counseling, including a thorough family history, is essential (as with any genetic testing) and should include residual risk after testing, potential need for specific familial mutation testing instead of general carrier screening, and issues with consanguinity.

Three essential screens

Regardless of the screening strategy chosen from the above options, 3 screening tests should be offered to all pregnant women or couples considering pregnancy (either individually or in the context of an expanded screening panel):

• Cystic fibrosis. At the least, a panel of the 23 most common mutations should be used. More expanded panels, which include hundreds of mutations, increase detection in non-Caucasian populations and for milder forms of the disease or infertility-related mutations.
• Hemoglobinopathies (sickle cell, α- and β-thalassemia). Complete blood count and red blood indices are recommended for all, with hemoglobin electrophoresis recommended for patients of African, Middle Eastern, Mediterranean, or West Indian descent or if mean corpuscular volume is low.
• Spinal muscular atrophy (SMA). The most recent addition to ACOG's recommendations for general carrier screening due to the relatively high carrier frequency (1-in-40 to 1-in-60) and the severity of the disease, SMA causes degeneration of the spinal cord neurons, skeletal muscular atrophy, and overall weakness. Screening is via polymerase chain reaction for SMN1 copy number: 2 copies are normal, and 1 copy indicates a carrier of the SMN1 deletion. About 3% to 4% of patients will screen negative but still will be "carriers" due to having 2 copies of the SMN1 gene on 1 chromosome and no copies on the other chromosome.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

The past year brought new information and guidance from the American College of Obstetricians and Gynecologists (ACOG) on many relevant obstetric topics, making it difficult to choose just a few for this Update. Opioid use in pregnancy was an obvious choice given the national media attention and the potential opportunity for intervention in pregnancy for both the mother and the fetus/newborn. Postpartum hemorrhage, an “oldie but goodie,” was chosen for several reasons: It got a new definition, a new focus on multidisciplinary care, and an exciting novel tool for the treatment toolbox. Finally, given the rapidly changing technology, new screening recommendations, and the complexity of counseling, carrier screening was chosen as a genetic hot topic for this year.

Opioids, obstetrics, and opportunities

Reddy UM, Davis JM, Ren Z, Greene MF; Opioid Use in Pregnancy, Neonatal Abstinence Syndrome, and Childhood Outcomes Workshop Invited Speakers. Opioid use in pregnancy, neonatal abstinence syndrome, and childhood outcomes: Executive summary of a joint workshop. Obstet Gynecol. 2017;130(1):10-28.

ACOG Committee on Obstetric Practice. ACOG committee opinion No. 711: Opioid use and opioid use disorder in pregnancy. Obstet Gynecol. 2017;130(2):e81-e94.

The term "opioid epidemic" is omnipresent in both the lay media and the medical literature. In the past decade, the United States has had a huge increase in the number of opioid prescriptions, the rate of admissions and deaths due to prescription opioid misuse and abuse, and an increased rate of heroin use attributed to prior prescription opioid use.

Obstetrics is unique in that opioid use and abuse disorders affect 2 patients simultaneously (the mother and fetus), and the treatment options are somewhat at odds in that they need to balance a stable maternal status and intrauterine environment with the risk of neonatal abstinence syndrome (NAS). Additionally, pregnancy is an opportunity for a woman with opioid use disorder to have access to medical care (possibly for the first time) leading to the diagnosis and treatment of her disease. As the clinicians on the front line, obstetricians therefore require education and guidance on best practice for management of opioid use in pregnancy.

In 2017, Reddy and colleagues, as part of a joint workshop on opioid use in pregnancy, and a committee opinion from ACOG provided the following recommendations.

Screening

Universally screen for substance use, starting at the first prenatal visit; this is recommended over risk factor-based screening.

Use a validated screening tool. A tool such as a questionnaire is recommended as the first-line screening test (for example, the 4Ps screen, the National Institute on Drug Abuse Quick Screen, and the CRAFFT Screening Interview).

Do not universally screen urine and hair for drugs. This type of screening has many limitations, such as the limited number of substances tested, false-positive results, and inaccurate determination of the frequency or timing of drug use. Information regarding the consequences of the test must be provided, and patient consent must be obtained prior to performing the test.

Treatment

Use medication-assisted treatment with buprenorphine or methadone, which is preferred to medically supervised withdrawal. Medication-assisted treatment prevents withdrawal symptoms and cravings, decreases the risk of relapse, improves compliance with prenatal care and addiction treatment programs, and leads to better obstetric outcomes (higher birth weight, lower rate of preterm birth, lower perinatal mortality).

Know that buprenorphine has several advantages over methadone, including the convenience of an outpatient prescription, a lower risk of overdose, and improved neonatal outcomes (higher birth weight, lower doses of morphine to treat NAS, shorter treatment duration).

Prioritize methadone as the preferred option for pregnant women who are already receiving methadone treatment (changing to buprenorphine may precipitate withdrawal), those with a long-standing history of or multi-substance abuse, and those who have failed other treatment programs.

Prenatal care

Screen for comorbid conditions such as sexually transmitted infections, other medications or substance use, social conditions, and mental health disorders.

Perform ultrasonography serially to monitor fetal growth because of the increased risk of fetal growth restriction.

Consult with anesthesiology for pain control recommendations for labor and delivery and with neonatalogy/pediatrics for NAS counseling.

Intrapartum/postpartum care

Recognize heightened pain. Women with opioid use disorder have increased sensitivity to painful stimuli.

Continue the maintenance dose of methadone or buprenorphine throughout hospitalization, with short-acting opioids added for a brief period for postoperative pain.

Prioritize regional anesthesia for pain control in labor or for cesarean delivery.

Consider alternative therapies such as regional blocks, nonopioid medications (nonsteroidal anti-inflammatory drugs, acetaminophen), or relaxation/mindfulness training.

Avoid mixed antagonist and agonist narcotics (butorphanol, nalbuphine, pentazocine) as they may cause acute withdrawal.

Encourage breastfeeding to decrease the severity of NAS and maternal stress and increase maternal-child bonding and maternal confidence.

Offer contraceptive counseling and services immediately postpartum in the hospital, with strong consideration for long-acting reversible contraception.

Opioid prescribing practices

Opioids are prescribed in excess post–cesarean delivery. Several recent studies have demonstrated that most women are prescribed opioids post–cesarean delivery in excess of the amount they use (median 30–40 tablets prescribed, median 20 tablets used).^1,2 The leftover opioid medication usually is not discarded and therefore is at risk for diversion or misuse. A small subset of patients will use all the opioids prescribed and feel as though they have not received enough medication.

Prescribe post–cesarean delivery opioids more appropriately by considering individual inpatient opioid requirements or a shared decision-making model.³

Prioritize acetaminophen and ibuprofen during breastfeeding. In a recent editorial in OBG Management, Robert L. Barbieri, MD, recommended that whenever possible, acetaminophen and ibuprofen should be the first-line treatment for breastfeeding women, and narcotics that are metabolized by CYP2D6 should be avoided to reduce the risk to the newborn.⁴

Read about new strategies for postpartum hemorrhage.

Postpartum hemorrhage: New definitions and new strategies for stemming the flow

ACOG Committee on Practice Bulletins—Obstetrics. ACOG practice bulletin No. 183: Postpartum hemorrhage. Obstet Gynecol. 2017;130(4):e168-e186.

From the very first sentence of the new ACOG practice bulletin, postpartum hemorrhage (PPH) is redefined as "cumulative blood loss greater than or equal to 1,000 mL or blood loss accompanied by signs or symptoms of hypovolemia within 24 hours after the birth process (includes intrapartum loss) regardless of route of delivery." Although this does not seem to be a huge change from the traditional teaching of a 500-mL blood loss at vaginal delivery and a 1,000-mL loss at cesarean delivery, it reflects a shift in focus from simply responding to a certain amount of bleeding to using a multidisciplinary action plan for treating this leading cause of maternal mortality worldwide.

Focus on developing a PPH action plan

As part of the shift toward a multidisciplinary action plan for PPH, all obstetric team members should be aware of the following:  

• For most postpartum women, by the time they begin to show signs of hemodynamic compromise, the amount of blood loss approaches 25% of their total blood volume (1,500 mL). Lactic acidosis, systemic inflammation, and a consumptive coagulopathy result.  
• Risk stratification prior to delivery, recognition and identification of the source of bleeding, and aggressive early resuscitation to prevent hypovolemia are paramount. Experience gleaned from trauma massive transfusion protocols suggests that judicious transfusion of packed red blood cells, fresh frozen plasma, and platelets in a 1:1:1 ratio is appropriate for obstetric patients. Additionally, patients with low fibrinogen levels should be treated with cryoprecipitate.  
• The use of fixed transfusion ratios and standardized protocols for recognition and management of PPH has been demonstrated to increase earlier intervention and resolution of hemorrhage at an earlier stage, although the maternal outcomes results have been mixed.  
• Multidisciplinary team drills and simulation exercises also should be considered to help solidify training of an institution's teams responsible for PPH response.

Novel management option: Tranexamic acid

In addition to these strategies, there is a new recommendation for managing refractory PPH: tranexamic acid, which works by binding to lysine receptors on plasminogen and plasmin, inhibiting plasmin-mediated fibrin degradation.5 Previously, tranexamic acid was known to be effective in trauma, heart surgery, and in patients with thrombophilias. Pacheco and colleagues recently demonstrated reduced mortality from obstetric bleeding if tranexamic acid was given within 3 hours of delivery, without increased thrombotic complications.⁵ ACOG recommends its use if initial medical therapy fails, while the World Health Organization strongly recommends that tranexamic acid be part of a standard PPH package for all cases of PPH (TABLE).⁶

Read about new ACOG guidance on prepregnancy and prenatal screening.

ACOG Committee on Genetics. Committee opinion No. 690: Carrier screening in the age of genomic medicine. Obstet Gynecol. 2017;129(3):e35-e40.

ACOG Committee on Genetics. Committee opinion No. 691: Carrier screening for genetic conditions. Obstet Gynecol. 2017;129(3):e41-e55.

Ideally, carrier screening should be offered prior to pregnancy to fully inform couples of their reproductive risks and options for pregnancy. If not performed in the preconception period, carrier screening should be offered to all pregnant women. If a patient chooses screening and screens positive for a particular disorder, her reproductive partner should then be offered screening so that the risk of having an affected child can be determined.

New ACOG guidance on prepregnancy and prenatal screening

Carrier screening recommendations have evolved as the technology available has expanded. All 3 of the following strategies now are considered "acceptable" according to 2 recently published ACOG committee opinions.

Traditional ethnic-specific carrier screening, previously ACOG's sole recommendation, involves offering specific genetic screening to patients from populations with a high prevalence for certain conditions. One such example is Tay-Sachs disease screening in Ashkenazi Jewish patients.

Panethnic screening, which takes into account mixed or uncertain backgrounds, involves screening for a certain panel of disorders and is available to all patients regardless of their background (for example, cystic fibrosis screening offered to all pregnant patients).

Expanded carrier screening is when a large number of disorders can be screened for simultaneously for a lower cost than previous testing strategies. Expanded carrier screening panels vary in number and which conditions are tested by the laboratory. An ideal expanded carrier screening panel has been debated in the literature but not agreed on.⁷

ObGyns and practices therefore are encouraged to develop a standard counseling and screening protocol to offer to all their patients while being flexible to make available any patient-requested screening that is outside their protocol. Pretest and posttest counseling, including a thorough family history, is essential (as with any genetic testing) and should include residual risk after testing, potential need for specific familial mutation testing instead of general carrier screening, and issues with consanguinity.

Three essential screens

Regardless of the screening strategy chosen from the above options, 3 screening tests should be offered to all pregnant women or couples considering pregnancy (either individually or in the context of an expanded screening panel):

• Cystic fibrosis. At the least, a panel of the 23 most common mutations should be used. More expanded panels, which include hundreds of mutations, increase detection in non-Caucasian populations and for milder forms of the disease or infertility-related mutations.
• Hemoglobinopathies (sickle cell, α- and β-thalassemia). Complete blood count and red blood indices are recommended for all, with hemoglobin electrophoresis recommended for patients of African, Middle Eastern, Mediterranean, or West Indian descent or if mean corpuscular volume is low.
• Spinal muscular atrophy (SMA). The most recent addition to ACOG's recommendations for general carrier screening due to the relatively high carrier frequency (1-in-40 to 1-in-60) and the severity of the disease, SMA causes degeneration of the spinal cord neurons, skeletal muscular atrophy, and overall weakness. Screening is via polymerase chain reaction for SMN1 copy number: 2 copies are normal, and 1 copy indicates a carrier of the SMN1 deletion. About 3% to 4% of patients will screen negative but still will be "carriers" due to having 2 copies of the SMN1 gene on 1 chromosome and no copies on the other chromosome.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

In this Update we discuss several exciting new recommendations for preventive treatments in pregnancy and prenatal diagnostic tests. Our A-to-Z coverage includes:

• antenatal steroids in late preterm pregnancy
• expanded list of high-risk conditions warranting low-dose aspirin for preeclampsia prevention
• chromosomal microarray analysis versus karyotype for specific clinical situations
• Zika virus infection evolving information.

Next: New recommendation for timing of late preterm antenatal steroids

New recommendation offered for timing of late preterm antenatal steroids

Gyamfi-Bannerman C, Thom EA, Blackwell SC, et al; for the NICHD Maternal-Fetal Medicine Units Network. Antenatal betamethasone for women at risk for late preterm delivery. N Engl J Med. 2016;374(14):1311-1320.

American College of Obstetricians and Gynecologists. Committee Opinion No. 677. Antenatal corticosteroidtherapy for fetal maturation. Obstet Gynecol. 2016;128(4):e187-e194.

Kamath-Rayne BD, Rozance PJ, Goldenberg RL, Jobe AH. Antenatal corticosteroids beyond 34 weeks gestation: what do we do now? Am J Obstet Gynecol. 2016;215(4):423-430.

A dramatic recommendation for obstetric practice change occurred in 2016: the option of administering antenatal steroids for fetal lung maturity after 34 weeks. In the Antenatal Late Preterm Steroids (ALPS) trial of betamethasone in the late preterm period in patients at "high risk" of imminent delivery, Gyamfi-Bannerman and colleagues demonstrated that the treated group had a significant decrease in the rate of neonatal respiratory complications.

The primary outcome, a composite of respiratory morbidities (including transient tachypnea of the newborn, surfactant use, and need for resuscitation at birth) within the first 72 hours of life, had significant differences between groups, occurring in 165 of 1,427 infants (11.6%) in the betamethasone-treated group and 202 of 1,400 (14.4%) in the placebo group (relative risk in the betamethasone group, 0.80; 95% confidence interval, 0.66-0.97; P = .02). However, there was no statistically significant difference in respiratory distress syndrome, apnea, or pneumonia between groups, and the significant difference noted in bronchopulmonary dysplasia was based on a total number of 11 cases.

In response to these findings, both the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) released practice advisories and interim updates, culminating in a final recommendation for a single course of betamethasone in patients at high risk of preterm delivery between 34 and 36 6/7 weeks who have not received a previous course.

Related article:
When could use of antenatal corticosteroids in the late preterm birth period be beneficial?

In a thorough review of the literature on antenatal steroid use, Kamath-Rayne and colleagues highlighted several factors that should be considered before adopting universal use of steroids at >34 weeks. These include:   

• The definition of "high risk of imminent delivery" as preterm labor with at least 3-cm dilation or 75% effacement, or spontaneous rupture of membranes. The effect of less stringent inclusion criteria in real-world clinical practice is not known, and many patients who will go on to deliver at term will receive steroids unnecessarily.
• Multiple gestation, patients with pre-existing diabetes, women who had previously received a course of steroids, and fetuses with anomalies were excluded from the ALPS study. Use of antenatal steroids in these groups at >34 weeks should be evaluated before universal adoption.

Related article:
What is the ideal gestational age for twin delivery to minimize perinatal deaths?

• The incidence of neonatal hypoglycemia in the treated group was significantly increased. This affects our colleagues in pediatrics considerably from a systems standpoint (need for changes to newborn protocols and communication between services).
• The long-term outcomes of patients exposed to steroids in the late preterm period are yet to be delineated, specifically, the potential neurodevelopmental effects of a medication known to alter preterm brain development as well as cardiovascular and metabolic consequences.

Next: Low-dose aspirin for reducing preeclampsia risk

Low-dose aspirin clearly is effective for reducing the risk of preeclampsia

American College of Obstetricians and Gynecologists. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013;122(5):1122-1131.

Henderson JT, Whitlock EP, O'Connor E, Senger CA, Thompson JH, Rowland MG. Low-dose aspirin for prevention of morbidity and mortality from preeclampsia: a systematic evidence review for the US Preventive Services Task Force. Ann Intern Med. 2014;160(10):695-703.

LeFevre ML; US Preventive Services Task Force. Low-dose aspirin use for the prevention of morbidity and mortality from preeclampsia: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;161(11):819-826.

American College of Obstetricians and Gynecologists. Practice advisory on low-dose aspirin and prevention of preeclampsia: updated recommendations. http://www.acog.org/About-ACOG/News-Room/Practice-Advisories/Practice-Advisory-Low-Dose-Aspirin-and-Prevention-of-Preeclampsia-Updated-Recommendations. Published July 11, 2016. Accessed December 6, 2016.

In the 2013 ACOG Task Force on Hypertension in Pregnancy report, low-dose aspirin (60-80 mg) was recommended to be initiated in the late first trimester to reduce preeclampsia risk for women with:

• prior early onset preeclampsia with preterm delivery at <34 weeks' gestation, or
• preeclampsia in more than one prior pregnancy.  

This recommendation was based on several meta-analyses that demonstrated a 10% to 17% reduction in risk with no increase in bleeding, placental abruption, or other adverse events.

In 2014, the US Preventive Services Task Force (USPSTF) conducted a systematic evidence review of low-dose aspirin use for prevention of morbidity and mortality from preeclampsia. That report revealed a 24% risk reduction of preeclampsia in high-risk women treated with low-dose aspirin, as well as a 14% reduction in preterm birth and a 20% reduction in fetal growth restriction. A final statement from the USPSTF in 2014 recommended low-dose aspirin (60-150 mg) starting between 12 and 28 weeks' gestation for women at "high" risk who have:

• a history of preeclampsia, especially if accompanied by an adverse outcome
• multifetal gestation
• chronic hypertension
• diabetes (type 1 or type 2)
• renal disease
• autoimmune disease (such as systematic lupus erythematosus, antiphospholipid syndrome).

Related article:
Start offering aspirin to pregnant women at high risk for preeclampsia

As of July 11, 2016, ACOG supports this expanded list of high-risk conditions. Additionally, the USPSTF identified a "moderate" risk group in which low-dose aspirin may be considered if a patient has several risk factors, such as obesity, nulliparity, family history of preeclampsia, age 35 years or older, or another poor pregnancy outcome. ACOG notes, however, that the evidence supporting this practice is uncertain and does not make a recommendation regarding aspirin use in this population. Further study should be conducted to determine the benefit of low-dose aspirin in these patients as well as the long-term effects of treatment on maternal and child outcomes.

Next: CMA for prenatal genetic diagnosis

Chromosomal microarray analysis is preferable to karyotype in certain situations  

Pauli JM, Repke JT. Update on obstetrics. OBG Manag. 2013;25(1):28-32.

Society for Maternal-Fetal Medicine (SMFM), Dugoff L, Norton ME, Kuller JA. The use of chromosomal microarray for prenatal diagnosis. Am J Obstet Gynecol. 2016;215(4):B2-B9.

American College of Obstetricians and Gynecologists. Committee Opinion No. 682. Microarrays and next- generation sequencing technology: the use of advanced genetic diagnostic tools in obstetrics and gynecology.Obstet  Gynecol. 2016;128(6):e262-e268.

We previously addressed the use of chromosomal microarray analysis (CMA) for prenatal diagnosis in our 2013 "Update on obstetrics," specifically, the question of whether CMA could replace karyotype. The main differences between karyotype and CMA are that 1) only karyotype can detect balanced translocations/inversions and 2) only CMA can detect copy number variants (CNV). There are some differences in the technology and capabilities of the 2 types of CMA currently available as well.

In our 2013 article we concluded that "The total costs of such an approach--test, interpretation, counseling, and long-term follow-up of uncertain results--are unknown at this time and may prove to be unaffordable on a population-wide basis." Today, the cost of CMA is still higher than karyotype, but it is expected to decrease and insurance coverage for this test is expected to increase.

Related article:
Cell-free DNA screening for women at low risk for fetal aneuploidy

Both SMFM and ACOG released recommendations in 2016 regarding the use of CMA in prenatal genetic diagnosis, summarized as follows:  

• CMA is recommended over karyotype for fetuses with structural abnormalities on ultrasound
  • The detection rate for clinically relevant abnormal CNVs in this population is about 6%
• CMA is recommended for diagnosis for stillbirth specimens
  • CMA does not require dividing cells and may be a quicker and more reliable test in this population
• Karotype or fluorescence in situ hybridization (FISH) is recommended for fetuses with ultrasound findings suggestive of aneuploidy
  • If it is negative, then CMA is recommended
• Karyotype or CMA is recommended for patients desiring prenatal diagnostic testing with a normal fetal ultrasound
  • The detection rate for clinically relevant CNVs in this population (advanced maternal age, abnormal serum screening, prior aneuploidy, parental anxiety) is about 1%
• Pretest and posttest counseling about the limitations of CMA and a 2% risk of detection of variants of unknown significance (VUS) should be performed by a provider who has expertise in CMA and who has access to databases with genotype/phenotype information for VUS
  • This counseling should also include the possibility of diagnosis of nonpaternity, consanguinity, and adult-onset disease
• Karyotype is recommended for couples with recurrent pregnancy loss
  • The identification of balanced translocations in this population is most relevant in this patient population
• Prenatal diagnosis with routine use of whole-genome or whole-exome sequencing is not recommended.

Next: Zika virus: Check for updates

Zika virus infection: Check often for the latest updates

American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine. Practice advisory on Zika virus. http://www.acog.org/About-ACOG/News-Room/Practice-Advisories/Practice-Advisory-Interim-Guidance-for-Care-of-Obstetric-Patients- During-a-Zika-Virus-Outbreak. Published December 5, 2016. Accessed December 6, 2016.

Centers for Disease Control and Prevention. Zika virus. http://www.cdc.gov/zika/pregnancy/index.html. Updated August 22, 2016. Accessed December 6, 2016.

Petersen EE, Meaney-Delman D, Neblett-Fanfair R, et al. Update: interim guidance for preconception counseling and prevention of sexual transmission of Zika virus for persons with possible Zika virus exposure--United States, September 2016. MMWR Morbid Mortal Wkly Rep. 2016;65(39):1077-1081.

A yearly update on obstetrics would be remiss without mention of the Zika virus and its impact on pregnancy and reproduction. That being said, any recommendations we offer may be out of date by the time this article is published given the rapidly changing picture of Zika virus since it first dominated the headlines in 2016. Here are the basics as summarized from ACOG and the Centers for Disease Control and Prevention (CDC):

Viral spread. Zika virus may be spread in several ways: by an infected Aedes species mosquito, mother to fetus, sexual contact, blood transfusion, or laboratory exposure.

Symptoms of infection include conjunctivitis, fever, rash, and arthralgia, but most patients (4/5) are asymptomatic.

Sequelae. Zika virus infection during pregnancy is believed to cause fetal and neonatal microcephaly, intracranial calcifications, and brain and eye abnormalities. The rate of these findings in infected individuals, as well as the rate of vertical transmission, is not known.

Travel advisory. Pregnant women should not travel to areas with active Zika infection (the CDC website regularly updates these restricted areas).

Preventive measures. If traveling to an area of active Zika infection, pregnant women should take preventative measures day and night against mosquito bites, such as use of insect repellents approved by the Environmental Protection Agency, clothing that covers exposed skin, and staying indoors.

Safe sex. Abstinence or consistent condom use is recommended for pregnant women with partners who travel to or live in areas of active Zika infection.

Delay conception. Conception should be postponed for at least 6 months in men with Zika infection and at least 8 weeks in women with Zika infection.

Testing recommendations. Pregnant women with Zika virus exposure should be tested, regardless of symptoms. Symptomatic exposed nonpregnant women and all men should be tested.

Prenatal surveillance. High-risk consultation and serial ultrasounds for fetal anatomy and growth should be considered in patients with Zika virus infection during pregnancy. Amniocentesis can be considered on a case-by-case basis.

Related article:
Zika virus update: A rapidly moving target

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

In this Update we discuss several exciting new recommendations for preventive treatments in pregnancy and prenatal diagnostic tests. Our A-to-Z coverage includes:

• antenatal steroids in late preterm pregnancy
• expanded list of high-risk conditions warranting low-dose aspirin for preeclampsia prevention
• chromosomal microarray analysis versus karyotype for specific clinical situations
• Zika virus infection evolving information.

Next: New recommendation for timing of late preterm antenatal steroids

New recommendation offered for timing of late preterm antenatal steroids

Gyamfi-Bannerman C, Thom EA, Blackwell SC, et al; for the NICHD Maternal-Fetal Medicine Units Network. Antenatal betamethasone for women at risk for late preterm delivery. N Engl J Med. 2016;374(14):1311-1320.

American College of Obstetricians and Gynecologists. Committee Opinion No. 677. Antenatal corticosteroidtherapy for fetal maturation. Obstet Gynecol. 2016;128(4):e187-e194.

Kamath-Rayne BD, Rozance PJ, Goldenberg RL, Jobe AH. Antenatal corticosteroids beyond 34 weeks gestation: what do we do now? Am J Obstet Gynecol. 2016;215(4):423-430.

A dramatic recommendation for obstetric practice change occurred in 2016: the option of administering antenatal steroids for fetal lung maturity after 34 weeks. In the Antenatal Late Preterm Steroids (ALPS) trial of betamethasone in the late preterm period in patients at "high risk" of imminent delivery, Gyamfi-Bannerman and colleagues demonstrated that the treated group had a significant decrease in the rate of neonatal respiratory complications.

The primary outcome, a composite of respiratory morbidities (including transient tachypnea of the newborn, surfactant use, and need for resuscitation at birth) within the first 72 hours of life, had significant differences between groups, occurring in 165 of 1,427 infants (11.6%) in the betamethasone-treated group and 202 of 1,400 (14.4%) in the placebo group (relative risk in the betamethasone group, 0.80; 95% confidence interval, 0.66-0.97; P = .02). However, there was no statistically significant difference in respiratory distress syndrome, apnea, or pneumonia between groups, and the significant difference noted in bronchopulmonary dysplasia was based on a total number of 11 cases.

In response to these findings, both the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) released practice advisories and interim updates, culminating in a final recommendation for a single course of betamethasone in patients at high risk of preterm delivery between 34 and 36 6/7 weeks who have not received a previous course.

Related article:
When could use of antenatal corticosteroids in the late preterm birth period be beneficial?

In a thorough review of the literature on antenatal steroid use, Kamath-Rayne and colleagues highlighted several factors that should be considered before adopting universal use of steroids at >34 weeks. These include:   

• The definition of "high risk of imminent delivery" as preterm labor with at least 3-cm dilation or 75% effacement, or spontaneous rupture of membranes. The effect of less stringent inclusion criteria in real-world clinical practice is not known, and many patients who will go on to deliver at term will receive steroids unnecessarily.
• Multiple gestation, patients with pre-existing diabetes, women who had previously received a course of steroids, and fetuses with anomalies were excluded from the ALPS study. Use of antenatal steroids in these groups at >34 weeks should be evaluated before universal adoption.

Related article:
What is the ideal gestational age for twin delivery to minimize perinatal deaths?

• The incidence of neonatal hypoglycemia in the treated group was significantly increased. This affects our colleagues in pediatrics considerably from a systems standpoint (need for changes to newborn protocols and communication between services).
• The long-term outcomes of patients exposed to steroids in the late preterm period are yet to be delineated, specifically, the potential neurodevelopmental effects of a medication known to alter preterm brain development as well as cardiovascular and metabolic consequences.

Next: Low-dose aspirin for reducing preeclampsia risk

Low-dose aspirin clearly is effective for reducing the risk of preeclampsia

American College of Obstetricians and Gynecologists. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013;122(5):1122-1131.

Henderson JT, Whitlock EP, O'Connor E, Senger CA, Thompson JH, Rowland MG. Low-dose aspirin for prevention of morbidity and mortality from preeclampsia: a systematic evidence review for the US Preventive Services Task Force. Ann Intern Med. 2014;160(10):695-703.

LeFevre ML; US Preventive Services Task Force. Low-dose aspirin use for the prevention of morbidity and mortality from preeclampsia: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;161(11):819-826.

American College of Obstetricians and Gynecologists. Practice advisory on low-dose aspirin and prevention of preeclampsia: updated recommendations. http://www.acog.org/About-ACOG/News-Room/Practice-Advisories/Practice-Advisory-Low-Dose-Aspirin-and-Prevention-of-Preeclampsia-Updated-Recommendations. Published July 11, 2016. Accessed December 6, 2016.

In the 2013 ACOG Task Force on Hypertension in Pregnancy report, low-dose aspirin (60-80 mg) was recommended to be initiated in the late first trimester to reduce preeclampsia risk for women with:

• prior early onset preeclampsia with preterm delivery at <34 weeks' gestation, or
• preeclampsia in more than one prior pregnancy.  

This recommendation was based on several meta-analyses that demonstrated a 10% to 17% reduction in risk with no increase in bleeding, placental abruption, or other adverse events.

In 2014, the US Preventive Services Task Force (USPSTF) conducted a systematic evidence review of low-dose aspirin use for prevention of morbidity and mortality from preeclampsia. That report revealed a 24% risk reduction of preeclampsia in high-risk women treated with low-dose aspirin, as well as a 14% reduction in preterm birth and a 20% reduction in fetal growth restriction. A final statement from the USPSTF in 2014 recommended low-dose aspirin (60-150 mg) starting between 12 and 28 weeks' gestation for women at "high" risk who have:

• a history of preeclampsia, especially if accompanied by an adverse outcome
• multifetal gestation
• chronic hypertension
• diabetes (type 1 or type 2)
• renal disease
• autoimmune disease (such as systematic lupus erythematosus, antiphospholipid syndrome).

Related article:
Start offering aspirin to pregnant women at high risk for preeclampsia

As of July 11, 2016, ACOG supports this expanded list of high-risk conditions. Additionally, the USPSTF identified a "moderate" risk group in which low-dose aspirin may be considered if a patient has several risk factors, such as obesity, nulliparity, family history of preeclampsia, age 35 years or older, or another poor pregnancy outcome. ACOG notes, however, that the evidence supporting this practice is uncertain and does not make a recommendation regarding aspirin use in this population. Further study should be conducted to determine the benefit of low-dose aspirin in these patients as well as the long-term effects of treatment on maternal and child outcomes.

Next: CMA for prenatal genetic diagnosis

Chromosomal microarray analysis is preferable to karyotype in certain situations  

Pauli JM, Repke JT. Update on obstetrics. OBG Manag. 2013;25(1):28-32.

Society for Maternal-Fetal Medicine (SMFM), Dugoff L, Norton ME, Kuller JA. The use of chromosomal microarray for prenatal diagnosis. Am J Obstet Gynecol. 2016;215(4):B2-B9.

American College of Obstetricians and Gynecologists. Committee Opinion No. 682. Microarrays and next- generation sequencing technology: the use of advanced genetic diagnostic tools in obstetrics and gynecology.Obstet  Gynecol. 2016;128(6):e262-e268.

We previously addressed the use of chromosomal microarray analysis (CMA) for prenatal diagnosis in our 2013 "Update on obstetrics," specifically, the question of whether CMA could replace karyotype. The main differences between karyotype and CMA are that 1) only karyotype can detect balanced translocations/inversions and 2) only CMA can detect copy number variants (CNV). There are some differences in the technology and capabilities of the 2 types of CMA currently available as well.

In our 2013 article we concluded that "The total costs of such an approach--test, interpretation, counseling, and long-term follow-up of uncertain results--are unknown at this time and may prove to be unaffordable on a population-wide basis." Today, the cost of CMA is still higher than karyotype, but it is expected to decrease and insurance coverage for this test is expected to increase.

Related article:
Cell-free DNA screening for women at low risk for fetal aneuploidy

Both SMFM and ACOG released recommendations in 2016 regarding the use of CMA in prenatal genetic diagnosis, summarized as follows:  

• CMA is recommended over karyotype for fetuses with structural abnormalities on ultrasound
  • The detection rate for clinically relevant abnormal CNVs in this population is about 6%
• CMA is recommended for diagnosis for stillbirth specimens
  • CMA does not require dividing cells and may be a quicker and more reliable test in this population
• Karotype or fluorescence in situ hybridization (FISH) is recommended for fetuses with ultrasound findings suggestive of aneuploidy
  • If it is negative, then CMA is recommended
• Karyotype or CMA is recommended for patients desiring prenatal diagnostic testing with a normal fetal ultrasound
  • The detection rate for clinically relevant CNVs in this population (advanced maternal age, abnormal serum screening, prior aneuploidy, parental anxiety) is about 1%
• Pretest and posttest counseling about the limitations of CMA and a 2% risk of detection of variants of unknown significance (VUS) should be performed by a provider who has expertise in CMA and who has access to databases with genotype/phenotype information for VUS
  • This counseling should also include the possibility of diagnosis of nonpaternity, consanguinity, and adult-onset disease
• Karyotype is recommended for couples with recurrent pregnancy loss
  • The identification of balanced translocations in this population is most relevant in this patient population
• Prenatal diagnosis with routine use of whole-genome or whole-exome sequencing is not recommended.

Next: Zika virus: Check for updates

Zika virus infection: Check often for the latest updates

American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine. Practice advisory on Zika virus. http://www.acog.org/About-ACOG/News-Room/Practice-Advisories/Practice-Advisory-Interim-Guidance-for-Care-of-Obstetric-Patients- During-a-Zika-Virus-Outbreak. Published December 5, 2016. Accessed December 6, 2016.

Centers for Disease Control and Prevention. Zika virus. http://www.cdc.gov/zika/pregnancy/index.html. Updated August 22, 2016. Accessed December 6, 2016.

Petersen EE, Meaney-Delman D, Neblett-Fanfair R, et al. Update: interim guidance for preconception counseling and prevention of sexual transmission of Zika virus for persons with possible Zika virus exposure--United States, September 2016. MMWR Morbid Mortal Wkly Rep. 2016;65(39):1077-1081.

A yearly update on obstetrics would be remiss without mention of the Zika virus and its impact on pregnancy and reproduction. That being said, any recommendations we offer may be out of date by the time this article is published given the rapidly changing picture of Zika virus since it first dominated the headlines in 2016. Here are the basics as summarized from ACOG and the Centers for Disease Control and Prevention (CDC):

Viral spread. Zika virus may be spread in several ways: by an infected Aedes species mosquito, mother to fetus, sexual contact, blood transfusion, or laboratory exposure.

Symptoms of infection include conjunctivitis, fever, rash, and arthralgia, but most patients (4/5) are asymptomatic.

Sequelae. Zika virus infection during pregnancy is believed to cause fetal and neonatal microcephaly, intracranial calcifications, and brain and eye abnormalities. The rate of these findings in infected individuals, as well as the rate of vertical transmission, is not known.

Travel advisory. Pregnant women should not travel to areas with active Zika infection (the CDC website regularly updates these restricted areas).

Preventive measures. If traveling to an area of active Zika infection, pregnant women should take preventative measures day and night against mosquito bites, such as use of insect repellents approved by the Environmental Protection Agency, clothing that covers exposed skin, and staying indoors.

Safe sex. Abstinence or consistent condom use is recommended for pregnant women with partners who travel to or live in areas of active Zika infection.

Delay conception. Conception should be postponed for at least 6 months in men with Zika infection and at least 8 weeks in women with Zika infection.

Testing recommendations. Pregnant women with Zika virus exposure should be tested, regardless of symptoms. Symptomatic exposed nonpregnant women and all men should be tested.

Prenatal surveillance. High-risk consultation and serial ultrasounds for fetal anatomy and growth should be considered in patients with Zika virus infection during pregnancy. Amniocentesis can be considered on a case-by-case basis.

Related article:
Zika virus update: A rapidly moving target

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

In this Update we discuss several exciting new recommendations for preventive treatments in pregnancy and prenatal diagnostic tests. Our A-to-Z coverage includes:

• antenatal steroids in late preterm pregnancy
• expanded list of high-risk conditions warranting low-dose aspirin for preeclampsia prevention
• chromosomal microarray analysis versus karyotype for specific clinical situations
• Zika virus infection evolving information.

Next: New recommendation for timing of late preterm antenatal steroids

New recommendation offered for timing of late preterm antenatal steroids

Gyamfi-Bannerman C, Thom EA, Blackwell SC, et al; for the NICHD Maternal-Fetal Medicine Units Network. Antenatal betamethasone for women at risk for late preterm delivery. N Engl J Med. 2016;374(14):1311-1320.

American College of Obstetricians and Gynecologists. Committee Opinion No. 677. Antenatal corticosteroidtherapy for fetal maturation. Obstet Gynecol. 2016;128(4):e187-e194.

Kamath-Rayne BD, Rozance PJ, Goldenberg RL, Jobe AH. Antenatal corticosteroids beyond 34 weeks gestation: what do we do now? Am J Obstet Gynecol. 2016;215(4):423-430.

A dramatic recommendation for obstetric practice change occurred in 2016: the option of administering antenatal steroids for fetal lung maturity after 34 weeks. In the Antenatal Late Preterm Steroids (ALPS) trial of betamethasone in the late preterm period in patients at "high risk" of imminent delivery, Gyamfi-Bannerman and colleagues demonstrated that the treated group had a significant decrease in the rate of neonatal respiratory complications.

The primary outcome, a composite of respiratory morbidities (including transient tachypnea of the newborn, surfactant use, and need for resuscitation at birth) within the first 72 hours of life, had significant differences between groups, occurring in 165 of 1,427 infants (11.6%) in the betamethasone-treated group and 202 of 1,400 (14.4%) in the placebo group (relative risk in the betamethasone group, 0.80; 95% confidence interval, 0.66-0.97; P = .02). However, there was no statistically significant difference in respiratory distress syndrome, apnea, or pneumonia between groups, and the significant difference noted in bronchopulmonary dysplasia was based on a total number of 11 cases.

In response to these findings, both the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) released practice advisories and interim updates, culminating in a final recommendation for a single course of betamethasone in patients at high risk of preterm delivery between 34 and 36 6/7 weeks who have not received a previous course.

Related article:
When could use of antenatal corticosteroids in the late preterm birth period be beneficial?

In a thorough review of the literature on antenatal steroid use, Kamath-Rayne and colleagues highlighted several factors that should be considered before adopting universal use of steroids at >34 weeks. These include:   

• The definition of "high risk of imminent delivery" as preterm labor with at least 3-cm dilation or 75% effacement, or spontaneous rupture of membranes. The effect of less stringent inclusion criteria in real-world clinical practice is not known, and many patients who will go on to deliver at term will receive steroids unnecessarily.
• Multiple gestation, patients with pre-existing diabetes, women who had previously received a course of steroids, and fetuses with anomalies were excluded from the ALPS study. Use of antenatal steroids in these groups at >34 weeks should be evaluated before universal adoption.

Related article:
What is the ideal gestational age for twin delivery to minimize perinatal deaths?

• The incidence of neonatal hypoglycemia in the treated group was significantly increased. This affects our colleagues in pediatrics considerably from a systems standpoint (need for changes to newborn protocols and communication between services).
• The long-term outcomes of patients exposed to steroids in the late preterm period are yet to be delineated, specifically, the potential neurodevelopmental effects of a medication known to alter preterm brain development as well as cardiovascular and metabolic consequences.

Next: Low-dose aspirin for reducing preeclampsia risk

Low-dose aspirin clearly is effective for reducing the risk of preeclampsia

American College of Obstetricians and Gynecologists. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013;122(5):1122-1131.

Henderson JT, Whitlock EP, O'Connor E, Senger CA, Thompson JH, Rowland MG. Low-dose aspirin for prevention of morbidity and mortality from preeclampsia: a systematic evidence review for the US Preventive Services Task Force. Ann Intern Med. 2014;160(10):695-703.

LeFevre ML; US Preventive Services Task Force. Low-dose aspirin use for the prevention of morbidity and mortality from preeclampsia: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;161(11):819-826.

American College of Obstetricians and Gynecologists. Practice advisory on low-dose aspirin and prevention of preeclampsia: updated recommendations. http://www.acog.org/About-ACOG/News-Room/Practice-Advisories/Practice-Advisory-Low-Dose-Aspirin-and-Prevention-of-Preeclampsia-Updated-Recommendations. Published July 11, 2016. Accessed December 6, 2016.

In the 2013 ACOG Task Force on Hypertension in Pregnancy report, low-dose aspirin (60-80 mg) was recommended to be initiated in the late first trimester to reduce preeclampsia risk for women with:

• prior early onset preeclampsia with preterm delivery at <34 weeks' gestation, or
• preeclampsia in more than one prior pregnancy.  

This recommendation was based on several meta-analyses that demonstrated a 10% to 17% reduction in risk with no increase in bleeding, placental abruption, or other adverse events.

In 2014, the US Preventive Services Task Force (USPSTF) conducted a systematic evidence review of low-dose aspirin use for prevention of morbidity and mortality from preeclampsia. That report revealed a 24% risk reduction of preeclampsia in high-risk women treated with low-dose aspirin, as well as a 14% reduction in preterm birth and a 20% reduction in fetal growth restriction. A final statement from the USPSTF in 2014 recommended low-dose aspirin (60-150 mg) starting between 12 and 28 weeks' gestation for women at "high" risk who have:

• a history of preeclampsia, especially if accompanied by an adverse outcome
• multifetal gestation
• chronic hypertension
• diabetes (type 1 or type 2)
• renal disease
• autoimmune disease (such as systematic lupus erythematosus, antiphospholipid syndrome).

Related article:
Start offering aspirin to pregnant women at high risk for preeclampsia

As of July 11, 2016, ACOG supports this expanded list of high-risk conditions. Additionally, the USPSTF identified a "moderate" risk group in which low-dose aspirin may be considered if a patient has several risk factors, such as obesity, nulliparity, family history of preeclampsia, age 35 years or older, or another poor pregnancy outcome. ACOG notes, however, that the evidence supporting this practice is uncertain and does not make a recommendation regarding aspirin use in this population. Further study should be conducted to determine the benefit of low-dose aspirin in these patients as well as the long-term effects of treatment on maternal and child outcomes.

Next: CMA for prenatal genetic diagnosis

Chromosomal microarray analysis is preferable to karyotype in certain situations  

Pauli JM, Repke JT. Update on obstetrics. OBG Manag. 2013;25(1):28-32.

Society for Maternal-Fetal Medicine (SMFM), Dugoff L, Norton ME, Kuller JA. The use of chromosomal microarray for prenatal diagnosis. Am J Obstet Gynecol. 2016;215(4):B2-B9.

American College of Obstetricians and Gynecologists. Committee Opinion No. 682. Microarrays and next- generation sequencing technology: the use of advanced genetic diagnostic tools in obstetrics and gynecology.Obstet  Gynecol. 2016;128(6):e262-e268.

We previously addressed the use of chromosomal microarray analysis (CMA) for prenatal diagnosis in our 2013 "Update on obstetrics," specifically, the question of whether CMA could replace karyotype. The main differences between karyotype and CMA are that 1) only karyotype can detect balanced translocations/inversions and 2) only CMA can detect copy number variants (CNV). There are some differences in the technology and capabilities of the 2 types of CMA currently available as well.

In our 2013 article we concluded that "The total costs of such an approach--test, interpretation, counseling, and long-term follow-up of uncertain results--are unknown at this time and may prove to be unaffordable on a population-wide basis." Today, the cost of CMA is still higher than karyotype, but it is expected to decrease and insurance coverage for this test is expected to increase.

Related article:
Cell-free DNA screening for women at low risk for fetal aneuploidy

Both SMFM and ACOG released recommendations in 2016 regarding the use of CMA in prenatal genetic diagnosis, summarized as follows:  

• CMA is recommended over karyotype for fetuses with structural abnormalities on ultrasound
  • The detection rate for clinically relevant abnormal CNVs in this population is about 6%
• CMA is recommended for diagnosis for stillbirth specimens
  • CMA does not require dividing cells and may be a quicker and more reliable test in this population
• Karotype or fluorescence in situ hybridization (FISH) is recommended for fetuses with ultrasound findings suggestive of aneuploidy
  • If it is negative, then CMA is recommended
• Karyotype or CMA is recommended for patients desiring prenatal diagnostic testing with a normal fetal ultrasound
  • The detection rate for clinically relevant CNVs in this population (advanced maternal age, abnormal serum screening, prior aneuploidy, parental anxiety) is about 1%
• Pretest and posttest counseling about the limitations of CMA and a 2% risk of detection of variants of unknown significance (VUS) should be performed by a provider who has expertise in CMA and who has access to databases with genotype/phenotype information for VUS
  • This counseling should also include the possibility of diagnosis of nonpaternity, consanguinity, and adult-onset disease
• Karyotype is recommended for couples with recurrent pregnancy loss
  • The identification of balanced translocations in this population is most relevant in this patient population
• Prenatal diagnosis with routine use of whole-genome or whole-exome sequencing is not recommended.

Next: Zika virus: Check for updates

Zika virus infection: Check often for the latest updates

American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine. Practice advisory on Zika virus. http://www.acog.org/About-ACOG/News-Room/Practice-Advisories/Practice-Advisory-Interim-Guidance-for-Care-of-Obstetric-Patients- During-a-Zika-Virus-Outbreak. Published December 5, 2016. Accessed December 6, 2016.

Centers for Disease Control and Prevention. Zika virus. http://www.cdc.gov/zika/pregnancy/index.html. Updated August 22, 2016. Accessed December 6, 2016.

Petersen EE, Meaney-Delman D, Neblett-Fanfair R, et al. Update: interim guidance for preconception counseling and prevention of sexual transmission of Zika virus for persons with possible Zika virus exposure--United States, September 2016. MMWR Morbid Mortal Wkly Rep. 2016;65(39):1077-1081.

A yearly update on obstetrics would be remiss without mention of the Zika virus and its impact on pregnancy and reproduction. That being said, any recommendations we offer may be out of date by the time this article is published given the rapidly changing picture of Zika virus since it first dominated the headlines in 2016. Here are the basics as summarized from ACOG and the Centers for Disease Control and Prevention (CDC):

Viral spread. Zika virus may be spread in several ways: by an infected Aedes species mosquito, mother to fetus, sexual contact, blood transfusion, or laboratory exposure.

Symptoms of infection include conjunctivitis, fever, rash, and arthralgia, but most patients (4/5) are asymptomatic.

Sequelae. Zika virus infection during pregnancy is believed to cause fetal and neonatal microcephaly, intracranial calcifications, and brain and eye abnormalities. The rate of these findings in infected individuals, as well as the rate of vertical transmission, is not known.

Travel advisory. Pregnant women should not travel to areas with active Zika infection (the CDC website regularly updates these restricted areas).

Preventive measures. If traveling to an area of active Zika infection, pregnant women should take preventative measures day and night against mosquito bites, such as use of insect repellents approved by the Environmental Protection Agency, clothing that covers exposed skin, and staying indoors.

Safe sex. Abstinence or consistent condom use is recommended for pregnant women with partners who travel to or live in areas of active Zika infection.

Delay conception. Conception should be postponed for at least 6 months in men with Zika infection and at least 8 weeks in women with Zika infection.

Testing recommendations. Pregnant women with Zika virus exposure should be tested, regardless of symptoms. Symptomatic exposed nonpregnant women and all men should be tested.

Prenatal surveillance. High-risk consultation and serial ultrasounds for fetal anatomy and growth should be considered in patients with Zika virus infection during pregnancy. Amniocentesis can be considered on a case-by-case basis.

Related article:
Zika virus update: A rapidly moving target

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.