ACOG releases Committee Opinion for Prenatal Corticosteroid Therapy for Fetal Maturation

An updated committee opinion from the American College of Obstetricians and Gynecologists (ACOG), was published in the August issue of Obstetrics & Gynecology.

Liggins and Howie published their landmark paper in 1972, that showed the benefits of single course of antenatal corticosteroid therapy administered to women at risk for preterm delivery in reducing RDS and mortality in offspring.

Since then countless trials have confirmed these findings and also shown that timely steroid administration reduces rates of intraventricular hemorrhage (IVH) and necrotizing enterocolitis.

An updated ACOG opinion published in October 2016 issue, expanded the use of steroids in women at high risk for late preterm birth (34 0/7 - 36 6/7 weeks).

The current recommendations are:

A single course of corticosteroids is recommended for pregnant women between 24 0/7 weeks and 33 6/7 weeks of gestation who are at risk of preterm delivery within 7 days, irrespective of intact or ruptured membranes and single or multiple gestations.

It could also be given at 23 0/7 weeks of gestation to women at risk of preterm delivery with 7 days based on discussion with family members regarding resuscitation of the newborn.

A decision to administer corticosteroids during the peri viable period (20 0/7 weeks to 25 6/7 weeks of gestation) should always be based on discussions with the patients and family members regarding resuscitation of the newborn.

A single course of betamethasone is recommended for pregnant women at risk of preterm birth between 34 0/7 weeks and 36 6/7 weeks of gestation, provided they have not received a previous course of antenatal corticosteroids.

A single repeat course can be given to women who are less than 34 0/7 weeks of gestation who are at risk of preterm delivery within 7 days, whose previous course was administered more than 14 days earlier and in some clinical scenarios 7 days earlier.

Repeated or serial administration of more than 2 doses is not recommended.

At present, no recommendation can be made for a repeat or rescue dose of corticosteroids in patients with preterm prelabor rupture of membranes (PROM).

ACOG also recommends long term follow up and surveillance of babies who received in utero corticosteroids administration.

It also advocates ongoing development of strategies to support timely administration of corticosteroids to women at risk of delivering with 7 days and avoid overuse in low risk patients.

The committee opinion full text can be accessed here.

Antenatal Corticosteroids administration just few hours before preterm delivery improves survival and health gains for the infants.

Genesis Research Trust.

Imminent preterm labor, with no time to give antenatal corticosteroids? Still give it says the result of a large population based study.

Antenatal corticosteroids given few hours before an imminent delivery is effective in improving survival says results of a large population-based study of 4594 European infants born before 32 weeks’ gestation. This study was published on line today in JAMA Pediatrics.

The interval between steroids administration and birth varies, and so does the benefits achieved by the preterm infant. When women at risk for preterm delivery receive antenatal corticosteroids(ANS) 1 to 7 days before delivery, it reduces respiratory distress syndrome by 34%, necrotizing enterocolitis by 54%, intraventricular hemorrhage by 46%, and reduces Infant mortality by nearly 30%.

According to recent Cochrane Review “a single course of a corticosteroids, given to the mother in preterm labor and before the baby is born, helps to develop the baby's lungs and reduces complications such as breathing problems.”

Use of corticosteroid within the 24 hours’ window before delivery has been labelled as ‘partial’ or’ suboptimal’ according to Mikael Norman, MD, PhD, of Karolinska Institutet in Stockholm, Sweden, and the lead investigator of this study.

In fact, the latest timing of corticosteroids administration has never been investigated till now.

But this study “challenge current thinking about the optimal timing” of antenatal corticosteroids and encourage “a more proactive management of women at risk for imminent preterm birth, which may help reduce infant mortality and severe neonatal brain injury,” said Mikael Norman.

The Effective Perinatal Intensive Care in Europe (EPICE) study, a population-based prospective cohort study, gathered data from 19 regions in 11 European countries in 2011 and 2012 on 4594 singleton infants with gestational ages between 24 and 31 weeks, without severe anomalies and unexposed to repeated courses of ANS.

The study also evaluated the effects of  3 other evidence based practices: delivery in a maternity unit with appropriate level of neonatal care; prevention of hypothermia (temperature on admission to neonatal unit ≥36°C); surfactant used within two hours of birth or early nasal continuous positive airway pressure.

Nearly 55% were boys and the mean (SD) gestational age was 28.5 (2.2) weeks and mean (SD) birth weight was 1213 (400) g.

The cohort was divided into 4 categories depending upon the timing of corticosteroids given: no injections (662 infants, or 14.4% of the study population), first injection at less than 24 hours before birth (1,111 infants, or 24.2%), first injection at the recommended 1-7 days before birth (1,871 infants, or 40.7%), and first injection more than 7 days before birth (950 infants, or 20.7%).

The study results show that:

Receiving ANS at any time before delivery is associated with significant reduction in neonatal morbidity as compared to receiving no steroids.

The largest benefit (> 50%) was achieved in group which received them at the recommended interval of 1-7 days before delivery.

Nearly 20% of the infants in the study received ANS more than 7 days before and showed an increased mortality by 40% as compared to women who received them in the recommended window of period.

Using this information on timing of administration and benefits derived, the investigators created a simulation model for 661 infants who did not received any corticosteroids. The model predicts that if these infants had received treatment at least 3 hours before delivery, overall mortality would have decreased by 26%; 3-5 hours before delivery, mortality would have decreased by 37%; and if received treatment at 6-12 hours before delivery it would have decreased by 51%.

The authors concluded that “Encouraging administration of antenatal corticosteroids when delivery is very imminent could result in substantial survival and health gains for very preterm infants.”

A current project Screening to Improve Health in Very Preterm Infants in Europe (SHIPS) is about follow-up programmes for children born preterm. The project builds on the EPICE cohort to follow them to pick up any early problem and is currently ongoing in all the 11 countries.

Updates on management of Preterm Births- News from ACOG Annual Clinical and Scientific Meeting 2016.

The 2016 Annual Clinical and Scientific Meeting of the American College of Obstetricians and Gynecologists is ongoing from May 14 to May 17 at the Washington Convention Center in Washington, DC.

Recent clinical trials have led to two important changes in recommendations by ACOG and SMFM on management of preterm births. Steroids are recommended at 23 weeks and at 34-36 weeks to reduce the risks associated with preterm delivery.

Dr. Uma Reddy, MD, MPH, Pregnancy and Perinatology Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health said “All of these changes in practice recommendations will have a real impact on preterm birth.”  “We have already seen a significant decrease in preterm births since a high of 12.8 percent in 2006,” she added. “Preterm birth fell to 11.4 percent in 2013, the last year for which we have complete data. We have had a positive impact in reducing preterm birth.”

The latest recommendations were discussed at Saturday clinical seminar at ACOG annual conference on Saturday May 14, 2016.

 ACOG and the Society for Maternal-Fetal Medicine (SMFM) is now suggesting a single course of steroids for pregnant women starting at 23 weeks who are at risk for preterm birth within seven days. This recommendation is based on a cohort study involving US top 23 academic pediatric centers. It was seen that infants born at 23 to 25 weeks who received antenatal steroids had lower rates of death and lower rates of neurodevelopmental impairment at 18 to 22 months.

The second important recommendation was based on results of the Antenatal Later Preterm Steroids (ALPS) trial reported earlier this year by the Maternal-Fetal Medicine Units Network. A single course of betamethasone in singleton pregnancies between 34 and 36 weeks in women at risk for preterm birth should be given.

The trial showed reduction in the need for respiratory support, reduction in severe respiratory complications, decreased transient tachypnea(TTN), bronchopulmonary dysplasia, and the need for postnatal surfactant. There was no increase in neonatal sepsis, chorioamnionitis, or endometritis, but hypoglycemia was more common in infants exposed to betamethasone. 

These new recommendations are in addition to old recommendations that suggest that all pregnant women between 24 and 34 weeks who are at risk for preterm delivery within seven days receive a single course of corticosteroids. A single rescue course should be considered if a prior course was given at least seven days earlier and the woman remains at risk for preterm birth before 34 weeks.

In summary:

• With the release of this new data and until further guidance is released, administration of betamethasone may be considered in women with a singleton pregnancy between 34 0/7 and 36 6/7 weeks gestation at imminent risk of preterm birth within 7 days. 
• For women in active labor, it is advised to wait for cervical dilatation up-to 3 cm or 75% effacement before administering betamethasone. 
• Tocolysis should not be used in order to delay delivery to allow for administration of late preterm antenatal corticosteroids, nor should an indicated late preterm delivery (such as for preeclampsia with severe features) be postponed for steroid administration.
• All hospitals should utilize standard guidelines for management of hypoglycemia in late preterm newborns.
• Late preterm antenatal corticosteroid administration should not be used in women diagnosed with chorioamnionitis.
• Administration of late preterm antenatal corticosteroids should not be given if the pregnancy was already exposed to antenatal corticosteroids.
• Because the ALPS trial excluded pregnant women with diabetes, multifetal gestations, previous exposure to steroids during pregnancy, or pregnancies with major non-lethal fetal malformations, ACOG is reviewing these topics and will issue any updated clinical guidance as appropriate.

References:

http://www.acogdailynews.com/latest-trials-change-preterm-birth-guidance/

http://www.acog.org/About-ACOG/News-Room/Practice-Advisories/Practice-Advisory-Antenatal-Corticosteroid-Administration-in-the-Late-Preterm-Period

http://www.nejm.org/doi/full/10.1056/NEJMoa1516783?af=R&rss=currentIssue