Antenatal corticosteroids before 24 weeks: is it time?

The anticipated delivery and birth of a periviable neonate at 22–23 weeks’ gestation presents several difficult issues for obstetricians, neonatologists and families alike. The decision to

resuscitate infants at these gestational ages is challenging, and practice variability exists within and across neonatal intensive care and labor and delivery units.1, 2, 3 When challenged

with these events, communication with parents is of the upmost importance. Antenatal counseling of families should provide essential information to aid in the decision making process. This

discourse includes not only expected outcomes of infants at extremely early gestational ages but also detailed options including (or excluding) treatments and therapies that may impact

survival and neurodevelopmental outcome.4 It is established that administration of antenatal corticosteroids to women who are likely to deliver before 34 weeks’ gestation is beneficial. In a

2006 Cochrane review of 21 studies, respiratory distress syndrome, intraventricular hemorrhage (IVH), necrotizing enterocolitis and neonatal mortality were all reduced in infants exposed to

maternal administration of antenatal corticosteroids.5 Consequently, treatment guidelines advise the use of antenatal corticosteroids in mothers with threatened preterm birth from 24 weeks’

to 32–34 weeks’ gestation. Of note, many of these studies lack data on infants born at <26–28 weeks’ gestation. Onland _et al._,6 in a systematic review of randomized controlled trials,

evaluated the effects of antenatal corticosteroids in infants born before 26 weeks’ gestation. They found no evidence to ‘support or refute the recommendation of administrating antenatal

corticosteroids’ in instances of threatened preterm delivery before 26 weeks’ gestation. However, in a large, retrospective cohort study of over 10 000 infants born at 23 US academic centers

between 1993 and 2009, antenatal corticosteroids showed significant benefit down to 23 weeks’ gestation.7 In infants born at 23 weeks whose mothers received antenatal corticosteroids,

death, severe IVH (grade 3 or 4) or periventricular leukomalacia and necrotizing enterocolitis were significantly reduced. At 18–22 months follow-up of survivors, moderate to severe cerebral

palsy, blindness and deafness were also all reduced. In this month’s issue of the _Journal of Perinatology_, Wei _et al._8 provide more evidence of the efficacy of maternal administration

of antenatal corticosteroids at these extremes of prematurity. They present data from the California Perinatal Quality Care Collaborative evaluating the association between antenatal

corticosteroid administration and IVH rates in infants ⩽32 weeks’ gestation (and <1500 g birth weight). Over 7 years, between 2007 and 2013, a total of 39 956 infants were admitted to

California Perinatal Quality Care Collaborative neonatal intensive care units. The authors excluded infants who were outborn as well as those with missing data on IVH and antenatal

corticosteroid administration. Just over 87% of the mothers of the 25 979 infants included in the analysis received either a partial or full course of antenatal corticosteroids. Of the

infants analyzed, 76.3% had no IVH although 23.7 and 7.5% had any grade hemorrhage or a severe (grade 3 or 4) hemorrhage, respectively. A quarter of infants with severe IVH were not exposed

to antenatal corticosteroids although only 11.4% of those without IVH were not exposed. When the authors adjusted for maternal socio-demographic and medical risk factors and stratified by

gestational age, they found that infants at 23 0/7–23 6/7 weeks’ gestation were significantly less likely to have any IVH or severe IVH. Although severe IVH was not impacted in infants

<23 0/7 weeks, there was a decrease in any IVH. In addition, in-hospital mortality rates were lower across all gestational ages in infants whose mothers received antenatal

corticosteroids. There are several limitations to this current study, including the lack of imaging data on a large number of infants and a lack of corticosteroid timing and dosing

administration information. Also missing are data on whether women did not receive antenatal corticosteroids because there was a contraindication (e.g., acute maternal illness or because

they delivered too quickly). Outcomes for those babies could be worse, skewing the unfavorable results to the no corticosteroid group and improving those data in babies for whom delivery

could be postponed for 24–48 h after corticosteroid administration, potentially allowing for a more stable delivery. Furthermore, the outcomes for babies at the earliest gestational ages,

specifically mortality rates, are potentially biased. Providers may not have equipoise in delivery room resuscitation between those babies whose mothers did or did not receive antenatal

corticosteroids. A number of guidelines prior to 2014 suggest the use of antenatal corticosteroids after 24 weeks’ gestation. In 2014, a Joint Workshop by the _Eunice Kennedy Shriver_

National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, American Academy of Pediatrics (AAP) and the American College of Obstetricians and

Gynecologists (ACOG) produced a recommendation for antenatal corticosteroids and newborn resuscitation for deliveries at 23 0/7 weeks or greater.9 A recommendation was also made to consider

antenatal corticosteroids after 22 0/7 weeks if ‘delivery at or later than 23 0/7 weeks is anticipated.’ More recently, after acceptance of the manuscript by Wei _et al._, ACOG revised their

practice bulletin on the management of preterm labor by the addition of the following: > A single course of corticosteroids is recommended for pregnant women > between 24 weeks and 34

 weeks of gestation and may be considered for > pregnant women starting at 23 weeks of gestation, who are at risk of > preterm delivery within 7 days.10 The different recommendations

between ACOG and the Joint Workshop make it challenging for clinicians to determine how best to counsel families and manage threatened delivery at or before periviable gestational ages. In

order to provide the best patient-centered care, prospective parents need clear information and clinicians require evidence of benefit and safety. To accomplish this, we suggest the

following practices: * Combine neonatal–obstetric counseling around periviability In a small study involving simulated counseling of women with ruptured membranes at 23 weeks’ gestation,

obstetricians and neonatologists provided counseling that was complementary; however, both fields deferred questions about corticosteroid administration to the other specialty.11 When

parents’ concerns go unanswered, the care team may appear ‘disjointed or disconnected rather than practicing a ‘team’ approach to care.’ Joint counseling will ensure team cohesiveness in

recommendations and also minimize redundant or inconsistent information. * Involve parents Parents should be the center of any discussion about resuscitation at the periviable age. Having

strict gestational age cutoffs is irrational as our knowledge of the precise dating of an individual fetus is, at best, a ‘guesstimate’ except in instances of _in vitro_ fertilization. Also,

ensuring the knowledge, understanding and acceptance by the parents of possible neonatal outcomes, and the contribution antenatal corticosteroids may provide to these outcomes are not to be

discounted. In addition, we urge the AAP and other professional organizations to include parents in the development of guidelines and clinical reports, especially regarding care practices

surrounding the periviable infant. It should be noted that neither the AAP clinical report on counseling parents in the periviable period nor the Joint Workshop executive summary had parents

on their working groups (although two neonatologists, recognized as experts in neonatal ethics, who have publically shared their personal NICU experience, were part of the Joint

Workshop).4, 9 As others have noted, clinical practice guidelines must be ‘led by specialty societies but with a new model that integrates other stakeholders, including patients.’12 *

Continue research on antenatal corticosteroids before 24 weeks Current data suggest that antenatal corticosteroids provide benefit when offered from 23 weeks’ gestation onward. However, most

of this evidence comes from cohort studies, which may show unintended bias.13 Evidence for administration before 23 weeks is limited. In addition, as more mothers are treated with

corticosteroids at these gestational ages but do not deliver within 1–2 weeks, more questions will arise regarding the timing and safety of repeated courses of corticosteroids. Follow-up

studies of infants of mothers who received antenatal corticosteroids at a periviable gestational age and then received a subsequent course have not been performed; results of such

investigations would add considerably to our understanding of antenatal corticosteroid safety and efficacy. * Provide a coherent message The study by Wei _et al._8 supports previous findings

that antenatal corticosteroids reduce death and IVH in infants born before 26 weeks’ gestation. Together, these studies provide helpful information aiding the bedside clinician and parents

in determining a reasonable course of action when faced with delivery before 24 weeks’ gestation. The message to obstetric and neonatology providers and to parents needs to be clear: if

resuscitation is to be offered at such early gestational ages as 22–23 weeks, then administration of antenatal corticosteroids might offer some advantages with low risk. Extrapolating from

older gestational age data, buying a minimum of 48 h for the corticosteroids to achieve optimum effect seems worthwhile. Nonetheless, there may indeed be birth weight and/or size limitations

that impede resuscitation and stabilization in the best of hands. The perinatal team must take the opportunity to fully disclose such possibilities to families lest having anyone

misconstrue antenatal corticosteroid administration as a panacea. REFERENCES * Arzuaga BH, Meadow W . National variability in neonatal resuscitation practices at the limit of viability. _Am

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references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Division of Neonatology, University of Virginia Children’s Hospital, Charlottesville, VA, USA J R Swanson & R A Sinkin Authors *

J R Swanson View author publications You can also search for this author inPubMed Google Scholar * R A Sinkin View author publications You can also search for this author inPubMed Google

Scholar CORRESPONDING AUTHOR Correspondence to R A Sinkin. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no conflict of interest. RIGHTS AND PERMISSIONS Reprints and

permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Swanson, J., Sinkin, R. Antenatal corticosteroids before 24 weeks: is it time?. _J Perinatol_ 36, 329–330 (2016).

https://doi.org/10.1038/jp.2016.39 Download citation * Published: 25 April 2016 * Issue Date: May 2016 * DOI: https://doi.org/10.1038/jp.2016.39 SHARE THIS ARTICLE Anyone you share the

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