In-utero corticosteroids exposure linked to smaller birth size

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Infants exposed to antenatal corticosteroid therapy (ACT) to accelerate lung maturation have a clinically significant reduction in birth size, according to a study of 278,508 birth by Alina Rodriguez of the University of Lincoln and Imperial College London, UK, and colleagues.

Guidelines currently recommend one dose, repeated over 24 hours, of ACT to accelerate lung maturation in cases of threatened preterm birth. However, many exposed infants end up born at term and are therefore exposed unnecessarily to any potential harms of ACT. In the study, researchers studied all live-born singleton births in Finland from 2006 through 2010. De-identified data were available on ACT exposure, birth weight, birth length, head circumference, Apgar scores, and medical care of infants.

4,887 women (1.75%) were treated with ACT and, of those exposed, more than 44% (2173) of infants were born at term. Adjusted analyses showed significant differences in birth weight between exposed and unexposed infants, with an apparent reduction in birth weight of 61.54 grams for very preterm babies exposed to ACT (±SE 28.62, P<.03), 222.78 grams for preterm babies (±SE 19.64, P<.001), 159.25 grams for near term babies (±SE 19.14, P<.001), and 91.62 grams for term babies (±SE 11.86, P<.03). Associations were also seen for birth length and head circumference. There were no significant differences in Apgar scores, but ACT-exposed infants generally required greater medical care during the first seven days of life and beyond.

“These findings provide strong evidence indicating that ACT is associated with reduced foetal growth in humans and provide an agenda for further studies,” the authors say. “Early care decisions need to identify high-risk patients and weigh benefits of ACT against potential harm of unnecessary exposure.”

Abstract
Background: Antenatal corticosteroid therapy (ACT) is used clinically to prepare the fetal lung for impending preterm birth, but animal and human studies link corticosteroids to smaller birth size. Whether ACT is associated with birth size is debated; therefore, we assessed differences in birth size in treated versus untreated pregnancies.
Methods and findings: This observational register-based study used data from the Finnish Medical Birth Register (FMBR) covering all births in Finland (January 1, 2006–December 31, 2010). We used unadjusted and adjusted regression analyses as well as propensity score matching (PSM) to analyze whether birth size differed by ACT exposure. PSM provides a stringent comparison, as subsamples were created matched on baseline and medical characteristics between treated and untreated women. All analyses were stratified by timing of birth. The primary study outcome was birth size: birth weight (BWT), birth length (BL), ponderal index (PI), and head circumference (HC) measured immediately after birth and recorded in the FMBR. Additional analyses explored indicators of neonatal health in relation to ACT exposure and birth size. A total of 278,508 live-born singleton births with ≥24 gestational completed weeks were registered in the FMBR during the 5-year study period. Over 4% of infants were born preterm, and 4,887 women were treated with ACT (1.75%). More than 44% of the exposed infants (n = 2,173) were born at term. First, results of unadjusted regression analyses using the entire sample showed the greatest reductions in BWT as compared to the other analytic methods: very preterm −61.26 g (±SE 24.12, P < 0.01), preterm −232.90 g (±SE 17.24, P < .001), near term −171.50 g (±SE 17.52, P < .001), and at term −101.95 g (±SE 10.89, P < .001). Second, using the entire sample, regression analyses adjusted for baseline and medical conditions showed significant differences in BWT between exposed and unexposed infants: very preterm −61.54 g (±SE 28.62, P < .03), preterm −222.78 g (±SE 19.64, P < .001), near term −159.25 g (±SE 19.14, P < .001), and at term −91.62 g (±SE 11.86, P < .03). Third, using the stringent PSM analyses based on matched subsamples, infants exposed to ACT weighed less at birth: −220.18 g (±SE 21.43, P < .001), −140.68 g (±SE 23.09, P < .001), and −89.38 g (±SE 14.16, P < .001), born preterm, near term, and at term, respectively. Similarly, significant reductions in BL and HC were also observed using the three analytic methods. There were no differences among postterm infants regardless of analytic method. Likewise, we observed no differences with respect to PI. Additional analyses showed that exposed and unexposed infants had generally similar Apgar scores at birth, yet the ACT-treated infants received greater medical care during the first 7 days of life and beyond. Our study is mainly limited by lack of data in FMBR specifying the interval between treatment and birth as well as other potential confounders that could not be tested.
Conclusions: In this study, ACT was consistently associated with reduction in birth size for infants born preterm, near term, or at term. Further investigation is warranted alongside reevaluation of guidelines. Efforts need to be made to correctly identify and target patients who will deliver preterm. Reduced growth should be considered when deliberating early care decisions.

Authors
Alina Rodriguez, Yingbo Wang, Anohki Ali Khan, Rufus Cartwright, Mika Gissler, Marjo-Riitta Järvelin

PLOS Medicine abstract

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