Date Published: February 26, 2019
Publisher: Public Library of Science
Author(s): Alina Rodriguez, Yingbo Wang, Anohki Ali Khan, Rufus Cartwright, Mika Gissler, Marjo-Riitta Järvelin, Lars Åke Persson
Abstract: BackgroundAntenatal 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 findingsThis 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.ConclusionsIn 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.
Partial Text: Complications arising from preterm birth are the primary cause of mortality in children under 5 years old  and a leading cause of morbidity across the life course . Antenatal corticosteroid therapy (ACT) accelerates maturation of fetal lung tissue. ACT is used prophylactically when preterm birth is threatened to reduce risk of respiratory distress syndrome (RDS), associated morbidity, and mortality in preterm infants . International guidelines [4–6] recommend that women between 24 and 34 weeks of gestation who are at risk of preterm delivery within 7 days should receive ACT. However, recent reports show that a large portion of women receive ACT inappropriately , with optimal timing of treatment administered in only 40.8% of patients . Moreover, the estimated number needed to treat with ACT to prevent one case of RDS varies widely [9–10]. As ACT is often initiated before a diagnosis of preterm birth is confirmed, and given the uncertainty in predicting parturition, as many as 40% [7–10] of infants exposed to ACT go on to be delivered at term. These infants would not be expected to develop RDS, with or without ACT, but have been exposed to any potential harms [11–13], thus raising concerns about risks.
There were 278,508 live-born singleton births recorded in Finland during the study period. Of these, 11,896 (4.27%) infants were born preterm, 4,887 women were treated with ACT (1.75%), and 44% of the exposed infants (n = 2,173) were born at term, as shown in Fig 1.
In this population cohort study of 278,508 live-born singleton births, exposure to ACT was associated with smaller size at birth in comparison to unexposed infants. Matched analyses on background and medical characteristics as well as timing of birth showed smaller birth size among infants prenatally exposed to ACT, though no difference in birth size was detected for the infants with shortest (24–29 weeks) or longest (≥42 weeks) gestation in the stringent PSM analyses. Consistent differences were observed in BWT in matched analyses among preterm, near-term, and term infants, with the greatest reduction in BWT seen in preterm infants. Similarly, BL and HC were most compromised in the preterm group, and clinically significant reductions were also observed for the near-term and term groups. Observed reductions in size in relation to ACT were generally symmetrical, i.e., no difference in PI.