University of Oulu

Rodriguez A, Wang Y, Ali Khan A, Cartwright R, Gissler M, Järvelin M-R (2019) Antenatal corticosteroid therapy (ACT) and size at birth: A population-based analysis using the Finnish Medical Birth Register. PLoS Med 16(2): e1002746.

Antenatal corticosteroid therapy (ACT) and size at birth : a population-based analysis using the Finnish Medical Birth Register

Saved in:
Author: Rodriguez, Alina1,2; Wang, Yingbo1; Khan, Anohki Ali1;
Organizations: 1Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom
2School of Psychology, University of Lincoln, Lincoln, United Kingdom
3Department of Obstetrics and Gynaecology, Oxford University Hospitals NHS Trust, Oxford, United Kingdom
4THL National Institute for Health and Welfare, Information Services Department, Helsinki, Finland
5Karolinska Institute, Department of Neurobiology, Care Sciences and Society, Division of Family Medicine, Stockholm, Sweden
6Unit of Primary Health Care, Oulu University Hospital, Oulu, Finland
7Biocenter Oulu, University of Oulu, Oulu, Finland
8Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland
9Department of Life Sciences, College of Health and Life Sciences, Brunel University London, London, United Kingdom
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1 MB)
Persistent link:
Language: English
Published: Public Library of Science, 2019
Publish Date: 2019-05-06


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.

see all

Series: PLoS medicine
ISSN: 1549-1277
ISSN-E: 1549-1676
ISSN-L: 1549-1277
Volume: 16
Issue: 2
Article number: e1002746
DOI: 10.1371/journal.pmed.1002746
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
Funding: Funding for this research was provided by Swedish Research Council for Health, Working Life, and Welfare (FAS 20111483; and VINNOVA Sweden’s Innovation Agency (200801003;, both to AR; Academy of Finland EGEA project (285547; and EU H2020 LifeCycle Action (grant agreement 733206) to MRJ; and EU H2020 DynaHEALTH action (grant agreement 633595; to MRJ (PI) and AR (collaborator). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
EU Grant Number: (733206) LIFECYCLE - Early-life stressors and LifeCycle health
(633595) DYNAHEALTH - Understanding the dynamic determinants of glucose homeostasis and social capability to promote Healthy and active aging
Academy of Finland Grant Number: 285547
Detailed Information: 285547 (Academy of Finland Funding decision)
Copyright information: © 2019 Rodriguez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.