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Antenatal Steroids Tied to Lower Infant Birth Weight

Antenatal corticosteroids were linked with lower birth weight and birth size in most infants, regardless of gestational age, researchers in England found.

Preterm, near-term, and term infants exposed to antenatal corticosteroids were associated with lower birth weight, smaller birth size, and smaller head circumference than unexposed infant counterparts, reported Alina Rodriguez, PhD, of Imperial College London, and colleagues, in PLoS Medicine.

Antenatal corticosteroids are given to reduce the risk of preterm birth, according to various international guidelines that state they should be given to women from 24 through 36 weeks of gestation who are at risk of preterm delivery within 7 days.

But the authors pointed out that recent research found only about 40% of women receive the treatment with “optimal timing,” and that therapy is often initiated before a diagnosis of preterm birth is confirmed, with some research indicating as many as 40% of infants exposed to antenatal corticosteroid therapy are delivered at term.

“We have known from animal studies that steroid treatment could affect [fetal] growth. It is still unclear whether the reduction in birthweight of the treated infants is directly caused by the drug or due to the complications that led to the treatment,” Rodriguez said in a statement.

Researchers examined data from the Finnish Medical Birth Register from January 2006 to December 2010. Primary outcomes of the study were birth weight, birth length, ponderal index, and head circumference measured immediately after birth. They used regression analyses, as well as propensity score matching “to analyze whether birth size varied by [antenatal corticosteroid] exposure.”

Very preterm infants were defined as 24-29 weeks gestation, while preterm were 30-34 weeks, near term were 35-37 weeks, and term were 38-41 weeks.

Overall, there were about 279,000 live-born singleton births with ≥24 gestational weeks during the study period. There were 4,887 women treated with antenatal corticosteroid therapy, and 44% of infants were born to these mothers at term.

Adjusted analyses found significant differences in birth weight in all groups of infants exposed to antenatal corticosteroids versus unexposed infants in all lengths of gestation except post-term (≥42 weeks).

When using propensity score matching analyses, the authors found associations with birth weight, birth length, and head circumference persisted among preterm, near-term, and term infants. Compared to their unexposed counterparts, exposed infants were:

  • Preterm: 220 g lighter, 1.43 cm shorter, 0.92 smaller head circumference
  • Near term: 140 g lighter, 0.71 cm shorter, 0.39 cm smaller head circumference
  • Term: 89 g lighter, 0.36 cm shorter, 0.21 cm smaller head circumference

Indeed, the authors found that antenatal corticosteroid-exposed infants born from 30 through 41 weeks were “consistently smaller in birth size, regardless of analytic strategy.” Taken together, they said significant differences were detected by all analytic strategies for birth weight, birth length, and head circumference, but there were “no consistent differences in ponderal index.”

Additional analyses found “generally similar” Apgar scores at birth for exposed and unexposed infants, though the authors did note that the antenatal corticosteroid-treated infants received “significantly more care after birth than controls.”

Co-author Marjo-Riitta Jarvelin, MD, also of Imperial College, said that while this was an observational study and does not prove causality, the evidence suggests this therapy “is not a one-size fits all approach.”

“Because of the wide-spread use of [antenatal corticosteroid therapy], it is critical that there is a clear understanding of other potential longer term effects,” Jarvelin said in a statement. “We may need better ways of determining which deliveries will eventually lead to preterm birth with the risk for serious neonatal outcomes. The fact that this treatment may reduce the [fetal] growth should be considered in future research and recommendations.”

The main study limitation was the lack of detail in the Finnish Medical Birth Registry about antenatal corticosteroid therapy, such as lag time between therapy initiation and birth, drug name, dose, or number of doses.

The study was funded by grants from the Swedish government, the Finnish government, and EU grants.

Rodriguez disclosed no relevant relationships with industry. Two co-authors disclosed moving to Novartis and Apple Tree Pediatrics after the study.