Steroid exposure in utero spells neurodevelopmental, neurosensory risk in children

Mums’ use of corticosteroids during pregnancy may put children at risk of developing psychological developmental and neurosensory disorders over the long term, as shown in a large cohort study.

Among 670,097 singleton children (51.1 percent boys) followed up from birth until age 1–12 years, antenatal corticosteroid exposure vs nonexposure contributed to increased risks of specific developmental disorders of speech and language (adjusted hazard ratios [aHRs], 1.38, 95 percent confidence interval [CI], 1.27–1.50; p<0.001), of scholastic skills (aHR, 1.32, 95 percent CI, 1.13–1.54; p=0.004), and of motor function (aHR, 1.32, 95 percent CI, 1.18–1.49; p<0.001). [JAMA Netw Open 2022;5:e2228518]

Elevated risks were also noted for pervasive developmental disorder (aHR, 1.35, 95 percent CI, 1.17–1.56; p<0.001), other or unspecified disorder of psychological development (aHR, 1.88, 95 percent CI, 1.58–2.25; p<0.001), and vision or hearing loss (aHR, 1.22, 95 percent CI, 1.04–1.43; p=0.02).

“Excess risk of these harms appeared to be nonspecific to the domain of neurodevelopment and neurosensory function and manifested in the children who, after treatment exposure, were born at term,” according to the investigators.

Specifically, in the term-born group, antenatal corticosteroid was significantly associated with higher risk estimates for specific developmental disorders of speech and language (aHR, 1.47, 95 percent CI, 1.31–1.66; p<0.001), of scholastic skills (aHR, 1.28, 95 percent CI, 1.01–1.63; p=0.04), of motor function (aHR, 1.38, 95 percent CI, 1.12–1.70; p<0.001), pervasive developmental disorder (aHR, 1.42, 95 percent CI, 1.16–1.75; p<0.001), other or unspecified disorder of psychological development (aHR, 1.92, 95 percent CI, 1.51–2.43; p<0.001), epilepsy (aHR, 1.57, 95 percent CI, 1.22–2.01; p<0.001), and cerebral palsy (aHR, 2.18, 95 percent CI, 1.47–3.23; p<0.001).

These associations persisted in a sibling-comparison design, where the risk of any psychological developmental and neurosensory disorder was 22-percent higher in the treatment-exposed sibling vs the nonexposed cosibling (aHR, 1.22, 95 percent CI, 1.04–1.42; p=0.01), the investigators pointed out.

On the other hand, “antenatal corticosteroids were not associated with either significant benefit or risk in the preterm group,” they added.

Corticosteroids are indicated for women at risk of imminent preterm birth and are considered to be one of the most effective ways to improve neonatal prognosis of infants born preterm. Nevertheless, guidelines limit the administration of antenatal corticosteroids until 34 gestational weeks. [Neonatology 2019;115:432-450; Int J Gynaecol Obstet 2021;155:26-30]

“The 2.3–4.3 percent lower rates of perinatal and neonatal mortality and respiratory distress syndrome among the treatment-exposed children outweigh the 0.5–2.6 percent higher rates of long-term psychological developmental and neurosensory disorders reported here. However, these long-term harms may call into question the benefits associated with antenatal corticosteroid administered in the late preterm window and at term before an elective caesarean delivery,” the investigators said.

They added that the benefits associated with antenatal corticosteroid administered in the late preterm window in previous studies are controversial, with some being based on evidence deemed as low or very low in certainty. [PLoS One 2021;16:e0248774; EClinicalMedicine 2022;44:101285; Cochrane Database Syst Rev 2021;12:CD006614]

While the investigators acknowledged not being able to draw causal inferences or rule out residual confounding, they believe that the study findings warrant careful consideration of risks and benefits when deciding on maternal antenatal corticosteroid treatment.