General health and social outcomes 50 years after exposure to antenatal betamethasone: follow-up of a randomised controlled trial

• Published in: BMC medicine Vol. 22; no. 1; pp. 505 - 11
• Main Authors: Walters, Anthony G. B., Gamble, Greg D., Crowther, Caroline A., Dalziel, Stuart R., Eagleton, Carl L., McKinlay, Christopher J. D., Milne, Barry J., Harding, Jane E.
• Format: Journal Article
• Language: English
• Published: London BioMed Central 04.11.2024; BioMed Central Ltd; BMC
• Subjects: Academic achievement; Acetic acid; Adult; Allergies; Antenatal corticosteroids; Anxiety disorders; Betamethasone; Betamethasone - administration & dosage; Betamethasone - therapeutic use; Binomial distribution; Biomedicine; Bipolar disorder; Bone cancer; Cancer; Chronic diseases; Chronic illnesses; Clustering; Convictions (Law); Corticoids; Corticosteroids; Datasets; Double-Blind Method; Employment; Exercise; Exposure; Female; Females; Follow-Up Studies; Fractures; Gestational age; Health aspects; Health services; Health Status; Humans; Infant mortality; Injections, Intramuscular; Kidney diseases; Long-term effects; Long-term outcomes; Male; Medicine; Medicine & Public Health; Mental depression; Mental disorders; Mental health; Mental illness; Middle Aged; Morbidity; Neonatal respiratory distress syndrome; Neonates; Newborn babies; Offspring; Osteoporosis; Patient outcomes; Pharmaceuticals; Physical activity; Placebos; Placebos - administration & dosage; Pregnancy; Premature birth; Prenatal drug exposure; Prenatal Exposure Delayed Effects; Preterm birth; Qualifications; Questionnaires; Risk factors; Schizophrenia; Self report; Social aspects; Sodium; Sodium phosphate; Statistical analysis; Statistics; Steroids; Surveys and Questionnaires; Women; Womens health; New Zealand; Long-term outcomes; Preterm birth; Neonatal respiratory distress syndrome; Betamethasone; Antenatal corticosteroids; Follow-up studies
• ISSN: 1741-7015; 1741-7015
• DOI: 10.1186/s12916-024-03732-1

Background Antenatal corticosteroids are recommended for women at risk of preterm birth from 24 to 34 weeks’ gestation as they reduce neonatal morbidity and mortality, but evidence regarding their long-term effects on offspring is limited. This study assessed general health and social outcomes 50 years after antenatal exposure to corticosteroids. Methods We assessed 424 adult offspring of women who participated in the first randomised, double-blind, placebo-controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome. The first 717 mothers received two intramuscular injections of betamethasone (6 mg betamethasone sodium phosphate and 6 mg betamethasone acetate) or placebo given 24 h apart and the subsequent 398 received two injections of double dose betamethasone (12 mg betamethasone sodium phosphate and 12 mg betamethasone acetate) or equivalent volume of placebo. Follow-up included a health questionnaire and consent for access to administrative data sources. Outcome categories included mental health (depression, anxiety, bipolar affective disorder, schizophrenia and treatment or hospital admission for any mental health disorder), general health (chronic kidney disease, cancer diagnosis, bone fracture, oral health, allergies, functional difficulties and physical activity) and social outcomes (educational attainment, employment and criminal convictions). Investigators remained blinded to treatment allocation. Analyses were adjusted for gestational age at entry, sex and clustering. Results We assessed 424 adult offspring (46% of survivors; mean [SD] age 49.3 [1.0] years; 212 [50%] female). There was no difference in mental health, general health and social outcomes between those exposed to betamethasone and those exposed to placebo, with the exception that osteoporotic site fracture in adulthood was more likely to have occurred in the betamethasone group compared with placebo (adjusted relative risk 1.57, 95% CI 1.00, 2.48, p  = 0.05). No dose–effect relationship was evident and there was no difference in the proportion with at least one fracture. Follow-up rate and lack of in-person assessments were the main limitations. Conclusions There is no evidence that antenatal corticosteroids have clinically important effects on general health and social outcomes up to 50 years of age.