Dosage escalation of antenatal steroids in preterm twin pregnancies does not improve long-term outcome

Abstract

Objectives: To analyze long-term effects of antenatal betamethasone (≤16 mg, =24 mg and >24 mg) in preterm twins on infant and childhood morbidity.

Methods: Retrospective cohort study among 198 preterm twins. Three follow up time points, including a total of 84 outcomes, were evaluated: first neonatal examination after birth and in the neonatal period up to 10 days after birth using data from the clinic charts; examination from the 21st to the 24th month of life and examination from the 60th to the 64th months, using data from copies of the children's examination booklets sent back by the parents. Dosage-dependent and sex-specific long-term effects of antenatal betamethasone treatment on neonatal, infant and early childhood development and morbidity up to 5.3 years of age were analyzed.

Results: Dosage escalation of >24 mg was not associated with improved neonatal, infant or early child hood outcome, independent of twin pair structure. In contrast, higher doses >24 mg were significantly linked to increased rates of congenital infections (OR 5.867, 95% CI 1.895-18.167). Male sex as a factor was obvious for lower rates of apnea-bradycardia-syndrome in neonates, higher rates of no free steps after 15 months in infancy and highest rates of motor clumsiness in early childhood.

Conclusions: Betamethasone dosage escalation >24 mg in twins born between 23⁺⁵ and 33⁺⁶ weeks of gestation did not improve neonatal, infant or early childhood morbidity. In contrast, higher doses >24 mg total dose resulted in significantly higher rates of congenital infections and are not recommended. For males, 24 mg betamethasone appears to be the preferable dose.

Keywords: antenatal betamethasone; antenatal steroid (ANS); dosage; fetal programming; follow up; multiple pregnancy; sex.