Prenatal 17-Alpha-Hydroxyprogesterone Caproate Exposure in Twins and Childhood Outcomes: 14-Year Follow-Up of a Randomised Trial

OBJECTIVE: Long-term child outcomes after intra-uterine exposure to 17-alpha-hydroxyprogesterone caproate (17-OHPC) versus placebo.

DESIGN: Follow-up of the AMPHIA randomised controlled trial assessing neonatal outcomes after weekly 17-OHPC injections compared to placebo in multiple pregnancies.

SETTING: Multicentre.

POPULATION OR SAMPLE: Children born in the AMPHIA study.

METHODS: Children were assessed at 11-14 years of age by record linkage and through self-reported, parental and teacher questionnaires. Mean differences or odds ratios (OR) with 95% confidence intervals (95% CI) were calculated with cluster robust standard errors for twins and adjustment for confounders using inverse probability weighting (IPW).

MAIN OUTCOME MEASURES: Child mortality, educational attainment, cognition, behaviour, gender identity, general health, and a composite of abnormal development.

RESULTS: Up to 14 years, 60/1356 children had died (n = 24 17-OHPC and n = 36 placebo (OR 0.75 95% CI 0.36-1.53)). Record linkage was completed for 1027/1296 (79%) surviving children (n = 517 17-OHPC and n = 510 placebo). No significant difference was found regarding educational attainment. Detailed developmental outcomes through questionnaires were collected for 303/1296 (23%) surviving children (n = 159 17-OHPC and n = 144 placebo). No differences in cognition, behaviour, gender identity, and general health up to 14 years of age were found between both groups. The composite of abnormal development did not differ between 17-OHPC (23.3%) and placebo (20.1%) groups (OR 1.31 95% CI 0.66-2.56).

CONCLUSION: In offspring of women with a multiple pregnancy, the use of 17-OHPC in pregnancy is unlikely to provide positive or negative effects on child outcome related to mortality, educational attainment, cognition and behaviour.