Prenatal exposure to vaginal progesterone for the prevention of preterm birth is not associated with abnormal psychopathological and cognitive profiles in dichorionic twins at 6 to 9 years of age: a follow-up study of a randomized controlled trial.

Abstract

BACKGROUND Current evidence indicates that administration of vaginal progesterone to women with a twin gestation and a short cervix reduces the risk of preterm birth occurring at early gestational ages and of neonatal morbidity and mortality. However, the potential long-term effects of prenatal administration of vaginal progesterone for preventing preterm birth on the psychopathological and cognitive profiles of twins remain unknown. OBJECTIVE To evaluate the psychopathological and cognitive profiles at 6 to 9 years of age of surviving children born to mothers who participated in a randomized controlled trial that compared two different daily doses of vaginal progesterone (200 mg and 400 mg) to placebo to prevent preterm birth in dichorionic twin gestations. STUDY DESIGN This is a follow-up study from a multicenter, double-blind, randomized controlled trial with three parallel groups (placebo, vaginal progesterone 200 mg/day, and vaginal progesterone 400 mg/day administered from 20 to 34 weeks of gestation or delivery, whichever came first; randomization ratio 1:1:1). The Child Behavior Checklist for ages 6 to 18 questionnaire and the Raven's Colored Progressive Matrices test of non-verbal intelligence were applied to the participating mothers and their surviving children aged 6 to 9 years, respectively. The participant mothers, questionnaire collector, and database organizer were blinded to the intervention received in the original trial. The primary outcomes were behavioral, emotional, and social problems evaluated by the Child Behavior Checklist for ages 6 to 18 -18 questionnaire, and the intelligence coefficient percentile evaluated by the Raven's Colored Progressive Matrices test. Analyses were performed on an intention-to-treat basis using descriptive and analytical tests. P values <0.05 were considered statistically significant. RESULTS A total of 206 children born to 104 mothers (35.4% of those included in the original randomized controlled trial) were included in the study: 75 were exposed to vaginal progesterone 200 mg/d, 63 to vaginal progesterone 400 mg/d, and 68 to placebo. Overall, there were no significant differences in maternal sociodemographic, pregnancy and neonatal characteristics between participants and non-participants in the follow-up study, as well as between the three participating study groups. The mean scores of the 11 psychopathological syndrome scales evaluated by the Child Behavior Checklist for ages 6 to 18 questionnaire among children exposed to vaginal progesterone 200 mg/d, 400 mg/d or 200 & 400 mg/d were not significantly different to those among children exposed to placebo. There were no significant differences in the mean total Child Behavior Checklist score between the vaginal progesterone groups (31.08 ± 22.58 for the 200 mg/d group, 37.48 ± 28.59 for the 400 mg/d group, and 34.00 ± 25.60 for the 200 & 400 mg/d group) and the placebo group (34.60 ± 25.55) (P=0.38, 0.54, and 0.87, respectively). The mean percentiles of the Raven's test were slightly higher among children exposed to vaginal progesterone 200 mg/d (63.11 ± 27.03) and 400 mg/d (60.40 ± 31.51) than among those exposed to placebo (59.40 ± 30.64) although these differences were not statistically significant (P = 0.44 and 0.85, respectively). CONCLUSION Exposure to 200 or 400 mg/day of vaginal progesterone in the second half of pregnancy for preterm birth prevention, had no effect on the psychopathological and cognitive profiles of dichorionic twins at 6-9 years of age.