OBJECTIVES: To determine the long-term effects of in utero progesterone exposure in twin children.
METHODS: This study evaluated the health and developmental outcomes of all surviving children born to mothers who participated in a double-blind, placebo-controlled trial of progesterone given for the prevention of preterm birth in twin pregnancies (STOPPIT, ISRCTN35782581). Follow-up was performed via record linkage and two parent-completed validated questionnaires, the Child Development Inventory and the Health Utilities Index.
RESULTS: Record linkage was successfully performed on at least one record in 759/781 (97%) children eligible for follow-up. There were no differences between progesterone-exposed and placebo-exposed twins with respect to incidence of death, congenital anomalies and hospitalisation, nor on routine national child health assessments. Questionnaire responses were received for 324/738 (44%) children. The mean age at questionnaire follow-up was 55.5 months. Delay in at least one developmental domain on the Child Development Inventory was observed in 107/324 (33%) children, with no evidence of difference between progesterone-exposed and placebo-exposed twins. There was no evidence of difference between the progesterone and placebo groups in global health status assessed using the Health Utilities Index: 89% of children were rated as having 'excellent' health and a further 8% as having 'very good' health.
CONCLUSIONS: In this cohort of twin children there was no evidence of a detrimental or beneficial impact on health and developmental outcomes at three to six years of age due to in utero exposure to progesterone.
Bibliographical noteFunding: This study was funded by the Chief Scientist Office, Scotland (grant number CZH/2/575) and the charity, Tommy’s. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Data Availability: The STOPPIT Baby Follow-up Study uses two linked datasets, the STOPPIT clinical trial data and routine NHS data collected by Information Services Division (ISD), NHS Scotland. The governance and ethics approvals for this project around anonymity for the participants do not permit us to deposit the linked dataset on a publicly available website. Individuals wishing to access the STOPPIT clinical trial data should contact Professor Jane E Norman email@example.com or Professor John Norrie firstname.lastname@example.org for access. General information on how to access data held by ISD for research purposes is available from ISD’s research coordination team – see http://www.isdscotland.org/Products-and-Services/eDRIS. Please contact Rachael Wood email@example.com for queries about the specific ISD data used in this study.