Long-term child follow-up after randomised controlled trials evaluating prevention of preterm birth interventions: A systematic review

Background: Obstetric interventions can have unexpected long-term effects on child development. However, evaluation of these outcomes is not standard in current research.

Objectives: To give an overview of long-term follow-up studies after randomised controlled trials (RCTs) evaluating interventions to prevent preterm birth in asymptomatic pregnancies.

Search strategy: Databases MEDLINE, Embase and Cochrane Central Library were searched for relevant RCTs. WebofScience was crosschecked for citations of these RCTs for publications on long-term child outcomes.

Selection criteria: RCTs evaluating interventions to prevent preterm birth in asymptomatic pregnant women. A long-term follow-up study was defined as such when child outcomes were assessed after discharge from hospital after birth.

Data collection and analysis: Proportion of RCTs with long-term child follow-up was calculated with 95% confidence intervals (CI). Data on child's age at follow-up, outcome domains evaluated and measurement instruments were extracted.

Main results: We included 188 RCTs that evaluated interventions to prevent preterm birth. Only 15 of these RCTs assessed long-term child outcomes (8.0%; 95% CI 4.5 to 12.8) with 17 publications (two RCTs performed two follow-up studies). In 13 out of 17 (76.5%) follow-up publications, neurodevelopment was the primary outcome domain studied for which seven different standardized measurement tools were used. In total, 14 different standardized measurement tools were used to assess long-term outcomes. Overall conclusion regarding the effectiveness of the intervention changed in six studies (6/14 studies; 42.9%) based on long-term follow-up findings compared to the original RCT.

Conclusion: Only a minority of the RCTs evaluating prevention of preterm birth interventions performed a long-term follow-up study to assess long-term outcomes on child development. However, the overall conclusions changed in one third of cases. Performance of follow-up studies should be standard in this population in order to counsel parents on potential childhood effects.

Funding: Amsterdam Reproduction and Development.