Re-examining the evidence: a meta-analysis of the 2017 expert working group's data on primodos and congenital malformations: Trust the Evidence Publications: Research report 3: 9th November 2026

Internet publication : Digital magazine

Background: In 2017, the Commission on Human Medicines’ Expert Working Group (EWG) concluded that the available epidemiological evidence did not, on balance, support a causal association between exposure to oral hormone pregnancy tests (HPTs), including Primodos, and congenital malformations. The EWG declined to undertake a formal meta-analysis, citing concerns about study quality, heterogeneity and statistical weighting. This report re-examines that decision and assesses whether quantitative synthesis of the EWG's underlying data provides additional evidence relevant to its conclusions.
Methods: Following the release of the EWG's extracted data in response to a Freedom of Information request, random-effects meta-analyses were conducted to estimate associations between HPT exposure and congenital heart defects, congenital malformations overall, urogenital defects, and other congenital abnormalities. The resulting estimates were compared with those reported in the systematic review and meta-analysis by Heneghan et al. The EWG's methodological objections to quantitative synthesis were also critically examined.
Results: Reanalysis of the EWG data identified statistically significant associations between HPT exposure and congenital heart defects (OR 1.91, 95% CI 1.36–2.68; I² = 22%) and any congenital malformation (OR 1.34, 95% CI 1.13–1.60; I² = 0%). These findings closely replicated the estimates reported by Heneghan et al. for congenital heart defects (OR 1.89, 95% CI 1.32–2.72) and all congenital malformations (OR 1.40, 95% CI 1.18–1.66). Urogenital malformations showed elevated but statistically inconclusive associations in both analyses. The close agreement between the two analyses supports the analytical reproducibility of the principal findings, although their overlapping evidence bases preclude interpretation as independent confirmation.
Conclusions: The reanalysis demonstrates that quantitative synthesis of the historical evidence assembled by the EWG was feasible and identified statistically significant associations between oral HPT exposure and congenital heart defects and congenital malformations overall. The consistency with the previously published Heneghan et al. meta-analysis strengthens confidence in the reproducibility of these associations. The findings challenge the EWG's decision to reject quantitative synthesis without formally investigating the effects of study quality, heterogeneity and statistical weighting. A more transparent assessment incorporating meta-analysis, risk-of-bias evaluation and sensitivity analyses provides a more complete account of the available evidence and its uncertainties.

Authors: Heneghan, C; Jefferson, T

• Publication status: Published
• Publisher: Trust the Evidence Publications
• Publication date: 2026-11-09
• Language: English
• Keywords: MHRA; hormone; pregnancy tests; congenital malformations; Primodos; congenital heart defects; Expert Working Group; meta-analysis; reproducibility
• Subtype: Digital magazine