Misleading meta-analyses of observational studies may generate unjustified alarms: The case of medications for nausea and vomiting in pregnancy

source extracted confidence: high 2026-04-09
#abnormalities-drug-induced #antiemetics #dicyclomine #doxylamine #drug-combinations

Misleading meta-analyses of observational studies may generate unjustified alarms: The case of medications for nausea and vomiting in pregnancy

Biffi et al., 2021 | Pharmacol Res | Meta Analysis

Citation

Biffi Annalisa, Rea Federico, ... Corrao Giovanni. Misleading meta-analyses of observational studies may generate unjustified alarms: The case of medications for nausea and vomiting in pregnancy. Pharmacol Res. 2021-Jan;163:105229. doi:10.1016/j.phrs.2020.105229

Abstract

OBJECTIVES: Because observational studies often use imperfect measurements, results are prone to misclassification errors. We used as a motivating example the possible teratogenic risks of antiemetic agents in pregnancy since a large observational study recently showed that first-trimester exposure to doxylamine-pyridoxine was associated with significantly increased risk of congenital malformations as a whole, as well as central nervous system defects, and previous observational studies did not show such associations. A meta-analysis on this issue was carried out with the aim to illustrate how differential exposure and outcome misclassifications may lead to uncertain conclusions. METHODS: Medline, searched to October 2019 for full text papers in English. Summary Odds Ratios (ORs) with confidence intervals (CIs) were calculated using random-effect models. Probabilistic sensitivity analyses were performed for evaluating the extension of differential misclassification required to account for the exposure-outcome association. RESULTS: Summary ORs were 1.02 (95 % CI, 0.92-1.15), 0.99 (0.82-1.19) and 1.25 (1.08-1.44) for overall congenital, cardiocirculatory, and central nervous system malformations respectively. By assuming exposure and outcome bias factor respectively of 0.95 (i.e., newborns with congenital defects had exposure specificity 5% lower than healthy newborns) and 1.12 (i.e., exposed newborns had outcome sensitivity 12 % higher than unexposed newborns), summary OR of central nervous system defects became 1.13 (95 % CI, 0.99-1.29) and 1.17 (95 % CI, 0.99-1.38). CONCLUSION: Observational investigations and meta-analyses of observational studies need cautious interpretations. Their susceptibility to several, often sneaky, sources of bias should be carefully evaluated.

Key Findings

Summary ORs were 1.02 (95 % CI, 0.92-1.15), 0.99 (0.82-1.19) and 1.25 (1.08-1.44) for overall congenital, cardiocirculatory, and central nervous system malformations respectively. By assuming exposure and outcome bias factor respectively of 0.95 (i.e., newborns with congenital defects had exposure specificity 5% lower than healthy newborns) and 1.12 (i.e., exposed newborns had outcome sensitivity 12 % higher than unexposed newborns), summary OR of central nervous system defects became 1.13 (95 %

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size See abstract
Age Range See abstract
Condition See abstract

MeSH Terms

  • Abnormalities, Drug-Induced
  • Antiemetics
  • Dicyclomine
  • Doxylamine
  • Drug Combinations
  • Female
  • Humans
  • Nausea
  • Observational Studies as Topic
  • Odds Ratio
  • Pregnancy
  • Pyridoxine
  • Scientific Experimental Error
  • Uncertainty
  • Vomiting

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't, Review
  • Vertical: vitamin-b6

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09