PARENTAL CONSANGUINITY AND ADVERSE PREGNANCY OUTCOMES: A SYSTEMATIC REVIEW AND META-ANALYSIS OF MAJOR CONGENITAL ANOMALIES

Abstract

Background: Consanguineous unions remain common in several populations in South Asia, the Middle East and North Africa, as well as in migrant communities originating from these regions. Parental biological relatedness increases the probability that an offspring inherits two copies of a deleterious recessive variant, although observed pregnancy outcomes are also shaped by maternal health, socioeconomic conditions and access to antenatal care. This review evaluated associations between consanguinity and major congenital anomalies, pregnancy loss, stillbirth, preterm birth, low birth weight and neonatal mortality. Methods: Comparative observational studies involving consanguineous and non-consanguineous couples were identified from PubMed/MEDLINE, PubMed Central, publisher repositories and reference lists through 31 July 2026. Adjusted estimates were preferred. For the primary outcome, risk-ratio-type estimates were converted to odds ratios using the reported non-consanguineous baseline risk. Odds ratios were pooled using a restricted maximum-likelihood random-effects model with Hartung-Knapp confidence intervals. Heterogeneity was summarized using Q, I², tau² and a prediction interval. Other clinically distinct outcomes were synthesized narratively. Results: Twenty-six comparative studies contributed to the qualitative synthesis, and four studies contributed compatible adjusted estimates for major congenital anomalies. The pooled odds ratio was 1.90 (95% CI 1.02-3.56), with substantial heterogeneity (I² = 85.1%; tau² = 0.133). The 95% prediction interval was wide (0.32-11.32), indicating marked variation across populations and settings. Leave-one-out estimates ranged from 1.63 to 2.12, although confidence intervals widened when only three studies remained. Earlier quantitative evidence suggested a modest association with low birth weight, whereas findings for miscarriage, stillbirth, preterm birth and neonatal mortality were less consistent. Conclusion: Consanguinity was associated with higher odds of major congenital anomalies, but the magnitude was not uniform and the certainty of the pooled evidence was very low because of observational designs, substantial heterogeneity and limited numbers of compatible studies. Clinical responses should emphasize individualized pedigree assessment, targeted carrier testing, appropriate fetal evaluation, and culturally respectful counselling rather than generalized or coercive messages.