Objective: To assess whether individuals born to consanguineous parents had a higher frequency of nonsyndromic orofacial clefts compared with those with no parental consanguinity.
Design: A prespecified plan for a search strategy, inclusion/exclusion criteria, and data extraction from studies reporting consanguinity in relation to nonsyndromic orofacial clefts (NSOFC) was carried out. Papers reporting observational studies with control populations were included, without language restrictions, and these reports were assessed for quality. Sensitivity analyses using subgroups, homogeneity evaluation, and assessment of publication bias were carried out, and meta-analyses of extracted data were performed.
Results: Sixteen studies fulfilled the selection criteria and were included in the meta-analyses. There were statistically significant relationships between consanguinity and NSOFC for all 16 studies combined (P = .0003), with odds ratio (OR) = 1.83 and 95% confidence interval (CI) = (1.31, 2.54); 10 case-control studies (P = .006), with OR = 2.06 and 95% CI = (1.23, 3.46); six cross-sectional studies (P = .03), with OR = 1.34 and 95% CI = (1.02, 1.76); first cousins consanguineous marriages (P = .04), with OR = 1.40 and 95% CI = (1.01, 1.93); cleft palate alone (P = .01), with OR = 1.89 and 95% CI = (1.14, 3.13); and cleft lip with or without cleft palate cases (P = .002), with OR = 1.56 and 95% CI = (1.18, 2.07).
Conclusion: Although there was a high level of study heterogeneity, the evidence is consistent in suggesting that consanguinity is a risk factor for NSOFC, with an overall OR of 1.83 (95% CI, 1.31 to 2.54), implying that there was almost twice the risk of a child with NSOFC being born if there was parental consanguinity.
Keywords: cleft lip; cleft palate; consanguinity; etiology; meta-analysis.