Association of gestational hypertension and preeclampsia with nonsyndromic orofacial clefts in China: a large prospective cohort study

Background: The associations between hypertensive disorders of pregnancy and nonsyndromic orofacial clefts (NSOFCs) are not consistent or based on case-control study design. We hypothesize that OFCs and NSOFCs are associated with hypertensive disease in pregnancy. Methods: Data were collected from the Project for Neural Tube Defects Prevention (1993-1996), a large population-based cohort study conducted in two southern provinces of China. We used a system to record all births after 20 complete gestational weeks, including live births and stillbirths, and all structural congenital anomalies regardless of gestational week. A total of 200 215 singleton live births without other external birth defects were finally included. Results: The incidence of NSOFCs was 20.2 per 10 000 for the whole population, and 20.5 and 39.2 per 10 000 for women with gestational hypertension and preeclampsia, respectively. Compared with the nonpreeclampsia group, preeclampsia was associated with an increased risk of NSOFCs [adjusted risk ratio (RR) = 2.02, 95% confidence interval (CI): 1.27-3.20], cleft lip with or without cleft palate (CL/P) [adjusted RR = 2.24, 95% CI 1.37-3.65], and cleft lip and palate (CLP) [adjusted RR = 2.60, 95% CI 1.45-4.67] but not cleft lip only (CLO) [adjusted RR = 1.66, 95% CI 0.68-4.07] or cleft palate only (CPO) [adjusted RR = 1.09, 95% CI 0.27-4.45]. No associations were observed between gestational hypertension and any types of NSOFCs. Conclusion: Our study supported that among hypertensive disorders of pregnancy, only preeclampsia increased the risk of NSOFCs and its subtypes (CL/P and CLP).