Maternal-related factors in the origin of isolated cleft palate-A population-based case-control study

Isolated cleft palate (CPO) is the rarest form of oral clefting affecting 1-25 per 10 000 newborns worldwide. There is increasing evidence for the different pathogenetic backgrounds of CPO and cleft lip with or without cleft palate. The role of environmental factors in the origin of non-syndromic and syndromic CPO is unclear in most patients. The aim of this study was to estimate possible maternal risk factors in the origin of CPO.

The Hungarian Case-Control Surveillance of Congenital Abnormalities contains data of 32 345 birth defect cases and 57 231 control newborns. The study samples included 751 cases with isolated CPO, 1196 matched controls and 57 231 population controls.

Maternal diseases during pregnancy in cases and population controls were compared, and adjusted ORs with 95% CI were calculated in a multivariable unconditional logistic regression model.

Beyond the well-known robust female excess (58.9%)-maternal smoking (OR with 95% CI: 2.34, 1.94-2.81) medically recorded maternal anaemia, threatened abortion and excessive vomiting in pregnancy were associated with a higher risk for CPO in the offspring. An elevated risk was found in Graves' disease (OR: 4.30, 1.74-10.62), epilepsy (OR: 4.64, 2.44-8.82), migraine (OR: 2.82, 1.18-6.76) and essential hypertension (OR: 2.33, 1.32-4.10). Among acute diseases common cold (OR: 4.94, 3.48-7.03), acute respiratory infections (OR: 4.20, 1.49-11.82), influenza (OR: 2.95, 1.75-4.95), pulpitis (OR: 7.85, 2.80-22.03), cholecystitis (OR: 3.15, 1.16-8.60), acute urinary tract infections (OR: 4.08, 2.22-7.49) and pelvic inflammatory diseases (OR: 3.93, 1.62-9.53) during pregnancy also were associated with an increased risk for developing CPO.

The findings of this study suggest that maternal diseases and lifestyle factors during the first trimester play a significant role in the development of isolated cleft palate.