Maternal factors in the origin of cleft lip/cleft palate: A population-based case-control study

Orofacial clefts are among the most common birth defects, with an estimated worldwide incidence of around 1.5-1.7 per 1000 live-born babies. The most frequent form of orofacial clefts is cleft lip with or without cleft palate (CL ± CP). The role of environmental factors in the development of clefts is unclear in most patients, thus the aim of this study was to estimate possible maternal risk factors in the origin of CL ± CP.

1648 CL ± CP cases, 2654 matched controls and 57 231 population controls were evaluated from The Hungarian Case-Control Surveillance of Congenital Abnormalities. Maternal factors during the critical period in cases and controls were compared. Adjusted odds ratios (OR) with 95% confidence intervals (CI) were estimated in a multivariable conditional logistic regression model.

Among socio-demographic data, we have found significant differences between maternal employment. The proportion of unskilled mothers (6.5%) were higher in the CL ± CP group than in controls (3.5%). Medically recorded maternal anaemia, excessive vomiting and threatened abortion were associated with a higher risk of CL ± CP. An elevated risk was also found in various acute illnesses such as influenza (OR: 2.4, 95% CI: 3.0-5.8), acute bronchitis (OR: 4.5, 95% CI: 1.6-12.6) and urinary tract infections (OR: 3.5, 95% CI: 2.0-6.0). Maternal migraine and essential hypertension occurred more frequently in the mothers of cases than in controls.

The findings of this study suggest that maternal diseases and lifestyle factors during the first trimester play a significant role in the development of CL ± CP.