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The amino acid citrulline is poorly represented in food, except for the Cucurbitaceae family of fruits (watermelons, etc.) and sap from birch trees, which have both been used in the treatment of reproductive disorders for centuries. Recently, an interesting observation was published regarding citrulline as a promising candidate biomarker of abnormal embryogenesis. Our study was undertaken to investigate the involvement of newborn citrulline concentrations as potential risk factors for orofacial clefting. We performed a retrospective analysis of citrulline concentrations obtained from the results of a newborn screening program. The study group consists of 52 children with isolated cleft lip with or without cleft palate. One hundred and seven healthy children without congenital anomalies serve as controls. Whole blood citrulline levels were measured using tandem mass spectrometry. Two cut-off points of citrulline concentrations were accepted and three groups of participants were analysed: those with (1) low concentrations (< 8 micromol/L), (2) medium concentrations (8 - 16 micromol/L), and (3) high concentrations (>16 micromol/L). Low citrulline levels were significantly more frequent in patients with clefts than in children without congenital anomalies. In the control group, a high level of citrulline was observed nearly two times more often than in affected children (p=0.03). The presented findings, confirming a possible association between newborn citrulline status and the risk of an orofacial cleft, call for further studies in this area and consideration of increased consumption of foods rich in citrulline (or supplements) by women of childbearing age.

Whole blood citrulline concentrations in newborns with non-syndromic oral clefts--a preliminary report.