Effects of Genomic and Metabolomic Variations of Choline on Risk of Preterm Birth and Clinical Outcomes in Preterms

Genomic and Metabolomic Differences of Choline on the Risk of Preterm Delivery and Their Effects on Clinical Outcomes in Preterms Receiving Total Parenteral Nutrition Therapy

The incidence of preterm birth increases annually. Premature delivery has become the leading cause of neonatal illness and death. For the survived premature babies, the incidence of sequelae is also higher than the full-term babies, which brings a heavy burden to a family and society. Preterm birth has become the important factor affecting the quality of births. The occurrence of premature birth is the outcome of combined action of genetic and environmental factors. However, its etiology is not clear. Recent studies have shown that the risk of preterm birth is associated with dietary factors. Choline is an essential nutrient for human health and it plays an important role in the growth and development of fetuses and neonates. The investigators previously found that serum levels of free choline in preterm mothers were lower than those in normal mothers with full-term birth. Serum levels of free choline also reduced in preterms after receiving parenteral nutrition (PN). However, the relationships between choline and preterm birth is not clear. Therefore, this study is aimed to explore the effect of choline intake during pregnancy and genetic polymorphisms on the risk of preterm birth and on the clinical outcomes in preterms receiving total PN therapy. Healthy Chinese pregnant women with their healthy term infants will be recruited as the control group, while Chinese women with preterm delivery and their preterm infants will be recruited as the preterm group. Dietary choline intake during pregnancy will be evaluated by semi-quantitative food frequency questionnaire and 24-h dietary recall questionnaire. Gene polymorphisms in the key enzymes of choline metabolism will be identified among the participated women and neonates through Real-time polymerase chain reaction. Choline and its related metabolites will be assayed using high performance liquid chromatography combined with mass spectrometry among all mothers and preterms before and after 7-days PN treatment. The influence of genetic risk factors and metabolic changes of choline on the physical and mental development of preterms will be evaluated. The results of this study will contribute to a comprehensive understanding of the role of choline and the relative gene polymorphisms on the risk of preterm birth, which will be helpful for estimating the high risk in advance. The results will also provide the scientific evidences to establish the personalized amount of choline intake among women and infants, optimize nutrition support for pregnant women and preterms, and promote better prenatal and postnatal care.

Inclusion Criteria:

1. Preterm group: preterm infants (gestational age < 37 w) and their mothers (125 pairs );
2. Control group: healthy full-term infants and their mothers (125 pairs );_
3. Admission to Xin Hua Hospital, Shanghai;_ 4.1600g ≤ birth weight ≤ 2100g for preterms;

5.Administration of total parenteral nutrition (TPN) ≥ 7d; 6.No contraindication of TPN therapy.

Exclusion Criteria:

1. Administration of TPN before enrollment;
2. Receive blood infusion during TPN treatment;
3. Liver or renal markers present at 2 times higher than the normal level;
4. Suspected or identified chromosome diseases, congenital metabolic disease, congenital digestive tract diseases and necrotizing enterocolitis;
5. Cytomegalovirus infection, viral hepatitis, and congenital or acquired immune deficiency.