Choline and its Metabolites Trimethylamine and Trimethylamine N-oxide Potentially Predict the Risk of Small Vulnerable Newborn and the Development of 1-Year Infants

Abstract Background: The concept of Small Vulnerable Newborns (SVN), encompassing small for gestational age (SGA), low birthweight (LBW), and preterm birth (PTB) has recently proposed [1, 2]. Collectively, these births represent the main cause of neonatal mortality and specific interventions to address SVN have great potential to improve maternal and infant outcomes. Choline is an essential nutrient for many aspects of fetal development and metabolism, but despite this, upwards of 90% of pregnant women fail to achieve recommend adequate intake [3]. At present, the role of choline deficiency in pregnancy on SVN risk remains unclear. Methods: Here, we measured choline and its metabolites, TMA an TMAO by liquid chromatography-mass spectrometry (LC-MS/MS) in first (11-14 weeks), second (22-28 weeks), and third (32-34 weeks) trimester plasma of 1231 pregnant women from the Complex Lipids in Mothers and Babies (CLIMB) cohort to investigate the relationship between choline TMA, TMAO in pregnancy and the risk of SVN. We also explored the relationship of these measures with later infant developmental outcomes of SVN and non-SVN births including physical and brain development. Results: Pregnant women with SVN births showed no differences in circulating choline throughout pregnancy but had significantly lower TMAO in the first two trimesters, and higher TMA in the third trimester, relative to non-SVN births. However, TMAO levels during pregnancy were positively correlated with the risk of SVN, while TMA levels were negatively correlated with the risk of LBW and PTB in SVN. Supporting findings included positive associationbetween TMAO during pregnancy and birth weight and birth length, while negative association between TMA and birth weight and birth length. In the receiver operating characteristic (ROC) curves, inclusion of choline and its metabolites TMA and TMAO during pregnancy in the models markedly increased the predictive performance for the model which contained traditional risk factors for SVN including age, body mass index, fasting blood glucose , one-hour postprandial blood glucose, two-hour postprandial blood glucose, and placental growth factor. Moreover, during pregnancy, the TMAO was not only positively correlated with fetal development, but also with the development of postnatal offspring at six months old and 1 year old, while TMA was the opposite. Conclusions: The abnormal choline metabolism is potentially associated with the risk of SVN and the development of fetus and postnatal offspring, with particular attention paid to the opposite association between TMAO and TMA in offspring development, which may be an effective means of preventing SVN and ensuring healthy fetal development.