Umbilical choline and related methylamines betaine and dimethylglycine in relation to birth weight

Abstract

Background: Low birth weight (LBW) is associated with increased morbidity and mortality for the newborn and risk of chronic disease in adulthood. Choline plays an essential role in the integrity of cell membranes, methylation reactions, and memory development. We examined whether choline, betaine, and dimethylglycine (DMG) concentrations were associated with LBW in Dutch women. Methods: Blood was sampled from umbilical cords (UCs) at delivery in singleton pregnancies (n = 1,126). Maternal blood was sampled at 30-34 wk of gestational age (GA) (n = 366). We calculated birth weights standardized for GA and defined LBW as standardized birth weight ≤2,500 g. results: Maternal concentrations were lower as compared with UC concentrations and were not associated with birth weight. UC choline and betaine were inversely associated with birth weight (β = −60 (−89, −31) and β = −65 (−94, −36), respectively), whereas UC DMG was positively associated with birth weight (β = 35 (6.1, 63)). Odds ratios for LBW were 4.12 (1.15, 14.78), 5.68 (1.24, 25.91), and 0.48 (0.09, 2.65) for the highest UC choline, betaine, and DMG quartiles, respectively, as compared with the lowest quartiles. conclusion: We observed an increased risk of LBW with increased umbilical choline and betaine in venous UC blood. These results might reflect a change in choline consumption or metabolism or a disturbed placental function. l ow birth weight (LBW) poses the newborn an increased risk of morbidity and mortality (1). LBW also relates to an increased risk of chronic disease in adulthood, e.g., hypertension, coronary heart disease, stroke, and diabetes (2), underlining the importance of revealing possible and moreover treatable risk factors for LBW.Choline is an essential nutrient and is involved in several metabolic processes including lipid metabolism, methylation reactions, and synthesis of acetylcholine. It also plays a role in the structural integrity and signaling functions of cell membranes, brain development, and neurotransmission (Figure 1) (3,4).Pregnancy places a heavy burden on maternal choline stores, and choline is critical for the rapidly growing fetus (5,6).In utero, the fetus lives in a high-choline environment because of a system actively transporting choline against a concentration gradient across the placenta to the fetus (7,8). Variation in maternal choline status could possibly influence fetal outcome through disturbances in cell membrane synthesis, increase in homocysteine concentrations, and/or perturbation of methylation reactions and changes in acetylcholine production. Choline also influences stem cell proliferation, apoptosis in the brain, and the developing hippocampus (memory center) in rodents (9). Maternal choline supplementation in rats during critical periods in pregnancy causes lifelong changes in brain structure (10). In addition, perinatal choline supplementation attenuates behavioral alterations associated with fetal or neonatal alcohol exposure in rats (11).Clinically, low maternal choline concentrations or intake rel...

Validation of a Food Frequency Questionnaire for Estimating Micronutrient Intakes in an Urban US Sample of Multi-Ethnic Pregnant Women

“…Despite the lack of significance, the strong correlations for vitamin B6 and iron are of interest given their importance in preeclampsia, birth weight, neuromotor development, and maternal anemia in pregnancy [21, 23]. Betaine is a relatively new methyl-nutrient being explored and thus the exact role of betaine during pregnancy is unclear, however it also appears to be important for fetal development, birth weight, and early brain development [28, 73]. …”

Newborn Urinary Metabolic Signatures of Prematurity and Other Disorders: A Case Control Study

“…Increased DMG has been correlated with higher birth weight, in a LBW vs normal weight cohort, due to alterations in choline metabolism. 63 Moreover, it has been suggested that alterations in methionine metabolism could impact on purine and pyrimidine metabolism, deoxyribonucleic acid (DNA) synthesis and/or cell proliferation, and affect fetal growth. 64 This is consistent with the noted disturbances in the tryptophannicotinamide adenine dinucleotide (tryptophan-NAD + ) pathway ( Figure 6) and the significant intensity decrease of purines/pyrimidines resonances at δ 6.0−6.5.…”

Maternal betaine status, but not that of choline or methionine, is inversely associated with infant birth weight

“…Methionine, also an essential amino acid, is particularly important during fetal development because of high demands for protein synthesis (18) . To date, only three epidemiologic studies have explored the association of maternal circulating choline and betaine with birth weight, and the results have been inconsistent (19)(20)(21) . While a large mother-offspring cohort reported an inverse association between maternal plasma betaine and birth characteristics included, that is, birth weight or birth length or abdominal fat mass (19) , other studies reported null association between either biomarkers and birth weight (20,21) .…”