Maternal Choline Status, but Not Fetal Genotype, Influences Cord Plasma Choline Metabolite Concentrations

Visentin, Carly; Masih, Shannon; Plumptre, Lesley; Malysheva, Olga; Nielsen, Daiva E.; Sohn, Kyoung‐Jin; Ly, Anna; Lausman, Andrea; Berger, Howard; Croxford, Ruth; El‐Sohemy, Ahmed; Caudill, Marie A.; O'Connor, Deborah L; Kim, Young–In

doi:10.3945/jn.115.211136

Cited by 36 publications

(31 citation statements)

References 37 publications

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“…, prior to the start of the intervention) was substantially <480 mg/d; otherwise, if usual choline intake was approximately equal to 480 mg/d, then all participants would have had the same duration of exposure to that amount of choline throughout pregnancy, regardless of the number of days the intervention was administered. This inference is consistent with the evidence, discussed above, indicating that the average choline intake of pregnant women in the U.S. is ~300‐350 mg choline/d, with fewer than 25% of women consuming the adequate intake (AI) level (39–41). Considered in that light, the intake duration effect we report suggests that, even a modest increase in typical maternal choline intake during pregnancy would be beneficial for infant information processing speed, with possible long‐term benefits for offspring cognitive function throughout life.…”

Section: Discussionsupporting

confidence: 90%

Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double‐blind, controlled feeding study

et al. 2018

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Rodent studies demonstrate that supplementing the maternal diet with choline during pregnancy produces life-long cognitive benefits for the offspring. In contrast, the two experimental studies examining cognitive effects of maternal choline supplementation in humans produced inconsistent results, perhaps because of poor participant adherence and/or uncontrolled variation in intake of choline or other nutrients. We examined the effects of maternal choline supplementation during pregnancy on infant cognition, with intake of choline and other nutrients tightly controlled. Women entering their third trimester were randomized to consume, until delivery, either 480 mg choline/d ( n = 13) or 930 mg choline/d ( n = 13). Infant information processing speed and visuospatial memory were tested at 4, 7, 10, and 13 mo of age ( n = 24). Mean reaction time averaged across the four ages was significantly faster for infants born to mothers in the 930 ( vs. 480) mg choline/d group. This result indicates that maternal consumption of approximately twice the recommended amount of choline during the last trimester improves infant information processing speed. Furthermore, for the 480-mg choline/d group, there was a significant linear effect of exposure duration (infants exposed longer showed faster reaction times), suggesting that even modest increases in maternal choline intake during pregnancy may produce cognitive benefits for offspring.-Caudill, M. A., Strupp, B. J., Muscalu, L., Nevins, J. E. H., Canfield, R. L. Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double-blind, controlled feeding study.

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Section: Discussionsupporting

confidence: 90%

Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double‐blind, controlled feeding study

et al. 2018

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“…OCTN2 is also responsible for carnitine intake in the placental tissue 22 . In general the clear increase in various trimethylated compounds may indicate the fetus’s high demand for choline and methyl donors, as has been suggested also earlier 30 . Previously, the rise in maternal plasma choline concentrations during pregnancy has been shown to reflect the mobilization of maternal hepatic choline stores and increase in estrogen.…”

Section: Discussionsupporting

confidence: 62%

A Non-Targeted LC-MS Profiling Reveals Elevated Levels of Carnitine Precursors and Trimethylated Compounds in the Cord Plasma of Pre-Eclamptic Infants

Jääskeläinen

Kärkkäinen

Jokkala

et al. 2018

Sci Rep

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Preeclampsia (PE) is a complex pregnancy disorder. It is not extensively known how the metabolic alterations of PE women contribute to the metabolism of newborn. We applied liquid chromatography-mass spectrometry (LC-MS) based non-targeted metabolomics to determine whether the metabolic profile of plasma from umbilical cord differs between infants born to PE and non-PE pregnancies in the FINNPEC study. Cord plasma was available from 42 newborns born from PE and 53 from non-PE pregnancies. 133 molecular features differed between PE and non-PE newborns after correction for multiple testing. Decreased levels of 4-pyridoxic acid were observed in the cord plasma samples of PE newborns when compared to non-PE newborns. Compounds representing following areas of metabolism were increased in the cord plasma of PE newborns: urea and creatine metabolism; carnitine biosynthesis and acylcarnitines; putrescine metabolites; tryptophan metabolism and phosphatidylcholines. To our knowledge, this study is the first one to apply LC-MS based metabolomics in cord plasma of PE newborns. We demonstrate that this strategy provides a global picture of the widespread metabolic alterations associated with PE and particularly the elevated levels of carnitine precursors and trimethylated compounds appear to be associated with PE at birth.

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“…Maternal plasma betaine have been found to remain constant from twenty-two gestational weeks to the rest of pregnancy (28,29) , a stage covering the period of our blood sample collection. A strong correlation between maternal betaine status and cord blood betaine status was observed (30) . Evidence from animal and human adult betaine supplementation trials as well as the GUSTO study suggested that the possible mechanisms of the observed decrease in birth weight related to betaine may involve adiposity reductions in infants (19,31,32) .…”

Section: Discussionmentioning

confidence: 91%

“…Associations between choline status with outcomes might be masked because we collected blood samples in a pregnancy stage during which plasma choline is increasing. Furthermore, it should also be noted that maternal plasma choline at delivery was not associated with cord plasma choline (30) .…”

Section: Discussionmentioning

confidence: 95%

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

Wei

Yang

et al. 2019

Br J Nutr

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Maternal one-carbon metabolism during pregnancy is crucial for fetal development and programming by DNA methylation. However, evidence on one-carbon biomarkers other than folate is lacking. We, therefore, investigated whether maternal plasma methyl donors, that is, choline, betaine and methionine, are associated with birth outcomes. Blood samples were obtained from 115 women during gestation (median 26·3 weeks, 90 % range 22·7–33·0 weeks). Plasma choline, betaine, methionine and dimethylglycine were measured using HPLC-tandem MS. Multivariate linear and logistic regression models were used to estimate the association between plasma biomarkers and birth weight, birth length, the risk of small-for-gestational-age and large-for-gestational-age (LGA). Higher level of maternal betaine was associated with lower birth weight (–130·3 (95 % CI –244·8, –15·9) per 1 sd increment for log-transformed betaine). Higher maternal methionine was associated with lower risk of LGA, and adjusted OR, with 95 % CI for 1 sd increase in methionine concentration was 0·44 (95 % CI 0·21, 0·89). Stratified analyses according to infant sex or maternal plasma homocysteine status showed that reduction in birth weight in relation to maternal betaine was only limited to male infants or to who had higher maternal homocysteine status (≥5·1 µmol/l). Higher maternal betaine status was associated with reduced birth weight. Maternal methionine was inversely associated with LGA risk. These findings are needed to be replicated in future larger studies.

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Maternal Choline Status, but Not Fetal Genotype, Influences Cord Plasma Choline Metabolite Concentrations

Abstract: These data collectively indicate that maternal choline status, but not fetal genotype, influences cord plasma concentrations of choline metabolites. This trial was registered at clinicaltrials.gov as NCT02244684.

Cited by 36 publications

References 37 publications

Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double‐blind, controlled feeding study

Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double‐blind, controlled feeding study

A Non-Targeted LC-MS Profiling Reveals Elevated Levels of Carnitine Precursors and Trimethylated Compounds in the Cord Plasma of Pre-Eclamptic Infants

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

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