Cord Blood Lysophosphatidylcholine 16: 1 is Positively Associated with Birth Weight

Background/Aims: Impaired birth outcomes, like low birth weight, have consistently been associated with increased disease susceptibility to hypertension in later life. Alterations in the maternal or fetal metabolism might impact on fetal growth and influence birth outcomes. Discerning associations between the maternal and fetal metabolome and surrogate parameters of fetal growth could give new insight into the complex relationship between intrauterine conditions, birth outcomes, and later life disease susceptibility. Methods: Using flow injection tandem mass spectrometry, targeted metabolomics was performed in serum samples obtained from 226 mother/child pairs at delivery. Associations between neonatal birth weight and concentrations of 163 maternal and fetal metabolites were analyzed. Results: After FDR adjustment using the Benjamini-Hochberg procedure lysophosphatidylcholines (LPC) 14: 0, 16: 1, and 18: 1 were strongly positively correlated with birth weight. In a stepwise linear regression model corrected for established confounding factors of birth weight, LPC 16: 1 showed the strongest independent association with birth weight (CI: 93.63 - 168.94; P = 6.94×10-11 ). The association with birth weight was stronger than classical confounding factors such as offspring sex (CI: -258.81- -61.32; P = 0.002) and maternal smoking during pregnancy (CI: -298.74 - -29.51; P = 0.017). Conclusions: After correction for multiple testing and adjustment for potential confounders, LPC 16: 1 showed a very strong and independent association with birth weight. The underlying molecular mechanisms linking fetal LPCs with birth weight need to be addressed in future studies.

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Prenatal maternal stress and birth outcomes in rural Ghana: sex-specific associations

BMC Pregnancy and Childbirth ◽

10.1186/s12884-019-2535-9 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Kenneth Ayuurebobi Ae-Ngibise ◽

Blair J. Wylie ◽

Ellen Boamah-Kaali ◽

Darby W. Jack ◽

Felix Boakye Oppong ◽

...

Keyword(s):

Birth Weight ◽

Birth Outcomes ◽

Fetal Growth ◽

Head Circumference ◽

Maternal Stress ◽

Birth Outcome ◽

Sub Saharan Africa ◽

Adverse Birth Outcome ◽

Prenatal Maternal Stress ◽

Rural Ghana

Abstract Background In developed countries, prenatal maternal stress has been associated with poor fetal growth, however this has not been evaluated in rural sub-Saharan Africa. We evaluated the effect of prenatal maternal stress on fetal growth and birth outcomes in rural Ghana. Methods Leveraging a prospective, rural Ghanaian birth cohort, we ascertained prenatal maternal negative life events, categorized scores as 0-2 (low stress; referent), 3-5 (moderate), and > 5 (high) among 353 pregnant women in the Kintampo North Municipality and Kintampo South District located within the middle belt of Ghana. We employed linear regression to determine associations between prenatal maternal stress and infant birth weight, head circumference, and length. We additionally examined associations between prenatal maternal stress and adverse birth outcome, including low birth weight, small for gestational age, or stillbirth. Effect modification by infant sex was examined. Results In all children, high prenatal maternal stress was associated with reduced birth length (β = − 0.91, p = 0.04; p-value for trend = 0.04). Among girls, moderate and high prenatal maternal stress was associated with reduced birth weight (β = − 0.16, p = 0.02; β = − 0.18, p = 0.04 respectively; p-value for trend = 0.04) and head circumference (β = − 0.66, p = 0.05; β = − 1.02, p = 0.01 respectively; p-value for trend = 0.01). In girls, high prenatal stress increased odds of any adverse birth outcome (OR 2.41, 95% CI 1.01-5.75; p for interaction = 0.04). Sex-specific analyses did not demonstrate significant effects in boys. Conclusions All infants, but especially girls, were vulnerable to effects of prenatal maternal stress on birth outcomes. Understanding risk factors for impaired fetal growth may help develop preventative public health strategies. Trial registration NCT01335490 (prospective registration). Date of Registration: April 14, 2011. Status of Registration: Completed.

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Genetics of early growth traits

Human Molecular Genetics ◽

10.1093/hmg/ddaa149 ◽

2020 ◽

Vol 29 (R1) ◽

pp. R66-R72

Author(s):

Diana L Cousminer ◽

Rachel M Freathy

Keyword(s):

Birth Weight ◽

Health Outcomes ◽

Fetal Growth ◽

Association Studies ◽

Later Life ◽

Early Growth ◽

Mr Studies ◽

European Ancestry ◽

Genome Wide Association Studies ◽

Genetic Contributions

Abstract In recent years, genome-wide association studies have shed light on the genetics of early growth and its links with later-life health outcomes. Large-scale datasets and meta-analyses, combined with recently developed analytical methods, have enabled dissection of the maternal and fetal genetic contributions to variation in birth weight. Additionally, longitudinal approaches have shown differences between the genetic contributions to infant, childhood and adult adiposity. In contrast, studies of adult height loci have shown strong associations with early body length and childhood height. Early growth-associated loci provide useful tools for causal analyses: Mendelian randomization (MR) studies have provided evidence that early BMI and height are causally related to a number of adult health outcomes. We advise caution in the design and interpretation of MR studies of birth weight investigating effects of fetal growth on later-life cardiometabolic disease because birth weight is only a crude indicator of fetal growth, and the choice of genetic instrument (maternal or fetal) will greatly influence the interpretation of the results. Most genetic studies of early growth have to date centered on European-ancestry participants and outcomes measured at a single time-point, so key priorities for future studies of early growth genetics are aggregation of large samples of diverse ancestries and longitudinal studies of growth trajectories.

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Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth

10.1101/663567 ◽

2019 ◽

Cited By ~ 3

Author(s):

Todd M. Everson ◽

Marta Vives-Usano ◽

Emie Seyve ◽

Andres Cardenas ◽

Marina Lacasaña ◽

...

Keyword(s):

Dna Methylation ◽

Birth Outcomes ◽

Fetal Growth ◽

Maternal Smoking ◽

Meta Analysis ◽

Growth Factor Signaling ◽

Hormone Activity ◽

Smoking During Pregnancy ◽

Placental Function ◽

Maternal Smoking During Pregnancy

AbstractMaternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. We meta-analyzed the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (7 studies, N=1700, 344 with any MSDP). We identified 1224 CpGs that were associated with MSDP, of which 341 associated with birth outcomes and 141 associated with gene expression. Only 6 of these CpGs were consistent with the findings from a prior meta-analysis of cord blood DNAm, demonstrating substantial tissue-specific responses to MSDP. The placental MSDP associated CpGs were enriched for growth-factor signaling, hormone activity, inflammation, and vascularization, which play important roles in placental function. We demonstrate links between placental DNAm, MSDP and poor birth outcomes, which may better inform the mechanisms through which MSDP impacts placental function and fetal growth.

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Haplotype genetic score analysis in 10,734 mother/infant pairs reveals complex maternal and fetal genetic effects underlying the associations between maternal phenotypes, birth outcomes and adult phenotypes

10.1101/737106 ◽

2019 ◽

Author(s):

Jing Chen ◽

Jonas Bacelis ◽

Pol Sole Navais ◽

Amit Srivastava ◽

Julius Juodakis ◽

...

Keyword(s):

Birth Weight ◽

Birth Outcomes ◽

Fetal Growth ◽

Late Onset ◽

Genetic Effects ◽

European Ancestry ◽

Birth Size ◽

Maternal Height ◽

Genetic Score ◽

Gestational Duration

ABSTRACTMany maternal traits are associated with a neonate’s gestational duration, birth weight and birth length. These birth outcomes are subsequently associated with late onset health conditions. Based on 10,734 mother/infant duos of European ancestry, we constructed haplotype genetic scores to dissect the maternal and fetal genetic effects underlying these observed associations. We showed that maternal height and fetal growth jointly affect the duration of gestation – maternal height positively influences the gestational duration, while faster fetal growth reduces gestational duration. Fetal growth is influenced by both maternal and fetal effects and can reciprocally influence maternal phenotypes: tall maternal stature and higher blood glucose causally increase birth size; in the fetus, the height and metabolic risk increasing alleles can lead to increased and decreased birth size respectively; birth weight-raising alleles in fetus may reduce gestational duration and increase maternal blood pressure. These maternal and fetal genetic effects can largely explain the observed associations between the studied maternal phenotypes and birth outcomes as well as the life-course associations between these birth outcomes and adult phenotypes.

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The Gestational Effects of Maternal Appetite Axis Molecules on Fetal Growth, Metabolism and Long-Term Metabolic Health: A Systematic Review

International Journal of Molecular Sciences ◽

10.3390/ijms23020695 ◽

2022 ◽

Vol 23 (2) ◽

pp. 695

Author(s):

Angelos Dimas ◽

Anastasia Politi ◽

George Papaioannou ◽

Thomas M. Barber ◽

Martin O. Weickert ◽

...

Keyword(s):

Birth Weight ◽

Fetal Growth ◽

Later Life ◽

Normal Pregnancy ◽

Review Literature ◽

Maternal Serum ◽

Metabolic Health ◽

Strong Correlations ◽

Gut Hormone ◽

Serum Ghrelin

Increased maternal food intake is considered a normal pregnancy adjustment. However, the overavailability of nutrients may lead to dysregulated fetal development and increased adiposity, with long-lasting effects on offspring in later life. Several gut-hormone molecules regulate maternal appetite, with both their orexigenic and anorectic effects being in a state of sensitive equilibrium. The aim of this manuscript is to systematically review literature on the effects of maternal gut-hormone molecules on fetal growth and metabolism, birth weight and the later metabolic health of offspring. Maternal serum ghrelin, leptin, IGF-1 and GLP-1 appear to influence fetal growth; however, a lack of consistent and strong correlations of maternal appetite axis hormones with birth weight and the concomitant correlation with fetal and birth waist circumference may suggest that these molecules primarily mediate fetal energy deposition mechanisms, preparing the fetus for survival after birth. Dysregulated intrauterine environments seem to have detrimental, sex-dependent effects on fetal energy stores, affecting not only fetal growth, fat mass deposition and birth weight, but also future metabolic and endocrine wellbeing of offspring.

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Perspective: L-arginine and L-citrulline Supplementation in Pregnancy: A Potential Strategy to Improve Birth Outcomes in Low-Resource Settings

Advances in Nutrition ◽

10.1093/advances/nmz015 ◽

2019 ◽

Vol 10 (5) ◽

pp. 765-777 ◽

Cited By ~ 4

Author(s):

Andrea M Weckman ◽

Chloe R McDonald ◽

Jo-Anna B Baxter ◽

Wafaie W Fawzi ◽

Andrea L Conroy ◽

...

Keyword(s):

Nitric Oxide ◽

Birth Weight ◽

Preterm Birth ◽

Birth Outcomes ◽

Fetal Growth ◽

Adverse Birth Outcomes ◽

Low Resource Settings ◽

Low Resource ◽

Arginine Supplementation ◽

In Pregnancy

ABSTRACT The available data support the hypothesis that L-arginine or L-citrulline supplementation would be suitable for implementation in resource-constrained settings and will enhance placental vascular development and improve birth outcomes. In resource-constrained settings, the rates of adverse birth outcomes, including fetal growth restriction, preterm birth, and low birth weight, are disproportionately high. Complications resulting from preterm birth are now the leading cause of mortality in children <5 y of age worldwide. Despite the global health burden of adverse birth outcomes, few effective interventions are currently available and new strategies are urgently needed, especially for low-resource settings. L-arginine is a nutritionally essential amino acid in pregnancy and an immediate precursor of nitric oxide. During pregnancy, placental and embryonic growth increases the demand for L-arginine, which can exceed endogenous synthesis of L-arginine from L-citrulline, necessitating increased dietary intake. In many low-resource settings, dietary intake of L-arginine in pregnancy is inadequate owing to widespread protein malnutrition and depletion of endogenous L-arginine due to maternal infections, in particular malaria. Here we examine the role of the L-arginine–nitric oxide biosynthetic pathway in pregnancy including placental vascular development and fetal growth. We review the evidence for the relations between altered L-arginine bioavailability and pregnancy outcomes, and strategies for arginine supplementation in pregnancy. Existing studies of L-arginine supplementation in pregnancy in high-resource settings have shown improved maternal and fetal hemodynamics, prevention of pre-eclampsia, and improved birth outcomes including higher birth weight and longer gestation. Arginine supplementation studies now need to be extended to pregnant women in low-resource settings, especially those at risk of malaria.

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Maternal Long-Chain Polyunsaturated Fatty Acid Status, Methylmercury Exposure, and Birth Outcomes in a High-Fish-Eating Mother–Child Cohort

Journal of Nutrition ◽

10.1093/jn/nxaa131 ◽

2020 ◽

Vol 150 (7) ◽

pp. 1749-1756 ◽

Cited By ~ 2

Author(s):

Alison Jayne Yeates ◽

Alexis Zavez ◽

Sally W Thurston ◽

Emeir M McSorley ◽

Maria S Mulhern ◽

...

Keyword(s):

Fatty Acid ◽

Birth Weight ◽

Birth Outcomes ◽

Fetal Growth ◽

Head Circumference ◽

Minor Allele ◽

Chain Polyunsaturated Fatty Acid ◽

Linear Regression Models ◽

Mehg Exposure ◽

Long Chain

ABSTRACT Background Maternal status of long-chain PUFAs (LC-PUFAs) may be related to fetal growth. Maternal fish consumption exposes the mother to the neurotoxicant methylmercury (MeHg), which, in contrast, may restrict fetal growth. Objective Our aim was to examine relations between maternal LC-PUFA status at 28 wk and birth outcomes (birth weight, length, and head circumference), controlling for MeHg exposure throughout pregnancy, in the Seychelles Child Development Study Nutrition Cohort 2. Our secondary aim was to examine the influence of maternal variation in genes regulating the desaturation of LC-PUFAs [fatty acid desaturase (FADS)] on birth outcomes. Methods From nonfasting blood samples collected at 28 wk of gestation, we measured serum total LC-PUFA concentrations and FADS1 (rs174537, rs174561), FADS1–FADS2rs3834458, and FADS2rs174575 genotypes, with hair total mercury concentrations assessed at delivery. Data were available for n = 1236 mother–child pairs. Associations of maternal LC-PUFAs, MeHg, and FADS genotype with birth outcomes were assessed by multiple linear regression models, adjusting for child sex, gestational age, maternal age, BMI, alcohol use, socioeconomic status, and parity. Results In our cohort of healthy mothers, neither maternal LC-PUFA status nor MeHg exposure were significant determinants of birth outcomes. However, when compared with major allele homozygotes, mothers who were heterozygous for the minor allele of FADS1 (rs174537 and rs174561, GT compared with TT, β = 0.205, P = 0.03; TC compared with CC, β = 0.203, P = 0.04) and FADS1–FADS2 (rs3834458, Tdel compared with DelDel, β = 0.197, P = 0.04) had infants with a greater head circumference (all P < 0.05). Homozygosity for the minor allele of FADS2 (rs174575) was associated with a greater birth weight (GG compared with CC, β = 0.109, P = 0.04). Conclusions In our mother–child cohort, neither maternal LC-PUFA status nor MeHg exposure was associated with birth outcomes. The observed associations of variation in maternal FADS genotype with birth outcomes should be confirmed in other populations.

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Maternal vitamin B12 status in early pregnancy and its association with birth outcomes in Canadian mother–newborn Dyads

British Journal Of Nutrition ◽

10.1017/s0007114521000581 ◽

2021 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Amy Tan ◽

Graham Sinclair ◽

Andre Mattman ◽

Hilary D. Vallance ◽

Yvonne Lamers

Keyword(s):

Birth Weight ◽

Birth Outcomes ◽

Early Pregnancy ◽

Screening Program ◽

Birth Outcome ◽

Secondary Analysis ◽

Outcome Data ◽

Maternal Serum ◽

Cognitive Outcomes ◽

Serum Samples

Abstract Vitamin B12 (B12) is a co-enzyme essential for fetal growth and development. Lower maternal B12 status has been associated with preterm birth (<37 gestational weeks) and low birth weight (<2500 g), which are linked to morbidity and mortality across the lifespan. In Canada, 17–25 % of women in early pregnancy had a serum total B12 concentration <148 pmol/l and maternal total B12 concentration decreased throughout pregnancy. This study aimed to determine the association between maternal B12 status and birth outcomes in Canadian mother–newborn dyads. A secondary analysis of 709 mother–newborn dyads in British Columbia (BC), Canada, was conducted. Bio-banked first- (n 656) and second-trimester (n 709) maternal serum samples of apparently healthy South Asian (50 %) and European (50 %) women from the BC Prenatal Genetic Screening Program were quantified for B12 biomarkers (total B12, holotranscobalamin (holoTC), methylmalonic acid (MMA) and total homocysteine (tHcy)). Obstetric history and birth outcome data were obtained from the BC Perinatal Data Registry. All associations were determined using multiple linear regression. Maternal serum total B12, holoTC, MMA and tHcy had a mean weekly decrease of 3·64 pmol/l, 1·04 pmol/l, 1·44 nmol/l and 0·104 μmol/l, respectively (P < 0·001). Despite a total B12 concentration <148 pmol/l among 20–25 % of the women, maternal B12 biomarker concentrations were not associated with birth weight z-score, head circumference z-score and gestational age at birth (P > 0·05). Additional research in women at high risk of adverse birth outcomes and the association between maternal B12 status and functional, for example, cognitive, outcomes is needed.

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Fetal growth restriction in a cohort of migrants in Germany

BMC Pregnancy and Childbirth ◽

10.1186/s12884-021-03620-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Juliane Ankert ◽

Tanja Groten ◽

Mathias W. Pletz ◽

Sasmita Mishra ◽

Gregor Seliger ◽

...

Keyword(s):

Birth Weight ◽

Preterm Birth ◽

Low Birth Weight ◽

Birth Outcomes ◽

Fetal Growth ◽

Gestational Age ◽

Fetal Growth Restriction ◽

Caesarian Section ◽

Growth Restriction ◽

Delivery Mode

Abstract Background Migrant women may have an increased risk of adverse birth outcomes. This study analyses the occurrence of low birth weight, preterm birth and intrauterine growth restriction / fetal growth restriction (IUGR/FGR) in pregnant migrants. Method Cross-sectional study of 82 mother-child pairs of pregnant migrants attending medical care in Germany. Results The Median age was 27 years, 49% of patients were of oriental-asian ethnicity and median year of migration was 2015. At least one previous pregnancy was reported in 76% of patients, in 40% the delivery mode was caesarian section. Median gestational age was 39.7 weeks. Preterm birth occurred in 6.1% of pregnancies. Median gestational age for preterm birth was 32.3 weeks. Low birth weight (< 2500 g) occurred in 6.1%. Birth weights below the 10th percentile of birth weight for gestational age were observed in 8.5% of the total cohort. Conclusions Compared to German data no increased occurrence of low birth weight, preterm birth or IUGR/FGR was found. We note that the rate of caesarian section births was higher than in the general population for reasons yet to be identified. The authors propose stratification according to migration status for the national documentation of birth outcomes in Germany.

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Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth

Nature Communications ◽

10.1038/s41467-021-24558-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Todd M. Everson ◽

Marta Vives-Usano ◽

Emie Seyve ◽

Andres Cardenas ◽

Marina Lacasaña ◽

...

Keyword(s):

Dna Methylation ◽

Birth Outcomes ◽

Fetal Growth ◽

Maternal Smoking ◽

Meta Analysis ◽

Growth Factor Signaling ◽

Environmental Response ◽

Smoking During Pregnancy ◽

Placental Function ◽

Maternal Smoking During Pregnancy

AbstractMaternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. Here we present a meta-analysis of the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (N = 1700, 344 with MSDP). We identify 443 CpGs that are associated with MSDP, of which 142 associated with birth outcomes, 40 associated with gene expression, and 13 CpGs are associated with all three. Only two CpGs have consistent associations from a prior meta-analysis of cord blood DNAm, demonstrating substantial tissue-specific responses to MSDP. The placental MSDP-associated CpGs are enriched for environmental response genes, growth-factor signaling, and inflammation, which play important roles in placental function. We demonstrate links between placental DNAm, MSDP and poor birth outcomes, which may better inform the mechanisms through which MSDP impacts placental function and fetal growth.

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