75 research outputs found

    Associations between Maternal Iron Supplementation in Pregnancy and Changes in Offspring Size at Birth Reflect Those of Multiple Micronutrient Supplementation.

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    It was previously observed that in a population of a high-income country, dietary multiple micronutrient supplementation in pregnancy was associated with an increased risk of gestational diabetes (GDM) and increased offspring size at birth. In this follow-up study, we investigated whether similar changes are observed with dietary iron supplementation. For this we used the prospective Cambridge Baby Growth Study with records of maternal GDM status, nutrient supplementation, and extensive offspring birth size measurements. Maternal iron supplementation in pregnancy was associated with GDM development (risk ratio 1.67 (1.01-2.77), p = 0.048, n = 677) as well as offspring size and adiposity (n = 844-868) at birth in terms of weight (β' = 0.078 (0.024-0.133); p = 0.005), head circumference (β' = 0.060 (0.012-0.107); p = 0.02), body mass index (β' = 0.067 (0.014-0.119); p = 0.01), and various skinfold thicknesses (β' = 0.067-0.094; p = 0.03-0.003). In a subset of participants for whom GDM statuses were available, all these associations were attenuated by adjusting for GDM. Iron supplementation also attenuated the associations between multiple micronutrient supplementation and these same measures. These results suggest that iron supplementation may mediate the effects associated with multiple micronutrient supplementation in pregnancy in a high-income country, possibly through the increased risk of developing GDM

    Suckling a protein-restricted rat dam leads to diminished albuminuria in her male offspring in adult life: a longitudinal study.

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    BACKGROUND: Previous studies have shown that in male rats, exposure to maternal protein restriction either in utero or whilst suckling can have profound effects on both longevity and kidney telomere lengths. This study monitored albuminuria longitudinally in male rats whose mothers had been protein restricted either during pregnancy or lactation. METHODS: Pregnant Wistar rats were fed either a 20% ('control') or an 8% protein ('low protein') diet. At two days of age some of the pups were cross-fostered to dams fed the diet that was not given to their biological mothers. At weaning all pups were fed standard chow. Urine samples were collected for the measurement of albumin and creatinine at monthly intervals from two months-of-age. Longitudinal analysis was then performed using repeated measures analysis of variance. RESULTS: Overall estimated marginal geometric mean (95 % confidence interval) urine albumin to creatinine ratios were: control animals 79.5 (57.2 to approximately 110.6) g/mol (n = 6 litters, 24 animals in total), those exposed in utero to maternal protein restriction 71.0 (47.4 to approximately 106.5) (n = 4 litters, 16 animals in total), those exposed to maternal protein restriction whilst suckling 21.2 (14.7 to approximately 30.4) (n = 5 litters, 20 animals in total) (p < 0.001). These latter animals had lower albumin to creatinine ratios than either of the two other groups (both p < 0.001), which had ratios that were indistinguishable from each other (p = 1.0). Similar results were gained using 24 h. urine albumin excretion rates. These differences became evident from three months-of-age and were long-lasting. CONCLUSION: Animals exposed to maternal protein restriction whilst suckling exhibited lower urine albumin excretions during much of adult life. As urine albumin can be nephrotoxic, these rats therefore appeared to be relatively protected against future nephron damage like that previously observed in animals exposed to maternal protein restriction in utero

    The association between age at menarche and later risk of gestational diabetes is mediated by insulin resistance.

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    AIMS: Associations have been reported between age at menarche and the later risk of gestational diabetes. However, it is not known whether these associations reflect differences in insulin sensitivity and/or pancreatic β-cell function in pregnancy. METHODS: We examined this question in women enrolled in the prospective Cambridge Baby Growth Study who recalled their age at menarche in questionnaires during pregnancy. Polynomial logistic and linear regression models were used to relate menarche timing to the risk of gestational diabetes, both unadjusted and adjusted for the Homeostasis Model Assessments of insulin resistance (HOMA IR) and pancreatic β-cell function (HOMA B) at week 28 of pregnancy. RESULTS: Age at menarche showed a U-shaped association with gestational diabetes risk (linear term: p = 9.5 × 10-4; quadratic term: p = 1.0 × 10-3; n = 889; overall model p = 8.1 × 10-3). Age at menarche showed a negative linear association with insulin resistance (HOMA IR: β = -0.13, p = 5.2 × 10-4, n = 771), which explained the relationship between age at menarche and gestational diabetes risk (adjusted linear term going from p = 0.03-0.08; adjusted quadratic term going from p = 0.04-0.08; n = 771). Age at menarche also showed a negative linear association with β-cell function (HOMA B: β = -0.11, p = 2.8 × 10-3, n = 771) but this did not attenuate the relationship between age at menarche and gestational diabetes (adjusted linear term p = 0.02; adjusted quadratic term p = 0.03, n = 771). CONCLUSIONS: These results suggest that the associations between age at menarche and risk of gestational diabetes and raised pregnancy glucose concentrations may be mediated by insulin resistance.Funding for this study has come from the Wellbeing of Women (the Royal College of Obstetricians and Gynaecologists, UK) (RG1644). Other core funding has come from the Medical Research Council (7500001180, G1001995, U106179472), European Union Framework 5 (QLK4-1999-01422), the Mothercare Charitable Foundation (RG54608), Newlife Foundation for Disabled Children (07/20), and the World Cancer Research Fund International (2004/03). In addition, there has been support from National Institute for Health Research Cambridge Biomedical Research Centre. KO is supported by the Medical Research Council (Unit Programme number: MC_UU_12015/2)

    The influence of maternal pregnancy glucose concentrations on associations between a fetal imprinted gene allele score and offspring size at birth

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    Abstract Objective Previously we found that certain fetal imprinted genes represented as an allele score are associated with maternal pregnancy glucose concentrations. Recently it was reported that fetal polymorphisms with strong associations with birth weight tend to mediate these independently of increases in maternal pregnancy glucose concentrations. We therefore investigated whether potential associations between the fetal allele score and birth weight were related to maternal glucose concentrations in the Cambridge Baby Growth Study. Results The fetal imprinted gene allele score was positively associated with birth weight (β = 63 (17–109) g/risk allele, β′ = 0.113, p = 7.6 × 10−3, n = 405). This association was partially attenuated by adjusting for maternal glucose concentrations (β = 50 (4–95) g/risk allele, β′ = 0.089, p = 0.03, n = 405). The allele score was also positively associated with risk of being large for gestational age at birth (odds ratio 1.60 (1.19–2.15) per risk allele, p = 2.1 × 10−3, n = 660) and negatively associated with risk of being small for gestational age at birth (odds ratio 0.65 (0.44–0.96) per risk allele, p = 0.03, n = 660). The large for gestational age at birth association was also partially attenuated by maternal glucose concentrations. These results suggest that associations between the fetal imprinted gene allele score and size at birth are mediated through both glucose-dependent and glucose-independent mechanisms

    Associations between paternally transmitted fetal IGF2 variants and maternal circulating glucose concentrations in pregnancy.

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    OBJECTIVE: To test the hypothesis that polymorphic variation in the paternally transmitted fetal IGF2 gene is associated with maternal glucose concentrations in the third trimester of pregnancy. RESEARCH DESIGN AND METHODS: A total of 17 haplotype tag single nucleotide polymorphisms in the IGF2 gene region were genotyped in 1,160 mother/partner/offspring trios from the prospective Cambridge Baby Growth Study (n = 845 trios) and the retrospective Cambridge Wellbeing Study (n = 315 trios) (3,480 samples in total). Associations were tested between inferred parent-of-origin fetal alleles, z scores of maternal glucose concentrations 60 min. after an oral glucose load performed at week 28 of pregnancy, and offspring birth weights. RESULTS: Using the minimum P value test, paternally transmitted fetal IGF2 polymorphisms were associated with maternal glucose concentrations; specifically, paternally transmitted fetal rs6578987 (P = 0.006), rs680 (P = 0.01), rs10770125 (P = 0.0002), and rs7924316 (P = 0.01) alleles were associated with increased maternal glucose concentrations in the third trimester of pregnancy and placental IGF-II contents at birth (P = 0.03). In contrast, there were no associations between maternal glucose concentrations and maternal or maternally transmitted fetal IGF2 genotypes. CONCLUSIONS: Polymorphic variation in paternally transmitted fetal IGF2 is associated with increased maternal glucose concentrations in pregnancy and could potentially alter the risk of gestational diabetes in the mother. The association may be at least partially mediated by changes in placental IGF2 expression

    An Unbiased Lipidomics Approach Identifies Early Second Trimester Lipids Predictive of Maternal Glycemic Traits and Gestational Diabetes Mellitus.

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    OBJECTIVE: To investigate the relationship between early second trimester serum lipidomic variation and maternal glycemic traits at 28 weeks and to identify predictive lipid biomarkers for gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: Prospective study of 817 pregnant women (discovery cohort, n = 200; validation cohort, n = 617) who provided an early second trimester serum sample and underwent an oral glucose tolerance test (OGTT) at 28 weeks. In the discovery cohort, lipids were measured using direct infusion mass spectrometry and correlated with OGTT results. Variable importance in projection (VIP) scores were used to identify candidate lipid biomarkers. Candidate biomarkers were measured in the validation cohort using liquid chromatography-mass spectrometry and tested for associations with OGTT results and GDM status. RESULTS: Early second trimester lipidomic variation was associated with 1-h postload glucose levels but not with fasting plasma glucose levels. Of the 13 lipid species identified by VIP scores, 10 had nominally significant associations with postload glucose levels. In the validation cohort, 5 of these 10 lipids had significant associations with postload glucose levels that were independent of maternal age and BMI, i.e., TG(51.1), TG(48:1), PC(32:1), PCae(40:3), and PCae(40:4). All except the last were also associated with maternal GDM status. Together, these four lipid biomarkers had moderate ability to predict GDM (area under curve [AUC] = 0.71 ± 0.04, P = 4.85 × 10-7) and improved the prediction of GDM by age and BMI alone from AUC 0.69 to AUC 0.74. CONCLUSIONS: Specific early second trimester lipid biomarkers can predict maternal GDM status independent of maternal age and BMI, potentially enhancing risk factor-based screening.This part of the Cambridge Baby Growth Study was funded by grants from the Wellbeing of Women (RG1644) and Diabetes UK (11/0004241). The lipidomics assays were supported by the Medical Research Council (UD99999906) and Cambridge Lipidomics Biomarker Research Initiative (G0800783). Core funding was also obtained through the Medical Research Council, European Union Framework 5 World Cancer Research Fund, Mothercare Foundation and the Newlife Foundation for Disabled Children. There has also been support from National Institute for Health Research Cambridge Biomedical Research Centre.This is the author accepted manuscript. The final version is available from the American Diabetes Association via https://doi.org/10.2337/dc16-086
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