4.7 Article

Higher maternal adiposity reduces offspring birthweight if associated with a metabolically favourable profile

期刊

DIABETOLOGIA
卷 64, 期 12, 页码 2790-2802

出版社

SPRINGER
DOI: 10.1007/s00125-021-05570-9

关键词

Adiposity; ALSPAC; BiB; BMI; EFSOCH; Glucose; HAPO; Insulin; Mendelian randomisation; UKB

资金

  1. US National Institute of Health [R01 DK10324]
  2. European Research Council [669545]
  3. British Heart Foundation [CS/16/4/32482, AA/18/7/34219]
  4. NIHR Biomedical Centre at the University Hospitals Bristol NHS Foundation Trust
  5. University of Bristol
  6. UK Medical Research Council
  7. Wellcome [217065/Z/19/Z]
  8. Wellcome Trust [WT088806, WT101597MA]
  9. UK Medical Research Council (MRC)
  10. UK Economic and Social Science Research Council (ESRC) [MR/N024397/1]
  11. National Institute for Health Research (NIHR)
  12. Collaboration for Applied Health Research and Care (CLAHRC)
  13. Clinical Research Network (CRN)
  14. South West NHS Research and Development
  15. Exeter NHS Research and Development
  16. Darlington Trust
  17. Peninsula National Institute of Health Research (NIHR) Clinical Research Facility at the University of Exeter
  18. Wellcome Trust
  19. Royal Society [104150/Z/14/Z]
  20. UK MRC Skills Development Fellowship [MR/P014054/1]
  21. Royal Society Sir Henry Dale Fellowship [104150/Z/14/Z]
  22. UK Medical Research Council [MC_UU_00011/6]
  23. NIHR Senior Investigator [NF-0616-10102]
  24. Wellcome Trust Senior Investigator award [098395/Z/12/Z]
  25. Wellcome Trust [098395/Z/12/Z] Funding Source: Wellcome Trust
  26. MRC [MC_PC_19009] Funding Source: UKRI

向作者/读者索取更多资源

The study shows that higher maternal adiposity does not necessarily lead to higher offspring birthweight. Higher maternal adiposity can lead to lower offspring birthweight if accompanied by a favourable metabolic profile.
Aims/hypothesis Higher maternal BMI during pregnancy is associated with higher offspring birthweight, but it is not known whether this is solely the result of adverse metabolic consequences of higher maternal adiposity, such as maternal insulin resistance and fetal exposure to higher glucose levels, or whether there is any effect of raised adiposity through non-metabolic (e.g. mechanical) factors. We aimed to use genetic variants known to predispose to higher adiposity, coupled with a favourable metabolic profile, in a Mendelian randomisation (MR) study comparing the effect of maternal 'metabolically favourable adiposity' on offspring birthweight with the effect of maternal general adiposity (as indexed by BMI). Methods To test the causal effects of maternal metabolically favourable adiposity or general adiposity on offspring birthweight, we performed two-sample MR. We used variants identified in large, published genetic-association studies as being associated with either higher adiposity and a favourable metabolic profile, or higher BMI (n = 442,278 and n = 322,154 for metabolically favourable adiposity and BMI, respectively). We then extracted data on the metabolically favourable adiposity and BMI variants from a large, published genetic-association study of maternal genotype and offspring birthweight controlling for fetal genetic effects (n = 406,063 with maternal and/or fetal genotype effect estimates). We used several sensitivity analyses to test the reliability of the results. As secondary analyses, we used data from four cohorts (total n = 9323 mother-child pairs) to test the effects of maternal metabolically favourable adiposity or BMI on maternal gestational glucose, anthropometric components of birthweight and cord-blood biomarkers. Results Higher maternal adiposity with a favourable metabolic profile was associated with lower offspring birthweight (-94 [95% CI -150, -38] g per 1 SD [6.5%] higher maternal metabolically favourable adiposity, p = 0.001). By contrast, higher maternal BMI was associated with higher offspring birthweight (35 [95% CI 16, 53] g per 1 SD [4 kg/m(2)] higher maternal BMI, p = 0.0002). Sensitivity analyses were broadly consistent with the main results. There was evidence of outlier SNPs for both exposures; their removal slightly strengthened the metabolically favourable adiposity estimate and made no difference to the BMI estimate. Our secondary analyses found evidence to suggest that a higher maternal metabolically favourable adiposity decreases pregnancy fasting glucose levels while a higher maternal BMI increases them. The effects on neonatal anthropometric traits were consistent with the overall effect on birthweight but the smaller sample sizes for these analyses meant that the effects were imprecisely estimated. We also found evidence to suggest that higher maternal metabolically favourable adiposity decreases cord-blood leptin while higher maternal BMI increases it. Conclusions/interpretation Our results show that higher adiposity in mothers does not necessarily lead to higher offspring birthweight. Higher maternal adiposity can lead to lower offspring birthweight if accompanied by a favourable metabolic profile.

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