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Maternal Obesity during Pregnancy and Premature Mortality from Cardiovascular Event in Adult Offspring: Follow-up of 1 323 275 Person Years

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Reynolds, R. M., Allan, K. M., Raja, E. A., Bhattacharya, S., McNeill, G., Hannaford, P. C., Sarwar, N., Lee, A. J. +2 more·2013·BMJ
DOI 10.1136/bmj.f4539PMC PMC3805484
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Abstract

OBJECTIVES: To determine whether maternal obesity during pregnancy is associated with increased mortality from cardiovascular events in adult offspring. DESIGN: Record linkage cohort analysis. SETTING: Birth records from the Aberdeen Maternity and Neonatal databank linked to the General Register of Deaths, Scotland, and the Scottish Morbidity Record systems. POPULATION: 37 709 people with birth records from 1950 to present day. MAIN OUTCOME MEASURES: Death and hospital admissions for cardiovascular events up to 1 January 2012 in offspring aged 34-61. Maternal body mass index (BMI) was calculated from height and weight measured at the first antenatal visit. The effect of maternal obesity on outcomes in offspring was tested with time to event analysis with Cox proportional hazard regression to compare outcomes in offspring of mothers in underweight, overweight, or obese categories of BMI compared with offspring of women with normal BMI. RESULTS: All cause mortality was increased in offspring of obese mothers (BMI >30) compared with mothers with normal BMI after adjustment for maternal age at delivery, socioeconomic status, sex of offspring, current age, birth weight, gestation at delivery, and gestation at measurement of BMI (hazard ratio 1.35, 95% confidence interval 1.17 to 1.55). In adjusted models, offspring of obese mothers also had an increased risk of hospital admission for a cardiovascular event (1.29, 1.06 to 1.57) compared with offspring of mothers with normal BMI. The offspring of overweight mothers also had a higher risk of adverse outcomes. CONCLUSIONS: Maternal obesity is associated with an increased risk of premature death in adult offspring. As one in five women in the United Kingdom is obese at antenatal booking, strategies to optimise weight before pregnancy are urgently required.

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  • Fetuses of obese mothers are exposed to an imbalance of cytokines and nutrients that can negatively affect fetal programming, leading to adverse long-term effects in the offspring.

    “Therefore, fetuses of obese mothers are exposed to an imbalance of cytokines, as well as nutrients that can negatively affect fetal programming, leading to adverse long-term effects in the offspring.”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [76]

    The Discussion (Possible physiological mechanisms) reports increased circulating inflammatory cytokines and nutrients in pregnant overweight women, and proposes that increased fetal nutrient supply could produce lasting changes. The Introduction describes possible long-term programmed effects in offspring. The paper does not establish that fetuses are exposed to a cytokine imbalance or that this proposed pathway causes the adverse outcomes; its Discussion says prenatal effects could not be separated from shared genetic and postnatal influences. (LLM, conf=0.84)

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  • Increased oxidative stress and inflammation markers have been found in the placenta of obese mothers, suggesting a decisive role of an abnormal intrauterine environment in modulating fetal programming.

    “Increased oxidative stress and inflammation markers have been found in the placenta of obese mothers, suggesting a decisive role of an abnormal intrauterine environment in modulating fetal programming [76,79].”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [76]

    The Introduction says maternal obesity may create an adverse intrauterine environment with long-term programmed effects. The Discussion (Possible physiological mechanisms) reports increased circulating inflammatory cytokines in pregnant overweight women, but does not report placental inflammation or oxidative-stress markers; Strengths and weaknesses also says the study cannot separate prenatal effects from shared genetic and postnatal influences. No page numbers are available in our copy. (LLM, conf=0.88)

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  • The negative effect of maternal obesity on offspring health might be mediated by an alteration in the inflammatory state and an increase in oxidative stress due to excess adipose tissue.

    “The negative effect of maternal obesity on offspring health might be mediated by an alteration in the inflammatory state and an increase in oxidative stress due to excess adipose tissue.”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [76]

    The Discussion’s “Possible physiological mechanisms” section reports increased inflammatory cytokines in pregnant overweight women and discusses possible pathways linking maternal obesity to offspring cardiovascular risk. It does not mention increased oxidative stress or attribute that mechanism to excess adipose tissue, so those parts of the claim are unsupported. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • In pregnancies complicated by obesity, the balance of pro-inflammatory and anti-inflammatory cytokines is shifted mainly towards a pro-inflammatory state.

    “Pregnancy is normally an inflammatory state caused by the remodeling of immunological system to allow embryo implantation, growth and life, regulated by a delicate balance of pro-inflammatory and anti-inflammatory cytokines; in pregnancies complicated by obesity, this balance is shifted mainly towards a pro-inflammatory state.”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [76]

    The Discussion section (‘Possible physiological mechanisms’; page unavailable) says pregnant overweight women have increased circulating concentrations of inflammatory cytokines. It does not distinguish pro-inflammatory from anti-inflammatory cytokines or establish that their balance shifts mainly toward a pro-inflammatory state in pregnancies complicated by obesity. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Reynolds et al. found an increase in mortality in offspring of overweight or obese mothers, particularly for cardiovascular events, and approximately 7.6% of offspring were hospitalized for a cardiovascular event.

    “The results showed an increase in mortality in offspring of overweight or obese mothers, particularly for cardiovascular events; moreover, approximately 7.6% of offspring were hospitalized for a cardiovascular event.”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [76]

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  1. [12]Dupout WD. Statistical modelling for biomedical researchers. 2nd ed. Cambridge University Press, 2008.

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Authors
Reynolds, R. M., Allan, K. M., Raja, E. A., Bhattacharya, S., McNeill, G., Hannaford, P. C., Sarwar, N., Lee, A. J., Bhattacharya, S., & Norman, J. E.
Affiliations
  • The Queen's Medical Research Institute (GB)
  • University of Aberdeen (GB)
  • MRC Centre for Reproductive Health (GB)
Corresponding author
Reynolds, R. M.
ORCID
Venue
BMJ
Publisher
BMJ
Published
2013-08-13
Volume
347
Issue
aug13 1
Pages
f4539-f4539
ISSN
1756-1833 (ISSN-L)
DOI
10.1136/bmj.f4539
PMC
PMC3805484
OpenAlex
W2071058949
Cited by
571
References
30
Citations by year
2026: 19 · 2025: 32 · 2024: 30 · 2023: 41 · 2022: 48 · 2021: 50 · 2020: 49 · 2019: 42 · 2018: 46 · 2017: 51 · 2016: 52 · 2015: 61 · 2014: 41 · 2013: 9
FWCI
50.72
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • BMJ (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Bristol Research (University of Bristol) (publishedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
  • Aberdeen University Research Archive (Aberdeen University) (submittedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
Funders
  • British Heart Foundation
  • Tommy's
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Obesity, Physical Activity, Diet
Keywords
maternal obesity, maternal body mass index, pregnancy, adult offspring, cardiovascular mortality, cardiovascular hospital admissions, premature mortality, maternal overweight
MeSH terms
Adult, Birth Weight, Cardiovascular Diseases, Epidemiologic Methods, Female, Hospitalization, Humans, Obesity, Pregnancy, Pregnancy Complications, Prenatal Exposure Delayed Effects, Scotland, Body Mass Index, Adult Children, Mortality, Premature

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