In Utero Exposure to Maternal Hyperglycemia Increases Childhood Cardiometabolic Risk in Offspring
Open accessAbstract
OBJECTIVE: The objective of this study was to evaluate the effect of maternal hyperglycemia during pregnancy on cardiometabolic risk in offspring during early childhood. RESEARCH DESIGN AND METHODS: A total of 970 mothers who had joined the Hyperglycemia and Adverse Pregnancy Outcome study were reevaluated, together with their child born during the study period, 7 years after delivery. RESULTS: Offspring born to mothers diagnosed with gestational diabetes mellitus (GDM), as defined by the World Health Organization 2013 GDM criteria, had higher rates of abnormal glucose tolerance (4.7% vs. 1.7%; P = 0.04), higher rates of overweight or obesity, greater BMI, higher blood pressure (BP), lower oral disposition index, and a trend toward reduced β-cell function compared with those born to mothers without GDM. For each SD increase in maternal fasting, 1-h, and 2-h glucose levels on oral glucose tolerance tests (OGTTs) between 24 and 32 weeks of the index pregnancy, the risk of abnormal glucose tolerance in the offspring showed a corresponding increase (adjusted odds ratio [OR] 1.85–2.00). The associations were independent of BMI before pregnancy, childhood obesity, or being born large for gestational age. The area under the curve for glucose levels during the five-point OGTT increased to a similar extent in boys and girls with each SD increase in maternal 1-h and 2-h plasma glucose on OGTTs during pregnancy. All three maternal glucose levels were also associated with increased adjusted ORs for childhood overweight or obesity and adiposity among girls, but not boys. CONCLUSIONS: Maternal hyperglycemia in pregnancy is independently associated with offsprings’ risk of abnormal glucose tolerance, obesity, and higher BP at 7 years of age. Its effect on childhood adiposity was apparent only in girls, not boys.
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Children born to mothers with GDM have a longer-term risk of obesity, type 2 diabetes, and cardiovascular disease.
“There is also a longer-term risk of obesity, type 2 diabetes, and cardiovascular disease in the child.”
From The Pathophysiology of Gestational Diabetes Mellitus (2018) · cites this paper as [68]
The Results (page not provided) report more overweight or obesity, abnormal glucose tolerance, and higher blood pressure among 7-year-old offspring of mothers with GDM. The Introduction discusses a possible future risk of type 2 diabetes, but this study does not establish longer-term type 2 diabetes or cardiovascular disease risk; higher blood pressure is not cardiovascular disease. (LLM, conf=0.90)
Experimental — accuracy not yet measuredChildren born to mothers with GDM have almost double the risk of developing childhood obesity compared with nondiabetic mothers, even after adjusting for confounders such as maternal BMI.
“Children born to mothers with GDM have almost double the risk of developing childhood obesity when compared with nondiabetic mothers, even after adjusting for confounders such as maternal BMI [67,68]”
From The Pathophysiology of Gestational Diabetes Mellitus (2018) · cites this paper as [68]
The Results (Tables 1–2; page unavailable) show more overweight or obesity among seven-year-old children of mothers with GDM, and Table 2 adjusts for prepregnancy maternal BMI. But the adjusted odds ratio for overweight or obesity is 1.59 (95% CI 0.97–2.59) overall; an approximately doubled, statistically significant association appears only among girls (2.16, 95% CI 1.09–4.27). The claim also says obesity, whereas the reported association concerns the combined category of overweight or obesity; obesity alone was not more frequent in the GDM group. (LLM, conf=0.92)
Experimental — accuracy not yet measuredData are lacking on how treatment of mother's hyperglycemia in pregnancy affects her offspring's risk for obesity, diabetes, and other metabolic disorders.
“Data are lacking on how the treatment of mother ' s hyperglycemia in pregnancy affects her offspring ' s risk for obesity, diabetes, and other metabolic disorders (219,220).”
From 2. Diagnosis and Classification of Diabetes: <i>Standards of Care in Diabetes—2024</i> (2024) · cites this paper as [220]
The Introduction (page unavailable) says two treatment-trial follow-ups found no reduction in childhood obesity or glucose intolerance, but neither trial was powered to assess long-term metabolic consequences. This supports a lack of adequate long-term evidence, not an unqualified claim that data on treatment effects are lacking; the Conclusions also report some treatment-related findings in offspring. (LLM, conf=0.84)
Experimental — accuracy not yet measuredData are lacking on how the treatment of mother's hyperglycemia in pregnancy affects her offspring's risk for obesity, diabetes, and other metabolic disorders.
“Data are lacking on how the treatment of mother's hyperglycemia in pregnancy affects her offspring's risk for obesity, diabetes, and other metabolic disorders (201,202).”
From 2. Diagnosis and classification of diabetes: standards of care in diabetes-2025 (2025) · cites this paper as [202]
The Introduction (page unavailable) says follow-up analyses of two treatment trials found no reduction in childhood obesity or glucose intolerance, but neither trial was powered to assess long-term metabolic consequences. This supports a lack of adequate long-term evidence, not an unqualified statement that data on offspring outcomes are lacking. (LLM, conf=0.84)
Experimental — accuracy not yet measuredA subgroup of the HAPO study from Hong Kong showed a significant but modest increase in BMI at age 7 years (15.3 kg/m2 from mothers with GDM vs. 15.0 kg/m2 from normoglycemic mothers).
“A subgroup of the HAPO study from Hong Kong showed a significant but modest increase in BMI at age 7 years (15.3 kg/m2 from mothers with GDM vs. 15.0 kg/m2 from normoglycemic mothers) [37].”
From Gestational Diabetes Mellitus: Diagnostic Approaches and Maternal-Offspring Complications (2022) · cites this paper as [37]
A novel finding of HAPO FUS was that maternal hyperglycemia during pregnancy was independently associated with risk of abnormal glucose tolerance in the offspring.
“Another novel finding of the HAPO FUS was that maternal hyperglycemia during pregnancy was independently associated with risk of abnormal glucose tolerance in the offspring.46”
From Gestational Diabetes Mellitus (2019) · cites this paper as [46]
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- Authors
- Tam, W. H., Ma, R. C. W., Ozaki, R., Li, A. M., Chan, M. H. M., Yuen, L. Y., Lao, T. T. H., Yang, X., Ho, C. S., Tutino, G. E., & Chan, J. C. N.
- Affiliations
- Chinese University of Hong Kong (HK)
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong
- Tianjin Medical University (CN)
- Corresponding author
- Tam, Wing Hung
- ORCID
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2017-03-09
- Volume
- 40
- Issue
- 5
- Pages
- 679-686
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC5399651
- OpenAlex
- W2593494122
- Semantic Scholar
- a7e707c5582cd37e48e8fcd16d5ab6fa90552676
- Cited by
- 366
- References
- 39
- Citations by year
- 2026: 22 · 2025: 39 · 2024: 50 · 2023: 37 · 2022: 50 · 2021: 54 · 2020: 42 · 2019: 28 · 2018: 35 · 2017: 8
- FWCI
- 36.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Child Health and Human Development (R01-HD34242)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01-HD34243)
- Research Grants Council of the Hong Kong SAR, China (CUHK 473408, CUHK 471713)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- maternal hyperglycemia, gestational diabetes mellitus, prenatal exposure, childhood obesity, childhood overweight, cardiometabolic risk, impaired glucose tolerance, blood pressure, beta-cell function, oral disposition index, sex differences, offspring adiposity
- MeSH terms
- Child, Female, Glucose Tolerance Test, Humans, Hyperglycemia, Hypertension, Male, Pregnancy, Pregnancy Complications, Hematologic, Prenatal Exposure Delayed Effects, Risk Factors, Odds Ratio, Diabetes, Gestational, Glucose Intolerance, Adiposity, Overweight, Pediatric Obesity
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