Abstract
Objective
Obesity in pregnancy increases risk of preterm birth (PTB), a leading cause of infant mortality and morbidity. The heritability of obesity suggests associations of grandmaternal obesity with grandoffspring outcomes, but a potential effect on PTB has not been interrogated. We studied whether grandmaternal (F0 generation) body mass index (BMI) in early pregnancy was related to grandoffspring (F2 generation) PTB risk by type, and to maternal (F1 generation) preeclampsia risk.
Methods
Among 315,240 singleton live-born infants from a countrywide three-generation Swedish cohort, we compared risks of spontaneous and medically indicated PTB, defined as gestational age <37 completed gestation weeks, between categories of maternal grandmaternal BMI in early pregnancy. We also interrogated associations of grandmaternal BMI categories with risk of maternal preeclampsia, a major cause of medically indicated PTB. We assessed whether the associations were mediated through consequences of obesity. In a subset, we examined associations with paternal grandmaternal BMI. To address unmeasured confounding by shared familial factors, we assessed the associations of parental full sisters’ BMI with PTB.
Results
Maternal grandmaternal obesity (BMI ≥ 30.0) was related to increased risks of grandoffspring medically indicated PTB and maternal preeclampsia, compared with normal BMI. Adjusted hazard and risk ratios (95% confidence intervals) were, respectively, 1.54 (1.28, 1.86) and 1.32 (1.16, 1.49). Maternal sisters’ BMI was unrelated to PTB or preeclampsia risks. Maternal obesity or preeclampsia mediated most (85%) of the maternal grandmaternal obesity-grandoffspring medically indicated PTB association, whereas the association with maternal preeclampsia was primarily mediated (61%) through maternal obesity. There were no associations with spontaneous PTB. Paternal grandmaternal obesity was unrelated to grandoffspring’s PTB risk.
Conclusion
Medically indicated PTB in grandoffspring is associated with maternal grandmaternal obesity.
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Data availability
The data that support the findings of this study are available from the Swedish National Board of Health and Welfare and Statistics Sweden but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available.
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Acknowledgements
This study was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development (HD106203).
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EV obtained funding, analyzed the data, wrote the first draft of the manuscript, and has primary responsibility for the final content. SC provided essential materials including access to the data, contributed to the study design, and aided in the interpretation of findings in the local context. Both authors read and approved the final manuscript.
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Approval was obtained from the Regional Ethical Review Board in Stockholm, Sweden (No. 2018/5:2). Since all data were anonymous, informed consent was not required. All methods were performed in accordance with the relevant guidelines and regulations.
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Villamor, E., Cnattingius, S. Grandmaternal obesity in early pregnancy and risk of grandoffspring preterm birth: a nationwide three-generation study. Int J Obes 49, 942–948 (2025). https://doi.org/10.1038/s41366-025-01731-7
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DOI: https://doi.org/10.1038/s41366-025-01731-7