Association of Maternal Prepregnancy Dyslipidemia With Adult Offspring Dyslipidemia in Excess of Anthropometric, Lifestyle, and Genetic Factors in the Framingham Heart Study
Open accessAbstract
IMPORTANCE: Dyslipidemia in young adults in the United States during their childbearing years is common, and the consequences for the next generation are poorly understood. Further understanding of the harmful consequences of elevated low-density lipoprotein cholesterol (LDL-C) levels in young adults may help to inform population screening and management strategies. OBJECTIVE: To examine whether adult levels of serum LDL-C are associated with maternal prepregnancy LDL-C levels beyond that attributable to inherited genetic sequence polymorphisms, diet, physical activity, and body mass index. DESIGN, SETTING, AND PARTICIPANTS: The Framingham Heart Study is a multigenerational, population-based inception cohort initiated in 1948 in Framingham, Massachusetts. In this study of families, the analyses included 538 parent-offspring pairs with parental LDL-C levels measured in the study prior to the offspring's birth. Parental prebirth, parental concurrent, and adult offspring assessments occurred in 1971-1983, 1998-2001, and 2002-2005, respectively. Data analyses were conducted between March 1, 2013, and May 30, 2015. EXPOSURES: Maternal prepregnancy LDL-C levels compared with paternal prepregnancy and parental concurrent LDL-C levels in association with adult offspring LDL-C levels. MAIN OUTCOMES AND MEASURES: Adult offspring LDL-C levels were examined as both a continuous and dichotomous outcome (using a threshold of 130 mg/dL). RESULTS: Among the 538 parent-offspring pairs, there were 241 mother-offspring and 297 father-offspring pairs with a mean (SD) offspring age of 26 (3) years. Adult offspring LDL-C levels were associated with maternal prepregnancy LDL-C levels after adjustment for family relatedness and offspring lifestyle, anthropometric factors, and inherited genetic variants (β = 0.32 [SE, 0.05] mg/dL; P < .001). After multivariable adjustment, adults who had been exposed to elevated maternal prepregnancy LDL-C levels were at a 3.8 (95% CI, 1.5-9.8) times higher odds of having elevated LDL-C levels (P = .005) and had an adjusted LDL-C level of 18 mg/dL (95% CI, 9-27 mg/dL) higher than did those without such exposure. Maternal prepregnancy LDL-C levels explained 13% of the variation in adult offspring LDL-C levels beyond common genetic variants and classic risk factors for elevated LDL-C levels. CONCLUSIONS AND RELEVANCE: Adult offspring dyslipidemia is associated with maternal prepregnancy dyslipidemia in excess of measured lifestyle, anthropometric, and inherited genetic factors. The findings support the possibility of a maternal epigenetic contribution to cardiovascular disease risk in the general population. Further research is warranted to determine whether ongoing public health efforts to identify and reduce dyslipidemia in young adults prior to their childbearing years may have additional potential health benefits for the subsequent generation.
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These findings support the likelihood for parental transmission of cardiometabolic disease risk factors and a possible epigenetic contribution to cardiovascular disease risk in the general population.
“These findings support the likelihood for parental transmission of cardiometabolic disease risk factors and a possible epigenetic contribution to CVD risk in the general population that merits further investigation [34].”
From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [34]
The Discussion reports an association between maternal pre-pregnancy LDL-C and adult offspring LDL-C, and says epigenetic mechanisms may contribute to CVD risk. It also reports a smaller, less robust paternal association. The claim broadens these findings to parental transmission of cardiometabolic risk factors generally, whereas the study examined LDL-C and did not establish transmission or directly test epigenetic mechanisms. (LLM, conf=0.83)
Experimental — accuracy not yet measuredExposure to elevated pre-pregnancy LDL cholesterol levels increased the risk for having elevated LDL cholesterol levels 3.8 times in adult offspring.
“Exposure to elevated pre-pregnancy LDL cholesterol levels increased the risk for having elevated LDL cholesterol levels 3.8 times in adult offspring [34].”
From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [34]
The Results section (Association of Maternal Pre-Pregnancy LDL-C with Adult Offspring LDL-C) reports that exposed adult offspring had 3.8 times higher adjusted odds of elevated LDL-C than unexposed offspring. The claim calls this a 3.8-fold increase in risk, although the reported measure is an odds ratio; its causal wording also goes beyond the paper’s reported association. (LLM, conf=0.86)
Experimental — accuracy not yet measuredMaternal pre-pregnancy LDL cholesterol levels are associated with adult offspring LDL cholesterol levels after adjustments for offspring lifestyle and inherited genetic variants.
“Mendelson et al. demonstrated that maternal pre-pregnancy LDL cholesterol levels were associated with adult offspring low-density lipoprotein (LDL) cholesterol levels after adjustments for offspring lifestyle and inherited genetic variants [34].”
From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [34]
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- Authors
- Mendelson, M. M., Lyass, A., O’Donnell, C. J., D’Agostino, R. B., & Levy, D.
- Affiliations
- Boston University (US)
- Corresponding author
- Levy, Daniel
- Venue
- JAMA Cardiology
- Publisher
- American Medical Association (AMA)
- Published
- 2016-04-01
- Volume
- 1
- Issue
- 1
- Pages
- 26
- ISSN
- 2380-6583 (ISSN-L)
- PMC
- PMC6391057
- OpenAlex
- W2292144533
- Cited by
- 60
- References
- 53
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 2 · 2023: 2 · 2022: 10 · 2021: 13 · 2020: 7 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 3
- FWCI
- 5.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99 HL999999, n01hc25195-41-0-1)
- National Heart, Lung, and Blood Institute (HHSN268201500001I, HHSN268201500001C, N01-HC-025195)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- parent-offspring pairs, LDL-C thresholds, genetic variants, diet, physical activity, body mass index, Framingham Heart Study, anthropometric factors
- MeSH terms
- Adult, Anthropometry, Female, Humans, Life Style, Cholesterol, LDL, Male, Pregnancy, Pregnancy Complications, Hematologic, Triglycerides, Dyslipidemias
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