Women with elevated low-density lipoprotein (LDL) cholesterol levels before becoming pregnant had an increased risk of their offspring having elevated LDL cholesterol, according to an analysis of the Framingham Heart Study.

The association remained after the researchers adjusted for the women’s body mass index (BMI) and smoking status and their adult offspring’s BMI, lifestyle factors and inherited genetic variants known to be associated with elevated LDL cholesterol.

Lead researcher Michael M. Mendelson, MD, ScM, of the National Institutes of Health in Framingham, Mass., and colleagues published their results online in JAMA Cardiology on March 2.

“The explanation for an enduring risk associated with elevated maternal prepregnancy LDL [cholesterol] levels beyond genetic variants and lifestyle factors is likely multifactorial and may be mediated by direct effects on the developing fetal organ systems and through epigenetic modifications transferred via gametes or introduced in utero owing to the nutrient milieu,” they wrote.

The researchers noted that elevated LDL cholesterol is a causal risk factor for atherosclerotic cardiovascular disease independent of adiposity and hyperglycemia. They also cited data from the 2007-2008 U.S. National Health and Nutrition Examination Survey that found a quarter of women of childbearing age had elevated LDL cholesterol, which they defined as more than 130 mg/dL.

In this analysis, they evaluated the offspring and third generation cohorts of the Framingham Heart Study. In 1971, 5,124 children and spouses of the original cohort enrolled in the offspring cohort. In 2002, 4,095 third generation cohort participants who had at least one parent in the offspring cohort enrolled in the third generation cohort.

This analysis included the offspring cohort examination cycles 1 (1971 to 1975), 2 (1979 to 1983) and 7 (1998 to 2001) and the third generation cohort cycle 1 (2002 to 2005).

The researchers studied participants in the third generation cohort from 2002 to 2005 who had at least one parent in the offspring generation cohort examined before the third generation participant’s birth. In all, there were 538 parent-offspring pairs: 241 mother-offspring and 297 father-offspring.

The mean age was 29 for the mothers and 27 for the fathers, while the mean BMI was 26 kg/m² and 22.3 kg/m², respectively. In addition, 45.6 percent of mothers and 40 percent of fathers were smokers.

Age- and sex-adjusted models found there was a significant correlation between maternal prepregnancy LDL cholesterol levels and adult offspring LDL cholesterol levels. The association remained significantly correlated after adjusting for anthropometric, lifestyle and inherited genetic factors.

The researchers said maternal prebirth LDL cholesterol explained 13 percent of the variation in adult offspring LDL cholesterol levels. They added that the odds of elevated LDL cholesterol levels among adult offspring were 3.8 times higher for individuals exposed to elevated maternal prepregnancy LDL cholesterol levels compared with those who were unexposed. In addition, the mean adult offspring LDL cholesterol level was 18 mg/dL greater among people exposed to elevated maternal prebirth LDL cholesterol compared with those who were unexposed.

“Although further research is required, our results support the possibility of benefits for the subsequent generation, and even beyond into further generations, from interventions in young adults,” the researchers wrote. “Additional studies with larger sample sizes would be needed to support our findings and improve the precision and confidence intervals of the effect estimates. Finally, incorporating intrauterine exposures into CVD risk prediction models may improve discriminative properties, although this possibility remains to be formally addressed.”