Poor Cardiometabolic Health in Pregnancy Tied to Higher BP for Young Offspring

Babies born to mothers with cardiometabolic risk factors—hypertensive disorders of pregnancy (HDP), gestational diabetes, and/or prepregnancy diabetes—tend to have higher blood pressure during early childhood, according to findings from the Environmental Influences on Child Health Outcomes (ECHO) program.

Lead author Zhongzheng Niu, PhD (University of Southern California, Los Angeles), told TCTMD that their study expands on earlier reports by including a large enough cohort—more than 12,000 mothers and their offspring—that the researchers could look at the risk posed by the three cardiometabolic risk factors both individually and in combination.

“We were able to show that if women have more than one risk factor, the children’s blood pressure will be even higher” than if the mothers had none or even a single risk factor present, Niu said. “I think that’s the real novel contribution.”

Notably, the researchers also included children as young as 2 years old, whereas most prior studies focused on those ages 8 to 17 years, and they were able to track changes in blood pressure over time.

Niu said the clinical applications of this study are many. Promoting better health among women of childbearing age is the first step, since addressing their risk factors could in turn lead to healthier future generations.  From the pediatric side, it makes sense to screen children born to a mother with risk factors and consider some sort of early intervention if needed.

“What we know about children’s blood pressure is that even small differences early on can magnify over time and that blood pressure does track linearly with age,” said Shohreh F. Farzan, PhD (University of Southern California), the study’s senior author. “And so children [who] are set on a different trajectory earlier, even just by a small amount, may end up in a higher blood pressure category later on in life.”

A key takeaway from their paper, published online recently in JAMA Network Open, is the need to consider both maternal and child health, Farzan highlighted.

“Targeting pregnancy as an intervention period could allow us to take a more holistic approach to family health overall,” she stressed to TCTMD. “Not only would this improve the health for mothers, but also for their children.”

A Gap That Grows

Niu, Farzan, and colleagues used data from ECHO, a collaborative research program with more than 50,000 children and families from 69 cohorts across the United States between 1994 and 2023, to identify 12,480 mother-offspring pairs. Mean maternal age during pregnancy was 29.9 years, and 44.4% of these women had at least one cardiometabolic risk factor: 24.6% had obesity before pregnancy, 13.6% hypertensive disorders of pregnancy, and 6.5% gestational diabetes. Most of the mothers (52.3%) were white, with 18.7% being Hispanic, 15.5% Black, 7.0% Asian, and 5.8% other race/ethnicity.

The researchers reported their BP data as change (β) in percentile to account for the impact of offspring age, height, and sex, and they adjusted for maternal age, race/ethnicity, education, income, marital status, parity, and smoking during pregnancy. Niu noted that their dataset lacked information on genetic and behavioral factors, however.

Babies born to mothers with any of the three cardiometabolic risk factors, compared with mothers who had none, had increases in systolic and diastolic blood pressure at their first blood pressure measurement, which occurred between ages 2 and 5 years. Looked at individually, the presence of each risk factor was independently linked to higher blood pressure. The only exception was gestational diabetes and diastolic blood pressure, for which there was no significant association.                          

Expected Increase in Offspring BP Percentile: Adjusted β (95% CI)

Various combinations of cardiometabolic risk factors appeared to have different impacts. Systolic BP increased the most among children born to mothers with both HDP and prepregnancy obesity (adjusted β 7.31; 95% CI 4.99-9.62), followed by those with both HDP and gestational diabetes (adjusted β 6.19; 95% CI 0.24-12.14). The greatest change in diastolic BP, on the other hand, was seen in the offspring of mothers with HDP and gestational diabetes (adjusted β 5.03; 95% CI 0.30-9.75), followed by those with both HDP and prepregnancy obesity (adjusted β 3.61; 95% CI 1.77-5.46).

When all three cardiometabolic risk factors were present—which occurred in just 0.9% of participants—risk trended higher but not significantly so. Among the various demographic groups, the strongest associations were seen for female (versus male) and Black (versus other race/ethnicity) offspring.

Niu pointed out that the differences are indeed clinically relevant. The 4.88 percentile point increase, for instance, puts children at “almost the cut point between elevated [blood pressure] and the pediatric hypertension,” he noted.

Around half the cohort had at least two BP measures, which allowed for longitudinal analysis showing that the impact of maternal cardiometabolic health accelerated between ages 2 and 18 years (0.5 and 0.7 percentile points per year for systolic and diastolic BP, respectively).

Children [who] are set on a different trajectory earlier, even just by a small amount, may end up in a higher blood pressure category later on in life. Shohreh F. Farzan

“Our findings that the combinations of prepregnancy obesity and HDP or gestational diabetes are more significantly associated with offspring blood pressure than either alone suggest a potential additive association of prepregnancy obesity with HDP and gestational diabetes,” the researchers conclude.

These interactions, they say, provide clues about mechanism.

“Aside from the possible contributions of shared genetic background and lifestyle, obesity can increase blood pressure, eg, by directly disrupting placental-fetal circulation via sphingolipids, such as ceramides, or interacting with HDP by inducing angiotensin II–elicited hypertensive responses,” the study authors write. Additionally, when obesity occurs alongside gestational diabetes, it “may increase insulin resistance and adiponectin suppression, which may subsequently modify fetal vascular tone by diminishing the production of nitric oxide and inducing endothelial dysfunction.”

Jennifer H. Klein, MD, MPH, and Michele Mietus-Snyder, MD (both from Children’s National Hospital, Washington, DC), in an invited commentary, agree that the findings while “not novel,” do “add substantively to the overwhelming evidence that an individual’s lifelong health is influenced by the intrauterine environment.”

The dynamic relationships “track back at least three generations . . . and potentially even further through multigenerational wombs, like nesting dolls,” they say, noting that epigenetics, the process through which the environment contributes to how each person’s genetic makeup is expressed, could be an explanation for the phenomenon.

No matter the exact mechanism, “heightened focus on maternal health and the fetal and early neonatal environment may hold untapped primordial preventive therapeutic potential, Klein and Mietus-Snyder conclude.