Vitamin D levels in the womb may modify the association between maternal pre-eclampsia and hypertension in childhood, found a Johns Hopkins study.
Children appear to be at greater risk of having high blood pressure when their mothers had the high blood pressure condition called pre-eclampsia during pregnancy – but this adverse association may be reduced or even eliminated for children who were exposed to higher levels of vitamin D in the womb, according to a study from researchers at Johns Hopkins Bloomberg School of Public Health.
The findings, based on an analysis of data on 754 mother-child pairs in Massachusetts, suggest that higher vitamin D levels in pregnancy may help protect children born to preeclamptic women from developing high blood pressure. High blood pressure in childhood is associated in turn with hypertension and heart disease in adulthood.
“There is increasing evidence that cardiovascular disease risk is, to a great extent, programmed in the womb, and we now see that it may be vitamin D that alters this programming in a beneficial fashion,” says study senior author Dr Noel Mueller, an assistant professor in the department of epidemiology at the Bloomberg School.
Preeclampsia, which can lead to strokes and/or organ failure, is a major cause of illness and death for pregnant women, and also is associated with a greater risk of stillbirth and preterm birth. Researchers have estimated that preeclampsia occurs in 2-8 percent of pregnancies worldwide. It is associated with maternal obesity, and the rate of severe preeclampsia in the US has risen sharply since the 1980s.
At the same time, the rate of high blood pressure among children in the US has risen by about 40% between 1988 and 2008. Studies have suggested that maternal preeclampsia may be a factor in that increase.
Studies also have linked maternal vitamin D deficiency to a higher risk of preeclampsia, and have suggested that lower levels of vitamin D in adulthood or even early in life bring a greater risk of hypertension.
“We wanted to know if vitamin D levels in the womb would modify this association between maternal preeclampsia and hypertension in childhood,” says study first author Mingyu Zhang, a PhD candidate in Mueller’s research group.
To investigate this question, the team analysed data that had been gathered on 754 mother-child pairs from 1998 to 2018 in a large epidemiological study conducted at the Boston Medical Centre in Massachusetts. The dataset included information on preeclampsia during pregnancy, tests on blood from the umbilical cord at birth, and the children’s blood pressure from age 3 to 18.
About 62% of the mothers in the study group were Black, and 52% were overweight or obese. Previous studies suggest that mothers who were Black or overweight or obese were at higher risk for preeclampsia. Darker-skinned people living in higher latitudes also are more likely to be deficient in vitamin D – a cholesterol-derived molecule that is present in some foods but also is synthesized in skin with the help of ultraviolet light.
Roughly 10% of the women in the study group had preeclampsia, and the analysis revealed that their children on average had higher systolic blood pressure than the children born to non-preeclamptic mothers – about 5 percentile points higher, when all the blood pressure readings were arranged on a 0 to 100 percentile scale.
Cord-blood vitamin D levels clearly modified these associations, and in a dose-related manner. Children in the lowest 25% range of vitamin D levels (lowest “quartile”) were about 11 percentile points higher in blood pressure, on average, if their mothers had had preeclampsia, compared to children of non-preeclamptic mothers.
For children in the highest vitamin D quartile, there appeared to be no difference in average blood pressure if their mothers had had preeclampsia – in other words, the results suggest that having relatively high vitamin D levels at birth, which could be achieved through dietary supplements, may completely mitigate the risk brought by preeclampsia.
“If other epidemiological studies confirm these findings, then randomised trials would be needed to determine conclusively if higher vitamin D in mothers at risk of preeclampsia protects against childhood high blood pressure,” Mueller says.
The research was supported by the National Institutes of Health.
Importance: Maternal preeclampsia may be one of the early risk factors for childhood and adolescence elevated blood pressure (BP). It is unknown whether the intergenerational association between maternal preeclampsia and offspring BP differs by cord blood vitamin D levels.
Objective: To assess the associations between maternal preeclampsia and offspring systolic BP (SBP) across childhood and adolescence and to test whether these associations vary by cord blood 25-hydroxyvitamin D [25(OH)D] concentrations (a biomarker of in utero vitamin D status).
Design, Setting, and Participants: This prospective cohort study analyzed 6669 SBP observations from 754 mother-child pairs from the Boston Birth Cohort, who were enrolled from December 1998 to June 2009. Data were analyzed from October 2019 to March 2020.
Exposures: Physician-diagnosed maternal preeclampsia. Plasma 25(OH)D concentrations measured in cord blood samples collected at delivery.
Main Outcomes and Measures: Repeated SBP measures between 3 and 18 years of age. The SBP percentile was calculated based on the 2017 American Academy of Pediatrics hypertension guidelines. Mean difference in SBP percentile in children born to mothers with vs without preeclampsia was compared across different cord blood 25(OH)D levels.
Results: There were 6669 SBP observations from the 754 children; 50.0% were female and 18.6% were born preterm. Of the 754 mothers, 62.2% were Black and 10.5% had preeclampsia. Median cord blood 25(OH)D was 12.2 (interquartile range, 7.9-17.2) ng/mL. Maternal preeclampsia was associated with 5.34 (95% CI, 1.37-9.30) percentile higher SBP after adjusting for confounders. This association varied by quartiles of cord blood 25(OH)D concentrations: the differences in SBP percentile comparing children born to mothers with vs without preeclampsia were 10.56 (95% CI, 2.54-18.56) for quartile 1 (lowest), 7.36 (95% CI, –0.17 to 14.88) for quartile 2, 4.94 (95% CI, –3.07 to 12.96) for quartile 3, and –1.87 (95% CI, –9.71 to 5.96) for quartile 4 (highest). When cord blood 25(OH)D was analyzed continuously, children born to mothers with preeclampsia had 3.47 (95% CI, 0.77-6.18) percentile lower SBP per 5 ng/mL 25(OH)D increment. These associations did not differ by child sex or developmental stages.
Conclusions and Relevance: In this study of a US high-risk birth cohort, maternal preeclampsia was associated with higher offspring SBP from early childhood to adolescence. These associations were attenuated by higher cord blood 25(OH)D levels in a dose-response fashion. Additional studies, including clinical trials, are warranted.
Mingyu Zhang; Erin D Michos; Guoying Wang; Xiaobin Wang; Noel T Mueller
Johns Hopkins University Bloomberg School of Public Health
JAMA Network Open abstract