Associations of Cord Blood Vitamin D and Preeclampsia With Offspring Blood Pressure in Childhood and Adolescence

Abstract

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.

Figure 1.. Mean Difference in Systolic Blood Pressure Percentile in Children Born to Mothers With Preeclampsia vs Mothers Without Preeclampsia, Overall and by Subgroup

BMI indicates body mass index (calculated as weight in kilograms divided by height in meters squared); NA; not available; SBP, systolic blood pressure. ^aModels were adjusted for maternal age at delivery, race/ethnicity (if not stratified by race/ethnicity), educational level, smoking status during pregnancy, and maternal prepregnancy BMI (if not stratified by maternal BMI).

Figure 2.. Mean Difference in Systolic Blood Pressure Percentile in Children Born to Mothers With Preeclampsia vs Mothers Without Preeclampsia, Overall and by Quartile (Q) of Cord Blood 25-Hydroxyvitamin D (25[OH]D) Concentration

The quartiles of cord blood 25(OH)D concentration were Q1, 1.4-7.9 ng/mL; Q2, 8.0-12.2 ng/mL; Q3, 12.3-17.1 ng/mL; and Q4, 17.2-73.5 ng/mL (to convert to nanomoles per liter, multiply by 2.496). Models were adjusted for maternal age at delivery, race/ethnicity, educational level, smoking status during pregnancy, and maternal prepregnancy body mass index. Point estimates and corresponding 95% CIs are in eTable 4 in the Supplement.

Figure 3.. Fractional Polynomial Prediction Plot Showing the Association Between Cord Blood 25-Hydroxyvitamin D (25[OH]D) Concentration and Child Systolic Blood Pressure Percentile

Observations with cord blood 25(OH)D concentration <1 percentile or >99 percentile were excluded. Shaded areas indicate 95% CIs. Q indicates quartile.