Association of N-Terminal Pro–Brain Natriuretic Peptide Concentration in Early Pregnancy With Development of Hypertensive Disorders of Pregnancy and Future Hypertension

Abstract

IMPORTANCEHypertensive disorders of pregnancy are associated with future cardiovascular disease, perhaps because of subclinical cardiac dysfunction before pregnancy leading to impaired adaptation to pregnancy. Natriuretic peptides are promising biomarkers for detecting subclinical cardiac dysfunction outside of pregnancy.OBJECTIVE To investigate whether higher concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) in early pregnancy would be associated with hypertensive disorders of pregnancy and hypertension 2 to 7 years post partum. DESIGN, SETTING, AND PARTICIPANTSThis cohort study used data from the The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be Heart Health Study, a prospective multicenter observational study. A total of 4103 nulliparous women with complete data and no prepregnancy hypertension or diabetes who were treated at 8 clinical sites were included. Women were followed up with for 2 to 7 years after pregnancy. Data were collected from October 2010 to October 2017, and data were analyzed from August 2020 to November 2021.EXPOSURES NT-proBNP concentration, measured using an electrochemiluminescence immunoassay from a first-trimester blood sample. MAIN OUTCOMES AND MEASURESHypertensive disorders of pregnancy and incident hypertension (systolic blood pressure of 130 mm Hg or diastolic blood pressure of 80 mm Hg or use of antihypertensive agents) at follow-up visit.RESULTS A total of 4103 women met inclusion criteria; the mean (SD) age was 27.0 (5.6) years. Among these women, 909 (22.2%) had an adverse pregnancy outcome, and 817 (19.9%) had hypertension at the follow-up visit. Higher NT-proBNP concentrations were associated with a lower risk of hypertensive disorders of pregnancy (adjusted odds ratio per doubling, 0.81; 95% CI, 0.73-0.91), which persisted after adjustment for age, self-reported race and ethnicity, early-pregnancy body mass index, smoking, and aspirin use. Similarly, higher NT-proBNP concentration in early pregnancy was also associated with a lower risk of incident hypertension 2 to 7 years after delivery (adjusted odds ratio per doubling, 0.84; 95% CI, 0.77-0.93), an association that persisted after controlling for confounders, including hypertensive disorders of pregnancy. CONCLUSIONS AND RELEVANCEIn this cohort study, higher NT-proBNP concentrations in early pregnancy were associated with a lower risk of hypertensive disorders of pregnancy and hypertension 2 to 7 years post partum. These findings suggest that normal early-pregnancy cardiovascular physiology, as assessed by NT-proBNP concentration, may provide biologic insights into both pregnancy outcome and cardiovascular disease risk.

Genome-wide meta-analysis identifies novel maternal risk variants and enables polygenic prediction of preeclampsia and gestational hypertension

“…Of note, our lead risk variant at the MTHFR-CLCN6 locus has been previously associated with reduced levels of circulating N-terminal pro-BNP 49 . A recent analysis from the nuMoM2b cohort found that first-trimester levels of N-terminal pro-BNP were unexpectedly lower among women who subsequently developed HDPs later in pregnancy after adjustment for race and BMI 50 . Collectively, these findings suggest that a relative deficiency in endogenous natriuretic peptide signaling may predispose to HDPs.…”

NT-proBNP in Early Pregnancy and Future Hypertension—More Explorations Needed

“…To the Editor We read with great interest the article by Hauspurg and colleagues, who found that serum N-terminal pro–brain natriuretic peptide (NT-proBNP) in early pregnancy may serve as a promising biomarker for the development of hypertensive disorders of pregnancy and future hypertension. This study underscores the importance of NT-proBNP monitoring at the early stage of pregnancy to identify women at risk of future hypertension who can benefit from timely preventive intervention or medical treatment.…”

“…Second, the threat of residual confounding by unaccounted obesity status post partum remains in the study by Hauspurg and colleagues . Evidence from a prospective analysis of 15 065 women with a first singleton birth indicates that the observation that women with gestational hypertension had significant higher levels of blood pressure than those without might, at least in part, be attributable to unaccounted confounding from current body mass index .…”

“…Third, the study by Hauspurg and colleagues is prospective in design, yet the derivation of effect size estimates in terms of odds ratio did not take time intervals before hypertension onset during follow-up into account. We hope to learn more details about the possible time-dependent effect of serum NT-proBNP levels on the incidence of postpartum hypertension.…”

“…Despite these concerns, we commend this work by Hauspurg and colleagues and expect more independent external validations to inform the implementation of NT-proBNP assaying programs in early pregnancy that could help reduce the maternity and childcare burdens globally.…”