Associations between neonatal serum bilirubin and childhood hypertension

PLoS One. 2019 Jul 18;14(7):e0219942. doi: 10.1371/journal.pone.0219942. eCollection 2019.

Abstract

Mild hyperbilirubinemia is inversely associated with cardiometabolic diseases in adults. The aim of this study was to evaluate the association between neonatal serum bilirubin levels and childhood hypertension. Data were obtained from the U.S. Collaborative Perinatal Project conducted at 12 U.S. medical centers from 1959 to 1965. This multicenter study recruited participants before phototherapy was routinely used, thereby excluding the influence of phototherapy. In 37,544 newborns (31,819 term and 5,725 preterm births), a generalized linear model and a logistic regression model were used to calculate the linear coefficients and adjusted odds ratios (ORs) of blood pressure and hypertension at 7 years of age based on neonatal serum bilirubin levels. No significant correlation was observed between serum bilirubin at 48 hours after birth and blood pressure at the age of 7 years in the whole study population and in the subgroup of term infants. In preterm infants, a lower total serum bilirubin and unconjugated bilirubin of 3 mg/dl were associated with a higher systolic blood pressure of 62 mmHg (0.38-0.86, p <0.001) and 0.70 mmHg (0.10-1.30, p <0.05) respectively. Relative to a total serum bilirubin level <3 mg/dl among preterm infants, total serum bilirubin levels of 3-6 mg/dl (adjusted OR 1.36; 95% CI: 0.98-1.89), 6-9 mg/dl (adjusted OR 1.35; 95% CI: 0.98-1.85), 9-12 mg/dl (adjusted OR 1.55; 95% CI: 1.10-2.19), and ≥12 mg/dl (adjusted OR 1.42; 95% CI: 1.01-2.00) were associated with higher risks of hypertension. After stratifying for the subtypes of bilirubin, the associations only existed for unconjugated bilirubin. In addition, consistent findings existed when using maximum neonatal serum bilirubin as an exposure factor. Neonatal serum bilirubin levels are positively associated with childhood blood pressure/hypertension in preterm infants. Our findings may shed some light on the role of bilirubin in the prevention of hypertension.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bilirubin / blood*
  • Biomarkers
  • Blood Pressure
  • Female
  • Humans
  • Hyperbilirubinemia, Neonatal / blood
  • Hypertension / blood*
  • Hypertension / epidemiology*
  • Hypertension / etiology
  • Infant
  • Infant, Newborn
  • Jaundice, Neonatal / blood
  • Male
  • Odds Ratio
  • Public Health Surveillance
  • United States / epidemiology

Substances

  • Biomarkers
  • Bilirubin

Grants and funding

This work was partly supported by the National Natural Science Foundation of China (https://isisn.nsfc.gov.cn/egrantweb/) with project number 81401280 to Xiaoping Lei, the Sichuan Science and Technology Program (http://kjt.sc.gov.cn/) with project number 2019YJ0696 to Xiaoping Lei and the Research Foundation of Southwest Medical University (http://xmgl.swmu.edu.cn/) with project number 2015SX-0056 to Xiaoping Lei. These founders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There was no additional external funding received for this study.