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Associations between neonatal serum bilirubin and childhood hypertension.

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.

SUBMITTER: Yu H

PROVIDER: S-EPMC6638957 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundHyperbilirubinemia affects many newborn infants and, if not treated appropriately, can lead to irreversible brain injury.ObjectiveThis study aims to develop predictive models of follow-up total serum bilirubin measurement and to compare their accuracy with that of clinician predictions.MethodsSubjects were patients born between June 2015 and June 2019 at 4 hospitals in Massachusetts. The prediction target was a follow-up total serum bilirubin measurement obtained <72 hours after a previous measurement. Birth before versus after February 2019 was used to generate a training set (27,428 target measurements) and a held-out test set (3320 measurements), respectively. Multiple supervised learning models were trained. To further assess model performance, predictions on the held-out test set were also compared with corresponding predictions from clinicians.ResultsThe best predictive accuracy on the held-out test set was obtained with the multilayer perceptron (ie, neural network, mean absolute error [MAE] 1.05 mg/dL) and Xgboost (MAE 1.04 mg/dL) models. A limited number of predictors were sufficient for constructing models with the best performance and avoiding overfitting: current bilirubin measurement, last rate of rise, proportion of time under phototherapy, time to next measurement, gestational age at birth, current age, and fractional weight change from birth. Clinicians made a total of 210 prospective predictions. The neural network model accuracy on this subset of predictions had an MAE of 1.06 mg/dL compared with clinician predictions with an MAE of 1.38 mg/dL (P<.0001). In babies born at 35 weeks of gestation or later, this approach was also applied to predict the binary outcome of subsequently exceeding consensus guidelines for phototherapy initiation and achieved an area under the receiver operator characteristic curve of 0.94 (95% CI 0.91 to 0.97).ConclusionsThis study developed predictive models for neonatal follow-up total serum bilirubin measurements that outperform clinicians. This may be the first report of models that predict specific bilirubin values, are not limited to near-term patients without risk factors, and take into account the effect of phototherapy.

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Associations between neonatal serum bilirubin and childhood hypertension.

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