Prematurity, Neonatal Complications, and the Development of Childhood Hypertension

Preterm children face a higher risk of cardiovascular conditions, including hypertension. However, studies have not isolated the associations of prematurity with cardiovascular conditions from the associations of subsequent complications with cardiovascular conditions, especially among those admitted to a neonatal intensive care unit (NICU).

To investigate prospective associations of prematurity and NICU complications with childhood hypertension while accounting for prenatal and perinatal factors.

This cohort study analyzed longitudinal data from the Boston Birth Cohort on 2459 infants (695 preterm, 468 with NICU admission) born between January 1, 1999, and December 31, 2014. Statistical analysis was performed from January 1, 1999, to December 31, 2020.

Children were categorized into 5 subgroups based on preterm birth status, NICU admission, and major complications (sepsis, chronic lung disease, necrotizing enterocolitis, and intraventricular hemorrhage). The primary end point was hypertension (episodic and persistent) per American Academy of Pediatrics guidelines, with elevated blood pressure (BP) and BP percentiles as secondary end points. Modified Poisson and proportional hazards regression were used to determine crude and adjusted relative risks (RRs) and hazard ratios (HRs). Secondary analyses used linear generalized estimating equations to assess repeated BP measurements over time, standardized to population-based BP percentiles.

Of the 2459 infants (695 preterm: mean [SD] gestational age, 33.2 [3.5] weeks; 358 boys [51.5%]; and 1764 full term: mean [SD] gestational age, 39.4 [1.3] weeks; 879 boys [49.7%]) in this study, 468 (19.0%) were admitted to the NICU. The incidence of persistent hypertension was higher among children born preterm compared with those born at full term (25.2% [175 of 695] vs 15.8% [278 of 1764]). Preterm infants and infants admitted to the NICU had a greater risk of developing persistent hypertension compared with full term-born children without NICU admission or neonatal complications, independent of pertinent maternal and infant characteristics. Preterm infants with an NICU stay, both with (adjusted RR, 1.87 [95% CI, 1.19-2.94]) and without (adjusted RR, 1.62 [95% CI, 1.27-2.07]) a neonatal complication, had the greatest risk for persistent hypertension. Cox proportional hazards regression analysis identified preterm infants with an NICU stay, particularly those with a complication, as having the highest risk of developing persistent hypertension (adjusted HR, 2.37 [95% CI, 1.44-3.89]). On average, infants born prematurely without an NICU admission or complication (β, 2.74 percentile points [95% CI, 0.38-5.10 percentile points]) and those born prematurely with an NICU admission but no complications (β, 4.06 percentile points [95% CI, 2.11-6.02 percentile points]) had higher systolic BP percentiles and those born prematurely with an NICU admission but no complications had higher diastolic BP percentiles (β, 4.01 percentile points [95% CI, 2.52-5.49 percentile points]) during follow-up up to 18 years of age.

This prospective cohort study found incrementally stronger associations for NICU admission, prematurity, and prematurity-related complications with the risk of developing persistent hypertension in childhood. These findings support the need for hypertension screening, coordinated primary and specialist care, and cardiovascular health promotion among children born preterm.