A study led by Johns Hopkins Children's Center researchers shows that some preterm infants admitted to the neonatal intensive care unit (NICU) — even without major complications of premature birth — have a heightened risk of persistent hypertension as they grow. Findings from the study, funded in part by the National Institutes of Health and published Sept. 5 in JAMA Network Open, not only add to evidence that prematurity and associated complications increase the risk of high blood pressure, but also suggest that in some cases the increased risk could be related to potential exposures in the NICU.
The researchers conclude that the findings underscore the need to screen prematurely born babies — and, in particular, those admitted to a NICU — throughout childhood for signs of high blood pressure.
Previous research, mostly from studies in Europe and Scandinavian countries, has shown that preterm birth and low birth weight are risk factors for hypertension. Left untreated, it contributes to adverse cardiovascular outcomes such as ischemic heart disease, cerebrovascular events and kidney failure. Moreover, experts say the prevalence of hypertension has been increasing among children and adolescents, with recent research estimating that 2%–5% of all children in the U.S. have hypertension, and 13%–18% have episodes of high blood pressure.
Because, generally, babies born before 37 weeks' gestation also spend time in a NICU to safely support growth, the Johns Hopkins researchers set out to clarify whether the NICU stay itself may contribute to hypertension risk.
For the study, a team led by Kartikeya Makker, M.B.B.S., interim director of the Division of Neonatal-Perinatal Medicine at the Children's Center, analyzed information on 2,459 children in the Boston Birth Cohort. The cohort, begun in 1998 at Boston Medical Center by Xiaobin Wang, M.D., Sc.D., M.P.H., now a Zanvyl Krieger Professor and director of the Center on the Early Life Origins of Disease at the Johns Hopkins Bloomberg School of Public Health, was designed to study babies and children over time. The children come from predominantly urban, low income, minority populations, and almost one-third in the cohort were born prematurely.
The team of investigators analyzed 19,736 blood pressure measurements from the 2,459 babies from newborn to 18 years old, and categorized the subjects into five subgroups based on preterm birth status, NICU admission and major complications that can develop in the NICU, including blood infections, chronic lung disease, brain hemorrhage and necrotizing enterocolitis (NEC), a serious intestinal condition.
Of those born preterm, 468 had NICU admissions with an average length of stay of 23 days. Of those infants, 90 (19.2%) faced at least one of the major complications of prematurity. Some 112 infants born full-term had NICU admission with an average length of stay of four days, and none suffered any major complications.
The team found the incidence of persistent hypertension (defined as hypertension for three clinic visits, not necessarily consecutive) was higher (25.2%) in children born preterm compared with children born full-term (15.8%), a not unexpected outcome.
Using standard statistical analysis tools, the researchers found that, on average, infants who were born prematurely and had NICU complications had the greatest risk for persistent hypertension, with higher systolic and diastolic blood pressure measurements during follow-up visits through 18 years of age. For example, those born preterm with a NICU admission and one of the major complications (intraventricular hemorrhage, sepsis, NEC or chronic lung disease) had an 87% higher risk of persistent hypertension in adjusted models compared with those without a complication.
The researchers say their findings support the need for early hypertension screening in children admitted to the NICU. "Children who are born prematurely and spend time in the NICU, regardless of whether they experienced complications, need to be closely followed and screened early for blood pressure changes and hypertension, and should continue to be followed throughout their lives," Makker says.
The investigators caution that their study did not take into account diet, sodium intake, weight and physical activity in their analysis, factors well known to affect blood pressure. Also, they say more research needs to be done to determine the specific exposures in the NICU that could attribute to the increase in hypertension.
Investigators say future studies will focus on using their data to create a hypertension risk scoring system for premature babies. The researchers also plan to look at kidney function in premature babies and how it may lead to hypertension.
Along with Makker and Wang, other authors from Johns Hopkins include Khyzer Aziz, Tammy Brady, Xiumei Hong and Guoying Wang. Additional authors include Jordan Kuiper from The George Washington University, Colleen Pearson from Boston Medical Center, and Keia Sanderson and Michael O'Shea from University of North Carolina.
The Boston Birth Cohort, which is one of the longest consecutively funded birth cohorts in the U.S., is supported in part by the U.S. National Institutes of Health (2R01HD041702, R01HD098232, R01ES031272, R01ES031521 and U01 ES034983) and by the Health Resources and Services Administration of the U.S. Department of Health and Human Services (UT7MC45949).
No authors declared conflicts of interest under Johns Hopkins University School of Medicine policies.
