Early blood pressure, antihypotensive therapy and outcomes at 18–22 months’ corrected age in extremely preterm infants

Abstract

Objective Investigate relationships between early blood pressure (BP) changes, receipt of anti-hypotensive therapy, and 18 – 22 month corrected age (CA) outcomes for extremely preterm infants. Design Prospective observational study of infants 230/7 – 266/7 weeks gestational age (GA). Hourly BP values and anti-hypotensive therapy exposure in the first 24 hours were recorded. Four groups were defined: infants who did or did not receive anti-hypotensive therapy in whom BP did or did not rise at the expected rate (defined as an increase in the mean arterial BP of ≥5 mmHg/day). Random-intercept logistic modeling controlling for center clustering, GA, and illness severity was used to investigate the relationship between BP, anti-hypotensive therapies, and infant outcomes. Setting Sixteen academic centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Main Outcome Measures Death or neurodevelopmental impairment / developmental delay (NIDD) at 18 – 22 months CA. Results Of 367 infants, 203 (55%) received an anti-hypotensive therapy, 272 (74%) survived to discharge, and 331 (90%) had a known outcome at 18 – 22 months CA. With logistic regression, there was an increased risk of death/NIDD with anti-hypotensive therapy versus no treatment (odds ratio: 1.836, 95% confidence interval: 1.092 – 3.086), but not NIDD alone (odds ratio: 1.53, 95% confidence interval: 0.708 – 3.307). Conclusion Independent of early BP changes, anti-hypotensive therapy exposure was associated with an increased risk of death/NIDD at 18 to 22 months CA when controlling for risk factors known to affect survival and neurodevelopment.

Abstention or intervention for isolated hypotension in the first 3 days of life in extremely preterm infants: association with short-term outcomes in the EPIPAGE 2 cohort study

“…Therefore, the numerous observational studies reporting no beneficial effect of antihypotensive treatment3 4 9 10 24 probably encourage therapeutic abstention by most clinicians today.…”

“…Randomised controlled trials conducted decades ago have not found volume expansion to be either beneficial or harmful,5 and we lack long-term data for most drugs used in this context 6–8. More recent observational studies have suggested a potentially harmful effect of antihypotensive therapies on long-term outcome 4 9…”

The Neonatal Research Network: History since 2003, future directions and challenges

“…Funding allocated to the Best Pharmacueticals for Childrens Act (BPCA) has been used for studies directed at neonatal blood pressure and neuromonitoring. 14–16 Several institutes as NIH including National Institute for Drug Abuse (NIDA), National Institute of Heart, Lung and Blood Disorders (NHLBI), and the National Eye Institute (NEI) have funded portions of studies. The Centers of Disease Control (CDC) has funded various sepsis protocols.…”

Treating hypotension in extremely preterm infants. The pressure is mounting

“…A study from Batton et al 4 also provides new information. The authors have previously demonstrated marked variation in hypotension treatment in their cohort, and a surprising lack of efficacy of antihypotensive therapy,5 6 blood pressure increasing just as quickly among untreated infants as among those who received antihypotensive agents.…”

“…Blood pressure changes dynamically, (and tends to progressively increase during the first 72 h of life), so many infants will dip below the postnatal age defined 10th centile at some point during the first 72 h. This is one of the differences between the data presented by Batton, and the previously mentioned data from the German Neonatal Network;3 the German Neonatal Network data compares the short-term outcomes in infants who had a single blood pressure (BP) less than the median low BP for their gestational age. Batton et al 4 in contrast looked at dynamic changes in BP during the immediate postnatal period. The two approaches are valid but teach us different things about hypotension and its treatment in the newborn infant.…”