Elimination of Intravenous Di-2-Ethylhexyl Phthalate Exposure Abrogates Most Neonatal Hypertension in Premature Infants with Bronchopulmonary Dysplasia

(1) Background: The incidence of hypertension in very low birthweight (VLBW) infants in a single neonatal intensive care unit (NICU) dropped markedly during a 2-year period when the IV fluid (IVF) in both the antenatal unit and the NICU temporarily changed to a di-2-ethylhexyl phthalate (DEHP)-free formulation. The objective of the current report is to document this observation and demonstrate the changes in incidence of hypertension were not associated with the variation in risk factors for hypertension; (2) Methods: The charts of all VLBW infants born in a single NICU during a 7-year span were reviewed. This time includes 32 months of baseline, 20 months of DEHP-free IVF, 20 months of IVF DEHP re-exposure, and two 4-month washout intervals. The group of interest was limited to VLBW infants with bronchopulmonary dysplasia (BPD). Chi-square analysis was used to compare incidence of hypertension among periods. Vermont Oxford NICU Registry data were examined for variation in maternal and neonatal risk factors for hypertension; Results: Incidence of hypertension in VLBW infants with BPD decreased from 7.7% (baseline) to 1.4% when IVF was DEHP-free, rising back to 10.1% when DEHP-containing IVF returned to use. Risk factors for neonatal hypertension were stable across the 3 study periods in the NICU’s group of VLBW infants; (3) Conclusions: Serendipitous removal of IVF containing DEHP resulted in near elimination of hypertension in one NICU—an effect entirely reversed after the same brand of DEHP-containing IVF returned to clinical use. These results suggest that DEHP exposure from IVF plays a major role in neonatal hypertension.

Fifteen-minute consultation: Neonatal hypertension

Neonatal hypertension is a rare but well recognised condition, especially in newborns needing invasive monitoring in the intensive care unit. Recognition of newborns with hypertension remains challenging because of natural variability in blood pressure with postconceptional age and the lack of reference data for different gestational ages. Investigation of neonates with hypertension can be challenging in light of the myriad differing aetiologies. This may be simplified by a systematic approach to investigation. There remains a relative paucity of data to guide the use of pharmacological therapies for hypertension in neonates. Clinicians rely on empirical management protocols based on experience and expert opinion. Much of the information on dosing regimens and protocols has simply been derived from the use of antihypertensive agents in older children and in adults, despite fundamental pathophysiological differences.

Neonatal hypertension caused by left-to-right shunt flow through a patent ductus arteriosus in a premature infant

ObjectivesThough it is rare and challenging to study, neonatal hypertension (HTN) has been explored and studied by many pediatricians. There were some causes reported in preterm infants such as renal diseases and bronchopulmonary dysplasia.Case presentationWe report a premature female infant who was born at a gestational age of 25 + 6 weeks and developed systemic hypertension on the day of a gestation age of 30 + 3 weeks. This case had a rare cause which involved high-normal serum aldosterone level that could possibly indicate hyperaldosteronism and over-stimulation of renin–angiotensin–aldosterone system (RAAS). We believe elevation of serum aldosterone was caused by a left-to-right shunt flow through a patent ductus arteriosus. Hypertension due to a patent ductus arteriosus sounds like a paradox. However, in our case, the shunt flow was shown to be a possible cause of the systemic hypertension. Surgical closure of the shunt was done and the hypertension resolved. We evaluated serum aldosterone levels and plasma renin activities both, before and after the closure to look for a possible cause.ConclusionsNeonatologist often treats systemic hypertensive infants considering possible causes in order to prevent hypertensive crisis. Our case shows that possibility of hyperaldosteronism and (RAAS) over-stimulation should be considered as causes in case of severe systemic hypertension in preterm infants with large left-to-right shunt flows.