Treatment of Hypotension of Prematurity: a Randomized, Non-blinded Cohort Clinical Trial

Rationale: Hypotension in the very preterm infant (gestational age [GA] <32wks) is a frequently occurring clinical problem. Although no real consensus has been reached on the definition of hypotension in the very preterm baby, in clinical practice a mean blood pressure (BP) in mmHg lower than the GA age in weeks is considered to be the starting point for anti-hypotensive therapy. However, although an association between neonatal hypotension and mortality and morbidity exists, there is no evidence of causation between hypotension and neonatal mortality and morbidity (including neurodevelopmental outcome at 2 and 3 years of age). In addition, using mean BP alone as the indication of treatment of neonatal cardiovascular compromise without taking into consideration information on the status of tissue perfusion may lead to unnecessary exposure of neonates to forceful vasoactive medications potentially causing harm to these extremely vulnerable patients.

Objective: To compare neonatal mortality and short-term (advanced MRI indices of structural brain injury at 40 weeks' GA) and long-term neurodevelopmental outcomes (Bayley scales of infant development III [BSID-III] at 24 months) between two groups of very preterm infants presenting with hypotension without clinical and laboratory evidence of compromised tissue perfusion during the first 72 postnatal hours (3 days). Hypotension will be defined as the mean BP (in mm Hg) lower than the infant's GA (in weeks). Patients randomized to "Group A" will be treated according to the treatment policy operative in the Neonatal Intensive Care Unit (NICU) of the Wilhelmina Children's Hospital/University Medical Centre Utrecht (UMCU) while "Group B" will receive no cardiovascular support for hypotension unless they have a mean BP lower than the current limit minus 5 mmHg and/or evidence of compromised tissue perfusion and end-organ function and thus meet established criteria (see below).

Study design: A single-centre randomized non-blinded cohort study in the NICU at the UMCU of preterm neonates <30 weeks' gestation during postnatal days 0 to 3.

Study population: All preterm infants with a GA of <30 weeks admitted on day of postnatal life 0 to the NICU at the UMCU. Patients will be managed according to their randomization to Group A or B until the end of postnatal day 3.

Intervention Patients randomized to "Group A" will be treated for hypotension according to the treatment protocol operative in the NICU at the UMCU. Patients randomized to "Group B" will receive no cardiovascular supportive therapy irrespective of their BP value unless their mean BP is >5 mmHg below GA in weeks for 30 minutes and/or they have indirect clinical or direct laboratory evidence of tissue hypoperfusion and/or end-organ dysfunction (i.e. rScO2 is <50% despite optimized ventilatory support and FiO2 administration, plasma lactate >6 mmol/L; and/or urine output <0.6 mL/kg/hour).