Can sonographic assessment of pulmonary vascular reactivity following maternal hyperoxygenation predict neonatal pulmonary hypertension (HOTPOT study protocol)

Background: Persistent pulmonary hypertension of the newborn (PPHN) is a condition that occurs in 0.5-7 per 1000 live births and can result in significant cardiovascular instability in the newborn. It occurs when there is a failure of the normal circulatory transition in the early newborn period. Recent studies have shown that fetal pulmonary vasculature reacts to maternal hyperoxygenation (MH). The aim of the study is to assess if the in-utero response to MH can predict pulmonary hypertension in the early newborn period. Methods: We will perform a prospective cohort study. It will evaluate the use of fetal echocardiographic Doppler assessment of the pulmonary vasculature prior to and following MH to predict fetuses that may develop pulmonary hypertension in the neonatal period. The study will be undertaken in the Rotunda Hospital, Dublin, Ireland. A fetal ultrasound and echocardiography will be performed on fetuses in the third trimester. Blood flow velocity waveforms will be recorded during periods of fetal quiescence. Pulsatility index (PI), Resistance index (RI), Peak systolic (PSV) and end diastolic velocity (EDV), time-averaged velocity (TAV), acceleration time (AT), and ejection time (ET) will be measured within the fetal distal pulmonary artery (PA). The acceleration-to-ejection time ratio (AT: ET) will be used to assess pulmonary vascular resistance (PVR). Doppler measurements will be taken at baseline and repeated immediately following MH for 10 min (O2 100% v/v inhalational gas) at a rate of 12L/min via a partial non-rebreather mask. Doppler waveform measurements from the umbilical artery (UAD), middle cerebral artery (MCA) ductus arteriosus (DA), aortic isthmus (AoI) and ductus venosus (DV) will also be obtained. After birth, a comprehensive neonatal functional echocardiogram will be performed within the first 24 hours of life. Discussion: This study proposes to validate methods described to date in investigating the fetal pulmonary vascular response to MH, with expansion of the study subjects to include fetuses at risk of PPHN. Evaluation of the different at-risk subgroups will be informative in relation to the fetal circulatory adaptation close to term. Prediction of neonatal pulmonary hypertension may help guide the pharmacological and neonatal ICU strategies that optimise postnatal survival.