Prophylactic Low-Dose Paracetamol Administration for Ductal Closure and Microstructural Brain Development in Preterm Infants

Abstract

<b><i>Introduction:</i></b> Prophylactic low-dose paracetamol administration is used to induce closure of the ductus arteriosus. Effects on the neurological outcome in preterm infants remain unknown. We compared microstructural brain development in very preterm infants with and without exposure to prophylactic paracetamol by using MR-based diffusion tensor imaging. <b><i>Materials and Methods:</i></b> Infants aged <32 gestational weeks born between October 2014 and December 2018 received prophylactic paracetamol (10 mg/kg intravenously every 8 h until echocardiography after at least 72 h) and form the paracetamol group; infants born between February 2011 and September 2014 form the control group. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) at term-equivalent age were measured in 14 defined cerebral regions and compared between the groups. <b><i>Results:</i></b> Included in the study were 340 infants, of whom 217 received prophylactic paracetamol, and 123 formed the control group. The paracetamol group showed significantly higher FA values and lower ADC values in the splenium of the corpus callosum, as well as higher FA values in the pons bilaterally, the left middle cerebellar peduncle, the right occipital white matter, and the right posterior limb of the internal capsule (<i>p</i> ≤ 0.02). <b><i>Conclusion:</i></b> The perceived safety of prenatal paracetamol exposure has been questioned in recent years. We found no impairment on microstructural maturation processes in the brain of preterm infants at term-equivalent age following early paracetamol administration. The clinical relevance of these imaging findings has to be determined in long-term follow-up studies on neurodevelopmental outcome.

Prophylactic low‐dose paracetamol for ductal closure and neurodevelopmental outcome in very preterm infants

“…Bearing this in mind, it is remarkable that we did not find any negative effect on neurodevelopmental outcome in infants who received prophylactic low‐dose paracetamol. Furthermore, the findings of the current study are supported by our previous work where we did not observe any impairment in microstructural and functional brain maturation after prophylactic low‐dose administration in the same cohort, but in some aspects even a maturational advance 21,22 …”

“…In our previous studies, we found no impairment of functional and microstructural maturation processes in the brain of very preterm infants following prophylactic low‐dose paracetamol administration 21,22 . For the current study, we can report that we did not observe any negative effect of prophylactic low‐dose paracetamol administration neurodevelopmental outcome until a corrected age of 24 months in our cohort including 345 closely monitored very preterm infants.…”

“…In two previous studies, we found neither an adverse effect on amplitude‐integrated electroencephalography signals during the neonatal period nor an impairment of microstructural maturation processes in the brain of very preterm infants (born at <32 gestational weeks) at term‐equivalent age following prophylactic low‐dose paracetamol administration to induce ductal closure 21,22 …”

Prophylactic Low-Dose Paracetamol Administration for Ductal Closure and Amplitude-Integrated Electroencephalography in Preterm Infants

“…Beyond that study, we further investigated the effect of prophylactic low-dose paracetamol administration on structural and functional brain development. We found no impairment on microstructural maturation processes in preterm infants following prophylactic low-dose paracetamol administration ( 12 ). The present study is the next step in the continuation of our investigations, in which we were the first to study functional brain development in very preterm infants with and without exposure to low-dose paracetamol exposure.…”

“…To shed some more light on the ongoing debate about the safety of prophylactic low-dose paracetamol administration and preterm brain development, we investigated its effect in a large cohort of very preterm infants. First we used magnetic resonance-based diffusion tensor imaging at term-equivalent age in preterm infants with and without exposure to prophylactic low-dose paracetamol and found no impairment of microstructural maturation processes ( 12 ).…”