Science & Research | November 8th, 2018

Evidence-Based Pharmacotherapy in Preterm Infants

Aiming at a Moving Target

Premature born infants require intensive care with many drugs. For most drugs knowledge is currently lacking on the correct dosage, side-effects and safety. This leads to large differences between hospitals in prescribed drugs for treatment of premature born infants, as described in the dissertation of Robert Flint entitled Evidence-Based Pharmacotherapy in Preterm Infants – Aiming at a moving target, under supervision of Prof. Tibboel (ErasmusMC), Prof. Burger (Radboudumc) and Dr. Simons (ErasmusMC). This could be improved through more consensus between hospitals on the optimal treatment, and through extensive research into optimal dosage regimens for preterm born infants.

As part of the funding programme Goed Gebruik Geneesmiddelen by ZonMw, this research has been granted to reduce this knowledge gap with four Dutch hospitals: Máxima MC - Veldhoven, Radboudumc - Nijmegen, MaastrichtUMC - Maastricht, ErasmusMC - Rotterdam. This enabled to study 9 frequently prescribed drugs in preterm born infants; paracetamol, fentanyl, phenobarbital, doxapram, ibuprofen, midazolam, fluconazole, sildenafil and levetiracetam. The first five have been described in the dissertation of Robert Flint. The drug amounts could be measured in a very small blood volume, and the effects were studied with appropriate instruments for these patients.

From this research we learn that premature born infants eliminate paracetamol, fentanyl, phenobarbital, doxapram and ibuprofen slower at lower gestational age than at higher gestational age. After birth, the elimination of drugs increased with age. This means that it is no longer appropriate to prescribe one dose per kilogram bodyweight for all premature born infants, but dosage regimens should take gestational age into account, as well as bodyweight, and age after birth. Furthermore, we succeeded to use good tools for effect measurement in premature born infants, despite the fact that the measurement of effects and side-effects is very complicated in preterm born infants.

This research reveals that often the smallest premature born infants may have been overtreated with drugs. The implementation of our suggested dosage reductions for these patients will be investigated in detail. The current research forms the basis for a collaboration to study several new initiatives to improve neonatal pharmacotherapy.

Author: Dr. Robert Flint
Contact: Should you wish to get in touch with Dr. Robert Flint, please write to the ESPR secretariat ( We would be glad to forward your request.