Neonates: the least studied patients in medicine
The babies in neonatal intensive care receive some of the most intensive drug treatment in medicine. Very little of it was ever tested in them.
In brief
Most drugs in neonatal intensive care were never tested in newborns. Why neonates are so hard to study, and what is starting to change.
- Most drugs used in neonatal intensive care are off-label or unlicensed for newborns.
- Gestational age creates huge variation in how newborns handle medicines.
- Conditions specific to preterm babies attract little commercial development.
A baby born at 24 weeks’ gestation may receive dozens of different medicines in the first weeks of life. Few of them have been formally studied in preterm infants, and some have never been studied in newborns at all.
Why neonates are different
“Neonate” covers an enormous range. A full-term baby and one born 16 weeks early differ in organ maturity, body water, protein binding and the enzymes that metabolise drugs. Kidney function is immature and changes daily. A dose that is right on the first day of life may be wrong a week later.
That variability makes neonates hard to study and easy to harm. It also means that data from older infants cannot simply be scaled down.
Why the gap persists
Several forces reinforce one another:
- Small numbers. Neonatal conditions affect relatively few babies, spread across many units.
- Ethical caution. Parents and clinicians are reluctant to add research procedures for very fragile infants.
- Commercial disincentive. Conditions specific to preterm babies, such as bronchopulmonary dysplasia and necrotising enterocolitis, have no adult market.
- Practical burden. Blood volume is tiny, which limits sampling for pharmacokinetic studies.
What is changing
The International Neonatal Consortium, founded in 2015, brings together regulators, industry, academics and parent groups to develop common tools, such as standard definitions of outcomes and adverse events in newborns. Shared definitions make it possible to compare and combine results across studies.
Opportunistic sampling, which uses blood already drawn for clinical care, and micro-sampling techniques reduce the burden of pharmacokinetic studies. Modelling can help design studies that need fewer babies.
Still, neonatal medicine remains the area of paediatrics where the distance between what is done and what is known is widest.
