Module232025

07/05/2025

Neonates and Premature Babies – challenges - 2

• Hepatic function is immature and undergoes significant changes during the early postnatal period includes glucose metabolism, bilirubin conjugation, and drug detoxification processes Cytochrome P450 enzymes are only at 30% of adult levels at birth. • Renal function is immature at birth but develops rapidly in the first few weeks of life newborn kidney is structurally complete by 36 weeks of gestation, but functionally immature • Limited physiologic reserve, particularly in cardiovascular and respiratory functions ability to increase cardiac output under stress < adults; more susceptible to hypotension and hypothermia. higher metabolic rate and oxygen demand compared to adults, immature respiratory system. smaller lungs, more compliant chest wall, less developed respiratory muscles, leading to reduced lung volumes and a higher work of breathing larger surface area to weight ratio and limited capacity to regulate body temperature, making them susceptible to hypothermia.

31

Neonates and Premature Babies – clinical trials

• NICUs have strong routines to optimize benefits and reduce threats to care 14 Accommodating trials can be difficult – requires even more collaboration • Limited opportunity for blood samples Impacts safety, PK, biomarkers – popPK requires more patients; use of dried blood spots and scavenged samples may need to be explored • Lab normal ranges may not exist • Dose estimation very complex Often drives lower (sub-effective) starting doses • Withholding standard treatment probably unacceptable – IMP must be added on Risk of drug-drug interactions • Parental permission often difficult Risk of therapeutic misconception – that trial will benefit baby. Information sheets need to be easily-assimilated, as time is often limited • Changing baseline as renal and hepatic functions mature or condition changes May require rapid dose adjustment • Impact on sponsor/CRO staff due to mortality rates Consider counselling programmes, especially for CRAs who will be on-site

32