Regulatory Science Symposium: Special Populations Session 5: Clinical Research in Pregnant Women and Neonates (2017)

1. Pregnancy and disease:
   1. Maternal complication:
      1. Pre-existing (asthma, epilepsy, hypertension, diabetes)
      2. Occurring during pregnancy (Hyperemesis gravidarum, Gestational diabetes, Preeclampsia)
      3. Environmental hazards
      4. Lifestyle or maternal behaviour from mothers, (smoking, alcohol consumption, drugs).
   2. Fetal malformations include genetic and environmental effects on the mother.
2. Obstetric Pharmacology:
   1. Changes to physiology during pregnancy affect absorption, distribution, metabolism and elimination of drugs by mother. This makes extrapolation from non-pregnant to pregnant women not possible.
   2. Other changes include body weight, fat composition, expansion of plasma volume, change in protein binding, enzyme activity, renal filtration and secretion due to multiple drug transporters activities.
   3. Less drugs studied on pregnant women
3. Safe Medication during Pregnancy:
   1. Treating for Two: National Strategy for Safer Medication use in Pregnancy initiatives seek to expand safety research, evaluate evidence, educate women to improve the quality of drugs.
   2. Major concerns for drugs during pregnancy: Drug to be studied, Period of drug lifecycle, Study population, design, data analysis and communication.
4.  Research Studies in Pregnant women:
   1. Pre-market studies:
      1. Study can only be done in pregnant patients and not healthy pregnant volunteers.
      2. There must be reliable animal experiment proving absence of teratogenicity and mutagenicity. Plan to incorporate short-term and long-term monitoring of mother and child.
      3. Alternative therapies are ineffective with no clinical response.
      4. Low risk to fetus
   2. Post marketing studies:
      1. More common.
      2. Registries provide prospective study data with internal/external control group under FDA amendments Act of 2007.
   3. Study protocols include risk/benefit considerations to fetal and maternal well-being, therapeutic alternatives, study endpoints and data collection mechanisms, gestational timing and duration of exposure, maternal complications record and pregnancy outcomes.
5. Neonates research:
   1. Gestational age (at which a newborn has 50% chance of survival) has been reducing with passing years.
   2. Defined as “Special pediatric population with unique diseases”
   3. Extrapolating from adult/pediatric diseases is impossible.
   4. Low interest from industry- small market, vulnerable population and difficulty in study conduction
6. Ethical considerations:
   1. Neonate Research Network: Conducts observational and interventional studies, to improve neonatal health outcomes.
   2. Ethical issues in maternal/fetal surgery: conflicting interests of mother and fetus mostly

Accompanying text created by Vaibhavi Chokshi | Regulatory Science Graduate Student Worker | vmchoksh@usc.edu