Pharmacology in Pregnancy and Lactation

Pharmacology in pregnancy and lactation studies how the physiological changes of pregnancy alter a person's handling of medicines, how drugs cross the placenta to reach the fetus, and how they pass into breast milk to reach the infant. It must weigh two intertwined concerns at once: maintaining effective therapy for the pregnant or breastfeeding person while limiting fetal or infant exposure. Because pregnant and lactating people are typically excluded from clinical trials, much of the evidence is observational.

Definition

The study of how pregnancy alters maternal drug pharmacokinetics, how drugs are transferred across the placenta and into breast milk, and how fetal and infant exposure relates to developmental risk, together with the methods used to evaluate that risk.

Scope

The entry covers pregnancy-related changes in pharmacokinetics, the placental and mammary transfer of drugs, the principles of developmental toxicology (teratology), and the difficulty of generating evidence in populations excluded from trials. It is a reference overview and does not provide drug-safety classifications, doses, or treatment advice for pregnancy or breastfeeding.

Core questions

• How do the physiological changes of pregnancy alter drug absorption, distribution, metabolism, and clearance?
• What determines whether and how much of a drug crosses the placenta or enters breast milk?
• How is developmental risk (teratogenicity) assessed when controlled trials are not ethical?
• Why is the evidence base for medicines in pregnancy and lactation comparatively weak?

Key concepts

• Pregnancy-induced pharmacokinetic changes
• Increased plasma volume and altered protein binding
• Changes in metabolic enzyme activity during pregnancy
• Placental drug transfer
• Transfer of drugs into breast milk (milk-to-plasma ratio, relative infant dose)
• Teratogenicity and critical windows of development
• Exclusion of pregnant and lactating people from trials

Mechanisms

Pregnancy alters maternal drug handling through expanded plasma volume and total body water, increased cardiac output and renal blood flow, reduced plasma albumin, and changes in the activity of several drug-metabolizing enzymes, which together can raise or lower drug exposure depending on the agent. Drugs reach the fetus chiefly by passive diffusion across the placenta, governed by lipid solubility, molecular size, ionization, and protein binding; the same physicochemical properties, together with milk composition, determine passage into breast milk, often summarized by the milk-to-plasma ratio and the relative infant dose. Developmental toxicity depends not only on the drug but on the timing of exposure relative to critical windows of organogenesis. Because randomized trials are generally not ethical in these populations, knowledge rests largely on observational data: Andrade and colleagues document the extent of prescription drug use in pregnancy, Diav-Citrin and colleagues provide a prospective controlled observational study of antidepressant exposure, and Sachs and the Committee on Drugs review the transfer of drugs into human milk. Briggs and colleagues compile the reference evidence used to summarize fetal and neonatal risk.

Clinical relevance

This topic underpins the cautious appraisal of drug-safety information in pregnancy and breastfeeding, an area where evidence is observational and uncertainty is high. It describes how transfer and developmental risk are reasoned about and supports critical reading of the literature; it does not provide pregnancy risk classifications, doses, or recommendations for use during pregnancy or lactation.

Epidemiology

Prescription and non-prescription drug use during pregnancy is common, yet the safety evidence for many agents is limited because pregnant and lactating people are routinely excluded from clinical trials. This mismatch between widespread exposure and sparse data is a recognized and persistent problem in the field.

History

Modern teratology and the regulation of drugs in pregnancy were transformed by the thalidomide disaster of the late 1950s and early 1960s, which caused severe limb malformations and demonstrated that maternal medication could cause structural fetal harm. The episode reshaped drug regulation and motivated the systematic study of developmental drug risk and the cautious framing of pregnancy drug information that followed.

Debates

Should pregnant and lactating people be included in clinical research?

Their routine exclusion protects against fetal harm but leaves clinicians reliant on observational data of uncertain quality; there is growing argument that carefully designed inclusion would generate better evidence, balanced against ethical caution about fetal and infant exposure.

Key figures

• Gerald Briggs
• Christof Schaefer
• Orna Diav-Citrin

Seminal works

• andrade-2004
• sachs-2013
• diav-citrin-2008

Frequently asked questions

Why is the evidence on medicines in pregnancy so limited?

Pregnant and lactating people are routinely excluded from clinical trials to avoid fetal and infant harm, so much of what is known comes from observational studies and registries rather than randomized experiments.

What determines how much of a drug reaches the fetus or a breastfed infant?

Passage across the placenta or into milk depends mainly on the drug's physicochemical properties — lipid solubility, molecular size, degree of ionization, and protein binding — and, for the fetus, on the timing of exposure during development.