What Crosses the Placenta: Nutrients, Gases, Antibodies, Drugs & Toxins

The placenta is a selective barrier. Substances cross via passive diffusion, facilitated diffusion, active transport, or pinocytosis—depending on molecular size, charge, lipid solubility, and protein binding.

Maternal → Fetal (Essential)

• O₂ (diffusion gradient)
• CO₂ (fetal → maternal)
• Glucose (GLUT1 facilitated transport; primary energy)
• Amino acids (active transport; System A, L, y+)
• Fatty acids (lipoprotein lipase hydrolysis + transport)
• Vitamins: Water-soluble (active); fat-soluble (diffusion)
• Minerals: Iron (transferrin receptor), calcium (active), zinc
• Water & electrolytes
• IgG antibodies: FcRn receptor-mediated active transport (peaks 3rd trimester) → passive immunity
• Hormones: Some (estriol, progesterone, cortisol partial); placental enzymes modulate (11β-HSD2 inactivates cortisol)

Maternal → Fetal (Potentially Harmful)

• Drugs: Most cross (lipophilic, low MW, low protein binding). Teratogens: thalidomide, isotretinoin, valproate, alcohol, warfarin, ACE inhibitors.
• Alcohol: Freely crosses → FASD (no safe level).
• Nicotine & cotinine: Vasoconstriction → growth restriction.
• Cocaine, opioids, cannabinoids: Cross readily; neonatal withdrawal (NAS).
• Environmental toxins: Lead, mercury (methylmercury), PCBs, pesticides.
• Infectious agents: CMV, toxoplasma, rubella, HSV, syphilis, Zika, HIV, parvovirus B19, SARS-CoV-2 (vertical transmission possible).

Fetal → Maternal

• CO₂, waste (urea, creatinine), hormones (hCG, hPL, estriol), fetal cells (microchimerism).

Placental transfer is dynamic; gestational age, placental health, and maternal physiology all modulate exchange.