Placental Function

The placenta separates maternal and fetal circulatory systems and regulates transport between the two systems. Transport occurs via the placental membrane, which is composed of fetal tissue.12 Maternal arterial blood is driven by the blood pressure into the intervil-lous spaces. Fetal blood is confined to the villous vascular system. Substances cross by simple diffusion, facilitated diffusion, active transport, or pinocytosis. Placental membrane interruptions can occur, especially toward the end of gestation, due to thinning of the membrane with time. The fetal capillary system also becomes progressively more exposed to the inter-villous spaces.

Several substances can easily transfer across this membrane, including most nutrients, waste products, proteins such as immunoglobin G antibodies, certain hormones, viruses, and water-soluble vitamins.9 Substances that are lipid-soluble, less plasma protein-bound, nonionized, or of low molecular weight are capable of crossing the placenta; most chemothera-peutic agents have similar qualities.9

In a retrospective review by Germann et al.,13 160 patient pregnancies exposed to anthracyclines were analyzed. Fetal outcome was normal in 73% cases. After intravenous injection of anthracyclines, only barely detectable concentrations were detected in the fetus. Table 106.1 illustrates the results of two studies of anthracycline concentrations in fetal tissues, amni-otic fluid, and placenta.1314

Transplacental studies have resulted in conflicting data. Roboz et al.15 reported that doxorubicin was undetectable in amniotic fluid at 4 and 16 hours post-maternal intravenous administration; this nonexis-tence in the amniotic fluid cannot exclude transpla-cental passage. D'Incalci et al.16 detected doxorubicin in fetal liver, kidney, and lung after elective termination; no levels were found in the amniotic fluid, fetal brain, or gastrointestinal tract 15 hours after administration. The fetal heart was not assessed.

Using liquid chromatography, Karp et al.17 illustrated that doxorubicin concentrations were greatest in placental tissue, with none in cord tissue or blood in a healthy infant born 48 hours after therapy. A dox-orubicin metabolite was detected in the cord, placental tissue, and neonatal spleen in a stillborn baby delivered 36 hours after maternal intravenous therapy.

At the time of delivery in a woman with acute promyelocytic leukemia (APL) undergoing therapy with all-trans retinoic acid (ATRA), its levels were measured in her venous blood and in the neonate's umbilical artery, vein, and peripheral blood.18 Maternal ATRA levels were detectable at 2 and 4 hours after

Table 106.1 Transplacental passage of anthracyclines in vivo

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