Fetal maternal ratio

An active transport mechanism has long been suspected to account for the placental barrier that causes maternal and fetal concentrations for many drugs to differ (96 97). Studies of maternal-fetal transport of medications used during pregnancy in HIV-positive women have shown variable penetration into the fetus (98 99). Whereas the maternal-fetal drug ratios for zidovudine lamivudine/ and nevirapine (approximately 0.85 1.0/ and 0.9/ respectively) demonstrate good fetal penetration/ most protease inhibitors/ nelhnavir/ ritonavh/ saquinivir/ and lopinavir/ are known P-gp substrates and do not cross the placenta in detectable levels (98). 

Rapid placental transfer was reported in goats and mice. In goats, the fetal plasma levels approached 50% of maternal values within 10 min of the mother receiving an intravenous dose, and the fetal/maternal plasma ratio remained at 0.5 for 1 h, whereas ratios in the liver, kidney, heart, and brain all approached 1 and showed a marked effect on fetal heart rate. In pregnant mice, radiolabeled chlorpromazine rapidly crossed the placenta and accumulated in the eyes of both fetuses and mothers. Marked radioactivity remained in tissues of the eye for 5 months after the drug had been eliminated from other tissues. 

Drug In Vitro Susceptibility (mcM ICr.o range) F (%) Vd (LAg) tl/2 (h) CL/F (L/h) Adult Dose (doses/day) Plasma tr n.ix/ inin (mcM) Ratio Fetal-Maternal Cone. Ratio eSF-Plasma Cone. 

Figure 9.2-4 Schematic representation of the ratio of fetal/maternal IgG concentrations throughout gestation in the macaque and relationship of the fetal antibody exposure relative to the period of organogenesis. Serum IgG concentrations shown in the graph have been adapted from data from Coe et al. (1993, 1994) and Fujimoto et al. (1983).

Basic Investigation. A lack of experimental data reporting linear velocities and length of flow channels for maternal and fetal streams required that these values be standardized for the present study. Two types of flow variations are possible. The linear velocities of maternal and fetal blood may change in such a way that the ratio of maternal to fetal volumetric blood flow remains constant. Conversely, maternal and fetal linear velocities may change in a way that will alter the maternal to fetal flow ratio. 

Bupivacaine is distributed into breast milk in small quantities. It crosses the placenta but the ratio of fetal-to-maternal concentrations is low. 

Serum samples from PBB-exposed women examined at parturition between 1973 9 had a mean value of 26.2 ppb, but ranged widely, from the detection limit of <1 ppb to 1150 ppb. The cord serum of 58 infants delivered during that period ranged from the detection limit to 104 ppb (mean 3.2). For 13 pairs studied, the mean maternal/fetal ratio found was 7.04, indicating that while PBB transfer does occur across the placenta, the latter does function as a barrier to some extent, in a similar manner to the placenta with PCB analogs (ref. 80, p. 449). 

A complete and up-to-date reproductive history should be obtained and available for all naval personnel (men and women active duty and reservists). Such a history should be updated annually or after a reproductive outcome. This would provide important baseline information and permit study of maternally and paternally mediated effects. The reproductive history should address sexual activity and inactivity, sexual libido, sexual dysfunction, semen analysis, menstruation history, pregnancy intentions, time-to-pregnancy (conception delays, fecundability, infertility), and pregnancy outcomes (e.g., ectopic pregnancy, spontaneous loss, fetal demise, birth size, secondary sex ratios, birth defects, mental retardation, developmental disabilities). Recording this information is in keeping with the definition for reproductive health and the need to address all health aspects of individuals. 

The developmental toxicity of a 20% lipid emulsion containing a 3 1 ratio of medium-chain to long-chain triglycerides has been examined in animals. Administration was once-daily intravenously to rats and rabbits during organogenesis. Maternal and embryo/fetal toxicity were also assessed. There were no adverse effects on fetal parameters for rats even in the presence of maternal toxicity. However, embryo and fetal toxicity (resorptions) and skeletal abnormahties were noted in rabbits (135). The adverse fetal effects were probably the result of dietary deprivation, maternal toxicity, or both rather than representing a direct teratogenic effect. 

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