Treatment of pregnant women with CMV-specific hyperimmune globulin is safe, and the findings of this nonrandomized study suggest that it may be effective in the treatment and prevention of congenital CMV infection. A controlled trial of this agent may now be appropriate.
In animal studies, exposure to organochlorine pesticides such as DDT and its metabolite DDE is associated with adverse reproductive outcomes. Human studies have, however, yielded inconsistent results. The authors analyzed data from the Child Health and Development Studies, a longitudinal follow-up study of 20,754 pregnancies in women living in the San Francisco Bay area in the years 1959-1967. Relationships were sought between maternal serum levels of DDT and DDE and preterm birth, small-for-gestational-age (SGA) birth, birth weight, and gestational age in 420 males. Multivariate logistic regression analysis was used for data on preterm and SGA births, and linear regression analysis for birth weight and gestational age.The median maternal serum levels of DDE and DDT were 43 and 11 g/L, respectively, figures several times higher than current concentrations in the United States. The adjusted odds ratio for preterm birth was 1.28 (95% confidence interval [CI], 0.73-2.23) for DDE and 0.94 (95% CI, 0.50-1.78) for DDT. For SGA birth, the odds ratios were 0.75 (95% CI, 0.44-1.26) for DDE and 0.69 (95% CI, 0.73-1.27) for DDT. No significant relationships or even trends were found between maternal serum concentrations of DDT or DDE and birth weight or length of gestation. None of the reproductive outcomes were significantly associated with the DDE:DTT ratio.These findings do not rule out the possibility that serum pesticide levels may have modest effects on reproductive outcomes, but there is no epidemiologic support for strong causal relationships between DDT or DDE and unfavorable outcomes in male infants. Further studies are appropriate because of the major current role of DDT in preventing malaria.
Human cytomegalovirus (HCMV) is the major viral cause of birth defects worldwide. Affected infants can have temporary symptoms that resolve soon after birth, such as growth restriction, and permanent disabilities, including neurological impairment. Passive immunization of pregnant women with primary HCMV infection is a promising treatment to prevent congenital disease. To understand the effects of sustained viral replication on the placenta and passive transfer of protective antibodies, we performed immunohistological analysis of placental specimens from women with untreated congenital infection, HCMV-specific hyperimmune globulin treatment, and uninfected controls. In untreated infection, viral replication proteins were found in trophoblasts and endothelial cells of chorionic villi and uterine arteries. Associated damage included extensive fibrinoid deposits, fibrosis, avascular villi, and edema, which could impair placental functions. Vascular endothelial growth factor and its receptor fms-like tyrosine kinase 1 (Flt1) were up-regulated, and amniotic fluid contained elevated levels of soluble Flt1 (sFlt1), an antiangiogenic protein, relative to placental growth factor. With hyperimmune globulin treatment, placentas appeared uninfected, vascular endothelial growth factor and Flt1 expression was reduced, and sFlt1 levels in amniotic fluid were lower. An increase in the number of chorionic villi and blood vessels over that in controls suggested compensatory development for a hypoxia-like condition. Taken together the results indicate that antibody treatment can suppress HCMV replication and prevent placental dysfunction, thus improving fetal outcome.
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