Risk factors for mother-to-child transmission of HIV-1.

Children born to women known to be infected with human immunodeficiency virus type 1 (HIV-1) before delivery were followed prospectively from birth in nineteen European centres. This analysis, encompassing the period end-December, 1984, to beginning-August, 1991, focuses on risk factors for mother-to-child transmission of HIV-1 infection. Rate of vertical transmission, based on 721 children born to 701 mothers more than 18 months before the time of analysis, was 14.4% (95% Cl 12.0-17.1%). Transmission was associated with maternal p24-antigenaemia and a CD4 count of less than 700/microliters. In a multivariate analysis, odds ratios of transmission were: 2.25 (95% Cl 0.97-5.23) in breastfed children vs never-breastfed children; 3.80 (1.62-8.91) in children born before 34 weeks' gestation; and 0.56 (0.30-1.04) in children delivered by caesarean section. Transmission was higher with vaginal deliveries in which episiotomy, scalp electrodes, forceps, or vacuum extractors were used, but only in centres where these procedures were not routine. On the basis of these results, HIV-infected women contemplating pregnancy should be counselled according to their immunological findings and, if they have p24-antigenaemia or a low CD4 count, warned of an increased risk of viral transmission. Caesarean deliveries may have a protective effect, although it is premature to recommend routine operative delivery. The mechanism for the higher infection rate in children born before 34 weeks' gestation is unclear, but could reflect inadequate passive or active immunity at that age, combined with substantial transmission during labour or delivery. The balance of evidence suggests that mothers with established infection can transmit HIV infection through breastmilk, although the relative importance of this route remains to be define

Perinatal findings in children born to HIV-infected mothers. The European Collaborative Study

OBJECTIVE: To explore in children born to HIV-infected women, the association between a child's HIV infection status and birthweight, gestational age, congenital abnormalities and other perinatal findings. DESIGN: A prospective study of children born to women known to be HIV-infected at or before the time of delivery enrolled in the European Collaborative Study. SETTING: Nineteen European centres. SUBJECTS: A cohort of 853 children with known HIV infection status. RESULTS: There was no evidence for an HIV dysmorphic syndrome, and the frequency of congenital abnormalities was similar in infected and uninfected children with no consistent pattern of defects. Injecting drug use during pregnancy had the most marked effect on birthweight and gestational age. Multivariate analysis demonstrated a weak association between birthweight and the child's HIV infection status, but this could partly be explained by the confounding effect of maternal immunological HIV status. HIV infection in the infant was not associated with gestational age, and the mean and distribution of gestational age were similar for infected and noninfected children. CONCLUSIONS: The finding that HIV-infected and noninfected children are of similar birthweight, the absence of a dysmorphic syndrome and no evidence of associated congenital abnormalities suggest that a substantial proportion of infection occurs late in pregnancy or at the time of delivery

Viral phenotype and host-cell susceptibility to HIV-1 infection as risk factors for mother-to-child HIV-1 transmission.

Objective: To investigate the role of maternal HIV-1 isolate phenotype and a child's cell susceptibility/resistance to viral infection in mother-to-child HIV-1 transmission. Patients and methods: Forty-nine women were studied at the time of delivery. Primary isolates, obtained by culturing patient peripheral blood mononuclear cells (PBMC) with PBMC from healthy donors, were characterized for tropism and syncytium-inducing capability in monocyte-derived macrophages (MDM), peripheral blood lymphocytes (PBL), and in the MT-2 and MOLT-3 T-cell lines. Results: Seven women transmitted HIV-1 to their children. Primary isolates were obtained from six and 28 transmitting and non-transmitting mothers, respectively. All primary isolates from transmitting mothers and their infants but only 50% of those from non-transmitting mothers replicated in MDM, regardless of their replication capacity in T-cell lines. PBL and MDM cells from six uninfected children were exposed to the corresponding maternal isolates. Polymerase chain reaction analysis of HIV-1 DNA in cells and p24 antigen assay in culture supernatants disclosed that two PBL and five MDM cultures were resistant to viral infection; two other PBL cultures, although HIV-l-infected, were negative for p24 production. Depletion of CD8+ cells only partially restored productive infection in CD4+ cell cultures. Moreover, all six PBL but only one MDM cultures were productively infected by an isolate obtained from a transmitting mother, thus suggesting that MDM resistance to HIV-1 infection is not viral isolate-restricted. Conclusions: Our findings strongly suggest that mother-to-child HIV-1 transmission is influenced by both monocyte-macrophage tropism of the maternal isolate and susceptibility of the child's target cells, in particular monocyte-macrophages, to HIV-1 infectio

Viral phenotype and host-cell susceptibility to HIV-1 infection as risk factors for mother-to-child HIV-1 transmission

OBJECTIVE: To investigate the role of maternal HIV-1 isolate phenotype and a child's cell susceptibility/resistance to viral infection in mother-to-child HIV-1 trasmission. PATIENTS AND METHODS: Forty-nine women were studied at the time of delivery. Primary isolates, obtained by culturing patient peripheral blood mononuclear cells (PBMC) with PBMC from healthy donors, were characterized fro tropism and syncytium-inducing capability in monocyte-derived macrophages (MDM), peripheral blood lymphocytes (PBL), and in the MT-2 and MOLT-3 T-cell lines. RESULTS: Seven women trasnmitted HIV-1 to their children. Primary isolates were obtained from six and 28 trasmitting and non-transmitting mothers, respectively. All primary isolates from transmitting mothers and theri infants but only 50% of those from non-transmitting mothers replicated in MDM, regardless of their replication capacity in T-cell lines. PBL and MDM cells from six uninfected children were exposed to the corresponding maternal isolates. Polymerase chain reaction analysis of HIV-1 DNA in cells and p24 antigen assay in culture supernatants discosed that two PBL and five MDM cultures were resistant to viral infection; two other pBL cultures, although HIV-1-infected, were negative for p24 production. Depletion of CD8+ cells only partially respored productive infection in CD4+ cell cultures. Moreover, all six PBL but only one MDM cultures were productively infected by an isolate obtained from a transmitting mother, thus suggesting that MDM resistance to HIV-1 infection is not viral isolate-restricted. CONCLUSIONS: Our findings strongly suggest that mother-to-child HIV-1 transmission is influenced by both monocyte-macrophage tropism of the maternal isolate and susceptibility of the child's target cells, in particular monocyte-macrophages, to HIV-1 infection

A prospective study of fifty-three consecutive calcium heparin treated pregnancies in patients with antiphospholipid antibody-related fetal loss.

Clin Exp Rheumatol. 1997 Sep-Oct;15(5):499-505. A prospective study of fifty-three consecutive calcium heparin treated pregnancies in patients with antiphospholipid antibody-related fetal loss. Ruffatti A, Orsini A, Di Lenardo L, Nardelli GB, Patrassi GM, Truscia D, Brigato G, Grella P, Todesco S. SourceChair and Division of Rheumatology, University of Padova, Italy. Abstract OBJECTIVE: In this study the efficacy and safety of calcium heparin administered alone for the prevention of fetal loss related to antiphospholipid antibodies (aPL) were evaluated. METHODS: Fifty-three consecutively ascertained pregnancies were followed in 53 patients who had a history of at least 2 consecutive miscarriages during the first trimester and/or 1 fetal death during the second or third trimesters. In addition, all patients had at least 2 positive aPL tests more than 8 weeks apart before pregnancy, or a positive aPL test at the beginning of pregnancy. They were treated with calcium heparin alone, self-administered subcutaneously 3 times daily at dosages varying between 15,000 and 37,500 units. Treatment was started soon after a sonogram demonstrated a live embryo and was continued throughout pregnancy until the end of puerperium. RESULTS: All pregnancies terminated favourably between the 25th and 40th weeks (mean +/- SD: 36.69 +/- 2.91) with planned caesarean section in 27 cases and vaginal delivery in 26. Delivery was brought forward due to maternal and/or fetal complications in 18 cases (33.96%). Calcium heparin was associated with intravenous immunoglobulin therapy in 2 patients with fetal problems unresponsive to anticoagulant treatment alone. The newborns, 30 females and 25 males, had a mean birth weight of 2,828.3 g +/- 706.5 and a mean Apgar score at 5 minutes of 9.60 +/- 0.68. No malformations were observed. Thirty of the 37 examined placentas (81.08%) showed signs of thrombotic events. Only minor side effects of calcium heparin were observed during treatment. CONCLUSION: Our study suggests that calcium heparin administered alone using the dosages and timing described here is effective in achieving the delivery of viable infants, and that it is well tolerated

The mode of delivery and the risk of vertical transmission of human immunodeficiency virus type 1--a meta-analysis of 15 prospective cohort studies. The International Perinatal HIV Group

Background To evaluate the relation between elective cesarean section and vertical transmission of human immunodeficiency virus type 1 (HIV-1), we performed a meta-analysis using data on individual patients from 15 prospective cohort studies. Methods North American and European studies of at least 100 mother-child pairs were included in the meta-analysis. Uniform definitions of modes of delivery were used. Elective cesarean sections were defined as those performed before onset of labor and rupture of membranes. Multivariate logistic-regression analysis was used to adjust for other factors known to be associated with vertical transmission. Results The primary analysis included data on 8533 mother-child pairs. After adjustment for receipt of antiretroviral therapy, maternal stage of disease, and infant birth weight, the likelihood of vertical transmission of HIV-1 was decreased by approximately 50 percent with elective cesarean section, as compared with other modes of delivery (adjusted odds ratio, 0.43; 95 percent confidence interval, 0.33 to 0.56). The results were similar when the study population was limited to those with rupture of membranes shortly before delivery. The likelihood of transmission was reduced by approximately 87 percent with both elective cesarean section and receipt of antiretroviral therapy during the prenatal, intrapartum, and neonatal periods, as compared with other modes of delivery and the absence of therapy (adjusted odds ratio, 0.13; 95 percent confidence interval, 0.09 to 0.19), Among mother-child pairs receiving antiretroviral therapy during the prenatal, intrapartum, and neonatal periods, rates of vertical transmission were 2.0 percent among the 196 mothers who underwent elective cesarean section and 7.3 percent among the 1255 mothers with other modes of delivery. Conclusions The results of this meta-analysis suggest that elective cesarean section reduces the risk of transmission of HIV-1 from mother to child independently of the effects of treatment with zidovudine