Intrapartum and neonatal zidovudine treatment in reduction of perinatal HIV-1 transmission in Bangkok.

OBJECTIVE: To evaluate the efficacy of zidovudine (ZDV) administered during labor and to the infants in the first 6 weeks of life in reduction of perinatal HIV-1 transmission. DESIGN: Open label clinical trial. SITE: King Chulalongkorn Memorial Hospital, Bangkok, Thailand. MATERIAL AND METHOD: One hundred asymptomatic, antiretroviral naive HIV-1 infected pregnant women who had either late or no prenatal care were recruited from the obstetric service of King Chulalongkorn Memorial Hospital, Bangkok, Thailand. They were given ZDV 300 mg orally every 3 hours during the intrapartum period until delivery. ZDV syrup 2 mg/kg orally every 6 hours were given to the infants immediately after birth for 6 weeks. Breast feeding was not allowed. Infant's blood for HIV-1 PCR test was obtained at age 1 day, and 1, 3 and 6 months. HIV-antibody test was determined at age 18 months. Infants with at least one positive HIV-1 PCR test performed at or after 1 month of age or positive HIV-antibody test at age 18 months were classified as HIV-1 infected infants. RESULTS: There were 100 healthy infants delivered without complication. Fourteen infants were excluded due to; 13 lost to follow-up and 1 drug intolerance. Of the remaining 86 infants who were followed-up, 27 infants (31.4%) did not receive intrapartum ZDV treatment and 9 infants were HIV-1 infected. The perinatal transmission rate was 10.5 per cent, (95% CI 3.9, 17.1). CONCLUSION: The result of this study suggests that intrapartum oral ZDV treatment in asymptomatic HIV-1 infected mothers together with ZDV treatment in the neonates for 6 weeks can reduce the rate of perinatal HIV-1 transmission. This regimen may be an alternative treatment for prevention of HIV-1 infection in infants born to HIV-1 seropositive mothers who have had either late or no prenatal care.

Short course zidovudine maternal treatment in HIV-1 vertical transmission: randomized controlled multicenter trial.

A multicenter randomized, double blind, placebo-controlled clinical trial was conducted to evaluate the effectiveness of a short course of oral zidovudine (ZDV) treatment in HIV-1 infected pregnant women, starting at 38 weeks of gestation plus ZDV infusion during labor until delivery, to reduce HIV-1 vertical transmission in non-breast fed infants. One hundred and eighty two asymptomatic antiretroviral naïve HIV-1 infected pregnant women were enrolled. Each patient was randomly allocated into either the ZDV or placebo group. The ZDV group received 250 mg ZDV orally twice a day initiated at 38 weeks' gestation until the onset of labor. During the intrapartum period, ZDV infusion at the rate of 2 mg/kg was administered within the first hour and then continuously infused at the rate of 1 mg/kg/h until delivery. The placebo group received an identical capsule during pregnancy and normal saline infusion during labor until delivery. HIV-1 transmission was documented by nested polymerase chain reaction in infants at birth and at 1, 3 and, 6 months of age. The estimated HIV-1 vertical transmission rate was 14.9 per cent (95% CI = 11.1 to 18.7) and 16.3 per cent (95% CI = 12.3 to 20.9) in ZDV and placebo group, respectively (p > 0.05). The short course ZDV in antiretroviral naïve pregnant women initiated at 38 weeks' gestation plus intrapartum ZDV infusion without treatment in the infants was not effective to prevent HIV-1 vertical transmission.

Intrapartum zidovudine infusion alone failed to reduce both maternal HIV-1 viral load and HIV-1 infection in infant.

A pilot clinical trial to assess the efficacy of intrapartum zidovudine (ZDV) infusion alone in the reduction of maternal viral load and its potential role in preventing vertical transmission of HIV-1. Twenty six, asymptomatic antiretroviral naïve HIV-1 infected pregnant women who had no prior antenatal care and were in labor were enrolled. Each patient received ZDV infusion at the rate of 2 mg/kg within the first hour. ZDV was then continuously infused at 1 mg/kg/h until delivery. Maternal plasma HIV-1 RNA prior to the commencement of ZDV infusion and within an hour after delivery were measured. HIV-1 transmission was documented by nested polymerase chain reaction in infants at six months of age. Median maternal plasma HIV-1 RNA prior to the ZDV infusion and after delivery was 29,401 and 32,555 copies/ml respectively, (p>0.05). The estimated HIV-1 transmission rate was 19.2 per cent (95% CI = 4-34). This result suggested that in asymptomatic HIV-1 infected pregnant women who were antiretroviral naïve and had no prior antenatal care, intrapartum ZDV infusion alone failed to reduce maternal HIV-1 viremia and the transmission rate of HIV-1.

Immune responses to measles immunization and the impacts on HIV-infected children.

This prospective cohort study was conducted to determine the seroconversion rate and the pattern of antibody response to measles vaccine administered at age 9 months in HIV infected and non-infected children born to HIV-1 seropositive mothers. Thirty children born to HIV-1 seropositive mothers and 3 born to HIV-1 seronegative mothers were recruited. One single dose of Schwarz strain of measles virus vaccine (Rouvax) was given to every child at 9 months of age. Clinical status and measles antibody levels were evaluated at the time just before vaccination, 2 and 12 weeks post-vaccination. Antibody was measured by an enzyme immunoassay commercial kit (Enzygnost, Dade Behring Manufacturer, Germany). Children were classified into 3 groups, groups 1 and 2 were children with and without HIV infection respectively. Group 3 children were those born to HIV-1 seronegative mothers. Of the 33 enrolled children, 16, 14 and 3 were classified as groups 1, 2 and 3 respectively. Four children, 2 of each, in groups 1 and 3 did not complete the study. Group 3 was excluded due to the small number of children recruited. There was no short term complication and no measles infection noted during the course of study. None of the children had pre-existing antibodies. The median (range) of CD4 count and CD4/CD8 ratio measured at the time of vaccination were statistically different between groups 1 and 2 children. Group 2 children had better antibody response than group 1 in terms of seroconversion rate and median of antibody levels at 12 weeks post-vaccination. Only 7 of 29 children (24.1%) had detectable measles antibodies at 2 weeks post-vaccination. A decrease in antibody was noted in 2 symptomatic HIV infected children as their disease had progressed. Various potential predictors of measles vaccine responses in HIV infected children including CD4 count and CD4/CD8 ratio were not statistically different between the responders and non-responders. All 4 asymptomatic HIV infected children were responders. This study demonstrated that all of the children had already lost their maternal acquired antibodies at age 9 months. HIV infected children had a poorerantibody response to measles vaccine than the non-infected children.

Safety and immunogenicity of Bacillus Calmette-Guerin vaccine in children born to HIV-1 infected women.

This prospective cohort study was conducted to determine the complication of Bacillus Calmette-Guerin (BCG) vaccination given to newborn infants born to HIV-1 seropositive mothers and to compare the tuberculin reaction 9 months after BCG vaccination between HIV-1 infected and non infected children. Two hundred and twenty-three infants with BCG immunization at birth were examined. No BCG complication was noted. Tuberculin skin tests were performed on 126 children (56.5%). Eleven of them were excluded because of failure to have skin tests read at 48 hours. Of the 115 infants enrolled to this study, 15 (13%) had no BCG scar and 50 (43.5%) had no tuberculin reaction. Twenty-six children were classified as group 1 or HIV-1 infected children and 89 children were group 2 or HIV-1 non infected. Group 1 children had a smaller tuberculin skin response (X+SD) than group 2 (1.15 +/- 2.82 vs 4.64 +/- 4.29 mm; p < 0.0001). Mean weight + SD of group 1 children was also significantly less than those in group 2 (8,013 +/- 741 vs 8,540 +/- 984 g; p < 0.05). The proportion of children with non reactivity to the tuberculin test, a negative tuberculin test and no BCG scar in group 1 was significantly higher than that in group 2 (76.9% vs 33.7%, 92.3% vs 52.8% and 36.4% vs 6.7% respectively; p < 0.0001 for all). But, the proportion of non reactivity to the tuberculin test in children with or without BCG scar of each group was not different (p > 0.05). Positive tuberculin tests were 7.7% and 47.2% in group 1 and 2 respectively. None of the children with positive tuberculin tests had clinical evidence of tuberculosis. The findings of this study indicate that BCG vaccine given to newborn infants of HIV-1 seropositive mothers is safe. Although tuberculin skin responses of HIV-1 infected children are less than those of HIV-1 non-infected children, it is possible that BCG vaccine might protect these children from developing severe tuberculosis.

Neonatal screening for hypothyroidism at a university hospital in Thailand.

Neonatal screening is an essential program for early identification of congenital hypothyroidism. Between July 1991 and May 1998, 37, 262 infants born at Chulalongkorn Hospital were enrolled to the screening program. Blood TSH levels were determined on infants at > or = 48 hours after birth. They were performed in dried blood sample taken by heel prick on filter papers. TSH levels were measured by fluoroimmunoassay from July 1991 to December 1997 and by immunoradiometric assay from January to May 1998. Infants with TSH screening level higher than the cut off level (20 mu/l) were recalled for re-evaluation which consist of complete physical examination and blood test for serum T4 and TSH. Bone age determination and thyroid scan using technetium-pertechnetate were performed if the serum T4 and TSH levels were abnormal. The recall rate was 0.28% and response rate was only 69%. Primary congenital hypothyroidism was diagnosed in 15 infants. Prevalence was 1: 2,484. Among these infants, 8 had ectopic thyroid, 3 had normal glands and 3 were athyrotic. One infant died before the thyroid scan could be performed and did not receive treatment. The median age at initiation of thyroxin therapy was 29 days (range, 20-67 days). The follow up result was satisfactory. This study demonstrated the potential vulnerability of congenital hypothyroid screening program in Thailand. Improvement of parents' education, communication and monitoring should be emphasized for a large screening program.

Maternal and neonatal effects of single-dose epidural anesthesia with lidocaine and morphine for cesarean delivery.

Two per cent lidocaine (18-20 ml) with epinephrine 1:200,000 plus 4 mg of morphine was given as a single epidural injection over 3 minutes for elective cesarean section in 60 healthy mothers at term. It provided effective, safe and adequate analgesia in the postoperative period. There was no evidence of neonatal depression related to the epidural morphine as judged by Apgar scores at 1 and 5 minutes and umbilical venous pH at birth. Maternal and umbilical venous levels of morphine were measured and found to be low at birth. However, this study was done only in healthy mothers not in labor and having a term fetus. We do not recommend using this technique in complicated obstetric patients.

Immunogenicity of hepatitis B vaccine in premature infants.

The immunogenicity of plasma-derived hepatitis B vaccine was studied in 39 premature neonates, whose weights were 1,800-2,400 g and gestational ages 32-37 weeks. All maternal antiHBc antibody were negative. Dosage of 5 micrograms of hepatitis B vaccine (Pasteur vaccine) was given at 0, 1, 2 and 12 months after birth. At the ages of 1, 2, 4, 9, 12 and 13 months, antiHBs antibody was found in 7.7%, 20%, 69.7%, 81.4%, 77.3% and 89.5%, respectively, while the geometric mean titer in this seropositive group, starting at age 2 months was 37, 121, 113, 69 and 1,016 mIU/ml. There was no severe reaction attributed to the vaccination. The result indicated that the vaccine was immunogenic. Although the conversion rate was low after primary injection, a satisfactory response developed at age 4 months after 3 doses of vaccine.

Elevation of depressed skull fracture in the neonate by obstetrical vacuum extractor.

In this article, three cases of neonatal depressed skull fracture were successfully elevated by means of an obstetrical vacuum extractor. No complications from the procedure were observed. Neonatal depressed skull fractures which are not associated with neurological signs may be safely elevated without surgery by using the obstetrical vacuum extractor. This simple, atraumatic procedure should be considered first for the management of uncomplicated depressed skull fracture in the newborn.