Chronic administration of nevirapine during pregnancy: impact of pregnancy on pharmacokinetics.

OBJECTIVES: To determine the impact of pregnancy on the pharmacokinetics (PK) of nevirapine (NVP) during chronic dosing in HIV-infected women and appropriate NVP dosing in this population. METHODS: Twenty-six pregnant women participating in two open-label Pediatric AIDS Clinical Trials Group studies (P1022 and P1026S) were evaluated. Each patient received 200 mg NVP every 12 h and had PK evaluations during the second or third trimester; these evaluations were repeated postpartum. Paired maternal and cord blood NVP concentrations were collected at delivery in nine patients. Ante- and postpartum comparisons were made using paired t-tests and using a 'bioequivalence' approach to determine confidence interval (CI). RESULTS: The average NVP Area Under the Curve (AUC) was 56 +/- 13 mcg(*)h/mL antepartum and 61 +/- 15 mcg(*)h/mL postpartum. The typical parameters +/- standard error were apparent clearance (CL/F)=3.51 +/- 0.18 L/h and apparent volume of distribution (Vd/F)=121 +/- 19.8 L. There were no significant differences between antepartum and postpartum AUC or pre-dose concentrations. The AUC ratio was 0.90 with a 90% CI of the mean equal to 0.80-1.02. The median (+/- standard deviation) cord blood to maternal NVP concentration ratio was 0.91 +/- 0.90. CONCLUSIONS: Pregnancy does not alter NVP PK and the standard dose (200 mg every 12 h) is appropriate during pregnancy.

Pharmacokinetics of oral zidovudine administered during labour: a preliminary study.

OBJECTIVES: The aim of this study was to determine whether oral zidovudine (ZDV) given during labour would provide a similar systemic exposure to the established intravenous regimen used to prevent mother-to-child transmission in HIV-infected pregnant women. METHODS: ZDV pharmacokinetic parameters following oral administration during labour were determined in 10 HIV-infected pregnant women in active labour. All subjects were converted to intravenous ZDV prior to delivery. RESULTS: In cohort 1 (n=6), subjects received 300 mg oral ZDV every 3 h for three doses. Oral therapy was well tolerated but plasma ZDV concentrations were substantially lower than previously reported with continuous intravenous therapy. Based on the pharmacokinetic results from cohort 1, women in cohort 2 (n=4) received an initial 600 mg dose followed by two 400 mg doses every 3 h. ZDV area under the curve and concentrations in cohort 2 increased approximately in proportion to the increase in dose but varied 6-7-fold. In both cohorts, ZDV pharmacokinetic parameters suggested erratic absorption. CONCLUSIONS: While ZDV exposure improved with the increased dosing regimen, our sample size was small and larger studies are needed to establish whether oral ZDV administration during labour can consistently provide equivalent exposure to intravenous administration.

Depo-medroxyprogesterone in women on antiretroviral therapy: effective contraception and lack of clinically significant interactions.

We conducted an open-label, steady-state pharmacokinetic (PK) study of drug interactions among HIV-infected women treated with depo-medroxyprogesterone acetate (DMPA) while on nucleoside analogues plus nelfinavir (N=21), efavirenz (N=17), or nevirapine (N=16); or nucleosides only or no antiretroviral therapy as a control group (N=16). PK parameters were estimated using non-compartmental analysis, with between-group comparisons of medroxyprogesterone acetate (MPA) PKs and within-subject comparisons of ARV PKs before and 4 weeks after DMPA dosing. Plasma progesterone levels were measured at baseline and at 2, 4, 6, 8, 10, and 12 weeks after DMPA dosing. There were no significant changes in MPA area under the concentration curve, peak or trough concentrations, or apparent clearance in the nelfinavir, efavirenz, or nevirapine groups compared to the control group. Minor changes in nelfinavir and nevirapine drug exposure were seen after DMPA, but were not considered clinically significant. Suppression of ovulation was maintained.

Increased tumor necrosis factor-alpha production after lipopolysaccharide stimulation of whole blood in patients with previous preterm delivery complicated by intra-amniotic infection or inflammation.

OBJECTIVE: To compare cytokine production after lipopolysaccharide stimulation of whole blood from women who were delivered of infants at term compared with women who were delivered of preterm infants with intra-amniotic evidence of infection or inflammation. STUDY DESIGN: Whole blood samples from 12 women who were not pregnant and who had previously had preterm deliveries before 32 weeks complicated by intra-amniotic infection or inflammation and samples from 12 age- and race-matched control subjects were stimulated with Escherichia coli lipopolysaccharide. Tumor necrosis factor-alpha and interleukin-6 levels were quantified at 6 hours and interleukin-10 at 24 hours by enzyme immunoassay. Results were compared with use of the Wilcoxon rank sum test. RESULTS: Tumor necrosis factor-alpha production was significantly higher in whole blood from women with histories of a preterm birth and intra-amniotic infection or inflammation (11,243 +/- 1030 pg/mL [mean +/- SEM]) compared with control subjects (3649 +/- 349 pg/mL) at a lipopolysaccharide concentration of 1 microg/mL (P =.002). There were no significant differences in interleukin-6 or interleukin-10 production. CONCLUSION: Women with previous early preterm deliveries who had evidence of intra-amniotic infection or inflammation had significantly higher tumor necrosis factor-alpha production after lipopolysaccharide stimulation of whole blood compared with women with previous term deliveries.

The effect of sequential use of vacuum and forceps for assisted vaginal delivery on neonatal and maternal outcomes.

OBJECTIVE: To determine the risk of neonatal and maternal disease associated with the sequential use of vacuum and forceps compared with spontaneous vaginal delivery. STUDY DESIGN: Using Washington state birth certificate data linked to hospital discharge records, we compared 3741 vaginal deliveries by both vacuum and forceps, 3741 vacuum deliveries, and 3741 forceps deliveries to 11,223 spontaneous vaginal deliveries. RESULTS: Compared with spontaneous vaginal deliveries, deliveries by sequential use of vacuum and forceps had significantly higher rates of intracranial hemorrhage (relative risk [RR], 3.9; 95% confidence interval [CI], 1.5 to 10.1), brachial plexus (RR, 3.2; 95% CI, 1.6 to 6.4), facial nerve injury (RR, 13.3; 95% CI, 4.7 to 37.7), seizure (RR, 13.7; 95% CI, 2.1 to 88.0), depressed 5-minute Apgar score (RR, 3.0; 95% CI, 2.2 to 4.0), assisted ventilation (RR, 4.8; 95% CI, 2.1 to 11.0), fourth-degree (RR, 11.4; 95% CI, 6.4 to 20.1 among multiparous women) and other lacerations, hematoma (RR, 6.2; 95% CI, 2.1 to 18.1 among multiparous women), and postpartum hemorrhage (RR, 1.6; 95% CI, 1.3 to 2.0). The relative risk of sequential vacuum and forceps use was greater than the sum of the individual relative risks of each instrument for intracranial hemorrhage, facial nerve injury, seizure, hematoma, and perineal and vaginal lacerations. CONCLUSION: Sequential use of vacuum and forceps is associated with increased risk of both neonatal and maternal injury.

A protein-protein interaction map of the Caenorhabditis elegans 26S proteasome.

The ubiquitin-proteasome proteolytic pathway is pivotal in most biological processes. Despite a great level of information available for the eukaryotic 26S proteasome-the protease responsible for the degradation of ubiquitylated proteins-several structural and functional questions remain unanswered. To gain more insight into the assembly and function of the metazoan 26S proteasome, a two-hybrid-based protein interaction map was generated using 30 Caenorhabditis elegans proteasome subunits. The results recapitulate interactions reported for other organisms and reveal new potential interactions both within the 19S regulatory complex and between the 19S and 20S subcomplexes. Moreover, novel potential proteasome interactors were identified, including an E3 ubiquitin ligase, transcription factors, chaperone proteins and other proteins not yet functionally annotated. By providing a wealth of novel biological hypotheses, this interaction map constitutes a framework for further analysis of the ubiquitin-proteasome pathway in a multicellular organism amenable to both classical genetics and functional genomics.

Genome sequence and comparative analysis of the solvent-producing bacterium Clostridium acetobutylicum.

The genome sequence of the solvent-producing bacterium Clostridium acetobutylicum ATCC 824 has been determined by the shotgun approach. The genome consists of a 3.94-Mb chromosome and a 192-kb megaplasmid that contains the majority of genes responsible for solvent production. Comparison of C. acetobutylicum to Bacillus subtilis reveals significant local conservation of gene order, which has not been seen in comparisons of other genomes with similar, or, in some cases closer, phylogenetic proximity. This conservation allows the prediction of many previously undetected operons in both bacteria. However, the C. acetobutylicum genome also contains a significant number of predicted operons that are shared with distantly related bacteria and archaea but not with B. subtilis. Phylogenetic analysis is compatible with the dissemination of such operons by horizontal transfer. The enzymes of the solventogenesis pathway and of the cellulosome of C. acetobutylicum comprise a new set of metabolic capacities not previously represented in the collection of complete genomes. These enzymes show a complex pattern of evolutionary affinities, emphasizing the role of lateral gene exchange in the evolution of the unique metabolic profile of the bacterium. Many of the sporulation genes identified in B. subtilis are missing in C. acetobutylicum, which suggests major differences in the sporulation process. Thus, comparative analysis reveals both significant conservation of the genome organization and pronounced differences in many systems that reflect unique adaptive strategies of the two gram-positive bacteria.

Amniotic fluid lipopolysaccharide-binding protein and soluble CD14 as mediators of the inflammatory response in preterm labor.

OBJECTIVE: Our purpose was to determine the association of lipopolysaccharide-binding protein (LBP) and soluble CD14 (sCD14) with the proinflammatory response among women in preterm labor. The binding of lipopolysaccharide (LPS) with LBP and sCD14 activates macrophages at LPS concentrations up to 1000 times lower than required with LPS alone. LBP and sCD14 in amniotic fluid could explain the high concentrations of cytokines present in the amniotic fluid of culture-positive women and the presence of cytokines in the amniotic fluid of culture-negative women. STUDY DESIGN: A cohort of 169 afebrile women in preterm labor with intact membranes had amniotic fluid collected by transabdominal amniocentesis for culture and for LBP, sCD14, and interleukin 6 (IL-6) determinations by enzyme-linked immunosorbent assay. IL-6 levels of >2 ng/mL were considered elevated. Statistical analyses included analysis of variance, multiple comparisons with Bonferroni correction, and linear regression. RESULTS: All 169 amniotic fluid samples had measurable LBP and sCD14. Subjects were categorized by amniotic fluid culture results and IL-6 concentration into 3 groups: (1) positive amniotic fluid culture, (2) negative amniotic fluid culture, elevated IL-6 concentration, and (3) negative amniotic fluid culture, low IL-6 level. Geometric mean LBP and sCD14 levels differed significantly among groups such that levels were approximately twice as high among pregnancies with positive amniotic fluid culture or elevated IL-6 compared with those without evidence of inflammation (both P <.001). sCD14 was inversely associated with enrollment gestational age independent of amniotic fluid culture results and IL-6 concentrations. Among culture negative, low IL-6 pregnancies, sCD14 decreased 3.5% for each additional week of gestation (95% confidence interval [CI], 0.01%-6.4%; P =.02). LBP levels showed a similar trend in this group (P =.09). One hundred eleven subjects had detectable IL-6 levels. Among these subjects, IL-6 increased by 2.1-fold for every 10-fold increase in LBP (95% CI, 1.1-4.0; P =.02) and by 28.4-fold for every 10-fold increase in sCD14 (95% CI, 10.4-77.4; P <.001) with adjustment for gestational age by linear regression. CONCLUSIONS: LBP and sCD14 are present in amniotic fluid of preterm pregnancies and are linearly associated with amniotic fluid IL-6 concentrations. These molecules may amplify the cytokine response and thereby help explain the presence of cytokines in amniotic fluid when culturable quantities of microbes are absent.

Perinatal mortality and neonatal morbidity rates among twin pairs at different gestational ages: optimal delivery timing at 37 to 38 weeks' gestation.

OBJECTIVE: The aim of this study was to determine the gestational age at delivery associated with the lowest rates of perinatal mortality, respiratory distress syndrome, and long hospital stays among twins, with pair rates used to account for both infants in each twin pregnancy. STUDY DESIGN: We conducted a population-based retrospective study that analyzed linked birth certificates, fetal and infant death certificates, and hospital discharge data for 8150 twin pairs born in Washington State during 1987 through 1997. The chi2 or Fisher exact test was used to assess the statistical significance. RESULTS: The nadirs of perinatal mortality rate, respiratory distress syndrome incidence, and long hospital stay rate were seen at delivery dates of 39, 40, and 38 weeks' gestation, respectively. Restriction to pairs delivered vaginally without the induction of labor revealed that the perinatal mortality rate was lowest for delivery at 37 weeks' gestation, the gestational age at which the highest numbers of such spontaneously timed pairs were born. CONCLUSION: Induction of labor should be routinely considered for twins at 37 to 38 weeks' gestation.

Open-reading-frame sequence tags (OSTs) support the existence of at least 17,300 genes in C. elegans.

The genome sequences of Caenorhabditis elegans, Drosophila melanogaster and Arabidopsis thaliana have been predicted to contain 19,000, 13,600 and 25,500 genes, respectively. Before this information can be fully used for evolutionary and functional studies, several issues need to be addressed. First, the gene number estimates obtained in silico and not yet supported by any experimental data need to be verified. For example, it seems biologically paradoxical that C. elegans would have 50% more genes than Drosophilia. Second, intron/exon predictions need to be tested experimentally. Third, complete sets of open reading frames (ORFs), or "ORFeomes," need to be cloned into various expression vectors. To address these issues simultaneously, we have designed and applied to C. elegans the following strategy. Predicted ORFs are amplified by PCR from a highly representative cDNA library using ORF-specific primers, cloned by Gateway recombination cloning and then sequenced to generate ORF sequence tags (OSTs) as a way to verify identity and splicing. In a sample (n=1,222) of the nearly 10,000 genes predicted ab initio (that is, for which no expressed sequence tag (EST) is available so far), at least 70% were verified by OSTs. We also observed that 27% of these experimentally confirmed genes have a structure different from that predicted by GeneFinder. We now have experimental evidence that supports the existence of at least 17,300 genes in C. elegans. Hence we suggest that gene counts based primarily on ESTs may underestimate the number of genes in human and in other organisms.

Vaginal indicators of amniotic fluid infection in preterm labor.

OBJECTIVE: To determine whether vaginal interleukin-6, interleukin-8, neutrophils, bacterial vaginosis, and selected vaginal bacteria are predictors of amniotic fluid (AF) infection among women in preterm labor. METHODS: One hundred ninety-seven afebrile women in preterm labor with intact membranes had vaginal and AF samples collected for Gram stain, culture, and interleukin-8 and interleukin-6 determinations. Vaginal interleukin-6, interleukin-8, neutrophils, and vaginal flora were compared in women with positive and negative AF cultures. The negative AF culture group was subdivided according to AF interleukin-6 concentration. Logistic regression was used to examine the associations between vaginal cytokines and flora and AF infection or elevated AF interleukin-6. RESULTS: The vaginal interleukin-8 concentration and neutrophil count were significantly higher with both AF infection and elevated concentrations of AF interleukin-6 and interleukin-8. The vaginal interleukin-6 concentration was not associated with AF infection or high concentration of AF cytokines. Amniotic fluid infection was associated with bacterial vaginosis or intermediate vaginal flora by Gram stain, absence of hydrogen peroxide-producing Lactobacillus, and presence of vaginal Bacteroides ureolyticus and Fusobacterium. Vaginal interleukin-8 levels greater than 30 ng/mL had 80% sensitivity and a positive predictive value of 35%, and an abnormal vaginal Gram stain (more than five neutrophils per 400x field, bacterial vaginosis species, or intermediate flora) had 90% sensitivity and a positive predictive value of 27% to detect AF infection or elevated AF interleukin-6. CONCLUSION: A high vaginal interleukin-8 concentration, abnormal vaginal Gram stain, absent hydrogen peroxide-producing Lactobacillus, and anaerobic vaginal flora were strongly associated with AF infection among women in preterm labor.

Amniotic fluid infection, cytokines, and adverse outcome among infants at 34 weeks' gestation or less.

OBJECTIVE: We examined the hypothesis that amniotic fluid (AF) infection and elevated cytokine concentrations may cause neonatal injury beyond that expected solely from prematurity. METHODS: The effects of exposure to AF infection and elevated cytokine concentrations were measured in 151 infants born to afebrile women in preterm labor with intact membranes at less than or equal to 34 weeks' gestation. Amniotic fluid was collected by amniocentesis for culture and determination of tumor necrosis factor-alpha and interleukin-6. Cytokine concentrations, stratified by AF infection, were compared for three gestational age groups. We then examined the associations between a positive AF culture or elevated AF tumor necrosis factor-alpha concentration and adverse neonatal outcomes, adjusted for birth weight. RESULTS: Amniotic fluid from 45 (30%) of 151 pregnancies had microorganisms, an elevated tumor necrosis factor-alpha concentration, or both. Amniotic fluid cytokine concentrations were significantly higher among women in preterm labor at less than or equal to 30 weeks, compared with 31-34 weeks. Nine of 11 infants who died at less than or equal to 24 hours of age had AF infection or elevated AF tumor necrosis factor-alpha. For the 140 surviving infants, AF infection and/or an elevated AF tumor necrosis factor-alpha was associated with respiratory distress syndrome (adjusted odds ratio [OR] 1.7), grade 3-4 intraventricular hemorrhage (adjusted OR 2.2), necrotizing enterocolitis (adjusted OR 1.8), and multiple organ dysfunction (adjusted OR 3.0). CONCLUSION: Among infants born at less than or equal to 34 weeks to women who have intact membranes and are initially afebrile, those exposed to AF bacteria or cytokines have more adverse neonatal outcomes than unexposed infants of similar birth weight.

Intrauterine infection and preterm delivery: evidence for activation of the fetal hypothalamic-pituitary-adrenal axis.

OBJECTIVE: We studied pregnant women in preterm labor with and without intrauterine infection to determine whether fetal hypothalamic-pituitary-adrenal axis activation occurs in the setting of infection-induced preterm parturition. STUDY DESIGN: Amniotic fluid collected by amniocentesis and maternal blood from patients in preterm labor with intact membranes at 24 to 34 weeks' gestation were analyzed by radioimmunoassay for the steroid hormones estrone, estradiol, progesterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and cortisol. Amniotic fluid was also obtained for microbial culture and for interleukin 6 measurements by enzyme immunoassay. RESULTS: Patients with intrauterine infection (n = 11) had significantly higher amniotic fluid concentrations of dehydroepiandrosterone (539 +/- 79 pg/mL) and of cortisol (5.28 +/- 1.0 microg/dL) than did patients with preterm labor and preterm delivery without infection (n = 11; 273 +/- 82 pg/mL and 1.61 +/- 1.05 microg/dL, respectively) or patients with preterm labor and subsequent term delivery (n = 11; 202 +/- 79 pg/mL and 1.82 +/- 1.0 microg/dL, respectively). Furthermore those patients who were delivered within 7 days after enrollment (who were also more likely to have intrauterine infection) had higher amniotic fluid concentrations than did those who were not delivered within 7 days of both estrone (586 +/- 101 pg/mL vs 314 +/- 98 pg/mL) and estradiol (238 +/- 44 pg/mL vs 91 +/- 43 pg/mL). CONCLUSION: Intrauterine infection was associated with increased fetal adrenal androgen and cortisol biosynthesis, and delivery within 7 days after the onset of preterm labor was associated with increased placental estrogen synthesis. These data are consistent with fetal hypothalamic-pituitary-adrenal axis activation in the setting of infection-associated preterm delivery.

Amniotic fluid interleukin-6 and preterm delivery: a review.

OBJECTIVE: To evaluate the potential role of amniotic fluid (AF) interleukin (IL)-6 as a predictor of preterm delivery and to consider possible explanations for the proportion of women with elevated AF IL-6 who deliver preterm yet lack microbiologically detectable intra-amniotic infection. DATA SOURCES: We searched the English language human literature in MEDLINE, 1966 through September 1999, using the keywords "labor/infant," "premature," "cytokines/interleukin-6," and "AF." We also examined abstracts from the 1999 meetings of the Society for Maternal-Fetal Medicine and the Society for Epidemiologic Research. We identified other studies by reviewing the reference lists of published articles. METHODS OF STUDY SELECTION: The MEDLINE search yielded 55 citations. We focused on studies that reported on the association between AF IL-6 and preterm delivery. TABULATION, INTEGRATION, AND RESULTS: There is consensus in the literature that elevated AF IL-6 is a stronger predictor of preterm delivery than intra-amniotic infection detected by either microbiologic culture or polymerase chain reaction (PCR). Among women with elevated AF IL-6, PCR could detect a higher proportion of intra-amniotic infection than culture. A number of women with elevated AF IL-6 (33-70%) deliver preterm and do not have evidence of intra-amniotic infection by either culture or PCR. Possible explanations for this observation are considered. CONCLUSION: Elevated AF IL-6 is strongly associated with preterm delivery and merits future consideration in clinical settings to predict preterm delivery and guide patient care. Development of improved polymerase chain reaction-based clinical methods to detect intra-amniotic infection is necessary to better understand the relationship between elevated AF IL-6, intra-amniotic infection, and preterm delivery.

Characteristics of women with clinical intra-amniotic infection who deliver preterm compared with term.

The authors sought to determine whether demographic factors, labor characteristics, and labor management for intra-amniotic infection (IAI) are different for IAI cases who deliver preterm compared with IAI cases who deliver at term. From 1990 through 1994, 610 women with intra-amniotic infection and 747 controls were enrolled from five hospitals in King County, Washington state. Intra-amniotic infection was diagnosed by fever 37.8 degrees C with two of the following signs: maternal or fetal tachycardia, uterine tenderness, elevated peripheral white blood cell count, and purulent amniotic fluid. Preterm IAI cases were significantly more likely than term IAI cases to have membrane rupture before contractions (odds ratio (OR) = 6.1) and prolonged membrane rupture (> 24 hours) (OR = 31.0). Term cases were more likely to experience a prolonged second stage of labor. After accounting for differences in labor characteristics, preterm IAI was less likely to be managed with a cesarean delivery, prolonged internal monitoring, or induction of labor and more likely to be managed with antimicrobials and antipyretics. When compared with preterm births without IAI, preterm IAI cases were more likely to be managed with labor augmentation. The authors believe that labor characteristics of women with preterm IAI and the risk of neonatal sepsis deserve further study.

Initial multicenter experience with double nucleoside therapy for human immunodeficiency virus infection during pregnancy.

OBJECTIVE: To study maternal and neonatal effects of combination nucleoside analog therapy administered to human immunodeficiency virus (HIV)-infected pregnant women for maternal indications. METHODS: A multicenter, prospective observational study was undertaken at six perinatal centers in the United States and Canada that supported regional referral programs for the treatment of HIV-infected pregnant women. Demographic, laboratory, and pregnancy outcome data were collected for 39 women whose antiretroviral treatment regimens were expanded to include more than one nucleoside analog for maternal indications. The 40 newborns were monitored at pediatric referral centers through at least three months of age to ascertain their HIV infection status. RESULTS: For all 39 women, zidovudine (ZDV) therapy was instituted at 13.4 +/- 8.2 weeks, with a second agent (lamivudine [3TC] in 85% of cases) being added at a mean gestational age of 17.6 weeks. Duration of therapy with two agents was 20.6 +/- 10.4 weeks overall, with no women stopping medications because of side effects or toxicity. No significant changes in maternal laboratory values were seen, except for an increase in mean corpuscular volume, over the course of pregnancy. No clinically significant adverse neonatal outcomes were noted, with all but the three preterm newborns leaving hospital with their mothers. Neonatal anemia (hematocrit < 50%) was seen in 62% of newborns, with no children needing transfusion; mild elevations of liver function tests, primarily aspartate aminotransferase, were noted in 58% of newborns tested, though none were clinically jaundiced. Overall rate of neonatal HIV infection was 2.5% (95% confidence interval: 0.1-13.2%). CONCLUSION: Combination antiretroviral therapy during pregnancy with two nucleoside analogs was well-tolerated by mothers and newborns, with no significant short-term toxicities or side effects noted. Surveillance of exposed newborns' hematologic and liver function appears warranted.

Herpes simplex virus seropositivity and reactivation at delivery among pregnant women infected with human immunodeficiency virus-1.

OBJECTIVE: Our purpose was to determine whether pregnant women infected with human immunodeficiency virus-1 have an increased risk of herpes simplex virus-2 seropositivity and herpes simplex virus reactivation at delivery. STUDY DESIGN: Sixty women infected with human immunodeficiency virus and 8408 other patients who were delivered at the University of Washington between 1989 and 1995 had herpes simplex virus serologic determinations at delivery. Genital herpes simplex virus cultures were obtained for 48 (80%) of the human immunodeficiency virus-infected women and 5567 (66%) of the controls. Logistic regression was used to adjust for possible confounding factors. RESULTS: Forty-five (75%) of human immunodeficiency virus-infected women and 2709 (32%) controls were seropositive for herpes simplex virus-2 (p < 0.0001). Eight percent of human immunodeficiency virus-infected women and 2% of controls had herpes simplex virus reactivation in labor (p < 0.05). CONCLUSIONS: Infection with herpes simplex virus-2 is common among pregnant women infected with human immunodeficiency virus. Herpes simplex virus reactivation complicates labor in this group more often than in other obstetric patients. The role of herpes simplex virus in perinatal human immunodeficiency virus transmission warrants further study.

Amniotic fluid tumor necrosis factor-alpha and the risk of respiratory distress syndrome among preterm infants.

OBJECTIVE: We examined the effect of exposure to amniotic fluid infection and cytokines on the pulmonary outcome of preterm infants. STUDY DESIGN: A cohort of 136 preterm infants born to women in preterm labor had amniotic fluid cultures and tumor necrosis factor-alpha assays performed. Amniotic fluid was collected by transabdominal amniocentesis. Outcome measures included respiratory distress syndrome and length of oxygen and ventilator support. Logistic regression and Cox proportional hazards regression adjusted for birth weight and other confounders. RESULTS: Respiratory distress syndrome developed in 67 (49%) of 136 infants. Elevated amniotic fluid tumor necrosis factor-alpha levels and amniotic fluid infection were significantly associated with respiratory distress syndrome. This association persisted after adjustment for birth weight. Infants exposed to tumor necrosis factor-alpha remained on supplemental oxygen and assisted ventilation longer and had longer hospital stays compared with nonexposed infants. CONCLUSION: Prenatal exposure to tumor necrosis factor-alpha may be a risk factor for respiratory distress syndrome and its complications.

Broad-spectrum bacterial rDNA polymerase chain reaction assay for detecting amniotic fluid infection among women in premature labor.

We amplified bacterial 16S rRNA encoding DNA (rDNA) with the polymerase chain reaction (PCR) to detect amniotic fluid infection in 69 women in premature labor whose membranes were intact. Bacterial rDNA was detected by PCR in samples from 15 (94%) of 16 patients with positive amniotic fluid cultures. Bacteria were detected by PCR in samples from 5 (36%) of 14 patients with negative cultures and elevated interleukin (IL)-6 levels vs. 1 (3%) of 39 patients with negative cultures and IL-6 levels of < or = 2,000 pg/mL (P < .01). The median amniotic fluid cytokine levels and the pregnancy outcomes were similar for patients with positive amniotic fluid cultures and those with negative cultures and positive rDNA PCR assays. The association between amniotic fluid infection and premature labor may be underestimated on the basis of amniotic fluid culture results. The broad-spectrum bacterial 16S rDNA PCR assay may prove useful for diagnosing amniotic fluid infection.

Effect of pregnancy and zidovudine therapy on viral load in HIV-1-infected women.

The objective of this study was to determine the effect of pregnancy and zidovudine (ZDV) on viral load in HIV-1 infected women. A prospective nonrandomized cohort study was conducted at a university medical center and affiliated clinic and included 44 HIV-1-seropositive pregnant women seen between June 1991 and September 1995. Twenty-three women initiated ZDV therapy during their pregnancy. Seventeen women did not take antiretrovirals, and four women took ZDV prior to and throughout pregnancy. HIV-1 viral load as determined by quantitative peripheral blood mononuclear cell (PBMC) culture and quantitative plasma RNA levels was measured at various times during pregnancy and in the postpartum period. HIV-1 load, by both infectivity and RNA levels, was relatively low and remained stable during pregnancy and through 6 weeks post partum. Initiation of ZDV therapy during pregnancy did not result in a significant decrease in viral load at delivery when controlling for the effect of pregnancy. In those women who received ZDV therapy only during pregnancy, there was a trend toward an increase in viral load measured by PBMC infectivity 6 months post partum compared with the levels before the initiation of ZDV. Mother-to-child transmission of HIV-1 occurred in one of 27 (4%) ZDV-treated women and in two of 16 (12.5%) untreated women. Among HIV-1-infected pregnant women with low viral levels, HIV-1 plasma RNA and infectivity remained stable during and after gestation. Although these results are based on a relatively small number of women and should be considered preliminary, the lack of significant ZDV-associated diminution in viral levels suggests that the protective effect of ZDV on the mother-to-child transmission of HIV-1 may not be due to the reduction in maternal viral levels but, by inference, may be due to the prevention of HIV-1 reverse transcription in the newborn.