Lactic acid measurement to identify risk of morbidity from sepsis in pregnancy.

OBJECTIVE: This study aims to assess the risk of morbidity associated with maternal lactic acid concentration in women with possible sepsis in pregnancy. STUDY DESIGN: Retrospective cohort of pregnant and postpartum patients with signs of sepsis. Morbidity outcomes were compared by lactic acid concentration. Linear regression was used to evaluate the association between lactic acid and adverse outcomes. RESULTS: Out of the 850 women included, 159 had lactic acid measured. Patients with lactic acid measured had higher morbidity: positive blood cultures (16.8 vs. 5.5%, p = 0.04), admission to the intensive care unit (5 vs. 0.1%, p < 0.01) or acute monitoring unit (17.2 vs. 0.9%, p < 0.01), longer hospital stay (median 3 vs. 2 days, p < 0.01), and preterm delivery (18.3 vs. 10.9%, p = 0.05). The mean lactic concentration was higher in patients admitted to the intensive care (2.6 vs. 1.6 mmol/L, p = 0.04) and telemetry unit (2.0 vs. 1.6, p = 0.03), and in those with positive blood cultures (2.2 vs. 1.6, p < 0.01). Lactic acid was positively associated with intensive care or telemetry unit admission, adjusted odds ratio per 1 mmol/L increase in lactic acid 2.34 (95% confidence interval, 1.33-4.12). CONCLUSION: Elevated lactic acid in pregnancy is associated with adverse maternal outcomes from presumed sepsis. In this cohort, lactic acid measurement was a marker of more severe infection.

Oxygen for intrauterine resuscitation: of unproved benefit and potentially harmful.

Maternal oxygen is often given to laboring women to improve fetal metabolic status or in an attempt to alleviate nonreassuring fetal heart rate patterns. However, the only 2 randomized trials investigating the use of maternal oxygen supplementation in laboring women do not support that such supplementation is likely to be of benefit to the fetus. And by increasing free radical activity, maternal oxygen supplementation may even be harmful. Based on a review of the available literature, we conclude that until it is studied properly in a randomized clinical trial, maternal oxygen supplementation in labor should be reserved for maternal hypoxia, and should not be considered an indicated intervention for nonreassuring fetal status.

The Sepsis in Obstetrics Score: a model to identify risk of morbidity from sepsis in pregnancy.

OBJECTIVE: We sought to design an emergency department sepsis scoring system to identify risk of intensive care unit (ICU) admission in pregnant and postpartum women. STUDY DESIGN: The Sepsis in Obstetrics Score (S.O.S.) was created by modifying validated scoring systems in accordance with recognized physiologic changes of pregnancy. The S.O.S. was applied to a retrospective cohort of pregnant and postpartum patients from February 2009 through May 2011 with clinical suspicion of sepsis. The primary outcome was ICU admission. Secondary outcomes were telemetry unit admission, length of stay, positive blood cultures, positive influenza swabs, perinatal outcome, and maternal mortality. Receiver operating characteristic curves were constructed to estimate the optimal score for identification of risk of ICU admission. RESULTS: In all, 850 eligible women were included. There were 9 ICU (1.1%) and 32 telemetry (3.8%) admissions, and no maternal deaths. The S.O.S. had an area under the curve of 0.97 for ICU admission. An S.O.S. ≥6 (maximum score 28) had an area under the curve of 0.92 with sensitivity of 88.9%, specificity of 95.2%, positive predictive value of 16.7%, and negative predictive value of 99.9% for ICU admission, with an adjusted odds ratio of 109 (95% confidence interval, 18-661). An S.O.S. ≥6 was independently associated with increased ICU or telemetry unit admissions, positive blood cultures, and fetal tachycardia. CONCLUSION: A sepsis scoring system designed specifically for an obstetric population appears to reliably identify patients at high risk for admission to the ICU. Prospective validation is warranted.

Pregnancy-induced changes in immune protection of the genital tract: defining normal.

OBJECTIVE: Both the state of pregnancy as well as disruption of vaginal flora and immune mediators may increase the risk of human immunodeficiency virus-1 acquisition. The objective of this study was to define immune changes in lower genital and systemic immunity associated with normal pregnancy. STUDY DESIGN: This prospective cohort enrolled low-risk pregnant and nonpregnant women ages 18-35 years. Pregnant women at <14 weeks and nonpregnant women in follicular phase of the menstrual cycle were included. Cervical and vaginal fluid was collected. Concentrations of immune mediators were measured using enzyme-linked immunosorbent assay-based methods or multiplex immunoassay. Samples were inoculated onto various culture media allowing for growth of Lactobacillus species, Gardnerella vaginalis, Escherichia coli, Enterococcus species, anaerobic gram-negative rods, Candida, Staphylococcus aureus, Ureaplasma species, and Mycoplasma hominis. Concentrations of immune mediators and vaginal colonization frequencies were compared between the pregnant and nonpregnant groups. RESULTS: Genital tract concentration of interleukin-1ß was higher during pregnancy compared to nonpregnant participants. Serum C-reactive protein concentrations were higher in all trimesters of pregnancy. Concentrations of secretory leukocyte protease inhibitor did not differ between groups. Lactobacillus was more commonly isolated from vaginal cultures of nonpregnant participants (100% vs 70.2%, P = .02). Identification of Candida, G vaginalis, M hominis, and S aureus was common and not different between groups. Ureaplasma species was isolated from >60% pregnant participants. CONCLUSION: The proinflammatory cytokine, interleukin-1ß, as well as the systemic marker of inflammation, C-reactive protein, are increased during pregnancy. The impact of these proinflammatory changes during pregnancy deserves further study.

Cytomegalovirus: should we screen pregnant women for primary infection?

Congenital cytomegalovirus (CMV) is a leading cause of neonatal morbidity, affecting ~0.5 to 1% of infants born each year. Primary maternal infection during early pregnancy is the greatest risk factor for severe neonatal morbidity/mortality. The current recommendation from national organizations advises against routine screening of pregnant women for primary infection. Recent advancements in diagnosis and treatment raise the issue of implementation of a national screening program. Prior to development of a major screening program for a highly prevalent and costly disease, the screening test must be safe, reliable, and valid with an effective and feasible intervention. This article reviews recent literature regarding available screening tests and potential interventions and whether criteria for a screening program are met in the current state of science. Although screening women using CMV immunoglobulin (Ig) G, IgM, and IgG avidity testing is reliable, effective intervention with hygiene modification or treatment with CMV-specific hyperimmune globulin is not as well established. More evidence from randomized controlled trials is needed prior to moving forward with a screening program for congenital CMV.

Effect of trichomoniasis therapy on genital HIV viral burden among African women.

BACKGROUND: Our objective was to test the hypothesis that treatment for trichomoniasis among HIV-infected women not taking antiretrovirals in South Africa would be associated with decreased HIV genital shedding. METHODS: HIV-infected women presenting for routine HIV care were screened for trichomoniasis using self-collected vaginal swabs with a rapid point-of-care immunochromatographic antigen test. Women testing positive were offered enrollment into a prospective cohort study, if they had documented HIV infection, were aged 18 to 50 years, and were not receiving antiretroviral therapy. Recent use of postexposure prophylaxis or antibiotic therapy, active genital ulcers, or systemic illness were exclusion criteria. Cervical swabs were collected for gonococcal and chlamydial testing, and those testing positive were excluded. Women were treated with directly observed oral therapy with 2 g of oral metronidazole. A follow-up visit was scheduled 1 month after therapy, and partner letters were provided. Paired cervical wicks and plasma were collected for viral load measurement. RESULTS: In all, 557 women were screened. Sixty tested positive for trichomoniasis, 10 subsequently met exclusion criteria, and 4 were lost to follow-up. Of 46 women evaluated at follow-up, 37 (80.4%) were cured. Plasma viral load was not significantly different after therapy (P = 0.93). Genital tract viral load decreased by 0.5 log10 (P < 0.01). The mean genital tract viral load (log10) decreased from 4.66 (<3.52-6.46) to 4.18 (<3.52-6.48) (P < 0.01) after therapy. CONCLUSIONS: Screening and treatment of vaginal trichomoniasis decrease genital shedding of HIV among South African women not receiving antiretrovirals at 1 month after therapy.

In vitro anti-HIV-1 activity in cervicovaginal secretions from pregnant and nonpregnant women.

OBJECTIVE: To evaluate whether cervicovaginal secretions inhibit HIV-1 infectivity in an in vitro model, and estimate concentration of immune mediators. STUDY DESIGN: We enrolled midtrimester pregnant and regularly menstruating (nonpregnant) women. Cervicovaginal lavage was collected at 2 visits and incubated with HIV-1 and TZM-bl cells. Infectivity was compared with positive controls. Concentrations of immune mediators were compared between groups. RESULTS: At enrollment, cervicovaginal lavage inhibited IIIB virus 88.2% and 82.4%, and BaL virus 72.8% and 77.9%, among pregnant (n = 13) and nonpregnant women (n = 9), respectively. At second visit, cervicovaginal lavage inhibited IIIB 89.7% and 82.5%, and BaL 77.4% and 69.9% among pregnant (n = 15) and nonpregnant women (n = 8), respectively (all P ≤ .04). Adjusting for body mass index, race, and protein content of cervicovaginal lavage, antimicrobials were suppressed but cytokines and chemokines were not markedly different in pregnancy. CONCLUSION: Cervicovaginal secretions significantly suppress HIV-1 infectivity in this model. Concentrations of certain immune mediators are altered in pregnancy.

First-trimester pyelonephritis is associated with later initiation of prenatal care: a retrospective cohort analysis.

We sought to determine the morbidity, frequency, and demographics of pregnant patients with pyelonephritis not yet receiving prenatal care compared with patients with prenatal care. We performed a retrospective cohort analysis of 254 consecutive admissions for pyelonephritis from January 2004 to June 2007 at a single tertiary hospital comparing patients with prenatal care versus patients with no prenatal care. The sample size was adequate to detect a 1-day difference in length of admission between the two groups with an α of 0.05 and 80% power. Categorical variables were compared by Fisher exact test, and continuous variables were compared by the Wilcoxon rank sum or Kruskal-Wallis test. Of the 254 cases, 35 (13.8%) occurred in women who had not established prenatal care. There was no difference in the primary outcome of hospital length of stay. Overall, 29 cases (11.4%) occurred prior to 12 weeks and of these, significantly more patients presented having not established prenatal care (18 versus 11, p < 0.0001). The majority of cases of pyelonephritis that occur prior to 12 weeks are among women with no prenatal care. Although the U.S. Preventative Services Task Force guidelines advise screening urine culture at 12 to 16 weeks, these findings support initiating screening at an earlier gestational age.

Neonatal characteristics and outcomes of pregnancies complicated by influenza infection during the 2009 pandemic.

The purpose of this study was to describe the neonatal characteristics and outcomes of infants who were born during the 2009 H1N1 influenza pandemic. A prospective cohort of pregnant women with influenza-like illness (ILI) was enrolled between the months of June 2009 and March 2010. Neonatal characteristics, complications, and outcomes were recorded. Forty-five women were included in the study. Birth outcomes were available in 41 cases; 16 women had 2009 H1N1 infection, and the remaining 25 women who tested negative were included in the ILI group. Live births were similar in both groups. Average gestational age at delivery was >39 weeks; Apgar scores and cord gas pH values were similar. Birthweights in the 2009 H1N1 group were on average 285 g lower (3186 vs 3471 g; P = .04). Three infants were admitted to the neonatal intensive care unit. In this cohort, 2009 H1N1 infection during pregnancy was associated with a lower birthweight when compared with ILI in pregnancy.

Clinical characteristics of pregnant women with influenza-like illness during the 2009 H1N1 pandemic and use of a standardized management algorithm.

We sought to describe the clinical characteristics of pregnant women with influenza-like illness during the 2009 H1N1 pandemic with the use of a standardized management algorithm. From June 2009 through March 2010, we assembled a prospective cohort of pregnant women with influenza-like illness at a single tertiary care center using a standardized algorithm. Clinical outcomes were compared between women with 2009 H1N1 virus and those without. In all, 45 women were included. Seventeen had 2009 H1N1 infection and 28 did not. Demographic characteristics were similar between groups. The median temperature upon presentation (99.7 vs 98.8°F, P = .004) was slightly higher among those with 2009 H1N1. All those with 2009 H1N1 influenza and 89% of those without were treated with oseltamivir. A total of 12 women (27%) were hospitalized. There were no endotracheal intubations or deaths. Among this cohort of pregnant women, most were treated as outpatients and had favorable maternal outcomes.

Subtle perturbations of genital microflora alter mucosal immunity among low-risk pregnant women.

OBJECTIVE: Alteration in the vaginal flora has been associated with adverse pregnancy outcomes. The objective of this study was to examine the impact of changes in individual microflora on genital immunity among low-risk pregnant women in early pregnancy. DESIGN: Cross-sectional study. SETTING: Large, tertiary care, academic hospital clinic. POPULATION: Low-risk women were enrolled prior to 14 weeks' gestation. METHODS: Women were included if they had no medical or previous obstetrical complications, were non-smokers, had no sexually transmitted infections and no intercourse in the last 48 hours. Consenting women underwent speculum examination for collection of vaginal culture and Dacron swabs for cytokine analysis. Semi-quantitative vaginal cultures were performed in a reference laboratory. MAIN OUTCOME MEASURES: Concentrations of immune mediators were compared in the presence of various organisms. Concentrations were converted to multiples of the median to standardize the values of each mediator. Regression analyses were performed to control for race. RESULTS: We enrolled 47 women. The frequencies of genital microorganisms were: H(2)O(2) -producing lactobacilli (70%), Ureaplasma urealyticum (66%), Gardnerella vaginalis (45%), anaerobic non-pigmented Gram-negative rods (ANPGNR, 40%), anaerobic pigmented Gram-negative rods (APGNR, 17%). After adjusting for race and body mass index, interleukin-1ß, interferon-γ, tumor necrosis factor-α and granulocyte macrophage-colony stimulating factor were increased in the presence of G. vaginalis, ANPGNR, and APGNR. There was no consistent impact on the other markers of immune activation. CONCLUSION: The presence of individual species impacts genital immunity among low-risk pregnant women. Perturbations in genital immunity could partially explain heterogeneity in adverse pregnancy outcomes.

Compliance with group B streptococcus testing prior to labor and delivery.

We tested whether group B streptococcus (GBS) screening is performed as recommended by the Centers for Disease Control and Prevention (CDC) and evaluated the need for a rapid GBS test for women with full-term pregnancies. A retrospective cohort analysis at a single, large academic institution was performed. Women who delivered full-term (>37 weeks) infants and had documented prenatal care were included. The primary outcome was documented screening. One hundred sixty-five full-term pregnancies were included; 158 women [95.76%; 95% confidence interval (CI), 92.68 to 98.83%] were screened prior to presentation at labor and delivery. This frequency was significantly greater than the a priori hypothesis of 90% ( P = 0.01). Of the 158 women ever screened, 15 had GBS bacteriuria and 143 had genital culture performed. However, only 118 of the 143 (80.61%; 95% CI, 74.57 to 86.64%) were cultured at the appropriate time as recommended by the CDC (between 35 and 37 weeks). This screening frequency was significantly lower than the a priori hypothesis of 90% ( P < 0.001). Most full-term women presenting to labor and delivery have been screened for GBS. However, screening performed at the appropriate gestational age per CDC recommendations was lower than expected. Rapid GBS testing does not appear to be necessary for this population.

Pregnancy and optimal care of HIV-infected patients.

Human immunodeficiency virus (HIV) infection during pregnancy is a condition that requires multidisciplinary care. Care must be rendered that is appropriate for both the mother and the fetus. Prevention of mother-to-child transmission of HIV is of paramount concern. To prevent transmission, universal testing for HIV infection in pregnant women is ideal. In the United States and other developed countries, great strides have been made toward decreasing the risk of HIV transmission to infants to <2% with use of a combination of highly active antiretroviral therapy during the antepartum period and during labor and delivery, scheduled cesarean section when appropriate, avoidance of breast-feeding, and 6 weeks of zidovudine prophylaxis for infants. The continuation of antiretroviral therapy after delivery depends on the needs of the mother with regard to treatment of her own health. In resource-limited countries, where simplified and shortened courses of antiretroviral regimens have been used, reduction in mother-to-child transmission has also been shown, although not as effectively as that with highly active antiretroviral therapy. In these settings, exclusive breast-feeding for 6 months is recommended to reduce the risk of postnatal transmission.

Impact of trimester on morbidity of acute pyelonephritis in pregnancy.

OBJECTIVE: We sought to compare maternal and neonatal morbidity as well as obstetric outcomes associated with pyelonephritis in pregnancy during the first compared to the second/third trimester. STUDY DESIGN: A retrospective cohort analysis was performed of all pregnant women admitted to a single tertiary care hospital between January 2004 and June 2007 with pyelonephritis. The primary outcome was length of hospitalization. The study had 80% power to detect a 1-day difference in length of stay. RESULTS: In all, 219 cases of acute pyelonephritis were identified: 23 diagnosed in the first trimester and 196 in the second/third trimester. Women were hospitalized for a median of 4 days in both the first (range, 2-7) and second/third (range, 2-9; P = .6) trimesters. Neonatal and obstetric outcomes were not statistically significant. CONCLUSION: Maternal morbidity and obstetric outcomes do not differ between first- and second-/third-trimester pyelonephritis. First-trimester pyelonephritis should be aggressively treated to prevent adverse outcomes.

Genital tract leukocytes and shedding of genital HIV type 1 RNA.

BACKGROUND: The mechanism of human immunodeficiency virus (HIV) transmission via heterosexual intercourse is unknown. We sought to determine whether the presence of inflammatory cells in the vagina is associated with the presence of genital tract HIV type 1 (HIV-1) RNA. METHODS: Analysis of a longitudinal prospective cohort was performed. Women with HIV-1 infection were assessed with use of paired plasma and cervicovaginal lavage specimens. Viral load measurements were performed using nucleic acid sequence-based amplification. White blood cells found in the genital tract (GT WBCs) were quantified using a hemacytometer. Common lower genital tract infections assessed for association with viral shedding (i.e., genital tract viral load [GTVL]) included bacterial vaginosis, candidiasis, and trichomoniasis. Generalized estimating equations were used to estimate the prevalence and odds of detectable GTVL by GT WBC. The association was examined both in the presence and in the absence of lower genital tract infections. RESULTS: A total of 97 women and 642 visits were included in the analysis. Median duration of follow-up was 30.4 months. Thirty women (31%) had detectable GTVL at any visit. The median CD4 cell count at baseline was 525 cells/muL. Most women were antiretroviral therapy naive at baseline. After adjustment for plasma viral load, the odds of detectable GTVL increased as GT WBC increased, with an odds ratio of 1.36 (95% confidence interval, 1.1-1.7) per 1000-cell increase in GT WBC among women without lower genital tract infections. After adjustment for plasma viral load and lower genital tract infections by incorporating them in a regression model, GT WBC remained significantly associated with GTVL, with an adjusted odds ratio of 1.22 (95% confidence interval, 1.08-1.37). CONCLUSIONS: The presence of GT WBC is associated with an increased risk of detectable GTVL.

Additional antibiotic use and preterm birth among bacteriuric and nonbacteriuric pregnant women.

OBJECTIVE: To determine the risk of preterm birth related to use of additional antibiotics. METHODS: Women with Group B streptococcal (GBS) bacteriuria and women with negative urine cultures in a hospital-wide research registry were included. The impact of prenatal antibiotics in addition to those used to treat GBS bacteriuria was assessed. Logistic regression was used to determine the risk of preterm birth among bacteriuric women who received "other antibiotics". RESULTS: A total of 203 women with GBS bacteriuria and 220 women with negative cultures were included. The frequency of preterm birth was 16% (35/220) for women in the control group, 16% (19/120) for women with bacteriuria not receiving additional antibiotics, and 28% (23/83) for women with bacteriuria who received antibiotics for "other indications". Among women with GBS bacteriuria, the risk of preterm birth was increased with the use of "other antibiotics" (adjusted odds ratio, 2.7; 95% confidence interval, 1.2-6.1). CONCLUSION: Among women with GBS bacteriuria, exposure to additional antibiotics is associated with an increased risk of preterm birth.

Untreated asymptomatic group B streptococcal bacteriuria early in pregnancy and chorioamnionitis at delivery.

OBJECTIVE: The objective of the study was to determine the frequency of adverse pregnancy outcomes in women with untreated asymptomatic group B beta-hemolytic streptococcal (GBS) bacteriuria during pregnancy. STUDY DESIGN: In this retrospective cohort, all women with antepartum GBS bacteriuria in a research registry were included. Controls were women with negative urine cultures. The frequency of chorioamnionitis was compared between groups. Chorioamnionitis was defined as intrapartum fever, fetal tachycardia, and histologic inflammation of the membranes. RESULTS: One hundred twenty-two women with bacteriuria (study group) and 183 women with negative antepartum cultures (controls) were included. There were no differences in demographic characteristics between the groups. Thirty-one women (10.2%) had chorioamnionitis. Untreated GBS bacteriuria was associated with chorioamnionitis after controlling for confounding variables, adjusted odds ratio 7.2 (95% confidence interval 2.4 to 21.2). There was also a significant positive rank correlation between increasing colony count of GBS bacteriuria and increasing grade of chorioamnionitis (P = .02). CONCLUSION: Untreated antepartum GBS bacteriuria is associated with chorioamnionitis.

Host immune consequences of asymptomatic Trichomonas vaginalis infection in pregnancy.

OBJECTIVE: The purpose of this study was to define the impact of asymptomatic trichomoniasis on lower genital tract neutrophil activation in pregnancy. STUDY DESIGN: In this nested cohort study, pelvic examination was performed on 65 asymptomatic pregnant women between 7 and 22 weeks' with vaginal pH > 4.4. Concentrations of cervical interleukin-8 and alpha-defensin were determined using enzyme-linked immunosorbent assay (ELISA). Trichomonas vaginalis was detected by culture. RESULTS: Median concentrations of vaginal fluid neutrophil defensins and cervical interleukin-8 were significantly greater among women with asymptomatic trichomoniasis (median defensins 18,622 ng/mL, median IL-8 9244 pg/mL) than their uninfected counterparts (median defensins 5144 ng/mL, median IL-8 2044 pg/mL) (P < .001). All women with asymptomatic trichomoniasis had detectable defensin and interleukin-8 concentrations. CONCLUSION: Asymptomatic trichomoniasis in pregnancy is accompanied by a state of neutrophil activation.

Communicable diseases.

Globally, infectious diseases often disproportionately affect women, and have implications for the health of future generations. The human immunodeficiency virus (HIV), tuberculosis, malaria, and schistosomiasis are four such pathogens. Infection with these organisms has a broad impact on maternal child health in many areas of the developing world, and global initiatives to control these diseases will significantly improve the health of generations to come.