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.

Ethnic variations in cervical cytokine concentrations and vaginal flora during pregnancy.

PROBLEM: Pregnancy-mediated changes in immunity may influence risk of HIV-1 acquisition. This risk appears greatest among non-Caucasian women. METHOD OF STUDY: Pregnant women with low risk of immune disruption were enrolled in a prospective observational cohort. Study visits occurred each trimester and postpartum. Semi-quantitative vaginal cultures and concentrations of cervical cytokines were compared between Caucasian and non-Caucasian women. RESULTS: In the second trimester, non-Caucasian women were more likely to be colonized with Gardnerella vaginalis (62% versus 25%, P = 0.02) and non-pigmented anaerobic gram-negative rods (43% versus 8%, P = 0.01). Mycoplasma hominis was more frequently isolated in non-Caucasian women throughout the second (29% versus 4%, P = 0.03) and third trimesters (35% versus 6%, P = 0.04). Non-Caucasian women had higher median interleukin (IL)-10 concentrations throughout the second (128 pg/mL versus 7 pg/mL, P = 0.05) and third trimesters (224 pg/mL versus 7 pg/mL, P = 0.05). CONCLUSION: Non-Caucasian women experienced a greater diversity of microorganisms and increased IL-10 in the second and third trimesters.

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.

Puerperal group A streptococcal infection: beyond Semmelweis.

Ignaz Semmelweiss made one of the most important contributions to modern medicine when he instituted handwashing in an obstetric clinic in Austria in 1847, decreasing mortality there from more than 10% to 2%. Unfortunately, puerperal sepsis remains a leading cause of maternal mortality throughout the world. Group A streptococcus (GAS), Streptococcus pyogenes, is an organism associated with high rates of morbidity and mortality from puerperal infections. When associated with sepsis, known as streptococcal toxic shock syndrome, mortality rates approach 30-50%. Group A streptococcus can cause invasive infections in the form of endometritis, necrotizing fasciitis, or streptococcal toxic shock syndrome. The clinical presentation of women with puerperal GAS infections is often atypical with extremes of temperature, unusual and vague pain, and pain in extremities. Toxin production by the organism may allow GAS to spread across tissue planes and cause necrosis while evading containment by the maternal immune system in the form of a discrete abscess. Endometrial aspiration in addition to blood cultures may be a useful rapid diagnostic tool. Imaging may appear normal and should not dissuade the clinician from aggressive management. When suspected, invasive GAS infections should be treated emergently with fluid resuscitation, antibiotic administration, and source control. The optimal antibiotic regimen contains penicillin and clindamycin. Source control may require extensive wound or vulvar debridement, hysterectomy, or a combination of these, which may be life-saving. The benefit of immunoglobulins in management of puerperal GAS infections is unclear.

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.

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.

Can hemoglobin A1c in early pregnancy predict adverse pregnancy outcomes in diabetic patients?

OBJECTIVE: To examine the association of elevated early pregnancy hemoglobin A1c (HbA1c) levels with adverse pregnancy outcomes in women with preexisting diabetes mellitus. STUDY DESIGN: Retrospective cohort study of 330 women with preexisting diabetes enrolled in a Diabetes in Pregnancy Program at an academic institution between 2003 and 2011 who had an early HbA1c determination. The frequencies of composite maternal adverse pregnancy outcomes (birth at<37 weeks, preeclampsia, and medically indicated birth <39 weeks), and composite fetal adverse pregnancy outcomes [shoulder dystocia, Apgar scores<7 at 5 minutes, small for gestational age (SGA), large for gestational age (LGA), and stillbirth] were compared between HbA1c categories (<6.5, 6.5-7.4, 7.5-8.4 and ≥ 8.5%). RESULTS: There was no statistically significant difference between composite adverse maternal pregnancy outcomes and composite adverse fetal pregnancy outcomes as well as other individual outcomes between different HbA1c categories. Of the vaginally delivered women in our cohort, the 37 patients with HbA1c levels of ≥ 8.5% had a significantly higher frequency of fetal shoulder dystocia than the 62 with HbA1c levels of < 8.5% (24.2 vs. 1.6%, P = 0.002). Neonates of patients with HbA1c ≥ 8.5% were more likely to have low five minute Apgar scores than neonates of patients with HbA1c < 8.5%, but this was of borderline statistical significance (7.4% vs. 0.5%, P = 0.05). CONCLUSION: In patients with preexisting diabetes mellitus, HbA1c levels of ≥ 8.5% during early pregnancy are not useful in predicting most adverse outcomes, although there may be an increased risk for shoulder dystocia.

Pregnancy with a severe hemoglobinopathy: unintended consequences of transfusions.

We report a case of a pregnant woman with a complex hemoglobinopathy who developed a symptomatic anemia at 28 weeks of gestation and was treated with multiple transfusions of type-specific packed red blood cells. Shortly thereafter, she developed a fever and joint pains, along with laboratory values consistent with hemolysis. Timing suggested a delayed transfusion reaction. An extensive evaluation including red blood cell antigen identification and cross-reaction failed to reveal the cause for her hemolysis. Despite her critically low hemoglobin levels, her transfusions were withheld in an attempt to allow the patient to recover conservatively. With this strategy, her hemoglobin remained below her baseline, but her symptoms began to improve. Her laboratory values normalized, and hemolysis was no longer evident. Three weeks later, her hemoglobin levels returned back to her baseline without additional intervention. She went on to deliver a full-term male infant.

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.

Evaluation of the clinical use of magnesium sulfate for cerebral palsy prevention.

OBJECTIVE: Clinical trials support the efficacy and safety of magnesium sulfate for cerebral palsy prevention. We evaluated the implementation of a clinical protocol for the use of magnesium for cerebral palsy prevention in our large women's hospital, focusing on uptake, indications, and safety. METHODS: We performed a review of selected gravidas with threatened or planned delivery before 32 weeks of gestation from October 2007 to February 2011. The primary study outcome was the change in the rate of predelivery administration of magnesium sulfate over this time period. RESULTS: Three hundred seventy-three patients were included. In 2007, before guideline implementation, 20% of eligible gravidas (95% confidence interval [CI] 9.1-35.6%) received magnesium before delivery compared with 93.9% (95% CI 79.8-99.3%) in the final 2 months of the study period (P<.001). Dosing did not vary significantly over the 4 study years: the median number of treatments was one, the total predelivery median dose ranged from 15 to 48 g, and the median duration of therapy ranged from 3 to 12 hours. After 3 years, magnesium administration was almost universal among patients diagnosed with preeclampsia, preterm labor, or preterm premature rupture of membranes (95.4%), whereas patients delivered preterm for fetal growth restriction were significantly less likely to receive predelivery magnesium (44%, P<.001). No maternal or perinatal magnesium-attributable morbidity was noted. Among patients eligible for the protocol who received magnesium, 84.2% delivered before 32 weeks of gestation. CONCLUSION: It is feasible to implement a magnesium sulfate cerebral palsy prevention protocol into clinical practice. LEVEL OF EVIDENCE: III.

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.

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.

Clinical parameters essential to methodology and interpretation of mucosal responses.

Research aimed at putting an end to the HIV pandemic is dynamic given the marked advances in understanding of pathogenesis since its origin. Attention has shifted from systemic management of disease to a focus on the most common site of acquisition, the female genital tract. Research on the female genital tract of humans requires consideration of a number of specific clinical parameters. If such parameters are not considered when enrolling subjects into studies, it could lead to faulty data ascertainment. This article reviews important clinical characteristics to consider when conducting studies of the human female genital tract in regard to mucosal immunity and HIV disease. Important topics to consider include the method and source of sample collection, the individual patient characteristics, and in the case of recruitment of HIV-infected women, HIV disease characteristics.