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.

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.

Impact of antepartum anemia on the development of chorioamnionitis at term.

OBJECTIVE: The aim of this study is to assess the association of antepartum anemia with chorioamnionitis at term. STUDY DESIGN: This is a case control study of women with and without chorioamnionitis who delivered following spontaneous or induced labor at ≥ 37 weeks' gestation. Cases had both intrapartum fever ≥ 38°C and histologic chorioamnionitis. Controls were afebrile and matched by physician practice group. Anemia was defined by CDC guidelines as hemoglobin < 10.5 g/dL (second trimester) or < 11.0 g/dL (third trimester). RESULTS: A total of 101 cases and 197 controls were identified. The prevalence of anemia at the second and third trimester complete blood count (CBC) was significantly higher in the chorioamnionitis group (p = 0.02). This association persisted after multiple logistic regression controlling for known clinical risk factors (adjusted odds ratios, 2.47; range, 1.24-4.94). CONCLUSION: Anemia at the time of the second and third trimester CBC was more prevalent among women who developed chorioamnionitis at term. Antepartum anemia may be a modifiable risk factor in the prevention of chorioamnionitis at term.

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.

Screening, prevention, and treatment of congenital cytomegalovirus.

Congenital cytomegalovirus (CMV) is a leading cause of permanent disability in children. The main source of maternal infection is from contact with young children. Primary maternal infection is diagnosed with demonstration of seroconversion or a positive CMV IgM in combination with a low-avidity CMV IgG. Fetal infection may be diagnosed with amniotic fluid polymerase chain reaction and culture. CMV-specific hyperimmune globulin has shown promise as a possible means to prevent congenital infection; large randomized trials are ongoing. To date, the only effective means of prevention is through reducing exposure to the virus. Rates of maternal infection may be reduced through education regarding sources of infection and improved hygiene.

Mother-to-Child Transmission of Cytomegalovirus and Prevention of Congenital Infection.

Mother-to-child transmission (MTCT) of cytomegalovirus (CMV) occurs transplacentally (congenital infection), during birth and through breast milk, although the latter 2 modes of transmission are not associated with the central nervous system sequelae that occur with congenital infection. CMV persists indefinitely in its human host, and MTCT can occur if the mother was infected in the past or during the current pregnancy. The goal of efforts to prevent MTCT of CMV is to prevent congenital infection, an important cause of disability due to hearing loss, impaired vision, cognitive impairment, and neuromotor deficits. Vaccines for prevention of maternal and congenital CMV infection are being developed but will not likely be available for at least a decade. Rather than waiting for an effective vaccine to solve the problem, more effort must be devoted to defining the potential for public health measures to prevent congenital CMV infection by reducing rates of maternal infection during pregnancy.

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.

Prevention of maternal and congenital cytomegalovirus infection.

Congenital cytomegalovirus (CMV) infection is an important cause of hearing impairment, mental retardation, and cerebral palsy. Principal sources of infection during pregnancy are young children and intimate contacts. Prevention of maternal and congenital CMV infection depends on counseling women regarding the sources of infection and hygienic measures that might prevent infection. There is currently insufficient evidence to support use of antiviral treatment or passive immunization for postexposure prophylaxis of pregnant women or as a maternal treatment aimed at preventing fetal infection. Vaccines for CMV are under development but it will be a number of years before one is licensed.

Is postpartum pyelonephritis associated with the same maternal morbidity as antepartum pyelonephritis?

OBJECTIVE: Pregnant women with pyelonephritis are at higher risk for significant morbidty than nonpregnant women with pyelonephritis. The risk from pregnancy may continue into the postpartum period. Many of the physiologic and hormonal changes that occur during pregnancy persist after delivery. The objective of this study was to compare maternal morbidity in postpartum and antepartum pyelonephritis. METHODS: A retrospective cohort analysis included all pregnant and postpartum women hospitalized for pyelonephritis at a single tertiary care hospital between January 2004 and June 2007. The postpartum period was defined as up to 6 weeks from delivery. The primary outcome measure was maternal morbidity measured by length of hospitalization. RESULTS: 256 cases of antepartum pyelonephritis and 23 cases of postpartum pyelonephritis were included in the analysis. Women in both groups were admitted for a mean of 4 days (p = 0.3). Women who were diagnosed in the postpartum period were more likely to be febrile (91.3% vs. 51.7%, p = 0.0001) and had a higher temperature on presentation (102.9°F vs. 99.1°F p < 0.0001). DISCUSSION: Pyelonephritis was equally morbid in the postpartum and antepartum periods. Postpartum pyelonephritis may warrant the same close inpatient observation as antepartum pyelonephritis.