Brenna L. Anderson

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.

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.

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.

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.

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.

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 womens 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-1β 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-1β, 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.

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.

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.

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.