Mark H. Yudin

Fertility desires and intentions of HIV-positive women of reproductive age in Ontario, Canada: a cross-sectional study.

Background Improvements in life expectancy and quality of life for HIV-positive women coupled with reduced vertical transmission will likely lead numerous HIV-positive women to consider becoming pregnant. In order to clarify the demand, and aid with appropriate health services planning for this population, our study aims to assess the fertility desires and intentions of HIV-positive women of reproductive age living in Ontario, Canada. Methodology/Principal Findings A cross-sectional study with recruitment stratified to match the geographic distribution of HIV-positive women of reproductive age (18–52) living in Ontario was carried out. Women were recruited from 38 sites between October 2007 and April 2009 and invited to complete a 189-item self-administered survey entitled “The HIV Pregnancy Planning Questionnaire” designed to assess fertility desires, intentions and actions. Logistic regression models were fit to calculate unadjusted and adjusted odds ratios of significant predictors of fertility intentions. The median age of the 490 participating HIV-positive women was 38 (IQR, 32–43) and 61%, 52%, 47% and 74% were born outside of Canada, living in Toronto, of African ethnicity and currently on antiretroviral therapy, respectively. Of total respondents, 69% (95% CI, 64%–73%) desired to give birth and 57% (95% CI, 53%–62%) intended to give birth in the future. In the multivariable model, the significant predictors of fertility intentions were: younger age (age<40) (p<0.0001), African ethnicity (p<0.0001), living in Toronto (p = 0.002), and a lower number of lifetime births (p = 0.02). Conclusions/Significance The proportions of HIV-positive women of reproductive age living in Ontario desiring and intending pregnancy were higher than reported in earlier North American studies. Proportions were more similar to those reported from African populations. Healthcare providers and policy makers need to consider increasing services and support for pregnancy planning for HIV-positive women. This may be particularly significant in jurisdictions with high levels of African immigration.

Clinical and cervical cytokine response to treatment with oral or vaginal metronidazole for bacterial vaginosis during pregnancy: a randomized trial.

OBJECTIVE To compare the efficacy of oral versus vaginal metronidazole treatment in pregnant women with bacterial vaginosis, and to compare cytokine profiles (interleukin-1β, -6, and -8) in the cervical secretions of these women before and after treatment. METHODS Pregnant women with bacterial vaginosis diagnosed both by Gram stain and clinical criteria were randomized to receive oral (n = 52) or vaginal (n = 50) metronidazole therapy. Cervical specimens for cytokine analysis and vaginal fluid for evaluation of bacterial vaginosis were obtained at baseline and 4 weeks after treatment. RESULTS There was no significant difference in therapeutic cure rates (defined as a Gram stain score of 0–3 and the absence of all four clinical signs of bacterial vaginosis) between the two groups (71% and 70% for the oral and vaginal groups, respectively, P = 1.0). Cervical levels of interleukin-1β, -6, and -8 were significantly lower after treatment among the 72 women cured of bacterial vaginosis (P < .001, P = .001, and P = .02, respectively) but not among women who failed to respond to therapy. For interleukin-1β and -6, a significant decrease in cytokine level was observed in both the oral and vaginal treatment groups. CONCLUSION One week of oral metronidazole and 5 days of intravaginal metronidazole are equally efficacious for treatment of bacterial vaginosis during pregnancy. The decrease in cervical interleukin-1β, -6, and -8 levels among women who established a normal flora after treatment but not among those with persistent bacterial vaginosis suggests a direct linkage between vaginal flora abnormalities and elevated cervical levels of interleukin-1β, -6, and -8.

Pregnant Women’s Knowledge of Influenza and the Use and Safety of the Influenza Vaccine During Pregnancy

INTRODUCTION We wished to assess pregnant womens knowledge of influenza, vaccine safety during pregnancy and breast feeding, and the recommendations for use of the influenza vaccine in pregnancy. METHODS We performed a cross-sectional survey of postpartum women during influenza season in 2006. RESULTS Pregnant womens overall knowledge of these subjects was poor. Most women (95%) knew that influenza is highly contagious, but almost 90% incorrectly believed that pregnant women have the same risk of complications as non-pregnant women. Only one half of the women were aware of national recommendations for vaccination during pregnancy and that the vaccine is safe during pregnancy and breast feeding, and 80% incorrectly believed that the vaccine can cause birth defects. Only 20% of women had been offered the vaccine during the current pregnancy or a prior pregnancy. CONCLUSIONS Pregnant womens knowledge about influenza vaccine recommendations and safety during pregnancy is poor. There is substantial room for improvement among prenatal care providers in both patient education and offering the vaccine.

Screening, Diagnosis, and Management of Cytomegalovirus Infection in Pregnancy

Congenital cytomegalovirus (CMV) is the most common intrauterine infection and the leading infectious cause of sensorineural hearing loss and mental retardation. This article reviews the issues that relate to the diagnosis and management of this disease, detailing the points that led to the recent published guidelines by the Society of Obstetricians and Gynaecologists of Canada. A MEDLINE/Cochrane search of CMV infection, pregnancy, and prenatal diagnosis found 195 studies between 1980 and 2010. Of these, we examined 59 relevant studies. The probability of intrauterine transmission following primary infection is 30% to 40%, but only 1% after secondary infection. About 10% to 15% of congenitally infected infants will have symptoms at birth, and 20% to 30% of them will die, whereas 5% to 15% of the asymptomatic infected neonates will develop sequelae later. Children with congenital CMV infection following first trimester infection are more likely to have central nervous system sequelae, whereas infection acquired in the third trimester has a high rate of intrauterine transmission but a favorable outcome. The prenatal diagnosis of fetal CMV infection should be based on amniocentesis performed 7 weeks after the presumed time of infection and after 21 weeks of gestation. Sonographic findings often imply poor prognosis, but their absence does not guarantee a normal outcome. The value of quantitative determination of CMV DNA in the amniotic fluid is not yet confirmed. The effectiveness of prenatal therapy for fetal CMV is not yet proven, although CMV-specific hyperimmune globulin may be beneficial. Routine serologic screening of pregnant women or newborns has never been recommended by any public health authority. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this educational activity, the obstetrician/gynecologist should be better able to evaluate the principles of prenatal diagnosis of congenital CMV infection so doctors will be familiar with the tests and procedures needed, in order to reach a diagnosis of congenital CMV; to assess the natural history and outcome of congenital CMV infection enabling obstetricians to counsel prenatally pregnant women with CMV; and to analyze the prognostic markers for fetal CMV, so managing physicians will be able to predict more accurately the outcomes of fetuses infected by CMV.

Cytomegalovirus Infection in Pregnancy

OBJECTIVES To review the principles of prenatal diagnosis of congenital cytomegalovirus (CMV) infection and to describe the outcomes of the affected pregnancies. OUTCOMES Effective management of fetal infection following primary and secondary maternal CMV infection during pregnancy. Neonatal signs include intrauterine growth restriction (IUGR), microcephaly, hepatosplenomegaly, petechiae, jaundice, chorioretinitis, thrombocytopenia and anemia, and long-term sequelae consist of sensorineural hearing loss, mental retardation, delay of psychomotor development, and visual impairment. These guidelines provide a framework for diagnosis and management of suspected CMV infections. EVIDENCE Medline was searched for articles published in English from 1966 to 2009, using appropriate controlled vocabulary (congenital CMV infection) and key words (intrauterine growth restriction, microcephaly). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. Searches were updated on a regular basis and incorporated into the guideline. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. RECOMMENDATIONS The quality of evidence reported in this document has been assessed using the evaluation of evidence criteria in the Report of the Canadian Task Force on Preventive Health Care (Table 1). 1. Diagnosis of primary maternal cytomegalovirus (CMV) infection in pregnancy should be based on de-novo appearance of virus-specific IgG in the serum of a pregnant woman who was previously seronegative, or on detection of specific IgM antibody associated with low IgG avidity. (II-2A) 2. In case of primary maternal infection, parents should be informed about a 30% to 40% risk for intrauterine transmission and fetal infection, and a risk of 20% to 25% for development of sequelae postnatally if the fetus is infected. (II-2A) 3. The prenatal diagnosis of fetal CMV infection should be based on amniocentesis, which should be done at least 7 weeks after presumed time of maternal infection and after 21 weeks of gestation. This interval is important because it takes 5 to 7 weeks following fetal infection and subsequent replication of the virus in the kidney for a detectable quantity of the virus to be secreted to the amniotic fluid. (II-2A) 4. The diagnosis of secondary infection should be based on a significant rise of IgG antibody titre with or without the presence of IgM and high IgG avidity. In cases of proven secondary infection, amniocentesis may be considered, but the risk-benefit ratio is different because of the low transmission rate. (III-C) 5. Following a diagnosis of fetal CMV infection, serial ultrasound examinations should be performed every 2 to 4 weeks to detect sonographic abnormalities, which may aid in determining the prognosis of the fetus, although it is important to be aware that the absence of sonographic findings does not guarantee a normal outcome. (II-2B) 6. Quantitative determination of CMV DNA in the amniotic fluid may assist in predicting the fetal outcome. (II-3B) 7. Routine screening of pregnant women for CMV by serology testing is currently not recommended. (III-B) 8. Serologic testing for CMV may be considered for women who develop influenza-like illness during pregnancy or following detection of sonographic findings suggestive of CMV infection. (III-B) 9. Seronegative health care and child care workers may be offered serologic monitoring during pregnancy. Monitoring may also be considered for seronegative pregnant women who have a young child in day care. (III-B).

High prevalence of unintended pregnancies in HIV-positive women of reproductive age in Ontario, Canada: a retrospective study.

There is speculation, but there are few data, on the high rates of unintended pregnancies in HIV‐positive women. We investigated rates and correlates of unintended pregnancies among HIV‐positive women of reproductive age.

Antibiotic Prophylaxis in Gynaecologic Procedures

Abstract Objective To review the evidence and provide recommendations on antibiotic prophylaxis for gynaecologic procedures. Outcomes Outcomes evaluated include need and effectiveness of antibiotics to prevent infections in gynaecologic procedures. Evidence Medline and The Cochrane Library were searched for articles published between January 1978 and January 2011 on the topic of antibiotic prophylaxis in gynaecologic procedures. Results were restricted to systematic reviews, randomized control trials/ controlled clinical trials, and observational studies. Searches were updated on a regular basis and incorporated in the guideline to June 2011. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Values The quality of evidence obtained was rated using the criteria described in the Report of the Canadian Task Force on Preventative Health Care (Table 1). Benefits, harms, and costs Guideline implementation should result in a reduction of cost and related harm of administering antibiotics when not required and a reduction of infection and related morbidities when antibiotics have demonstrated a proven benefit. Recommendations 1. All women undergoing an abdominal or vaginal hysterectomy should receive antibiotic prophylaxis. (I-A) 2. All women undergoing laparoscopic hysterectomy or laparoscopically assisted vaginal hysterectomy should receive prophylactic antibiotics. (III-B) 3. The choice of antibiotic for hysterectomy should be a single dose of a first-generation cephalosporin. If patients are allergic to cephalosporin, then clindamycin, erythromycin, or metronidazole should be used. (I-A) 4. Prophylactic antibiotics should be administered 15 to 60 minutes prior to skin incision. No additional doses are recommended. (I-A) 5. If an open abdominal procedure is lengthy (e.g., > 3 hours), or if the estimated blood loss is > 1500 mL, an additional dose of the prophylactic antibiotic may be given 3 to 4 hours after the initial dose. (III-C) 6. Antibiotic prophylaxis is not recommended for laparoscopic procedures that involve no direct access from the abdominal cavity to the uterine cavity or vagina. (l-E) 7. All women undergoing surgery for pelvic organ prolapse and/or stress urinary incontinence should receive a single dose of firstgeneration cephalosporin. (III-B) 8. Antibiotic prophylaxis is not recommended for hysteroscopic surgery. (II-2D) 9. All women undergoing an induced (therapeutic) surgical abortion should receive prophylactic antibiotics to reduce the risk of postabortal infection. (I-A) 10. Prophylactic antibiotics are not suggested to reduce infectious morbidity following surgery for a missed or incomplete abortion. (I-E) 11. Antibiotic prophylaxis is not recommended for insertion of an intrauterine device. (I-E) However, health care professionals could consider screening for sexually transmitted infections in high-risk populations. (III-C) 12. There is insufficient evidence to support the use of antibiotic prophylaxis for an endometrial biopsy. (III-L) 13. The best method to prevent infection after hysterosalpingography is unknown. Women with dilated tubes found at the time of hysterosalpingography are at highest risk, and prophylactic antibiotics (e.g., doxycycline) should be given. (II-3B) 14. Antibiotic prophylaxis is not recommended for urodynamic studies in women at low risk, unless the incidence of urinary tract infection post-urodynamics is > 10%. (1-E) 15. In patients with morbid obesity (BMI > 35 kg/m2), doubling the antibiotic dose may be considered. (III-B) 16 Administration of antibiotics solely to prevent endocarditis is not recommended for patients who undergo a genitourinary procedure. (III-E)

Cytokines, Pregnancy, and Bacterial Vaginosis: Comparison of Levels of Cervical Cytokines in Pregnant and Nonpregnant Women with Bacterial Vaginosis

BACKGROUND Pregnancy has been considered to be a time of relative immune compromise. Lower-genital-tract immune response appears to be influenced by pregnancy. The objective of this study was to compare, in pregnant versus nonpregnant women, endocervical proinflammatory-cytokine expression in response to bacterial vaginosis. METHODS Endocervical levels of interleukin (IL)-1 beta , IL-6, and IL-8 in 99 pregnant and 99 nonpregnant women, all with bacterial vaginosis and without concurrent sexually transmitted infections, were assessed by ELISA. Vaginal flora was characterized on the basis of quantitative vaginal cultures. RESULTS Women in the 2 groups differed with respect to smoking status and microbiological constituents responsible for bacterial vaginosis. When the data were stratified by these potential confounders, the levels of all 3 proinflammatory endocervical cytokines were significantly higher in pregnant women than in nonpregnant women. CONCLUSIONS The proinflammatory cytokine milieu in the cervix is enhanced in pregnant women with bacterial vaginosis, compared with that in nonpregnant women. The notion of pregnancy as an immune-compromised state may be anatomically compartment specific.

Acceptability of maternal immunization against influenza: the critical role of obstetricians

Introduction: Pregnant women and infants are at increased risk of vaccine-preventable complications due to influenza. In Switzerland, immunization was first recommended to all pregnant women in 2009. We assessed the acceptability of this recommendation and its determinants two seasons later. Methods: Women having delivered in the University Hospitals of Geneva during March 2011 were asked to fill in a questionnaire assessing their knowledge, beliefs and acceptability of influenza vaccination during pregnancy. Results: The questionnaire was completed by 261/323 (80%) women. Out of 261, 213 (82%) were aware of increased risks of influenza during pregnancy, and 119/261 (46%) knew that immunization was recommended during pregnancy. Only 110/261 (42%) recalled an immunization advise during their pregnancy and only 47/261 (18%) had been immunized. A direct recommendation was the main predictor of immunization, associated with a 107-fold increased likelihood of vaccination. Factors identified by multivariate analyses as independently associated with the likelihood of immunization were to have been recommended immunization by a private (OR 9.1) or hospital (OR 4.7) obstetrician rather than a midwife, to have no fear that immunization could cause preterm delivery (OR 0.3) and to have been immunized in previous years (OR 10.7). Conclusion: Two years after the recommendation of influenza immunization during pregnancy, most post-partum women recalled being neither recommended nor adequately informed about influenza vaccine and its safety. This identifies major gaps in awareness and/or communication in healthcare workers and suggests that improving immunization safety/efficacy awareness among obstetricians as the most likely method to improve flu immunization during pregnancy.

HIV protease inhibitor use during pregnancy is associated with decreased progesterone levels, suggesting a potential mechanism contributing to fetal growth restriction.

BACKGROUND Protease inhibitor (PI)-based combination antiretroviral therapy (cART) is administered during pregnancy to prevent perinatal human immunodeficiency virus (HIV) transmission. However, PI use has been associated with adverse birth outcomes, including preterm delivery and small-for-gestational-age (SGA) births. The mechanisms underlying these outcomes are unknown. We hypothesized that PIs contribute to these adverse events by altering progesterone levels. METHODS PI effects on trophoblast progesterone production were assessed in vitro. A mouse pregnancy model was used to assess the impact of PI-based cART on pregnancy outcomes and progesterone levels in vivo. Progesterone levels were assessed in plasma specimens from 27 HIV-infected and 17 HIV-uninfected pregnant women. RESULTS PIs (ritonavir, lopinavir, and atazanavir) but not nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors reduced trophoblast progesterone production in vitro. In pregnant mice, PI-based cART but not dual-NRTI therapy was associated with significantly lower progesterone levels that directly correlated with fetal weight. Progesterone supplementation resulted in a significant improvement in fetal weight. We observed lower progesterone levels and smaller infants in HIV-infected women receiving PI-based cART, compared with the control group. In HIV-infected women, progesterone levels correlated significantly with birth weight percentile. CONCLUSIONS Our data suggest that PI use in pregnancy may lead to lower progesterone levels that could contribute to adverse birth outcomes.