Begoña Martinez de Tejada

Maternal Immunization Earlier in Pregnancy Maximizes Antibody Transfer and Expected Infant Seropositivity Against Pertussis

Guidelines recommend that pregnant women be vaccinated against pertussis between gestational weeks 26 and 36. We show that this narrow window can be widened, as optimal neonatal antibody concentrations and expected infant seropositivity rates are elicited between weeks 13 and 33.

Effects of recommended levels of physical activity on pregnancy outcomes

OBJECTIVE We sought to examine the relation between recommended levels of physical activity during pregnancy and pregnancy outcomes. STUDY DESIGN We conducted an observational study with energy expenditure, aerobic fitness, and sleeping heart rate measured in 44 healthy women in late pregnancy. Medical records were examined for pregnancy outcome. RESULTS Active women, who engaged in > or = 30 minutes of moderate physical activity per day, had significantly better fitness and lower sleeping heart rate compared to the inactive. Duration of second stage of labor was 88 and 146 minutes in the active vs inactive women, respectively (P = .05). Crude odds ratio of operative delivery in the inactive vs the active was 3.7 (95% confidence interval, 0.87-16.08). Birthweight, maternal weight gain, and parity adjusted odds ratio was 7.6 (95% confidence interval, 1.23-45.8). Neonatal condition and other obstetric outcomes were similar between groups. CONCLUSION Active women have better aerobic fitness as compared to inactive women. The risk for operative delivery is lower in active women compared to inactive, when controlled for birthweight, maternal weight gain, and parity. Further studies with larger sample size are required to confirm the association between physical activity and pregnancy outcomes.

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.

Intravenous iron treatment in pregnancy: comparison of high-dose ferric carboxymaltose vs. iron sucrose.

Abstract Objective: Oral iron substitution has shown to be insufficient for treatment of severe iron deficiency anemia in pregnancy. Ferric carboxymaltose is a new intravenous (i.v.) iron formulation promising to be more effective and as safe as iron sucrose. We aimed to assess side effects and tolerance of ferric carboxymaltose compared to i.v. iron sucrose in pregnant women. Methods: We performed a retrospective analysis of 206 pregnant women who were treated either with ferric carboxymaltose or iron sucrose for iron-deficiency anemia with intolerability to oral iron substitution, or insufficient hemoglobin increase after oral iron treatment, or need for rapid hemoglobin reconstitution. Primary endpoint was to evaluate the maternal safety and tolerability. Secondary endpoint was to assess efficacy of the treatment and exclude safety concerns for the fetus. Results: The incidence of drug-related adverse events was low and mostly mild in both groups. Mild adverse events occurred in 7.8% for ferric carboxymaltose and in 10.7% for iron sucrose. The mean rise of hemoglobin value was 15.4 g/L for ferric carboxymaltose and 11.7 g/L for iron sucrose. Conclusion: Ferric carboxymaltose administration in pregnant women is well tolerated and is not associated with any relevant clinical safety concerns. Ferric carboxymaltose has a comparable safety profile to iron sucrose but offers the advantage of a much higher iron dosage at a time reducing the need for repeated applications and increasing patients’ comfort. Ferric carboxymaltose is the drug of choice, if i.v. iron treatment becomes necessary in the second or third trimester of pregnancy.

Determination of unbound antiretroviral drug concentrations by a modified ultrafiltration method reveals high variability in the free fraction.

Total plasma concentrations are used for therapeutic drug monitoring of antiretroviral drugs, whereas antiviral activity is expected to depend on unbound concentrations. The determination of free (unbound) concentrations by ultrafiltration may be flawed by the irreversible adsorption of many drugs onto the membrane filters and plastic components of the device. The authors describe a modified ultrafiltration method enabling the accurate measurement of unbound concentrations of 10 antiretroviral drugs by liquid chromatography-tandem mass spectroscopy, which circumvents the problem of loss by adsorption in the early ultrafiltration fractions. The method was applied to assess the variability of free fractions of antiretroviral drugs during routine therapeutic drug monitoring in 144 patients with HIV. In in vitro experiments, ultrafiltrate collected in four fractions (0-8, 8-16, 16-24, and 24-30 minutes) gave much lower and more variable free drug concentrations in the first ultrafiltrate fraction than in the last three fractions for lopinavir, nelfinavir, saquinavir, tipranavir, and efavirenz. In the last two fractions, free concentrations remained constant, indicating saturable adsorption. The adsorption was modest for indinavir, amprenavir, and ritonavir, and unnoticeable for atazanavir and nevirapine. Free fraction values obtained with this modified ultrafiltration method reveal substantial interindividual variability, suggesting that monitoring unbound antiretroviral drug concentrations may increase its clinical usefulness, especially for lopinavir, saquinavir, and efavirenz.

Missed opportunities among HIV-positive women to control viral replication during pregnancy and to have a vaginal delivery.

Introduction:Most national guidelines for the prevention of mother-to-child transmission of HIV in Europe updated between 2001 and 2010 recommend vaginal deliveries for women with undetectable or very low viral load (VL). Our aim was to explore the impact of these new guidelines on the rates of vaginal deliveries among HIV-positive women in Europe. Methods:In a pooled analysis of data on HIV-positive pregnant women enrolled in the Swiss Mother & Child HIV Cohort Study and the European Collaborative Study 2000 to 2010, deliveries were classified as occurring pre- or postpublication of national guidelines recommending vaginal delivery. Results:Overall, 2663 women with 3013 deliveries were included from 10 countries; 28% women were diagnosed with HIV during pregnancy. Combination antiretroviral therapy was used in most pregnancies (2020, 73%), starting during the first or second trimester in 78% and during the third trimester in 22%; in 25% pregnancies, the woman conceived on combination antiretroviral therapy. Overall, in 86% pregnancies, a VL < 400 copies per milliliter was achieved before delivery. The proportion of vaginal deliveries increased from 17% (414/2377) before the change in guidelines to 52% (313/600) after; elective Caesarean section rates decreased from 65% to 27%. The proportion of women with undetectable VL having a Caesarean section was 55% after implementation of new guidelines. We observed a decrease of late preterm deliveries from 16% (377/2354) before to 7% (42/599) after the change in guidelines (P < 0.001). Conclusion:There are still missed opportunities for women with HIV to fully suppress their VL and to deliver vaginally in Europe.

Frequency of Gynecologic Follow-Up and Cervical Cancer Screening in the Swiss HIV Cohort Study

Background:According to current recommendations, HIV-infected women should have at least 1 gynecologic examination per year. Objectives:To analyze factors associated with frequency of gynecologic follow-up and cervical cancer screening among HIV-infected women followed in the Swiss HIV Cohort Study (SHCS). Methods:Half-yearly questionnaires between April 2001 and December 2004. At every follow-up visit, the women were asked if they had had a gynecologic examination and a cervical smear since their last visit. Longitudinal models were fitted with these variables as outcomes. Results:A total of 2186 women were included in the analysis. Of the 1146 women with complete follow-up in the SHCS, 35.3% had a gynecologic examination in each time period, whereas 7.4% had never gone to a gynecologist. Factors associated with a poor gynecologic follow-up were older age, nonwhite ethnicity, less education, underweight, obesity, being sexually inactive, intravenous drug use, smoking, having a private infectious disease specialist as a care provider, HIV viral load <400 copies/mL, and no previous cervical dysplasia. No association was seen for living alone, CD4 cell count, and positive serology for syphilis. Conclusions:Gynecologic care among well-followed HIV-positive women is poor and needs to be improved.

Antibiotic Use and Misuse during Pregnancy and Delivery: Benefits and Risks

Although pregnancy is considered as a physiological state, most pregnant women in developed countries receive multiple medications to prevent maternal or neonatal complications, with antibiotics among the most frequently prescribed. During pregnancy, antibiotics are often prescribed in the context of preterm labor, intrapartum fever, prevention of neonatal Group B Streptococcus fever, and cesarean section. Outside this period, they are commonly prescribed in the community setting for respiratory, urinary, and ear, nose and throat infection symptoms. Whereas some of the current indications have insightful reasons to justify their use, potential risks related to overuse and misuse may surpass the benefits. Of note, the recent 2014 World Health Assembly expressed serious concern regarding antibiotic resistance due to antibiotic overuse and misuse and urged immediate action to combat antibiotic resistance on a global scale. Most studies in the obstetrics field have focused on the benefits of antibiotics for short-term maternal and neonatal complications, but with very little (if any) interest in long-term consequences.

Antiretroviral treatment during pregnancy

Objective: Virologic failure of HIV-positive patients is of special concern during pregnancy. We compared virologic failure and the frequency of treatment changes in pregnant and non-pregnant women of the Swiss HIV Cohort Study. Methods: Using data on 372 pregnancies in 324 women we describe antiretroviral therapy during pregnancy. Pregnant women on HAART at conception (n = 131) were matched to 228 non-pregnant women (interindividual comparison) and to a time period of equal length before and after pregnancy (intraindividual comparison). Women starting HAART during pregnancy (n = 145) were compared with 578 non-pregnant women starting HAART. Findings: The median age at conception was 31 years, 16% (n = 50) were infected through injecting drug use and the median CD4 cell count was 489 cells/μl. In the majority of pregnancies (n = 220, 59%), women had started ART before conception. When ART was started during pregnancy (n = 145, 39%), it was mainly during the second trimester (n = 100, 69%). Two thirds (n = 26) of 35 women starting in the third trimester were diagnosed with HIV during pregnancy. The risk of virologic failure tended to be lower in pregnant than in non-pregnant women [adjusted odds ratio 0.52 (95% confidence interval 0.25–1.09, P = 0.08)], but was similar in the intraindividual comparison (adjusted odds ratio 1.04, 95% confidence interval 0.48–2.28). Women starting HAART during pregnancy changed the treatment less often than non-pregnant women. Conclusion: Despite the physiological changes occurring during pregnancy, HIV infected pregnant women are not at higher risk of virologic failure.

Pertussis Antibody Transfer to Preterm Neonates After Second- Versus Third-Trimester Maternal Immunization

Abstract Preterm infants are most vulnerable to pertussis. Whether they might benefit from maternal immunization is unknown. Extending our previous results in term neonates, this observational study demonstrates that second- rather than third-trimester maternal vaccination results in higher birth anti–pertussis toxin titers in preterm neonates.