Profile of Chronic Comorbid Conditions and Obstetrical Complications Among Pregnant Women With Human Immunodeficiency Virus and Receiving Antiretroviral Therapy in the United States.

BACKGROUND: To evaluate the frequency and associated characteristics of chronic comorbid conditions and obstetrical complications among pregnant women with human immunodeficiency virus (HIV) and receiving antiretroviral therapy (ART) in comparison to those without HIV. METHODS: We compared 2 independent concurrent US pregnancy cohorts: (1) with HIV (International Maternal Pediatric Adolescent AIDS Clinical Trials Protocol P1025, 2002-2013) and (2) without HIV (Consortium for Safe Labor Study, 2002-2007). Outcomes were ≥2 chronic comorbid conditions and obstetrical complications. For women with HIV, we assessed whether late prenatal care (≥14 weeks), starting ART in an earlier era (2002-2008), and a detectable viral load at delivery (≥400 copies/mL) were associated with study outcomes. RESULTS: We assessed 2868 deliveries (n = 2574 women) with HIV and receiving ART and 211 910 deliveries (n = 193 170 women) without HIV. Women with HIV were more likely to have ≥2 chronic comorbid conditions versus those without HIV (10 vs 3%; adjusted OR [AOR]: 2.96; 95% CI: 2.58-3.41). Women with HIV were slightly less likely to have obstetrical complications versus those without HIV (both 17%; AOR: .84; 95% CI: .75-.94), but secondarily, higher odds of preterm birth <37 weeks. Late entry to prenatal care and starting ART in an earlier era were associated with a lower likelihood of ≥2 chronic comorbidities and obstetrical complications; detectable viral load at delivery was associated with a higher likelihood of obstetric complications. CONCLUSIONS: Pregnant women with HIV receiving ART have more chronic comorbid conditions, but not necessarily obstetrical complications, than their peers without HIV.

Peripartum Maternal Hepatitis B Care in a US Nationwide Data Set.

BACKGROUND: Hepatitis B virus (HBV) screening during pregnancy is standard of care to prevent vertical transmission to infants, yet the mothers themselves may not receive appropriate follow-up. GOALS: Using a national database, we sought to determine rates of maternal peripartum follow-up with a HBV specialist and identify factors associated with a lack of follow-up. MATERIALS AND METHODS: We identified women who delivered in 2000 to 2012 and were diagnosed with HBV according to International Classification of Diseases-9 codes using a national database (Optum) derived from commercial insurance claims with ∼46 million members ages 0 to 64 in all 50 states. Our primary outcome was follow-up during or after pregnancy with a HBV specialist (gastroenterology/infectious diseases). RESULTS: The prevalence of HBV was 0.27% (2558/959,747 pregnancies), and median follow-up was 45 months. Only 21% of women had peripartum HBV specialist follow-up. On multivariable regression, predictors of peripartum follow-up at 1-year included younger age [odds ratio (OR), 0.97/y; 95% confidence interval (CI), 0.94, 0.99], Asian race/ethnicity (OR, 1.56 vs. white; 95% CI, 1.13, 2.17), and residing in the Northeast (OR, 1.70; 95% CI, 1.09, 2.66) and Midwest (OR, 1.73; 95% CI, 1.07, 2.81) versus West. Predictors of testing for HBV DNA and alanine aminotransferase at 1 year included Asian race (OR, 1.72; 95% CI, 1.23, 2.41), a primary care physician visit within 2 years of delivery (OR, 1.63; 95% CI, 1.19, 2.22), and peripartum HBV specialist follow-up within 1 year (OR, 15.68; 95% CI, 11.38, 21.60). CONCLUSIONS: Maternal HBV specialist follow-up rates were extremely low in this large, diverse cohort representing all United States regions. Referral to a HBV specialist was the strongest predictor of appropriate postpartum HBV laboratory testing. Follow-up rates may be even lower in uninsured populations.

Peripartum Care for Mothers Diagnosed with Hepatitis B During Pregnancy: A Survey of Provider Practices.

Objectives Hepatitis B (HBV) remains a significant public health burden, despite effective therapy. Routine HBV screening is recommended during pregnancy to reduce the risk of vertical transmission, but the rates of follow-up care peri-partum are low. The aim of this study was to evaluate physician practices and knowledge regarding HBV in women diagnosed perinatally. Methods A survey was distributed to obstetricians and midwives within the Partners HealthCare system at Brigham and Women's Hospital and Massachusetts General Hospital. Results Of 118 survey respondents (response rate 56%), 97% reported that they always tested for hepatitis B, and 77% referred new diagnoses of HBV during pregnancy to a HBV specialist for further care. Only 10% of respondents reported that there was formal referral mechanism in place to facilitate follow-up care for mothers diagnosed with hepatitis B infection. 91% of survey respondents selected hepatitis B surface antigen as the correct screening test, and 76% selected hepatitis B immune globulin with vaccination for the newborn as the correct prophylaxis regimen. Only 40 and 51% of respondents accurately identified serologies that were consistent with acute and chronic infection, respectively. Conclusions for Practice Routine screening for HBV in this population presents an important opportunity to identify cases and to reduce the public health burden of this disease. Providers were somewhat knowledgeable about HBV, but the lack of formal referral mechanism may explain why HBV follow-up is suboptimal in this healthcare system. Supplemental provider education and formal linkage to care programs may increase rates of follow-up HBV care.

Postpartum Laboratory Follow-up in Women With Hepatitis B in Massachusetts From 2007 to 2012.

GOALS: To determine postpartum hepatitis B virus (HBV) laboratory testing rates and identify factors associated with a lack of follow-up testing in Massachusetts. BACKGROUND: Screening for HBV infection in pregnant women is standard of care. Guidelines recommend that patients with chronic HBV have ongoing care and laboratory testing, but little is known about postpartum maternal HBV care outcomes. STUDY: We conducted a retrospective cohort study using Massachusetts Virtual Epidemiologic Network, an electronic public health surveillance system maintained by the Massachusetts Department of Public Health. We identified women who tested hepatitis B surface antigen positive during their first reported (index) pregnancy in Massachusetts from 2007 to 2012 and measured HBV-related laboratory tests reported to Massachusetts Department of Public Health during and after pregnancy. RESULTS: We identified 983 hepatitis B surface antigen positive pregnant women. Half (492/983) did not have evidence of additional postpartum HBV laboratory testing following their index pregnancy. Women who had postpartum laboratory tests reported were younger [mean age (SD): 29 (5.3) vs. 31 (5.5) y, P=0.0001] and more likely to have >1 pregnancy during the study period (41% vs. 1%, P<0.0001). There were no differences in race, ethnicity, and US born status. On multivariable logistic regression, older age predicted a lower likelihood of having postpartum laboratory testing (odds ratio, 0.77; 95% confidence interval, 0.70-0.90). CONCLUSIONS: Postpartum maternal HBV follow-up laboratory testing occurred in only half of Massachusetts women and did not vary by race, ethnicity, or US born status. Our results were limited to a single state surveillance database, which likely underestimates the number of tests ordered.

Defining Physiological Predictors of Peripartum Maternal Bacteremia.

OBJECTIVE: This study aims to examine physiological and laboratory parameters associated with peripartum maternal bacteremia. STUDY DESIGN: This case-control study matched 115 cases (women with fever and bacteremia during the peripartum period) to 285 controls (defined as the next two febrile women with negative blood cultures at the same institution) from two academic medical centers from 2009 to 2013. Conditional logistic regression models were used to evaluate the association of physiological and laboratory parameters with maternal bacteremia at the time of initial and maximum fever. RESULTS: At the time of initial fever, temperature > 103°F (adjusted odds ratio [aOR]: 5.58, 95% confidence interval [CI]: 2.05-15.19) and respiratory rate (RR) > 20 respirations per minute (aOR: 5.27, 95% CI: 2.32-11.96) were associated with bacteremia. At the time of maximum fever, temperature (> 102°F, aOR: 3.37, 95% CI: 1.61-7.06; > 103°F, aOR: 7.96, 95% CI: 3.56-17.82), heart rate > 110 beats per minute (aOR: 2.20, 95% CI: 1.21-3.99), and RR > 20 (aOR: 3.65, 95% CI: 1.65-8.08) were associated with bacteremia. Bandemia > 10% (aOR: 2.44, 95% CI: 1.07-5.54) was associated with bacteremia. CONCLUSION: Physiological and laboratory parameters associated with maternal bacteremia differed from those reported with sepsis in the adult critical care population. Further studies of objective markers are needed to improve detection and treatment of peripartum bacteremia.

Oral Nirmatrelvir-Ritonavir Use and Clinical Outcomes in Pregnant Patients With Coronavirus Disease 2019 (COVID-19).

We conducted a retrospective cohort study of pregnant patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by RNA polymerase chain reaction test or home test who were counseled about taking nirmatrelvir-ritonavir if they were within 5 days of symptom onset. Obstetric and coronavirus disease 2019 (COVID-19) outcomes were compared between patients who did and did not take the medication. Overall, 114 individuals took nirmatrelvir-ritonavir and 323 did not. The cohorts were comparable, including high rates of vaccination in both groups. Nirmatrelvir-ritonavir was well-tolerated, with no patients discontinuing medication due to side effects. There were no intensive care unit admissions in either group. Most obstetric and medical outcomes were similar between those taking and not taking nirmatrelvir-ritonavir. Patients taking nirmatrelvir-ritonavir had significantly higher rates of surgical site infection (3 [2.7%] vs 0 [0%], P =.02) and preeclampsia (11 [9.6%] vs 12 [3.7%], P =.02). Outcome event numbers were too small for multivariable modeling. These preliminary data may be reassuring to clinicians and patients who would like to use nirmatrelvir-ritonavir in pregnancy.

Influence of body weight, ethnicity, oral contraceptives, and pregnancy on the pharmacokinetics of azithromycin in women of childbearing age.

Women of childbearing age commonly receive azithromycin for the treatment of community-acquired infections, including during pregnancy. This study determined azithromycin pharmacokinetics in pregnant and nonpregnant women and identified covariates contributing to pharmacokinetic variability. Plasma samples were collected by using a sparse-sampling strategy from pregnant women at a gestational age of 12 to 40 weeks and from nonpregnant women of childbearing age receiving oral azithromycin for the treatment of an infection. Pharmacokinetic data from extensive sampling conducted on 12 healthy women were also included. Plasma samples were assayed for azithromycin by high-performance liquid chromatography. Population data were analyzed by nonlinear mixed-effects modeling. The population analysis included 53 pregnant and 25 nonpregnant women. A three-compartment model with first-order absorption and a lag time provided the best fit of the data. Lean body weight, pregnancy, ethnicity, and the coadministration of oral contraceptives were covariates identified as significantly influencing the oral clearance of azithromycin and, except for oral contraceptive use, intercompartmental clearance between the central and second peripheral compartments. No other covariate relationships were identified. Compared to nonpregnant women not receiving oral contraceptives, a 21% to 42% higher dose-adjusted azithromycin area under the plasma concentration-time curve (AUC) occurred in non-African American women who were pregnant or receiving oral contraceptives. Conversely, azithromycin AUCs were similar between pregnant African American women and nonpregnant women not receiving oral contraceptives. Although higher levels of maternal and fetal azithromycin exposure suggest that lower doses be administered to non-African American women during pregnancy, the consideration of azithromycin pharmacodynamics during pregnancy should guide any dose adjustments.

Prenatal protease inhibitor use and risk of preterm birth among HIV-infected women initiating antiretroviral drugs during pregnancy.

BACKGROUND: Conflicting results have been reported among studies of protease inhibitor (PI) use during pregnancy and preterm birth. Uncontrolled confounding by indication may explain some of the differences among studies. METHODS: In total, 777 human immunodeficiency virus (HIV)-infected pregnant women in a prospective cohort who were not receiving antiretroviral (ARV) treatment at conception were studied. Births <37 weeks gestation were reviewed, and deliveries due to spontaneous labor and/or rupture of membranes were identified. Risk of preterm birth and low birth weight (<2500 g) were evaluated by using multivariable logistic regression. RESULTS: Of the study population, 558 (72%) received combination ARV with PI during pregnancy, and a total of 130 preterm births were observed. In adjusted analyses, combination ARV with PI was not significantly associated with spontaneous preterm birth, compared to ARV without PI (odds ratio [OR], 1.22; 95% confidence interval [CI], 0.70-2.12). Sensitivity analyses that included women who received ARV prior to pregnancy also did not identify a significant association (OR, 1.34; 95% CI, 0.84-2.16). Low birth weight results were similar. CONCLUSIONS: No evidence of an association between use of combination ARV with PI during pregnancy and preterm birth was found. Our study supports current guidelines that promote consideration of combination ARV for all HIV-infected pregnant women.

Microbiology and Antibiotic Resistance in Peripartum Bacteremia.

OBJECTIVE: To examine the microbiology and associated antibiotic resistance patterns among febrile peripartum women with positive blood cultures. METHODS: We conducted a retrospective cohort study in which we reviewed all bacteremia cases between 2009 and 2016 that occurred between 7 days before and 30 days after delivery. Institutional guidelines include obtaining blood cultures and promptly initiating intravenous antibiotics for all obstetric patients with fever of 100.4°F or higher. We describe antibiotic resistance patterns for the most frequently isolated organisms and perform univariate analyses regarding maternal and neonatal outcomes based on type of bacteremia. RESULTS: Among 56,835 deliveries, 3,797 (6.7%) obstetric patients had blood cultures drawn and 120 (3.2%) had documented bacteremia. The most commonly cultured organisms were Escherichia coli (17.5%, n=21), Bacteroides species (10.8%, n=13), Enterococcus species (10.8%, n=13), group B streptococci (10.8%, n=13), and group A streptococci (5.0%, n=6). E coli had high rates of resistance to ampicillin (n=17, 81.0%) and extended spectrum beta lactams (n=10, 47.6%). Gram-positive bacteremia was noted in 65/120 patients (54.2%), gram-negative bacteremia in 39/120 (32.5%), and anaerobic bacteremia in 16/120 (13.3%) (P=.02). Neonatal bacteremia was identified in 8/120 cases (6.7%), of which 7/8 (87.5%) were attributable to gram-negative bacteria and 1/8 (12.5%) were attributable to gram-positive bacteremia (P=.004). There were no differences in neonatal death or maternal intensive care unit admission. CONCLUSION: Peripartum bacteremia is uncommon, with the most frequently isolated organism being E coli. The evolution of antibiotic resistance patterns in E coli at our institution may be of clinical significance in determining antibiotic choice for peripartum fever.

Diagnostic Validity of the Proposed Eunice Kennedy Shriver National Institute of Child Health and Human Development Criteria for Intrauterine Inflammation or Infection.

OBJECTIVE: To investigate the test characteristics of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) criteria for intrauterine inflammation or infection or both (triple I) and rates of adverse outcomes in a cohort of febrile intrapartum women. METHODS: This retrospective cohort study included women at 24 weeks of gestation or greater from June 2015 to September 2017 at a single tertiary hospital with a temperature 100.4°F or greater (38.0°C) during labor or within 1 hour postpartum, all of whom had blood culture data. Women with a fetal demise, expectantly managed preterm prelabor rupture of membranes, or nonobstetric infections were excluded. Documented fever was defined as a single temperature 102.2°F or greater (39.0°C) or a temperature 100.4°F or greater (38.0°C) but less than 102.2°F (39.0°C) on two measurements 45 minutes apart. We defined two analysis groups: 1) suspected triple I, defined as women with documented fever with clinical signs of infection; and 2) isolated maternal fever, defined as women with at least one temperature 100.4°F or greater (38.0°C) who did not meet criteria for suspected triple I. We assessed test characteristics of suspected triple I to predict 1) confirmed triple I, defined as suspected triple I with placental pathology diagnostic of infection; and 2) adverse clinical infectious outcome, defined as a composite of maternal and neonatal adverse infectious outcomes. We also calculated the incidence of adverse clinical infectious outcomes for both groups. RESULTS: Three hundred thirty-nine women were analyzed: 212 with suspected triple I and 127 with isolated maternal fever. Baseline demographic and obstetric characteristics were similar between groups. The incidence of adverse clinical infectious outcomes was 11.8% among women with suspected triple I and 9.5% among women with isolated maternal fever (P=.50). The sensitivity and specificity of suspected triple I for confirmed triple I were 71.4% (95% CI 61.4-80.1%) and 40.5% (95% CI 33.6-47.8%), respectively, and for an adverse clinical infectious outcome were 67.6% (95% CI 50.2-82.0%) and 38.1% (95% CI 32.6-43.8%), respectively. CONCLUSION: Applying the NICHD criteria to guide clinical diagnosis and management of intrauterine infection or inflammation may overlook an important proportion of laboring febrile women at risk for adverse infectious outcomes.

No association between antepartum serologic and genital tract evidence of herpes simplex virus-2 coinfection and perinatal HIV-1 transmission.

OBJECTIVE: The purpose of this study was to assess the risk of perinatal HIV-1 transmission in women who are coinfected with herpes simplex virus-2 (HSV-2). STUDY DESIGN: We performed a nested case-control study of 26 women whose HIV-1 was transmitted to their infants and 52 control subjects whose HIV-1 was not transmitted. We assessed antepartum serologic evidence of HSV-2 by HSV-2 serostatus and genital tract evidence of HSV-2 by presence of HSV-2 DNA. RESULTS: There was no significant association between antepartum serologic evidence of HSV-2 coinfection and the risk of perinatal HIV-1 transmission. There was also no association between antepartum genital tract evidence of HSV-2 coinfection and risk of perinatal HIV-1 transmission. CONCLUSION: Women who were infected with HIV-1 with antepartum serologic and genital tract evidence of HSV-2 coinfection did not appear to have an increased risk of perinatal HIV-1 transmission. However, further investigations are needed to assess HSV-2 reactivation and the risk of perinatal HIV-1 transmission at the time of delivery.

Changing Patterns and Factors Associated With Mode of Delivery Among Pregnant Women With Human Immunodeficiency Virus Infection in the United States.

OBJECTIVE: To describe patterns and factors associated with mode of delivery among pregnant women with human immunodeficiency virus (HIV) infection in the United States in relation to evolving HIV-in-pregnancy guidelines. METHODS: We conducted an analysis of two observational studies, Pediatric AIDS Clinical Trials Group and International Maternal Pediatric Adolescent AIDS Clinical Trials Network Protocol P1025, which enrolled pregnant women with HIV infection from 1998 to 2013 at more than 60 U.S. acquired immunodeficiency syndrome clinical research sites. Multivariable analyses of factors associated with an HIV-indicated cesarean delivery (ie, for prevention of mother-to-child transmission) compared with other indications were conducted and compared according to prespecified time periods of evolving HIV-in-pregnancy guidelines: 1998-1999, 2000-2008, and 2009-2013. RESULTS: Among 6,444 pregnant women with HIV infection, 21% delivered in 1998-1999, 58% in 2000-2008, and 21% in 2009-2013; 3,025 (47%) delivered by cesarean. Cesarean delivery increased from 30% in 1998 to 48% in 2013. Of all cesarean deliveries, repeat cesarean deliveries increased from 16% in 1998 to 42% in 2013; HIV-indicated cesarean deliveries peaked at 48% in 2004 and then dropped to 12% by 2013. In multivariable analyses, an HIV diagnosis during pregnancy, initiation of antiretroviral therapy in the third trimester, a plasma viral load 500 copies/mL or greater, and delivery between 37 and 40 weeks of gestation increased the likelihood of an HIV-indicated cesarean delivery. In analyses by time period, an HIV diagnosis during pregnancy, initiation of antiretroviral therapy in the third trimester, and a plasma viral load of 500 copies/mL or greater were progressively more likely to be associated with an HIV-indicated cesarean delivery over time. CONCLUSION: Almost 50% of pregnant women with HIV infection underwent cesarean delivery. Over time, the rate of repeat cesarean deliveries increased, whereas the rate of HIV-indicated cesarean deliveries decreased; cesarean deliveries were more likely to be performed in women at high risk of mother-to-child transmission. These findings reinforce the need for both early diagnosis and treatment of HIV infection in pregnancy and the option of vaginal delivery after cesarean among pregnant women with HIV infection.

High prevalence of primary lamivudine and nelfinavir resistance in HIV-1-infected pregnant women in the United States, 1998-2004.

Using a highly sensitive allele-specific polymerase chain reaction assay we detected the M184V mutation for lamivudine resistance in plasma from 9.4% of HIV-1-infected pregnant women enrolled in the Women and Infant Transmission Study between 1998 and 2004. The prevalence of nelfinavir resistance (D30N) was 6.3%. These results suggest a high prevalence of primary lamivudine and nelfinavir resistance among HIV-1-infected pregnant women in the United States, and support routine genotypic resistance testing before initiating mother-to-child-transmission prophylaxis.

Antiretroviral therapy during pregnancy and the risk of an adverse outcome.

BACKGROUND: Some studies suggest that combination antiretroviral therapy in pregnant women with human immunodeficiency virus type 1 (HIV-1) infection increases the risk of premature birth and other adverse outcomes of pregnancy. METHODS: We studied pregnant women with HIV-1 infection who were enrolled in seven clinical studies and delivered their infants from 1990 through 1998. The cohort comprised 2123 women who received antiretroviral therapy during pregnancy (monotherapy in 1590, combination therapy without protease inhibitors in 396, and combination therapy with protease inhibitors in 137) and 1143 women who did not receive antiretroviral therapy. RESULTS: After standardization for the CD4+ cell count and use or nonuse of tobacco, alcohol, and illicit drugs, the rate of premature delivery (<37 weeks of gestation) was similar among the women who received antiretroviral therapy and those who did not (16 percent and 17 percent, respectively); the rate of low birth weight (<2500 g) was 16 percent among the infants born to both groups; and the rate of very low birth weight (<1500 g) was 2 percent for the group that received antiretroviral therapy and 1 percent for the group that did not. The rates of low Apgar scores (<7) and stillbirth were also similar or the same in the two groups. After adjustment for multiple risk factors, combination antiretroviral therapy was not associated with an increased risk of premature delivery as compared with monotherapy (odds ratio, 1.08; 95 percent confidence interval, 0.71 to 1.62) or delivery of an infant with low birth weight (odds ratio, 1.03; 95 percent confidence interval, 0.64 to 1.63). Seven of the women who received combination therapy with protease inhibitors (5 percent) had infants with very low birth weight, as compared with nine women who received combination therapy without protease inhibitors (2 percent) (adjusted odds ratio, 3.56; 95 percent confidence interval, 1.04 to 12.19). CONCLUSIONS: As compared with no antiretroviral therapy or monotherapy, combination therapy for HIV-1 infection in pregnant women is not associated with increased rates of premature delivery or with low birth weight, low Apgar scores, or stillbirth in their infants. The association between combination therapy with protease inhibitors and an increased risk of very low birth weight requires confirmation.

How Effective are New Milestones Assessments at Demonstrating Resident Growth? 1 Year of Data.

OBJECTIVE: Assessment tools that accrue data for the Accreditation Council for Graduate Medical Education Milestones must evaluate residents across multiple dimensions, including medical knowledge, procedural skills, teaching, and professionalism. Our objectives were to: (1) develop an assessment tool to evaluate resident performance in accordance with the Milestones and (2) review trends in resident achievements during the inaugural year of Milestone implementation. DESIGN: A novel venue and postgraduate year (PGY) specific assessment tool was built, tested, and implemented for both operating room and labor and delivery "venues." Resident development of competence and independence was captured over time. To account for variable rotation schedules, the year was divided into thirds and compared using two-tailed Fisher's exact test. SETTING: Brigham and Women's and Massachusetts General Hospitals, Boston MA. PARTICIPANTS: Faculty evaluators and obstetrics and gynecology residents. RESULTS: A total of 822 assessments of 44 residents were completed between 9/2014 and 6/2015. The percentage of labor and delivery tasks completed "independently" increased monotonically across the start of all years: 8.4% for PGY-1, 60.3% for PGY-2, 73.7% for PGY-3, and 87.5% for PGY-4. Assessments of PGY-1 residents demonstrated a significant shift toward "with minimal supervision" and "independent" for the management of normal labor (p = 0.03). PGY-3 residents demonstrated an increase in "able to be primary surgeon" in the operating room, from 36% of the time in the first 2/3 of the year, to 62.3% in the last 1/3 (p < 0.01). CONCLUSION: Assessment tools developed to assist with Milestone assignments capture the growth of residents over time and demonstrate quantifiable differences in achievements between PGY classes. These tools will allow for targeted teaching opportunities for both individual residents and residency programs.

Mode of delivery and postpartum HIV-1 disease progression: the Women and Infants Transmission Study.

OBJECTIVE: To assess the relationship between mode of delivery and subsequent maternal HIV-1 disease progression. DESIGN AND METHODS: Changes in CD4+ lymphocyte percentage (CD4%) and plasma HIV-1 RNA concentration (HIV RNA), and time to progression to AIDS or death among HIV-1-infected women were compared according to mode of delivery [cesarean section before labor and ruptured membranes (SCS), cesarean section after labor and/or after ruptured membranes (NSCS), and vaginal delivery]. Generalized estimating equations were used to compare changes in adjusted mean CD4% and HIV RNA counts by mode of delivery. Cox proportional hazard models were used to assess differences in time to AIDS or death. RESULTS: In adjusted analyses, there were no clinically important differences in HIV-1 disease progression according to mode of delivery (SCS, n = 183; NSCS, n = 221; vaginal, n = 1087), as assessed by changes in CD4% and HIV RNA during the 18 months following delivery, and by progression to AIDS or death during a mean postpartum follow-up of 2.66 years. CONCLUSIONS: The present results suggest that, among HIV-1-infected women in North America, mode of delivery is not associated with subsequent HIV-1 disease progression.

Complications and Route of Delivery in a Large Cohort Study of HIV-1-Infected Women-IMPAACT P1025.

OBJECTIVE: To investigate complications of cesarean section in a cohort of HIV-infected pregnant women. METHODS: IMPAACT P1025 is a prospective cohort study of HIV-1-infected women and infants, enrolled 2002-2013, at clinical sites in the United States and Puerto Rico. Demographic, medical, and obstetric data were collected and analyzed including cesarean indications. The delivery route was categorized as elective cesarean (ECS) (before labor and <5 minutes before membrane rupture), nonelective cesarean (NECS) (all other cesareans) or vaginal delivery. Logistic regression models evaluated associations between delivery route and maternal intrapartum/postpartum morbidities. Composite morbidity of vaginal delivery was compared with ECS and NECS. RESULTS: This study included 2297 women. Of note, 99% used antiretroviral medication and 89% were on a combination antiretroviral therapy regimen; 84% had a HIV-1 viral load ≤400 copies per milliliter before delivery; 46% (1055) delivered vaginally, 35% (798) by ECS, and 19% (444) by NECS. Although interruption of HIV-1 infection was the second most frequent indication for cesarean after repeat cesarean, it decreased as an indication over time. There were no delivery-related maternal mortalities. Overall, 19% of women had ≥1 complication(s)-primarily wound complications (14%) or other infections (11%). Vaginal delivery had the lowest complication rate (13%), followed by ECS (23%), and highest NECS (28%) with an overall P < 0.001. HIV-1 mother-to-child transmission rates were low and did not differ by delivery mode group. CONCLUSIONS: HIV interruption as cesarean indicator declined during the study. Morbidity was more common in HIV-infected women delivering by NECS than ECS and lowest with vaginal delivery. CLINICAL TRIAL REGISTRATION: Prenatal and Postnatal Studies of Interventions for Prevention of Mother-To-Child Transmission https://clinicaltrials.gov/ct2/show/NCT00028145?term=impaact+1025&rank=2 NCT00028145.

Herpes simplex virus hepatitis causing acute liver dysfunction and thrombocytopenia in pregnancy.

BACKGROUND: Herpes simplex virus (HSV) hepatitis in pregnant women is a rare condition. We report a case confirmed by liver biopsy and successfully treated with empiric intravenous acyclovir. CASE: A 25-year-old primigravida at 34 weeks of gestation presented with fever, thrombocytopenia, and markedly elevated liver enzymes. The patient was treated empirically and was delivered by cesarean. After delivery failed to correct her condition, a liver biopsy revealed HSV hepatitis. The fetus was unaffected and the patient recovered with an extended course of acyclovir. CONCLUSION: Pregnant women are susceptible to disseminated HSV causing hepatitis. A high index of suspicion is necessary to diagnose HSV hepatitis and begin appropriate treatment with acyclovir. Herpes simplex virus hepatitis should be included in the differential diagnosis for liver failure during pregnancy.

Peripartum bacteremia in the era of group B streptococcus prophylaxis.

OBJECTIVE: To define the microbial epidemiology and clinical risk factors associated with peripartum bacteremia in the era of group B streptococcus prophylaxis. METHODS: We identified all cases of maternal bacteremia occurring during the peripartum time period (defined as from 7 days before delivery until 30 days after delivery) in a large maternity center from 2000 to 2008. Chart review was performed to determine the clinical factors associated with bacteremia. RESULTS: During the study period, blood cultures were obtained from 1,295 febrile peripartum women (1.6% of all parturients); 172 of 1,295 febrile peripartum women (13.3%) had bacteremia (2.2 cases per 1,000 deliveries) with 194 microbial isolates and 1 yeast. The most frequent bacterial isolates were Escherichia coli (35.9%), enterococci (23.6%), and anaerobic species (9.2%); group B streptococcus was isolated in only eight cases (4.1%). Clinical diagnoses among infected women included endometritis (56%), chorioamnionitis (21%), and urosepsis (8%). Among women with endometritis, 77% underwent cesarean delivery (compared with vaginal delivery; relative risk [RR] 10.85, 95% confidence interval [CI] 6.75-17.45) and 39% delivered at less than 37 weeks of gestation (compared with 37 weeks or more; RR 3.21, 95% CI 2.42-4.25). Severe maternal complications of bacteremia were noted; six women required intensive care unit admission, five women had development of ileus, and one death occurred because of urosepsis. CONCLUSION: In the era of group B streptococcus prophylaxis, E coli and enterococci are the most frequent bacteria isolated in peripartum bacteremia. Group B streptococcus accounted for only 4% of cases. LEVEL OF EVIDENCE: III.

Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy.

BACKGROUND: Pregnancy-limited antiretroviral therapy (PLAT) drastically reduces HIV-1 transmission to the newborn, but may select for antiretroviral drug resistance mutations in mothers. METHODS: We evaluated antiretroviral-naive, HIV-1-infected pregnant women who received PLAT between 1998 and 2005, and had 2-month or 6-month postpartum plasma samples available with HIV-1 RNA levels more than 500 copies/ml. Postpartum drug resistance mutation rates were assessed blindly using population sequencing and allele-specific PCR (ASPCR) of the M184V, K103N and D30N mutations. Factors associated with selection of drug resistance mutations were investigated. RESULTS: One hundred and forty-six women were included. All women received zidovudine and lamivudine during pregnancy; 76% also received nelfinavir and 8.2% nevirapine. Resistance data were available from 114 women (78%). Postpartum rates of single-class, dual-class, and triple-class resistance were, respectively, 43, 6.1 and 0% (63.2, 10.5 and 1.7% by ASPCR). In women receiving dual or triple PLAT, respectively, postpartum M184V/I rates were 65% (95% by ASPCR) and 28.7% (51.6% by ASPCR), respectively (P < 0.01). Postpartum nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance rates among women receiving nevirapine were 25% for K103N (37.5% by ASPCR) and 12.5% for Y188C. Protease inhibitor resistance rates in women receiving nelfinavir were 1.1% for D30N (1.1% by ASPCR) and 1.1% for L90M. Dual versus triple PLAT and prolonged zidovudine exposure were associated with selection of M184V. Nevirapine use and length of zidovudine and lamivudine exposure were associated with selection of K103N. CONCLUSION: PLAT is associated with frequent selection of resistance to drugs with low-genetic barrier. Triple-drug PLAT decreases the odds for M184V selection. Routine postpartum genotypic resistance testing may be useful to guide future treatment decisions in mothers.