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.

Innovating Evaluation and Treatment of Intrapartum Fevers: Where Do We Go from Here?

As intrapartum fevers are not always infectious in origin, determining whether antibiotics are indicated is challenging. We previously sought to create a point-of-care calculator using clinical data available at the time of an intrapartum fever to identify the subset of women who require antibiotic treatment to avoid maternal and neonatal morbidity. Despite the use of a comprehensive dataset from our institutions, we were unable to propose a valid and highly predictive model. In this commentary, we discuss why our model failed, as well as future research directions to identify and treat true intraamniotic infection. Developing a risk-stratification model is paramount to minimizing maternal and neonatal exposure to unnecessary antibiotics while allowing for early identification of women and babies at risk for infectious morbidity. KEY POINTS: · Determining whether antibiotics are indicated in intrapartum fever is challenging.. · Developing a risk-stratification model for febrile laboring women is critical to decreasing harm.. · A point-of-care calculator based on clinical and biomarker data is the necessary approach..

Perinatal Depressive Symptoms, Human Immunodeficiency Virus (HIV) Suppression, and the Underlying Role of Antiretroviral Therapy Adherence: A Longitudinal Mediation Analysis in the IMPAACT P1025 Cohort.

BACKGROUND: Women with HIV have higher risk of depressive symptoms in the perinatal period. Evidence on how perinatal depressive symptoms affect viral suppression (VS) and adherence to antiretroviral therapy (ART) remains limited. METHODS: Perinatal depressive symptoms were assessed using 6 items from the AIDS Clinical Trials Group (ACTG) Quality of Life questionnaire. VS (viral load <400 copies/mL) was the outcome. Adherence was defined as no missed dose in the past 1-4 weeks using the ACTG Adherence Questionnaire. Generalized mixed-effects structural equation models estimated the association of depressive symptoms on VS and the mediating role of ART adherence among women enrolled in the IMPAACT P1025 Perinatal Core Protocol (2002-2013). RESULTS: Among 1869 participants, 47.6% were 21-29 years, 57.6% non-Hispanic Black. In the third trimester, the mean depressive symptoms score was 14.0 (±5.2), 68.0% had consistent adherence, and 77.3% achieved VS. At 6 months postpartum, depressive symptoms declined while adherence and VS fell to 59.8% and 53.0%, respectively. In the fully adjusted model, a 1-SD increase in depressive symptoms was associated with a 3.8-percentage-point (95% CI: -5.7, -1.9) decline in VS. This effect is the sum of the indirect effect of depressive symptoms on VS via ART adherence (-0.4; 95% CI: -.7, -.2) and the direct effect through other pathways (-3.4; -5.2, -1.5). The decline in adherence driven by depressive symptoms accounted for ≥11% of the total negative effect of depressive symptoms on VS. CONCLUSIONS: Perinatal depressive symptoms were associated with decreased adherence and VS, highlighting the need to screen for, diagnose, and treat perinatal depression to optimize maternal outcomes. CLINICAL TRIALS REGISTRATION: NCT00028145.

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.

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.

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.

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.

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.

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.

Disparities in Care for Publicly Insured Women With Pregestational Diabetes.

OBJECTIVE: To investigate the association among public health insurance, preconception care, and pregnancy outcomes in pregnant women with pregestational diabetes. METHODS: This is a retrospective cohort of pregnant women with pregestational type 1 or type 2 diabetes from 2006 to 2011 in Massachusetts-a state with universal insurance coverage since 2006. Women delivering after 24 weeks of gestation and receiving endocrinology and obstetric care in a multidisciplinary clinic were included. Rates of preconception consultation, our primary outcome of interest, were then compared between publicly and privately insured women. We used univariate analysis followed by logistic regression to compare receipt of preconception consultation and other secondary diabetes care measures and pregnancy outcomes according to insurance status. RESULTS: Fifty-four percent (n=106) of 197 women had public insurance. Publicly insured women were younger (median age 30.4 compared with 35.3 years, P<.01) with lower rates of college education (12.3% compared with 45.1%, P<.01). Women with public insurance were less likely to receive a preconception consult (5.7% compared with 31.9%, P<.01), had lower rates of hemoglobin A1C less than 6% at the onset of pregnancy (37.2% compared with 58.4%, P=.01), and experienced higher rates of pregnancies affected by congenital anomalies (10.4% compared with 2.2%, P=.02) compared with those with private insurance. In adjusted analyses controlling for educational attainment, maternal age, and body mass index, women with public insurance were less likely to receive a preconception consult (adjusted odds ratio [OR] 0.21, 95% CI 0.08-0.58), although the odds of achieving the target hemoglobin A1C (adjusted OR 0.45, 95% CI 0.20-1.02) and congenital anomaly (adjusted OR 2.23, 95% CI 0.37-13.41) were similar after adjustment. CONCLUSION: Despite continuous access to health insurance, publicly insured women were less likely than privately insured women to receive a preconception consult-an evidence-based intervention known to improve pregnancy outcomes. Improving use of preconception care among publicly insured women with diabetes is critical to reducing disparities in outcomes.

Clinical Risk Factors Associated With Peripartum Maternal Bacteremia.

OBJECTIVE: To evaluate risk factors associated with maternal bacteremia in febrile peripartum women. METHODS: We performed a case-control study of women with fevers occurring between 7 days before and up to 42 days after delivery of viable neonates at two academic hospitals. Women with positive blood cultures were matched with the next two febrile women meeting inclusion criteria with negative blood cultures in the microbiology data without other matching parameters. We compared maternal and neonatal characteristics and outcomes between women in the case group and those in the control group with univariate analysis. We then used logistic regression to examine the association between clinical characteristics and maternal bacteremia. RESULTS: After excluding blood cultures positive only for contaminants, we compared 115 women in the case group with 285 in the control group. Bacteremic women were more likely to experience their initial fever during labor (40.9% compared with 22.8%, P<.01) and more likely to have fever at or above 102°F (62.6% compared with 31.6%, P<.01). These associations persisted in the adjusted analysis: multiparity (adjusted odds ratio [OR] 1.75, 95% CI 1.07-2.87), initial fever during labor (adjusted OR 2.82, 95% CI 1.70-4.70), and fever at or above 102°F (adjusted OR 3.83, 95% CI 2.37-6.19). In an analysis restricted to neonates whose mothers had initial fevers before or in the immediate 24 hours after delivery, neonates born to women in the case group had higher rates of bacteremia compared with those born to women in the control group (9.0% compared with 1.3%, P<.01). Eight of the nine bacteremic neonates born to bacteremic mothers (89%) grew the same organism as his or her mother in blood culture. CONCLUSION: Maternal bacteremia is associated with multiparity, initial fever during labor, and fever at or above 102°F; however, 37.5% of cases of bacteremia occurred in women with maximum fevers below this threshold. Obstetricians should maintain a heightened suspicion for an infectious source of fever in women with these clinical characteristics.

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.

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.

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.

Factors associated with lack of viral suppression at delivery among highly active antiretroviral therapy-naive women with HIV: a cohort study.

BACKGROUND: A high delivery maternal plasma HIV-1 RNA level (viral load [VL]) is a risk factor for mother-to-child transmission and poor maternal health. OBJECTIVE: To identify factors associated with detectable VL at delivery despite initiation of highly active antiretroviral therapy (HAART) during pregnancy. DESIGN: Multicenter observational study. (ClinicalTrial.gov: NCT00028145). SETTING: 67 U.S. AIDS clinical research sites. PATIENTS: Pregnant women with HIV who initiated HAART during pregnancy. MEASUREMENTS: Descriptive summaries and associations among sociodemographic, HIV disease, and treatment characteristics; pregnancy-related risk factors; and detectable VL (>400 copies/mL) at delivery. RESULTS: Between 2002 and 2011, 671 women met inclusion criteria and 13.1% had detectable VL at delivery. Factors associated with detectable VL included multiparity (16.4% vs. 8.0% nulliparity; P = 0.002), black ethnicity (17.6% vs. 6.6% Hispanic and 6.6% white; P < 0.001), 11th grade education or less (17.6% vs. 12.1% had a high school diploma; P = 0.013), initiation of HAART in the third trimester (23.9% vs. 12.3% and 8.6% in the second and trimesters, respectively; P = 0.003), having an HIV diagnosis before the current pregnancy (16.1% vs. 11.0% during the current pregnancy; P = 0.051), and having the first prenatal visit in the third trimester (33.3% vs. 14.3% and 10.5% in the second and third trimesters, respectively; P = 0.002). Women who had treatment interruptions or reported poor medication adherence were more likely to have detectable VL at delivery. LIMITATION: Data on many covariates were incomplete because women entered the study at varying times during pregnancy. CONCLUSION: A total of 13.1% of women who initiated HAART during pregnancy had detectable VL at delivery. The timing of HAART initiation and prenatal care, along with medication adherence during pregnancy, were associated with detectable VL at delivery. Social factors, including ethnicity and education, may help identify women who could benefit from focused efforts to promote early HAART initiation and adherence. PRIMARY FUNDING SOURCE: U.S. Department of Health and Human Services.

Postpartum care for mothers diagnosed with hepatitis B during pregnancy.

OBJECTIVE: We sought to determine rates of maternal postpartum hepatitis B virus (HBV) follow-up with a HBV specialist and identify factors associated with poor follow-up, as prior research has focused on infant outcomes and not maternal care. STUDY DESIGN: We conducted a retrospective review of data from Partners HealthCare system, the largest health care system in Massachusetts, and identified women with chronic HBV who delivered from 2002 through 2012. RESULTS: We identified 291 women (mean age 31.5 years, 51% Asian) with incident HBV during pregnancy. In all, 47% had postpartum follow-up with a HBV specialist, but only 19% also had appropriate laboratory tests (hepatitis B e antigen [HBeAg], hepatitis B e antibody, HBV DNA, and ALT) within 1 year of their HBV diagnosis. Mothers with HBV follow-up were more likely to have a primary care physician (PCP) within the Partners HealthCare system (66% vs 38%, P < .0001), a positive HBeAg (20% vs 8%, P = .004), and elevated AST values (17% vs 8%, P = .02). On multivariable logistic regression analysis, a mother who had a PCP (odds ratio, 2.50; 95% confidence interval, 1.37-4.59) or positive HBeAg (odds ratio, 4.45; 95% confidence interval, 1.64-12.06) had a greater likelihood of having HBV follow-up. CONCLUSION: Only 19% of HBV-infected mothers met care guidelines 1 year after being diagnosed with HBV. Inadequate postpartum HBV care affects women of all races/ethnicities. Women who had a PCP as well as those who were HBeAg positive were more likely to be referred for postpartum follow-up with a HBV specialist, suggesting that providers might be referring patients when they perceive HBV to be more serious or complex.

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.

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.