Screening for Chagas Disease during Pregnancy in the United States-A Literature Review.

Obstetrician-gynecologists in the United States have little clinical experience with the epidemiology, pathophysiology, diagnosis, and treatment of Chagas disease. The number of US parturients born in Central and South America has continued to increase over the last 20 years, making US obstetricians more and more likely to care for Chagas-infected mothers who may never be identified until dealing with long-term consequences of the disease. A literature search demonstrates that few US obstetric care providers recognize the risk of vertical transmission for the neonate and the missed opportunity of infant treatment to decrease disease prevalence. Most women will be asymptomatic during pregnancy, as will their neonates, making routine laboratory screening a necessity for the identification of at-risk neonates. While the benefits of treating asymptomatic women identified in pregnancy are not as clear as the benefits for the infants, future health screenings for evidence of the progression of Chagas disease may be beneficial to these families. The literature suggests that screening for Chagas in pregnancy in the US can be done in a cost-effective way. When viewed through an equity lens, this condition disproportionately affects families of lower socioeconomic means. Improved education of healthcare providers and appropriate resources for diagnosis and treatment can improve this disparity in health outcomes.

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.

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.

Intrahepatic Cholestasis of Pregnancy: A Review of Diagnosis and Management.

IMPORTANCE: Intrahepatic cholestasis of pregnancy (ICP) complicates approximately 0.2% to 2% of pregnancies and can lead to increased fetal risks in pregnancy. OBJECTIVE: This review aims to increase the knowledge of women's health care providers regarding the diagnosis, management, and fetal risks associated with ICP. RESULTS: The diagnosis of ICP is based on symptoms of pruritus that typically include the palms and soles, as well as elevated bile acid levels. Other liver function tests such as alanine aminotransferase and aspartate aminotransferase are also frequently elevated, and other causes of liver dysfunction should be ruled out. Fetal risks of ICP include increased risk of preterm birth, meconium-stained amniotic fluid, respiratory distress syndrome, or stillbirth. There is evidence that as bile acid levels increase, so does the risk of adverse neonatal outcomes. Ursodeoxycholic acid treatment has been shown to improve maternal pruritus symptoms, as well as biochemical tests, but no treatment has been shown to definitively improve fetal outcomes. CONCLUSIONS AND RELEVANCE: Providers should be aware of the signs and symptoms of ICP and provide accurate diagnosis and management of affected women. Women with a diagnosis of ICP should be treated with ursodeoxycholic acid to improve maternal symptoms. Given the increased risk of stillbirth in the setting of ICP, delivery may be considered at 37 weeks' gestation.

Birth Weight and Preterm Delivery Outcomes of Perinatally vs Nonperinatally Human Immunodeficiency Virus-Infected Pregnant Women in the United States: Results From the PHACS SMARTT Study and IMPAACT P1025 Protocol.

BACKGROUND: Pregnancy outcomes of perinatally human immunodeficiency virus-infected women (PHIV) are poorly defined. METHODS: We compared preterm delivery and birth weight (BW) outcomes (low BW [LBW], <2500 g), small-for-gestational-age [SGA], and BW z scores [BWZ]) in HIV-exposed uninfected infants of PHIV vs nonperinatally HIV-infected (NPHIV) pregnant women in the Pediatric HIV/AIDS Cohort Study Surveillance Monitoring of ART Toxicities or International Maternal Pediatric Adolescent AIDS Clinical Trials P1025 studies. Mixed effects models and log binomial models were used to assess the association of maternal PHIV status with infant outcomes. Age-stratified analyses were performed. RESULTS: From 1998 to 2013, 2270 HIV-infected pregnant women delivered 2692 newborns (270 born to PHIV and 2422 to NPHIV women). PHIV women were younger, (mean age 21 vs 25 years, P < .01) and more likely to have a pregnancy CD4 count <200 cells/mm3 (19% vs 11%, P = .01). No associations between maternal PHIV status and preterm delivery, SGA, or LBW were observed. After adjustment, BWZ was 0.12 lower in infants of PHIV vs NPHIV women (adjusted mean, -0.45 vs -0.33; P = .04). Among women aged 23-30 years (n = 1770), maternal PHIV was associated with LBW (aRR = 1.74; 95% confidence interval, 1.18, 2.58; P < .01). CONCLUSION: The overall lack of association between maternal PHIV status and preterm delivery or infant BW outcomes is reassuring. The higher rates of LBW observed in PHIV women aged 23-30 years warrants further mechanism-based investigations as this is a rapidly growing and aging population worldwide. CLINICAL TRIALS REGISTRATION: PHACS SMARTT study, NCT01310023. CLINICAL TRIALS REGISTRATION: IMPAACT 1025, NCT00028145.

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.

Infant growth outcomes after maternal tenofovir disoproxil fumarate use during pregnancy.

OBJECTIVE: To determine whether maternal use of tenofovir disoproxil fumarate for treatment of HIV in pregnancy predicts fetal and infant growth. METHODS: The study population included HIV-uninfected live-born singleton infants of mothers enrolled in the International Maternal Pediatric Adolescent AIDS Clinical Trials Group protocol P1025 (born 2002-2011) in the United States and exposed in utero to a combined (triple or more) antiretroviral regimen. Infant weight at birth and 6 months was compared between infants exposed and unexposed to tenofovir in utero using 2-sample t test, χ test, and multivariable linear and logistic regression models, including demographic and maternal characteristics. RESULTS: Among 2025 infants with measured birth weight, there was no difference between those exposed (N = 630, 31%) versus unexposed to tenofovir in mean birth weight (2.75 vs. 2.77 kg, P = 0.64) or mean gestational age- and sex-adjusted birth weight z-score (WASZ) (0.14 vs. 0.14, P = 0.90). Among 1496 infants followed for 6 months, there was no difference in mean weight at 6 months between tenofovir-exposed (N = 457, 31%) and tenofovir-unexposed infants (7.64 vs. 7.59 kg, P = 0.52) or in mean WASZ (0.29 vs. 0.26, P = 0.61). Tenofovir exposure during the second/third trimester, relative to no exposure, significantly predicted underweight (WASZ < 5%) at age 6 months [odds ratio (95% confidence interval): 2.06 (1.01 to 3.95), P = 0.04]. Duration of tenofovir exposure did not predict neonatal or infant growth. CONCLUSIONS: By most measures, in utero exposure to tenofovir did not significantly predict infant birth weight or growth through 6 months of age.

Mode of delivery and infant respiratory morbidity among infants born to HIV-1-infected women.

OBJECTIVE: To estimate risk of infant respiratory morbidity associated with cesarean delivery before labor and ruptured membranes among HIV-1-infected women. METHODS: In a prospective cohort study of HIV-1-infected women and their infants, mode of delivery was determined by clinicians at the participating sites. For this analysis, "elective cesarean delivery" was defined as any cesarean delivery, regardless of gestational age, without labor and with duration of ruptured membranes of less than 5 minutes. Nonelective cesarean deliveries were those performed after the onset of labor, rupture of membranes, or both. Vaginal delivery included normal spontaneous and instrument deliveries. Associations between mode of delivery and infant respiratory morbidity were assessed using chi or Fisher's exact test. Adjusted odds of respiratory distress syndrome by delivery mode were assessed using multivariable logistic regression. RESULTS: Among 1,194 mother-infant pairs, there were significant differences according to mode of delivery in median gestational age (weeks) at delivery (vaginal, n=566, median=38.8; nonelective cesarean, n=216, median=38.0; and elective cesarean, n=412, median 38.1; P<.001) and incidence of respiratory distress syndrome (vaginal, n=9, 1.6%, reference; nonelective cesarean, n=16, 7.4%; elective cesarean, n=18; 4.4%; (P<.001). In analyses adjusted for gestational age and birth weight, mode of delivery was not statistically significantly associated with infant respiratory distress syndrome (P=.10), although a trend toward an increased risk of respiratory distress syndrome among infants delivered by cesarean was suggested (nonelective cesarean adjusted odds ratio [OR] 2.32, 95% confidence interval [CI] 0.95-5.67; elective cesarean OR 2.56, 95% CI 1.01-6.48). CONCLUSION: Respiratory distress syndrome rates associated with elective cesarean delivery among HIV-1-infected women are low, comparable with published rates among uninfected women. There is minimal neonatal respiratory morbidity risk in near-term infants born by elective cesarean delivery to HIV-1-infected women. LEVEL OF EVIDENCE: II.

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.

Lipids and lactate in human immunodeficiency virus-1 infected pregnancies with or without protease inhibitor-based therapy.

OBJECTIVE: To evaluate the effect of protease inhibitors on lipid and lactate levels and gastrointestinal symptoms in pregnancy. METHODS: Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Group (ACTG) A5084 was an observational cohort study of human immunodeficiency virus (HIV)-infected pregnant women. Women recruited between 20 and 34 weeks of gestation were required to be on a stable, highly active antiretroviral therapy (HAART) regimen, stratified by protease inhibitor compared with no protease inhibitor regimens. Interval history was assessed, and lipid and lactate levels were drawn every 8 weeks during pregnancy and 12 weeks postpartum, with levels closest to delivery and postpartum used for analysis. Statistical comparisons used Kruskal-Wallis and Fisher exact tests. RESULTS: One-hundred fifty-eight women were evaluated. Total cholesterol levels (median 230 mg/dL, interquartile range [197, 259], compared with 212 [179, 246] mg/dL, P=.042) and triglycerides (median 224 mg/dL, interquartile range [187, 288], compared with 185 [142, 230] mg/dL, P<.001] were elevated in the protease inhibitor group during pregnancy and remained higher in this group after delivery (total cholesterol 185 [163, 224] mg/dl compared with 171 [140, 190] mg/dL, P<.004; triglycerides 122 [87, 175] mg/dL compared with 89 [66, 150] mg/dL, P=.02). No difference was seen in lactate levels or rates of gastrointestinal symptoms between groups. Obstetric outcomes were similar between the two groups. A higher number of low birth weight infants were born to women in the highest twentieth percentile of triglycerides compared with the lowest across medication groups. CONCLUSION: Cholesterol and triglycerides were higher in protease inhibitor-treated women in pregnancy. Lactate and gastrointestinal symptoms were not different. A higher number of low birth weight infants were noted in women with high triglycerides, but other elevated lipid levels did not affect pregnancy outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00017797 LEVEL OF EVIDENCE: II.

Management of HIV in pregnancy.

In the US, transmission of HIV infection from pregnant women to their infants is now highly preventable. HIV infection is sufficiently common to justify extension of HIV screening to all pregnant women. Once HIV infection is identified, the degree of immunocompromise may be ascertained through evaluation of CD4 cell number and HIV viral load levels. Use of antiretroviral medications can slow progression to AIDS or death, and prevent mother-to-child HIV transmission. Cesarean section plays a role in prevention of vertical HIV transmission in women with virus incompletely suppressed by medication. Simple, safe, and effective methods of preventing mother-to-child transmission are needed for the developing world.