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BackgroundTo 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.MethodsWe 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.ResultsWe 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 ConclusionsPregnant women with HIV receiving ART have more chronic comorbid conditions, but not necessarily obstetrical complications, than their peers without HIV.

HIV in pregnancy assumes additional importance because of the risk of perinatal transmission. With the increase in number of people living the HIV–AIDS worldwide, better ART policies and improved heath condition, more women with HIV are getting pregnant. Perinatal transmission occurs mostly during labour and delivery; transmission during antenatal period may also occur. Timely administration of appropriate ART, suppressed viral load, appropriate mode of delivery and safe feeding practices can reduce the risk of perinatal transmission to minimal. ART has evolved from single dose therapy to daily fixed-dose lifelong ART to all women irrespective of the clinical stage and CD4 count. NACO recommends tenofovir 300 mg + lamivudine 300 mg + efavirenz 600 mg once daily (TDF + 3TC + EFV) for all pregnant women to be continued lifelong after delivery. ART for the mother, safe mode of delivery, ART for newborn and exclusive breast feeding can together ensure a safe pregnancy for the mother and with minimal risk of perinatal transmission. This assumes importance in developing counties like India.

Introduction Learning to elicit a sexual history and counsel patients on sexual pain aligns with the Association of Professors of Gynecology and Obstetrics clerkship objectives. This topic can be challenging to cover due to lack of exposure in clinical encounters and inadequate coverage in preclinical studies. Methods Second-year medical students in the OB/GYN clerkship participated in a standardized patient (SP) encounter on dyspareunia, receiving formative feedback on sexual history taking, differential diagnosis and management plan, and their SP's comfort during the encounter. Student feedback was obtained mid- and postclerkship. Summary statistics and regression models comparing SP encounter scores with shelf exam and clerkship scores are reported. Results From September 2018 through July 2019, 101 students completed the encounter. Students asked an average of 3.9 of 13 sexual history questions. Sixty-six percent of students identified a correct diagnosis; 48% provided a management plan. The majority of students were very good or excellent at creating a safe environment. Most reported the encounter enhanced their learning (62%) and identified knowledge gaps (72%). SP encounter score was not associated with shelf exam score or clerkship letter grade but was associated with final clerkship score (unadjusted ß = 0.2, p = .009; adjusted ß = 0.1, p = .2). A summary didactic session was developed following student feedback. Discussion This SP encounter and summary didactic session allowed students to improve their sexual history taking and may be associated with clerkship performance. These skills are necessary to advocate for patients with sensitive complaints across specialties.

Typically, in higher education STEM classes, teaching assistants (TAs) perform teaching duties such as leading and running discussion sections where students apply concepts they have encountered in lectures. Nevertheless, research studies show that TAs struggle to effectively implement collaborative problem solving activities. One contributing factor is the lack of actual guidelines that can help TAs translate the theoretical ideas about implementing collaborative problem solving into concrete actions. This paper presents guidelines that can be used by TAs to implement collaborative problem solving activities in undergraduate engineering classrooms. Three researchers and two engineering teaching assistants participated in two, two-hour long workshops and co-designed the guidelines as part of a design-based implementation research project (blinded for review) that aims to develop tools to support collaborative learning in undergraduate engineering courses. Both workshops were audio recorded. Two researchers extracted the teaching strategies the team discussed during the workshops. All members of the team were asked to review the guidelines separately, and then met to approve and finalize the guidelines. The co-designed guidelines can be implemented at the beginning, during, and end of class to support students’ collaboration. In order to set the stage for effective collaboration to happen, TAs need to stress the importance of developing collaborative practices as a major objective of the course. They need to create common expectations and understanding of collaboration with the students and embed collaboration in the assessment metrics for the course. At the beginning of class, the TAs need to remind students to create a joint space to explore and test out solutions as a group; giving them details about the task-related concepts and procedures during the introductions can hinder this process. During class and before intervening TAs need to monitor a group to diagnose the group’s difficulties and decide if an intervention is necessary. When TAs intervene, providing the group with explicit problem solving procedures or answers takes away the need to co-construct knowledge. Instead, TAs can ask group members to check their answers with each other. They can also demonstrate desired collaborative behaviors to groups by addressing all group members when speaking and by challenging students’ ideas. At the end of class, TAs need to discuss different groups’ answers and ask students to comment on successful collaborative instances. The co-designed guidelines were used by the TAs to create concrete collaborative tips that can help future TAs facilitate collaboration when students are working on specific worksheets. They can also be used to inform the content of preparation programs that aim at helping TAs better perform their teaching duties. Future studies must assess the impact of using these guidelines on how TAs implement collaborative problem solving activities in undergraduate engineering classes. They must also assess the impact of using these guidelines on the TAs’ perceptions of collaboration and the development of teaching practices to orchestrate collaborative problem solving classrooms.

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 Cl

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.

Chronic rheumatic disease may interfere with procreation in women of childbearing age. Female patients should have counseling in regard to family planning and parenting. Preconception counseling requires risk assessment of possible maternal or fetal risks, screening for biomarkers with predictive value for adverse pregnancy outcomes, adjustment of therapy, and a schedule for monitoring and follow-up during pregnancy. Delivering comprehensive information and addressing all patient concerns are both essential for enabling patients to engage actively in decision making.

In the L&D setting, especially in high risk academic centers, medical students often, though unintentionally, may be excluded from care given the pace and sensitive nature of this field. Additionally, students are often paired with residents who manage multiple patients simultaneously, limiting the students’ ability to experience the full spectrum of labor care. Here we describe the development, implementation, and evaluation of an interprofessional education (IPE) program within the Obstetrics clerkship at a university-based allopathic medical school whereby students are paired to L&D nurses for a portion of their clerkship. During this pilot, students were paired with nurses for a shift managing labor and a half-shift managing neonatal transitions to extrauterine life and encouraged to participate actively in all aspects of patient care. A voluntary and anonymous post-experience survey was developed by subject matter experts and included a validated IPE instrument. This was distributed to both participating groups at the end of the clerkship. Results demonstrated that the addition of an IPE to the Obstetrics sub-clerkship was low cost, feasible, and may improve unit culture. Both medical students and L&D nurses perceived personal benefit and a positive impact on unit culture from IPE. For medical students, IPE improved their Ob/Gyn clerkship experience. The following resources are included: student handbook overview and instructions.

Intrahepatic cholestasis of pregnancy (ICP) complicates approximately 0.2% to 2% of pregnancies and can lead to increased fetal risks in pregnancy.This review aims to increase the knowledge of women's health care providers regarding the diagnosis, management, and fetal risks associated with ICP.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.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.

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]

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

Depot medroxyprogesterone acetate (DMPA) was associated with increased HIV transmission and accelerated disease progression in untreated women. The potential underlying mechanisms include immune modulation. We evaluated the effect of a single DMPA injection on cell-mediated immunity (CMI), T-cell activation, T-cell regulation (Treg), and inflammation in HIV-infected women on combination antiretroviral regimen (cART).Women with HIV plasma RNA ≤ 400 copies per milliliter on stable cART received DMPA and had immunologic and medroxyprogesterone acetate (MPA) measurements at baseline, 4 weeks [peak MPA concentration (Cmax)], and 12 weeks [highest MPA area under the concentration curve].At baseline, among 24 women with median age of 32 years and 622 CD4(+) cells per microliter, ≥ 68% had HIV, varicella-zoster virus, phytohemagglutinin A and CD3/CD28 CMI measured by lymphocyte proliferation, and/or IFNγ/IL2 dual-color fluorospot. CMI did not significantly change after DMPA administration except for a 1.4-fold increase in IL2/IFNγ varicella-zoster virus fluorospot at week 12. T-cell activation decreased after DMPA administration, reaching statistical significance at week 12 for CD4(+)CD25+%. Treg behaved heterogeneously with an increase in CD8+FOXP3+% at week 4 and a decrease in CD4+IL35+% at week 12. There was a decrease in TGFβ at week 12 and no other changes in plasma biomarkers. Correlation analyses showed that high MPA Cmax and/or area under the concentration curve were significantly associated with increases of IFNγ HIV enzyme-linked ImmunoSpot, CD4+IL35+%, and CD4+TGFβ+% Treg and decreases of plasma IL10 from baseline to weeks 4 and/or 12.A single dose of DMPA did not have immune-suppressive or pro-inflammatory effects in HIV-infected women on cART. Additional studies need to assess the effect of multiple doses.

Over the past 20 years, there has been tremendous progress in the reduction of mother-to-child transmission of HIV-1 in the United States and other countries. This decrease in mother-to-child transmission of HIV-1 is temporally related to an increase in the use of antiretrovirals (for prophylaxis or for treatment) during pregnancy and in delivery by cesarean before labor and before ruptured membranes (elective cesarean delivery). The European mode of delivery trial randomized HIV-1-infected women to delivery at 38 weeks to avoid the onset of labor and successfully halved the risk of mother-to-child transmission.1 Based on the results of this trial and of an individual patient data meta-analysis of prospective cohort studies in North America and Europe,2 both the American College of Obstetricians and Gynecologists and the U.S. Public Health Service have issued guidelines indicating that elective cesarean delivery is recommended for HIV-1-infected pregnant women with peripheral blood viral loads greater than 1,000 copies/mL irrespective of antiretroviral regimen.3,4 From 1994 to 2000, cesarean delivery rates increased among HIV-1- infected women in the United States from 20% to 50%.5 Data from the European Collaborative Study suggest there may be some benefit of elective cesarean delivery even in pregnancies in which the viral load is undetectable (200 copies/mL or lower, depending on clinical assay).6 Elective cesarean delivery is likely to remain an important tool in the prevention of mother-to-child transmission of HIV-1 in the United States and elsewhere. Cesarean delivery is associated with higher rates of maternal morbidity, delivery cost, occupational risk to the operative team, and neonatal morbidity.7-15 Neonates delivered by elective cesarean long have been recognized to be at increased risk for respiratory morbidity.16-21 The risk of respiratory morbidity with elective cesarean delivery is directly correlated with gestational age, with neonates delivered at 39 weeks or greater having rates that more closely approximate the rate with vaginal delivery.20 The American College of Obstetricians and Gynecologists recommends that elective cesarean delivery be performed at 39 completed weeks of gestation or later to avoid iatrogenic prematurity3 but recommends that cesarean delivery for prevention of mother-to-child transmission of HIV-1 be performed at 38 completed weeks to avoid the onset of labor and rupture of membranes.3 Our objective was to estimate risk of infant respiratory morbidity associated with cesarean delivery before labor and ruptured membranes among HIV-1-infected women.

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.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. Births37 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.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.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.

Background To investigate the effect of exposure to protease inhibitor (PI) therapy in utero on cord blood lipids in infants born to mothers enrolled in AIDS Clinical Trials Group protocol 5084, a prospective, multi-centre, observational study of antiretroviral therapy (ART) during pregnancy. Methods Clinical outcome was determined in 80 infants born to women treated with PIs and 73 infants born to women treated with other antiretrovirals during pregnancy. Cord blood serum from 117 of these infants was assayed for total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglyceride, apolipoprotein A1 (apoA1), apolipoprotein B100 (apoB) and lipoprotein (a). Covariates considered in the analysis included race/ethnicity, gestational age, infant gender, infant birth weight, mode of delivery, maternal tobacco and alcohol use, post-partum body mass index, and ART duration. Results Cord blood total and HDL cholesterol, triglyceride, apoA1, apoB, lipoprotein (a) and apoB/apoA1 ratio were not different between the two groups. Cord blood lipid levels in these HIV-exposed infants were similar to those reported in other neonatal cohorts. Controlling for race/ethnicity, infants born to women treated with PIs had higher LDL cholesterol than those born to women not treated with PIs (29 mg/dl versus 27 mg/dl, P=0.006). Conclusion Only LDL cholesterol was significantly higher in the cord blood of PI-exposed infants versus those not exposed to PIs in utero. As the difference between the two groups was small, the clinical relevance of the effect of maternal PI treatment on infant LDL cholesterol levels at birth is not clear.

The effects of gestational nucleoside reverse transcriptase inhibitors (NRTIs) on mitochondrial DNA (mtDNA) are controversial. The effects of mtDNA depletion on mitochondrial function have not been assessed.In peripheral blood mononuclear cells (PBMCs) from infants born to HIV-infected women and infants born to HIV-1-uninfected women, mtDNA copy numbers were determined by quantitative PCR; nuclear (COXIV)- and mitochondrial (COXII)-encoded polypeptides of the oxidative phosphorylation enzyme cytochrome c-oxidase (COX or complex IV) were quantified by Western blot.Overall, 86 infants born to HIV-infected women and 50 controls were studied. HIV-infected mothers had a median CD4 count of 506 cells/microL; 59% had HIV RNA 50 copies/mL. No infant had clinical evidence of mitochondrial disease. The birth weight was lower (p = .016) and the body length higher (p = .002) in the HIV-exposed newborns. Eighty-one HIV-infected women had received gestational NRTIs (median duration 162 days). Median mtDNA copies/PBMC in the HIV-exposed infants were 505 (range, 120-1365) vs. 213 (27-426) in controls (p.001). COX II/IV ratios were similar in both groups. Although mtDNA levels correlated inversely with maternal lactate, mitochondrial indices did not correlate with maternal CD4+ count, HIV RNA, smoking, or alcohol consumption.We found elevated mtDNA copy numbers in PBMC of infants born to HIV-infected women, the majority of whom received NRTI-based therapy, when compared to those born to healthy HIV-negative controls, but there was no difference in mtDNA-encoded respiratory chain protein. The clinical consequence of these findings is unknown and requires further investigations.

To evaluate the effect of protease inhibitors on lipid and lactate levels and gastrointestinal symptoms in pregnancy.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.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.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.ClinicalTrials.gov, www.clinicaltrials.gov, NCT00017797II.

Minimizing time to HIV viral suppression is critical in pregnancy. Integrase strand transfer inhibitors (INSTIs), like raltegravir, are known to rapidly suppress plasma HIV RNA in nonpregnant adults. There are limited data in pregnant women.We describe time to clinically relevant reduction in HIV RNA in pregnant women using INSTI-containing and non-INSTI-containing antiretroviral therapy (ART) options.We conducted a retrospective cohort study of pregnant HIV-infected women in the United States from 2009 through 2015. We included women who initiated ART, intensified their regimen, or switched to a new regimen due to detectable viremia (HIV RNA40 copies/mL) at ≥20 weeks gestation. Among women with a baseline HIV RNA permitting 1-log reduction, we estimated time to 1-log RNA reduction using the Kaplan-Meier estimator comparing women starting/adding an INSTI in their regimen vs other ART. To compare groups with similar follow-up time, we also conducted a subgroup analysis limited to women with ≤14 days between baseline and follow-up RNA data.This study describes 101 HIV-infected pregnant women from 11 US clinics. In all, 75% (76/101) of women were not taking ART at baseline; 24 were taking non-INSTI containing ART, and 1 received zidovudine monotherapy. In all, 39% (39/101) of women started an INSTI-containing regimen or added an INSTI to their ART regimen. Among 90 women with a baseline HIV RNA permitting 1-log reduction, the median time to 1-log RNA reduction was 8 days (interquartile range [IQR], 7-14) in the INSTI group vs 35 days (IQR, 20-53) in the non-INSTI ART group (P.01). In a subgroup of 39 women with first and last RNA measurements ≤14 days apart, median time to 1-log reduction was 7 days (IQR, 6-10) in the INSTI group vs 11 days (IQR, 10-14) in the non-INSTI group (P.01).ART that includes INSTIs appears to induce more rapid viral suppression than other ART regimens in pregnancy. Inclusion of an INSTI may play a role in optimal reduction of HIV RNA for HIV-infected pregnant women presenting late to care or failing initial therapy. Larger studies are urgently needed to assess the safety and effectiveness of this approach.

We conducted an open-label, steady-state pharmacokinetic (PK) study of drug-drug interactions between depot medroxyprogesterone acetate (DMPA) and twice-daily lopinavir (LPV) plus low-dose ritonavir (RTV) (LPV/r) among 24 HIV-infected women and compared the results to those for HIV-infected women receiving DMPA while on no antiretroviral therapy or on nucleosides only ( n = 14 subjects from the control arm of AIDS Clinical Trials Group [ACTG] study 5093). The objectives of the study were to address the effect of LPV/r on DMPA and to address the effect of DMPA on LPV/r therapy. PK parameters were estimated using noncompartmental analysis with between-group comparisons of medroxyprogesterone acetate (MPA) PKs and within-subject comparisons of LPV and RTV PKs before and 4 weeks after DMPA dosing. Plasma progesterone concentrations were measured every 2 weeks after DMPA dosing through week 12. Although the MPA area under the concentration-time curve and maximum concentration of drug in plasma were statistically significantly increased in the study women on LPV/r compared to those in the historical controls, these increases were not considered clinically significant. There were no changes in LPV or RTV exposure after DMPA. DMPA was well tolerated, and suppression of ovulation was maintained. (This study has been registered at ClinicalTrials.gov under registration no. NCT01296152.)

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.To identify factors associated with detectable VL at delivery despite initiation of highly active antiretroviral therapy (HAART) during pregnancy.Multicenter observational study. (ClinicalTrial.gov: NCT00028145).67 U.S. AIDS clinical research sites.Pregnant women with HIV who initiated HAART during pregnancy.Descriptive summaries and associations among sociodemographic, HIV disease, and treatment characteristics; pregnancy-related risk factors; and detectable VL (400 copies/mL) at delivery.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.Data on many covariates were incomplete because women entered the study at varying times during pregnancy.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.U.S. Department of Health and Human Services.

A mosaic chromosome complement, 46,XY/47,XY,+r(15), was detected at prenatal diagnosis. Family studies showed the mother and one of her two children to have a bisatellited supernumerary marker chromosome (SMC) in all lymphocytes examined. The maternal grandfather also showed a bisatellited SMC, but in only 2 per cent of his lymphocytes. NOR, DA/DAPI, and chromosome 15 centromere and short arm-specific probes confirmed the identify of the bisatellited SMC and of ring SMC as derived from chromosome 15. An apparently normal male was born at full term. At age 1 year, the baby continues to have normal growth and development. The bisatellited 15 likely originated by somatic mutation in the grandfather (2 per cent cells), was transmitted unchanged to the daughter and grandson (germline transmission, no mosaicism), and then evolved by excising the satellites and forming a ring SMC in the index case. Progressive changes in the frequency and subsequent changes in the structure of this SMC illustrate the unusual characteristics of chromosome 15.

Objective:To study maternal and neonatal effects of combination nucleoside analog therapy administered to human immunodeficiency virus (HIV)-infected pregnant women for maternal indications.Methods:A multicenter, prospective observational study was undertaken at six perinatal centers in the United States and Canada that supported regional referral programs for the treatment of HIV-infected pregnant women. Demographic, laboratory, and pregnancy outcome data were collected for 39 women whose antiretroviral treatment regimens were expanded to include more than one nucleoside analog for maternal indications. The 40 newborns were monitored at pediatric referral centers through at least three months of age to ascertain their HIV infection status.Results:For all 39 women, zidovudine (ZDV) therapy was instituted at 13.4 ± 8.2 weeks, with a second agent (lamivudine [3TC] in 85% of cases) being added at a mean gestational age of 17.6 weeks. Duration of therapy with two agents was 20.6±10.4 weeks overall, with no women stopping medications because of side effects or toxicity. No significant changes in maternal laboratory values were seen, except for an increase in mean corpuscular volume, over the course of pregnancy. No clinically significant adverse neonatal outcomes were noted, with all but the three preterm newborns leaving hospital with their mothers. Neonatal anemia (hematocrit < 50%) was seen in 62% of newborns, with no children needing transfusion; mild elevations of liver function tests, primarily aspartate aminotransferase, were noted in 58% of newborns tested, though none were clinically jaundiced. Overall rate of neonatal HIV infection was 2.5% (95% confidence interval: 0.1–13.2%).Conclusion:Combination antiretroviral therapy during pregnancy with two nucleoside analogs was well-tolerated by mothers and newborns, with no significant short-term toxicities or side effects noted. Surveillance of exposed newborns’ hematologic and liver function appears warranted.

The objectives of our study were to determine the prevalence of cervical intraepithelial neoplasia (CIN) in a southeastern human immunodeficiency virus (HIV)-positive population relative to an HIV-negative control group and to compare these findings with published reports from other geographic regions. Demographic, medical, and cytopathologic data were collected on 89 HIV-positive women receiving care at the Duke Adult Infectious Disease Clinic. Comparisons were made with 100 HIV-negative obstetric patients who delivered at Duke and with published reports from other regions of the United States and abroad. Cervical intraepithelial neoplasia was present in 43 (49%) of 87 HIV-positive women compared with 23% of the 100 HIV-negative patients. Two of the HIV-positive patients had invasive cancer. Comparison of these patients with patients from other geographic regions revealed similar odds ratios for the presence of CIN in HIV-positive patients compared with HIV-negative patients. These results suggest a significantly increased risk for cervical dysplasia in HIV-positive women in this southeastern population.

Objective To assess the usefulness of the recently introduced TDx-FLM assay in managing pregnant women with diabetes. Methods Participating institutions were recruited from the 1993 and 1994 Society of Perinatal Obstetricians Diabetes Special Interest Group meetings. Study patients consisted of insulin-dependent diabetic women who had undergone transabdominal amniocentesis with assay of the fluid by the TDx-FLM method. Pertinent data were requested concerning pregnancy and respiratory outcomes of the corresponding neonates. Results Data from 261 pregnancies at 13 institutions were collected. Eight of the 182 infants born within 4 days of amniocentesis developed respiratory distress syndrome (RDS); five of the eight infants with RDS required intubation, and all five had TDx-FLM values less than 70 mg of surfactant per gram of albumin. Three of the eight infants with RDS required hood oxygen only; two of these infants had TDx-FLM values at least 70 mg/g. Thirteen of 144 (9%) subjects who delivered within 4 days of amniocentesis and for whom a TDx-FLM assay and phosphatidylglycerol level were both reported had a TDx-FLM level of at least 70 mg/g and a negative phosphatidylglycerol result. No infant with this combination of results developed RDS. Fifteen of the 40 patients who delivered more than 4 days after amniocentesis, with both tests available, had TDx-FLM values at least 70 mg/g and were phosphatidylglycerol negative. Conclusion In infants of diabetic mothers, TDx-FLM values at least 70 mg/g were not associated with RDS requiring intubation. The TDx-FLM assay may be useful in determining the best time of delivery for pregnant patients with diabetes, especially in a situation in which the TDx-FLM assay is mature and the phosphatidylglycerol result is immature.

Retinoids play important roles in many diverse biological functions such as cell growth, morphogenesis, differentiation, and reproduction. Previous studies demonstrated that retinol administration to ewes, followed by natural service, resulted in embryos with improved competence to develop under standard in vitro conditions (5% CO(2) in air). Additional studies provided evidence that retinol may have some antioxidant effect by improving blastocyst development in cattle under atmospheric conditions (5% CO(2) in air). Glutathione is an important non-protein, sulphydryl compound found in oocytes and embryos, which acts to decrease oxidative stress. The purpose of the present study was to evaluate the effects of retinol administration to ewes on the content of glutathione and glutathione-related and antioxidant enzymes in in vivo matured sheep oocytes. Briefly, ewes were administered retinol or vehicle during superovulation, and after 60h the oviducts were removed and mature oocytes collected. Glutathione content did not differ significantly between oocytes collected from retinol-treated ewes (6.78+/-3.81pmol/oocyte) and control ewes (6.38+/-1.58pmol/oocyte). Transcripts encoding for manganese superoxide dismutase (Mn-SOD), copper zinc superoxide dismutase (Cu-Zn SOD), glutathione synthetase (GS), and glutathione transferase pi (GSTp) were detected in single ovine oocytes; however, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis did not reveal any significant differences in transcripts between oocytes from retinol-treated ewes and those from control ewes.

To investigate the effect of exposure to protease inhibitor (PI) therapy in utero on cord blood lipids in infants born to mothers enrolled in AIDS Clinical Trials Group protocol 5084, a prospective, multicentre, observational study of antiretroviral therapy (ART) during pregnancy.Clinical outcome was determined in 80 infants born to women treated with PIs and 73 infants born to women treated with other antiretrovirals during pregnancy. Cord blood serum from 117 of these infants was assayed for total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglyceride, apolipoprotein A1 (apoA1), apolipoprotein B100 (apoB) and lipoprotein (a). Covariates considered in the analysis included race/ethnicity, gestational age, infant gender, infant birth weight, mode of delivery, maternal tobacco and alcohol use, post-partum body mass index, and ART duration.Cord blood total and HDL cholesterol, triglyceride, apoA1, apoB, lipoprotein (a) and apoB/apoA1 ratio were not different between the two groups. Cord blood lipid levels in these HIV-exposed infants were similar to those reported in other neonatal cohorts. Controlling for race/ethnicity, infants born to women treated with PIs had higher LDL cholesterol than those born to women not treated with PIs (29 mg/dl versus 27 mg/dl, P = 0.006).Only LDL cholesterol was significantly higher in the cord blood of PI-exposed infants versus those not exposed to PIs in utero. As the difference between the two groups was small, the clinical relevance of the effect of maternal PI treatment on infant LDL cholesterol levels at birth is not clear.

Zidovudine-based antiretroviral therapies (ARTs) for treatment of HIV-infected pregnant women have markedly reduced mother-to-child transmission of the human immunodeficiency virus (HIV-1) from approximately 25% to

The B-Lynch uterine suture brace has been used for the surgical treatment of postpartum hemorrhage. To date, no complications of this procedure have been reported. We describe B-Lynch suture erosion through the uterine wall identified at a 6-week postpartum visit.A 19-year-old primigravida underwent a primary low transverse cesarean section at term for arrest of descent. The surgery was complicated by postpartum hemorrhage secondary to uterine atony unresponsive to medical management. The patient underwent successful placement of a B-Lynch suture using delayed, absorbable suture for control of the hemorrhage and had an uneventful postoperative course. At her 6-week postpartum examination, she was found to have the suture protruding from the uterine cervical os. The suture was removed in its entirety without difficulty. Follow-up sonohysterography at 6 months identified a small defect in the anterior wall of the lower uterine segment, corresponding to the probable site of suture erosion.Erosion of suture through the uterine wall can be a complication of the B-Lynch uterine suture brace. Delayed, absorbable suture is less desirable than absorbable suture for this procedure due to the risk of erosion through the uterine wall.

Objective. This study compares transperineal and endovaginal ultrasonography of the gravid cervix to evaluate image quality and assess for a systematic difference in cervical lengths measured by the 2 techniques. Methods. Transperineal and endovaginal ultrasonography of the cervix was performed on 64 pregnant women. Two physicians reviewed the images and rated the relative diagnostic value of the techniques for assessing the cervix and for evaluating for placenta previa Cervical length was measured prospectively in both techniques. Data were analyzed to determine if there is a systematic difference in length using the 2 approaches and if length differences are dependent on gestational age. Results. There was a strong reviewer preference for endovaginal ultrasonographic images over transperineal images for both assessing the cervix (P

Didanosine (ddI) pharmacokinetics in antepartum and postpartum human immunodeficiency virus (HIV)‐infected women and their neonates were studied. HIV-infected pregnant women received an intravenous (iv) ddI infusion (1.6 mg/kg/h) or an oral dose (200 mg bid or 125 mg bid) at 31 weeks antepartum and 6 weeks postpartum. Blood samples were obtained regularly up to 6 or 8 h after drug administration. The same oral dose of ddI (bid) was administered until labor began. Then, ddI was infused iv until delivery. An oral pharmacokinetic study (60 mg/m 2 ) was conducted in infants at day 1 and at week 6 after birth. Plasma concentrations of ddI were measured by radioimmunoassay. After iv ddI administration, only the maternal plasma clearance was found to be significantly increased antepartum (1028 5 mL/min) versus postpartum ( mL/min). No pharmacokinetic parameters after 231 707 5 213 oral administration were significantly affected by pregnancy. The pharmacokinetics of ddI in the neonates were highly variable. We conclude that the oral ddI dose need not be adjusted during pregnancy.

To assess the frequency of fetal gallbladder visualization through gestation and to determine the prognostic importance of nonvisualization.Demonstration of the gallbladder was prospectively attempted in 578 consecutive second- and third-trimester obstetric ultrasound examinations. Data regarding gallbladder visualization were stratified into subgroups on the basis of estimated gestational age. Postnatal follow-up was performed in 80 fetuses with nonvisualization of the gallbladder.The gallbladder was seen on 477 of 578 (82.5%) fetal sonograms. The likelihood of gallbladder visualization increased with advancing gestational age, reaching a plateau of approximately 95% between 24 and 32 weeks. After 32 weeks, the frequency of visualization declined. Seventy-five of the 80 fetuses with nonvisualized gallbladders who underwent follow-up had normal outcomes. Except for one fetus with trisomy 21, all fetuses with abnormalities had relatively minor, non-life threatening problems that did not involve the gallbladder or biliary tract.Most fetuses with nonvisualization of the gallbladder have normal outcomes. The rate of nonvisualization of the fetal gallbladder is sufficiently high to undermine the utility of gallbladder visualization as a screen for fetal abnormality.

A 39-year-old woman undergoing immunosuppressive therapy following kidney transplantation for systemic lupus erythematosus presented with a uterine adenomatoid tumor that diffusely infiltrated the entire myometrium and contained a serosal papillary cystic component that resembled a cystic mesothelioma. This is the first reported case of an adenomatoid tumor showing both of these features. Although adenomatoid tumors are considered benign, the patient may be at risk for recurrence of the papillary cystic component (which is known to recur in 50% of cases) if this tumor reflects an inability to limit neoplastic processes.

Objective The objective of the study was to determine whether protease inhibitors increase glucose intolerance and insulin resistance in pregnancy. Study Design In this multicenter, prospective, observational study, 149 human immunodeficiency virus-1-infected pregnant women had fasting insulin, glucose, and C-peptide measured followed by a 1 hour, 50 g glucose test. Glucose intolerance was defined as a 1 hour glucose greater than 130 mg/dL. Glucose intolerance, homeostasis model assessment of insulin resistance and pancreatic β-cell function, and pregnancy outcomes were compared between those taking protease inhibitors and those not. Results Fifty-seven of 149 subjects (38%) had glucose intolerance. Body mass index, Hispanic ethnicity, and maternal age, but not protease inhibitors, were associated with glucose intolerance. There were no differences in insulin resistance, β-cell function, or pregnancy outcome associated with protease inhibitor use. Conclusions Protease inhibitors do not increase risk of glucose intolerance or insulin resistance among pregnant women.