Browsing by Subject "Pregnancy Complications, Infectious"
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Item Open Access Acute infectious morbidity in multiple gestation.(Infect Dis Obstet Gynecol, 2015) Dotters-Katz, Sarah K; Patel, Emily; Grotegut, Chad A; Heine, R PhillipsOBJECTIVES: Physiologic and immunologic changes in pregnancy result in increased susceptibility to infection. These shifts are more pronounced in pregnancies complicated by multiple gestation. The objective of this study was to determine the association between multiple gestation and risk of infectious morbidity. STUDY DESIGN: The Nationwide Inpatient Sample for the years 2008-2010 was used to identify pregnant women during admission for delivery with International Classification of Diseases codes. Logistic regression was used to compute odds ratios and 95% confidence intervals for demographic data, preexisting medical conditions, and acute medical and infectious complications for women with multiple versus singleton gestations. RESULTS: Among women with multiple gestation, 38.4 per 1,000 women had an infectious complication compared to 12.8 per 1,000 women with singletons. The most significant infectious morbidity associated with multiple gestation was intestinal infections, pyelonephritis, influenza, and pneumonia. After controlling for confounding variables, infectious complications at delivery persisted for women with multiples, though the association was dependent on mode of delivery. CONCLUSIONS: Women with multiple gestations are at increased risk for infectious morbidity identified at the time of delivery. This association was diminished among women who had a cesarean suggesting that operative delivery is not responsible for this association.Item Open Access Antichlamydial antibodies, human fertility, and pregnancy wastage.(Infectious diseases in obstetrics and gynecology, 2011-01) Stephens, Amanda J; Aubuchon, Mira; Schust, Danny JGenital infections with Chlamydia trachomatis (C. trachomatis) continue to be a worldwide epidemic. Immune response to chlamydia is important to both clearance of the disease and disease pathogenesis. Interindividual responses and current chlamydial control programs will have enormous effects on this disease and its control strategies. Humoral immune response to C. trachomatis occurs in humans and persistent antibody levels appear to be most directly correlated with more severe and longstanding disease and with reinfection. There is a close correlation between the presence of antichlamydial antibodies in females and tubal factor infertility; the closest associations have been found for antibodies against chlamydial heat shock proteins. The latter antibodies have also been shown to be useful among infertile patients with prior ectopic pregnancy, and their presence has been correlated with poor IVF outcomes, including early pregnancy loss. We review the existing literature on chlamydial antibody testing in infertile patients and present an algorithm for such testing in the infertile couple.Item Open Access Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1.(J Virol, 2015-10) Pollara, Justin; McGuire, Erin; Fouda, Genevieve G; Rountree, Wes; Eudailey, Josh; Overman, R Glenn; Seaton, Kelly E; Deal, Aaron; Edwards, R Whitney; Tegha, Gerald; Kamwendo, Deborah; Kumwenda, Jacob; Nelson, Julie AE; Liao, Hua-Xin; Brinkley, Christie; Denny, Thomas N; Ochsenbauer, Christina; Ellington, Sascha; King, Caroline C; Jamieson, Denise J; van der Horst, Charles; Kourtis, Athena P; Tomaras, Georgia D; Ferrari, Guido; Permar, Sallie RUNLABELLED: Infants born to HIV-1-infected mothers in resource-limited areas where replacement feeding is unsafe and impractical are repeatedly exposed to HIV-1 throughout breastfeeding. Despite this, the majority of infants do not contract HIV-1 postnatally, even in the absence of maternal antiretroviral therapy. This suggests that immune factors in breast milk of HIV-1-infected mothers help to limit vertical transmission. We compared the HIV-1 envelope-specific breast milk and plasma antibody responses of clade C HIV-1-infected postnatally transmitting and nontransmitting mothers in the control arm of the Malawi-based Breastfeeding Antiretrovirals and Nutrition Study using multivariable logistic regression modeling. We found no association between milk or plasma neutralization activity, antibody-dependent cell-mediated cytotoxicity, or HIV-1 envelope-specific IgG responses and postnatal transmission risk. While the envelope-specific breast milk and plasma IgA responses also did not reach significance in predicting postnatal transmission risk in the primary model after correction for multiple comparisons, subsequent exploratory analysis using two distinct assay methodologies demonstrated that the magnitudes of breast milk total and secretory IgA responses against a consensus HIV-1 envelope gp140 (B.con env03) were associated with reduced postnatal transmission risk. These results suggest a protective role for mucosal HIV-1 envelope-specific IgA responses in the context of postnatal virus transmission. This finding supports further investigations into the mechanisms by which mucosal IgA reduces risk of HIV-1 transmission via breast milk and into immune interventions aimed at enhancing this response. IMPORTANCE: Infants born to HIV-1-infected mothers are repeatedly exposed to the virus in breast milk. Remarkably, the transmission rate is low, suggesting that immune factors in the breast milk of HIV-1-infected mothers help to limit transmission. We compared the antibody responses in plasma and breast milk of HIV-1-transmitting and -nontransmitting mothers to identify responses that correlated with reduced risk of postnatal HIV-1 transmission. We found that neither plasma nor breast milk IgG antibody responses were associated with risk of HIV-1 transmission. In contrast, the magnitudes of the breast milk IgA and secretory IgA responses against HIV-1 envelope proteins were associated with reduced risk of postnatal HIV-1 transmission. The results of this study support further investigations of the mechanisms by which mucosal IgA may reduce the risk of HIV-1 transmission via breastfeeding and the development of strategies to enhance milk envelope-specific IgA responses to reduce mother-to-child HIV transmission and promote an HIV-free generation.Item Open Access Effects of the Pratt pouch model of dispensing nevirapine prophylaxis on HIV exposed infant completion of 6 weeks of prophylaxis in Uganda.(PloS one, 2021-01) Bitarakwate, Edward; Ashburn, Kim; Kazooba, Patrick; Khamasi, Ronald; Natumanya, Eliab; Herrera, Nicole; Owomugisha, Boaz; Malkin, Robert A; Kisaakye, LindaIntroduction
The innovative Pratt pouch could optimize dispensing nevirapine prophylaxis to HIV-exposed infants in pre-measured single dose pouches to increase completion of the full 6 week infant nevirapine regimen.Materials and methods
Nineteen health facilities with highest HIV positivity rates among pregnant women across 9 districts in southwest and central Uganda were assigned to control and intervention groups. HIV-positive women enrolled at intervention facilities received pouches filled with premeasured single doses of nevirapine using Uganda national guidelines, which were integrated into the existing drug distribution system. During antenatal care (ANC) women received 14 pouches to cover time until the 6 day postpartum visit, with an additional 8 pouches if women were delayed in returning to the facility, and 28 pouches after delivery. Women enrolled at control facilities received standard nevirapine syrup following delivery for postnatal infant prophylaxis. In a select number of intervention facilities, during ANC, women received all 42 pouches needed to complete the 6 weeks regimen. Medical record data from enrolled women were extracted; interviews with HIV-positive women during postnatal care visits were conducted. Data were collected January to August 2018 (control sites) and October 2019 to February 2020 (intervention sites). Unadjusted and adjusted logistic regression models were used to identify factors associated with facility delivery, postnatal care follow-up visit, and completion of the full 6 weeks infant nevirapine regimen.Results
Significantly more women in the intervention (n = 320) versus control (n = 340) group had facility delivery (292/316, 92.4% versus 169/340, 49.7%, p<0.0001), postnatal visits within 2 weeks postpartum (295/297, 99.3% versus 133/340, 39.1%, p<0.0001) and reported their infants completing the full 6 weeks infant prophylaxis regimen (299/313, 95.5% versus 210/242, 86.8%, p = 0.0002). Dispensing 42 versus 14 pouches during ANC did not have negative effects on these outcomes. Among out-of-facility deliveries, a higher proportion of infants received nevirapine within 72 hours of birth in the intervention versus control group, 95.8% versus 77.9%. In multivariate models, the intervention group was the only significant factor associated with facility delivery or completion of the full 6 weeks infant prophylaxis.Conclusions
Use of the Pratt pouch resulted in an increase in HIV-exposed infants completing the full 6weeks prophylaxis regimen and associated benefits including increasing facility delivery and women's adherence to postnatal care services.Item Open Access Efficacy of mobile phone intervention to increase male partner antenatal care attendance for HIV testing in Moshi municipal, Tanzania: a randomized controlled trial.(BMC pregnancy and childbirth, 2024-04) Lyimo, Angela; Mmbaga, Blandina; Mahmoud, Ashraf; Eliamini, Wilson Saimon; Ngowi, Nicolaus Bartholomew; Mitao, Modesta; Pancras, Godwin; Malindisa, Evangelista; Kidayi, Paulo; Conserve, Donaldson F; Bartlett, John; Sunguya, Bruno; Lyamuya, Eligius; Kidenya, Benson; Balandya, Emmanuel; Ngocho, James SamwelBackground
HIV partner counselling and testing in antenatal care (ANC) is a crucial strategy to raise the number of males who know their HIV status. However, in many settings like Tanzania, male involvement in antenatal care remains low, and there is a definite need for innovative strategies to increase male partner involvement. This study was designed to evaluate the efficacy of mobile phone intervention increase male partner ANC attendance for HIV testing in Moshi municipal, Tanzania.Methods
Between April and July 2022, we enrolled pregnant women presenting to a first ANC visit at Majengo and St. Joseph reproductive health facilities without their male partners. Eligible pregnant women were randomly assigned to invitation of their male partners either via phone calls, text messages from clinic staff and verbal invites from pregnant partners (intervention arm) or verbal invites only from the pregnant partners (control arm). Neither healthcare provider nor participant were blinded. The primary outcome was the proportion of male partners who attended ANC with their pregnant partners during a follow-up period of two consecutive visits. The secondary outcome measure was HIV testing among male partners following the invitation. Participants were analyzed as originally assigned (intention to treat).Results
A total of 350 pregnant women presenting to ANC for the first time were enrolled, with 175 women enrolled in each arm. The efficacy of male attendance with their pregnant women following the invitations was 83.4% (147/175) in the intervention arm and 46.3% (81/175) in the control arm. Overall, the results suggest a positive and statistically significant average treatment effect among men who received mobile phone intervention on ANC attendance. For the secondary outcome, the percent of male partners who accepted HIV counselling and testing was 99.3% (146/147) in the intervention arm and 93.8% (76/81) in the control arm. Married men were having higher odds of ANC attendance compared with single men (aOR:6.40(3.26-12.56), Males with multigravida women were having lower odds of ANC attendance compared with primigravida women (aOR:0.17(0.09-0.33).Conclusion
The study demonstrates that supplementing verbal invitations with mobile phone calls and text messages from clinic staff can significantly increase male partner ANC attendance and HIV testing. This combined approach is recommended in improving ANC attendance and HIV testing of male partners who do not accompany their pregnant partners to antenatal clinics in the first visits.Trial registration
PACTR202209769991162.Item Open Access Exposure-safety relationship for acyclovir in the treatment of neonatal herpes simplex virus disease.(Early human development, 2022-07) Ericson, Jessica E; Benjamin, Daniel K; Boakye-Agyeman, Felix; Balevic, Stephen J; Cotten, C Michael; Adler-Shohet, Felice; Laughon, Matthew; Poindexter, Brenda; Harper, Barrie; Payne, Elizabeth H; Kaneshige, Kim; Smith, P Brian; Best Pharmaceuticals for Children Act - Pediatric Trials NetworkBackground
Neonatal herpes simplex virus (HSV) disease has been treated with high-dose (20 mg/kg/dose) acyclovir since 1991.Aims
Determine the safety of acyclovir in infants with neonatal HSV treated with high-dose acyclovir; examine the association between acyclovir dose and exposure with adverse events (AEs).Study design
We obtained demographic information and acyclovir dosing via medical records. Acyclovir exposure was calculated using an established pharmacokinetic model.Subjects
Infants <120 days of age with neonatal HSV discharged from four academic children's hospitals.Outcome measures
We identified clinical and laboratory adverse events (AEs).Results and conclusions
We identified 49 infants with neonatal HSV treated with acyclovir; 42 infants had complete 21-day dosing information. Median mean daily dose was 59 mg/kg/day. Clinical AEs were common among all gestational and postnatal age groups. Rash was the most common clinical AE (37 %). Mild laboratory AEs occurred in 2-37 % of infants. The median maximum doses (mg/kg/day) were higher among infants with hypokalemia, elevated blood urea nitrogen, and thrombocytosis. For all other laboratory AEs, the median maximum doses for infants without events were higher or equal to the median maximum dose of infants with the AE. The odds of experiencing any clinical or laboratory AE did not differ by predicted acyclovir exposure for either area under the curve (AUC) or maximum concentration (Cmax) (odds ratio [OR] = 1.00 [0.98, 1.03] and OR = 1.01 [0.93, 1.12], respectively). Although AEs were common with high-dose acyclovir exposure, severe AEs were rare. Acyclovir exposure was not associated with AEs.Item Open Access Gestational Stage and IFN-λ Signaling Regulate ZIKV Infection In Utero.(Cell host & microbe, 2017-09) Jagger, Brett W; Miner, Jonathan J; Cao, Bin; Arora, Nitin; Smith, Amber M; Kovacs, Attila; Mysorekar, Indira U; Coyne, Carolyn B; Diamond, Michael SAlthough Zika virus (ZIKV)-induced congenital disease occurs more frequently during early stages of pregnancy, its basis remains undefined. Using established type I interferon (IFN)-deficient mouse models of ZIKV transmission in utero, we found that the placenta and fetus were more susceptible to ZIKV infection at earlier gestational stages. Whereas ZIKV infection at embryonic day 6 (E6) resulted in placental insufficiency and fetal demise, infections at midstage (E9) resulted in reduced cranial dimensions, and infection later in pregnancy (E12) caused no apparent fetal disease. In addition, we found that fetuses lacking type III IFN-λ signaling had increased ZIKV replication in the placenta and fetus when infected at E12, and reciprocally, treatment of pregnant mice with IFN-λ2 reduced ZIKV infection. IFN-λ treatment analogously diminished ZIKV infection in human midgestation fetal- and maternal-derived tissue explants. Our data establish a model of gestational stage dependence of ZIKV pathogenesis and IFN-λ-mediated immunity at the maternal-fetal interface.Item Open Access Is SARS-CoV-2 Infection a Risk Factor for Early Pregnancy Loss? ACE2 and TMPRSS2 Coexpression and Persistent Replicative Infection in Primitive Trophoblast.(The Journal of infectious diseases, 2021-12) Zhou, Jie; Choi, Sehee; Liu, Heidi; Zhang, Jialin; Tian, Yuchen; Edlow, Andrea G; Ezashi, Toshihiko; Roberts, R Michael; Ma, Wenjun; Schust, Danny JBackground
SARS-CoV-2 infection in term placenta is rare. However, growing evidence suggests that susceptibility of the human placenta to infection may vary by gestational age and pathogen. For several viral infections, susceptibility appears to be greatest during early gestation. Peri-implantation placental infections that result in pre-clinical pregnancy loss would typically go undetected. Little is known about the effects of SARS-CoV-2 on the peri-implantation human placenta since this time in pregnancy can only be modeled in vitro.Methods
We used a human embryonic stem cell (hESC)-derived model of peri-implantation placental development to assess patterns of ACE2 and TMPRSS2 transcription and protein expression in primitive trophoblast. We then infected the same trophoblast cell model with a clinical isolate of SARS-CoV-2 and documented infection dynamics.Results
ACE2 and TMPRSS2 were transcribed and translated in hESC-derived trophoblast, with preferential expression in syncytialized cells. These same cells supported replicative and persistent infection by SARS-CoV-2, while non-syncytialized trophoblast cells in the same cultures did not.Conclusions
Co-expression of ACE2 and TMPRSS2 in hESC-derived trophoblast and the robust and replicative infection limited to syncytiotrophoblast equivalents support the hypothesis that increased viral susceptibility may be a defining characteristic of primitive trophoblast.Item Open Access Maternal HIV-1 envelope-specific antibody responses and reduced risk of perinatal transmission.(J Clin Invest, 2015-07-01) Permar, Sallie R; Fong, Youyi; Vandergrift, Nathan; Fouda, Genevieve G; Gilbert, Peter; Parks, Robert; Jaeger, Frederick H; Pollara, Justin; Martelli, Amanda; Liebl, Brooke E; Lloyd, Krissey; Yates, Nicole L; Overman, R Glenn; Shen, Xiaoying; Whitaker, Kaylan; Chen, Haiyan; Pritchett, Jamie; Solomon, Erika; Friberg, Emma; Marshall, Dawn J; Whitesides, John F; Gurley, Thaddeus C; Von Holle, Tarra; Martinez, David R; Cai, Fangping; Kumar, Amit; Xia, Shi-Mao; Lu, Xiaozhi; Louzao, Raul; Wilkes, Samantha; Datta, Saheli; Sarzotti-Kelsoe, Marcella; Liao, Hua-Xin; Ferrari, Guido; Alam, S Munir; Montefiori, David C; Denny, Thomas N; Moody, M Anthony; Tomaras, Georgia D; Gao, Feng; Haynes, Barton FDespite the wide availability of antiretroviral drugs, more than 250,000 infants are vertically infected with HIV-1 annually, emphasizing the need for additional interventions to eliminate pediatric HIV-1 infections. Here, we aimed to define humoral immune correlates of risk of mother-to-child transmission (MTCT) of HIV-1, including responses associated with protection in the RV144 vaccine trial. Eighty-three untreated, HIV-1-transmitting mothers and 165 propensity score-matched nontransmitting mothers were selected from the Women and Infants Transmission Study (WITS) of US nonbreastfeeding, HIV-1-infected mothers. In a multivariable logistic regression model, the magnitude of the maternal IgG responses specific for the third variable loop (V3) of the HIV-1 envelope was predictive of a reduced risk of MTCT. Neutralizing Ab responses against easy-to-neutralize (tier 1) HIV-1 strains also predicted a reduced risk of peripartum transmission in secondary analyses. Moreover, recombinant maternal V3-specific IgG mAbs mediated neutralization of autologous HIV-1 isolates. Thus, common V3-specific Ab responses in maternal plasma predicted a reduced risk of MTCT and mediated autologous virus neutralization, suggesting that boosting these maternal Ab responses may further reduce HIV-1 MTCT.Item Open Access Maternal SARS-CoV-2 infection elicits sexually dimorphic placental immune responses.(Science translational medicine, 2021-10) Bordt, Evan A; Shook, Lydia L; Atyeo, Caroline; Pullen, Krista M; De Guzman, Rose M; Meinsohn, Marie-Charlotte; Chauvin, Maeva; Fischinger, Stephanie; Yockey, Laura J; James, Kaitlyn; Lima, Rosiane; Yonker, Lael M; Fasano, Alessio; Brigida, Sara; Bebell, Lisa M; Roberts, Drucilla J; Pépin, David; Huh, Jun R; Bilbo, Staci D; Li, Jonathan Z; Kaimal, Anjali; Schust, Danny J; Gray, Kathryn J; Lauffenburger, Douglas; Alter, Galit; Edlow, Andrea GThere is a persistent bias toward higher prevalence and increased severity of coronavirus disease 2019 (COVID-19) in males. Underlying mechanisms accounting for this sex difference remain incompletely understood. Interferon responses have been implicated as a modulator of COVID-19 disease in adults and play a key role in the placental antiviral response. Moreover, the interferon response has been shown to alter Fc receptor expression and therefore may affect placental antibody transfer. Here, we examined the intersection of maternal-fetal antibody transfer, viral-induced placental interferon responses, and fetal sex in pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Placental Fc receptor abundance, interferon-stimulated gene (ISG) expression, and SARS-CoV-2 antibody transfer were interrogated in 68 human pregnancies. Sexually dimorphic expression of placental Fc receptors, ISGs and proteins, and interleukin-10 was observed after maternal SARS-CoV-2 infection, with up-regulation of these features in placental tissue of pregnant individuals with male fetuses. Reduced maternal SARS-CoV-2–specific antibody titers and impaired placental antibody transfer were also observed in pregnancies with a male fetus. These results demonstrate fetal sex-specific maternal and placental adaptive and innate immune responses to SARS-CoV-2.Item Open Access Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials.(Nature communications, 2021-04-15) Axfors, Cathrine; Schmitt, Andreas M; Janiaud, Perrine; Van't Hooft, Janneke; Abd-Elsalam, Sherief; Abdo, Ehab F; Abella, Benjamin S; Akram, Javed; Amaravadi, Ravi K; Angus, Derek C; Arabi, Yaseen M; Azhar, Shehnoor; Baden, Lindsey R; Baker, Arthur W; Belkhir, Leila; Benfield, Thomas; Berrevoets, Marvin AH; Chen, Cheng-Pin; Chen, Tsung-Chia; Cheng, Shu-Hsing; Cheng, Chien-Yu; Chung, Wei-Sheng; Cohen, Yehuda Z; Cowan, Lisa N; Dalgard, Olav; de Almeida E Val, Fernando F; de Lacerda, Marcus VG; de Melo, Gisely C; Derde, Lennie; Dubee, Vincent; Elfakir, Anissa; Gordon, Anthony C; Hernandez-Cardenas, Carmen M; Hills, Thomas; Hoepelman, Andy IM; Huang, Yi-Wen; Igau, Bruno; Jin, Ronghua; Jurado-Camacho, Felipe; Khan, Khalid S; Kremsner, Peter G; Kreuels, Benno; Kuo, Cheng-Yu; Le, Thuy; Lin, Yi-Chun; Lin, Wu-Pu; Lin, Tse-Hung; Lyngbakken, Magnus Nakrem; McArthur, Colin; McVerry, Bryan J; Meza-Meneses, Patricia; Monteiro, Wuelton M; Morpeth, Susan C; Mourad, Ahmad; Mulligan, Mark J; Murthy, Srinivas; Naggie, Susanna; Narayanasamy, Shanti; Nichol, Alistair; Novack, Lewis A; O'Brien, Sean M; Okeke, Nwora Lance; Perez, Léna; Perez-Padilla, Rogelio; Perrin, Laurent; Remigio-Luna, Arantxa; Rivera-Martinez, Norma E; Rockhold, Frank W; Rodriguez-Llamazares, Sebastian; Rolfe, Robert; Rosa, Rossana; Røsjø, Helge; Sampaio, Vanderson S; Seto, Todd B; Shahzad, Muhammad; Soliman, Shaimaa; Stout, Jason E; Thirion-Romero, Ireri; Troxel, Andrea B; Tseng, Ting-Yu; Turner, Nicholas A; Ulrich, Robert J; Walsh, Stephen R; Webb, Steve A; Weehuizen, Jesper M; Velinova, Maria; Wong, Hon-Lai; Wrenn, Rebekah; Zampieri, Fernando G; Zhong, Wu; Moher, David; Goodman, Steven N; Ioannidis, John PA; Hemkens, Lars GSubstantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/ ). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.Item Open Access Placental Expression of ACE2 and TMPRSS2 in Maternal Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Are Placental Defenses Mediated by Fetal Sex?(The Journal of infectious diseases, 2021-12) Shook, Lydia L; Bordt, Evan A; Meinsohn, Marie-Charlotte; Pepin, David; De Guzman, Rose M; Brigida, Sara; Yockey, Laura J; James, Kaitlyn E; Sullivan, Mackenzie W; Bebell, Lisa M; Roberts, Drucilla J; Kaimal, Anjali J; Li, Jonathan Z; Schust, Danny; Gray, Kathryn J; Edlow, Andrea GBackground
Expression of angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2), host molecules required for viral entry, may underlie sex differences in vulnerability to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated whether placental ACE2 and TMPRSS2 expression vary by fetal sex in the presence of maternal SARS-CoV-2 infection.Methods
Placental ACE2 and TMPRSS2 expression was quantified by quantitative reverse transcription polymerase chain reaction (RT-PCR) and by Western blot in 68 pregnant women (38 SARS-CoV-2 positive, 30 SARS-CoV-2 negative) delivering at Mass General Brigham from April to June 2020. The impact of fetal sex and maternal SARS-CoV-2 exposure on ACE2 and TMPRSS2 was analyzed by 2-way analysis of variance (ANOVA).Results
Maternal SARS-CoV-2 infection impacted placental TMPRSS2 expression in a sexually dimorphic fashion (2-way ANOVA interaction, P = .002). We observed no impact of fetal sex or maternal SARS-CoV-2 status on ACE2. TMPRSS2 expression was significantly correlated with ACE2 expression in males (Spearman ρ = 0.54, P = .02) but not females (ρ = 0.23, P = .34) exposed to maternal SARS-CoV-2.Conclusions
Sex differences in placental TMPRSS2 but not ACE2 were observed in the setting of maternal SARS-CoV-2 infection, which may have implications for offspring vulnerability to placental infection.Item Open Access Prenatal protease inhibitor use and risk of preterm birth among HIV-infected women initiating antiretroviral drugs during pregnancy.(J Infect Dis, 2010-04-01) Patel, Kunjal; Shapiro, David E; Brogly, Susan B; Livingston, Elizabeth G; Stek, Alice M; Bardeguez, Arlene D; Tuomala, Ruth E; P1025 team of the International Maternal Pediatric Adolescent AIDS Clinical Trials GroupBACKGROUND: 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.Item Open Access Psychological Impact of COVID-19 on Pregnancy.(The Journal of nervous and mental disease, 2021-06) Robinson, Gail Erlick; Benders-Hadi, Nikole; Conteh, Nkechi; Brown, Kara M; Grigoriadis, Sophie; Nadelson, Carol C; Mittal, Leena P; Wald, Marla; GAP Committee on Gender and Mental HealthItem Open Access The effects of anemia on pregnancy outcome in patients with pyelonephritis.(Infect Dis Obstet Gynecol, 2013) Dotters-Katz, Sarah K; Grotegut, Chad A; Heine, R PhillipsOBJECTIVE: Pyelonephritis is a common infectious morbidity of pregnancy. Though anemia is commonly associated with pyelonephritis, there are little data describing the effect of pyelonephritis with anemia on pregnancy outcomes. The purpose of this study was to further assess the association of anemia with infectious morbidity and pregnancy complications among women with pyelonephritis. STUDY DESIGN: We conducted a retrospective cohort study of pregnant women admitted to Duke University Hospital between July 2006 and May 2012 with pyelonephritis. Demographic, laboratory, and clinical data from the subject's pregnancy and hospitalizations were analyzed. Patients with pyelonephritis and anemia (a hematocrit < 32) were compared to those without anemia. Descriptive statistics were used to compare the two groups. RESULTS: 114 pregnant women were admitted with pyelonephritis and 45 (39.5%) had anemia on admission. There was no significant difference in age, race, preexisting medical conditions, or urine bacterial species between patients with anemia and those without. Women with anemia were more likely to deliver preterm (OR 3.3 (95% CI 1.07, 11.4), P = 0.04). When controlling for race and history of preterm delivery, women with anemia continued to have increased odds of preterm birth (OR 6.0, CI 1.4, 35, P = 0.012). CONCLUSION: Women with pyelonephritis and anemia are at increased risk for preterm delivery.Item Open Access The impact of structured support groups for pregnant South African women recently diagnosed HIV positive.(Women Health, 2011-08-31) Mundell, Jonathan P; Visser, Maretha J; Makin, Jennifer D; Kershaw, Trace S; Forsyth, Brian WC; Jeffery, Bridget; Sikkema, Kathleen JThe authors of this study evaluated a structured 10-session psychosocial support group intervention for newly HIV-diagnosed pregnant South African women. Participants were expected to display increases in HIV disclosure, self-esteem, active coping and positive social support, and decreases in depression, avoidant coping, and negative social support. Three hundred sixty-one pregnant HIV-infected women were recruited from four antenatal clinics in Tshwane townships from April 2005 to September 2006. Using a quasi-experimental design, assessments were conducted at baseline and two and eight months post-intervention. A series of random effects regression analyses were conducted, with the three assessment points treated as a random effect of time. At both follow-ups, the rate of disclosure in the intervention group was significantly higher than that of the comparison group (p<0.001). Compared to the comparison group at the first follow-up, the intervention group displayed higher levels of active coping (t=2.68, p<0.05) and lower levels of avoidant coping (t=-2.02, p<0.05), and those who attended at least half of the intervention sessions exhibited improved self-esteem (t=2.11, p<0.05). Group interventions tailored for newly HIV positive pregnant women, implemented in resource-limited settings, may accelerate the process of adjusting to one's HIV status, but may not have sustainable benefits over time.Item Open Access The Role of Congenital Cytomegalovirus Infection in Adverse Birth Outcomes: A Review of the Potential Mechanisms.(Viruses, 2020-12-24) Njue, Annete; Coyne, Carolyn; Margulis, Andrea V; Wang, Dai; Marks, Morgan A; Russell, Kevin; Das, Rituparna; Sinha, AnushuaHuman cytomegalovirus (CMV) is a major cause of nonhereditary adverse birth outcomes, including hearing and visual loss, neurologic deficits, and intrauterine growth retardation (IUGR), and may contribute to outcomes such as stillbirth and preterm delivery. However, the mechanisms by which CMV could cause adverse birth outcomes are not fully understood. This study reviewed proposed mechanisms underlying the role of CMV in stillbirth, preterm birth, and IUGR. Targeted literature searches were performed in PubMed and Embase to identify relevant articles. Several potential mechanisms were identified from in vitro studies in which laboratory-adapted and low-passage strains of CMV and various human placental models were used. Potential mechanisms identified included impairment of trophoblast progenitor stem cell differentiation and function, impairment of extravillous trophoblast invasiveness, dysregulation of Wnt signaling pathways in cytotrophoblasts, tumor necrosis factor-α mediated apoptosis of trophoblasts, CMV-induced cytokine changes in the placenta, inhibition of indoleamine 2,3-dioxygenase activity, and downregulation of trophoblast class I major histocompatibility complex molecules. Inherent challenges for the field remain in the identification of suitable in vivo animal models. Nonetheless, we believe that our review provides useful insights into the mechanisms by which CMV impairs placental development and function and how these changes could result in adverse birth outcomes.