Distinct cytokine profiles in late pregnancy in Ugandan people with HIV.

During pregnancy, multiple immune regulatory mechanisms establish an immune-tolerant environment for the allogeneic fetus, including cellular signals called cytokines that modify immune responses. However, the impact of maternal HIV infection on these responses is incompletely characterized. We analyzed paired maternal and umbilical cord plasma collected during labor from 147 people with HIV taking antiretroviral therapy and 142 HIV-uninfected comparators. Though cytokine concentrations were overall similar between groups, using Partial Least Squares Discriminant Analysis we identified distinct cytokine profiles in each group, driven by higher IL-5 and lower IL-8 and MIP-1α levels in pregnant people with HIV and higher RANTES and E-selectin in HIV-unexposed umbilical cord plasma (P-value < 0.01). Furthermore, maternal RANTES, SDF-α, gro α -KC, IL-6, and IP-10 levels differed significantly by HIV serostatus (P < 0.01). Although global maternal and umbilical cord cytokine profiles differed significantly (P < 0.01), umbilical cord plasma profiles were similar by maternal HIV serostatus. We demonstrate that HIV infection is associated with a distinct maternal plasma cytokine profile which is not transferred across the placenta, indicating a placental role in coordinating local inflammatory response. Furthermore, maternal cytokine profiles in people with HIV suggest an incomplete shift from Th2 to Th1 immune phenotype at the end of pregnancy.

Prevalence and Risk Factors for Newborn Anemia in Southwestern Uganda: A Cross-Sectional Study.

Introduction: The global prevalence of maternal anemia is about 42%, and in sub-Saharan Africa, the prevalence of newborn anemia ranges from 25% to 30%. Anemia in newborn babies may cause complications such as delayed brain maturation and arrested growth. However, there is limited data on the prevalence of newborn anemia and its risk factors in people living in resource-limited settings. Objectives: We determined the prevalence and risk factors for newborn anemia and its correlation with maternal anemia in southwestern Uganda. Methods: This was a cross sectional study of 352 pregnant women presenting to the Mbarara Regional Referral Hospital for delivery. We collected maternal blood in labor and umbilical cord blood from the placental vein. We measured hemoglobin using a point-of-care Hemocue machine. We used summary statistics to characterize the study participants and compared demographic characteristics and outcomes using chi-square, t-test, and Wilcoxon rank sum analyses. We defined newborn anemia as umbilical cord hemoglobin <13 g/dl and measured the relationship between maternal and umbilical cord hemoglobin using linear regression analysis. Results: The prevalence of newborn anemia was 17%. Maternal parity was significantly higher for anemic than nonanemic newborns (3 versus 2, P=0.01). The mean age in years (SD) was significantly lower for participants with umbilical cord hemoglobin <13 g/dl than those ≥13 g/dl (26 years [5.6] versus 28 [6.3], P=0.01). In multivariable linear regression analysis, a 1-point decrease in maternal hemoglobin was associated with a 0.14-point decrease in umbilical cord hemoglobin (P=0.02). Each one-unit increase in parity was associated with a 0.25-point decrease in umbilical cord hemoglobin (P=0.01). Cesarean delivery was associated with a 0.46-point lower umbilical cord hemoglobin level compared with vaginal delivery (P=0.03). Conclusions: We found a significant association between maternal and newborn hemoglobin, underscoring the importance of preventing and correcting maternal anemia in pregnancy. Furthermore, maternal anemia should be considered a risk factor for neonatal anemia.

Effects of Maternal HIV Infection and Alcohol Use in Pregnancy on Birth Outcomes in Uganda.

Alcohol use and HIV infection are prevalent in sub-Saharan Africa (sSA), and both are associated with low birth weight. Yet, few studies have evaluated the combined effects of maternal HIV infection and alcohol use on birth outcomes. We analyzed data from a prospective cohort study of HIV-related placental changes in Ugandan women. We defined alcohol use as self-reported alcohol use within the last year, using the AUDIT questionnaire and used linear and logistic regression to measure associations between maternal alcohol use, HIV serostatus, and birth weight. In a subsample, we measured alcohol exposure using phosphatidylethanol (PEth) in neonatal heelstick dried blood spots to confirm maternal alcohol use. Of 352 participants, 176 (50%) were women with HIV (WHIV). Three of 176 (2%) HIVuninfected women and 17/176 (10%) of WHIV self-reported alcohol use (P = 0.002). Maternal HIV infection was associated with lower birth weight (ß = -0.12, 95% CI [-0.20, -0.02], P = 0.02), but self-reported alcohol use was not (ß = 0.06, 95% CI [-0.15, 0.26], P = 0.54), and the interaction between HIV serostatus and alcohol use was not significant (P = 0.13). Among the PEth subsample, neither HIV status nor PEthconfirmed alcohol use were associated with low birth weight. Maternal HIV infection was associated with lower birth weight, but alcohol use was not, and there was no significant interaction between maternal HIV infection and alcohol use. Alcohol use was more prevalent in WHIV and under-reporting was common. A larger study of the effects of laboratory-confirmed alcohol and HIV exposure on birth outcomes is warranted.

Prevalence and risk factors for newborn anemia in southwestern Uganda: a prospective cohort study.

Introduction: The global prevalence of anemia in pregnancy is about 42%, and in sub-Saharan Africa, the prevalence of newborn anemia ranges from 25-30%. Anemia in newborn babies may cause complications such as delayed brain maturation and arrested growth. However, there is limited data on prevalence of newborn anemia and its risk factors in people living in resource-limited settings. Objectives: We determined the prevalence and risk factors for newborn anemia and its correlation with maternal anemia in southwestern Uganda. Methods: This was a prospective cohort study of 352 pregnant women presenting to Mbarara Regional Referral Hospital for delivery. We collected maternal blood in labor and umbilical cord blood from the placental vein, as a proxy for newborn hemoglobin. We estimated hemoglobin using a point-of-care Hemocue machine. We used summary statistics to characterize the cohort, and compared demographic characteristics and outcomes using Chi-square, t-test, and Wilcoxon Ranksum analyses. We defined newborn anemia as umbilical cord hemoglobin < 13g/dl and estimated the relationship between maternal and umbilical cord hemoglobin using linear regression analysis, adjusting for potential confounders. Results: The prevalence of newborn anemia was 17%. The average maternal parity was significantly higher for anemic and non-anemic newborns (3.5 versus 2.8, P = 0.01). Mean age [SD] was significantly lower for participants with umbilical cord hemoglobin < 13g/dl than those > = 13 g/dl, (26 [5.6] versus 28 [6.3], P = 0.01). In multivariable linear regression analysis, a 1-point decrease in maternal hemoglobin was associated with a 0.14-point decrease in umbilical cord hemoglobin (P = 0.02). Each one-unit increase in maternal parity was associated with a 0.25-point decrease in umbilical cord hemoglobin (P = 0.01). Cesarean delivery was associated with a 0.46-point lower umbilical cord hemoglobin level compared to vaginal delivery (P = 0.03). Conclusions: We found a significant correlation between maternal and newborn hemoglobin levels, underscoring the importance of preventing and correcting maternal anemia in pregnancy. Furthermore, maternal anemia should be considered a risk factor neonatal anemia.

Preferred Language Mediates Association Between Race, Ethnicity, and Delayed Presentation in Critically Ill Patients With COVID-19.

Which social factors explain racial and ethnic disparities in COVID-19 access to care and outcomes remain unclear. OBJECTIVES: We hypothesized that preferred language mediates the association between race, ethnicity and delays to care. DESIGN SETTING AND PARTICIPANTS: Multicenter, retrospective cohort study of adults with COVID-19 consecutively admitted to the ICU in three Massachusetts hospitals in 2020. MAIN OUTCOME AND MEASURES: Causal mediation analysis was performed to evaluate potential mediators including preferred language, insurance status, and neighborhood characteristics. RESULTS: Non-Hispanic White (NHW) patients (157/442, 36%) were more likely to speak English as their preferred language (78% vs. 13%), were less likely to be un- or under-insured (1% vs. 28%), lived in neighborhoods with lower social vulnerability index (SVI) than patients from racial and ethnic minority groups (SVI percentile 59 [28] vs. 74 [21]) but had more comorbidities (Charlson comorbidity index 4.6 [2.5] vs. 3.0 [2.5]), and were older (70 [13.2] vs. 58 [15.1] years). From symptom onset, NHW patients were admitted 1.67 [0.71-2.63] days earlier than patients from racial and ethnic minority groups (p < 0.01). Non-English preferred language was associated with delay to admission of 1.29 [0.40-2.18] days (p < 0.01). Preferred language mediated 63% of the total effect (p = 0.02) between race, ethnicity and days from symptom onset to hospital admission. Insurance status, social vulnerability, and distance to the hospital were not on the causal pathway between race, ethnicity and delay to admission. CONCLUSIONS AND RELEVANCE: Preferred language mediates the association between race, ethnicity and delays to presentation for critically ill patients with COVID-19, although our results are limited by possible collider stratification bias. Effective COVID-19 treatments require early diagnosis, and delays are associated with increased mortality. Further research on the role preferred language plays in racial and ethnic disparities may identify effective solutions for equitable care.

Maternal anemia is associated with adverse maternal and neonatal outcomes in Mbarara, Uganda.

PURPOSE: Maternal anemia is a significant risk factor for maternal morbidity and mortality, increasing risk of preterm birth, intrauterine growth restriction, stillbirth, and death. Moderate and severe anemia in pregnancy is defined as hemoglobin (Hb) <10 g/dl and Hb < 7 g/dl, respectively. We aimed to characterize the association of maternal anemia with maternal, neonatal, and placental outcomes in a resource-limited setting. METHODS: Data were collected from a prospective cohort of 352 pregnant women at a tertiary academic Ugandan hospital. One hundred and seventy-six (50%) of women were living with HIV. Hemoglobin was measured in labor, and placentas were collected postpartum. Maternal outcomes included mode of delivery, hemorrhage, blood transfusion, intensive care unit admission, and maternal mortality. Neonatal outcomes included gestational age at delivery, birthweight, stillbirth, and neonatal mortality. Placental descriptors included weight and thickness. Categorical variables were analyzed using Chi-squared and Fisher's exact tests. RESULTS: Hemoglobin < 10 g/dl, was present in 17/352 (5%) of women. Significantly more women with moderate or severe anemia were HIV-infected: 14/17 (82%) versus 162/335 (48%) (p = .006). Blood transfusions (2/17, 12% versus 5/335, 2%, p = .04) and neonatal deaths (2/17, 12% versus 9/335, 3%, p = .01) were more common in the anemia group. Placental thickness was lower in the anemia group (1.4 cm versus 1.7 cm, p = .04). CONCLUSIONS: Moderate and severe anemia was associated with maternal HIV infection, maternal blood transfusion, neonatal death, and decreased placental thickness. The overall rate of moderate and severe anemia among this cohort was lower than previously reported.

Paenibacillus spp infection among infants with postinfectious hydrocephalus in Uganda: an observational case-control study.

BACKGROUND: Paenibacillus thiaminolyticus is a cause of postinfectious hydrocephalus among Ugandan infants. To determine whether Paenibacillus spp is a pathogen in neonatal sepsis, meningitis, and postinfectious hydrocephalus, we aimed to complete three separate studies of Ugandan infants. The first study was on peripartum prevalence of Paenibacillus in mother-newborn pairs. The second study assessed Paenibacillus in blood and cerebrospinal fluid (CSF) from neonates with sepsis. The third study assessed Paenibacillus in CSF from infants with hydrocephalus. METHODS: In this observational study, we recruited mother-newborn pairs with and without maternal fever (mother-newborn cohort), neonates (aged ≤28 days) with sepsis (sepsis cohort), and infants (aged ≤90 days) with hydrocephalus with and without a history of neonatal sepsis and meningitis (hydrocephalus cohort) from three hospitals in Uganda between Jan 13, 2016 and Oct 2, 2019. We collected maternal blood, vaginal swabs, and placental samples and the cord from the mother-newborn pairs, and blood and CSF from neonates and infants. Bacterial content of infant CSF was characterised by 16S rDNA sequencing. We analysed all samples using quantitative PCR (qPCR) targeting either the Paenibacillus genus or Paenibacillus thiaminolyticus spp. We collected cranial ultrasound and computed tomography images in the subset of participants represented in more than one cohort. FINDINGS: No Paenibacillus spp were detected in vaginal, maternal blood, placental, or cord blood specimens from the mother-newborn cohort by qPCR. Paenibacillus spp was detected in 6% (37 of 631 neonates) in the sepsis cohort and, of these, 14% (5 of 37 neonates) developed postinfectious hydrocephalus. Paenibacillus was the most enriched bacterial genera in postinfectious hydrocephalus CSF (91 [44%] of 209 patients) from the hydrocephalus cohort, with 16S showing 94% accuracy when validated by qPCR. Imaging showed progression from Paenibacillus spp-related meningitis to postinfectious hydrocephalus over 1-3 months. Patients with postinfectious hydrocephalus with Paenibacillus spp infections were geographically clustered. INTERPRETATION: Paenibacillus spp causes neonatal sepsis and meningitis in Uganda and is the dominant cause of subsequent postinfectious hydrocephalus. There was no evidence of transplacental transmission, and geographical evidence was consistent with an environmental source of neonatal infection. Further work is needed to identify routes of infection and optimise treatment of neonatal Paenibacillus spp infection to lessen the burden of morbidity and mortality. FUNDING: National Institutes of Health and Boston Children's Hospital Office of Faculty Development.

Maternal HIV infection drives altered placental Mtb-specific antibody transfer.

Introduction: Placental transfer of maternal antibodies is essential for neonatal immunity over the first months of life. In the setting of maternal HIV infection, HIV-exposed uninfected (HEU) infants are at higher risk of developing severe infections, including active tuberculosis (TB). Given our emerging appreciation for the potential role of antibodies in the control of Mycobacterium tuberculosis (Mtb), the bacteria that causes TB, here we aimed to determine whether maternal HIV status altered the quality of Mtb-specific placental antibody transfer. Methods: Antigen-specific antibody systems serology was performed to comprehensively characterize the Mtb-specific humoral immune response in maternal and umbilical cord blood from HIV infected and uninfected pregnant people in Uganda. Results: Significant differences were noted in overall antibody profiles in HIV positive and negative maternal plasma, resulting in heterogeneous transfer of Mtb-specific antibodies. Altered antibody transfer in HIV infected dyads was associated with impaired binding to IgG Fc-receptors, which was directly linked to HIV viral loads and CD4 counts. Conclusions: These results highlight the importance of maternal HIV status on antibody transfer, providing clues related to alterations in transferred maternal immunity that may render HEU infants more vulnerable to TB than their HIV-unexposed peers.

Risk factors for postpartum maternal mortality and hospital readmission in low- and middle-income countries: a systematic review.

BACKGROUND: In low- and middle-income countries, approximately two thirds of maternal deaths occur in the postpartum period. Yet, care for women beyond 24 h after discharge is limited. The objective of this systematic review is to summarize current evidence on socio-demographic and clinical risk factors for (1) postpartum mortality and (2) postpartum hospital readmission. METHODS: A combination of keywords and subject headings (i.e. MeSH terms) for postpartum maternal mortality or readmission were searched. Articles published up to January 9, 2021 were identified in MEDLINE, EMBASE, and CINAHL databases, without language restrictions. Studies reporting socio-demographic or clinical risk factors for postpartum mortality or readmission within six weeks of delivery among women who delivered a livebirth in a low- or middle-income country were included. Data were extracted independently by two reviewers based on study characteristics, population, and outcomes. Included studies were assessed for quality and risk of bias using the Downs and Black checklist for ratings of randomized and non-randomized studies. RESULTS: Of 8783 abstracts screened, seven studies were included (total N = 387,786). Risk factors for postpartum mortality included Caesarean mode of delivery, nulliparity, low or very low birthweight, and shock upon admission. Risk factors for postpartum readmission included Caesarean mode of delivery, HIV positive serostatus, and abnormal body temperature. CONCLUSIONS: Few studies reported individual socio-demographic or clinical risk factors for mortality or readmission after delivery in low- and middle-income countries; only Caesarean delivery was consistently reported. Further research is needed to identify factors that put women at greatest risk of post-discharge complications and mortality. Understanding post-discharge risk would facilitate targeted postpartum care and reduce adverse outcomes in women after delivery. TRIAL REGISTRATION: PROSPERO registration number: CRD42018103955.

Prolonged Prone Position Ventilation Is Associated With Reduced Mortality in Intubated COVID-19 Patients.

BACKGROUND: Prone position ventilation (PPV) is resource-intensive, yet the optimal strategy for PPV in intubated patients with COVID-19 is unclear. RESEARCH QUESTION: Does a prolonged (24 or more h) PPV strategy improve mortality in intubated COVID-19 patients compared with intermittent (∼16 h with daily supination) PPV? STUDY DESIGN AND METHODS: Multicenter, retrospective cohort study of consecutively admitted intubated COVID-19 patients treated with PPV between March 11 and May 31, 2020. The primary outcome was 30-day all-cause mortality. Secondary outcomes included 90-day all-cause mortality and prone-related complications. Inverse probability treatment weights (IPTW) were used to control for potential treatment selection bias. RESULTS: Of the COVID-19 patients who received PPV, 157 underwent prolonged and 110 underwent intermittent PPV. Patients undergoing prolonged PPV had reduced 30-day (adjusted hazard ratio [aHR], 0.475; 95% CI, 0.336-0.670; P < .001) and 90-day (aHR, 0.638; 95% CI, 0.461-0.883; P = .006) mortality compared with intermittent PPV. In patients with Pao2/Fio2 ≤ 150 at the time of pronation, prolonged PPV was associated with reduced 30-day (aHR, 0.357; 95% CI, 0.213-0.597; P < .001) and 90-day mortality (aHR, 0.562; 95% CI, 0.357-0.884; P = .008). Patients treated with prolonged PPV underwent fewer pronation and supination events (median, 1; 95% CI, 1-2 vs 3; 95% CI, 1-4; P < .001). PPV strategy was not associated with overall PPV-related complications, although patients receiving prolonged PPV had increased rates of facial edema and lower rates of peri-proning hypotension. INTERPRETATION: Among intubated COVID-19 patients who received PPV, prolonged PPV was associated with reduced mortality. Prolonged PPV was associated with fewer pronation and supination events and a small increase in rates of facial edema. These findings suggest that prolonged PPV is a safe, effective strategy for mortality reduction in intubated COVID-19 patients.

Prognostic algorithms for post-discharge readmission and mortality among mother-infant dyads: an observational study protocol.

Introduction: In low-income country settings, the first six weeks after birth remain a critical period of vulnerability for both mother and newborn. Despite recommendations for routine follow-up after delivery and facility discharge, few mothers and newborns receive guideline recommended care during this period. Prediction modelling of post-delivery outcomes has the potential to improve outcomes for both mother and newborn by identifying high-risk dyads, improving risk communication, and informing a patient-centered approach to postnatal care interventions. This study aims to derive post-discharge risk prediction algorithms that identify mother-newborn dyads who are at risk of re-admission or death in the first six weeks after delivery at a health facility. Methods: This prospective observational study will enroll 7,000 mother-newborn dyads from two regional referral hospitals in southwestern and eastern Uganda. Women and adolescent girls aged 12 and above delivering singletons and twins at the study hospitals will be eligible to participate. Candidate predictor variables will be collected prospectively by research nurses. Outcomes will be captured six weeks following delivery through a follow-up phone call, or an in-person visit if not reachable by phone. Two separate sets of prediction models will be built, one set of models for newborn outcomes and one set for maternal outcomes. Derivation of models will be based on optimization of the area under the receiver operator curve (AUROC) and specificity using an elastic net regression modelling approach. Internal validation will be conducted using 10-fold cross-validation. Our focus will be on the development of parsimonious models (5-10 predictor variables) with high sensitivity (>80%). AUROC, sensitivity, and specificity will be reported for each model, along with positive and negative predictive values. Discussion: The current recommendations for routine postnatal care are largely absent of benefit to most mothers and newborns due to poor adherence. Data-driven improvements to postnatal care can facilitate a more patient-centered approach to such care. Increasing digitization of facility care across low-income settings can further facilitate the integration of prediction algorithms as decision support tools for routine care, leading to improved quality and efficiency. Such strategies are urgently required to improve newborn and maternal postnatal outcomes. Clinical trial registration: https://clinicaltrials.gov/, identifier (NCT05730387).

The interaction between antenatal care and abnormal temperature during delivery and its relationship with postpartum care: a prospective study of 1,538 women in semi-rural Uganda.

BACKGROUND: Postnatal care (PNC) is an important tool for reducing maternal and neonatal morbidity and mortality. However, what predicts receipt and maintenance in PNC, particularly events during pregnancy and the peripartum period, is not well understood. We hypothesized that fever or hypothermia during delivery would engender greater health consciousness among those attending antenatal care, leading to greater PNC engagement after hospital discharge and our objective was to evaluate this relationship. METHODS: Women were prospectively enrolled immediately postpartum at Mbarara Regional Referral Hospital (MRRH). We collected postpartum vital signs and surveyed women by telephone about PNC receipt, fever, and infection at two and six weeks postpartum. Our outcome of interest was receipt of PNC post-discharge, defined as whether a participant visited a health facility and/or was hospitalized in the postpartum period. Our explanatory variables were whether a participant was ever febrile (> 38.0˚C) or hypothermic (< 36.0˚C) during delivery stay and whether a participant attended at least 4 antenatal care (ANC) visits. We used logistic regressions to estimate the association between ANC and fever/hypothermia with PNC, including an interaction term between ANC and fever/hypothermia to determine whether there was a modifying relationship between variables on PNC. Regression models were adjusted for age, marital status, parity, HIV serostatus, Mbarara residency, and whether the participant was referred to MRRH, RESULTS: Of the 1,541 women, 86 (5.6%) reported visiting a health facility and/or hospitalization and 186 (12.0%) had an abnormal temperature recorded during delivery stay. Of those who reported at least one visit, 59/86 (68.6%) delivered by cesarean, 37/86 (43.0%) reported post-discharge fever, and 44/86 (51.2%) reported post-discharge infection. Neither ANC attendance, abnormal temperature after delivery, nor their interaction term, were significantly associated with post-discharge PNC. The included covariates were not significantly associated with the outcome. CONCLUSIONS: While the overall proportion of women reporting post-discharge PNC was low, those who reported visiting a health facility and/or hospitalization had high proportions of post-discharge fever, post-discharge infection, and cesarean delivery, which suggests that these visits may have been related to problem-focused care. No significant associations between ANC and PNC were observed in this cohort. Further research assessing ANC quality and PNC visit focus is needed to ensure ANC and PNC are optimized to reduce morbidity and mortality.

Building Perinatal Pathology Research Capacity in Sub-Saharan Africa.

Introduction: Over two million stillbirths and neonatal deaths occur in sub-Saharan Africa (sSA) annually. Despite multilateral efforts, reducing perinatal mortality has been slow. Although targeted pathologic investigation can often determine the cause of perinatal death, in resource-limited settings, stillbirths, early neonatal deaths, and placentas are rarely examined pathologically. However, the placenta is a key source of diagnostic information and is the main determinant of fetal growth and development in utero, influencing child health outcomes. Methods: In 2016, our collaborative intercontinental group began investigating infectious perinatal death and adverse child health outcomes in Uganda. We developed and initiated a 4-day combined didactic/practical curriculum to train health workers in placental collection, gross placental examination, and tissue sampling for histology. We also trained a local technician to perform immunohistochemistry staining. Results: Overall, we trained 12 health workers who performed gross placental assessment for > 1,000 placentas, obtaining > 5,000 formalin-fixed tissue samples for research diagnostic use. Median placental weights ranged from 425 to 456 g, and 33.3% of placentas were < 10th percentile in weight, corrected for gestational age. Acute chorioamnionitis (32.3%) and maternal vascular malperfusion (25.4%) were common diagnoses. Discussion: Through a targeted training program, we built capacity at a university-affiliated hospital in sSA to independently perform placental collection, gross pathologic examination, and placental tissue processing for histology and special stains. Our training model can be applied to other collaborative research endeavors in diverse resource-limited settings to improve research and clinical capacity and competency for diagnostics and management of stillbirth, neonatal death, and child health outcomes.

Altered Maternal Antibody Profiles in Women With Human Immunodeficiency Virus Drive Changes in Transplacental Antibody Transfer.

BACKGROUND: Human immunodeficiency virus (HIV)-exposed, uninfected (HEU) children have a higher risk of severe infection, but the causes are poorly understood. Emerging data point to altered antibody transfer in women with HIV (WHIV); however, specific perturbations and the influence of antiretroviral therapy (ART) and HIV viremia remain unclear. METHODS: We evaluated antigen-specific transplacental antibody transfer across 14 antigens in paired maternal and umbilical cord plasma from 352 Ugandan women; 176 were WHIV taking ART. We measured antigen-specific immunoglobulin G (IgG) sub-class (IgG1, 2, 3, 4) levels and antibody Fcγ receptor (FcγRn, 2a, 2b, 3a, 3b) binding profiles. We used partial least squares discrimi-nant analysis to define antigen-specific transplacental antibody transfer features. RESULTS: Global antibody transfer patterns were similar by maternal HIV serostatus, pointing to effective placental function in WHIV. However, HEU umbilical cord antibody profiles were altered, driven by perturbed WHIV seroprofiles, with higher levels of herpesvirus antibodies (P < .01 for Epstein-Barr virus, herpes simplex virus) and lower levels of classic vaccine-induced antibodies (P < .01 for tetanus, polio, Haemophilus influenzae type b), suggesting that umbilical cord antibody profile differences arise from imbalanced WHIV immunity. Abnormal WHIV antibody profiles were associated with HIV viremia, lower CD4 count, and postconception ART initiation (P = .01). CONCLUSIONS: Perturbed immune-dominance profiles in WHIV shift the balance of immunity delivered to neonates. Perturbed HIV-associated maternal antibody profiles are a key determinant of com-promised neonatal immunity. Maternal vaccination interventions may promote transfer of relevant, effective antibodies to protect HEU children against early-life infections.

Code status orders in patients admitted to the intensive care unit with COVID-19: A retrospective cohort study.

Purpose: Code status orders impact clinical outcomes as well as patients' and surrogates' experiences. This is the first multicenter cohort examining code status orders of ICU patients with COVID-19 reported to date. Materials and methods: This is a retrospective cohort study including adult patients who tested positive for SARS-CoV-2 and were admitted to the ICU at three hospitals in Massachusetts from March 11, 2020 - May 31, 2020. We examined differences in code status orders at multiple timepoints and performed multivariable regression analysis to identify variables associated with code status at admission. Results: Among 459 ICU patients with COVID-19, 421 (91.7%) were Full Code at hospital admission. Age and admission from a facility were positively associated with DNR status (adjusted OR 1.10, 95% CI 1.05-1.15, p < 0.001 and adjusted OR 2.68, CI 1.23-5.71, p = 0.011, respectively) while non-English preferred language was negatively associated with DNR status (adjusted OR 0.29, 95% CI 0.10-0.74, p = 0.012). Among 147 patients who died during hospitalization, 95.2% (140) died with DNR code status; most (86.4%) died within two days of final code status change. Conclusions: The association of non-English preferred language with Full Code status in critically ill COVID-19 patients highlights the importance of medical interpreters in the ICU. Patients who died were transitioned to DNR more than in previous studies, possibly reflecting changes in practice during a novel pandemic.

Cytomegalovirus infections in infants in Uganda: Newborn-mother pairs, neonates with sepsis, and infants with hydrocephalus.

OBJECTIVES: To estimate the prevalence of cytomegalovirus (CMV) infections among newborn-mother pairs, neonates with sepsis, and infants with hydrocephalus in Uganda. DESIGN AND METHODS: Three populations-newborn-mother pairs, neonates with sepsis, and infants (≤3 months) with nonpostinfectious (NPIH) or postinfectious (PIH) hydrocephalus-were evaluated for CMV infection at 3 medical centers in Uganda. Quantitative PCR (qPCR) was used to characterize the prevalence of CMV. RESULTS: The overall CMV prevalence in 2498 samples across all groups was 9%. In newborn-mother pairs, there was a 3% prevalence of cord blood CMV positivity and 33% prevalence of maternal vaginal shedding. In neonates with clinical sepsis, there was a 2% CMV prevalence. Maternal HIV seropositivity (adjusted odds ratio [aOR] 25.20; 95% confidence interval [CI] 4.43-134.26; p = 0.0001), residence in eastern Uganda (aOR 11.06; 95% CI 2.30-76.18; p = 0.003), maternal age <25 years (aOR 4.54; 95% CI 1.40-19.29; p = 0.02), and increasing neonatal age (aOR 1.08 for each day older; 95% CI 1.00-1.16; p = 0.05), were associated risk factors for CMV in neonates with clinical sepsis. We found a 2-fold higher maternal vaginal shedding in eastern (45%) vs western (22%) Uganda during parturition (n = 22/49 vs 11/50, the Fisher exact test; p = 0.02). In infants with PIH, the prevalence in blood was 24% and in infants with NPIH, it was 20%. CMV was present in the cerebrospinal fluid (CSF) of 13% of infants with PIH compared with 0.5% of infants with NPIH (n = 26/205 vs 1/194, p < 0.0001). CONCLUSIONS: Our findings highlight that congenital and postnatal CMV prevalence is substantial in this African setting, and the long-term consequences are uncharacterized.