Acceptability of a Randomized Trial of Anti-depressant Medication or Interpersonal Therapy for Treatment of Perinatal Depression in Women with HIV.

Postpartum depression (PPD) affects nearly 20% of postpartum women in Sub-Saharan Africa (SSA), where HIV prevalence is high. Depression is associated with worse HIV outcomes in non-pregnant adults and mental health disorders may worsen HIV outcomes for postpartum women and their infants. PPD is effectively treated with psychosocial or pharmacologic interventions; however, few studies have evaluated the acceptability of treatment modalities in SSA. We analyzed interviews with 23 postpartum women with HIV to assess the acceptability of two depression treatments provided in the context of a randomized trial. Most participants expressed acceptability of treatment randomization and study visit procedures. Participants shared perceptions of high treatment efficacy of their assigned intervention. They reported ongoing HIV and mental health stigma in their communities and emphasized the importance of social support from clinic staff. Our findings suggest a full-scale trial of PPD treatment will be acceptable among women with HIV in Zambia.

Diagnostic Accuracy of an Integrated AI Tool to Estimate Gestational Age From Blind Ultrasound Sweeps.

Importance: Accurate assessment of gestational age (GA) is essential to good pregnancy care but often requires ultrasonography, which may not be available in low-resource settings. This study developed a deep learning artificial intelligence (AI) model to estimate GA from blind ultrasonography sweeps and incorporated it into the software of a low-cost, battery-powered device. Objective: To evaluate GA estimation accuracy of an AI-enabled ultrasonography tool when used by novice users with no prior training in sonography. Design, Setting, and Participants: This prospective diagnostic accuracy study enrolled 400 individuals with viable, single, nonanomalous, first-trimester pregnancies in Lusaka, Zambia, and Chapel Hill, North Carolina. Credentialed sonographers established the "ground truth" GA via transvaginal crown-rump length measurement. At random follow-up visits throughout gestation, including a primary evaluation window from 14 0/7 weeks' to 27 6/7 weeks' gestation, novice users obtained blind sweeps of the maternal abdomen using the AI-enabled device (index test) and credentialed sonographers performed fetal biometry with a high-specification machine (study standard). Main Outcomes and Measures: The primary outcome was the mean absolute error (MAE) of the index test and study standard, which was calculated by comparing each method's estimate to the previously established GA and considered equivalent if the difference fell within a prespecified margin of ±2 days. Results: In the primary evaluation window, the AI-enabled device met criteria for equivalence to the study standard, with an MAE (SE) of 3.2 (0.1) days vs 3.0 (0.1) days (difference, 0.2 days [95% CI, -0.1 to 0.5]). Additionally, the percentage of assessments within 7 days of the ground truth GA was comparable (90.7% for the index test vs 92.5% for the study standard). Performance was consistent in prespecified subgroups, including the Zambia and North Carolina cohorts and those with high body mass index. Conclusions and Relevance: Between 14 and 27 weeks' gestation, novice users with no prior training in ultrasonography estimated GA as accurately with the low-cost, point-of-care AI tool as credentialed sonographers performing standard biometry on high-specification machines. These findings have immediate implications for obstetrical care in low-resource settings, advancing the World Health Organization goal of ultrasonography estimation of GA for all pregnant people. Trial Registration: ClinicalTrials.gov Identifier: NCT05433519.

Risk of Adverse Birth Outcomes in Two Cohorts of Pregnant Women With HIV in Zambia.

BACKGROUND: A trial of progesterone to prevent preterm birth among HIV-infected Zambian women [Improving Pregnancy Outcomes with Progesterone (IPOP)] found no treatment effect, but the risk of the primary outcome was among the lowest ever documented in women with HIV. In this secondary analysis, we compare the risks of preterm birth (<37 weeks), stillbirth, and a composite primary outcome comprising the two in IPOP versus an observational pregnancy cohort [Zambian Preterm Birth Prevention Study (ZAPPS)] in Zambia, to evaluate reasons for the low risk in IPOP. METHODS: Both studies enrolled women before 24 gestational weeks, during August 2015-September 2017 (ZAPPS) and February 2018-January 2020 (IPOP). We used linear probability and log-binomial regression to estimate risk differences and risk ratios (RR), before and after restriction and standardization with inverse probability weights. RESULTS: The unadjusted risk of composite outcome was 18% in ZAPPS (N = 1450) and 9% in IPOP (N = 791) (RR = 2.0; 95% CI = 1.6, 2.6). After restricting and standardizing the ZAPPS cohort to the distribution of IPOP baseline characteristics, the risk remained higher in ZAPPS (RR = 1.6; 95% CI = 1.0, 2.4). The lower risk of preterm/stillbirth in IPOP was only partially explained by measured risk factors. CONCLUSIONS: Possible benefits in IPOP of additional monetary reimbursement, more frequent visits, and group-based care warrant further investigation.

Neurodevelopmental Outcomes of Children Following In Utero Exposure to Zika in Nicaragua.

BACKGROUND: Neurodevelopmental outcomes of asymptomatic children exposed to Zika virus (ZIKV) in utero are not well characterized. METHODS: We prospectively followed 129 newborns without evidence of congenital Zika syndrome (CZS) up to 24 months of age. Participants were classified as ZIKV exposed or ZIKV unexposed. The Mullen Scales of Early Learning (MSEL) was administered in the participants' homes at 6, 12, 15, 18, 21, and 24 months of age by trained psychologists. Sociodemographic data, medical history, and infant anthropometry at birth were collected at each home visit. Our primary outcome was the Mullen Early Learning Composite Score (ECL) at 24 months of age between our 2 exposure groups. Secondary outcomes were differences in MSEL subscales over time and at 24 months. RESULTS: Of 129 infants in whom exposure status could be ascertained, 32 (24.8%) met criteria for in utero ZIKV exposure and 97 (75.2%) did not. There were no differences in maternal age, maternal educational attainment, birthweight, or gestational age at birth between the 2 exposure groups. The adjusted means and standard errors (SEs) for the ELC score between the ZIKV-exposed children compared to ZIKV-unexposed children were 91.4 (SE, 3.1) vs 96.8 (SE, 2.4) at 12 months and 93.3 (SE, 2.9) vs 95.9 (SE, 2.3) at 24 months. In a longitudinal mixed model, infants born to mothers with an incident ZIKV infection (P = .01) and low-birthweight infants (<2500 g) (P = .006) had lower composite ECL scores. CONCLUSIONS: In this prospective cohort of children without CZS, children with in utero ZIKV exposure had lower neurocognitive scores at 24 months.

Misclassification in defining and diagnosing microcephaly.

BACKGROUND: Several health agencies define microcephaly for surveillance purposes using a single criterion, a percentile or Z-score cut-off for newborn head circumference. This definition, however, conflicts with the reported prevalence of microcephaly even in populations with endemic Zika virus. OBJECTIVE: We explored possible reasons for this conflict, hypothesising that the definition of microcephaly used in some studies may be incompletely described, lacking the additional clinical criteria that clinicians use to make a formal diagnosis. We also explored the potential for misclassification that can result from differences in these definitions, especially when applying a percentile cut-off definition in the presence of the much lower observed prevalence estimates that we believe to be valid. METHODS: We conducted simulations under a theoretical bimodal distribution of head circumference. For different definitions of microcephaly, we calculated the sensitivity and specificity using varying cut-offs of head circumference. We then calculated and plotted the positive predictive value for each of these definitions by prevalence of microcephaly. RESULTS: Simple simulations suggest that if the true prevalence of microcephaly is approximately what is reported in peer-reviewed literature, then relying on cut-off-based definitions may lead to very poor positive predictive value under realistic conditions. CONCLUSIONS: While a simple head circumference criterion may be used in practice as a screening or surveillance tool, the definition lacks clarification as to what constitutes true pathological microcephaly and may lead to confusion about the true prevalence of microcephaly in Zika-endemic areas, as well as bias in aetiologic studies.

Emergency Care Utilization Among Pregnant Medicaid Recipients in North Carolina: An Analysis Using Linked Claims and Birth Records.

Objectives To estimate the rate of pregnancy-associated emergency care visits and identify maternal and pregnancy characteristics associated with high utilization of emergency care among pregnant Medicaid recipients in North Carolina. Methods A retrospective cohort study using linked Medicaid hospital claims and birth records of 107,207 pregnant Medicaid recipients who delivered a live-born infant in North Carolina between January 1, 2008 and December 31, 2009. Rates were estimated per 1000 member months of Medicaid coverage. High utilization was defined as ≥ 4 visits. Emergency care visits included encounters in the emergency department or obstetric triage unit during pregnancy that did not result in hospital admission. Results During the study period, 57.5% of pregnant Medicaid recipients sought emergency care at least once during pregnancy. There were 171,909 emergency care visits with an overall rate of 202.3 visits per 1000 member months. Among the subset of pregnant women with Medicaid coverage for the majority of their pregnancy (n = 75,157), 18.1% were high utilizers. High emergency care utilization was associated with young age, black race, lower education, tobacco use, late preterm delivery, multifetal gestation, and having ≥ 1 comorbidity. Threatened labor and abdominal pain were the leading indications for visits. Conclusion Utilization of hospital-based emergency care services was common in this cohort of pregnant Medicaid recipients. Additional research is needed to assess the drivers for accessing care through the emergency department, and to examine differences in pregnancy outcomes and health care costs between high and low utilizers.

Maternal Decision-Making and Uptake of Health Services for the Prevention of Mother-to-Child HIV Transmission: A Secondary Analysis.

Objectives We investigated whether a woman's role in household decision-making was associated with receipt of services to prevent mother-to-child HIV transmission (PMTCT). Methods We conducted a secondary analysis of the PEARL study, an evaluation of PMTCT effectiveness in Cameroon, Cote d'Ivoire, South Africa, and Zambia. Our exposure of interest was the women's role (active vs. not active) in decision-making about her healthcare, large household purchases, children's schooling, and children's healthcare (i.e., four domains). Our primary outcomes were self-reported engagement at three steps in PMTCT: maternal antiretroviral use, infant antiretroviral prophylaxis, and infant HIV testing. Associations found to be significant in univariable logistic regression were included in separate multivariable models. Results From 2008 to 2009, 613 HIV-infected women were surveyed and provided information about their decision-making roles. Of these, 272 (44.4%) women reported antiretroviral use; 281 (45.9%) reported infant antiretroviral prophylaxis; and 194 (31.7%) reported infant HIV testing. Women who reported an active role were more likely to utilize infant HIV testing services, across all four measured domains of decision-making (adjusted odds ratios [AORs] 2.00-2.89 all p < .05). However, associations between decision-making and antiretroviral use-for both mother and infant-were generally not significant. An exception was active decision-making in a woman's own healthcare and reported maternal antiretroviral use (AOR 1.69, p < 0.05). Conclusions for Practice Associations between decision-making and PMTCT engagement were inconsistent and may be related to specific characteristics of individual health-seeking behaviors. Interventions seeking to improve PMTCT uptake should consider the type of health-seeking behavior to better optimize health services.

17-Hydroxyprogesterone caproate (17OHP-C) coverage among eligible women delivering at 2 North Carolina hospitals in 2012 and 2013: A retrospective cohort study.

BACKGROUND: Although a weekly injection of 17-hydroxyprogestone caproate is recommended for preventing recurrent preterm birth, clinical experience in North Carolina suggested that many eligible patients were not receiving the intervention. OBJECTIVE: Our study sought to assess how well practices delivering at 2 major hospitals were doing in providing access to 17-hydroxyprogesterone caproate treatment for eligible patients. STUDY DESIGN: This retrospective cohort analysis studied all deliveries occurring between January 1, 2012, and December 31, 2013, at 2 large hospitals in North Carolina. Women were included if they had a singleton pregnancy and history of a prior spontaneous preterm birth. We extracted demographic, payer, and medical information on each pregnancy, including whether women had been offered, accepted, and received 17-hydroxyprogesterone caproate. Our outcome of 17-hydroxyprogesterone caproate coverage was defined as documentation of ≥1 injection of the drug. RESULTS: Over the 2-year study period, 1216 women with history of a prior preterm birth delivered at the 2 study hospitals, of which 627 were eligible for 17-hydroxyprogesterone caproate eligible after medical record review. Only 296 of the 627 eligible women (47%; 95% confidence interval, 43-51%) received ≥1 dose of the drug. In multivariable analysis, hospital of delivery, later presentation for prenatal care, fewer prenatal visits, later gestation of prior preterm birth, and having had a term delivery immediately before the index pregnancy were all associated with failed coverage. Among those women who were "covered," the median number of 17-hydroxyprogesterone caproate injections was 9 (interquartile range, 4-15), with 84 of 296 charts (28%) not having complete information on the number of doses. CONCLUSION: Even under our liberal definition of coverage, less than half of eligible women received 17-hydroxyprogesterone caproate in this sample. Low overall use suggests that there is opportunity for improvement. Quality improvement strategies, including population-based measurement of 17-hydroxyprogesterone caproate coverage, are needed to fully implement this evidence-based intervention to decrease preterm birth.

Integrase inhibitors in late pregnancy and rapid HIV viral load reduction.

BACKGROUND: 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. OBJECTIVE: We describe time to clinically relevant reduction in HIV RNA in pregnant women using INSTI-containing and non-INSTI-containing antiretroviral therapy (ART) options. STUDY DESIGN: 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 RNA >40 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. RESULTS: 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). CONCLUSION: 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.

A Worldwide Epidemic: The Problem and Challenges of Preterm Birth in Low- and Middle-Income Countries.

Preterm birth (PTB) is the most common cause of neonatal death worldwide and the second leading cause of under-5 mortality. Low- and middle-income countries (LMICs) bear a disproportionate burden of this disease. An estimated 1 million preterm infants die in the neonatal period each year and many of those who survive face lifelong disability. In this review, we explore the global burden of PTB through an examination of risk factors and predisposing clinical conditions found in LMICs. We then discuss current interventions available to prevent PTB and/or mitigate its clinical sequelae. A major finding of this review is that although the majority of the global PTB disease burden is shouldered by LMICs, very little of the research evidence for its prevention and treatment derives from these settings. Primary research and implementation studies that involve LMIC populations are urgently needed.

Universal combination antiretroviral regimens to prevent mother-to-child transmission of HIV in rural Zambia: a two-round cross-sectional study.

OBJECTIVE: To evaluate if a pilot programme to prevent mother-to-child transmission (PMTCT) of the human immunodeficiency virus (HIV) was associated with changes in early childhood survival at the population level in rural Zambia. METHODS: Combination antiretroviral regimens were offered to pregnant and breastfeeding, HIV-infected women, irrespective of immunological status, at four rural health facilities. Twenty-four-month HIV-free survival among children born to HIV-infected mothers was determined before and after PMTCT programme implementation using community surveys. Households were randomly selected and women who had given birth in the previous 24 months were asked to participate. Mothers were tested for HIV antibodies and children born to HIV-infected mothers were tested for viral deoxyribonucleic acid. Multivariable models were used to determine factors associated with child HIV infection or death. FINDINGS: In the first survey (2008-2009), 335 of 1778 women (18.8%) tested positive for HIV. In the second (2011), 390 of 2386 (16.3%) tested positive. The 24-month HIV-free survival in HIV-exposed children was 0.66 (95% confidence interval, CI: 0.63-0.76) in the first survey and 0.89 (95% CI: 0.83-0.94) in the second. Combination antiretroviral regimen use was associated with a lower risk of HIV infection or death in children (adjusted hazard ratio: 0.33, 95% CI: 0.15-0.73). Maternal knowledge of HIV status, use of HIV tests and use of combination regimens during pregnancy increased between the surveys. CONCLUSION: The PMTCT programme was associated with an increased HIV-free survival in children born to HIV-infected mothers. Maternal utilization of HIV testing and treatment in the community also increased.

Sedation and anesthesia of hatchling leatherback sea turtles (Dermochelys coriacea) for auditory evoked potential measurement in air and in water.

Sedation or anesthesia of hatchling leatherback sea turtles was employed to acquire auditory evoked potential (AEP) measurements in air and in water to assess their hearing sensitivity in relation to potential consequences from anthropogenic noise. To reduce artifacts in AEP collection caused by muscle movement, hatchlings were sedated with midazolam 2 or 3 mg/kg i.v. for in-air (n = 7) or in-water (n = 11) AEP measurements; hatchlings (n = 5) were anesthetized with ketamine 6 mg/kg and dexmedetomidine 30 microg/kg i.v. reversed with atipamezole 300 microg/kg, half i.m. and half i.v. for in-air AEP measurements. Midazolam-sedated turtles were also physically restrained with a light elastic wrap. For in-water AEP measurements, sedated turtles were brought to the surface every 45-60 sec, or whenever they showed intention signs for breathing, and not submerged again until they took a breath. Postprocedure temperature-corrected venous blood pH, pCO2, pO2, and HCO3- did not differ among groups, although for the midazolam-sedated in-water group, pCO2 trended lower, and in the ketamine-dexmedetomidine anesthetized group there was one turtle considered clinically acidotic (temperature-corrected pH = 7.117). Venous blood lactate was greater for hatchlings recently emerged from the nest than for turtles sedated with midazolam in air, with the other two groups falling intermediate between, but not differing significantly from the high and low lactate groups. Disruptive movements were less frequent with anesthesia than with sedation in the in-air group. Both sedation with midazolam and anesthesia with ketamine-dexmedetomidine were successful for allowing AEP measurements in hatchling leatherback sea turtles. Sedation allowed the turtle to protect its airway voluntarily while limiting flipper movement. Midazolam or ketamine-dexmedetomidine (and reversal with atipamezole) would be useful for other procedures requiring minor or major restraint in leatherback sea turtle hatchlings and other sea turtles, although variable susceptibilities may require dose adjustments.

Measuring coverage in MNCH: population HIV-free survival among children under two years of age in four African countries.

BACKGROUND: Population-based evaluations of programs for prevention of mother-to-child HIV transmission (PMTCT) are scarce. We measured PMTCT service coverage, regimen use, and HIV-free survival among children ≤24 mo of age in Cameroon, Côte D'Ivoire, South Africa, and Zambia. METHODS AND FINDINGS: We randomly sampled households in 26 communities and offered participation if a child had been born to a woman living there during the prior 24 mo. We tested consenting mothers with rapid HIV antibody tests and tested the children of seropositive mothers with HIV DNA PCR or rapid antibody tests. Our primary outcome was 24-mo HIV-free survival, estimated with survival analysis. In an individual-level analysis, we evaluated the effectiveness of various PMTCT regimens. In a community-level analysis, we evaluated the relationship between HIV-free survival and community PMTCT coverage (the proportion of HIV-exposed infants in each community that received any PMTCT intervention during gestation or breastfeeding). We also compared our community coverage results to those of a contemporaneous study conducted in the facilities serving each sampled community. Of 7,985 surveyed children under 2 y of age, 1,014 (12.7%) were HIV-exposed. Of these, 110 (10.9%) were HIV-infected, 851 (83.9%) were HIV-uninfected, and 53 (5.2%) were dead. HIV-free survival at 24 mo of age among all HIV-exposed children was 79.7% (95% CI: 76.4, 82.6) overall, with the following country-level estimates: Cameroon (72.6%; 95% CI: 62.3, 80.5), South Africa (77.7%; 95% CI: 72.5, 82.1), Zambia (83.1%; 95% CI: 78.4, 86.8), and Côte D'Ivoire (84.4%; 95% CI: 70.0, 92.2). In adjusted analyses, the risk of death or HIV infection was non-significantly lower in children whose mothers received a more complex regimen of either two or three antiretroviral drugs compared to those receiving no prophylaxis (adjusted hazard ratio: 0.60; 95% CI: 0.34, 1.06). Risk of death was not different for children whose mothers received a more complex regimen compared to those given single-dose nevirapine (adjusted hazard ratio: 0.88; 95% CI: 0.45, 1.72). Community PMTCT coverage was highest in Cameroon, where 75 of 114 HIV-exposed infants met criteria for coverage (66%; 95% CI: 56, 74), followed by Zambia (219 of 444, 49%; 95% CI: 45, 54), then South Africa (152 of 365, 42%; 95% CI: 37, 47), and then Côte D'Ivoire (3 of 53, 5.7%; 95% CI: 1.2, 16). In a cluster-level analysis, community PMTCT coverage was highly correlated with facility PMTCT coverage (Pearson's r = 0.85), and moderately correlated with 24-mo HIV-free survival (Pearson's r = 0.29). In 14 of 16 instances where both the facility and community samples were large enough for comparison, the facility-based coverage measure exceeded that observed in the community. CONCLUSIONS: HIV-free survival can be estimated with community surveys and should be incorporated into ongoing country monitoring. Facility-based coverage measures correlate with those derived from community sampling, but may overestimate population coverage. The more complex regimens recommended by the World Health Organization seem to have measurable public health benefit at the population level, but power was limited and additional field validation is needed.

Single-center serological surveillance of SARS-CoV-2 in pregnant patients presenting to labor and delivery.

OBJECTIVE: To measure maternal/fetal SARS-CoV-2 antibody levels. METHODS: A prospective observational study of eligible parturients admitted to the hospital for infant delivery was conducted between April and September 2020. SARS-CoV-2 antibody levels were measured in maternal and umbilical cord specimens using an in-house ELISA based on the receptor-binding domain (RBD) of the spike protein. Among SARS-CoV-2 seropositive patients, spike RBD antibody isotypes (IgG, IgM, and IgA) and ACE2 inhibiting antibodies were measured. RESULTS: In total, 402 mothers were enrolled and spike RBD antibodies in 388 pregnancies were measured (336 maternal and 52 cord specimens). Of them, 19 were positive (15 maternal, 4 cord) resulting in a seroprevalence estimate of 4.8% (95% confidence interval 2.9-7.4). Of the 15 positive maternal specimens, all had cord blood tested. Of the 15 paired specimens, 14 (93.3%) were concordant. Four of the 15 pairs were from symptomatic mothers, and all four showed high spike-ACE2 blocking antibody levels, compared to only 3 of 11 (27.3%) from asymptomatic mothers. CONCLUSION: A variable antibody response to SARS-CoV-2 in pregnancy among asymptomatic infections compared to symptomatic infections was found, the significance of which is unknown. Although transfer of transplacental neutralizing antibodies occurred, additional research is needed to determine how long maternal antibodies can protect the infant against SARS-CoV-2 infection.

Antibody Immunity to Zika Virus among Young Children in a Flavivirus-Endemic Area in Nicaragua.

Objective: To understand the dynamics of Zika virus (ZIKV)-specific antibody immunity in children born to mothers in a flavivirus-endemic region during and after the emergence of ZIKV in the Americas. Methods: We performed serologic testing for ZIKV cross-reactive and type-specific IgG in two longitudinal cohorts, which enrolled pregnant women and their children (PW1 and PW2) after the beginning of the ZIKV epidemic in Nicaragua. Quarterly samples from children over their first two years of life and maternal blood samples at birth and at the end of the two-year follow-up period were studied. Results: Most mothers in this dengue-endemic area were flavivirus-immune at enrollment. ZIKV-specific IgG (anti-ZIKV EDIII IgG) was detected in 82 of 102 (80.4%) mothers in cohort PW1 and 89 of 134 (66.4%) mothers in cohort PW2, consistent with extensive transmission observed in Nicaragua during 2016. ZIKV-reactive IgG decayed to undetectable levels by 6-9 months in infants, whereas these antibodies were maintained in mothers at the year two time point. Interestingly, a greater contribution to ZIKV immunity by IgG3 was observed in babies born soon after ZIKV transmission. Finally, 43 of 343 (13%) children exhibited persistent or increasing ZIKV-reactive IgG at ≥9 months, with 10 of 30 (33%) tested demonstrating serologic evidence of incident dengue infection. Conclusions: These data inform our understanding of protective and pathogenic immunity to potential flavivirus infections in early life in areas where multiple flaviviruses co-circulate, particularly considering the immune interactions between ZIKV and dengue and the future possibility of ZIKV vaccination in women of childbearing potential. This study also shows the benefits of cord blood sampling for serologic surveillance of infectious diseases in resource-limited settings.

Maternal mid-upper arm circumference to predict small for gestational age: Findings in a Zambian cohort.

OBJECTIVE: To compare the performance of mid upper arm circumference (MUAC) and body mass index (BMI) for prediction of small for gestational age (SGA) in Zambia. METHODS: This is a secondary analysis of an ongoing clinical cohort that included women with a single gestation and MUAC measured before 24 weeks of pregnancy. We assessed relationships between maternal MUAC and birth weight centile using regression. The performance of MUAC and BMI to predict SGA was compared using receiver operating characteristic curves and the effect of maternal HIV was investigated in sub-group analyses. RESULTS: Of 1117 participants, 847 (75%) were HIV-negative (HIV-) and 270 (24%) were HIV-positive (HIV+). Seventy-four (7%) delivered severe SGA infants (<3rd centile), of whom 56 (76%) were HIV- and 18 (24%) were HIV+ (odds ratio [OR] 1.01, 95% confidence interval [CI] 0.58-1.75). MUAC was associated with higher birth weight centile (+1.2 centile points, 95% CI 0.7-1.6; P < 0.001); this relationship was stronger among HIV+ women (+1.7 centile points, 95% CI 0.8-2.6; P < 0.001) than HIV- women (+0.9 centile points, 95% CI 0.4-1.4; P = 0.001). The discriminatory power was similar, albeit poor (area under the curve [AUC] < 0.7), between MUAC and BMI for the prediction of SGA. In stratified analysis, MUAC and BMI showed excellent discrimination predicting severe SGA among HIV+ (AUC 0.83 and 0.81, respectively) but not among HIV- women (AUC 0.64 and 0.63, respectively). CONCLUSION: Maternal HIV infection increased the discrimination of both early pregnancy MUAC and BMI for prediction of severe SGA in Zambia. CLINICAL TRIAL NUMBER: ClinicalTrials.gov (NCT02738892).

Visual findings in children exposed to Zika in utero in Nicaragua.

Knowledge regarding the frequency of ocular abnormalities and abnormal visual function in children exposed to Zika virus (ZIKV) in utero but born without congenital Zika syndrome (CZS) is limited. We hypothesized that children exposed to ZIKV in utero born without CZS may have visual impairments in early childhood. We performed ophthalmic examination between 16 and 21 months of age and neurodevelopment assessment at 24 months of age with the Mullen Scales of Early Learning test (MSEL) on children enrolled in a cohort born to women pregnant during and shortly after the ZIKV epidemic in Nicaragua (2016-2017). ZIKV exposure status was defined based on maternal and infant serological testing. Visual impairment was defined as abnormal if the child had an abnormal ophthalmic exam and/or low visual reception score in the MSEL assessment. Of 124 children included in the analysis, 24 (19.4%) were classified as ZIKV-exposed and 100 (80.6%) unexposed according to maternal or cord blood serology. Ophthalmic examination showed that visual acuity did not differ significantly between groups, thus, 17.4% of ZIKV-exposed and 5.2% of unexposed had abnormal visual function (p = 0.07) and 12.5% of the ZIKV-exposed and 2% of the unexposed had abnormal contrast testing (p = 0.05). Low MSEL visual reception score was 3.2-fold higher in ZIKV-exposed than unexposed children, but not statistically significant (OR 3.2, CI: 0.8-14.0; p = 0.10). Visual impairment (a composite measure of visual function or low MESL visual reception score) was present in more ZIKV-exposed than in unexposed children (OR 3.7, CI: 1.2, 11.0; p = 0.02). However, the limited sample size warrants future investigations to fully assess the impact of in utero ZIKV exposure on ocular structures and visual function in early childhood, even in apparently healthy children.

Anaerobic oral flora in the North American black bear (Ursus americanus) in eastern North Carolina.

Microbial flora can provide insight into the ecology and natural history of wildlife in addition to improving understanding of health risks. This study examines the anaerobic oral flora of hunter killed black bears (Ursus americanus) in eastern North Carolina. Oral swabs from the buccal and lingual supragingival tooth surfaces of the first and second mandibular and maxillary molars of 22 black bears were inoculated onto Brucella Blood Agar plates supplemented with hemin and vitamin K after transport from the field using reduced oxoid nutrient broth. Sixteen anaerobic bacterial species, representing nine genera were identified using the RapID ANA II Micromethod Kit system and a number of organisms grown that could not be identified with the system. The most frequently identified anaerobes were Peptostreptococcus prevotii, Streptococcus constellatus, and Porphyromonas gingivalis. The diversity in the anaerobic oral flora of black bear in eastern North Carolina suggests the importance of including these organisms in basic health risk assessment protocols and suggests a potential tool for assessment of bear/habitat interactions.

Risk factors associated with perianesthetic mortality of stranded free-ranging California sea lions (Zalophus californianus) undergoing rehabilitation.

The objective of this study was to identify risk factors associated with perianesthetic mortality of stranded free-ranging California sea lions (Zalophus californianus) undergoing rehabilitation. Hospital records of California sea lions that underwent heavy sedation or general anesthesia from 2004 through 2008 were reviewed, including records from 419 anesthetic events. Procedures that resulted in death during or in the subsequent 72 hr of anesthesia were classified as cases (n = 15). Procedures in which the animal survived were classified as controls (n = 334). Procedures that resulted in euthanasia (n = 70) were removed from subsequent analysis. The following risk factors were reviewed: gender, age class, health status, duration of anesthetic period, atropine premedication, induction protocols, maintenance protocols, and history of prior anesthesia. The prevalence of fatalities during anesthesia was 3.4% (n = 12) over the 5-yr period. With the inclusion of animals that died within 72 hr after anesthesia, the total mortality prevalence rose to 4.3% (n = 15). The most common time of death was during anesthetic maintenance. Health status was the single best predictor of anesthetic outcome, and sea lions premedicated with atropine had increased odds of anesthetic-related death.