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BACKGROUND: Data on long-term neurodevelopmental outcomes of normocephalic children (born with normal head circumference) exposed to Zika virus in utero are scarce. We aimed to compare neurodevelopmental outcomes in normocephalic children up to age 48 months with and without Zika virus exposure in utero. METHODS: In this prospective cohort study, we included infants from two cohorts of normocephalic children born in León and Managua, Nicaragua during the 2016 Zika epidemic. In León, all women pregnant during the two enrolment periods were eligible. In Managua, mother-child pairs were included from three districts in the municipality of Managua: all women who became pregnant before June 15, 2016, and had a due date of Sept 15, 2016 or later were eligible. Infants were serologically classified as Zika virus-exposed or Zika virus-unexposed in utero and were followed up prospectively until age 48 months. At 36 months and 48 months of age, the Mullen Scales of Early Learning (MSEL) assessment was administered. Primary outcomes were MSEL early learning composite (ELC) scores at 30-48 months in León and 36-48 months in Managua. We used an inverse probability weighting generalised estimating equations model to assess the effect of Zika virus exposure on individual MSEL cognitive domain scores and ELC scores, adjusted for maternal education and age, poverty status, and infant sex. FINDINGS: The initial enrolment period for the León cohort was between Jan 31 and April 5, 2017 and the second was between Aug 30, 2017, and Feb 22, 2018. The enrolment period for the Managua cohort was between Oct 24, 2019, and May 5, 2020. 478 mothers (482 infants) from the León cohort and 615 mothers (609 infants) from the Managua cohort were enrolled, of whom 622 children (303 from the León cohort; 319 from the Managua cohort) were included in the final analysis; four children had microcephaly at birth and thus were excluded from analyses, two from each cohort. 33 (11%) of 303 children enrolled in León and 219 (69%) of 319 children enrolled in Managua were exposed to Zika virus in utero. In both cohorts, no significant differences were identified in adjusted mean ELC scores between Zika virus-exposed and unexposed infants at 36 months (between-group difference 1·2 points [95% CI -4·2 to 6·5] in the León cohort; 2·8 [-2·4 to 8·1] in the Managua cohort) or at 48 months (-0·9 [-10·8 to 8·8] in the León cohort; 0·1 [-5·1 to 5·2] in the Managua cohort). No differences in ELC scores between Zika virus-exposed and unexposed infants exceeded 6 points at any time between 30 months and 48 months in León or between 36 months and 48 months in Managua, which was considered clinically significant in other settings. INTERPRETATION: We found no significant differences in neurodevelopmental scores between normocephalic children with in-utero Zika virus exposure and Zika virus-unexposed children at age 36 months or 48 months. These findings are promising, supporting typical neurodevelopment in Zika virus-exposed normocephalic children, although additional follow-up and research is warranted. FUNDING: National Institute of Child Health and Development, National Institute of Allergy and Infectious Diseases, and Fogarty International Center. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

BACKGROUNDUndifferentiated systemic autoinflammatory diseases (USAIDs) present diagnostic and therapeutic challenges. Chronic interferon (IFN) signaling and cytokine dysregulation may identify diseases with available targeted treatments.METHODSSixty-six consecutively referred USAID patients underwent underwent screening for the presence of an interferon signature using a standardized type-I IFN-response-gene score (IRG-S), cytokine profiling, and genetic evaluation by next-generation sequencing.RESULTSThirty-six USAID patients (55%) had elevated IRG-S. Neutrophilic panniculitis (40% vs. 0%), basal ganglia calcifications (46% vs. 0%), interstitial lung disease (47% vs. 5%), and myositis (60% vs. 10%) were more prevalent in patients with elevated IRG-S. Moderate IRG-S elevation and highly elevated serum IL-18 distinguished 8 patients with pulmonary alveolar proteinosis (PAP) and recurrent macrophage activation syndrome (MAS). Among patients with panniculitis and progressive cytopenias, 2 patients were compound heterozygous for potentially novel LRBA mutations, 4 patients harbored potentially novel splice variants in IKBKG (which encodes NF-κB essential modulator [NEMO]), and 6 patients had de novo frameshift mutations in SAMD9L. Of additional 12 patients with elevated IRG-S and CANDLE-, SAVI- or Aicardi-Goutières syndrome-like (AGS-like) phenotypes, 5 patients carried mutations in either SAMHD1, TREX1, PSMB8, or PSMG2. Two patients had anti-MDA5 autoantibody-positive juvenile dermatomyositis, and 7 could not be classified. Patients with LRBA, IKBKG, and SAMD9L mutations showed a pattern of IRG elevation that suggests prominent NF-κB activation different from the canonical interferonopathies CANDLE, SAVI, and AGS.CONCLUSIONSIn patients with elevated IRG-S, we identified characteristic clinical features and 3 additional autoinflammatory diseases: IL-18-mediated PAP and recurrent MAS (IL-18PAP-MAS), NEMO deleted exon 5-autoinflammatory syndrome (NEMO-NDAS), and SAMD9L-associated autoinflammatory disease (SAMD9L-SAAD). The IRG-S expands the diagnostic armamentarium in evaluating USAIDs and points to different pathways regulating IRG expression.TRIAL REGISTRATIONClinicalTrials.gov NCT02974595.FUNDINGThe Intramural Research Program of the NIH, NIAID, NIAMS, and the Clinical Center.

The article discusses the establishment of trustworthiness criteria for meta-analyses of randomized controlled trials (RCTs) in obstetrics and gynecology (OBGYN) journals. The criteria aim to ensure the exclusion of low-quality or fabricated studies from meta-analyses by assessing various aspects such as governance, ethics, registration, and methodology. Authors conducting meta-analyses are encouraged to adhere to these criteria, which are divided into 'absolute' and 'other quality' criteria, to enhance the integrity and reliability of their research. The guidelines also emphasize the importance of prospective registration, adherence to CONSORT guidelines, and risk-of-bias assessment to promote transparency and reproducibility in research. [Extracted from the article]

As antiretroviral therapy (ART) expands in resource-limited settings, understanding the impact of ART on pregnancy outcomes is critical. We analyzed women who became pregnant on ART while enrolled in a clinical trial (HPTN 052, ACTG A5208, and ACTG A5175); the majority of women were from Africa, with a median age of 29 years. Eligible women were on ART at conception and had a documented date of a last menstrual period and a pregnancy outcome. The primary outcome was non-live birth (stillbirth; spontaneous abortion; elective termination; or ectopic pregnancy) versus live birth. Preterm birth (

Background: The Edinburgh Postnatal Depression Scale (EPDS) is a widely used tool for assessing postpartum depression, but its cut-off scores have not been examined in Zambia. The present study aimed to identify factors associated with severe depressive symptoms and determine the optimal cutoff scores for the EPDS among postpartum women with HIV in Lusaka, Zambia using the Mini International Neuropsychiatric Interview (MINI) as the gold standard. Methods: As part of a depression treatment trial, we screened HIV positive women with the EPDS between 6-10 weeks postpartum. To identify women at the lower symptom threshold, those scoring ≥ 6 (out of 30) on the EPDS were referred for a diagnostic Mini International Neuropsychiatric Interview (MINI). We investigated risk factors associated with severe depressive symptom scores. Additionally, we estimated the optimal EPDS screening threshold for probable diagnosis of depression with a receiver operating characteristic (ROC) curve. Based on literature, we defined an EPDS of 6-13 as "mild depressive symptoms" and an EPDS ≥ 14 as "moderate/severe depressive symptoms". Results: Out of 240 women screened, 192 (80%) scored ≥ 6 on the EPDS, of whom 120 (63%) agreed to undergo MINI evaluation. Of these, 61/120 (51 %) scored between 6 and 13 (inclusive) and 59/120 (49%) scored ≥ 14. In unadjusted analysis, factors associated with severe depressive symptom scores were not being married or living with partner (odds ratio [OR]=3.11; 95% CI 1.03, 9.37; p=0.04) and having more life stressors (mean difference 1.0; 95% CI 0.2, 1.8; p=0.01). Having more life stressors remained significant in an adjusted logistic regression model (aOR 1.23; 95% CI 1.02,1.50; p=0.04), with each additional life stressor increasing odds of moderate/severe depression by 23%. An EPDS score of ≥ 11 performed best at discriminating MINI-diagnosed depression with a sensitivity of 83% and a specificity of 57%. Conclusions: An EPDS score ≥ 11 was the optimal threshold for determining probable depression in HIV positive postpartum women. Women with a greater number of life stressors were more likely to score higher on the EPDS. ClinicalTrials.gov Registration Number: NCT04094870 [ABSTRACT FROM AUTHOR]

This report details the case of a 17-month old boy with refractory multifocal pyoderma gangrenosum responsive to anti-TNF therapy.

Historically, high school chemistry has been the predominate venue for the introduction of food science curriculum to students. With the current decline in chemistry as a required course for graduation, the possibility of exposure to food science in high school could equally decline. The purpose of this research was to determine if high school students in a biology class without a chemistry background could comprehend eight basic food science principles equally as well as students in a chemistry class that were taught the same principles. This study assessed baseline knowledge of high school students, determined the effect of food science-based lessons on baseline knowledge and level of understanding, and determined the effect of food science-based lessons on students' awareness of and interest in food science. Baseline knowledge and awareness of food science was low. Food science-based instruction resulted in higher posttest scores. Results indicated no differences in students' knowledge base and level of understanding between biology and chemistry classes and supported the idea of further incorporating a food science curriculum into high school biology.

Key Points: Question: Can novice clinicians accurately estimate gestational age using a low-cost, battery-powered ultrasonography probe with integrated artificial intelligence (AI) image interpretation? Findings: This prospective study enrolled 400 pregnant individuals with due dates confirmed by first-trimester ultrasonography. At follow-up visits randomly assigned throughout gestation, novice clinicians using an AI-enabled device estimated gestational age as accurately as credentialed sonographers using traditional ultrasonography devices (difference, 0.2 days). Meaning: Obstetrical care in low-resource settings may benefit from reliable gestational age assessment using AI integration with point-of-care ultrasonography. 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 This prospective diagnostic study examines the accuracy of an AI-enabled ultrasonography tool in estimating gestational age when used by those with no prior training in sonography. [ABSTRACT FROM AUTHOR]

INTRODUCTION Depression is a leading global cause of disability [1, 2]. Peripartum depression, defined as an episode of moderate or severe depression beginning during pregnancy or within 4 weeks of [...], : Introduction: Postpartum depression (PPD) is a prevalent and debilitating disease that may affect medication adherence and thus maternal health and vertical transmission among women with HIV. We assessed the feasibility of a trial of interpersonal psychotherapy (IPT) versus antidepressant medication (ADM) to treat PPD and/or anxiety among postpartum women with HIV in Lusaka, Zambia. Methods: Between 29 October 2019 and 8 September 2020, we pre?screened women 6?8 weeks after delivery with the Edinburgh Postnatal Depression Scale (EPDS) and diagnosed PPD or anxiety with the Mini International Neuropsychiatric Interview. Consenting participants were randomized 1:1 to up to 11 sessions of IPT or daily self?administered sertraline and followed for 24 weeks. We assessed EPDS score, Clinical Global Impression?Severity of Illness (CGI?S) and medication side effects at each visit and measured maternal HIV viral load at baseline and final study visit. Retention, visit adherence, change in EPDS, CGI?S and log viral load were compared between groups with t?tests and Wilcoxon signed rank tests; we report mean differences, relative risks and 95% confidence intervals. A participant satisfaction survey assessed trial acceptability. Results: 78/80 (98%) participants were retained at the final study visit. In the context of the COVID?19 pandemic, visit adherence was greater among women allocated to ADM (9.9 visits, SD 2.2) versus IPT (8.9 visits, SD 2.4; p = 0.06). EPDS scores decreased from baseline to final visit overall, though mean change was greater in the IPT group (?13.8 points, SD 4.7) compared to the ADM group (?11.4 points, SD 5.5; p = 0.04). Both groups showed similar changes in mean log viral load from baseline to final study visit (mean difference ?0.43, 95% CI ?0.32, 1.18; p = 0.48). In the IPT group, viral load decreased significantly from baseline (0.9 log copies/ml, SD 1.7) to final visit (0.2 log copies/ml, SD 0.9; p = 0.01). Conclusions: This pilot study demonstrates that a trial of two forms of PPD treatment is feasible and acceptable among women with HIV in Zambia. IPT and ADM both improved measures of depression severity; however, a full?scale trial is required to determine whether treatment of PPD and anxiety improves maternal?infant HIV outcomes.

HIV protease inhibitors (PIs) show antimalarial activity in vitro and in animals. Whether this translates into a clinical benefit in HIV-infected patients residing in malaria-endemic regions is unknown. We studied the incidence of malaria, as defined by blood smear positivity or a positive Plasmodium falciparum histidine-rich protein 2 antigen test, among 444 HIV-infected women initiating antiretroviral treatment (ART) in the OCTANE trial (A5208; ClinicalTrials.gov: NCT00089505). Participants were randomized to treatment with PI-containing vs. PI-sparing ART, and were followed prospectively for ≥48 weeks; 73% also received cotrimoxazole prophylaxis. PI-containing treatment was not associated with protection against malaria in this study population.

Author(s): Catherine J. Vladutiu [sup.1] [sup.2] , Elizabeth M. Stringer [sup.2] , Veni Kandasamy [sup.3] , Jill Ruppenkamp [sup.4] , M. Kathryn Menard [sup.2] Author Affiliations: (Aff1) 0000 0004 0405 [...], 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 [greater than or equal to] 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 [greater than or equal to] 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.

This article discusses the prevention and treatment of postpartum hemorrhage (PPH), which is the leading cause of maternal morbidity and mortality worldwide. The International Federation of Gynecology and Obstetrics (FIGO) provides updated recommendations for the prevention and treatment of PPH, emphasizing the importance of training and access to essential medicines and equipment, particularly in low- and middle-income countries. The article also discusses the use of uterotonics for PPH prevention, as well as various treatment options for PPH, including uterine massage, uterotonics, tranexamic acid, non-pneumatic anti-shock garments, and surgical interventions. Additionally, the article briefly mentions the prevention and treatment of malaria in pregnancy, highlighting the use of sulfadoxine-pyrimethamine (SP) and dihydroartemisinin-piperaquine (DHA/PQP) as potential options. However, the study mentioned in the article found that DHA/PQP was associated with higher rates of adverse pregnancy outcomes compared to SP, suggesting that countries should consider these results before changing their approach to intermittent prophylactic treatment in pregnancy (IPTp). [Extracted from the article]