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BACKGROUND: The use of azithromycin reduces maternal infection in women during unplanned cesarean delivery, but its effect on those with planned vaginal delivery is unknown. Data are needed on whether an intrapartum oral dose of azithromycin would reduce maternal and offspring sepsis or death. METHODS: In this multicountry, placebo-controlled, randomized trial, we assigned women who were in labor at 28 weeks' gestation or more and who were planning a vaginal delivery to receive a single 2-g oral dose of azithromycin or placebo. The two primary outcomes were a composite of maternal sepsis or death and a composite of stillbirth or neonatal death or sepsis. During an interim analysis, the data and safety monitoring committee recommended stopping the trial for maternal benefit. RESULTS: A total of 29,278 women underwent randomization. The incidence of maternal sepsis or death was lower in the azithromycin group than in the placebo group (1.6% vs. 2.4%), with a relative risk of 0.67 (95% confidence interval [CI], 0.56 to 0.79; P<0.001), but the incidence of stillbirth or neonatal death or sepsis was similar (10.5% vs. 10.3%), with a relative risk of 1.02 (95% CI, 0.95 to 1.09; P = 0.56). The difference in the maternal primary outcome appeared to be driven mainly by the incidence of sepsis (1.5% in the azithromycin group and 2.3% in the placebo group), with a relative risk of 0.65 (95% CI, 0.55 to 0.77); the incidence of death from any cause was 0.1% in the two groups (relative risk, 1.23; 95% CI, 0.51 to 2.97). Neonatal sepsis occurred in 9.8% and 9.6% of the infants, respectively (relative risk, 1.03; 95% CI, 0.96 to 1.10). The incidence of stillbirth was 0.4% in the two groups (relative risk, 1.06; 95% CI, 0.74 to 1.53); neonatal death within 4 weeks after birth occurred in 1.5% in both groups (relative risk, 1.03; 95% CI, 0.86 to 1.24). Azithromycin was not associated with a higher incidence in adverse events. CONCLUSIONS: Among women planning a vaginal delivery, a single oral dose of azithromycin resulted in a significantly lower risk of maternal sepsis or death than placebo but had little effect on newborn sepsis or death. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; A-PLUS ClinicalTrials.gov number, NCT03871491.).
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Antibacterianos , Azitromicina , Parto Obstétrico , Morte Perinatal , Complicações Infecciosas na Gravidez , Sepse , Feminino , Humanos , Recém-Nascido , Gravidez , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Azitromicina/uso terapêutico , Morte Perinatal/etiologia , Morte Perinatal/prevenção & controle , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/mortalidade , Complicações Infecciosas na Gravidez/prevenção & controle , Sepse/epidemiologia , Sepse/mortalidade , Sepse/prevenção & controle , Natimorto/epidemiologia , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Parto Obstétrico/métodos , Sepse Neonatal/epidemiologia , Sepse Neonatal/mortalidade , Sepse Neonatal/prevenção & controle , Administração Oral , Resultado da Gravidez/epidemiologia , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: To describe the intrapartum and postpartum use of non-study antibiotics in low- and middle-income countries (LMICs) during the double-blinded NICHD Global Network Azithromycin in Labor (A-PLUS) trial. DESIGN: The antibiotic use sub-study was a planned prospective, observational sub-study of the A-PLUS trial. SETTINGS: The study was carried out in hospitals or health centres affiliated with eight sites of the Global Network for Women's and Children's Health Research (Global Network) in seven countries: Bangladesh, Pakistan, India (two sites), Kenya, Zambia, The Democratic Republic of the Congo (DRC) and Guatemala. POPULATION: Totally, 29 278 pregnant women enrolled in the A-PLUS trial. METHODS: We collected data on 29 278 pregnant women admitted to a facility for delivery related to non-study antibiotic use overall and during three time periods: (1) in the facility prior to delivery, (2) after delivery until facility discharge and (3) after discharge to 42 days post-partum. MAIN OUTCOME MEASURES: Non-study antibiotic use overall and for treatment or prophylaxis by the site during the three time periods. RESULTS: Of the 29 278 women in the study, 5020 (17.1%; 95% CI 16.7%-17.6%) received non-study antibiotics in the facility prior to delivery, 11 956 (40.8%; 95% CI 40.3%-41.4%) received non-study antibiotics in the facility after delivery, and 13 390 (47.6%; 95% CI 47.0%-48.2%) women received non-study antibiotics after delivery and after facility discharge. Antibiotics were prescribed more often among women in the Asian and Guatemalan sites than in the African sites. In the three time-periods, among those receiving antibiotics, prophylaxis was the indication in 82.3%, 97.7% and 90.7% of the cases, respectively. The type of antibiotics used varied substantially by time-period and site, but generally, penicillin-type drugs, cephalosporin-type drugs and metronidazole were used more frequently than other types. CONCLUSIONS: Across the eight sites of the Global Network, in the facility before delivery, and in the post-partum periods before and after facility discharge, antibiotics were used frequently, but use was highly variable by site and time-period.
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Rationale: Extremely preterm infants with evolving bronchopulmonary dysplasia (BPD) are at risk for development of BPD-associated pulmonary hypertension (BPD-PH). A patent ductus arteriosus (PDA) shunt may be a modifiable risk factor for BPD-PH development. Objective: To determine whether the presence and duration of ductus arteriosus patency differs between extremely preterm infants with and without BPD-PH. Methods: We conducted a retrospective case-control study among preterm infants of gestational age 22 weeks, 0 days, to 28 weeks, 6 days, who remained on respiratory support on postnatal day 28 at the University of Alabama at Birmingham from 2017 to 2020. Infants who were diagnosed with PH (cases) by echocardiography were compared with infants without PH (control subjects). Data from echocardiograms performed during the hospitalization after postnatal day 28 were included. Logistic regression adjusted for covariates that differed significantly between groups. A probit analysis related the duration of ductal patency to the development of BPD-PH. Measurements and Main Results: A total of 138 infants developed BPD alone, and 82 infants developed BPD-PH. After adjustment for differing covariates between groups, both PDA (adjusted odds ratio, 4.29; 95% confidence interval, 1.89-9.77) and moderate to large PDA (adjusted odds ratio, 4.15; 95% confidence interval, 1.78-9.64) remained significantly related to BPD-PH at discharge. By probit analysis, each additional month of PDA and hemodynamically significant PDA exposure was associated with an increased probability for the composite outcome of BPD-PH at discharge or death with coefficients of 0.40 (P < 0.001) and 0.45 (P < 0.001), respectively. Conclusions: In extremely preterm infants on respiratory support on postnatal day 28, both the presence of and a longer duration of ductus arteriosus patency were associated with the development of BPD-PH.
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Displasia Broncopulmonar , Permeabilidade do Canal Arterial , Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Lactente , Recém-Nascido , Humanos , Displasia Broncopulmonar/complicações , Displasia Broncopulmonar/epidemiologia , Permeabilidade do Canal Arterial/complicações , Permeabilidade do Canal Arterial/diagnóstico por imagem , Estudos Retrospectivos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/etiologia , Estudos de Casos e Controles , Lactente Extremamente Prematuro , Hipertensão Arterial Pulmonar/complicaçõesRESUMO
Rationale: Bedside biomarkers that allow early identification of infants with bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) are critically important, given the higher risk of death in these infants. Objectives: We hypothesized that infants with BPD-PH have patterns of intermittent hypoxemia (IH) that differ from infants with BPD without PH. Methods: We conducted a matched case-control study of extremely preterm infants from 22 weeks 0 days to 28 weeks 6 days born between 2018 and 2020 at the University of Alabama at Birmingham. BPD-PH status was determined using echocardiographic data performed after postnatal Day 28. Physiologic data were compared between infants with BPD-PH (cases) and BPD alone (control subjects). Receiver operating characteristic (ROC) analysis estimated the predictive ability of cumulative hypoxemia, desaturation frequency, and duration of intermittent hypoxemic events in the week preceding echocardiography to discriminate between cases and control subjects. Measurements and Main Results: Forty infants with BPD-PH were compared with 40 infants with BPD alone. Infants with and without PH had a similar frequency of IH events, but infants with PH had more prolonged hypoxemic events for desaturations below 80% (7 s vs. 6 s; P = 0.03) and 70% (105 s vs. 58 s; P = 0.008). Among infants with BPD-PH, infants who died had longer hypoxemic events below 70% (145 s vs. 72 s; P = 0.01). Using the duration of hypoxemic events below 70%, the areas under the ROC curves for diagnosis of BPD-PH and death in BPD-PH infants were 0.71 and 0.77, respectively. Conclusions: Longer duration of intermittent hypoxemic events was associated both with a diagnosis of BPD-PH and with death among infants with BPD-PH.
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Displasia Broncopulmonar , Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Lactente , Recém-Nascido , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/diagnóstico por imagem , Estudos de Casos e Controles , Idade Gestacional , Lactente Extremamente Prematuro , Hipóxia/complicações , Hipertensão Arterial Pulmonar/complicaçõesRESUMO
BACKGROUND: The maternal mortality and perinatal mortality rate in Cameroon are among the highest worldwide. To improve these outcomes, we conducted a formative qualitative assessment to inform the adaptation of a mobile provider-to-provider intervention in Cameroon. We explored the complex interplay of structural barriers on maternity care in this low-resourced nation. The study aimed to identify structural barriers to maternal care during the early adaptation of the mobile Medical Information Service via Telephone (mMIST) program in Cameroon. METHODS: We conducted in-depth interviews and focus groups with 56 key stakeholders including previously and currently pregnant women, primary healthcare providers, administrators, and representatives of the Ministry of Health, recruited by purposive sampling. Thematic coding and analysis via modified grounded theory approach were conducted using NVivo12 software. RESULTS: Three main structural barriers emerged: (1) civil unrest (conflict between Ambazonian militant groups and the Cameroonian government in the Northwest), (2) limitations of the healthcare system, (3) inadequate physical infrastructure. Civil unrest impacted personal security, transportation safety, and disrupted medical transport system. Limitations of healthcare system involved critical shortages of skilled personnel and medical equipment, low commitment to evidence-based care, poor reputation, ineffective health system communication, incentives affecting care, and inadequate data collection. Inadequate physical infrastructure included frequent power outages and geographic distribution of healthcare facilities leading to logistical challenges. CONCLUSION: Dynamic inter-relations among structural level factors create barriers to maternity care in Cameroon. Implementation of policies and intervention programs addressing structural barriers are necessary to facilitate timely access and utilization of high-quality maternity care.
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Acessibilidade aos Serviços de Saúde , Serviços de Saúde Materna , Pesquisa Qualitativa , Humanos , Camarões , Serviços de Saúde Materna/normas , Feminino , Gravidez , Adulto , Mortalidade Materna , Grupos Focais , Pessoal de Saúde/psicologiaRESUMO
Importance: Maternal milk feeding of extremely preterm infants during the birth hospitalization has been associated with better neurodevelopmental outcomes compared with preterm formula. For infants receiving no or minimal maternal milk, it is unknown whether donor human milk conveys similar neurodevelopmental advantages vs preterm formula. Objective: To determine if nutrient-fortified, pasteurized donor human milk improves neurodevelopmental outcomes at 22 to 26 months' corrected age compared with preterm infant formula among extremely preterm infants who received minimal maternal milk. Design, Setting, and Participants: Double-blind, randomized clinical trial conducted at 15 US academic medical centers within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants younger than 29 weeks 0 days' gestation or with a birth weight of less than 1000 g were enrolled between September 2012 and March 2019. Intervention: Preterm formula or donor human milk feeding from randomization to 120 days of age, death, or hospital discharge. Main Outcomes and Measures: The primary outcome was the Bayley Scales of Infant and Toddler Development (BSID) cognitive score measured at 22 to 26 months' corrected age; a score of 54 (score range, 54-155; a score of ≥85 indicates no neurodevelopmental delay) was assigned to infants who died between randomization and 22 to 26 months' corrected age. The 24 secondary outcomes included BSID language and motor scores, in-hospital growth, necrotizing enterocolitis, and death. Results: Of 1965 eligible infants, 483 were randomized (239 in the donor milk group and 244 in the preterm formula group); the median gestational age was 26 weeks (IQR, 25-27 weeks), the median birth weight was 840 g (IQR, 676-986 g), and 52% were female. The birthing parent's race was self-reported as Black for 52% (247/478), White for 43% (206/478), and other for 5% (25/478). There were 54 infants who died prior to follow-up; 88% (376/429) of survivors were assessed at 22 to 26 months' corrected age. The adjusted mean BSID cognitive score was 80.7 (SD, 17.4) for the donor milk group vs 81.1 (SD, 16.7) for the preterm formula group (adjusted mean difference, -0.77 [95% CI, -3.93 to 2.39], which was not significant); the adjusted mean BSID language and motor scores also did not differ. Mortality (death prior to follow-up) was 13% (29/231) in the donor milk group vs 11% (25/233) in the preterm formula group (adjusted risk difference, -1% [95% CI, -4% to 2%]). Necrotizing enterocolitis occurred in 4.2% of infants (10/239) in the donor milk group vs 9.0% of infants (22/244) in the preterm formula group (adjusted risk difference, -5% [95% CI, -9% to -2%]). Weight gain was slower in the donor milk group (22.3 g/kg/d [95% CI, 21.3 to 23.3 g/kg/d]) compared with the preterm formula group (24.6 g/kg/d [95% CI, 23.6 to 25.6 g/kg/d]). Conclusions and Relevance: Among extremely preterm neonates fed minimal maternal milk, neurodevelopmental outcomes at 22 to 26 months' corrected age did not differ between infants fed donor milk or preterm formula. Trial Registration: ClinicalTrials.gov Identifier: NCT01534481.
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Enterocolite Necrosante , Leite Humano , Criança , Lactente , Recém-Nascido , Feminino , Humanos , Masculino , Lactente Extremamente Prematuro , Fórmulas Infantis , Peso ao Nascer , Método Duplo-Cego , Enterocolite Necrosante/epidemiologia , Unidades de Terapia Intensiva NeonatalRESUMO
BACKGROUND: Limited data suggest that higher hemoglobin thresholds for red-cell transfusions may reduce the risk of cognitive delay among extremely-low-birth-weight infants with anemia. METHODS: We performed an open, multicenter trial in which infants with a birth weight of 1000 g or less and a gestational age between 22 weeks 0 days and 28 weeks 6 days were randomly assigned within 48 hours after delivery to receive red-cell transfusions at higher or lower hemoglobin thresholds until 36 weeks of postmenstrual age or discharge, whichever occurred first. The primary outcome was a composite of death or neurodevelopmental impairment (cognitive delay, cerebral palsy, or hearing or vision loss) at 22 to 26 months of age, corrected for prematurity. RESULTS: A total of 1824 infants (mean birth weight, 756 g; mean gestational age, 25.9 weeks) underwent randomization. There was a between-group difference of 1.9 g per deciliter (19 g per liter) in the pretransfusion mean hemoglobin levels throughout the treatment period. Primary outcome data were available for 1692 infants (92.8%). Of 845 infants in the higher-threshold group, 423 (50.1%) died or survived with neurodevelopmental impairment, as compared with 422 of 847 infants (49.8%) in the lower-threshold group (relative risk adjusted for birth-weight stratum and center, 1.00; 95% confidence interval [CI], 0.92 to 1.10; P = 0.93). At 2 years, the higher- and lower-threshold groups had similar incidences of death (16.2% and 15.0%, respectively) and neurodevelopmental impairment (39.6% and 40.3%, respectively). At discharge from the hospital, the incidences of survival without severe complications were 28.5% and 30.9%, respectively. Serious adverse events occurred in 22.7% and 21.7%, respectively. CONCLUSIONS: In extremely-low-birth-weight infants, a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity. (Funded by the National Heart, Lung, and Blood Institute and others; TOP ClinicalTrials.gov number, NCT01702805.).
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Anemia/terapia , Transfusão de Eritrócitos , Hemoglobinas/análise , Recém-Nascido de Peso Extremamente Baixo ao Nascer/sangue , Lactente Extremamente Prematuro/sangue , Doenças do Prematuro/terapia , Transtornos do Neurodesenvolvimento/prevenção & controle , Algoritmos , Anemia/sangue , Anemia/mortalidade , Paralisia Cerebral/prevenção & controle , Transtornos Cognitivos/prevenção & controle , Transfusão de Eritrócitos/efeitos adversos , Perda Auditiva/prevenção & controle , Humanos , Recém-Nascido/sangue , Recém-Nascido Prematuro/sangue , Doenças do Prematuro/sangue , Doenças do Prematuro/mortalidade , Taxa de Sobrevida , Transtornos da Visão/prevenção & controleRESUMO
OBJECTIVE: To characterize the relationships between social determinants of health (SDOH) and outcomes for children born extremely preterm. STUDY DESIGN: This is a cohort study of infants born at 22-26 weeks of gestation in National Institute of Child Health and Human Development Neonatal Research Network centers (2006-2017) who survived to discharge. Infants were classified by 3 maternal SDOH: education, insurance, and race. Outcomes included postmenstrual age (PMA) at discharge, readmission, neurodevelopmental impairment (NDI), and death postdischarge. Regression analyses adjusted for center, perinatal characteristics, neonatal morbidity, ethnicity, and 2 SDOH (eg, group comparisons by education adjusted for insurance and race). RESULTS: Of 7438 children, 5442 (73%) had at least 1 risk-associated SDOH. PMA at discharge was older (adjusted mean difference 0.37 weeks, 95% CL 0.06, 0.68) and readmission more likely (aOR 1.27, 95% CL 1.12, 1.43) for infants whose mothers had public/no insurance vs private. Neither PMA at discharge nor readmission varied by education or race. NDI was twice as likely (aOR 2.36, 95% CL 1.86, 3.00) and death 5 times as likely (aOR 5.22, 95% CL 2.54, 10.73) for infants with 3 risk-associated SDOH compared with those with none. CONCLUSIONS: Children born to mothers with public/no insurance were older at discharge and more likely to be readmitted than those born to privately insured mothers. NDI and death postdischarge were more common among children exposed to multiple risk-associated SDOH at birth compared with those not exposed. Addressing disparities due to maternal education, insurance coverage, and systemic racism are potential intervention targets to improve outcomes for children born preterm.
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Assistência ao Convalescente , Lactente Extremamente Prematuro , Recém-Nascido , Lactente , Gravidez , Feminino , Humanos , Criança , Estudos de Coortes , Determinantes Sociais da Saúde , Alta do Paciente , Idade GestacionalRESUMO
BACKGROUND: The current study evaluated the hypothesis that the COVID-19 pandemic is associated with higher stillbirth but lower neonatal mortality rates. METHODS: We compared three epochs: baseline (2016-2019, January-December, weeks 1-52, and 2020, January-February, weeks 1-8), initial pandemic (2020, March-December, weeks 9-52, and 2021, January-June, weeks 1-26), and delta pandemic (2021, July-September, weeks 27-39) periods, using Alabama Department of Public Health database including deliveries with stillbirths ≥20 weeks or live births ≥22 weeks gestation. The primary outcomes were stillbirth and neonatal mortality rates. RESULTS: A total of 325,036 deliveries were included (236,481 from baseline, 74,076 from initial pandemic, and 14,479 from delta pandemic period). The neonatal mortality rate was lower in the pandemic periods (4.4 to 3.5 and 3.6/1000 live births, in the baseline, initial, and delta pandemic periods, respectively, p < 0.01), but the stillbirth rate did not differ (9 to 8.5 and 8.6/1000 births, p = 0.41). On interrupted time-series analyses, there were no significant changes in either stillbirth (p = 0.11 for baseline vs. initial pandemic period, and p = 0.67 for baseline vs. delta pandemic period) or neonatal mortality rates (p = 0.28 and 0.89, respectively). CONCLUSIONS: The COVID-19 pandemic periods were not associated with a significant change in stillbirth and neonatal mortality rates compared to the baseline period. IMPACT: The COVID-19 pandemic could have resulted in changes in fetal and neonatal outcomes. However, only a few population-based studies have compared the risk of fetal and neonatal mortality in the pandemic period to the baseline period. This population-based study identifies the changes in fetal and neonatal outcomes during the initial and delta COVID-19 pandemic period as compared to the baseline period. The current study shows that stillbirth and neonatal mortality rates were not significantly different in the initial and delta COVID-19 pandemic periods as compared to the baseline period.
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COVID-19 , Natimorto , Recém-Nascido , Gravidez , Feminino , Humanos , Natimorto/epidemiologia , Pandemias , Alabama/epidemiologia , Mortalidade InfantilRESUMO
With the paucity of data available regarding COVID-19 in pregnancy in low- and middle-income countries (LMICs), near the start of the pandemic, the Global Network for Women's and Children's Health Research, funded by the National Institute of Child Health and Human Development (NICHD), initiated four separate studies to better understand the impact of the COVID-19 pandemic in eight LMIC sites. These sites included: four in Asia, in Bangladesh, India (two sites) and Pakistan; three in Africa, in the Democratic Republic of the Congo (DRC), Kenya and Zambia; and one in Central America, in Guatemala. The first study evaluated changes in health service utilisation; the second study evaluated knowledge, attitudes and practices of pregnant women in relationship to COVID-19 in pregnancy; the third study evaluated knowledge, attitude and practices related to COVID-19 vaccination in pregnancy; and the fourth study, using antibody status at delivery, evaluated changes in antibody status over time in each of the sites and the relationship of antibody positivity with various pregnancy outcomes. Across the Global Network, in the first year of the study there was little reduction in health care utilisation and no apparent change in pregnancy outcomes. Knowledge related to COVID-19 was highly variable across the sites but was generally poor. Vaccination rates among pregnant women in the Global Network were very low, and were considerably lower than the vaccination rates reported for the countries as a whole. Knowledge regarding vaccines was generally poor and varied widely. Most women did not believe the vaccines were safe or effective, but slightly more than half would accept the vaccine if offered. Based on antibody positivity, the rates of COVID-19 infection increased substantially in each of the sites over the course of the pandemic. Most pregnancy outcomes were not worse in women who were infected with COVID-19 during their pregnancies. We interpret the absence of an increase in adverse outcomes in women infected with COVID-19 to the fact that in the populations studied, most COVID-19 infections were either asymptomatic or were relatively mild.
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COVID-19 , Criança , Gravidez , Feminino , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Saúde da Criança , Pandemias/prevenção & controle , Vacinas contra COVID-19 , Saúde da Mulher , Zâmbia , Paquistão , Países em DesenvolvimentoRESUMO
OBJECTIVE: To determine the relation of COVID-19 symptoms to COVID-19 antibody positivity among unvaccinated pregnant women in low- and middle-income countries (LMIC). DESIGN: COVID-19 infection status measured by antibody positivity at delivery was compared with the symptoms of COVID-19 in the current pregnancy in a prospective, observational cohort study in seven LMICs. SETTING: The study was conducted among women in the Global Network for Women's and Children's Health's Maternal and Newborn Health Registry (MNHR), a prospective, population-based study in Kenya, Zambia, the Democratic Republic of the Congo (DRC), Bangladesh, Pakistan, India (Belagavi and Nagpur sites) and Guatemala. POPULATION: Pregnant women enrolled in the ongoing pregnancy registry at study sites. METHODS: Data on COVID-19 symptoms during the current pregnancy were collected by trained staff between October 2020 and June 2022. COVID-19 antibody testing was performed on samples collected at delivery. The relation between COVID-19 antibody positivity and symptoms was assessed using generalised linear models with a binomial distribution adjusting for site and symptoms. MAIN OUTCOME MEASURES: COVID-19 antibody status and symptoms of COVID-19 among pregnant women. RESULTS: Among 19 218 non-vaccinated pregnant women who were evaluated, 14.1% of antibody-positive women had one or more symptoms compared with 13.4% in antibody-negative women. Overall, 85.3% of antibody-positive women reported no COVID-19 symptoms during the present pregnancy. Reported fever was significantly associated with antibody status (relative risk [RR] 1.10, 95% CI 1.03-11.18; P = 0.008). A multiple variable model adjusting for site and all eight symptoms during pregnancy showed similar results (RR 1.13, 95% CI 1.04-1.23; P = 0.012). None of the other symptoms was significantly related to antibody positivity. CONCLUSIONS: In a population-based cohort in LMICs, unvaccinated pregnant women who were antibody-positive had slightly more symptoms during their pregnancy and a small but significantly greater increase in fever. However, for prevalence studies, evaluating COVID-19-related symptoms does not appear to be useful in differentiating pregnant women who have had a COVID-19 infection.
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COVID-19 , Gestantes , Feminino , Humanos , Recém-Nascido , Gravidez , Saúde da Criança , COVID-19/diagnóstico , COVID-19/epidemiologia , Teste para COVID-19 , Países em Desenvolvimento , Estudos Prospectivos , Saúde da MulherRESUMO
OBJECTIVE: To assess the impact of low-dose aspirin (LDA) starting in early pregnancy on delaying preterm hypertensive disorders of pregnancy. DESIGN: Non-prespecified secondary analysis of a randomised masked trial of LDA. SETTING: The study was conducted among women in the Global Network for Women's and Children's Health's Maternal and Newborn Health Registry (MNHR) clusters, a prospective, population-based study in Kenya, Zambia, the Democratic Republic of the Congo (DRC), Pakistan, India (two sites-Belagavi and Nagpur) and Guatemala. POPULATION: Nulliparous singleton pregnancies between 6+0 weeks and 13+6 weeks in six low-middle income countries (Democratic Republic of Congo, Guatemala, India, Kenya, Pakistan, Zambia) enrolled in the ASPIRIN Trial. METHODS: We compared the incidence of HDP at delivery at three gestational age periods (<28, <34 and <37 weeks) between women who were randomised to aspirin or placebo. Women were included if they were randomised and had an outcome at or beyond 20 weeks (Modified Intent to Treat). MAIN OUTCOME MEASURES: Our primary outcome was pregnancies with HDP associated with preterm delivery (HDP@delivery) before <28, <34 and <37 weeks. Secondary outcomes included small for gestational age (SGA) <10th percentile, <5th percentile, and perinatal mortality. RESULTS: Among the 11 976 pregnancies, LDA did not significantly lower HDP@delivery <28 weeks (relative risk [RR] 0.18, 95% confidence interval [CI] 0.02-1.52); however, it did lower HDP@delivery <34 weeks (RR 0.37, 95% CI 0.17-0.81) and HDP@delivery <37 weeks (RR 0.66, 95% CI 0.49-0.90). The overall rate of HDP did not differ between the two groups (RR 1.08, 95% CI 0.94-1.25). Among those pregnancies who had HDP, SGA <10th percentile was reduced (RR 0.81, 95% CI 0.67-0.99), though SGA <5th percentile was not (RR 0.84, 95% CI 0.64-1.09). Similarly, perinatal mortality among pregnancies with HDP occurred less frequently (RR 0.55, 95% CI 0.33-0.92) in those receiving LDA. Pregnancies randomised to LDA delivered later with HDP compared with those receiving placebo (median gestational age 38.5 weeks vs. 37.9 weeks; p = 0.022). CONCLUSIONS: In this secondary analysis of a study of low-risk nulliparous singleton pregnancies, early administration of LDA resulted in lower rates of preterm HDP and delivery before 34 and 37 weeks but not in the overall rate of HDP. These results suggest that LDA works in part by delaying HDP.
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Hipertensão Induzida pela Gravidez , Morte Perinatal , Recém-Nascido , Criança , Gravidez , Feminino , Humanos , Lactente , Aspirina/uso terapêutico , Gestantes , Saúde da Criança , Hipertensão Induzida pela Gravidez/epidemiologia , Hipertensão Induzida pela Gravidez/prevenção & controle , Hipertensão Induzida pela Gravidez/tratamento farmacológico , Estudos Prospectivos , Saúde da Mulher , Paridade , Retardo do Crescimento Fetal/tratamento farmacológicoRESUMO
OBJECTIVE: To understand trends in the knowledge, attitudes and practices (KAP) of pregnant women related to COVID-19 in seven low- and middle-income countries. DESIGN: Multi-country population-based prospective observational study. SETTING: Study sites in Bangladesh, the Demographic Republic of Congo (DRC), Guatemala, India (two sites), Kenya, Pakistan and Zambia. POPULATION: Pregnant women in the Global Network's Maternal and Neonatal Health Registry (MNHR). METHODS: Pregnant women enrolled in the MNHR were interviewed to assess their KAP related to COVID-19 from September 2020 through July 2022 across all study sites. MAIN OUTCOME MEASURES: Trends of COVID-19 KAP were assessed using the Cochran-Armitage test for trend. RESULTS: A total of 52 297 women participated in this study. There were wide inter-country differences in COVID-19-related knowledge. The level of knowledge of women in the DRC was much lower than that of women in the other sites. The ability to name COVID-19 symptoms increased over time in the African sites, whereas no such change was observed in Bangladesh, Belagavi and Guatemala. All sites observed decreasing trends over time in women avoiding antenatal care visits. CONCLUSIONS: The knowledge and attitudes of pregnant women related to COVID-19 varied substantially among the Global Network sites over a period of 2 years; however, there was very little change in knowledge related to COVID-19 over time across these sites. The major change observed was that fewer women reported avoiding medical care because of COVID-19 across all sites over time.
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COVID-19 , Gestantes , Feminino , Humanos , Gravidez , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Transversais , Países em Desenvolvimento , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
OBJECTIVES: To determine COVID-19 antibody positivity rates over time and relationships to pregnancy outcomes in low- and middle-income countries (LMICs). DESIGN: With COVID-19 antibody positivity at delivery as the exposure, we performed a prospective, observational cohort study in seven LMICs during the early COVID-19 pandemic. SETTING: The study was conducted among women in the Global Network for Women's and Children's Health's Maternal and Newborn Health Registry (MNHR), a prospective, population-based study in Kenya, Zambia, the Democratic Republic of the Congo (DRC), Bangladesh, Pakistan, India (two sites), and Guatemala. POPULATION: Pregnant women enrolled in an ongoing pregnancy registry at study sites. METHODS: From October 2020 to October 2021, standardised COVID-19 antibody testing was performed at delivery among women enrolled in MNHR. Trained staff masked to COVID-19 status obtained pregnancy outcomes, which were then compared with COVID-19 antibody results. MAIN OUTCOME MEASURES: Antibody status, stillbirth, neonatal mortality, maternal mortality and morbidity. RESULTS: At delivery, 26.0% of women were COVID-19 antibody positive. Positivity increased over the four time periods across all sites: 13.8%, 15.4%, 21.0% and 40.9%. In the final period, positivity rates were: DRC 27.0%, Kenya 33.1%, Pakistan 32.8%, Guatemala 37.0%, Zambia 37.8%, Bangladesh 47.2%, Nagpur, India 57.4% and Belagavi, India 62.4%. Adjusting for site and maternal characteristics, stillbirth, neonatal mortality, low birthweight and preterm birth were not significantly associated with COVID-19. The adjusted relative risk (aRR) for stillbirth was 1.27 (95% CI 0.95-1.69). Postpartum haemorrhage was associated with antibody positivity (aRR 1.44; 95% CI 1.01-2.07). CONCLUSIONS: In pregnant populations in LMICs, COVID-19 antibody positivity has increased. However, most adverse pregnancy outcomes were not significantly associated with antibody positivity.
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COVID-19 , Nascimento Prematuro , Criança , Gravidez , Feminino , Recém-Nascido , Humanos , Resultado da Gravidez/epidemiologia , Natimorto/epidemiologia , Saúde da Criança , Países em Desenvolvimento , Estudos Prospectivos , Teste para COVID-19 , Pandemias , Nascimento Prematuro/epidemiologia , COVID-19/epidemiologia , Saúde da Mulher , Mortalidade InfantilRESUMO
BACKGROUND: Fontan associated liver disease (FALD) potentially impacts Fontan patients undergoing heart transplant. This multi-center study sought to identify pre-transplant risk factors and characterize any post-transplant liver recovery in those patients undergoing heart-alone transplant. METHODS: Review of Fontan patients at 12 pediatric institutions who underwent heart transplant between 2001-2019. Radiologists reviewed pre and post-transplant liver imaging for fibrosis. Laboratory, pathology and endoscopy studies were reviewed. RESULTS: 156 patients underwent transplant due to decreased ventricular function (49%), protein losing enteropathy (31%) or plastic bronchitis (10%); median age at transplant was 13.6 years (interquartile range IQR 7.8, 17.2) with a median of 9.3 years (IQR 3.2, 13.4) between the Fontan operation and transplant. Few patients had pre-transplant endoscopy (18%), and liver biopsy (19%). There were 31 deaths (20%). The median time from transplant to death was 0.5 years (95% Confidence Interval CI 0.0, 3.6). The five-year survival was 73% (95% CI 64%, 83%). Deaths were related to cardiac causes in 68% (21/31) and infection in 6 (19%). A pre-transplant elevation in bilirubin was a predictor of death. Higher platelet levels were protective. Immediate post-transplant elevations in creatinine, AST, ALT, and INR were predictive of death. Advanced liver fibrosis identified on ultrasound, computed tomography, or magnetic resonance imaging was not predictive of death. Liver imaging suggested some improvement in liver congestion post-transplant. CONCLUSIONS: Elevated bilirubin, but not fibrosis on liver imaging, was associated with post-heart transplant mortality in Fontan patients in this multicenter retrospective study. Additionally, heart transplant may alter the progression of FALD.
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Técnica de Fontan , Cardiopatias Congênitas , Transplante de Coração , Hepatopatias , Humanos , Bilirrubina , Técnica de Fontan/efeitos adversos , Cardiopatias Congênitas/cirurgia , Cardiopatias Congênitas/complicações , Fígado/patologia , Cirrose Hepática/cirurgia , Cirrose Hepática/complicações , Hepatopatias/etiologia , Hepatopatias/cirurgia , Hepatopatias/patologia , Estudos Retrospectivos , AdolescenteRESUMO
BACKGROUND: Patients after Fontan palliation represent a growing pediatric population requiring heart transplant (HTx) and often have lymphopenia (L) and/or hypogammaglobinemia that may be exacerbated by protein-losing enteropathy (PLE, P). The post-HTx effects of this altered immune phenotype are not well studied. METHODS: In this study of the Pediatric Heart Transplant Society Registry, 106 Fontan patients who underwent HTx between 2005 and 2018 were analyzed. The impact of lymphopenia and PLE on graft survival, infection, rejection, and malignancy was analyzed at 1 and 5 years post-HTx. RESULTS: The following combinations of lymphopenia and PLE were noted: +L+P, n = 37; +L-P, n = 23; -L+P, n = 10; and -L-P, n = 36. Graft survival between the groups was similar within the first year after transplant (+L+P: 86%, +L-P: 86%, -L+P: 87%, -L-P: 89%, p = .9). Freedom from first infection post-HTx was greatest among -L-P patients compared to patients with either PLE, lymphopenia, or both; with a 22.1% infection incidence in the -L-P group and 41.4% in all others. These patients had a significantly lower infection rate in the first year after HTx (+L+P: 1.03, +L-P: 1, -L+P: 1.3, -L-P: 0.3 infections/year, p < .001) and were similar to a non-single ventricle CHD control group (0.4 infections/year). Neither freedom from rejection nor freedom from malignancy 1 and 5 years post-HTx, differed among the groups. CONCLUSIONS: Fontan patients with altered immunophenotype, with lymphopenia and/or PLE, are at increased risk of infection post-HTx, although have similar early survival and freedom from rejection and malignancy. These data may encourage alternative immunosuppression strategies and enhanced monitoring for this growing subset of patients.
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Doenças da Medula Óssea , Técnica de Fontan , Transplante de Coração , Linfopenia , Neoplasias , Enteropatias Perdedoras de Proteínas , Criança , Humanos , Enteropatias Perdedoras de Proteínas/etiologia , Linfopenia/complicações , Técnica de Fontan/efeitos adversos , Terapia de Imunossupressão/efeitos adversos , Neoplasias/complicações , Estudos RetrospectivosRESUMO
BACKGROUND: Low birth weight (LBW, < 2500 g) infants are at significant risk for death and disability. Improving outcomes for LBW infants requires access to advanced neonatal care, which is a limited resource in low- and middle-income countries (LMICs). Predictive modeling might be useful in LMICs to identify mothers at high-risk of delivering a LBW infant to facilitate referral to centers capable of treating these infants. METHODS: We developed predictive models for LBW using the NICHD Global Network for Women's and Children's Health Research Maternal and Newborn Health Registry. This registry enrolled pregnant women from research sites in the Democratic Republic of the Congo, Zambia, Kenya, Guatemala, India (2 sites: Belagavi, Nagpur), Pakistan, and Bangladesh between January 2017 - December 2020. We tested five predictive models: decision tree, random forest, logistic regression, K-nearest neighbor and support vector machine. RESULTS: We report a rate of LBW of 13.8% among the eight Global Network sites from 2017-2020, with a range of 3.8% (Kenya) and approximately 20% (in each Asian site). Of the five models tested, the logistic regression model performed best with an area under the curve of 0.72, an accuracy of 61% and a recall of 72%. All of the top performing models identified clinical site, maternal weight, hypertensive disorders, severe antepartum hemorrhage and antenatal care as key variables in predicting LBW. CONCLUSIONS: Predictive modeling can identify women at high risk for delivering a LBW infant with good sensitivity using clinical variables available prior to delivery in LMICs. Such modeling is the first step in the development of a clinical decision support tool to assist providers in decision-making regarding referral of these women prior to delivery. Consistent referral of women at high-risk for delivering a LBW infant could have extensive public health consequences in LMICs by directing limited resources for advanced neonatal care to the infants at highest risk.
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Saúde da Criança , Países em Desenvolvimento , Gravidez , Criança , Lactente , Recém-Nascido , Humanos , Feminino , Estudos Prospectivos , Saúde da Mulher , Mães , Recém-Nascido de Baixo PesoRESUMO
BACKGROUND: Malaria can have deleterious effects early in pregnancy, during placentation. However, malaria testing and treatment are rarely initiated until the second trimester, leaving pregnancies unprotected in the first trimester. To inform potential early intervention approaches, we sought to identify clinical and demographic predictors of first-trimester malaria. METHODS: We prospectively recruited women from sites in the Democratic Republic of the Congo (DRC), Kenya, and Zambia who participated in the ASPIRIN (Aspirin Supplementation for Pregnancy Indicated risk Reduction In Nulliparas) trial. Nulliparous women were tested for first-trimester Plasmodium falciparum infection by quantitative polymerase chain reaction. We evaluated predictors using descriptive statistics. RESULTS: First-trimester malaria prevalence among 1513 nulliparous pregnant women was 6.3% (95% confidence interval [CI], 3.7%-8.8%] in the Zambian site, 37.8% (95% CI, 34.2%-41.5%) in the Kenyan site, and 62.9% (95% CI, 58.6%-67.2%) in the DRC site. First-trimester malaria was associated with shorter height and younger age in Kenyan women in site-stratified analyses, and with lower educational attainment in analyses combining all 3 sites. No other predictors were identified. CONCLUSIONS: First-trimester malaria prevalence varied by study site in sub-Saharan Africa. The absence of consistent predictors suggests that routine parasite screening in early pregnancy may be needed to mitigate first-trimester malaria in high-prevalence settings.
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Malária Falciparum , Malária , Aspirina/uso terapêutico , República Democrática do Congo/epidemiologia , Feminino , Humanos , Quênia/epidemiologia , Malária/epidemiologia , Malária Falciparum/parasitologia , Plasmodium falciparum , Gravidez , Primeiro Trimestre da Gravidez , Prevalência , Zâmbia/epidemiologiaRESUMO
OBJECTIVE: We hypothesized that a cumulative heart rate characteristics (HRC) index in real-time throughout the neonatal intensive care unit (NICU) hospitalization, alone or combined with birth demographics and clinical characteristics, can predict a composite outcome of death or neurodevelopmental impairment (NDI). STUDY DESIGN: We performed a retrospective analysis using data from extremely low birth weight infants who were monitored for HRC during neonatal intensive care. Surviving infants were assessed for NDI at 18-22 months of age. Multivariable predictive modeling of subsequent death or NDI using logistic regression, cross-validation with repeats, and step-wise feature elimination was performed each postnatal day through day 60. RESULTS: Among the 598 study participants, infants with the composite outcome of death or moderate-to-severe NDI had higher mean HRC scores during their stay in the NICU (3.1 ± 1.8 vs 1.3 ± 0.8; P < .001). Predictive models for subsequent death or NDI were consistently higher when the cumulative mean HRC score was included as a predictor variable. A parsimonious model including birth weight, sex, ventilatory status, and cumulative mean HRC score had a cross-validated receiver-operator characteristic curve as high as 0.84 on days 4, 5, 6, and 8 and as low as 0.78 on days 50-52 and 56-58 to predict subsequent death or NDI. CONCLUSIONS: In extremely low birth weight infants, higher mean HRC scores throughout their stay in the NICU were associated with a higher risk of the composite outcome of death or NDI. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00307333.
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Recém-Nascido de Peso Extremamente Baixo ao Nascer , Unidades de Terapia Intensiva Neonatal , Peso ao Nascer , Frequência Cardíaca/fisiologia , Humanos , Lactente , Recém-Nascido , Estudos RetrospectivosRESUMO
BACKGROUND: Critically ill extremely preterm infants fed human milk are often underrepresented in neonatal nutrition trials aimed to determine the effects of enteral protein supplementation on body composition outcomes. METHODS: Masked randomized trial in which 56 extremely preterm infants 25-28 weeks of gestation were randomized to receive either fortified milk enriched with a fixed amount of extensively hydrolyzed protein (high protein group) or fortified milk without additional protein (standard protein group). RESULTS: Baseline characteristics were similar between groups. In a longitudinal analysis, the mean percent body fat (%BF) at 30-32 weeks of postmenstrual age (PMA), 36 weeks PMA, and 3 months of corrected age (CA) did not differ between groups (17 ± 3 vs. 15 ± 4; p = 0.09). The high protein group had higher weight (-0.1 ± 1.2 vs. -0.8 ± 1.3; p = 0.03) and length (-0.8 ± 1.3 vs. -1.5 ± 1.3; p = 0.02) z scores from birth to 3 months CA. The high protein group also had higher fat-free mass (FFM) z scores at 36 weeks PMA (-0.9 ± 1.1 vs. -1.5 ± 1.1; p = 0.04). CONCLUSIONS: Increased enteral intake of protein increased FFM accretion, weight, and length in extremely preterm infants receiving protein-enriched, fortified human milk. IMPACT: Extremely preterm infants are at high risk of developing postnatal growth failure, particularly when they have low fat-free mass gains. Protein supplementation increases fat-free mass accretion in infants, but several neonatal nutrition trials aimed to determine the effects of enteral protein supplementation on body composition outcomes have systematically excluded critically ill extremely preterm infants fed human milk exclusively. In extremely preterm infants fed fortified human milk, higher enteral protein intake increases fat-free mass accretion and promotes growth without causing excessive body fat accretion.