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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
Antenatal steroid therapy is increasingly central to the obstetrical management of women at imminent risk of preterm birth. For women likely to deliver between 24 and 34 weeks' gestation, antenatal steroid therapy is the standard of care, conferring sizable benefits and few risks in high-resource environments when appropriately targeted. Recent studies have focused on antenatal steroid use in periviable and late preterm populations, and in term cesarean deliveries. As a result, antenatal steroid therapy has now been applied from 22 to 39+6 weeks of estimated gestational age. There is also an increased appreciation that the vast majority of randomized control data informing the use of antenatal steroids are derived from predominantly high-resource, White populations. Accordingly, a sizable amount of work has recently been undertaken to test how to safely use antenatal steroids in low- and middle-resource environments, wherein the often high rates of preterm birth make these low-cost, easily administered interventions an attractive proposition. It is likely underappreciated by the obstetrical and neonatal communities that the overall efficacy of antenatal steroid therapy is highly variable (including when preterm risk is accurately assessed), the treatment regimens used are largely arbitrary, dosing is suprapharmacologic for effect, and the benefit-risk balance is significantly and differentially modified by gestation. It is also very likely that the patients consenting to receive these treatments are similarly unaware of the complex balance of potential benefits and harms. Although a small number of follow-up studies present a generally benign picture of long-term antenatal steroid risk, several large, population-based retrospective studies have identified associations between antenatal steroid use, childhood mental disease, and newborn infections that warrant urgent attention. Of particular contemporary importance are emergent efforts to optimize antenatal steroid regimens on the basis of the pharmacokinetics and pharmacodynamics of the agents themselves, the need for better targeting of these potent drugs, and clear articulation of the potential benefits and harms of antenatal steroid use at differing stages of pregnancy and in different delivery contexts.
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Nascimento Prematuro , Gravidez , Feminino , Recém-Nascido , Humanos , Criança , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/prevenção & controle , Nascimento Prematuro/tratamento farmacológico , Estudos Retrospectivos , Corticosteroides , Glucocorticoides/uso terapêutico , Esteroides/uso terapêutico , Cuidado Pré-NatalRESUMO
OBJECTIVE: To examine the association of placental and fetal DNA copy number variants (CNVs) with fetal structural malformations (FSMs) in stillborn fetuses. DESIGN: A secondary analysis of stillbirth cases in the Stillbirth Collaborative Research Network (SCRN) study. SETTING: Multicenter, 59 hospitals in five geographic regions in the USA. POPULATION: 388 stillbirth cases of the SCRN study (2006-2008). METHODS: Fetal structural malformations were grouped by anatomic system and specific malformation type (e.g. central nervous system, thoracic, cardiac, gastrointestinal, skeletal, umbilical cord and craniofacial defects). Single-nucleotide polymorphism array detected CNVs of at least 500 kb. CNVs were classified into two groups: normal, defined as no CNVs >500 kb or benign CNVs, and abnormal, defined as pathogenic or variants of unknown clinical significance. MAIN OUTCOME MEASURES: The proportions of abnormal CNVs and normal CNVs were compared between stillbirth cases with and without FSMs using the Wald Chi-square test. RESULTS: The proportion of stillbirth cases with any FSMs was higher among those with abnormal CNVs than among those with normal CNVs (47.5 versus 19.1%; P-value <0.001). The most common organ system-specific FSMs associated with abnormal CNVs were cardiac defects, followed by hydrops, craniofacial defects and skeletal defects. A pathogenic deletion of 1q21.1 involving 46 genes (e.g. CHD1L) and a duplication of 21q22.13 involving four genes (SIM2, CLDN14, CHAF1B, HLCS) were associated with a skeletal and cardiac defect, respectively. CONCLUSION: Specific CNVs involving several genes were associated with FSMs in stillborn fetuses. The findings warrant further investigation and may inform counselling and care surrounding pregnancies affected by FSMs at risk for stillbirth.
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Variações do Número de Cópias de DNA , Natimorto , Gravidez , Feminino , Humanos , Natimorto/epidemiologia , Natimorto/genética , Variações do Número de Cópias de DNA/genética , Aberrações Cromossômicas , Placenta , Feto/anormalidades , Diagnóstico Pré-Natal , Fator 1 de Modelagem da Cromatina/genética , DNA Helicases/genética , Proteínas de Ligação a DNA/genéticaRESUMO
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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Multiple factors influence infant and child neurodevelopment in low resource settings. In offspring of participants in the preconception maternal nutrition trial, Women First (WF), we examined the impact of providing a preconception (Arm 1) or prenatal (Arm 2) nutrient supplement (compared to controls, Arm 3) on neurodevelopmental outcomes at 24 months; predictors of neurodevelopment scores; and associations of infant anthropometrics with neurodevelopmental scores. Follow-up visits for anthropometry were conducted at 6-, 12-, 18- and 24-month of age. At 24-months, in a randomized subset, the Bayley Scales of Infant Development, 3rd edition (BSID-III), including cognitive, motor and social-emotional subscales, and the Family Care Indicators (FCI) questionnaire, assessing family and home environment, were completed. Multiple covariates (intervention arm, site, maternal sociodemographic characteristics, FCI subscales, birthweight and 6-24 months' change in anthropometry z-scores, (e.g., ΔLAZ6-2 4) were evaluated by linear regression to predict BSID-III outcomes and to assess associations of anthropometric changes with BSID-III scores. The analysis consisted of 1386 infants (n = 441, 486, 459 for Arms 1, 2 and 3, respectively). None of the domain-specific BSID-III subscale scores differed by maternal intervention arm. Four covariates significantly predicted (p ≤ 0.01) all 3 BSID-III subscales: secondary maternal education, ΔLAZ6 - 24, birthweight >2500 g, and FCI play materials. Linear growth was associated with all domains of neurodevelopment. The results underscore the multi-dimensional aspects of child development represented by the nurturing care framework, including prenatal maternal nutrition, post-natal growth, maternal education for responsive caregiving and opportunities for early learning.
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BACKGROUND: We identified pathogens found in internal organs and placentas of deceased preterm infants cared for in hospitals in India and Pakistan. METHODS: Prospective, observational study conducted in delivery units and neonatal intensive care units. Tissue samples from deceased neonates obtained by minimally invasive tissue sampling and placentas were examined for 73 different pathogens using multiplex polymerase chain reaction (PCR). RESULTS: Tissue for pathogen PCR was obtained from liver, lung, brain, blood, cerebrospinal fluid, and placentas from 377 deceased preterm infants. Between 17.6% and 34.1% of each type of tissue had at least 1 organism identified. Organism detection was highest in blood (34.1%), followed by lung (31.1%), liver (23.3%), cerebrospinal fluid (22.3%), and brain (17.6%). A total of 49.7% of the deceased infants had at least 1 organism. Acinetobacter baumannii was in 28.4% of the neonates compared with 14.6% for Klebsiella pneumoniae, 11.9% for Escherichia coli/Shigella, and 11.1% for Haemophilus influenzae. Group B streptococcus was identified in only 1.3% of the neonatal deaths. A. baumannii was rarely found in the placenta and was found more commonly in the internal organs of neonates who died later in the neonatal period. The most common organism found in placentas was Ureaplasma urealyticum in 34% of the samples, with no other organism found in >4% of samples. CONCLUSIONS: In organ samples from deceased infants in India and Pakistan, evaluated with multiplex pathogen PCR, A. baumannii was the most commonly identified organism. Group B streptococcus was rarely found. A. baumannii was rarely found in the placentas of these deceased neonates.
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Morte Perinatal , Lactente , Gravidez , Feminino , Recém-Nascido , Humanos , Recém-Nascido Prematuro , Estudos Prospectivos , Paquistão/epidemiologia , Reação em Cadeia da Polimerase Multiplex , Escherichia coliRESUMO
BACKGROUND: Fetal growth abnormalities are associated with a higher incidence of stillbirth, with small and large for gestational age infants incurring a 3 to 4- and 2 to 3-fold increased risk, respectively. Although clinical risk factors such as diabetes, hypertension, and placental insufficiency have been associated with fetal growth aberrations and stillbirth, the role of underlying genetic etiologies remains uncertain. OBJECTIVE: This study aimed to assess the relationship between abnormal copy number variants and fetal growth abnormalities in stillbirths using chromosomal microarray. STUDY DESIGN: A secondary analysis utilizing a cohort study design of stillbirths from the Stillbirth Collaborative Research Network was performed. Exposure was defined as abnormal copy number variants including aneuploidies, pathogenic copy number variants, and variants of unknown clinical significance. The outcomes were small for gestational age and large for gestational age stillbirths, defined as a birthweight <10th percentile and greater than the 90th percentile for gestational age, respectively. RESULTS: Among 393 stillbirths with chromosomal microarray and birthweight data, 16% had abnormal copy number variants. The small for gestational age outcome was more common among those with abnormal copy number variants than those with a normal microarray (29.5% vs 16.5%; P=.038). This finding was consistent after adjusting for clinically important variables. In the final model, only abnormal copy number variants and maternal age remained significantly associated with small for gestational age stillbirths, with an adjusted odds ratio of 2.22 (95% confidence interval, 1.12-4.18). Although large for gestational age stillbirths were more likely to have an abnormal microarray: 6.2% vs 3.3% (P=.275), with an odds ratio of 2.35 (95% confidence interval, 0.70-7.90), this finding did not reach statistical significance. CONCLUSION: Genetic abnormalities are more common in the setting of small for gestational age stillborn fetuses. Abnormal copy number variants not detectable by traditional karyotype make up approximately 50% of the genetic abnormalities in this population.
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Variações do Número de Cópias de DNA , Natimorto , Lactente , Gravidez , Feminino , Humanos , Natimorto/epidemiologia , Natimorto/genética , Peso ao Nascer/genética , Estudos de Coortes , Placenta , Desenvolvimento Fetal/genética , Idade Gestacional , Retardo do Crescimento Fetal/epidemiologia , Retardo do Crescimento Fetal/genéticaRESUMO
BACKGROUND: Bacterial vaginosis (BV) increases preterm delivery (PTD) risk, but treatment trials showed mixed results in preventing PTD. OBJECTIVES: Determine, using individual participant data (IPD), whether BV treatment during pregnancy reduced PTD or prolonged time-to-delivery. DATA SOURCES: Cochrane Systematic Review (2013), MEDLINE, EMBASE, journal searches, and searches (January 2013-September 2022) ("bacterial vaginosis AND pregnancy") of (i) clinicaltrials.gov; (ii) Cochrane Central Register of Controlled Trials; (iii) World Health Organization International Clinical Trials Registry Platform Portal; and (iv) Web of Science ("bacterial vaginosis"). STUDY SELECTION AND DATA EXTRACTION: Studies randomising asymptomatic pregnant individuals with BV to antibiotics or control, measuring delivery gestation. Extraction was from original data files. Bias risk was assessed using the Cochrane tool. Analysis used "one-step" logistic and Cox random effect models, adjusting gestation at randomisation and PTD history; heterogeneity by I2 . Subgroup analysis tested interactions with treatment. In sensitivity analyses, studies not providing IPD were incorporated by "multiple random-donor hot-deck" imputation, using IPD studies as donors. RESULTS: There were 121 references (96 studies) with 23 eligible trials (11,979 participants); 13 studies (6915 participants) provided IPD; 12 (6115) were incorporated. Results from 9 (4887 participants) not providing IPD were imputed. Odds ratios for PTD for metronidazole and clindamycin versus placebo were 1.00 (95% CI 0.84, 1.17), I2 = 62%, and 0.59 (95% CI 0.42, 0.82), I2 = 0 before; and 0.95 (95% CI 0.81, 1.11), I2 = 59%, and 0.90 (95% CI: 0.72, 1.12), I2 = 0, after imputation. Time-to-delivery did not differ from null with either treatment. Including imputed IPD, there was no evidence that either drug was more effective when administered earlier, or among those with a PTD history. CONCLUSIONS: Clindamycin, but not metronidazole, was beneficial in studies providing IPD, but after imputing data from missing IPD studies, treatment of BV during pregnancy did not reduce PTD, nor prolong pregnancy, in any subgroup or when started earlier in gestation.
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Nascimento Prematuro , Vaginose Bacteriana , Feminino , Humanos , Recém-Nascido , Gravidez , Antibacterianos/uso terapêutico , Clindamicina/uso terapêutico , Metronidazol/uso terapêutico , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/prevenção & controle , Vaginose Bacteriana/tratamento farmacológico , Vaginose Bacteriana/prevenção & controleRESUMO
OBJECTIVE: To evaluate the usefulness of data to determine cause of stillbirth in India and Pakistan. DESIGN: Prospective, observational study. SETTINGS: Study hospitals in India and Pakistan. POPULATION: 200 fetal deaths with placental evaluation and minimally invasive tissue sampling (MITS) of internal organs and polymerase chain reaction (PCR) test for 75 pathogens. MAIN OUTCOME MEASURES: Data defined as useful to determine stillbirth causes. RESULTS: Placental pathology was the most useful to determine cause of stillbirth. Comparing placental and fetal weight with standard weights was useful in 44.5% and 48.5%, respectively. Lung histology was useful in 42.5%. Most of the other findings of internal organ histology were only occasionally useful. Signs of abruption, by maternal history or placental evaluation, were always deemed useful. Placenta, brain and cord blood PCR were also useful, but less often than histology. CONCLUSION: Based on this analysis, maternal clinical history, placental histology and fetal examination were most informative. Comparing the placental and fetal weights with recognised standards was useful in nearly half the cases. Fetal tissue histology and PCR were also informative. Of all the potential tests of MITS-obtained specimens, we would first recommend histological evaluation of the lungs, and using a multiplex PCR platform would determine pathogens in blood and brain/CSF. We recognise that this approach will not identify some causes, including some genetic and internal organ anomalies, but will confirm most common causes of stillbirth and most of the preventable causes of stillbirth in low- and middle-income countries.
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Placenta , Natimorto , Gravidez , Feminino , Humanos , Natimorto/epidemiologia , Placenta/patologia , Ásia Meridional , Estudos Prospectivos , Causas de Morte , Peso FetalRESUMO
OBJECTIVE: To explore potential reasons for differences in preterm neonatal mortality in neonatal intensive care units (NICUs) in India and Pakistan. DESIGN: A prospective observational study, the Project to Understand and Research Stillbirth and Preterms in Southeast Asia (PURPOSe) was conducted July 2018 to February 2020. SETTING: Three hospitals in Davangere, India, and a large public hospital in Karachi, Pakistan. POPULATION: Of a total of 3,202 preterm infants enrolled, 1,512 were admitted to a study NICU. METHODS: We collected data for neonates, including length of stay, diagnoses, and diagnostic tests. MAIN OUTCOME MEASURES: Neonatal mortality, tests performed, diagnoses ascertained. RESULTS: For infants of equivalent weights and gestational ages, neonatal mortality in Pakistan was twice that in the Indian NICU. The mean newborn length of stay in Pakistan was 2 days compared with 10 days for India. Fewer diagnostics and other investigations were used to determine neonatal condition or guide treatment in the Pakistani NICU. Because of limited information from testing in Pakistan concerning clinical respiratory distress, respiratory distress syndrome appeared to be over-diagnosed, whereas other conditions including pneumonia, sepsis, necrotising entercolitis and intraventricular haemorrhage were rarely diagnosed. CONCLUSION: In the Pakistani site, the limited resources available to the NICU appeared related to a shorter length of stay and decreased diagnostic testing, likely explaining the higher mortality. With improved care, reduction in mortality among preterm neonates should be achievable.
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Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Humanos , Recém-Nascido , Mortalidade Infantil , Paquistão/epidemiologia , Estudos ProspectivosRESUMO
OBJECTIVE: To evaluate perinatal outcomes in preterm multiple compared with singleton pregnancies in India and Pakistan. DESIGN: Prospective, observational study. SETTINGS: Study hospitals in India and Pakistan. POPULATION: We evaluated 3897 preterm pregnancies. These mothers gave birth to 3615 (92.8%) singleton infants, 267 (6.8%) sets of twins, 14 (0.4%) sets of triplets and one set of quadruplets. MAIN OUTCOME MEASURES: Neonatal mortality, stillbirth, cause of death. RESULTS: Of the singleton infants, 691 (19.1%) were stillborn and 2924 (80.9%) live born. Of the 534 infants from twin pregnancies, 41 (7.7%) were stillborn and 493 (92.3%) were live born. Of the 267 sets of twins, in 14 cases (5.2%) both were stillborn, in 13 cases (4.8%) one was stillborn and one live born, and in 240 cases (90.0%) both were live born. In both preterm twins and preterm singletons, the three most common causes of death were intrauterine hypoxia, infections acquired prior to birth and infections acquired at or after birth. The preterm twins appeared less likely to have died from intrauterine hypoxia but more likely to have died from infections acquired at or after birth. Respiratory distress syndrome (RDS) was less likely considered by the panel to be the primary cause of death in either the twins (9.6%) or singletons (9.7%). Congenital anomalies were also not often judged to be the cause of death in either the preterm twins 2 (2.4%) or singletons 27 (5.3%). CONCLUSION: In the PURPOSe study, neonatal mortality rates in preterm twins compared with singletons when evaluated by sex, GA, birthweight and SGA, were generally similar to rates of preterm singleton neonatal mortality in those groups. Thus, the higher rate of mortality in live-born twin infants is related to the fact that these infants were more likely to be born earlier rather than to any inherent characteristics of the babies themselves.
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Resultado da Gravidez , Nascimento Prematuro , Feminino , Humanos , Recém-Nascido , Gravidez , Hipóxia , Recém-Nascido de Baixo Peso , Paquistão/epidemiologia , Resultado da Gravidez/epidemiologia , Gravidez Múltipla , Gravidez de Gêmeos , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Natimorto/epidemiologiaRESUMO
OBJECTIVE: To examine inflammatory lesions in placentas of stillbirths, preterm neonatal deaths and term controls in India and Pakistan. DESIGN: Prospective, observational study. SETTING: Three hospitals in India and a large maternity hospital in Pakistan. POPULATION: The enrolled participants with placentas available for histology evaluation included stillbirths (n = 814), preterm live births who died within 28 days of birth (n = 618) and term live birth controls (n = 201). From this same population, polymerase chain reaction (PCR) analysis for pathogens was performed on 809 stillbirth placentas, 614 neonatal death placentas and the placentas of 201 term controls. Placentas from preterm infants who lived beyond day 28 (n = 1432) were only available from India. METHODS: A prospective observational study of placental inflammatory lesions defined by the Amsterdam criteria and on the same placentas, multiplex PCR evaluation for 75 pathogens using TaqMan Array Cards. MAIN OUTCOME MEASURES: Any placental inflammatory lesions, including chorioamnionitis, funisitis, villitis and intervillitis and their association with various pathogens. RESULTS: In the Indian liveborn preterm infants, placental inflammation of any kind was present in 26.2% of those who died versus 16.6% of those who lived (p = 0.0002). Chorioamnionitis was present in 25.8% of those who died versus 16.3% of those who lived (p = 0.0002) and funisitis was present in 4.1% of those who died versus 1.5% of those who lived, (p = 0.005). Across all three sites, in the placentas of the 201 term controls, 18.9% had any inflammation, 16.9% had chorioamnionitis, 5.5% had funisitis, 0.5% had intervillitis and none had villitis. Overall, for stillbirths, any inflammation was observed in 30.2%, chorioamnionitis in 26.9%, funisitis in 5.7%, intervillitis in 6.0% and villitis in 2.2%. For the neonatal deaths, any inflammation was present in 24.9%, chorioamnionitis in 23.3%, funisitis in 8.1%, intervillitis in 1.9% and villitis in 0.5%. Compared with the placentas of term controls, in neonatal deaths, only chorioamnionitis was significantly increased (23.3% versus 16.9%, p = 0.05). Among stillbirths, the rates of any inflammation, chorioamnionitis, intervillitis and villitis were similar across the birthweight groups. However, funisitis was more common in the placentas of stillborn fetuses weighing 2500 g or more (13.8%) compared with 1.0% for those weighing less than 1000 g and 4.8% for stillborn fetuses weighing 1000-2499 g. In the PCR studies, Ureaplasma spp. were by far the most common pathogens found and generally were more commonly found in association with inflammatory lesions. CONCLUSIONS: Chorioamnionitis was the most common type of placental inflammatory lesion regardless of whether the placentas evaluated were from term controls, stillbirths or neonatal deaths. For stillbirths, inflammation in each inflammation category was more common than in the term controls and significantly more so for any inflammation, chorioamnionitis, intervillitis and villitis. For neonatal deaths, compared with the placentas of term controls, all inflammation categories were more common, but only significantly so for chorioamnionitis. Ureaplasma spp. were the most common organisms found in the placentas and were significantly associated with inflammation.
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Corioamnionite , Morte Perinatal , Nascimento Prematuro , Feminino , Gravidez , Recém-Nascido , Humanos , Placenta/patologia , Corioamnionite/epidemiologia , Natimorto/epidemiologia , Estudos Prospectivos , Ásia Meridional , Recém-Nascido Prematuro , Inflamação/patologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/patologiaRESUMO
OBJECTIVE: Growing evidence suggests that environmental heat stress negatively influences fetal growth and pregnancy outcomes. However, few studies have examined the impact of heat stress on pregnancy outcomes in low-resource settings. We combined data from a large multi-country maternal-child health registry and meteorological data to assess the impacts of heat stress. DESIGN: Retrospective cohort study. SETTING: Three sites based in south Asia as part of the Global Network for Women's and Children's Health research in India (Belagavi and Nagpur) and Pakistan (Thatta). POPULATION OR SAMPLE: Data from women enrolled between 2014 and 2020 in the Global Network's Maternal Newborn Health Registry (MNHR), a prospective, population-based registry of pregnancies, were used. METHODS: A total of 126 273 pregnant women were included in this analysis. Daily maximal air temperatures (Tmax ) were acquired from local meteorological records. Associations between averages of daily maximal temperatures for each trimester and main outcomes were analysed using a modified Poisson regression approach. MAIN OUTCOMES MEASURES: Incidence of stillbirth, preterm birth, low birthweight (<2500 g) or evidence of pregnancy hypertension or pre-eclampsia. RESULTS: In the overall cohort, risk of preterm birth was positively associated with greater temperature in the second trimester (relative risk [RR] 1.05, 95% CI 1.02-1.07, p = 0.0002). Among individual sites, the risk of preterm birth was greatest in Nagpur (RR 1.07, 95% CI 1.03-1.11, p = 0.0005) and associated with second-trimester temperature. The overall risk of low birthweight was associated with ambient temperature in second trimester (RR 1.02, 95% CI 1.01-1.04, p = 0.01). The risk for LBW was associated with first-trimester heat in Thatta and with second-trimester heat in Nagpur. Finally, the overall risk of gestational hypertensive disease was associated with greater temperature in the third trimester among all sites (RR 1.07, 95% CI 1.02-1.12, p = 0.005) and was particularly significant for Nagpur (RR 1.13, 95% CI 1.05-1.23, p = 0.002). These findings highlight the increased risk of detrimental obstetric and neonatal outcomes with greater temperature. CONCLUSION: In a multi-country, community-based study, greater risk of adverse outcomes was observed with increasing temperature. The study highlights the need for deeper understanding of covarying factors and intervention strategies, especially in regions where high temperatures are common.
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Pré-Eclâmpsia , Nascimento Prematuro , Gravidez , Feminino , Recém-Nascido , Humanos , Criança , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Temperatura , Peso ao Nascer , Saúde do Lactente , Saúde da Criança , Estudos Prospectivos , Estudos Retrospectivos , Saúde da Mulher , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/etiologia , Sistema de RegistrosRESUMO
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: Group B streptococcus (GBS) has been associated with adverse pregnancy outcomes, but few prospective studies have assessed its prevalence in low- and middle-income country settings. We sought to evaluate the prevalence of GBS by polymerase chain reaction (PCR) in internal organ tissues and placentas of deceased neonates and stillbirths. DESIGN: This was a prospective, observational study. SETTING: The study was conducted in hospitals in India and Pakistan. POPULATION: Pregnant women with stillbirths or preterm births were recruited at delivery, as was a group of women with term, live births, to serve as a control group. METHODS: A rectovaginal culture was collected from the women in Pakistan to assess GBS carriage. Using PCR, we evaluated GBS in various tissues of stillbirths and deceased neonates and their placentas, as well as the placentas of live-born preterm and term control infants. MAIN OUTCOME MEASURES: GBS identified by PCR in various tissues and the placentas; rate of stillbirths and 28-day neonatal deaths. RESULTS: The most obvious finding from this series of analyses from India and Pakistan was that no matter the country, the condition of the subject, the tissue studied or the methodology used, the prevalence of GBS was low, generally ranging between 3% and 6%. Among the risk factors evaluated, only GBS positivity in primigravidae was increased. CONCLUSIONS: GBS diagnosed by PCR was identified in <6% of internal organs of stillbirths and neonatal deaths, and their placentas, and control groups in South Asian sites. This is consistent with other reports from South Asia and is lower than the reported GBS rates from the USA, Europe and Africa.
Assuntos
Morte Perinatal , Complicações Infecciosas na Gravidez , Infecções Estreptocócicas , Feminino , Humanos , Recém-Nascido , Gravidez , Ásia Meridional , Morte Perinatal/etiologia , Placenta , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/diagnóstico , Prevalência , Estudos Prospectivos , Natimorto/epidemiologia , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/diagnóstico , Streptococcus agalactiae/genéticaRESUMO
OBJECTIVE: To compare placental findings in women with and without pre-eclampsia. DESIGN: The PURPOSe study included women with stillbirths, women with preterm births and women at term as controls. The placenta of each case was evaluated using the Amsterdam criteria. SETTING: Two sites and five tertiary care hospitals of south Asia (Three in India and two in Pakistan). POPULATION: Pregnancies in India and Pakistan with placental histology including women with documented hypertension and documented proteinuria and women with neither hypertension nor proteinuria. METHODS: We compared the placental findings of the two groups using the Amsterdam criteria and further evaluated the placental findings in women with and without pre-eclampsia who had a stillbirth, preterm live birth, or term live birth (control). MAIN OUTCOME MEASURES: The main outcome measures were the frequency of maternal and fetal vascular malperfusion and the frequency of placental inflammation and its components, chorioamnionitis, funisitis, villitis and intervillitis in women with and without pre-eclampsia. RESULTS: A total of 733 women had pre-eclampsia and 2334 women had neither hypertension nor proteinuria. In the placentas of women with pre-eclampsia, 57.3% had maternal vascular malperfusion compared with 37.1% in women without pre-eclampsia (p < 0.0001). There was not a significant difference in the prevalence of fetal vascular hypertension between mothers with (17.1%) and without (14.8%, p = 0.6118) pre-eclampsia. When placentas were classified as 'histologically normal' or not, 61.3% of those from pre-eclamptic pregnancies were classified as abnormal, whereas if there was no pre-eclampsia, only 45.0% were classified as histologically abnormal (p < 0.0001). We also considered rates of placental maternal vascular malperfusion in women with and without pre-eclampsia with stillbirth, preterm neonatal death, and term live birth. In women at term with no pre-eclampsia, 16.7% of the placentas had features of maternal vascular malperfusion. This occurred in 79.9% of women with stillbirths with pre-eclampsia compared with 51.8% of those without pre-eclampsia. Maternal vascular malperfusion was present in 49.7% of preterm live births with pre-eclampsia compared with 33.8% without pre-eclampsia. We also evaluated the inflammatory lesions by whether the mother had or did not have pre-eclampsia. When all inflammatory lesions were considered, women with pre-eclampsia had significantly fewer inflammatory lesions than those women without pre-eclampsia (17.1% versus 23.6% p = 0.001). Each of the specific inflammatory lesions was less common in placentas of women with pre-eclampsia than those with chorioamnionitis (16.1% versus 21.9%, p = 0.004) and funisitis (1.5% versus. 5.1%, p = 0.0004). CONCLUSIONS: Of placental lesions in women with pre-eclampsia, maternal vascular malperfusion was the most common. Inflammatory lesions were less common in women with pre-eclampsia.
Assuntos
Corioamnionite , Hipertensão , Pré-Eclâmpsia , Nascimento Prematuro , Recém-Nascido , Gravidez , Feminino , Humanos , Placenta/irrigação sanguínea , Corioamnionite/epidemiologia , Natimorto/epidemiologia , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/patologia , Estudos Prospectivos , Paquistão/epidemiologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/patologia , Proteinúria/epidemiologia , Proteinúria/etiologiaRESUMO
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.
Assuntos
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.
Assuntos
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.
Assuntos
COVID-19 , Gestantes , Feminino , Humanos , Gravidez , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Transversais , Países em Desenvolvimento , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
The PURPOSe study was a prospective, observational study conducted in India and Pakistan to determine the cause of death for stillbirths and preterm neonatal deaths, using clinical data together with minimally invasive tissue sampling (MITS) and the histologic and polymerase chain reaction (PCR) evaluation of fetal/neonatal tissues and the placenta. After evaluating all available data, an independent panel chose a maternal, a placental and a fetal/neonatal cause of death. Here, we summarise the major results. Among the most important findings were that most stillbirths were caused by fetal asphyxia, often preceded by placental malperfusion, and clinically associated with pre-eclampsia, placental abruption and a small-for-gestational-age fetus. The preterm neonatal deaths were primarily caused by birth asphyxia, followed by various infections. An important finding was that many of the preterm neonatal deaths were caused by a nosocomial infection acquired after neonatal intensive care (NICU) admission; the most common organisms were Acinetobacter baumannii, followed by Klebsiella pneumoniae, Escherichia coli/Shigella and Haemophilus influenzae. Group B streptococcus was less commonly present in the placentas or internal organs of the neonatal deaths.