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Neonatal invasive candidiasis in low- and middle-income countries: Data from the NeoOBS study.

ABSTRACT: Neonatal invasive candidiasis (NIC) has significant morbidity and mortality. Reports have shown a different profile of those neonates affected with NIC and of fluconazole-resistant Candida spp. isolates in low- and middle-income countries (LMICs) compared to high-income countries (HICs). We describe the epidemiology, Candida spp. distribution, treatment, and outcomes of neonates with NIC from LMICs enrolled in a global, prospective, longitudinal, observational cohort study (NeoOBS) of hospitalized infants <60 days postnatal age with sepsis (August 2018-February 2021). A total of 127 neonates from 14 hospitals in 8 countries with Candida spp. isolated from blood culture were included. Median gestational age of affected neonates was 30 weeks (IQR: 28-34), and median birth weight was 1270 gr (interquartile range [IQR]: 990-1692). Only a minority had high-risk criteria, such as being born <28 weeks, 19% (24/127), or birth weight <1000 gr, 27% (34/127). The most common Candida species were C. albicans (n = 45, 35%), C. parapsilosis (n = 38, 30%), and Candida auris (n = 18, 14%). The majority of C. albicans isolates were fluconazole susceptible, whereas 59% of C. parapsilosis isolates were fluconazole-resistant. Amphotericin B was the most common antifungal used [74% (78/105)], followed by fluconazole [22% (23/105)]. Death by day 28 post-enrollment was 22% (28/127). To our knowledge, this is the largest multi-country cohort of NIC in LMICs. Most of the neonates would not have been considered at high risk for NIC in HICs. A substantial proportion of isolates was resistant to first choice fluconazole. Understanding the burden of NIC in LMIC is essential to guide future research and treatment guidelines.

SUBMITTER: Cook A

PROVIDER: S-EPMC10026246 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Neonatal invasive candidiasis in low- and middle-income countries: Data from the NeoOBS study.

Cook Aislinn A Ferreras-Antolin Laura L Adhisivam Bethou B Ballot Daynia D Berkley James A JA Bernaschi Paola P Carvalheiro Cristina G CG Chaikittisuk Napaporn N Chen Yunsheng Y Chibabhai Vindana V Chitkara Shweta S Chiurchiu Sara S Chorafa Elisavet E Dien Tran Minh TM Dramowski Angela A de Matos Samantha Faria SF Feng Jinxing J Jarovsky Daniel D Kaur Ravinder R Khamjakkaew Warunee W Laoyookhong Premsak P Machanja Edwin E Mussi-Pinhata Marisa M MM Namiiro Flavia F Natraj Gita G Naziat Hakka H Ngoc Hoang Thi Bich HTB Ondongo-Ezhet Claude C Preedisripipat Kanchana K Rahman Hafizur H Riddell Amy A Roilides Emmanuel E Russell Neal N Sastry Apurba S AS Tasimwa Hannington Baluku HB Tongzhen Ji J Wadula Jeannette J Wang Yajuan Y Whitelaw Andrew A Wu Dan D Yadav Varsha V Yang Gao G Stohr Wolfgang W Bielicki Julia Anna JA Ellis Sally S Warris Adilia A Heath Paul T PT Sharland Michael M

Medical mycology 20230301 3

Neonatal invasive candidiasis (NIC) has significant morbidity and mortality. Reports have shown a different profile of those neonates affected with NIC and of fluconazole-resistant Candida spp. isolates in low- and middle-income countries (LMICs) compared to high-income countries (HICs). We describe the epidemiology, Candida spp. distribution, treatment, and outcomes of neonates with NIC from LMICs enrolled in a global, prospective, longitudinal, observational cohort study (NeoOBS) of hospitaliz ...[more]

PMID: 36881725

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Project description:BackgroundOligohydramnios is a condition of abnormally low amniotic fluid volume that has been associated with poor pregnancy outcomes. To date, the prevalence of this condition and its outcomes has not been well described in low and low-middle income countries (LMIC) where ultrasound use to diagnose this condition in pregnancy is limited. As part of a prospective trial of ultrasound at antenatal care in LMICs, we sought to evaluate the incidence of and the adverse maternal, fetal and neonatal outcomes associated with oligohydramnios.MethodsWe included data in this report from all pregnant women in community settings in Guatemala, Pakistan, Zambia and the Democratic Republic of Congo (DRC) who received a third trimester ultrasound as part of the First Look Study, a randomized trial to assess the value of ultrasound at antenatal care. Using these data, we conducted a planned secondary analysis to compare pregnancy outcomes of women with to those without oligohydramnios. Oligohydramnios was defined as measurement of an Amniotic Fluid Index less than 5 cm in at least one ultrasound in the third trimester. The outcomes assessed included maternal morbidity and fetal and neonatal mortality, preterm birth and low-birthweight. We used pairwise site comparisons with Tukey-Kramer adjustment and multivariable logistic models using general estimating equations to account for the correlation of outcomes within cluster.ResultsOf 12,940 women enrolled in the clusters in Guatemala, Pakistan, Zambia and the DRC in the First Look Study who had a third trimester ultrasound examination, 87 women were diagnosed with oligohydramnios, equivalent to 0.7% of those studied. Prevalence of detected oligohydramnios varied among study sites; from the lowest of 0.2% in Zambia and the DRC to the highest of 1.5% in Pakistan. Women diagnosed with oligohydramnios had higher rates of hemorrhage, fetal malposition, and cesarean delivery than women without oligohydramnios. We also found unfavorable fetal and neonatal outcomes associated with oligohydramnios including stillbirths (OR 5.16, 95%CI 2.07, 12.85), neonatal deaths < 28 days (OR 3.18, 95% CI 1.18, 8.57), low birth weight (OR 2.10, 95% CI 1.44, 3.07) and preterm births (OR 2.73, 95%CI 1.76, 4.23). The mean birth weight was 162 g less (95% CI -288.6, - 35.9) with oligohydramnios.ConclusionsOligohydramnos was associated with worse neonatal, fetal and maternal outcomes in LMIC. Further research is needed to assess effective interventions to diagnose and ultimately to reduce poor outcomes in these settings.Trial registrationNCT01990625.

Project description:ObjectiveDetermine the sensitivity and specificity of neonatal jaundice visual estimation by primary healthcare workers (PHWs) and physicians as predictors of hyperbilirubinaemia.DesignMulticentre observational cohort study.SettingHospitals in Chandigarh and Delhi, India; Dhaka, Bangladesh; Durban, South Africa; Kumasi, Ghana; La Paz, Bolivia.ParticipantsNeonates aged 1-20 days (n=2642) who presented to hospitals for evaluation of acute illness. Infants referred for any reason from another health facility or those needing immediate cardiopulmonary resuscitation were excluded.Outcome measuresInfants were evaluated for distribution (head, trunk, distal extremities) and degree (mild, moderate, severe) of jaundice by PHWs and physicians. Serum bilirubin level was determined for infants with jaundice, and analyses of sensitivity and specificity of visual estimations of jaundice used bilirubin thresholds of >260 µmol/L (need for phototherapy) and >340 µmol/L (need for emergency intervention in at-risk and preterm babies).Results1241 (47.0%) neonates had jaundice. High sensitivity for detecting neonates with serum bilirubin >340 µmol/L was found for 'any jaundice of the distal extremities (palms or soles) OR deep jaundice of the trunk or head' for both PHWs (89%-100%) and physicians (81%-100%) across study sites; specificity was more variable. 'Any jaundice of the distal extremities' identified by PHWs and physicians had sensitivity of 71%-100% and specificity of 55%-95%, excluding La Paz. For the bilirubin threshold >260 µmol/L, 'any jaundice of the distal extremities OR deep jaundice of the trunk or head' had the highest sensitivity across sites (PHWs: 58%-93%, physicians: 55%-98%).ConclusionsIn settings where serum bilirubin cannot be measured, neonates with any jaundice on the distal extremities should be referred to a hospital for evaluation and management, where delays in serum bilirubin measurement and appropriate treatment are anticipated following referral, the higher sensitivity sign, any jaundice on the distal extremities or deep jaundice of the trunk or head, may be preferred.

Project description:ObjectiveTo estimate the associations between gestational weight gain (GWG) during pregnancy and neonatal outcomes in low and middle income countries.DesignIndividual participant data meta-analysis.SettingProspective pregnancy studies from 24 low and middle income countries.Main outcome measuresNine neonatal outcomes related to timing (preterm birth) and anthropometry (weight, length, and head circumference) at birth, stillbirths, and neonatal death.Analysis methodsA systematic search was conducted in PubMed, Embase, and Web of Science which identified 53 prospective pregnancy studies published after the year 2000 with data on GWG, timing and anthropometry at birth, and neonatal mortality. GWG adequacy was defined as the ratio of the observed maternal weight gain over the recommended weight gain based on the Institute of Medicine body mass index specific guidelines, which are derived from data in high income settings, and the INTERGROWTH-21st GWG standards. Study specific estimates, adjusted for confounders, were generated and then pooled using random effects meta-analysis models. Maternal age and body mass index before pregnancy were examined as potential modifiers of the associations between GWG adequacy and neonatal outcomes.ResultsOverall, 55% of participants had severely inadequate (<70%) or moderately inadequate (70% to <90%) GWG, 22% had adequate GWG (90-125%), and 23% had excessive GWG (≥125%). Severely inadequate GWG was associated with a higher risk of low birthweight (adjusted relative risk 1.62, 95% confidence interval 1.51 to 1.72; 48 studies, 93 337 participants; τ2=0.006), small for gestational age (1.44, 1.36 to 1.54; 51 studies, 93 191 participants; τ2=0.016), short for gestational age (1.47, 1.29 to 1.69; 40 studies, 83 827 participants; τ2=0.074), and microcephaly (1.57, 1.31 to 1.88; 31 studies, 80 046 participants; τ2=0.145) compared with adequate GWG. Excessive GWG was associated with a higher risk of preterm birth (1.22, 1.13 to 1.31; 48 studies, 103 762 participants; τ2=0.008), large for gestational age (1.44, 1.33 to 1.57; 47 studies, 90 044 participants; τ2=0.009), and macrosomia (1.52, 1.33 to 1.73; 29 studies, 68 138 participants; τ2=0) compared with adequate GWG. The direction and magnitude of the associations between GWG adequacy and several neonatal outcomes were modified by maternal age and body mass index before pregnancy.ConclusionsInadequate and excessive GWG are associated with a higher risk of adverse neonatal outcomes across settings. Interventions to promote optimal GWG during pregnancy are likely to reduce the burden of adverse neonatal outcomes, however further research is needed to assess optimal ranges of GWG based on data from low and middle income countries.

Project description:BackgroundBabies born weighing ≥ 2500 g account for more than 80% of the births in most resource-limited locations and for nearly 50% of the 28-day neonatal deaths. In contrast, in high-resource settings, 28-day neonatal mortality among this group represents only a small fraction of the neonatal deaths. Yet mortality risks for birth weight of ≥ 2500 g is limited. Knowledge regarding the factors associated with mortality in these babies will help in identifying interventions that can reduce mortality.MethodsThe Global Network's Maternal Newborn Health Registry (MNHR) is a prospective, population-based observational study that includes all pregnant women and their pregnancy outcomes in defined geographic communities that has been conducted in research sites in six low-middle income countries (India, Pakistan, Democratic Republic of Congo, Guatemala, Kenya and Zambia). Study staff enroll all pregnant women as early as possible during pregnancy and conduct follow-up visits to ascertain delivery and 28-day neonatal outcomes. We analyzed the neonatal mortality rates (NMR) and risk factors for deaths by 28 days among all live-born babies with a birthweight ≥ 2500 g from 2010 to 2018 across the Global Network sites.ResultsBabies born in the Global Network sites from 2010 to 2018 with a birthweight ≥ 2500 g accounted for 84.8% of the births and 45.4% of the 28-day neonatal deaths. Among this group, the overall NMR was 13.1/1000 live births. The overall 28-day NMR for ongoing clusters was highest in Pakistan (29.7/1000 live births) and lowest in the Zambian/Kenyan sites (9.3/1000) for ≥ 2500 g infants. ≥ 2500 g NMRs declined for Zambia/Kenya and India. For Pakistan and Guatemala, the NMR remained almost unchanged over the period. The ≥ 2500 g risks related to maternal, delivery and newborn characteristics varied by site. Maternal factors that increased risk and were common for all sites included nulliparity, hypertensive disease, previous stillbirth, maternal death, obstructed labor, severe postpartum hemorrhage, and abnormal fetal presentation. Neonatal characteristics including resuscitation, hospitalization, congenital anomalies and male sex, as well as lower gestational ages and birthweights were also associated with increased mortality.ConclusionsNearly half of neonatal deaths in the Global Network sites occurred in infants born weighing ≥ 2500 g. The NMR for those infants was 13.1 per 1000 live births, much higher than rates usually seen in high-income countries. The changes in NMR over time varied across the sites. Even among babies born ≥ 2500 g, lower gestational age and birthweight were largely associated with increased risk of mortality. Since many of these deaths should be preventable, attention to preventing mortality in these infants should have an important impact on overall NMR.Trial registrationhttps://ClinicalTrials.gov Identifier: NCT01073475.

Dataset Information

Neonatal invasive candidiasis in low- and middle-income countries: Data from the NeoOBS study.

Publications

Neonatal invasive candidiasis in low- and middle-income countries: Data from the NeoOBS study.

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