South Indian Children's Neurodevelopmental Outcomes After Group B Streptococcus Invasive Disease: A Matched-Cohort Study.

BACKGROUND: This study is part of a multicountry matched-cohort study designed to estimate the risk of long-term neurodevelopmental impairment (NDI) of children exposed to invasive group B Streptococcus (iGBS). The specific objective of this paper is to compare NDI across domains of iGBS survivors with a matched non iGBS group in our population. METHODS: Survivors of iGBS in a South Indian hospital were identified and recruited between January 2020 and April 2021. Cases were compared with age- and gender-matched non iGBS children. Participants were assessed using Bayley Scales of Infant and Toddler Development-3rd edition (BSID-III), Wechsler Preschool and Primary Scale of Intelligence-4th edition (WPPSI-IV), Wechsler Intelligence Scale for Children-5th edition (WISC-V), Child Behavior Checklist (CBCL), and Bruininks-Oseretsky Test of Motor Proficiency, 2nd edition (BOT-2), depending on age. RESULTS: Our cohort comprised 35 GBS-exposed and 65 matched non iGBS children, aged 1-14 years. The iGBS-exposed group had 17 (48.6%) children with impairment in ≥1 domain compared to 25 (38%) in the non iGBS group (unadjusted OR, 1.51; 95% CI, .65-3.46), 9 (26%) children with "multi-domain impairment" compared to 10 (15.4%) in the non iGBS group (unadjusted OR, 1.90; 95% CI, .69-5.24), and 1 (2.9%) child with moderate to severe impairment compared to 3 (4.6%) in the non iGBS group (unadjusted OR, .60; 95% CI, .06-6.07). In the iGBS group, more children had motor impairments compared with the non iGBS group (unadjusted OR, 10.7; 95% CI, 1.19-95.69; P = .034). CONCLUSIONS: Children with iGBS seem at higher risk of developing motor impairments compared with a non iGBS group.

Breast milk contains red cell isohaemagglutinins: An observational study of 176 mothers.

BACKGROUND AND OBJECTIVES: Maternal antibodies are transferred to the child, predominantly IgG, via the transplacental route, and mostly IgA through breast milk. Cases reported by us and others have shown the transfer of red cell allo-antibodies through breast milk. This study was conducted to assess the presence of isohaemagglutinins in breast milk, the range of titres, and the correlation between breast milk and maternal plasma titres. MATERIALS AND METHODS: A total of 176 mothers were recruited in this study. Breast milk was collected after sufficient feeding was established and within 2-5 days of delivery in a sterile container without any anticoagulant. Antibody screen, identification and titres were performed on maternal plasma as well as breast milk. RESULTS: Anti-A and anti-B in breast milk corresponding to their respective maternal blood groups were found in all the samples. This study has shown titres in the breast milk of anti-A and anti-B ranging from 2 to 1024 in both saline and Coombs phases. There was no association between plasma and breast milk titres, thus making it impossible to predict which mother may potentially transfer a larger amount of these haemagglutinins. Isotypes of anti-A and anti-B were evaluated in both plasma and breast milk of 11 samples, which showed predominantly IgG in 7 (63.63%) and predominantly IgA in 4 (36.36%) samples. CONCLUSION: Our study demonstrates the presence of a wide range of titres for IgG antibodies of the ABO blood group system in breast milk. The clinical impact of this finding needs to be studied further, as it assumes great relevance in developing countries where anaemia continues to challenge young infants.

Prediction of probability of rubella based on eye outcomes (PORBEO Nomogram)-a cross-sectional sentinel surveillance of 1134 infants.

INTRODUCTION: Rubella is an important infectious, vaccine-preventable etiology of congenital defects. The aim of the study was to develop a prediction nomogram to assess the probability of an infant being at risk for congenital rubella based on demographics and ophthalmological findings. METHODS: This was a cross-sectional sentinel surveillance study conducted at 5 centers spanning pan-India and involved 1134 infants. The diagnosis of rubella was made using standard guidelines. For the construction of the prediction model, laboratory-confirmed cases were grouped as "at-risk" (AR) infants and the discarded cases into "not at risk" (NAR) infants. Univariate analysis (p value cut-off < 0.05) followed by multivariate binary logistic regression model development was performed. RESULTS: The average (median) age of the suspected CRS infants was 3 (IQR 1-6) months, and the average (mean) age of their mothers was 25.8 ± 4.1 years. Out of the total infants, 81 (7.3%) died, 975 (88%) were alive, and 55 (5.0%) were lost to follow-up. The final model showed that the odds of cataract, retinopathy, glaucoma, microcornea, and age of the infant at presentation were 3.1 (2.2-4.3), 4.9(2.3-10.4), 2.7(1.1-5.9), 2.3(1.1-4.7), and 1.1 (1-1.1), respectively, for the AR infant as compared to NAR infant. AUC of final model was 0.68 (95% CI Delong, 0.64-0.72). Bootstrapping for calibration of the model showed satisfactory results. Nomogram, along with a web version, was developed. CONCLUSION: The developed nomogram would have a wide community-based utilization and will help in prioritizing attention to high-risk children, thereby avoiding loss to follow-up.

Neurodevelopmental Outcomes of Very Low Birth Weight Infants at 18-24 Months, Corrected Gestational Age in a Tertiary Health Centre: A Prospective Cohort Study.

OBJECTIVE: To determine the prevalence and risk factors for poor neurodevelopmental outcome in a cohort of very low birth weight (VLBW) infants. SUBJECTS AND METHODS: Four hundred and twenty-two infants of a total of 643 VLBW survivors from a teaching hospital in South India were followed up to assess their neurodevelopmental outcomes. RESULTS: Among the 422 children who completed the assessment, results of 359 children whose assessments were done between 18 and 24 months were analysed. Thirty-seven children (10.31%) had poor neurodevelopmental outcome, six children [1.67%] had cerebral palsy, one child had visual impairment and another had hearing impairment. Poor post-natal growth was independently associated with poor neurodevelopmental outcomes in the multivariate analysis (p = 0.045). Neonatal complications were not associated with the developmental outcome. CONCLUSION: Despite lower rates of neonatal complications compared with Western cohorts, significant proportion of VLBW infants had poor neurodevelopmental outcomes. Poor post-natal growth was an important determinant of the developmental outcome.

Sentinel Surveillance for Congenital Rubella Syndrome - India, 2016-2017.

Rubella infection during pregnancy can result in miscarriage, fetal death, stillbirth, or a constellation of congenital malformations known as congenital rubella syndrome (CRS). The 11 countries in the World Health Organization (WHO) South-East Asia Region are committed to the elimination of measles and control of rubella and CRS by 2020. Until 2016, when the Government of India's Ministry of Health and Family Welfare and the Indian Council of Medical Research initiated surveillance for CRS in five sentinel sites, India did not conduct systematic surveillance for CRS. During the first 8 months of surveillance, 207 patients with suspected CRS were identified. Based on clinical details and serologic investigations, 72 (34.8%) cases were classified as laboratory-confirmed CRS, four (1.9%) as congenital rubella infection, 11 (5.3%) as clinically compatible cases, and 120 (58.0%) were excluded as noncases. The experience gained during the first phase of surveillance will be useful in expanding the surveillance network, and data from the surveillance network will be used to help monitor progress toward control of rubella and CRS in India.

Dispersion curves for Lamb wave propagation in prestressed plates using a semi-analytical finite element analysis.

Acoustoelastic techniques have been recently used to characterize the state of prestress in structures such as plates. The velocity of guided wave modes propagating through plates is sensitive to the magnitude and orientation of the initial state of stress. Dispersion curves for phase velocities of plate guided waves can be computed using the superposition of partial bulk waves (SPBW) method. Here, a semi-analytical finite element (SAFE) method is formulated for the acoustoelastic problem of guided waves in weakly nonlinear elastic plates. The SAFE formulation is shown to provide phase velocity dispersion curve results identical with those provided by the SPBW method for the problem of a plate under a uniaxial and uniform tensile stress. Analytical phase and group velocity dispersion curves are also obtained for a plate with an initial prestress gradient through its thickness using the SAFE method. The magnitude of the prestress gradient is shown to have a significant effect on phase and group velocities of the fundamental and first order Lamb modes, only in certain frequency-thickness regimes.

Postnatal Weight Gain Patterns in Preterm Very-Low-Birth-Weight Infants Born in a Tertiary Care Center in South India.

Background: Extrauterine growth retardation is a common problem in preterm, very-low-birth-weight (VLBW) babies, as well as paucity of growth charts that follow their postnatal growth. Aim: To evaluate and plot postnatal weight gain patterns of preterm VLBW babies of <34 weeks' gestation born at a tertiary care neonatal unit in South India. Methods: Weight gain patterns of all preterm (27 to < 34 weeks' gestation) and VLBW (<1500 g) neonates were used for plotting the centile curves by retrospective review of electronic medical records. The growth velocity was calculated from birth and from the time baby regained their birth weight. Results: Mean growth rate (±SD) of these babies was 16.2 ± 2.4 g/kg/day and average time to regain birth weight was 14.2 days (range 12.0-17.6). Conclusion: The recommended growth velocity of 10-15 g/kg/day can be achieved using unfortified expressed breast milk, though at higher feeding volumes of 200 ml/kg/day. These centile curves can be useful for monitoring postnatal growth.

Perinatal Risk Factors for Neonatal Early-onset Group B Streptococcal Sepsis after Initiation of Risk-based Maternal Intrapartum Antibiotic Prophylaxis-A Case Control Study.

OBJECTIVES: To identify the perinatal risk factors for early-onset Group B Streptococcus (EOGBS) sepsis in neonates after inception of a risk-based maternal intrapartum antibiotic prophylaxis strategy in 2004. DESIGN: Case control study. METHODS: All newborn with early onset GBS sepsis (born between 2004 and 2013) were deemed to be "cases" and controls were selected in a 1:4 ratio. RESULTS: More than three per vaginal (PV) examinations [odds ratio (OR) 8.57, 95% confidence interval (CI) 3.10-23.6] was a significant risk factors. Peripartum fever (OR 3.54, 95% CI 1.3-9.67), urinary tract infection (OR 2.88, 95% CI 1.08-7.63), meconium-stained amniotic fluid (MSAF) (OR 2.52, 95% CI 1.18-5.37) and caesarean section (OR 1.99, 95% CI 1.16-3.43) were also found to be associated with EOGBS sepsis. CONCLUSION: Multiple vaginal examinations are the strongest risk factors for peripartum Group B Streptococcal (GBS) sepsis. The association of MSAF and caesarean section indicates that foetal distress is an early symptom of perinatal GBS infection.

Long-term healthcare utilisation, costs and quality of life after invasive group B Streptococcus disease: a cohort study in five low-income and middle-income countries.

INTRODUCTION: There are no published data on the long-term impact of invasive group B Streptococcus disease (iGBS) on economic costs or health-related quality of life (HRQoL) in low-income and middle-income countries. We assessed the impact of iGBS on healthcare utilisation, costs and HRQoL in Argentina, India, Kenya, Mozambique and South Africa. METHODS: Inpatient and outpatient visits, out-of-pocket (OOP) healthcare payments in the 12 months before study enrolment, and health-state utility of children and caregivers (using the EuroQol 5-Dimensions-3-Level) were collected from iGBS survivors and an unexposed cohort matched on site, age at recruitment and sex. We used logistic or Poisson regression for analysing healthcare utilisation and zero-inflated gamma regression models for family and health system costs. For HRQoL, we used a zero-inflated beta model of disutility pooled data. RESULTS: 161 iGBS-exposed and 439 unexposed children and young adults (age 1-20) were included in the analysis. Compared with unexposed participants, iGBS was associated with increased odds of any healthcare utilisation in India (adjusted OR 11.2, 95% CI 2.9 to 43.1) and Mozambique (6.8, 95% CI 2.2 to 21.1) and more frequent healthcare visits (adjusted incidence rate ratio (IRR) for India 1.7 (95% CI 1.4 to 2.2) and for Mozambique 6.0 (95% CI 3.2 to 11.2)). iGBS was also associated with more frequent days in inpatient care in India (adjusted IRR 4.0 (95% CI 2.3 to 6.8) and Kenya 6.4 (95% CI 2.9 to 14.3)). OOP payments were higher in the iGBS cohort in India (adjusted mean: Int$682.22 (95% CI Int$364.28 to Int$1000.16) vs Int$133.95 (95% CI Int$72.83 to Int$195.06)) and Argentina (Int$244.86 (95% CI Int$47.38 to Int$442.33) vs Int$52.38 (95% CI Int$-1.39 to Int$106.1)). For all remaining sites, differences were in the same direction but not statistically significant for almost all outcomes. Health-state disutility was higher in iGBS survivors (0.08, 0.04-0.13 vs 0.06, 0.02-0.10). CONCLUSION: The iGBS health and economic burden may persist for years after acute disease. Larger studies are needed for more robust estimates to inform the cost-effectiveness of iGBS prevention.

Rubella immunity among pregnant women and the burden of congenital rubella syndrome (CRS) in India, 2022.

BACKGROUND: India aims to eliminate rubella and congenital rubella syndrome (CRS) by 2023. We conducted serosurveys among pregnant women to monitor the trend of rubella immunity and estimate the CRS burden in India following a nationwide measles and rubella vaccination campaign. METHODS: We surveyed pregnant women at 13 sentinel sites across India from Aug to Oct 2022 to estimate seroprevalence of rubella IgG antibodies. Using age-specific seroprevalence data from serosurveys conducted during 2017/2019 (prior to and during the vaccination campaign) and 2022 surveys (after the vaccination campaign), we developed force of infection (FOI) models and estimated incidence and burden of CRS. RESULTS: In 2022, rubella seroprevalence was 85.2% (95% CI: 84.0, 86.2). Among 10 sites which participated in both rounds of serosurveys, the seroprevalence was not different between the two periods (pooled prevalence during 2017/2019: 83.5%, 95% CI: 82.1, 84.8; prevalence during 2022: 85.1%, 95% CI: 83.8, 86.3). The estimated annual incidence of CRS during 2017/2019 in India was 218.3 (95% CI: 209.7, 226.5) per 100, 000 livebirths, resulting in 47,120 (95% CI: 45,260, 48,875) cases of CRS every year. After measles-rubella (MR) vaccination campaign, the estimated incidence of CRS declined to 5.3 (95% CI: 0, 21.2) per 100,000 livebirths, resulting in 1141 (95% CI: 0, 4,569) cases of CRS during the post MR-vaccination campaign period. CONCLUSION: The incidence of CRS in India has substantially decreased following the nationwide MR vaccination campaign. About 15% of women in childbearing age in India lack immunity to rubella and hence susceptible to rubella infection. Since there are no routine rubella vaccination opportunities for this age group under the national immunization program, it is imperative to maintain high rates of rubella vaccination among children to prevent rubella virus exposure among women of childbearing age susceptible for rubella.

Serotype distribution and antimicrobial susceptibility profile of invasive group B streptococcal disease-in South Indian population.

PURPOSE: Invasive group B Streptococcal disease (iGBS) is an important cause of morbidity and mortality in neonates for which the development of an efficacious vaccine remains a global health imperative. The knowledge about the serotype distribution of iGBS is important component for formulation of Capsular polysaccharide (CPS)-based vaccine. However, there were absolute lack of information on serotype distribution in invasive GBS isolates from Indian subcontinent. Methods This study has assessed the serotype distribution and antimicrobial susceptibility profile of invasive group B streptococcal isolates for a period of 13 years from 2009 to 2022 from a tertiary care Center in South India. A total of 155 iGBS isolates were subjected to serotyping by conventional multiplex PCR for identification of all ten GBS serotype. Antimicrobial susceptibility profile and demographic details were extracted from microbiological records. Results Overall, the most common serotype causing invasive GBS were Ia (29%), V (26%), III (15%), II (12%), VI (6%), VII (5%) and Ib (5%). Serotypes IV, VIII and XI were not detected. Among the early-onset iGBS, the common serotype were Ia (36%), V (27%), and III (8%). In late onset iGBS, Serotype III (44%) was predominant. The common serotype in adults were Serotype V (31%) and III (20%). All the invasive GBS isolates were susceptible for penicillin (100%), but the susceptibility for clindamycin and erythromycin were 72% and 80% respectively. Conclusion The serotype distribution of invasive Group B streptococcal isolates from India suggest that hexavalent group B CPS vaccine will cover only 90% of GBS isolates causing invasive disease among the infants in India. Continued surveillance monitoring for serotype distribution and antimicrobial resistance patterns for iGBS are warranted to make public health interventions.

Congenital rubella syndrome surveillance in India, 2016-21: Analysis of five years surveillance data.

Background: In India, facility-based surveillance for congenital rubella syndrome (CRS) was initiated in 2016 to estimate the burden and monitor the progress made in rubella control. We analyzed the surveillance data for 2016-2021 from 14 sentinel sites to describe the epidemiology of CRS. Method: We analyzed the surveillance data to describe the distribution of suspected and laboratory confirmed CRS patients by time, place and person characteristics. We compared clinical signs of laboratory confirmed CRS and discarded case-patients to find independent predictors of CRS using logistic regression analysis and developed a risk prediction model. Results: During 2016-21, surveillance sites enrolled 3940 suspected CRS case-patients (Age 3.5 months, SD: 3.5). About one-fifth (n = 813, 20.6%) were enrolled during newborn examination. Of the suspected CRS patients, 493 (12.5%) had laboratory evidence of rubella infection. The proportion of laboratory confirmed CRS cases declined from 26% in 2017 to 8.7% in 2021. Laboratory confirmed patients had higher odds of having hearing impairment (Odds ratio [OR] = 9.5, 95% confidence interval [CI]: 5.6-16.2), cataract (OR = 7.8, 95% CI: 5.4-11.2), pigmentary retinopathy (OR = 6.7, 95 CI: 3.3-13.6), structural heart defect with hearing impairment (OR = 3.8, 95% CI: 1.2-12.2) and glaucoma (OR = 3.1, 95% CI: 1.2-8.1). Nomogram, along with a web version, was developed. Conclusions: Rubella continues to be a significant public health issue in India. The declining trend of test positivity among suspected CRS case-patients needs to be monitored through continued surveillance in these sentinel sites.

Profile of cardiac lesions among laboratory confirmed congenital rubella syndrome (CRS) infants: a nationwide sentinel surveillance, India, 2016-22.

Background: The phenotypical profile of cardiovascular malformations in patients with congenital rubella syndrome (CRS) is varied. We aimed to describe the profile of cardiac defects among CRS patients detected in the sentinel CRS surveillance in India during 2016-22. Methods: Sentinel sites enrolled infants with suspected CRS based on presence of cardiac defects, hearing impairment, eye signs, or maternal history of febrile rash illness. Suspected CRS cases underwent detailed systemic examination, including echocardiography and serological investigation for rubella. Cardiac defects were categorized as 'Simple' or 'Complex' as per the National Heart, Lung, and Blood Institute classification. We compared the distribution of cardiac defects among laboratory confirmed CRS cases and seronegative discarded cases. Findings: Of the 4578 suspected CRS cases enrolled by 14 sites, 558 (12.2%) were laboratory confirmed. 419 (75.1%) laboratory confirmed cases had structural heart defects (simple defects: n = 273, 65.2%, complex defects: n = 144, 34.4%), with ventricular septal defect (42.7%), atrial septal defect (39.4%), patent ductus arteriosus (36.5%), and tetralogy of Fallot as the commonest defects (4.5%). Laboratory confirmed CRS cases had higher odds of left to right shunt lesions (OR = 1.58, 95% CI: 1.15-2.17). This was mainly on account of a significant association of PDA with CRS (OR = 1.77, 95% CI: 1.42-2.21). Mortality was higher among CRS patients with complex heart defects (HR = 2.04, 95% CI: 1.26-3.30). Interpretation: Three-fourths of the laboratory confirmed CRS cases had structural heart defects. CRS patients with complex cardiac defects had higher mortality. Detecting CRS infection early and providing timely intervention for cardiovascular defects is critical for the management of CRS patients. Funding: Ministry of Health and Family Welfare, Govt of India, through Gavi, the Vaccine Alliance.

A randomized control trial comparing two enteral feeding volumes in very low birth weight babies.

Poor post-natal growth of preterm neonates is common and fortification is recommended. However, this is not always practical in low-resource areas. Hypothesizing that increasing the volume of feeds would be safe and lead to better post-natal weight gain, we randomized 64 babies with birth weight <1500 g, once they reached full feeds, to continue feeds at 200 ml/kg/day (standard volume) or increase to 300 ml/kg/day (high volume) of expressed breast milk. There was a significantly higher daily weight gain in the high-volume group as compared to the standard volume group (24.9 vs. 18.7 g/kg/day, p < 0.0001). There were no differences in complications like feed intolerance, tachypnoea, sepsis, patent ductus arteriosus or necrotizing enterocolitis. High-volume feeds at 300 ml/kg/day was safe and resulted in better weight gain than standard volume feeds in very low birth weight babies.

On the examination of the viscous response of the brachial artery during flow-mediated dilation.

In this study, mechanotransduction is investigated through a physics-based viscoelastic model describing the arterial diameter response during a brachial artery flow mediated dilation (BAFMD) test. The study is a significant extension of two earlier studies by the same group, where only the elastic response was considered. Experimental BAFMD responses were collected from 12 healthy volunteers. The arterial wall's elastic and viscous properties were treated as local variable quantities depending on the wall shear stress (WSS) sensed by mechanotransduction. The dimensionless parameters, arising from the model which serve as a quantitative assessment of the artery's physical state, were adjusted to replicate the experimental response. Among those dimensionless parameters, the viscoelastic ratio, which reflects the relative strength of the viscous response compared to its elastic counterpart, is of special relevance to this paper's main conclusion. Based on the results, it is concluded that the arterial wall's mechanical behavior is predominantly elastic, at least in the strict context of the BAFMD test. Recommendations for potential future research and applications are provided.

Etiology, clinical profile and outcome of neonatal pneumothorax in tertiary care center in South India: 13 years experience.

BACKGROUND: Pneumothorax is a medical emergency and is associated with a significant increase in morbidity and mortality in newborns. It may lead to acute respiratory failure, systemic hypoperfusion, intraventricular hemorrhage (IVH), and death. There is a paucity of data from developing countries about the epidemiology of pneumothorax. OBJECTIVE: This descriptive study was planned to study the clinical and epidemiological profile of hospitalized neonates with pneumothorax. MATERIAL AND METHODS: In this retrospactive study neonates admitted to Neonatal Intensive Care Unit (NICU) from 1 January 2004 to 31 December 2016 were reviewed.Relevant statistical analyses were done. RESULTS: There were 144,166 live births and 189 inborn cases of pneumothorax; hence, the incidence was 1.3 per 1000 live births. Males outnumbered females by a ratio of 2:1. 50.1% of affected neonates were preterm, mean gestational age being 35.2 ± 3.9 weeks. The mean birth weight was 2238 ± 794 g. Overall median age at diagnosis was 21 h (IQR: 4-48 h), longer in preterm neonates compared to term. Hyaline membrane disease (HMD) was the most common underlying pulmonary disorder. Pneumothorax was drained in 89.2% of tension and only 16.3% of nontension pneumothoraces. Approximately 20% of the neonates were treated with needle aspiration alone and about 24% were treated conservatively. Mortality rate among neonates with pneumothorax was 21.6%. Statistically significant risk factors for mortality were very low birth weight (VLBW) (OR: 2.47, 1.31-4.68), tension pneumothorax (OR: 2.79, 1.05-7.4), and pulmonary hypoplasia (OR: 7.5, 2.8-20.2). Multiple attempts of needle drainage were needed in 2.5% of the cases. The neonates, both term and preterm, requiring drainage had longer duration of hospital stay when compared to those without requirement of drainage. CONCLUSION: We propose a trial of needle aspiration prior to ICD insertion and intubation which will prevent the complications related to intubation.

Genetic Heterogeneity and Challenges in the Management of Permanent Neonatal Diabetes Mellitus: A Single-Centre Study from South India.

Aim and Objectives: 1. To study the clinical outcome, growth and glycaemic control, 2. To study the frequency and type of genetic mutations. Methods: This is a retrospective study with a review of data of medical records from 2008 till date. Results: Twelve patients (six males) with neonatal diabetes mellitus (NDM) were identified. Median (interquartile range - (IQR)) age at diagnosis was 72 (31-95) days with a history of consanguinity in 75%. The median birth weight (range) was 2345 (900-3300) g. Follow-up data were available for eight patients with a median age at (IQR) follow-up of 3.3 (3-5.3) years. At follow-up, the mean annual HbA1c was 8.2% at a mean insulin dose of 1.1 U/kg/d. One patient with Wolcott-Rallison syndrome (WRS) and 21α-hydroxylase deficiency had poor growth and intellectual difficulty. The rest demonstrated satisfactory growth with an increase of mean weight centile from 2nd to 13th, height centile from 6.5th to 20th and normal neuro-cognitive development. Eleven patients underwent genetic testing with a molecular diagnosis in 54% (6/11): EIF2AK3 (n = 2) and one each in INS, PDX1, IL2RA and FOXP3. None had variants in ABCC8 or KCNJ11. One with immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome underwent haematopoietic stem cell transplant (HSCT) and later succumbed. Conclusion: Our study demonstrates good clinical outcomes among NDM patients without immune dysfunction. Molecular diagnosis was attained only in around half of the patients (54%) with a great genetic heterogeneity.

Neurodevelopmental and growth outcomes after invasive Group B Streptococcus in early infancy: A multi-country matched cohort study in South Africa, Mozambique, India, Kenya, and Argentina.

Background: Data are limited regarding long-term consequences of invasive GBS (iGBS) disease in early infancy, especially from low- and middle-income countries (LMIC) where most cases occur. We aimed to estimate risk of neurodevelopmental impairment (NDI) in children with a history of iGBS disease. Methods: A multi-country matched cohort study was undertaken in South Africa, India, Mozambique, Kenya, and Argentina from October 2019 to April 2021. The exposure of interest was defined as a history of iGBS disease (sepsis or meningitis) before 90 days of age, amongst children now aged 1·5-18 years. Age and sex-matched, children without history of GBS were also recruited. Age-appropriate, culturally-adapted assessments were used to define NDI across multiple domains (cognitive, motor, hearing, vision, emotional-behaviour, growth). Pooled NDI risk was meta-analysed across sites. Association of iGBS exposure and NDI outcome was estimated using modified Poisson regression with robust variance estimator. Findings: Amongst 138 iGBS survivors and 390 non-iGBS children, 38·1% (95% confidence interval [CI]: 30·0% - 46·6%) of iGBS children had any NDI, compared to 21·7% (95% CI: 17·7% - 26·0%) of non- iGBS children, with notable between-site heterogeneity. Risk of moderate/severe NDI was 15·0% (95% CI: 3·4% - 30·8%) among GBS-meningitis, 5·6% (95% CI: 1·5% - 13·7%) for GBS-sepsis survivors. The adjusted risk ratio (aRR) for moderate/severe NDI among iGBS survivors was 1.27 (95% CI: 0.65, 2.45), when compared to non-GBS children. Mild impairment was more frequent in iGBS (27.6% (95% CI: 20.3 - 35.5%)) compared to non-GBS children (12.9% (95% CI: 9.7% - 16.4%)). The risk of emotional-behavioural problems was similar irrespective of iGBS exposure (aRR=0.98 (95% CI: 0.55, 1.77)). Interpretation: Our findings suggest that iGBS disease is on average associated with a higher risk of moderate/severe NDI, however substantial variation in risk was observed between sites and data are consistent with a wide range of values. Our study underlines the importance of long-term follow-up for at-risk neonates and more feasible, standardised assessments to facilitate diagnosis in research and clinical practice. Funding: This work was supported by a grant (INV-009018) from the Bill & Melinda Gates Foundation to the London School of Hygiene &Tropical Medicine.

Group B streptococcus infection during pregnancy and infancy: estimates of regional and global burden.

BACKGROUND: Group B streptococcus (GBS) colonisation during pregnancy can lead to invasive GBS disease (iGBS) in infants, including meningitis or sepsis, with a high mortality risk. Other outcomes include stillbirths, maternal infections, and prematurity. There are data gaps, notably regarding neurodevelopmental impairment (NDI), especially after iGBS sepsis, which have limited previous global estimates. In this study, we aimed to address this gap using newly available multicountry datasets. METHODS: We collated and meta-analysed summary data, primarily identified in a series of systematic reviews published in 2017 but also from recent studies on NDI and stillbirths, using Bayesian hierarchical models, and estimated the burden for 183 countries in 2020 regarding: maternal GBS colonisation, iGBS cases and deaths in infants younger than 3 months, children surviving iGBS affected by NDI, and maternal iGBS cases. We analysed the proportion of stillbirths with GBS and applied this to the UN-estimated stillbirth risk per country. Excess preterm births associated with maternal GBS colonisation were calculated using meta-analysis and national preterm birth rates. FINDINGS: Data from the seven systematic reviews, published in 2017, that informed the previous burden estimation (a total of 515 data points) were combined with new data (17 data points) from large multicountry studies on neurodevelopmental impairment (two studies) and stillbirths (one study). A posterior median of 19·7 million (95% posterior interval 17·9-21·9) pregnant women were estimated to have rectovaginal colonisation with GBS in 2020. 231 800 (114 100-455 000) early-onset and 162 200 (70 200-394 400) late-onset infant iGBS cases were estimated to have occurred. In an analysis assuming a higher case fatality rate in the absence of a skilled birth attendant, 91 900 (44 800-187 800) iGBS infant deaths were estimated; in an analysis without this assumption, 58 300 (26 500-125 800) infant deaths from iGBS were estimated. 37 100 children who recovered from iGBS (14 600-96 200) were predicted to develop moderate or severe NDI. 40 500 (21 500-66 200) maternal iGBS cases and 46 200 (20 300-111 300) GBS stillbirths were predicted in 2020. GBS colonisation was also estimated to be potentially associated with considerable numbers of preterm births. INTERPRETATION: Our analysis provides a comprehensive assessment of the pregnancy-related GBS burden. The Bayesian approach enabled coherent propagation of uncertainty, which is considerable, notably regarding GBS-associated preterm births. Our findings on both the acute and long-term consequences of iGBS have public health implications for understanding the value of investment in maternal GBS immunisation and other preventive strategies. FUNDING: Bill & Melinda Gates Foundation.