Publications by authors named "Sridhar Santhanam"

45 Publications

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

EClinicalMedicine 2022 May 28;47:101358. Epub 2022 Apr 28.

Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, United Kingdom.

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.
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http://dx.doi.org/10.1016/j.eclinm.2022.101358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9142788PMC
May 2022

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

Indian J Endocrinol Metab 2022 Jan-Feb;26(1):79-86. Epub 2022 Apr 27.

Department of Paediatrics, Paediatric Unit-1, Paediatric Endocrinology and Metabolism Division, Christian Medical College and Hospital, Vellore, Tamil Nadu, 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 2 to 13, height centile from 6.5 to 20 and normal neuro-cognitive development. Eleven patients underwent genetic testing with a molecular diagnosis in 54% (6/11): ( = 2) and one each in , , and . None had variants in or . 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.
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http://dx.doi.org/10.4103/ijem.ijem_429_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9162257PMC
April 2022

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

J Mech Behav Biomed Mater 2022 Jul 27;131:105255. Epub 2022 Apr 27.

Department of Mechanical Engineering, Villanova University, PA, 19085, USA; Cellular Biomechanics and Sport Science Laboratory, Villanova University, PA, 19085, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jmbbm.2022.105255DOI Listing
July 2022

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

Lancet Glob Health 2022 06 28;10(6):e807-e819. Epub 2022 Apr 28.

Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK; Maternal, Adolescent, Reproductive & Child Health Centre, London School of Hygiene & Tropical Medicine, London, UK.

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.
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http://dx.doi.org/10.1016/S2214-109X(22)00093-6DOI Listing
June 2022

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

Vox Sang 2022 Jun 26;117(6):847-852. Epub 2022 Jan 26.

Department of Transfusion Medicine and Immunohaematology, Christian Medical College, Vellore, India.

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.
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http://dx.doi.org/10.1111/vox.13253DOI Listing
June 2022

Emotional and Behavioral Outcomes in Childhood for Survivors of Invasive Group B Streptococcus Disease in Infancy: Findings From 5 Low- and Middle-Income Countries.

Clin Infect Dis 2022 01;74(Suppl_1):S35-S43

Maternal, Adolescent, Repr oductive & Child Health Centre, London School of Hygiene & Tropical Medicine, London, United Kingdom.

Background: Survivors of invasive group B Streptococcus (iGBS) disease, notably meningitis, are at increased risk of neurodevelopmental impairment. However, the limited studies to date have a median follow-up to 18 months and have mainly focused on moderate or severe neurodevelopmental impairment, with no previous studies on emotional-behavioral problems among iGBS survivors.

Methods: In this multicountry, matched cohort study, we included children aged 18 months to 17 years with infant iGBS sepsis and meningitis from health demographic surveillance systems, or hospital records in Argentina, India, Kenya, Mozambique, and South Africa. Children without an iGBS history were matched to iGBS survivors for sex and age. Our primary outcomes were emotional-behavioral problems and psychopathological conditions as measured with the Child Behavior Checklist (CBCL). The CBCL was completed by the child's primary caregiver.

Results: Between October 2019 and April 2021, 573 children (mean age, 7.18 years) were assessed, including 156 iGBS survivors and 417 non-iGBS comparison children. On average, we observed more total problems and more anxiety, attention, and conduct problems for school-aged iGBS survivors compared with the non-iGBS group. No differences were found in the proportion of clinically significant psychopathological conditions defined by the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition).

Conclusions: Our findings suggested that school-aged iGBS survivors experienced increased mild emotional behavioral problems that may affect children and families. At-risk neonates including iGBS survivors need long-term follow-up with integrated emotional-behavioral assessments and appropriate care. Scale-up will require simplified assessments that are free and culturally adapted.
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http://dx.doi.org/10.1093/cid/ciab821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8776308PMC
January 2022

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

Clin Infect Dis 2022 01;74(Suppl_1):S24-S34

Department of Neonatology, Christian Medical College, Vellore, India.

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.
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http://dx.doi.org/10.1093/cid/ciab792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8775645PMC
January 2022

Quantifying long-term health and economic outcomes for survivors of group B Streptococcus invasive disease in infancy: protocol of a multi-country study in Argentina, India, Kenya, Mozambique and South Africa.

Gates Open Res 2020 19;4:138. Epub 2021 Jul 19.

Maternal and Child Health Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.

Sepsis and meningitis due to invasive group B (iGBS) disease during early infancy is a leading cause of child mortality. Recent systematic estimates of the worldwide burden of GBS suggested that there are 319,000 cases of infant iGBS disease each year, and an estimated 147,000 stillbirths and young-infant deaths, with the highest burden occurring in Sub-Saharan Africa.  The following priority data gaps were highlighted: (1) long-term outcome data after infant iGBS, including mild disability, to calculate quality-adjusted life years (QALYs) or disability-adjusted life years (DALYs) and (2) economic burden for iGBS survivors and their families. Geographic data gaps were also noted with few studies from low- and middle- income countries (LMIC), where the GBS burden is estimated to be the highest. In this paper we present the protocol for a multi-country matched cohort study designed to estimate the risk of long-term neurodevelopmental impairment (NDI), socioemotional behaviors, and economic outcomes for children who survive invasive GBS disease in Argentina, India, Kenya, Mozambique, and South Africa. Children will be identified from health demographic surveillance systems, hospital records, and among participants of previous epidemiological studies. The children will be aged between 18 months to 17 years. A tablet-based custom-designed application will be used to capture data from direct assessment of the child and interviews with the main caregiver. In addition, a parallel sub-study will prospectively measure the acute costs of hospitalization due to neonatal sepsis or meningitis, irrespective of underlying etiology. In summary, these data are necessary to characterize the consequences of iGBS disease and enable the advancement of effective strategies for survivors to reach their developmental and economic potential. In particular, our study will inform the development of a full public health value proposition on maternal GBS immunization that is being coordinated by the World Health Organization.
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http://dx.doi.org/10.12688/gatesopenres.13185.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313848PMC
July 2021

On the modeling of mechanotransduction in flow-mediated dilation.

J Mech Behav Biomed Mater 2021 08 24;120:104606. Epub 2021 May 24.

Department of Mechanical Engineering, Villanova University, PA, 19085, USA; Cellular Biomechanics and Sport Science Laboratory, Villanova University, PA, 19085, USA. Electronic address:

In this paper, we report a physics based mathematical model to describe the mechanotransduction at the luminal surface of the brachial artery during a flow-mediated dilation (FMD) process. To account for the effect of the released vasodilators in response to the sudden blood flow resurgence, a scalar property is introduced as a signal radially diffusing through the arterial wall, locally affecting its compliance. The model was evaluated on 19 in vivo responses of brachial artery FMD (BAFMD) in 12 healthy subjects. It successfully reproduces the time-dependent dilation of the brachial artery. The predicted artery's outer-to-inner radius ratio was also found to be consistent with the measurements within an acceptable margin of error. Physically meaningful dimensionless parameters quantifying the artery's physical state arose from the model, providing a description to how sensitive or responsive the artery is to the changes of wall shear stress (WSS). Future applications of this model, via incorporating inexpensive, relatively quick, and non-invasive imaging, could potentially help detect early stages of developing forms of cardiovascular diseases.
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http://dx.doi.org/10.1016/j.jmbbm.2021.104606DOI Listing
August 2021

Maternal and Perinatal Outcomes of Influenza in Pregnancy after Treatment with Oseltamivir.

J Glob Infect Dis 2021 Jan-Mar;13(1):20-26. Epub 2021 Jan 29.

Global Health Center, Cincinnati Children's Hospital, Cincinnati, OH, USA.

Context: Influenza infection in pregnancy causes 4%-8% case fatality and five times more perinatal mortality. Influenza is a major contributor to mortality in developing countries; however, the morbidity has largely been underestimated. Public health interventions for prevention are also lacking.

Aims: This study aimed to determine the seasonality of influenza in pregnant Indian women and to estimate the maternal and perinatal morbidity after treatment with oseltamivir.

Settings And Design: This was a prospective observational cohort study, conducted in a tertiary hospital.

Subjects And Methods: Pregnant women with ILI (influenza-like illness) were recruited into Cohort 1 (polymerase chain reaction [PCR] positive) and Cohort 2 (PCR negative). Gestational age-matched asymptomatic controls formed Cohort 3. Women in Cohort 1 received oseltamivir for 5 days. The incidence of small-for-gestational age (SGA) and preterm birth were the primary outcomes. Maternal and neonatal morbidity formed the secondary outcomes.

Statistical Analysis: Unmatched (Cohort 1 and 2) and matched analysis (Cohort 1 and 3) were done. Student's -test and Chi-square test were used to compare between variables.

Results: Year-round incidence of influenza was recorded. Severe illness was more in Cohort 1 compared to Cohort 2 (36.2% vs. 6.3%; < 0.001). SGA was comparable in all the cohorts (13%). Preterm birth (7.8% vs. 3.3%; < 0.08; relative risk-2.75) was considerably high in Cohort 1. Secondary maternal and neonatal outcomes were similar between the groups.

Conclusion: Influenza in pregnancy showed year-round incidence and increased maternal and neonatal morbidity despite treatment with oseltamivir. We suggest the need for newer interventions to curtail the illness in pregnancy.
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http://dx.doi.org/10.4103/jgid.jgid_157_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054794PMC
January 2021

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

Graefes Arch Clin Exp Ophthalmol 2021 May 29;259(5):1333-1342. Epub 2020 Oct 29.

National Institute of Epidemiology, ICMR, Chennai, Tamil Nadu, India.

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.
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http://dx.doi.org/10.1007/s00417-020-04973-5DOI Listing
May 2021

Do red cell alloantibodies continue to challenge breast fed babies?

Transfus Med 2020 Aug 21;30(4):281-286. Epub 2020 Feb 21.

Department of Transfusion Medicine and Immunohaematology, Christian Medical College, Vellore, India.

Background: Newborns have limited specific immune capability at birth, owing to delayed and constrained development of adaptive immunity. To supplement this period the mother passively transfers antibodies to the child either transplacentally or through breast milk. When maternal alloimmunisation occurs through foreign or fetal red cell surface antigens, stimulating the production of immunoglobulin G (IgG) antibodies, these IgG antibodies can cross the placenta and cause haemolytic disease of the fetus and the newborn.

Objective: We present two case reports of a neonate and an infant in whom IgG red cell alloantibodies were transferred through maternal breast milk.

Methods: Maternal serum, baby's serum and expressed breast milk samples were tested for the presence of red cell alloantibodies using gel card. Antibody screening, antibody identifications and titres alongside monospecific direct antiglobulin test, IgG subtypes were performed using the standard methods.

Results: In the first case, a 6-month-old child was incidentally found to have positive antibody screen. Anti-KELL1 was identified, which was also present in maternal serum and breast milk. The second neonate was evaluated for haemolysis and was found to have anti-D. Anti-D was also detected in the maternal serum and breast milk. Both babies did not have any sensitising events. The first baby was asymptomatic, but the second baby had ongoing haemolysis until 1 month.

Conclusion: We report that maternal anti-KELL1 and anti-D antibodies were present in breast milk and were capable of being transferred to a feeding child. Our case report also raises interesting and unanswered immunologic fundamentals that should be considered in neonates with unexplained anaemia or delayed and persistent haemolysis.
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http://dx.doi.org/10.1111/tme.12672DOI Listing
August 2020

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

J Matern Fetal Neonatal Med 2022 Feb 19;35(3):520-524. Epub 2020 Feb 19.

Christian Medical College and Hospital, Vellore, India.

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.
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http://dx.doi.org/10.1080/14767058.2020.1727880DOI Listing
February 2022

Epidemiology of Congenital Rubella Syndrome (CRS) in India, 2016-18, based on data from sentinel surveillance.

PLoS Negl Trop Dis 2020 02 3;14(2):e0007982. Epub 2020 Feb 3.

All India Institute of Medical Sciences, Jodhpur, India.

Background: Government of India is committed to eliminate measles and control rubella/congenital rubella syndrome (CRS) by 2020. In 2016, CRS surveillance was established in five sentinel sites. We analyzed surveillance data to describe the epidemiology of CRS in India.

Methodology/principal Findings: We used case definitions adapted from the WHO-recommended standards for CRS surveillance. Suspected patients underwent complete clinical examination including cardiovascular system, ophthalmic examination and assessment for hearing impairment. Sera were tested for presence of IgM and IgG antibodies against rubella. Of the 645 suspected CRS patients enrolled during two years, 137 (21.2%) were classified as laboratory confirmed CRS and 8 (1.2%) as congenital rubella infection. The median age of laboratory confirmed CRS infants was 3 months. Common clinical features among laboratory confirmed CRS patients included structural heart defects in 108 (78.8%), one or more eye signs (cataract, glaucoma, pigmentary retinopathy) in 82 (59.9%) and hearing impairment in 51. (38.6%) Thirty-three (24.1%) laboratory confirmed CRS patients died over a period of 2 years. Surveillance met the quality indicators in terms of adequacy of investigation, adequacy of sample collection for serological diagnosis as well as virological confirmation.

Conclusions/significance: About one fifth suspected CRS patients were laboratory confirmed, indicating significance of rubella as a persistent public health problem in India. Continued surveillance will generate data to monitor the progress made by the rubella control program in the country.
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http://dx.doi.org/10.1371/journal.pntd.0007982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996802PMC
February 2020

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

J Trop Pediatr 2019 12;65(6):552-560

Department of Biostatistics, Christian Medical College, Vellore, Tamil Nadu, India.

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.
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http://dx.doi.org/10.1093/tropej/fmz006DOI Listing
December 2019

A randomized controlled trial comparing the effect of fortification of human milk with an infant formula powder versus unfortified human milk on the growth of preterm very low birth weight infants.

J Matern Fetal Neonatal Med 2020 Aug 6;33(15):2507-2515. Epub 2019 Jan 6.

Department of Neonatology, Christian Medical College and Hospital, Vellore, India.

To optimize growth in very low birth weight (VLBW) infants, human milk fortification is standard of care in neonatal units of high-income countries. However, commercial fortifiers may not be available or it may be too expensive in resource-limited settings. As an alternative to using human milk fortifiers, we studied the effects of milk fortification with an infant formula on growth and biochemical parameters of very low birth weight (VLBW) infants We undertook a prospective, randomized controlled trial in the neonatal unit of a tertiary care hospital in South India. Preterm infants weighing <1500 grams and <34 weeks of gestation were randomized after stratification according to birth weight into two groups (<1250 g and 1250 to <1500 g). One group received fortified human milk while the other received exclusive human milk. The fortification was done with a commercially available infant milk powder added to expressed breast milk (when the infant reached 150 ml/kg/day of feeds) and continued till the infant reached 1800 g. The primary outcome was the rate of weight gain/kg/day. Secondary outcome measures were linear growth, head circumference increase, biochemical parameters to assess the adequacy or excess of protein supplementation and comorbidities like feed intolerance, sepsis, and necrotizing enterocolitis (NEC). Total of 163 babies were randomized during the study period, of whom 148 babies (73 in the standard arm and 75 in the fortification arm) completed the trial. Baseline demographic data among the two groups were comparable. Weight gain/kg/day (mean difference (MD) 1.98 g/kg/day; 95% CI: 1.03-2.92; <.001) and linear growth (MD 0.09 cm/week; 95% CI: 0.02-0.2; =.02) was significantly higher in the fortification arm as compared to the control arm. The head growth (head circumference gain in cm/week) was higher and length of hospital stay lesser in the fortification arm, though not statistically significant. Biochemical parameters, rates of sepsis, feed intolerance, and necrotizing enterocolitis (NEC) were not different between the two groups. Fortification with Infant milk powder achieves better growth parameters than unfortified human milk and can be a useful alternative for feeding preterm VLBW infants in low resource settings.
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http://dx.doi.org/10.1080/14767058.2018.1554046DOI Listing
August 2020

Sero-prevalence of rubella among pregnant women in India, 2017.

Vaccine 2018 12 15;36(52):7909-7912. Epub 2018 Nov 15.

Christian Medical College, Vellore, Tamil Nadu, India.

Background: We conducted a sero-survey among pregnant women attending antenatal clinics of six hospitals which also function as sentinel sites for CRS surveillance, to estimate the prevalence of IgG antibodies against rubella.

Methods: We systematically sampled 1800 pregnant women attending antenatal clinics and tested their sera for IgG antibodies against rubella. We classified sera as seropositive (titre ≥10 IU/ml), sero-negative (titre <8 IU/ml) or indeterminate (titre 8-9.9 IU/ml) per manufacturer's instructions. In a sub-sample, we estimated the titers of IgG antibodies against rubella. IgG titer of ≥10 IU/mL was considered protective.

Results: Of 1800 sera tested, 1502 (83.4%) were seropositive and 24 (1.3%) were indeterminate and 274 (15.2%) were sero-negative. Rubella sero-positivity did not differ by age group, educational status or place of residence. Three hundred and eighty three (87.8%) of the 436 sera had IgG concentrations ≥10 IU/mL.

Conclusion: The results of the serosurvey indicate high levels of rubella sero-positivity in pregnant women. High sero-prevalence in the absence of routine childhood immunization indicates continued transmission of rubella virus in cities where sentinel sites are located.
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http://dx.doi.org/10.1016/j.vaccine.2018.11.013DOI Listing
December 2018

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

MMWR Morb Mortal Wkly Rep 2018 Sep 14;67(36):1012-1016. Epub 2018 Sep 14.

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.
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http://dx.doi.org/10.15585/mmwr.mm6736a4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146948PMC
September 2018

Activity based group therapy reduces maternal anxiety in the Neonatal Intensive Care Unit - a prospective cohort study.

Early Hum Dev 2018 08 19;123:17-21. Epub 2018 Jul 19.

Department of Occupational Therapy, Christian Medical College, Vellore, India.

Background: A large proportion of mothers in the Neonatal Intensive Care Unit (NICU) experience psychological distress, which is associated with adverse infant and parenting outcomes. Interventions addressing maternal anxiety in the NICU are scarce.

Aims: To assess the effect of activity based group therapy on maternal anxiety in the NICU when compared to a control group.

Study Design: The study was a prospective phase lag cohort study. In Phase 1 the control group was recruited and assessed using the State-Trait Anxiety Inventory (STAI-S) once at recruitment and again 4 weeks later. In phase 2, mothers were invited to take part in activity-based groups of 1 h duration once a week for 4 weeks. The STAI-S was administered before and after every group session.

Subjects: Mothers of babies admitted in the NICU who consented to participate, had a working knowledge of Tamil or English and were likely to stay for 4 weeks for the treatment were included.

Outcome Measures: State anxiety assessed using the STAI-S.

Results: Seventeen mothers each in the control and experimental groups completed the study. In the experimental group, there was a significant reduction in the post-test anxiety scores when compared to the pre-test in the first (p = 0.005), third (p = 0.07) and fourth (p = 0.009) sessions. The post-test anxiety scores of the intervention group was significantly lower than that of the control group (p = 0.009).

Conclusion: Activity based group therapy is effective as an intervention in reducing maternal anxiety in the NICU.

Summary: Anxiety in mothers of infants admitted in the NICU has been associated with adverse infant and parenting outcomes. This study evaluated the feasibility and effectiveness of an activity based group intervention to reduce anxiety levels in mothers in the NICU. The study was a prospective phase lag cohort study. Anxiety levels were assessed in mothers in the control group at recruitment and then 4 weeks later. In the intervention group, activity based group sessions were conducted once a week for 4 weeks. State anxiety was assessed before and after every group session. In the intervention group the anxiety levels were significantly lower in the post-test, when compared to the pre-test. Also the number of mothers suffering from moderate to severe anxiety and the anxiety scores in the post-test were significantly lower in the intervention group when compared to the control group. We conclude that activity based group sessions are effective in reducing the state anxiety in mothers in the NICU. Improving maternal psychological wellbeing may indirectly contribute to better infant outcomes.
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http://dx.doi.org/10.1016/j.earlhumdev.2018.07.001DOI Listing
August 2018

Molecular characterisation for clonality and transmission dynamics of an outbreak of amongst neonates in a tertiary care centre in South India.

Indian J Med Microbiol 2018 Jan-Mar;36(1):54-60

Department of Clinical Microbiology, Christian Medical College, Vellore, Tamil Nadu, India.

Purpose:: Sepsis is a significant cause of morbidity and mortality amongst neonates. Klebsiella pneumoniae is a common cause of nosocomial outbreaks causing bacteraemia and having potential of acquiring plasmids enhancing antimicrobial resistance. In the present study, we investigate K. pneumoniae outbreak causing bacteraemia amongst neonates over a span of 2 months. Isolates were characterised for antimicrobial resistance, virulence, molecular typing for clonality and plasmid typing for transmission dynamics, and patient outcome was investigated.

Methods: Thirteen isolates of K. pneumoniae were obtained during October-November 2016. Antimicrobial susceptibility testing was performed, and multiplex polymerase chain reaction (PCR) for β-lactamases and PCR for ompK35 and ompK36 were performed. To study hypervirulence, string test and PCR for rmpA and rmpA2 were performed. Multilocus sequence typing and Inc plasmid typing were carried out to study transmission dynamics.

Results: Amongst 13 isolates, all isolates harboured blaand bla; 12 isolates carried bla. ompK35 was present in all, but ompK36 was absent in 12 isolates. Ten isolates belonged to ST48, 6 amongst which contained IncFII (K) plasmid. One isolate each belonged to ST29, ST111 and ST2647 (novel clone). None of the isolates was hypervirulent.

Conclusion: Extended-spectrum β-lactamase K. pneumoniae is commonly seen in Indian hospitals and main mechanisms being production of SHV, TEM and CTX-M enzymes as seen in the present study. Outer membrane porins contribute significantly to antimicrobial resistance. Emergence of new clones such as ST2647 implies continuous evolution of the organism and also potential for rapid genetic recombination leading to multidrug resistance. Outbreaks amongst neonates lead to fatal outcome, and stringent hospital infection control is necessary.
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http://dx.doi.org/10.4103/ijmm.IJMM_17_426DOI Listing
September 2018

Ex Utero Intrapartum Treatment (EXIT) for a Large Fetal Neck Mass.

J Obstet Gynaecol India 2018 Apr 5;68(2):142-144. Epub 2017 Jun 5.

4Department of Neonatology, Christian Medical College, Vellore, Tamil Nadu 632004 India.

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http://dx.doi.org/10.1007/s13224-017-1017-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5895544PMC
April 2018

Tumour lysis in newborn: spontaneous or secondary to antenatal steroids?

BMJ Case Rep 2018 Apr 4;2018. Epub 2018 Apr 4.

Department of Obstetrics, Christian Medical College, Vellore, Tamil Nadu, India.

Malignancies are rare in the early neonatal period. Common congenital tumours include malignant teratoma and neuroblastomas. Tumour lysis syndrome is a serious condition usually seen after commencement of chemotherapy for a malignancy. Rare case reports of spontaneous tumour lysis have been reported though not in the newborn period. We report here an instance of tumour lysis syndrome in a newborn with congenital rhabdoid tumour, where the cause was either spontaneous or related to antenatal steroid exposure.
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http://dx.doi.org/10.1136/bcr-2017-223107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5893956PMC
April 2018

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

J Acoust Soc Am 2018 02;143(2):829

Mechanical Engineering Department, Villanova University, Villanova, Pennsylvania 19085, USA.

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.
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http://dx.doi.org/10.1121/1.5023335DOI Listing
February 2018

A prospective observational study comparing cardiac function of small for gestational age with appropriate for gestational age babies using serial echocardiographic studies.

J Matern Fetal Neonatal Med 2019 Jul 31;32(13):2194-2199. Epub 2018 Jan 31.

a Department of Neonatology , Christian Medical College , Vellore , India.

Background: Approximately 30% of babies born in India are low birth weight (LBW) and about 70% of LBW babies are small for gestational age (SGA). Though there are several trials that have evaluated cardiac function of intrauterine growth restricted (IUGR) babies in utero, there is limited data about postnatal cardiac function in SGA babies during early neonatal period. This study was conducted to evaluate the cardiac functions of SGA babies by serial echocardiographic measurements and compare this with appropriate for gestational age (AGA) babies during the early postnatal period.

Material And Methods: Seventy babies were enrolled in this prospective observational study with 35 each in the SGA and AGA groups. Echocardiography was performed for all babies on days 1, 2, and 3 of life. Myocardial performance index (MPI) was used as the primary measure to compare cardiac function. MPI was calculated for both ventricles using pulse wave Doppler and tissue Doppler.

Results: MPI of the left ventricle was significantly higher in the SGA group as compared to AGA babies during all the three measurement periods with SGA babies having significantly higher MPI of right ventricle on day 1 and day 2 but not on day 3. Left ventricular internal diameter index during diastole and systole (LVIDD index and LVIDS index), left atrium: aortic root ratio (LA:AO ratio) were significantly increased in SGA babies on all the occasions. Fractional shortening, ejection fraction, and area shortening were similar in two groups.

Conclusions: Myocardial performance index of left and right ventricle, which evaluates both systolic and diastolic function of ventricles, was significantly increased in SGA babies in comparison to AGA babies during the first 3 days of life except MPI of the right ventricle on day 3. Thus, SGA babies have compromised cardiac function through all phases of the cardiac cycle with the performance improving spontaneously over time.
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http://dx.doi.org/10.1080/14767058.2018.1429392DOI Listing
July 2019

Prevalence of group B Streptococcal colonization among pregnant women and neonates in a tertiary hospital in India.

J Turk Ger Gynecol Assoc 2017 Dec;18(4):181-184

Department of Obstetrics and Gynecology, Christian Medical College, Vellore, India.

Objective: To estimate the prevalence of group B Streptococcus (GBS) carriage among pregnant women attending the antenatal clinic, and the colonization rates among newborn born to colonized mothers.

Material And Methods: Women attending the antenatal clinic between 35-37 weeks were screened using rectal and lower vaginal swab. Swabs were initially plated on sheep blood agar and LIM broth. The LIM broth was subcultured after 24 hours onto blood agar and CHROMagar StrepB plates with all plates checked for growth at 24 and 48 hours. All babies born to mothers in the study had surface swabs taken to estimate the vertical transmission rate.

Results: Between September 2012 and March 2013, 305 consecutive mothers were screened. Of these, eight mothers were GBS positive in 5% blood agar (2.6%) and 23 mothers showed GBS positivity in enriched media (7.6%). Sixteen of 238 babies (6.7%) were colonized.

Conclusion: Though lower than rates from most countries, 7.6% of mothers attending an antenatal clinic in south India were colonized with GBS. Use of enrichment media markedly increased the detection rate. Approximately two-thirds of newborn born to colonized mothers were also colonized. There were no instances of invasive GBS disease, indirectly proving the efficacy of intrapartum prophylaxis in preventing neonatal GBS disease.
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http://dx.doi.org/10.4274/jtgga.2017.0032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5776156PMC
December 2017

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

J Trop Pediatr 2018 Aug;64(4):312-316

Neonatology Department, Christian Medical College, Vellore 632004, India.

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.
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http://dx.doi.org/10.1093/tropej/fmx068DOI Listing
August 2018

Whole genome shotgun sequencing of Indian strains of .

Genom Data 2017 Dec 2;14:63-65. Epub 2017 Oct 2.

Department of Clinical Microbiology, Christian Medical College, Vellore 632004, India.

Group B streptococcus is known as a leading cause of neonatal infections in developing countries. The present study describes the whole genome shotgun sequences of four Group B Streptococcus (GBS) isolates. Molecular data on clonality is lacking for GBS in India. The present genome report will add important information on the scarce genome data of GBS and will help in deriving comparative genome studies of GBS isolates at global level. This Whole Genome Shotgun project has been deposited at DDBJ/ENA/GenBank under the accession numbers NHPL00000000 - NHPO00000000.
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http://dx.doi.org/10.1016/j.gdata.2017.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5633162PMC
December 2017

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

J Trop Pediatr 2018 04;64(2):126-131

Department of Biostatistics, Christian Medical College and Hospital, Vellore, Tamil Nadu 632004, 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.
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http://dx.doi.org/10.1093/tropej/fmx038DOI Listing
April 2018

Draft Genome Sequence of an Extended-Spectrum-β-Lactamase-Positive Hypervirulent Klebsiella pneumoniae Strain with Novel Sequence Type 2318 Isolated from a Neonate.

Genome Announc 2016 Nov 10;4(6). Epub 2016 Nov 10.

Department of Clinical Microbiology, Christian Medical College, Vellore, Tamil Nadu, India

Antimicrobial resistance among hypervirulent Klebsiella pneumoniae is increasingly reported. Here, we report the draft genome sequence of a hypervirulent K. pneumoniae strain isolated from a neonate with sepsis belonging to novel sequence type 2318 (ST2318).
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http://dx.doi.org/10.1128/genomeA.01273-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5105110PMC
November 2016
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