Sugandha Arya

Comparison of Human Neonatal and Adult Blood Leukocyte Subset Composition Phenotypes

The human peripheral leukocyte subset composition depends on genotype variation and pre-natal and post-natal environmental influence diversity. We quantified this composition in adults and neonates, and compared the median values and dispersal ranges of various subsets in them. We confirmed higher frequencies of monocytes and regulatory T cells (Tregs), similar frequencies of neutrophils, and lower frequencies of CD8 T cells, NKT cells, B1 B cells and gamma-delta T cells in neonatal umbilical cord blood. Unlike previous reports, we found higher frequencies of eosinophils and B cells, higher CD4:CD8 ratios, lower frequencies of T cells and iNKT cells, and similar frequencies of CD4 T cells and NK cells in neonates. We characterized monocyte subsets and dendritic cell (DC) subsets in far greater detail than previously reported, using recently described surface markers and gating strategies and observed that neonates had lower frequencies of patrolling monocytes and lower myeloid dendritic cell (mDC):plasmacytoid DC (pDC) ratios. Our data contribute to South Asian reference values for these parameters. We found that dispersal ranges differ between different leukocyte subsets, suggesting differential determination of variation. Further, some subsets were more dispersed in adults than in neonates suggesting influences of postnatal sources of variation, while some show the opposite pattern suggesting influences of developmental process variation. Together, these data and analyses provide interesting biological possibilities for future exploration.

Changing Spectrum of Retinopathy of Prematurity (ROP) and Variations Among Siblings of Multiple Gestation

ObjectiveTo assess the changing spectrum of ROP, and to compare the siblings of multiple gestations with regard to incidence and severity of ROP.MethodsA prospective study was done among a total of 158 infants (including 19 twin pairs), selected for ROP screening as per American Academy of Pediatrics (AAP) criteria. Data collected was analysed to assess the changing ROP spectrum in comparison to year 2002 ROP screening data from the authors’ centre, and the variations among siblings of multiple gestation.ResultsOverall incidence of ROP was about 45.57% in 2009 as compared to 44.60% in 2002. 17 risk factors were found significantly associated with ROP on univariate analysis with low gestational age, low birth weight and multiple gestation (not analyzed in the 2002 data) confirmed as independent risk factors for ROP .The absolute number of subjects with severe ROP (>stage III) has decreased at the authors’ centre. Twins with ROP were sicker as compared to the other sibling.ConclusionsThough overall incidence of ROP has remained the same over the last decade at the authors’ centre, absolute number of severe forms of ROP has decreased. Multiple gestations may be taken as an independent risk factor for ROP causation. Sicker the twin infant is, the more are the chances that he/she will develop ROP.

Complementary feeding at 4 versus 6 months of age for preterm infants born at less than 34 weeks of gestation: a randomised, open-label, multicentre trial

Summary Background Evidence on the optimal time to initiation of complementary feeding in preterm infants is scarce. We examined the effect of initiation of complementary feeding at 4 months versus 6 months of corrected age on weight for age at 12 months corrected age in preterm infants less than 34 weeks of gestation. Methods In this open-label, randomised trial, we enrolled infants born at less than 34 weeks of gestation with no major malformation from three public health facilities in India. Eligible infants were tracked from birth and randomly assigned (1:1) at 4 months corrected age to receive complementary feeding at 4 months corrected age (4 month group), or continuation of milk feeding and initiation of complementary feeding at 6 months corrected age (6 month group), using computer generated randomisation schedule of variable block size, stratified by gestation (30 weeks or less, and 31–33 weeks). Iron supplementation was provided as standard. Participants and the implementation team could not be masked to group assignment, but outcome assessors were masked. Primary outcome was weight for age Z-score at 12 months corrected age (WAZ12) based on WHO Multicentre Growth Reference Study growth standards. Analyses were by intention to treat. The trial is registered with Clinical Trials Registry of India, number CTRI/2012/11/003149. Findings Between March 20, 2013, and April 24, 2015, 403 infants were randomly assigned: 206 to receive complementary feeding from 4 months and 197 to receive complementary feeding from 6 months. 22 infants in the 4 month group (four deaths, two withdrawals, 16 lost to follow-up) and eight infants in the 6 month group (two deaths, six lost to follow-up) were excluded from analysis of primary outcome. There was no difference in WAZ12 between two groups: −1·6 (SD 1·2) in the 4 month group versus −1·6 (SD 1·3) in the 6 month group (mean difference 0·005, 95% CI −0·24 to 0·25; p=0·965). There were more hospital admissions in the 4 month group compared with the 6 month group: 2·5 episodes per 100 infant-months in the 4 month group versus 1·4 episodes per 100 infant-months in the 6 month group (incidence rate ratio 1·8, 95% CI 1·0–3·1, p=0·03). 34 (18%) of 188 infants in the 4 month group required hospital admission, compared with 18 (9%) of 192 infants in the 6 month group. Interpretation Although there was no evidence of effect for the primary endpoint of WAZ12, the higher rate of hospital admission in the 4 month group suggests a recommendation to initiate complementary feeding at 6 months over 4 months of corrected age in infants less than 34 weeks of gestation. Funding Indian Council of Medical Research supported the study until Nov 14, 2015. Subsequently, Shuchita Guptas salary was supported for 2 months by an institute fellowship from All India Institute Of Medical Sciences, and a grant by Wellcome Trust thereafter.

Underweight Full-Term Indian Neonates Show Differences in Umbilical Cord Blood Leukocyte Phenotype: A Cross-Sectional Study

Background While infections are a major cause of neonatal mortality in India even in full-term neonates, this is an especial problem in the large proportion (~20%) of neonates born underweight (or small-for-gestational-age; SGA). One potential contributory factor for this susceptibility is the possibility that immune system maturation may be affected along with intrauterine growth retardation. Methods In order to examine the possibility that differences in immune status may underlie the susceptibility of SGA neonates to infections, we enumerated the frequencies and concentrations of 22 leukocyte subset populations as well as IgM and IgA levels in umbilical cord blood from full-term SGA neonates and compared them with values from normal-weight (or appropriate-for-gestational-age; AGA) full-term neonates. We eliminated most SGA-associated risk factors in the exclusion criteria so as to ensure that AGA-SGA differences, if any, would be more likely to be associated with the underweight status itself. Results An analysis of 502 such samples, including 50 from SGA neonates, showed that SGA neonates have significantly fewer plasmacytoid dendritic cells (pDCs), a higher myeloid DC (mDC) to pDC ratio, more natural killer (NK) cells, and higher IgM levels in cord blood in comparison with AGA neonates. Other differences were also observed such as tendencies to lower CD4:CD8 ratios and greater prominence of inflammatory monocytes, mDCs and neutrophils, but while some of them had substantial differences, they did not quite reach the standard level of statistical significance. Conclusions These differences in cellular lineages of the immune system possibly reflect stress responses in utero associated with growth restriction. Increased susceptibility to infections may thus be linked to complex immune system dysregulation rather than simply retarded immune system maturation.

Cardiac rhabdomyoma--a case report.

Cardiac tumors are rare in neonates, most are benign hamartomas (rhabdomyomas) of the muscle cells. Due of large size, they may cause homodynamic instability and even death in neonatal period. They are rarely diagnosed prenatally and are found in multiple forms. In ∼50% of the cases, rhabdomyoma is associated with tuberous sclerosis.

Alarming rates of antimicrobial resistance and fungal sepsis in outborn neonates in North India.

Background There is a paucity of data on the epidemiology of sepsis in outborn neonates being referred to level-3 units in low- and middle-income countries (LMIC). The objective of the present study was to evaluate the prevalence of sepsis and outcomes of outborn neonates with sepsis, and to characterize the pathogen profile and antimicrobial resistance (AMR) patterns of common isolates in them. Methods In this prospective observational cohort study (2011–2015), a dedicated research team enrolled all neonates admitted to an outborn level-3 neonatal unit and followed them until discharge/death. Sepsis work-up including blood culture(s) was performed upon suspicion of sepsis. All the isolates were identified and tested for antimicrobial susceptibility. Gram-negative pathogens resistant to any three of the five antibiotic classes (extended-spectrum cephalosporins, carbapenems, aminoglycosides, fluoroquinolones, and piperacillin-tazobactam) were labeled multi-drug resistant. Results Of the total of 2588 neonates enrolled, culture positive sepsis and total sepsis–i.e. culture positive and/or culture negative sepsis–was diagnosed in 13.1% (95% CI 11.8% to 14.5%) and 54.7% (95% CI 52.8% to 56.6%), respectively. The case fatality rates were 23.4% and 11.0% in culture-positive and total sepsis, respectively. Sepsis accounted for two-thirds of total neonatal deaths (153/235, 63.0%). Bacterial isolates caused about three-fourths (296/401; 73.8%) of the infections. The two common pathogens–Klebsiella pneumoniae (n = 50, 12.5%) and Acinetobacter baumannii (n = 46, 11.5%)–showed high degree of multi-drug resistance (78.0% and 91.3%, respectively) and carbapenem resistance (84.0% and 91.3%, respectively). About a quarter of infections were caused by Candida spp. (n = 91; 22.7%); almost three-fourths (73.7%) of these infections occurred in neonates born at or after 32 weeks’ gestation and about two-thirds (62.1%) in those weighing 1500 g or more at birth. Conclusions In this large outborn cohort, we report high burden of sepsis, high prevalence of systemic fungal infections, and alarming rates of antimicrobial resistance among bacterial pathogens.

Situs inversus and dextrocardia in epigastric heteropagus twins: An uncommon entity explored!!

Epigastric heteropagus twin is a rare form of parasitic twins. Though heart defects may be found in 28% of these babies, an association with situs inversus and dextrocardia is extremely uncommon. We present a rare case of epigastric heteropagus twinning with dextrocardia and situs inversus.

Metabolic bone disease in low birth weight babies between 1500 and 2000 g on exclusive breast feeding

Background: Metabolic bone disease of prematurity due to reduced bone mineralization is mostly described in infants of less than 1500 g. Although various guidelines recommend calcium and phosphate supplementation for low birth weight (LBW) newborns less than 1500 g and on exclusive breast feeding but there are no guidelines for those weighing above 1500 g and on exclusive breast feeding. Moreover, there is insufficient data on incidence of rickets and serum biochemical status in these babies of birth weight more than 1500g and on unsupplemented breast feeding and among term growth retarded babies. Objectives: To determine the incidence of rickets and changes in biochemical profile including serum calcium, phosphate, and alkaline phosphatase in preterm appropriate for gestational age (PTAGA) and term small for date (TSFD) babies with birth weight between 1500 and 2000 g and on unsupplemented breast feeding. Materials and Methods: It is an observational cohort study done at a tertiary care centre in northern India over a period of one year, including LBW babies between 1500 and 2000 g and on unsupplemented breast feeds. In group I, 116 PTAGA babies with birth weight 1500-2000g and on unsupplemented breast feeds were enrolled and 100 PTAGA babies completed follow up till 6 months. In group II 124 TSFD babies with birth weight 1500-2000 g and on unsupplemented breast feeds were enrolled and 100 TSFD babies completed follow up till 6 months. Biochemical parameters were done at baseline (before discharge) and were followed-up for a period of 6 months. Radiological assessment was done if clinical features of rickets appeared or serum biochemistry was suggestive of rickets. Results: Both groups, of babies, developed progressive decrease in serum calcium and phosphate levels, which was statistically significant as shown by time trend. Serum alkaline phosphatase showed significant increase from baseline in both the groups. Fourteen out of 200 (7%) babies developed radiological rickets at end of 3 months, which increased to 34/200 (17%) at end of 6 months. Serum alkaline phosphatase showed most consistent correlation with occurrence of rickets. Conclusion: LBW babies 1500-2000 g and on exclusive breast feeding are at significant risk of developing metabolic bone disease including rickets and need extra supplementation with calcium and phosphate besides Vitamin D.

Evaluation of platelet indices as additional diagnostic tool for neonatal sepsis

Introduction: Search for newer markers to enhance sensitivity and specificity of the existing sepsis screen and attempts toward this has been in place for a long time. Platelet indices are one such marker. Materials and Methods: Babies with signs and symptoms or born with risk factors for sepsis were enrolled. Those with positive culture or with clinical sepsis as per Centre for Disease Control definition were classified under the group “cases” (n = 188), whereas all neonates initially suspected to have sepsis but who had a negative blood culture and no clinical sepsis as per definition were classified under the group “control” (n = 188). Blood culture, sepsis screen, and platelet indices [platelet count, mean platelet volume (MPV), platelet distribution width (PDW)] were performed on all these babies. Results: The platelet count was decreased, whereas PDW and MPV were increased in septic babies (P < 0.0001). Thrombocytopenia and increased MPV were frequently observed in babies with late-onset sepsis (P = 0.012). Thrombocytopenia was the most predictive marker for culture positivity in septic babies (83.08%), and when all the platelet indices (MPV + PDW + PC) or (MPV + PDW) were combined (46.34%) it was found to be highly specific marker for prediction of sepsis. Platelet indices had a better sensitivity (83.08%) than sepsis screen (60%). When sepsis screen and platelet indices were combined, it increased the specificity (62.6%). The receiver operating characteristics curve suggested that MPV is a good marker having highest area under curve. Conclusion: Although data on platelet indices are still nascent, platelet indices may be used as a sensitive marker and combined with sepsis screen to exclude a non-septic case.

Anencephaly with placental adhesion

Abstract Anencephaly is a serious neural tube defect, in which the brain and cranial vault are grossly malformed. It occurs due to failure of cranial neurulation during embryonic development of cranial tissues. Anomalous placental attachment on an anencephalic head of a newborn is extremely rare. We report two cases of anencephaly in which the placenta were anomalously attached on an anencephalic head.