Anil Narang

Retinopathy of prematurity in Asian Indian babies weighing greater than 1250 grams at birth: Ten year data from a tertiary care center in a developing country.

Background: Retinopathy of prematurity (ROP) is an important cause of childhood blindness in developing countries. Aim: To report the spectrum of ROP and associated risk factors in babies weighing > 1250 g at birth in a developing country. Setting and Design: Institutional, retrospective, non-randomized, observational clinical case series. Materials and Methods: Retrospective analysis (10 years) of 275 eyes (138 babies) with ROP. Statistical Analysis: Qualitative data with the Chi-square test. Quantitative data using the unpaired t test or the ANOVA and further tested using multivariate logistic regression. Results: The mean birth weight was 1533.9 g (range 1251 to 2750 g) and the mean period of gestation was 30.9 weeks (range 26 to 35). One hundred and twenty-four of 275 eyes (45.1%) had threshold or worse ROP. Risk factors for threshold or worse disease were, ′outborn babies′ ( P < 0.001), respiratory distress syndrome ( P = 0.007) and exchange transfusion ( P = 0.003). The sensitivity of the American and British screening guidelines to pick up threshold or worse ROP in our study group was 82.4% and 77.4% respectively. Conclusions: Severe ROP is often encountered in babies weighing greater than 1250 g at birth in developing countries. Western screening guidelines may require modifications before application in developing countries.

Etiology of Bacteremia in Young Infants in Six Countries

Background: Neonatal illness is a leading cause of death worldwide; sepsis is one of the main contributors. The etiologies of community-acquired neonatal bacteremia in developing countries have not been well characterized. Methods: Infants <2 months of age brought with illness to selected health facilities in Bangladesh, Bolivia, Ghana, India, Pakistan and South Africa were evaluated, and blood cultures taken if they were considered ill enough to be admitted to hospital. Organisms were isolated using standard culture techniques. Results: Eight thousand eight hundred and eighty-nine infants were recruited, including 3177 0–6 days of age and 5712 7–59 days of age; 10.7% (947/8889) had a blood culture performed. Of those requiring hospital management, 782 (54%) had blood cultures performed. Probable or definite pathogens were identified in 10.6% including 10.4% of newborns 0–6 days of age (44/424) and 10.9% of infants 7–59 days of age (39/358). Staphylococcus aureus was the most commonly isolated species (36/83, 43.4%) followed by various species of Gram-negative bacilli (39/83, 46.9%; Acinetobacter spp., Escherichia coli and Klebsiella spp. were the most common organisms). Resistance to second and third generation cephalosporins was present in more than half of isolates and 44% of the Gram-negative isolates were gentamicin-resistant. Mortality rates were similar in hospitalized infants with positive (5/71, 7.0%) and negative blood cultures (42/557, 7.5%). Conclusions: This large study of young infants aged 0–59 days demonstrated a broad array of Gram-positive and Gram-negative pathogens responsible for community-acquired bacteremia and substantial levels of antimicrobial resistance. The role of S. aureus as a pathogen is unclear and merits further investigation.

Epidemiology of Systemic Candidiasis in a Tertiary Care Neonatal Unit

143 neonates were diagnosed to have acquired systemic candidiasis out of a total 4530 admissions (3.2 per cent) to the neonatal intensive care unit (NICU) during a period of 6 1/2 years from January 1990 to June 1996. Mean age at onset was 10.4 days, mean birth weight 1454 g, and mean gestation was 31.7 weeks. Ninety-four per cent were premature, 95 per cent low birth weight (LBW), and all had undergone peripheral vein catheterization and had received broad spectrum antibiotics, except one, prior to the diagnosis. Fifty-eight per cent were ventilated and 15 per cent received parenteral nutrition. Persistent/recurrent pneumonia, apnoea, lethargy, high gastric aspirates, and abdominal distension were the common clinical manifestations. Candida tropicalis, C. albicans, and C. guillermondii were the most common isolates. Blood and urine were the predominant sites for isolation of Candida. Fluconazole was the most used antifungal agent, with 24 per cent resistance against it. Fifty per cent of babies died due to all causes. Of all the deaths, two-thirds were Candida related. Candida-attributable deaths occurred in 24 cases (17 per cent).

UGT1A1 Gene Polymorphisms in North Indian Neonates Presenting with Unconjugated Hyperbilirubinemia

Genetic factors are implicated in pathogenesis of neonatal hyperbilirubinemia. In this nested case-control study, we determined 1) frequency of thymine-adenine (TA)n promoter polymorphism and Gly71Arg mutation in uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1) gene in neonates ≥35-wk gestation presenting with bilirubin levels ≥18 mg/dL and controls, 2) interaction among (TA)n promoter polymorphism, glucose-6-phosphate dehydrogenase (G6PD) gene mutations, and peak bilirubin. The number of TA repeats was assessed by PCR-single-strand conformation polymorphism (SSCP) analysis and Gly71Arg mutation by PCR-RFLP. Fifty samples of both mutations were verified with DNA sequencing. One hundred twenty-seven neonates were enrolled (77 hyperbilirubinemics, 50 controls). The incidence of (TA)n polymorphism was higher in babies with hyperbilirubinemia [89.6% vs. 50%, OR 8.63 (95% CI, 3.2-24.1)]. Gly71Arg mutation was not found either in hyperbilirubinemics or controls. A novel polymorphism (Ala72Pro) at codon position 72 of exon 1 was detected in all 50 samples (21 hyperbilirubinemics, 29 controls), which were sequenced. Presence of variant (TA)n promoter (adjusted OR, 10.6; 95% CI, 3.3-34.2), G6PD deficiency (adjusted OR, 20.6; 95% CI, 3.6-117.3), and history of jaundice in sibling requiring phototherapy (adjusted OR, 12.6; 95% CI, 1.1-141.6) were independent risk factors for bilirubin levels ≥18 mg/dL.

A randomized controlled trial of phenobarbital in neonates with hypoxic ischemic encephalopathy.

Background. Phenobarbital is one of the oldest, cheapest and most easily available cerebro-protective drugs for the hypoxic brain. It has multiple actions that could be of benefit to the asphyxiated brain. However, its potential has not been fully explored. Objective. To study the effect of phenobarbital given within six hours of life to term and near-term asphyxiated neonates, on mortality, neurological abnormality at discharge and seizures. Methods. This was a randomized controlled trial set in a tertiary care referral perinatal centre. Asphyxiated neonates (gestational age ⩾34 weeks) manifesting with hypoxic ischemic encephalopathy (HIE) in the first six hours of life were randomized to receive either injection of phenobarbital 20 mg/kg IV or to the control group. The primary outcome was death or abnormal neurological examination at discharge while seizures, need for ventilation and multi-organ dysfunction were secondary outcomes. Results. Twenty-five babies received phenobarbital and 20 were in the control group. The mortality (20% vs. 15%) and abnormal neurological outcome at discharge (30% vs. 53%, p = 0.15) were statistically not different between the two groups. In the phenobarbital group, 8% of neonates developed seizures while 40% of babies in the control group developed seizures (p = 0.01, relative risk (RR) = 0.20 (0.05–0.84)). Phenobarbital was well tolerated and did not increase the need for respiratory support. Conclusions. Phenobarbital in the dose of 20 mg/kg IV given within six hours of life to term and near-term neonates with HIE, significantly decreased the incidence of neonatal seizures and was well tolerated. However, it did not alter the mortality and neurologic outcome at discharge.

Predictive Clinical Scores for Diagnosis of Late Onset Neonatal Septicemia

There is a paucity of data regarding predictive values and likelihood ratios of clinical signs for the diagnosis of late onset neonatal septicemia. This study aimed to determine these parameters in a prospective fashion, deriving a score by combining the most useful signs and determining the diagnostic utility of the score. All neonates admitted to a neonatal unit over a 1-year period were monitored for the occurrence of 16 pre-defined clinical signs. Symptomatic episodes (105 episodes in 80 neonates) were investigated for sepsis, and diagnosed as definite sepsis (n = 30), most probable sepsis (n = 17), and no sepsis (n = 58). Seven clinical signs (grunting, abdominal distension, increased pre-feed aspirates, tachycardia, hyperthermia, chest retractions, and lethargy) had positive likelihood ratios (PLR) greater than 1, and were combined to make a composite score. When a weighted clinical score (WCS) was used to diagnose definite sepsis, a cut-off score of 2 gave the best positive predictive value (PPV) and PLR (52 per cent and 2.65, respectively), and a cut-off score of 1 gave the best negative predictive value (NPV) and negative likelihood ratio (NLR) (85 per cent and 0.44, respectively). A cut-off score of 2 had a PPV of 65 per cent for definite and/or probable sepsis. In conclusion, physicians who attempt to make a diagnosis of neonatal sepsis on purely clinical grounds can use a seven-item weighted clinical score.

Diagnosis of neonatal sepsis using universal primer polymerase chain reaction before and after starting antibiotic drug therapy.

OBJECTIVE To study universal primer 16S rRNA gene polymerase chain reaction (PCR) for diagnosis of blood culture-positive neonatal sepsis before and after starting antibiotic drug therapy. DESIGN Prospective study of diagnostic tests. SETTING Level III neonatal intensive care unit. Patients Neonates with a fresh episode of clinically suspected sepsis were enrolled; those with major malformations, life expectancy less than 12 hours, or contaminated blood cultures were excluded. INTERVENTIONS Before starting antibiotic drug therapy, PCR (0 hour), blood culture, and sepsis screening (complete blood cell counts, micro-erythrocyte sedimentation rate, and C-reactive protein level) were performed. The PCR was repeated 12, 24, and 48 hours after starting antibiotic drug therapy. MAIN OUTCOME MEASURES The primary outcomes were the sensitivity and specificity of 0-hour PCR for diagnosing blood culture-positive sepsis, and the secondary outcome was the proportion of 0-hour PCR-positive patients who remained positive after antibiotic drug therapy. RESULTS Of 306 patients evaluated, 242 were included (mean [SD] gestation, 32.2 [3.1] weeks; and mean [SD] birth weight, 1529.2 [597.2] g). Blood culture was positive in 52 patients and 0-hour PCR in 57. The sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios of PCR were 96.2%, 96.3%, 87.7%, 98.8%, 26.1, and 0.04, respectively. Two patients were blood culture positive but 0-hour PCR negative, whereas 7 were 0-hour PCR positive but blood culture negative. Of the 0-hour PCR-positive patients, 7 remained positive at 12 hours and none at 24 and 48 hours after starting antibiotic drug therapy. In 0-hour PCR-positive patients, no predictors of positive 12-hour PCR were identified. CONCLUSION Universal primer PCR can accurately diagnose neonatal sepsis before but not after antibiotic drugs are given.

Enterobacter sakazakii in infants: Novel phenomenon in India

E. sakazakii has been implicated in necrotizing enterocolitis, bloodstream and central nervous system infections, with mortality rates of 40-80%. Two cases of E. sakazakii infections; one preterm very low birth weight neonate with meningitis and a two month infant with bacteraemia, are described for the first time in India. The first baby succumbed to the infection while the other responded to appropriate therapy. Powdered infant milk formulae have been implicated in causing neonatal infections and the first baby was on formula feed with classic signs of sepsis and meningitis. The second infant was on breast feed and probably developed nosocomial E. sakazakii bacteraemia.

Bone and joint infection in neonates

A retrospective study was done to review the clinical experience of septic arthritis and osteomyelitis in the newborns in our centre. Case records of all the neonates born from January 1989 to August 1994 and those admitted to outborn nursery from 1985 to 1993 were reviewed. Diagnosis of septic arthritis/osteomyelitis was made in the presence of relevant clinical signs and supported by positive culture from blood or joint fluid and abnormal X-ray or ultrasound findings. The incidence of septic arthritis and osteomyelitis among inborn babies was 1 in 1500. There were 25 neonates with mean gestational age 34.5 (range 27–40) weeks and mean birth weight 2269 (range 990–4750) gms.Limitation of movement (64%) and local swelling (60%) were commonest presentations. A total of 33 joints were involved in 25 babies. Eight babies (32%) had multiple joint involvement. Hip and knee were the most commonly involved joints (48% each). In 19 babies (76%) joint involvement occurred in association with a generalized septicemic illness while 6 babies (24%) had localised signs and symptoms. Joint aspirate was positive for gram stain or culture in 12 (48%) and 10 babies (40%) had positive blood culture.Klebsiella pneumoniae andStaphylococcus aureus were commonest isolates. Radiological changes were seen in 13 (52%) babies. All were treated with appropriate antibiotics and open surgical drainage was done in 5 (20%) cases.Bone and joint infections are important complications in sick septicemic neonates and need early diagnosis, appropriate management with antibiotics, surgical drainage in selected cases to prevent long term morbidity.

Prediction of feed intolerance and necrotizing enterocolitis in neonates with absent end diastolic flow in umbilical artery and the correlation of feed intolerance with postnatal superior mesenteric artery flow.

Objectives. To evaluate the role of postnatal superior mesenteric artery (SMA) flow in predicting feed intolerance and NEC in the babies who had AEDF in comparison with gestation matched SGA and AGA with normal flow. Design. This was a prospective cohort study conducted in 62 eligible babies admitted in NICU. Babies were enrolled in 3 groups. Group 1 (n = 23) was SGA and AEDF, group 2 (n = 20) was SGA and group 3 (n = 19) was AGA and both with normal UA flow. In all babies baseline SMA flow was measured before test feed (0.5 ml) and repeated every 15 minutes for 1 hour after the feed. Results. Feed intolerance was seen in 69.5% of babies in group1 (p = <0.001) as compared to 20% and 17.5% in group 2 and 3. Four (17.3%) babies developed NEC in group1 (p = 0.02) but none in other 2 groups. Baseline peak systolic velocity (PSV) and time average mean velocity (TAMV) at 60 min post feed were significantly (p = 0.01 and 0.028 respectively) lower in group1 than group3. TAMV and PSV at 60 min post feed were significantly lower (p = 0.028 and 0.03) in babies with feed intolerance as compared to no feed intolerance group. Absent end diastolic flow and hypoglycemia were independent risk factors for feed intolerance. Conclusion. SGA babies with AEDF had higher incidence of feed intolerance and NEC. Serial SMA flow studies specially the 60 min post feed study may help in differentiating which babies are likely to develop feed intolerance.