Systemic humicolus cryptococcosis.

We report a 71/2-year-boy with disseminated systemic cryptococcosis. Although other species have been incriminated, this appears to be the first report of Cryptococcus humicolus. The child was HIV negative. He was treated with amphotericin B and fluconazole with intensive supportive care. The child responded after 6 weeks and is now on maintenance fluconazole therapy.

Insulin resistance syndrome in 8-year-old Indian children: small at birth, big at 8 years, or both?

We have studied 477 8-year-old Indian children to define the relationship between birth weight and cardiovascular risk factors, including insulin resistance syndrome (IRS) variables and plasma total and LDL cholesterol concentrations. All risk factors were strongly related to current weight. After adjustment for current weight, age, and sex, lower birth weight was associated with higher systolic blood pressure (P = 0.008), fasting plasma insulin and 32-33 split proinsulin concentrations (P = 0.08 and 0.02), glucose and insulin concentrations 30 min postglucose (P = 0.06 and 0.04), subscapular/triceps skinfold ratio (P = 0.003), and plasma total and LDL cholesterol concentrations (P = 0.002 and 0.001). Lower birth weight was associated with increased calculated insulin resistance (homeostasis model assessment [HOMA], P = 0.03), but was not related to the HOMA index of beta-cell function. The highest levels of IRS variables and total and LDL cholesterol were in children of low birth weight but high fat mass at 8 years. Taller height at 8 years predicted higher fasting plasma insulin concentrations, insulin resistance, and plasma total and LDL cholesterol concentrations. The most insulin-resistant children were those who had short parents but had themselves grown tall. Although the implications of our findings in relation to height are unclear, interventions to improve fetal growth and to control obesity in childhood are likely to be important factors in the prevention of cardiovascular disease and IRS in India.

Pune low birth weight study--a six year follow up.

OBJECTIVE: To evaluate the intelligence, visuo-motor perception, emotional problems and preschool skills in low birth weight (LBW) infants and the impact of social and environmental factors on their development. DESIGN: A prospective cohort study. SETTING: Infants discharged from a Neonatal Special Care Unit of a referral hospital with birth weight less than 2000 g followed up in the High Risk Clinic. METHODS: Low birth weight infants were assessed by Stanford Binet Scales of intelligence, Bender Gestalt Test for visuo-motor perception, Human Figure Drawing for emotional indicators and occupational therapy assessment. A detailed evaluation of their environment and socio-economic status was done. Hearing and ophthalmic assessment was also done and the school progress report was scrutinized. RESULTS: Two hundred and one LBW and seventy one control children were assessed. The mean IQ of LBW children was within normal limits (94.3), though significantly lower than controls (101.3). Preterm SGA children had the lowest mean IQ. Visuo-motor perception and preschool skills and language development was poorer in LBW children. There was no difference in the emotional indicators. Thirteen per cent of LBW children had borderline IQ, as compared to 5.6% in controls (p<0.05). Mother's education and spaciousness of the house had a positive impact and chronic medical problems had a negative impact on the IQ. CONCLUSIONS: The mean IQ of LBW children was within normal limits. The incidence of children with borderline intelligence (IQ 70-85) was significantly higher than controls. Mother's education had a positive impact on the intelligence of the children. A longer follow up is necessary to identify "slow learners".

Fulminant hepatic failure: etiology, viral markers and outcome.

OBJECTIVE: To investigate the etiology and outcome of fulminant hepatic failure (FHF) in children. SETTING: Hospital based descriptive. METHODS: 36 children (22 males and 14 females) presenting with FHF over a period of one year were investigated. The ages ranged from 1.5 to 9 years. FHF was defined as occurrence of encephalopathy within eight weeks of onset of jaundice with no evidence of pre-existing liver disease. Detailed history, clinical examination, routine biochemical parameters and relevant diagnostic tests were carried out. Viral markers studied were anti HAV-IgM, HBsAg, anti HBc-IgM, anti-HCV and anti HEV-IgM. RESULTS: A viral etiology could be established in 22 children (61.1%). Hepatitis A (n = 12), Hepatitis B (n = 3), Hepatitis A and B (n = 2), and Hepatitis A and E (n = 4). Two children had enteric fever (1 with associated HEV), 2 children had Wilson's disease, 1 child had Indian Childhood Cirrhosis (ICC) and 2 children had drug induced hepatitis. Etiological diagnosis was not possible in 8 children (22%). Fourteen children (39%) died. Poor outcome was associated with spontaneous bleeding, raised prothrombin time, lower transaminases and higher bilirubin on admission. CONCLUSION: Viral hepatitis is the commonest cause of FHF in children. HAV alone or in combination is responsible for upto 50% of all FHF in children. Chronic liver disease can also present as FHF. Etiological diagnosis is not possible to upto one-fourth of all cases.

Neurologic sequelae in high risk infants--a three year follow up.

OBJECTIVE: To determine the neurologic sequelae in high risk infants. DESIGN: A three year longitudinal follow up. SETTING: Inborn and outborn infants discharged from the Neonatal Special Care Unit (NSCU) of a referral hospital. METHODS: High risk infants were identified for follow up using predetermined risk criteria. A detailed neurodevelopmental examination was done 3 monthly in the first year and 6 monthly subsequently. The Amiel-Tison Method, Bayley Scales of Infant Development and Raval's Scale for social maturity were used. EEG was done in children with seizures. Hearing and ophthalmic assessments were done at 6 months. RESULTS: Three hundred and thirty six high risk infants and 70 normal control infants came for regular follow up. Out of these, 16 (4.8%) had cerebral palsy and 11 had associated mental retardation. Six other children had mental retardation without motor problems. None of the children in the control group had any neurological problems. Sensorineural hearing loss was present in 5 (1.5%) children while 1 subject had corfical blindness. Three children with cerebral palsy had infantile myoclonus, nine had generalized seizures and one child had a focal seizure. The incidence of seizure disorders was 3.9%. CONCLUSIONS: The incidence of major handicap in our study was low. Many of the risk factors which caused adverse outcome, could have been prevented by good antenatal and perinatal care.

Long term survival in Indian childhood cirrhosis treated with D-penicillamine.

Indian childhood cirrhosis (ICC) is an almost uniformly fatal disease whose outcome may be modified with penicillamine if given at a sufficiently early stage. Twenty nine children with ICC seen in Pune, India, in 1980-7, who had survived at least five years from onset of penicillamine treatment, were reviewed aged 6.3 to 13 years. They were assessed clinically, biochemically, histologically, and by duplex Doppler ultrasound examination. None had symptoms suggestive of liver disease. There were no toxic effects of penicillamine other than asymptomatic proteinuria. Hepatosplenomegaly reduced significantly and liver function tests returned to normal in all. In four children, significant hepatosplenomegaly was associated with an abnormal duplex Doppler hepatic vein flow pattern and micronodular cirrhosis on biopsy. Clinical findings, growth and development, and ultrasound examination were normal in the remainder. Review of serial liver biopsy specimens showed a sequence of recovery from ICC through inactive micronodular cirrhosis to virtually normal histological appearances. The four children who still have micronodular cirrhosis beyond four years from onset remain on penicillamine treatment. In the others penicillamine was stopped after 1-7 (mean 3.5) years without relapse, strong evidence that ICC is not due to an inborn error of copper metabolism.

Size at birth and plasma insulin-like growth factor-1 concentrations.

OBJECTIVE: To test the hypothesis that reduced fetal growth leads to altered plasma insulin-like growth factor-1 (IGF-1) concentrations in childhood. DESIGN: A follow up study of 4 year old children whose birth weights were recorded, and of 7 year old children whose weight, length, head circumference, and placental weight were measured at birth. SETTING: Pune, India, and Salisbury, England. SUBJECTS: 200 children born during October 1987 to April 1989 in the King Edward Memorial Hospital, Pune, weighing over 2.0 kg at birth and not requiring special care, and 244 children born during July 1984 to February 1985 in the Salisbury Health District and still living there. MAIN OUTCOME MEASURE: Plasma IGF-1 concentrations. RESULTS: In both groups of children, and consistent with findings in other studies, plasma IGF-1 concentrations were higher in taller and heavier children, and higher in girls than boys. Allowing for sex and current size, concentrations were inversely related to birth weight (Pune p = 0.002; Salisbury p = 0.003). Thus at any level of weight or height, children of lower birth weight had higher IGF-1 concentrations. The highest concentrations were in children who were below average birth weight and above average weight or height when studied. Systolic blood pressures were higher in children with higher IGF-1 concentrations (Pune p = 0.01; Salisbury p = 0.04). CONCLUSIONS: Children of lower birth weight develop higher circulating concentrations of IGF-1 than expected for their height and weight. This is consistent with the hypothesis that under-nutrition in utero leads to reprogramming of the IGF-1 axis. The increase of plasma IGF-1 concentrations in low birthweight children may also be linked to postnatal catch-up growth. High IGF-1 concentrations may be one of the mechanisms linking reduced fetal growth and high blood pressure in later life.

Ultrasonography of the brain in preterm infants and its correlation with neurodevelopmental outcome.

Two hundred and eighteen preterm neonates had ultrasonography (USG) brain done on third, and/or seventh and fourteenth day of life. Fifty eight (26.3%) had intraventricular/ periventricular hemorrhage, 3 had parenchymal lesions. 46 had Grade I hemorrhage, 9 had Grade II, 2 had Grade III and 1 had Grade IV hemorrhage. Grade III and IV hemorrhages occurred in neonates below 34 weeks gestation. There was an inverse relationship between gestation age and hemorrhage (p = 0.0001). A comparison of incidence of hemorrhage between preterms who were appropriate for gestational age was not significant. Out of the 63 neonates who had serial USGs on the third and seventh day of life, 15 of the 16 bleeds (94%) were detected on the third day itself, indicating it to be a opportune time for doing an USG. USG at term (40 weeks postconceptual age) was done in 99 infants to see if it could correctly predict the neurodevelopmental outcome using the Bayley Scales of Infant Development. Out of these 99 infants, 72 came for the developmental assessment at one year. One neonate who had periventricular leucomalacia with cystic changes on USG at term, was grossly abnormal with cerebral palsy and mental retardation. Six infants showed delayed development with a mean mental development quotient of 79.1 +/- 1.72 at 2 years. The specificity of USG at term for predicting outcome was 89.2% and negative predictive outcome was 90%, indicating that a normal USG at term predicted a good neurodevelopmental outcome.

Fetal growth and glucose and insulin metabolism in four-year-old Indian children.

Studies in Britain have shown that adults who had a low birthweight have high plasma glucose concentrations 30 and 120 min after an oral glucose load, and an increased risk of Type 2 diabetes and impaired glucose tolerance. Both Type 2 diabetes and low birthweight are common in India. To determine whether low birthweight is associated with reduced glucose tolerance in Indian children, glucose tolerance tests were carried out on 379 4-year-old children, whose birthweights were recorded, in Pune, India. Among 201 children who had been looked after on the routine postnatal wards at birth, those with lower birthweights had higher plasma glucose and insulin concentrations 30 min after an oral glucose load, independently of their current size (p = 0.01 and 0.04, respectively). Mean glucose and insulin concentrations were 8.1 mmol l-1 and 321 pmol l-1 in children whose birthweight had been 2.4 kg or less, compared with 7.5 mmol l-1 and 289 pmol l-1 in those who weighted more than 3.0 kg. Among 178 children who had been looked after in the Special Care Baby Unit, those with lower birthweights also had higher plasma insulin concentrations at 30 min but there were no trends with plasma glucose. Our findings suggest that Indian children with reduced intra-uterine growth have reduced glucose homeostasis after a glucose challenge. This is consistent with the hypothesis that Type 2 diabetes mellitus in India may be programmed in fetal life.

Parenteral nutrition (PN) in the management of very low birth weight (VLBW) babies--a randomized controlled trial.

Eighty five very low birth weight (VLBW) babies with birthweight less than 1250 g were randomly assigned such that 43 received parenteral nutrition (PN) with amino acid based glucose electrolyte solution (Vamin) and lipid emulsion (Intralipid) in the first 16 days of life. The other 42 (control group) received conventional intravenous dextrose with or without electrolytes plus enteral milk regimen. Baseline clinical parameters and neonatal problems encountered in the two groups were similar. There was no significant difference in the mortality rate in the two groups (48.9% in PN group and 42.9% in control group: X2 = 0.3, p > 0.05). The commonest cause of mortality in both the groups was septicemia (16.3% and 26.1% in PN and control groups, respectively). Local complications, sepsis and fluid electrolyte disturbances were similar in the two groups. Azotemia (25.6%), hyperlipidemia (9.3%), metabolic acidosis (9.3%) and prolonged cholestasis (14%) were commoner in the PN group but were reversible with early recognition. Time taken to regain birthweight was also similar in the two groups (X2 = 14.2 and 15.2 days for PN and control groups, respectively). Thus, PN failed to improve the survival or early weight gain in the routine management of the VLBW babies in our unit.

Reversal of Indian childhood cirrhosis by D-penicillamine therapy.

Serial liver biopsy changes have been reviewed in 30 patients with Indian childhood cirrhosis (ICC) who were randomly allocated to receive treatment with penicillamine in a dose of 20 mg/kg/day, 10 of whom also received prednisolone, and five receiving placebo. The latter died within 185 (mean, 149) days of starting treatment. Nine receiving penicillamine died within 540 (mean, 338) days, but the remainder are well 5.1-9.3 years after commencing treatment. Initial biopsies showed severe hepatocellular injury, pericellular fibrosis, inflammatory infiltration, and orcein-staining granules. Second biopsies taken within 6 months of starting penicillamine usually showed persistence of inflammation and an increase in nodularity with thick and thin active septae. Subsequently the appearances were of an inactive micronodular cirrhosis, with reduction in septal inflammatory infiltrate, hepatocellular injury, and intensity of orcein staining. This further improved to a stage of incomplete fibrous septae. The last liver biopsies at 6-60 months (in 21 survivors) showed almost normal histology in four, incomplete fibrous septae in five, and inactive micronodular cirrhosis with thin septae in 12. Mean liver copper concentrations decreased from 1,407 (SEM, 121) micrograms/g at presentation to 925 (183), 317 (100), and 127 (35) at 6, 6-18, and > 18 months after starting treatment. By contrast, a second biopsy taken in the 6 months after diagnosis in placebo-treated children showed persistence of ICC with increase in inflammation, fibrosis, and orcein staining.

Catch up growth and its determinants in low birth weight babies: a study using Z scores.

Two hundred and forty seven low birthweight (LBW) survivors of our Neonatal Intensive Care Unit and 164 normal birthweight controls were followed up longitudinally from birth to 4 years and their growth trends (weight, height, head circumference) were expressed as mean Z scores in 500 g birthweight categories. Whereas LBW's demonstrated rapid growth in the first 6 months of life, followed by generally parallel trends with some tendency to rise, controls showed distinct growth faltering especially after one year. Only 30.8% of LBWs (and 49% of controls) were within the designated catch up levels for weight by age 4 years. The corresponding number for catch up of height and head circumference in LBW's was 22.8% and 26.5%, respectively. On multiple regression analysis, the most important determinants of catch up (at 4 years) in LBW's were weight at 1 year (beta = 0.51), height at 1 year (beta = 0.31) and mother's weight (beta = 0.04). Thus, Z scores enabled the demonstration of changing growth trends, simultaneous comparisons with local controls and international standards and comparison within indices. Growth charts incorporating Z score should be made available in a simplified manner for use in the community.

Vegetable oil fortified feeds in the nutrition of very low birthweight babies.

Two kinds of oils (i) Polyunsaturated fatty acids (PUFA) rich Safflower oil, and (ii) Medium chain triglyceride (MCT) rich Coconut oil were added to the feeds of 46 very low birthweight (VLBW) babies to see if such a supplementation is capable of enhancing their weight gain. Twenty two well matched babies who received no fortification served as controls. The oil fortification raised the energy density of the feeds from approximately 67 kcal/dl to 79 kcal/dl. Feed volumes were restricted to a maximum of 200 ml/kg/day. The mean weight gain was highest and significantly higher than the controls in the Coconut oil group (19.47 +/- 8.67 g/day or 13.91 g/day). Increase in the triceps skinfold thickness and serum triglycerides were also correspondingly higher in this group. The lead in the weight gain in this group continued in the follow up period (corrected age 3 months). As against this, higher weight gain in Safflower oil group (13.26 +/- 6.58 g/day) as compared to the controls (11.59 +/- 5.33 g/day), failed to reach statistically significant proportions, probably because of increased statistically significant proportions, probably because of increased steatorrhea (stool fat 4+ in 50% of the samples tested). The differences in the two oil groups are presumably because of better absorption of MCT rich coconut oil. However, individual variations in weight gain amongst the babies were wide so that some control babies had higher growth rates than oil fortified ones. The technique of oil fortification is fraught with dangers of intolerance, contamination and aspiration. Long term effects of such supplementation are largely unknown.(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: During a period of 12 months, polyunsaturated fatty acids (PUFA) rich safflower oil and medium chain triglyceride (MCI) rich coconut oil were added to the feeds of 46 very low birth weight (VLBW) babies (birth weight of 1250-1500 g) to see if such a supplementation could augment their weight gain. In the safflower oil fortification group, 22 babies completed the study, and in the coconut oil fortification group, 24 did. 22 babies who received no fortification served as controls. The oil fortification raised the energy density of the feeds from approximately 67 kcal/dl to 79 kcal.dl. Feed volumes were restricted to a maximum of 200 ml/kg/day. 3 babies of the safflower oil group and 2 each of the 2 other groups developed loose motions, but they all survived and completed the study. The diarrhea in the safflower oil group was related to addition of oil exceeding 0.5 ml and responded to discontinuation of oil. An increase in serum triglyceride values was seen in all 3 study groups, but the increase in the coconut oil group was significantly greater than the increase in the controls (p 0.05). The mean weight gain per day, weight gain per kg per day (19.47 +or- 8.67 g/day or 13.91 g/day), and mean weekly increment in skinfold thickness were significantly greater in the coconut oil group as compared to controls (p 0.05). The lead in the weight gain in this group continued in the follow-up period (corrected age, 3 months). Higher weight gain in the safflower oil group (13.26 +or- 6.58 g/day) as compared to the controls (11.59 +or- 5.33 g/day) failed to reach statistical significance, probably because of increased steatorrhea (stool fat 4+ in 50% of the samples tested). The differences in the 2 oil groups presumably occurred because of better absorption of MCI rich coconut oil. The technique of oil fortification is fraught with dangers because of aspiration and contamination. Accordingly, such fortification should be used in selected situations only, rather than as a routine nursery policy.

The prevention of Indian childhood cirrhosis.

Previous studies have led to the hypothesis that the gross hepatic copper storage characteristic of Indian childhood cirrhosis (ICC) is due to the early introduction of animal milk feeds which have been contaminated with copper from brass household utensils. Amongst the families of 100 cases of ICC, the incidence of ICC in children born after dietary advice had been given (1/86) was significantly lower than in older siblings (12/125). This study attempted to document the incidence of ICC and the usage of brass before and after an intervention programme in Pune District advising against this pattern of infant feeding. The study encountered numerous difficulties in data gathering, but documented a fall in ICC prevalence resulting in its virtual disappearance in Pune District. This contrasted with an unchanged incidence in Chandigarh. Although a fall in brass usage was seen in Pune District, this was actually a spontaneous sociological change rather than a result of health education.

Neonatal septicemia: a reappraisal with special reference to the use of cefotaxime.

In a study period of one year, 381 babies (38.7% of all nursery admissions) were clinically diagnosed to have sepsis. Of these, 156 (40.9%) had positive blood cultures. Klebsiella was by far the commonest organism isolated (41%) followed by other Gram negative organisms. Gram positive organisms were uncommon (8%). Sensitivity of Gram negative organisms was poor to penicillin (11%) and ampicillin (18%); significantly better to kanamycin (65%), gentamicin (74%) and best to cefotaxime (79%). Only 8% isolates were resistant to all antibiotics. Combination of cefotaxime and gentamicin was effective against 90% of the isolates (in vitro) as compared to 74% for gentamicin and ampicillin. In vivo, mortality in the cefotaxime treated group was significantly lower (24.3%) than control group (47%) although both groups were clinically and bacteriologically comparable (p less than 0.05).

A study of Baroda Development Screening Test for infants.

Baroda Development Screening Test for Infants based on Baroda Norms on BSID-Research Form 1961 were studied at the Child Development Unit of the Department of Pediatrics in the K.E.M. Hospital, Pune. Screening validity, sensitivity, specificity, over-referrals and under-referrals were calculated in three samples--(i) 730 records of 130 babies evaluated on BSID-Baroda Norms during 1979 and December 1984; (ii) 101 records of babies tested at six months out of the first sample; and (iii) 50 babies screened by interviewing the mothers and tested on the full scales by the experts. Screening validity, sensitivity and specificity were more than 76, 66 and 77%, respectively. Over-referrals were highest (35%) in the sample screened by interview. Suggestions are made to improve the screening by interview. Baroda Development Screening Test for Infants is recommended for use in the field for further evaluation.