WINROP algorithm for prediction of sight threatening retinopathy of prematurity: Initial experience in Indian preterm infants

Purpose: To determine the efficacy of the online monitoring tool, WINROP (https://winrop.com/) in detecting sight-threatening type 1 retinopathy of prematurity (ROP) in Indian preterm infants. Methods: Birth weight, gestational age, and weekly weight measurements of seventy preterm infants (<32 weeks gestation) born between June 2014 and August 2016 were entered into WINROP algorithm. Based on weekly weight gain, WINROP algorithm signaled an alarm to indicate that the infant is at risk for sight-threatening Type 1 ROP. ROP screening was done according to standard guidelines. The negative and positive predictive values were calculated using the sensitivity, specificity, and prevalence of ROP type 1 for the study group. 95% confidence interval (CI) was calculated. Results: Of the seventy infants enrolled in the study, 31 (44.28%) developed Type 1 ROP. WINROP alarm was signaled in 74.28% (52/70) of all infants and 90.32% (28/31) of infants treated for Type 1 ROP. The specificity was 38.46% (15/39). The positive predictive value was 53.84% (95% CI: 39.59–67.53) and negative predictive value was 83.3% (95% CI: 57.73–95.59). Conclusion: This is the first study from India using a weight gain-based algorithm for prediction of ROP. Overall sensitivity of WINROP algorithm in detecting Type 1 ROP was 90.32%. The overall specificity was 38.46%. Population-specific tweaking of algorithm may improve the result and practical utility for ophthalmologists and neonatologists.

Glutamic acid decarboxylase (anti-GAD) & tissue transglutaminase (anti-TTG) antibodies in patients with thyroid autoimmunity.

Background & objectives: Several autoimmune disorders have been reported to be associated with autoimmune thyroiditis and may coexist with other organ-specific autoantibodies. The aim of the present study was to evaluate the presence of tissue transglutaminase (anti-TTG) and glutamic acid decarboxylase (anti-GAD) antibodies in patients suffering from autoimmune thyroiditis as diagnosed by anti-thyroid peroxidase (anti-TPO) antibodies, which may indicate high risk for developing celiac disease or type 1 diabetes mellitus. Methods: Five thousand children and 2800 adults were screening as part of a general health examination done on a voluntary basis in four different parts of Delhi. A total of 577 subjects positive for anti-TPO antibody constituted the cases. Equal number of age and sex matched anti-TPO antibody negative controls were randomly selected from the same cohort to form paired case control study. The cases and controls were further divided into two groups as follows: group-1 (children and adolescent <18 yr), group-2 (adults >18 yr). Serum samples of cases and controls were analysed for thyroid function test (FT3, FT4, and TSH), anti-TTG and anti-GAD antibodies. Results: A total of 1154 subjects (577 cases and 577 controls) were included in this study. Hypothyroidism was present in 40.2 per cent (232) cases compared to only 4.7 per cent (27) in controls (P<0.001). Anti-TTG and anti-GAD antibodies were present in 6.9 and 12.5 per cent subjects among cases compared to 3.5 per cent (P=0.015) and 4.3 per cent (P=0.001) in controls, respectively. Only anti-GAD antibody were significantly positive in cases among children and adolescents (P =0.0044) and adult (P=0.001) compared to controls. Levels of anti-TTG and anti-GAD antibodies increased with increasing titre of anti-TPO antibody. Interpretation & conclusions: Our findings showed high positivity of anti-GAD and anti-TTG antibodies among subjects with thyroid autoimmunity. It is, therefore, important to have high clinical index of suspicion for celiac disease or type 1 diabetes mellitus in patients with autoimmune thyroiditis.

Neonatal cytomegalovirus infection: diagnostic modalities available for early disease detection.

CMV is a ubiquitous virus. In India, there is high seroendemicity with almost 99% adults showing IgG antibodies. Infection or re-activation becomes important in immunocompromised host (Transplant recipients, Cancer therapy patients and patients with HIV/AIDS). Neonates form a distinctive high risk population for congenital CMV infection and suffer disastrous sequlae of the same. Neonatal infections may be congenital in nature or may be acquired after birth during first month of life via infected breast milk or due to exposure to high risk blood products. The risk for transmission of the virus to the fetus is higher in primary infected mothers than in mothers with reactivated disease. Primary CMV infections are reported in 1-4% of seronegative women during pregnancy and the risk for viral transmission to fetus is 30-40%. Reactivation of a CMV infection during pregnancy is reported in 10-30% of seropositive women and the risk of transmitting the virus is about 1-3%. The adverse outcome of congenital neonatal CMV infection includes- microcephaly (70%), intellectual impairment (60%), sensineural hearing loss (35%), choriorenitis (22%), hepatosplenomegaly (70%), jaundice (68%), thrombocytopenia (65%), low birth weight (65%), pneumonitis (2-5%) and congenital heart disease (<5%). About 5-10% of congenitally infected asymptomatic infants will have neurological problems later in life the most common of which is unilateral or bilateral sensory neural hearing loss. All immunocompromised hosts, including pre-term neonates, mount weak antibody responses (IgM), making serological detection of CMV infection in them, fallacious. Thus, it is imperative to use antigen detection methods such as quantitative PCR or PP65 Antigenaemia assays to detect CMV infection in immunocompromised host. Sakhuja et al and Minz et al have demonstrated that PP65 Antigenaemia assay is very good for diagnosing CMV disease in renal transplant recipients. The present review tends to highlight the role of newer diagnostic modalities in early CMV infection detection in neonatal population.

Hepatitis B prevalence during pregnancy.

In order to determine the efficacy of a new hepatitis B immune globulin (HBIG), a phase 3, vertical transmission (mother to child) clinical interventional trial of hepatitis B virus (HBV) post exposure prophylaxis (PEP) was conducted at selected sites (n=15) throughout India. This required a large screening program for HBsAg positivity at prenatal clinics located in tertiary care hospitals. 36,379 pregnant women consented to be tested for Hepatitis B surface antigen (HBsAg) by Rapid Test and if positive-confirmed by ELISA. The weighted mean prevalence was 0.82% (95% CI, 0.72, 0.91). In conclusion, the prevalence of HBV carrier state during pregnancy in India in this study was low compared to previous reports.

Clinical risk factors associated with extubation failure in ventilated neonates.

We conducted this study to find out the incidence of extubation failure (EF) in ventilated neonates and associated clinical risk factors. Eighty two ventilated neonates were followed up to 48 hours post-extubation to look for EF. Twenty two babies (26.8%) had EF. The common risk factors for EF were presence of patent ductus arteriosus, post-extubation lung collapse and acquired pneumonia. The duration of ventilation, and maximum and pre-extubation alveolar arterial oxygen gradients (AaDO2) were significantly higher (P<0.05) in EF group. The incidence of sepsis (P=0.034), anemia (P=0.004) and pneumonia (P=0.001) were significantly higher in EF group. Detection of significant PDA and adequate post extubation care may help to reduce rate of extubation failure in neonates.

Homocysteine – Risk factor for ischemic stroke.

The present study was undertaken to compare the homocysteine levels in patients of ischemic stroke with controls. Our study included 117 patients of ischemic stroke and 101 controls. The mean homocysteine levels in patients with ischemic stroke were 16.80±6.71 umol/L while in controls it was 12.30±4.68 umol/L, the difference being statistically significant (P<0.01). The increased homocysteine levels in patients with ischemic stroke are independent of diabetes mellitus, age and sex. The homocysteine levels were higher in hypertensive subjects than non-hypertensive (P<0.05).

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.

Clinico-epidemiological profile and validation of symptoms and signs of severe illness in young infants (< 60 days) reporting to a district hospital.

OBJECTIVES: To describe the clinical and epidemiological profile of infants less than 2 months of age reporting to a district hospital and to assess the ability of simple clinical symptoms and signs used by health workers to detect severe illness warranting hospital admission. METHODS: It was an observational study done at a general district hospital at Chandigarh, North India. Infants less than 2 months of age presenting to this hospital were enrolled. All infants were first evaluated by an auxiliary nurse midwife (ANM) to record a pre-determined set of symptoms and signs. A pediatrician who was blinded to the findings of the ANM did an independent assessment for severe illness needing urgent hospitalization. RESULTS: A total of 1268 infants were enrolled. Of these, 356 (28%) were below 7 days of age. Overall, regurgitation, vomiting and stool problems (25%) were the most common presenting complaints in the first 2 months of life, followed by jaundice (22%) and respiratory symptoms (15%). 112 (8.8%) infants were classified as having "severe illness requiring urgent hospital management" by the pediatrician. Nearly half (46%) of the admissions were because of jaundice while 17% each were due to sepsis and pneumonia / lower respiratory tract infection (LRTI). A history of not feeding well (OR 14.7, 8.0 and 11.3 in 0-6, 7-27 and 28-59 days age groups, respectively) and a respiratory rate >60/min (OR 21.5, 6.2 and 10.5 in 0-6, 7-27 and 28-59 days age groups, respectively) had significant positive predictive value to predict severe illness (except jaundice) in all the 3 age groups studied. In the second month of life, severe chest in-drawing (OR 4.6) was also a significant predictor. CONCLUSIONS: Simple clinical signs are useful in hands of health worker for identifying neonates with serious illness warranting hospital admission. These will be of use in the further development of clinical algorithms for the national integrated management of childhood illnesses.

Status of lipid peroxidation and plasma iron level in bronchial asthmatic patients.

Low antioxidant levels and oxidative stress due to airway inflammation may be determinant of asthma severity. The study was conducted to find the extent of lipid peroxidation and change in the levels of plasma iron in asthmatic patients with severity of disease. Study included 155 asthmatic and 156 healthy volunteers of the age groups 18-45 of either sex. Asthmatic patients were grouped into mild, moderate and severe groups on the basis of Forced Expiratory Volume in first second percent (FEV1%). Level of plasma malondialdhyde (MDA) was used as index of lipid peroxidation. A significant increase (P<0.01) in plasma MDA and plasma iron levels was found in asthmatic subjects as compared to controls. There was maximum increase in plasma MDA and iron levels in moderate asthmatic group. A positive correlation between plasma MDA and iron (r = +0.3) has been found in asthmatic patients. An increased plasma iron levels in asthmatics may contribute to aggravate lipid peroxidation.

Changes in vitamin C and vitamin E during oxidative stress in myocardial reperfusion.

Injury to the myocardial tissue due to ischemia and reperfusion occurs because of imbalance between the formation of oxidants and available antioxidants in the heart. Levels of vitamin C (ascorbic acid) and vitamin E (alpha--tocopherol) were evaluated in 52 patients of acute myocardial infarction (AMI) treated by streptokinase. They were further divided into reperfused group (39 patients) and non-reperfused group (13 patients). Twenty normal healthy subjects served as controls. Vitamin C and vitamin E were estimated in study group before and after thrombolytic therapy and in controls. Vitamin C levels were low in AMI cases as compared to controls (8.74 +/- 1.87 and 10.63 +/- 3.26 mg/L, respectively, P < 0.001). Trend of fall in vitamin C levels in the two study groups was not statistically significant. Vitamin E levels declined from 12.19 +/- 6.71 to 9.96 +/- 6.50 mg/L by 4 hours which was significant (P < 0.01) in the reperfused group, but the change in non-reperfused group (9.28 +/- 6.37 to 9.35 +/- 6.07 mg/dL by 4 hours) was non-significant. This is because of increased consumption of this antioxidant in suppressing the oxidative stress which occurs with reperfusion. Vitamin E can be proposed as a valid marker for reperfusion.

Resuscitation of asphyxiated newborns with room air or 100% oxygen at birth: a multicentric clinical trial.

OBJECTIVE: To compare the short-term efficacy of room air versus 100% oxygen for resuscitation of asphyxic newborns at birth. DESIGN: Multicentric quasi randomized controlled trial. SETTING: Teaching hospitals. INCLUSION CRITERIA: Asphyxiated babies weighing greater than 1000 grams, with heart rate less than 100 per min and/or apnea, unresponsive to nasopharyngeal suction and tactile stimuli and having no lethal abnormalities. INTERVENTION: Asphyxiated neonates born on odd dates were given oxygen and those on even dates room air for resuscitation. OUTCOME MEASURES: Primary: Apgar score at 5 minutes; Secondary: Mortality and Hypoxic ischaemic encephalopathy (HIE) during first 7 days of life. RESULTS: A total of 431 asphyxiated babies, 210 in the room air and 221 in 100% oxygen group were enrolled for the study. Both the groups were comparable for maternal, intrapartum and neonatal characteristics. The heart rates in room air and 100% oxygen groups were comparable at 1 minute (94 bpm and 88 bpm), 5 minutes (131 bpm and 131 bpm) and 10 minutes (135 bpm and 136 bpm). Median apgar scores at 5 min [7 versus 7] and 10 minutes [8 versus 8 ], in the room air and oxygen groups respectively, were found to be comparable. Median time to first breath (1.5 versus 1.5 minutes) was similar in the room air and oxygen group. Median time to first cry (2.0 versus 3.0 minutes) and median duration of resuscitation (2.0 versus 3 minutes) were significantly shorter in the room air group. The number of babies with HIE during first seven days of life in the two treatment groups (35.7% babies in room air and 37.1% in the 100% oxygen group) were similar. There was also no statistically significant difference in the overall and asphyxia related mortality in the two treatment groups (12.4% and 10.0% in room air versus 18.1% and 13.6% in oxygen group). CONCLUSION: Room air appears as good as 100% oxygen for resuscitation of asphyxic newborn babies at birth.

Neonatal hyperbilirubinemia and its association with thyroid hormone levels and urinary iodine excretion.

OBJECTIVE: To investigate, if, urinary iodine contents as a marker of iodine deficiency and hypothyroidism are associated with the incidence of neonatal hyperbilirubinemia. METHODS: One hundred neonates with total serum bilirubin > or = 15 mg/dl and with no known cause of jaundice were included in the study as a jaundice group. An equal number (n = 100) of non-jaundiced neonates (bilirubin < or = 14.9 mg/dl) with matching for age, gestation period and weight were enrolled in the study as a control group. RESULTS: Thirteen neonates (13%) in the study group had urinary iodine levels < 100 mg/dl as against only 2 (2%) in the control group (p < 0.05). Thirty-four (34/200-17%) neonates i.e. 17 each in the study and control groups had serum TSH > 5 mU/ml and hence an indirect indicator of iodine deficiency in the study population. The mean serum levels of total T3, T4 and TSH in the study neonates were 1.52 +/- 1.23 ng/ml, 15.8 +/- 12.0 micrograms/dl & 3.13 +/- 3.0 mU/ml respectively and did not differ significantly from the mean levels in the control group. Only one neonate in the study group had serum TSH > 20 mU/ml which was suggestive of hypothyroidism, but had normal T3 & T4. Seven neonates in the study group and 8 in the control group had low T4. There was no significant correlation between the maternal and neonatal urine iodine levels, thyroid functions and the bilirubin levels (p > 0.01). CONCLUSION: The jaundiced babies had lower urine oidine levels than the control population. Since, there was no significant difference in the levels of the thyroid hormones, no cause and effect relationship could be inferred between iodine deficiency and jaundice.

A preliminary study on pharmacokinetics of oral indomethacin in premature infants in north India.

BACKGROUND & OBJECTIVES: Patent ductus arteriosus (PDA) is a frequent complication in premature infants. Intravenous indomethacin is the standard mode of medical therapy and has been shown to be efficacious in closing the ductus. In our setup, oral indomethacin is being regularly used for medical treatment of suspected or clinically diagnosed PDA. Non-availability of the parenteral preparation and lack of information regarding the pharmacokinetic disposition of indomethacin in the premature infants in north Indian population led us to conduct this pharmacokinetic study with oral indomethacin. METHODS: Twenty premature infants with gestational age 30.3 +/- 0.3 wk and birth weight, 1209.8 +/- 39.5 g; admitted to the neonatal unit of the Nehru Hospital, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh were enrolled in the study. Indomethacin was administered in a single oral dose of 0.2 mg/kg and blood samples were collected through an indwelling vascular catheter at 0 and 1, 2, 4, 8 and 12 h after administration of indomethacin. Plasma indomethacin concentrations were assayed by spectrofluorometric technique. RESULTS: Large interindividual variability was observed for peak plasma concentrations (Cmax; 137.9 +/- 14.0 ng/ml), elimination half-life (t1/2 el; 21.4 +/- 1.7 h) and area under the plasma concentrations time curve (AUC0-infinity;4172 +/- 303 ng.h/ml) in these infants. Variables like birth weight, and sex did not have any sigiificant effect on indomethacin pharmacokinetics. However, the plasma t1/2 el of indomethacin was significantly (P < 0.01) larger in older infants (gestational age > 30 wk) in comparison to younger ones (gestational age < or = 30 wk). There was a negative correlation between gestational age and elimination t1/2 (r = -0.77). INTERPRETATION & CONCLUSION: In conclusion, indomethacin pharmacokinetics showed a wide variability in premature infants. In view of these findings it can be suggested that infants of smaller gestational age are at greater risk of cumulative toxicity if more than one dose of indomethacin is given. With advancing age, metabolism as well as elimination of drug is faster that may require modification in indomethacin dose to achieve therapeutic response. These preliminary results may be of use in designing future pharmacokinetic studies of oral indomethacin in preterm neonates on a larger sample.

Melanotic neuroectodermal tumour of infancy: a case report.

Melanotic Neuroectodermal Tumour of Infancy is a rare tumour. Prompt recognition of such a case is essential for the Pediatric Dentist Presented here is a case of a four and a half month old child who reported in the dental out patient department of Guru Teg Bahadur Hospital with a swelling in the right anterior maxillary ridge region.

Postasphyxial encephalopathy in preterm neonates.

OBJECTIVE: Perinatal asphyxia is an important determinant of infant neurological outcome. There are very few studies looking exclusively at postasphyxial encephalopathy in preterm neonates. METHODS: We studied the neurologic and sonographic abnormalities in 40 preterm babies with severe birth asphyxia during their hospital stay and till 3 months corrected age. RESULT: 87.5 % of the asphyxiated preterm babies had neonatal neurologic abnormality, compared to only 17% of the control babies (p<0.0001). Generalised hypotonia and reduced activity were the commonest abnormalities (observed in 85% of asphyxiated babies) while depressed sensorium (60%) and seizures (35%) were seen in more severe cases. White matter disease (WMD-including periventricular flare, cerebral edema and periventricular leucomalacia) was significantly more frequent in the study cases (34.5% in study cases vs 7.5% in controls, p<0.0001) as was grade 3/4 intraventricular hemorrhage(IVH) (25% in study cases vs 2.5% in controls, p<0.0001). There was 11 fold higher mortality among the asphyxiated babies (23 deaths in study cases vs 2 in controls, p<0.0001). CONCLUSION: The survivors had a significantly higher incidence of both mild and severe neurological abnormalities at corrected age of 3 months among the asphyxiated babies. There was a good correlation between the severity of the neonatal encephalopathy as well as the sonographic findings and the outcome.

Early onset mixed Morganella and Klebsiella sepsis in a neonate.

A premature baby girl was delivered vaginally to a mother who had an otherwise normal pregnancy, and spontaneous premature onset of labour. She had early onset neonatal sepsis with pneumonia. The baby's blood culture as well as the amniotic membrane culture grew Morganella and Klebsiella. She recovered on appropriate antibiotics. This is only the second reported case of early onset neonatal sepsis due to Morganella. The literature is reviewed.