Inflammatory markers in meconium induced lung injury in neonates and effect of steroids on their levels: a randomized controlled trial.

PURPOSE: To determine the levels of TNFa and IL-1beta in tracheal aspirates of neonates with meconium aspiration syndrome (MAS) and to ascertain whether the use of steroids by systemic or nebulized routes suppresses the levels of these inflammatory markers. METHODS: This was a double blind, randomized, controlled, prospective, interventional study done over one year period in the neonatal unit of the Lady Hardinge Medical College. Fifty-one babies of MAS which were randomly distributed into three groups; control, systemic and nebulized steroids; were included in the study. Methyl prednisolone was given intravenously in the dosage of 0.5 mg/kg/day in two divided doses while nebulized budecort was given in a dosage of 50 mcg/dose twice daily. Tracheal aspirates were taken on day 1, 3 and 4 and were analyzed for TNFa and IL-1b by ELISA technique. RESULTS: TNFa in tracheal aspirates showed an increasing trend in babies of MAS in first four days, thereby signifying an inflammatory process underlying the condition. The levels of TNFa were suppressed by use of steroids. Higher levels of TNFa were associated with longer stay in hospital. IL-1b did not show any significant correlation. CONCLUSIONS: TNFa is associated with meconium-associated inflammation. Its level is suppressed with the use of steroids and can also be used to assess prognosis of neonates with MAS.

Free oxygen radicals--predictors of neonatal outcome following perinatal asphyxia.

The study was undertaken to evaluate the role of free oxygen radicals in asphyxiated neonates. Thirty term neonates appropriate for gestational age and with severe birth asphyxia (Apgar score of 3 or less at 1 minute of life) formed the study subjects. The levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), creatine phosphokinase (CPK) and lipid peroxidase (LPO) in the CSF of these neonates were estimated between 12 and 48 hrs of life. Enzyme estimation was performed by standard methods and the results were analysed statistically using Multivariate Logistic Regression analysis and non parametric tests namely Kruskal Wallis test and Wilcoxon's rank sum test. Out of the thirty babies, 14 were observed to be neurologically normal, 9 had significant morbidity and 7 died. The SOD levels ranged from 12.4 to 140 units/ml, GPx from 128 to 1933 nmol/min/dl, CPK from 2 to 2098 IU/dl and LPO from 5.4 to 30.8 umol/hr/dl. The SOD and GPx levels had an inverse relationship whereas rise in LPO and CPK levels were directly proportional to the extent of neurological damage and ultimate clinical outcome. CPK levels higher than 140 IU/ml were lethal and associated with 100% mortality whereas all normal neonates had CPK below 37 IU/ml. The levels of antioxidant enzymes can reliably and significantly predict mortality and morbidity whereas level of an enzyme cannot confidently confer normalcy. Hence antioxidant enzyme levels with a cut off value can be a useful marker and serve as a prognostic indicator in times to come.

Neonatal mechanical ventilation--experience at a level II care centre.

One hundred and fifty nine neonates were ventilated over a period of one year of whom 74 (46.54%) survived. This study aims to analyse the indications, complications and outcome of babies requiring mechanical ventilation. The early outcome measures were (i) survival rate with respect to birth weight, gestation and indication of ventilation, and (ii) Complications of assisted ventilation. One hundred and forty seven babies received IPPV and 34 received CPAP. Twenty two out of these 34 required IPPV later. Survival was cent percent on exclusive CPAP mode. HMD was the commonest indication for ventilation followed by Birth asphyxia, Apnea of prematurity, Meconium Aspiration Syndrome and Persistent Pulmonary Hypertension of the New born. Survival rates increased with increasing birth weight and gestational age, changing from 25% for < 1000 gm and 20% for < 28 wks to 53% for > 2500 gms and 50.2% for > 37 wks. Prolonged ventilatory support was needed for HMD (mean 114 hrs) and PPHN (mean 156 hrs). Commonest complication was Sepsis (26%) followed by Pulmonary hemorrhage, Pneumothorax and IVH. Lower success rates in ventilation is due to the poor survival of babies weighing < 1000 gms and those with a gestation of < 28 wks with nosocomial infections as a major complication of assisted ventilation being an additional factor.

Immunogenicity and tolerance of H. influenzae type b, tetanus toxoid conjugate vaccine given concurrently or in combination.

The present prospective, open, controlled, randomised comparative trial was undertaken to evaluate the sero response and side effects of PRP-T Conjugate Vaccine (ACT-HIB) in infants and children aged 2 months and 16-24 months. Fifty four babies aged 2 months formed group A, 56 children aged 16-24 months formed group B. Groups A and B were further subdivided into two sub groups each destined to receive either PRP-T vaccine in association with DPT vaccine at different sites (I) or PRP-T and DPT both vaccines at the same site mixed in the same syringe (II). Group A received 3 doses at 2, 3 and 4 months of age and group B received one dose between 16-24 months. The Geometric mean titres of Anti PRP antibodies observed in primary immunisation schedule (A) and single dose vaccination schedule (B) were comparable and significantly higher to prevaccination titres. A serum anti PRP level of > 1.0 mcg/ml after immunisation is believed to correlate with long term protection. Ninety-six percent of infants in Group A and 98% in Group B achieved titres > 1.0 mcg/ml. The side effects were minimal, local and were comparable between the study and control groups, suggesting that PRP-T vaccine is highly immunogenic and well tolerated in Indian infants and children.

Seroconversion following killed polio vaccine in neonates.

The study was carried out to evaluate the efficacy of IPV in neonates and to study the additive effect of IPV or OPV at birth on seroconversion with three subsequent doses of OPV. Addition of IPV or OPV at birth to the conventional OPV schedule resulted in significantly higher seroconversion rates than in the controls, who received three doses of OPV. Three doses of IPV beginning from birth resulted in significantly better seroconversion rates than in the control group. Children receiving 3 doses of IPV showed significantly greater seroconversion rates against type III polio virus than those receiving IPV/OPV at birth followed by 3 doses of OPV. The difference in the seroconversion rates against the other virus types was not significant. A significantly greater number of children who received some vaccine at birth (IPV or OPV) were protected against poliomyelitis by 6 weeks age as compared to those who received no immunization at birth. The study recommends that seroconversion rates following three doses of IPV are satisfactory. Addition of IPV or OPV at birth to the conventional schedule markedly increases the seroconversion rates. Immunization can be started at birth to ensure early protection against poliomyelitis.

End tidal carbon dioxide monitoring--its reliability in neonates.

End tidal Carbon dioxide monitoring was undertaken prospectively in all Ventilated neonates in our NICU admitted from March 1995 to August 1995 irrespective of the birth weight, gestational age and indication of ventilation. The aim was to determine the correlation between ETCO2 and PaCO2 in various clinical situations. The arterial blood gases were obtained in all ventilated babies with simultaneous and continuous ETCO2 monitoring and were analysed by AVL 995 Hb blood gas analyser. ETCO2 was analysed by side stream technique by Datex Cardiocap II monitor. A total of 152 samples from in-dwelling radial artery catheters were analysed from babies with birth weight from 900 g to 3400 g, gestation age from 28 to 42 wks and were ventilated for various indications like Severe Birth Asphyxia (SBA), Meconium Aspiration Syndrome (MAS), Recurrent Apnoea and Hyaline Membrane Disease (HMD). Statistical analysis was done in 10 groups to see if the ETCO2 correlated with its corresponding PaCO2 value. The study groups comprised three groups based on birth weight being < 1.5-2.5 kg and > 2.5 kg three groups as per the gestational age being 28-31+6 wks, 32-36+6 wks and 37-41+6 wks and four groups as per the need for ventilation being Severe Birth Asphyxia, Meconium Aspiration Syndrome, Apnoea of Prematurity and Hyaline Membrane Disease. Results of the correlation analysis revealed that the correlation coefficient in the study group ranged from 0.55 to 0.96 and was statistically significant in babies > 2.5 kg and 1.5-2.5 kg, in term and preterms 32-36 wks, and in babies with MAS, SBA and Recurrent Apnoea. The correlation coefficient was lowest in babies with HMD, being 0.55. The study showed that ETCO2 correlates closely with PaCO2 in most clinical situations in neonates and we recommend its use in all level III NICUs in ventilated babies.

Phototherapy induced hypocalcemia.

Sixty neonates with hyperbilirubinemia were included in the study. There were 20 preterm (Group A) and 20 full term (Group B) neonates. Ten neonates from each group formed the control group. The study group neonates were managed with phototherapy while the control group neonates were not subjected to phototherapy. Serum calcium levels of the two groups were studied. Ninety per cent preterm neonates and seventy-five per cent full term neonates developed hypocalcemia after being subjected to phototherapy. There was a highly significant fall in the total as well as ionized calcium levels in the study group in contrast to the control group. It is recommended that neonates under phototherapy should be given supplemental calcium to prevent hypocalcemia.

Hemostatic profile in septicemic neonates with and without bleeding.

Hemostatic profile was studied in 25 full term, non-asphyxiated neonates with blood culture-proven septicemia. Nine (36%) of these neonates manifested bleeding. Detailed coagulation tests and platelet studies were deranged in 24 (96%) of neonates with septicemia. Abnormalities in coagulation tests did not differ in those with and without bleeding. Only platelet aggregation with ADP was deranged to a significantly greater extent in those with bleeding as compared with those without bleeding.

Reliability of capillary blood gas estimation in neonates.

In order to compare the reliability of capillary blood gases to the arterial blood gases, we studied fifty one neonates with moderate birth asphyxia. A significant difference (p less than 0.05) was found between the capillary and the arterial blood gas values with respect to blood pH, PCO2 PO2 and oxygen saturation. However, the levels of blood bicarbonate as assessed by the 2 samples were comparable. Capillary blood gas values are unsatisfactory indicators of the arterial blood gas values and may result in inappropriate management.

Hemostatic profile in neonatal septicemia.

Hemostatic profile was studied in 25 full term non-asphyxiated neonates with blood culture-proven septicemia. Observations were compared with that of 25 healthy, non-asphyxiated, full term, birth weight and age-matched controls. Detailed coagulation tests & platelet studies were done in each of the 50 neonates by standard techniques. Hemostatic defects occurred in 96% of the septicemic neonates and none in the control group irrespective of the occurrence of clinical bleeding. The coagulation tests were deranged in 805 and platelet function tests in 92% of patients. These tests were significantly deranged in septicemic neonates as compared to control group.

Stress associated gastric bleeding in newborn--role of ranitidine.

Stress associated gastric bleeding in sick neonates is an ominous sign and frequently heralds mortality. This study was aimed at evaluating the H2 receptor antagonist drug-ranitidine in the treatment of this bleeding. Thirty eight neonates with gastric hemorrhage were included in the study. Twenty neonates were given ranitidine while 18 acted as controls. Both groups were well matched with respect to various parameters. Gastric bleeding was controlled earlier in the ranitidine group in contrast to the control group. No untoward side effects were observed with the use of ranitidine. The use of this drug in stress associated gastric bleeding in neonates is recommended.

Neonatal mortality patterns in an urban hospital.

Neonatal mortality rate is perhaps the most reliable indicator of the perinatal outcome. An assessment of perinatal outcome can be made through knowledge of causes of death. This study was carried out to evaluate the neonatal deaths in our hospital. Live births (n = 7309) and deaths (n = 328) during a 6 months period were retrospectively analyzed. These were grouped into non-preventable and potentially preventable causes of death. The single most important factor contributing to the mortality was respiratory distress (29.3%) followed by sepsis (24.4%) and birth asphyxia (16.2%). The non-preventable causes of mortality (e.g., lethal congenital malformations, extremely low birth weight) accounted for 10.4% of the total mortality. The idealized neonatal mortality rate was 4.6/1000 live births, while the salvageable death rate was 40.2/1000 live births. The mortality increased significantly if the birth weight fell below 2 kg. The salvageable deaths could perhaps be prevented through better antenatal and intranatal care, ventilatory support and prevention of sepsis.

Acute renal failure in asphyxiated newborns.

The study was undertaken to evaluate the occurrence of renal failure following perinatal asphyxia in the newborns. Thirty newborns with severe birth asphyxia were included in the study along with 30 normal newborns who comprised the control group. Any neonate presenting with oliguria or blood urea more than 40 mg/dl or creatinine more than 1 mg/dl was subjected to a fluid and diuretic challenge. If oliguria or renal dysfunction persisted then the child was labelled as renal failure and these subjects were further investigated. It was observed that 43% of asphyxiated babies developed acute renal failure (ARF); 69.2% babies had oliguric renal failure. While no significant correlation could be seen between Apgar scores at 5 and 10 min and development of ARF, a significant relationship was seen between hypoxic-ischemic encephalopathy and ARF. Patients with oliguric ARF carried a poorer prognosis as compared to non-oliguric ARF.