Effect of kangaroo mother care on pain during orogastric tube insertion in low-birthweight newborns: An open label, randomised trial.

AIM: Non-pharmacological methods are commonly used to reduce the procedural pain in newborns. In this open label, randomised control trial, we studied the pain-reducing effect of kangaroo mother care (KMC) during orogastric tube insertion. METHODS: Newborns, with birthweight 1500-2499 g and admitted to nursery, were randomised into control (no-KMC) or intervention (KMC) arms. In intervention arm, KMC was given for 60 min before and after the procedure. Premature Infant Pain Profile-Revised (PIPP-R) score was used to assess the pain response and the pain severity was graded as minimal or no pain (≤6), mild-to-moderate (7-12) and severe (>12). The PIPP-R scoring was done before, during and at 3- and 15-min after procedure. Change in PIPP-R scores from baseline was calculated. RESULTS: Newborns included in no-KMC (n = 40) or KMC (n = 40) arms were comparable for major confounders (P > 0.05). Pre-procedural pain scores were comparable (P = 0.72). Pain scores measured during and after procedure were significantly higher in no-KMC group than KMC arm. The KMC reduced the pain score by 39%, 32% and 30% during and at 3- and 15-min after procedure respectively as compared to control (P < 0.01). The increase in PIPP-R score from pre-procedural level was 40%, 35% and 31% lower in KMC than no-KMC arm (P < 0.01). A greater proportion of newborns had significantly less severe grades of pain in the intervention arm compared to the no-KMC arm (P < 0.01). CONCLUSION: Orogastric tube placement is a painful procedure. KMC significantly reduces periprocedural pain and its effect continues for at least 15 min after the procedure.

Phase III, Randomized, Double-blind, Placebo controlled trial of Efficacy, Safety and Tolerability of Antiviral drug Umifenovir vs Standard care of therapy in non-severe COVID-19 patients.

OBJECTIVE: To test efficacy, safety and tolerability of Umifenovir in non-severe COVID-19 adult patients. METHODS: We carried out randomized, double-blind, placebo-controlled, multicenter, phase III trials involving adult (18-75 years), non-severe COVID19 patients, randomized 1:1 on placebo or Umifenovir (800 mg BID, maximum 14 days) respectively along with standard-of-care. The primary endpoint for Asymptotic-mild patients was time to nasopharyngeal swab RT-PCR test negativity. For Moderate patients, the average change in the ordinal scale from the baseline scores on the eight-point WHO ordinal scale was assessed. RESULTS: 132 patients were recruited between 3rd October to 28th April 2021, of which 9 discontinued due to various reasons. In Mild-asymptomatic patients (n=82), we found that 73% patients in the Umifenovir arm were RT-PCR negative, while 40% patients in the placebo arm were negative (P=0.004) on day 5. However, in the moderate group (n=41), the WHO scores for the Umifenovir arm was not statistically significant (P=0.125 on day 3), while it was statistically significant in the Mild-asymptomatic group (P=0.019 on day 5). CONCLUSION: Umifenovir meets the primary and secondary endpoint criteria and exhibits statistically significant efficacy for Mild-asymptomatic patients. It is efficacious, safe and well-tolerated at the tested dosage of 800mg BID, maximum 14 days.

Review of long term immunogenicity and tolerability of live hepatitis A vaccine.

Hepatitis A represents one of the major public health problems worldwide including India. Vaccination is the most effective way to prevent hepatitis A infection. Two types of hepatitis A vaccines-live attenuated (H2 strain) and inactivated (killed) are available for use in clinical practice in India with former having advantage of a single-dose compared to two-dose killed vaccine. One of the important characteristic of an ideal vaccine includes its ability to provide life-long protection. In this article we reviewed the available long-term (≥10 years follow-up) published data on live attenuated hepatitis A (H2 strain) vaccine. The data from country of origin of the vaccine (China) and India establish the long-term immunogenicity, protection, and tolerability. Based on the results of several clinical trials showing long-term protection, single dose of live attenuated hepatitis vaccine can be widely used to protect high-risk population against hepatitis A virus infection and related complications.

Revisiting ABO incompatibility as a risk factor for significant neonatal hyperbilirubinemia.

Babies with ABO incompatibility are often advised frequent biochemical screening and prolonged hospital stay. Our primary objective of the study was to compare serum bilirubin levels at 48 h and 96 h of age in neonates with and without ABO incompatibility. Our prospective study included neonates with gestation ≥ 34 weeks, with or without ABO incompatibility (92 in each group). A direct Coombs test was performed on cord blood. The mean serum bilirubin and haematocrit levels in both groups at 48 h and 96 h were comparable. The mean reticulocyte count of babies with ABO incompatibility was, however, significantly higher. Late preterm and term neonates with and without ABO incompatibility have similar bilirubin levels and no increased risk of significant hyperbilirubinemia. Prolonged hospitalisation of these neonates appears to be unnecessary.

Long term follow-up study to evaluate immunogenicity and safety of a single dose of live attenuated hepatitis a vaccine in children.

Worldwide, viral hepatitis continues to be a cause of considerable morbidity and mortality. Mass immunization with a single dose of live attenuated HAV has been shown to significantly reduce disease burden in the community. This was a phase IV, 5-year follow up study carried out at 4 centers (Kolkata, Delhi, Mumbai and Chennai) across India. The subjects with antibody titer <20 mIU/mL at baseline were evaluated for long term immunogenicity. Of the 503 subjects enrolled, 349 subjects were baseline seronegative with an anti-HAV antibody titer <20 mIU/mL. Overall, 343 subjects could be followed up at some point of time during this 5 y post vaccination period. In the last year (60 months) of follow-up, 108 subjects (97.3%) of 111 subjects (who came for follow-up at the end of 5 y) had a protective antibody titer (anti-HAV antibody titer >20 mIU/mL). The seroconversion rates considering seroprotection levels of anti-HAV antibody titer >20 mIU/mL, following vaccination starting from 6 weeks, 6 months, 12 months, 24 months, 36 months, 48 months and 60 months were 95.1%, 97.9%, 98.3%, 96.2%, 97.8%, 92.6% and 97.3%, respectively. The geometric mean concentration (GMC) over the years increased from 64.9 mIU/mL at 6 weeks to 38.1 mIU/mL and 135.2 mIU/mL at 6 months and 12 months, respectively and was maintained at 127.1 mIU/mL at 60 months. In conclusion, the result of this 5-year follow up study showed that the single dose of live attenuated vaccine is well tolerated and provides long-term immunogenicity in healthy Indian children.

Safety and immunogenicity of single dose live attenuated varicella vaccine (VR 795 Oka strain) in healthy Indian children: a randomized controlled study.

Varicella, an acute viral systemic infection that may cause lifelong latent infection with the potential for causing clinical reactivation, may be prevented by immunization. The present study was an open label, randomized, controlled, phase III, multicentre trial, conducted to evaluate and compare the safety, tolerability and immunogenicity of a freeze dried live attenuated Oka strain Varicella Vaccine (VR 795 Oka strain) with Varilrix (Oka-RIT strain) in children. A total of 268 healthy Indian children aged 12 months to 12 y with baseline VZV IgG antibody (<100 mIU/ mL) were enrolled, and 256 children completed the study. The extent of rise of VZV IgG antibody titer assessed as 3-fold and 4-fold rise from baseline was found to be significantly higher (89.1% and 85.2%) in the test group as compared to control group (73.4% and 61.7%). The post-vaccination GMT of the test group was significantly higher (112.5 mIU/mL) as compared with the control group (67.8 mIU/mL) (P < 0.001). The seroconversion rate considering the 5 gp ELISA units/ml equivalent to 10mIU/ml were similar in the control (96.5%) and the test (98.3%) groups. The adverse events were not different in the control and test groups (P > 0.05). The test live attenuated vaccine was found to be highly immunogenic, safe and comparable to Varilrix used in control arm.

Genital injuries in neonates following breech presentation.

Breech presentation is seen in 3-4% of babies born. Delivering a breech baby through vaginal route is difficult and carries a much higher complication rate than cesarean sections. Breech born babies carry an overall increased risk of maternal morbidity, neonatal mortality, birth asphyxia and birth injuries. Various types of birth injuries to the babies have been reported following breech delivery, but genital injuries are less commonly reported and thus, less anticipated. We report series of five babies with spectrum of genital injuries following breech delivery. These injuries led to significant short and long term morbidity in these babies. Keeping high index of suspicion, an early cesarean section can be an aide in preventing these complications. Once the baby is born, careful examination and early intervention should be done to prevent long term complications.

Disseminated bacillus calmette guerin disease in a twin infant with severe combined immunodeficiency disease.

Fatal-disseminated Bacillus Calmette Guerin (BCG) disease is well known in infants with severe combined immunodeficiency after BCG vaccination. We report a 7 month male infant delivered as a product of in vitro fertilization and twin gestation that presented with fever, cough and multiple nodular skin lesions. A biopsy of skin lesions revealed the presence of acid fast bacilli. Mycobacterium bovis infection was confirmed by polymerase chain reaction (PCR) and molecular studies. Immunological profile confirmed the diagnosis of severe combined immunodeficiency. Only few reports of similar case exist in the literature.

Tuberculin conversion and leukocyte migration inhibition test after BCG vaccination in newborn infants.

BACKGROUND: There are reports that BCG vaccine take-up may be delayed or poor among preterm and low birth weight babies OBJECTIVE: The present study was conducted with the objective of (a) studying BCG take-up through tuberculin conversion by Mantoux test at 12 weeks and 6 months of age in babies vaccinated with BCG at birth and (b) evaluating the Leukocyte Migration Inhibition Test (LMIT) in BCG vaccinated babies who did not react to Mantoux test. DESIGN: Prospective observational study. METHODS: BCG vaccine was administered to 143 neonates of 31-41 weeks gestation within 7 days of birth. At 12 weeks of age, Purified Protein Derivative (1 TU PPD-RT 23 with Tween 80) was injected to all the babies and induration was measured at the injection site after 48 hours. Mantoux negative babies were subjected to the LMIT. All the Mantoux test and LMIT negative babies were followed up and given another Mantoux test at 6 months. Those babies who showed a negative Mantoux test at 6 months and negative LMIT at 12 weeks were subjected to another LMIT at 6 months. RESULTS: Local BCG reaction was exhibited by 95.5% babies at 8 weeks and scar formed in 47.2% of them by 12(+1) weeks. The tuberculin conversion rate after 12 weeks of BCG vaccination was 42.7%. The rate of tuberculin conversion was significantly more in babies with birth weight>2500 g as compared to low birth weight babies. Also, the rate of tuberculin conversion was significantly more in term infants as compared to preterm babies. Six months after BCG vaccination, 41.5% of previously Mantoux negative babies showed tuberculin conversion. Overall, 66.4% babies reacted to PPD after 6 months. LMIT was positive in 84.1% babies who had a negative Mantoux test at 12 weeks. Six months after BCG vaccination, 53.8% of babies who had LMIT negative at 3 months became LMIT positive. Thus out of 143 babies, 95.8% had either a reactive Mantoux test or positive LMIT 6 months after BCG vaccination. There were only 6 babies (4.2%) who did not show adequate responses to BCG vaccination. CONCLUSION: Preterm babies of 31 to 36 weeks of gestation and low birth weight babies weighing <2,500 gram at birth can be effectively vaccinated with BCG vaccine in the early neonatal period. However, tuberculin conversion is not a reliable indicator to assess responses induced by BCG vaccination either 12 weeks or 6 months after vaccination because inspite of negative Mantoux test, the vaccinated infant may still be having an adequate response to BCG vaccine. The local BCG reaction at 8 weeks corresponds to cell mediated immunity conferred by BCG vaccination.

A prospective study of iron status in exclusively breastfed term infants up to 6 months of age.

BACKGROUND: Can exclusive breastfeeding until six months of age maintain optimum iron status in term babies? We evaluated iron status of exclusively breastfed term infants in relation to breast milk iron and lactoferrin. METHODS: In this prospective study in Delhi, India, during the period 2003-2004 normally delivered babies of non-anemic [(Hemoglobin (Hb) = 11 g/dl, n = 68] and anemic (Hb 7 - 10.9 g/dl, n = 61) mothers were followed until 6 months of age. Iron parameters were measured in the cord blood at 14 weeks and 6 months. Breast milk iron and lactoferrin were measured at the same intervals. RESULTS: Iron parameters in babies of both groups were within normal limits at birth, 14 weeks and 6 months. Mean breast milk iron and lactoferrin in non-anemic (day 1: 0.89, 6 months: 0.26 mg/l; day 1: 12.02, 6 months: 5.85 mg/ml) and anemic mothers (day 1: 0.86, 6 months: 0.27 mg/l; day 1: 12.91, 6 months: 6.37 mg/ml) were not different on day one or at other times. No relationship was found between breast milk iron, lactoferrin and iron status of the babies. CONCLUSION: Exclusively breastfed infants of non-anemic and anemic mothers did not develop iron deficiency or iron deficiency anemia by six months of age.

Complementary feeding--reasons for inappropriateness in timing, quantity and consistency.

OBJECTIVE: To assess the practice of complementary feeding (CF) in infants 6 month to 2 year, knowledge of mothers regarding CF, and reasons for inappropriate CF practices. METHODS: CF practices were assessed in children aged 6 months to 2 years using semi-structured questionnaire. Demographic profile and mother's knowledge regarding CF was recorded. Cause of inappropriate CF was ascertained by open-ended questions. RESULTS: Among the 200 children studied, 32(16%) were not started on CF at all, and only 35 (17.5%) received CF from 6 months. Of the 168 who were started CF, mean age of starting feeds was 13.37 months. Quantity was adequate in 42(25%) and consistency of food was thick in 64(38%) cases. Only 7(3.5%) mothers started CF at proper time, in adequate quantity and with proper consistency. Knowledge of proper timing was present in 46% of children, adequate quantity in 46.5% and thick consistency in 25.5%. Only 16(8%) mothers had proper knowledge of all three aspects of CF. Knowledge regarding appropriate timing and consistency varied significantly with maternal education and paternal education (Chi-square P< 0.05). On multiple logistic regression only maternal education of graduate level correlated with knowledge of timing of CF (P=0.089. OR-3.5, CI 0.826-15.2). Most common reason for inappropriate practice in 154 mothers who delayed feeds was "tried but did not eat, vomits everything" (52%). CONCLUSION: CF practices were inappropriate and knowledge inadequate in majority of the children studied.