Evaluation of the impact of continuous Kangaroo Mother Care (KMC) initiated immediately after birth compared to KMC initiated after stabilization in newborns with birth weight 1.0 to < 1.8 kg on neurodevelopmental outcomes: Protocol for a follow-up study.

BACKGROUND: Preterm birth or low birth weight is the single largest cause of death in newborns, however this mortality can be reduced through newborn care interventions, including Kangaroo Mother Care (KMC). Previously, a multi-country randomized controlled trial, coordinated by the World Health Organization (WHO), reported a significant survival advantage with initiation of continuous KMC immediately after birth compared with initiation of continuous KMC a few days after birth when the baby is considered clinically stable. Whether the survival advantage would lead to higher rates of neurodevelopmental morbidities, or the immediate KMC will also have a beneficial effect on cognitive development also, has not been investigated. We therefore propose to test the hypothesis that low-birth-weight infants exposed to immediate KMC will have lower rates of neurodevelopmental impairment in comparison to traditional KMC-treated infants, by prospectively following up infants already enrolled in the immediate KMC trial for the first 2 years of life, and assessing their growth and neurodevelopment. METHODS: This prospective cohort study will enroll surviving neonates from the main WHO immediate KMC trial. The main trial as well as this follow-up study are being conducted in five low- and middle-income countries in South Asia and sub-Saharan Africa. The estimated sample size for comparison of the risk of neurodevelopmental impairment is a total of 2200 children. The primary outcome will include rates of cerebral palsy, hearing impairment, vision impairment, mental and motor development, and epilepsy and will be assessed by the age of 3 years. The analysis will be by intention to treat. DISCUSSION: Immediate KMC can potentially reduce low-birth-weight-associated complications such as respiratory disease, hypothermia, hypoglycemia, and infection that can result in impaired neurocognitive development. Neuroprotection may also be mediated by improved physiological stabilization that may lead to better maturation of neural pathways, reduced risk of hypoxia, positive parental impact, improved sleep cycles, and improved stress responses. The present study will help in evaluating the overall impact of KMC by investigating the long-term effect on neurodevelopmental impairment in the survivors. TRIAL REGISTRATION: Clinical Trials Registry-India CTRI/2019/11/021899. Registered on 06 November 2019. Trials registration of parent trial: ACTRN12618001880235; Clinical Trials Registry-India: CTRI/2018/08/015369.

Changing trend in bacterial etiology and antibiotic resistance in sepsis of intramural neonates at a tertiary care hospital.

BACKGROUND: Septicemia is an important cause of neonatal morbidity and mortality. However, organized data on causative organisms and their resistant pattern are scanty from developing countries. The changing trend in causative organisms and their antibiotic resistance is yet to be documented in India. The present study examines the trends in bacterial profile and antibiotic resistance of the organisms causing sepsis in hospitalized neonates. MATERIALS AND METHODS: A retrospective laboratory-based analysis of blood cultures obtained from Neonatal Intensive Care Unit of a tertiary care hospital in New Delhi was done for the period of 1999-2014, divided into five phases. RESULTS: A total of 4700 isolates were considered. Over time, Gram-negative organisms have replaced Gram-positives as frequent isolates. Initially, there was predominance of Klebsiella pneumoniae, then of Staphylococcus aureus which recently has been changed with coagulase negative-Staphylococcus and Acinetobacter. Growing resistance against the first and second line of drugs has been noted, including methicillin-resistant S. aureus and vancomycin-resistant Enterococcus. CONCLUSION: The etiological profile of neonatal sepsis has changed tremendously in the past 15 years. High resistance against common drugs necessitates continued surveillance and review of empirical antibiotic policy for neonatal sepsis. These steps are important to effectively curtail the surge of further antibiotic resistance.

A prospective, randomized controlled trial comparing the left lateral, modified lateral and sitting positions for spinal block characteristics for Cesarean delivery.

BACKGROUND: Maternal position affects spinal block characteristics. We investigated the effect of lateral, modified lateral and sitting position for spinal anesthesia with 2 mL hyperbaric bupivacaine 0.5% on spinal block characteristics in this prospective, randomized study. METHODS: Seventy-five ASA physical status I parturients were randomly allocated to the left lateral to supine-wedged, modified lateral to supine-wedged with a10°head-up tilt or the sitting to supine-wedged position for induction of spinal anesthesia for Cesarean delivery. Neural block was assessed by pin prick and modified Bromage scale. Data were analyzed using ANOVA, Chi-square test and Wilcoxon rank sum test, where appropriate. P<0.05 was considered significant. RESULTS: Onset time (mean ± SD) for sensory block to T5 dermatome for the lateral, modified lateral and sitting groups was 6.8 ± 2.7, 13.6 ± 6.2 and 9.7 ± 5.5 min, respectively; P<0.001. The median (interquartile range) maximum dermatomal level was significantly lower in the modified lateral group (T5[T3-T5]) compared with the lateral (T3[T2-T4]) and sitting (T3[T3-T4]) groups, respectively; P=0.022 and P=0.030, respectively. Three women in the modified lateral group required general anesthesia compared with none in the other groups; P= 0.044. Apgar scores and cord blood pH, PO2 and PCO2 were similar between groups. CONCLUSION: The modified lateral position with 10 mg of hyperbaric bupivacaine was associated with a slower onset and a lower maximum sensory block necessitating higher requirement for conversion to general anesthesia. It did not offer any advantage over lateral and sitting positions for induction of spinal anesthesia for elective Cesarean delivery and cannot be recommended.

Effect of vitamin D supplementation of low birth weight term Indian infants from birth on cytokine production at 6 months.

BACKGROUND/OBJECTIVES: Vitamin D deficiency has been associated with impaired resistance to infection, which may be mediated by alterations in cytokine responses. We investigated the effect of vitamin D supplementation to infants on whole blood in-vitro cytokine production and on the inflammatory marker, plasma C-reactive protein (CRP). SUBJECTS/METHODS: Blood samples were taken at 6 months of age from infants participating in the DIVIDS (Delhi Infant Vitamin D Supplementation) randomized controlled trial of weekly vitamin D supplements (1400 IU = recommended intake) from birth to 6 months with the aim of decreasing mortality and severe morbidity. We measured plasma CRP and whole blood in-vitro production of tumour necrosis factor-α (TNFα), interferon-γ (INFγ), interleukin (IL)-10 and IL-13 following no stimulation or stimulation with lipopolysaccharide or phytohemagglutinin. RESULTS: Although the intervention improved vitamin D status in a severely deficient population, there were no differences between treatment groups in plasma CRP or in the production of any of the cytokines in either unstimulated or stimulated cultures. Recent illness had limited association with immunological markers. Plasma 25-hydroxyvitamin D levels were not associated with CRP or production of any cytokines. CONCLUSIONS: Vitamin D supplementation did not affect plasma CRP or whole blood cytokine production of vitamin D-deficient low birth weight infants. This is consistent with the lack of effect of vitamin D on mortality and severe morbidity among infants in the DIVIDS trial.

Maternal and neonatal effects of bolus administration of ephedrine and phenylephrine during spinal anaesthesia for caesarean delivery: a randomised study.

BACKGROUND: Maternal haemodynamic changes and neonatal well-being following bolus administration of ephedrine and phenylephrine were compared in 60 term parturients undergoing elective caesarean delivery under spinal anaesthesia. METHODS: In a randomised double-blind study, women received boluses of either ephedrine 6 mg (group E; n=30) or phenylephrine 100 microg (group P; n=30) whenever maternal systolic pressure was 80% of baseline. RESULTS: Changes in systolic pressure were comparable in the two groups. There were no differences in the incidence of bradycardia (group E: 0% vs. group P: 16.7%; P>0.05), nausea (group E: 13% vs. group: P 0; P>0.05) and vomiting (group E: 3.3% vs. group P: 0; P>0.05). Umbilical artery (UA) pH (group E: 7.29 +/- 0.04 vs. group P: 7.32 +/- 0.04; P=0.01) and venous pH (group E: 7.34 +/- 0.04 vs. group P: 7.38 +/- 0.05; P=0.002) were significantly greater in group P than in group E. UA base excess was significantly less in group E (-2.83 +/- 0.94 mEq/L) than in group P (-1.61 +/- 1.04 mEq/L; P<0.001). Apgar scores at 1, 5 and 10min and neurobehavioural scores at 2-4 h, 24 h and 48 h were similar in the two groups (P>0.05). CONCLUSIONS: Phenylephrine 100 mug and ephedrine 6 mg had similar efficacy in the treatment of maternal hypotension during spinal anaesthesia for elective caesarean delivery. Neonates in group P had significantly higher umbilical arterial pH and base excess values than those in group E, which is consistent with other studies.

Clinicoepidemiological profile and predictors of severe illness in young infants (< 60 days) reporting to a hospital in North India.

OBJECTIVES: To describe the clinical and epidemiological profile of young infants reporting to a hospital and assess previously proposed simple clinical signs for their value in enabling health workers to detect young infants with severe illness warranting hospital admission. METHODS: Observational study of infants less than 2 months of age presenting consecutively to a large public hospital in South Delhi who were evaluated by a health worker (nurse), on a standardized list of signs and symptoms, and the ability of these were evaluated against the need for hospital admission which was assessed by an independent pediatrician. RESULTS: Of the 1624 young infants triaged, 878 were enrolled into the study. Of these 100 (11%) were below 7 days of age, for whom the common reasons for seeking care were jaundice (52%), not feeding well (6%) and fever (5%). The remaining 778 (89%) were 7-59 days of age with respiratory symptoms as the main presenting complaints (29.1%). The primary clinical diagnoses in infants with serious illness needing admission to hospital in the age group <7 days (n = 66) were hyperbilirubinemia (56%) and sepsis (21%). In those between 7-27 days of age (n = 60), primary diagnoses were sepsis (27%), pneumonia (13%), diarrhea, dysentery or dehydration (10%), while in the age group 28-59 days of age (n = 47) pneumonia (40%), sepsis (19%) and diarrhea or dehydration (13%) were the common primary diagnoses. Signs that had at least a prevalence of 5% and were strong predictors for all the age categories studied were history of difficult feeding (OR 6.8 for 0-6 days, 15.1 for 2-27 days and 6.2 for 28-59 days age groups), not feeding well on observation (OR 13.7, 27.6 and 20.9 respectively for the 3 age groups), temperature > 37.5C (OR 21.8, 14.6 and 30.0 respectively for the 3 age groups) and respiratory rate > 60 per minute (OR 6.8, 15.1 and 21.0 respectively for the 3 age groups). Additional strong predictors with > 5% prevalence were history of convulsions (OR 7.9, only in 0-6 day age group), lethargy (OR 26.1, only in 7-27 day age group), and history of diarrhea (OR 3.0 for 2-27 days and 2.2 for 28-59 days age groups). 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.

Hepatitis B immunization in low birthweight infants: do they need an additional dose?

AIM: To determine the influence of gestation and weight on the development of protective anti-HB levels and geometric mean titres after three doses of HBV vaccine and to ascertain the need for a fourth dose in low birthweight infants. METHODS: Hepatitis B vaccine (Enivac HB, Panacea Biotec Ltd., India) was given to 82 preterm (PT) and 60 term intrauterine growth-retarded (T-IUGR) infants at birth and at 6, 10 and 14wk of life. RESULTS: Protective anti-HB levels (>10 mIU/ml) were reached in 86.6% (71/82) of PT infants and 96.7% (58/60) of T-IUGR infants after three doses of HBV vaccine (p = 0.044). The odds of having a protective response after the third dose of HBV vaccine was 1.25 (95% CI 1.02-1.53) with every one-week increase in gestation (p = 0.032). Birthweight was not associated with the development of a protective immune response. After the third dose, only 66.7% (8/12) of the PT infants whose mothers had anti-HB antibodies, developed protective anti-HB levels compared with 90% (63/70) of those with no maternal antibodies (p = 0.028). In PT infants after the fourth dose, there was a significant increase in the proportion of infants with protective antibody levels (8.6%, 95% CI 0.6-16.6%) among those with no maternal antibodies and 12.2% overall (95% CI 6.0-21.3) (p = 0.031 to 0.002) over that reached with the third dose. Administration of the fourth dose to T-IUGR infants did not confer such a benefit. CONCLUSION: In HBV-endemic areas, PT infants, irrespective of their birthweights, may benefit from an additional dose of hepatitis B vaccine in a schedule starting at birth. This approach will prevent vertical transmission and bring their immune response up to par with term infants. Term intrauterine growth-retarded infants should be vaccinated as per the schedule recommended for normal term infants. However, studies in other settings with different vaccine formulations and a longer follow-up period will be required before this strategy can be practised more widely.

Sonographic diagnosis of congenital tuberculosis: an experience with four cases.

Abdominal sonography of four infants with pyrexia and hepatomegaly demonstrated multiple hypoechoeic hepatic and splenic foci, guided biopsies of which showed caseating granulomas with acid-fast bacilli. Evidence of tuberculosis in maternal endometrium and its exclusion in the contacts further confirmed a diagnosis of congenital tuberculosis. Clinical suspicion supplemented by careful sonography facilitated early detection and antemortem diagnosis of this potentially fatal disease.

Hemostatic profile in nephrotic syndrome.

OBJECTIVE: To evaluate the coagulation profile and its relation to steroid therapy, and the frequency of thromboembolic complications and its correlation with coagulation parameters in nephrotic syndrome (NS). SETTING: Hospital based. SUBJECTS AND METHODS: Forty children with NS were subdivided into four groups, namely, fresh cases, steroid dependent, remission after therapy and steroid resistant. An equal number of age and sex matched children served as controls. In all the study and control subjects, detailed clinical examination, liver function tests, renal function tests and detailed coagulation profile were done. Evaluation of renal veins and inferior vena cava for the presence of thrombosis was also done by abdominal ultrasonography. RESULTS: Thrombocytosis was detected in 57.5% and the degree of thrombocytosis was directly related to the amount of proteinuria. The mean prothrombin and thrombin times were within normal range in the study children. The activated partial thromboplastine time (APTT) was prolonged in six cases (15%) and three out of these six children had thromboembolic complications. Antithrombin-III level was significantly lower (p < 0.001) whereas protein C and S were significantly elevated (p < 0.001) as compared to controls. The levels became normal with remission of the disease. Steroid therapy significantly increased the levels of proteins C, protein S. AT-III and fibrinogen as compared to controls. Thromboembolic complications were seen in 3 cases (7.6%) and were associated with very low levels of AT-III and protein C and all three had serum albumin below 2 g/dl. CONCLUSIONS: The importance of coagulation profile in nephrotic syndrome is highlighted and a high index of suspicion for thromboembolic complications is warranted in patients with thrombocytosis, hyper fibrinogenemia, prolonged APTT and in children with low levels of AT-III, protein C and protein S.

Congenital sulfhemoglobin and transient methemoglobinemia secondary to diarrhoea.

Sulfhemoglobinemia and Methemoglobinemia are common causes of cyanosis arising due to accumulation of abnormal heme pigment. We present an unusual case of congenital sulfhemoglobinemia along with diarrhoea induced methemo-globinemia in a neonate. A high index of suspicion and a proper diagnostic approach is needed to determine the true frequency of their occurrence together.

Assessment of thyroid functions and its role in body growth in thalassemia major.

The present study was done to establish the role of thyroid gland in causing growth retardation in regularly transfused thalassemic children. Growth, skeletal maturation and thyroid functions were assessed in 25 patients of thalassemia major in the age range of 5-17 years (mean age 10.3 +/ 3.6 years). Thirteen patients were migrants from Pakistan and 12 were of Indian origin. Twenty-five age and sex matched children who were not anemic served as controls. Thalassemic children received multiple blood transfusions ranging from 36-350 units with a mean of 168.4 +/ 98.9 (+/ 1 SD). The mean pretransfusion hemoglobin was 8.7 +/ 1.6 g/dl. Twenty eight per cent patients were below the 5th percentile for height and another 24% between 5th and 10th percentiles. The height age retardation was more pronounced than bone age retardation. The mean serum total T3 and T4 levels were significantly lower (p < 0.001) and the mean serum TSH levels were significantly higher (p < 0.005) in patients with thalassemia major as compared to the controls. Eight patients had high TSH levels; of these 5 had compensated primary subclinical hypothyroidism (elevated TSH with normal T3 and T4) and 3 had uncompensated primary sub-clinical hypothyroidism (elevated TSH, low T4 and normal T3). Two patients had low T4 with normal T3 and TSH levels. Thyroid dysfunction was not related to age, sex, hemoglobin levels and country of origin but transfused iron load (units/kg, units/year) was significantly higher in patients with hypothyroid function compared to those with euthyroid function (p < 0.005). Height age, weight age and bone age retardations were more pronounced in patients with hypothyroid function; however, the difference was not statistically significant. It is concluded that hypothyroidism is unlikely to be the sole cause of growth retardation; however, it may have a potentiating or permissive role. The strong association of high transfused iron load and decreased thyroid function stresses the need for intensive chelation therapy.

Evaluation of thyroid functions in critically ill infants.

The degree to which thyroid functions are affected by non-thyroid illness and an assessment of its correlation with mortality was evaluated. Thirty infants (20 M, 10 F) with a mean age of 433 +/- 3.28 months (+/- 1 SD), with severe acute systemic illness and 30 healthy controls, age and sex matched, were studied for total serum T3, T4 and TSH levels at admission and recovery or before death. Serum thyroid hormones were measured using standard techniques. There was no significant change in thyroid indices with age, sex, nutritional status, serum protein and C-reactive protein. Serum T3 levels in infants were significantly lower (0.62 +/- 0.63 ng/ml) than the controls (1.90 +/- 0.62) (p < 0.001), with normal T4 and TSH levels at admission. Both serum T3 and T4 levels increased with recovery. Out of 30 infants studied, 14 died whereas 16 were discharged. It was noticed that T3 and T4 values were significantly reduced at or near death when compared with the admission levels (p < 0.001). Prognosis could not be determined at the time of admission, as thyroid indices at admission of patients who died, when compared to infants who were discharged, showed no significant difference in T3, T4 or TSH levels. The above mentioned changes in thyroid indices probably occur as a temporary adaptive mechanism to limit catabolism in states of stress such as infection. Hence, it is suggested that thyroid function tests be interpreted with caution in patients with non-thyroid illness.

Intrauterine growth predictors.

The present study was conducted to construct standards for midarm circumference and midarm/head circumference ratio to identify neonates at risk for metabolic complications and to assess the anthropometric variable which could be used to substitute weight to identify low birth weight neonates. A study of 2925 consecutive live births showed significant correlation (p less than or equal to 0.001) between different anthropometric variables studied. Since midarm circumference (MAC), midarm circumference/head circumference ratio (MAC/HC) and ponderal index (PI) had the least correlation with gestation, these were used as independent markers for gestation. Among these three, MAC had the best correlation with birth weight (r = 0.808). A midarm circumference of less than or equal to 8.6 cm and less than or equal to 7.4 cm had the best sensitivity and specificity for identifying neonates with a birth weight of less than or equal to 2500 and less than or equal to 2000 g, respectively. All the anthropometric variable studied can rule out low birth weight with great accuracy (high negative predictive value greater than 90%).

Congenital syphilitic hepatitis.

Hepatitis is a known manifestation of congenital syphilis, however hepatitis developing during penicillin therapy is unknown. Ten patients of congenital syphilis were studied and serial liver enzymes were done before and after starting penicillin therapy. Eight of the ten patients developed hepatitis after initiating penicillin therapy. Whether hepatitis in these cases was secondary to toxic reaction to the products of treponemal lysis or an autoimmune reaction needs to be investigated.