Efficacy of daily supplementation of 800 IU vitamin D on vitamin D status at 6 months of age in term healthy Indian infants.

OBJECTIVES: Most authorities recommend daily supplementation of 400 IU vitamin D for all term healthy neonates throughout infancy, however this dose was shown to be inadequate in an earlier study from our institution. We planned to evaluate if supplementation of 800 IU/day in term Indian infants would reduce the prevalence of vitamin D insufficiency (VDI) at 6 months of age. METHODS: In a prospective study, we supplemented 800 IU/day of vitamin D in 70 term infants from birth till 6 months of age. Serum 25-hydroxy cholecalciferol [25(OH)D] was measured at birth and 6 months for all infants; and at 6, 10 and 14 weeks of age in subsets of 23 infants each. The primary outcome was prevalence of VDI (defined as serum 25(OH)D level < 50 nmol/L) at 6 months of age. RESULTS: A total of 58 out of 70 (83%) infants were followed up until 6 months of age. The median (nmol/L; IQR) serum 25(OH)D at birth and 6 months of age was 25 (12.5-35) and 92.5 (72.5-137.5), respectively. The prevalence of VDI at birth was 91.3% (63/69), which reduced to 6.9% (4/58) at 6 months of age. However, four infants (6.9%, 95% CI 1.9-16.7) developed vitamin D excess (serum 25(OH)D 250-375 nmol/L) requiring reduction of the dose of supplementation. No infant developed vitamin D toxicity (serum 25(OH)D > 375 nmol/L). CONCLUSIONS: Daily supplementation of 800 IU of vitamin D resulted in vitamin D sufficiency in most term healthy infants at 6 months of age but with potential risk of toxicity.

Complementary feeding at 4 versus 6 months of age for preterm infants born at less than 34 weeks of gestation: a randomised, open-label, multicentre trial.

BACKGROUND: Evidence on the optimal time to initiation of complementary feeding in preterm infants is scarce. We examined the effect of initiation of complementary feeding at 4 months versus 6 months of corrected age on weight for age at 12 months corrected age in preterm infants less than 34 weeks of gestation. METHODS: In this open-label, randomised trial, we enrolled infants born at less than 34 weeks of gestation with no major malformation from three public health facilities in India. Eligible infants were tracked from birth and randomly assigned (1:1) at 4 months corrected age to receive complementary feeding at 4 months corrected age (4 month group), or continuation of milk feeding and initiation of complementary feeding at 6 months corrected age (6 month group), using computer generated randomisation schedule of variable block size, stratified by gestation (30 weeks or less, and 31-33 weeks). Iron supplementation was provided as standard. Participants and the implementation team could not be masked to group assignment, but outcome assessors were masked. Primary outcome was weight for age Z-score at 12 months corrected age (WAZ12) based on WHO Multicentre Growth Reference Study growth standards. Analyses were by intention to treat. The trial is registered with Clinical Trials Registry of India, number CTRI/2012/11/003149. FINDINGS: Between March 20, 2013, and April 24, 2015, 403 infants were randomly assigned: 206 to receive complementary feeding from 4 months and 197 to receive complementary feeding from 6 months. 22 infants in the 4 month group (four deaths, two withdrawals, 16 lost to follow-up) and eight infants in the 6 month group (two deaths, six lost to follow-up) were excluded from analysis of primary outcome. There was no difference in WAZ12 between two groups: -1·6 (SD 1·2) in the 4 month group versus -1·6 (SD 1·3) in the 6 month group (mean difference 0·005, 95% CI -0·24 to 0·25; p=0·965). There were more hospital admissions in the 4 month group compared with the 6 month group: 2·5 episodes per 100 infant-months in the 4 month group versus 1·4 episodes per 100 infant-months in the 6 month group (incidence rate ratio 1·8, 95% CI 1·0-3·1, p=0·03). 34 (18%) of 188 infants in the 4 month group required hospital admission, compared with 18 (9%) of 192 infants in the 6 month group. INTERPRETATION: Although there was no evidence of effect for the primary endpoint of WAZ12, the higher rate of hospital admission in the 4 month group suggests a recommendation to initiate complementary feeding at 6 months over 4 months of corrected age in infants less than 34 weeks of gestation. FUNDING: Indian Council of Medical Research supported the study until Nov 14, 2015. Subsequently, Shuchita Gupta's salary was supported for 2 months by an institute fellowship from All India Institute Of Medical Sciences, and a grant by Wellcome Trust thereafter.

Phenobarbitone in Rh hemolytic disease of the newborn: a randomized double-blinded placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy of prophylactic oral phenobarbitone (PB) in neonates with Rh hemolytic disease of the newborn. STUDY DESIGN: In this double-blind randomized trial conducted in a tertiary care unit, we randomly allocated neonates with Rh hemolytic disease of the newborn born at or after 32 weeks' gestation to PB (10 mg/kg/day on day 1 followed by 5 mg/kg/day on days 2-5) (n = 23) or oral glucose (n = 21). The primary outcome was the duration of phototherapy. RESULTS: Baseline variables were comparable. There was no difference in the median duration of phototherapy [54 (range: 0-180) vs. 35 h (0-127); p = 0.39] and in the incidences of failure of phototherapy or significant rebounds of serum bilirubin. However, the proportion of infants with cholestasis was significantly lower in the PB group (0 vs. 19%; p = 0.04). CONCLUSIONS: PB does not reduce duration of phototherapy or its episodes. Its potential to reduce cholestasis needs validation in larger studies.

Poor zinc status in early infancy among both low and normal birth weight infants and their mothers in Delhi.

BACKGROUND: Low birth weight (LBW) infants are at high risk of zinc deficiency, but there is a paucity of data on their zinc status. OBJECTIVE: To evaluate zinc status of LBW (BW <2,500 g) and normal birth weight (NBW; BW ≥ 2,500 g) infants at birth and in early infancy. METHODS: A total of 339 infants (LBW, n = 220; NBW, n = 119) were enrolled, and venous blood samples of mother-infant dyad were taken within 48 h of birth. Infants' levels were repeated between 2 and 10 months of age. Serum zinc levels were estimated using an inductively coupled plasma mass spectrometer. Primary outcome was zinc deficiency, defined as serum zinc <65 µg/dl. RESULTS: Zinc results were available for 182 LBW and 103 NBW infants at birth and for 100 LBW and 66 NBW infants at follow-up with a median postnatal age of 14 and 15.5 weeks, respectively. Median zinc levels were low and comparable at birth as well as at follow-up, with zinc deficiency being present in 51.0% of LBW and 42.4% of NBW infants at birth and in 79.0% of LBW and 66.7% of NBW infants at follow-up. Zinc levels decreased significantly in both groups from birth to follow-up, irrespective of zinc multivitamin supplementation. Zinc levels of infants with BW <2,000 g at follow-up were significantly lower compared to infants with higher BW. CONCLUSION: Zinc status was poor in many infants at birth irrespective of BW. Zinc status worsened significantly during early infancy, with infants with BW <2,000 g having the lowest zinc levels.

Curcumin for maintenance of remission in ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory condition of the colon characterized by episodes of disease activity and symptom-free remission.There is paucity of evidence regarding the efficacy and safety of complementary or alternative medicines for the management of UC. Curcumin, an anti-inflammatory agent, has been used in many chronic inflammatory conditions such as rheumatoid arthritis, esophagitis and post-surgical inflammation. The efficacy of this agent for maintenance of remission in patients with UC has not been systematically evaluated. OBJECTIVES: The primary objective was to systematically review the efficacy and safety of curcumin for maintenance of remission in UC. SEARCH METHODS: A computer-assisted literature search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Inflammatory Bowel Disease Specialized Trial Register was performed on July 11, 2012 to identify relevant publications. Proceedings from major gastroenterology meetings and references from published articles were also searched to identify additional studies. SELECTION CRITERIA: Randomized placebo-controlled trials (RCT) of curcumin for maintenance of remission in UC were included. Studies included patients (of any age) who were in remission at the time of recruitment. Co-interventions were allowed. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed the methodological quality of the included studies using the Cochrane risk of bias tool. Data were analyzed using Review Manager (RevMan 5.1). We calculated the relative risk (RR) and 95% confidence interval (95% CI) for each dichotomous outcome. For continuous outcomes we calculated the mean difference (MD) and 95% CI. MAIN RESULTS: Only one trial (89 patients) fulfilled the inclusion criteria. This trial randomized 45 patients to curcumin and 44 patients to placebo. All patients received treatment with sulfasalazine or mesalamine. The study was rated as low risk of bias. Curcumin was administered orally in a dose of 2 g/day for six months. Fewer patients relapsed in the curcumin group than the placebo group at six months. Four per cent of patients in the curcumin group relapsed at six months compared to 18% of patients in the placebo group (RR 0.24, 95% CI 0.05 to 1.09; P = 0.06). There was no statistically significant difference in relapse rates at 12 months. Twenty-two per cent of curcumin patients relapsed at 12 months compared to 32% of placebo patients (RR 0.70, 95% CI 0.35 to 1.40; P = 0.31). A total of nine adverse events were reported in seven patients. These adverse events included sensation of abdominal bulging, nausea, transient hypertension, and transient increase in the number of stools. The authors did not report which treatment group the patients who experienced adverse events belonged to. The clinical activity index (CAI) at six months was significantly lower in the curcumin group compared to the placebo group (1.0 + 2.0 versus 2.2 + 2.3; MD -1.20, 95% CI -2.14 to -0.26). The endoscopic index (EI) at six months was significantly lower in the curcumin group than in the placebo group (0.8 + 0.6 versus 1.6 + 1.6; MD -0.80, 95% CI -1.33 to -0.27). AUTHORS' CONCLUSIONS: Curcumin may be a safe and effective therapy for maintenance of remission in quiescent UC when given as adjunctive therapy along with mesalamine or sulfasalazine. However, further research in the form of a large scale methodologically rigorous randomized controlled trial is needed to confirm any possible benefit of curcumin in quiescent UC.

Evaluation of phototherapy devices used for neonatal hyperbilirubinemia.

OBJECTIVE: To compare phototherapy devices based on their physical and photo-biological characteristics viz spectral properties, maximum and mean irradiance, treatable percentage of body surface area, decay of irradiance over time and in vitro photoisomerisation of bilirubin. DESIGN: In vitro experimental study. SETTING: Ocular pharmacy laboratory at a tertiary care hospital. METHODLOGY: All the characteristics were measured at a fixed distance of 35 cm from one compact fluorescent lamp (CFL) and three light emitting diode (LED) phototherapy devices in a dark room with an irradiance of <0.1uW/cm2/nm. Estimation of products of in vitro photoisomerisation was done using liquid chromatography - tandem mass spectroscopy (LC-MS/MS). RESULTS: The emission spectral data were comparable between the phototherapy devices. The devices, however, differed in their maximum irradiance with the spot and indigenous LED units having the highest and lowest values, respectively (56.5 and 16.8uW/cm2/nm). The mean irradiance measured in 5x5cm grids falling within the silhouette of a term baby of the spot and improvised LED devices were low (26.8uW/cm2/nm and 11.5uW/cm2/nm, respectively) possibly due to unevenness in the irradiance of light falling within the silhouette. There was a significant difference in the amount of bilirubin left after exposure to light over a 2hour time period (% reduction of bilirubin) among the four devices (P=0.001); at 120 minutes after exposure, the amount of bilirubin left was lowest for the CFL (16%) and spot LED (17%) devices and highest for the indigenous LED unit (41%). CONCLUSIONS: The four phototherapy devices differed markedly in their physical and photobiological characteristics. Since the efficacy of a device is dependent not only on the maximum irradiance but also on the mean irradiance, rate of decay of irradiance, and treatable surface area of the foot print of light, each phototherapy device should have these parameters verified and confirmed before being launched for widespread use.

Early iron supplementation in very low birth weight infants--a randomized controlled trial.

AIM: To evaluate if supplementing iron at 2 weeks of age improves serum ferritin and/or haematological parameters at 2 months of life in very low birth weight (VLBW) infants. METHODS: Preterm VLBW infants who received at least 100 mL/kg/day of oral feeds by day 14 of life were randomized to either 'early iron' (3-4 mg/kg/day orally from 2 weeks) or 'control' (no iron until 60 days) groups. Infants were followed up fortnightly and all morbidities were prospectively recorded. Serum ferritin was measured at 60 days by enzyme immunoassay method. RESULTS: Forty-six infants were included in the study; primary outcome was available for 42 infants.There was no difference in either serum ferritin (mean: 50.8 vs. 45.3 microg/L; adjusted difference in means: 5.8, 95% CI: -3.0, 14.6; p = 0.19) or haematocrit (32.5 +/- 5.3 vs. 30.8 +/- 6.3%; p = 0.35)at 60 days between the early iron and control groups. The magnitude of fall in serum ferritin from baseline to the end of study period was also not different between the groups (4.9 vs. 13.8 microg/L; difference in means: 8.8; 95% CI: -0.3, 17.9; p = 0.06). The requirement of blood transfusions (9.5 vs. 13%; p = 0.63) and a composite outcome of common neonatal morbidities (19% vs. 21.7%; p = 0.55) were also not different between the two groups. CONCLUSION: Supplementing iron at 2 weeks of age in preterm VLBW infants did not improve either serum ferritin or the haematological parameters at 2 months when compared to the standard practice of starting iron from 8 weeks of age.