Feasibility, Sustainability, and Effectiveness of the Implementation of "Facility-Team-Driven" Approach for Improving the Quality of Newborn Care in South India.

OBJECTIVES: The primary objective of the study was to assess the feasibility and sustainability of the implementation of the point of care quality improvement (POCQI) methodology for improving the quality of neonatal care at the level 2 special newborn care unit (SNCU). Additional objective was to evaluate the effectiveness of the quality improvement (QI) and preterm baby package training model. METHODS: This study was conducted in a level-II SNCU. The study period was divided into baseline; intervention and sustenance phases. The primary outcome i.e., feasibility was defined as completion of training for 80% or more health care professionals (HCPs) through workshops, their attendance in subsequent review meetings and, successful accomplishment of at least two plan-do-study-act (PDSA) cycles in each project. RESULTS: Of the total, 1217 neonates were enrolled during the 14 mo study period; 80 neonates in the baseline, 1019 in intervention and 118 in sustenance phases. Feasibility of training was achieved within a month of initiation of intervention phase; 22/24 (92%) nurses and 14/15 (93%) doctors attended the meetings. The outcomes of individual projects suggested an improvement in proportion of neonates being given exclusive breast milk on day 5 (22.8% to 78%); mean difference (95% CI) [55.2 (46.5 to 63.9)]. Neonates on any antibiotics declined, proportion of any enteral feeds on day one and duration of kangaroo mother care (KMC) increased. Proportion of neonates receiving intravenous fluids during phototherapy decreased. CONCLUSIONS: The present study demonstrates the feasibility, sustainability, and effectiveness of a facility-team-driven QI approach augmented with capacity building and post-training supportive supervision.

Fortification of Breast Milk With Preterm Formula Powder vs Human Milk Fortifier in Preterm Neonates: A Randomized Noninferiority Trial.

Importance: Fortification of expressed breast milk (EBM) using commercially available human milk fortifiers (HMF) increases short-term weight and length in preterm very low-birth-weight (VLBW) neonates. However, the high cost and increased risk of feed intolerance limit their widespread use. Preterm formula powder fortification (PTF) might be a better alternative in resource-limited settings. Objective: To demonstrate that fortification of EBM by preterm formula powder is noninferior to fortification by HMF, in terms of short-term weight gain, in VLBW neonates. Design, Setting, and Participants: Open-label, noninferiority, randomized trial conducted from December 2017 to June 2019 at a level 3 neonatal unit in India. The trial enrolled preterm (born at or before 34 weeks of gestation) VLBW neonates receiving at least 100 mL/kg/d of feeds and consuming 75% of milk or more as EBM. Interventions: Neonates were randomly assigned to receive fortification by either PTF or HMF. Calcium, phosphorus, iron, vitamin D, and multivitamins were supplemented in PTF and only vitamin D in the HMF group to meet the recommended dietary allowances. Main Outcomes and Measures: The primary outcome was the weight gain until discharge from the hospital or 40 weeks' postmenstrual age, whichever was earlier; the prespecified noninferiority margin was 2 g/kg/d. Secondary outcomes included morbidities such as necrotizing enterocolitis, feed intolerance, and extrauterine growth restriction (<10th percentile on the Fenton chart at 40 weeks' postmenstrual age). Results: Of the 123 neonates enrolled, 60 and 63 were randomized to the PTF and HMF groups, respectively. The mean gestation (30.5 vs 29.9 weeks) and birth weight (1161 vs 1119 g) were comparable between the groups. There was no difference in the mean (SD) weight gain between the PTF and HMF groups (15.7 [3.9] vs 16.3 [4.0] g/kg/d; mean difference, -0.5 g/kg/d; 95% CI, -1.9 to 0.7). The lower bound of 95% CI did not cross the noninferiority margin. The incidence of feed intolerance was lower in the PTF group (1.4 vs 6.8 per 1000 patient-days; incidence rate ratio 0.19; 95% CI, 0.04 to 0.95), and fewer neonates required withholding of fortification for 24 hours or more (5% vs 22%; risk ratio, 0.22; 95% CI, 0.07 to 0.75). The incidence of necrotizing enterocolitis stage II or more (0 vs 5%) and extrauterine growth restriction (73% vs 81%) was comparable between the groups. Conclusions and Relevance: Fortification with preterm formula powder is not inferior to fortification with human milk fortifiers in preterm neonates. Given the possible reduction in feed intolerance and lower costs, preterm formula might be a better option for fortification, especially in resource-restricted settings. Trial Registration: Clinical Trial Registry, India Identifier: CTRI/2017/11/010593.

Effect of Umbilical Cord Milking vs Delayed Cord Clamping on Venous Hematocrit at 48 Hours in Late Preterm and Term Neonates: A Randomized Controlled Trial.

OBJECTIVE: To compare the effect of intact umbilical cord milking (MUC) and delayed cord clamping (DCC) on venous hematocrit at 48 (±6) hours in late preterm and term neonates (350/7- 426/7 wk). STUDY DESIGN: Randomized trial. SETTING AND PARTICIPANTS: All late preterm and term neonates (350/7 - 426/7 wk) neonates born in the labor room and maternity operation theatre of tertiary care unit were included. INTERVENTION: We randomly allocated enrolled neonates to MUC group (cord milked four times towards the baby while being attached to the placenta; n=72) or DCC group (cord clamped after 60 seconds; n=72). OUTCOME: Primary outcome was venous hematocrit at 48 (±6) hours of life. Additional outcomes were venous hematocrit at 48 (±6) hours in newborns delivered through lower segment caesarean section (LSCS), incidence of polycythemia requiring partial exchange transfusion, incidence of hyperbilirubinemia requiring phototherapy, and venous hematocrit and serum ferritin levels at 6 (±1) weeks of age. RESULTS: The mean (SD) hematocrit at 48 (±6) hours in the MUC group was higher than in DCC group [57.7 (4.3) vs. 55.9 (4.4); P=0.002]. Venous hematocrit at 6 (±1) weeks was higher in MUC than in DCC group [mean (SD), 37.7 (4.3) vs. 36 (3.4); mean difference 1.75 (95% CI 0.53 to 2.9); P=0.005]. Other parameters were similar in the two groups. CONCLUSION: MUC leads to a higher venous hematocrit at 48 (±6) hours in late preterm and term neonates when compared with DCC.

Delayed cord clamping in Rh-alloimmunised infants: a randomised controlled trial.

Despite advancement in medical care, Rh alloimmunisation remains a major cause of neonatal hyperbilirubinaemia, neuro-morbidity, and late-onset anaemia. Delayed cord clamping (DCC), a standard care now-a-days, is yet not performed in Rh-alloimmunised infants due to paucity of evidence. Hence, we randomised these infants of 28- to 41-week gestation to delayed cord clamping (N = 36) or early cord clamping (N = 34) groups. The primary outcome variable was venous packed cell volume (PCV) at 2 h of birth. The secondary outcomes were incidence of double volume exchange transfusion (DVET) and partial exchange transfusion (PET), duration of phototherapy (PT), functional echocardiography (parameters measured: superior vena cava flow, M-mode fractional shortening, left ventricular output, myocardial perfusion index, and inferior vena cava collapsibility) during hospital stay, and blood transfusion (BT) until 14 weeks of life. Neonates were managed as per unit protocol. The baseline characteristics of enrolled infants were comparable between the groups. The median (IQR) gestation and mean (SD) birth weight of enrolled infants were 35 (33-37) weeks and 2440 (542) g, respectively. The DCC group had a higher mean PCV at 2 h of life (48.4 ± 9.2 vs. 43.5 ± 8.7, mean difference 4.9% (95% CI 0.6-9.1), p = 0.03). However, incidence of DVET and PET, duration of PT, echocardiography parameters, and BT until 14 weeks of postnatal age were similar between the groups.Conclusion: DCC in Rh-alloimmunised infants improved PCV at 2 h of age without significant adverse effects.Trial registration: Clinical Trial Registry of India (CTRI), Ref/2016/11/012572 http://ctri.nic.in/Clinicaltrials, date of trial registration 19.12.2016, date of first patient enrolment 1 January 2017.What is Known:•Delayed cord clamping improves haematocrit, results in better haemodynamic stability, and decreases the need of transfusion in early infancy.•However, due to lack of evidence, potential risk of hyperbilirubinaemia, and exacerbation of anaemia (following delayed cord clamping), early cord clamping is the usual norm in Rh-alloimmunised infantsinfants.What is New:•Delayed cord clamping in Rh-alloimmunised infants improves haematocrit at 2 h of life without any increase in incidence of serious adverse effects.

Mineral and bone physiology in the foetus, preterm and full-term neonates.

Mother is the major source of minerals in foetal life with placenta actively transporting against a concentration and electrochemical gradient. The foetal serum mineral concentration is thereby higher as compared to maternal values, which possibly help in its rapid accretion in developing bones and for counteracting postnatal fall in calcium levels at birth. Parathyroid hormone related peptide (PTHrP) and parathyroid hormone (PTH) play a major role in mineral physiology during foetal life with hormones like calcitriol, calcitonin, FGF-23 and sex steroids having minimal role. PTHrP and PTH also play a major role in endochondral bone formation and mineralization of skeleton. At the birth, as the cord is clamped, there is loss of active transport of minerals through placenta and the neonate has to rely on enteral intake of minerals to meet the demands of growing bones and metabolisms. The calcium levels fall after birth, reaching a nadir at 24-48 h and gradually rise to adult values over several days, probably resulting from a fall in PTHrP levels and hyporesponsiveness of parathyroid glands. As PTH and calcitriol levels increase postnatally, there is a rise in calcium levels with maturation in functioning of kidneys and intestines. However, there may be significant delay in intestinal maturation in preterm infants along with an increased demand for mineral accretion, which predispose them to osteopenia of prematurity.

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.

Iron Stores in Term and Late Preterm Small for Gestational Age and Appropriate for Gestational Age Neonates at Birth and in Early Infancy.

OBJECTIVE: To compare body iron stores in late preterm and term small for gestational age (SGA) infants with gestation matched appropriate-for-gestational age (AGA) infants at birth and at 2 mo of age. METHODS: In this prospective observational study, live births of 34-42 wk gestation and SGA (<10th centile for GA) were enrolled along with gestation matched AGA (10th-90th centile for GA) infants. Infants' blood samples were taken within 2 h of delivery, and repeated at 60 ± 7 d of life. Primary outcome was serum ferritin at birth and 60 d of age. Secondary outcomes were hematocrit at birth and 60 d and need for transfusion until 60 d of life. RESULTS: A total of 37 SGA (gestation 37.2 ± 1.9 wk, birth weight 1861 ± 401 g) and 30 AGA infants (gestation 37.3 ± 1.9 wk, birth weight 2607 ± 405 g) were enrolled in the study. There was no difference in the serum ferritin between AGA and SGA infants at birth {median [IQR]: 254.0 [214.3-293.8] vs. 259.7 [217.8-301.5] µg/L; p = 0.85} or 60 d of life {147.2 [101.4-193.0] vs. 155.0 [106.6-203.6] µg/L; p = 0.81}. Mean hematocrit was 55.5 ± 9.6 vs. 52.4 ± 5.0 at birth (p = 0.10) and 32.1 ± 4.9 vs. 31.6 ± 3.8 at 60 d (p = 0.77) in SGA and AGA infants respectively. No infant required blood transfusion during the study period. CONCLUSIONS: Iron stores of late preterm and term SGA infants are comparable to term AGA infants at birth and 2 mo of age. Recommendations on iron supplementation to these infants need to be formulated through appropriately designed randomized trials.

Topical Oil Application and Trans-Epidermal Water Loss in Preterm Very Low Birth Weight Infants-A Randomized Trial.

OBJECTIVE: Topical emollient application reduces trans-epidermal water loss (TEWL) in preterm neonates. Coconut oil used traditionally for infant massage in India has not been evaluated for the same. PATIENTS AND METHODS: Very low birth weight (VLBW) neonates were randomized at 12 h of age to Oil (n = 37) or Control (n = 37) groups. Oil group neonates received twice-daily coconut oil application without massage, and Control group received standard care. TEWL was measured every 12 h using an evaporimeter till Day 7 when skin swabs were obtained for bacterial growth and skin condition was assessed using a validated score. RESULTS: Birth weight (g; mean ± SD: 1213 + 214 vs. 1164 + 208, p = 0.31), gestation [week; median (interquartile range): 32 (31-33) vs. 32 (29-33), p = 0.10] and other baseline variables were comparable. TEWL was significantly reduced (g/m(2)/h, mean difference: -6.80, 95% confidence interval: -3.48, -10.15; p < 0.01) with better skin condition and lower bacterial growth in the Oil group (20% vs. 60%, p < 0.01). CONCLUSION: Coconut oil application reduced TEWL without increasing skin colonization in VLBW neonates. CLINICAL TRIALS REGISTRATION: NCT01758068.

Oral zinc for the prevention of hyperbilirubinaemia in neonates.

BACKGROUND: Between 6% and 15% of neonates develop hyperbilirubinaemia requiring treatment. Successful management of neonatal hyperbilirubinaemia relies on prevention and early treatment, with phototherapy being the mainstay of treatment. Oral zinc has been reported to decrease the serum total bilirubin (STB), presumably by decreasing the enterohepatic circulation. OBJECTIVES: To determine the effect of oral zinc supplementation compared to placebo or no treatment on the incidence of hyperbilirubinaemia in neonates during the first week of life and to assess the safety of oral zinc in enrolled neonates. SEARCH METHODS: We searched CENTRAL (The Cochrane Library 2014, Issue 1), MEDLINE (1966 to November 30, 2014), and EMBASE (1990 to November 30, 2014). SELECTION CRITERIA: Randomised controlled trials were eligible for inclusion if they enrolled neonates (term and preterm) to whom oral zinc, in a dose of 10 to 20 mg/day, was initiated within the first 96 hours of life, for any duration until day seven, compared with no treatment or placebo. DATA COLLECTION AND ANALYSIS: We used the standard methods of The Cochrane Collaboration and its Neonatal Review Group for data collection and analysis. MAIN RESULTS: Only one study met the criteria of inclusion in the review. This study compared oral zinc with placebo. Oral zinc was administered in a dose of 5 mL twice daily from day 2 to day 7 postpartum. The drug was administered into the mouth of the infant by the plastic measure provided with the bottle or with a spoon. Incidence of hyperbilirubinaemia, defined as serum total bilirubin (STB) ≥ 15 mg/dL, was similar between groups (N = 286; risk ratio (RR) 0.94, 95% confidence interval (CI) 0.58 to 1.52). Mean STB levels, mg/dL, at 72 ± 12 hours were comparable in both the groups (N = 286; mean difference (MD) -0.20; 95% CI -1.03 to 0.63). Although the duration of phototherapy in the zinc group was significantly shorter compared to the placebo group (N = 286; MD -12.80, 95% CI -16.93 to -8.67), the incidence of need for phototherapy was comparable across both the groups (N = 286; RR 1.20; 95% CI 0.66 to 2.18). Incidences of side effects like vomiting (N = 286; RR 0.65, 95% CI 0.19 to 2.25), diarrhoea (N = 286; RR 2.92, 95% CI 0.31 to 27.71), and rash (N = 286; RR 2.92, 95% CI 0.12 to 71.03) were found to be rare and statistically comparable between groups. AUTHORS' CONCLUSIONS: The limited evidence available has not shown that oral zinc supplementation given to infants up to one week old reduces the incidence of hyperbilirubinaemia or need for phototherapy.

Trial of daily vitamin D supplementation in preterm infants.

OBJECTIVE: To compare the effect of 800 vs 400 IU of daily oral vitamin D3 on the prevalence of vitamin D deficiency (VDD) at 40 weeks' postmenstrual age (PMA) in preterm infants of 28 to 34 weeks' gestation. METHODS: In this randomized double-blind trial, we allocated eligible infants to receive either 800 or 400 IU of vitamin D3 per day (n = 48 in both groups). Primary outcome was VDD (serum 25-hydroxyvitamin D levels <20 ng/mL) at 40 weeks' PMA. Secondary outcomes were VDD, bone mineral content, and bone mineral density at 3 months' corrected age (CA). RESULTS: Prevalence of VDD in the 800-IU group was significantly lower than in the 400-IU group at 40 weeks (38.1% vs. 66.7%; relative risk: 0.57; 95% confidence interval: 0.37-0.88) and at 3 months' CA (12.5% vs. 35%; relative risk: 0.36; 95% confidence interval: 0.14-0.90). One infant (2.4%) in the 800-IU group had vitamin D excess (100-150 ng/mL). Bone mineral content (mean ± SD: 79.6 ± 16.8 vs. 84.7 ± 20.7 g; P = .27) and bone mineral density (0.152 ± 0.019 vs. 0.158 ± 0.021 g/cm2; P = .26) were not different between the 2 groups. CONCLUSIONS: Daily supplementation with 800 IU of vitamin D reduces the prevalence of VDD at 40 weeks' PMA and at 3 months' CA in preterm infants without showing any improvement in bone mineralization. However, there is a possibility that this dose may occasionally result in vitamin D excess.

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.

Vitamin D status of low birth weight infants in Delhi: a comparative study.

OBJECTIVE: To evaluate vitamin D status of preterm and term low birthweight (LBW) and term normal birth weight (NBW; weight ≥ 2500 g) infants at birth and in early infancy. METHODS: We enrolled 220 LBW and 119 NBW infants along with their mothers. Blood samples of both infants and mothers were taken within 48 h of birth, and that of infants were repeated at 3 months. Serum levels of calcium, phosphate, alkaline phosphatase, 25 hydroxyvitamin D (25OHD) and parathormone (PTH) were estimated using standard tests. Our primary outcome was vitamin D deficiency (VDD; serum 25OHD <20 ng/ml in mothers and <15 ng/ml in infants). Other outcomes were raised PTH (>46 pg/ml), raised AlkP (>120 U/l in mothers and 420 U/l in infants), and clinical rickets. FINDINGS: VDD was present in 186 (87.3%) of LBW and 103 (88.6%) of NBW infants at birth, and in 77 (60.6%) of LBW and 55 (71.6%) of NBW infants at a median corrected age of 12 and 15 weeks, respectively. VDD was almost universal (93-97%) among mothers of both groups. Raised PTH was present in 138 (63.6%) of LBW and 48 (41.4%) of NBW infants at birth, and in 58 (45.7%) of LBW and 38 (49.3%) of NBW infants at follow-up. Clinical rickets was present in 17 (13.4%) of LBW and 4 (4.9%) of NBW infants at 12-14 weeks of corrected age. CONCLUSIONS: High prevalence of VDD in LBW as well as NBW infants with clinical rickets at an early age underlines the need to study the effect of various vitamin D supplementation regimens in these infants to identify the optimal dose.

Efficacy of zinc in reducing hyperbilirubinemia among at-risk neonates: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy of oral zinc salt on the incidence of hyperbilirubinemia and need for phototherapy between 25 and 168 h of age in term and late-preterm at-risk neonates cared at a tertiary care hospital in New Delhi, India. METHODS: In all neonates born at ≥35 wks' gestation, serum total bilirubin (STB) was assayed at 24 ± 6 h of age. At-risk neonates, neonates with STB levels ≥6 mg/dL, were given either 10 mg of zinc gluconate salt (n = 148) or placebo (n = 146) in twice daily doses till day seven of age. Jaundice was assessed clinically and STB was measured by spectrophotometry. Neonates were followed up until day seven of age. Primary outcome measure was incidence of hyperbilirubinemia (STB ≥ 15 mg/dl). Secondary outcome measures were mean STB level at 72 ± 12 h of age, proportion of infants requiring phototherapy, and duration there of. RESULTS: Risk factors for hyperbilirubinemia, including male gender, gestational age, birth-weight, incidence of birth trauma, ABO incompatibility, hyperbilirubinemia in previous sib, etc. were comparable in zinc and placebo groups. The incidence of hyperbilirubinemia was comparable in both the groups (17.9% vs 19.1% in zinc and placebo groups respectively; OR = 0.95, 95% CI: 0.50 to 1.67; P = 0.92). The requirement of phototherapy (14.5% and 12.0% in zinc and placebo groups respectively; OR = 1.24, 95% CI: 0.95 to 2.6; P = 0.54) was comparable in both the groups; however, duration of phototherapy was shorter in zinc group (duration in hours, 22.8 ± 19.4 vs 35.6 ± 16.1 in zinc and placebo group respectively; mean difference = -12.8, 95% CI: -24.73 to -0.92; P = 0.04). There was no difference in the mean STB levels at 72 ± 12 h of age between zinc and placebo groups (mean difference in mg/dL: 0.20, 95% CI: 1.0 to -0.64). No significant adverse effects related to oral zinc administration were noted. CONCLUSIONS: Twice daily administration of oral zinc in a dose of 10 mg/day does not reduce the incidence of hyperbilirubinemia in at-risk term and late-preterm neonates during first wk of age.

Vitamin D deficiency in healthy breastfed term infants at 3 months & their mothers in India: seasonal variation & determinants.

BACKGROUND & OBJECTIVES: Vitamin D deficiency with a resurgence of rickets and tetany are increasingly being reported in young infants from temperate regions, African Americans and also from India. The data on vitamin D status of healthy term breastfed Indian infants and mothers are scant. Therefore, we undertook this study to determine the prevalence of vitamin D deficiency and insufficiency [serum 25 hydroxyvitamin D (25OHD) ≤ 15 ng/ml and 15-20 ng/ml, respectively] among healthy term breastfed 3 month old infants and their mothers, evaluate for clinical and radiological rickets in those infants having 25OHD < 10 ng/ml, and check for seasonal variation and predictors of infants' vitamin D status. METHODS: A total of 98 infants aged 2.5 to 3.5 months, born at term with appropriate weight and their mothers were enrolled; 47 in winter (November- January) and 51 in summer (April-June). Details of infants' feeding, vitamin D supplementation, sunlight exposure and mothers' calcium and vitamin D intake were recorded. Serum calcium, phosphate, alkaline phosphatase, 25 hydroxyvitamin D (25OHD) and parathormone were estimated. RESULTS: Vitamin D deficiency was found in 66.7 per cent of infants and 81.1 per cent of mothers; and insufficiency in an additional 19.8 per cent of infants and 11.6 per cent of mothers. Radiological rickets was present in 30.3 per cent of infants with 25OHD < 10 ng/ml. 25OHD did not show seasonal variation in infants but maternal concentrations were higher in summer [11.3 (2.5 - 31) ng/ml] compared to winter [5.9 (2.5-25) ng/ml, P=0.003]. Intake of vitamin supplement, sunlight exposure and mother's 25OHD were predictors of infants' 25OHD levels. INTERPRETATION & CONCLUSIONS: Prevalence of vitamin D deficiency and insufficiency was found to be high in breastfed infants and their mothers, with radiological rickets in a third of infants with 25OHD < 10 ng/ml in this study. Studies with large sample need to be done in different parts of the country to confirm these findings.

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.

Hypocalcemia in the newborn.

Hypocalcemia is a frequently observed clinical and laboratory abnormality in neonates. Ionic calcium is crucial for many biochemical processes including blood coagulation, neuromuscular excitability, cell membrane integrity, and many of the cellular enzymatic activities. Healthy term infants undergo a physiological nadir in serum calcium levels by 24-48 h of age. This nadir may drop to hypocalcemic levels in high-risk neonates including infants of diabetic mothers, preterm infants and infants with perinatal asphyxia. The early onset hypocalcemia which presents within 72 h requires treatment with calcium supplementation for at least 72 h. In contrast, late onset hypocalcemia usually presents after 7 days and requires longer term therapy.

Transcutaneous bilirubin levels in healthy term and late preterm Indian neonates.

OBJECTIVE: To provide normative data for transcutaneous bilirubin (TcB) measurements in healthy term and late-preterm Indian neonates during first 72 h of age using a multiwavelength reflectance transcutaneous bilimeter. METHODS: TcB measurements were performed in healthy neonates (gestation 35 wk), in a well-baby ward, using a multiwavelength transcutaneous bilimeter (BiliCheck, SpectRx Inc, Norcross, GA). Age-specific percentiles values for each 6-h epoch starting at 0 h of age were calculated and an age-specific TcB nomogram was developed using different percentile values. Diagnostic ability of each percentile curve for prediction of hyperbilirubinemia, defined as requirement of phototherapy, was calculated. RESULTS: We performed 925 TcB measurements on 625 healthy newborn infants (gestation: 35 to 41 wk; age: 0 to 72 h; mean birth weight: 2808+/-437 g). TcB increased in a linear manner with maximum rate of rise observed during first 24 h of age (50th percentile: 0.22 mg/dL/h). 50th percentile curve of age-specific TcB nomogram had high negative predictive value (99.8%) and acceptable positive predictive value (16.4%) for prediction of hyperbilirubinemia. CONCLUSION: We provided age-specific nomogram of TcB for first 72 h of age in healthy term and late-preterm Indian neonates. Percentile curves and rate of rise in TcB may help in identification of neonates at low-risk of development of hyperbilirubinemia facilitating their safer discharge from the hospital. Diagnostic utility of this nomogram for predicting hyperbilirubinemia needs to be tested in a separate validation cohort.

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.