Kangaroo mother care for preterm or low birth weight infants: a systematic review and meta-analysis.

IMPORTANCE: The Cochrane review (2016) on kangaroo mother care (KMC) demonstrated a significant reduction in the risk of mortality in low birth weight infants. New evidence from large multi-centre randomised trials has been available since its publication. OBJECTIVE: Our systematic review compared the effects of KMC vs conventional care and early (ie, within 24 hours of birth) vs late initiation of KMC on critical outcomes such as neonatal mortality. METHODS: Eight electronic databases, including PubMed®, Embase, and Cochrane CENTRAL, from inception until March 2022, were searched. All randomised trials comparing KMC vs conventional care or early vs late initiation of KMC in low birth weight or preterm infants were included. DATA EXTRACTION AND SYNTHESIS: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered with PROSPERO. MAIN OUTCOMES AND MEASURES: The primary outcome was mortality during birth hospitalization or 28 days of life. Other outcomes included severe infection, hypothermia, exclusive breastfeeding rates, and neurodevelopmental impairment. Results were pooled using fixed-effect and random-effects meta-analyses in RevMan 5.4 and Stata 15.1 (StataCorp, College Station, TX). RESULTS: In total, 31 trials with 15 559 infants were included in the review; 27 studies compared KMC with conventional care, while four compared early vs late initiation of KMC. Compared with conventional care, KMC reduces the risks of mortality (relative risk (RR) 0.68; 95% confidence interval (CI) 0.53 to 0.86; 11 trials, 10 505 infants; high certainty evidence) during birth hospitalisation or 28 days of age and probably reduces severe infection until the latest follow-up (RR 0.85, 95% CI 0.79 to 0.92; nine trials; moderate certainty evidence). On subgroup analysis, the reduction in mortality was noted irrespective of gestational age or weight at enrolment, time of initiation, and place of initiation of KMC (hospital or community); the mortality benefits were greater when the daily duration of KMC was at least 8 hours per day than with shorter-duration KMC. Studies comparing early vs late-initiated KMC demonstrated a reduction in neonatal mortality (RR 0.77, 95% CI 0.66 to 0.91; three trials, 3693 infants; high certainty evidence) and a probable decrease in clinical sepsis until 28-days (RR 0.85, 95% CI 0.76 to 0.96; two trials; low certainty evidence) following early initiation of KMC. CONCLUSIONS AND RELEVANCE: The review provides updated evidence on the effects of KMC on mortality and other critical outcomes in preterm and low birth weight infants. The findings suggest that KMC should preferably be initiated within 24 hours of birth and provided for at least 8 hours daily.

Effect of whole-body massage on growth and neurodevelopment in term healthy newborns: A systematic review.

Background: Infant massage is commonly practiced in many parts of the world. However, the effectiveness of this intervention has not been reviewed for term, healthy newborns. Methods: This systematic review of randomized and quasi-randomized controlled trials assessed the effect of whole-body massage with or without oil, compared to no massage in term healthy newborns. Key outcomes were neonatal mortality, systemic infections, growth, behaviour (crying or fussing time, sleep duration), and neurodevelopment. We searched MEDLINE via PubMed, Cochrane CENTRAL, EMBASE, and CINAHL (updated till November 2021), and clinical trials databases and reference lists of retrieved articles. Two authors separately evaluated the risk of bias, extracted data, and synthesized effect estimates using mean difference (MD) and standardized mean difference (SMD). The GRADE approach was used to assess the certainty of evidence. Results: We included 31 randomized and quasi-randomized trials involving 3860 participants. Infant massage was performed by different care providers starting in the neonatal period and continuing for 1-2 months in most studies. Thirteen studies reported the use of oil with body massage. No study reported neonatal mortality or systemic infections. Meta-analyses suggested that whole-body massage may increase infant length at the end of the intervention period (median assessment age 6 weeks; mean difference (MD) = 1.6 cm, 95% confidence interval (CI) = 1.4 to 1.7 cm; low certainty evidence), but the effect on weight (MD = 340 g, 95% CI = 240 to 441 g), head circumference (MD = 0.8 cm, 95% CI = 0.6 to 1.1 cm), sleep duration (MD = 0.62 hours/d, 95% CI = 0.12 to 1.12 hours/d) and bilirubin levels (MD = -31.8 mmol/L or -1.8 mg/dL, 95% CI = -23.5 to -40.0 mmol/L) was uncertain. The effect on crying/fussing time at median 3 months of age, sleep duration at 6 months of age, weight, length, and head circumference at 6-12 months follow-up, and neurodevelopment outcomes, both at the end of the intervention period and follow-up was uncertain. Conclusions: Whole-body massage may improve the infant length at the end of the intervention period (median age 6 weeks, range 1-6 months) but the effect on other short- or long-term outcomes is uncertain. There is a need for further well-designed trials in future. Registration: Priyadarshi M, Balachander B, Rao S, Gupta S, Sankar MJ. Effect of body massage on growth and neurodevelopment in term healthy newborns: a systematic review. PROSPERO 2020 CRD42020177442.

Timing of first bath in term healthy newborns: A systematic review.

Background: This systematic review of intervention trials and observational studies assessed the effect of delaying the first bath for at least 24 hours after birth, compared to conducting it within the first 24 hours, in term healthy newborns. Methods: We searched MEDLINE via PubMed, Cochrane CENTRAL, Embase, CINAHL (updated till November 2021), and clinical trials databases and reference lists of retrieved articles. Key outcomes were neonatal mortality, systemic infections, hypothermia, hypoglycaemia, and exclusive breastfeeding (EBF) rates. Two authors separately evaluated the risk of bias, extracted data, and synthesized effect estimates using relative risk (RR) or odds ratio (OR). The GRADE approach was used to assess the certainty of evidence. Results: We included 16 studies (two trials and 14 observational studies) involving 39 020 term or near-term healthy newborns. Delayed and early baths were defined variably in the studies, most commonly as >24 hours (six studies) and as ≤6 hours (12 studies), respectively. We performed a post-hoc analysis for studies that defined early bath as ≤6 hours. Low certainty evidence suggested that bathing the newborn 24 hours after birth might reduce the risk of infant mortality (OR = 0.46, 95% confidence interval (CI) = 0.28 to 0.77; one study, 789 participants) and neonatal hypothermia (OR = 0.50, 95% CI = 0.28-0.88; one study, 660 newborns), compared to bathing within first 24 hours. The evidence on the effect on EBF at discharge was very uncertain. Delayed bath beyond 6 hours (at or after nine, 12, or 24 hours) after birth compared to that within 6 hours might reduce the risk of hypothermia (OR = 0.47, 95% CI = 0.36-0.61; four studies, 2711 newborns) and hypoglycaemia (OR = 0.39, 95% CI = 0.23-0.66; three studies, 2775 newborns) and improve the incidence of EBF at discharge (OR = 1.12, 95% CI = 1.08-1.34; six studies, 6768 newborns); the evidence of the effect on neonatal mortality was very uncertain. Conclusion: Delayed first bath for at least 24 hours may reduce infant mortality and hypothermia. Delayed bath for at least 6 hours may prevent hypothermia and hypoglycaemia and improve EBF rates at discharge. However, most of these conclusions are limited by low certainty evidence. Registration: PROSPERO 2020 CRD42020177430.

COVID-19 infection, and reinfection, and vaccine effectiveness against symptomatic infection among health care workers in the setting of omicron variant transmission in New Delhi, India.

Background: Surge of SARS CoV-2 infections ascribed to omicron variant began in December 2021 in New Delhi. We determined the infection and reinfection density in a cohort of health care workers (HCWs) along with vaccine effectiveness (VE) against symptomatic infection within omicron transmission period (considered from December 01, 2021 to February 25, 2022. Methods: This is an observational study from the All India Institute of Medical Sciences, New Delhi. Data were collected telephonically. Person-time at risk was counted from November 30, 2021 till date of infection/ reinfection, or date of interview. Comparison of clinical features and severity was done with previous pandemic periods. VE was estimated using test-negative case-control design [matched pairs (for age and sex)]. Vaccination status was compared and adjusted odds ratios (OR) were computed by conditional logistic regression. VE was estimated as (1-adjusted OR)X100-. Findings: 11474 HCWs participated in this study. The mean age was 36⋅2 (±10⋅7) years. Complete vaccination with two doses were reported by 9522 (83%) HCWs [8394 (88%) Covaxin and 1072 Covishield (11%)]. The incidence density of all infections and reinfection during the omicron transmission period was 34⋅8 [95% Confidence Interval (CI): 33⋅5-36⋅2] and 45⋅6 [95% CI: 42⋅9-48⋅5] per 10000 person days respectively. The infection was milder as compared to previous periods. VE was 52⋅5% (95% CI: 3⋅9-76⋅5, p = 0⋅036) for those who were tested within 14-60 days of receiving second dose and beyond this period (61-180 days), modest effect was observed. Interpretation: Almost one-fifth of HCWs were infected with SARS CoV-2 during omicron transmission period, with predominant mild spectrum of COVID-19 disease. Waning effects of vaccine protection were noted with increase in time intervals since vaccination. Funding: None.

Bed sharing versus no bed sharing for healthy term neonates.

BACKGROUND: There is great global variation in the sleeping arrangements for healthy newborn infants. Bed sharing is a type of sleeping practice in which the sleeping surface (e.g. bed, couch or armchair, or some other sleeping surface) is shared between the infant and another person. The possible physiological benefits include better oxygen and cardiopulmonary stability, fewer crying episodes, less risk of hypothermia, and a longer duration of breastfeeding. On the other hand, the most important harmful effect of bed sharing is that it may increase the risk of sudden infant death syndrome (SIDS). Studies have found conflicting evidence regarding the safety and efficacy of bed sharing during infancy. OBJECTIVES: To evaluate the efficacy and safety of bed sharing, started during the neonatal period, on breastfeeding status (exclusive and total duration of breastfeeding), incidence of SIDS, rates of hypothermia, neonatal and infant mortality, and long-term neurodevelopmental outcomes. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2020, Issue 7) in the Cochrane Library; MEDLINE via PubMed (1966 to 23 July 2020), CINAHL (1982 to 23 July 2020), and LILACS (1980 to 23 July 2020). We also searched clinical trials databases, and the reference lists of retrieved articles, for randomised controlled trials (RCTs) and quasi-RCTS. SELECTION CRITERIA: We planned to include RCTs or quasi-RCTs (including cluster-randomised trials) that included term neonates initiated on bed sharing within 24 hours of birth (and continuing to bed share with the mother in the first four weeks of life, followed by a variable time period thereafter), and compared them to a 'no bed sharing' group. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as recommended by Cochrane. We planned to use the GRADE approach to assess the certainty of evidence. MAIN RESULTS: Our search strategy yielded 6231 records. After removal of duplicate records, we screened 2745 records by title and abstract. We excluded 2739 records that did not match our inclusion criteria. We obtained six full-text studies for assessment. These six studies did not meet the eligibility criteria and were excluded. AUTHORS' CONCLUSIONS: We did not find any studies that met our inclusion criteria. There is a need for RCTs on bed sharing in healthy term neonates that directly assess efficacy (i.e. studies in a controlled setting, like hospital) or effectiveness (i.e. studies conducted in community or home settings) and safety. Future studies should assess outcomes such as breastfeeding status and risk of SIDS. They should also include neonates from high-income countries and low- and middle-income countries, especially those countries where bed sharing is more prevalent because of cultural practices (e.g. Asian countries).

'Lip-to-Tip' study: comparison of three methods to determine optimal insertion length of endotracheal tube in neonates.

The aim of this prospective observational study was to compare the incidence of endotracheal tube (ETT) malposition using weight-based (Tochen), gestation-based (Kempley), and nasotragal length (NTL) methods in deceased neonates and fresh stillbirths. We enrolled deceased neonates and fresh stillbirths within 2 ± 1 h of death or delivery, respectively; without hydrops, tracheostomy or major congenital anomalies affecting face, neck, or thorax. Each enrolled subject was intubated orotracheally, with lip-to-tip distance determined by three methods in random succession. Chest X-ray was acquired after each insertion. The primary outcome was proportion of malpositioned ETTs on chest X-ray (defined as ETT tip not lying between upper border of T1 and lower border of T2 vertebrae), assessed by two experts masked to the methods used. The proportion of malpositioned tubes was not significantly different with any of the three methods: (weight 27/50 (54%), gestation 35/50 (70%), and NTL 35/50 (70%), p value 0.055). The malpositioned tubes were too far in (87/150; 58%) than too far out (10/150; 6.7%).Conclusions: None of the currently recommended methods accurately predicts optimal ETT length in neonates. There is an urgent need for newer bedside modalities for estimating ETT position in neonates. What is known? • NRP guidelines recommend gestation-based and nasotragal length (NTL) methods to estimate initial ETT depth in neonates. Weight-based (Tochen) method is still widely used in neonatal units for ETT depth estimation. Evidence till date has not proven superiority of one method over the other. What is new? • All three methods for ETT depth estimation (Tochen, gestation-based, and NTL) resulted in high rates of ETT malposition in neonates. Formulae, devised from this study based on linear regression models, did not perform well for estimation of optimal ETT position.

Effect of home-based newborn care on neonatal and infant mortality: a cluster randomised trial in India.

BACKGROUND: Home-based newborn care has been found to reduce neonatal mortality in rural areas. Study evaluated effectiveness of home-based care delivered by specially recruited newborn care workers- Shishu Rakshak (SR) and existing workers- anganwadi workers (AWW) in reducing neonatal and infant mortality rates. METHODS: This three-arm, community-based, cluster randomised trial was conducted in five districts in India. Intervention package consisted of pregnancy surveillance, health education, care at birth, care of normal/low birthweight neonates, identification and treatment of sick neonates and young infants using oral and injectable antibiotics and community mobilisation. The package was similar in both intervention arms-SR and AWW; difference being healthcare provider. The control arm received routine health services from the existing health system. Primary outcomes were neonatal and young infant mortality rates at 'endline' period (2008-2009) assessed by an independent team from January to April 2010 in the study clusters. FINDINGS: A total of 6623, 6852 and 5898 births occurred in the SR, AWW and control arms, respectively, during the endline period; the proportion of facility births were 69.0%, 64.4% and 70.6% in the three arms. Baseline mortality rates were comparable in three arms. During the endline period, the risk of neonatal mortality was 25% lower in the SR arm (adjusted OR 0.75, 95% CI 0.57 to 0.99); the risks of early neonatal mortality, young infant mortality and infant mortality were also lower by 32%, 27%, and 33%, respectively. The risks of neonatal, early neonatal, young infant, infant mortality in the AWW arm were not different from that of the control arm. INTERPRETATION: Home-based care is effective in reducing neonatal and infant mortality rates, when delivered by a dedicated worker, even in settings with high rates of facility births. TRIAL REGISTRATION NUMBER: The study was registered with Clinical Trial Registry of India (CTRI/2011/12/002181).

Outcome of extremely low birth weight (ELBW) infants from a birth cohort (2013-2018) in a tertiary care unit in North India.

OBJECTIVE: To evaluate mortality and short-term morbidities in extremely low birth weight (ELBW) infants (<1000 g) in a birth cohort in North India. METHODS: In-hospital data of 231 ELBW infants (Jan 2013 to Sept 2018) were collected from a prospectively maintained electronic database by using standard definitions. RESULTS: The mean (SD) gestation and birth weight were 27.9 (2.2) weeks and 783 (133) g, respectively. Major morbidities included respiratory distress syndrome (n = 132, 57%), moderate-to-severe bronchopulmonary dysplasia (n = 62, 26.8%), hemodynamically significant patent ductus arteriosus (n = 65, 28%), intracranial hemorrhage ≥ grade II (n = 38, 16%), and culture-positive sepsis (n = 44, 19%). Median (IQR) duration of hospital stay (survivors) was 50 (17-79) days. The overall survival was 62%. On logistic regression, severe birth asphyxia, gestation ≤26 weeks, and respiratory distress syndrome were major predictors of mortality. CONCLUSION: In the current ELBW cohort, nearly two-thirds survived until discharge, who had considerable morbidities needing prolonged hospital stay. This study can be utilized for counseling and planning of care of ELBW infants in similar settings.

Quality improvement initiative for reduction of false alarms from multiparameter monitors in neonatal intensive care unit.

INTRODUCTION: Unnecessary and excessive activation of alarms ("false alarm") in neonatal intensive care unit (NICU) often results in alarm fatigue among health-care professionals, which can potentially result in deleterious effects in sick neonates. AIMS AND OBJECTIVES: The aim of this study is to reduce the frequency of false alarms from multiparameter monitors (MPM) by 50% from the existing baseline level over a period of 12 weeks. METHODS: In this quality improvement (QI) project conducted over 1 year (November 2016-October 2017) at All India Institute of Medical Sciences, New Delhi, we collected data on activation of false alarms from MPM (outcome measure) over a period of 2 months in 134 randomly selected observations of 1-h duration (baseline phase [10 days, 20 observations] and developing and testing the changes in five Plan-Do-study-Act (PDSA) cycles over the next 50 days, 114 observations. We also measured the pre- and postassessment of knowledge level in use of MPM among health-care professionals using checklist (process measure). Following that, we continued data collection for next 10 months to check sustenance of the project. RESULTS: Baseline characteristics including gestation, birth weight, and sickness level did not vary during the study period. The median (range) number of activation of false alarms/hour/MPM was 23 (18-35) in the baseline phase. This reduced to 22 (17-30), 19 (15-30), 16 (14-30), 14 (8-17), and 9 (6-12) at the end of 1st, 2nd, 3rd, 4th, and 5th PDSA cycles, respectively. In sustenance phase, it could be maintained in target range from January 2017 to October 2017. CONCLUSIONS: Small sustained changes can contribute a lot in continuous QI in decreasing false alarms and subsequent improvement of neurodevelopmental outcomes discharged neonates.

Congenital sigmoid mesocolic defect as a cause of neonatal intestinal obstruction.

Internal herniation through congenital sigmoid mesocolic defect as a cause of neonatal intestinal obstruction is rarely reported. Clinical judgement combined with judicious use of investigations and prompt exploration is essential to provide immediate relief of the obstruction and salvage the herniated loop of bowel, which otherwise might lead to morbidity and even death. We present a neonate with internal herniation of the ileum through a congenital mesocolic defect which was diagnosed by a prompt abdominal exploration in view of persistent clinical signs of intestinal obstruction. The relevant literature is also discussed highlighting the rarity of neonatal presentation of sigmoid mesocolic defect.

Improving quality of care during childbirth in primary health centres: a stepped-wedge cluster-randomised trial in India.

BACKGROUND: Low/middle-income countries need a large-scale improvement in the quality of care (QoC) around the time of childbirth in order to reduce high maternal, fetal and neonatal mortality. However, there is a paucity of scalable models. METHODS: We conducted a stepped-wedge cluster-randomised trial in 15 primary health centres (PHC) of the state of Haryana in India to test the effectiveness of a multipronged quality management strategy comprising capacity building of providers, periodic assessments of the PHCs to identify quality gaps and undertaking improvement activities for closure of the gaps. The 21-month duration of the study was divided into seven periods (steps) of 3 months each. Starting from the second period, a set of randomly selected three PHCs (cluster) crossed over to the intervention arm for rest of the period of the study. The primary outcomes included the number of women approaching the PHCs for childbirth and 12 directly observed essential practices related to the childbirth. Outcomes were adjusted with random effect for cluster (PHC) and fixed effect for 'months of intervention'. RESULTS: The intervention strategy led to increase in the number of women approaching PHCs for childbirth (26 vs 21 women per PHC-month, adjusted incidence rate ratio: 1.22; 95% CI 1.17 to 1.28). Of the 12 practices, 6 improved modestly, 2 remained near universal during both intervention and control periods, 3 did not change and 1 worsened. There was no evidence of change in mortality with a majority of deaths occurring either during referral transport or at the referral facilities. CONCLUSION: A multipronged quality management strategy enhanced utilisation of services and modestly improved key practices around the time of childbirth in PHCs in India. TRIAL REGISTRATION NUMBER: CTRI/2016/05/006963.

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.

Anti-vascular endothelial growth factor (VEGF) drugs for treatment of retinopathy of prematurity.

BACKGROUND: Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis in foetal life. Researchers have recently attempted to use anti-VEGF agents for the treatment of retinopathy of prematurity (ROP), a vasoproliferative disorder. The safety and efficacy of these agents in preterm infants with ROP is currently uncertain. OBJECTIVES: To evaluate the efficacy and safety of anti-VEGF drugs when used either as monotherapy, that is without concomitant cryotherapy or laser therapy, or in combination with planned cryo/laser therapy in preterm infants with type 1 ROP (defined as zone I any stage with plus disease, zone I stage 3 with or without plus disease, or zone II stage 2 or 3 with plus disease). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 11), MEDLINE (1966 to 11 December 2016), Embase (1980 to 11 December 2016), CINAHL (1982 to 11 December 2016), and conference proceedings. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that evaluated the efficacy or safety of administration, or both, of anti-VEGF agents compared with conventional therapy in preterm infants with ROP. DATA COLLECTION AND ANALYSIS: We used standard Cochrane and Cochrane Neonatal methods for data collection and analysis. We used the GRADE approach to assess the quality of the evidence. MAIN RESULTS: Six trials involving a total of 383 infants fulfilled the inclusion criteria. Five trials compared intravitreal bevacizumab (n = 4) or ranibizumab (n = 1) with conventional laser therapy (monotherapy), while the sixth study compared intravitreal pegaptanib plus conventional laser therapy with laser/cryotherapy (combination therapy).When used as monotherapy, bevacizumab/ranibizumab did not reduce the risk of complete or partial retinal detachment (3 studies; 272 infants; risk ratio (RR) 1.04, 95% confidence interval (CI) 0.21 to 5.13; risk difference (RD) 0.00, 95% CI -0.04 to 0.04; very low-quality evidence), mortality before discharge (2 studies; 229 infants; RR 1.50, 95% CI 0.26 to 8.75), corneal opacity requiring corneal transplant (1 study; 286 eyes; RR 0.34, 95% CI 0.01 to 8.26), or lens opacity requiring cataract removal (3 studies; 544 eyes; RR 0.15, 95% CI 0.01 to 2.79). The risk of recurrence of ROP requiring retreatment also did not differ between groups (2 studies; 193 infants; RR 0.88, 95% CI 0.47 to 1.63; RD -0.02, 95% CI -0.12 to 0.07; very low-quality evidence). Subgroup analysis showed a significant reduction in the risk of recurrence in infants with zone I ROP (RR 0.15, 95% CI 0.04 to 0.62), but an increased risk of recurrence in infants with zone II ROP (RR 2.53, 95% CI 1.01 to 6.32). Pooled analysis of studies that reported eye-level outcomes also revealed significant increase in the risk of recurrence of ROP in the eyes that received bevacizumab (RR 5.36, 95% CI 1.22 to 23.50; RD 0.10, 95% CI 0.03 to 0.17). Infants who received intravitreal bevacizumab had a significantly lower risk of refractive errors (very high myopia) at 30 months of age (1 study; 211 eyes; RR 0.06, 95% CI 0.02 to 0.20; RD -0.40, 95% CI -0.50 to -0.30; low-quality evidence).When used in combination with laser therapy, intravitreal pegaptanib was found to reduce the risk of retinal detachment when compared to laser/cryotherapy alone (152 eyes; RR 0.26, 95% CI 0.12 to 0.55; RD -0.29, 95% CI -0.42 to -0.16; low-quality evidence). The incidence of recurrence of ROP by 55 weeks' postmenstrual age was also lower in the pegaptanib + laser therapy group (76 infants; RR 0.29, 95% CI 0.12 to 0.7; RD -0.35, 95% CI -0.55 to -0.16; low-quality evidence). There was no difference in the risk of perioperative retinal haemorrhages between the two groups (152 eyes; RR 0.62, 95% CI 0.24 to 1.56; RD -0.05, 95% CI -0.16 to 0.05; very low-quality evidence). However, the risk of delayed systemic adverse effects with any of the three anti-VEGF drugs is not known. AUTHORS' CONCLUSIONS: Implications for practice: Intravitreal bevacizumab/ranibizumab, when used as monotherapy, reduces the risk of refractive errors during childhood but does not reduce the risk of retinal detachment or recurrence of ROP in infants with type 1 ROP. While the intervention might reduce the risk of recurrence of ROP in infants with zone I ROP, it can potentially result in higher risk of recurrence requiring retreatment in those with zone II ROP. Intravitreal pegaptanib, when used in conjunction with laser therapy, reduces the risk of retinal detachment as well as the recurrence of ROP in infants with type 1 ROP. However, the quality of the evidence was very low to low for most outcomes due to risk of detection bias and other biases. The effects on other critical outcomes and, more importantly, the long-term systemic adverse effects of the drugs are not known. Insufficient data precludes strong conclusions favouring routine use of intravitreal anti-VEGF agents - either as monotherapy or in conjunction with laser therapy - in preterm infants with type 1 ROP. IMPLICATIONS FOR RESEARCH: Further studies are needed to evaluate the effect of anti-VEGF agents on structural and functional outcomes in childhood and delayed systemic effects including adverse neurodevelopmental outcomes.

Assisted Physical Exercise for Improving Bone Strength in Preterm Infants Less than 35 Weeks Gestation: A Randomized Controlled Trial.

OBJECTIVE: To compare the efficacy of daily assisted physical exercise (starting from one week of postnatal age) on bone strength at 40 weeks of post menstrual age to no intervention in infants born between 27 and 34 weeks of gestation. DESIGN: Open-label randomized controlled trial. SETTING: Tertiary-care teaching hospital in northern India from 16 May, 2013 to 21 November, 2013. PARTICIPANTS: 50 preterm neonates randomized to Exercise group (n=26) or Control group (n=24). INTERVENTION: Neonates in Exercise group underwent one session of physical exercise daily from one week of age, which included range-of-motion exercises with gentle compression, flexion and extension of all the extremities with movements at each joint done five times, for a total of 10-15 min. Infants in Control group underwent routine care and were not subjected to any massage or exercise. MAIN OUTCOME MEASURES: Primary: Bone speed of sound of left tibia measured by quantitative ultrasound at 40 weeks post menstrual age. Secondary: Anthropometry (weight length and head circumference) and biochemical parameters (calcium, phosphorus, alkaline phosphatase) at 40 weeks post menstrual age. RESULTS: The tibial bone speed of sound was comparable between the two groups [2858 (142) m/s vs. 2791 (122) m/s; mean difference 67.6 m/s; 95% CI - 11 to 146 m/s; P=0.38]. There was no difference in anthropometry or biochemical parameters. CONCLUSIONS: Daily assisted physical exercise does not affect the bone strength, anthropometry or biochemical parameters in preterm (27 to 34 weeks) infants.

Antenatal corticosteroids for women at risk of imminent preterm birth in low-resource countries: the case for equipoise and the need for efficacy trials.

The scientific basis for antenatal corticosteroids (ACS) for women at risk of preterm birth has rapidly changed in recent years. Two landmark trials-the Antenatal Corticosteroid Trial and the Antenatal Late Preterm Steroids Trial-have challenged the long-held assumptions on the comparative health benefits and harms regarding the use of ACS for preterm birth across all levels of care and contexts, including resource-limited settings. Researchers, clinicians, programme managers, policymakers and donors working in low-income and middle-income countries now face challenging questions of whether, where and how ACS can be used to optimise outcomes for both women and preterm newborns. In this article, we briefly present an appraisal of the current evidence around ACS, how these findings informed WHO's current recommendations on ACS use, and the knowledge gaps that have emerged in the light of new trial evidence. Critical considerations in the generalisability of the available evidence demonstrate that a true state of clinical equipoise exists for this treatment option in low-resource settings. An expert group convened by WHO concluded that there is a clear need for more efficacy trials of ACS in these settings to inform clinical practice.

Integrated Interventions Delivered in Health Systems, Home, and Community Have the Highest Impact on Breastfeeding Outcomes in Low- and Middle-Income Countries.

Background: Improving breastfeeding rates is critical. In low- and middle-income countries (LMICs), only subtle improvements in breastfeeding rates have been observed over the past decade, which highlights the need for accelerating breastfeeding promotion interventions.Objective: The objective of this article is to update evidence on the effect of interventions on early initiation of and exclusive (<1 and 1-5 mo) and continued (6-23 mo) breastfeeding rates in LMICs when delivered in health systems, in the home or in community environments, or in a combination of settings.Methods: A systematic literature search was conducted in PubMed, Cochrane, and CABI databases to identify new articles relevant to our current review, which were published after the search date of our earlier meta-analysis (October 2014). Nine new articles were found to be relevant and were included, in addition to the other 52 studies that were identified in our earlier meta-analysis. We reported the pooled ORs and corresponding 95% CIs as our outcome estimates. In cases of high heterogeneity, random-effects models were used and causes were explored by subgroup analysis and meta-regression.Results: Early initiation of and exclusive (<1 and 1-5 mo) and continued (6-23 mo) breastfeeding rates in LMICs improved significantly as a result of interventions delivered in health systems, in the home or community, or a combination of these. Interventions delivered concurrently in a combination of settings were found to show the largest improvements in desired breastfeeding outcomes. Counseling provided in any setting and baby-friendly support in health systems appear to be the most effective interventions to improve breastfeeding.Conclusions: Improvements in breastfeeding practices are possible in LMICs with judicious use of tested interventions, particularly when delivered in a combination of settings concurrently. The findings can be considered for inclusion in the Lives Saved Tool model.

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.