Postdischarge Iron Status in Very Preterm Infants Receiving Prophylactic Iron Supplementation after Birth.

OBJECTIVE: To determine postdischarge iron status and associated factors in very preterm infants. STUDY DESIGN: A retrospective cohort study was conducted through a provincial database on all very preterm infants born in Nova Scotia between 2005 and 2018. As a standard of care, all infants received prophylactic iron supplements starting at 2-4 weeks of chronological age and were tested for iron deficiency at 4 or 6 months corrected age. Iron deficiency was defined as serum ferritin <20 g/L at 4 months or <12 g/L at 6 months. Multivariate logistic regression analysis identified factors associated with iron deficiency. RESULTS: Among 411 infants, 132 (32.1%) had iron deficiency and 11 (2.7%) had iron deficiency anemia. The prevalence of iron deficiency decreased over time, from 37.6% in 2005-2011 to 25.8% in 2012-2018. Gestational hypertension in the mother (P = .01) and gestational age <27 weeks (P = .02) were independent risk factors for iron deficiency. In addition, the odds of iron deficiency were lower in the mixed-fed group (ie, with breast milk and formula combined) compared with the exclusive formula-fed group (P = .01). CONCLUSIONS: Iron deficiency was prevalent in 32% of the very preterm infants despite early iron prophylaxis. These results demonstrate the importance of monitoring iron stores during preterm follow-up. Information about risk factors is important to mitigate iron deficiency in very preterm infants.

The Impact of Restrictive Family Presence Policies in Response to COVID-19 on Family Integrated Care in the NICU: A Qualitative Study.

OBJECTIVES: To conduct a needs assessment with families and their healthcare team to understand the impact of restrictive family presence policies in the neonatal intensive care unit (NICU) in response to COVID-19. BACKGROUND: In response to the COVID-19 pandemic, significant restrictive family presence policies were instituted in most NICUs globally intended to protect infants, families, and HCPs. However, knowledge on the impact of the stress of the pandemic and policies restricting family presence in the NICU on vulnerable neonates and their families remains limited. METHODS: Individuals were eligible to participate if they were a caregiver of an infant requiring NICU care or a healthcare provider (HCP) in the NICU after March 1, 2020. Semi-structured interviews were conducted using a virtual communication platform, and transcripts were analyzed using inductive thematic qualitative content analysis. RESULTS: Twenty-three participants were interviewed (12 families and 11 HCPs). Three themes emerged: (1) successes (family-integrated care, use of technology), (2) challenges (lack of standardized messaging and family engagement, impact on parental wellbeing, institutional barriers, and virtual care), and (3) moving forward (responsive and supportive leadership). CONCLUSIONS: Our findings highlight the significant impact of family restrictions on the mental well-being of families, physical closeness with parents, and empathetic stress to HCPs. Further study of potential long-term impact is warranted.

Nutritional management in newborn babies receiving therapeutic hypothermia: two retrospective observational studies using propensity score matching.

BACKGROUND: Therapeutic hypothermia is standard of care for babies with moderate to severe hypoxic-ischaemic encephalopathy. There is limited evidence to inform provision of nutrition during hypothermia. OBJECTIVES: To assess the association during therapeutic hypothermia between (1) enteral feeding and outcomes, such as necrotising enterocolitis and (2) parenteral nutrition and outcomes, such as late-onset bloodstream infection. DESIGN: A retrospective cohort study using data held in the National Neonatal Research Database and applying propensity score methodology to form matched groups for analysis. SETTING: NHS neonatal units in England, Wales and Scotland. PARTICIPANTS: Babies born at ≥ 36 gestational weeks between 1 January 2010 and 31 December 2017 who received therapeutic hypothermia for 72 hours or who died during treatment. INTERVENTIONS: Enteral feeding analysis - babies who were enterally fed during therapeutic hypothermia (intervention) compared with babies who received no enteral feeds during therapeutic hypothermia (control). Parenteral nutrition analysis - babies who received parenteral nutrition during therapeutic hypothermia (intervention) compared with babies who received no parenteral nutrition during therapeutic hypothermia (control). OUTCOME MEASURES: Primary outcomes were severe and pragmatically defined necrotising enterocolitis (enteral feeding analysis) and late-onset bloodstream infection (parenteral nutrition analysis). Secondary outcomes were survival at neonatal discharge, length of neonatal stay, breastfeeding at discharge, onset of breastfeeding, time to first maternal breast milk, hypoglycaemia, number of days with a central line in situ, duration of parenteral nutrition, time to full enteral feeds and growth. RESULTS: A total of 6030 babies received therapeutic hypothermia. Thirty-one per cent of babies received enteral feeds and 25% received parenteral nutrition. Seven babies (0.1%) were diagnosed with severe necrotising enterocolitis, and further comparative analyses were not conducted on this outcome. A total of 3236 babies were included in the matched enteral feeding analysis. Pragmatically defined necrotising enterocolitis was rare in both groups (0.5% vs. 1.1%) and was lower in babies who were fed during hypothermia (rate difference -0.5%, 95% confidence interval -1.0% to -0.1%; p = 0.03). Higher survival to discharge (96.0% vs. 90.8%, rate difference 5.2%, 95% confidence interval 3.9% to 6.6%; p < 0.001) and higher breastfeeding at discharge (54.6% vs. 46.7%, rate difference 8.0%, 95% confidence interval 5.1% to 10.8%; p < 0.001) rates were observed in enterally fed babies who also had a shorter neonatal stay (mean difference -2.2 days, 95% confidence interval -3.0 to -1.2 days). A total of 2480 babies were included in the matched parenteral nutrition analysis. Higher levels of late-onset bloodstream infection were seen in babies who received parenteral nutrition (0.3% vs. 0.9%, rate difference 0.6%, 95% confidence interval 0.1% to 1.2%; p = 0.03). Survival was lower in babies who did not receive parenteral nutrition (90.0% vs. 93.1%, rate difference 3.1%, 95% confidence interval 1.5% to 4.7%; p < 0.001). LIMITATIONS: Propensity score methodology can address imbalances in observed confounders only. Residual confounding by unmeasured or poorly recorded variables cannot be ruled out. We did not analyse by type or volume of enteral or parenteral nutrition. CONCLUSIONS: Necrotising enterocolitis is rare in babies receiving therapeutic hypothermia, and the introduction of enteral feeding is associated with a lower risk of pragmatically defined necrotising enterocolitis and other beneficial outcomes, including rates of higher survival and breastfeeding at discharge. Receipt of parenteral nutrition during therapeutic hypothermia is associated with a higher rate of late-onset infection but lower mortality. These results support introduction of enteral feeding during therapeutic hypothermia. FUTURE WORK: Randomised trials to assess parenteral nutrition during therapeutic hypothermia. TRIAL REGISTRATION: Current Controlled Trials ISRCTN474042962. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 36. See the NIHR Journals Library website for further project information.

Every year, approximately 1200 babies in the UK suffer a lack of oxygen to the brain around birth. This is called hypoxic­ischaemic encephalopathy and can lead to brain injury or death. To treat hypoxic­ischaemic encephalopathy, babies receive cooling treatment in which their body temperature is lowered. Doctors do not know the best way to give nutrition to babies receiving cooling treatment. Babies can either be fed milk into their stomach (enteral nutrition) or be given nutrients through their veins (parenteral nutrition). We compared babies who were fed milk while they were being cooled with babies from whom milk was withheld while they were being cooled to see if there was a difference in the frequency of necrotising enterocolitis, a severe gut disease. In addition, we compared babies who received parenteral nutrition while they were being cooled with babies who did not to see if there was a difference in infections. Finally, we looked at other outcomes, including survival and breastfeeding. We used the National Neonatal Research Database, which holds de-identified (i.e. no baby can be identified) information on all babies who have received NHS neonatal care. We used a statistical approach to match babies in each group (i.e. fed babies and not fed babies) as closely as possible so that any difference in outcomes was because of different nutrition and not because of other differences. We included > 6000 babies with hypoxic­ischaemic encephalopathy. Approximately one in three babies received milk feeds and one in four babies received parenteral nutrition during cooling. Necrotising enterocolitis was very rare. More babies who were fed milk during cooling had good outcomes (e.g. being breastfed at discharge) and fewer had necrotising enterocolitis. Most of these babies received only a small amount of milk in the first 3 days. More babies given parenteral nutrition had infections, but also more survived. This suggests that it is probably safe and may be beneficial to feed babies milk during cooling. More research should look at milk feeding and parenteral nutrition during cooling.

Administration of parenteral nutrition during therapeutic hypothermia: a population level observational study using routinely collected data held in the National Neonatal Research Database.

BACKGROUND: Parenteral nutrition is commonly administered during therapeutic hypothermia. Randomised trials in critically ill children indicate that parenteral nutrition may be harmful. OBJECTIVE: To examine the association between parenteral nutrition during therapeutic hypothermia and clinically important outcomes. DESIGN: Retrospective, population-based cohort study using the National Neonatal Research Database; propensity scores were used to create matched groups for comparison. SETTING: National Health Service neonatal units in England, Scotland and Wales. PARTICIPANTS: 6030 term and near-term babies, born 1/1/2010 and 31/12/2017, who received therapeutic hypothermia; 2480 babies in the matched analysis. EXPOSURE: We compared babies that received any parenteral nutrition during therapeutic hypothermia with babies that did not. MAIN OUTCOME MEASURES: Primary outcome: blood culture confirmed late-onset infection; secondary outcomes: treatment for late onset infection, necrotising enterocolitis, survival, length of stay, measures of breast feeding, hypoglycaemia, central line days, time to full enteral feeds, discharge weight. RESULTS: 1475/6030 babies (25%) received parenteral nutrition. In comparative matched analyses, the rate of culture positive late onset infection was higher in babies that received parenteral nutrition (0.3% vs 0.9%; difference 0.6; 95% CI 0.1, 1.2; p=0.03), but treatment for presumed infection was not (difference 0.8%, 95% CI -2.1 to 3.6, p=0.61). Survival was higher in babies that received parenteral nutrition (93.1% vs 90.0%; rate difference 3.1, 95% CI 1.5, 4.7; p<0.001). CONCLUSIONS: Receipt of parenteral nutrition during therapeutic hypothermia is associated with higher late-onset infection but lower mortality. This finding may be explained by residual confounding. Research should address the risks and benefits of parenteral nutrition in this population.

Education of family members to support weaning to solids and nutrition in later infancy in term-born infants.

BACKGROUND: Education of family members about infant weaning practices could affect nutrition, growth, and development of children in different settings across the world. OBJECTIVES: To compare effects of family nutrition educational interventions for infant weaning with conventional management on growth and neurodevelopment in childhood. SEARCH METHODS: We used the standard strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 5), MEDLINE via PubMed (1966 to 26 June 2018), Embase (1980 to 26 June 2018), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 26 June 2018). We searched clinical trials databases, conference proceedings, and references of retrieved articles. We ran an updated search from 1 January 2018 to 12 December 2019 in the following databases: CENTRAL via CRS Web, MEDLINE via Ovid, and CINAHL via EBSCOhost. SELECTION CRITERIA: We included randomised controlled trials that examined effects of nutrition education for weaning practices delivered to families of infants born at term compared to conventional management (standard care in the population) up to one year of age. DATA COLLECTION AND ANALYSIS: Two review authors independently identified eligible trial reports from the literature search and performed data extraction and quality assessments for each included trial. We synthesised effect estimates using risk ratios (RRs), risk differences (RDs), and mean differences (MDs), with 95% confidence intervals (CIs). We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included 21 trials, recruiting 14,241 infants. Five of the trials were conducted in high-income countries and the remaining 16 were conducted in middle- and low-income countries. Meta-analysis showed that nutrition education targeted at improving weaning-related feeding practices probably increases both weight-for-age z scores (WAZ) (MD 0.15 standard deviations, 95% CI 0.07 to 0.22; 6 studies; 2551 infants; I² = 32%; moderate-certainty evidence) and height-for-age z scores (0.12 standard deviations, 95% CI 0.05 to 0.19; 7 studies; 3620 infants; I² = 49%; moderate-certainty evidence) by 12 months of age. Meta-analysis of outcomes at 18 months of age was heterogeneous and inconsistent in the magnitude of effects of nutrition education on WAZ and weight-for-height z score across studies. One trial that assessed effects of nutrition education on growth at six years reported an uncertain effect on change in height and body mass index z score. Two studies investigated effects of nutrition education on neurodevelopment at 12 to 24 months of age with conflicting results. No trials assessed effects of nutrition education on long-term neurodevelopmental outcomes. AUTHORS' CONCLUSIONS: Nutrition education for families of infants may reduce the risk of undernutrition in term-born infants (evidence of low to moderate certainty due to limitations in study design and substantial heterogeneity of included studies). Modest effects on growth during infancy may not be of clinical significance. However, it is unclear whether these small improvements in growth parameters in the first two years of life affect long-term childhood growth and development. Further studies are needed to resolve this question.

Study protocol: optimising newborn nutrition during and after neonatal therapeutic hypothermia in the United Kingdom: observational study of routinely collected data using propensity matching.

INTRODUCTION: Therapeutic hypothermia is standard of care for infants born ≥36 weeks gestation with hypoxic ischaemic encephalopathy (HIE); consensus on optimum nutrition during therapeutic hypothermia is lacking. This results in variation in enteral feeding and parenteral nutrition (PN) for these infants. In this study, we aim to determine the optimum enteral nutrition and PN strategy for newborns with HIE during therapeutic hypothermia. METHODS AND ANALYSIS: We will undertake a retrospective cohort study using routinely recorded electronic patient data held on the United Kingdom (UK) National Neonatal Research Database (NNRD). We will extract data from infants born ≥36 weeks gestational age between 1 January 2008 and 31 December 2016, who received therapeutic hypothermia for at least 72 hours or died during therapeutic hypothermia, in neonatal units in England, Wales and Scotland. We will form matched groups in order to perform two comparisons examining: (1) the risk of NEC between infants enterally fed and infants not enterally fed, during therapeutic hypothermia; (2) the risk of late-onset blood stream infections between infants who received intravenous dextrose without any PN and infants who received PN, during therapeutic hypothermia. The following secondary outcomes will also be examined: survival, length of stay, breast feeding at discharge, hypoglycaemia, time to full enteral feeds and growth. Comparison groups will be matched on demographic, maternal, infant and organisational factors using propensity score matching. ETHICS AND DISSEMINATION: In this study, we will use deidentifed data held in the NNRD, an established national population database; parents can opt out of their baby's data being held in the NNRD. This study holds study-specific Research Ethics Committee approval (East Midlands Leicester Central, 17/EM/0307). These results will help inform optimum nutritional management in infants with HIE receiving therapeutic hypothermia; results will be disseminated through conferences, scientific publications and parent-centred information produced in partnership with parents. TRIAL REGISTRATION NUMBER: NCT03278847; pre-results, ISRCTN47404296; pre-results.

Oropharyngeal colostrum in preventing mortality and morbidity in preterm infants.

BACKGROUND: Placing a small volume of colostrum directly onto the buccal mucosa of preterm infants during the early neonatal period may provide immunological and growth factors that stimulate the immune system and enhance intestinal growth. These benefits could potentially reduce the risk of infection and necrotising enterocolitis (NEC) and improve survival and long-term outcome. OBJECTIVES: To determine if early (within the first 48 hours of life) oropharyngeal administration of mother's own fresh or frozen/thawed colostrum can reduce rates of NEC, late-onset invasive infection, and/or mortality in preterm infants compared with controls. To assess trials for evidence of safety and harm (e.g. aspiration pneumonia). To compare effects of early oropharyngeal colostrum (OPC) versus no OPC, placebo, late OPC, and nasogastric colostrum. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 8), MEDLINE via PubMed (1966 to August 2017), Embase (1980 to August 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to August 2017). We also searched clinical trials registries for ongoing and recently completed trials (clinicaltrials.gov; the World Health Organization International Trials Registry (www.whoint/ictrp/search/en/), and the ISRCTN Registry), conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We performed the last search in August 2017. We contacted trial investigators regarding unpublished studies and data. SELECTION CRITERIA: We searched for published and unpublished randomised controlled trials comparing early administration of oropharyngeal colostrum (OPC) versus sham administration of water, oral formula, or donor breast milk, or versus no intervention. We also searched for studies comparing early OPC versus early nasogastric or nasojejunal administration of colostrum. We considered only trials that included preterm infants at < 37 weeks' gestation. We did not limit the review to any particular region or language. DATA COLLECTION AND ANALYSIS: Two review authors independently screened retrieved articles for inclusion and independently conducted data extraction, data analysis, and assessments of 'Risk of bias' and quality of evidence. We graded evidence quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We contacted study authors for additional information or clarification when necessary. MAIN RESULTS: We included six studies that compared early oropharyngeal colostrum versus water, saline, placebo, or donor, or versus no intervention, enrolling 335 preterm infants with gestational ages ranging from 25 to 32 weeks' gestation and birth weights of 410 to 2500 grams. Researchers found no significant differences between OPC and control for primary outcomes - incidence of NEC (typical risk ratio (RR) 1.42, 95% confidence interval (CI) 0.50 to 4.02; six studies, 335 infants; P = 0.51; I² = 0%; very low-quality evidence), incidence of late-onset infection (typical RR 0.86, 95% CI 0.56 to 1.33; six studies, 335 infants; P = 0.50; I² = 0%; very low-quality evidence), and death before hospital discharge (typical RR 0.76, 95% CI 0.34 to 1.71; six studies, 335 infants; P = 0.51; I² = 0%; very low-quality evidence). Similarly, meta-analysis showed no difference in length of hospital stay between OPC and control groups (mean difference (MD) 0.81, 95% CI -5.87 to 7.5; four studies, 293 infants; P = 0.65; I² = 49%). Days to full enteral feeds were reduced in the OPC group with MD of -2.58 days (95% CI -4.01 to -1.14; six studies, 335 infants; P = 0.0004; I² = 28%; very low-quality evidence).The effect of OPC was uncertain because of small sample sizes and imprecision in study results (very low-quality evidence).No adverse effects were associated with OPC; however, data on adverse effects were insufficient, and no numerical data were available from the included studies.Overall the quality of included studies was low to very low across all outcomes. We downgraded GRADE outcomes because of concerns about allocation concealment and blinding, reporting bias, small sample sizes with few events, and wide confidence intervals. AUTHORS' CONCLUSIONS: Large, well-designed trials would be required to evaluate more precisely and reliably the effects of oropharyngeal colostrum on important outcomes for preterm infants.