Oropharyngeal colostrum in preventing mortality and morbidity in preterm infants

BackgroundPlacing 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. ObjectivesTo 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 methodsWe 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 We contacted trial investigators regarding unpublished studies and data. Selection criteriaWe searched for published and unpublished randomised controlled trials comparing early administration of oropharyngeal colostrum (OPC) versus sham administration of water, oral formula, or donor breast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 analysisTwo 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 resultsWe 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' conclusionsLarge, well‐designed trials would be required to evaluate more precisely and reliably the effects of oropharyngeal colostrum on important outcomes for preterm infants

Education of family members to support weaning to solids and nutrition in infants born preterm (Review) Education of family members to support weaning to solids and nutrition in infants born preterm (Review)

BackgroundWeaning refers to the period of introduction of solid food to complement breast milk or formula milk. Preterm infants are known to acquire extrauterine growth restriction by the time of discharge from neonatal units. Hence, the postdischarge and weaning period are crucial for optimal growth. Optimisation of nutrition during weaning may have long‐term impacts on outcomes in preterm infants. Family members of preterm infants may require nutrition education to promote ideal nutrition practices surrounding weaning in preterm infants who are at high risk of nutritional deficit.ObjectivesTo investigate the role of nutrition education of family members in supporting weaning in preterm infants with respect to their growth and neurodevelopment compared with conventional management.Search methodsWe used the standard search 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 CINAHL (1982 to 26 June 2018). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi‐RCTs.Selection criteriaRCTs and quasi‐RCTs were eligible for inclusion if they examined the effects of nutrition education of family members as compared to conventional management for weaning of preterm infants up to one year of corrected gestational age. We defined prematurity as less than 37 completed weeks of gestation.Data collection and analysisAt least two review authors independently screened potential studies for inclusion and planned to identify, extract data, and assess the quality of eligible studies. We resolved any differences in opinion through discussion with a third review author and consensus among all three review authors.Main resultsNo eligible trials looking at the impact of nutrition education of family members in weaning of preterm infants fulfilled the inclusion criteria of this systematic review. Two studies investigating the ideal timing for weaning in premature infants reported conflicting results,Authors' conclusionsWe were unable to assess the impact of nutrition education of family members in weaning of preterm infants as there were no eligible studies. This may be due to the lack of evidence to determine the ideal weaning strategies for preterm infants with regards to the time of initiating weaning and type of solids to introduce. Trials are needed to assess the many aspects of infant weaning in preterm infants. Long‐term neurodevelopment and metabolic outcomes should also be assessed in addition to growth parameters

Fifteen minute consultation: stabilisaton of the high risk newborn infant beside the mother

Paediatric and adult resuscitation is often performed with family present. Current guidelines recommend deferred umbilical cord clamping as part of immediate neonatal care, requiring neonatal assessment next to the mother. This paper describes strategies for providing care beside the mother using both standard resuscitation equipment and a trolley designed for this purpose

A deathly silence: why has the number of people found decomposed in England and Wales been rising?

Objectives: The number of deaths occurring in private homes in England and Wales had been rising for years, increasingly rapidly from 2020. Media stories and research linked decomposing bodies found in private homes with pandemic-related social isolation. We aim to explore whether these incidents are one-offs or part of a wider trend. Design: Descriptive analysis of publicly available Office for National Statistics (ONS) data. Setting: England and Wales. Participants: All residents of England and Wales, 1979 to 2020. Main outcome measures: Using data from the Office for National Statistics, we calculate European Age Standardised Rates for deaths coded as R98 (‘unattended death’) and R99 (‘other ill-defined and unknown causes of mortality’) in the 10th version of the International Classification of Diseases (ICD-10), and the corresponding codes in ICD-9, by sex and age group from 1979 (when ICD-9 began) to 2020. These are proxy markers for deaths where decomposition precludes attribution of a specific cause at postmortem. Results: While mortality from all other causes decreased from 1979 to 2020, the opposite was seen for deaths from R98 and R99 (or ‘undefined deaths’), with men more affected than women. There was a sharp rise in these deaths in both sexes but in men particularly in the 1990s and 2000s, coinciding with a time when overall mortality was rapidly improving. Conclusions: The increase in people found dead from unknown causes suggests wider societal breakdowns of both formal and informal social support networks. They are concerning and warrant urgent further investigation. We call on national and international authorities to consider measures that would make it possible to identify these deaths more easily in routine data

Multicentre prospective observational study of feeding practices in 30–33 weeks preterm infants

Background: Current evidence supports progressive feeding in preterm infants. Due to lower necrotising enterocolitis risk, recent studies suggest starting total enteral feeding from birth in 30–33 weeks preterm infants. The feasibility of this practice is unclear.Aim: Explore feeding practices in 30–33 weeks preterm infants.Design: Prospective, multicentre, observational study recruiting 10 consecutive 30–33 weeks preterm infants from each of the eight UK hospitals.Results: Eighty infants received their first feed at median of 24 hours, achieving total enteral (without intravenous nutrition) and full feeds (≥150 ml/kg/day) at median of 5 and 8 days, respectively. Eleven infants who achieved total enteral feeding within 24 hours after birth achieved full feeds earlier (p=0.02) with shorter hospital stay (p=0.009) but were also of older gestation (p=0.004).Conclusion: Current early feeding approaches in 30–33 weeks preterm infants were found to be conservative. Total enteral feeding from birth is possible in these infants but further studies are needed

Sedation and analgesia from prolonged pain and stress during mechanical ventilation in preterm infants: is dexmedetomidine an alternative to current practice?

Mechanical ventilation is an uncomfortable and potentially painful intervention. Opioids, such as morphine and fentanyl, are used for analgesia and sedation but there is uncertainty whether they reduce pain in mechanically ventilated infants. Moreover, there may be short-term and long-term adverse consequences such as respiratory depression leading to prolonged mechanical ventilation and detrimental long-term neurodevelopmental effects. Despite this, opioids are widely used, possibly due to a lack of alternatives.Dexmedetomidine, a highly selective alpha-2-adrenergic agonist with analgesic and sedative effects, currently approved for adults, has come into use in newborn infants. It provides analgesia and simulates natural sleep with maintenance of spontaneous breathing and upper airway tone. Although data on pharmacokinetics–pharmacodynamics in preterm infants are scant, observational studies report that using dexmedetomidine in conjunction with opioids/benzodiazepines or on its own can reduce the cumulative exposure to opioids/benzodiazepines. As it does not cause respiratory depression, dexmedetomidine could enable quicker weaning and extubation. Dexmedetomidine has also been suggested as an adjunct to therapeutic hypothermia in hypoxic ischaemic encephalopathy and others have used it during painful procedures and surgery. Dexmedetomidine infusion can cause bradycardia and hypotension although most report clinically insignificant effects.The increasing number of publications of observational studies and clinical use demonstrates that dexmedetomidine is being used in newborn infants but data on safety and efficacy are scant and not of high quality. Importantly, there are no data on long-term neurodevelopmental impact on preterm or term-born infants. The acceptance of dexmedetomidine in routine clinical practice must be preceded by clinical evidence. We need adequately powered and well-designed randomised controlled trials investigating whether dexmedetomidine alone or with opioids/benzodiazepines in infants on mechanical ventilation reduces the need for opioids/benzodiazepine and improves neurodevelopment at 24 months and later as compared with the use of opioids/benzodiazepines alone

Feed thickener for infants up to six months of age with gastro-oesophageal reflux (Review)

Background Gastro-oesophageal reflux (GOR) is common in infants, and feed thickeners are often used to manage it in infants as they are simple to use and perceived to be harmless. However, conflicting evidence exists to support the use of feed thickeners. Objectives To evaluate the use of feed thickeners in infants up to six months of age with GOR in terms of reduction in a) signs and symptoms of GOR, b) reflux episodes on pH probe monitoring or intraluminal impedance or a combination of both, or c) histological evidence of oesophagitis. Search methods We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 2), MEDLINE via PubMed (1966 to 22 November 2016), Embase (1980 to 22 November 2016), and CINAHL (1982 to 22 November 2016). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials. Selection criteria We included randomised controlled trials if they examined the effects of feed thickeners as compared to unthickened feeds (no treatment or placebo) in treating GOR in term infants up to six months of age or six months of corrected gestational age for those born preterm. Data collection and analysis Two review authors independently identified eligible studies from the literature search. Two review authors independently performed data extraction and quality assessments of the eligible studies. Differences in opinion were resolved by discussion with a third review author, and consensus was reached among all three review authors.We used the GRADE approach to assess the quality of the evidence. Main results Eight trials recruiting a total of 637 infants met the inclusion criteria for the systematic review. The infants included in the review were mainly formula-fed term infants. The trials were of variable methodological quality. Formula-fed term infants with GOR on feed thickeners had nearly two fewer episodes of regurgitation per day (mean difference -1.97 episodes per day, 95% confidence interval (CI) -2.32 to -1.61; 6 studies, 442 infants, moderate-certainty evidence) and were 2.5 times more likely to be asymptomatic from regurgitation at the end of the intervention period (risk ratio 2.50, 95% CI 1.38 to 4.51; number needed to treat for an additional beneficial outcome 5, 95% CI 4 to 13; 2 studies, 186 infants, low-certainty evidence) when compared to infants with GOR on unthickened feeds. No studies reported failure to thrive as an outcome. We found low-certainty evidence based on 2 studies recruiting 116 infants that use of feed thickeners improved the oesophageal pH probe parameters of reflux index (i.e. percentage of time pH < 4), number of reflux episodes lasting longer than 5 minutes, and duration of longest reflux episode. No major side effects were reported with the use of feed thickeners. Information was insufficient to conclude which type of feed thickener is superior. Authors’ conclusions Gastro-oesophageal reflux is a physiological self resolving phenomenon in infants that does not necessarily require any treatment. However, we found moderate-certainty evidence that feed thickeners should be considered if regurgitation symptoms persist in term bottle-fed infants. The reduction of two episodes of regurgitation per day is likely to be of clinical significance to caregivers. Due to the limited information available, we were unable to assess the use of feed thickeners in infants who are breastfeeding or preterm nor could we conclude which type of feed thickener is superior

Feed thickeners in gastro-oesophageal reflux in infants

Gastro-oesophageal reflux (GOR) is the involuntary retrograde passage of gastric contents into the oesophagus with or without regurgitation. This is a common physiological, self-limiting condition in healthy infants with a prevalence peaking at 3–4 months of age, occurring more than once a day in 50% of healthy infants. As infants achieve upright posture with neurodevelopment maturation and acquire a more solid diet with age, symptoms usually improve by 6 months old with resolution by 12–14 months old.1 Transient inappropriate relaxation of the lower oesophageal sphincter and delayed gastric emptying are common mechanisms leading to GOR.This is further exaggerated in preterm infants who have shorter and immature oesophagus with non-peristaltic motility

Risk of severe intraventricular haemorrhage in the first week of life in preterm infants transported before 72 hours of age

Objectives: Evaluate the risk of severe intraventricular hemorrhage, in the first week of life, in preterm infants undergoing early interhospital transport.Design: Retrospective cohort study.Setting: Tertiary neonatal centers of the Trent Perinatal Network in the United Kingdom.Patients: Preterm infants less than 32 weeks gestation, who were either born within and remained at the tertiary neonatal center (inborn), or were transferred (transported) between centers in the first 72 hours of life.Interventions: None.Measurements and Main Results: Multivariable logistic regression models adjusting for key confounders were used to calculate odds ratios for intraventricular hemorrhage with 95% CIs for comparison of inborn and transported infants. Cranial ultrasound findings on day 7 of life. Secondary analyses were performed for antenatal steroid course and gestational age subgroups. A total of 1,047 preterm infants were included in the main analysis. Transported infants (n = 391) had a significantly higher risk of severe (grade III/IV) intraventricular hemorrhage compared with inborns (n = 656) (9.7% vs 5.8%; adjusted odds ratio, 1.69; 95% CI, 1.04–2.76), especially for infants born at less than 28 weeks gestation (adjusted odds ratio, 1.83; 95% CI, 1.03–3.21). Transported infants were less likely to receive a full antenatal steroid course (47.8% vs 64.3%; p < 0.001). A full antenatal steroid course significantly decreased the risk of severe intraventricular hemorrhage irrespective of transport status (odds ratio, 0.33; 95% CI, 0.2–0.55). However, transported infants less than 28 weeks gestation remained significantly more likely to develop a severe intraventricular hemorrhage despite a full antenatal steroid course (adjusted odds ratio, 2.84; 95% CI, 1.08–7.47).Conclusions: Preterm infants transported in the first 72 hours of life have an increased risk of early-life severe intraventricular hemorrhage even when maternal antenatal steroids are given. The additional burden of postnatal transport could be an important component in the pathway to severe intraventricular hemorrhage. As timely in-utero transfer is not always possible, we need to focus research on improving the transport pathway to reduce this additional risk