Human lactation has evolved to produce a milk composition that is uniquely-designed for the human infant. Not only does human milk optimize infant growth and development, it also provides protection ...from infection and disease. More recently, the importance of human milk and breastfeeding in the programming of infant health has risen to the fore. Anchoring of infant feeding in the developmental origins of health and disease has led to a resurgence of research focused in this area. Milk composition is highly variable both between and within mothers. Indeed the distinct maternal human milk signature, including its own microbiome, is influenced by environmental factors, such as diet, health, body composition and geographic residence. An understanding of these changes will lead to unravelling the adaptation of milk to the environment and its impact on the infant. In terms of the promotion of breastfeeding, health economics and epidemiology is instrumental in shaping public health policy and identifying barriers to breastfeeding. Further, basic research is imperative in order to design evidence-based interventions to improve both breastfeeding duration and women’s breastfeeding experience.
Background
When sufficient maternal breast milk is not available, alternative forms of enteral nutrition for preterm or low birth weight (LBW) infants are donor breast milk or artificial formula. ...Donor breast milk may retain some of the non‐nutritive benefits of maternal breast milk for preterm or LBW infants. However, feeding with artificial formula may ensure more consistent delivery of greater amounts of nutrients. Uncertainty exists about the balance of risks and benefits of feeding formula versus donor breast milk for preterm or LBW infants.
Objectives
To determine the effect of feeding with formula compared with donor breast milk on growth and development in preterm or low birth weight (LBW) infants.
Search methods
We used the Cochrane Neonatal search strategy, including electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 5), Ovid MEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature (3 May 2019), as well as conference proceedings, previous reviews, and clinical trials.
Selection criteria
Randomised or quasi‐randomised controlled trials (RCTs) comparing feeding with formula versus donor breast milk in preterm or LBW infants.
Data collection and analysis
Two review authors assessed trial eligibility and risk of bias and extracted data independently. We analysed treatment effects as described in the individual trials and reported risk ratios (RRs) and risk differences (RDs) for dichotomous data, and mean differences (MDs) for continuous data, with respective 95% confidence intervals (CIs). We used a fixed‐effect model in meta‐analyses and explored potential causes of heterogeneity in subgroup analyses. We assessed the certainty of evidence for the main comparison at the outcome level using GRADE methods.
Main results
Twelve trials with a total of 1879 infants fulfilled the inclusion criteria. Four trials compared standard term formula versus donor breast milk and eight compared nutrient‐enriched preterm formula versus donor breast milk. Only the five most recent trials used nutrient‐fortified donor breast milk. The trials contain various weaknesses in methodological quality, specifically concerns about allocation concealment in four trials and lack of blinding in most of the trials. Most of the included trials were funded by companies that made the study formula.
Formula‐fed infants had higher in‐hospital rates of weight gain (mean difference (MD) 2.51, 95% confidence interval (CI) 1.93 to 3.08 g/kg/day), linear growth (MD 1.21, 95% CI 0.77 to 1.65 mm/week) and head growth (MD 0.85, 95% CI 0.47 to 1.23 mm/week). These meta‐analyses contained high levels of heterogeneity. We did not find evidence of an effect on long‐term growth or neurodevelopment. Formula feeding increased the risk of necrotising enterocolitis (typical risk ratio (RR) 1.87, 95% CI 1.23 to 2.85; risk difference (RD) 0.03, 95% CI 0.01 to 0.05; number needed to treat for an additional harmful outcome (NNTH) 33, 95% CI 20 to 100; 9 studies, 1675 infants).
The GRADE certainty of evidence was moderate for rates of weight gain, linear growth, and head growth (downgraded for high levels of heterogeneity) and was moderate for neurodevelopmental disability, all‐cause mortality, and necrotising enterocolitis (downgraded for imprecision).
Authors' conclusions
In preterm and LBW infants, moderate‐certainty evidence indicates that feeding with formula compared with donor breast milk, either as a supplement to maternal expressed breast milk or as a sole diet, results in higher rates of weight gain, linear growth, and head growth and a higher risk of developing necrotising enterocolitis. The trial data do not show an effect on all‐cause mortality, or on long‐term growth or neurodevelopment.
Background
Kangaroo mother care (KMC), originally defined as skin‐to‐skin contact between a mother and her newborn, frequent and exclusive or nearly exclusive breastfeeding, and early discharge from ...hospital, has been proposed as an alternative to conventional neonatal care for low birthweight (LBW) infants.
Objectives
To determine whether evidence is available to support the use of KMC in LBW infants as an alternative to conventional neonatal care before or after the initial period of stabilization with conventional care, and to assess beneficial and adverse effects.
Search methods
We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches in CENTRAL (Cochrane Central Register of Controlled Trials; 2016, Issue 6), MEDLINE, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), LILACS (Latin American and Caribbean Health Science Information database), and POPLINE (Population Information Online) databases (all from inception to June 30, 2016), as well as the WHO (World Health Organization) Trial Registration Data Set (up to June 30, 2016). In addition, we searched the web page of the Kangaroo Foundation, conference and symposia proceedings on KMC, and Google Scholar.
Selection criteria
Randomized controlled trials comparing KMC versus conventional neonatal care, or early‐onset KMC versus late‐onset KMC, in LBW infants.
Data collection and analysis
Data collection and analysis were performed according to the methods of the Cochrane Neonatal Review Group.
Main results
Twenty‐one studies, including 3042 infants, fulfilled inclusion criteria. Nineteen studies evaluated KMC in LBW infants after stabilization, one evaluated KMC in LBW infants before stabilization, and one compared early‐onset KMC with late‐onset KMC in relatively stable LBW infants. Sixteen studies evaluated intermittent KMC, and five evaluated continuous KMC.
KMC versus conventional neonatal care: At discharge or 40 to 41 weeks' postmenstrual age, KMC was associated with a statistically significant reduction in the risk of mortality (risk ratio RR 0.60, 95% confidence interval CI 0.39 to 0.92; eight trials, 1736 infants), nosocomial infection/sepsis (RR 0.35, 95% CI 0.22 to 0.54; five trials, 1239 infants), and hypothermia (RR 0.28, 95% CI 0.16 to 0.49; nine trials, 989 infants; moderate‐quality evidence). At latest follow‐up, KMC was associated with a significantly decreased risk of mortality (RR 0.67, 95% CI 0.48 to 0.95; 12 trials, 2293 infants; moderate‐quality evidence) and severe infection/sepsis (RR 0.50, 95% CI 0.36 to 0.69; eight trials, 1463 infants; moderate‐quality evidence). Moreover, KMC was found to increase weight gain (mean difference MD 4.1 g/d, 95% CI 2.3 to 5.9; 11 trials, 1198 infants; moderate‐quality evidence), length gain (MD 0.21 cm/week, 95% CI 0.03 to 0.38; three trials, 377 infants) and head circumference gain (MD 0.14 cm/week, 95% CI 0.06 to 0.22; four trials, 495 infants) at latest follow‐up, exclusive breastfeeding at discharge or 40 to 41 weeks' postmenstrual age (RR 1.16, 95% CI 1.07 to 1.25; six studies, 1453 mothers) and at one to three months' follow‐up (RR 1.20, 95% CI 1.01 to 1.43; five studies, 600 mothers), any (exclusive or partial) breastfeeding at discharge or at 40 to 41 weeks' postmenstrual age (RR 1.20, 95% CI 1.07 to 1.34; 10 studies, 1696 mothers; moderate‐quality evidence) and at one to three months' follow‐up (RR 1.17, 95% CI 1.05 to 1.31; nine studies, 1394 mothers; low‐quality evidence), and some measures of mother‐infant attachment and home environment. No statistically significant differences were found between KMC infants and controls in Griffith quotients for psychomotor development at 12 months’ corrected age (low‐quality evidence). Sensitivity analysis suggested that inclusion of studies with high risk of bias did not affect the general direction of findings nor the size of the treatment effect for main outcomes.
Early‐onset KMC versus late‐onset KMC in relatively stable infants: One trial compared early‐onset continuous KMC (within 24 hours post birth) versus late‐onset continuous KMC (after 24 hours post birth) in 73 relatively stable LBW infants. Investigators reported no significant differences between the two study groups in mortality, morbidity, severe infection, hypothermia, breastfeeding, and nutritional indicators. Early‐onset KMC was associated with a statistically significant reduction in length of hospital stay (MD 0.9 days, 95% CI 0.6 to 1.2).
Authors' conclusions
Evidence from this updated review supports the use of KMC in LBW infants as an alternative to conventional neonatal care, mainly in resource‐limited settings. Further information is required concerning the effectiveness and safety of early‐onset continuous KMC in unstabilized or relatively stabilized LBW infants, as well as long‐term neurodevelopmental outcomes and costs of care.
This systematic review and meta-analysis synthesised the post-1990 literature examining the effect of human milk on morbidity, specifically necrotising enterocolitis (NEC), late onset sepsis (LOS), ...retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD) and neurodevelopment in infants born ≤28 weeks' gestation and/or publications with reported infant mean birth weight of ≤1500 g. Online databases including Medline, PubMed, CINAHL, Scopus, and the Cochrane Central Register of Controlled Trials were searched, and comparisons were grouped as follows: exclusive human milk (EHM) versus exclusive preterm formula (EPTF), any human milk (HM) versus EPTF, higher versus lower dose HM, and unpasteurised versus pasteurised HM. Experimental and observational studies were pooled separately in meta-analyses. Risk of bias was assessed for each individual study and the GRADE system used to judge the certainty of the findings. Forty-nine studies (with 56 reports) were included, of which 44 could be included in meta-analyses. HM provided a clear protective effect against NEC, with an approximate 4% reduction in incidence. HM also provided a possible reduction in LOS, severe ROP and severe NEC. Particularly for NEC, any volume of HM is better than EPTF, and the higher the dose the greater the protection. Evidence regarding pasteurisation is inconclusive, but it appears to have no effect on some outcomes. Improving the intake of mother's own milk (MOM) and/or donor HM results in small improvements in morbidity in this population.
To identify changes in mortality and neonatal morbidities for infants with birth weight 501 to 1500 g born from 2000 to 2009.
There were 355806 infants weighing 501 to 1500 g who were born in ...2000-2009. Mortality during initial hospitalization and major neonatal morbidity in survivors (early and late infection, chronic lung disease, necrotizing enterocolitis, severe retinopathy of prematurity, severe intraventricular hemorrhage, and periventricular leukomalacia) were assessed by using data from 669 North American hospitals in the Vermont Oxford Network.
From 2000 to 2009, mortality for infants weighing 501 to 1500 g decreased from 14.3% to 12.4% (difference, -1.9%; 95% confidence interval, -2.3% to -1.5%). Major morbidity in survivors decreased from 46.4% to 41.4% (difference, -4.9%; 95% confidence interval, -5.6% to -4.2%). In 2009, mortality ranged from 36.6% for infants 501 to 750 g to 3.5% for infants 1251 to 1500 g, whereas major morbidity in survivors ranged from 82.7% to 18.7%. In 2009, 49.2% of all very low birth weight infants and 89.2% of infants 501 to 750 g either died or survived with a major neonatal morbidity.
Mortality and major neonatal morbidity in survivors decreased for infants with birth weight 501 to 1500 g between 2000 and 2009. However, at the end of the decade, a high proportion of these infants still either died or survived after experiencing ≥ 1 major neonatal morbidity known to be associated with both short- and long-term adverse consequences.
Understanding the causes and timing of death in extremely premature infants may guide research efforts and inform the counseling of families.
We analyzed prospectively collected data on 6075 deaths ...among 22,248 live births, with gestational ages of 22 0/7 to 28 6/7 weeks, among infants born in study hospitals within the National Institute of Child Health and Human Development Neonatal Research Network. We compared overall and cause-specific in-hospital mortality across three periods from 2000 through 2011, with adjustment for baseline differences.
The number of deaths per 1000 live births was 275 (95% confidence interval CI, 264 to 285) from 2000 through 2003 and 285 (95% CI, 275 to 295) from 2004 through 2007; the number decreased to 258 (95% CI, 248 to 268) in the 2008-2011 period (P=0.003 for the comparison across three periods). There were fewer pulmonary-related deaths attributed to the respiratory distress syndrome and bronchopulmonary dysplasia in 2008-2011 than in 2000-2003 and 2004-2007 (68 95% CI, 63 to 74 vs. 83 95% CI, 77 to 90 and 84 95% CI, 78 to 90 per 1000 live births, respectively; P=0.002). Similarly, in 2008-2011, as compared with 2000-2003, there were decreases in deaths attributed to immaturity (P=0.05) and deaths complicated by infection (P=0.04) or central nervous system injury (P<0.001); however, there were increases in deaths attributed to necrotizing enterocolitis (30 95% CI, 27 to 34 vs. 23 95% CI, 20 to 27, P=0.03). Overall, 40.4% of deaths occurred within 12 hours after birth, and 17.3% occurred after 28 days.
We found that from 2000 through 2011, overall mortality declined among extremely premature infants. Deaths related to pulmonary causes, immaturity, infection, and central nervous system injury decreased, while necrotizing enterocolitis-related deaths increased. (Funded by the National Institutes of Health.).
To study how antenatal growth affects cognitive outcome in very preterm infants and to determine whether there is an association between growth in any particular time period between birth and 5 years ...of age and cognitive outcome. Small for gestational age (SGA) and non-SGA infants were analyzed separately, because antenatal growth may affect postnatal growth.
Very low birth weight (<1501 g) infants born between 2001 and 2006 and infants born at <32 gestational weeks between 2004 and 2006 who were treated at Turku University Hospital (n = 181) were followed. Weight, length, and head circumference (HC) of the infants were measured at 9 time points between birth and 5 years. The growth was determined as a z score change between measurement points. Cognitive development was assessed at 5 years of age with the Wechsler Preschool and Primary Scales of Intelligence-Revised. The association between growth and full-scale IQ (FSIQ) was studied.
Growth in length and height was not associated with 5-year cognitive outcome. However, weight (r = 0.18, P = .04) and HC growth (r = 0.25, P = .01) between birth and 2 years of corrected age correlated to FSIQ in non-SGA children. In SGA children, HC growth (r = 0.33, P = .03) around term age correlated to FSIQ.
Cognitive outcome was similar in SGA and non-SGA very preterm infants. Growth affected cognition positively in both subgroups, but the critical time period was different.
Limited data suggest that higher hemoglobin thresholds for red-cell transfusions may reduce the risk of cognitive delay among extremely-low-birth-weight infants with anemia.
We performed an open, ...multicenter trial in which infants with a birth weight of 1000 g or less and a gestational age between 22 weeks 0 days and 28 weeks 6 days were randomly assigned within 48 hours after delivery to receive red-cell transfusions at higher or lower hemoglobin thresholds until 36 weeks of postmenstrual age or discharge, whichever occurred first. The primary outcome was a composite of death or neurodevelopmental impairment (cognitive delay, cerebral palsy, or hearing or vision loss) at 22 to 26 months of age, corrected for prematurity.
A total of 1824 infants (mean birth weight, 756 g; mean gestational age, 25.9 weeks) underwent randomization. There was a between-group difference of 1.9 g per deciliter (19 g per liter) in the pretransfusion mean hemoglobin levels throughout the treatment period. Primary outcome data were available for 1692 infants (92.8%). Of 845 infants in the higher-threshold group, 423 (50.1%) died or survived with neurodevelopmental impairment, as compared with 422 of 847 infants (49.8%) in the lower-threshold group (relative risk adjusted for birth-weight stratum and center, 1.00; 95% confidence interval CI, 0.92 to 1.10; P = 0.93). At 2 years, the higher- and lower-threshold groups had similar incidences of death (16.2% and 15.0%, respectively) and neurodevelopmental impairment (39.6% and 40.3%, respectively). At discharge from the hospital, the incidences of survival without severe complications were 28.5% and 30.9%, respectively. Serious adverse events occurred in 22.7% and 21.7%, respectively.
In extremely-low-birth-weight infants, a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity. (Funded by the National Heart, Lung, and Blood Institute and others; TOP ClinicalTrials.gov number, NCT01702805.).
Despite a major decrease in the incidence of sudden infant death syndrome (SIDS) since the American Academy of Pediatrics (AAP) released its recommendation in 1992 that infants be placed for sleep in ...a nonprone position, this decline has plateaued in recent years. Concurrently, other causes of sudden unexpected infant death occurring during sleep (sleep-related deaths), including suffocation, asphyxia, and entrapment, and ill-defined or unspecified causes of death have increased in incidence, particularly since the AAP published its last statement on SIDS in 2005. It has become increasingly important to address these other causes of sleep-related infant death. Many of the modifiable and nonmodifiable risk factors for SIDS and suffocation are strikingly similar. The AAP, therefore, is expanding its recommendations from being only SIDS-focused to focusing on a safe sleep environment that can reduce the risk of all sleep-related infant deaths including SIDS. The recommendations described in this report include supine positioning, use of a firm sleep surface, breastfeeding, room-sharing without bed-sharing, routine immunization, consideration of a pacifier, and avoidance of soft bedding, overheating, and exposure to tobacco smoke, alcohol, and illicit drugs. The rationale for these recommendations is discussed in detail in this technical report. The recommendations are published in the accompanying "Policy Statement--Sudden Infant Death Syndrome and Other Sleep-Related Infant Deaths: Expansion of Recommendations for a Safe Infant Sleeping Environment," which is included in this issue (www.pediatrics.org/cgi/doi/10.1542/peds.2011-2220).
Objectives To describe neurodevelopmental outcomes at 2 years corrected age for children born alive at 22-26, 27-31, and 32-34 weeks’ gestation in 2011, and to evaluate changes since ...1997.Design Population based cohort studies, EPIPAGE and EPIPAGE-2.Setting France.Participants 5567 neonates born alive in 2011 at 22-34 completed weeks’ gestation, with 4199 survivors at 2 years corrected age included in follow-up. Comparison of outcomes reported for 3334 (1997) and 2418 (2011) neonates born alive in the nine regions participating in both studies.Main outcome measures Survival; cerebral palsy (2000 European consensus definition); scores below threshold on the neurodevelopmental Ages and Stages Questionnaire (ASQ; at least one of five domains below threshold) if completed between 22 and 26 months corrected age, in children without cerebral palsy, blindness, or deafness; and survival without severe or moderate neuromotor or sensory disabilities (cerebral palsy with Gross Motor Function Classification System levels 2-5, unilateral or bilateral blindness or deafness). Results are given as percentage of outcome measures with 95% confidence intervals.Results Among 5170 liveborn neonates with parental consent, survival at 2 years corrected age was 51.7% (95% confidence interval 48.6% to 54.7%) at 22-26 weeks’ gestation, 93.1% (92.1% to 94.0%) at 27-31 weeks’ gestation, and 98.6% (97.8% to 99.2%) at 32-34 weeks’ gestation. Only one infant born at 22-23 weeks survived. Data on cerebral palsy were available for 3599 infants (81.0% of the eligible population). The overall rate of cerebral palsy at 24-26, 27-31, and 32-34 weeks’ gestation was 6.9% (4.7% to 9.6%), 4.3% (3.5% to 5.2%), and 1.0% (0.5% to 1.9%), respectively. Responses to the ASQ were analysed for 2506 children (56.4% of the eligible population). The proportion of children with an ASQ result below threshold at 24-26, 27-31, and 32-34 weeks’ gestation were 50.2% (44.5% to 55.8%), 40.7% (38.3% to 43.2%), and 36.2% (32.4% to 40.1%), respectively. Survival without severe or moderate neuromotor or sensory disabilities among live births increased between 1997 and 2011, from 45.5% (39.2% to 51.8%) to 62.3% (57.1% to 67.5%) at 25-26 weeks’ gestation, but no change was observed at 22-24 weeks’ gestation. At 32-34 weeks’ gestation, there was a non-statistically significant increase in survival without severe or moderate neuromotor or sensory disabilities (P=0.61), but the proportion of survivors with cerebral palsy declined (P=0.01).Conclusions In this large cohort of preterm infants, rates of survival and survival without severe or moderate neuromotor or sensory disabilities have increased during the past two decades, but these children remain at high risk of developmental delay.
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