BACKGROUND: Although recent reports suggest that supplementation with probiotics may enhance intestinal function in premature infants, the mechanisms are unclear, and questions remain regarding the ...safety and efficacy of probiotics in extremely low-birth-weight infants. OBJECTIVE: The objective was to evaluate the efficacy of probiotics on the digestive tolerance to enteral feeding in preterm infants born with a very low or extremely low birth weight. DESIGN: In a bicentric, double-blind, randomized controlled clinical trial that was stratified for center and birth weight, 45 infants received enteral probiotics (Bifidobacterium longum BB536 and Lactobacillus rhamnosus GG; BB536-LGG) and 49 received placebo. The primary endpoint was the percentage of infants receiving >50% of their nutritional needs via enteral feeding on the 14th day of life. A triangular test was used to perform sequential analysis. RESULTS: The trial was discontinued after the fourth sequential analysis concluded a lack of effect. The primary endpoint was not significantly different between the probiotic (57.8%) and placebo (57.1%) groups (P = 0.95). However, in infants who weighed >1000 g, probiotic supplementation was associated with a shortening in the time to reach full enteral feeding (P = 0.04). Other than colonization by the probiotic strains, no alteration in the composition of intestinal microbiota or changes in the fecal excretion of calprotectin was observed. No colonization by probiotic strains was detected in infants who weighed less-than or equal to1000 g, presumably because of more frequent suspensions of enteral feeding, more courses of antibiotic treatment, or both. CONCLUSIONS: Supplementation with BB536-LGG may not improve the gastrointestinal tolerance to enteral feeding in very-low-birth-weight infants but may improve gastrointestinal tolerance in infants weighing >1000 g. This trial was registered at clinicaltrials.gov as NCT 00290576.
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.
Aim
A 2016 Cochrane review showed that Kangaroo mother care (KMC) had a moderate impact on preterm growth, with high heterogeneity among studies. This systematic review and meta‐analysis considered ...new evidence on KMC, particularly the duration.
Method
Databases were searched for papers published in English, French, Spanish and Portuguese up to 2017. Randomised controlled trials (RCT) of preterm or low birth weight infants were included if they compared growth between KMC and conventional care. Anthropometric measures were related to duration.
Results
We identified 1368 papers, and 13 RCTs covering 743 KMC infants and 718 controls met the selection criteria. Infants held in KMC for at least 6 h/d gained more weight than the controls, with a mean difference of 8.99 g/d (95% confidence interval 8.14‐9.84, I2 = 0%). This difference persisted between 2 and 6 h/d and disappeared with 2 hours or less. When we used g/kg/d, the weight gain was higher when the duration was at least 8 h/d. Only babies who received 6 h/d gained more length and head circumference.
Conclusions
The effect of the KMC on growth was directly related to the duration.
This study aimed to evaluate the predictive ability of lung ultrasound (LU) in the development of bronchopulmonary dysplasia (BPD) in very low birth weight (VLBW) infants. A total of 130 VLBW infants ...with gestational age < 32 weeks were included; LU was performed at days 1, 2, 3, 6, 9, 12, and 15 postnatally. We calculated the LU score by 12-region, 10-region, and 6-region protocols. The incidence of BPD according to the National Institutes of Health (NIH) 2001 definition and 2019 criteria was 38.5% and 64.6%, respectively. By 12-region and 10-region protocols, LU predicted BPD from the 9
th
to 15
th
days of life (DOLs) regardless of the criteria used, with an area under the curve (AUC) ranging from 0.826 (95% confidence interval (CI): 0.750–0.887) to 0.877 (95% CI: 0.807–0.928). According to the 2019 BPD definition, the LU score incorporated gestational age, and invasive mechanical ventilation >6 days predicted BPD on the 6
th
DOL with an AUC of 0.862 (95% CI: 0.790–0.916). The 6-region protocol had significantly smaller AUC values on the 6
th
and 9
th
DOLs than the other two protocols.
Conclusion
: The 12-region and 10-region LU scoring protocols are superior to the 6-region protocol in the prediction of BPD. LU can predict the development of BPD from the 9
th
to 15
th
DOLs. With the addition of clinical variables, the earliest prediction time was the 6
th
DOL.
What is Known:
•
Bronchopulmonary dysplasia is the most common and adverse complication of prematurity. Recent four studies found that lung ultrasound score or findings predicted the development of bronchopulmonary dysplasia
.
What is New:
•
We present analysis by classical 6-region and the other two lung ultrasound score (10-region and 12-region) which include an assessment of the posterior lung to allow to understand what is the best score to be used. In addition, we explore whether LU-incorporated clinical variables could improve the predictive value for BPD
.
Aim
To establish differences in health‐related quality of life (HRQoL) in adults born term and those born very preterm (VPT) and/or with a very low birth weight (VLBW).
Methods
Our systematic review ...is preregistered under PROSPERO‐ID CRD42018084005. Studies were eligible for inclusion if their authors had stated the HRQoL of adults (18 years or older) born VPT (<32 weeks of gestation) or VLBW (<1500 g of birth weight) had been measured, if written in English, and if they reported a comparison with a control group or valid norms. We searched Pubmed, Scopus, Psycinfo, Web of Science, Embase and contacted experts in this field. Non‐response and other bias‐related problems were evaluated.
Results
We included 18 studies of 15 unique cohorts from 11 countries. In 11 studies, no differences in HRQoL between VPT or VLBW and term‐born adults were found; four studies found lower HRQoL in VPT/VLB adults; and evidence from three studies was inconclusive. Disability, sex and age were associated with HRQoL.
Conclusion
There is no conclusive evidence that HRQoL differs between term‐born adults and those born VPT or with a VLBW. The comparability of studies was restricted by differences between HRQoL measurements, age ranges at assessment and definition of disability.
Assisted reproduction technology (ART) is used worldwide, at increasing rates, and data show that some adverse outcomes occur more frequently than following spontaneous conception (SC). Possible ...explanatory factors for the well-known adverse perinatal outcome in ART singletons were evaluated.
PubMed and Cochrane databases from 1982 to 2012 were searched. Studies using donor or frozen oocytes were excluded, as well as those with no control group or including <100 children. The main outcome measure was preterm birth (PTB defined as delivery <37 weeks of gestation), and a random effects model was used for meta-analyses of PTB. Other outcomes were very PTB, low-birthweight (LBW), very LBW, small for gestational age and perinatal mortality.
The search returned 1255 articles and 65 of these met the inclusion criteria. The following were identified as predictors for PTB in singletons: SC in couples with time to pregnancy (TTP) > 1 year versus SC singletons in couples with TTP ≤ 1 year adjusted odds ratio (AOR) 1.35, 95% confidence interval (CI) 1.22, 1.50; IVF/ICSI versus SC singletons from subfertile couples (TTP > 1 year; AOR 1.55, 95% CI 1.30, 1.85); conception after ovulation induction and/or intrauterine insemination versus SC singletons where TTP ≤ 1 year (AOR 1.45, 95% CI 1.21, 1.74); IVF/ICSI singletons versus their non-ART singleton siblings (AOR 1.27, 95% CI 1.08, 1.49). The risk of PTB in singletons with a 'vanishing co-twin' versus from a single gestation was AOR of 1.73 (95% CI 1.54, 1.94) in the narrative data. ICSI versus IVF (AOR 0.80, 95% CI 0.69-0.93), and frozen embryo transfer versus fresh embryo transfer (AOR 0.85, 95% CI 0.76, 0.94) were associated with a lower risk of PTB.
Subfertility is a major risk factor for adverse perinatal outcome in ART singletons, however, even in the same mother an ART singleton has a poorer outcome than the non-ART sibling; hence, factors related to the hormone stimulation and/or IVF methods per se also may play a part. Further research is required into mechanisms of epigenetic modification in human embryos and the effects of cryopreservation on this, whether milder ovarian stimulation regimens can improve embryo quality and endometrial conditions, and whether longer culture times for embryos has a negative influence on the perinatal outcome.
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.
In this open, randomized, multicenter trial involving extremely-low-birth-weight preterm infants, the use of 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.
IMPORTANCE: Birth before 32 weeks’ gestation (very preterm VPT) and birth weight below 1500 g (very low birth weight VLBW) have been associated with lower cognitive performance in childhood. However, ...there are few investigations of the association of neonatal morbidities and maternal educational levels with the adult cognitive performance of individuals born VPT or VLBW (VPT/VLBW). OBJECTIVE: To assess differences in adult IQ between VPT/VLBW and term-born individuals and to examine the association of adult IQ with cohort factors, neonatal morbidities, and maternal educational level among VPT/VLBW participants. DATA SOURCES: Systematic review of published data from PubMed and meta-analysis of individual participant data (IPD) of cohorts from 2 consortia (Research on European Children and Adults Born Preterm RECAP and Adults Born Preterm International Collaboration APIC). STUDY SELECTION: The meta-analysis included prospective longitudinal cohort studies that assessed the full-scale IQ of adults born VPT or VLBW and respective control groups comprising term-born adults. DATA EXTRACTION AND SYNTHESIS: The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline for analyses of individual participant data and identified 8 studies that provided data from 2135 adults (1068 VPT/VLBW and 1067 term-born participants) born between 1978 and 1995. Meta-analyses of IPD were performed using a 1-stage approach, treating VPT birth or VLBW and cohort as random effects. MAIN OUTCOMES AND MEASURES: Full-scale IQ scores were converted to z scores within each cohort using the combined SD of VPT/VLBW participants and a control group of term-born participants, with scores centered on the mean of the control group. RESULTS: A total of 426 records were identified and screened. After exclusions, 13 studies were included in the aggregate meta-analysis. The IPD meta-analysis included 8 of the 9 RECAP and APIC cohorts with adult IQ data. The mean (SD) age among the 8 IPD cohorts was 24.6 (4.3) years, and 1163 participants (54.5%) were women. In unadjusted analyses, VPT/VLBW participants had mean adult IQ scores that were 0.78 SD (95% CI, −0.90 to −0.66 SD) lower than term-born participants, equivalent to a difference of 12 IQ points. Among VPT/VLBW participants, lower gestational age (score difference per week of gestation, 0.11; 95% CI, 0.07-0.14), lower birth weight z scores (score difference per 1.0 SD, 0.21; 95% CI, 0.14-0.28), the presence of neonatal bronchopulmonary dysplasia (score difference, −0.16; 95% CI, −0.30 to −0.02) or any grade of intraventricular hemorrhage (score difference, −0.19; 95% CI, −0.33 to −0.05), and lower maternal educational level (score difference, 0.26; 95% CI, 0.17-0.35) were all significantly associated with lower IQ scores in adulthood. CONCLUSIONS AND RELEVANCE: In this IPD meta-analysis, lower gestational age, lower weight for gestational age, neonatal morbidities, and lower maternal educational levels were all important risk factors associated with lower IQ among young adults born VPT or VLBW.
Necrotizing enterocolitis (NEC) is a costly morbidity in very low birth weight (VLBW; <1,500 g birth weight) infants that increases hospital length of stay and requires expensive treatments.
To ...evaluate the cost of NEC as a function of dose and exposure period of human milk (HM) feedings received by VLBW infants during the neonatal intensive care unit (NICU) hospitalization and determine the drivers of differences in NICU hospitalization costs for infants with and without NEC.
This study included 291 VLBW infants enrolled in an NIH-funded prospective observational cohort study between February 2008 and July 2012. We examined the incidence of NEC, NICU hospitalization cost, and cost of individual resources used during the NICU hospitalization.
Twenty-nine (10.0%) infants developed NEC. The average total NICU hospitalization cost (in 2012 USD) was USD 180,163 for infants with NEC and USD 134,494 for infants without NEC (p = 0.024). NEC was associated with a marginal increase in costs of USD 43,818, after controlling for demographic characteristics, risk of NEC, and average daily dose of HM during days 1-14 (p < 0.001). Each additional ml/kg/day of HM during days 1-14 decreased non-NEC-related NICU costs by USD 534 (p < 0.001).
Avoidance of formula and use of exclusive HM feedings during the first 14 days of life is an effective strategy to reduce the risk of NEC and resulting NICU costs in VLBW infants. Hospitals investing in initiatives to feed exclusive HM during the first 14 days of life could substantially reduce NEC-related NICU hospitalization costs.
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