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.
The aim of this study was to review the effects of developmental care in neonatal intensive care unit (NICU) setting on mental and motor development of preterm infants.
We searched PubMed, EMBASE, ...CINAHL, Scopus, Web of Science and Cochrane library until October 8th 2017, and included randomized controlled trials that assessed effects of developmental care in NICU on mental and motor development of preterm infants at 12 and 24 months of age, using the Bayley scale of infant development in this systematic review. In addition, data were pooled by random effects model and Standardized Mean Difference (SMD) with 95% confidence intervals (CI), calculated for meta-analysis.
Twenty one studies were eligible to be included in this systematic review; however, only thirteen studies had data suitable for meta-analysis. According to statistical analysis, developmental care in NICU improved mental developmental index (MDI) (standardized mean difference SMD 0.55, 95% confidence interval CI 0.23-0.87; p < 0.05), and psychomotor developmental index (PDI) (SMD 0.33, CI 95% CI 0.08-0.57; p < 0.05) of BSID at 12 months of age and PDI at 24 months of age (SMD 0.15, 95% CI -0.02-0.32; p < 0.1) of preterm infants. However, the benefit was not detected at 24 months of age on MDI (SMD 0.15, 95% CI -0.05-0.35; p = 0.15).
Current evidence suggests that developmental care in only NICU setting could have significant effect on mental and motor development of preterm infants, especially at 12 months of age. However, because of clinical heterogeneity, more studies are needed to evaluate the effects of developmental NICU care in the development of preterm infants.
Background Children born preterm or with a small size for gestational age are at increased risk for childhood asthma. Objective We sought to assess the hypothesis that these associations are ...explained by reduced airway patency. Methods We used individual participant data of 24,938 children from 24 birth cohorts to examine and meta-analyze the associations of gestational age, size for gestational age, and infant weight gain with childhood lung function and asthma (age range, 3.9-19.1 years). Second, we explored whether these lung function outcomes mediated the associations of early growth characteristics with childhood asthma. Results Children born with a younger gestational age had a lower FEV1 , FEV1 /forced vital capacity (FVC) ratio, and forced expiratory volume after exhaling 75% of vital capacity (FEF75 ), whereas those born with a smaller size for gestational age at birth had a lower FEV1 but higher FEV1 /FVC ratio ( P < .05). Greater infant weight gain was associated with higher FEV1 but lower FEV1 /FVC ratio and FEF75 in childhood ( P < .05). All associations were present across the full range and independent of other early-life growth characteristics. Preterm birth, low birth weight, and greater infant weight gain were associated with an increased risk of childhood asthma (pooled odds ratio, 1.34 95% CI, 1.15-1.57, 1.32 95% CI, 1.07-1.62, and 1.27 95% CI, 1.21-1.34, respectively). Mediation analyses suggested that FEV1 , FEV1 /FVC ratio, and FEF75 might explain 7% (95% CI, 2% to 10%) to 45% (95% CI, 15% to 81%) of the associations between early growth characteristics and asthma. Conclusions Younger gestational age, smaller size for gestational age, and greater infant weight gain were across the full ranges associated with childhood lung function. These associations explain the risk of childhood asthma to a substantial extent.
Background
Early enteral feeding practices are potentially modifiable risk factors for necrotising enterocolitis (NEC) in very preterm or very low birth weight (VLBW) infants. Observational studies ...suggest that conservative feeding regimens, including slowly advancing enteral feed volumes, reduce the risk of NEC. However, slow feed advancement may delay establishment of full enteral feeding and may be associated with metabolic and infectious morbidities secondary to prolonged exposure to parenteral nutrition.
Objectives
To determine effects of slow rates of enteral feed advancement on the incidence of NEC, mortality, and other morbidities in very preterm or VLBW infants.
Search methods
We used the standard Cochrane Neonatal search strategy to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 5), MEDLINE via PubMed (1966 to June 2017), Embase (1980 to June 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to June 2017). We searched clinical trials databases, conference proceedings, previous reviews, and reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi‐randomised trials.
Selection criteria
Randomised or quasi‐randomised controlled trials that assessed effects of slow (up to 24 mL/kg/d) versus faster rates of advancement of enteral feed volumes upon the incidence of NEC in very preterm or VLBW infants.
Data collection and analysis
Two review authors assessed trial eligibility and risk of bias and independently extracted data. We analysed treatment effects in individual trials and reported risk ratio (RR) and risk difference (RD) for dichotomous data, and mean difference (MD) for continuous data, with respective 95% confidence intervals (CIs). We used a fixed‐effect model for meta‐analyses and explored potential causes of heterogeneity via sensitivity analyses. We assessed the quality of evidence at the outcome level using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
Main results
We identified 10 RCTs in which a total of 3753 infants participated (2804 infants participated in one large trial). Most participants were stable very preterm infants of birth weight appropriate for gestation. About one‐third of all participants were extremely preterm or extremely low birth weight (ELBW), and about one‐fifth were small for gestational age (SGA), growth‐restricted, or compromised in utero, as indicated by absent or reversed end‐diastolic flow velocity (AREDFV) in the fetal umbilical artery. Trials typically defined slow advancement as daily increments of 15 to 20 mL/kg, and faster advancement as daily increments of 30 to 40 mL/kg. Trials generally were of good methodological quality, although none was blinded.
Meta‐analyses did not show effects on risk of NEC (typical RR 1.07, 95% CI 0.83 to 1.39; RD 0.0, 95% CI ‐0.01 to 0.02) or all‐cause mortality (typical RR 1.15, 95% CI 0.93 to 1.42; typical RD 0.01, 95% CI ‐0.01 to 0.03). Subgroup analyses of extremely preterm or ELBW infants, or of SGA or growth‐restricted or growth‐compromised infants, showed no evidence of an effect on risk of NEC or death. Slow feed advancement delayed establishment of full enteral nutrition by between about one and five days. Meta‐analysis showed borderline increased risk of invasive infection (typical RR 1.15, 95% CI 1.00 to 1.32; typical RD 0.03, 95% CI 0.00 to 0.05). The GRADE quality of evidence for primary outcomes was "moderate", downgraded from "high" because of lack of blinding in the included trials.
Authors' conclusions
Available trial data do not provide evidence that advancing enteral feed volumes at daily increments of 15 to 20 mL/kg (compared with 30 to 40 mL/kg) reduces the risk of NEC or death in very preterm or VLBW infants, extremely preterm or ELBW infants, SGA or growth‐restricted infants, or infants with antenatal AREDFV. Advancing the volume of enteral feeds at a slow rate results in several days of delay in establishing full enteral feeds and may increase the risk of invasive infection.
The incidence of neonatal early-onset sepsis (EOS) has declined substantially over the last 2 decades, primarily because of the implementation of evidence-based intrapartum antimicrobial therapy. ...However, EOS remains a serious and potentially fatal illness. Laboratory tests alone are neither sensitive nor specific enough to guide EOS management decisions. Maternal and infant clinical characteristics can help identify newborn infants who are at risk and guide the administration of empirical antibiotic therapy. The incidence of EOS, the prevalence and implications of established risk factors, the predictive value of commonly used laboratory tests, and the uncertainties in the risk/benefit balance of antibiotic exposures all vary significantly with gestational age at birth. Our purpose in this clinical report is to provide a summary of the current epidemiology of neonatal sepsis among infants born at ≥35 0/7 weeks' gestation and a framework for the development of evidence-based approaches to sepsis risk assessment among these infants.
Objective To evaluate associations between neonatal intensive care unit (NICU) room type (open ward and private room) and medical outcomes; neurobehavior, electrophysiology, and brain structure at ...hospital discharge; and developmental outcomes at 2 years of age. Study design In this prospective longitudinal cohort study, we enrolled 136 preterm infants born <30 weeks gestation from an urban, 75-bed level III NICU from 2007-2010. Upon admission, each participant was assigned to a bedspace in an open ward or private room within the same hospital, based on space and staffing availability, where they remained for the duration of hospitalization. The primary outcome was developmental performance at 2 years of age (n = 86 infants returned for testing, which was 83% of survivors) measured using the Bayley Scales of Infant and Toddler Development, 3rd Edition. Secondary outcomes were: (1) medical factors throughout the hospitalization; (2) neurobehavior; and (3) cerebral injury and maturation (determined by magnetic resonance imaging and electroencephalography). Results At term equivalent age, infants in private rooms were characterized by a diminution of normal hemispheric asymmetry and a trend toward having lower amplitude integrated electroencephalography cerebral maturation scores ( P = .02; β = −0.52 CI −0.95, −0.10). At age 2 years, infants from private rooms had lower language scores ( P = .006; β = −8.3 CI −14.2, −2.4) and a trend toward lower motor scores ( P = .02; β = −6.3 CI −11.7, −0.99), which persisted after adjustment for potential confounders. Conclusion These findings raise concerns that highlight the need for further research into the potential adverse effects of different amounts of sensory exposure in the NICU environment.
Summary In this Series paper, we review trends since the 2005 Lancet Series on Neonatal Survival to inform acceleration of progress for newborn health post-2015. On the basis of multicountry analyses ...and multi-stakeholder consultations, we propose national targets for 2035 of no more than 10 stillbirths per 1000 total births, and no more than 10 neonatal deaths per 1000 livebirths, compatible with the under-5 mortality targets of no more than 20 per 1000 livebirths. We also give targets for 2030. Reduction of neonatal mortality has been slower than that for maternal and child (1–59 months) mortality, slowest in the highest burden countries, especially in Africa, and reduction is even slower for stillbirth rates. Birth is the time of highest risk, when more than 40% of maternal deaths (total about 290 000) and stillbirths or neonatal deaths (5·5 million) occur every year. These deaths happen rapidly, needing a rapid response by health-care workers. The 2·9 million annual neonatal deaths worldwide are attributable to three main causes: infections (0·6 million), intrapartum conditions (0·7 million), and preterm birth complications (1·0 million). Boys have a higher biological risk of neonatal death, but girls often have a higher social risk. Small size at birth—due to preterm birth or small-for-gestational-age (SGA), or both—is the biggest risk factor for more than 80% of neonatal deaths and increases risk of post-neonatal mortality, growth failure, and adult-onset non-communicable diseases. South Asia has the highest SGA rates and sub-Saharan Africa has the highest preterm birth rates. Babies who are term SGA low birthweight (10·4 million in these regions) are at risk of stunting and adult-onset metabolic conditions. 15 million preterm births, especially of those younger than 32 weeks' gestation, are at the highest risk of neonatal death, with ongoing post-neonatal mortality risk, and important risk of long-term neurodevelopmental impairment, stunting, and non-communicable conditions. 4 million neonates annually have other life-threatening or disabling conditions including intrapartum-related brain injury, severe bacterial infections, or pathological jaundice. Half of the world's newborn babies do not get a birth certificate, and most neonatal deaths and almost all stillbirths have no death certificate. To count deaths is crucial to change them. Failure to improve birth outcomes by 2035 will result in an estimated 116 million deaths, 99 million survivors with disability or lost development potential, and millions of adults at increased risk of non-communicable diseases after low birthweight. In the post-2015 era, improvements in child survival, development, and human capital depend on ensuring a healthy start for every newborn baby—the citizens and workforce of the future.
Background
In‐hospital growth of preterm infants remains a challenge in clinical practice. The high nutrient demands of preterm infants often lead to growth faltering. For preterm infants who cannot ...be fed maternal or donor breast milk or may require supplementation, preterm formulas with fat in the form of medium chain triglycerides (MCTs) or long chain triglycerides (LCTs) may be chosen to support nutrient utilization and to improve growth. MCTs are easily accessible to the preterm infant with an immature digestive system, and LCTs are beneficial for central nervous system development and visual function. Both have been incorporated into preterm formulas in varying amounts, but their effects on the preterm infant's short‐term growth remain unclear. This is an update of a review originally published in 2002, then in 2007.
Objectives
To determine the effects of formula containing high as opposed to low MCTs on early growth in preterm infants fed a diet consisting primarily of formula.
Search methods
We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 8), in the Cochrane Library; Ovid MEDLINE Epub Ahead of Print, In‐Process & Other Non‐Indexed Citations, Ovid MEDLINE(R) Daily, and Ovid MEDLINE(R); MEDLINE via PubMed for the previous year; and Cumulative Index to Nursing and Allied Health Literature (CINAHL), on 16 September 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomized controlled trials (RCTs) and quasi‐RCTs.
Selection criteria
We included all randomized and quasi‐randomized trials comparing the effects of feeding high versus low MCT formula (for a minimum of five days) on the short‐term growth of preterm (< 37 weeks' gestation) infants. We defined high MCT formula as 30% or more by weight, and low MCT formula as less than 30% by weight. The infants must be on full enteral diets, and the allocated formula must be the predominant source of nutrition.
Data collection and analysis
The review authors assessed each study's quality and extracted data on growth parameters as well as adverse effects from included studies. All data used in analysis were continuous; therefore, mean differences with 95% confidence intervals were reported. We used the GRADE approach to assess the certainty of evidence.
Main results
We identified 10 eligible trials (253 infants) and extracted relevant growth data from 7 of these trials (136 infants). These studies were found to provide evidence of very low to low certainty. Risk of bias was noted, as few studies described specific methods for random sequence generation, allocation concealment, or blinding. We found no evidence of differences in short‐term growth parameters when high and low MCT formulas were compared.
As compared to low MCT formula, preterm infants fed high MCT formula showed little to no difference in weight gain velocity (g/kg/d) during the intervention, with a typical mean difference (MD) of ‐0.21 g/kg/d (95% confidence interval (CI) ‐1.24 to 0.83; 6 studies, 118 infants; low‐certainty evidence). The analysis for weight gain (g/d) did not show evidence of differences, with an MD of 0.00 g/d (95% CI ‐5.93 to 5.93; 1 study, 18 infants; very low‐certainty evidence), finding an average weight gain of 20 ± 5.9 versus 20 ± 6.9 g/d for high and low MCT groups, respectively. We found that length gain showed no difference between low and high MCT formulas, with a typical MD of 0.10 cm/week (95% CI ‐0.09 to 0.29; 3 studies, 61 infants; very low‐certainty evidence). Head circumference gain also showed little to no difference during the intervention period, with an MD of ‐0.04 cm/week (95% CI ‐0.17 to 0.09; 3 studies, 61 infants; low‐certainty evidence). Two studies reported skinfold thickness with different measurement definitions, and evidence was insufficient to determine if there was a difference (2 studies, 32 infants; very low‐certainty evidence). There are conflicting data (5 studies) as to formula tolerance, with 4 studies reporting narrative results of no observed clinical difference and 1 study reporting higher incidence of signs of gastrointestinal intolerance in high MCT formula groups. There is no evidence of effect on the incidence of necrotizing enterocolitis (NEC), based on small numbers in two trials. Review authors found no studies addressing long‐term growth parameters or neurodevelopmental outcomes.
Authors' conclusions
We found evidence of very low to low certainty suggesting no differences among short‐term growth data for infants fed low versus high MCT formulas. Due to lack of evidence and uncertainty, neither formula type could be concluded to improve short‐term growth outcomes or have fewer adverse effects. Further studies are necessary because the results from included studies are imprecise due to small numbers and do not address important long‐term outcomes. Additional research should aim to clarify effects on formula tolerance and on long‐term growth and neurodevelopmental outcomes, and should include larger study populations to better evaluate effect on NEC incidence.
Approximately 3500 infants die annually in the United States from sleep-related infant deaths, including sudden infant death syndrome (SIDS), ill-defined deaths, and accidental suffocation and ...strangulation in bed. After an initial decrease in the 1990s, the overall sleep-related infant death rate has not declined in more recent years. Many of the modifiable and nonmodifiable risk factors for SIDS and other sleep-related infant deaths are strikingly similar. The American Academy of Pediatrics recommends a safe sleep environment that can reduce the risk of all sleep-related infant deaths. Recommendations for a safe sleep environment include supine positioning, use of a firm sleep surface, room-sharing without bed-sharing, and avoidance of soft bedding and overheating. Additional recommendations for SIDS risk reduction include avoidance of exposure to smoke, alcohol, and illicit drugs; breastfeeding; routine immunization; and use of a pacifier. New evidence and rationale for recommendations are presented for skin-to-skin care for newborn infants, bedside and in-bed sleepers, sleeping on couches/armchairs and in sitting devices, and use of soft bedding after 4 months of age. In addition, expanded recommendations for infant sleep location are included. The recommendations and strength of evidence for each recommendation are published in the accompanying policy statement, "SIDS and Other Sleep-Related Infant Deaths: Updated 2016 Recommendations for a Safe Infant Sleeping Environment," which is included in this issue.
The goal of this study was to test the association of mean adult word counts at 32 and 36 weeks' postmenstrual age in the NICU with Bayley Scales of Infant and Toddler Development, 3rd Edition ...(Bayley-III), cognitive and language scores. It was hypothesized that preterm infants exposed to higher word counts would have higher cognitive and language scores at 7 and 18 months' corrected age.
This prospective cohort study included 36 preterm infants with a birth weight ≤1250 g. Sixteen-hour recordings were made in the NICU by using a digital language processor at 32 and 36 weeks' postmenstrual age. Regression analyses were performed on adult word count per hour, with Bayley-III measures correcting for birth weight.
Adult word counts in the NICU were positively correlated with 7- and 18-month Bayley-III scores. For the 32-week recording, in regression analyses adjusting for birth weight, adult word count per hour independently accounted for 12% of the variance in language composite scores (P = .04) and 20% of the variance in expressive communication scores at 18 months (P = .008). For the 36-week recording, adult word count per hour independently accounted for 26% of the variance in cognitive composite scores at 7 months (P = .0049).
Increased amount of parent talk with preterm infants in the NICU was associated with higher 7- and 18-month corrected age Bayley-III language and cognitive scores. These findings offer an opportunity for language intervention starting in the NICU.
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