Relationship between birth weight and chronic kidney disease: evidence from systematics review and two-sample Mendelian randomization analysis.

Observational studies showed an inverse association between birth weight and chronic kidney disease (CKD) in adulthood existed. However, whether such an association is causal remains fully elusive. Moreover, none of prior studies distinguished the direct fetal effect from the indirect maternal effect. Herein, we aimed to investigate the causal relationship between birth weight and CKD and to understand the relative fetal and maternal contributions. Meta-analysis (n = ~22 million) showed that low birth weight led to ~83% (95% confidence interval [CI] 37-146%) higher risk of CKD in late life. With summary statistics from large scale GWASs (n = ~300 000 for birth weight and ~481 000 for CKD), linkage disequilibrium score regression demonstrated birth weight had a negative maternal, but not fetal, genetic correlation with CKD and several other kidney-function related phenotypes. Furthermore, with multiple instruments of birth weight, Mendelian randomization showed there existed a negative fetal casual association (OR = 1.10, 95% CI 1.01-1.16) between birth weight and CKD; a negative but non-significant maternal casual association (OR = 1.09, 95% CI 0.98-1.21) was also identified. Those associations were robust against various sensitivity analyses. However, no maternal/fetal casual effects of birth weight were significant for other kidney-function related phenotypes. Overall, our study confirmed the inverse association between birth weight and CKD observed in prior studies, and further revealed the shared maternal genetic foundation between low birth weight and CKD, and the direct fetal and indirect maternal causal effects of birth weight may commonly drive this negative relationship.

High versus standard volume enteral feeds to promote growth in preterm or low birth weight infants.

BACKGROUND: Human milk is the best enteral nutrition for preterm infants. However, human milk, given at standard recommended volumes, is not adequate to meet the protein, energy, and other nutrient requirements of preterm or low birth weight infants. One strategy that may be used to address the potential nutrient deficits is to give a higher volume of enteral feeds. High volume feeds may improve nutrient accretion and growth, and in turn may improve neurodevelopmental outcomes. However, there are concerns that high volume feeds may cause feed intolerance, necrotising enterocolitis, or complications related to fluid overload such as patent ductus arteriosus and chronic lung disease. This is an update of a review published in 2017. OBJECTIVES: To assess the effect on growth and safety of high versus standard volume enteral feeds in preterm or low birth weight infants. In infants who were fed fortified human milk or preterm formula, high and standard volume feeds were defined as > 180 mL/kg/day and ≤ 180 mL/kg/day, respectively. In infants who were fed unfortified human milk or term formula, high and standard volume feeds were defined as > 200 mL/kg/day and ≤ 200 mL/kg/day, respectively. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials (CENTRAL; 2020 Issue 6) in the Cochrane Library; Ovid MEDLINE (1946 to June 2020); Embase (1974 to June 2020); and CINAHL (inception to June 2020); Maternity & Infant Care Database (MIDIRS) (1971 to April 2020); as well as previous reviews, and trial registries. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared high versus standard volume enteral feeds for preterm or low birth weight 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 for dichotomous data, and mean difference (MD) for continuous data, with respective 95% confidence intervals (CIs). We used the GRADE approach to assess the certainty of evidence. The primary outcomes were weight gain, linear and head growth during hospital stay, and extrauterine growth restriction at discharge. MAIN RESULTS: We included two new RCTs (283 infants) in this update. In total, we included three trials (347 infants) in this updated review. High versus standard volume feeds with fortified human milk or preterm formula Two trials (283 infants) met the inclusion criteria for this comparison. Both were of good methodological quality, except for lack of masking. Both trials were performed in infants born at < 32 weeks' gestation. Meta-analysis of data from both trials showed high volume feeds probably improves weight gain during hospital stay (MD 2.58 g/kg/day, 95% CI 1.41 to 3.76; participants = 271; moderate-certainty evidence). High volume feeds may have little or no effect on linear growth (MD 0.05 cm/week, 95% CI -0.02 to 0.13; participants = 271; low-certainty evidence), head growth (MD 0.02 cm/week, 95% CI -0.04 to 0.09; participants = 271; low-certainty evidence), and extrauterine growth restriction at discharge (RR 0.71, 95% CI 0.50 to 1.02; participants = 271; low-certainty evidence). We are uncertain of the effect of high volume feeds with fortified human milk or preterm formula on the risk of necrotising enterocolitis (RR 0.74, 95% CI 0.12 to 4.51; participants = 283; very-low certainty evidence). High versus standard volume feeds with unfortified human milk or term formula One trial with 64 very low birth weight infants met the inclusion criteria for this comparison. This trial was unmasked but otherwise of good methodological quality. High volume feeds probably improves weight gain during hospital stay (MD 6.2 g/kg/day, 95% CI 2.71 to 9.69; participants = 61; moderate-certainty evidence). The trial did not provide data on linear and head growth, and extrauterine growth restriction at discharge. We are uncertain as to the effect of high volume feeds with unfortified human milk or term formula on the risk of necrotising enterocolitis (RR 1.03, 95% CI 0.07 to 15.78; participants = 61; very low-certainty evidence). AUTHORS' CONCLUSIONS: High volume feeds (≥ 180 mL/kg/day of fortified human milk or preterm formula, or ≥ 200 mL/kg/day of unfortified human milk or term formula) probably improves weight gain during hospital stay. The available data is inadequate to draw conclusions on the effect of high volume feeds on other growth and clinical outcomes. A large RCT is needed to provide data of sufficient quality and precision to inform policy and practice.

Enteral zinc supplementation for prevention of morbidity and mortality in preterm neonates.

BACKGROUND: Preterm and low birth weight infants are born with low stores in zinc, which is a vital trace element for growth, cell differentiation and immune function. Preterm infants are at risk of zinc deficiency during the postnatal period of rapid growth. Systematic reviews in the older paediatric population have previously shown that zinc supplementation potentially improves growth and positively influences the course of infectious diseases. In paediatric reviews, the effect of zinc supplementation was most pronounced in those with low nutritional status, which is why the intervention could also benefit preterm infants typically born with low zinc stores and decreased immunity. OBJECTIVES: To determine whether enteral zinc supplementation, compared with placebo or no supplementation, affects important outcomes in preterm infants, including death, neurodevelopment, common morbidities and growth. SEARCH METHODS: Our searches are up-to-date to 20 February 2020. For the first search, we used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 8), MEDLINE via PubMed (1966 to 29 September 2017), Embase (1980 to 29 September 2017), and CINAHL (1982 to 29 September 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. We ran an updated search from 1 January 2017 to 20 February 2020 in the following databases: CENTRAL via CRS Web, MEDLINE via Ovid, and CINAHL via EBSCOhost. SELECTION CRITERIA: We included RCTs and quasi-RCTs that compared enteral zinc supplementation versus placebo or no supplementation in preterm infants (gestational age < 37 weeks), and low birth weight babies (birth weight < 2500 grams), at any time during their hospital admission after birth. We included zinc supplementation in any formulation, regimen, or dose administered via the enteral route. We excluded infants who underwent gastrointestinal (GI) surgery during their initial hospital stay, or had a GI malformation or another condition accompanied by abnormal losses of GI juices, which contain high levels of zinc (including, but not limited to, stomas, fistulas, and malabsorptive diarrhoea). DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane Neonatal. Two review authors separately screened abstracts, evaluated trial quality and extracted data. We synthesised effect estimates using risk ratios (RR), risk differences (RD), and standardised mean differences (SMD). Our primary outcomes of interest were all-cause mortality and neurodevelopmental disability. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included five trials with a total of 482 preterm infants; there was one ongoing trial. The five included trials were generally small, but of good methodological quality. Enteral zinc supplementation compared to no zinc supplementation Enteral zinc supplementation started in hospitalised preterm infants may decrease all-cause mortality (between start of intervention and end of follow-up period) (RR 0.55, 95% CI 0.31 to 0.97; 3 studies, 345 infants; low-certainty evidence). No data were available on long-term neurodevelopmental outcomes at 18 to 24 months of (post-term) age. Enteral zinc supplementation may have little or no effect on common morbidities such as bronchopulmonary dysplasia (RR 0.66, 95% CI 0.31 to 1.40, 1 study, 193 infants; low-certainty evidence), retinopathy of prematurity (RR 0.14, 95% CI 0.01 to 2.70, 1 study, 193 infants; low-certainty evidence), bacterial sepsis (RR 1.11, 95% CI 0.60 to 2.04, 2 studies, 293 infants; moderate-certainty evidence), or necrotising enterocolitis (RR 0.08, 95% CI 0.00 to 1.33, 1 study, 193 infants; low-certainty evidence). The intervention probably improves weight gain (SMD 0.46, 95% CI 0.28 to 0.64; 5 studies, 481 infants; moderate-certainty evidence); and may slightly improve linear growth (SMD 0.75, 95% CI 0.36 to 1.14, 3 studies, 289 infants; low-certainty evidence), but may have little or no effect on head growth (SMD 0.21, 95% CI -0.02 to 0.44, 3 studies, 289 infants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Enteral supplementation of zinc in preterm infants compared to no supplementation or placebo may moderately decrease mortality and probably improve short-term weight gain and linear growth, but may have little or no effect on common morbidities of prematurity. There are no data to assess the effect of zinc supplementation on long-term neurodevelopment.

High versus low medium chain triglyceride content of formula for promoting short-term growth of preterm infants.

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.

Effect of community-initiated kangaroo mother care on survival of infants with low birthweight: a randomised controlled trial.

BACKGROUND: Coverage of kangaroo mother care remains very low despite WHO recommendations for its use for babies with low birthweight in health facilities for over a decade. Initiating kangaroo mother care at the community level is a promising strategy to increase coverage. However, knowledge of the efficacy of community-initiated kangaroo mother care is still lacking. We aimed to assess the effect of community-initiated kangaroo mother care provided to babies weighing 1500-2250 g on neonatal and infant survival. METHODS: In this randomised controlled, superiority trial, undertaken in Haryana, India, we enrolled babies weighing 1500-2250 g at home within 72 h of birth, if not already initiated in kangaroo mother care, irrespective of place of birth (ie, home or health facility) and who were stable and feeding. The first eligible infants in households were randomly assigned (1:1) to the intervention (community-initiated kangaroo mother care) or control group by block randomisation using permuted blocks of variable size. Twins were allocated to the same group. For second eligible infants in the same household as an enrolled infant, if the first infant was assigned to the intervention group the second infant was also assigned to this group, whereas if the first infant was assigned to the control group the second infant was randomly assigned (1:1) to the intervention or control group. Mothers and infants in the intervention group were visited at home (days 1-3, 5, 7, 10, 14, 21, and 28) to support kangaroo mother care (ie, skin-to-skin contact and exclusive breastfeeding). The control group received routine care. The two primary outcomes were mortality between enrolment and 28 days and between enrolment and 180 days. Analysis was by intention to treat and adjusted for clustering within households. The effect of the intervention on mortality was assessed with person-time in the denominator using Cox proportional hazards model. This study is registered with ClinicalTrials.gov, NCT02653534 and NCT02631343, and is now closed to new participants. FINDINGS: Between July 30, 2015, and Oct 31, 2018, 8402 babies were enrolled, of whom 4480 were assigned to the intervention group and 3922 to the control group. Most births (6837 [81·4%]) occurred at a health facility, 36·2% (n=3045) had initiated breastfeeding within 1 h of birth, and infants were enrolled at an average of about 30 h (SD 17) of age. Vital status was known for 4470 infants in the intervention group and 3914 in the control group at age 28 days, and for 3653 in the intervention group and 3331 in the control group at age 180 days. Between enrolment and 28 days, 73 infants died in 4423 periods of 28 days in the intervention group and 90 deaths in 3859 periods of 28 days in the control group (hazard ratio [HR] 0·70, 95% CI 0·51-0·96; p=0·027). Between enrolment and 180 days, 158 infants died in 3965 periods of 180 days in the intervention group and 184 infants died in 3514 periods of 180 days in the control group (HR 0·75, 0·60-0·93; p=0·010). The risk ratios for death were almost the same as the HRs (28-day mortality 0·71, 95% CI 0·52- 0·97; p=0·032; 180-day mortality 0·76, 0·60-0·95; p=0·017). INTERPRETATION: Community-initiated kangaroo mother care substantially improves newborn baby and infant survival. In low-income and middle-income countries, incorporation of kangaroo mother care for all infants with low birthweight, irrespective of place of birth, could substantially reduce neonatal and infant mortality. FUNDING: Research Council of Norway and University of Bergen.

How does gestational age affect growth and body composition of preterm twins?

BACKGROUND: Twins experience altered growth compared to singletons. The primary aim of this study was to compare growth and body composition (BC) of twin and singleton preterm infants from birth to 3 months according to gestational age (GA). Secondary aims were to evaluate the effect of chorionicity and mode of feeding on twins' BC. METHODS: Anthropometric measurements and BC were performed at term and 3 months in preterm infants (GA < 37 weeks). Infants were categorized as: extremely, very, moderate and late preterm infants. Chorionicity was assigned as monochorionic, dichorionic or multichorionic. Mode of feeding was recorded as any human milk feeding vs formula feeding. RESULTS: Five hundred and seventy-six preterm infants were included (223 twins). Late-preterm twins were lighter and shorter at each study point; fat-free mass (FFM) was lower in these infants at each study point, compared to singletons. No differences were found between twins and singleton on the other category. Multichorionic infants had an FFM deficit compared to monochorionic and dichorionic at term, whereas no differences were found at 3 months. FFM at term was negatively associated with being twin and formula-fed. CONCLUSIONS: Twins and singletons born before 34 weeks' GA showed similar anthropometry and BC. Conversely, twin late-preterm infants showed different growth and BC compared to singletons.

Higher versus lower protein intake in formula-fed low birth weight infants.

BACKGROUND: The ideal quantity of dietary protein for formula-fed low birth weight infants is still a matter of debate. Protein intake must be sufficient to achieve normal growth without leading to negative effects such as acidosis, uremia, and elevated levels of circulating amino acids. OBJECTIVES: To determine whether higher (≥ 3.0 g/kg/d) versus lower (< 3.0 g/kg/d) protein intake during the initial hospital stay of formula-fed preterm infants or low birth weight infants (< 2.5 kilograms) results in improved growth and neurodevelopmental outcomes without evidence of short- or long-term morbidity. Specific objectives were to examine the following comparisons of interventions and to conduct subgroup analyses if possible. 1. Low protein intake if the amount was less than 3.0 g/kg/d. 2. High protein intake if the amount was equal to or greater than 3.0 g/kg/d but less than 4.0 g/kg/d. 3. Very high protein intake if the amount was equal to or greater than 4.0 g/kg/d. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 8), in the Cochrane Library (August 2, 2019); OVID MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily, and Ovid MEDLINE(R) (to August 2, 2019); MEDLINE via PubMed (to August 2, 2019) for the previous year; and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (to August 2, 2019). We also searched clinical trials databases and the reference lists of retrieved articles for randomized controlled trials (RCTs) and quasi-randomized trials. SELECTION CRITERIA: We included RCTs contrasting levels of formula protein intake as low (< 3.0 g/kg/d), high (≥ 3.0 g/kg/d but < 4.0 g/kg/d), or very high (≥ 4.0 g/kg/d) in formula-fed hospitalized neonates weighing less than 2.5 kilograms. We excluded studies if infants received partial parenteral nutrition during the study period, or if infants were fed formula as a supplement to human milk. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane and the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We identified six eligible trials that enrolled 218 infants through searches updated to August 2, 2019. Five studies compared low (< 3 g/kg/d) versus high (3.0 to 4.0 g/kg/d) protein intake using formulas that kept other nutrients constant. The trials were small (n = 139), and almost all had methodological limitations; the most frequent uncertainty was about attrition. Low-certainty evidence suggests improved weight gain (mean difference [MD] 2.36 g/kg/d, 95% confidence interval [CI] 1.31 to 3.40) and higher nitrogen accretion in infants receiving formula with higher protein content (3.0 to 4.0 g/kg/d) versus lower protein content (< 3 g/kg/d), while other nutrients were kept constant. No significant differences were seen in rates of necrotizing enterocolitis, sepsis, or diarrhea. We are uncertain whether high versus low protein intake affects head growth (MD 0.37 cm/week, 95% CI 0.16 to 0.58; n = 18) and length gain (MD 0.16 cm/week, 95% CI -0.02 to 0.34; n = 48), but sample sizes were small for these comparisons. One study compared high (3.0 to 4.0 g/kg/d) versus very high (≥ 4 g/kg/d) protein intake (average intakes were 3.6 and 4.1 g/kg/d) during and after an initial hospital stay (n = 77). Moderate-certainty evidence shows no significant differences in weight gain or length gain to discharge, term, and 12 weeks corrected age from very high protein intake (4.1 versus 3.6 g/kg/d). Three of the 24 infants receiving very high protein intake developed uremia. AUTHORS' CONCLUSIONS: Higher protein intake (≥ 3.0 g/kg/d but < 4.0 g/kg/d) from formula accelerates weight gain. However, limited information is available regarding the impact of higher formula protein intake on long-term outcomes such as neurodevelopment. Research is needed to investigate the safety and effectiveness of protein intake ≥ 4.0 g/kg/d.

Factors Associated with the Development of Childhood Asthma in Japan: A Nationwide Longitudinal Study.

INTRODUCTION: Many environmental factors are related to the development of asthma. However, the key factors of childhood asthma onset have not been sufficiently elucidated. Further, low-weight births have increased in Japan. The aim of this study was to examine the risk factors for the incidence of childhood asthma and to evaluate whether these risk factors differ according to birth weight in Japan. METHODS: We used the National Longitudinal Survey from 2001 to 2010. Multiple logistic regression analyses were conducted to determine the effects of gender, birth weight, single vs. multiple births, birth order, nutrition, keeping pets in the home, place of residence, annual household income, and parent ages, smoking behaviors, and educational backgrounds on asthma-related hospital visits. RESULTS: Overall, 45,060 children were analyzed. The rate of cumulative hospital visits until age 10 was 18.9%. Birth weight < 2500 g (adjusted odds ratio [AOR] = 1.14, 95% confidence interval [CI] 1.03-1.26), being a boy (AOR = 1.27, 95% CI 1.21-1.33), having older siblings (AOR = 1.07, 95% CI 1.02-1.14), parental smoking behavior, mother`s age, and low household income (AOR = 1.17, 95% CI 1.10-1.24) were associated with asthma-related hospital visits. DISCUSSION: Parental smoking behavior is a key risk factor for the development of asthma. Among low birth weight infants, being a boy, having older siblings, and father`s smoking behavior were predictive factors for the development of asthma. However, low birth weight was not associated with the development of asthma after 6 years of age.

Maternal Anaemia in Pregnancy: A Significantly Greater Risk Factor for Anaemia in Australian Aboriginal Children than Low Birth Weight or Prematurity.

OBJECTIVES: To identify maternal and perinatal risk factors associated with childhood anaemia. METHODS: A retrospective cohort study was conducted in three remote Katherine East Aboriginal communities in Northern Territory, Australia. Children born 2004-2014 in Community A and 2010-2014 in Community B and C, and their respective mothers were recruited into the study. Maternal and child data were linked to provide a longitudinal view of each child for the first 1000 days from conception to 2-years of age. Descriptive analyses were used to calculate mean maternal age, and proportions were used to describe other antenatal and perinatal characteristics of the mother/child dyads. The main outcome was the prevalence of maternal anaemia in pregnancy and risk factors associated with childhood anaemia at age 6 months. RESULTS: Prevalence of maternal anaemia in pregnancy was higher in the third trimester (62%) compared to the first (46%) and second trimesters (48%). There was a strong positive linear association (R2 = 0.46, p < 0.001) between maternal haemoglobin (Hb) in third trimester pregnancy and child Hb at age 6 months. Maternal anaemia in pregnancy (OR 4.42 95% CI 2.08-9.36) and low birth weight (LBW, OR 2.62, 95% CI 1.21-5.70) were associated with an increased risk of childhood anaemia at 6 months of age. CONCLUSIONS FOR PRACTICE: This is the first study to identify the association of maternal anaemia with childhood anaemia in the Australian Aboriginal population. A review of current policies and practices for anaemia screening, prevention and treatment during pregnancy and early childhood would be beneficial to both mother and child. Our findings indicate that administering prophylactic iron supplementation only to children who are born LBW or premature would be of greater benefit if expanded to include children born to anaemic mothers.

Establishment of an ideal gut microbiota to boost healthy growth of neonates.

For decades, supporting the optimal growth of low birth weight (LBW) infants has been considered one of the most important paediatric challenges, despite advances in neonatal intensive care technology and nutrition interventions. Since gut microbiota affects such diverse phenotypes in adults, the difference in gut microbiota composition between normal infants and LBW infants raises the possibility of gut microbiota playing an important role in different growth rates of neonates. Based on the concept that probiotics are generally beneficial to the health, numerous studies have been made on probiotics as a supplement to the diet of the LBW infants. However, clinical results on the effects of probiotics on LBW infant growth are either inconsistent or contradictory with each other, and thus the contribution of gut microbiota in neonatal growth has remained inconclusive. In this review, recent researches on neonatal gut microbiota are discussed to develop a new strategy for targeting gut microbiota as a solution to growth retardation in LBW infants. We also discuss how to establish the ideal gut microbiota to support optimal growth of LBW infants.

Steady Growth in Early Infancy Is Associated with Greater Anthropometry in Indian Children Born Low Birth Weight at Term.

BACKGROUND: Patterns of early growth are associated with later body composition and risk of adult noncommunicable disease but information from low-income countries is limited. OBJECTIVES: The aim of this study was to investigate early growth trajectories and later anthropometric and bone density outcomes among children born term low birth weight (LBW: 1.8-2.5 kg). METHODS: We used data from 902 children from the Delhi Infant Vitamin D Supplementation study of LBW term infants (which collected monthly anthropometry from birth to 6 mo) and who had height, weight, midupper arm circumference (MUAC), midupper arm muscle circumference (MUAMC), subscapular and triceps skinfold thicknesses, tibia and radius bone density measured at age 4-6 y. We investigated how growth in the first 6 mo of life, modeled using the SuperImposition by Translation and Rotation (SITAR) growth curve model, was related to these outcomes. SITAR summarizes each infant's weight and length trajectory in terms of a population mean curve and child-specific growth parameters: size, timing, and intensity. These were included as explanatory variables in linear regression models for the childhood outcomes. RESULTS: Considering the infant weight and length SITAR parameters jointly, childhood weight was strongly associated with infant length timing [estimated regression coefficient ß = 0.25 (95% CI: 0.10, 0.39)] and with weight size, timing, and intensity [ß = 9.01 (6.75, 11.27), ß = -0.25 (-0.43, -0.07), ß = 5.03 (3.22, 6.84), respectively]. Childhood height was associated only with the length parameters [ß = 0.97 (0.71, 1.23), ß = -0.43 (-0.77, -0.09), ß = 11.68 (8.60, 14.75), respectively]; childhood MUAC, MUAMC, and skinfolds with all parameters; and bone density with none. Overall, delayed and sustained growth in infant weight and length resulted in higher values of all outcomes except bone density, with the period up to 15 wk of age appearing critical for setting childhood anthropometry in this population. CONCLUSIONS: The explanation for the effects of delayed growth and length of the period in which trajectories are set is unclear; however, sustained and delayed growth in early infancy appears to be beneficial for these LBW children at least in the short-term. The trial was registered at clinicaltrials.gov as BT/PR7489/PID/20/285/2006.

How does birth weight affect health and human capital? A short- and long-term evaluation.

In utero shocks have been shown to have long-lasting consequences. However, we hardly know whether these effects tend to fade out over time and whether they can be compensated by post-natal investments. This paper examines the effect of birth endowment over time by employing a long panel of individuals born in 1983 in Cebu (Philippines) that includes relevant information on the pregnancy. We build a refined health endowment measure netted out from prenatal investments. We find that initial endowments affect trajectories both through the human capital production function and subsequent parental investment. The effect of birth endowment remains until adulthood and the fading out is very limited for health outcomes but more pronounced for educational outcomes. We also find that parents tend to reinforce initial health endowments, but the effect of this behaviour has almost no effect on final outcomes.

Formula versus maternal breast milk for feeding preterm or low birth weight infants.

BACKGROUND: Artificial formula can be manipulated to contain higher amounts of macro-nutrients than maternal breast milk but breast milk confers important immuno-nutritional advantages for preterm or low birth weight (LBW) infants. OBJECTIVES: To determine the effect of feeding preterm or LBW infants with formula compared with maternal breast milk on growth and developmental outcomes. SEARCH METHODS: We used the standard strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 9), and Ovid MEDLINE, Ovid Embase, Ovid Maternity & Infant Care Database, and CINAHL to October 2018. We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that compared feeding preterm or low birth weight infants with formula versus maternal breast milk. DATA COLLECTION AND ANALYSIS: Two review authors planned independently to assess trial eligibility and risk of bias, and extract data. We planned to analyse treatment effects as described in the individual trials and report risk ratios and risk differences for dichotomous data, and mean differences for continuous data, with 95% confidence intervals. We planned to use a fixed-effect model in meta-analyses and to explore potential causes of heterogeneity in subgroup analyses. We planned to use the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We did not identify any eligible trials. AUTHORS' CONCLUSIONS: There are no trials of formula versus maternal breast milk for feeding preterm or low birth weight infants. Such trials are unlikely to be conducted because of the difficulty of allocating an alternative form of nutrition to an infant whose mother wishes to feed with her own breast milk. Maternal breast milk remains the default choice of enteral nutrition because observational studies, and meta-analyses of trials comparing feeding with formula versus donor breast milk, suggest that feeding with breast milk has major immuno-nutritional advantages for preterm or low birth weight infants.

Nutrient-enriched formula versus standard formula for preterm infants.

BACKGROUND: Preterm infants may accumulate nutrient deficits leading to extrauterine growth restriction. Feeding preterm infants with nutrient-enriched rather than standard formula might increase nutrient accretion and growth rates and might improve neurodevelopmental outcomes. OBJECTIVES: To compare the effects of feeding with nutrient-enriched formula versus standard formula on growth and development of preterm infants. SEARCH METHODS: We used the Cochrane Neonatal standard search strategy. This included electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 11), MEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature (until November 2018), as well as conference proceedings, previous reviews, and clinical trials databases. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials that compared feeding preterm infants with nutrient-enriched formula (protein and energy plus minerals, vitamins, or other nutrients) versus standard formula. DATA COLLECTION AND ANALYSIS: We extracted data using the Cochrane Neonatal standard methods. Two review authors separately evaluated trial quality and extracted and synthesised data using risk ratios (RRs), risk differences, and mean differences (MDs). We assessed certainty of evidence at the outcome level using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods. MAIN RESULTS: We identified seven trials in which a total of 590 preterm infants participated. Most participants were clinically stable preterm infants of birth weight less than 1850 g. Few participants were extremely preterm, extremely low birth weight, or growth restricted at birth. Trials were conducted more than 30 years ago, were formula industry funded, and were small with methodological weaknesses (including lack of masking) that might bias effect estimates. Meta-analyses of in-hospital growth parameters were limited by statistical heterogeneity. There is no evidence of an effect on time to regain birth weight (MD -1.48 days, 95% confidence interval (CI) -4.73 to 1.77) and low-certainty evidence suggests that feeding with nutrient-enriched formula increases in-hospital rates of weight gain (MD 2.43 g/kg/d, 95% CI 1.60 to 3.26) and head circumference growth (MD 1.04 mm/week, 95% CI 0.18 to 1.89). Meta-analysis did not show an effect on the average rate of length gain (MD 0.22 mm/week, 95% CI -0.70 to 1.13). Fewer data are available for growth and developmental outcomes assessed beyond infancy, and these do not show consistent effects of nutrient-enriched formula feeding. Data from two trials did not show an effect on Bayley Mental Development Index scores at 18 months post term (MD 2.87, 95% CI -1.38 to 7.12; moderate-certainty evidence). Infants who received nutrient-enriched formula had higher Bayley Psychomotor Development Index scores at 18 months post term (MD 6.56. 95% CI 2.87 to 10.26; low-certainty evidence), but no evidence suggested an effect on cerebral palsy (typical RR 0.79, 95% CI 0.30 to 2.07; 2 studies, 377 infants). Available data did not indicate any other benefits or harms and provided low-certainty evidence about the effect of nutrient-enriched formula feeding on the risk of necrotising enterocolitis in preterm infants (typical RR 0.72, 95% CI 0.41 to 1.25; 3 studies, 489 infants). AUTHORS' CONCLUSIONS: Available trial data show that feeding preterm infants nutrient-enriched (compared with standard) formulas has only modest effects on growth rates during their initial hospital admission. No evidence suggests effects on long-term growth or development. The GRADE assessment indicates that the certainty of this evidence is low, and that these findings should be interpreted and applied with caution. Further randomised trials would be needed to resolve this uncertainty.

Formula versus donor breast milk for feeding preterm or low birth weight infants.

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.

Fetal and Infant Growth Patterns and Risk of Lower Lung Function and Asthma. The Generation R Study.

RATIONALE: Children with lower birth weight are at increased risk of asthma symptoms. OBJECTIVES: To examine associations of fetal and infant growth with childhood lung function and asthma. METHODS: This study was embedded in a population-based prospective cohort study of 5,635 children. Growth was estimated by repeated ultrasounds in the second and third trimesters, and measured at birth and at 3, 6, and 12 months. At age 10 years, spirometry was performed and asthma was assessed by parental questionnaire. Restricted and accelerated growth were defined as the growth percentile change between time periods less than -0.67 and more than 0.67 SD scores (SDSs), respectively. We applied multiple regression analyses, including conditional regression analyses, to account for correlations between repeated growth measures. MEASUREMENTS AND MAIN RESULTS: Overall greater weight in the second and third trimesters, at birth, and at 12 months was associated with higher FEV1 and FVC (range of z-score difference, 0.04-0.08, per SDS increase in weight). Greater weight at 3 months was associated with lower FEV1/FVC and forced expiratory flow at 75% of the pulmonary volume (FEF75%) (z-score differences [95% confidence interval]: -0.09 [-0.14 to -0.05] and -0.09 [-0.13 to -0.05] per SDS increase in weight, respectively). Restricted fetal weight growth was associated with lower childhood lung-function measures, partly depending on infant weight growth patterns (range of z-score difference, -0.25 to -0.13). Accelerated fetal weight growth was associated with higher FVC and lower FEV1/FVC only if followed by accelerated infant weight growth. Fetal and infant weight growth was not associated with childhood asthma. CONCLUSIONS: Both restricted fetal weight growth, partly depending on infant weight growth, and accelerated fetal and infant weight growth predispose children to lower lung function and a potential risk for respiratory diseases later in life.

First-year growth of 834 preterm infants in a Chinese population: a single-center study.

BACKGROUND: The aim of this study was to follow the growth and hematological indicators of preterm infants during their first year. METHODS: Neonates below 37 gestational weeks had routine follow-ups up through 1 year from January 2012 to December 2015 at West China 2nd University Hospital, Sichuan University. Weight, length and head circumference (HC) were measured monthly during the first 6 months, followed by monitoring every second month until 12 months. The catch-up growth defined as a gain of Z-score > 0.67 according to previous study. All preterm infants were prescribed iron prophylaxis based on national guideline. The hemoglobin concentration was examined at 6 and 12 months. RESULTS: Altogether, 132 very-low-birth-weight (VLBW), 504 low-birth-weight (LBW) and 198 normal-birth-weight (NBW) infants were followed. The rates of catch-up growth for weight, length and HC 12 months of corrected age (CA) were 22.6, 29.1 and 14.6%, respectively. SGA and VLBW infants showed higher catch-up growth rates. The overall prevalence of anemia was 6.8% at 6 months and 7.8% at 12 months. The Z-scores for weight-for-length, length and HC were lower in the VLBW and SGA preterm infant groups than in the other preterm groups throughout the first year of life. The incidences of stunting, microcephaly and wasting changed from 5, 1.3 and 3.7% to 2, 1.1, 0.9 and 2.4%, respectively, during the first year. However, the incidences of wasting and stunting were higher for the VLBW infants than for the LBW and NBW infants at 12 months (9.3% vs. 1.4%, p < 0.01; 9.3% vs. 1%, p < 0.01,respectively; 4.7% vs. 0.8%, p < 0.01, 4.7% vs. 0%, p < 0.01,respectively). Similar results were observed between SGA and AGA infants (8.7% vs. 1.5%, p < 0.01; 5.8% vs. 0.4%, p < 0.01). Logistic regression revealed SGA and VLBW as risk factors for poor growth (WLZ < -2SD) at 12 months (OR = 5.5, 95% CI: 2.1-14.8, p < 0.01: OR = 4.8, 95% CI: 1.8-12.8, p < 0.01, respectively). CONCLUSION: The VLBW and SGA preterm infants showed significant catch-up growth during their first year of life. However, SGA and VLBW were risk factors for poor growth during the preterm infants' first year of life. Prophylactic iron supplementation in preterm infants appears to reduce the prevalence of anemia.

A Population-Based Study of School Readiness Determinants in a Large Urban Public School District.

Objectives We examined biologic and social determinants of school readiness in an urban population and whether childcare altered these associations. Methods A retrospective cohort study was conducted using school readiness data linked to birth certificates of first-time kindergarten students (n = 39,463) in a large, urban public-school district during 2002-2012. Multivariate linear regression models compared mean readiness scores (MRS) for students born low birthweight (LBW) or preterm (PTB) and by childcare type, adjusting for other student and parent risk factors. Results MRSs for moderately LBW (1000-2499 g), extremely LBW (< 1000 g), moderately PTB (28-36 weeks), early-term (37-38 weeks) and post-term (42 + weeks) students were significantly lower than scores for their normal weight or full-term peers, adjusting for childcare type and other student and parent characteristics. Childcare was an important predictor of MRSs. MRSs were highest for district prekindergarten (PK) students and for students of mothers with greater years of education. Conclusions for Practice Social and biologic differences in MRSs for children entering school in a large urban public-school district suggest the need for greater attention to family and child health backgrounds. Increased enrollment in formal childcare may improve school readiness in these settings.

Neighborhood Gun Violence and Birth Outcomes in Chicago.

OBJECTIVES: To examine the association between gun violence and birth outcomes among women in Chicago. METHODS: Using a 5-year set of birth files (2011-2015) merged with census and police data, birth outcomes including low birth weight (LBW, BW < 2500 g), preterm birth (PTB, < 37 weeks gestation), and small-for-gestational-age (SGA, BW < 10th percentile) were examined among non-Hispanic (NH) white, NH black, and Hispanic women in Chicago. Gun violence rates were categorized into tertiles. Multilevel, multiple logistic regression examined the effects of gun violence and race/ethnicity on birth outcomes. RESULTS: Of 175,065 births, 10.6% of LBW, 10.6% of PTB, and 9.1% of SGA occurred in high violence tertile. Using white women in low violence tertile as reference, the OR for LBW among black women ranged 1.9-2.1 across all tertiles, and 0.8-1.2 among Hispanic women. OR for PTB for black women were 1.6-1.7 and 1.0-1.2 for Hispanic women, and OR for SGA for black women were 1.6-1.7 and for Hispanic women 0.9-1.0. CONCLUSIONS FOR PRACTICE: In Chicago, race/ethnicity was associated with birth outcomes, regardless of the level of exposure to gun violence, in 2011-2015. The differences in racial/ethnic composition across the violence exposure levels suggest that, rather than gun violence alone, residential segregation and the geographic inequities likely contribute to disparate birth outcomes.

Extrauterine Growth Restriction in Low Birth Weight Infants.

Extrauterine growth restriction (EUGR) affects a significant number of very low birth weight (VLBW) infants and has the potential to impact neurodevelopmental outcome as well as other aspects of long-term health. More aggressive nutritional approaches have reduced the incidence of postnatal growth failure but many questions remain about the expected rate of growth for very preterm infants, the best ways to measure growth velocity, and the optimal approaches to supporting growth. This article examines some of the outstanding issues regarding postnatal growth failure and summarizes current practice recommendations.