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Background: There is no consensus on optimal nutrition for preterm infants, leading to substantial practice variation. We aimed to assess the quality of nutrition guidelines for preterm infants, the consistency of recommendations, and the gaps in recommendations. Methods: We searched databases and websites for nutrition guidelines for preterm infants before first hospital discharge, which were endorsed, prepared, or authorized by a regional, national, or international body, written in English, and published between 2012 and 2023. Two reviewers independently screened articles and extracted the recommendations. Four reviewers appraised the included guidelines using Appraisal of Guidelines, Research, and Evaluation II. Results: A total of 7051 were identified, with 27 guidelines included, 26% of which were high in quality. Most guidelines lacked stakeholder involvement and rigor of development. We found considerable variation in recommendations, many of which lacked details on certainty of evidence and strength of recommendation. Recommendations for type of feed and breastmilk fortification were consistent among high‐quality guidelines, but recommendations varied for intakes of almost all nutrients and monitoring of nutrition adequacy. Different guidelines gave different certainty of evidence for the same recommendations. Most gaps in recommendations were due to very low certainty of evidence. Conclusion: Future development of nutrition guidelines for preterm infants should follow the standard guideline development method and ensure the rigorous process, including stakeholders' involvement, to improve the reporting of strength of recommendation, certainty of evidence, and gaps in recommendation. Evidence is needed to support recommendations about macro and micronutrient intakes, breastmilk fortification, and markers on adequacy of intake of different nutrients. [ABSTRACT FROM AUTHOR]

Aim: To examine the relationship between neonatal hypoglycaemia and specific areas of executive function and behaviour in mid‐childhood. Method: Participants in a prospective cohort study of infants born late preterm or at term at risk of neonatal hypoglycaemia were assessed at 9 to 10 years. We assessed executive function using performance‐based (Cambridge Neuropsychological Tests Automated Battery) and questionnaire‐based (Behavior Rating Inventory of Executive Function) measures and behaviour problems with the Strengths and Difficulties Questionnaire. Data are reported as adjusted odds ratio (aOR) with 95% confidence intervals, and standardized regression coefficients. Results: We assessed 480 (230 females, 250 males; mean age 9 years 5 months [SD 4 months, range 8 years 8 months–11 years 0 months]) of 587 eligible children (82%). There were no differences in performance‐based executive function between children who did and did not experience neonatal hypoglycaemia (blood glucose <2.6 mmoL/L). However, children who experienced hypoglycaemia, especially if severe or recurrent, were at greater risk of parent‐reported metacognition difficulties (aOR 2.37–3.71), parent‐reported peer (aOR 1.62–1.89) and teacher‐reported conduct (aOR 2.14 for severe hypoglycaemia) problems. Both performance‐ and questionnaire‐based executive functions were associated with behaviour problems. Interpretation: Neonatal hypoglycaemia may be associated with difficulties in specific aspects of parent‐reported executive functions and behaviour problems in mid‐childhood. [ABSTRACT FROM AUTHOR]

Nutritional intake can promote early neonatal brain development in very preterm born neonates (< 32 weeks' gestation). In a group of 7-year-old very preterm born children followed since birth, we examined whether early nutrient intake in the first weeks of life would be associated with long-term brain function and neurocognitive skills at school age. Children underwent resting-state functional MRI (fMRI), intelligence testing (Wechsler Intelligence Scale for Children, 5th Ed) and visual-motor processing (Beery-Buktenica, 5th Ed) at 7 years. Relationships were assessed between neonatal macronutrient intakes, functional connectivity strength between thalamic and default mode networks (DMN), and neuro-cognitive function using multivariable regression. Greater functional connectivity strength between thalamic networks and DMN was associated with greater intake of protein in the first week (β = 0.17; 95% CI 0.11, 0.23, p < 0.001) but lower intakes of fat (β = − 0.06; 95% CI − 0.09, − 0.02, p = 0.001) and carbohydrates (β = − 0.03; 95% CI − 0.04, − 0.01, p = 0.003). Connectivity strength was also associated with protein intake during the first month (β = 0.22; 95% CI 0.06, 0.37, p = 0.006). Importantly, greater thalamic-DMN connectivity strength was associated with higher processing speed indices (β = 26.9; 95% CI 4.21, 49.49, p = 0.02) and visual processing scores (β = 9.03; 95% CI 2.27, 15.79, p = 0.009). Optimizing early protein intake may contribute to promoting long-term brain health in preterm-born children. [ABSTRACT FROM AUTHOR]

Background: Nutritional supplements may improve short-term growth of infants born small (preterm or small for gestational age), but there are few data on long-term effects and concerns that body composition may be adversely affected. Effects also may differ between girls and boys. Our systematic review and meta-analysis assessed the effects of macronutrient supplements for infants born small on later growth.Methods and Findings: We searched OvidMedline, Embase, Cochrane CENTRAL, and Cochrane Database of Systematic Reviews from inception to January 30, 2020, and controlled-trials.com, clinicaltrials.gov, and anzctr.org.au on January 30, 2020. Randomised or quasirandomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born small and growth was assessed after discharge. Primary outcome was body mass index (BMI) in childhood. Data were pooled using random-effect models. Outcomes were evaluated in toddlers (< 3 years), childhood (3 to 8 years), adolescence (9 to 18 years), and adulthood (>18 years). Forty randomised and 2 quasirandomised trials of variable methodological quality with 4,352 infants were included. Supplementation did not alter BMI in childhood (7 trials, 1,136 children; mean difference [MD] -0.10 kg/m2, [95% confidence interval (CI) -0.37 to 0.16], p = 0.45). In toddlers, supplementation increased weight (31 trials, 2,924 toddlers; MD 0.16 kg, [0.01 to 0.30], p = 0.03) and length/height (30 trials, 2,889 toddlers; MD 0.44 cm, [0.10 to 0.77], p = 0.01), but not head circumference (29 trials, 2,797 toddlers; MD 0.15 cm, [-0.03 to 0.33], p = 0.10). In childhood, there were no significant differences between groups in height (7 trials, 1,136 children; MD 0.22 cm, [-0.48 to 0.92], p = 0.54) or lean mass (3 trials, 354 children; MD -0.07 kg, [-0.98 to 0.85], p = 0.88), although supplemented children appeared to have higher fat mass (2 trials, 201 children; MD 0.79 kg, [0.19 to 1.38], p = 0.01). In adolescence, there were no significant differences between groups in BMI (2 trials, 216 adolescents; MD -0.48 kg/m2, [-2.05 to 1.08], p = 0.60), height (2 trials, 216 adolescents; MD -0.55 cm, [-2.95 to 1.86], p = 0.65), or fat mass (2 trials, 216 adolescents; MD -1.3 5 kg, [-5.76 to 3.06], p = 0.55). In adulthood, there also were no significant differences between groups in weight z-score (2 trials, 199 adults; MD -0.11, [-0.72 to 0.50], p = 0.73) and height z-score (2 trials, 199 adults; MD -0.07, [-0.36 to 0.22], p = 0.62). In subgroup analysis, supplementation was associated with increased length/height in toddler boys (2 trials, 173 boys; MD 1.66 cm, [0.75 to 2.58], p = 0.0003), but not girls (2 trials, 159 girls; MD 0.15 cm, [-0.71 to 1.01], p = 0.74). Limitations include considerable unexplained heterogeneity, low to very low quality of evidence, and possible bias due to low or unbalanced followup.Conclusions: In this systematic review and meta-analysis, we found no evidence that early macronutrient supplementation for infants born small altered BMI in childhood. Although supplements appeared to increase weight and length in toddlers, effects were inconsistent and unlikely to be clinically significant. Limited data suggested that supplementation increased fat mass in childhood, but these effects did not persist in later life. PROSPERO registration: CRD42019126918. [ABSTRACT FROM AUTHOR]

Background: Antenatal corticosteroids (ANC) reduce mortality and morbidity in preterm babies, but prescription practices vary. Aims: To assess obstetricians' compliance with the recommendations of the Australian and New Zealand clinical practice guidelines on use of ANC. Materials and Methods: An anonymous online questionnaire was distributed to Fellows of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists. Results: All respondents reported prescribing an initial course of ANC according to the guidelines if preterm birth at 28 weeks' gestation was expected within 24 or 72 h. However, 22% reported prescribing ANC even if birth was not expected within seven days. This was reported more often by practitioners not using adjunct tests to predict preterm birth (14% vs 69%; P < 0.001). An initial course of ANC at ≥35 weeks was prescribed by 52% of respondents. However, 93% reported prescribing ANC at ≥35 weeks prior to elective caesarean section. Repeat courses of ANC were prescribed by 76% of respondents. Of these, 89% reported prescribing repeat courses beyond the guideline recommendations at ≥33 weeks and 29% exceeded the recommendations on number of repeat courses. Conclusions: For infants born at <35 weeks, current ANC prescribing patterns in Australia and New Zealand are consistent with the guideline recommendations and result in high rates of administration in this group. However, administration of ANC to groups where benefits have not been demonstrated is commonly reported. Adherence to the guideline recommendations would decrease ANC exposure to babies for whom there is no strong evidence of benefit. [ABSTRACT FROM AUTHOR]

BACKGROUND: Repeat dose(s) of antenatal betamethasone are recommended for women at <32 weeks with ongoing risk of preterm birth. However, there is concern that use of repeat dose(s) in fetal growth restriction (FGR) may increase the risk of later cardiometabolic disease. METHODS: We undertook secondary analysis of data from the Australasian Collaborative Trial of Repeat Doses of Corticosteroids Midchildhood Outcome Study to determine if FGR influences the effect of repeat betamethasone on growth and cardiometabolic function. At 6 to 8 years, children underwent anthropometry, dual energy x-ray absorptiometry, intravenous glucose tolerance testing, ambulatory blood pressure monitoring, and spirometry. FGR was defined as severe FGR at entry, cesarean delivery for FGR, or customized birth weight below the third centile. RESULTS: Of 266 children assessed, FGR occurred in 43 of 127 (34%) exposed to repeat betamethasone and 44 of 139 (32%) exposed to placebo. There was an interaction between FGR and repeat betamethasone treatment for the effect on height (z score mean difference [95% confidence interval]; FGR: 0.59 [0.01 to 1.17]; non-FGR: -0.29 [-0.69 to 0.10]; P = .01). However, FGR did not influence the effect of repeat betamethasone on cardiometabolic function, which was similar in treatment groups, both in FGR and non-FGR subgroups. CONCLUSIONS: Repeat antenatal betamethasone treatment had no adverse effects on cardiometabolic function, even in the presence of FGR. It may have a positive effect on height in FGR. Clinicians should use repeat doses of antenatal corticosteroids when indicated before preterm birth, regardless of FGR, in view of the associated neonatal benefits. [ABSTRACT FROM AUTHOR]

The article presents e results of the Protein Intravenous Nutrition on Development (ProVIDe) trial of an extra 1 g of parenteral amino acids for the first 5 days after birth. Topics include the value of a protein is predicated on its amino acid composition that addressed the issue of protein quality; and assessment of the potential benefit of supplemental protein for infants with extremely low birth weight.

The long-term scarring burden of preterm infants undergoing modern neonatal intensive care is not known. This observational cohort study aimed to document the presence and pattern of scarring in children born <30 weeks' gestation or <1500 g birth weight and cared for at the National Women's Health neonatal intensive care unit, Auckland, New Zealand. Children were examined at 7 years' corrected age and the presence, size, number and distribution of scars documented. Scarring was seen in 90% of 129 children assessed, with 81% having multiple scars, 60% having large scars (85% of whom had no history of major neonatal surgery) and 75% having more than one body area scarred. Scarring was more common in boys and in children of non-European ethnicity. Despite modern neonatal intensive care practices, children born very preterm are frequently and extensively scarred at school age. [ABSTRACT FROM AUTHOR]

Background: Both dexamethasone and betamethasone, given to women at risk of preterm birth, substantially improve short-term neonatal health, increase the chance of the baby being discharged home alive, and reduce childhood neurosensory disability, remaining safe into adulthood. However, it is unclear which corticosteroid is of greater benefit to mother and child. This study aims to determine whether giving dexamethasone to women at risk of preterm birth at less than 34 weeks' gestation increases the chance of their children surviving free of neurosensory disability at two years' corrected age, compared with betamethasone. Methods/Design: Design randomised, multicentre, placebo controlled trial. Inclusion criteria women at risk of preterm birth at less than 34 weeks' gestation with a singleton or twin pregnancy and no contraindications to the use of antenatal corticosteroids and who give informed consent. Trial entry & randomisation at telephone randomisation eligible women will be randomly allocated to either the dexamethasone group or the betamethasone group, allocated a study number and corresponding treatment pack. Study groups women in the dexamethasone group will be administered two syringes of 12 mg dexamethasone (dexamethasone sodium phosphate) and women in the betamethasone group will be administered two syringes of 11.4 mg betamethasone (Celestone Chronodose). Both study groups consist of intramuscular treatments 24 hours apart. Primary study outcome death or any neurosensory disability measured in children at two years' corrected age. Sample size a sample size of 1449 children is required to detect either a decrease in death or any neurosensory disability from 27.0% to 20.1% with dexamethasone compared with betamethasone, or an increase from 27.0% to 34.5% (two-sided alpha 0.05, 80% power, 5% loss to follow up, design effect 1.2). Discussion: This study will provide high-level evidence of direct relevance for clinical practice. If one drug clearly results in significantly fewer deaths and fewer disabled children then it should be used consistently in women at risk of preterm birth and would be of great importance to women at risk of preterm birth, their children, health services and communities. [ABSTRACT FROM AUTHOR]

We aimed to evaluate insulin secretion and insulin sensitivity in adults born preterm and their children. Subjects were adults born both preterm and at term, with their children aged 5-10 years born at term. Insulin sensitivity and secretion were assessed using hyperglycemic clamps in adults and frequently sampled intravenous glucose tolerance tests using Bergman minimal model in children. In total, 52 adults aged 34-38 years participated (31 born preterm, mean gestational age 33.3 weeks). Adults born preterm were less insulin sensitive than those born at term (19.0 ± 2.5 vs. 36.3 ± 5.2 mg ⋅ kg-1 ⋅ min21mU ⋅ L; P < 0.05) with compensatory increased first-phase insulin secretion (56.1 6 8.5 vs. 25.3 ± 3.7 mU/L; P < 0.001) but similar disposition index indicating appropriate insulin secretion. These differences were independent of sex and remained when subjects born ,32 weeks' gestation were excluded from analyses. In total, 61 children were studied (37 of preterm parents, mean age 7.9 ± 0.3 years). Children of parents born preterm had similar insulin sensitivity to children of parents born at term, but a correlation between parental and offspring insulin sensitivity was noted only among children of parents born preterm. In conclusion, adults born preterm have insulin resistance in midadulthood, but this was not associated with insulin resistance in their children. [ABSTRACT FROM AUTHOR]

Administration of antenatal glucocorticoids to women at risk of preterm birth has major benefits for infants but the use of repeat dose(s) is controversial. We performed a systematic review of randomized trials, using standard Cochrane methodology, to assess the effectiveness and safety of 1 or more repeat doses given to women at risk of preterm birth 7 or more days after an initial course. Ten trials were included involving over 4730 women and 5700 infants. Treatment with repeat dose(s) compared with no repeat treatment reduced the risk of respiratory distress syndrome (risk ratio, 0.83; 95% confidence interval, 0.75–0.91) and serious neonatal morbidity (risk ratio, 0.84; 95% confidence interval, 0.75–0.94). At 2- to 3-year follow-up (4 trials, 4170 children), there was no evidence of either significant benefit or harm. Repeat doses of glucocorticoids should be considered in women at risk of preterm birth 7 or more days after an initial course, in view of the neonatal benefits. [ABSTRACT FROM AUTHOR]

Background: The use of postnatal corticosteroids to treat or prevent chronic lung disease is common in very preterm infants. Medullary nephrocalcinosis has been noted as a possible side effect.Objective: This prospective study was designed to assess the incidence of nephrocalcinosis in extremely preterm infants exposed to dexamethasone.Patients and Methods: A prospective study of extremely preterm infants, recruited to a randomized trial of dexamethasone treatment for chronic lung disease, was initiated. Infants had US of the renal tract scheduled on entry into the study, at day 28 and at discharge or at the corrected gestational age of 36 weeks.Results: Thirty-three infants were enrolled in the study. Birth weight ranged between 440 and 990 g and gestation between 24 and 28 weeks. Nine infants died and six had incomplete data. Because there was no difference in incidence of calcification between those on the short course and those on the long course of dexamethasone, analysis was made on the entire cohort. One infant had nephrocalcinosis at the time of the initial US examination on day 26 of life. By day 28, nephrocalcinosis was present in 31% of those with complete data. By discharge, or corrected gestational age of 36 weeks, US evidence of nephrocalcinosis was present in 15 (83%) of 18 infants. All infants had at least one course of an aminoglycoside antibiotic during the study. All infants had parenteral nutrition. Only four infants received furosemide more regularly than single doses. The longest course was 10 days, received by an infant who did not develop nephrocalcinosis.Conclusion: The incidence of nephrocalcinosis is high in this group of sick, extremely preterm infants. Dexamethasone may be a factor in the development of nephrocalcinosis. Future research should focus on the natural history of nephrocalcinosis in extremely preterm infants. [ABSTRACT FROM AUTHOR]

Early macronutrient supplementation in preterm and/or small-for-gestational-age (SGA) infants may improve growth but have detrimental effects on later cardio-metabolic health which may be sex-specific. We systematically reviewed the long-term effects of early macronutrient supplementation in preterm and SGA animals and whether these differ by sex. Using Cochrane Neonatal and SYRCLE methodologies we included random or quasi-random studies that allocated non-human mammals to macronutrient supplements or no supplements between birth and weaning and assessed post-weaning outcomes. We used random-effects models to calculate standardized mean differences (SMD) with 95% confidence intervals (CIs). Six studies provided low to very-low-quality evidence that macronutrient supplementation increased weight in juvenile rats (SMD; 95% CI: 2.13; 1.00, 3.25; 1 study, n = 24), increased leptin concentrations in older adults (1.31; 0.12, 2.51; 1 study, n = 14 male rats), but decreased leptin concentrations in young adults (−1.13; −2.21, −0.05; 1 study, n = 16 female rats) and improved spatial learning and memory (qualitative data; 1 study). There was no evidence of sex-specific effects and no overall effect on length, serum lipids, body composition, HOMA-IR, or blood pressure. Macronutrient supplements may affect later growth, metabolism, and neurodevelopment of preterm and SGA animals, but evidence is limited and low quality. [ABSTRACT FROM AUTHOR]

BACKGROUND Most moderate-to-late--preterm infants need nutritional support until they are feeding exclusively on their mother's breast milk. Evidence to guide nutrition strategies for these infants is lacking. METHODS We conducted a multicenter, factorial, randomized trial involving infants born at 32 weeks 0 days' to 35 weeks 6 days' gestation who had intravenous access and whose mothers intended to breast-feed. Each infant was assigned to three interventions or their comparators: intravenous amino acid solution (parenteral nutrition) or dextrose solution until full feeding with milk was established; milk supplement given when maternal milk was insufficient or mother's breast milk exclusively with no supplementation; and taste and smell exposure before gastric-tube feeding or no taste and smell exposure. The primary outcome for the parenteral nutrition and the milk supplement interventions was the body-fat percentage at 4 months of corrected gestational age, and the primary outcome for the taste and smell intervention was the time to full enteral feeding (150 ml per kilogram of body weight per day or exclusive breast-feeding). RESULTS A total of 532 infants (291 boys [55%]) were included in the trial. The mean (±SD) body-fat percentage at 4 months was similar among the infants who received parenteral nutrition and those who received dextrose solution (26.0±5.4% vs. 26.2±5.2%; adjusted mean difference, -0.20; 95% confidence interval [CI], -1.32 to 0.92; P=0.72) and among the infants who received milk supplement and those who received mother's breast milk exclusively (26.3±5.3% vs. 25.8±5.4%; adjusted mean difference, 0.65; 95% CI, -0.45 to 1.74; P=0.25). The time to full enteral feeding was similar among the infants who were exposed to taste and smell and those who were not (5.8±1.5 vs. 5.7±1.9 days; P=0.59). Secondary outcomes were similar across interventions. Serious adverse events occurred in one infant. CONCLUSIONS This trial of routine nutrition interventions to support moderate-to-late--preterm infants until full nutrition with mother's breast milk was possible did not show any effects on the time to full enteral feeding or on body composition at 4 months of corrected gestational age. (Funded by the Health Research Council of New Zealand and others; DIAMOND Australian New Zealand Clinical Trials Registry number, ACTRN12616001199404. [ABSTRACT FROM AUTHOR]

Background: Babies born at moderate-late preterm gestations account for > 80% of all preterm births. Although survival is excellent, these babies are at increased risk of adverse neurodevelopmental outcomes. They also are at increased risk of adverse long-term health outcomes, such as cardiovascular disease, obesity and diabetes. There is little evidence guiding optimal nutritional practices in these babies; practice, therefore, varies widely. This factorial design clinical trial will address the role of parenteral nutrition, milk supplementation and exposure of the preterm infant to taste and smell with each feed on time to tolerance of full feeds, adiposity, and neurodevelopment at 2 years.Methods/design: The DIAMOND trial is a multi-centre, factorial, randomised, controlled clinical trial. A total of 528 babies born between 32+ 0 and 35+ 6 weeks' gestation receiving intravenous fluids and whose mothers intend to breastfeed will be randomised to one of eight treatment conditions that include a combination of each of the three interventions: (i) intravenous amino acid solution vs. intravenous dextrose solution until full milk feeds established; (ii) milk supplement vs. exclusive breastmilk, and (iii) taste/smell given or not given before gastric tube feeds. Babies will be excluded if a particular mode of nutrition is clinically indicated or there is a congenital abnormality. Primary study outcome: For parenteral nutrition and milk supplement interventions, body composition at 4 months' corrected age. For taste/smell intervention, time to full enteral feeds defined as 150 ml.kg- 1.day- 1 or exclusive breastfeeding.Secondary Outcomes: Days to full sucking feeds; days in hospital; body composition at discharge; growth to 2 years' corrected age; development at 2 years' corrected age; breastfeeding rates.Discussion: This trial will provide the first direct evidence to inform feeding practices in moderate- to late-preterm infants that will optimise their growth, metabolic and developmental outcomes.Trial Registration: Australian New Zealand Clinical Trials Registry - ACTRN12616001199404 . This trial is endorsed by the IMPACT clinical trials network ( https://impact.psanz.com.au ). [ABSTRACT FROM AUTHOR]

Handgrip strength (HGS) indicates current and future health. Although preterm infants have an increased risk of poor grip strength in later life, its determinants and relationship with neurodevelopment are not well understood. To determine HGS in children born preterm and explore the relationship of HGS with demography, anthropometry, nutritional factors, and neurodevelopmental outcomes. A prospective cohort study of moderate-late preterm babies enrolled in a randomised trial of nutritional support strategies, the DIAMOND trial. A total of 116 children born between 32 and 35 weeks' gestation, whose HGS was measured at 2 years' corrected age. HGS was measured using a dynamometer, and neurodevelopment was assessed using the Bayley Scales of Infant Development-III. Anthropometry and body composition were assessed at birth, discharge, and at 4 months' and 2 years' corrected age. Information on demographics and breastfeeding practices, including type of milk at discharge and duration of exclusive breastfeeding, was collected using questionnaires. The mean (standard deviation) HGS was 2.26 (1.07) kg. The Bayley scores were < 85 (−1 standard deviation) in 6 %, 20 %, and 1 % for the cognitive, language, and motor scales, respectively. Multiple regression analysis revealed that HGS was positively associated with language and motor scores (p <.05) after adjusting for confounding factors. HGS was not associated with sex, anthropometry, body composition, or breastfeeding practices. Maternal education was independently associated with HGS (p <.01). HGS at age 2 years in children born moderate-late preterm is associated with language and motor development and maternal education level. • Handgrip strength at age 2 years in children born moderate-late preterm was 2.26 kg. • Lower handgrip strength was associated with poorer language and motor development. • Maternal education was an independent determinant of handgrip strength. • Handgrip strength did not depend on sex, anthropometry, and body composition. • Breastfeeding practices in the first 6 months were not related to handgrip strength. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess if exposure to repeat dose(s) of antenatal corticosteroids has beneficial effects on neurodevelopment and general health in mid-childhood, at 6 to 8 years' corrected age. METHODS: Women at risk for very preterm birth, who had received a course of corticosteroids ≥7 days previously, were randomized to intramuscular betamethasone (11.4 mg Celestone Chronodose) or saline placebo, repeated weekly if risk of very preterm birth remained. Mid-childhood assessments included neurocognitive function, behavior, growth, lung function, blood pressure, health-related quality of life, and health service utilization. The primary outcome was survival free of neurosensory disability. RESULTS: Of the 1059 eligible long-term survivors, 963 (91%) were included in the primary outcome; 479 (91%) in the repeat corticosteroid group and 484 (91%) in the placebo group. The rate of survival free of neurosensory disability was similar in both groups (78.3% repeat versus 77.3% placebo; risk ratio 1.00, 95% confidence interval, 0.94-1.08). Neurodevelopment, including cognitive function, and behavior, body size, blood pressure, spirometry, and health-related quality of life were similar in both groups, as was the use of health services. CONCLUSIONS: Treatment with repeat dose(s) of antenatal corticosteroids was associated with neither benefit nor harm in mid-childhood. Our finding of long-term safety supports the use of repeat dose(s) of antenatal corticosteroids, in view of the related neonatal benefits. For women at risk for preterm birth before 32 weeks' gestation, ≥7 days after an initial course of antenatal corticosteroids, clinicians could consider using a single injection of betamethasone, repeated weekly if risk remains. [ABSTRACT FROM AUTHOR]

Background: We previously reported the results of a randomized, controlled trial showing that repeat doses of antenatal corticosteroids reduced the risk of respiratory distress syndrome and serious neonatal morbidity. However, data have not been available regarding longer-term effects of this treatment. Methods: Women who had received an initial course of corticosteroid treatment 7 or more days previously were randomly assigned to receive an intramuscular injection of corticosteroid (11.4 mg of betamethasone) or saline placebo; the dose was repeated weekly if the mother was still considered to be at risk for preterm delivery and the duration of gestation was less than 32 weeks. We assessed survival free of major neurosensory disability and body size of the children at 2 years of corrected age. Results: Of the 1085 children who were alive at 2 years of age, 1047 (96.5%) were seen for assessment (521 exposed to repeat-corticosteroid treatment and 526 exposed to placebo). The rate of survival free of major disability was similar in the repeat-corticosteroid and placebo groups (84.4% and 81.0%, respectively; adjusted relative risk, 1.04, 95% confidence interval, 0.98 to 1.10; adjusted P=0.20). There were no significant differences between the groups in body size, blood pressure, use of health services, respiratory morbidity, or child behavior scores, although children exposed to repeat doses of corticosteroids were more likely than those exposed to placebo to warrant assessment for attention problems (P=0.04). Conclusions: Administration of repeat doses of antenatal corticosteroids reduces neonatal morbidity without changing either survival free of major neurosensory disability or body size at 2 years of age. (Current Controlled Trials number, ISRCTN48656428.) N Engl J Med 2007;357:1179-89. [ABSTRACT FROM AUTHOR]

Background: Children born very preterm are at higher risk of adverse neurocognitive and educational outcomes. However, how low intelligence (IQ) and low executive function may each contribute to poorer academic outcomes at school age requires clarification.Aim: To examine the associations between intelligence, executive function and academic achievement in children born very preterm.Design/methods: This cohort study assessed children born <30 weeks' gestation or <1500 g at age 7 years using the Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV) for IQ, and the Test of Everyday Attention for Children (TEA-Ch) and Behavior Rating Inventory of Executive Function (BRIEF) for executive function. Academic achievement was rated by teachers against curriculum standards.Results: Of the 76 children (35 girls, 41 boys, mean age = 7.2 year), 22 (28%) were rated below expected level for reading, 32 (42%) for writing and 38 (50%) for mathematics. After adjustment for sex and socioeconomic status, low IQ (OR's 9.0-12.3) and most low executive function measures (OR's 4.1-9.3) were associated with below-expected achievement. After further adjustment for IQ, low cognitive flexibility (OR = 9.3, 95% CI = 1.2-71.5) and teacher ratings of executive function (OR = 5.3, 95% CI = 1.4-20.2) were associated with below-expected achievement. Mediation analysis showed IQ had indirect effects on writing (b = 1.5, 95% CI = 0.6-3.1) via attentional control; and on reading (b = 1.0, 95% CI = 0.2-3.2) and writing (b = 0.8, 95% CI = 0.1-2.5) via cognitive flexibility.Conclusions: Both low IQ and low executive function are associated with below-expected teacher-rated academic achievement in children born very preterm. IQ may influence academic achievement in part through executive function. [ABSTRACT FROM AUTHOR]