Growth patterns by birth size of preterm children born at 24-29 gestational weeks for the first 3 years.

BACKGROUND: Concerns are prevalent about preterm infant long-term growth regarding plotting low on growth charts at discharge, stunting, underweight, high body fat and subsequent cardiometabolic morbidities. OBJECTIVES: To examine (a) longitudinal growth patterns of extremely and very preterm infants to 3 years corrected age (CA) (outcome), categorised by their birthweight for gestational age: small, appropriate and large for gestational age (SGA, AGA and LGA, respectively) (exposure); and (b) the ability of growth faltering (<-2 z-scores) to predict suboptimal cognitive scores at 3 years CA. METHODS: Post-discharge head, length, weight and weight-4-length growth patterns of the PreM Growth cohort study infants born <30 weeks and < 1500 g, who had dietitian and multi-disciplinary support before and after discharge, were plotted against the World Health Organization growth standard. Infants with brain injuries, necrotising enterocolitis and bronchopulmonary dysplasia were excluded. RESULTS: Of the included 405 infants, the proportions of infants with anthropometric measures > - 2 z-scores improved with age. The highest proportions <-2 z-scores for length (24.2%) and weight (24.0%) were at 36 gestational weeks. The proportion with small heads was low by 0 months CA (1.8%). By 3 years CA, only a few children plotted lower than -2 z-scores for length, weight-4-length and weight (<6%). After zero months CA, high weight-4-length and body mass index > + 2 z-scores were rare (2.1% at 3 years CA). Those born SGA had higher proportions with shorter heights (16.7% vs. 5.2%) and lower weights (27.8% vs. 3.5%) at 3 years CA compared to those born AGA. The ability of growth faltering to predict cognitive scores was limited (AUROC 0.42, 95% CI 0.39, 0.45 to 0.52, 95% CI 0.41, 0.63). CONCLUSIONS: Although children born <30 weeks gestation without major neonatal morbidities plot low on growth charts at 36 weeks CA most catch up to growth chart curves by 3 years CA.

Prevalence, Risk Factors, and Outcomes of Adult Interstitial Lung Abnormalities: A Systematic Review and Meta-Analysis.

Rationale: Incidental parenchymal abnormalities detected on chest computed tomography scans are termed interstitial lung abnormalities (ILAs). ILAs may represent early interstitial lung disease (ILD) and are associated with an increased risk of progressive fibrosis and mortality. The prevalence of ILAs is unknown, with heterogeneity across study populations. Objectives: Estimate the pooled prevalence of ILAs in lung cancer screening, general population-based, and at-risk familial cohorts using meta-analysis; identify variables associated with ILA risk; and characterize ILA-associated mortality. Methods: The study protocol was registered on PROSPERO (CRD42022373203), and Meta-analyses of Observational Studies in Epidemiology recommendations were followed. Relevant studies were searched on Embase and Medline. Study titles were screened and abstracts reviewed for full-text eligibility. Random effect models were used to pool prevalence estimates for specified subgroups and ILA-associated mortality risk. Risk of ILAs was estimated based on age, sex, and FVC. Quality assessment was conducted using an adapted Assessment Tool for Prevalence Studies. Measurements and Main Results: The search identified 9,536 studies, with 22 included, comprising 88,325 participants. The pooled ILA prevalence was 7% (95% confidence interval [CI], 0.01-0.13) in lung cancer screening, 7% (95% CI, 0.04-0.10) in general population, and 26% (95% CI, 0.20-0.32) in familial cohorts. Pooled mortality risk was increased in those with ILAs (odds ratio, 3.56; 95% CI, 2.19-5.81). Older age, male sex, and lower FVC% were associated with greater odds of ILA. Conclusions: Populations undergoing imaging for non-ILD indications demonstrate high ILA prevalence. Standardized reporting and follow-up of ILAs is needed, including defining those at greatest risk of progression to ILD.

Small for gestational age preterm infants and later adiposity and height: A systematic review and meta-analysis.

BACKGROUND: Overweight and obesity and their consequent morbidities are important worldwide health problems. Some research suggests excess adiposity origins may begin in fetal life, but unknown is whether this applies to infants born preterm. OBJECTIVE: The objective of the study was to assess the association between small for gestational age (SGA) birth and later adiposity and height among those born preterm. DATA SOURCES: MEDLINE, EMBASE and CINAHL until October 2022. STUDY SELECTION AND DATA EXTRACTION: Studies were included if they reported anthropometric (adiposity measures and height) outcomes for participants born preterm with SGA versus non-SGA. Screening, data extraction and risks of bias assessments were conducted in duplicate by two reviewers. SYNTHESIS: We meta-analysed across studies using random-effects models and explored potential heterogeneity sources. RESULTS: Thirty-nine studies met the inclusion criteria. In later life, preterm SGA infants had a lower body mass index (-0.66 kg/m2 , 95% CI -0.79, -0.53; 32 studies, I2 = 16.7, n = 30,346), waist circumference (-1.20 cm, 95% CI -2.17, -0.23; 13 studies, I2 = 19.4, n = 2061), lean mass (-2.62 kg, 95% CI -3.45, 1.80; 7 studies, I2 = 0, n = 205) and height (-3.85 cm, 95% CI -4.73, -2.96; 26 studies, I2 = 52.6, n = 4174) compared with those preterm infants born non-SGA. There were no differences between preterm SGA and preterm non-SGA groups in waist/hip ratio, body fat, body fat per cent, truncal fat per cent, fat mass index or lean mass index, although power was limited for some analyses. Studies were rated at high risk of bias due to potential residual confounding and low risk of bias in other domains. CONCLUSIONS: Compared to their preterm non-SGA peers, preterm infants born SGA have lower BMI, waist circumference, lean body mass and height in later life. No differences in adiposity were observed between SGA preterm infants and non-SGA preterm infants.

Small for date preterm infants and risk of higher blood pressure in later life: A systematic review and meta-analysis.

BACKGROUND: Historical reports suggest that infants born small for gestational age (SGA) are at increased risk for high blood pressure (BP) at older ages after adjustment for later age body size. Such adjustment may be inappropriate since adiposity is a known cause of cardiovascular and metabolic disease. OBJECTIVES: To assess the association between SGA births and later BP among preterm births, considering potential background confounders and over-adjustment for later body size. METHODS: A database search of studies up to October 2022 included MEDLINE, EMBASE and CINAHL. Studies were included if they reported BP (systolic [SBP] or diastolic [DBP]) (outcomes) for participants born preterm with SGA (exposure) or non-SGA births. All screening, extraction steps, and risk of bias (using the Risk of Bias In Non-randomised Studies of Interventions [ROBINS-I] tool) were conducted in duplicate by two reviewers. Data were pooled in meta-analysis using random-effects models. We explored potential sources of heterogeneity. RESULTS: We found no meaningful difference in later BP between preterm infants with and without SGA status at birth. Meta-analysis of 25 studies showed that preterm SGA, compared to preterm non-SGA, was not associated with higher BP at age 2 and older with mean differences for SBP 0.01 mmHg (95% CI -0.10, 0.12, I2  = 59.8%, n = 20,462) and DBP 0.01 mm Hg (95% CI -0.10, 0.12), 22 studies, (I2  = 53.0%, n = 20,182). Adjustment for current weight did not alter the results, which could be due to the lack of differences in later weight status in most of the included studies. The included studies were rated to be at risk of bias due to potential residual confounding, with a low risk of bias in other domains. CONCLUSIONS: Evidence indicates that preterm infants born SGA are not at increased risk of developing higher BP as children or as adults as compared to non-SGA preterm infants.

Does the evidence support in utero influences on later health and disease? A systematic review of highly cited Barker studies on developmental origins.

The developmental origins of health and disease hypothesis proposes that early exposure to adverse conditions during fetal development and early life have strong detrimental consequences on long-term health and susceptibility to chronic diseases. We conducted a systematic review to critically appraise Barker's highest cited publications using the risk-of-bias assessment tool (ROBINS-I) and investigate effects of overadjustment by later body weight. Our findings revealed that all included studies displayed high risks of bias, with particular concerns regarding confounding (8/8), selection of reported results (8/8), classification of exposure (7/8), selection of participants (5/8) and high rates of missing data (ranged from 15 to 87%). Later body weight was over-adjusted in most (6/8) of the studies. As all studies displayed high bias risk due to confounding, missing data and overadjustment, evidence is insufficient to support causal relationships between low birthweight and adult disease, warranting caution in clinical application. PROTOCOL REGISTRATION: PROSPERO CRD42023433179.

Expected and Desirable Preterm and Small Infant Growth Patterns.

Adequate nutrition is necessary for achieving optimal growth and neurodevelopment. Growth is a natural and expected process that happens concomitantly with rapid advancements in neurodevelopment. Serial weight, length, and head circumference growth measures are essential for monitoring development, although identifying pathological deviations from normal growth can pose challenges. Appropriate growth assessments require considerations that a range of sizes for length, head circumference, and weight are expected and appropriate. Because of genetic differences and morbidities, there is a considerable overlap between the growth of healthy infants and those with growth alterations. Parents tend to be over-concerned about children who plot low on growth charts and often need reassurance. Thus, the use of terms such as "poor" growth or growth "failure" are discouraged when growth is approximately parallel to growth chart curves even if their size is smaller than specific percentiles. No specific percentile should be set as a growth goal; individual variability should be expected. An infant's size at birth is important information that goes beyond the common use of prognostic predictions of appropriate compared with small or large for gestational age. The lower the birthweight, the lower the nutrient stores and the more important the need for nutrition support. Compared to term infants, preterm infants at term-equivalent age have a higher percentage of body fat, but this diminishes over the next months. Current research findings support expert recommendations that preterm infants should grow, after early postnatal weight loss, similar to the fetus and then term-born infants, which translates to growth approximately parallel to growth chart curves. There is no need for a trade-off between optimum cognition and optimum future health. Each high-risk infant needs individualized nutrition and growth assessments. This review aims to examine infant growth expectations and messaging for parents of preterm and term-born infants within the broader causal framework.

Scoping review of exposure questionnaires and surveys in interstitial lung disease.

BACKGROUND: Many interstitial lung diseases (ILDs) have clear causal relationships with environmental and occupational exposures. Exposure identification can assist with diagnosis, understanding disease pathogenesis, prognostication and prevention of disease progression and occurrence in others at risk. Despite the importance of exposure identification in ILD, there is no standardised assessment approach. Many questionnaires are in clinical and research use, yet their utility, applicability, relevance and performance characteristics are unknown. OBJECTIVES: This scoping review aimed to summarise the available evidence relating to ILD exposure assessment questionnaires, identify research gaps and inform the content for a future single evidence-based ILD questionnaire. METHODS: A scoping review based on Arksey and O'Malley's methodological framework was conducted. ELIGIBILITY CRITERIA: Any questionnaire that elicited exposures specific to ILD was included. A modified COSMIN Risk of Bias Framework was used to assess quality. SOURCES OF EVIDENCE: Relevant articles were identified from MEDLINE and EMBASE up to 23 July 2023. RESULTS: 22 exposure questionnaires were identified, including 15 generally pertaining to ILD, along with several disease-specific questionnaires for hypersensitivity pneumonitis (n=4), chronic beryllium disease, sarcoidosis and silicosis (1 questionnaire each). For most questionnaires, quality was low, whereby the methods used to determine exposure inclusion and questionnaire validation were not reported or not performed. Collectively the questionnaires covered 158 unique exposures and at-risk occupations, most commonly birds, mould/water damage, wood dust, asbestos, farming, automotive mechanic and miners. Only five questionnaires also provided free-text fields, and 13 queried qualifiers such as temporality or respiratory protection. CONCLUSIONS: Designing a robust ILD-specific questionnaire should include an evidence-based and relevance-based approach to exposure derivation, with clinicians and patients involved in its development and tested to ensure relevance and feasibility.

Dosages of Nutrient Supplements and Potential Long-Term Toxicity in Attention-Deficit/Hyperactivity Disorder Micronutrient Study.

We read with interest the article by Johnstone et al.1 reporting their vitamin-mineral randomized trial that found that children with attention-deficit/hyperactivity disorder (ADHD) showed global benefit over placebo by blinded clinician rating, but not by parent-report CASI-5 composite rating in a population with ADHD and irritability. Because some of the mineral dosing was in potentially toxic ranges, we sought to examine the trial findings. Given that the producing company is promoting their supplement for long-term use,2 the scientific and consumer communities might value some additional information about potential toxicity from long-term dosing.

The Importance of Reporting Energy Values of Human Milk as Metabolizable Energy.

Nutrition science has a convention to report metabolizable energy instead of gross energy. Metabolizable energy at 4 kilocalories per gram for protein and carbohydrate, 9 kcal per gram for fat (kilojoules: 17 and 37, respectively) represents the food energy available for metabolism. However, this convention to use metabolizable energy has not been uniformly applied to human milk. Human milk is often reported as gross energy, which is about 5-10% higher than metabolizable energy. To obtain accurate human milk energy estimates, milk samples need to contain the same proportion of high fat hind milk that an infant obtains.

Are small-for-gestational-age preterm infants at increased risk of overweight? Statistical pitfalls in overadjusting for body size measures.

OBJECTIVE: The objective of this study is to analyze the effect of adjusting for body measures on the association between small for gestational age (SGA) and overweight at 3 years. STUDY DESIGN: Data were obtained from the Preterm Infant Multicenter Growth Study (n = 1089). Logistic regression was used, to adjust for confounders with additional adjustments separately for weight and height at 21 months. Marginal structural models (MSMs) estimated the direct effect of SGA on overweight. RESULTS: The crude and adjusted for confounders models yielded null associations between SGA and overweight. Adjusting for height yielded a positive association (odds ratio (OR): 2.31, 95% CI: 0.52-10.26) and adjusting for weight provided a significantly positive association (OR: 6.60, 95% CI: 1.10-37.14). The MSMs, with height and weight held constant, provided no evidence for a direct effect of SGA on overweight (OR: 0.83, 95% CI: 0.14-5.01, OR: 0.71, 95% CI: 0.18-2.81, respectively). CONCLUSION: Adjusting for body measures can change the association between SGA and overweight, providing spurious estimates.

Critical examination of relationships between early growth and childhood overweight in extremely preterm infants.

OBJECTIVES: To identify the prevalence and risk factors for childhood overweight and obesity (OWO) at 3-year corrected age in children born <1500 g <29 weeks gestation. STUDY DESIGN: A multicentre retrospective cohort study for preterm infants admitted to neonatal intensive care units between 2001 and 2014. RESULTS: Data were available for 911 (89.4%) of the 1019 infants who met the inclusion criteria. Of them, 22 (2.4%) had OWO. There were no associations between OWO and being small for gestational age (RR = 1.3, 95% confidence interval (CI): 0.3-5.4) or weight <10th percentile at 36 weeks (RR = 1.1, 95% CI: 0.4-2.8). OWO was associated with low maternal education (RR = 7.4, 95% CI: 2.1-26), maternal diabetes (RR = 5.2, 95% CI: 1.9-15) and neonatal brain injury (RR = 4.9, 95% CI: 1.8-14). Adjusting for concurrent child weight at 3 years of age resulted in an overadjustment bias. CONCLUSION: Small size at birth or at 36 weeks gestation in extremely preterm infants is not associated with increased risk of early childhood overgrowth or obesity. CLINICAL TRIAL REGISTRATION: NCT03064022.

Obesity and mortality among endometrial cancer survivors: A systematic review and meta-analysis.

Excess body fat is a major risk factor for endometrial cancer incidence, but its impact on recurrence and survival remains unclear. The aim of this systematic review and meta-analysis was to assess the association between excess body fat with recurrence, cancer-specific, and all-cause mortality among endometrial cancer survivors. We searched MEDLINE and EMBASE databases up to July 2021. Risk of bias was assessed with the Ottawa Newcastle Scale. Random effects models estimated pooled hazard ratios for the main associations between body mass index (BMI) and survival outcomes and stratified by endometrial cancer type. Potential heterogeneity and publication bias were evaluated with sensitivity analyses, funnel plots, and Egger's test. Forty-six studies were included, of which 45 estimated body fat with BMI and six used direct waist circumference measures or CT/MRI scans. Higher BMI (≥30 kg/m2 ) was associated with increased all-cause mortality (HR = 1.34, 95%CI = 1.12-1.59) and recurrence (HR = 1.28, 95%CI = 1.06-1.56). In sub-group analysis, associations between higher BMI and all-cause mortality were observed for both Types I and II survivors, while recurrence associations were only significant among Type I cases. Obesity at endometrial cancer diagnosis was associated with increased cancer recurrence and all-cause mortality among endometrial cancer survivors but not endometrial cancer-specific mortality.

"Extrauterine growth restriction" and "postnatal growth failure" are misnomers for preterm infants.

Preterm infants are increasingly diagnosed as having "extrauterine growth restriction" (EUGR) or "postnatal growth failure" (PGF). Usually EUGR/PGF is diagnosed when weight is <10th percentile at either discharge or 36-40 weeks postmenstrual age. The reasons why the phrases EUGR/PGF are unhelpful include, they: (i) are not predictive of adverse outcome; (ii) are based only on weight without any consideration of head or length growth, proportionality, body composition, or genetic potential; (iii) ignore normal postnatal weight loss; (iv) are usually assessed prior to growth slowing of the reference fetus, around 36-40 weeks, and (v) are usually based on an arbitrary statistical growth percentile cut-off. Focus on EUGR/PGF prevalence may benefit with better attention to nutrition but may also harm with nutrition delivery above infants' actual needs. In this paper, we highlight challenges associated with such arbitrary cut-offs and opportunities for further refinement of understanding growth and nutritional needs of preterm neonates.

Preconceptional and gestational weight trajectories and risk of delivering a small-for-gestational-age baby in rural Gambia.

Background: Maternal nutritional status is a key determinant of small for gestational age (SGA), but some knowledge gaps remain, particularly regarding the role of the energy balance entering pregnancy.Objective: We investigated how preconceptional and gestational weight trajectories (summarized by individual-level traits) are associated with SGA risk in rural Gambia.Design: The sample comprised 670 women in a trial with serial weight data (7310 observations) that were available before and during pregnancy. Individual trajectories from 6 mo before conception to 30 wk of gestation were produced with the use of multilevel modeling. Summary traits were expressed as weight z scores [weight z score at 3 mo preconception (zwt-3 mo), weight z score at conception, weight z score at 3 mo postconception, weight z score at 7 mo postconception (zwt+7 mo), and conditional measures that represented the change from the preceding time] and were related to SGA risk with the use of Poisson regression with confounder adjustment; linear splines were used to account for nonlinearity.Results: Maternal weight at each time point had a consistent nonlinear relation with SGA risk. For example, the zwt-3 mo estimate was stronger in women with values ≤0.5 (RR: 0.736; 95% CI: 0.594, 0.910) than in women with values >0.5 (RR: 0.920; 95% CI: 0.682, 1.241). The former group had the highest observed SGA prevalence. Focusing on weight change, only conditional zwt+7 mo was associated with SGA and only in women with values >-0.5 (RR: 0.579; 95% CI: 0.463, 0.724).Conclusions: Protection against delivering an SGA neonate offered by greater preconceptional or gestational weight may be most pronounced in more undernourished and vulnerable women. Independent of this possibility, greater second- and third-trimester weight gain beyond a threshold may be protective. This trial was registered at http://www.isrctn.com/ as ISRCTN49285450.