Human milk, breastfeeding, and early neurodevelopmental outcomes for infants with critical CHD.

Human milk improves neurodevelopment for preterm infants, but relationships between human milk and neurodevelopment for infants with critical CHD are unknown. We aimed to (1) explore associations between human milk/direct breastfeeding and neurodevelopment at 1-year and 2-year follow-up and (2) describe patterns of human milk (maternal, donor) and commercial formula during hospitalisation in the first year of life.This retrospective cohort study included infants who underwent surgery for CHD < 6 months old. The primary outcome was neurodevelopment via Bayley Scales of Infant Development-IV. Analysis included adjusted linear regression for associations between exclusive human milk while inpatient during the first 6 months or any direct breastfeeding while inpatient during the first year of life and 1-year Bayley-IV scores. Models were adjusted for race, insurance type, genetic diagnosis, and length of stay.Of 98 eligible infants, 40% followed up at 1 year; 27% at 2 years. There were differences in follow-up related to demographics (race, ethnicity) and social determinants of health (insurance type, distance from clinic). In adjusted models, infants who directly breastfed had 13.18 points higher cognition (95% CI: 0.84-25.53, p = 0.037); 14.04 points higher language (2.55-25.53, p = 0.018); and 15.80 points higher motor scores (3.27-28.34, p = 0.015) at 1-year follow-up. Infants fed exclusive human milk had 12.64 points higher cognition scores (-0.53-25.82, p = 0.059).Future investigation into nutrition and neurodevelopment in the context of critical CHD is warranted. As neurodevelopmental follow-up becomes standard of care in this population, efforts are needed to mitigate disparities in access to this care.

Insulin-like growth factor-1 and insulin-like growth factor binding protein-3 as early predictors of growth, body composition, and neurodevelopment in preterm infants.

OBJECTIVE: To investigate the relationship between insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3) and long-term growth, body composition, and neurodevelopment in preterm infants. STUDY DESIGN: Prospective data were collected from ≤32 weeks gestational age infant cohort (N = 50). IGF-1 and IGFBP-3 concentrations were measured at 1 week (early) and 35 weeks (late) post-menstrual age (PMA). Growth, body composition, and neurodevelopment outcomes were measured at 4 and 12 months PMA. Relationships were measured by linear regression analysis. RESULTS: Early IGFBP-3 concentration was positively associated with neurodevelopment at 12 months PMA. Early IGF-1 concentration was positively associated with weight at 4 months PMA, head circumference at 12 months PMA, and body mass index at 12 months PMA. Late IGFBP-3 concentration was positively associated with weight at 4 months PMA. CONCLUSION: Further investigation of these associations may lead to novel biomarkers and/or treatments to optimize health outcomes in preterm infants.

Body composition after implementation of an enhanced parenteral nutrition protocol in the neonatal intensive care unit: a randomised pilot trial.

BACKGROUND: Very low birthweight (VLBW) infants are at risk for growth failure and poor neurodevelopment. Optimised parenteral nutrition may help promote optimal growth and development, but concerns that provision of enhanced nutrition may contribute to increased early adiposity and later metabolic disease remain. AIM: To determine associations between provision of an early enhanced parenteral nutrition protocol or standard parenteral nutrition protocol and growth and body composition for VLBW preterm infants in the neonatal intensive care unit. SUBJECTS: This is a secondary analysis of data from a clinical trial aimed at assessing the feasibility and safety of randomising VLBW preterm infants to Standard (n = 45) or Intervention (n = 42) parenteral nutrition groups between August 2017 and June 2019. METHODS: We evaluated associations between weekly infant growth and body composition measurements from n = 55 infants (Standard = 29, Intervention = 26) that were clinically stable enough to have body composition measurements taken before discharge using mixed effects linear regression models. RESULT: No statistically significant associations between nutrition group and infant growth or body composition measures were observed (p >.05). CONCLUSION: In this pilot trial, enhanced parenteral nutrition in the first week of life was not associated with significant differences in infant growth or body composition during hospitalisation.

An exploratory study of clinical factors associated with IGF-1 and IGFBP-3 in preterm infants.

BACKGROUND: Despite advances in parenteral nutrition, postnatal growth failure in very low birthweight (VLBW) preterm infants is common and associated with chronic health problems. Insulin-like growth factor 1 (IGF-1) is positively associated with improved infant growth, but factors which promote IGF-1 levels in this population have not been clearly identified. The objective of this study was to explore early factors that influence IGF-1 in VLBW preterm infants. METHODS: VLBW infants were enrolled into a prospective, randomized controlled nutrition trial (N = 87). Outcome measures included IGF-1 and IGFBP-3 levels measured at 35 weeks PMA. Linear regression analyses tested the relationships between candidate clinical predictors and levels of IGF-1 and IGFBP-3. RESULTS: Higher protein intake, longer duration of parenteral nutrition, and lower IGFBP-3 levels at 1 week of life were associated with lower IGF-1 levels at 35 weeks PMA. Neither early markers of insulin resistance nor degree of illness were associated with IGF-1 levels at 35 weeks PMA. CONCLUSION: Optimization of early nutrient intake, and attention to route of delivery, may have a lasting influence on IGF-1/IGFBP-3, and in turn, long-term health outcomes. IMPACT: In very low birthweight preterm infants, early protein intake, duration of parenteral nutrition, and insulin-like growth factor binding protein 3 (IGFBP-3) levels at 1 week of life are positively associated with insulin-like growth factor 1 (IGF-1) levels at 35 weeks postmenstrual age. Data from this study highlight the influence of early nutrition on components of the endocrine axis in preterm infants. Strategies aimed at early initiation of enteral nutrition, as well as optimizing composition of parenteral nutrition, may bolster hormones involved in promoting preterm infant growth.

Feeding characteristics of healthy infants without reported feeding impairments throughout the first month of life.

OBJECTIVE: Elucidate characteristics of feeding performance in healthy infants without reported feeding problems throughout the first month of life. STUDY DESIGN: Feeding was monitored in 61 healthy infants by caregiver report for 48 h a week from birth to 4 weeks old. Outcomes included feeding modality, how much they consumed, how long the feed lasted, and how many coughing episodes the infant exhibited. Data were analyzed with descriptive and non-parametric statistics. RESULT: The majority of infants (68%) exhibited at least one problematic feeding behavior. Infants consumed 68 ml/feed over 20 min, though the milk volumes and feed durations were highly variable. Coughing occurred an average of 2 feeds per day. No significant change in coughing was observed throughout the first month of life (p = 0.64). Infants coughed significantly less during breast feeds than bottle feeds (p = 0.02). CONCLUSION: Healthy term infants exhibit what appear to be normal developmental imperfections in feeding performance throughout the first month of life.

Establishing Normative Values for Healthy Term Infant Feeding Performance: Neonatal Eating Assessment Tool-Mixed, Oral Feeding Scale, and Early Feeding Skills Assessment.

PURPOSE: Infants with perceived feeding problems are frequently referred for assessment of their feeding abilities. However, little is known regarding how healthy nondysphagic infants perform on commonly used assessments, making determination of impairment difficult. The aim of this investigation was to elucidate the characteristics of healthy term infant feeding performance using three commonly employed clinical assessments: Neonatal Eating Assessment Tool-Mixed (NeoEat-Mixed), Oral Feeding Scale, and Early Feeding Skills (EFS). METHOD: In this prospective case-control study, we recruited 30 infants without feeding impairments to undergo video-monitored bottle feeds under their normal feeding conditions. Caregiver perception of infant feeding was evaluated using the NeoEat-Mixed. Milk ingestion was monitored real time using the Oral Feeding Scale for rate of milk transfer and modified proficiency as characterized by the total volume consumed out of the total volume the caregiver provided. Videos were analyzed by two speech pathologists using the EFS assessment. Descriptive statistics were used to characterize performance. RESULTS: Participants underwent feeding monitoring at an average chronological age of 4 ± 2 months. Caregivers primarily reported normal, nonconcerning feeding patterns across all of the NeoEAT-Mixed outcomes. Infants consumed milk at an average rate of transfer of 7 ± 3 ml/min, a modified proficiency of 50 ± 21%, and achieved the highest OFS score of 4 (93%, n = 28). The majority of infants scored the best EFS score (mature-3) as it related to the absence of color changes during the feed (97%, n = 29), although commonly scored in the worst EFS score (immature-1) in their presentation of one or more compelling stress cues (63%, n = 19). CONCLUSION: Establishing healthy term infant normative values for commonly used feeding assessments is critical in accurately distinguishing infants with feeding impairments from those with normal developmental variants.

Dilemmas in parenteral glucose delivery and approach to glucose monitoring and interpretation in the neonate.

Glucose control continues to be challenging for intensivists, in particular in high-risk neonates. Many factors play a role in glucose regulation including intrinsic and extrinsic factors. Optimal targets for euglycemia are debatable with uncertain short and long-term effects. Glucose measurement technology has continued to advance over the past decade; unfortunately, the availability of these advanced devices outside of research continues to be problematic. Treatment approaches should be individualized depending on etiology, symptoms, and neonatal conditions. Glucose infusions should be titrated based upon variations in organ glucose uptake, co-morbidities and postnatal development. In this article we summarize the most common dilemmas encountered in the NICU: ranges for euglycemia, physiological differences, approach for glucose measurements, monitoring and best strategies to control parenteral glucose delivery.

Identification of clinical factors associated with timing and duration of spontaneous regression of retinopathy of prematurity not requiring treatment.

OBJECTIVE: Identify clinical factors that delay or prolong spontaneous regression of retinopathy of prematurity (ROP). STUDY DESIGN: Secondary analysis of three prospective studies with 76 infants with ROP not requiring treatment, born ≤30 weeks postmenstrual age (PMA) and ≤1500 grams. Outcomes were PMA at greatest severity of ROP (PMA MSROP), at which regression began, at time of complete vascularization (PMA CV), and regression duration. Pearson's correlation coefficients, t-tests, or analyses of variance were calculated. RESULTS: Increased positive bacterial cultures, hyperglycemia, transfusion volume of platelets and red blood cells and severity of ROP were associated with later PMA MSROP. Positive bacterial cultures, maternal chorioamnionitis, and less iron deficiency were associated with later PMA CV and prolonged regression duration. Slower length gain was associated with later PMA CV. P < 0.05 for all. CONCLUSIONS: Preterm infants with inflammatory exposures or linear growth impairment may require longer surveillance for ROP resolution and complete vascularization.

Enhanced Parenteral Nutrition Is Feasible and Safe in Very Low Birth Weight Preterm Infants: A Randomized Trial.

OBJECTIVE: The objective of this study was to determine the feasibility and safety of enhanced early (PN) (early initiation of intralipids and faster advancement of glucose infusion rate) during the first week of life for very low birth weight (VLBW) preterm infants. METHODS: 90 VLBW preterm infants (<32 weeks gestational age at birth) admitted to the University of Minnesota Masonic Children's Hospital between August 2017 and June 2019 were included. Enrolled infants were stratified by gestational age-groups and randomized to either the enhanced nutrition protocol (intervention group) or the standard PN protocol (standard group). Welch's two-sample t tests were used to investigate differences in calorie and protein intake, insulin use, days of hyperglycemia, hyperbilirubinemia, and hypertriglyceridemia, and proportion of bronchopulmonary dysplasia, necrotizing enterocolitis, and death between groups. RESULTS: Intervention and standard groups were similar in baseline characteristics. The intervention group received higher weekly mean caloric intake (102.6 [SD 24.9] kcal/kg/day versus 89.7 [SD 30.2] kcal/kg/day; p = 0.001) and higher mean caloric intake on days of life 2-4 (p < 0.05 for all). Both groups received the recommended protein intake (≥4 g/kg/day). There were no significant differences in safety or feasibility outcomes between groups (all p values >0.12). CONCLUSION: Utilization of an enhanced nutrition protocol during the first week of life resulted in increased caloric intake and was feasible with no evidence of harm. Follow-up of this cohort is needed to determine if enhanced PN will result in improved growth and neurodevelopment.

Preterm infant body composition, working memory, and temperament.

Altered body composition in preterm infants is associated with risks to cognitive development, but the effect specific to prefrontal cortex (PFC) development is unknown. We were interested in the impact of fat mass (FM) and fat free mass (FFM) gains out to 4 months corrected gestational age (CGA) on PFC development, as indexed by working memory and temperament. This is a prospective observational pilot study recruiting 100 preterm (<33 weeks gestation), appropriate for gestational age, and very low birth weight infants, of which 49 infants met inclusion criteria. Body composition was measured using air displacement plethysmography at hospital discharge and 4 months CGA. Questionnaire based temperament assessments were completed at 12 and 24 months CGA and a working memory assessment was completed at 24 months CGA. Associations between developmental tests and body composition obtained at term and 4 months were analyzed. Increased FM at discharge was associated with increased fear and decreased soothability at 12 months. Increased FM at 4 months was associated with increased activity level, increased distress from limitations at 12 months and decreased attentional shifting, decreased frustration, and decreased inhibitory control at 24 months. Increased FFM at 4 months was associated with increased activity level at 12 months and increased impulsivity and decreased low intensity pleasure at 24 months. In this exploratory pilot study, increased FM out to 4 months and increased FFM after discharge are associated with negative markers of infant temperament. Infant temperament may be sensitive to body composition status at least to 4 months CGA.

Body composition measurement for the preterm neonate: using a clinical utility framework to translate research tools into clinical care.

Body composition analysis to distinguish between fat mass and fat-free mass is an established research approach to assess nutritional status. Within neonatal medicine, preterm infant body composition is linked with later health outcomes including neurodevelopment and cardiometabolic health. Mounting evidence establishing fat-free mass as an indicator of nutritional status, coupled with the availability of testing approaches that are feasible to use in preterm infants, have enhanced interest in measuring body composition in the neonatal intensive care unit (NICU) setting. In this paper, we use the concept of clinical utility-the added value of a new methodology over current standard care-as a framework for assessing several existing body composition methodologies with potential for clinical application to preterm neonates. We also use this framework to identify remaining knowledge gaps and prioritize efforts to advance our understanding of clinically-oriented body composition testing in the NICU.

Randomized Trial of Early Enhanced Parenteral Nutrition and Later Neurodevelopment in Preterm Infants.

Retrospective studies indicate that the parenteral provision of calories, proteins, and lipids in the first week of life is associated with improved later neurodevelopment. We aimed to determine whether infants randomized to an enhanced parenteral nutrition protocol had improved developmental outcomes at 4, 12, or 24 months corrected age (CA). In total, 90 preterm infants (<32 weeks gestational age and <1500 g) were randomized to receive enhanced parenteral nutrition (PN) or standard PN during the first week of life. The enhanced group received a higher glucose infusion rate and intralipids. Neurodevelopmental outcomes included pattern-reversal visually evoked potentials (VEP) at 4 months CA (n = 33) and the Bayley Scales of Infant Development (BSID) at 12 (n = 46) and 24 (n = 29) months CA. P100 latency was longer in the intervention group, indicating slower processing speed (145 vs. 178 ms, p = 0.01). This association did not hold in multivariable analysis adjusting for potentially confounding variables. BSID scores were not associated with enhanced PN. Higher enteral energy and protein intake regardless of randomization group were associated with faster processing speed at 4 months CA (p ≤ 0.02 for both). Enhanced early PN was not associated with improved neurodevelopment; however, first-week enteral caloric and protein intake were associated with improved speed of processing.

The Impact of Human Milk on Outcomes for Infants with Congenital Heart Disease: A Systematic Review.

Background: Infants with congenital heart disease (CHD) are at risk for feeding-related morbidity and mortality, with growth failure and oral feeding problems associated with poor outcomes. The benefits of human milk (HM) for preterm infants have been well documented, but evidence on HM for infants with CHD has recently begun to emerge. Objectives: Our primary aim was to examine the impact of HM feeding on outcomes for infants with CHD. Methods: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines, a search was conducted using MEDLINE, CINAHL, and Cochrane Database of Systematic Reviews. The quality of each study was assessed using the Joanna Briggs Critical Appraisal Tools. A total of 16 studies were included. Results: There was evidence that an exclusive HM diet reduces the risk of necrotizing enterocolitis (NEC) for infants with CHD. Evidence with a higher risk for bias indicated that a well-managed HM diet may be associated with improved growth, shorter length of stay, and improved postoperative feeding and nutritional outcomes. Chylothorax outcomes were similar between modified HM and medium-chain triglyceride formula. The studies had significant limitations related to power, lack of control for covariates, and inconsistent delineation of feeding groups. Conclusions: Based on the reduced risk for NEC and given the conclusive benefits in other vulnerable populations, we recommend that clinicians and institutions prioritize programs to support HM feeding for infants with CHD. Large high-quality studies are needed to validate these results. Future work should clarify best practices in managing an HM diet to support optimal growth and development for these infants.

Systemic Inflammation in the First 2 Weeks after Birth as a Determinant of Physical Growth Outcomes in Hospitalized Infants with Extremely Low Gestational Age.

OBJECTIVE: To examine associations of systemic inflammation with growth outcomes at neonatal intensive care unit discharge or transfer among infants with extremely low gestational ages. STUDY DESIGN: We studied 850 infants at born at 23-27 weeks of gestation. We defined inflammatory protein elevation as the highest quartile of C-reactive protein (CRP), Interleukin (IL)-6, tumor necrosis factor-∝, or IL-8 on postnatal days 1, 7, and 14. We compared z-scores of weight, length, and head circumference at neonatal intensive care unit discharge or transfer between infants with vs without inflammatory protein elevation, adjusting in linear regression for birth size z-score, sex, gestational age, diet, comorbidities, medications, and length of hospitalization. RESULTS: The mean gestational age was 25 weeks (range, 23-27 weeks) and birth weight z-score 0.14 (range, -2.73 to 3.28). Infants with a high CRP on day 7 had lower weights at discharge or transfer (-0.17 z-score; 95% CI, -0.27 to -0.06) than infants without CRP elevation, with similar results on day 14. Infants with CRP elevation on day 14 were also shorter (-0.21 length z-scores; 95% CI, -0.38 to -0.04), and had smaller head circumferences (-0.18 z-scores; 95% CI, -0.33 to -0.04) at discharge or transfer. IL-6 elevation on day 14 was associated with lower weight (-0.12; 95% CI, -0.22 to -0.02); IL-6 elevation on day 7 was associated with shorter length (-0.27; 95% CI, -0.43 to -0.12). Tumor necrosis factor-∝ and IL-8 elevation on day 14 were associated with a lower weight at discharge or transfer. CONCLUSIONS: Postnatal systemic inflammation may contribute to impaired nutrient accretion during a critical period in development in infants with extremely low gestational ages.

Long-Term Outcomes after Early Neonatal Hyperglycemia in VLBW Infants: A Systematic Review.

INTRODUCTION: Long-term effects of early hyperglycemia in VLBW infants are poorly characterized. The objective of this study was to systematically review the effect of early hyperglycemia on growth, metabolic health, and neurodevelopment after neonatal intensive care unit discharge in VLBW infants. METHODS: The systematic review was conducted in accordance with the PRISMA guidelines. A study protocol was registered in PROSPERO (CRD42019123335). Data sources included Ovid MEDLINE, Embase, Cochrane Library, CINAHL, and Scopus. Selected studies included infants with a blood glucose concentration >150 mg/dL (8.3 mmol/L) during the first 28 days of life, a gestational age (GA) <32 weeks, and/or a birth weight <1,500 g and longitudinal data on growth, metabolic health, or neurodevelopment outcomes. The GRADE system was used to assess quality of evidence. RESULTS: Eight studies (n = 987 infants) reported long-term outcomes from 4-month corrected GA to 7 years old. Most studies compared long-term outcomes of preterm infants with and without hyperglycemia. Two studies addressed outcomes related to interventions following early hyperglycemia. Some studies found differences in growth, metabolic health, and neurodevelopment outcomes between VLBW preterm infants with hyperglycemia and without hyperglycemia, while other studies found no differences between groups. The overall graded quality of evidence was low. CONCLUSIONS: Well-designed randomized controlled and prospective studies are necessary to determine the effect of early hyperglycemia and its treatment on later metabolic and neurodevelopmental outcomes in VLBW infants. Authors propose a potential study design for standardizing the assessment of long-term metabolic and neurodevelopmental outcomes following early hyperglycemia in preterm infants.

Ultrasound measurements of abdominal muscle thickness are associated with postmenstrual age at full oral feedings in preterm infants: A preliminary study.

BACKGROUND: A premature infant's discharge from the neonatal intensive care unit (NICU) is dependent on factors such as respiratory stability, adequate growth, and the ability to consume oral feeds. Once infants have achieved respiratory stability, a tool that can better predict age at discharge is desirable. Thus, we conducted a secondary data analysis to assess the association between ultrasound measurements of abdominal muscle thickness and postmenstrual age (PMA) at full oral feedings. METHODS: Forty-nine (n = 49) healthy, premature infants (mean gestational age = 32 weeks) were recruited from the NICU. Anthropometric measurements and ultrasound measurements of the rectus abdominis were conducted when infants were medically stable. Fat-free mass (FFM) was obtained using air displacement plethysmography. The relationship between ultrasound measurements of muscle thickness and PMA at full oral feedings was assessed using linear regression analysis. The relationship between FFM z-scores and PMA at full oral feedings was also assessed for comparison. RESULTS: When adjusting for gestational age at birth, PMA at measurement, days of positive pressure respiratory support, weight, and length, ultrasound measurements of abdominal muscle thickness were independently, negatively associated with PMA at full oral feedings (ß estimate: -0.71, P = .03). CONCLUSION: Preliminary results suggest infants with greater abdominal muscle thickness may reach full oral feedings at an earlier PMA (nearly 1 week per millimeter). Thus, ultrasound measurements of abdominal muscle thickness may be helpful in assessing readiness for discharge in healthy preterm infants. Further research is needed for development and validation of a prediction equation.

Can Ultrasound Measures of Muscle and Adipose Tissue Thickness Predict Body Composition of Premature Infants in the Neonatal Intensive Care Unit?

BACKGROUND: Premature infants are at risk for adverse metabolic and neurodevelopmental outcomes due to growth alterations in early infancy. Monitoring body composition by tracking gains in fat mass (FM) and fat-free mass (FFM) may assist clinicians in preventing obesity and metabolic disease while promoting optimal growth and development. A prospective, observational study was conducted to determine the ability of ultrasound (US) measurements of muscle and adipose tissue thickness to predict whole-body composition (FFM, FM, percent body fat [%BF]). METHODS: Sixty-three healthy premature infants were recruited from the University of Minnesota's Neonatal Intensive Care Unit. Anthropometric measurements, air displacement plethysmography, and US measurements of abdomen, biceps, and quadriceps muscle and of adipose tissue thickness were conducted when infants were medically stable. The relationship between US measurements and body composition was assessed using stepwise linear regression analysis. RESULTS: In linear regression analyses, biceps adipose and the sum of adipose thickness measurements were significant predictors of %BF, but prediction models had low R2 (0.17 and 0.16, respectively) and high root-mean-square error. US measurements of muscle thickness were not predictive of whole-body FFM. CONCLUSION: US measurements of muscle and adipose tissue thickness at the examined sites are not adequate surrogates for whole-body composition in preterm infants. Exploration of alternate measurement sites may improve predictive ability.

Weight for length measures may not accurately reflect adiposity in preterm infants born appropriate for gestational age during hospitalisation or after discharge from the neonatal intensive care unit.

BACKGROUND: Weight/length (W/L) indices are poor surrogates for adiposity in preterm infants born appropriate for gestational age (AGA) at birth, but whether the association subsequently improves is unknown. OBJECTIVE: To determine if W/L indices accurately reflect adiposity in premature infants born AGA in later infancy. METHODS: Associations between W/L indices and fat mass, fat mass index and percent body fat (%BF) obtained via air displacement plethysmography (ADP) were examined in 260 preterm infants (majority born AGA) at 28 to 63 weeks' postmenstrual age (PMA). Accuracy of W/L indices as indicators of adiposity was assessed by proportion of variance explained (R2 ) and root mean square error from linear regression of adiposity on W/L indices and proportion of infants misclassified by W/L indices. Accuracy was further compared in term vs preterm infants at term-equivalent age. The impact of early vs late preterm status on associations between W/L indices and %BF was also examined. RESULTS: BMI and W/L were most strongly associated with %BF but yielded poorly fitting models (maximum R2 = 0.35; 53% misclassification). A significant interaction of W/L indices and early vs late preterm status on %BF revealed that estimation of %BF differs by status. Accuracy of W/L indices was worse in preterm infants at term-equivalent age. CONCLUSIONS: W/L indices were not good indicators of adiposity in preterm infants from 28 to 63 weeks' PMA (born AGA) with all categories of W/L indices combined. Future research should examine whether results are similar in preterm infants born with disproportionate W/L or who experience disproportionate growth postnatally.