Does Fetal Growth Adequacy Affect the Nutritional Composition of Mothers' Milk?: A Historical Cohort Study.

OBJECTIVE: The study aimed to assess the association between intrauterine growth of preterm infants and energy and macronutrient contents in their mothers' milk. STUDY DESIGN: A historical cohort of mothers of preterm infants was assessed according to offspring's intrauterine growth. Fetal growth restriction (FGR) was defined as small-for-gestational age or appropriate for gestational age with fetal growth deceleration. During the first 4 weeks after delivery, the composition of daily pool samples of mothers' milk was measured by using a mid-infrared human milk analyzer. Explanatory models for milk energy, true protein, total carbohydrate, and fat contents were obtained by generalized additive mixed effects regression models. RESULTS: In total, 127 milk samples were analyzed from 73 mothers who delivered 92 neonates. Energy content was significantly higher in mothers with chronic hypertension (average: +6.28 kcal/dL; 95% confidence interval [CI]: 0.54-12.01; p = 0.034) and for extremely preterm compared with very preterm infants (average: +5.95 kcal/dL; 95% CI: 2.16-9.73; p = 0.003), and weakly associated with single pregnancies (average: +3.38 kcal/dL; 95% CI: 0.07-6.83; p = 0.057). True protein content was significantly higher in mothers with chronic hypertension (average: +0.91 g/dL; 95% CI: 0.63-1.19; p < 0.001) and with hypertension induced by pregnancy (average: +0.25 g/dL, 95% CI: 0.07-0.44; p = 0.007), and for extremely preterm compared with very and moderate preterm infants (average: +0.19; 95% CI: 0.01-0.38; p = 0.043 and +0.28 g/dL; 95% CI: 0.05-0.51; p = 0.017, respectively). Fat content was weakly and negatively associated with FGR, both in SGA infants and AGA infants with fetal growth deceleration (average: -0.44 g/dL; 95% CI: -0.92 to -0.05; p = 0.079 and average: -0.36 g/dL; 95% CI: -0.74 to -0.02; p = 0.066, respectively). CONCLUSION: Energy and macronutrient contents in mothers' milk of preterm infants was significantly and positively associated with the degree of prematurity and hypertension. The hypothesis that the composition of milk is associated with FGR was not demonstrated. KEY POINTS: · Energy and protein are higher for more immature infants.. · Energy and/or protein is higher in hypertension.. · Fat may be lower for infants with intrauterine growth restriction..

Associations of Measured Protein and Energy Intakes with Growth and Adiposity in Human Milk-Fed Preterm Infants at Term Postmenstrual Age: A Cohort Study.

OBJECTIVE: To determine the associations of measured protein, energy, and protein-to-energy (PER) intakes with body composition in human milk (HM)-fed preterm infants. STUDY DESIGN: Neonates born at < 33 gestational weeks were eligible. Standard fortification method with modular supplements was used and the HM composition was measured. The weight gain velocity was calculated, and body composition was assessed by air displacement plethysmography at 40 weeks' postmenstrual age (PMA). The fat mass percentage and fat mass index were used as indicators of adiposity, with convenience cut-offs ≤ -1 and ≥ + 1 z-scores for low and high adiposity, respectively. RESULTS: Thirty-three infants were included (median [interquartile range] gestational age: 30 [28-31] weeks; birth weight: 1.175 [1.010-1.408] g); 36.4 and 84.8% did not receive the minimum recommended protein and energy intakes, respectively. Weight gain velocity showed positive weak-to-moderate correlations with nutrient intakes. Overall, no correlations between nutrient intakes and body composition were found. Infants with lower adiposity received lower energy, protein, and PER intakes, while those with higher adiposity received lower energy intake but higher PER intake. CONCLUSION: Overall, no correlations of nutrient intakes with body composition were found; however, differences in nutrient intakes were found between infants with lower and higher adiposity at term PMA.

Is intrauterine growth appropriate to monitor postnatal growth of preterm neonates?

When using the useful 2013 Fenton Chart, data should be interpreted with caution taking into account two aspects: the physiologic loss of body water after birth for the weight curves, and the questionable accuracy of the birth length curves considering the heterogeneity and reliability of the methods used in the original measurements.

The adjusted effect of maternal body mass index, energy and macronutrient intakes during pregnancy, and gestational weight gain on body composition of full-term neonates.

OBJECTIVE: To evaluate the effect of prepregnancy body mass index (BMI), energy and macronutrient intakes during pregnancy, and gestational weight gain (GWG) on the body composition of full-term appropriate-for-gestational age neonates. STUDY DESIGN: This is a cross-sectional study of a systematically recruited convenience sample of mother-infant pairs. Food intake during pregnancy was assessed by food frequency questionnaire and its nutritional value by the Food Processor Plus (ESHA Research Inc, Salem, OR). Neonatal body composition was assessed both by anthropometry and air displacement plethysmography. Explanatory models for neonatal body composition were tested by multiple linear regression analysis. RESULTS: A total of 100 mother-infant pairs were included. Prepregnancy overweight was positively associated with offspring weight, weight/length, BMI, and fat-free mass in the whole sample; in males, it was also positively associated with midarm circumference, ponderal index, and fat mass. Higher energy intake from carbohydrate was positively associated with midarm circumference and weight/length in the whole sample. Higher GWG was positively associated with weight, length, and midarm circumference in females. CONCLUSION: Positive adjusted associations were found between both prepregnancy BMI and energy intake from carbohydrate and offspring body size in the whole sample. Positive adjusted associations were also found between prepregnancy overweight and adiposity in males, and between GWG and body size in females.

Eating Habits During Pregnancy of Women Giving Birth Very Prematurely: An Exploratory Analysis.

INTRODUCTION: Preterm birth is increasing worldwide, representing a major cause of death and long-term loss of human potential among survivors. Some morbidities during pregnancy are well-known risk factors for preterm labor, but it is not yet known whether deviations from adequate dietary patterns are associated with preterm delivery. Diet may be an important modulator of chronic inflammation, and pro-inflammatory diets during pregnancy were reported to be associated with preterm birth. The aim of this study was to assess the food consumption during pregnancy of Portuguese women giving birth very prematurely and the association between the food consumption and the major maternal morbidities during pregnancy related with preterm delivery. MATERIAL AND METHODS: A single-center cross-sectional observational study including consecutive Portuguese women giving birth before 33 weeks of gestation was conducted. Recall of eating habits during pregnancy was obtained within the first week after delivery, using a semi quantitative food frequency questionnaire validated for Portuguese pregnant women. RESULTS: Sixty women with a median age of 36.0 years were included. Of these, 35% were obese or overweight at the beginning of pregnancy, 41.7% and 25.0% gained excessive or insufficient weight during pregnancy, respectively. Pregnancy-induced hypertension was present in 21.7% of cases, gestational diabetes in 18.3%, chronic hypertension in 6.7%, and type 2 diabetes mellitus in 5.0%. Pregnancy-induced hypertension was significantly associated with increased daily consumption of pastry products (31.2 vs 10.0 g, p = 0.022), fast food (39.6 vs 29.7 g, p = 0.028), bread (90.0 vs 50.0 g, p = 0.005), pasta, rice and potatoes (225.7 vs 154.3 g, p = 0.012). In a multivariate analysis, only bread consumption maintained a significant, albeit weak, association (OR = 1.021; 1.003 - 1.038, p = 0.022). CONCLUSION: Pregnancy-induced hypertension was associated with increased consumption of pastry products, fast food, bread, pasta, rice, and potatoes, although only bread consumption had a weak but statistically significant association with pregnancy-induced hypertension in a multivariate analysis.

Individualized Fortification Based on Measured Macronutrient Content of Human Milk Improves Growth and Body Composition in Infants Born Less than 33 Weeks: A Mixed-Cohort Study.

The optimal method for human milk (HM) fortification has not yet been determined. This study assessed whether fortification relying on measured HM macronutrient content (Miris AB analyzer, Upsala, Sweden) composition is superior to fortification based on assumed HM macronutrient content, to optimize the nutrition support, growth, and body composition in infants born at <33 weeks' gestation. In a mixed-cohort study, 57 infants fed fortified HM based on its measured content were compared with 58 infants fed fortified HM based on its assumed content, for a median of 28 and 23 exposure days, respectively. The ESPGHAN 2010 guidelines for preterm enteral nutrition were followed. Growth assessment was based on body weight, length, and head circumference Δ z-scores, and the respective growth velocities until discharge. Body composition was assessed using air displacement plethysmography. Fortification based on measured HM content provided significantly higher energy, fat, and carbohydrate intakes, although with a lower protein intake in infants weighing ≥ 1 kg and lower protein-to-energy ratio in infants weighing < 1 kg. Infants fed fortified HM based on its measured content were discharged with significantly better weight gain, length, and head growth. These infants had significantly lower adiposity and greater lean mass near term-equivalent age, despite receiving higher in-hospital energy and fat intakes, with a mean fat intake higher than the maximum recommended and a median protein-to-energy ratio intake (in infants weighing < 1 kg) lower than the minimum recommended.

Changes in Microbiota Profile in the Proximal Remnant Intestine in Infants Undergoing Surgery Requiring Enterostomy.

Early-life gut dysbiosis has been associated with an increased risk of inflammatory, metabolic, and immune diseases later in life. Data on gut microbiota changes in infants undergoing intestinal surgery requiring enterostomy are scarce. This prospective cohort study examined the enterostomy effluent of 29 infants who underwent intestinal surgery due to congenital malformations of the gastrointestinal tract, necrotizing enterocolitis, or spontaneous intestinal perforation. Initial effluent samples were collected immediately after surgery and final effluent samples were collected three weeks later. Gut microbiota composition was analysed using real-time PCR and 16S rRNA gene sequencing. Three weeks after surgery, an increase in total bacteria number (+21%, p = 0.026), a decrease in Staphylococcus (-21%, p = 0.002) and Candida spp. (-16%, p = 0.045), and an increase in Lactobacillus (+3%, p = 0.045) and in less abundant genera belonging to the Enterobacteriales family were found. An increase in alpha diversity (Shannon's and Simpson's indexes) and significant alterations in beta diversity were observed. A correlation of necrotizing enterocolitis with higher Staphylococcus abundance and higher alpha diversity was also observed. H2-blockers and/or proton pump inhibitor therapy were positively correlated with a higher total bacteria number. In conclusion, these results suggest that positive changes occur in the gut microbiota profile of infants three weeks after intestinal surgery.

Body Composition Evaluation and Clinical Markers of Cardiometabolic Risk in Patients with Phenylketonuria.

Cardiovascular diseases are the main cause of mortality worldwide. Patients with phenylketonuria (PKU) may be at increased cardiovascular risk. This review provides an overview of clinical and metabolic cardiovascular risk factors, explores the connections between body composition (including fat mass and ectopic fat) and cardiovascular risk, and examines various methods for evaluating body composition. It particularly focuses on nutritional ultrasound, given its emerging availability and practical utility in clinical settings. Possible causes of increased cardiometabolic risk in PKU are also explored, including an increased intake of carbohydrates, chronic exposure to amino acids, and characteristics of microbiota. It is important to evaluate cardiovascular risk factors and body composition in patients with PKU. We suggest systematic monitoring of body composition to develop nutritional management and hydration strategies to optimize performance within the limits of nutritional therapy.

Body Composition of Infants Born with Intrauterine Growth Restriction: A Systematic Review and Meta-Analysis.

Intrauterine growth restriction (IUGR) may predispose metabolic diseases in later life. Changes in fat-free mass (FFM) and fat mass (FM) may explain this metabolic risk. This review studied the effect of IUGR on body composition in early infancy. Five databases and included studies from all countries published from 2000 until August 2021 were searched. Participants were IUGR or small-for-gestational age (SGA) infants, and the primary outcomes were FFM and FM. Eighteen studies met the inclusion criteria, of which seven were included in the meta-analysis of primary outcomes. Overall, intrauterine growth-restricted and SGA infants were lighter and shorter than normal intrauterine growth and appropriate-for-gestational age infants, respectively, from birth to the latest follow up. They had lower FFM [mean difference −429.19 (p = 0.02)] and FM [mean difference −282.9 (p < 0.001)]. The issue of whether lower FFM and FM as reasons for future metabolic risk in IUGR infants is intriguing which could be explored in further research with longer follow-up. This review, the first of its kind can be useful for developing nutrition targeted interventions for IUGR infants in future.

Mycotoxin Exposure during the First 1000 Days of Life and Its Impact on Children's Health: A Clinical Overview.

The first 1000 days of life are very sensitive to any event that alters health programming, and they represent a window for intervention to improve population health. Pregnant women, fetuses, and infants are particularly vulnerable to exposure to food contaminated with mycotoxins. This review aimed to gather data from the literature on mycotoxins exposure during intrauterine life and early childhood, and associated health risks, as assessed through human biomonitoring and mycotoxins occurrence in foods, in different continents. Maternal internal exposure to aflatoxins is associated with fetal growth restriction, while exposure to fumonisins increases the risk of offspring's neural tube defects. Mycotoxin contamination of breast milk is reported worldwide, but data on adverse effects of the lactational transfer of mycotoxins on infant health are lacking. Young children are exposed to mycotoxins through contaminated infant formulas and baby foods. Both external and internal exposure to aflatoxins and fumonisins in children are reported to be associated with growth impairment. In low-income settings, where other co-factors can affect growth, this association should be interpreted with caution. Further studies on human biomonitoring of mother-infant pairs and young children are needed to guide management strategies aiming to minimize mycotoxin exposure at critical developmental stages.

The Role of Nutrition in the Prevention and Management of Bronchopulmonary Dysplasia: A Literature Review and Clinical Approach.

Bronchopulmonary dysplasia (BPD) remains the most common severe complication of preterm birth, and nutrition plays a crucial role in lung growth and repair. A practical nutritional approach for infants at risk of BPD or with established BPD is provided based on a comprehensive literature review. Ideally, infants with BPD should receive a fluid intake of not more than 135-150 mL/kg/day and an energy intake of 120-150 kcal/kg/day. Providing high energy in low volume remains a challenge and is the main cause of growth restriction in these infants. They need a nutritional strategy that encompasses early aggressive parenteral nutrition and the initiation of concentrated feedings of energy and nutrients. The order of priority is fortified mother's own milk, followed by fortified donor milk and preterm enriched formulas. Functional nutrient supplements with a potential protective role against BPD are revisited, despite the limited evidence of their efficacy. Specialized nutritional strategies may be necessary to overcome difficulties common in BPD infants, such as gastroesophageal reflux and poorly coordinated feeding. Planning nutrition support after discharge requires a multidisciplinary approach to deal with multiple potential problems. Regular monitoring based on anthropometry and biochemical markers is needed to guide the nutritional intervention.

Customized Human Milk Fortification Based on Measured Human Milk Composition to Improve the Quality of Growth in Very Preterm Infants: A Mixed-Cohort Study Protocol.

Adequate nutrition of very preterm infants comprises fortification of human milk (HM), which helps to improve their nutrition and health. Standard HM fortification involves a fixed dose of a multi-nutrient HM fortifier, regardless of the composition of HM. This fortification method requires regular measurements of HM composition and has been suggested to be a more accurate fortification method. This observational study protocol is designed to assess whether the target HM fortification method (contemporary cohort) improves the energy and macronutrient intakes and the quality of growth of very preterm infants, compared with the previously used standard HM fortification (historical cohorts). In the contemporary cohort, a HM multi-nutrient fortifier and modular supplements of protein and fat are used for HM fortification, and the enteral nutrition recommendations of the European Society for Paediatric Gastroenterology Hepatology and Nutrition for preterm infants will be considered. For both cohorts, the composition of HM is assessed using the Miris Human Milk analyzer (Uppsala, Sweden). The quality of growth will be assessed by in-hospital weight, length, and head circumference growth velocities and a single measurement of adiposity (fat mass percentage and fat mass index) performed just after discharge, using the air displacement plethysmography method (Pea Pod, Cosmed, Italy). ClinicalTrials.gov registration number: NCT04400396.

Congenital Glucagon-like Peptide-1 Deficiency in the Pathogenesis of Protracted Diarrhea in Mitchell-Riley Syndrome.

CONTEXT: Mitchell-Riley syndrome due to RFX6 gene mutations is characterized by neonatal diabetes and protracted diarrhea. The RFX6 gene encodes a transcription factor involved in enteroendocrine cell differentiation required for beta-cell maturation. In contrast to the pathway by which RFX6 mutations leads to diabetes, the mechanisms underlying protracted diarrhea are unknown. OBJECTIVE: To assess whether glucagon-like peptide-1 (GLP-1) was involved in the pathogenesis of Mitchell-Riley syndrome protracted diarrhea. METHODS: Two case report descriptions. in a tertiary pediatric hospital. "Off-label" treatment with liraglutide. We describe 2 children diagnosed with Mitchell-Riley syndrome, presenting neonatal diabetes and protracted diarrhea. Both patients had nearly undetectable GLP-1 plasma levels and absence of GLP-1 immunostaining in distal intestine and rectum. The main outcome was to evaluate whether GLP-1 analogue therapy could improve Mitchell-Riley syndrome protracted diarrhea. RESULTS: "Off-label" liraglutide treatment, licensed for type 2 diabetes treatment in children, was started as rescue therapy for protracted intractable diarrhea resulting in rapid improvement during the course of 12 months. CONCLUSION: Congenital GLP-1 deficiency was identified in patients with Mitchell-Riley syndrome. The favorable response to liraglutide further supports GLP-1 involvement in the pathogenesis of protracted diarrhea and its potential therapeutic use.

Evolution of Resting Energy Expenditure, Respiratory Quotient, and Adiposity in Infants Recovering from Corrective Surgery of Major Congenital Gastrointestinal Tract Anomalies: A Cohort Study.

This cohort study describes the evolution of resting energy expenditure (REE), respiratory quotient (RQ), and adiposity in infants recovering from corrective surgery of major congenital gastrointestinal tract anomalies. Energy and macronutrient intakes were assessed. The REE and RQ were assessed by indirect calorimetry, and fat mass index (FMI) was assessed by air displacement plethysmography. Longitudinal variations over time are described. Explanatory models for REE, RQ, and adiposity were obtained by multiple linear regression analysis. Twenty-nine infants were included, 15 born preterm and 14 at term, with median gestational age of 35.3 and 38.1 weeks and birth weight of 2304 g and 2935 g, respectively. In preterm infants, median REE varied between 55.7 and 67.4 Kcal/kg/d and median RQ increased from 0.70 to 0.86-0.92. In term infants, median REE varied between 57.3 and 67.9 Kcal/kg/d and median RQ increased from 0.63 to 0.84-0.88. Weight gain velocity was slower in term than preterm infants. FMI, assessed in a subset of 15 infants, varied between a median of 1.7 and 1.8 kg/m2 at term age. This low adiposity may be related to poor energy balance, low fat intakes, and low RQ¸ that were frequently recorded in several follow-up periods.

Nutritional Assessment in Preterm Infants: A Practical Approach in the NICU.

A practical approach for nutritional assessment in preterm infants under intensive care, based on anthropometric measurements and commonly used biochemical markers, is suggested. The choice of anthropometric charts depends on the purpose: Fenton 2013 charts to assess intrauterine growth, an online growth calculator to monitor intra-hospital weight gain, and Intergrowth-21st standards to monitor growth after discharge. Body weight, though largely used, does not inform on body compartment sizes. Mid-upper arm circumference estimates body adiposity and is easy to measure. Body length reflects skeletal growth and fat-free mass, provided it is accurately measured. Head circumference indicates brain growth. Skinfolds estimate reasonably body fat. Weight-to-length ratio, body mass index, and ponderal index can assess body proportionality at birth. These and other derived indices, such as the mid-upper arm circumference to head circumference ratio, could be proxies of body composition but need validation. Low blood urea nitrogen may indicate insufficient protein intake. Prealbumin and retinol binding protein are good markers of current protein status, but they may be affected by non-nutritional factors. The combination of a high serum alkaline phosphatase level and a low serum phosphate level is the best biochemical marker for the early detection of metabolic bone disease.

Male sex is an independent risk factor for poor neurodevelopmental outcome at 20 months' corrected age, in human milk-fed very preterm infants: a cohort study.

OBJECTIVE: To determine associations between sex and neurodevelopmental outcomes in human milk-fed very preterm infants, adjusted to early measured nutrient intakes and other neonatal cofactors. METHODS: Consecutive inborn human milk-fed infants, with gestational age <33 weeks, were eligible. In-hospital energy and protein intakes have relied on measured human milk composition. The Bayley Scales of Infant Development II mental and psychomotor developmental indexes were used to assess neurodevelopment at 20 months' corrected age. After univariate analysis, some covariables were used for linear multiple regression. RESULTS: Thirty-two infants were included, with a mean (standard deviation) gestational age of 29.8 (1.8) weeks, and a median birth weight of 1168g (interquartile range 990-1419g). Minimum recommended intakes were achieved in 63.6% and 15.2% of infants for protein and energy, respectively. The mental and psychomotor developmental indexes were within normal limits in 93.8% of infants. The mean mental and psychomotor developmental indexes were significantly lower in males. Only male sex negatively and significantly affected the mental and psychomotor developmental indexes (B=-9.44; 95%CI: -17.64- -1.23; adjusted r2=0.17; p=0.026), adjusted to gestational age and measured energy intake. CONCLUSION: In human milk-fed very preterm infants, males had a significantly lower mental and psychomotor developmental indexes score at 20 months' corrected age, adjusted for gestational age and measured energy intake.

Comparison of Growth Curve Estimates of Infants in São Tomé Island, Africa, with the WHO Growth Standards: A Birth Cohort Study.

This birth cohort study compared the infant growth curve estimates in São Tomé Island to the WHO growth standards. Despite this island belonging to a lower-middle-income country, there were several factors favorable for growth that were present. Four-hundred and seventy-five full-term singleton appropriate for-gestational-age infants were enrolled and followed-up to 24 months of age. Weight-for-age, length-for-age, weight-for-length, body mass index-for-age, head circumference-for-age, weight velocity, and length velocity curves were estimated and compared to the WHO standards. In the first 6 months of age, the weight gain was adequate in the presence of a high prevalence of exclusive breastfeeding. Thereafter, weight trajectories tracked close to the WHO standards, except for a progressive decline in the infants growing in higher percentiles, especially in girls. Median length at birth was below the median WHO standards, followed by an early postnatal velocity spurt, which probably reflected the transition from an unfavorable to a more favorable postnatal environment. Thereafter, linear growth faltering was observed without relevant deterioration up to 24 months of age, which was probably due to the presence of protective factors. These results may be useful to implement strategies to further approximate infant growth in São Tomé Island to the WHO standards.

Colonisation of the proximal intestinal remnant in newborn infants with enterostomy: a longitudinal study protocol.

INTRODUCTION: The gut microbiota plays a main role in the maintenance of host's health. Exposure to different conditions in early life contributes to distinct 'pioneer' bacterial communities in the intestine, which shape the newborn infant development. Newborn infants with congenital malformations of the gastrointestinal tract (CMGIT), necrotising enterocolitis (NEC) and spontaneous intestinal perforation (SIP) commonly require abdominal surgery and enterostomy. The knowledge about the colonisation of these newborns' intestine by microorganisms is scarce. This protocol is designed to explore the microbial colonisation over time of the proximal intestinal remnant in newborn infants who underwent surgery for CMGIT, NEC or SIP and require enterostomy. METHODS AND ANALYSIS: The literature about microbiota colonisation in newborn infants with enterostomy was reviewed and an observational, longitudinal, prospective study was designed. The infants will be recruited at the Neonatal Intensive Care Unit of the Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central. Samples of the enterostomy effluent will be collected every 3 days, through 21 days after the first collection. The microorganisms colonising the proximal intestinal remnant will be identified using the 16S rRNA sequence analysis and a subset of microorganisms will be quantified using real-time PCR. This protocol may serve as basis for future observational and interventional studies on the modulation of the intestinal microbiota (eg, probiotics) on short and long-term outcomes in this population. ETHICS AND DISSEMINATION: This study protocol was approved by the Ethics Committee of Centro Hospitalar Universitário de Lisboa Central (441/2017) and by the Ethics Committee of NOVA Medical School, Universidade Nova de Lisboa (n°50/2018/CEFCM). The results will be spread through peer-reviewed publications and presentations at international scientific meetings. TRIAL REGISTRATION NUMBER: NCT03340259.