Use of Genetically Modified Organism (GMO)-Containing Food Products in Children.

Families increasingly raise questions about the use of genetically modified organism (GMO)-containing food products. These products are widely found in the US food supply but originate from a narrow list of crops. Although GMO technology could be used to increase the micronutrient content of foods, this does not occur in the United States; instead, GMO technology has been used to make crops resistant to chemical herbicides. As a result, herbicide use has increased exponentially. The World Health Organization's International Agency on Research for Cancer has determined that glyphosate, an herbicide widely used in producing GMO food crops, is a probable human carcinogen. Measurable quantities of glyphosate are detected in some GMO foods. Families who wish to minimize GMO food products can do so by focusing on a dietary pattern of primarily whole, plant-based foods while minimizing ultra-processed foods. Pediatricians play a vital role in their efforts to minimize fear-based messaging and support families through shared decision-making. Pediatrician awareness of GMO labeling can guide individualized conversations, particularly that non-GMO labeling does not indicate organic status and that increased cost of some non-GMO foods, especially if also organic, may limit this choice for many families.

Older Infant-Young Child "Formulas".

The category of "formulas" directed at older infants and toddlers 6 to 36 months of age has increased in prominence over the last years but is characterized by lack of standardization in nomenclature and composition as well as questionable marketing practices. There has been uncertainty and misperception regarding some of the roles of these beverages in ensuring adequate childhood nutrition. The aim of this clinical report is to review the context, evidence, and rationale for older infant-young child formulas, followed by recommendations.

Prenatal Weight Change Trajectories and Perinatal Outcomes among Twin Gestations.

OBJECTIVE: Despite an increase in twin pregnancies in recent decades, the Institute of Medicine twin weight gain recommendations remain provisional and provide no guidance for the pattern or timing of weight change. We sought to characterize gestational weight change trajectory patterns and examine associations with birth outcomes in a cohort of twin pregnancies. STUDY DESIGN: Prenatal and delivery records were examined for 320 twin pregnancies from a maternal-fetal medicine practice in Austin, TX 2011-2019. Prenatal weights for those with >1 measured weight in the first trimester and ≥3 prenatal weights were included in analyses. Trajectories were estimated to 32 weeks (mean delivery: 33.7 ± 3.3 weeks) using flexible latent class mixed models with low-rank thin-plate splines. Associations between trajectory classes and infant outcomes were analyzed using multivariable Poisson or linear regression. RESULTS: Weight change from prepregnancy to delivery was 15.4 ± 6.3 kg for people with an underweight body mass index, 15.4 ± 5.8 kg for healthy weight, 14.7 ± 6.9 kg for overweight, and 12.5 ± 6.4 kg for obesity. Three trajectory classes were identified: low (Class 1), moderate (Class 2), or high gain (Class 3). Class 1 (24.7%) maintained weight for 15 weeks and then gained an estimated 6.6 kg at 32 weeks. Class 2 (60.9%) exhibited steady gain with 13.5 kg predicted total gain, and Class 3 (14.4%) showed rapid gain across pregnancy with 21.3 kg predicted gain. Compared to Class 1, Class 3 was associated with higher birth weight z-score (ß = 0.63, 95% confidence interval [CI]: 0.31,0.96), increased risk for large for gestational age (IRR = 5.60, 95% CI: 1.59, 19.67), and birth <32 weeks (IRR = 2.44, 95%CI: 1.10, 5.4) that was attenuated in sensitivity analyses. Class 2 was associated with moderately elevated birth weight z-score (ß = 0.24, 95%CI: 0.00, 0.48, p = 0.050). CONCLUSION: Gestational weight change followed a low, moderate, or high trajectory; both moderate and high gain patterns were associated with increased infant size outcomes. Optimal patterns of weight change that balance risk during the prenatal, perinatal, and neonatal periods require further investigation, particularly in high-risk twin pregnancies. KEY POINTS: · A majority gained weight below IOM twin recommendations.. · Three patterns of GWC across pregnancy were identified.. · Moderate or high GWC was associated with infant size..

Infant burn injuries related to water heating for powdered infant formula preparation.

Background: Guidance for preparing powdered infant formula (PIF) helps to ensure it meets the nutritional needs of infants and is safe to consume. Among safety concerns is Cronobacter sakazakii contamination which can lead to serious infections and death. PIF preparation guidance varies; there is a lack of consensus on whether there is a need to boil water to inactivate potential Cronobacter and for how long to let the water cool before reconstitution. We sought to quantify the burden of burn injuries among infants related to water heating for PIF preparation. Estimating this burden may help inform preparation recommendations. Methods: Burn injuries among infants <18 months of age were identified from 2017 to 2019 National Electronic Injury Surveillance System data collected from sampled hospital emergency departments. Injuries were classified as related to PIF water heating, potentially related to PIF water heating but with undetermined causation, related to other infant feeding aspects, or unrelated to infant formula or breast milk feeding. Unweighted case counts for each injury classification were determined. Results: Across sampled emergency departments, 7 PIF water heating injuries were seen among the 44,395 injuries reported for infants <18 months. No reported PIF water heating injuries were fatal, but 3 required hospitalization. Another 238 injuries potentially related to PIF water heating but with undetermined causation were also seen. Conclusion: Preparation guidance should consider both the potential risk for Cronobacter infection and the potential risk for burns.

Estimation of skeletal muscle mass in 4-year-old children using the D3-creatine dilution method.

BACKGROUND: Given limited experience in applying the creatine-(methyl-D3) (D3Cr) dilution method to measure skeletal muscle mass (SMM) in young children, the feasibility of deployment in a fielding setting and performance of the method was assessed in a cohort of 4-year-old children in Dhaka, Bangladesh. METHODS: Following D3Cr oral dose (10 mg) administration, single fasting urine samples were collected at 2-4 days (n = 100). Twenty-four-hour post-dose collections and serial spot urine samples on days 2, 3 and 4 were obtained in a subset of participants (n = 10). Urinary creatine, creatinine, D3Cr and D3-creatinine enrichment were analyzed by liquid chromatography-tandem mass spectrometry. Appendicular lean mass (ALM) was measured by dual-energy x-ray absorptiometry and grip strength was measured by a hand-held dynamometer. RESULTS: SMM was measured successfully in 91% of participants, and there were no adverse events. Mean ± SD SMM was greater than ALM (4.5 ± 0.4 and 3.2 ± 0.6 kg, respectively). Precision of SMM was low (intraclass correlation = 0.20; 95% CI: 0.02, 0.75; n = 10). Grip strength was not associated with SMM in multivariable analysis (0.004 kg per 100 g of SMM; 95% CI: -0.031, 0.038; n = 91). CONCLUSIONS: The D3Cr dilution method was feasible in a community setting. However, high within-child variability in SMM estimates suggests the need for further optimization of this approach. IMPACT: The D3-creatine (D3Cr) stable isotope dilution method was considered a feasible method for the estimation of skeletal muscle mass (SMM) in young children in a community setting and was well accepted among participants. SMM was weakly associated with both dual-energy x-ray absorptiometry-derived values of appendicular lean mass and grip strength. High within-child variability in estimated values of SMM suggests that further optimization of the D3Cr stable isotope dilution method is required prior to implementation in community research settings.

Perspective: Is It Time to Revise the Current Nutrient Requirements for Infant Formulas Principally Established in 1980?

Because of the production of nutrient-deficient infant formulas (IFs), the United States Congress passed regulations on the composition and production of IF, referred to as the Infant Formula Act (IFA), in 1980, which was amended in 1986. More detailed FDA rules have been created since then, specifying the ranges or minimum intakes of nutrients and providing details for the safe production and evaluation of infant formulas. Although generally effective in ensuring safe IF, recent events have made it clear that a re-evaluation of aspects of all the nutrient composition regulations for IF is needed, including consideration of adding requirements related to bioactive nutrients not mentioned in the IFA. We propose that, as principal examples, the requirement for iron content needs to be re-evaluated and that DHA and AA should be considered for addition to the nutrient requirements after scientific review by a panel such as those established by the National Academies of Sciences, Engineering, and Medicine. Additionally, there is no specific requirement in current FDA regulations for the energy density of IF, and this should be added alongside potential revisions of the protein requirement. It would also be ideal to have specific FDA rules on nutrient intakes for premature infants as these are exempted from the specific nutrient regulations of the amended IFA.

Neurodevelopmental outcomes of extremely preterm infants fed an exclusive human milk-based diet versus a mixed human milk + bovine milk-based diet: a multi-center study.

OBJECTIVE: The objective of this multi-center study was to compare, in infants ≤1250 g birth weight (BW) with neurodevelopmental assessment at 18-22 months of corrected age (CA), whether their neurodevelopmental outcomes differed based on exposure to an exclusive human milk-based (HUM) or to a bovine milk-based fortifier and/or preterm formula (BOV). STUDY DESIGN: Retrospective multi-center cohort study of infants undergoing neurodevelopmental assessment as to whether HUM or BOV exposure related to differences in outcomes of infants at 18-22 months CA, using the Bayley Scales of Infant Development III (BSID-III). BSID-III cognitive, language, and motor scores were adjusted for BW, sex, study site, and necrotizing enterocolitis. RESULTS: 252 infants from 6 centers were included. BSID-III cognitive scores were higher in the HUM group (96.5 ± 15.1 vs 89.6 ± 14.1, adjusted p = 0.0001). Mean BSID-III language scores were 85.5 ± 15.0 in HUM and 82.2 ± 14.1 in BOV (adjusted p = 0.09). Mean BSID-III motor scores were 92.9 ± 11.7 in HUM and 91.4 ± 14.6 in BOV (adjusted p = 0.32). CONCLUSION: In this cohort of infants undergoing neurodevelopmental assessment, infants receiving HUM diet had significantly higher cognitive BSID-III scores at 18-22 months CA. Further investigation is needed of this potential for HUM to positively influence infant cognitive outcomes.

Infant and child formula shortages: now is the time to prevent recurrences.

An acute shortage of infant formulas in the United States occurred in early 2022, exacerbating a longer-standing, less severe shortage that has occurred over the last several years. The shortage has been particularly problematic for specialized formulas such as those needed for infants and children with food allergies, intestinal failure, kidney disease, and metabolic disorders. Although undoubtedly the magnitude of the current shortage will abate over time, it has affected many children and caused tremendous distress for thousands of families. We propose a series of interventions to be undertaken as soon as feasible to help ensure that the conditions that led to this problem do not recur and families regain confidence in the safety and supply reliability of formulas for infants and young children regardless of their medical needs.

Daily Intake of a Functional Synbiotic Yogurt Increases Calcium Absorption in Young Adult Women.

BACKGROUND: Foods containing both prebiotics and probiotics (synbiotics) might enhance calcium bioavailability. OBJECTIVES: We investigated the acute effect in young adult women on calcium absorption of consuming (185 mL) a synbiotic yogurt (SYN) containing inulin (4 g) and Lactobacillus rhamnosus GG (>1 × 107 CFU/mL) compared with a control yogurt (CON). METHODS: Adult normal-weight women (25.0 ± 3.5 y, n = 30) participated in a 3-wk crossover study testing daily consumption of SYN compared with CON. Habitual dietary intake, bone mineral density (BMD), calcium biomarkers, and serum 25-hydroxyvitamin D were measured at baseline. Calcium absorption was tested after each phase of the study using a 42Ca oral tracer. Cumulative tracer recovery was measured in 0-4-h,  0-24-h, and 0-36-h urine pools collected postdosing. The SYN/CON tracer ratio from the timed urine pools was the primary outcome. A beneficial response to SYN was defined as 0-36-h SYN/CON tracer ratio >1. RESULTS: Net 42Ca recovered increased over time in each of the SYN and CON urine pools postdosing (Friedman, P < 0.001), with a trend for higher 42Ca recovery in the 0-36-h urine pool postdosing in the SYN (1.14%) compared with the CON (0.90%) study (Wilcoxon, P = 0.07). For CON, the majority of total tracer was recovered in the 0-24-h pool (86%), whereas for SYN only 50% of total tracer was recovered in the 0-24-h pool (Friedman, P = 0.001). The SYN/CON tracer ratio in the 0-36-h pool (1.24) was >1 (Wilcoxon, P = 0.015). About two-thirds (n = 19) of women studied responded to the SYN treatment. Responders had higher vegetable intake (P = 0.03), tended to have higher potassium and calcium intakes (P ≤ 0.08), and had higher total body BMD (P = 0.09), than nonresponders. CONCLUSIONS: Short-term daily consumption of a synbiotic yogurt enhanced calcium absorption relative to a control yogurt in adult women. Given the observed time delays in tracer recovery, enhancement of calcium absorption likely occurred in the large intestine.The study was registered at clinicaltrials.gov (study registration ID: NCT03420716).

Vitamin K and the Newborn Infant.

Intramuscular administration of vitamin K for prevention of vitamin K deficiency bleeding (VKDB) has been a standard of care since the American Academy of Pediatrics recommended it in 1961. Despite the success of prevention of VKDB with vitamin K administration, the incidence of VKDB appears to be on the rise. This increase in incidence of VKDB is attributable to parental refusal as well as lowered efficacy of alternate methods of administration. The aim of this statement is to discuss the current knowledge of prevention of VKDB with respect to the term and preterm infant and address parental concerns regarding vitamin K administration.

Interventions to improve calcium intake through foods in populations with low intake.

Calcium intake remains inadequate in many low- and middle-income countries, especially in Africa and South Asia, where average intakes can be below 400 mg/day. Given the vital role of calcium in bone health, metabolism, and cell signaling, countries with low calcium intake may want to consider food-based approaches to improve calcium consumption and bioavailability within their population. This is especially true for those with low calcium intake who would benefit the most, including pregnant women (by reducing the risk of preeclampsia) and children (by reducing calcium-deficiency rickets). Specifically, some animal-source foods that are naturally high in bioavailable calcium and plant foods that can contribute to calcium intake could be promoted either through policies or educational materials. Some food processing techniques can improve the calcium content in food or increase calcium bioavailability. Staple-food fortification with calcium can also be a cost-effective method to increase intake with minimal behavior change required. Lastly, biofortification is currently being investigated to improve calcium content, either through genetic screening and breeding of high-calcium varieties or through the application of calcium-rich fertilizers. These mechanisms can be used alone or in combination based on the local context to improve calcium intake within a population.

Effect of maternal prenatal and postpartum vitamin D supplementation on offspring bone mass and muscle strength in early childhood: follow-up of a randomized controlled trial.

BACKGROUND: Maternal vitamin D status during pregnancy and lactation is a modifiable factor that may influence offspring musculoskeletal outcomes. However, few randomized trials have tested the effects of prenatal or postpartum vitamin D supplementation on offspring bone and muscle development. OBJECTIVES: The aim was to examine hypothesized effects of improvements in early-life vitamin D status on childhood musculoskeletal health in Dhaka, Bangladesh. METHODS: In a previously completed, double-blind, dose-ranging trial, healthy pregnant women (n = 1300) were recruited at 17-24 weeks' gestation and randomly assigned to a prenatal/postpartum regimen of 0/0, 4200/0, 16,800/0, 28,000/0, or 28,000/28,000 IU cholecalciferol (vitamin D3)/wk until 26 wk postpartum. In this new report, we describe additional follow-up at 4 y of age (n = 642) for longer-term outcomes. Bone mineral content (BMC) and areal bone mineral density (aBMD) were measured by DXA. Grip strength was tested using a hand-held dynamometer. The primary comparison was children of women assigned to 28,000 IU/wk prenatally compared with placebo. Differences are expressed as means and 95% CIs. RESULTS: Total-body-less-head (TBLH) BMC, TBLH aBMD, and grip strength were similar in the combined high-dose prenatal (28,000/0 and 28,000/28,000 IU/wk) compared with placebo groups (mean difference [95% CI] = 0.61 g [-10.90, 12.13], 0.0004 g/cm2 [-0.0089, 0.0097], and 0.02 kg [-0.26, 0.31], respectively). In dose-ranging analyses, TBLH BMC and aBMD, whole-body BMC and aBMD, and grip strength in each of the prenatal vitamin D groups were not significantly different from placebo (P > 0.05 for all comparisons). Only head aBMD was greater in children of women assigned to the 28,000/28,000-IU regimen compared with placebo (mean difference [95% CI] = 0.024 g/cm2 [0.0009, 0.047], P = 0.042); the effect was attenuated upon adjustment for child height, weight, and sex (P = 0.11). CONCLUSIONS: Maternal prenatal, with or without postpartum, vitamin D supplementation does not improve child BMC, aBMD, or grip strength at 4 y of age. The MDIG trial and present follow-up study were registered prospectively at www.clinicaltrials.gov as NCT01924013 and NCT03537443, respectively.

Bone Health in School Age Children: Effects of Nutritional Intake on Outcomes.

The maximum rate of bone mass accumulation is during early adolescence. As such, a focus on optimizing mineral nutrition in school age children, defined here as approximately 5 to 15 years of age, is crucial to minimize the risk of bone loss that occurs later in life leading to osteoporosis and fractures. Optimizing bone mass in this age group requires attention to an overall healthy diet including adequate calcium, phosphorus, magnesium, and vitamin D. Special concerns may exist related to children who follow a restricted diet such as a vegan diet, those with intolerance or allergies to dairy, and those with chronic health conditions including young adolescents with eating disorders. Public policy messages should focus on positive aspects of bone health nutrition in this age group and avoid overly specific statements about the exact amounts of foods needed for healthy bones. In this regard, dietary recommendations for minerals vary between North America and Europe and these are higher than the values that may be necessary in other parts of the world. The management of many children with chronic illnesses includes the use of medications that may affect their bone mineral metabolism. Routine lab testing for bone mineral metabolism including the serum 25-hydroxyvitamin D level is not indicated, but is valuable for at-risk children, especially those with chronic illnesses.

Vitamin D and bone minerals in neonates.

Osteopenia and rickets remain a problem for high-risk infants, especially preterm infants <1500 g birthweight (very low birth weight, VLBW). The primary cause of osteopenia in VLBW infants is a low intake of calcium and phosphorus compared to requirements for the rapidly growing skeleton. Human milk is a relatively low mineral containing substance and cannot meet the bone mineral needs of very low birth weight infants. As such, most VLBW infants need additional bone minerals and in many neonatal care units these are provided as part of human milk fortificants or specialized infant formulas. In some nurseries, these are given to all infants < 1800-2000 g birthweight. Management of full-term infants who are small for gestational age at birth is less clear, but in general bone mineral content is associated more with body size than gestational age and supplementation is often provided to these infants. Although all infants, including preterm ones need a source of vitamin D, the benefits of providing high doses of vitamin D to healthy preterm neonates is unproven. Some evidence indicates that most calcium absorption is non-vitamin D dependent in the first weeks of life in both preterm and term infants. However, after achieving full feeds in the preterm infant, it is prudent to provide vitamin D at amounts comparable to that used in full-term infants. Higher doses increase serum 25-hydroxyvitamin D levels more rapidly, but evidence is inconclusive as to the relative benefits vs possible risks of higher doses. In healthy full-term infants, although vitamin D provision via supplement drops to the breastfed infant, high dose maternal supplementation to the lactating mother or infant formula is generally recommended, the current evidence only strongly supports its use in identified at-risk infants.

Growth outcomes of small for gestational age preterm infants before and after implementation of an exclusive human milk-based diet.

OBJECTIVE: Small for gestational age (SGA) preterm infants (PT) are at greatest risk for growth failure. Our objective was to assess the impact of an exclusive human milk diet (HUM) on growth velocities and neonatal morbidities from birth to discharge in a SGA population. STUDY DESIGN: Multicenter, retrospective cohort study, subgroup analysis of SGA PT comparing a cow's milk diet (CMD) with HUM diet. RESULTS: At birth 420 PT were classified as SGA (197 CMD group, 223 HUM group). Demographics and anthropometric measurements were similar. HUM group PT showed improvement in length Z score at discharge (p = 0.024) and reduction in necrotizing enterocolitis (NEC) (p = 0.004). CONCLUSION: SGA PT fed a HUM diet had significantly decreased incidence of NEC, surgical NEC, and late-onset sepsis. Due to concerns about growth in a HUM diet, it is reassuring SGA infants fed the HUM diet had similar growth to CMD diet with trends toward improvement.

Lessons Learned from Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets Patients on Vitamin D Functions.

We summarize here lessons learned from studies on skeletal and extra-skeletal functions of vitamin D in hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) patients with a mutant, nonfunctioning vitamin D receptor (VDR). During childhood, HVDRR patients are dependent on intestinal VDR, demonstrate low intestinal fraction calcium absorption, and have a bone calcium accretion rate that leads to hypocalcemia and rickets. After puberty, there is recovery in intestinal calcium absorption and in bone calcium accretion and structure. HVDRR monocytes and lymphocytes show impairment in the expression of antimicrobial proteins and demonstrate a proinflammatory cytokine profile. However, HVDRR patients do not exhibit increased rates of infections or inflammatory diseases. Vitamin D deficiency is associated with asthmatic exacerbations. Surprisingly, HVDRR patients do not usually develop asthma. They have normal allergic tests and lung functions and are protected against provoked bronchial hyperactivity. HVDRR patients have decreased IL-5 levels in their exhaled breath condensate. Given that IL-5 is a key cytokine in the development of airway inflammation and hyperactivity and that VDR is important for IL-5 generation, it is plausible that low lung IL-5 protects HVDRR patients from asthma. Vitamin D metabolites have suppressive effects on the renin angiotensin system. However, no HVDRR patient showed hypertension or echocardiographic pathology, and their renin angiotensin metabolites were normal. The VDR is expressed throughout the reproductive system, suggesting a role in reproduction. However, the reproductive history of HVDRR patients is normal despite the lack of a normal VDR. HVDRR patients provide a unique opportunity to study the role of the VDR and the role of vitamin D in various human systems.

A Substantial Proportion of 6- to 12-Month-Old Infants Have Calculated Daily Absorbed Iron below Recommendations, Especially Those Who Are Breastfed.

OBJECTIVE: To calculate the amount of bioavailable iron consumed among 6- to 12- month-old infants considering differences in iron bioavailability among dietary iron sources and to compare this with current recommended intakes. STUDY DESIGN: We used the Feeding Infants and Toddlers Study database of dietary intakes from 2016 and the estimated bioavailability of dietary iron sources to evaluate the proportion of infants whose calculated total daily absorbed iron fell below physiologic requirements, that is, the recommended amount needed to fully support growth and erythropoiesis. RESULTS: The calculated daily iron absorption was below the recommended amount in 54.3% of infants evaluated ranging from 19.5% of 448 exclusively formula-fed infants, to 95.8% of 296 exclusively breastfed infants and 72.2% of 102 mixed fed infants. The calculated mean iron absorption of 6- to 9- month-old breastfed infants was 0.27 mg/day, far less than the estimated physiologic requirement of 0.69 mg/day. The most highly bioavailable iron, heme iron, was <12% of the contributor to total iron absorbed in breastfed infants. CONCLUSIONS: These data indicate a need for further education and public health policies to support increased iron intake in 6- to 12- month-old infants, emphasizing those receiving any breast milk. Exclusively formula-fed infants are at lower risk, but rates of low absorbed iron indicate that all infants may need monitoring for clinical evidence of low iron status. Consideration should be given to increasing the proportion of heme iron obtained from animal products in the diet where feasible.