Formula-fed Groups Research Articles

Effects of Breastfeeding and Formula Feeding on the Expression Level of FTO, CPT1A and PPAR-α Genes in Healthy Infants.

PurposeThe study aimed to investigate the effect of breastfeeding, formula feeding and mix feeding (breastfed plus formula-fed) on the expression level of obesity-predisposing genes including fat mass and obesity-associated (FTO), carnitine palmitoyltransferase 1A (CPT1A), and peroxisome proliferator-activated receptor-α (PPAR-α) in 5- to 6-month-old infants.Patients and MethodsA total of 150 infants participated in this case–control study. All subjects were healthy infants aged 5–6 months that divided into 3 groups: breastfed, formula-fed, and mix-fed. The expression level of FTO, CPT1A, and PPAR-α genes in peripheral blood mononuclear cells (PBMC) was evaluated in each group using reverse transcription-polymerase chain reaction (RT-PCR) method.ResultsOur findings showed that the current weight, height, and head circumference of infants in the formula feeding and mix feeding groups were significantly higher than those in the exclusive breastfeeding group. The expression level of FTO and CPT1A genes in formula-fed and mix-fed infants was significantly higher (p<0.001) than that in breastfed infants, while the expression level of PPAR-α gene was significantly lower (p<0.05).ConclusionBreastfeeding showed modulatory effects on the expression level of obesity-predisposing genes and can protect against obesity and subsequent non-communicable diseases. However, more investigations are required to explain the epigenetic effects of breast milk.

Comparing Gut Microbiome in Mothers' Own Breast Milk- and Formula-Fed Moderate-Late Preterm Infants.

Gut microbiome plays an important role in adult human health and diseases. However, how nutritional factors shape the initial colonization of gut bacteria in infants, especially in preterm infants, is still not completely known. In this study, we compared the effects of feeding with mothers’ own breast milk (MBM) and formula on the initial composition and gene expression of gut bacteria in moderate–late preterm infants. Fecal samples were collected from ten formula-fed and ten MBM healthy infants born between 32 and 37 weeks’ gestation after they reached full-volume enteral feedings. Total DNAs were extracted from fecal samples for amplicon sequencing of 16S ribosomal RNA (rRNA) gene and total RNA with rRNA depletion for metatranscriptome RNA-Seq 16S rRNA gene amplicon sequencing results showed that the alpha-diversity was similar between the MBM- and formula-fed preterm infants, but the beta-diversity showed a significant difference in composition (p = 0.002). The most abundant taxa were Veillonella (18.4%) and Escherichia/Shigella (15.2%) in MBM infants, whereas the most abundant taxa of formula-fed infants were Streptococcus (18.6%) and Klebsiella (17.4%). The genera Propionibacterium, Streptococcus, and Finegoldia and order Clostridiales had significantly higher relative abundance in the MBM group than the formula group, whereas bacteria under family Enterobacteriaceae, genera Enterococcus and Veillonella, and class Bacilli were more abundant in the formula group. In general, microbiomes from both diet groups exhibited high functional levels of catalytic activity and metabolic processing when analyzed for gene ontology using a comparative metatranscriptome approach. Statistically, the microbial genes in the MBM group had an upregulation in expression related to glycine reductase, periplasmic acid stress response in Enterobacteria, acid resistance mechanisms, and L-fucose utilization. In contrast, the formula-fed group had upregulations in genes associated with methionine and valine degradation functions. Our data suggest that the nutritional source plays a role in shaping the moderate–late preterm gut microbiome as evidenced by the differences in bacterial composition and gene expression profiles in the fecal samples. The MBM group enriched Propionibacterium. Glycine reductase was highly upregulated in the microbiota from MBM along with the upregulated acid stress tolerance genes, suggesting that the intensity of fermentation process was enhanced.

Lactation Versus Formula Feeding: Insulin, Glucose, and Fatty Acid Metabolism During the Postpartum Period.

Milk production may involve a transient development of insulin resistance in nonmammary tissues to support redistribution of maternal macronutrients to match the requirements of the lactating mammary gland. In the current study, adipose and liver metabolic responses were measured in the fasting state and during a two-step (10 and 20 mU/m2/min) hyperinsulinemic-euglycemic clamp with stable isotopes, in 6-week postpartum women who were lactating (n = 12) or formula-feeding (n = 6) their infants and who were closely matched for baseline characteristics (e.g., parity, body composition, and intrahepatic lipid). When controlling for the low insulin concentrations of both groups, the lactating women exhibited a fasting rate of endogenous glucose production (EGP) that was 2.6-fold greater and a lipolysis rate that was 2.3-fold greater than the formula-feeding group. During the clamp, the groups exhibited similar suppression rates of EGP and lipolysis. In the lactating women only, higher prolactin concentrations were associated with greater suppression rates of lipolysis and lower intrahepatic lipid and plasma triacylglycerol concentrations. These data suggest that whole-body alterations in glucose transport may be organ specific and facilitate nutrient partitioning during lactation. Recapitulating a shift toward noninsulin-mediated glucose uptake could be an early postpartum strategy to enhance lactation success in women at risk for delayed onset of milk production.

Infant Formula Feeding Changes the Proliferative Status in Piglet Neonatal Mammary Glands Independently of Estrogen Signaling

Background:Soy infant formula contains isoflavones, which are able to bind to and activate estrogen receptor (ER) pathways. The mammary gland is sensitive to estrogens, raising concern that the use of soy formulas may promote premature development. Objective:We aimed to determine if soy formula feeding increases mammary gland proliferation and differentiation in comparison to other infant postnatal diets. Methods:White-Dutch Landrace piglets aged 2 d received either sow milk (Sow), or were provided milk formula (Milk), soy formula (Soy), milk formula supplemented with 17-beta-estradiol (2 mg/(kgd); M + E2), or milk formula supplemented with genistein (84 mg/L of diet; M + G) until day 21. Mammary gland proliferation and differentiation was assessed by histology, and real-time RT-PCR confirmation of differentially expressed genes identified by microarray analysis. Results:Mammary terminal end bud numbers were 19–31% greater in the Milk, Soy, and M+G groups relative to the Sow and M+E2, P <0.05. Microarray analysis identified differentially expressed genes between each formula-fed group relative to the Sow (±1.7-fold, P <0.05). Real-time RT-PCR confirmed 2- to 4-fold increases in mRNA transcripts of genes involved in cell proliferation, insulin-like growth factor 1 (IGF1), fibroblast growth factor 10 (FGF10), and fibroblast growth factor 18 (FGF18), in all groups relative to the Sow, P <0.05. In contrast, genes involved in cell differentiation and ductal morphogenesis, angiotensin II receptor type 2 (AGTR2), microtubule associated protein 1b (MAP1B), and kinesin family member 26b (KIF26B), were significantly upregulated by 2-, 4-, and 13-fold, respectively, in the M+E2 group. Additionally, mRNA expression of ER-specific gene targets, progesterone receptor (PGR), was increased by 12-fold, and amphiregulin (AREG) and Ras-like estrogen regulated growth inhibitor (RERG) expression by 1.5-fold in the M+E2 group, P <0.05. In the soy and M+G groups, mRNA expressions of fatty acid synthesis genes were increased 2- to 4-fold. Conclusions:Our data indicate soy formula feeding does not promote ER-signaling in the piglet mammary gland. Infant formula feeding (milk- or soy-based) may initiate proliferative pathways independently of estrogenic signaling.

The Role of Protein and Free Amino Acids on Intake, Metabolism, and Gut Microbiome: A Comparison Between Breast-Fed and Formula-Fed Rhesus Monkey Infants.

Background: Compared to breast-fed (BF), formula-fed (FF) infants exhibit more rapid weight gain, a different fecal microbial profile, as well as elevated serum insulin, insulin growth factor 1 (IGF-1), and branched chain amino acids (BCAAs). Since infant formula contains more protein and lower free amino acids than breast milk, it is thought that protein and/or free amino acids may be key factors that explain phenotypic differences between BF and FF infants.Methods: Newborn rhesus monkeys (Macaca mulatta) were either exclusively BF or fed regular formula or reduced protein formula either supplemented or not with a mixture of amino acids. Longitudinal sampling and clinical evaluation were performed from birth to 16 weeks including anthropometric measurements, intake records, collection of blood for hematology, serum biochemistry, hormones, and metabolic profiling, collection of urine for metabolic profiling, and collection of feces for 16s rRNA fecal microbial community profiling.Results: Reducing protein in infant formula profoundly suppressed intake, lowered weight gain and improved the FF-specific metabolic phenotype in the first month of age. This time-dependent change paralleled an improvement in serum insulin. All lower protein FF groups showed reduced protein catabolism with lower levels of blood urea nitrogen (BUN), urea, ammonia, albumin, creatinine, as well as lower excretion of creatinine in urine compared to infants fed regular formula. Levels of fecal microbes (Bifidobacterium and Ruminococcus from the Ruminococcaceae family), that are known to have varying ability to utilize complex carbohydrates, also increased with protein reduction. Adding free amino acids to infant formula did not alter milk intake or fecal microbial composition, but did significantly increase urinary excretion of amino acids and nitrogen-containing metabolites. However, despite the lower protein intake, these infants still exhibited a distinct FF-specific metabolic phenotype characterized by accelerated weight gain, higher levels of insulin and C-peptide as well as elevated amino acids including BCAA, lysine, methionine, threonine and asparagine.Conclusions: Reducing protein and adding free amino acids to infant formula resulted in growth and metabolic performance of infants that were more similar to BF infants, but was insufficient to reverse the FF-specific accelerated growth and insulin-inducing high BCAA phenotype.

Optimal nutrition in gastrointestinal distress among infants aged 6-8 weeks: An observational study in India

The ambiguity among the gastrointestinal (GI) disease symptoms and aetiology in apparently healthy, well-fed term infants make the diagnosis and interventions of GI disease challenging. We assessed if there was a difference in the GI tolerance of lactose predominant formula-fed and human-milk fed infants. The study divided mother and infant (68 weeks of age) pairs into predominantly breastfeeding (BF) and predominantly infant formula (IF) feeding groups. The Infant Gastrointestinal Symptom Questionnaire (IGSQ-13) index score and symptom-wise (stooling, spitting/vomiting, crying, fussiness, and flatulence) analysis showed no statistically significant difference between the study groups. The role of optimal nutrition which is closer to breastmilk in providing gut comfort has been elicited by this study. 100% lactose-based formula can be considered as a promising alternative to the management of infants with GI distress, however, IF should always be considered as a substitute and not a replacement to breastmilk.

Real-world study in infants fed an infant formula with two human milk oligosaccharides

Introduction: human milk oligosaccharides (HMOs) are an important component of human milk supporting the development of a balanced intestinal microbiota and immune protection in breastfed infants. Randomized controlled trials (RCTs) have demonstrated that infant formulas supplemented with the HMOs 2'-fucosyllactose (2'FL) and lacto-N-neotetraose (LNnT) are safe, well-tolerated, and support normal growth. This Real-World Evidence (RWE) study aimed to evaluate growth and tolerance in infants consuming a formula supplemented with 1 g/L of 2'FL and 0.5 g/L of LNnT, and included a mixed-feeding group never studied before in RCTs. Participants and methods: this open-label, prospective study was conducted at six centers in Spain, and included healthy, exclusively breastfed infants (BF group), an exclusively formula-fed group (FF) who received a milk-based formula with 2' FL and LNnT, and a group mixed fed with both formula and human milk (MF), for 8 weeks. Co-primary outcomes were growth (anthropometry) and gastrointestinal tolerance (Infant Gastrointestinal Symptom Questionnaire, IGSQ). Secondary outcomes included formula satisfaction and adverse events (AEs). Results: 159 infants completed the study (66 FF, 48 MF, and 45 BF). Mean z-scores for growth were similar between all groups and within ± 0.5 of WHO medians at week 8. Composite IGSQ scores demonstrated low GI distress in all groups, with no significant group differences at baseline, week 4, or week 8. Incidence of AEs was low overall, and comparable across groups. Conclusions: in this RWE study examining a HMO-supplemented infant formula, growth and tolerance outcomes were similar to RCT findings, supporting the effectiveness of this early feeding option.

Clinical characteristics and treatment of infantile lactose intolerance and evaluation of the diagnostic value of fecal pH

Objective To investigate the clinical characteristics, diagnostic approach, and treatment of infantile lactose intolerance, and to evaluate the diagnostic value of fecal pH. Methods The feces and clinical data of all infants(less than 1 year old) diagnosed with simple diarrhea but without signs of infection were collected, who were treated at 4 Grade Ⅲ-Class-A hospitals within the period of June 2012 to June 2015 in Beijing were collected.Lactose intolerance was diagnosed based on urine galactose level, lactose tolerance test, and fecal pH.The clinical characteristics, therapeutic effects and detection methods of lactose tolerance group and intolerance group were analyzed.Then the diagnostic value of fecal pH was evaluated. Results A total of 217 infants were enrolled in the study, consisting of 113 boys and 104 girls.Their age ranged from 3 to 330 days, 174 infants (80.2%) were less than 6 months old.Among them, 156 infants were diagnosed with lactose intolerance (71.9%), their median age 90.0 days (3-330 days), while the median age of the lactose tolerant group was 51.5 days (3-300 days). The incidence of lactose intolerance in infants less than 6 months old was 70.6%, and 76.7% in those older than 6 months.Clinical characteristics showed that more infants in the lactose intolerant group were breastfed compared with the lactose tolerant group [73/156 cases(46.8%) vs.16/61 cases(26.2%), χ2=7.666, P 6 months, between the breastfeeding group and formula-feeding group, or between those with infection and those without infection (all P>0.05). Conclusions Infants with lactose intolerance often manifest foamy feces and tend to be breastfed.Lactose-free treatment efficacy was better than that with lactase.Clinical symptoms when combined with urine galactose level and lactose tolerance test can help diagnosis.However, the decrease of fecal pH proves to be unhelpful in aiding diagnosis. Key words: Lactose intolerance; Clinical characteristics; Treatment; Fecal pH

Fluoride Exposure from Infant Formula and Child IQ in a Canadian Birth Cohort

OPS 36: Health effects of dietary exposures, Room 210, Floor 2, August 27, 2019, 4:30 PM - 5:30 PM Background: Consumption of infant formula reconstituted with fluoridated water can lead to excessive intake of fluoride in infants. We examined the association between water fluoride concentration and intellectual ability (IQ) among preschool children who lived in fluoridated or non-fluoridated cities in Canada and were either formula-fed or breastfed during the first six months after birth. Methods: We measured water fluoride concentration using municipal water reports matched to the child’s birthdate to six-months of age. We restricted our analyses to 398 mother-child dyads enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort who reported drinking tap water. We evaluated Full Scale IQ (FSIQ) using the Wechsler Primary and Preschool Scale of Intelligence-III at 3 to 4 years. We used multiple linear regression analyses with an interaction to examine how the covariate-adjusted association between water fluoride concentration and FSIQ scores differs according to feeding status. In secondary analyses, we controlled for prenatal fluoride exposure. Results: Thirty-eight percent of mother-child dyads lived in communities supplied with fluoridated municipal water. An increase of 0.5 mg/L fluoride concentration (the difference between fluoridated and non-fluoridated region) corresponded to a drop of 4.4 FSIQ points (95% CI: -8.34, -0.46, p=.03) in the formula-fed group. In contrast, this relationship was not significant in the breastfed group (B=-1.34, 95% CI: -5.04, 2.38, p=.48). Controlling for prenatal fluoride exposure weakened the association between water fluoride concentration and FSIQ in the formula-fed group (B=-3.88, 95% CI = -8.12, 0.37, p=.07). Conclusions: The results, which indicate that fluoride concentration in drinking water was associated with lower FSIQ in children who were formula fed, underscore the need to reduce the use of fluoridated water to reconstitute formula during infancy.

Feeding Infants Formula With Probiotics or Milk Fat Globule Membrane: A Double-Blind, Randomized Controlled Trial

Purpose: To evaluate effects on growth and infection rates of supplementing infant formula with the probiotic Lactobacillus paracasei ssp. paracasei strain F19 (F19) or bovine milk fat globule membrane (MFGM).Methods: In a double-blind, randomized controlled trial, 600 infants were randomized to a formula supplemented with F19 or MFGM, or to standard formula (SF). A breastfed group was recruited as reference (n = 200).The intervention lasted from age 21 ± 7 days until 4 months, and infants were followed until age one year.Results: Both experimental formulas were well tolerated and resulted in high compliance. The few reported adverse events were not likely related to formula, with the highest rates in the SF group, significantly higher than for the F19-supplemented infants (p = 0.046). Weight or length gain did not differ during or after the intervention among the formula-fed groups, with satisfactory growth. During the intervention, overall, the experimental formula groups did not have more episodes of diarrhea, fever, or days with fever than the breastfed infants. However, compared to the breastfed infants, the SF group had more fever episodes (p = 0.021) and days with fever (p = 0.036), but not diarrhea. Compared with the breastfed group, the F19-supplemented infants but not the other two formula groups had more visits/unscheduled hospitalizations (p = 0.015) and borderline more episodes of upper respiratory tract infections (p = 0.048).Conclusions: Both the MFGM- and F19-supplemented formulas were safe and well-tolerated, leading to few adverse effects, similar to the breastfed group and unlike the SF group. During the intervention, the MFGM-supplemented infants did not differ from the breastfed infants in any primary outcome.

Association of Parity and Infant Feeding Method with Breast Density on Mammography

Mammography (MMG) is widely used for the screening and diagnosis of breast cancer. High breast density on MMG prevents breast cancer detection. In the present study, we analyzed the effects of parity and infant feeding method on mammographic breast density. Ninety women diagnosed as having breast cancer were analyzed. Using the results of medical questionnaires, subjects were grouped according to their parity and infant feeding method, into either nulliparity or parity, and formula-feeding or breastfeeding. Each group consisted of 30 consecutive women from 45 to 49 years. Nulliparous group was unaffected by either parity or breastfeeding, formula-feeding group was affected by parity but not breastfeeding, and breastfeeding group was affected by both parity and breastfeeding. Mammographic breast density was evaluated on the contralateral and cancer-free breast, and was classified into ≥ 50% dense as high breast density and < 50% dense according to the Boyd quantitative scale. The association of parity and infant feeding method with breast density on MMG was analyzed using the Fisher's exact test. Regarding parity, high breast densities were observed in 40% and 17% of nulliparous and parous breasts, respectively. Nulliparous breasts had significantly higher density than parous breasts (p = 0.010). Regarding infant feeding method, 17% of breasts in both the formula-feeding and breastfeeding groups had high densities. Infant feeding method was not associated with mammographic breast density (p = 1.0). Nulliparity is associated with higher breast density, and parity, regardless of infant feeding method, induces atrophic changes of breast tissue.

Assessment of Iron Status in a Sample of Infants Aged 6-12 Months in Jerash Governorate, Jordan

This study aimed at investigating the relationship between iron status and the type of milk and weaning solid foods in a group of infants aged 6 - 12 months in Sakeb Health Center in Jerash Governorate, Jordan. In this cross-sectional study, a sample of 119 infants (59 females, 60 males), were recruited , A special questionnaire was used to collect socioeconomic data for the infants’ families, and three- day food recall was also used to collect infants dietary intake data. Body weight, length and head circumference were measured, and z-score was calculated for evaluating the anthropometric status. Hemoglobin (Hb), mean cell volume (MCV) and serum ferritin concentrations (SF) were measured on nonfasting venipuncture blood samples. The studied sample was divided into three groups according to type of feeding: exclusively breastfed group (n=41), formula-fed group (n=49) and mixed-fed group (n=29).The results showed that among infants with Hb &lt;110 g/l, MCV&lt;70fl and SF &lt;12 µg/l, 10.1% had iron deficiency anemia (IDA). Anemia was found in 36.9% when hemoglobin cutoff was taken to be &lt;110 g/l, and depleted iron stores were found in 27.7% using a ferritin cutoff &lt;12 µg/l. Among the breastfed group, incidence of IDA, anemia and depleted iron stores were the highest compared to the other two groups. No significant differences for Hb, MCV, and SF values existed between males and females although female infants tended to have higher hemoglobin, MCV, and serum ferritin values than male infants.Mean intake of iron was the highest among infants of formula-fed group (7.82 mg/day), as compared with breastfed and mixed-fed groups (2.75 and 4.23 mg/day respectively).No significant differences were observed between infants in any of the anthropometric measurements. Based on z-score, 1.7% of infants in breastfed group and formula-fed group were stunted compared with 0.8% in the mixed-fed group, whereas 2.5% of infants were overweight in the formula-fed group.It could be concluded that iron deficiency is common in infants in Jerash Governorate, since up to 10% of the recruited infants developed IDA, 37% developed anemia, and 28% had depleted iron stores. Keywords: iron, iron deficiency, anemia, breastfeeding, formula feeding DOI : 10.7176/JHMN/59-05

Fecal Calprotectin Level of Breast Milk-Formula vs Formula Feeding in Preterm and Low Birth Weight Neonates with Necrotizing Enterocolitis

Necrotizing enterocolitis (NE) is inflammatory disease and its prevalence was increase in preterm and low birth weight (LBW) neonates. This study was aimed to investigate the differences of fecal calprotectin level in breast milk-formula vs formula feeding infants in preterm and low birth weight neonates with necrotizing enterocolitis. There are 32 preterm and LBW neonates with NE were divided into two group (breast milk-formula and formula only feeding group). Fecal calprotectin level was measured using ELISA method. This study showed that fecal calprotectin level in breast milk-formula feeding group was insignificantly lower as compared to formula feeding group (independent t-test, p = 0.503). Further analysis showed that fecal calprotectin level was negatively correlated with patient’s outcome (Spearman correlation test, p = 0.03, r = 0.512). We concluded that fecal calprotectin level in breast milk-formula feeding group was insignificantly lower as compared to formula feeding only group in preterm and low birth weight neonates diagnosed with necrotizing enterocolitis. There was negative correlation between fecal calprotectin level and patient’s outcome.

Growth Indices of Exclusively Breastfed Until 6 Months Age and Formula-Fed Infants in Southwest of Iran.

Background:Formula milk is prepared as a nutritional substitution for human breast milk, but because of biologic and constituent differences, it might cause obesity and growth disorders in infants. In this study, we compared the growth pattern of formula-fed and breastfed infants living in Yasuj, southwest of Iran.Methods:Infants 7–14 months of age in southwest of Iran were classified as exclusively breastfed (n = 200) and formula-fed (n = 200) in their first 6 months of life. Growth velocity and Z-scores of weight for age, length for age, weight for length, and head circumference were estimated using WHO Anthro Plus software (2010) and SPSS Version 19 (SPSS Inc., Chicago, IL, USA) using World Health Organization reference for growth data.Results:The study showed that Z-score of length for age and head circumference for age at the birth were significantly lower in formula-fed group than exclusively breastfed group (P < 0.05), but the Z-score of weight for length did not differ significantly. At the sixth month of age, Z-score of weight for length was significantly higher in formula-fed group (P < 0.05), but Z-score of length for age had no significant difference and Z-score of head circumference was higher in exclusively breastfed group yet (P < 0.05). Growth velocity, prevalence of obesity, wasting, underweight, and stunting did not differ between two groups.Conclusions:Our findings suggest that formula feeding can lead to greater weight gain and may help the catch up of length, but evidences are not convincing enough to suggest the formula as an obesogenic feeding in the studied area. To make a conclusion, we suggest comparing the privileged and unprivileged areas and controlling for confounding variables including family hygiene and infant feeding practices between formula-fed and breastfed infants.

Milk Fat Globule Membrane Supplementation in Formula-fed Rat Pups Improves Reflex Development and May Alter Brain Lipid Composition

Human milk contains nutritional, immunoprotective and developmental components that support optimal infant growth and development. The milk fat globule membrane (MFGM) is one unique component, comprised of a tri-layer of polar lipids, glycolipids, and proteins, that may be important for brain development. MFGM is not present in most infant formulas. We tested the effects of bovine MFGM supplementation on reflex development and on brain lipid and metabolite composition in rats using the “pup in a cup” model. From postnatal d5 to d18, rats received either formula supplemented with MFGM or a standard formula without MFGM; a group of mother-reared animals was used as reference/control condition. Body and brain weights did not differ between groups. MFGM supplementation reduced the gap in maturation age between mother-reared and standard formula-fed groups for the ear and eyelid twitch, negative geotaxis and cliff avoidance reflexes. Statistically significant differences in brain phospholipid and metabolite composition were found at d13 and/or d18 between mother-reared and standard formula-fed groups, including a higher phosphatidylcholine:phosphatidylethanolamine ratio, and higher phosphatidylserine, glycerol-3 phosphate, and glutamine in mother-reared compared to formula-fed pups. Adding MFGM to formula narrowed these differences. Our study demonstrates that addition of bovine MFGM to formula promotes reflex development and alters brain phospholipid and metabolite composition. Changes in brain lipid metabolism and their potential functional implications for neurodevelopment need to be further investigated in future studies.

Lactating Mothers and Infants Residing in an Area with an Effective Salt Iodization Program Have No Need for Iodine Supplements: Results from a Double-Blind, Placebo-Controlled, Randomized Controlled Trial

The necessity of iodine supplementation in lactating mothers residing in countries with sustained salt iodization programs for iodine sufficiency of breast-fed infants remains unclear. The aims of this study were to investigate the effect of iodine supplementation on iodine status and growth parameters of lactating mothers and breast-fed infants and to compare these data with that of formula-feeding mothers and their infants during the first year of infancy. In this multicenter, double-blinded, randomized clinical trial conducted in four healthcare centers in Tehran (Iran), healthy lactating mothers and their term newborns aged 3-5 days were randomly assigned to treatment groups: placebo, 150 μg/day iodine, or 300 μg/day iodine. They were followed up for 12 months. Formula-fed infants aged 30-45 days and their mothers were randomly selected from the same centers. The primary outcomes were maternal and infant urinary iodine concentrations (UICs), breast-milk iodine concentrations (BMICs), and infant growth parameters, measured at 1, 2, 4, 6, 9, and 12 months during routine health visits. The formula-fed group was assessed at 2, 4, 6, 9, and 12 months of age. Analysis was by per protocol principle using mixed-effects models. Mother-newborn pairs (n = 180) in treatment groups and partially/exclusively formula-feeding mother-infant pairs (n = 60) participated between October 2014 and January 2016. Median baseline UICs in the treatment groups were 84 μg/L (interquartile range [IQR] 41-143 μg/L) in mothers and 208 μg/L (IQR 91-310 μg/L) in their infants. The values in the formula-fed group were 76 μg/L (IQR 40-144 μg/L) in mothers and 121 μg/L (IQR 66-243 μg/L) in infants. The 300 μg/day iodine group showed significantly higher UICs and BMICs than did the other treatment groups; infant UICs in the 150 μg/day iodine, placebo, and formula-fed groups were similar. Infants in all groups showed iodine sufficiency (median UIC ≥100 μg/L) throughout the study period. Anthropometric measurements were similar between the treatment and formula-fed groups over the study period, except at the last follow-up visit at 12 months. Supplementation of breast-feeding mothers with either 300 or 150 μg/day iodine improved their iodine status. However, the iodine status of infants in all groups studied indicated iodine sufficiency during the first year of infancy, demonstrating that in countries with effective salt iodization program, iodine supplementation for lactating mothers is unnecessary.

The effects of breastfeeding versus formula-feeding on cerebral cortex maturation in infant rhesus macaques

Breastfeeding is positively associated with several outcomes reflecting early brain development and cognitive functioning. Brain neuroimaging studies have shown that exclusively breastfed children have increased white matter and subcortical gray matter volume compared to formula-fed children. However, it is difficult to disentangle the effects of nutrition in breast milk from other confounding factors that affect brain development, particularly in studies of human subjects. Among the nutrients provided by human breast milk are the carotenoid lutein and the natural form of tocopherol, both of which are selectively deposited in brain. Lutein is the predominant carotenoid in breast milk but not in most infant formulas, whereas infant formulas are supplemented with the synthetic form of tocopherol. In this study, a non-human primate model was used to investigate the effects of breastfeeding versus formula-feeding, as well as lutein and natural RRR-α-tocopherol supplementation of infant formula, on brain maturation under controlled experimental conditions. Infant rhesus macaques (Macaca mulatta) were exclusively breastfed, or were fed infant formulas with different levels and sources of lutein and α-tocopherol. Of note, the breastfed group were mother-reared whereas the formula-fed infants were nursery-reared. Brain structural and diffusion MR images were collected, and brain T2 was measured, at two, four and six months of age. The mother-reared breastfed group was observed to differ from the formula-fed groups by possessing higher diffusion fractional anisotropy (FA) in the corpus callosum, and lower FA in the cerebral cortex at four and six months of age. Cortical regions exhibiting the largest differences include primary motor, premotor, lateral prefrontal, and inferior temporal cortices. No differences were found between the formula groups. Although this study did not identify a nutritional component of breast milk that could be provided to infant formula to facilitate brain maturation consistent with that observed in breastfed animals, our findings indicate that breastfeeding promoted maturation of the corpus callosum and cerebral cortical gray matter in the absence of several confounding factors that affect studies in human infants. However, differences in rearing experience remain as a potential contributor to brain structural differences between breastfed and formula fed infants.

Relationships of carotenoid-related gene expression and serum cholesterol and lipoprotein levels to retina and brain lutein deposition in infant rhesus macaques following 6 months of breastfeeding or formula feeding

The purpose of this study was to investigate if the enhanced bioaccumulation of lutein in retina and brain of breastfed, compared to formula-fed, infant monkeys was associated with higher levels of serum total and HDL cholesterol, apolipoproteins, or mRNA/protein expression of carotenoid-related genes. Newborn rhesus macaques were either breastfed, fed a carotenoid-supplemented formula, or fed an unsupplemented formula for 6 months (n = 8, 8, 7). Real-time qPCR and western blotting were performed in two brain regions (occipital cortex and cerebellum) and two retina regions (macular and peripheral retina). Breastfed infants had higher serum total cholesterol, HDL cholesterol, apoA-I, and apoB-100 levels than the combined formula-fed groups (P < 0.05). Breast milk or infant formulas did not alter expression of the nine genes (CD36, SCARB1, SCARB2, LDLR, STARD3, GSTP1, BCO1, BCO2, RPE65) examined except for SCARB2 in the retina and brain regions. In conclusion, dietary regimen did not impact the expression of carotenoid-related genes except for SCARB2. However, carotenoid-related genes were differentially expressed across brain and retina regions. Breastfed infants had higher serum total and HDL cholesterol, and apolipoproteins, suggesting that lipoprotein levels might be important for delivering lutein to tissues, especially the macular retina, during infancy.

Breastfeeding and growth during infancy among offspring of mothers with gestational diabetes mellitus: a prospective cohort study.

Breastfeeding (BF) may protect against obesity and type 2 diabetes mellitus in children exposed to maternal diabetes in utero, but its effects on infant growth among this high-risk group have rarely been evaluated. The objective of this study was to evaluate BF intensity and duration in relation to infant growth from birth through 12months among offspring of mothers with gestational diabetes mellitus (GDM). Prospective cohort of 464 GDM mother-infant dyads (28% White, 36% Hispanic, 26% Asian, 8% Black, 2% other). Weight and length measured at birth, 6-9weeks, 6months and 12months. Categorized as intensive BF or formula feeding (FF) groups at 6-9weeks (study baseline), and intensity from birth through 12months as Group 1: consistent exclusive/mostly FF, Group 2: transition from BF to FF within 3-9months and Group 3: consistent exclusive/mostly BF. Multivariable mixed linear regression models estimated adjusted mean (95% confidence interval) change in z-scores; weight-for-length (WLZ), weight-for-age and length-for-age. Compared with intensive BF at 6-9weeks, FF showed greater increases in WLZ-scores from 6 to 9weeks to 6months [+0.38 (0.13 to 0.62) vs. +0.02 (-0.15 to 0.19); p=0.02] and birth to 12months [+1.11 (0.87 to 1.34) vs. +0.53 (0.37 to 0.69); p<0.001]. For 12-month intensity and duration, Groups 2 and 3 had smaller WLZ-score increases than Group 1 from 6 to 9weeks to 6months [-0.05 (-0.27 to 0.18) and +0.07 (-0.19 to 0.23) vs. +0.40 (0.15 to 0.64); p=0.01 and 0.07], and birth to 12months [+0.60 (0.39 to 0.82) and +0.59 (0.33 to 0.85) vs. +0.97 (0.75 to 1.19); p<0.05]. Among offspring of mothers with GDM, high intensity BF from birth through 1year is associated with slower infant ponderal growth and lower weight gain.

Is there any difference between the iodine statuses of breast-fed and formula-fed infants and their mothers in an area with iodine sufficiency?

Despite substantial progress in the global elimination of iodine deficiency, lactating mothers and their infants remain susceptible to insufficient iodine intake. This cross-sectional study was conducted to compare iodine statuses of breast-fed and formula-fed infants and their mothers at four randomly selected health care centres in Tehran. Healthy infants <3 months old and their mothers were randomly selected for inclusion in this study. Iodine was measured in urine and breast milk samples from each infant and mother as well as commercially available infant formula. The study included 124 postpartum mothers (29·2 (sd 4·9) years old) and their infants (2·0 (sd 0·23) months old). The iodine concentrations were 50-184 µg/l for infant formula, compared with a median breast milk iodine concentration (BMIC) of 100 µg/l in the exclusive breast-feeding group and 122 µg/l in the partial formula feeding group. The median values for urinary iodine concentration in the exclusive breast-feeding group were 183 µg/l (interquartile range (IQR) 76-285) for infants and 78 µg/l (IQR 42-145) for mothers, compared with 140 µg/l (IQR 68-290) for infants and 87 µg/l (IQR 44-159) for mothers in the formula feeding group. These differences were not statistically significant. After adjustment for BMIC, ANCOVA revealed that feeding type (exclusive breast-feeding v. partial formula feeding) did not significantly affect the infants' or mother's urinary iodine levels. Thus, in an area with iodine sufficiency, there was no difference in the iodine statuses of infants and mothers according to their feeding type.