Gestational exposure to organophosphate esters and infant anthropometric measures in the first 4 weeks after birth.

BACKGROUND: Few studies have examined whether gestational exposure to organophosphate esters (OPEs), widely used chemicals with potential endocrine-disrupting potency and developmental toxicity, is associated with impaired infant growth. METHODS: We analyzed data from 329 mother-infant pairs in the Health Outcomes and Measures of the Environment (HOME) Study (2003-2006, Cincinnati, Ohio, USA). We quantified concentrations of four OPE metabolites in maternal urine collected at 16 and 26 weeks of gestation, and at delivery. We calculated z-scores using 2006 World Health Organization (WHO) child growth standards for the 4-week anthropometric measures (weight, length, and head circumference), the ponderal index, and weekly growth rates. We used multiple informant models to examine window-specific associations between individual OPE metabolites and anthropometric outcomes. We further modeled OPEs as a mixture for window-specific associations with 4-week anthropometric outcomes using mean field variational Bayesian inference procedure for lagged kernel machine regression (MFVB-LKMR). We stratified the models by infant sex. RESULTS: Diphenyl phosphate (DPHP) in mothers at 16 weeks, and bis(2-chloroethyl) phosphate (BCEP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) at delivery were positively associated with z-scores of weight, length, and head circumference in all infants at 4 weeks of age. After stratifying by infant sex, positive associations were only observed in males for DPHP at 16 weeks and BCEP at delivery and in females for BDCIPP at delivery. Negative associations not present in all infants were observed in males for di-n-butyl phosphate (DNBP) at 26 weeks of gestation with weight z-score and DPHP at delivery with head circumference z-score. Results were generally similar using MFVB-LKMR models with more conservative 95 % credible intervals. We did not identify consistent associations of gestational OPE metabolite concentrations with the ponderal index and weekly growth rates. CONCLUSION: In this cohort, exposure to OPEs during gestation was associated with altered infant anthropometry at 4 weeks after birth.

Multiple Indicators of Undernutrition, Infection, and Inflammation in Lactating Women Are Associated with Maternal Iron Status and Infant Anthropometry in Panama: The MINDI Cohort.

Maternal infections, nutrient deficiencies, and inflammation (MINDI) co-exist in lactating indigenous women in Panama, but their impact on maternal iron status and infant growth is unknown. For this secondary analysis of cross-sectional data of lactating mothers from our MINDI cohort, we investigated associations of MINDI variables with maternal anemia, elevated serum transferrin receptor (sTfR), low serum iron, hepcidin, ferritin, and infant weight-for-age (WAZ), length-for-age (LAZ), and head-circumference-for-age (HCAZ) Z-scores in 99 mother-infant dyads. A bootstrapping resampling procedure preselected covariates for inclusion in multivariable regressions models from chronic maternal infections and nutritional status [folate, vitamins A, D, retinol-binding protein (RBP), insulin-growth factor-1 (IGF-1)] and inflammation [C-reactive protein (CRP), cytokines, platelet indices] indicators. Anemia was prevalent (53.5%) but underestimated due to widespread low plasma volume (<2.2 L, 79.9%) and was associated with indicators of malnutrition [lower IGF-1, body mass index (BMI), vitamin D, and intake of green/leafy vegetables], but not inflammation. Higher CRP was associated with lower serum iron, and higher hepcidin and ferritin, whereas maternal platelets were associated with lower HCAZ (ß = −0.22), WAZ (ß = −0.17), and LAZ (ß = −0.17). Higher LAZ was also associated with maternal serum vitamin D (ß = 0.23), whereas maternal iron supplementation lowered LAZ (ß = −0.22). Assessment of iron status in this MINDI cohort is complex and supplementation strategies must consider consequences for both the mother and the infant.

Nesfatin-1 in Human Milk and Its Association with Infant Anthropometry.

Breastfed infants have different growth patterns to formula-fed infants and are less likely to develop obesity later in life. Nesfatin-1 is an anorexigenic adipokine that was discovered in human milk more than a decade ago, and its role in infant appetite regulation is not clear. Our aim was to describe nesfatin-1 levels in human milk collected 3-4 months postpartum, associations with infant anthropometry, and factors (maternal pre-pregnancy body mass index (mBMI), high weight gain during pregnancy, milk fat, and energy content) possibly influencing nesfatin-1 levels. We hypothesized that nesfatin-1 levels in mother's milk would differ for infants that were large (high weight-for-age Z-score (WAZ)) or small (low WAZ) at the time of milk sample collection. We used enzyme-linked immunosorbent assay to detect the nesfatin-1 concentration in milk samples from mothers to high WAZ (n = 50) and low WAZ (n = 50) infants. We investigated associations between nesfatin-1 levels and infant anthropometry at 3-4 months of age and growth since birth, using linear regression adjusted for mBMI, birth weight, infant sex, and exclusivity of breastfeeding. We found no difference in nesfatin-1 levels between the two groups and no association with infant anthropometry, even after adjusting for potential confounders. However, high nesfatin-1 levels were correlated with low mBMI. Future research should investigate serum nesfatin-1 level in both mothers, infants and associations with growth in breastfed children.

Infant Anthropometry and Growth Velocity Before 6 Months are Associated with Breastfeeding Practices and the Presence of Subclinical Mastitis and Maternal Intestinal Protozoa in Indigenous Communities in Guatemala.

BACKGROUND: The possibility that maternal health status and breastfeeding practices contribute to growth faltering before 6 mo is underexplored. OBJECTIVES: This longitudinal study investigated whether indicators of subclinical mastitis (SCM) and breast inflammation, maternal fecal-oral contamination, and/or breastfeeding practices were associated with infant anthropometry or growth velocity before 6 mo. METHODS: Indigenous Mam-Mayan mother-infant dyads (n = 140) were recruited. Breast milk was collected at early (<6 wk) and established (4-6 mo) lactation when maternal and infant anthropometry were measured. Milk Na:K ratio as an indicator of SCM and concentrations of 4 proinflammatory cytokines were measured. Maternal stool samples were examined for the presence of intestinal parasites including nonpathogenic protozoa (Endolimax nana, Iodamoeba bütschlii, Entamoeba coli, Blastocystis hominis). Questionnaires characterized breastfeeding and hygiene practices. Multiple linear regression identified factors associated with infant growth attainment [weight-for-age z-score (WAZ), length-for-age z-score (LAZ), and head circumference-for-age z-score (HCAZ)] and growth velocity (expressed as change per day from early to established lactation). Multiple logistic regression identified factors associated with increased odds of underweight, stunting, and low head circumference at both lactation stages. RESULTS: A higher Na:K ratio, individual nonpathogenic protozoa, and specific breastfeeding and hygiene practices were associated with impaired growth before 6 wk and at 4-6 mo in exclusively breastfed infants. Growth velocity for weight was inversely associated with Entamoeba coli but cranial growth was associated positively with Iodamoeba bütschlii whereas feeding colostrum in early lactation was protective and decreased the odds of an HCAZ < -2 SD. Finally, the presence of SCM in early lactation increased the likelihood of both WAZ < -2 SD and LAZ < -2 SD by 6 wk. CONCLUSIONS: Prevention of SCM can improve early infant weight, but measures that promote the feeding of colostrum and reduce exposure to fecal-oral contamination might be required to minimize infant growth faltering in breastfed infants.

Maternal urinary concentrations of organophosphate ester metabolites: associations with gestational weight gain, early life anthropometry, and infant eating behaviors among mothers-infant pairs in Rhode Island.

BACKGROUND: Organophosphate esters (OPEs)-used as flame retardants and plasticizers-are associated with adverse pregnancy outcomes such as reduced fecundity and live births and increased preterm delivery. OPEs may interfere with growth and metabolism via endocrine-disruption, but few studies have investigated endocrine-related outcomes. The objective of this pilot study (n = 56 mother-infant pairs) was to evaluate associations of OPEs with gestational weight gain (GWG), gestational age at delivery, infant anthropometry, and infant feeding behaviors. METHODS: We quantified OPE metabolites (bis-2-chloroethyl phosphate [BCEP], bis (1,3-dichloro-2-propyl) phosphate [BDCPP], diphenyl phosphate [DPHP]) in pooled maternal spot urine collected throughout pregnancy (~ 12, 28, and 35 weeks' gestation). We obtained maternal sociodemographic characteristics from questionnaires administered at enrollment and perinatal characteristics from medical record abstraction. Trained research assistants measured infant weight, length, head and abdominal circumferences, and skinfold thicknesses at birth and 6 weeks postpartum. Mothers reported infant feeding behavior via the Baby Eating Behavior Questionnaire (BEBQ). Using multiple linear regression, we assessed associations of log2-transformed maternal urinary OPE metabolites with GWG, gestational age at delivery, infant anthropometry at birth, weekly growth rate, and BEBQ scores at 6 weeks postpartum. We used linear mixed effects (LME) models to analyze overall infant anthropometry during the first 6 weeks of life. Additionally, we considered effect modification by infant sex. RESULTS: We observed weak positive associations between all OPE metabolites and GWG. In LME models, BDCPP was associated with increased infant length (ß = 0.44 cm, 95%CI = 0.01, 0.87) and weight in males (ß = 0.14 kg, 95%CI = 0.03, 0.24). BDCPP was also associated with increased food responsiveness (ß = 0.23, 95%CI = 0.06, 0.40). DPHP was inversely associated with infant abdominal circumference (ß = - 0.50 cm, 95%CI = - 0.86, - 0.14) and female weight (ß = - 0.19 kg, 95%CI = - 0.36, - 0.02), but positively associated with weekly growth in iliac skinfold thickness (ß = 0.10 mm/wk., 95%CI = 0.02, 0.19). Further, DPHP was weakly associated with increased feeding speed. BCEP was associated with greater infant thigh skinfold thickness (ß = 0.34 mm, 95%CI = 0.16, 0.52) and subscapular skinfold thickness in males (ß = 0.14 mm, 95%CI = 0.002, 0.28). CONCLUSIONS: Collectively, these findings suggest that select OPEs may affect infant anthropometry and feeding behavior, with the most compelling evidence for BDCPP and DPHP.

Anthropometry before Day 46 and Growth Velocity before 6 Months of Guatemalan Breastfed Infants Are Associated with Subclinical Mastitis and Milk Cytokines, Minerals, and Trace Elements.

BACKGROUND: Subclinical mastitis (SCM) is an inflammatory condition of the mammary gland, but its association with human milk composition and infant growth is not well described. OBJECTIVES: We investigated whether SCM, milk cytokines, and/or estimated intakes of milk minerals and trace elements were associated with infant anthropometry or growth velocity before 6 mo. METHODS: Breast milk was collected from Mam-Mayan mothers (n = 114) at both early (2-46 d) and established (4-6 mo) lactation. Concentrations of 9 elements (sodium, potassium, calcium, magnesium, copper, iron, manganese, selenium, zinc) analyzed by inductively-coupled plasma mass spectrometry were used to estimate infants' daily intakes. Concentrations of 4 cytokines were measured. Milk concentrations and infants' estimated elemental intakes and anthropometric measurements during early and established lactation were compared by SCM status. Multiple regression was used to identify factors associated with infant growth attainment (<46 d) for infant weight- (WAZ), length- (LAZ), and head circumference-for-age (HCAZ) and weight-for-length (WLZ) z scores and with growth velocity (expressed as Δ/d) from early to established lactation. RESULTS: SCM prevalence was higher in early (30%) than established (10%) lactation. Breast milk of SCM mothers had higher cytokine concentrations and higher magnesium in early and higher selenium concentrations in both early and established lactation (Padj < 0.0121). At day 46, regression models showed inverse associations of SCM with WLZ and IL-1ß with LAZ (Padj < 0.0150). In contrast, linear growth velocity was positively associated with IL-1ß measured in early lactation (Padj < 0.0124), whereas cranial growth velocity was positively associated with IL-8 measured during established lactation ( Padj < 0.0124). CONCLUSIONS: Despite a high prevalence of inadequate intakes, only infants' intake of milk magnesium during early lactation was associated with linear growth velocity in breastfed infants <6 mo. Evidence shows that SCM, breast-milk cytokines, and infants' estimated intakes of select elements are independently associated with growth attainment and growth velocity during lactation.

Transgenerational cycle of obesity and diabetes: investigating possible metabolic precursors in cord blood from the PREOBE study.

AIMS: Offspring of mothers suffering from obesity and/or gestational diabetes mellitus (GDM) were reported to be at risk of higher birth weight (BW), later obesity and diabetes. We hypothesize that infant anthropometry changes related to maternal pathological status are due to dysregulated infant metabolism. METHODS: First, we inspected differences in BMI z-scores (z-BMI) between three infant groups: born to normal weight (NW; n = 49), overweight/obese (OV/OB; n = 40) and GDM mothers (n = 27) at birth and 1 year. Then, we inspected associations between cord blood metabolites and 1-year Δ z-BMI in the three infant groups at birth and 1 year. RESULTS: No statistically significant difference was detected in z-BMI between the study groups at birth; however, GDM was associated with heavier infants at 1 year. Regarding the associations between the metabolites and z-BMI, phospholipids, especially those containing polyunsaturated fatty acids, were the species most impacted by the maternal metabolic status, since numerous phosphatidylcholines-PUFA were positively associated with z-BMI in NW but negatively in OV/OB and GDM groups at birth. Conversely, the sum of lysophosphatidylcholines was only positively associated with z-BMI in NW at birth but of no relation in the other two groups. At 1 year, most of the associations seen at birth were reversed in NW and lost in OV/OB and GDM groups. In the NW group, PC-PUFA were found to be negatively associated with Δ z-BMI at 1 year in addition to some medium-chain acylcarnitines, tricarboxylic acid metabolites, Asp and Asn-to-Asp ratio. In OV/OB and GDM groups, the non-esterified fatty acid (NEFA26:0) and His correlated with Δ z-BMI at 1 year in negative and positive directions, respectively. CONCLUSIONS: GDM was associated with overweight in offspring at 1 year, independent of the BW with lack of evidence on existing correlation of this finding with metabolic alterations detected in cord blood metabolome. Associations were found between cord blood metabolites and infant anthropometry at birth and were influenced by maternal OB and GDM. However, an extension of the findings monitored at birth among the three groups was not detected longitudinally showing a lack of predictive power of cord blood metabolome for later development at least 1 year.

Pre- and postnatal environmental boron exposure and infant growth: Results from a mother-child cohort in northern Argentina.

BACKGROUND: Experimental studies show developmental toxicity of boron and we recently found impaired weight and length in newborns of mothers exposed to boron through drinking water during pregnancy. OBJECTIVES: To evaluate potential impact of pre- and postnatal boron exposure on infant anthropometry. METHODS: In our mother-child cohort (n = 177) in Argentinean Andes, where drinking water concentrations of boron, lithium and arsenic have been found to vary considerably, we collected maternal blood and urine during and after pregnancy, placenta, breast milk, as well as infant urine and blood during the first 6 months of life. In all samples, boron and other potentially toxic elements were measured by ICP-MS. Infant weight (g), length (cm) and head circumference (cm) were measured at birth, 0-3 (n = 120) and/or 3-6 months (n = 120; 79 overlap) of age. RESULTS: Boron concentrations in breast milk (range: 46-786 µg/L) correlated strongly with those in maternal serum (range: 47-624 µg/L; rs = 0.94) 0-3 months post-partum. In multivariable-adjusted linear regression, urinary boron (log2-transformed; range 60-9200 µg/L) in the youngest infants, but not maternal serum boron during pregnancy, was inversely associated with body weight at both 0-3 months (B: -141, 95% CI: -240; -42, p = 0.006) and 3-6 months (B: -200, 95% CI: -377; -23, p = 0.027). Infant urinary boron was also inversely associated with head circumference at 0-3 months (B: -0.39, 95% CI: -0.74; -0.04, p = 0.028), as well as length (B: -0.57, 95% CI: -1.1; -0.03, p = 0.040) and head circumference (B: -0.30, 95% CI: -0.64; 0.04, p = 0.083) at 3-6 months. CONCLUSIONS: The observed first evidence that elevated environmental boron exposure in early infancy may adversely affect growth supports previous findings of boron-related impaired fetal growth. More research is needed to verify the findings at older age and in other populations.

Minerals and Trace Elements in Human Breast Milk Are Associated with Guatemalan Infant Anthropometric Outcomes within the First 6 Months.

BACKGROUND: Breast milk is the recommended source of nutrients for infant growth, but its adequacy to meet infants' mineral and trace element needs is unknown. OBJECTIVES: We used breast-milk mineral and trace element concentrations of Guatemalan mothers at 3 lactation stages to estimate total daily intakes and to determine whether intakes were associated with early infant growth. METHODS: In this cross-sectional study, breast-milk samples were collected from Mam-Mayan mothers during transitional (5-17 d, n = 56), early (18-46 d, n = 75), and established (4-6 mo, n = 103) lactation; z scores for weight (WAZ), length (LAZ), and head circumference (HCAZ) were measured. Concentrations of 11 minerals (calcium, potassium, magnesium, sodium, copper, iron, manganese, rubidium, selenium, strontium, and zinc) were analyzed by inductively coupled plasma-mass spectrometry (ICP-MS). WHO equations were used to calculate the estimated energy requirement, which was divided by the energy density of breast milk to estimate daily milk volume, and this number was multiplied by breast-milk mineral concentrations to estimate intakes. Principal component analyses identified clusters of minerals; principal components (PCs) were used in regression analyses for anthropometric outcomes. RESULTS: Estimated breast-milk intakes during established lactation were insufficient to compensate for the lower milk sodium, copper, manganese, and zinc concentrations in male infants and the lower sodium, iron and manganese concentrations in female infants. Estimated intakes of calcium, magnesium, potassium, sodium, and selenium were below the Institute of Medicine Adequate Intake for both sexes at all 3 stages of lactation. In early lactation, multiple linear regressions showed that PC1 (calcium, magnesium, potassium, rubidium, and strontium intakes) was positively associated with WAZ, LAZ, and HCAZ. In established lactation, the same PC with sodium added was positively associated with all 3 anthropometric outcomes; a second PC (PC2: zinc, copper, and selenium intakes) was associated with WAZ and LAZ but not HCAZ. CONCLUSIONS: Breast milk may be inadequate in selected minerals and trace elements where higher estimated intakes were associated with greater infant growth.