Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odense, Denmark (JLT-P, HRA, PG, and TKJ); the Research Unit for Dietary Studies, Institute of Preventive Medicine, Copenhagen University Hospitals, Frederiksberg, Denmark (JLT-P and BLH); the National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark (BLH); the Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, Sydney Medical School, Sydney, Australia (BLH); the Department of Occupational Medicine and Public Health, Tórshavn, Faroe Islands (US); and the Department of Environmental Medicine, Faroese Hospital System, Tórshavn, Faroe Islands (PW).
Chemicals with endocrine-disrupting abilities may act as obesogens and interfere with the body's natural weight-control mechanisms, especially if exposure occurs during prenatal life.
We examined the association between prenatal exposure to polychlorinated biphenyls (PCBs) and p,p'-dichlorodiphenyldichloroethylene (DDE) and subsequent obesity at 5 and 7 y of age.
From 1997 to 2000, 656 pregnant Faroese women were recruited. PCB and DDE were measured in maternal serum and breast milk, and children's weight, height, and waist circumference (WC) were measured at clinical examinations at 5 and 7 y of age. The change in body mass index (BMI) from 5 to 7 y of age was calculated. Analyses were performed by using multiple linear regression models for girls and boys separately, taking into account maternal prepregnancy BMI.
For 7-y-old girls who had overweight mothers, PCB was associated with increased BMI (ß = 2.07, P = 0.007), and PCB and DDE were associated with an increased change in BMI from 5 to 7 y of age (PCB: ß = 1.23, P = 0.003; DDE: ß = 1.11, P = 0.008). No association was observed with BMI in girls with normal-weight mothers. PCB was associated with increased WC in girls with overweight mothers (ß = 2.48, P = 0.001) and normal-weight mothers (ß = 1.25, P = 0.04); DDE was associated with increased WC only in girls with overweight mothers (ß = 2.21, P = 0.002). No associations were observed between PCB or DDE and BMI in 5-y-old girls. For boys, no associations were observed.
Results suggest that prenatal exposure to PCB and DDE may play a role for subsequent obesity development. Girls whose mothers have a high prepregnancy BMI seem most affected.
Brominated flame retardants (BFRs) have been in widespread use in a vast array of consumer products since the 1970s. The metabolites of some BFRs show a structural similarity to thyroid hormones and experimental animal studies have confirmed that they may interfere with thyroid hormone homeostasis. A major concern has been whether intrauterine exposure to BFRs may disturb thyroid homeostasis since the fetal brain is particularly susceptible to alterations in thyroid hormones. However, few reports on newborns have been published to date.
To evaluate the association between BFRs and neonatal thyroid-stimulating hormone (TSH).
We studied six polybrominated diphenyl ethers (PBDEs) measured in milk samples from 239 women who were part of the "Norwegian Human Milk Study" (HUMIS), 2003-2006. Hexabromocyclododecane (HBCD) and BDE-209 were measured in a subset of the women (193 and 46 milk samples, respectively). The milk was sampled at a median of 33 days after delivery. TSH was measured in babies three days after delivery as part of the routine national screening program for early detection of congenital hypothyroidism. Additional information was obtained through the Medical Birth Registry and questionnaires to the mothers.
The PBDE concentrations in human milk in Norway were comparable to concentrations reported from other European countries and Asia, but not the US and Canada where levels are approximately one order of higher magnitude. We observed no statistically significant associations between BDE-47, 99, 153, 154, 209 and HBCD in human milk and TSH in models adjusted for possible confounders and other environmental toxicants including polychlorinated biphenyls (PCBs).
We did not observe an association between TSH and exposure to HBCD and PBDEs within the exposure levels observed.
BACKGROUND: Only limited data exist on lactation as an exposure source of persistent perfluorinated chemicals (PFCs) for children. OBJECTIVES: We studied occurrence and levels of PFCs in human milk in relation to maternal serum together with the temporal trend in milk levels between 1996 and 2004 in Sweden. Matched, individual human milk and serum samples from 12 primiparous women in Sweden were analyzed together with composite milk samples (25-90 women/year) from 1996 to 2004. RESULTS: Eight PFCs were detected in the serum samples, and five of them were also above the detection limits in the milk samples. Perfluorooctanesulfonate (PFOS) and perfluorohexanesulfonate (PFHxS) were detected in all milk samples at mean concentrations of 0.201 ng/mL and 0.085 ng/mL, respectively. Perfluorooctanesulfonamide (PFOSA), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) were detected less frequently. DISCUSSION: The total PFC concentration in maternal serum was 32 ng/mL, and the corresponding milk concentration was 0.34 ng/mL. The PFOS milk level was on average 1% of the corresponding serum level. There was a strong association between increasing serum concentration and increasing milk concentration for PFOS (r(2) = 0.7) and PFHxS (r(2) = 0.8). PFOS and PFHxS levels in composite milk samples were relatively unchanged between 1996 and 2004, with a total variation of 20 and 32% coefficient of variation, respectively. CONCLUSION: The calculated total amount of PFCs transferred by lactation to a breast-fed infant in this study was approximately 200 ng/day. Lactation is a considerable source of exposure for infants, and reference concentrations for hazard assessments are needed.
Maternal exposures to organochlorines prior to pregnancy are considered a risk to neonatal welfare, specifically in relation to neurocognitive functions. There is growing interest in the evaluation of maternal blood testing as a marker for fetal exposure as well as the variable geographic distribution of these priority chemicals.
Three hundred and twenty-three women in the second trimester of pregnancy entered the study at a prenatal clinic providing genetic counselling information. Subjects who had an indication for genetic amniocentesis based on late maternal age were eligible to participate. Two hundred and thirty-eight completed an environmental questionnaire. A sample of amniotic fluid was taken for karyotype analysis in 323 women and blood samples during pregnancy (209), at birth (105) and from the umbilical cord (97) and breast milk (47) were also collected. These samples were tested for 29 PCB congeners and organochlorine pesticides.
The concentrations of PCB 153 in these media were relatively low in relation to other studies. Sigma PCBs measurements in samples taken during the second trimester of pregnancy, at birth and in the umbilical cord were strongly correlated. Specific measurements of PCB 153 and PCB 180 among those subjects with completed sampling of blood samples from mothers and cord samples were significantly correlated. The concentrations of PCBs and pesticides did not differ in relation to prior spontaneous abortion history. There were no organochlorines present in the amniotic fluid at the current level of quantification.
Pregnant women from the Western Canada region of Calgary, Alberta are exposed to relatively low concentrations of organochlorines. Measurement of maternal blood during the second trimester of pregnancy can reliably estimate the fetal exposure to PCBs. This estimate is reliable for Group 2 and 3 PCBs as well as PCB 153 and PCB 180. The amniotic fluid does not contain measurable concentrations of pesticides and PCBs under the conditions of the levels of quantification.
Thyroid hormones (THs) regulate many biological functions in the human body and are essential for normal brain development. Epidemiological studies have observed diverging associations between halogenated persistent organic pollutant (POP) exposure and concentrations of THs in pregnant women and their infants. We investigated whether background exposure to polybrominated diphenyl ethers (PBDEs) is related to TH status in a Swedish population of pregnant women and their infants. Furthermore, we examined associations between polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) and TH status in early pregnancy as an extension of an earlier study focusing on late pregnancy TH status.
Free thyroxine (T4), total triiodo-thyronine (T3) and thyroid stimulating hormone (TSH) were analysed in serum from first-time mothers (N?=?220-281) in the first and third trimester, and in infants (N?=?115-150) 3 weeks and 3 months after delivery. Antibodies to thyroid peroxidase (anti-TPO) (N?=?260) were measured in maternal third trimester serum. Maternal body burdens of PCBs (N?=?281) were estimated from serum lipid PCB concentrations in late pregnancy, and PCDD/F (N?=?97) and PBDE (N?=?186) body burdens were estimated from concentrations in mother's milk lipids 3 weeks after delivery. Linear regression models allowed for covariate adjustment of the associations between ln-transformed POP body burdens and concentrations of TH and anti-TPO.
Maternal body burden of BDE-153 was inversely associated with first trimester total T3, otherwise no associations between PBDEs and first and second trimester THs were observed. No associations were found between maternal PBDE body burdens and infant THs. Maternal body burden of PCDD/Fs were inversely associated with first trimester total T3. No associations were observed between PCBs and first trimester THs. Third trimester anti-TPO was not associated with maternal PCBs, PCDD/Fs and PBDEs.
Our results suggest that maternal PCDD/F and BDE-153 body burdens influence maternal TH status in early pregnancy, which is a critical period when maternal TH status influences fetal development.
Breast milk is the best source of nutrition for the newborn infant. However, since all infants cannot be breast-fed, there is a need for background data for setting adequate daily intakes. Previously, concentration data on major essential elements and some toxic elements in breast milk, based on different analytical techniques, have been published. There is no recent study on a large number of metals and trace elements in breast milk, using a sensitive analytical method for determination of low element concentrations.
Breast milk concentrations of 32 metals and elements in early lactation (days 14-21) were determined in a random sample of first time Swedish mothers (n?=?60) using inductively coupled plasma mass spectrometry (ICPMS).
There were small inter-individual concentration variations in the macroelements Ca, K, Mg, P and S, and striking similarities across studies and over time, supporting a tight regulation of these elements in breast milk. Large inter-individual and over time differences were detected for Na concentrations, which may reflect an increase in salt consumption in Swedish women. Large inter-individual differences were also detected for the microelements Co, Cr, Mn and Mo, and the toxic metals As, Cd, Pb, Sb and V. Arsenic and B were positively correlated with fish consumption, indicating influence of maternal intake on breast milk concentrations. Observed differences in breast milk element concentrations across studies and over time could be attributed to the timing of sampling and a general decline over time of lactation (Cu, Fe, Mo, Zn), a possible lack of regulation of certain elements in breast milk (As, B, Co, Mn, Se) and time trends in environmental exposure (Pb), or in some cases to differences in analytical performance (Cr, Fe).
This study provides reliable updated information on a number of metals and elements in breast milk, of which some have not previously been reported.
Infants are exposed to persistent environmental contaminants through breast milk, yet studies assessing the health effects of postnatal exposure are lacking. Existing postnatal exposure assessment is either too simple (lactation exposure model, LEM) or requires complex physiologically-based pharmacokinetic (PBPK) models.
We present equations for postnatal exposure calculations. We applied these equations to study the effect of hexachlorobenzene (HCB) on infant growth in the two first years of life.
HCB was measured in breast milk samples in 449 mother-child pairs participating in the Norwegian birth cohort study HUMIS. We used these concentrations, mother's weight, height and age, together with child's weight at 8 age points, and proportion of milk consumed each month, to calculate HCB concentrations in the infant over age. We then estimated the association between HCB and infant growth using a linear mixed model.
Children exposed to HCB via mother's milk reached concentrations 1-5 times higher than the mother. HCB was associated with lower weight gain in the first 2years (-33g per unit HCB and month, 95% CI: -38, -27 at 6months). Associations were stronger during the first 3months (-57g per unit HCB and month, 95% CI: -67, -49 at 1month), indicating a critical window of effect. Our equations gave more precise estimates than the LEM.
Our equations for postnatal exposure of lipophilic environmental toxicants give better results than the LEM and are easier to implement than the complex PBPK models. HCB exposure, especially during the first three months of life, has a negative effect on infant growth up to 2years.
Perfluoroalkyl substances (PFASs) are chemicals with potential neurotoxic effects although the current evidence is still limited. This study investigated the association between perinatal exposure to perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) and neuropsychological development assessed at 6, 12 and 24 months. We measured PFOS and PFOA in breast milk samples collected one month after delivery by mothers of children participating in the HUMIS study (Norway). Cognitive and psychomotor development was measured at 6 and at 24 months using the Ages and Stages Questionnaire (ASQ-II). Behavioral development was assessed using the infant-toddler symptom checklist (ITSC) at 12 and at 24 months. Weighted logistic regression and weighted negative binomial regression models were applied to analyze the associations between PFASs and ASQ-II and ITSC, respectively. The median concentration of PFOS was 110 ng/L, while the median for PFOA was 40 ng/L. We did not detect an increased risk of having an abnormal score in ASQ-II at 6 months or 24 months. Moreover, no consistent increase in behavioral problems assessed at 12 and 24 months by ITSC questionnaire was detected. We observed no association between perinatal PFOS and PFOA exposure and early neuropsychological development. Further longitudinal studies are needed to confirm the effects of these compounds on neuropsychological development in older children.
Experimental studies have shown that dioxin-like chemicals may interfere with aspects of the endocrine system including growth. However, human background population studies are, however, scarce. We aimed to investigate whether early exposure of healthy infants to dioxin-like chemicals was associated with changes in early childhood growth and serum IGF1. In 418 maternal breast milk samples of Danish children (born 1997-2001) from a longitudinal cohort, we measured polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and polychlorinated biphenyls (pg or ng/g lipid) and calculated total toxic equivalent (total TEQ). SDS and SDS changes over time (?SDS) were calculated for height, weight, BMI, and skinfold fat percentage at 0, 3, 18, and 36 months of age. Serum IGF1 was measured at 3 months. We adjusted for confounders using multivariate regression analysis. Estimates (in parentheses) correspond to a fivefold increase in total TEQ. TEQ levels in breast milk increased significantly with maternal age and fish consumption and decreased with maternal birth year, parity, and smoking. Total TEQ was associated with lower fat percentage (-0.45 s.d., CI: -0.89; -0.04), non-significantly with lower weight and length at 0 months, accelerated early height growth (increased ?SDS) (?SDS 0-18 months: +0.77 s.d., CI: 0.34; 1.19) and early weight increase (?SDS 0-18: +0.52 s.d., CI: 0.03; 1.00), and increased IGF1 serum levels at 3 months (+13.9?ng/ml, CI: 2.3; 25.5). Environmental exposure to dioxin-like chemicals was associated with being skinny at birth and with higher infant levels of circulating IGF1 as well as accelerated early childhood growth (rapid catch-up growth).
Prenatal exposure to polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) may influence birth weight among infants in a Swedish cohort with background exposure: a cross-sectional study.
Prenatal exposure to persistent organic pollutants, e.g. polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) has been suggested to negatively affect birth weight although epidemiological evidence is still inconclusive. We investigated if prenatal exposure to PCBs and PBDEs is related to birth weight in a Swedish population with background exposure.
Breast milk was sampled during the third week after delivery from first-time mothers in Uppsala county, Sweden 1996-2010 (POPUP cohort) (N?=?413). Samples were analysed for di-ortho PCBs (CB-138, 153, 180) and tetra- to hexa- brominated PBDEs (BDE-47, 99, 100, 153). Simple and multiple linear regression models were used to investigate associations between lipid-adjusted, ln-transformed PCB and PBDE concentrations, and birth weight. Covariates included in the multivariate regression model were PCB and PBDE exposure, maternal age, pre-pregnancy BMI, weight gain during pregnancy, education, smoking, gender of the infant and gestational length. The effect of including fish consumption was also investigated.
In the multivariate model, prenatal exposure to di-ortho PCBs was significantly associated with increased birth weight (ß?=?137; p?=?0.02). The result did not change when gestational length was added to the model. An inverse association between PBDE(4) (sum of BDE-47, -99, -100 and -153) and birth weight was observed in the multivariate model including gestational length (ß?=?-106; p?=?0.04). Maternal pre-pregnancy BMI and weight gain during pregnancy were important confounders of the association between di-ortho PCBs and birth weight. The associations were not alleviated after adjustment for fish consumption, a major source of PCB and PBDE exposure. The observed associations were stronger for boys than for girls.
Our results indicate that prenatal exposure to di-ortho PCBs and PBDE(4) may influence birth weight in different directions, i.e. PCB exposure was associated with higher birth weight and PBDE exposure with lower birth weight. Maternal pre-pregnancy BMI and weight gain during pregnancy were important confounders that may hide positive association between di-ortho PCB exposure and birth weight if they are not included in the statistical model. We speculate that even small PCB- and PBDE-induced shifts in the distribution of birth weight may influence future public health in populations with background exposure.