Corine Koopman-Esseboom

Effects of Dioxins and Polychlorinated Biphenyls on Thyroid Hormone Status of Pregnant Women and Their Infants

ABSTRACT: Dioxins [polychlorinated dibenzo-p-dioxins (PCDD), dibenzofurans (PCDF)] and polychlorinated biphenyls (PCB) are potentially hazardous compounds. Animal studies have demonstrated that PCDD, PCDF, and PCB can alter thyroid hormone homeostasis. We investigated thyroid hormone levels in 105 mother-infant pairs. To estimate maternal and infant exposure, four nonplanar PCB congeners were measured in maternal plasma during the last month of pregnancy and in umbilical cord plasma. Seventeen PCDD and PCDF congeners, three planar PCB congeners, and 23 nonplanar PCB congeners were measured in human milk. Higher PCDD, PCDF, and PCB levels in human milk, expressed as toxic equivalents, correlated significantly with lower plasma levels of maternal total triiodothyronine and total thyroxine, and with higher plasma levels of TSH in the infants in the 2nd wk and 3rd mo after birth. Infants exposed to higher toxic equivalents levels had also lower plasma free thyroxine and total thyroxine levels in the 2nd wk after birth. We conclude that elevated levels of dioxins and PCB can alter the human thyroid hormone status.

Perinatal exposure to polychlorinated biphenyls and dioxins and its effect on neonatal neurological development

Polychlorinated biphenyls (PCBs) and dioxins (polychlorinated dibenzo-p-dioxins (PCDDs), and dibenzofurans (PCDFs)) are widespread environmental contaminants which are neurotoxic in animals. Perinatal exposure to PCBs, PCDDs, and PCDFs occurs prenatally via the placenta and postnatally via breast milk. To investigate whether such an exposure affects the neonatal neurological condition, the neurological optimality of 418 Dutch newborns was evaluated with the Prechtl neurological examination. Half of the infants were breast-fed, the other half were formula-fed, representing a relatively high against a relatively low postnatally exposed group, respectively. As an index of prenatal exposure, four non-planar PCBs in cord and maternal plasma were used. These PCB levels were not related to neurological function. As measures of combined pre- and early neonatal exposure, 17 dioxin congeners, three planar, and 23 non-planar PCB congeners were determined in human milk in the second week after delivery. Higher levels of PCBs, PCDDs, and PCDFs in breast milk were related to reduced neonatal neurological optimality. Higher levels of planar PCBs in breast milk were associated with a higher incidence of hypotonia. This study confirms previous reports about the neurotoxic effects of these compounds on the developing brain of newborn infants.

Increased perinatal mortality and morbidity in monochorionic versus dichorionic twin pregnancies: clinical implications of a large Dutch cohort study

Objective  To evaluate mortality and morbidity in a large cohort of twin pregnancies according to chorionicity. We aimed to estimate the optimal time of delivery.

Effects of Environmental Exposure to Polychlorinated Biphenyls and Dioxins on Birth Size and Growth in Dutch Children

Lower birth weight and growth retardation has been found in studies with laboratory animals, in children born of mothers exposed to accidental high levels of polychlorinated biphenyls (PCBs) and related compounds, and in children born of mothers who consumed PCB-contaminated fish. The effect of background exposure to PCBs and dioxins on birth size and growth in human newborns, however, is still unknown. This study examined birth size and postnatal growth of term newborns in relation to their background PCB and dioxin exposure. Birth weight and weight, length, and head circumference were measured at 10 d and 3, 7, 18, and 42 mo of age in 207 children, of whom 105 were breast-fed and 102 were formula-fed during infancy. The effect of in utero exposure to PCBs on birth size, assessed by cord and maternal plasma PCB levels, was investigated in the whole group. The effect of prenatal PCB exposure on postnatal growth was studied in the formula-fed group, whereas the effect of prenatal as well as lactational exposure to PCBs and dioxins on postnatal growth was studied in the breast-fed group. After adjustment for covariates, cord and maternal plasma PCB levels where both negatively associated with birth weight. Infants with high cord plasma PCB levels (P90 = 0.80 µg/L) weighed 165 g less compared with infants with low cord plasma PCB levels (P10 = 0.20 µg/L). Cord and maternal plasma PCB levels where both significantly associated with lower growth rate, defined as change in SD score (SDS) of weight, length, and head circumference from birth to 3 mo in the formula-fed group (all p values <0.05). No negative effects of prenatal PCB exposure on growth rate were found from 3 to 42 months of age. Postnatal PCB and dioxin exposure was not negatively associated with growth rate in the breast-fed group. In utero exposure to environmental levels of PCBs is negatively associated with birth weight and postnatal growth until 3 mo of age. Although this growth delay was described in healthy term born infants, intrauterine and postnatal growth retardation are potentially harmful to the developing human and should be avoided by reducing maternal PCB and dioxin body burden, and consequently fetal exposure to these pollutants.

Immunologic Effects of Background Prenatal and Postnatal Exposure to Dioxins and Polychlorinated Biphenyls in Dutch Infants

ABSTRACT: Immunologic effects of pre- and postnatal polychlorinated biphenyl (PCB)/dioxin exposure in Dutch infants from birth to 18 mo of age are explored. The total study group consisted of 207 healthy mother-infant pairs, of which 105 infants were breast-fed and 102 children were bottle-fed. Prenatal PCB exposure was estimated by the PCB sum (PCB congeners 118, 138, 153, and 180) in maternal blood and the total toxic equivalent (TEQ) level in human milk (17 dioxin and 8 dioxin-like PCB congeners). Postnatal PCB/dioxin exposure was calculated as a product of the total TEQ level in human milk multiplied by the weeks of breast-feeding. The number of periods with rhinitis, bronchitis, tonsillitis, and otitis during the first 18 mo of life was used as an estimate of the health status of the infants. Humoral immunity was measured at 18 mo of age by detecting antibody levels to mumps, measles, and rubella. White blood cell counts (monocytes, granulocytes, and lymphocytes) and immunologic marker analyses CD4+ T-lymphocytes, CD8+ T-lymphocytes, activated T-lymphocytes (HLA-DR+CD3+), as well as T cell receptor (TcR) αβ+, TcRγδ+, CD4+CD45RA+ and CD4+CD45RO+ T-lymphocytes, B-lymphocytes (CD19+ and/or CD20+) and NK cells (CD16+ and/or CD56+/CD3−) in cord blood and venous blood at 3 and 18 mo of age were assessed in a subgroup of 55 infants. There was no relationship between pre-and postnatal PCB/dioxin exposure and upper or lower respiratory tract symptoms or humoral antibody production. A higher prenatal PCB/ dioxin exposure was associated with an increase in the number of TcRγδ+ T cells at birth and with an increase in the total number of T cells and the number of CD8+ (cytotoxic), TcRαβ+, and TcRγδ+ T cells at 18 mo of age. A higher prenatal as well as postnatal PCB/dioxin exposure was associated with lower monocyte and granulocyte counts at 3 mo of age. In conclusion, our study suggests that background levels of PCB/dioxin exposure influences the human fetal and neonatal immune system.

Neurological condition in 18-month-old children perinatally exposed to polychlorinated biphenyls and dioxins

The neurological optimality of 418 Dutch children was evaluated at the age of 18 months, in order to determine whether prenatal and breast milk mediated exposure to polychlorinated biphenyls (PCBs) and dioxins affected neurological development. Half of the infants were breast-fed, the other half were formula-fed. PCB concentrations in cord and maternal plasma were used as a measure of prenatal exposure to PCBs. To measure postnatal exposure, PCB and dioxin congeners were determined in human milk and in formula milk. After adjusting for covariates, transplacental PCB exposure was negatively related to the neurological condition at 18 months. Although greater amounts of PCBs and dioxins are transferred via nursing than via placental passage, an effect of lactational exposure to PCBs and dioxins could not be detected. We even found a beneficial effect of breast-feeding on the fluency of movements. We conclude that transplacental PCB passage has a small negative effect on the neurological condition in 18-month-old toddlers.

PCB AND DIOXIN LEVELS IN PLASMA AND HUMAN MILK OF 418 DUTCH WOMEN AND THEIR INFANTS. PREDICTIVE VALUE OF PCB CONGENER LEVELS IN MATERNAL PLASMA FOR FETAL AND INFANT'S EXPOSURE TO PCBs AND DIOXINS.

Polychlorinated biphenyls (PCBs) as well as dioxins (polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs)) are potentially hazardous compounds in the environment for human beings. In order to investigate PCB and dioxin exposure of Dutch women and their neonates, levels were examined in 418 mother-infant pairs. Four non-planar PCB congener levels (PCB 118, 138, 153 and 180) were measured in maternal plasma and in umbilical cord plasma. The 209 mothers who breast-fed their infants collected human milk samples for the analysis of seventeen 2,3,7,8-substituted PCDD and PCDF congener levels, three planar PCB and twenty-three non-planar PCB congener levels. The dioxin and planar PCB levels we measured in human milk (mean 30 respectively 16 pg TEQ/g fat), belong to the highest background levels analysed all over the world but they are in the normal range for highly industrialised, densely populated countries in Western Europe. Correlation coefficients between PCB 118, 138, 153 and 180 congener levels in maternal plasma and PCB levels in cord plasma or PCB and dioxin levels in human milk are highly significant. However, the 95% predictive interval is too wide to predict accurately the PCB and dioxin levels to which an individual infant is exposed in utero or postnatally by breast-feeding, from the PCB levels in maternal plasma.

EFFECTS OF POLYCHLORINATED-BIPHENYLS (PCBS) AND DIOXINS ON GROWTH AND DEVELOPMENT

Polychlorinated biphenyls (PCBs) and dioxins are potentially toxic compounds which occur widely in the environment. Their effects on the growth and development of infants at the levels currently found in highly industrialised western countries is not well known. This Dutch multicenter study, combining animal and human studies, tries to answer this question. Animal studies showed that PCB 169, given once during pregnancy at a dose of 1.8 g kg-1 bodyweight, has an effect on developmental parameters, dopamine regulation and fertility. Effects on thyroid hormones were also found in animals, probably due to both a competitive binding of PCB metabolites to the thyroxine binding protein and increased glucuronidation, Perhaps to compensate for this, an increased diodase activity in the brain was found. Human studies involved 400 mother-infant pairs, half of them being breast-fed, the other half were fed a formula devoid of PCBs and dioxins. PCB levels were measured in serum and dioxin and PCB levels in breastmilk. Levels were found to be as high as previously found in highly industrialised countries. Growth and development were carefully documented, but no data are as yet available. In pregnant women, a significant negative correlation was found between some dioxin and PCB congeners in milk and plasma thyroid hormones, while newborn infants showed higher thyroid stimulating hormone (TSH) at higher levels of dioxin exposure. In summary, data from this combined multicenter study involving animals and humans increases our insight into the potentially negative effects of PCBs and dioxins on growth and development.

Dioxin and PCB levels in blood and human milk in relation to living areas in the Netherlands

Dioxins and polychlorinated biphenyls (PCBs) are ubiquitous toxic compounds in the environment. Negative influences of these compounds on the health status of human beings have been described. Especially susceptible might be the fetus, which is exposed in utero, and the newborn breast-fed infant, since both are exposed to relatively high levels of dioxins and PCBs during a critical period of organ growth and development. We investigated PCB levels in 406 maternal plasma samples as well as PCB and dioxin levels in 172 human milk samples with relation to living area of women living for at least five years in the western industrialized part of the Netherlands or the northern more rural part. The western part was further subdivided into one urban and two highly industrialized areas. After correction for covariates, we found significantly higher levels of PCB 118 in maternal plasma as well as significantly higher levels of the dioxin-TEQ and of ten individual dioxin and PCB congener levels in human milk in the western more industrialized areas of the Netherlands compared to the northern more rural part. We did not find significant differences in planar, mono-ortho or di-ortho PCB-TEQ levels in human milk between all different areas. We conclude that significantly higher levels of a number of dioxin and PCB congeners are found in women living in industrialized areas compared to women living in rural areas in the Netherlands.

Plasma polychlorinated biphenyl levels in Dutch preschool children either breast-fed or formula-fed during infancy

OBJECTIVES This study examined the influence of lactational and in utero exposure to polychlorinated biphenyls (PCBs) on plasma PCB levels in children. METHODS Plasma PCB levels were measured in 173 children at 3.5 years, of whom 91 were breast-fed and 82 were formula-fed in infancy. RESULTS Median plasma PCB levels were 3.6 times higher in breast-fed children (0.75 microgram/L) than in their formula-fed peers (0.21 microgram/L). Breast-feeding period and breast-milk PCB levels were important predictors for PCB levels in the breast-fed group. For children in the formula-fed group, PCB levels were significantly related to their material plasma PCB levels. CONCLUSIONS PCB levels in Dutch preschool children are related to transfer of maternal PCBs; therefore, strategies should be aimed at reducing maternal PCB body burden.