P. J. J. Sauer

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.

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.

Feeding premature newborn infants palmitic acid in amounts and stereoisomeric position similar to that of human milk: effects on fat and mineral balance.

The effect of the structure of human milk triglycerides on intestinal fat absorption remains controversial. Twelve infants were each fed, for 1 wk in a crossover design, two formulas that differed only in triglyceride configuration. The beta formula contained triglycerides similar to those in human milk (26% palmitic acid, esterified predominantly to the sn-2 position) whereas in the alpha formula, which contained triglycerides similar to those in formulas currently marketed, palmitate was mainly at the sn-1,3 positions. Fatty acid, fat, and mineral balances were measured at the end of each 1-wk period. Myristic, palmitic, and stearic acids were absorbed better from the beta formula, but total fat excretion was not reduced. During the feeding of beta formula fecal calcium excretion was lower, urinary calcium higher, and urinary phosphate lower. A formula containing triglycerides similar to those in human milk has significant effects on fatty acid intestinal absorption and improves mineral balance in comparison with a conventional formula.

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.

Neurological condition in 42-month-old children in relation to pre- and postnatal exposure to polychlorinated biphenyls and dioxins.

Adverse neurological effects of exposure to PCBs have been found up to 18 months of age. Now we report on the effect of pre- and postnatal exposure to PCBs and dioxins on the neurological condition at 42 months of age. For this purpose, PCB levels were determined in cord and maternal plasma, and used as a measure of prenatal exposure. Breast milk was analyzed for PCBs and dioxins. In addition, PCBs were determined in plasma sampled from the child at 42 months of age. We evaluated the neurological condition of 394 children using the Touwen/Hempel method. After adjustment for covariates, neither prenatal PCB exposure nor postnatal exposure to PCBs and dioxins was found to be related to the neurological condition at 42 months of age.

Ceftazidime pharmacokinetics in preterm infants: Effects of renal function and gestational age

The objectives of this study were (1) to determine the effects of gestational age on ceftazidime pharmacokinetics in the preterm infant, (2) to relate these effects to changes in glomerular filtration rate (GFR), and (3) to establish appropriate dosage recommendations for preterm infants on day 3 of life.

Longitudinal Studies on Metabolic Rate, Heat Loss, and Energy Cost of Growth in Low Birth Weight Infants

Summary: Longitudinal studies on total and resting metabolic rate and total heat loss were made in 14 LBW infants, age 1-58 d. Metabolic rate was calculated from indirect calorimetry, heat loss was measured by direct calorimetry. Total metabolic rate and total heat loss were lowest during the first week of life, 178.9 ± 18.0 and 171.8 ± 15.5 kJ·kg-1·24 h-1, respectively. During the age period of 8-58 d both total metabolic rate and heat loss showed a very slight increase with age: mean total metabolic rate was 278.8 ± 2.6 and mean total heat loss 257.0 ± 3.4 kJ·kg-1·24 h-1. Resting metabolic rate was 171.0 ± 25.2 kJ· kg-124 h-1during the first week of life and 248.0 ± 2.5 during d 8-58.The energy cost of components of new tissue was calculated from the energy balance equation. Ecomponents during the second week of life was 25.5 ± 4.9 kJ/g weight gain and 11.9 ± 0.4 kJ/ g weight gain over subsequent weeks. The net energy cost of tissue synthesis, calculated from the difference between indirect and direct calorimetry was 3.2 ±1.1 kJ/g weight gain during the second week and 1.1 ± 0.1 kJ/g weight gain in the following weeks. A neonate who receives a caloric intake of 535 kJ · kg-1 · 24 h-1and is growing at a rate of 17 g ·kg-1· 24 h-1 will use 42% of the caloric intake for maintenance and thermoregulation, 6% for activity, 38% for the components of new tissue, 4% for tissue synthesis and 10% for loss in faeces and urine.

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

OBJECTIVESnThis study examined the influence of lactational and in utero exposure to polychlorinated biphenyls (PCBs) on plasma PCB levels in children.nnnMETHODSnPlasma PCB levels were measured in 173 children at 3.5 years, of whom 91 were breast-fed and 82 were formula-fed in infancy.nnnRESULTSnMedian 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.nnnCONCLUSIONSnPCB levels in Dutch preschool children are related to transfer of maternal PCBs; therefore, strategies should be aimed at reducing maternal PCB body burden.