Beth C. Gladen

Neonatal effects of transplacental exposure to PCBs and DDE

Neonatal effects of transplacental exposure to polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) were examined in a study of 912 infants. Birth weight, head circumference, and neonatal jaundice showed no relationship to PCBs or DDE. We also administered the Brazelton Neonatal Behavioral Assessment Scales, which are psychologic and neurologic tests designed for use in newborn infants. The results of these tests showed that higher PCB levels were associated with hypotonicity and hyporeflexia and that higher DDE levels were associated with hyporeflexia.

Polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) in human milk: effects of maternal factors and previous lactation.

The authors measured polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) in maternal serum, cord blood, placenta, and serial samples of breast milk from 868 women. Almost all samples of breast milk showed detectable levels of both chemicals. Overall, values for DDE in this study are within the range of those found previously, whereas those for PCBs are somewhat higher. Possible causes of variation in levels were investigated. For DDE, older women, Black women, cigarette smokers, and women who consumed sport fish during pregnancy had higher levels; only age and race showed large effects. For PCBs, older women, women who regularly drink alcohol, and primiparae had higher levels. In addition, both chemicals showed modest variation across occupational groupings. Casual exposure to a PCB spill did not result in chemical levels different from background. In general, women have higher levels in their first lactation and in the earlier samples of a given lactation, and levels decline both with time spent breast-feeding and with number of children nursed. These striking declines are presumably a measure of exposure to the child.

Development after exposure to polychlorinated biphenyls and dichlorodiphenyl dichloroethene transplacentally and through human milk

OBJECTIVE To determine whether exposure to polychlorinated biphenyls (PCBs) or dichlorodiphenyl dichloroethene (DDE), either transplacentally or through breast feeding, affected scores on the Bayley Scales of Infant Development at 6 or 12 months of age. DESIGN Cohort followed from birth to 1 year of age. SETTING General community. PARTICIPANTS Volunteer sample of 858 infants, of whom 802 had Bayley scores available at either 6 months or 12 months or both. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Bayley scales and chemical measurements were done independently. Higher transplacental exposure to PCBs was associated with lower psychomotor scores at both 6 and 12 months of age; the difference between the mean scores in the lowest and highest PCB groups was 7 points at 6 months and 8 points at 12 months. Higher transplacental exposure to DDE was associated with higher mental scores at 6 months of age (the difference between the mean scores in the lowest and highest DDE groups was 6 points), but no relationship was seen at 12 months. Exposure to either chemical through breast feeding was apparently unrelated to Bayley scores. CONCLUSIONS Transplacental exposure to PCBs was associated with lower psychomotor scores. No deleterious effects were associated with breast feeding.

Effects of perinatal polychlorinated biphenyls and dichlorodiphenyl dichloroethene on later development

OBJECTIVE Determining whether early developmental effects of perinatal exposure to polychlorinated biphenyls (PCBs) or dichlorodiphenyl dichloroethene (DDE) persist. DESIGN Cohort followed from birth; ages now 5 1/2 to 10 1/2 years. SETTING General community. PARTICIPANTS Volunteer sample of 859 children, of whom 712 had been examined with the McCarthy Scales of Childrens Abilities at 3, 4, or 5 years; 506 sent report cards. INTERVENTIONS None. MEASUREMENTS AND RESULTS Neither transplacental nor breast-feeding exposure to PCBs or DDE affected McCarthy scores at 3, 4, or 5 years. There was no statistically significant relationship between poorer grades and PCB or DDE exposure by either route. CONCLUSIONS The deficits seen in these children on the Bayley Scales of Infant Development through 2 years of age are no longer apparent.

Pubertal growth and development and prenatal and lactational exposure to polychlorinated biphenyls and dichlorodiphenyl dichloroethene

OBJECTIVES Polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) are ubiquitous toxic environmental contaminants. Prenatal and early life exposures affect pubertal events in experimental animals. We studied whether prenatal or lactational exposures to background levels of PCBs or DDE were associated with altered pubertal growth and development in humans. STUDY DESIGN Follow-up of 594 children from an existing North Carolina cohort whose prenatal and lactational exposures had previously been measured. Height, weight, and stage of pubertal development were assessed through annual mail questionnaires. RESULTS Height of boys at puberty increased with transplacental exposure to DDE, as did weight adjusted for height; adjusted means for those with the highest exposures (maternal concentration 4+ ppm fat) were 6.3 cm taller and 6.9 kg larger than those with the lowest (0 to 1 ppm). There was no effect on the ages at which pubertal stages were attained. Lactational exposures to DDE had no apparent effects; neither did transplacental or lactational exposure to PCBs. Girls with the highest transplacental PCB exposures were heavier for their heights than other girls by 5.4 kg, but differences were significant only if the analysis was restricted to white girls. CONCLUSIONS Prenatal exposures at background levels may affect body size at puberty.

Breast-feeding and cognitive development

Eight-hundred fifty-five newborns were enrolled in a prospective study between 1978 and 1982 and then followed through school age. To determine whether the mode of infant feeding affected developmental scores or school grades, prospective data were collected on how the children were fed; 788 of the children had Bayley tests at 6 months, 720 at 12 months, 676 at 18 months and 670 at 2 years. McCarthy testing was done on 645 children at 3 years, 628 at 4 years and 636 at 5 years. Testers were not specifically blind to feeding method. The families provided report cards from grade 3 or higher for 366 children. There were statistically significant but small increases in scores among breast-fed children on at least some subscales of the Bayley and McCarthy at all time points from 2 years through 5 years and slightly higher English grades on report cards in both crude analyses and in multivariate analyses that allowed adjustment for the most plausible confounding variables. We conclude that, in a volunteer, 95% white sample of middle class children, those breast-fed scored slightly better than those bottle fed; the effect is small but still detectable at school age.

Polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) in human milk: effects on growth, morbidity, and duration of lactation

We followed 858 children from birth to one year of age to determine whether the presence of polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) in breast milk affected their growth or health. Neither chemical showed an adverse effect on weight or frequency of physician visits for various illnesses, although differences were seen between breast-fed and bottle-fed children, with bottle-fed children being heavier and having more frequent gastroenteritis and otitis media. Children of mothers with higher levels of DDE were breast-fed for markedly shorter times, but adjustments for possible confounders and biases did not change the findings. In absence of any apparent effect on the health of the children, we speculate that DDE may be interfering with the mothers ability to lactate, possibly because of its estrogenic properties.

Levels of lipid peroxides in uncomplicated pregnancy : a review of the literature

The literature on lipid peroxide levels in uncomplicated pregnancy is limited, but some reasonable conclusions are possible. Despite the lack of precision in the predominant measure of lipid oxidation, there is agreement across a large number of studies that the level of lipid peroxides in blood is generally higher in pregnant women than in nonpregnant women. During gestation, elevations appear by the second trimester and may taper off later in gestation, decreasing further after delivery. Lipid peroxides also are produced in placenta, but their pattern of change over the course of pregnancy is unclear. Lipid peroxides are important because their uncontrolled production can result in oxidative stress, with significant damage to cell integrity. There is a growing literature that associates oxidative stress with preeclampsia, a major cause of maternal and fetal morbidity. The higher levels of lipid peroxides seen in blood and the production of lipid peroxides in the placenta, even in uncomplicated pregnancies, make new baseline studies a priority. These studies should include measurements of lipids and blood volume, because they can influence marker values, with sensitive and specific measures of lipid peroxidation made at various points of gestation. From our review of the existing literature we conclude that the importance of oxidative stress in reproduction is just beginning to be appreciated and studied.

Biomarkers of oxidative stress study: are plasma antioxidants markers of CCl4 poisoning?☆

Abstract Antioxidants in the blood plasma of rats were measured as part of a comprehensive, multilaboratory validation study searching for noninvasive biomarkers of oxidative stress. For this initial study an animal model of CCl 4 poisoning was studied. The time (2, 7, and 16 h) and dose (120 and 1200 mg/kg, intraperitoneally)-dependent effects of CCl 4 on plasma levels of α-tocopherol, coenzyme Q (CoQ) , ascorbic acid, glutathione (GSH and GSSG), uric acid, and total antioxidant capacity were investigated to determine whether the oxidative effects of CCl 4 would result in losses of antioxidants from plasma. Concentrations of α-tocopherol and CoQ were decreased in CCl 4 -treated rats. Because of concomitant decreases in cholesterol and triglycerides, it was impossible to dissociate oxidation of α-tocopherol and the loss of CoQ from generalized lipid changes, due to liver damage. Ascorbic acid levels were higher with treatment at the earliest time point; the ratio of GSH to GSSG generally declined, and uric acid remained unchanged. Total antioxidant capacity showed no significant change except for 16 h after the high dose, when it was increased. These results suggest that plasma changes caused by liver malfunction and rupture of liver cells together with a decrease in plasma lipids do not permit an unambiguous interpretation of the results and impede detection of any potential changes in the antioxidant status of the plasma.

DDE and shortened duration of lactation in a northern Mexican town

OBJECTIVES Worldwide declines in the duration of lactation are cause for public health concern. Higher levels of dichlorodiphenyl dichloroethene (DDE) have been associated with shorter durations of lactation in the United States. This study examined whether this relationship would hold in an agricultural town in northern Mexico. METHODS Two hundred twenty-nine women were followed every 2 months from childbirth until weaning or until the child reached 18 months of age. DDE was measured in breast milk samples taken at birth, and women were followed to see how long they lactated. RESULTS Median duration was 7.5 months in the lowest DDE group and 3 months in the highest. The effect was confined to those who had lactated previously, and it persisted after statistical adjustment for other factors. These results are not due to overtly sick children being weaned earlier. Previous lactation lowers DDE levels, which produces an artifactual association, but simulations using best estimates show that an effect as large as that found here would arise through this mechanism only 6% of the time. CONCLUSIONS DDE may affect womens ability to lactate. This exposure may be contributing to lactation failure throughout the world.