Walter J. Rogan

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.

Polychlorinated biphenyls and the developing nervous system: Cross-species comparisons

Polychlorinated biphenyls are stable, lipophilic industrial compounds that are present in residue levels in human tissue, wildlife, and freshwater sediment. They are toxic, and are known to cross the placenta and intoxicate the fetus. Two large outbreaks of PCB poisoning have occurred in Asia; women pregnant at or after the exposures had children who were developmentally impaired. Laboratory experiments in rhesus monkeys and rodents, designed to assess neural or developmental effects, show altered activity levels, impaired learning, and delayed ontogeny of reflexes. Children exposed transplacentally to levels considered to be background in the U.S. have hypotonia and hyporeflexia at birth, delay in psychomotor development at 6 and 12 months, and poorer visual recognition memory at 7 months. Allowing for differences in testing, effects are roughly similar across species, but current methods used to calculate allowable or reference doses give results up to 4 orders of magnitude apart, with the lowest level based on the neurotoxicology level coming from the human data.

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.

The Effect of Chelation Therapy with Succimer on Neuropsychological Development in Children Exposed to Lead

BACKGROUND Thousands of children, especially poor children living in deteriorated urban housing, are exposed to enough lead to produce cognitive impairment. It is not known whether treatment to reduce blood lead levels prevents or reduces such impairment. METHODS We enrolled 780 children with blood lead levels of 20 to 44 microg per deciliter (1.0 to 2.1 micromol per liter) in a randomized, placebo-controlled, double-blind trial of up to three 26-day courses of treatment with succimer, a lead chelator that is administered orally. The children lived in deteriorating inner-city housing and were 12 to 33 months of age at enrollment; 77 percent were black, and 5 percent were Hispanic. Follow-up included tests of cognitive, motor, behavioral, and neuropsychological function over a period of 36 months. RESULTS During the first six months of the trial, the mean blood lead level in the children given succimer was 4.5 microg per deciliter (0.2 micromol per liter) lower than the mean level in the children given placebo (95 percent confidence interval, 3.7 to 5.3 microg per deciliter [0.2 to 0.3 micromol per liter]). At 36 months of follow-up, the mean IQ score of children given succimer was 1 point lower than that of children given placebo, and the behavior of children given succimer was slightly worse as rated by a parent. However, the children given succimer scored slightly better on the Developmental Neuropsychological Assessment, a battery of tests designed to measure neuropsychological deficits thought to interfere with learning. All these differences were small, and none were statistically significant. CONCLUSIONS Treatment with succimer lowered blood lead levels but did not improve scores on tests of cognition, behavior, or neuropsychological function in children with blood lead levels below 45 microg per deciliter. Since succimer is as effective as any lead chelator currently available, chelation therapy is not indicated for children with these blood lead levels.

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.

Health risks and benefits of bis(4-chlorophenyl)-1,1,1-trichloroethane (DDT)

DDT (bis[4-chlorophenyl]-1,1,1-trichloroethane) is a persistent insecticide that was used worldwide from the mid 1940s until its ban in the USA and other countries in the 1970s. When a global ban on DDT was proposed in 2001, several countries in sub-Saharan Africa claimed that DDT was still needed as a cheap and effective means for vector control. Although DDT is generally not toxic to human beings and was banned mainly for ecological reasons, subsequent research has shown that exposure to DDT at amounts that would be needed in malaria control might cause preterm birth and early weaning, abrogating the benefit of reducing infant mortality from malaria. Historically, DDT has had mixed success in Africa; only the countries that are able to find and devote substantial resources towards malaria control have made major advances. DDT might be useful in controlling malaria, but the evidence of its adverse effects on human health needs appropriate research on whether it achieves a favourable balance of risk versus benefit.

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.