Birth weight, early weight gain and pubertal maturation: a longitudinal study.

OBJECTIVE: To investigate the effect of birth weight and early weight gain on the timing of various measures of puberty in both girls and boys. METHODS: A total of 856 newborns enrolled in the North Carolina Infant Feeding Study were followed to age 5 years, with 600 children followed up at adolescence. Birth weight was obtained from medical records and children were weighed at study visits until age 5 years; gains in standardized weights were calculated over four early age intervals: 0-6 months, 6-12 months, 1-2 years and 2-5 years. Age at menarche in girls and age at advanced Tanner stages in both girls and boys were reported by adolescents and their parents. Survival models were used to analyse the effects of birth weight and early weight gain on these outcomes. RESULTS: Girls with higher birth weight and greater weight gains during the four early age intervals were younger when they reached menarche and advanced Tanner stages; boys with greater early weight gains also were younger when they reached advanced Tanner stages, but few of these effects were statistically significant. CONCLUSIONS: Higher birth weights and greater weight gains during infancy and early childhood can lead to earlier sexual maturation in girls.

Preventing lead poisoning in children: can the US experience inform other countries? The case of Poland.

Exposure to excess lead during childhood is preventable, but nowhere has that goal been achieved. In the US, recommendations for prevention of childhood lead poisoning are issued by the Centres for Disease Control and Prevention, based on periodically updated population-based data on the prevalence of lead poisoning by age and blood lead level. A well developed public health infrastructure is to provide case management to the lead exposed children. In Poland, the social and economic transitions of the last decade changed the potential for childhood lead exposure, and there has been a profound restructuring of the health care system. Blood lead testing in children is performed outside the primary care. Data on blood lead levels are not collected and analysed centrally. The range of follow-up services may differ among the regions, depending on the local expertise. An updated approach to prevention of childhood lead poisoning, making better use of the existing expertise and involving primary care providers, needs consideration. Complex public health programs like this of lead poisoning prevention cannot be transplanted whole to other countries. However, experiences gained by the US might provide valuable suggestions for others, even though the US policy has flaws and is not fully implemented. Discussing proposal for Poland in light of the current US practice highlights the necessity of reliable estimates of the exposed population for rational policy. It also helps to define research questions relevant to public health practice in Poland, and confirms that prevention of lead poisoning in children requires the coordinated work of different professionals.

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.

Menstruation and reproduction in women with polychlorinated biphenyl (PCB) poisoning: long-term follow-up interviews of the women from the Taiwan Yucheng cohort.

BACKGROUND: In 1979 in Taiwan, about 2000 people were poisoned by cooking oil contaminated with heat-degraded polychlorinated biphenyls (PCBs). Victims developed chloracne and other symptoms; the illness is called Yucheng (oil disease). The chemicals persist in the victims' bodies and some are toxic to the female reproductive system in experimental animals. METHODS: In 1993-1994, we identified the living Yucheng women and neighbourhood controls and interviewed them about their reproductive experience. Of the 596 living Yucheng women aged 30-59 years, we found 368, and interviewed 356. We identified 329 controls, and interviewed 312. RESULTS: Of the Yucheng women, 16% reported abnormal menstrual bleeding compared to 8% (P < 0.05) of control women; 4.2% versus 1.7% reported a stillbirth since 1979 (P = 0.068). Other characteristics of the menses, fertility, frequency of intercourse, and age at menopause appeared unaffected. More of the Yucheng women reported that one of their offspring had died during childhood (10.2% versus 6.1%, P < 0. 05), and that they had decided to limit childbearing because of health problems (7% versus 2%, P = 0.01). CONCLUSIONS: These findings suggest that high level PCB/polychlorinated dibenzofuran (PCDF) exposure has some effect on female endocrine and reproductive function.

X-ray evidence of increased asbestos exposure in the US population from NHANES I and NHANES II, 1973-1978. National Health Examination Survey.

OBJECTIVES: Jobs involving heavy asbestos exposure increase risk for lung cancer and mesothelioma substantially, and low-level exposures may carry some risk. At least one indicator of asbestos exposure, mesothelioma, has been increasing in the US for decades. We investigated the prevalence of another indicator, pleural thickening on x-ray, in a defined sample of the US population. METHODS: Certified physicians read 1060 x-rays from the second National Health and Nutrition Examination Survey (1976-1980) for pleural changes consistent with pneumoconiosis, which are a reasonably specific indicator of asbestos exposure. RESULTS: Prevalence estimates, in NHANES II, in the age group 35-74 years, are 6.4% (+/- 0.9%) among males, 1.7% (+/- 0.6%) among females, and 3.9% (+/- 0.6%) overall. These prevalences are approximately twice those estimated from NHANES I data (1971-1975). CONCLUSIONS: X-ray evidence of asbestos exposure was common in the late 1970s and increasing. The increase may be due to occupational asbestos exposure, but it is so large as to suggest some contribution from environmental, non-occupational asbestos exposure.

Polychlorinated biphenyl (PCB) exposure in relation to thyroid hormone levels in neonates.

Polychlorinated biphenyls (PCBs) are industrially produced environmentally persistent compounds. In developed countries all humans have detectable levels in blood and other tissues. PCBs alter thyroid hormone metabolism in animal experiments, and human data suggest background-level exposure may have similar effects in neonates. We evaluated this possible effect among 160 North Carolina children whose in utero PCB exposure was estimated on the basis of the mother's PCB levels in milk and blood, in 1978-1982 (estimated median PCB level in milk at birth, 1.8 mg/kg lipid). Their umbilical cord sera were thawed in 1998 and assayed for total thyroxine, free thyroxine, and thyroid stimulating hormone. We found that PCB exposure was not strongly related to any of the thyroid measures. For example, for a one unit change in milk PCB concentration (mg/kg lipid), the associated multivariate-adjusted increase in thyroid stimulating hormone level was 7% (95% confidence limits (CL) = -6, 21). Despite the possibility of sample degradation, these data suggest that within the range of background-level exposure in the United States, in utero PCB exposure is only slightly related to serum concentration of total thyroxine, free thyroxine, and thyroid stimulating hormone at birth.

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.

Chloracne, goiter, arthritis, and anemia after polychlorinated biphenyl poisoning: 14-year follow-Up of the Taiwan Yucheng cohort.

In 1979, a mass poisoning involving 2,000 people occurred in central Taiwan from ingestion of cooking oil contaminated by polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs). We studied the prevalence of medical conditions in the exposed individuals and in a neighborhood control group. Starting with a registry of the exposed individuals from 1983, we updated the addresses of exposed individuals and identified a control group matched for age, sex, and neighborhood in 1979. In 1993, individuals 30 years of age or older were interviewed by telephone. We obtained usable information from 795 exposed subjects and 693 control subjects. Lifetime prevalence of chloracne, abnormal nails, hyperkeratosis, skin allergy, goiter, headache, gum pigmentation, and broken teeth were observed more frequently in the PCB/PCDF-exposed men and women. The exposed women reported anemia 2. 3 times more frequently than controls. The exposed men reported arthritis and herniated intervertebral disks 4.1 and 2.9 times, respectively, more frequently than controls. There was no difference in reported prevalences of other medical conditions. We conclude that Taiwanese people exposed to high levels of PCBs and PCDFs reported more frequent medical problems, including skin diseases, goiter, anemia, and joint and spine diseases.

Recall of a lead-contaminated vitamin and mineral supplement in a clinical trial.

PURPOSE: The Treatment of Lead-exposed Children (TLC) trial tested whether developmental outcome differed between children treated for lead poisoning with succimer or placebo. On 7 July 1997, TLC was informed that the vitamin and mineral supplements it gave to all children were contaminated with about 35 microg of lead per tablet. METHODS: TLC recalled the contaminated supplements and measured the children's exposure. RESULTS: The families of 96% of the children were contacted with 30 days. Among the 571 children to whom the contaminated supplements were dispensed, the mean increase in blood lead was 0.06+/-0.01 micromol/L (1.2+/-0.2 microg/dL); among 78 children to whom they were not, it was 0.09+/-0.03 micromol/L (1.8+/-0.7 microg/dL). There was no evidence of a dose-response relation between estimated supplement consumption and increase in blood lead concentration. CONCLUSIONS: The children's blood lead concentrations were not detectably affected by the contamination. Since the association of cognitive delay with lead exposure is best described for blood lead, we believe that the trial's inference about the effect of drug therapy on lead induced cognitive delay should be unaffected.

Increased mortality from chronic liver disease and cirrhosis 13 years after the Taiwan "yucheng" ("oil disease") incident.

In 1979, a mass poisoning involving some 2,000 persons occurred in central Taiwan from cooking oil contaminated by polychlorinated biphenyls (PCBs) and their heat-degraded byproducts, including polychlorinated dibenzofurans (PCDFs). The responsible health department registered cases for clinical purposes between 1979 and 1983. The exposed persons are referred to as the "yucheng" (oil disease) cohort. PCBs and PCDFs are toxic chemicals widely dispersed in the environment and in human tissue, which persist long after exposure. The consequences of exposure to these agents are not well understood. We traced the cohort through December 31, 1991, and compared overall and cause-specific mortality of 1,837 "yucheng" subjects with age, gender, and calendar time-specific mortality rates for the Taiwan general population. Eighty-three deaths were identified from 23,404 observed person-years. Even though the overall standardized mortality ratio (SMR) was 0.8 (95% confidence interval (CI) 0.7-1.0), there was a substantial elevation in the mortality rate for chronic liver disease and cirrhosis (10 deaths, SMR = 2.7, 95% CI = 1.3-4.9). Mortality from malignant neoplasms and other causes was not significantly different from that of the Taiwan population. PCB/PCDF exposure appears to promote the development of severe liver disease, perhaps in combination with known risk factors such as infection with hepatitis B virus. Further follow-up of this young cohort is necessary to see if the consequences include hepatic cancer.

The human health effects of DDT (dichlorodiphenyltrichloroethane) and PCBS (polychlorinated biphenyls) and an overview of organochlorines in public health.

Organochlorines are a diverse group of persistent synthetic compounds, some of which are detectable in nearly everyone. Many organochlorines are endocrine disruptors or carcinogens in experimental assays. p,p'-DDE (dichlorodiphenyl-dichloroethene) and PCBs (polychlorinated biphenyls) comprise the bulk of organochlorine residues in human tissues. We reviewed relevant human data cited in the 1991-1995 Medline database and elsewhere. High-level exposure to selected organochlorines appears to cause abnormalities of liver function, skin (chloracne), and the nervous system. Of more general interest, however, is evidence suggesting insidious effects of background exposure. Of particular concern is the finding of neonatal hypotonia or hyporeflexia in relation to PCB exposure. The epidemiologic data reviewed, considered in isolation, provide no convincing evidence that organochlorines cause a large excess number of cancers. A recent risk assessment that considered animal data, however, gives a cancer risk estimate for background exposure to dioxin and dioxin-like compounds (e.g. some PCBs) with an upper bound in the range of 10(-4) per year.

Pollutants in breast milk.

OBJECTIVE: To review data on the occurrence and toxicity of the commonly reported pesticides and industrial environmental pollutant chemicals in breast milk. DATA SOURCES: Continuous automated literature surveillance plus contact with investigators and governmental agencies. STUDY SELECTIONS: For data on occurrence, the most recent data from the largest data sets on the most representative donors were used. For data on toxicity, the primary report that was publicly available was used. DATA EXTRACTION: When necessary, data were reexpressed or concentrations were rescaled. The original investigator was contacted if necessary. DATA SYNTHESIS: Although pollutant chemicals are readily detected in most human milk worldwide, there is little evidence for consequent morbidity in nurslings. There have been several mass poisonings in which chemicals that were transmitted through breast milk clearly affected children who were breast-fed, and there is some evidence that prenatal exposure to background levels resulted in mild developmental delay and that lactation per se was disturbed. CONCLUSIONS: Breast-feeding is recommended despite the presence of chemical residues. The prenatal period in the child and the initiation of lactation in the mother may be sensitive periods to the toxicity of the chemicals that are considered here, and the potential for poisoning at higher levels is clear. However, in the vast majority of women, the benefits of breast-feeding appear to outweigh the risks, and those who advise women about infant nutrition should continue to support breast-feeding.

Environmental poisoning of children--lessons from the past.

Children have physiologic and behavioral characteristics that make them vulnerable to damage from environmental chemicals. In the past, there have been episodes in which children became ill or died from environmental exposures that spared adults or affected them less severely. Among the characteristics leading to children's sensitivity are their limited diets, dividing cells, differentiating organs and organ systems, slow or absent detoxification mechanisms, long life expectancy with the resulting ability to express damage with delayed consequences, and the severe metabolic demands of growth. There have been large outbreaks of poisonings involving children in Asia and Turkey, and some of the less obvious effects of chemicals have appeared in children in the United States. Although the United States has been spared a widespread outbreak of severe poisoning, such an incident is possible and would likely have greater consequences for children than adults.

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 women's ability to lactate. This exposure may be contributing to lactation failure throughout the world.

Chemical contaminants, pharmacokinetics, and the lactating mother.

We review the commonly occurring persistent pesticides and industrial chemicals in breast milk. These chemicals are dichlorodiphenyl trichloroethane as dichlorodiphenyl dichloroethene dieldrin, chlordane as oxychlordane, heptachlor, polychlorinated biphenyls, polychlorinated dibenzofurans, and polychlorinated dibenzodioxins. We present a worked example of the kinds of pharmacokinetic assumptions and calculations necessary for setting regulatory limits of contaminants in the food supply, calculating dose of chemical contaminants to the nursed infant, converting risks from lifetime exposure in laboratory animals to risks for short-term exposure in humans, and estimating the excess cancer risk to the nursed infant.

A 6-year follow-up of behavior and activity disorders in the Taiwan Yu-cheng children.

OBJECTIVES: The relationship of behavior and activity levels to the interval between outbreak and year of birth and to age of children is explored in Taiwanese children exposed in utero to heat-degraded polychlorinated biphenyls (PCBs)--the Yu-cheng children. Additionally, the relationship of the scores to chemical, physical, and cognitive findings is described. METHODS: With Rutter's Child Behavior Scale A and a modified Werry-Weiss-Peters Activity Scale, 118 Yu-chen children and matched controls were followed biannually from 1985 to 1991. RESULTS: At each year, the Yu-cheng children scored 7% to 43% worse (mean = 23%) than control children on the Rutter scale. At any fixed age, the Yu-cheng children scored 11% to 63% (mean = 28%) worse. The effect for children born later did not differ from that for those born earlier; neither was there any improvement as the children aged. A similar but weaker picture was seen for the activity score. These behavioral findings were not related to physical or cognitive findings or to serum PCB levels. CONCLUSIONS: In utero exposure to heat-degraded PCBs appears to cause mildly disordered behavior and increased activity level; the effect persists over time and is similar in children born up to 6 years after the mothers were exposed.