Serum n-3 polyunsaturated fatty acids are inversely associated with longitudinal changes in depressive symptoms during pregnancy.

BACKGROUNDS: N-3 polyunsaturated fatty acids (PUFAs) have been hypothesised to be protective for depression during pregnancy. However, there are few data and no consensus regarding this association. In this line, we aim to evaluate if the concentration of n-3 and n-6 PUFAs, and their ratio, are associated with depressive symptoms throughout pregnancy. METHOD: A prospective cohort of 172 Brazilian women was followed at 5-13th, 20-26th and 30-36th weeks of gestation. The presence of depressive symptoms was evaluated using the Edinburgh Postnatal Depression Scale (EPDS) at each pregnancy trimester. Depression was defined as an EPDS score ≥11. The concentrations of n-3 [α-linolenic acid; eicosapentaenoic acid (EPA); docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA)] and n-6 PUFAs [linoleic acid; γ linolenic acid; eicosadienoic acid; eicosatrienoic acid; arachidonic acid; docosatetraenoic acid and docosapentaenoic acid] were expressed as absolute (µg/ml) values. The total n-6/n-3 ratio was calculated. Statistical analyses were performed using univariate and adjusted random intercept logistic model for each fatty acid (FA) considering the longitudinal nature of data. Covariates were selected as potential confounders based on their biological plausibility of having an association with the concentration of FA and depressive symptoms during pregnancy. RESULTS: The prevalence of depressive symptoms was high in all pregnancy trimesters (1st = 33.7%; 2nd = 18.9%; 3rd = 17.4%). We did not find differences in means FA concentrations by depressive symptom classification, for each follow-up visit. The women presented a 5% decrease in the odds of having depressive symptoms for each one-week increase in the gestational age. As individual women progressed through pregnancy, higher concentrations of EPA (odds ratio (OR) = 0.92; 95% CI: 0.86-0.99), DHA (OR = 0.96; 95% CI: 0.93-0.99), DPA (OR = 0.87; 95% CI: 0.77-0.99) and total n-3 (OR = 0.98; 95% CI: 0.96-0.99) were associated with a lower odds of depressive symptoms, while higher total n-6/n-3 ratio were associated with greater odds of depressive symptoms (OR = 1.40; 95% CI: 1.09-1.79). We detected a decrease in the probability of depressive symptoms as concentrations of total n-3 FA, α-linolenic acid, DPA, and DHA increased. We also observed a sharper decline for women with initial greater chance of depressive symptoms compared with those with lower chance of having these symptoms. CONCLUSIONS: We found a high prevalence of depressive symptoms in low-income Brazilian pregnant women and no significant associations between n-6 FA and depressive symptoms. Lower serum concentrations of DHA, EPA and DPA and a higher n-6/n-3 ratio at each pregnancy trimester were associated with higher odds of depressive symptoms throughout pregnancy.

Prognostic profiles and the effectiveness of assisted conception: secondary analyses of individual patient data.

BACKGROUND: At present, it is unclear which treatment strategy is best for couples with unexplained or mild male subfertility. We hypothesized that the prognostic profile influences the effectiveness of assisted conception. We addressed this issue by analysing individual patient data (IPD) from randomized controlled trials (RCTs). METHODS: We performed an IPD analysis of published RCTs on treatment strategies for subfertile couples. Eligible studies were identified from Cochrane systematic reviews and we also searched Medline and EMBASE. The authors of RCTs that compared expectant management (EM), intracervical insemination (ICI), intrauterine insemination (IUI), all three with or without controlled ovarian stimulation (COS) and IVF in couples with unexplained or male subfertility, and had reported live birth or ongoing pregnancy as an outcome measure, were invited to share their data. For each individual patient the chance of natural conception was calculated with a validated prognostic model. We constructed prognosis-by-treatment curves and tested whether there was a significant interaction between treatment and prognosis. RESULTS: We acquired data from 8 RCTs, including 2550 couples. In three studies (n = 954) the more invasive treatment strategies tended to be less effective in couples with a high chance of natural conception but this difference did not reach statistical significance (P-value for interaction between prognosis and treatment outcome were 0.71, 0.31 and 0.19). In one study (n = 932 couples) the strategies with COS (ICI and IUI) led to higher pregnancy rates than unstimulated strategies (ICI 8% versus 15%, IUI 13% versus 22%), regardless of prognosis (P-value for interaction in all comparisons >0.5), but at the expense of a high twin rate in the COS strategies (ICI 6% versus 23% and IUI 3% versus 30%, respectively). In two studies (n = 373 couples), the more invasive treatment strategies tended to be more effective in couples with a good prognosis but this difference did not reach statistical significance (P-value for interaction: 0.38 and 0.68). In one study (n = 253 couples) the differential effect of prognosis on treatment effect was limited (P-value for interaction 0.52), perhaps because prognosis was incorporated in the inclusion criteria. The only study that compared EM with IVF included 38 couples, too small for a precise estimate. CONCLUSIONS: In this IPD analysis of couples with unexplained or male subfertility, we did not find a large differential effect of prognosis on the effectiveness of fertility treatment with IUI, COS or IVF.

The Early Determinants of Adult Health Study.

This issue of the Journal features collaborative follow-up studies of two unique pregnancy cohorts recruited during 1959-1966 in the United States. Here we introduce the Early Determinants of Adult Health (EDAH) study. EDAH was designed to compare health outcomes in midlife (age 40s) for same-sex siblings discordant on birthweight for gestational age. A sufficient sample of discordant siblings could only be obtained by combining these two cohorts in a single follow-up study. All of the subsequent six papers are either based upon the EDAH sample or are related to it in various ways. For example, three papers report results from studies that significantly extended the 'core' EDAH sample to address specific questions. We first present the overall design of and rationale for the EDAH study. Then we offer a synopsis of past work with the two cohorts to provide a context for both EDAH and the related studies. Next, we describe the recruitment and assessment procedures for the core EDAH sample. This includes the process of sampling and recruitment of potential participants; a comparison of those who were assessed and not assessed based on archived data; the methods used in the adult follow-up assessment; and the characteristics at follow-up of those who were assessed. We provide online supplementary tables with much further detail. Finally, we note further work in progress on EDAH and related studies, and draw attention to the broader implications of this endeavor.

Associations between birth weight, preeclampsia and cognitive functions in middle-aged adults.

Both reductions in birth weight and preeclampsia (PE) have been associated with decrements in scores on tests of intelligence in children and adolescents. We examined whether these decrements persist into middle adulthood and expand into other domains of cognitive functioning. Using data from the Early Determinants of Adult Health project and from the ancillary project, Fetal Antecedents of Major Depression and Cardiovascular Disease, we selected term same-sex sibling sets or singletons from these sets, from the New England Family Study (NEFS) and the Child Health and Development Studies (CHDS), discordant on either fetal growth or PE, to test the hypotheses that prenatal exposure to inflammation was associated with decrements in attention, learning and executive function 40 years later. Exposure was defined as a continuous measure of percentile birth weight for gestational age, reduced fetal growth (<20th percentile of birth weight for gestational age) or maternal PE. Given that the sample was comprised, in part, of sibling sets, the analyses were performed using mixed models to account for the inter-sibling correlations. Analyses were performed separately by study site (i.e. NEFS and CHDS). We found few statistically significant associations (suggesting a possible type II error) consistent with previous literature, suggesting that the associations with low birth weight do not persist into midlife. We discuss the possible reasons for the lack of associations, which include the possible mediating effects of the postnatal environment.

Effect of maternal coffee, smoking and drinking behavior on adult son's semen quality: prospective evidence from the Child Health and Development Studies.

Fetal exposure to caffeine is associated with adverse pregnancy outcomes. Animal and human studies suggest that caffeine may have effects on the developing reproductive system. Here we report on mothers' smoking, coffee and alcohol use, recorded during pregnancy, and semen quality in sons in the age group of 38-47 years. Subjects were a subset of the Child Health and Development Studies, a pregnancy cohort enrolled between 1959 and 1967 in the Kaiser Foundation Health Plan near Oakland, California. In 2005, adult sons participated in a follow-up study (n = 338) and semen samples were donated by 196 participants. Samples were analyzed for sperm concentration, motility and morphology according to the National Cooperative Reproductive Medicine Network (Fertile Male Study) Protocol. Mean sperm concentration was reduced by approximately 16 million sperms for sons with high prenatal exposure (5 cups of maternal coffee use per day) compared with unexposed sons (P-value for decreasing trend = 0.09), which translates to a proportionate reduction of 25%. Mean percent motile sperm decreased by approximately 7 points (P-value = 0.04), a proportionate decline of 13%, and mean percent sperm with normal morphology decreased by approximately 2 points (P-value = 0.01), a proportionate decline of 25%. Maternal cigarette and alcohol use were not associated with son's semen quality. Adjusting for son's contemporary coffee, alcohol and cigarette use did not explain the maternal associations. Findings for son's coffee intake and father's prenatal coffee, cigarette and alcohol use were non-significant and inconclusive. These results contribute to the evidence that maternal coffee use during pregnancy may impair the reproductive development of the male fetus.

Hydroxylated PCB metabolites (OH-PCBs) in archived serum from 1950-60s California mothers: a pilot study.

We are studying participants selected from the Child Health and Development Studies (CHDS), a longitudinal birth cohort of over 20,000 California pregnancies between 1959 and 1967, for associations between maternal body burden of organochlorine contaminants and thyroid function. We designed a pilot study using 30 samples selected among samples with high and low PCB concentrations to evaluate the feasibility of measuring OH-PCBs in the larger study population. GC-ECD and GC-NCI/MS were used to determine PCBs and OH-PCBs as methyl derivatives, respectively. Maternal serum levels of Sigma11PCBs and Sigma8OH-PCB metabolites varied from 0.74 to 7.99 ng/mL wet wt. with a median of 3.05 ng/mL, and from 0.12 to 0.98 ng/mL wet wt. with a median of 0.39 ng/mL, respectively. Average concentrations of Sigma8OH-PCB metabolites in the high PCB group were significantly higher than those in the low PCB group (p < 0.05). The levels of OH-PCB metabolites were dependent on PCB levels (r = 0.58, p < 0.05) but approximately an order of magnitude lower (p < 0.05). The average ratio of Sigma8OH-PCBs to Sigma11PCBs was 0.14 +/- 0.08. The primary metabolite was 4-OH-CB187 followed by 4-OH-CB107. Both of these metabolites interfere with the thyroid system in in vitro, animal, and human studies. OH-PCBs were detectable in all archived sera analyzed, supporting the feasibility to measure OH-PCB metabolites in the entire cohort.

Blood harmane concentrations and dietary protein consumption in essential tremor.

BACKGROUND: Beta-carboline alkaloids (e.g., harmane) are highly tremorogenic chemicals. Animal protein (meat) is the major dietary source of these alkaloids. The authors previously demonstrated that blood harmane concentrations were elevated in patients with essential tremor (ET) vs controls. Whether this difference is due to greater animal protein consumption by patients or their failure to metabolize harmane is unknown. OBJECTIVE: The aim of this study was to determine whether patients with ET and controls differ with regard to 1) daily animal protein consumption and 2) the correlation between animal protein consumption and blood harmane concentration. METHODS: Data on current diet were collected with a semiquantitative food frequency questionnaire and daily calories and consumption of animal protein and other food types was calculated. Blood harmane concentrations were log-transformed (logHA). RESULTS: The mean logHA was higher in 106 patients than 161 controls (0.61 +/- 0.67 vs 0.43 +/- 0.72 g(-10)/mL, p = 0.035). Patients and controls consumed similar amounts of animal protein (50.2 +/- 19.6 vs 49.4 +/- 19.1 g/day, p = 0.74) and other food types (animal fat, carbohydrates, vegetable fat) and had similar caloric intakes. In controls, logHA was correlated with daily consumption of animal protein (r = 0.24, p = 0.003); in patients, there was no such correlation (r = -0.003, p = 0.98). CONCLUSIONS: The similarity between patients and controls in daily animal protein consumption and the absence of the normal correlation between daily animal protein consumption and logHA in patients suggests that another factor (e.g., a metabolic defect) may be increasing blood harmane concentration in patients.

Essential tremor: occupational exposures to manganese and organic solvents.

Occupational exposures to manganese and organic solvents cause parkinsonism as well as prominent action tremor, resembling essential tremor (ET), yet their association with ET has not been studied. These chemicals cause cerebellar pathology. Cerebellar changes have been linked with ET. Using lifetime occupational histories, the authors demonstrated that occupational exposures were similar in cases and controls, which does not support an etiologic link between occupational exposures to these chemicals and ET.

Elevation of blood beta-carboline alkaloids in essential tremor.

BACKGROUND: beta-Carboline alkaloids are normal body constituents but are also potent tremor-producing chemicals that are naturally present in the food chain. OBJECTIVE: To explore the hypothesis that high concentrations of beta-carboline alkaloids are associated with essential tremor (ET). METHODS: One hundred cases and 100 controls were frequency matched on age, sex, and ethnicity. Blood concentrations of harmane and harmine were quantified by high-performance liquid chromatography, blinded to clinical information. RESULTS: The mean log blood concentration of harmane was higher in cases than controls (0.72 +/- 0.53 vs 0.51 +/- 0.64 g(-10)/mL; p = 0.01). A nonparametric test on nontransformed data (median harmane = 5.21 g(-10)/mL in cases and 2.28 g(-10)/mL in controls) confirmed this difference (p = 0.005). The mean log blood concentration of harmine was 0.20 +/- 0.48 g(-10)/mL in cases and 0.10 +/- 0.65 g (-10)/mL in controls (p = 0.20). Log harmane concentrations were stratified based on the median value; 62% of cases vs 39% of controls had a high log harmane concentration (p = 0.001). Mean log harmane concentration was similar in the cases with (0.74 +/- 0.58 g(-10)/mL) and without (0.71 +/- 0.50 g(-10)/mL) an affected relative (p = 0.83). CONCLUSIONS: Blood concentrations of harmane were measured in ET cases compared with controls. Concentrations were elevated in cases with and without a family history of ET.

Methodology, inference and causation: environmental lead exposure and childhood intelligence.

Kaufman's critique of the literature on the associations between lead exposure and child intelligence raises important methodological and inferential points. We address the concerns he raises regarding measuring known and unknown confounders, statistical modeling, reverse causality and quality control. Mismeasurement of potential confounders of the lead-IQ relationship, such as parenting skills, parental intelligence, maternal smoking during pregnancy, or otitis media can either strengthen or weaken the estimated association between exposure and child intelligence. Despite some variability in design and measurement, a series of comprehensive prospective investigations in varied populations, by different sets of investigators, provided consistent replication; taken together these studies point to the conclusion that lead exposure has adverse consequences for child development, and that the deficits are likely to be small in comparison to the contribution of measured social factors.

Sperm morphology, motility, and concentration in fertile and infertile men.

BACKGROUND: Although semen analysis is routinely used to evaluate the male partner in infertile couples, sperm measurements that discriminate between fertile and infertile men are not well defined. METHODS: We evaluated two semen specimens from each of the male partners in 765 infertile couples and 696 fertile couples at nine sites. The female partners in the infertile couples had normal results on fertility evaluation. The sperm concentration and motility were determined at the sites; semen smears were stained at the sites and shipped to a central laboratory for an assessment of morphologic features of sperm with the use of strict criteria. We used classification-and-regression-tree analysis to estimate threshold values for subfertility and fertility with respect to the sperm concentration, motility, and morphology. We also used an analysis of receiver-operating-characteristic curves to assess the relative value of these sperm measurements in discriminating between fertile and infertile men. RESULTS: The subfertile ranges were a sperm concentration of less than 13.5 x 10(6) per milliliter, less than 32 percent of sperm with motility, and less than 9 percent with normal morphologic features. The fertile ranges were a concentration of more than 48.0 x 10(6) per milliliter, greater than 63 percent motility, and greater than 12 percent normal morphologic features. Values between these ranges indicated indeterminate fertility. There was extensive overlap between the fertile and the infertile men within both the subfertile and the fertile ranges for all three measurements. Although each of the sperm measurements helped to distinguish between fertile and infertile men, none was a powerful discriminator. The percentage of sperm with normal morphologic features had the greatest discriminatory power. CONCLUSIONS: Threshold values for sperm concentration, motility, and morphology can be used to classify men as subfertile, of indeterminate fertility, or fertile. None of the measures, however, are diagnostic of infertility.

Use of complementary and alternative medicine among women in New York City: a pilot study.

OBJECTIVE: This study documents the use of complementary and alternative medicine (CAM), among White, African American, and Hispanic/Latina women living in New York City. A pilot to a national survey of CAM use among American women, this study explores women's use of categories of CAM and various CAM practitioners, racial and ethnic differences in CAM use, and women's perceptions regarding the effectiveness of CAM. DESIGN AND LOCATION: Data were collected from women residing in New York City using random digit dialing/computer-assisted telephone interviewing (CATI). The sample of 300 had equal numbers of women (n = 100) who self-identified as White, Hispanic/Latina, and African American, equally stratified by age (below and above age 40). SUBJECTS: Eligibility requirements included self-identification as Anglo/white, African American, or Hispanic/Latina and between ages 18 and 80. MEASURES: Three distinct categories of CAM were explored: (1) medicinal teas, homeopathic remedies, herbs, vitamins; (2) yoga, meditation, spiritual practices; and (3) manual therapies including chiropractic, massage, acupressure. Health concerns of interest were those frequently described in prior focus groups, and included reproductive health issues (e.g., pregnancy, menstruation, menopause) as well as other common women's health problems (e.g., heart disease, high blood pressure, headaches). RESULTS: More than half the sample has used a CAM treatment or remedy, and 40% have visited a CAM practitioner. Among users, half have used only one of the CAM categories, approximately one third have used two, and 16% used all three. The category of CAM used most often was medicinal tea/herbs/vitamins; the practitioners visited most frequently were chiropractors (18%) and nutritionists (17%). Racial and ethnic differences in CAM use were minimal, and approximately one third of all treatments used were rated "very effective" by users. CONCLUSIONS: Substantial utilization of CAM remedies and treatments for a variety of women's health concerns is observed. Further inquiry with larger samples of women is recommended.

The Yugoslavia Prospective Lead Study: contributions of prenatal and postnatal lead exposure to early intelligence.

To investigate associations between the timing of lead (Pb) exposure on early intelligence, we examined the results of psychometric evaluations at ages 3, 4, 5, and 7 years, from 442 children whose mothers were recruited during pregnancy from a smelter town and a non-lead-exposed town in Yugoslavia. We compared the relative contribution of prenatal blood lead (BPb) with that of relative increases in BPb in either the early (0-2 years) or the later (from 2 years on) postnatal period to child intelligence measured longitudinally at ages 3 and 4 (McCarthy GCI), 5 (Wechsler Preschool and Primary Scale of Intelligence-Revised, WPPSI-R IQ), and 7 (Wechsler Intelligence Scale for Children-version III, WISC-III IQ), controlling for: Home Observation for Measurement of the Environment (HOME) quality; maternal age, intelligence, education, and ethnicity; and birthweight and gender. Elevations in both prenatal and postnatal BPb were associated with small decrements in young children's intelligence.

Lead exposure and motor functioning in 4(1/2)-year-old children: the Yugoslavia prospective study.

OBJECTIVE: To investigate associations between lead exposure and early motor development. STUDY DESIGN: We conducted standardized assessments of motor function (Bruininks-Oseretsky Test of Motor Proficiency and Beery Developmental Test of Visual-Motor Integration) at age 54 months in 283 children whose mothers were recruited in pregnancy from a smelter town and a non-lead-exposed town in Yugoslavia and who have been monitored twice yearly since birth. Blood lead concentration (BPb) was summarized in a measure reflecting the average of the child's semiannual serial log BPbs through 54 months. RESULTS: Multiple regression showed that taken together, anthropometric measures (birth weight, body mass index) and markers of a stimulating and organized home life (HOME scale, parental education and intelligence, availability of siblings) explained a significant 10% to 18% of the variance in motor functioning. Beyond these contributions, BPb was significantly associated with poorer fine motor and visual motor function but was unrelated to gross motor coordination. CONCLUSIONS: Modest associations between early lead exposure and fine motor and visual motor functioning appear even after statistical adjustment is done for other contributors to motor development. Associations with BPb are specific to these areas of motor skill; gross motor development was unaffected.

Use of complementary and alternative medicine among African-American and Hispanic women in New York City: a pilot study.

OBJECTIVE: To explore the use of complementary and alternative medicine (CAM) among African-American and Hispanic women residing in New York City, including use of specific treatments and practitioners, perceived effectiveness of CAM, and culturally specific words or expressions for CAM. METHODS: Focus groups were conducted with two groups of African-American and two groups of Hispanic women (age 18-40 and 41-80) as preparation for the development of a quantitative instrument to assess the prevalence and determinants of CAM use among women of various ethnic backgrounds. Participants were recruited using a standard random digit dial procedure. RESULTS: The most commonly used CAM remedies were teas and herbs, vitamins and nutritional supplements, prayer and spiritual healing, meditation and relaxation techniques. Practitioners most frequently seen were chiropractors, herbalists, and acupuncturists. Use of alternative remedies and practitioners, particularly the latter, was most common among older women in both groups. Younger Hispanic women reported the most skepticism toward CAM, especially when it was used by relatives as a substitute for conventional medical care. Overall, these African-American and Hispanic women used CAM for a wide range of health conditions and for prevention. Few racial and ethnic differences emerged in patterns of CAM use for either self-care or treatment by practitioners, but there was a distinct age variation, especially in attitudes toward CAM.

The Yugoslavia Prospective Study of environmental lead exposure.

The Yugoslavia Prospective Study of environmental lead exposure has studied the associations between exposure to lead and pregnancy outcomes; childhood neuropsychological, behavioral, and physical development; and hematologic, renal, and cardiovascular function. The cohort comprises 577 children born to women recruited at midpregnancy in two towns in Kosovo, Yugoslavia; one town is the site of a lead smelter, refinery, and battery plant and the other is 25 miles away and relatively unexposed. A sample of these children has been followed at 6-month intervals through 7.5 years of age. Blood lead concentrations ranged from 1 to 70 microg/dl. Exposure to lead was not associated with adverse pregnancy outcomes. Exposure was associated with modest decrements in intelligence, small increases in blood pressure, higher risks of proteinuria, small increases in behavior problems, and perturbed hematopoiesis. Only at low level exposures (i.e., <16 microg/dl) were small associations with decreased height found. We discuss methodological problems that may hinder causal interpretation of these data, namely, use of blood lead concentration as an exposure measure, confounding, and town-specific associations. We conclude that while reported associations are small, collectively they lend support to the notion that lead is a toxicant with numerous adverse health effects.

Efficacy of superovulation and intrauterine insemination in the treatment of infertility. National Cooperative Reproductive Medicine Network.

BACKGROUND: Induction of superovulation with gonadotropins and intrauterine insemination are frequently used to treat infertility. We conducted a large, randomized, controlled clinical trial of these treatments. METHODS: We studied 932 couples in which the woman had no identifiable infertility factor and the man had motile sperm. The couples were randomly assigned to receive intracervical insemination, intrauterine insemination, superovulation and intracervical insemination, or superovulation and intrauterine insemination. Treatment continued for four cycles unless pregnancy was achieved. RESULTS: The 231 couples in the group treated with superovulation and intrauterine insemination had a higher rate of pregnancy (33 percent) than the 234 couples in the intrauterine-insemination group (18 percent), the 234 couples in the group treated with superovulation and intracervical insemination (19 percent), or the 233 couples in the intracervical-insemination group (10 percent). Stratified, discrete-time Cox proportional-hazards analysis showed that the couples in the group treated with superovulation and intrauterine insemination were 3.2 times as likely to become pregnant as those in the intracervical-insemination group (95 percent confidence interval, 2.0 to 5.3) and 1.7 times as likely as those in the intrauterine-insemination group (95 percent confidence interval, 1.2 to 2.6). The couples in the intrauterine-insemination group and in the group treated with superovulation and intracervical insemination were nearly twice as likely to conceive as those in the intracervical-insemination group. CONCLUSIONS: Among infertile couples, treatment with induction of superovulation and intrauterine insemination is three times as likely to result in pregnancy as is intracervical insemination and twice as likely to result in pregnancy as is treatment with either superovulation and intracervical insemination or intrauterine insemination alone.

Hyperproduction of erythropoietin in nonanemic lead-exposed children.

Lead (Pb) poisoning has numerous effects on the erythropoietic system, but the precise mechanism whereby high dose exposure causes anemia is not entirely clear. We previously reported that Pb exposure is associated with depressed serum erythropoietin (EPO) in pregnant women residing in a Pb mining town and in a nonexposed town in Kosovo, Yugoslavia. In a prospective study, we tested the hypothesis that blood Pb concentration (BPb) may be associated with depressed EPO in children. BPb, hemoglobin (Hgb), and serum EPO were measured at ages 4.5, 6.5, and 9.5 years in 211, 178, and 234 children, respectively. At 4.5 years of age, mean BPbs were 38.9 and 9.0 microg/dl in the exposed and nonexposed towns, respectively; BPbs gradually declined to 28.2 and 6.5 microg/dl, respectively, by age 9.5 years. No differences were found in Hgb at any age. At age 4. 5 years, a positive association between BPb and EPO (beta = 0.21; p = 0.0001), controlled for Hgb, was found. The magnitude of this association declined to 0.11 at age 6.5 years (p = 0.0103) and 0.03 at age 9.5 years (p = 0.39). These results were confirmed using repeated measures analyses. We concluded that in Pb-exposed children, the maintenance of normal Hgb requires hyperproduction of EPO. With advancing age (and continuing exposure), this compensatory mechanism appears to be failing, suggesting a gradual loss of renal endocrine function due to Pb exposure.

Lead exposure and intelligence in 7-year-old children: the Yugoslavia Prospective Study.

For a prospective study of lead exposure and early development, we recruited pregnant women from a lead smelter town and from an unexposed town in Yugoslavia and followed their children through 7 years of age. In this paper we consider associations between lifetime lead exposure, estimated by the area under the blood lead (BPb) versus time curve (AUC7), and intelligence, with particular concern for identifying lead's behavioral signature. The Wechsler Intelligence Scales for Children-Version III (WISC-III) was administered to 309 7-year-old children, 261 of whom had complete data on intelligence, blood lead, and relevant sociodemographic covariates (i.e., Home Observation for the Measurement of the Environment (HOME), birth weight, gender, sibship size, and maternal age, ethnicity, intelligence, and education). These showed anticipated associations with 7-year intelligence, explaining 41-4% of the variance in Full Scale, Performance, and Verbal IQ. Before covariate adjustment, AUC7 was unrelated to intelligence; after adjustment, AUC7 explained a significant 2.8%-4.2% of the variance in IQ. After adjustment, a change in lifetime BPb from 10 to 30 micro/dl related to an estimated decrease of 4.3 Full Scale IQ points; estimated decreases for Verbal and Performance IQ were 3.4 and 4.5 points, respectively. AUC7 was significantly and negatively related to three WISC-III factor scores: Freedom from Distractibility, Perceptual Organization, and Verbal Comprehension; the association with Perceptual Organization was the strongest. Consistent with previous studies, the IQ/lead association is small relative to more powerful social factors. Findings offer support for lead's behavioral signature; perceptual-motor skills are significantly more sensitive to lead exposure than are the language-related aspects of intelligence.

Blood lead and blood pressure in young children.

We examined associations between blood lead concentration (BPb) and blood pressure in 282 children age 5.5 years, residing in an exposed or unexposed town in Kosovo, Yugoslavia. Mean BPb in the exposed town was 37.3 micrograms per dl (standard deviation = 12.0 micrograms per dl) and in the unexposed town was 8.7 micrograms per dl (standard deviation = 2.8 micrograms per dl). After adjustment, a 10 micrograms per dl increase in BPb was associated with a 0.5 (95% CL = -0.2, 1.3) mmHg increase in systolic and a 0.4 (95%, CL = -0.1, 0.9) mmHg increase in diastolic blood pressure. These associations, although compatible with no relation, are similar to those observed in adults; and the data are most consistent with a small association between BPb and blood pressure.