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Biomedical subjects

Matthew P Longnecker

Publications and source records attributed to Matthew P Longnecker.

At least 19 recordsLinked to original sources

Serum organochlorines and breast cancer: a case-control study among African-American women.

This population-based case-control study of African-American women (355 breast cancer case patients, 327 controls) examined the association between breast cancer and circulating levels of PCBs and dichlorodiphenyldichloroethene (DDE), a metabolite of DDT. Case patients were diagnosed with invasive breast carcinoma and interviewed between June 1995 and July 1998, and control subjects were identified by random digit dialing methods. Serum levels of DDE and total PCBs were adjusted for total lipid content. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable unconditional logistic regression methods. Effect modification by tumor receptor status and cancer treatment was investigated. Breast cancer risk was not associated with increasing quintiles of lipid-adjusted PCBs or DDE (highest versus lowest quintile adjusted for age, body mass index (BMI) and breastfeeding for DDE: OR = 1.02, 95% CI = (0.61, 1.72), p-trend = 0.74; for PCBs: OR = 1.01, 95% CI = (0.63, 1.63), p-trend = 0.56). Risk did not differ by strata of BMI, breastfeeding, parity, menopausal status or tumor receptor status. This study, the largest study of African-American women to date, does not support a role of DDE and total PCBs in breast cancer risk at the levels measured.

Adult↗

Maternal hormone levels and perinatal characteristics: implications for testicular cancer.

PURPOSE: It was hypothesized that the risk for testicular germ cell tumors (TGCTs) is associated with maternal hormone levels. To examine the hypothesis, some studies used perinatal factors as surrogates for hormone levels. To determine the validity of this assumption, hormone-perinatal factor relationships were examined in the Collaborative Perinatal Project. METHODS: Maternal estradiol, estriol, and testosterone levels in first- and third-trimester serum samples were correlated with perinatal factors in 300 mothers representative of populations at high (white Americans) or low (black Americans) risk for TGCT. RESULTS: For white participants, testosterone levels were associated negatively with maternal height (p < 0.01) and age (p = 0.02) and positively with maternal weight (p = 0.02) and body mass index (BMI; p < 0.01), whereas estradiol levels were associated negatively with height (p = 0.03) and positively with son's birth weight (p = 0.04). For black participants, estriol levels were associated negatively with maternal weight (p = 0.01), BMI (p = 0.02), and gestational age p < 0.01) and positively with son's birth weight (p < 0.01), length (p = 0.04), and head circumference (p = 0.03). CONCLUSIONS: These findings indicate that use of perinatal characteristics as surrogates for hormone levels should be limited to a specific ethnic group. For white men, previously reported associations of TGCT with maternal weight and age may be caused by lower maternal testosterone levels.

Black or African American↗

Prenatal exposure to 1,1-dichloro-2,2-bis (p-chlorophenyl)ethylene (p,p'-DDE) in relation to child growth.

OBJECTIVE: To examine the relation between prenatal 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) exposure (a metabolite of the insecticide DDT) and child growth during the first 7 years of life. Design Prospective cohort study. Participants 1,712 children born between 1959 and 1966 with measured p,p'-DDE concentrations in their mother's serum samples from pregnancy. Setting Multicenter US Collaborative Perinatal Project (CPP). RESULTS: The highest prenatal concentrations of p,p'-DDE (>or=60 microg/l), as compared with the lowest (<15 microg/l), were associated with decreased height at age 1 year [adjusted coefficient (SE) = -0.72 cm (0.37), n = 1,540], 4 years [-1.14 cm (0.56), n = 1,289], and 7 years [-2.19 (0.46), n = 1,371]. Among subjects in lower categories of exposure no association was observed. CONCLUSIONS: The findings suggest that high prenatal exposure to p,p'-DDE decreases height in children. Impaired growth may be a general indicator of toxicity and suggests that specific organ systems (e.g. endocrine) could be affected.

Adult↗

Risk factors for cryptorchism among populations at differing risks of testicular cancer.

BACKGROUND: Cryptorchism is strongly associated with the development of testicular germ cell tumours (TGCTs), possibly owing to a common aetiology. However, while TGCT incidence varies greatly between white and black men, little variability has been reported between the two groups in cryptorchism prevalence. This may suggest that cryptorchism risk factors differ by ethnicity. METHODS: To examine this hypothesis, a prospective analysis was conducted among black and white participants in the US Collaborative Perinatal Project. White participants included 238 cryptorchid sons and 12,296 non-cryptorchid sons, while black participants included 188 cryptorchid sons and 11,942 non-cryptorchid sons. RESULTS: While cryptorchism was significantly more common among white sons (1.90% vs 1.55%; P = 0.04), the difference was incompatible with the 5-fold difference in TGCT rates. The principal maternal risk factors among white sons were age (P = 0.03), hypertension/proteinuria (P = 0.006), and length of time to become pregnant (P = 0.055), while major maternal risk factors among black sons were age (P = 0.06), height (P = 0.007), weight (P = 0.06), and radiation exposure (P = 0.02). Only maternal height, however, had a different relationship with risk among black and white sons. Neonatal associations with risk (shorter gestational age, lower birthweight, shorter length) were similar in the two groups. CONCLUSIONS: These results do not support the hypothesis that the risk factors for cryptorchism vary dramatically by ethnicity but may suggest that cryptorchism is not as closely linked to TGCT among black men as among white men.

Birth Weight↗

Volatile organic compounds and pulmonary function in the Third National Health and Nutrition Examination Survey, 1988-1994.

BACKGROUND: Volatile organic compounds (VOCs) are present in much higher concentrations indoors, where people spend most of their time, than outdoors and may have adverse health effects. VOCs have been associated with respiratory symptoms, but few studies address objective respiratory end points such as pulmonary function. Blood levels of VOCs may be more indicative of personal exposures than are air concentrations; no studies have addressed their relationship with respiratory outcomes. OBJECTIVE: We examined whether concentrations of 11 VOCs that were commonly identified in blood from a sample of the U.S. population were associated with pulmonary function. METHODS: We used data from 953 adult participants (20-59 years of age) in the Third National Health and Nutrition Examination Survey (1988-1994) who had VOC blood measures as well as pulmonary function measures. Linear regression models were used to evaluate the relationship between 11 VOCs and measures of pulmonary function. RESULTS: After adjustment for smoking, only 1,4-dichlorobenzene (1,4-DCB) was associated with reduced pulmonary function. Participants in the highest decile of 1,4-DCB concentration had decrements of -153 mL [95% confidence interval (CI) , -297 to -8] in forced expiratory volume in 1 sec and -346 mL/sec (95% CI, -667 to -24) in maximum mid-expiratory flow rate, compared with participants in the lowest decile. CONCLUSIONS: Exposure to 1,4-DCB, a VOC related to the use of air fresheners, toilet bowl deodorants, and mothballs, at levels found in the U.S. general population, may result in reduced pulmonary function. This common exposure may have long-term adverse effects on respiratory health.

Adult↗

Maternal smoking during pregnancy in relation to child overweight: follow-up to age 8 years.

BACKGROUND: Data from several studies indicate that children of mothers who smoked during pregnancy may be at a risk of overweight compared with children of non-smoking mothers. The size of this relation, however, is unclear, as is the age at which it becomes detectable. METHODS: Prospective data for 34 866 children enrolled in the US Collaborative Perinatal Project were analysed to examine maternal pregnancy smoking in relation to weight, height, and body mass index (BMI) in offspring at ages 1, 3, 4, 7, and 8 years. RESULTS: Compared with offspring of non-smokers, children of smokers had (i) weight that was lower at birth but then quickly equalled or exceeded that of non-smokers, (ii) consistently decreased height, and (iii) increased risk of overweight, particularly in girls. For example, at age 7 years, the adjusted odds ratio of BMI>or=85th percentile in boys of mothers who smoked on an average>or=20 cigarettes per day while pregnant was 1.22 (95% confidence interval 1.03-1.46), and in girls it was 1.30 (1.08-1.56). CONCLUSIONS: In these data, maternal smoking during pregnancy was associated with a modest increase in risk of overweight in children before the age of 8 years.

Birth Weight↗

Maternal serum levels of polychlorinated biphenyls and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) and time to pregnancy.

Polychlorinated biphenyls (PCBs), once used widely in transformers and other applications, and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), the main metabolite of the pesticide 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), are hormonally active agents. Changes in menstrual cycle functioning associated with PCBs and DDE, and increased odds of spontaneous abortion associated with DDE, suggest that these compounds could affect fertility. The authors investigated the association between PCB and DDE exposure and time to pregnancy by using serum levels measured in 390 pregnant women in the Collaborative Perinatal Project enrolled at 12 study centers in the United States from 1959 to 1965. They estimated adjusted fecundability odds ratios by using Cox proportional hazards modeling for discrete time data. Compared with time to pregnancy for women in the lowest exposure category (PCBs < 1.24 microg/liter, DDE < 14 microg/liter), time to pregnancy increased for women in the highest exposure category in terms of both PCBs (fecundability odds ratio for PCBs > or = 5.00 microg/liter = 0.65, 95% confidence interval: 0.36, 1.18) and DDE (fecundability odds ratio for DDE > or = 60 microg/liter = 0.65, 95% confidence interval: 0.32, 1.31). Overall, time to pregnancy increased with increasing serum PCB levels but was less suggestive of an association with DDE. Both trends were imprecise and attenuated when expressed on a lipid basis. Overall, evidence of an association between PCB or DDE exposure and time to pregnancy was weak and inconclusive.

Adult↗

In utero exposure to background levels of polychlorinated biphenyls and cognitive functioning among school-age children.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants. In utero exposure to background levels of PCBs has been associated with intellectual impairment among children in most, but not all, studies. The authors evaluated prenatal PCB exposure in relation to cognitive test (intelligence quotient (IQ)) scores on the Wechsler Intelligence Scale for Children at age 7 years. Pregnant women were recruited from 12 US study centers from 1959 to 1965, and their children were followed until age 7 years (the Collaborative Perinatal Project). Third trimester serum was analyzed for PCBs in 1997-1999 for 732 women selected at random and for an additional 162 women whose children had either a low or a high IQ score. The PCB-IQ association was examined in multivariate models. Among those in the lowest exposure category (<1.25 microg of PCB/liter of serum), the fully adjusted mean IQ score was 93.6 (standard error: 1.8); among those in the highest category (> or =5 microg of PCB/liter), the mean IQ was 97.6 (standard error: 1.2); and overall the increase in IQ per unit increase in PCB level (microg/liter) was 0.22 (95% confidence interval: -0.28, 0.71). In these data, in utero exposure to background levels of PCBs was not associated with lower IQ at age 7 years.

Abnormalities, Drug-Induced↗

Blood mercury level and blood pressure among US women: results from the National Health and Nutrition Examination Survey 1999-2000.

Exposure to mercury has been linked to elevations in blood pressure (BP), though few data are available. We examined the cross-sectional relationship between blood mercury concentration and BP in a representative US sample of 1240 women, aged 16-49 years, from the National Health and Nutrition Examination Survey 1999-2000. We found no association overall between mercury and BP in multivariate models. We stratified our data by dietary fish intake (presumably reflecting the consumption of long-chain n-3 fatty acids that may reduce BP) resulting in 759 fish consumers and 481 non-fish consumers. We found that for each 1.3 microg/L (interquartile distance) increase in mercury, systolic BP significantly increased by 1.83 mm Hg (95% CI: 0.36, 3.30) among non-fish consumers. A similar pattern was seen for diastolic BP, although it was non-significant. While an adverse effect of mercury exposure at background levels on BP was not present overall, an adverse association was present among non-fish-consuming young and middle-aged women.

Adolescent↗

Maternal serum level of the DDT metabolite DDE in relation to fetal loss in previous pregnancies.

Use of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) continues in about 25 countries. This use has been justified partly by the belief that it has no adverse consequences on human health. Evidence has been increasing, however, for adverse reproductive effects of DDT, but additional data are needed. Pregnant women who enrolled in the Collaborative Perinatal Project (United States, 1959-1965) were asked about their previous pregnancy history; blood samples were drawn and the serum frozen. In 1997-1999, the sera of 1717 of these women who had previous pregnancies were analyzed for 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), the major breakdown product of DDT. The odds of previous fetal loss was examined in relation to DDE level in logistic regression models. Compared with women whose DDE level was <15 microg/L, the adjusted odds ratios of fetal loss according to category of DDE were as follows: 15-29 microg/L, 1.1; 30-44 microg/L, 1.4; 45-59 microg/L, 1.6; and 60+ microg/L, 1.2. The adjusted odds ratio per 60 microg/L increase was 1.4 (95% confidence interval 1.1-1.6). The results were consistent with an adverse effect of DDE on fetal loss, but were inconclusive owing to the possibility that previous pregnancies ending in fetal loss decreased serum DDE levels less than did those carried to term.

Abortion, Spontaneous↗

Polychlorinated biphenyls and menstrual cycle characteristics.

BACKGROUND: Experimental studies in nonhuman primates provide evidence that low-level exposure to persistent organochlorine pollutants such as polychlorinated biphenyls (PCBs) may affect aspects of their menstrual cycle, including cycle length, regularity, and bleeding duration. Few studies have examined these associations in humans. METHODS: We used data from 2314 pregnant women who participated in the Collaborative Perinatal Project, a cohort study that enrolled pregnant women in the 1960s in 12 centers in the United States. Information about usual (prepregnancy) menstrual cycle length, regularity, bleeding duration, and dysmenorrhea was collected at enrollment, and 11 PCBs and p,p'-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) were measured in stored blood samples collected during the third trimester of pregnancy. We used multivariate linear and logistic regression to examine the association between organochlorine levels and menstrual cycles, adjusting for demographic factors, cholesterol, and triglycerides. RESULTS: Total PCBs were positively associated with increasing menstrual cycle length (adjusted difference across 5 categories of PCB exposure = 0.7 days, trend-test P value = 0.02). Irregular cycles were slightly more frequent among those in the 2 highest categories of PCB exposure (odds ratio for highest category = 1.5; 95% confidence interval = 0.70-3.3), and there also was some evidence of an association with DDE. The strengths of these associations increased with various exclusions made to decrease potential misclassification of the outcome and the exposures. There was little evidence for associations between DDE or PCBs and bleeding duration, heavy bleeding, or dysmenorrhea. CONCLUSIONS: This study supports experimental studies in monkeys showing an effect of low-dose PCB exposure on menstrual function.

Adolescent↗

Maternal levels of polychlorinated biphenyls in relation to preterm and small-for-gestational-age birth.

BACKGROUND: In developed countries, polychlorinated biphenyls (PCBs) are ubiquitous contaminants of the environment, including foods. Within the range of the resulting low-level exposure, associations of PCBs with lower birth weight have been observed in several studies. METHODS: To examine further the association of PCBs with birth outcomes, we measured serum levels in 1034 pregnant women who were enrolled in the U.S. Collaborative Perinatal Project in 1959 to 1965 before PCB manufacturing was banned. RESULTS: The multivariate-adjusted odds ratio for preterm birth among those with PCB levels of >/=4 microg/L of total PCBs, compared with those with <2 microg/L, was 1.1 (95% confidence interval = 0.6-2.2); for the same exposure contrast, the odds ratio for delivering an infant who was small-for-gestational-age at birth was 1.6 (0.7-3.7). Birth weight and length of gestation were essentially unrelated to PCB level. CONCLUSIONS: In these data, maternal levels of PCBs during pregnancy were essentially unrelated to preterm birth, birth weight, or length of gestation. An association of PCBs with small-for-gestational-age birth was observed, but the results were inconclusive and occurred in the absence of an overall decrease in birth weight.

Adult↗

Maternal hormone levels and risk of cryptorchism among populations at high and low risk of testicular germ cell tumors.

Cryptorchism is one of the few well-described risk factors for testicular cancer. It has been suggested that both conditions are related to increased in utero estrogen exposure. The evidence supporting the "estrogen hypothesis" has been inconsistent, however. An alternative hypothesis suggests that higher in utero androgen exposure may protect against the development of cryptorchism and testicular cancer. In order to examine both hypotheses, we studied maternal hormone levels in two populations at diverse risks of testicular cancer; Black Americans (low-risk) and White Americans (high-risk). The study population of 200 mothers of cryptorchid sons and 200 mothers of noncryptorchid sons was nested within the Collaborative Perinatal Project, a cohort study of pregnant women and their children. Third trimester serum levels of estradiol (total, free, bioavailable), estriol, testosterone (total, free, bioavailable), sex hormone-binding globulin, alpha-fetoprotein, and the ratios of estradiols to testosterones were compared between the case and control mothers. The results found no significant differences in the levels of testosterone (total, free, bioavailable), alpha-fetoprotein, sex hormone-binding globulin, or in the ratios of estrogens to androgens. Total estradiol, however, was significantly lower in the cases versus the controls (P = 0.03) among all mothers and, separately, among White mothers (P = 0.05). Similarly, estriol was significantly lower among all cases (P = 0.05) and among White cases (P = 0.05). These results do not support either the estrogen or the androgen hypothesis. Rather, lower estrogens in case mothers may indicate that a placental defect increases the risk of cryptorchism and, possibly, testicular cancer.

Adult↗

Anogenital distance in human male and female newborns: a descriptive, cross-sectional study.

BACKGROUND: In animal studies of the effects of hormonally active agents, measurement of anogenital distance (AGD) is now routine, and serves as a bioassay of fetal androgen action. Although measurement of AGD in humans has been discussed in the literature, to our knowledge it has been measured formally in only two descriptive studies of females. Because AGD has been an easy-to-measure, sensitive outcome in animals studies, we developed and implemented an anthropometric protocol for measurement of AGD in human males as well as females. METHODS: We first evaluated the reliability of the AGD measures in 20 subjects. Then measurements were taken on an additional 87 newborns (42 females, 45 males). All subjects were from Morelos, Mexico. RESULTS: The reliability (Pearson r) of the AGD measure was, for females 0.50, and for males, 0.64. The between-subject variation in AGD, however, was much greater than the variation due to measurement error. The AGD measure was about two-fold greater in males (mean, 22 mm) than in females (mean, 11 mm), and there was little overlap in the distributions for males and females. CONCLUSION: The sexual dimorphism of AGD in humans comprises prima facie evidence that this outcome may respond to in utero exposure to hormonally active agents.

Anal Canal↗

Ovarian cancer risk and use of phenolphthalein-containing laxatives.

PURPOSE: Experimental studies in rodents demonstrated the carcinogenic potential of phenolphthalein, the active ingredient in some laxatives, administered at doses similar to the dose that could be used by humans. Ovarian cancer was one of the cancers observed in these studies. We examined the association between epithelial ovarian cancer and use of phenolphthalein-containing laxatives in a population-based case-control study. METHODS: The study includes 356 epithelial ovarian cancer cases (256 invasive, 100 borderline) and 424 controls. Cases were identified through a population-based registry in Los Angeles County in 1992-1998, and controls were matched to cases by age, race/ethnicity and neighborhood. Data on laxative use (specific brands, frequency of use, usual dose) were obtained by structured in-person interview. RESULTS: Compared to women who never used a laxative, ever use of a phenolphthalein-containing laxative was not associated with an increased risk of invasive ovarian cancer (odds ratio (OR) 1.1, 95% confidence interval (CI) 0.75, 1.5) or of borderline ovarian cancer (OR 0.75, 95%CI 0.37, 1.5). Total days used, mean number of pills per day and cumulative dose were also unrelated to risk. CONCLUSIONS: This study provides some assurance that phenolphthalein-containing laxatives do not increase the risk of ovarian cancer in humans. These findings are of particular importance to those countries in which phenolphthalein is still used in over-the-counter medications.

Adult↗

Fish intake during pregnancy and early cognitive development of offspring.

BACKGROUND: Fish is a source of many nutrients that can be beneficial during pregnancy, as well as a source of neurotoxicant contaminants such as methylmercury. Previous investigations of fish intake in relation to neurodevelopment have focused on possible damage from contaminants, whereas potential benefits of fish consumption have been relatively unexplored METHODS: We evaluated the association between maternal fish intake during pregnancy and offspring's early development of language and communication skills in a cohort of 7421 British children born in 1991-1992. Fish intake by the mother and child was measured by questionnaire. The child's cognitive development was assessed using adaptations of the MacArthur Communicative Development Inventory at 15 months of age and the Denver Developmental Screening Test at 18 months of age. Mercury was measured in umbilical cord tissue for a subset of 1054 children RESULTS: Total mercury concentrations were low and were not associated with neurodevelopment. Fish intake by the mother during pregnancy, and by the infant postnatally, was associated with higher mean developmental scores. For example, the adjusted mean MacArthur comprehension score for children whose mothers consumed fish 4 or more times per week was 72 (95% confidence interval = 71-74), compared with 68 (66-71) among those whose mothers did not consume fish. CONCLUSIONS: When fish is not contaminated, moderate fish intake during pregnancy and infancy may benefit development.

Adult↗