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B Eskenazi

Publications and source records attributed to B Eskenazi.

At least 19 recordsLinked to original sources

The effects of male age on sperm DNA damage in healthy non-smokers.

BACKGROUND: The trend for men to have children at older age raises concerns that advancing age may increase the production of genetically defective sperm, increasing the risks of transmitting germ-line mutations. METHODS: We investigated the associations between male age and sperm DNA damage and the influence of several lifestyle factors in a healthy non-clinical group of 80 non-smokers (mean age: 46.4 years, range: 22-80 years) with no known fertility problems using the sperm Comet analyses. RESULTS: The average percentage of DNA that migrated out of the sperm nucleus under alkaline electrophoresis increased with age (0.18% per year, P = 0.006), but there was no age association for damage measured under neutral conditions (P = 0.7). Men who consumed >3 cups coffee per day had approximately 20% higher percentage tail DNA under neutral but not alkaline conditions compared with men who consumed no caffeine (P = 0.005). CONCLUSIONS: Our findings indicate that (i) older men have increased sperm DNA damage associated with alkali-labile sites or single-strand DNA breaks and (ii) independent of age, men with substantial daily caffeine consumption have increased sperm DNA damage associated with double-strand DNA breaks. DNA damage in sperm can be converted to chromosomal aberrations and gene mutations after fertilization, increasing the risks of developmental defects and genetic diseases among offspring.

Adult↗

Exogenous shocks to the human sex ratio: the case of September 11, 2001 in New York City.

BACKGROUND: The human secondary sex ratio reportedly falls in populations subjected to exogenous stressors such as earthquakes or political and social upheavals. Explanations of the association include reduced conception of males and increased fetal deaths among males. The latter explanation has been supported by research reporting that the sex ratio in California fell 3 months, but not 8, 9 or 10 months, after the terrorist attacks of September 11, 2001. California's distance from the attacks raises the questions of whether the results arose from chance and would be found elsewhere. We contribute to the literature by testing the association between the secondary sex ratio and the events of September 11 in New York City. METHODS: We replicate the California tests by applying interrupted time-series methods, which control for secular trends, seasonality and other forms of autocorrelation, to 91 cohorts born in New York City during 28-day periods from January 1996 to June 2002. RESULTS: As hypothesized, the sex ratio in New York City in the period 1 January to 28 January 2002 fell to 1, which was the lowest observed value during the test period and significantly (i.e. P < 0.01, two-tailed test) below the value expected from history. CONCLUSIONS: Our findings support the male fetal loss explanation of the association between exogenous population shocks and the secondary sex ratio.

Birth Rate↗

Quantitative effects of male age on sperm motion.

BACKGROUND: Semen quality is associated with fertility status, but there is little quantitative information on risk factors that affect semen quality, especially in non-clinical populations. Advancing male age has been associated with a decline in semen quality, with the largest effect being on sperm motility. However, there is little quantitative data on the specific components of sperm motion that are affected by male age. METHODS: We performed linear regression analyses of 14 aspects of semen quality measured by computer-assisted semen analysis (CASA) in a non-clinical cohort of 90 non-smoking men, aged 22-80 years, who had no history of infertility or reproductive problems. RESULTS: We found age-associated declines in CASA-determined motility (% motile, 0.8% per year; % progressively motile, 0.9% per year; % rapidly motile, 0.4% per year, P <or= 0.001) and three quantitative aspects of sperm motion [linearity (LIN), 0.2% per year; straight line velocity (VSL), 0.2% per year, and average path velocity (VAP), 0.3% per year, P < 0.05], with no evidence for age thresholds and no significant association with abstinence duration. Age was not significantly associated with amplitude of lateral head (ALH) displacement, beat cross frequency (BCF) and nuclear elongation or size. CONCLUSIONS: Quantitative analysis of sperm motion indicates that as men age, they produce fewer motile sperm, which are able to travel less along a linear path, thus covering less forward distance per unit time. These findings may have fertility implications for men who choose to delay fatherhood.

Adult↗

Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm.

This study compares the relative effects of advancing male age on multiple genomic defects in human sperm [DNA fragmentation index (DFI), chromatin integrity, gene mutations, and numerical chromosomal abnormalities], characterizes the relationships among these defects and with semen quality, and estimates the incidence of susceptible individuals for a well characterized nonclinical nonsmoking group of 97 men (22-80 years). Adjusting for confounders, we found major associations between age and the frequencies of sperm with DFI and fibroblast growth factor receptor 3 gene (FGFR3) mutations associated with achondroplasia (P < 0.01) with no evidence for age thresholds. However, we found no associations between age and the frequencies of sperm with immature chromatin, aneuploidies/diploidies, FGFR2 mutations (Apert syndrome), or sex ratio in this cohort. There were also no consistent correlations among genomic and semen-quality endpoints, except between DFI and sperm motility (r = -0.65, P < 0.001). These findings suggest there are multiple spermatogenic targets for genomically defective sperm with substantially variable susceptibilities to age. Our findings predict that as healthy males age, they have decreased pregnancy success with trends beginning in their early reproductive years, increased risk for producing offspring with achondroplasia mutations, and risk of fathering offspring with Apert syndrome that may vary across cohorts, but with no increased risk for fathering aneuploid offspring (Down, Klinefelter, Turner, triple X, and XYY syndromes) or triploid embryos. Our findings also suggest that the burden of genomic damage in sperm cannot be inferred from semen quality, and that a small fraction of men are at increased risk for transmitting multiple genetic and chromosomal defects.

Achondroplasia↗

Antioxidant intake is associated with semen quality in healthy men.

BACKGROUND: We seek to determine whether dietary and supplement intake of specific micronutrients (zinc and folate) and antioxidants (vitamins C, E and beta-carotene) is associated with semen quality. METHODS: Ninety-seven healthy, non-smoking men provided semen and were interviewed. Average daily nutrient intake from food and supplements was derived from a self-administered food frequency questionnaire. Intake levels were summarized as low, moderate and high. Semen volume, sperm concentration, total sperm count, motility, progressive motility and total progressively motile sperm count (TPMS) were measured. RESULTS: After controlling for covariates, a high intake of antioxidants was associated with better semen quality but, in almost all cases, there was no clear dose relationship in that moderate intake groups had the poorest semen quality. For example, positive associations were observed between vitamin C intake and sperm number as reflected in the higher mean count (P=0.04), concentration (P=0.05) and TPMS (P = 0.09); between vitamin E intake and progressive motility (P = 0.04) and TPMS (P = 0.05); and between beta-carotene intake and sperm concentration (P = 0.06) and progressive motility (P = 0.06). Folate and zinc intake were not associated with improved semen quality. CONCLUSIONS: In a convenience sample of healthy non-smoking men from a non-clinical setting, higher antioxidant intake was associated with higher sperm numbers and motility.

Adult↗

Uterine leiomyoma and menstrual cycle characteristics in a population-based cohort study.

BACKGROUND: We examined the association of uterine leiomyoma with menstrual cycle characteristics in a population of non-care-seeking women. METHODS: This cross-sectional study uses data from the Seveso Women's Health Study (SWHS), a population-based cohort in Italy. Participants included 341 premenopausal women, 30-60 years old, who had an intact uterus and were not pregnant, lactating, or using oral contraception or intra-uterine devices. We examined the presence of any ultrasound-detected uterine leiomyoma in relation to self-reported menstrual cycle length, flow length and heaviness of flow. The association of leiomyoma number, volume, tissue layer location and axial position with menstrual cycle characteristics was also examined. RESULTS: Uterine leiomyomata were detected in 73 women (21.4%). After adjustment for covariates, the presence of a leiomyoma was not significantly related to menstrual cycle length, flow length or heaviness of flow [odds ratio (OR) for scanty flow =1.9, 95% confidence interval (CI) 0.8-4.3; OR for heavy flow =1.3, 95% CI 0.7-2.5; relative to moderate flow]. Number, volume, tissue layer location (subserosal or intramural) and axial position (anterior or posterior) of the leiomyoma were also not related to menstrual cycle characteristics. CONCLUSION: In this Italian population of women not seeking gynaecological care, menstrual characteristics are not related to leiomyoma.

Adult↗

The association of age and semen quality in healthy men.

BACKGROUND: Although the effect of maternal age on fertility is well known, it is unclear whether paternal age also affects fertility. This cross-sectional study sought to characterize the association between age and semen quality, a well-known proxy of fertility status. METHODS: A convenience sample of 97 non-smoking men (aged 22-80 years) without known fertility problems was recruited from a national government laboratory. The men provided semen samples and information relating to lifestyle, diet, medical and occupational details. Semen volume (ml), sperm concentration (x10(6)/ml), total sperm count (x10(6)), motility (%), progressive motility (%) and total progressively motile sperm count (x10(6)) were measured. RESULTS: After adjusting for covariates, semen volume decreased by 0.03 ml per year of age (95% CI: -0.05, -0.01); motility decreased by 0.7% per year (95% CI: -0.92, -0.43); progressive motility decreased by 3.1% per year (95% CI: -4.5, -1.6); and total progressively motile sperm count decreased by 4.7% per year (95% CI: -7.2, -2.2). There was a suggested decrease in sperm concentration and count. The proportion of men with abnormal volume, concentration and motility was significantly increased across the age decades. CONCLUSIONS: In a convenience sample of healthy men from a non-clinical setting, semen volume and sperm motility decreased continuously between 22-80 years of age, with no evidence of a threshold.

Adult↗

Sperm aneuploidy in fathers of children with paternally and maternally inherited Klinefelter syndrome.

BACKGROUND: It is unclear whether frequency of sperm aneuploidy is associated with risk of fathering children with trisomy. METHODS: We recruited 36 families with a boy with Klinefelter syndrome (KS), interviewed the fathers about their exposures and medical history, received a semen sample from each father, and collected blood samples from the mother, father and child. We applied a multicolour fluorescent in-situ hybridization assay to compare the frequencies of sperm carrying XY aneuploidy and disomies X, Y and 21 in fathers of maternally and paternally inherited KS cases. RESULTS: Inheritance of the extra X chromosome was paternal in 10 and maternal in 26 families. Fathers of paternal KS cases produced higher frequencies of XY sperm (P = 0.02) than fathers of maternal KS cases. After controlling for age, the major confounding variable, the difference between the two groups was no longer significant (P less-than-or-equal 0.2). Also, there were no significant differences between the parental origin groups for disomy X, Y or 21. CONCLUSIONS: Men who fathered a child with a Klinefelter syndrome produced higher frequencies of XY sperm aneuploidy, which is explained, in part, by both paternal age and parent of origin.

Adult↗

Frequency of XY sperm increases with age in fathers of boys with Klinefelter syndrome.

With increasing availability of drugs for impotence and advanced reproductive technologies for the treatment of subfertility, more men are fathering children at advanced ages. We conducted a study of the chromosomal content of sperm of healthy men aged 24-57 years to (a) determine whether father's age was associated with increasing frequencies of aneuploid sperm including XY, disomy X, disomy Y, disomy 21, and sperm diploidy, and (b) examine the association between the frequencies of disomy 21 and sex-chromosomal aneuploidies. The study group consisted of 38 fathers of boys with Klinefelter syndrome (47, XXY) recruited nationwide, and sperm aneuploidy was assessed using multicolor X-Y-21 sperm FISH ( approximately 10,000 sperm per donor). Paternal age was significantly correlated with the sex ratio of sperm (Y/X; P=.006) and with the frequency of XY sperm (P=.02), with a clear trend with age by decades (P<.006). Compared with fathers in their 20s (who had an average frequency of 7.5 XY sperm per 10,000), the frequencies of XY sperm were 10% higher among fathers in their 30s, 31% higher among those in their 40s, and 160% higher among those in their 50s (95% CI 69%-300%). However, there was no evidence for age effects on frequencies of sperm carrying nullisomy sex; disomies X, Y, or 21; or meiosis I or II diploidies. The frequencies of disomy 21 sperm were significantly associated with sex-chromosomal aneuploidy (P=.04)-in particular, with disomy X (P=.004), but disomy 21 sperm did not preferentially carry either sex chromosome. These findings suggest that older fathers produce higher frequencies of XY sperm, which may place them at higher risk of fathering boys with Klinefelter syndrome, and that age effects on sperm aneuploidy are chromosome specific.

Adult↗

Effects of male age on semen quality and fertility: a review of the literature.

OBJECTIVE: To review the literature on the association between male age and semen quality (semen volume, concentration, motility, and morphology) and fertility status (pregnancy rate and time to pregnancy/subfecundity). METHOD(S): Review of English language-published research over the last 20 years from January 1, 1980, through December 31, 1999, using MEDLINE and Biosis databases. Studies with insufficient numbers of subjects, case reports, case series, or anecdotal data were excluded. RESULT(S): Among the methodologically stronger studies, decreases in semen volume of 3%-22%, decreases in sperm motility of 3%-37%, and decreases in percent normal sperm of 4%-18% were likely when comparing 30-year-old men to 50-year-old men. Most studies examining fertility status suggest a relationship between male age and fertility, but the results are most likely confounded by female partner age. Among studies that did control for female age, comparisons between men under 30 and men over 50 found relative decreases in pregnancy rates between 23% and 38%. A comparison of the various age categories showed that the increased risks for subfecundity ranged from 11% to 250%. CONCLUSION(S): The weight of the evidence suggests that increased male age is associated with a decline in semen volume, sperm motility, and sperm morphology but not with sperm concentration.

Adult↗

Validation study of nonsurgical diagnosis of endometriosis.

OBJECTIVE: To determine whether the surgical diagnosis of endometriosis can be predicted using symptoms, signs, and ultrasound findings. DESIGN: Prospective study (study sample); retrospective record review (test sample). SETTING: Hospital of Desio (study sample) and Mangiagalli Hospital (test sample), Italy. PATIENT(S): Ninety women scheduled to undergo laparoscopy or laparotomy (study sample); 120 women who underwent laparoscopy (test sample). INTERVENTION: The study sample group was interviewed before surgery about infertility and dysmenorrhea, dyspareunia, and noncyclic pelvic pain and each member had a pelvic examination and a transvaginal ultrasound. At surgery, endometriosis was noted. For the test sample, the same information was abstracted from medical records after laparoscopy. MAIN OUTCOME MEASURE(S): The ability of symptoms, signs, and ultrasound to predict endometriosis at surgery. A classification tree was developed with the study sample and evaluated with the test sample. RESULT(S): Ovarian endometriosis, but not nonovarian endometriosis, could be reliably predicted with noninvasive tools. Ultrasound and examination best predicted ovarian endometriosis, correctly classifying 100% of cases with no false positive diagnoses in the study sample. Similar results were found in the test sample. CONCLUSION(S): Noninvasive tools may be used to identify women with ovarian, but not nonovarian endometriosis, with excellent agreement with surgical diagnosis.

Adult↗

Iron deficiency associated with higher blood lead in children living in contaminated environments.

The evidence that iron deficiency increases lead child exposure is based primarily on animal data and limited human studies, and some of this evidence is contradictory. No studies of iron status and blood lead levels in children have accounted for environmental lead contamination and, therefore, the source of their exposure. Thus, no studies have directly determined whether iron deficiency modifies the relationship of environmental lead and blood lead. In this study, we compared blood lead levels of iron-deficient and iron-replete children living in low, medium, or highly contaminated environments. Measurements of lead in paint, soil, dust, and blood, age of housing, and iron status were collected from 319 children ages 1-5. We developed two lead exposure factors to summarize the correlated exposure variables: Factor 1 summarized all environmental measures, and Factor 2 was weighted for lead loading of house dust. The geometric mean blood lead level was 4.9 microg/dL; 14% exceeded 10 microg/dL. Many of the children were iron deficient (24% with ferritin < 12 ng/dL). Seventeen percent of soil leads exceeded 500 microg/g, and 23% and 63% of interior and exterior paint samples exceeded 5,000 microg/g. The unadjusted geometric mean blood lead level for iron-deficient children was higher by 1 microg/dL; this difference was greater (1.8 microg/dL) after excluding Asians. Blood lead levels were higher for iron-deficient children for each tertile of exposure as estimated by Factors 1 and 2 for non-Asian children. Elevated blood lead among iron-deficient children persisted after adjusting for potential confounders by multivariate regression; the largest difference in blood lead levels between iron-deficient and -replete children, approximately 3 microg/dL, was among those living in the most contaminated environments. Asian children had a paradoxical association of sufficient iron status and higher blood lead level, which warrants further investigation. Improving iron status, along with reducing exposures, may help reduce blood lead levels among most children, especially those living in the most contaminated environments.

Child Welfare↗

Smoking and blood pressure patterns in normotensive pregnant women.

This paper examines the relationship between smoking levels and blood pressure patterns of normotensive pregnant women in a prospective cohort of 2193 primiparous and 3176 multiparous, normotensive, Caucasian women selected from the Child Health and Development Studies in Oakland, California, 1959-67. Regression lines were fitted to each woman's blood pressure; mean intercept and slope estimates of the individual regressions were used to create summary profile lines for each smoking dose. Multivariable regression analysis controlled for maternal age, number of visits to the doctor after 20 weeks' gestation, body mass index and maternal education level. Overall, smokers had lower average diastolic blood pressure (smokers vs. nonsmokers adjusted mean: primiparas, 66.1 vs. 67.2 mmHg; and multiparas, 64.0 vs. 64.7 mmHg) but higher systolic blood pressure (smokers vs. nonsmokers adjusted mean: primiparas, 117.0 vs. 116.0; and multiparas, 112.5 vs. 110.0) than nonsmokers among primiparous and multiparous pregnant women after adjusting for potential confounders. However, these differences are small and there was no clear dose-response relationship between smoking level and blood pressure.

Adult↗

Association of prenatal maternal or postnatal child environmental tobacco smoke exposure and neurodevelopmental and behavioral problems in children.

We review the potential neurodevelopmental and behavioral effects of children's prenatal and/or postnatal exposure to environmental tobacco smoke (ETS). Children's exposure to ETS has been assessed in epidemiologic studies as a risk factor for a variety of behavioral and neurodevelopmental problems including reduced general intellectual ability, skills in language and auditory tasks, and academic achievement, and behavioral problems such as hyperactivity and decreased attention spans. We review 17 epidemiologic studies that have attempted to separate the effects of maternal active smoking during pregnancy from passive ETS smoke exposure by the pregnant mother or the child. Based on the available data, we found that ETS exposure could cause subtle changes in children's neurodevelopment and behavior. However, studies to date are difficult to interpret because of the unknown influence of uncontrolled confounding factors, imprecision in measurements of smoking exposure, and collinearity of pre- and postnatal maternal smoking. Although some evidence suggests that maternal smoking during pregnancy may be associated with deficits in intellectual ability and behavioral problems in children, the impact of prenatal or postnatal ETS exposure remains less clear.

Child Behavior Disorders↗

Exposures of children to organophosphate pesticides and their potential adverse health effects.

Recent studies show that young children can be exposed to pesticides during normal oral exploration of their environment and their level of dermal contact with floors and other surfaces. Children living in agricultural areas may be exposed to higher pesticide levels than other children because of pesticides tracked into their homes by household members, by pesticide drift, by breast milk from their farmworker mother, or by playing in nearby fields. Nevertheless, few studies have assessed the extent of children's pesticide exposure, and no studies have examined whether there are adverse health effects of chronic exposure. There is substantial toxicologic evidence that repeated low-level exposure to organophosphate (OP) pesticides may affect neurodevelopment and growth in developing animals. For example, animal studies have reported neurobehavorial effects such as impairment on maze performance, locomotion, and balance in neonates exposed (italic)in utero(/italic) and during early postnatal life. Possible mechanisms for these effects include inhibition of brain acetylcholinesterase, downregulation of muscarinic receptors, decreased brain DNA synthesis, and reduced brain weight in offspring. Research findings also suggest that it is biologically plausible that OP exposure may be related to respiratory disease in children through dysregulation of the autonomic nervous system. The University of California Berkeley Center for Children's Environmental Health Research is working to build a community-university partnership to study the environmental health of rural children. This Center for the Health Assessment of Mothers and Children of Salinas, or CHAMACOS in Monterey County, California, will assess (italic)in utero(/italic) and postnatal OP pesticide exposure and the relationship of exposure to neurodevelopment, growth, and symptoms of respiratory illness in children. The ultimate goal of the center is to translate research findings into a reduction of children's exposure to pesticides and other environmental agents, and thereby reduce the incidence of environmentally related disease.

Adult↗

Associations between maternal decaffeinated and caffeinated coffee consumption and fetal growth and gestational duration.

Because of concern about the potential adverse effects of consuming caffeinated beverages during pregnancy, pregnant women may choose to replace caffeinated with decaffeinated coffee. In a population-based study of 7,855 livebirths in California's San Joaquin Valley, we examined the relation of maternal decaffeinated and caffeinated coffee consumption during pregnancy to measures of fetal growth and gestational duration. Mothers answered a questionnaire in the hospital at the time of completing the birth certificate. Compared with women who drank neither decaffeinated nor caffeinated coffee, those who consumed only decaffeinated coffee showed no increased odds of small-for-gestational age birth, low birth weight, or preterm delivery, nor lowered mean birth weight or shortened mean gestational age. Women who consumed caffeinated coffee alone had an adjusted odds ratio of 1.3 [95% confidence limits (CL) = 1.0, 1.7] for preterm delivery, whereas those who consumed both caffeinated and decaffeinated coffee had an adjusted odds of 2.3 (95% CL = 1.3, 4.0). When caffeinated and decaffeinated coffee were considered as continuous variables, we found a reduction in adjusted mean birth weight of -3.0 gm per cup per week (95% CL = -5.9, -0.6) for caffeinated coffee and an increase of +0.4 gm per cup per week (95% CL = -3.7, 4.5) for decaffeinated coffee.

Adult↗