Prior studies report that penile size and male anogenital distance (AGD), sensitive markers of an... more Prior studies report that penile size and male anogenital distance (AGD), sensitive markers of androgen action in utero, may be shortened by prenatal exposure to certain phthalates, including diethylhexyl phthalate (DEHP), but no human study has investigated the importance of exposure timing in these associations. The aim of this study was to examine the significance of exposure timing on the action of prenatal phthalates in particular DEHP, on male infant penile size and AGD. In The Infant Development and the Environment Study (TIDES) we measured penile width (PW) as well as anoscrotal distance (AGDAS ) and anopenile distance (AGPAP ) in newborn males. We modeled these endpoints in relation to phthalate metabolite concentrations in maternal urine samples collected in each trimester (T1, T2, and T3) in a subset of TIDES mothers (N = 168). PW was inversely associated with T2 oxidized DEHP metabolites, mono-2-ethyl-5-oxohexyl (MEOHP, β=-0.48; 95% confidence interval, -0.93, -0.02), ME...
OBJECTIVES. Phthalates are man-made chemicals found in personal care and other products. Recent s... more OBJECTIVES. Phthalates are man-made chemicals found in personal care and other products. Recent studies suggest that some phthalates can alter human male reproductive development, but sources of infant exposure have not been well characterized. We investigated the relationship between phthalate metabolite concentrations in infant urine and maternal reported use of dermally applied infant care products. METHODS. We measured 9 phthalate metabolites in 163 infants who were born in 2000-2005. An infant was considered to have been exposed to any infant care product that the mother reported using on her infant within 24 hours of urine collection. Results of multiple linear regression analyses are reported as the ratio of metabolite concentrations (with 95% confidence intervals) in exposed and unexposed infants. We standardized concentrations by forming z scores and examined combined exposure to multiple metabolites. RESULTS. In most (81%) infants, Ն7 phthalate metabolites were above the limit of detection. Exposure to lotion was predictive of monoethyl phthalate and monomethyl phthalate concentrations, powder of monoisobutyl phthalate, and shampoo of monomethyl phthalate. Z scores increased with number of products used. Most associations were stronger in younger infants. CONCLUSIONS. Phthalate exposure is widespread and variable in infants. Infant exposure to lotion, powder, and shampoo were significantly associated with increased urinary concentrations of monoethyl phthalate, monomethyl phthalate, and monoisobutyl phthalate, and associations increased with the number of products used. This association was strongest in young infants, who may be more vulnerable to developmental and reproductive toxicity of phthalates given their immature metabolic system capability and increased dosage per unit body surface area.
OBJECTIVE-To describe associations between serum inhibin-b and sperm counts adjusted for effect o... more OBJECTIVE-To describe associations between serum inhibin-b and sperm counts adjusted for effect of time of blood sampling in larger cohorts than previously reported. DESIGN-Cross-sectional studies of spermatogenesis markers.
Background: Di(2)ethyl hexyl phthalate (DEHP) and bisphenol A (BPA) are endocrine disrupting chem... more Background: Di(2)ethyl hexyl phthalate (DEHP) and bisphenol A (BPA) are endocrine disrupting chemicals that affect hormone physiology which leads to adverse reproductive and endocrine health outcom...
American Journal of Obstetrics and Gynecology, 2006
To examine how maternal work hours (MWH) and workrelated stress (WRS) affect gestational age at d... more To examine how maternal work hours (MWH) and workrelated stress (WRS) affect gestational age at delivery and birth weight. STUDY DESIGN: Between 1999-2005, pregnancy and delivery information in spontaneously conceived pregnancies was obtained. This data was collected for the Study for Future Families, a prospective cohort study conducted at four US centers (Los Angeles, Minneapolis, Iowa City and Columbia, MO). Women reported the average weekly number of work hours and rated their WRS on a 4-increment scale. The influence of MWH and WRS on gestational age and birth weight was evaluated by analysis of variance. Covariates included maternal age, race, nulliparity, tobacco use, educational level and infant gender. Twin gestations (14 infants) and infants !2500 g (15 infants) were excluded. A value of p!.05 was considered to be statistically significant. RESULTS: The 371 mothers included in the analysis were predominantly Caucasian (83%), college-educated (90%), employed (84%), !35 years old (81%), and parous (62%). Only fourteen infants were preterm (3.8%). Average gestational age at delivery was 39.3 G .1 weeks (mean G se). Gestational age at delivery decreased as MWH increased. Women working O40 hours/week delivered at 38.9 G .2 weeks compared to women working !40 hours/week who delivered at 39.5 G .1 weeks (p=0.04). Gestational age at delivery decreased as WRS increased (p=0.028). WRS was not associated with MWH. Average birth weight was 3561 g G 27.2 g. Birth weight of these O2500 g infants did not differ based on MWH. However, the average birth weight was lowest for women with the highest WRS (3409 g G 97 g) versus lowest WRS (3577 g G 66 g) (p = 0.2). CONCLUSION: Women who work longer hours tend to deliver at an earlier gestation. However, self-reported work-stress has a greater impact on gestational age and birth weight than absolute number of hours worked.
International Journal of Environmental Research and Public Health
Urinary concentrations of several endocrine disrupting chemicals, including phthalate metabolites... more Urinary concentrations of several endocrine disrupting chemicals, including phthalate metabolites, bisphenol A (BPA), and benzophenone (BP)-type ultraviolet (UV) filters, have been associated with a longer time-to-pregnancy (TTP). Potential modification of these associations by couple’s age has not been studied. TTP was defined as the number of prospectively observed menstrual cycles a couple attempted pregnancy until the occurrence of a human chorionic gonadotropic-detected pregnancy. Urinary concentrations of two BP-type UV filters and three phthalate metabolites were measured at baseline. Fecundability odds ratios (FORs) and 95% confidence intervals (CIs) were estimated for each chemical adjusting for age, body mass index, serum cotinine, creatinine, and accounting for right censoring and left truncation. Models evaluated effect modification between EDC concentrations and TTP by partner’s age, dichotomized at 35 years. Separate models were run for male and female partners. No sig...
Use of antifungal vaginal tablets (active ingredients clotrimazole or miconazole) and oral flucon... more Use of antifungal vaginal tablets (active ingredients clotrimazole or miconazole) and oral fluconazole and in relation to anogenital distance (AGDas, AGDap) and penile width measurements among 25 mother/boy pairs. Table S2. Mean (SD) penile width in mm in boys at three months according to maternal use of antifungal medicine in pregnancy. Beta values represent adjusted mean difference (95% confidence intervals, 95% CI) in penile width in boys whose mothers used antifungal medicine in pregnancy, and non-users. (DOCX 110Â kb)
Figure S4. Effects of glyphosate or Roundup Bioflow exposure on hormones in males (meanâ Âąâ SEM)... more Figure S4. Effects of glyphosate or Roundup Bioflow exposure on hormones in males (meanâ Âąâ SEM); coefficient of variation in square brackets. (DOCX 23 kb)
We analyzed data from a prospective study of menstrual cycle function and early pregnancy loss to... more We analyzed data from a prospective study of menstrual cycle function and early pregnancy loss to explore further the effects of trihalomethanes (THM) on reproductive end points. Premenopausal women (n = 403) collected urine samples daily during an average of 5.6 cycles for measurement of steroid metabolites that were used to define menstrual parameters such as cycle and phase length. Women were asked about consumption of various types of water as well as other habits and demographics. A THM level was estimated for each cycle based on residence and quarterly measurements made by water utilities during a 90-day period beginning 60 days before the cycle start date. We found a monotonic decrease in mean cycle length with increasing total THM (TTHM) level; at> 60 µg/L, the adjusted decrement was 1.1 days [95 % confidence interval (CI), –1.8 to –0.40], compared with ≤ 40 µg/L. This finding was also reflected as a reduced follicular phase length (difference –0.94 day; 95 % CI, –1.6 to ...
The "common sense" intervention by toxicology journal editors regarding proposed European Union e... more The "common sense" intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU.
Background: In 1999 NHANES began measuring phthalates and other nonpersistent pollutants in a rep... more Background: In 1999 NHANES began measuring phthalates and other nonpersistent pollutants in a representative sample of the US population. The development of the high-throughput sensitive assays nec...
Background: Concern has been raised over the potential neurobehavioral effects of prenatal phthal... more Background: Concern has been raised over the potential neurobehavioral effects of prenatal phthalate exposure but available data are inconsistent. Aims: To examine associations between prenatal uri...
Phthalates are used as plasticizers in soft polyvinyl chloride (PVC) and found in a large number ... more Phthalates are used as plasticizers in soft polyvinyl chloride (PVC) and found in a large number of commonly used consumer products. Due to reported health risk, di-isononyl phthalate (DiNP) has be...
Journal of Developmental Origins of Health and Disease
Prenatal hormones have been proposed as key factors impacting child development as well as long-t... more Prenatal hormones have been proposed as key factors impacting child development as well as long-term health and disease. Digit ratio (the ratio of the lengths of the second to fourth digits; 2D:4D) has been proposed as a sexually dimorphic, noninvasive marker of prenatal androgen exposure that can be reliably measured in children and adults. To date, few longitudinal pregnancy cohort studies have examined childhood digit ratio in relation to other relevant measures including prenatal hormones and androgen-sensitive outcomes. To augment the current literature on this topic, we measured right-hand digit ratio in 4-year-old children participating in The Infant Development and the Environment Study, a multicenter longitudinal cohort study that has been following mother–child dyads since the first trimester of pregnancy (n = 321). We assessed sex differences in digit ratio and fit multivariable linear regression models to examine digit ratio in relation to: (1) child sex; (2) maternal se...
International Journal of Environmental Research and Public Health
The purpose of this study was to determine whether maternal urinary phthalate metabolite concentr... more The purpose of this study was to determine whether maternal urinary phthalate metabolite concentrations are associated with the development of higher blood pressure or pregnancy-induced hypertension (PIH). Participants were women without chronic hypertension who enrolled in The Infant Development and the Environment Study, a prospective pregnancy cohort conducted at four U.S. academic medical centers from 2010–2012. Prenatal records were reviewed to obtain blood pressure measurements and diagnoses of PIH (gestational hypertension, preeclampsia, eclampsia, and HELLP syndrome, defined as hemolysis, elevated liver enzymes, and low platelet count). Complete-case analyses used multivariable linear and logistic regression for analysis of blood pressure measurements and PIH diagnoses, respectively. In the final dataset (N = 668), higher concentrations of first-trimester monoethyl phthalate (MEP) and mono-3-carboxypropyl phthalate (MCPP) and third-trimester mono-isobutyl phthalate (MiBP) we...
Prior studies report that penile size and male anogenital distance (AGD), sensitive markers of an... more Prior studies report that penile size and male anogenital distance (AGD), sensitive markers of androgen action in utero, may be shortened by prenatal exposure to certain phthalates, including diethylhexyl phthalate (DEHP), but no human study has investigated the importance of exposure timing in these associations. The aim of this study was to examine the significance of exposure timing on the action of prenatal phthalates in particular DEHP, on male infant penile size and AGD. In The Infant Development and the Environment Study (TIDES) we measured penile width (PW) as well as anoscrotal distance (AGDAS ) and anopenile distance (AGPAP ) in newborn males. We modeled these endpoints in relation to phthalate metabolite concentrations in maternal urine samples collected in each trimester (T1, T2, and T3) in a subset of TIDES mothers (N = 168). PW was inversely associated with T2 oxidized DEHP metabolites, mono-2-ethyl-5-oxohexyl (MEOHP, β=-0.48; 95% confidence interval, -0.93, -0.02), ME...
OBJECTIVES. Phthalates are man-made chemicals found in personal care and other products. Recent s... more OBJECTIVES. Phthalates are man-made chemicals found in personal care and other products. Recent studies suggest that some phthalates can alter human male reproductive development, but sources of infant exposure have not been well characterized. We investigated the relationship between phthalate metabolite concentrations in infant urine and maternal reported use of dermally applied infant care products. METHODS. We measured 9 phthalate metabolites in 163 infants who were born in 2000-2005. An infant was considered to have been exposed to any infant care product that the mother reported using on her infant within 24 hours of urine collection. Results of multiple linear regression analyses are reported as the ratio of metabolite concentrations (with 95% confidence intervals) in exposed and unexposed infants. We standardized concentrations by forming z scores and examined combined exposure to multiple metabolites. RESULTS. In most (81%) infants, Ն7 phthalate metabolites were above the limit of detection. Exposure to lotion was predictive of monoethyl phthalate and monomethyl phthalate concentrations, powder of monoisobutyl phthalate, and shampoo of monomethyl phthalate. Z scores increased with number of products used. Most associations were stronger in younger infants. CONCLUSIONS. Phthalate exposure is widespread and variable in infants. Infant exposure to lotion, powder, and shampoo were significantly associated with increased urinary concentrations of monoethyl phthalate, monomethyl phthalate, and monoisobutyl phthalate, and associations increased with the number of products used. This association was strongest in young infants, who may be more vulnerable to developmental and reproductive toxicity of phthalates given their immature metabolic system capability and increased dosage per unit body surface area.
OBJECTIVE-To describe associations between serum inhibin-b and sperm counts adjusted for effect o... more OBJECTIVE-To describe associations between serum inhibin-b and sperm counts adjusted for effect of time of blood sampling in larger cohorts than previously reported. DESIGN-Cross-sectional studies of spermatogenesis markers.
Background: Di(2)ethyl hexyl phthalate (DEHP) and bisphenol A (BPA) are endocrine disrupting chem... more Background: Di(2)ethyl hexyl phthalate (DEHP) and bisphenol A (BPA) are endocrine disrupting chemicals that affect hormone physiology which leads to adverse reproductive and endocrine health outcom...
American Journal of Obstetrics and Gynecology, 2006
To examine how maternal work hours (MWH) and workrelated stress (WRS) affect gestational age at d... more To examine how maternal work hours (MWH) and workrelated stress (WRS) affect gestational age at delivery and birth weight. STUDY DESIGN: Between 1999-2005, pregnancy and delivery information in spontaneously conceived pregnancies was obtained. This data was collected for the Study for Future Families, a prospective cohort study conducted at four US centers (Los Angeles, Minneapolis, Iowa City and Columbia, MO). Women reported the average weekly number of work hours and rated their WRS on a 4-increment scale. The influence of MWH and WRS on gestational age and birth weight was evaluated by analysis of variance. Covariates included maternal age, race, nulliparity, tobacco use, educational level and infant gender. Twin gestations (14 infants) and infants !2500 g (15 infants) were excluded. A value of p!.05 was considered to be statistically significant. RESULTS: The 371 mothers included in the analysis were predominantly Caucasian (83%), college-educated (90%), employed (84%), !35 years old (81%), and parous (62%). Only fourteen infants were preterm (3.8%). Average gestational age at delivery was 39.3 G .1 weeks (mean G se). Gestational age at delivery decreased as MWH increased. Women working O40 hours/week delivered at 38.9 G .2 weeks compared to women working !40 hours/week who delivered at 39.5 G .1 weeks (p=0.04). Gestational age at delivery decreased as WRS increased (p=0.028). WRS was not associated with MWH. Average birth weight was 3561 g G 27.2 g. Birth weight of these O2500 g infants did not differ based on MWH. However, the average birth weight was lowest for women with the highest WRS (3409 g G 97 g) versus lowest WRS (3577 g G 66 g) (p = 0.2). CONCLUSION: Women who work longer hours tend to deliver at an earlier gestation. However, self-reported work-stress has a greater impact on gestational age and birth weight than absolute number of hours worked.
International Journal of Environmental Research and Public Health
Urinary concentrations of several endocrine disrupting chemicals, including phthalate metabolites... more Urinary concentrations of several endocrine disrupting chemicals, including phthalate metabolites, bisphenol A (BPA), and benzophenone (BP)-type ultraviolet (UV) filters, have been associated with a longer time-to-pregnancy (TTP). Potential modification of these associations by couple’s age has not been studied. TTP was defined as the number of prospectively observed menstrual cycles a couple attempted pregnancy until the occurrence of a human chorionic gonadotropic-detected pregnancy. Urinary concentrations of two BP-type UV filters and three phthalate metabolites were measured at baseline. Fecundability odds ratios (FORs) and 95% confidence intervals (CIs) were estimated for each chemical adjusting for age, body mass index, serum cotinine, creatinine, and accounting for right censoring and left truncation. Models evaluated effect modification between EDC concentrations and TTP by partner’s age, dichotomized at 35 years. Separate models were run for male and female partners. No sig...
Use of antifungal vaginal tablets (active ingredients clotrimazole or miconazole) and oral flucon... more Use of antifungal vaginal tablets (active ingredients clotrimazole or miconazole) and oral fluconazole and in relation to anogenital distance (AGDas, AGDap) and penile width measurements among 25 mother/boy pairs. Table S2. Mean (SD) penile width in mm in boys at three months according to maternal use of antifungal medicine in pregnancy. Beta values represent adjusted mean difference (95% confidence intervals, 95% CI) in penile width in boys whose mothers used antifungal medicine in pregnancy, and non-users. (DOCX 110Â kb)
Figure S4. Effects of glyphosate or Roundup Bioflow exposure on hormones in males (meanâ Âąâ SEM)... more Figure S4. Effects of glyphosate or Roundup Bioflow exposure on hormones in males (meanâ Âąâ SEM); coefficient of variation in square brackets. (DOCX 23 kb)
We analyzed data from a prospective study of menstrual cycle function and early pregnancy loss to... more We analyzed data from a prospective study of menstrual cycle function and early pregnancy loss to explore further the effects of trihalomethanes (THM) on reproductive end points. Premenopausal women (n = 403) collected urine samples daily during an average of 5.6 cycles for measurement of steroid metabolites that were used to define menstrual parameters such as cycle and phase length. Women were asked about consumption of various types of water as well as other habits and demographics. A THM level was estimated for each cycle based on residence and quarterly measurements made by water utilities during a 90-day period beginning 60 days before the cycle start date. We found a monotonic decrease in mean cycle length with increasing total THM (TTHM) level; at> 60 µg/L, the adjusted decrement was 1.1 days [95 % confidence interval (CI), –1.8 to –0.40], compared with ≤ 40 µg/L. This finding was also reflected as a reduced follicular phase length (difference –0.94 day; 95 % CI, –1.6 to ...
The "common sense" intervention by toxicology journal editors regarding proposed European Union e... more The "common sense" intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU.
Background: In 1999 NHANES began measuring phthalates and other nonpersistent pollutants in a rep... more Background: In 1999 NHANES began measuring phthalates and other nonpersistent pollutants in a representative sample of the US population. The development of the high-throughput sensitive assays nec...
Background: Concern has been raised over the potential neurobehavioral effects of prenatal phthal... more Background: Concern has been raised over the potential neurobehavioral effects of prenatal phthalate exposure but available data are inconsistent. Aims: To examine associations between prenatal uri...
Phthalates are used as plasticizers in soft polyvinyl chloride (PVC) and found in a large number ... more Phthalates are used as plasticizers in soft polyvinyl chloride (PVC) and found in a large number of commonly used consumer products. Due to reported health risk, di-isononyl phthalate (DiNP) has be...
Journal of Developmental Origins of Health and Disease
Prenatal hormones have been proposed as key factors impacting child development as well as long-t... more Prenatal hormones have been proposed as key factors impacting child development as well as long-term health and disease. Digit ratio (the ratio of the lengths of the second to fourth digits; 2D:4D) has been proposed as a sexually dimorphic, noninvasive marker of prenatal androgen exposure that can be reliably measured in children and adults. To date, few longitudinal pregnancy cohort studies have examined childhood digit ratio in relation to other relevant measures including prenatal hormones and androgen-sensitive outcomes. To augment the current literature on this topic, we measured right-hand digit ratio in 4-year-old children participating in The Infant Development and the Environment Study, a multicenter longitudinal cohort study that has been following mother–child dyads since the first trimester of pregnancy (n = 321). We assessed sex differences in digit ratio and fit multivariable linear regression models to examine digit ratio in relation to: (1) child sex; (2) maternal se...
International Journal of Environmental Research and Public Health
The purpose of this study was to determine whether maternal urinary phthalate metabolite concentr... more The purpose of this study was to determine whether maternal urinary phthalate metabolite concentrations are associated with the development of higher blood pressure or pregnancy-induced hypertension (PIH). Participants were women without chronic hypertension who enrolled in The Infant Development and the Environment Study, a prospective pregnancy cohort conducted at four U.S. academic medical centers from 2010–2012. Prenatal records were reviewed to obtain blood pressure measurements and diagnoses of PIH (gestational hypertension, preeclampsia, eclampsia, and HELLP syndrome, defined as hemolysis, elevated liver enzymes, and low platelet count). Complete-case analyses used multivariable linear and logistic regression for analysis of blood pressure measurements and PIH diagnoses, respectively. In the final dataset (N = 668), higher concentrations of first-trimester monoethyl phthalate (MEP) and mono-3-carboxypropyl phthalate (MCPP) and third-trimester mono-isobutyl phthalate (MiBP) we...
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