Associations between Prenatal Exposure to Phthalates and Timing of Menarche and Growth and Adiposity into Adulthood: A Twenty-Years Birth Cohort Study

Phthalates are ubiquitous environmental chemicals with endocrine disrupting properties and potentially obesogenic effects. We hypothesised that antenatal phthalate exposure may influence growth and adiposity patterns in girls through childhood into adolescence. Among 1342 Raine Study singleton females, 462 had maternal serum and at least one outcome available up to 20 years of age. Individuals’ maternal serum collected at 18 and 34 weeks gestation was pooled and analyzed for concentrations of 32 metabolites of 15 phthalate diesters. Cox regression and linear models were used to determine associations between maternal phthalate levels and age at menarche, change in height and weight z-scores between birth and two years, height from birth to 20 years, BMI from two to 20 years, deviation from mid-parental height at age 20 and DEXA scan measures at age 20. Weak negative associations were detected with some phthalate metabolites and change in height and weight z-score during infancy. Weak positive associations between some of the high molecular weight phthalate metabolites and height z-score were detected during childhood. While still within the normal range, age at menarche was slightly delayed in girls with higher prenatal exposure to the higher molecular weight phthalate metabolites. We derived some associations between prenatal phthalate exposure with early growth patterns and age at menarche.

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The influence of antenatal exposure to phthalates on subsequent female reproductive development in adolescence: a pilot study

Reproduction ◽

10.1530/rep-13-0331 ◽

2014 ◽

Vol 147 (4) ◽

pp. 379-390 ◽

Cited By ~ 48

Author(s):

Roger Hart ◽

Dorota A Doherty ◽

Hanne Frederiksen ◽

Jeffrey A Keelan ◽

Martha Hickey ◽

...

Keyword(s):

Solid Phase ◽

Maternal Serum ◽

Sex Hormone Binding Globulin ◽

Age At Menarche ◽

Phthalate Metabolites ◽

Reproductive Effects ◽

Ovarian Morphology ◽

Early Follicular Phase ◽

Liquid Chromatography Tandem Mass ◽

Ethylhexyl Phthalate

We hypothesised that antenatal exposure to ubiquitous phthalates may lead to an earlier menarche and a lower prevalence of polycystic ovarian syndrome (PCOS) and polycystic ovarian morphology (PCO) in adolescence. The Western Australian Pregnancy Cohort (Raine) Study recruited 3000 women at 18 weeks of gestation in 1989–1991, 1377 had antenatal serum stored without thawing at −80 °C. An unselected subset was evaluated in the early follicular phase for PCO and PCOS by ultrasound and serum evaluation in adolescence. Serum was analysed for anti-Müllerian hormone (AMH), inhibin B, sex hormone binding globulin (SHBG), testosterone, androstenedione and DHEAS. Four hundred microlitres of the frozen maternal serum underwent isotope-diluted liquid chromatography–tandem mass spectrometry, with preceding enzymatic deconjugation followed by solid-phase extraction to determine phthalate exposure. Two hundred and forty four girls attended assessment and most common phthalate metabolites were detectable in the majority of the 123 samples available. Several phthalates were negatively associated with maternal SHBG, and associations with maternal androgens were less consistent. The sum of the metabolites of di-(2-ethylhexyl) phthalate was associated with a non-significant tendency towards an earlier age at menarche (P=0.069). Uterine volume was positively associated with mono-(carboxy-iso-octyl) phthalate (P=0.018). Exposure to monoethyl phthalate (MEP) and the sum of all phthalate metabolites (Σall phth.m) were protective against PCOS in adolescence (P=0.001 and P=0.005 respectively). There were negative associations of MEP with PCO (P=0.022) and of MEP with serum AMH (P=0.031). Consequently, our data suggest that antenatal exposure to environmental phthalates may be associated with oestrogenic and/or anti-androgenic reproductive effects in adolescent girls.

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Associations of Prenatal Exposure to Phthalates with Measures of Cognition in 4.5-Month-Old Infants

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18041838 ◽

2021 ◽

Vol 18 (4) ◽

pp. 1838

Author(s):

Francheska M. Merced-Nieves ◽

Kelsey L. C. Dzwilewski ◽

Andrea Aguiar ◽

Salma Musaad ◽

Susan A. Korrick ◽

...

Keyword(s):

Eye Tracking ◽

Prenatal Exposure ◽

Prospective Cohort ◽

Maternal Age ◽

Effect Modification ◽

Phthalate Metabolites ◽

Physical Reasoning ◽

Phthalate Exposure ◽

Infant Sex ◽

Pooled Sample

The association of prenatal phthalate exposure with physical reasoning was assessed in 159 (78 female; 81 male) 4.5-month-old infants from a prospective cohort. Phthalate metabolites were quantified in urine from 16–18 gestational weeks and a pool of five urines from across pregnancy. Infants’ looking times to physically impossible and possible events were recorded via infrared eye-tracking. Infants that recognize that one of the events is impossible will look at that event longer. Associations of phthalate biomarkers with looking time differences (impossible–possible) were adjusted for maternal age, infant sex, and order of event presentation, and effect modification by infant sex was assessed. Each interquartile range (IQR) increase of monoethyl phthalate in the pooled sample was associated with females’ increased looking time (β = 1.0; 95%CI = 0.3, 1.7 s) to the impossible event. However, for males, an IQR increase in monoethyl phthalate at 16–18 weeks (β = −2.5; 95%CI = −4.4,−0.6 s), the sum of di(isononyl) phthalate metabolites in the pooled sample (β = −1.0; 95%CI = −1.8, −0.1 s), and the sum of all phthalate metabolites in both samples (β = −2.3; 95%CI = −4.4, −0.2 s) were associated with increased looking to the possible event, suggesting that higher prenatal phthalate exposure is associated with poorer physical reasoning in male infants.

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Association between prenatal exposure to perfluoroalkyl substances and asthma in 5-year-old children in the Odense Child Cohort

Environmental Health ◽

10.1186/s12940-019-0541-z ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 1

Author(s):

Iben Have Beck ◽

Clara Amalie Gade Timmermann ◽

Flemming Nielsen ◽

Greet Schoeters ◽

Camilla Jøhnk ◽

...

Keyword(s):

Prenatal Exposure ◽

Sulfonic Acid ◽

Communicable Disease ◽

Diagnostic Testing ◽

International Study ◽

Maternal Serum ◽

Environmental Chemicals ◽

Perfluoroalkyl Substances ◽

Perfluorodecanoic Acid ◽

Maternal Educational Level

Abstract Background Asthma is the most common non-communicable disease in children. Prenatal exposure to perfluoroalkyl substances (PFASs), a group of persistent environmental chemicals with endocrine disrupting abilities, has been associated with immunomodulation and may contribute to the aetiology of asthma. We investigated the associations between prenatal exposure to five PFASs and asthma in 5-year-old children. Methods We studied 981 mother-child pairs within the Odense Child Cohort (OCC), Denmark. We measured perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) in maternal serum donated in early pregnancy. A standardized questionnaire based on the International Study of Asthma and Allergies in Childhood (ISAAC) was used to assess wheeze, self-reported asthma and doctor-diagnosed asthma among children at age 5 years. Associations were examined using logistic regression analyses adjusting for parity, maternal educational level, maternal pre-pregnancy BMI, asthma predisposition and child sex. Results Among the 5-year-old children 18.6% reported wheeze and 7.1% reported asthma. We found no association between prenatal exposure to PFAS and doctor-diagnosed asthma or wheeze. Prenatal PFAS exposure was associated with self-reported asthma, although only significant for PFNA (OR = 1.84, 95% CI 1.03,3.23). Conclusion Our findings support the suggested immunomodulatory effects of PFASs, however, additional studies are warranted. In order to verify our findings, it is important to re-examine the children with postnatal measurements of serum PFAS concentrations and additional clinical diagnostic testing at an older age where an asthma diagnosis is more valid.

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Prenatal Exposure to Mixtures of Phthalates, Parabens, and Other Phenols and Obesity in Five-Year-Olds in the CHAMACOS Cohort

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18041796 ◽

2021 ◽

Vol 18 (4) ◽

pp. 1796

Author(s):

Kimberly Berger ◽

Carly Hyland ◽

Jennifer L. Ames ◽

Ana M. Mora ◽

Karen Huen ◽

...

Keyword(s):

Prenatal Exposure ◽

Hierarchical Modeling ◽

Health Assessment ◽

Complex Mixture ◽

The Body ◽

Z Score ◽

Phthalate Metabolites ◽

Childhood Adiposity ◽

Child Height ◽

Obesity Status

Exposures to phthalates, parabens, and other phenols are often correlated due to their ubiquitous use in personal care products and plastics. Examining these compounds as a complex mixture may clarify inconsistent relationships between individual chemicals and childhood adiposity. Using data from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a longitudinal cohort of children in Salinas Valley, California (n = 309), we examined biomarkers of 11 phthalate metabolites and 9 phenols, including several parabens and bisphenol A, measured in maternal urine at two time points during pregnancy. We measured child height and weight at age five to calculate the body mass index (BMI) z-scores and overweight/obesity status. The association between prenatal urinary concentrations of biomarkers with the childhood BMI z-score and overweight/obesity status was analyzed using single-pollutant models and two mixture methods: Bayesian hierarchical modeling (BMH) and Bayesian kernel machine regression (BKMR). Urinary concentrations of monoethyl phthalate, monocarboxy-isononly phthalate (metabolites of diethyl phthalate and di-isodecyl phthalate, respectively), and propylparaben were consistently associated with an increased BMI z-score and overweight/obesity status across all modeling approaches. Higher prenatal exposures to the cumulative biomarker mixture also trended with greater childhood adiposity. These results, robust across two methods that control for co-pollutant confounding, suggest that prenatal exposure to certain phthalates and parabens may increase the risk for obesity in early childhood.

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Nutritional Status in Childhood Cancer Survivors with Solid Tumors: A Longitudinal Study

10.22541/au.163975504.41100024/v1 ◽

2021 ◽

Author(s):

Nancy Sacks ◽

Wendy Hobbie ◽

Laura Byham-Gray ◽

Robert Denmark ◽

Yuane Jia ◽

...

Keyword(s):

Longitudinal Study ◽

Nutritional Status ◽

Solid Tumors ◽

Weight Status ◽

Nutritional Assessment ◽

Childhood Cancer Survivors ◽

Growth Patterns ◽

Adverse Outcomes ◽

Z Score ◽

Large Tumor

Background: Malnutrition (under and overnutrition) occurs in children with solid tumors and has been linked with adverse outcomes during and after treatment. Assessment of nutritional status (NS) can be challenging due to large tumor burdens, atypical growth patterns and different methods for assessing NS. Methods: Retrospective longitudinal study of children with solid tumors (n=61). Anthropometric data assessed [(diagnosis, after diagnosis (1.5, 3, 6 and 12 months, 5 years), end of treatment (EOT), initial cancer survivorship program (CSP) visit]. Registered dietitian nutritionist nutritional assessment (NA) during treatment and Intensity of Treatment Rating (ITR) documented. Results: At diagnosis, prevalence of undernutrition [(Z-score -1.0 to -2.99)] and overnutrition (Z-score ≥ +2.0) were 13.8% and 8.6%, respectively; weight status categories, 8.6%, 6.9%/13.8% were underweight, overweight/obese, respectively. Weight loss and decreased weight-for-age Z-score (WAZ) occurred in 31.9% and 74.5% patients, respectively, at 1.5 months. At EOT, compared to diagnosis, WAZ and height-for-age Z-score (HAZ) decreased and BMIZ increased. From EOT to CSP visit, overweight/obesity doubled, 7.7%/5.8% and 15.2/11.9%, respectively. Thirty-one percent of patients received a NA, occurring at lowest WAZ. Over 50% had ITR of level 3 or 4 and 88.9% had NA in level 4. Conclusions: Suboptimal NS continues at diagnosis, during treatment and survivorship. Normalized measures, accounting for expected growth, should be used instead of raw numbers. More than one nutrition indicator will identify atypical growth patterns and a proactive approach would help prevent malnutrition. Evidence based research is essential and collaboration necessary to meet the needs of this population.

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Prenatal Exposure to Dexamethasone in the Mouse Alters Cardiac Growth Patterns and Increases Pulse Pressure in Aged Male Offspring

PLoS ONE ◽

10.1371/journal.pone.0069149 ◽

2013 ◽

Vol 8 (7) ◽

pp. e69149 ◽

Cited By ~ 27

Author(s):

Lee O'Sullivan ◽

James S. M. Cuffe ◽

Tamara M. Paravicini ◽

Sally Campbell ◽

Hayley Dickinson ◽

...

Keyword(s):

Prenatal Exposure ◽

Pulse Pressure ◽

Growth Patterns ◽

Male Offspring ◽

Cardiac Growth

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Phthalate Exposure and Breast Cancer Incidence: A Danish Nationwide Cohort Study

Journal of Clinical Oncology ◽

10.1200/jco.18.02202 ◽

2019 ◽

Vol 37 (21) ◽

pp. 1800-1809 ◽

Cited By ~ 13

Author(s):

Thomas P. Ahern ◽

Anne Broe ◽

Timothy L. Lash ◽

Deirdre P. Cronin-Fenton ◽

Sinna Pilgaard Ulrichsen ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Cancer Incidence ◽

Dibutyl Phthalate ◽

Cox Regression ◽

Breast Cancer Incidence ◽

Drug Products ◽

Phthalate Exposure ◽

Long Term Treatment ◽

High Level

PURPOSE Phthalate exposure is ubiquitous and especially high among users of drug products formulated with phthalates. Some phthalates mimic estradiol and may promote breast cancer. Existing epidemiologic studies on this topic are small, mostly not prospective, and have given inconsistent results. We estimated associations between longitudinal phthalate exposures and breast cancer risk in a Danish nationwide cohort, using redeemed prescriptions for phthalate-containing drug products to measure exposure. METHODS We ascertained the phthalate content of drugs marketed in Denmark using an internal Danish Medicines Agency ingredient database. We enrolled a Danish nationwide cohort of 1.12 million women at risk for a first cancer diagnosis on January 1, 2005. By combining drug ingredient data with the Danish National Prescription registry, we characterized annual, cumulative phthalate exposure through redeemed prescriptions. We then fit multivariable Cox regression models to estimate associations between phthalate exposures and incident invasive breast carcinoma according to tumor estrogen receptor status. RESULTS Over 9.99 million woman-years of follow-up, most phthalate exposures were not associated with breast cancer incidence. High-level dibutyl phthalate exposure (≥ 10,000 cumulative mg) was associated with an approximately two-fold increase in the rate of estrogen receptor–positive breast cancer (hazard ratio, 1.9; 95% CI, 1.1 to 3.5), consistent with in vitro evidence for an estrogenic effect of this compound. Lower levels of dibutyl phthalate exposure were not associated with breast cancer incidence. CONCLUSION Our results suggest that women should avoid high-level exposure to dibutyl phthalate, such as through long-term treatment with pharmaceuticals formulated with dibutyl phthalate.

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Prenatal lead exposure in relation to age at menarche: results from a longitudinal study in Mexico City

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174418000223 ◽

2018 ◽

Vol 9 (4) ◽

pp. 467-472 ◽

Cited By ~ 3

Author(s):

E. C. Jansen ◽

L. Zhou ◽

P. X. K. Song ◽

B. N. Sánchez ◽

A. Mercado ◽

...

Keyword(s):

Lead Exposure ◽

Regression Models ◽

Cox Regression ◽

Blood Lead ◽

Blood Lead Levels ◽

Age At Menarche ◽

Second Trimester ◽

Interval Censored ◽

Lead Levels ◽

Prenatal Lead Exposure

AbstractAnimal and cross-sectional epidemiological studies suggest that prenatal lead exposure is related to delayed menarche, but this has not been confirmed in longitudinal studies. We analyzed this association among 200 girls from Mexico City who were followed since the first trimester of gestation. Maternal blood lead levels were analyzed once during each trimester of pregnancy, and daughters were asked about their first menstrual cycle at a visit between the ages of 9.8 and 18.1 years. We estimated hazard ratios (HRs) and 95% confidence intervals (CI) for probability of menarche over the follow-up period using interval-censored Cox models, comparing those with prenatal blood lead level ⩾5 µg/dl to those with prenatal blood lead <5 µg/dl. We also estimated HRs and 95% CI with conventional Cox regression models, which utilized the self-reported age at menarche. In adjusted analyses, we accounted for maternal age, maternal parity, maternal education, and prenatal calcium treatment status. Across trimesters, 36−47% of mothers had blood lead levels ⩾5 µg/dl. Using interval-censored models, we found that during the second trimester only, girls with ⩾5 µg/dl prenatal blood lead had a later age at menarche compared with girls with prenatal blood lead levels <5 µg/dl (confounder-adjusted HR=0.59, 95% CI 0.28–0.90; P=0.05). Associations were in a similar direction, although not statistically significant, in the conventional Cox regression models, potentially indicating measurement error in the self-recalled age at menarche. In summary, higher prenatal lead exposure during the second trimester could be related to later onset of sexual maturation.

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