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Cited by 202Effects and risks of endocrine disrupting chemicalsSexual Differentiation and DisordersToxic Organic Pollutants Impact

Prenatal phthalate exposure and performance on the neonatal behavioral assessment scale in A multiethnic BIRTH cohort

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Engel, Stephanie M., Zhu, Chenbo, Berkowitz, Gertrud S., Calafat, Antonia M., Silva, Manori J., Miodovnik, Amir, Wolff, Mary S.·2009·NeuroToxicology
DOI 10.1016/j.neuro.2009.04.001PMC PMC4026936
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Abstract

We investigated the relationship between prenatal maternal urinary concentrations of phthalate metabolites and neonatal behavior in their 295 children enrolled in a multiethnic birth cohort between 1998 and 2002 at the Mount Sinai School of Medicine in New York City. Trained examiners administered the Brazelton Neonatal Behavioral Assessment Scale (BNBAS) to children within 5 days of delivery. We measured metabolites of 7 phthalate esters in maternal urine that was collected between 25 and 40 weeks' gestation. All but two phthalate metabolites were over 95% detectable. We summed metabolites on a molar basis into low and high molecular weight phthalates. We hypothesized the existence of sex-specific effects from phthalate exposure a priori given the hormonal activity of these chemicals. Overall we found few associations between individual phthalate metabolites or their molar sums and most of the BNBAS domains. However, we observed significant sex-phthalate metabolite interactions (p<0.10) for the Orientation and Motor domains and the overall Quality of Alertness score. Among girls, there was a significant linear decline in adjusted mean Orientation score with increasing urinary concentrations of high molecular weight phthalate metabolites (B=-0.37, p=0.02). Likewise, there was a strong linear decline in their adjusted mean Quality of Alertness score (B=-0.48, p<0.01). In addition, boys and girls demonstrated opposite patterns of association between low and high molecular weight phthalate metabolite concentrations and motor performance, with some indication of improved motor performance with increasing concentration of low molecular weight phthalate metabolites among boys. This is the first study to report an association between prenatal phthalate exposure and neurological effects in humans or animals, and as such requires replication.

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  • Prenatal exposure to phthalate metabolites has been associated with impaired cognitive development.

    “Prenatal exposure to phthalate metabolites has been associated with impaired cognitive development.”

    From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Engel et al., 2009

    The Results and Discussion (page unavailable) associate prenatal phthalate metabolite exposure with lower neonatal orientation and quality-of-alertness scores among girls. The study measured behavior within five days of birth, not cognitive development; the Discussion says further research is needed to extend the findings to childhood cognitive development. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Girls exposed to higher concentrations of high-molecular-weight phthalate metabolites showed significantly lower orientation scores on the Brazelton Neonatal Behavioral Assessment Scale, indicating deficits in attention, visual and auditory stimulus processing, and alertness within the first days of life.

    “Girls exposed to higher concentrations of high-molecular-weight phthalate metabolites showed significantly lower orientation scores on the Brazelton Neonatal Behavioral Assessment Scale, indicating deficits in attention, visual and auditory stimulus processing, and alertness within the first days of life (Engel et al., 2009).”

    From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Engel et al., 2009

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Research works printed but not linked: 53

  1. Andrade AJ Grande SW Talsness CE Grote K Chahoud I A dose-response study following in utero and lactational exposure to di-(2-ethylhexyl)-phthalate (DEHP): non-monotonic dose-response and low dose effects on rat brain aromatase activity. Toxicology 2006 227 3 185 92 16949715
  2. Berkowitz GS Obel J Deych E Lapinski R Godbold J Liu Z Landrigan PJ Wolff MS Exposure to indoor pesticides during pregnancy in a multiethnic, urban cohort. Environ Health Perspect 2003 111 1 79 84 12515682 PMC1241309
  3. Berkowitz GS Wetmur JG Birman-Deych E Obel J Lapinski RH Godbold JH Holzman IR Wolff MS In utero pesticide exposure, maternal paraoxonase activity, and head circumference. Environ Health Perspect 2004 112 3 388 91 14998758 PMC1241872
  4. Braissant O Wahli W Differential expression of peroxisome proliferator-activated receptor-alpha, -beta, and -gamma during rat embryonic development. Endocrinology 1998 139 6 2748 54 9607781
  5. Brazelton TB Nugent JK Neonatal Behavioral Assessment Scale 1995 Mac Keith Press London
  6. Breous E Wenzel A Loos U The promoter of the human sodium/iodide symporter responds to certain phthalate plasticisers. Mol Cell Endocrinol 2005 244 1-2 75 8 16257484
  7. Canals J Esparo G Fernandez-Ballart JD Neonatal behaviour characteristics and psychological problems at 6 years. Acta Paediatr 2006 95 11 1412 7 17062469
  8. Colciago A Negri-Cesi P Pravettoni A Mornati O Casati L Celotti F Prenatal Aroclor 1254 exposure and brain sexual differentiation: effect on the expression of testosterone metabolizing enzymes and androgen receptors in the hypothalamus of male and female rats. Reprod Toxicol 2006 22 4 738 45 16938428
  9. Committee on the Health Risks of Phthalates, N. R. C. Phthalates and Cumulative Risk Assessment The Task Ahead 2008 National Academies Press Washington, DC 25009926
  10. Corton JC Lapinskas PJ Peroxisome proliferator-activated receptors: mediators of phthalate ester-induced effects in the male reproductive tract? Toxicol Sci 2005 83 1 4 17 15496498
  11. Datta-Bhutada S Johnson HL Rosen TS Intrauterine cocaine and crack exposure: neonatal outcome. J Perinatol 1998 18 3 183 8 9659645
  12. Fenster L Eskenazi B Anderson M Bradman A Hubbard A Barr DB In utero exposure to DDT and performance on the Brazelton neonatal behavioral assessment scale. Neurotoxicology 2007 28 3 471 7 17287022
  13. Haddow JE Palomaki GE Allan WC Williams JR Knight GJ Gagnon J O'Heir CE Mitchell ML Hermos RJ Waisbren SE Faix JD Klein RZ Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med 1999 341 8 549 55 10451459
  14. Hatch EE Nelson JW Qureshi MM Weinberg J Moore LL Singer M Webster TF Association of urinary phthalate metabolite concentrations with body mass index and waist circumference: a cross-sectional study of NHANES data, 1999-2002. Environ Health 2008 7 27 18522739 PMC2440739
  15. Hauser R Meeker JD Duty S Silva MJ Calafat AM Altered semen quality in relation to urinary concentrations of phthalate monoester and oxidative metabolites. Epidemiology 2006 17 6 682 91 17003688
  16. Hauser R Meeker JD Park S Silva MJ Calafat AM Temporal variability of urinary phthalate metabolite levels in men of reproductive age. Environ Health Perspect 2004 112 17 1734 40 15579421 PMC1253667
  17. Hauser R Meeker JD Singh NP Silva MJ Ryan L Duty S Calafat AM DNA damage in human sperm is related to urinary levels of phthalate monoester and oxidative metabolites. Hum Reprod 2007 22 3 688 95 17090632
  18. Hays T Rusyn I Burns AM Kennett MJ Ward JM Gonzalez FJ Peters JM Role of peroxisome proliferator-activated receptor-alpha (PPARalpha) in bezafibrate-induced hepatocarcinogenesis and cholestasis. Carcinogenesis 2005 26 1 219 27 15447978
  19. Hinton RH Mitchell FE Mann A Chescoe D Price SC Nunn A Grasso P Bridges JW Effects of phthalic acid esters on the liver and thyroid. Environ Health Perspect 1986 70 195 210 3830106 PMC1474287
  20. Huang PC Kuo PL Guo YL Liao PC Lee CC Associations between urinary phthalate monoesters and thyroid hormones in pregnant women. Hum Reprod 2007 22 10 2715 22 17704099
  21. Kato K Silva MJ Needham LL Calafat AM Determination of 16 phthalate metabolites in urine using automated sample preparation and on-line preconcentration/high-performance liquid chromatography/tandem mass spectrometry. Anal Chem 2005 77 9 2985 91 15859620
  22. Latini G Scoditti E Verrotti A De Felice C Massaro M Peroxisome proliferator-activated receptors as mediators of phthalate-induced effects in the male and female reproductive tract: epidemiological and experimental evidence. PPAR Res 2008 2008 359267 18288285 PMC2225463
  23. Lester BM Als H Brazelton TB Regional obstetric anesthesia and newborn behavior: a reanalysis toward synergistic effects. Child Dev 1982 53 3 687 92 7094677
  24. Meeker JD Calafat AM Hauser R Di(2-ethylhexyl) phthalate metabolites may alter thyroid hormone levels in men. Environ Health Perspect 2007 115 7 1029 34 17637918 PMC1913587
  25. Morreale de Escobar G The role of thyroid hormone in fetal neurodevelopment. J Pediatr Endocrinol Metab 14 Suppl 2001 6 1453 62 11837499
  26. Morreale de Escobar G Obregon MJ Escobar del Rey F Role of thyroid hormone during early brain development. Eur J Endocrinol 151 Suppl 2004 3 U25 37 15554884
  27. Myers BJ Dawson KS Britt GC Lodder DE Meloy LD Saunders MK Meadows SL Elswick RK Prenatal cocaine exposure and infant performance on the Brazelton Neonatal Behavioral Assessment Scale. Subst Use Misuse 2003 38 14 2065 96 14677782
  28. Ohara N Tsujino T Maruo T The role of thyroid hormone in trophoblast function, early pregnancy maintenance, and fetal neurodevelopment. J Obstet Gynaecol Can 2004 26 11 982 90 15560861
  29. Ohgi S Arisawa K Takahashi T Kusumoto T Goto Y Akiyama T Saito H Neonatal behavioral assessment scale as a predictor of later developmental disabilities of low birth-weight and/or premature infants. Brain Dev 2003 25 5 313 21 12850509
  30. Ohgi S Takahashi T Nugent JK Arisawa K Akiyama T Neonatal behavioral characteristics and later behavioral problems. Clin Pediatr (Phila) 2003 42 8 679 86 14601916
  31. Pereira C Mapuskar K Vaman Rao C A two-generation chronic mixture toxicity study of Clophen A60 and diethyl phthalate on histology of adrenal cortex and thyroid of rats. Acta Histochem 2007 109 1 29 36 17113135
  32. Peters JM Cattley RC Gonzalez FJ Role of PPAR alpha in the mechanism of action of the nongenotoxic carcinogen and peroxisome proliferator Wy-14,643. Carcinogenesis 1997 18 11 2029 33 9395198
  33. Peters JM Lee SS Li W Ward JM Gavrilova O Everett C Reitman ML Hudson LD Gonzalez FJ Growth, adipose, brain, and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptor beta(delta). Mol Cell Biol 2000 20 14 5119 28 10866668 PMC85961
  34. Poon R Lecavalier P Mueller R Valli VE Procter BG Chu I Subchronic oral toxicity of di-n-octyl phthalate and di(2-Ethylhexyl) phthalate in the rat. Food Chem Toxicol 1997 35 2 225 39 9146736
  35. Pop VJ Kuijpens JL van Baar AL Verkerk G van Son MM de Vijlder JJ Vulsma T Wiersinga WM Drexhage HA Vader HL Low maternal free thyroxine concentrations during early pregnancy are associated with impaired psychomotor development in infancy. Clin Endocrinol (Oxf) 1999 50 2 149 55 10396355
  36. Price SC Chescoe D Grasso P Wright M Hinton RH Alterations in the thyroids of rats treated for long periods with di-(2-ethylhexyl) phthalate or with hypolipidaemic agents. Toxicol Lett 1988 40 1 37 46 3341048
  37. Richardson GA Hamel SC Goldschmidt L Day NL The effects of prenatal cocaine use on neonatal neurobehavioral status. Neurotoxicol Teratol 1996 18 5 519 28 8888016
  38. Rogan WJ Gladen BC McKinney JD Carreras N Hardy P Thullen J Tinglestad J Tully M Neonatal effects of transplacental exposure to PCBs and DDE. J Pediatr 1986 109 2 335 41 3090217
  39. Sagiv SK Nugent JK Brazelton TB Choi AL Tolbert PE Altshul LM Korrick SA Prenatal organochlorine exposure and measures of behavior in infancy using the Neonatal Behavioral Assessment Scale (NBAS). Environ Health Perspect 2008 116 5 666 73 18470320 PMC2367684
  40. Shearer BG Hoekstra WJ Recent advances in peroxisome proliferator-activated receptor science. Curr Med Chem 2003 10 4 267 80 12570700
  41. Silva MJ Barr DB Reidy JA Malek NA Hodge CC Caudill SP Brock JW Needham LL Calafat AM Urinary levels of seven phthalate metabolites in the U.S. population from the National Health and Nutrition Examination Survey (NHANES) 1999-2000. Environ Health Perspect 2004 112 3 331 8 14998749 PMC1241863
  42. Silva MJ Preau JL Jr. Needham LL Calafat AM Cross validation and ruggedness testing of analytical methods used for the quantification of urinary phthalate metabolites. J Chromatogr B Analyt Technol Biomed Life Sci 2008 873 2 180 6 18790687
  43. Stahlhut RW van Wijngaarden E Dye TD Cook S Swan SH Concentrations of urinary phthalate metabolites are associated with increased waist circumference and insulin resistance in adult U.S. males. Environ Health Perspect 2007 115 6 876 82 17589594 PMC1892109
  44. Stewart P Reihman J Lonky E Darvill T Pagano J Prenatal PCB exposure and neonatal behavioral assessment scale (NBAS) performance. Neurotoxicol Teratol 2000 22 1 21 9 10642111
  45. Sugiyama S Shimada N Miyoshi H Yamauchi K Detection of thyroid system-disrupting chemicals using in vitro and in vivo screening assays in Xenopus laevis. Toxicol Sci 2005 88 2 367 74 16179385
  46. Swan SH Main KM Liu F Stewart SL Kruse RL Calafat AM Mao CS Redmon JB Ternand CL Sullivan S Teague JL Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environ Health Perspect 2005 113 8 1056 61 16079079 PMC1280349
  47. Teitelbaum SL Britton JA Calafat AM Ye X Silva MJ Reidy JA Galvez MP Brenner BL Wolff MS Temporal variability in urinary concentrations of phthalate metabolites, phytoestrogens and phenols among minority children in the United States. Environ Res 2008 106 2 257 69 17976571
  48. Tirosh E Harel J Abadi J Berger A Cohen A Relationship between neonatal behavior and subsequent temperament. Acta Paediatr 1992 81 10 829 31 1421891
  49. Wolff MS Engel S Berkowitz G Teitelbaum S Siskind J Barr DB Wetmur J Prenatal pesticide and PCB exposures and birth outcomes. Pediatr Res 2007 61 2 243 50 17237730
  50. Wolff MS Engel SM Berkowitz GS Ye X Silva MJ Zhu C Wetmur J Calafat AM Prenatal phenol and phthalate exposures and birth outcomes. Environ Health Perspect 2008 116 8 1092 7 18709157 PMC2516577
  51. Xu Y Agrawal S Cook TJ Knipp GT Di-(2-ethylhexyl)-phthalate affects lipid profiling in fetal rat brain upon maternal exposure. Arch Toxicol 2007 81 1 57 62 16951938
  52. Young JG Eskenazi B Gladstone EA Bradman A Pedersen L Johnson C Barr DB Furlong CE Holland NT Association between in utero organophosphate pesticide exposure and abnormal reflexes in neonates. Neurotoxicology 2005 26 2 199 209 15713341
  53. Zhang YH Zheng LX Chen BH Phthalate exposure and human semen quality in Shanghai: a cross-sectional study. Biomed Environ Sci 2006 19 3 205 9 16944777

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Authors
Engel, S. M., Zhu, C., Berkowitz, G. S., Calafat, A. M., Silva, M. J., Miodovnik, A., & Wolff, M. S.
Affiliations
  • Icahn School of Medicine at Mount Sinai (US)
  • Centers for Disease Control and Prevention (US)
Corresponding author
Engel, Stephanie M.
ORCID
Venue
NeuroToxicology
Publisher
Elsevier BV
Published
2009-07
Volume
30
Issue
4
Pages
522-528
ISSN
0161-813X (ISSN-L)
DOI
10.1016/j.neuro.2009.04.001
PMC
PMC4026936
OpenAlex
W2027021333
Cited by
202
References
1
Citations by year
2026: 3 · 2025: 3 · 2024: 5 · 2023: 8 · 2022: 9 · 2021: 14 · 2020: 10 · 2019: 19 · 2018: 11 · 2017: 14 · 2016: 12 · 2015: 17 · 2014: 20 · 2013: 20 · 2012: 7
FWCI
8.76
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • NeuroToxicology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • UNC Libraries
Funders
  • Centers for Disease Control and Prevention
  • National Institute of Environmental Health Sciences (ES09584, P01ES009584, R827039)
  • Agency for Toxic Substances and Disease Registry (R827039)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD049311)
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
Keywords
prenatal phthalate exposure, phthalate metabolites, maternal urinary biomarkers, neonatal behavior, Brazelton Neonatal Behavioral Assessment Scale, sex-specific effects, high molecular weight phthalates, low molecular weight phthalates, endocrine disruptors
MeSH terms
Adolescent, Adult, Behavior, Environmental Pollutants, Ethnicity, Female, Humans, Infant, Infant, Newborn, Male, Molecular Weight, New York City, Phthalic Acids, Pregnancy, Pregnancy Trimester, Third, Prenatal Exposure Delayed Effects, Psychological Tests, Retrospective Studies, Cohort Studies, Maternal Exposure, Young Adult

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