ORIGINAL ARTICLE Transplacental passage of antimicrobial paraben preservatives Craig V. Towers 1 , Paul D. Terry 2,3 , David Lewis 4 , Bobby Howard 1 , Wesley Chambers 4 , Casey Armistead 4 , Beth Weitz 1 , Stephanie Porter 1 , Christopher J. Borman 5 , Rebekah C. M. Kennedy 3 and Jiangang Chen 3 Parabens are widely used preservatives suspected of being endocrine disruptors, with implications for human growth and development. The most common paraben found in consumer products is methylparaben. To date, no study has examined whether these substances cross the human placenta. A total of 100 study subjects (50 mother–child pairs) were enrolled at two medical institutions, serving primarily African-American and Caucasian women, respectively. A maternal blood sample was drawn on admission and a paired cord blood sample was obtained at delivery. Of the 50 mothers, 47 (94%) showed methylparaben in their blood (mean level 20.41 ng/l), and 47 in cords bloods (mean level 36.54 ng/l). There were 45 mother–child pairs where methylparaben was found in both samples. Of these, the fetal level was higher than the maternal level in 23 (51%). For butylparaben, only 4 mothers (8%) showed detectable levels (mean 40.54 ng/l), whereas 8 cord blood samples (16%) were positive (mean 32.5 ng/l). African-American mothers and infants showed higher prevalence of detectable levels (P = 0.017). Methylparaben and butylparaben demonstrate transplacental passage. Additional studies are needed to examine potential differences in exposure by geography and demographics, what products are used by pregnant women that contain these preservatives, as well as any potential long-term effects in the growth and development of exposed children. Journal of Exposure Science and Environmental Epidemiology advance online publication, 6 May 2015; doi:10.1038/jes.2015.27 Keywords: consumer product safety; cross-sectional studies; endocrine-disrupting chemicals; parabens; transplacental exposure INTRODUCTION Parabens are the esters of p-hydroxybenzoic acid that are commonly used as preservatives in foods, cosmetics, pharmaceu- ticals, and personal care products. 1,2 These compounds are suspected endocrine disruptors with potentially harmful effects on exposed offspring in animal studies. 3–11 The most commonly used paraben is methylparaben, but butylparaben and others are also found in many consumer products. To date, no study has examined whether these substances cross the human placenta. A small number of human studies suggest urine excretion levels vary between men and women, as well as, between Caucasian and African-American individuals. 12–16 Studies have also shown detectable levels in pregnant women through urine evaluation, 15,17 but did not evaluate fetal levels. Regarding any potential concern for the developing fetus and newborn post- delivery, it is necessary to first determine whether these substances cross the placenta. If they do not cross the utero- placental barrier, then the only concern in pregnancy, if detected in maternal blood, would be whether or not these chemicals increase obstetrical problems. However, if parabens are found in fetal blood, then further research is needed to determine what paraben-containing products pregnant women use to potentially modify behavior and perform long-term studies on neonates to determine any untoward effects. Therefore, our objective was to evaluate the first step in the question regarding potential fetal concerns with exposure to parabens by analyzing maternal and fetal blood at the time of delivery for the presence of methylparaben and butylparaben. METHODS All pregnant patients who entered labor and delivery at the University of Tennessee Medical Center, Knoxville, and the Medical Center of University of South Alabama, Mobile, were eligible. We enrolled 25 pregnant patients from each center in order to obtain a primarily bi-racial sample, Caucasian and African-American. This produced a cross-sectional study of 50 mother– child pairs or 100 study subjects. Eligible patients were approached to participate in the study once they were admitted in active labor. If they agreed, an informed consent form was signed. The study was reviewed and approved by the institutional review boards for both medical centers. Once mothers were consented, an additional tube of blood was collected at the time their admission blood work was obtained. An additional tube of cord blood was obtained at delivery, creating paired samples for mothers and newborns. For patient confidentiality, the two tubes were numbered from 1 to 100 and were otherwise designated only maternal or fetal. Each sample was then analyzed for the presence of methylparaben and butylparaben. Information collected on the participating pregnant mothers included age, ethnicity, body mass index (BMI), gestational age, type of delivery, other medication usage, and any major medical disorders (such as hypertension or diabetes, etc.). Regarding BMI, there were 9 morbidly obese patients, 30 obese patients, 8 overweight patients, and only 3 normal weight patients. Neonatal data collection included birth weight, gender, Apgar score, and any neonatal complications. Statistical analysis included χ 2 , Fisher’s exact, and T-test where appropriate. A P-value o0.05 (two-sided) was considered statistically significant. Sample Preparation, Solid Phase Extraction and Analysis by GC-MS Solid phase extractions were performed with Phenomenex Strata-X 33 u Polymeric Reversed Phase SPE cartridges (30 mg/ml; lot# S300-175— Torrance, CA, USA). 1 Department of Obstetrics and Gynecology, Division of Maternal-Fetal, Medicine, University of Tennessee Medical Center, Knoxville, TN, USA; 2 Department of Surgery, University of Tennessee Medical Center, Knoxville, TN, USA; 3 Department of Public Health, University of Tennessee, Knoxville, TN, USA; 4 Department of Obstetrics and Gynecology, University of South Alabama, Mobile, AL, USA and 5 Center for Environmental Biotechnology, University of Tennessee, Knoxville, TN, USA. Correspondence: Paul D. Terry, Department of Public Health, University of Tennessee, 1914 Andy Holt Avenue, HPER 390, Knoxville, TN 37996, USA. Tel.: +865 974 1108. E-mail: pdterry@utk.edu Received 18 November 2014; revised 25 February 2015; accepted 26 February 2015 Journal of Exposure Science and Environmental Epidemiology (2015), 1 – 4 © 2015 Nature America, Inc. All rights reserved 1559-0631/15 www.nature.com/jes