Research Maternal Serum Polychlorinated Biphenyl Concentrations across Critical Windows of Human Development Michael S. Bloom,1 Germaine M. Buck Louis,1 Enrique F. Schisterman,1 Aiyi Liu,2 and Paul J. Kostyniak3 1Epidemiology Branch, and 2Biometry and Mathematical Statistics Branch, Division of Epidemiology, Statistics and Prevention Research, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA; 3Department of Biotechnical and Clinical Laboratory Sciences, School of Medicine and Biomedical Sciences, University at Buffalo, the State University of New York, Buffalo, New York, USA BACKGROUND: Few data are available on polychlorinated biphenyl (PCB) concentrations over critical windows of human reproduction and development inclusive of the periconception window. OBJECTIVES: Our goal was to measure changes in PCB concentrations from preconception to pregnancy, through pregnancy, or after a year without becoming pregnant. METHODS: Seventy-nine women planning pregnancies were prospectively enrolled and followed for up to 12 menstrual cycles of attempting pregnancy. Blood specimens were obtained from partici- pating women preconceptionally (n = 79), after a positive pregnancy test leading to a live birth (n = 54) or pregnancy loss (n = 10), at approximately 6 weeks postpartum (n = 53), and after 12 unsuc- cessful cycles (n = 9) for toxicologic analysis of 76 PCB congeners. We estimated overall and daily rate of change in PCB concentration (nanograms per gram serum) adjusting for relevant covariates, serum lipids, and baseline PCB concentration. RESULTS: Signiﬁcant (p < 0.0001) decreases in the mean overall and daily rate of change in PCB concentrations were observed between the preconception and first pregnancy samples for total (–1.012 and –0.034, respectively), estrogenic (–0.444 and –0.016, respectively), and antiestrogenic (–0.106 and –0.004, respectively) PCBs among women with live births. Similar significant decreases in total (–1.452 and –0.085), estrogenic (–0.647 and –0.040), and antiestrogenic (–0.093 and –0.004) PCB concentrations were seen for women with pregnancy losses. No significant changes were observed for PCB congener 153. CONCLUSIONS: These data suggest that PCB concentrations may change during the periconception interval, questioning the stability of persistent compounds during this critical window. KEY WORDS: critical windows, infertility, periconception, persistent organic pollutants, polychlori- nated biphenyls (PCBs), pregnancy loss. Environ Health Perspect 115:1320–1324 (2007). doi:10.1289/ehp.10086 available via http://dx.doi.org/ [Online 9 July 2007] 14 women were already pregnant and there- fore excluded. The final study cohort com- prised 99 women, of whom 20 withdrew over the course of the 12 months of attempting pregnancy. The distribution of reproductive outcomes among participating women com- pleting the study included 54 (68%) women whose pregnancies resulted in live births, 10 (13%) women whose pregnancies ended in early losses, 4 (5%) women whose pregnancies ended after clinical recognition, and 11 (14%) women who were unable to conceive within 12 menstrual cycles of trying. Data collection. Participation required a baseline interview, completion of a daily diary, and provision of nonfasting blood spec- imens at baseline (preconception) and after a positive home pregnancy test result or after 12 unsuccessful menstrual cycles without pregnancy. For women giving birth, an addi- tional blood specimen was obtained at approx- imately 6 weeks after delivery (postpartum). The research nurse instructed women in the proper use of home pregnancy kits reported to be capable of detecting 50 mIU of human chorionic gonadotropin (hCG). Approximately 25 mL of blood yielding approximately 10 mL of serum were obtained as follows: from all 79 participating women at baseline or preconception; from 54 women after a positive pregnancy test resulting in a live birth (prenatal); from 10 women after a positive pregnancy test approximately 2 weeks postimplantation that resulted in an early pregnancy loss (EPL); from 4 women after a positive pregnancy test resulting in a clinical pregnancy loss (CPL); from 54 women Address correspondence to G.M. Buck Louis, 6100 Executive Blvd., Rm. 7B03, Rockville, MD 20852 USA. Telephone: (301) 496-6155. Fax: (301) 402- 2084. E-mail: louisg@mail.nih.gov Supplemental Material is available online at http://www.ehponline.org/docs/2007/10086/suppl.pdf The authors acknowledge the earlier efforts of J.E. Vena and B. McGuinness in the establishment of the prospective pregnancy study. This research was supported in part with funding from the Great Lakes Protection Fund (RM791- 3021), the Agency for Toxic Substances and Disease Registry (H751 ATH 298338), and the Intramural Research Program of the National Institute of Child Health and Human Development. The authors declare they have no competing ﬁnancial interests. Received 17 January 2007; accepted 6 July 2007. VOLUME 115 | NUMBER 9 | September 2007 • Environmental Health Perspectives The environmental persistence and lipophilic- ity of polychlorinated biphenyls (PCBs) in the Great Lakes basin and elsewhere has lead to bioaccumulation within the aquatic food chain and human exposure (Ayotte et al. 1995; Bloom et al. 2005; He et al. 2001). Dietary PCB exposure has been associated with adverse reproductive (Buck et al. 2000; Mendola et al. 2005) and developmental outcomes (Jacobson and Jacobson 1997), underscoring the impor- tance of exposures during critical or sensitive windows (Morford et al. 2004). Although past research has focused on in utero PCB exposure for clinically recognized pregnancies in relation to human develop- ment, only limited investigation of periconcep- tion exposures has been undertaken (Chapin et al. 2004). This impairs our ability to accu- rately model the effects of pregnancy and/or lactation in assessing reproductive outcomes conditional on pregnancy. We assessed con- centrations of PCB congeners from preconcep- tion through pregnancy and postpartum to better understand their dynamics over critical windows. Materials and Methods Study population and sample. We used a prospective cohort design to recruit women 1320 from the New York State Angler Cohort Study (NYSACS), a population-based cohort com- prising licensed anglers 18–40 years of age who were randomly selected from 16 contiguous counties along Lakes Erie and Ontario (Vena et al. 1996). The purpose of this prospective pregnancy study with preconception enroll- ment was twofold: to obtain longitudinally collected biospecimens for the quantiﬁcation of PCBs over sensitive critical windows, and to evaluate periconception data collection methodologies appropriate for population- based epidemiologic research. The study pro- tocol complied with the U.S. regulations on the protection of human subjects; all study participants gave written informed consent before participation in any aspect of the study. In 1996–1997, introductory recruitment letters were mailed to 2,637 female partici- pants in the NYSACS who had stated interest in possibly becoming pregnant in 1995–1996. After repeated telephone attempts, 1,031 (39%) women were successfully screened, of whom 244 were eligible for participation— defined as planning pregnancy in the next 6 months, age 18–34 years, and no physician diagnosis of infertility. The study sample com- prised 113 women (46%) who reported plan- ning pregnancies within 6 months; however,