Preconception Hair Mercury and Serum Omega-3 Fatty Acids in Relation to Gestational Weight Gain Among Women Seeking Fertility Care
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Assessment of Hair Hg
2.3. Assessment of Serum Omega-3 Fatty Acids
2.4. Assessment of Maternal Weight
2.5. Covariates
2.6. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Institute of Medicine and National Research Council. Weight Gain During Pregnancy: Reexamining the Guidelines; Rasmussen, K.M., Yaktine, A.L., Eds.; The National Academies Collection; Reports funded by National Institutes of Health; National Academies Press (US): Washington, DC, USA, 2009; ISBN 978-0-309-13113-1. [Google Scholar]
- Al Mamun, A.; Mannan, M.; O’Callaghan, M.J.; Williams, G.M.; Najman, J.M.; Callaway, L.K. Association between Gestational Weight Gain and Postpartum Diabetes: Evidence from a Community Based Large Cohort Study. PLoS ONE 2013, 8, e75679. [Google Scholar] [CrossRef]
- Goldstein, R.F.; Abell, S.K.; Ranasinha, S.; Misso, M.; Boyle, J.A.; Black, M.H.; Li, N.; Hu, G.; Corrado, F.; Rode, L.; et al. Association of Gestational Weight Gain with Maternal and Infant Outcomes: A Systematic Review and Meta-Analysis. JAMA 2017, 317, 2207–2225. [Google Scholar] [CrossRef]
- Kirkegaard, H.; Bliddal, M.; Støvring, H.; Rasmussen, K.M.; Gunderson, E.P.; Køber, L.; Sørensen, T.I.A.; Nøhr, E.A. Maternal Weight Change from Prepregnancy to 18 Months Postpartum and Subsequent Risk of Hypertension and Cardiovascular Disease in Danish Women: A Cohort Study. PLoS Med. 2021, 18, e1003486. [Google Scholar] [CrossRef]
- Hinkle, S.N.; Mumford, S.L.; Grantz, K.L.; Mendola, P.; Mills, J.L.; Yeung, E.H.; Pollack, A.Z.; Grandi, S.M.; Sundaram, R.; Qiao, Y.; et al. Gestational Weight Change in a Diverse Pregnancy Cohort and Mortality over 50 Years: A Prospective Observational Cohort Study. Lancet 2023, 402, 1857–1865. [Google Scholar] [CrossRef]
- Deputy, N.P.; Sharma, A.J.; Kim, S.Y. Gestational Weight Gain—United States, 2012 and 2013. MMWR Morb. Mortal. Wkly. Rep. 2015, 64, 1215–1220. [Google Scholar] [CrossRef]
- US EPA. How People Are Exposed to Mercury. Available online: https://www.epa.gov/mercury/how-people-are-exposed-mercury (accessed on 26 May 2025).
- Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for Mercury; Agency for Toxic Substances and Disease Registry (ATSDR) Toxicological Profiles; Agency for Toxic Substances and Disease Registry (US): Atlanta, GA, USA, 2024. [Google Scholar]
- Sakamoto, M.; Kakita, A.; Bezerra de Oliveira, R.; Sheng Pan, H.; Takahashi, H. Dose-Dependent Effects of Methylmercury Administered during Neonatal Brain Spurt in Rats. Dev. Brain Res. 2004, 152, 171–176. [Google Scholar] [CrossRef] [PubMed]
- Yamamoto, M.; Motomura, E.; Yanagisawa, R.; Hoang, V.A.T.; Mogi, M.; Mori, T.; Nakamura, M.; Takeya, M.; Eto, K. Evaluation of Neurobehavioral Impairment in Methylmercury-Treated KK-Ay Mice by Dynamic Weight-Bearing Test. J. Appl. Toxicol. 2019, 39, 221–230. [Google Scholar] [CrossRef]
- Ferrer, B.; Prince, L.M.; Tinkov, A.A.; Santamaria, A.; Farina, M.; Rocha, J.B.; Bowman, A.B.; Aschner, M. Chronic Exposure to Methylmercury Enhances the Anorexigenic Effects of Leptin in C57BL/6J Male Mice. Food Chem. Toxicol. 2021, 147, 111924. [Google Scholar] [CrossRef] [PubMed]
- Zhang, W.; Du, J.; Li, H.; Yang, Y.; Cai, C.; Gao, Q.; Xing, Y.; Shao, B.; Li, G. Multiple-Element Exposure and Metabolic Syndrome in Chinese Adults: A Case-Control Study Based on the Beijing Population Health Cohort. Environ. Int. 2020, 143, 105959. [Google Scholar] [CrossRef]
- Moon, M.K.; Lee, I.; Lee, A.; Park, H.; Kim, M.J.; Kim, S.; Cho, Y.H.; Hong, S.; Yoo, J.; Cheon, G.J.; et al. Lead, Mercury, and Cadmium Exposures Are Associated with Obesity but Not with Diabetes Mellitus: Korean National Environmental Health Survey (KoNEHS) 2015–2017. Environ. Res. 2022, 204, 111888. [Google Scholar] [CrossRef] [PubMed]
- Rothenberg, S.E.; Korrick, S.A.; Fayad, R. The Influence of Obesity on Blood Mercury Levels for U.S. Non-Pregnant Adults and Children: NHANES 2007–2010. Environ. Res. 2015, 138, 173–180. [Google Scholar] [CrossRef]
- Bulka, C.M.; Persky, V.W.; Daviglus, M.L.; Durazo-Arvizu, R.A.; Argos, M. Multiple Metal Exposures and Metabolic Syndrome: A Cross-Sectional Analysis of the National Health and Nutrition Examination Survey 2011–2014. Environ. Res. 2019, 168, 397–405. [Google Scholar] [CrossRef]
- Li, T.; Yu, L.; Yang, Z.; Shen, P.; Lin, H.; Shui, L.; Tang, M.; Jin, M.; Chen, K.; Wang, J. Associations of Diet Quality and Heavy Metals with Obesity in Adults: A Cross-Sectional Study from National Health and Nutrition Examination Survey (NHANES). Nutrients 2022, 14, 4038. [Google Scholar] [CrossRef]
- Niehoff, N.M.; Keil, A.P.; O’Brien, K.M.; Jackson, B.P.; Karagas, M.R.; Weinberg, C.R.; White, A.J. Metals and Trace Elements in Relation to Body Mass Index in a Prospective Study of US Women. Environ. Res. 2020, 184, 109396. [Google Scholar] [CrossRef] [PubMed]
- Mozaffarian, D.; Rimm, E.B. Fish Intake, Contaminants, and Human Health: Evaluating the Risks and the Benefits. JAMA 2006, 296, 1885–1899. [Google Scholar] [CrossRef] [PubMed]
- Messerlian, C.; Williams, P.L.; Ford, J.B.; Chavarro, J.E.; Mínguez-Alarcón, L.; Dadd, R.; Braun, J.M.; Gaskins, A.J.; Meeker, J.D.; James-Todd, T.; et al. The Environment and Reproductive Health (EARTH) Study: A Prospective Preconception Cohort. Hum. Reprod. Open 2018, 2018, hoy001. [Google Scholar] [CrossRef]
- McDowell, M.A.; Dillon, C.F.; Osterloh, J.; Bolger, P.M.; Pellizzari, E.; Fernando, R.; de Oca, R.M.; Schober, S.E.; Sinks, T.; Jones, R.L.; et al. Hair Mercury Levels in U.S. Children and Women of Childbearing Age: Reference Range Data from NHANES 1999–2000. Environ. Health Perspect. 2004, 112, 1165–1171. [Google Scholar] [CrossRef] [PubMed]
- WHO. Guidance for Identifying Populations at Risk from Mercury Exposure. Available online: https://www.who.int/publications/m/item/guidance-for-identifying-populations-at-risk-from-mercury-exposure (accessed on 19 May 2025).
- Baylin, A.; Kabagambe, E.K.; Siles, X.; Campos, H. Adipose Tissue Biomarkers of Fatty Acid Intake. Am. J. Clin. Nutr. 2002, 76, 750–757. [Google Scholar] [CrossRef]
- Zock, P.L.; Gerritsen, J.; Katan, M.B. Partial Conservation of the Sn-2 Position of Dietary Triglycerides in Fasting Plasma Lipids in Humans. Eur. J. Clin. Investig. 1996, 26, 141–150. [Google Scholar] [CrossRef]
- Zock, P.L.; Mensink, R.P.; Harryvan, J.; de Vries, J.H.; Katan, M.B. Fatty Acids in Serum Cholesteryl Esters as Quantitative Biomarkers of Dietary Intake in Humans. Am. J. Epidemiol. 1997, 145, 1114–1122. [Google Scholar] [CrossRef]
- Gilmore, L.A.; Redman, L.M. Weight Gain in Pregnancy and Application of the 2009 IOM Guidelines: Toward a Uniform Approach. Obesity 2015, 23, 507–511. [Google Scholar] [CrossRef]
- US EPA What EPA Is Doing to Reduce Mercury Pollution, and Exposures to Mercury. Available online: https://www.epa.gov/mercury/what-epa-doing-reduce-mercury-pollution-and-exposures-mercury (accessed on 21 May 2025).
- Cohen, A.K.; Kazi, C.; Headen, I.; Rehkopf, D.H.; Hendrick, C.E.; Patil, D.; Abrams, B. Educational Attainment and Gestational Weight Gain among U.S. Mothers. Women’s Health Issues 2016, 26, 460–467. [Google Scholar] [CrossRef]
- Awata, H.; Linder, S.; Mitchell, L.E.; Delclos, G.L. Biomarker Levels of Toxic Metals among Asian Populations in the United States: NHANES 2011–2012. Environ. Health Perspect. 2017, 125, 306–313. [Google Scholar] [CrossRef] [PubMed]
- Murphy, R.A.; Devarshi, P.P.; Ekimura, S.; Marshall, K.; Mitmesser, S.H. Long-Chain Omega-3 Fatty Acid Serum Concentrations across Life Stages in the USA: An Analysis of NHANES 2011–2012. BMJ Open 2021, 11, e043301. [Google Scholar] [CrossRef] [PubMed]
- Roman, H.A.; Walsh, T.L.; Coull, B.A.; Dewailly, É.; Guallar, E.; Hattis, D.; Mariën, K.; Schwartz, J.; Stern, A.H.; Virtanen, J.K.; et al. Evaluation of the Cardiovascular Effects of Methylmercury Exposures: Current Evidence Supports Development of a Dose–Response Function for Regulatory Benefits Analysis. Environ. Health Perspect. 2011, 119, 607–614. [Google Scholar] [CrossRef]
- Neuhouser, M.L.; Prentice, R.L.; Tinker, L.F.; Lampe, J.W. Enhancing Capacity for Food and Nutrient Intake Assessment in Population Sciences Research. Annu. Rev. Public Health 2023, 44, 37–54. [Google Scholar] [CrossRef]
- FDA Advice About Eating Fish. Available online: https://www.fda.gov/food/consumers/advice-about-eating-fish (accessed on 20 October 2025).
- Middleton, P.; Gomersall, J.C.; Gould, J.F.; Shepherd, E.; Olsen, S.F.; Makrides, M. Omega-3 Fatty Acid Addition during Pregnancy. Cochrane Database Syst. Rev. 2018, 2018, CD003402. [Google Scholar] [CrossRef]
- Marshall, N.E.; Abrams, B.; Barbour, L.A.; Catalano, P.; Christian, P.; Friedman, J.E.; Hay, W.W.; Hernandez, T.L.; Krebs, N.F.; Oken, E.; et al. The Importance of Nutrition in Pregnancy and Lactation: Lifelong Consequences. Am. J. Obstet. Gynecol. 2022, 226, 607–632. [Google Scholar] [CrossRef]
- Cave, C.; Hein, N.; Smith, L.M.; Anderson-Berry, A.; Richter, C.K.; Bisselou, K.S.; Appiah, A.K.; Kris-Etherton, P.; Skulas-Ray, A.C.; Thompson, M.; et al. Omega-3 Long-Chain Polyunsaturated Fatty Acids Intake by Ethnicity, Income, and Education Level in the United States: NHANES 2003–2014. Nutrients 2020, 12, 2045. [Google Scholar] [CrossRef] [PubMed]
- Choi, A.L.; Cordier, S.; Weihe, P.; Grandjean, P. Negative Confounding in the Evaluation of Toxicity: The Case of Methylmercury in Fish and Seafood. Crit. Rev. Toxicol. 2008, 38, 877–893. [Google Scholar] [CrossRef]
- Mínguez-Alarcón, L.; Williams, P.L.; Souter, I.; Sacha, C.; Amarasiriwardena, C.J.; Ford, J.B.; Hauser, R.; Chavarro, J.E. Hair Mercury Levels, Intake of Omega-3 Fatty Acids and Ovarian Reserve among Women Attending a Fertility Center. Int. J. Hyg. Environ. Health 2021, 237, 113825. [Google Scholar] [CrossRef] [PubMed]

| Overall | Hair Hg Concentrations a | ||
|---|---|---|---|
| ≤1 ppm | >1 ppm | ||
| Number of participants | 120 | 81 | 39 |
| Hair Hg concentrations, ppm | 0.62 (0.33, 1.12) | 0.40 (0.25, 0.62) | 1.43 (1.18, 2.07) |
| Age, years | 35.0 (33.0, 39.0) | 34.0 (32.0, 38.0) | 38.0 (34.0, 40.0) |
| White, N (%) | 96 (80.0) | 68 (84.0) | 28 (71.8) |
| Educational attainment | |||
| Less than graduate degree | 42 (35.0) | 34 (42.0) | 8 (20.5) |
| Graduate degree | 66 (55.0) | 38 (46.9) | 28 (71.8) |
| Missing | 12 (10.0) | 9 (11.1) | 3 (7.7) |
| Ever smoked, N (%) | 31 (25.8) | 20 (24.7) | 11 (28.2) |
| Primary infertility diagnosis, N (%) | |||
| Male factor | 44 (36.7) | 26 (32.1) | 18 (46.2) |
| Female factor | 31 (25.8) | 21 (25.9) | 10 (25.6) |
| Unexplained | 45 (37.5) | 34 (42.0) | 11 (28.2) |
| Plurality, N (%) | |||
| Singleton | 90 (75.0) | 59 (72.8) | 31 (79.5) |
| Multiples b | 30 (25.0) | 22 (27.2) | 8 (20.5) |
| Total physical activity, hours/week | 5.0 (1.5, 9.5) | 5.5 (1.50 10.0) | 5.0 (1.8, 6.0) |
| Pre-pregnancy BMI, kg/m2 | 24.1 (21.8, 28.0) | 24.7 (21.8, 28.2) | 23.2 (21.7, 26.2) |
| Pre-pregnancy BMI categories | |||
| Underweight (<18.5 kg/m2) | 1 (0.8) | 1 (1.2) | 0 (0.0) |
| Normal (18.5–24.9 kg/m2) | 67 (55.8) | 41 (50.6) | 26 (66.7) |
| Overweight (25–29.9 kg/m2) | 37 (30.8) | 29 (35.8) | 8 (20.5) |
| Obesity (≥30 kg/m2) | 15 (12.5) | 10 (12.3) | 5 (12.8) |
| Gestational age at first-trimester weight measurement, weeks | 10.1 (9.5, 11.0) | 10.1 (9.6, 11.0) | 10.1 (9.4, 11.5) |
| Missing, N (%) | 4 (3.3) | 2 (2.5) | 2 (5.1) |
| Weight at first-trimester measurement, kg | 66.2 (60.3, 75.1) | 68.0 (61.2, 75.7) | 64.4 (59.6, 72.1) |
| Gestational age at delivery, weeks | 38.4 (36.6, 39.7) | 38.4 (36.9, 39.7) | 38.0 (36.4, 39.1) |
| Missing, N (%) | 4 (3.3) | 4 (4.9) | 0 (0) |
| Weight at delivery, kg | 80.5 (73.5, 90.0) | 83.0 (75.3, 91.2) | 77.1 (71.0, 87.8) |
| Total gestational weight gain, kg | 13.6 (10.9, 17.2) | 14.5 (11.3, 17.7) | 12.7 (10.4, 15.0) |
| IOM-recommended ranges for total gestational weight gain c | |||
| Below | 35 (29.2) | 19 (23.5) | 16 (41.0) |
| Within | 45 (37.5) | 32 (39.5) | 13 (33.3) |
| Above | 40 (33.3) | 30 (37.0) | 10 (25.6) |
| Serum omega-3 fatty acids, % of total fatty acids | |||
| EPA | 0.7 (0.5, 1.3) | 0.7 (0.5, 1.2) | 0.8 (0.6, 1.6) |
| DHA | 2.3 (1.8, 3.3) | 2.1 (1.7, 3.0) | 2.7 (2.3, 4.0) |
| EPA + DHA | 3.0 (2.4, 4.7) | 2.8 (2.3, 4.1) | 3.7 (2.9, 6.1) |
| Hair Hg Concentrations, ppm | Model 1 a | Model 2 b | Model 3 c |
|---|---|---|---|
| Tertiles (range, ppm) | |||
| T1 (≤0.40 ppm) | Ref. | Ref. | Ref. |
| T2 (0.40–0.98 ppm) | −0.02 (−2.10, 2.07) | −0.76 (−2.85, 1.33) | −0.90 (−3.01, 1.22) |
| T3 (0.98–4.47 ppm) | −1.83 (−3.92, 0.26) | −0.62 (−2.72, 1.48) | −0.85 (−3.02, 1.32) |
| P for trend | 0.09 | 0.53 | 0.41 |
| EPA reference level | |||
| <1 ppm | Ref. | Ref. | Ref. |
| ≥1 ppm | −1.89 (−3.70, −0.08) | −0.40 (−2.29, 1.50) | −0.53 (−2.46, 1.40) |
| p value | 0.04 | 0.68 | 0.59 |
| N | Hair Hg Concentration | |||||||
|---|---|---|---|---|---|---|---|---|
| T1 (≤0.40 ppm) | T2 (0.40–0.98 ppm) | T3 (0.98–4.47 ppm) | P for Trend | <1 ppm | ≥1 ppm | p Value | ||
| Serum EPA + DHA tertile (range b) | ||||||||
| T1 (1.4–2.6%) | 40 | Ref. | 0.23 (−3.88, 4.34) | −3.22 (−7.79, 1.35) | 0.25 | Ref. | −3.26 (−7.69, 1.17) | 0.14 |
| T2 (2.6–3.9%) | 40 | Ref. | 0.64 (−4.09, 5.36) | 0.78 (−4.60, 6.17) | 0.75 | Ref. | 0.44 (−4.21, 5.09) | 0.85 |
| T3 (3.9–22.8%) | 40 | Ref. | 1.69 (−2.60, 5.98) | 0.49 (−3.83, 4.82) | 0.98 | Ref. | −1.05 (−4.13, 2.02) | 0.49 |
| Pre-pregnancy BMI | ||||||||
| <25 kg/m2 | 68 | Ref. | 0.89 (−1.42, 3.20) | −0.20 (−2.30, 1.90) | 0.88 | Ref. | −0.57 (−2.44, 1.30) | 0.55 |
| ≥25 kg/m2 | 52 | Ref. | −2.65 (−6.52, 1.22) | −2.00 (−6.29, 2.29) | 0.29 | Ref. | −0.62 (−4.51, 3.28) | 0.75 |
| Plurality | ||||||||
| Singleton | 90 | Ref. | −0.29 (−2.77, 2.19) | 0.09 (−2.50, 2.68) | 0.97 | Ref. | 0.10 (−2.22, 2.43) | 0.93 |
| Twins | 30 | Ref. | −3.76 (−9.63, 2.10) | −2.38 (−8.41, 3.65) | 0.37 | Ref. | −0.49 (−5.86, 4.88) | 0.85 |
| Educational attainment | ||||||||
| Less than graduate degree | 54 | Ref. | −2.51 (−5.87, 0.86) | −3.24 (−7.20, 0.72) | 0.08 | Ref. | −1.81 (−5.50, 1.89) | 0.33 |
| Graduate degree | 66 | Ref. | 1.39 (−1.53, 4.31) | 0.34 (−2.23, 2.92) | 0.77 | Ref. | −0.20 (−2.51, 2.10) | 0.86 |
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Han, H.; Liang, X.; Shen, X.; Williams, P.L.; James-Todd, T.; Allan, Y.; Keshet, R.P.; Ford, J.B.; Rexrode, K.M.; Chavarro, J.E.; et al. Preconception Hair Mercury and Serum Omega-3 Fatty Acids in Relation to Gestational Weight Gain Among Women Seeking Fertility Care. Toxics 2025, 13, 962. https://doi.org/10.3390/toxics13110962
Han H, Liang X, Shen X, Williams PL, James-Todd T, Allan Y, Keshet RP, Ford JB, Rexrode KM, Chavarro JE, et al. Preconception Hair Mercury and Serum Omega-3 Fatty Acids in Relation to Gestational Weight Gain Among Women Seeking Fertility Care. Toxics. 2025; 13(11):962. https://doi.org/10.3390/toxics13110962
Chicago/Turabian StyleHan, Han, Xinxiu Liang, Xilin Shen, Paige L. Williams, Tamarra James-Todd, Yazeed Allan, Roe P. Keshet, Jennifer B. Ford, Kathryn M. Rexrode, Jorge E. Chavarro, and et al. 2025. "Preconception Hair Mercury and Serum Omega-3 Fatty Acids in Relation to Gestational Weight Gain Among Women Seeking Fertility Care" Toxics 13, no. 11: 962. https://doi.org/10.3390/toxics13110962
APA StyleHan, H., Liang, X., Shen, X., Williams, P. L., James-Todd, T., Allan, Y., Keshet, R. P., Ford, J. B., Rexrode, K. M., Chavarro, J. E., Hauser, R., & Mínguez-Alarcón, L. (2025). Preconception Hair Mercury and Serum Omega-3 Fatty Acids in Relation to Gestational Weight Gain Among Women Seeking Fertility Care. Toxics, 13(11), 962. https://doi.org/10.3390/toxics13110962

