Clinical Epidemiology (Apr 2022)

Nitrate in Drinking Water and Time to Pregnancy or Medically Assisted Reproduction in Women and Men: A Nationwide Cohort Study in the Danish National Birth Cohort

  • Ebdrup NH,
  • Knudsen UB,
  • Schullehner J,
  • Arendt LH,
  • Liew Z,
  • Lyngsø J,
  • Bay B,
  • Clemmensen PJ,
  • Sigsgaard T,
  • Hansen B,
  • Ramlau-Hansen CH

Journal volume & issue
Vol. Volume 14
pp. 475 – 487

Abstract

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Ninna Hinchely Ebdrup,1– 3 Ulla Breth Knudsen,1,3 Jörg Schullehner,2,4 Linn Håkonsen Arendt,2,5 Zeyan Liew,6,7 Julie Lyngsø,2,5 Bjørn Bay,1,8 Pernille Jul Clemmensen,2 Torben Sigsgaard,2,9,10 Birgitte Hansen,4 Cecilia Høst Ramlau-Hansen2 1Department of Obstetrics and Gynecology, Horsens Regional Hospital, Horsens, Denmark; 2Department of Public Health, Aarhus University, Aarhus, Denmark; 3Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 4Geological Survey of Denmark and Greenland, Aarhus, Denmark; 5Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark; 6Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA; 7Yale Center for Perinatal, Pediatric, and Environmental Epidemiology, Yale School of Public Health, New Haven, CT, USA; 8Maigaard Fertility Clinic, Aarhus, Denmark; 9Centre for Integrated Register-based Research at Aarhus University, Aarhus, Denmark; 10Danish Big Data Centre for Environment and Health (BERTHA), Aarhus University, Aarhus, DenmarkCorrespondence: Ninna Hinchely Ebdrup, Department of Obstetrics and Gynecology, Horsens Regional Hospital, Regionshospitalet Horsens, Sundvej 30, Horsens, 8700, Denmark, Tel +4528472111, Email [email protected]: No studies have investigated if drinking water nitrate affects human fecundity. Experimental studies point at detrimental effects on fetal development and on female and male reproduction. This cohort study aimed to explore if female and male preconception and long-term exposure to nitrate in drinking water was associated with fecundability measured as time to pregnancy (TTP) or use of medically assisted reproduction (MAR) treatment.Methods: The study population consisted of pregnant women recruited in their first trimester in 1996– 2002 to the Danish National Birth Cohort. Preconception drinking-water nitrate exposure was estimated for the pregnant women (89,109 pregnancies), and long-term drinking water nitrate exposure was estimated from adolescence to conception for the pregnant women (77,474 pregnancies) and their male partners (62,000 pregnancies) by linkage to the national drinking water quality-monitoring database Jupiter. Difference in risk of TTP > 12 months or use of MAR treatment between five exposure categories and log-transformed continuous models of preconception and long-term nitrate in drinking water were estimated. Binominal regression models for risk ratios (RR) were adjusted for age, occupation, education, population density, and lifestyle factors.Results: Nitrate in drinking water (median preconception exposure: 1.9 mg/L; median long-term exposure: 3.3 mg/L) was not associated with TTP > 12 months or use of MAR treatment, neither in the categorical nor in the continuous models.Conclusion: We found no association between preconception or long-term exposure to drinking water nitrate and fecundability.Keywords: environmental pollutant, subfecundity, time to pregnancy, public health, groundwater

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