Nerea Martín-Calvo1, Lidia Mínguez-Alarcón2, Audrey J Gaskins3, Feiby L Nassan4, Paige L Williams5, Irene Souter6, Russ Hauser7, Jorge E Chavarro8. 1. University of Navarra, Department of Preventive Medicine and Public Health, Instituto de Investigación Sanitaria de Navarra (IdISNA), Pamplona, Spain; CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Carlos III Institute of Health, Madrid, Spain. 2. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston MA, USA. 3. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 25 Shattuck Street, Boston MA, USA; Department of Epidemiology, University of Emory. Atlanta GA, USA. 4. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston MA, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston MA, USA. 5. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston MA, USA. 6. Vincent Obstetrics and Gynecology, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA. 7. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston MA, USA; Vincent Obstetrics and Gynecology, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA. 8. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 25 Shattuck Street, Boston MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston MA, USA. Electronic address: jchavarr@hsph.harvard.edu.
Abstract
RESEARCH QUESTION: Studies in rodents have shown that paternal folate intake prior to conception is associated with pregnancy and offspring outcomes. The aim of this study was to assess whether those associations might apply to humans as well. DESIGN: Between 2007 and 2017, the study prospectively analysed data from 108 couples participating in a preconception cohort of couples undergoing fertility treatment using their own gametes, whose treatment resulted in 113 pregnancies during the course of the study. Paternal and maternal preconception folate intake was assessed using a validated food frequency questionnaire. Linear mixed models were used to assess whether paternal preconception folate intake was associated with gestational age at delivery and gestational age-specific birthweight, while accounting for correlated data and potential confounders. RESULTS: In a multivariable-adjusted model, a 400 μg/day increase in preconception paternal folate intake was associated with a 2.6-day longer gestation (95% confidence interval 0.8-4.3) after adjusting for potential confounders, including maternal folate intake. Similar associations were found for folate from food and supplements. Maternal folate intake was not associated with gestational age at delivery. Neither paternal nor maternal folate intake was associated with gestational-age-specific birthweight. CONCLUSIONS: Higher paternal preconception folate intake was associated with slightly longer gestation among live births achieved through assisted reproduction. The results suggest that preconception exposures of the father may have an impact on the health of his offspring, and therefore that preconception care should shift from a woman-centric to a couple-based approach.
RESEARCH QUESTION: Studies in rodents have shown that paternal folate intake prior to conception is associated with pregnancy and offspring outcomes. The aim of this study was to assess whether those associations might apply to humans as well. DESIGN: Between 2007 and 2017, the study prospectively analysed data from 108 couples participating in a preconception cohort of couples undergoing fertility treatment using their own gametes, whose treatment resulted in 113 pregnancies during the course of the study. Paternal and maternal preconception folate intake was assessed using a validated food frequency questionnaire. Linear mixed models were used to assess whether paternal preconception folate intake was associated with gestational age at delivery and gestational age-specific birthweight, while accounting for correlated data and potential confounders. RESULTS: In a multivariable-adjusted model, a 400 μg/day increase in preconception paternal folate intake was associated with a 2.6-day longer gestation (95% confidence interval 0.8-4.3) after adjusting for potential confounders, including maternal folate intake. Similar associations were found for folate from food and supplements. Maternal folate intake was not associated with gestational age at delivery. Neither paternal nor maternal folate intake was associated with gestational-age-specific birthweight. CONCLUSIONS: Higher paternal preconception folate intake was associated with slightly longer gestation among live births achieved through assisted reproduction. The results suggest that preconception exposures of the father may have an impact on the health of his offspring, and therefore that preconception care should shift from a woman-centric to a couple-based approach.
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