Does Fatherhood Matter? Preconception Use of Biologics and Immunomodulators by Fathers With Immune-Mediated Diseases and Birth Outcomes of Their Offspring

Friedman, Sonia; Nørgård, Bente Mertz

doi:10.1053/j.gastro.2021.04.045

Cited by 4 publications

(7 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1,2 The question of how future fathers with autoimmune diseases should be treated to improve (or at least not impair) their chances of achieving a successful pregnancy and a healthy offspring remains a challenge for physicians and researchers. [1][2][3] Accumulating evidence has demonstrated that preconception paternal factors do affect the offspring. [3][4][5][6][7][8] Paternal preconception stress, diet and exposure to environmental toxins have been associated with altered hypothalamic-pituitary-adrenal axis function, birth defects, cancers, growth, obesity and cardiometabolic risk factors in the offspring.…”

Section: Introductionmentioning

confidence: 99%

“…7,8 Chemical and environmental exposures may induce oxidative stress that results in mitochondrial or nuclear DNA damage or affect the sperm epigenome by altering DNA methyltransferase or histone deacetylase activity and thus interfering with hormonal regulation or sperm development. [2][3][4]8 Thus, preconception toxigenic exposures could increase the risk of offspring disease by epigenetic modifications in the germline, and expectant fathers' use of disease-modifying medication before conception should be considered from this perspective. Based on these arguments, there is a great demand for studies to determine the response of sperm epigenetics in relation to early life environmental exposures.…”

Section: Introductionmentioning

confidence: 99%

“…Men and women with inflammatory bowel disease (IBD) are commonly diagnosed at a time in their lives when they are considering having children. While there is increasing knowledge of the effect of maternal immunosuppressive medications taken during pregnancy and child outcomes, there is a lack of data on the impact of paternal medications on child health outcomes 1,2 . The question of how future fathers with autoimmune diseases should be treated to improve (or at least not impair) their chances of achieving a successful pregnancy and a healthy offspring remains a challenge for physicians and researchers 1–3 .…”

Section: Introductionmentioning

confidence: 99%

“…While there is increasing knowledge of the effect of maternal immunosuppressive medications taken during pregnancy and child outcomes, there is a lack of data on the impact of paternal medications on child health outcomes 1,2 . The question of how future fathers with autoimmune diseases should be treated to improve (or at least not impair) their chances of achieving a successful pregnancy and a healthy offspring remains a challenge for physicians and researchers 1–3 . Accumulating evidence has demonstrated that preconception paternal factors do affect the offspring 3–8 .…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, animal studies have documented that epigenetic modifications encoded in sperm are heritable and influence offspring phenotypes 7,8 . Chemical and environmental exposures may induce oxidative stress that results in mitochondrial or nuclear DNA damage or affect the sperm epigenome by altering DNA methyltransferase or histone deacetylase activity and thus interfering with hormonal regulation or sperm development 2–4,8 . Thus, preconception toxigenic exposures could increase the risk of offspring disease by epigenetic modifications in the germline, and expectant fathers' use of disease‐modifying medication before conception should be considered from this perspective.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Paternal use of medications for inflammatory bowel disease and the risk of hospital‐diagnosed infections in the offspring: a nationwide cohort study

Friedman

Garvik

Nielsen

et al. 2022

Aliment Pharmacol Ther

Self Cite

View full text Add to dashboard Cite

Summary Background Information regarding the impact of paternal inflammatory bowel disease (IBD) medications on child outcomes is scarce. Aim To examine the risk of childhood infections associated with fathers' use of anti‐inflammatory/immunosuppressive medications taken before conception. Methods This is a nationwide cohort study based on Danish health registries, comprising all live‐born singleton children born between January 1997 and February 2019 who were fathered by men with IBD. Exposed cohorts included children fathered by men treated with 5‐aminosalicylates (5‐ASAs), thiopurines, corticosteroids or anti‐tumour necrosis factor‐α (anti‐TNF‐α) agents within 3 months before conception. The unexposed cohort included children not exposed to paternal IBD medications. Outcomes were the first infection, diagnosed in the hospital setting in the first year of life, and from the age of 1 to 3 years. Results In all, 2178 children were fathered by men exposed to 5‐ASAs, 843 to thiopurines, 417 to systemic corticosteroids and 436 to anti‐TNF‐α agents; 6799 children were unexposed. The adjusted hazard ratio (aHR) for infections within the first year of life for 5‐ASAs was 0.78 (95% CI, 0.66–0.91), thiopurines 0.89 (95% CI, 0.73–1.09), systemic corticosteroids 0.95 (95% CI, 0.70–1.29), and anti‐TNF‐α agents 1.17 (95% CI, 0.94–1.46). The aHR for infections from 1 to 3 years for 5‐ASAs was 0.97 (95% CI, 0.83–1.13), thiopurines 0.87 (95% CI, 0.71–1.07), systemic corticosteroids 1.25 (95% CI, 0.94–1.65), and anti‐TNF‐α agents 0.79 (95% CI, 0.60–1.03). Conclusion Fathers' use of anti‐inflammatory/immunosuppressive medications before conception was not significantly associated with childhood infections. These results fill an important research gap regarding paternal medication safety.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Paternal use of medications for inflammatory bowel disease and the risk of hospital‐diagnosed infections in the offspring: a nationwide cohort study

Friedman

Garvik

Nielsen

et al. 2022

Aliment Pharmacol Ther

Self Cite

View full text Add to dashboard Cite

show abstract

Paternal Inflammatory Bowel Disease and the Risk of Pregnancy Loss

Friedman,

Thorarinsson,

Wod

et al. 2024

Inflammatory Bowel Diseases

View full text Add to dashboard Cite

Background Only about 30% of conceptions end in live births, yet there are little data on paternal causes of pregnancy loss. Men with inflammatory bowel disease may have multiple disease-related issues that may affect fertility. We aimed to examine pregnancy outcomes in women undergoing assisted reproduction whose male partners had Crohn’s disease or ulcerative colitis. Methods This nationwide study included all embryo transfers registered in the Danish Assisted Reproduction Registry from January 2, 2006, to September 3, 2019. The exposed cohort included embryo transfers from couples in which the male partners had Crohn’s disease or ulcerative colitis. The unexposed cohort included embryo transfers in which male partners did not have inflammatory bowel disease. Results For fathers with ulcerative colitis, the adjusted odds ratio for a positive biochemical pregnancy (positive human chorionic gonadotropin) was 1.14 (95% confidence interval [CI], 0.92-1.42), for a clinical pregnancy (positive vaginal ultrasonography at 7-8 weeks) was 0.91 (95% CI, 0.59-1.40), and for a live birth was 0.99 (95% CI, 0.71-1.60). For fathers with Crohn’s disease, the adjusted odds ratio for a biochemical pregnancy was 0.83 (95% CI, 0.63-1.09), for a clinical pregnancy was 0.58 (95% CI, 0.34-0.97), and for a live birth was 0.88 (95% CI, 0.51-1.55). Conclusions These findings may indicate that partners of men with Crohn’s disease may have an increased risk of early pregnancy loss. Future studies should confirm these results and examine the impact of paternal medications, paternal disease activity, and other factors associated with chronic inflammatory bowel disease.

show abstract

Paternal preconception exposure to non‐steroid anti‐inflammatory drugs or opioids and adverse birth outcomes: A nationwide registry‐based cohort study

Lund,

Garvik,

Aagaard

et al. 2023

Andrology

View full text Add to dashboard Cite

Background and aimPaternal use of analgesics during the time of conception and adverse birth outcomes are poorly studied. We investigated the association between paternal exposure to non‐steroid anti‐inflammatory drugs and opioids within 3 months before the date of conception and the risk of adverse birth outcomes (preterm birth, small for gestational age, low Apgar score, and major congenital malformations).MethodsWe used nationwide data from the Danish health registers. We included information on all singleton live births, and their fathers and mothers from 1997 to 2018. We created two exposed cohorts, children with preconception paternal exposure to (1) non‐steroid anti‐inflammatory drugs and (2) opioids. The unexposed cohort was children without preconception paternal exposure to non‐steroid anti‐inflammatory drugs or opioids, and we performed a sub‐analysis against paternal use of acetaminophen (paracetamol). We used logistic regression models to estimate the odds ratios of adverse birth outcomes including 95% confidence intervals.ResultsWe identified 1,260,934 children, 45,667 children with paternal exposure to non‐steroid anti‐inflammatory drugs, 10,086 children with paternal exposure to opioids, and 1,205,181 unexposed children. The adjusted odds ratio for preterm birth was 1.08 (95% confidence interval, 1.03–1.13) after paternal exposure to non‐steroid anti‐inflammatory drugs and 1.21 (95% confidence interval, 1.08–1.35) after paternal exposure to opioids. The adjusted odds ratio for small for gestational age was 1.09 (95% confidence interval, 1.03–1.17) after paternal exposure to non‐steroid anti‐inflammatory drugs, and 1.03 (95% confidence interval, 0.88–1.21) after paternal exposure to opioids. We found null‐associations for a low Apgar score and major congenital malformations. Estimates were attenuated when compared against paternal paracetamol exposure.ConclusionsOverall, we found null‐associations across the comparisons made. Weak associations were found for paternal exposure to non‐steroid anti‐inflammatory drugs or opioids and preterm birth and small for gestational age, but not with low Apgar score or major congenital malformation. All associations were attenuated when compared against an active comparator of paternal paracetamol exposure. The effect sizes were small and less likely to be of clinical relevance.

show abstract

Does Fatherhood Matter? Preconception Use of Biologics and Immunomodulators by Fathers With Immune-Mediated Diseases and Birth Outcomes of Their Offspring

Cited by 4 publications

References 20 publications

Paternal use of medications for inflammatory bowel disease and the risk of hospital‐diagnosed infections in the offspring: a nationwide cohort study

Paternal use of medications for inflammatory bowel disease and the risk of hospital‐diagnosed infections in the offspring: a nationwide cohort study

Paternal Inflammatory Bowel Disease and the Risk of Pregnancy Loss

Paternal preconception exposure to non‐steroid anti‐inflammatory drugs or opioids and adverse birth outcomes: A nationwide registry‐based cohort study

Contact Info

Product

Resources

About