• About Us
    • Contact Us
    • Login
    • ObGFirst
  • COVID-19
  • Alerts
  • OB
  • 2T US Atlas
  • The Genome
  • GYN
    • GYN
    • Sexual Health
  • Primary Care
  • Your Practice
  • GrandRounds
  • My Bookshelf
  • Now@ObG
  • Media
About Us Contact Us Login ObGFirst
  • COVID-19
  • Alerts
  • OB
  • 2T US Atlas
  • The Genome
  • GYN
    • GYN
    • Sexual Health
  • Primary Care
  • Your Practice
  • GrandRounds
  • My Bookshelf
  • Now@ObG
  • Media
Grand Rounds

Is Paternal Metformin Use Associated with Higher Odds of Birth Defects in Offspring?

image_pdfFavoriteLoadingFavorite

BACKGROUND AND PURPOSE: 

  • Diabetes medications, such as metformin, have effects on the male reproductive system 
    • Reduces serum testosterone levels independently of glycemic control 
    • Unclear if this association can impact offspring  
  • Wensink et al. (Annals of Internal Medicine, 2022) evaluated whether the risk for birth defects in offspring varies with preconceptional pharmacologic treatment of fathers with diabetes 

METHODS: 

  • Nationwide prospective registry-based cohort study 
    • Medical Birth Registry (1997 to 2016) 
    • Contains all registered pregnancies in Denmark >20 weeks  
  • Participants 
    • All liveborn singletons  
    • Mothers without a history of diabetes or hypertension 
  • Exposures 
    • Paternal diabetes medication exposure 
      • Father filled ≥1 prescriptions for a diabetes drug during the development of fertilizing sperm 
  • Study design 
    • Associations were adjusted for  
      • Birth year | Paternal age, income, and education | Maternal age, smoking status, and education 
    • The primary outcomes were compared  
      • Across drugs | Times of exposure | Siblings 
  • Primary outcomes 
    • Offspring sex 
    • Frequencies of major birth defects 

RESULTS: 

  • 1,116,779 offspring 
    • Insulin exposure: 5298 | metformin exposure: 1451 
    • Offspring with ≥1 major birth defects: 3.3% 
  • Insulin-exposed offspring were not at higher odds of having birth defects than non-exposed offspring 
    • Adjusted odds ratio (aOR) 0.98 (95% CI, 0.85 to 1.14) 
  • Metformin-exposed offspring had an elevated birth defect frequency 
    • aOR 1.40 (95% CI, 1.08 to 1.82) 
  • There were no differences in birth defect frequencies if fathers filled a metformin prescription in the year before or the year after sperm development 
    • Before: aOR 0.88 (95% CI, 0.59 to 1.31) 
    • After: aOR 0.92 (95% CI, 0.68 to 1.26) 
  • Unexposed siblings of exposed offspring also had no differences in birth defect frequencies 
    • Exposed: 3.2% 
    • OR 1.54 (95% CI, 0.94 to 2.53) 
  • Among metformin-exposed offspring, genital birth defects, all in boys, were more common 
    • aOR 3.39 (95% CI, 1.82 to 6.30) 
  • Proportion of male offspring was lower among metformin-exposed offspring but not significant  
    • Exposed: 49.4%  
    • Non-exposed: 51.4% 
    • P=0.073 

CONCLUSION: 

  • The paternal use of metformin prior to conception is associated with increased odds of major birth defects, especially genital birth defects in boys 
  • Results demonstrate association but not causation, which would require further studies  
  • Limitations include lack of data on important confounders such glycemic control or obesity  
    • However, birth defects were not found among insulin group or preconception type 2 diabetes and not receiving metformin 
  • The authors state 

The observed effect size is similar to that of maternal age greater than 45 years, a recognized risk factor, with 4.8% birth defects among liveborn singletons in our data 

The sheer size of the diabetes pandemic suggests that treatment of prospective fathers with diabetes, including pharmacologic management and counseling on diet, physical exercise, and weight loss, should be subject to further study 

Learn More – Primary Sources: 

Preconception Antidiabetic Drugs in Men and Birth Defects in Offspring 

A Nationwide Cohort Study 

image_pdfFavoriteLoadingFavorite
< Previous
All Grand Rounds Posts
Next >

Related ObG Topics:

Does Advanced Paternal Age Introduce Perinatal Risk?
Meta-Analysis Results: Does Paternal Smoking Increase the Risk for Pregnancy Loss?
Does Paternal Antidepressant Use Impact Offspring?

Sections

  • COVID-19
  • Alerts
  • OB
  • GYN
    • GYN
    • Sexual Health
  • 2T US Atlas
  • The Genome
  • Primary Care
  • Your Practice
  • Grand Rounds
  • My Bookshelf
  • Now@ObG
  • Media

Are you an
ObG Insider?

Get specially curated clinical summaries delivered to your inbox every week for free

  • Site Map/
  • © ObG Project/
  • Terms and Conditions/
  • Privacy/
  • Contact Us/
© ObG Project
SSL Certificate


  • Already an ObGFirst Member?
    Welcome back

    Log In

    Want to sign up?
    Get guideline notifications
    CME Included

    Sign Up

Get Guideline Alerts Direct to Your Phone
Try ObGFirst Free!

Sign In

Lost your password?

Sign Up for ObGFirst and Stay Ahead

  • - Professional guideline notifications
  • - Daily summary of a clinically relevant
    research paper
  • - Includes 1 hour of CME every month

ObGFirst Free Trial

Already a Member of ObGFirst®?

Please log in to ObGFirst to access the 2T US Atlas

Password Trouble?

Not an ObGFirst® Member Yet?

  • - Access 2T US Atlas
  • - Guideline notifications
  • - Daily research paper summaries
  • - And lots more!
ObGFirst Free Trial

Media - Internet

Computer System Requirements

OBG Project CME requires a modern web browser (Internet Explorer 10+, Mozilla Firefox, Apple Safari, Google Chrome, Microsoft Edge). Certain educational activities may require additional software to view multimedia, presentation, or printable versions of their content. These activities will be marked as such and will provide links to the required software. That software may be: Adobe Flash, Apple QuickTime, Adobe Acrobat, Microsoft PowerPoint, Windows Media Player, or Real Networks Real One Player.

Disclosure of Unlabeled Use

This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. The planners of this activity do not recommend the use of any agent outside of the labeled indications.

The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of the planners. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.

Disclaimer

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information
presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications and/or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.

Jointly provided by

NOT ENOUGH CME HOURS

It appears you don't have enough CME Hours to take this Post-Test. Feel free to buy additional CME hours or upgrade your current CME subscription plan

Subscribe

JOIN OBGFIRST AND GET CME/CE CREDITS

One of the benefits of an ObGFirst subscription is the ability to earn CME/CE credits from the ObG entries you read. Tap the button to learn more about ObGFirst

Learn More
Leaving ObG Website

You are now leaving the ObG website and on your way to PRIORITY at UCSF, an independent website. Therefore, we are not responsible for the content or availability of this site