Paternal use of metformin during sperm production not associated with major birth defects

Embargoed for release until 5:00 p.m. ET on Monday 17 June 2024    

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Below please find summaries of new articles that will be published in the next issue of Annals of Internal Medicine. The summaries are not intended to substitute for the full articles as a source of information. This information is under strict embargo and by taking it into possession, media representatives are committing to the terms of the embargo not only on their own behalf, but also on behalf of the organization they represent.    
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1. Paternal use of metformin during sperm production not associated with major birth defects 

Authors caution that familial risk profile, lifestyle factors may play a role 

Abstract: https://www.acpjournals.org/doi/10.7326/M23-1405    

Editorial:  https://www.acpjournals.org/doi/10.7326/M24-0883    

URL goes live when the embargo lifts       

 

A study of almost 400,000 live births found that paternal use of metformin monotherapy was not associated with major congenital malformations (MCMs) in newborns. Associations between metformin in polytherapy and birth defects could potentially be explained by worse underlying parental cardiometabolic risk profile of those taking multiple diabetes medications. The study is published in Annals of Internal Medicine.  

 

Researchers from Harvard T.H. Chan School of Public Health, Kahn-Sagol-Maccabi (KSM) Research and Innovation Institute, and Brigham and Women’s Hospital studied data from a large Israeli health fund from 1999 to 2020 to assess the potential adverse intergenerational effect of metformin use during the sperm production period preceding conception. MCMs and parental cardiometabolic conditions were ascertained using clinical diagnoses, medication dispensing information, and laboratory test results. Although crude findings suggested that metformin was associated with increased risk of MCM (6.2% versus 4.7% when father used no diabetic medication), this association did not persist with adjustment for paternal cardiovascular and metabolic co-morbid conditions and exclusion of children born to mothers with diabetes or hyperglycemia (to eliminate possible effects mediated through the mother). Fathers prescribed metformin and other diabetic medication were more likely to be older, with co-existent cardiovascular and metabolic conditions, to be smokers and to have fertility problems. Similarly, mothers were more likely to have cardiovascular co-morbidity and to have experienced fertility problems when the father used metformin.

 

The author of an accompanying editorial from the University of Dundee suggests that these findings underscore the importance of considering paternal health in the context of reproductive planning and prenatal care. The author notes that metformin is a safe and effective treatment option for type 2 diabetes for men and women trying to conceive as well as for managing hyperglycemia in pregnant women in the first trimester. As such, it may be time to reconsider current prenatal care guidelines that advocate switching to insulin therapy for those trying to conceive. 

 

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with the corresponding author, please contact Ran S. Rotem, SM, ScD, at ran.rotem@mail.harvard.edu.  

 

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2. Continuing metformin during first trimester does not increase risk for major malformations

Abstract: https://www.acpjournals.org/doi/10.7326/M23-2038    

URL goes live when the embargo lifts       

A study of more than 12,000 pregnant women with type 2 diabetes receiving metformin monotherapy before conception found that compared with switching to insulin monotherapy, continuing metformin and adding insulin in early pregnancy resulted in little to no increased risk for major malformations in the infant. The analysis is published in Annals of Internal Medicine.  

 

Researchers from Harvard T.H. Chan School of Public Health use real-world data from the U.S. Medicaid health care administration database from 2000 to 2018 to evaluate the teratogenicity of metformin use in the first trimester of pregnancy. Women taking metformin were either switched to insulin monotherapy  or prescribed insulin in addition to metformin within 90 days of last menstrual period (LMP). Outcomes considered were non-chromosomal fetal malformations and non-live births, comprised of spontaneous abortion, termination and stillbirth. The estimated risk for non-live birth was 32.7% under insulin monotherapy and 34.3% under insulin plus metformin. The authors also found that the estimated risk for live birth with congenital malformations was 8.0% under insulin monotherapy and 5.7% under insulin plus metformin. Based on these findings, current recommendations that suggest switching from metformin to insulin before pregnancy for fetal safety concerns may require reconsideration. 

 

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with the corresponding author, Yu-Han Chiu, MD, ScD, please contact Jack MacDonald at jmacdonald@hsph.harvard.edu. 

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3. Diet quality remains poor among socioeconomically disadvantaged populations   

Abstract: https://www.acpjournals.org/doi/10.7326/M24-0190  

URL goes live when the embargo lifts 

A study of U.S. dietary trends found that diet quality among U.S. adults improved modestly between 1999 and 2020, but the proportion of socioeconomically disadvantaged people with poor diet quality remained high, and dietary disparities persisted or worsened. The report is published in Annals of Internal Medicine.   

 

Researchers from the Department of Population Science and Policy at Icahn School of Medicine at Mount Sinai and the Food is Medicine Institute at the Friedman School of Nutrition Science and Policy at Tufts University studied data from 51,703 adults responding to the National Health and Nutrition Examination Survey (NHANES) to evaluate trends in diet quality by race, ethnicity, and socioeconomic disadvantage. Participants’ diet quality was assessed using the American Heart Association (AHA) 2020 continuous diet score, which is measured based on a higher intake of healthy, unprocessed foods, and a lower intake of sugar, sodium, and processed foods. They also looked at energy-adjusted consumption of the diet components and other individual food groups and nutrients. Poor diet was defined as less than 40% adherence to the AHA score, intermediate as 40% to 79.9% adherence, and ideal as at least 80% adherence. The researchers found that from 1999 to 2020, the proportion of U.S. adults with poor diet quality decreased by more than 11%, the proportion with intermediate quality increased by more than 10%, and the proportion with ideal quality increased slightly. However, worsening disparities in diet quality remained among those in disadvantaged socioeconomic groups. The proportion of adults with poor diet quality decreased from 47.9% to 33.0% among those with food security but did not change among those experiencing food insecurity.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak to the corresponding author, please contact Taraneh Pettinato at Taraneh.Pettinato@tufts.edu.

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4. Scoping review identifies factors taxing physicians’ attention

Abstract: https://www.acpjournals.org/doi/10.7326/M23-3229  

Editorial:  

URL goes live when the embargo lifts     

Researchers from the University of Colorado Anschutz Medical Campus systematically reviewed 6,448 studies to identify and characterize the literature on clinician attention, compile the metrics used to measure attention, and create a framework of key concepts related to clinician attention. The findings are published in Annals of Internal Medicine.

 

The authors defined attention as a state of presence, focus, and selective incorporation of information within clinical environments. The concept of an “ecology of attention” was used to describe an analogous interrelationship between clinician attention and the clinical environment, suggesting key measurable factors that influence the ability of clinicians to maintain presence and focus. Of the studies reviewed, 585 met inclusion criteria. About 80% were descriptive, and 20% were investigational. More studies (66%) focused on barriers to clinician attention than on facilitators of attention. A 6-category framework was derived to organize the literature that included definitions of attention; evaluation of the clinical environment’s effect on attention; personal factors affecting attention; relationships between interventions and factors that affect attention and patient outcomes; the effect of clinical alarms and alarm fatigue on attention; and the effect of health information technology on attention. The authors believe the findings from their scoping review and the analytic framework will help researchers or quality improvement experts studying or looking to improve the “ecology of attention.”

 

The authors of an accompanying editorial from Stanford University School of Medicine say that clinician attention should be spent in the right places. Incremental initiatives intended to enhance safety may not work if they overwhelm working memory and take attention away from other important activities, especially considering that the complexity of daily work for most health care professionals now exceeds human beings’ finite cognitive load capacity. The authors suggest that adoption of human factors and ergonomics principles can help the health care delivery system address this issue and enable the provision of high-quality, compassionate, and cost-effective care in a sustainable manner.

 

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with the corresponding author, please contact Kelsey Hussey at KELSEY.HUSSEY@CUANSCHUTZ.EDU.

 

 

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