Carrier Screening for SMA

Recorded on November 21st, 2022 at 8 pm ET

---

FREE for ObGFirst® Members and ObG Resident CORE™ Members!

Includes CME | Event will be recorded

---

Faculty: Esther Rose, MS CGC and Tamar Goldwaser, MD, FACOG, FACMG 
Moderator: Tracy Shevell, MD

Learning Objectives 

1. The learner will be able to recognize signs and symptoms of SMA
2. The learner will be able to interpret SMA carrier screening result
3. The learner will be able to identify reproductive options for SMA carrier couples

Disclosure of Conflicts of Interest

Postgraduate Institute for Medicine (PIM) requires faculty, planners, and others in control of educational content to disclose all their financial relationships with ineligible companies. All identified conflicts of interest (COI) are thoroughly vetted and mitigated according to PIM policy. PIM is committed to providing its learners with high-quality accredited continuing education activities and related materials that promote improvements or quality in healthcare and not a specific proprietary business interest of an ineligible company.

The faculty reported the following relevant financial relationships with ineligible entities related to the educational content of this CE activity:

Esther Rose, MS CGC and Tamar Goldwaser, MD, FACOG, FACMG have nothing to disclose
The PIM and ObGProject planners and others have nothing to disclose

Joint Accreditation Statement

In support of improving patient care, this activity has been planned and implemented by the Postgraduate Institute for Medicine and The ObG Project. Postgraduate Institute for Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Physician Continuing Medical Education 

Postgraduate Institute for Medicine designates this live activity for a maximum of 1 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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.

Atrial Fibrillation: Diagnosis and Management

SUMMARY:

Atrial fibrillation, the most common cardiac arrhythmia, increases stroke risk and can exacerbate underlying heart disease. The 2014 ACC/AHA/HRS Guideline for the Management of Patients with Atrial Fibrillation offers a comprehensive approach to treating this condition. A focused update released in 2019 includes new evidence in support of novel drugs and devices to prevent thromboembolism, as well as other clinical considerations. Of note, these recommendations apply to atrial fibrillation (AF) and atrial flutter, regardless of the pattern of arrhythmia (i.e. paroxysmal, persistent, or permanent).

• Diagnosis and Workup
• Treatment Highlights
• Risk stratification
• Anticoagulation
• Alternatives to Anticoagulation
• Rate Control
• Rhythm Control

Diagnosis and Workup

• Diagnosed by EKG or cardiac monitoring: Characteristic irregular rhythm without discrete p-waves
• Workup at time of diagnosis should include
  • TTE | Thyroid function tests | CBC | Renal function and electrolytes | LFTs | CXR (if suspicion for heart failure or pulmonary disease) | Sleep study (if suspicion for sleep apnea)
• Outpatient management appropriate for hemodynamically stable patients without evidence of severe volume overload or acute coronary syndrome

Note: Routine screening for AF in the general population is not currently recommended by the USPSTF | The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for AF (I statement)

Treatment Highlights

• Mainstays of treatment for most patients are anticoagulation (warfarin vs. NOAC) and rate control (typically beta blocker or nondihydropyridine calcium channel blocker)
• For some patients, attempted cardioversion to sinus rhythm may be preferred initially
• Invasive procedures to ablate AF or occlude the LAA are appropriate for select patients

KEY POINTS:

• Valvular vs. non-valvular AF
  • Valvular: AF associated with moderate to severe mitral stenosis or mechanical heart valve
  • Non-valvular: All other AF (much more common)

Risk stratification

• CHA₂DS₂-VASc:  Estimates annual stroke risk for non-valvular AF, based on various demographic and comorbid factors
  • Anticoagulation is recommended for score ≥2 in men, ≥3 in women
  • Anticoagulation “may be considered” for score 1 in men, 2 in women; aspirin is also an option
• Stroke risk can be weighed against bleeding risk using clinical calculators such as HAS-BLED
  • However per ACC/AHA “their clinical utility is insufficient for use as evidence”
  • Higher bleeding risk may warrant closer monitoring of anticoagulated patients, but should not necessarily preclude anticoagulation

Anticoagulation

Choosing an anticoagulant

• Goal is to prevent thromboembolic events
• Decision to start anticoagulation should always involve discussion of risks vs benefits

Medications

• Warfarin
  • Indicated for all valvular AF
  • Goal INR 2-3
• Novel oral anticoagulants (NOACs) recommended over warfarin for non-valvular AF in absence of contraindications
  • Dabigatran (Pradaxa) | Rivaroxaban (Xarelto) | Apixaban (Eliquis) | Edoxaban (Savaysa)
  • All either superior or non-inferior to warfarin | Do not require INR monitoring | Have lower risk of major bleeding
  • All have reduced dose options for CKD

• ESRD
  • Use warfarin or apixaban (limited data to support this)
• Bridging
  • For patients with mechanical heart valves undergoing surgery or other invasive procedure, bridge with unfractionated or low molecular weight heparin to provide uninterrupted anticoagulation
  • For all others, a brief interruption of therapy without bridging is considered safe

• Anticoagulation with antiplatelet therapy
  • Patients with AF and recent coronary stenting who are on triple therapy (oral anticoagulant + aspirin + P2Y₁₂ inhibitor) may be narrowed to double therapy (warfarin, dabigatran, or rivaroxaban + P2Y₁₂ inhibitor) to reduce bleeding risk

Dosing

• Apixaban (Eliquis)
  • Usual dose: 5 mg twice a day
  • Adjusted dose: 2.5 mg twice a day if ≥2 of the following
    • Age: ≥80 years
    • Body weight: ≤60 kg
    • Serum creatinine: ≥1.5 mg/dL

Note:  Caution with use of apixaban and the following 

• Other medications that can interfere with hemostasis: May increase risk of bleeding
  • Aspirin and antiplatelet agents | Other anticoagulants | Heparin | Thrombolytic agents | SSRIs | SNRIs | NSAIDs (chronic use) | Fibrinolytics
• Combined P-gp and strong CYP3A4 inhibitors
  • Ketoconazole | Itraconazole | Ritonavir
  • Reduce dose by 50% in usual dosing regimen and do not use with 2.5 mg reduced dose | Dose does not need to be altered with clarithromycin
• Combined P-gp and strong CYP3A4 inducers: Avoid concomitant use
  • Rifampin | Carbamazepine | Phenytoin | St. John’s wort

---

• Dabigatran (Pradaxa)
  • CrCl >30 mL/min: 150 mg orally, twice daily
  • CrCl 15 to 30 mL/min: 75 mg orally, twice daily

Note: Exercise caution with use of dabigatran and the following

• P-gp inducers rifampin: Avoid coadministration
• P-gp inhibitors in patients with CrCl 30-50 mL/min: Reduce dose or avoid
• P-gp inhibitors in patients with CrCl <30 mL/min: Not recommended

---

• Rivaroxaban (Xarelto)
  • 15 or 20 mg, once daily with food

Note: Exercise caution with use of rivaroxaban and the following

• Avoid combined P-gp and strong CYP3A inhibitors and inducers
• Anticoagulants: Avoid concomitant use
• Renal impairment: Avoid or adjust dose
• Hepatic impairment: Avoid use in Child-Pugh B and C hepatic impairment or with any degree of hepatic disease associated with coagulopathy

Alternatives to Anticoagulation

• Since thromboemboli tend to develop in the left atrial appendage (LAA), non-pharmacologic strategies for minimizing stroke risk involve occluding or removing the LAA
  • Percutaneous LAA occlusion (Watchman device): For patients with a contraindication to long-term anticoagulation (however, must be able to receive periprocedural anticoagulation)
  • Surgical LAA occlusion/excision: Only for patients already undergoing cardiac surgery for another indication

Rate Control

• Goal: To reduce symptoms, improve intra-cardiac hemodynamics and perfusion, and prevent tachycardia-induced cardiomyopathy
• Choosing a rate control strategy
  • Beta blockers (metoprolol, carvedilol, atenolol) or nondihydropyridine calcium channel blockers (diltiazem, verapamil) are first-line
  • Avoid CCBs in heart failure with reduced EF
  • Second-line options include digoxin (possibly associated with increased mortality) and amiodarone (not for long-term use due to toxicities)
• Strict (<80 bpm) vs. lenient (<110 bpm) rate control
  • Lenient approach acceptable as long as patient is asymptomatic and with preserved EF

Rhythm Control

• Not superior to rate control and associated with increase in hospitalizations
• May be indicated for new-onset AF, persistent symptoms, difficulty achieving rate control, young age, or tachycardia-induced cardiomyopathy
  • These approaches generally require expert consultation
• Electrical cardioversion
  • In non-emergent setting, requires anticoagulation three weeks pre- and four weeks post-procedure (if duration of AF >48 hours or unknown)
  • Often preceded by TEE to exclude LA thrombus
• Maintaining sinus rhythm
  • Typically achieved with antiarrhythmics (e.g. amiodarone, dofetilide, flecainide)
  • Caution: These drugs have significant side effects and toxicities
• Catheter ablation
  • For symptomatic paroxysmal AF not responding to antiarrhythmic therapy

Pregnancy for Women with Substance Use Disorders

Recorded on October 19th, 2022 at 8 pm ET

---

FREE for ObGFirst® Members and ObG Resident CORE™ Members!

Includes CME | Event will be recorded

---

Faculty: Marcela Smid, MD, MA, MS
Moderator: Tracy Shevell, MD

Learning Objectives 

1. Define the difference between substance use and substance use disorder diagnosis
2. Recognize the course of substance use among pregnant and postpartum individuals
3. Explain the role of overdose in maternal morbidity and mortality in the United States

Disclosure of Conflicts of Interest

Postgraduate Institute for Medicine (PIM) requires faculty, planners, and others in control of educational content to disclose all their financial relationships with ineligible companies. All identified conflicts of interest (COI) are thoroughly vetted and mitigated according to PIM policy. PIM is committed to providing its learners with high-quality accredited continuing education activities and related materials that promote improvements or quality in healthcare and not a specific proprietary business interest of an ineligible company.

The faculty reported the following relevant financial relationships with ineligible entities related to the educational content of this CE activity:

Marcela Smid, MD, MA, MS has nothing to disclose
The PIM and ObGProject planners and others have nothing to disclose

Joint Accreditation Statement

In support of improving patient care, this activity has been planned and implemented by the Postgraduate Institute for Medicine and The ObG Project. Postgraduate Institute for Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Physician Continuing Medical Education 

Postgraduate Institute for Medicine designates this live activity for a maximum of 1 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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.

Evaluation and Management of Overactive Bladder and Stress Urinary Incontinence 

Recorded on September 21st, 2022 at 8 pm ET

---

FREE for ObGFirst® Members and ObG Resident CORE™ Members!

Includes CME | Event will be recorded

---

Faculty: Brian Hines, MD
Moderator: Tracy Shevell, MD

Learning Objectives 

1. Describe the evaluation of a patient with urinary incontinence 

2. Explain the risks and benefits of medical and surgical approaches used in the management of urinary incontinence 

Disclosure of Conflicts of Interest

Postgraduate Institute for Medicine (PIM) requires faculty, planners, and others in control of educational content to disclose all their financial relationships with ineligible companies. All identified conflicts of interest (COI) are thoroughly vetted and mitigated according to PIM policy. PIM is committed to providing its learners with high-quality accredited continuing education activities and related materials that promote improvements or quality in healthcare and not a specific proprietary business interest of an ineligible company.

The faculty reported the following relevant financial relationships with ineligible entities related to the educational content of this CE activity:

Brian Hines, MD has nothing to disclose
The PIM and ObGProject planners and others have nothing to disclose

Joint Accreditation Statement

In support of improving patient care, this activity has been planned and implemented by the Postgraduate Institute for Medicine and The ObG Project. Postgraduate Institute for Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Physician Continuing Medical Education 

Postgraduate Institute for Medicine designates this live activity for a maximum of 1 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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.

Managing Persistent Pelvic Pain: Less Stress, Better Care in Clinical Practice

Recorded on August 17, 2022 at 8 pm ET

---

FREE for ObGFirst® Members and ObG Resident CORE™ Members!

Includes CME | Event will be recorded

---

Faculty: Georgine Lamvu, MD, MPH 
Moderator: Lia Wrenn, MD

Learning Objectives 

1. Outline impact of CPP on patients and clinicians 
2. Review evidence-based recommendation for treatment of CPP that will help you in your practice 
3. Propose a multidisciplinary way for incorporating care of CPP into general gynecology practice  

Disclosure of Conflicts of Interest

Postgraduate Institute for Medicine (PIM) requires faculty, planners, and others in control of educational content to disclose all their financial relationships with ineligible companies. All identified conflicts of interest (COI) are thoroughly vetted and mitigated according to PIM policy. PIM is committed to providing its learners with high-quality accredited continuing education activities and related materials that promote improvements or quality in healthcare and not a specific proprietary business interest of an ineligible company.

The faculty reported the following relevant financial relationships with ineligible entities related to the educational content of this CE activity:

Georgine Lamvu, MD MPH has nothing to disclose
The PIM and ObGProject planners and others have nothing to disclose

Joint Accreditation Statement

In support of improving patient care, this activity has been planned and implemented by the Postgraduate Institute for Medicine and The ObG Project. Postgraduate Institute for Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Physician Continuing Medical Education 

Postgraduate Institute for Medicine designates this live activity for a maximum of 1 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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.

Urine Good Hands: Evaluation and Management of Bladder Pain

Recorded on July 20, 2022 at 8 pm ET

---

FREE for ObGFirst® Members and ObG Resident CORE™ Members!

Includes CME

---

Faculty: Jocelyn Fitzgerald, MD FACOG
Moderator: Lia Wrenn, MD

Learning Objectives 

1. Define chronic urinary and bladder pain syndromes 
2. Discuss the differential diagnosis and evaluation of patients with urinary pain 
3. Decide how and when to refer patients to other specialist providers 
4. Identify some research opportunities and emerging therapeutics 

Disclosure of Conflicts of Interest

Postgraduate Institute for Medicine (PIM) requires faculty, planners, and others in control of educational content to disclose all their financial relationships with ineligible companies. All identified conflicts of interest (COI) are thoroughly vetted and mitigated according to PIM policy. PIM is committed to providing its learners with high-quality accredited continuing education activities and related materials that promote improvements or quality in healthcare and not a specific proprietary business interest of an ineligible company.

The faculty reported the following relevant financial relationships with ineligible entities related to the educational content of this CE activity:

Jocelyn Fitzgerald, MD FACOG has nothing to disclose
The PIM and ObGProject planners and others have nothing to disclose

Joint Accreditation Statement

In support of improving patient care, this activity has been planned and implemented by the Postgraduate Institute for Medicine and The ObG Project. Postgraduate Institute for Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Physician Continuing Medical Education 

Postgraduate Institute for Medicine designates this live activity for a maximum of 1 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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.

Chronic HTN & Pregnancy

Recorded on June 22, 2022 at 8 pm ET

---

FREE for ObGFirst® Members and ObG Resident CORE™ Members!

Includes CME

---

Faculty: Kim Boggess, MD
Moderator: Ashley Comfort, MD, FACOG

Learning Objectives 

1. Recognize treatment thresholds for hypertension in pregnancy 
2. Discuss pregnancy outcomes following medical treatment of chronic hypertension 

Disclosure of Conflicts of Interest

Postgraduate Institute for Medicine (PIM) requires faculty, planners, and others in control of educational content to disclose all their financial relationships with ineligible companies. All identified conflicts of interest (COI) are thoroughly vetted and mitigated according to PIM policy. PIM is committed to providing its learners with high-quality accredited continuing education activities and related materials that promote improvements or quality in healthcare and not a specific proprietary business interest of an ineligible company.

The faculty reported the following relevant financial relationships with ineligible entities related to the educational content of this CE activity:

Jeffrey D. Sperling, MD, MS has nothing to disclose
The PIM and ObGProject planners and others have nothing to disclose

Joint Accreditation Statement

In support of improving patient care, this activity has been planned and implemented by the Postgraduate Institute for Medicine and The ObG Project. Postgraduate Institute for Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Physician Continuing Medical Education 

Postgraduate Institute for Medicine designates this live activity for a maximum of 1 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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.

Thyroid Disease in Pregancy

Recorded on May 27, 2022 at 10 am ET

---

FREE for ObGFirst® Members and ObG Resident CORE™ Members!

Includes CME

---

Faculty: Jeffrey D. Sperling, MD, MS 
Moderator: Ashley Comfort, MD, FACOG

Learning Objectives 

1. Discuss the diagnosis and management of common thyroid diseases in pregnancy
2. Identify discrepancies (there are many) in the guidelines on management of thyroid disease in pregnancy
3. Describe the recent ACOG Practice Bulletin on thyroid disease in pregnancy

Disclosure of Conflicts of Interest

Postgraduate Institute for Medicine (PIM) requires faculty, planners, and others in control of educational content to disclose all their financial relationships with ineligible companies. All identified conflicts of interest (COI) are thoroughly vetted and mitigated according to PIM policy. PIM is committed to providing its learners with high-quality accredited continuing education activities and related materials that promote improvements or quality in healthcare and not a specific proprietary business interest of an ineligible company.

The faculty reported the following relevant financial relationships with ineligible entities related to the educational content of this CE activity:

Jeffrey D. Sperling, MD, MS has nothing to disclose
The PIM and ObGProject planners and others have nothing to disclose

Joint Accreditation Statement

In support of improving patient care, this activity has been planned and implemented by the Postgraduate Institute for Medicine and The ObG Project. Postgraduate Institute for Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Physician Continuing Medical Education 

Postgraduate Institute for Medicine designates this live activity for a maximum of 1 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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.

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

• 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 

• 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 

• 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 

• 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 

Meta-Analysis: Risks and Benefits of LMWH vs Direct Oral Anticoagulants for Thromboprophylaxis Prior to Surgery 

• The best method of thromboprophylaxis for non-cardiac surgery is still uncertain  
• Marcucci et al. (BMJ, 2022) systematically compared the effect of direct oral anticoagulants vs low-molecular weight heparin (LMWH) as thromboprophylaxis for patients undergoing non-cardiac surgery 

• Systematic review and network meta-analysis 
• Inclusion criteria 
  • RCTs 
  • Studies in adults undergoing non-cardiac surgery that compared prophylactic LMWH (low or higher dose) with direct oral anticoagulants or with no active treatment 
• Study design 
  • Network meta-analysis with multivariate random effects models used to assess odds ratios for primary outcomes 
  • GRADE criteria used to evaluate certainty of the evidence 
• Primary outcomes 
  • Symptomatic venous thromboembolism 
  • Symptomatic pulmonary embolism 
  • Major bleeding 

• 68 RCTs (51 orthopedic, 10 general, 4 gynecological, 2 thoracic, 1 urological) 
  • 45,445 patients 
• All treatments reduced symptomatic venous thromboembolism, compared to no active treatment 
  • Low-dose LMWH: OR 0.33 (95% CI, 0.16 to 0.67) 
  • High-dose LMWH: OR 0.19 (95% CI, 0.07 to 0.54)  
  • Direct oral anticoagulants: OR 0.17 (95% CI, 0.07 to 0.41) 
  • Certainty of evidence: Moderate to high 
  • Absolute risk differences varied between 1 and 100 per 1000 patients, depending on baseline risks  
• None of the active agents reduced symptomatic pulmonary embolism 
  • Certainty of evidence: Low to moderate 
• Compared with no treatment, direct oral anticoagulants and LMWH were both associated with a 2- to 3-fold increase in the odds of major bleeding 
  • Certainty of evidence: Moderate to high 
  • Absolute risk differences were as high as 50 per 1000 in patients at high risk 
• Compared with low dose LMWH, high dose LMWH 
  • Did not reduce symptomatic venous thromboembolism 
    • OR 0.57 (95% CI, 0.26 to 1.27) 
  • Did increase major bleeding 
    • OR 1.87 (95% CI, 1.06 to 3.31) 
• Direct oral anticoagulants  
  • Reduced symptomatic venous thromboembolism 
    • OR 0.53 (95% CI, 0.32 to 0.89) 
  • Did not increase major bleeding 
    • OR 1.23 (95% CI, 0.89 to 1.69) 

• Compared to no treatment, both LMWH and direct oral anticoagulants reduced the odds of venous thromboembolism 
  • However, both treatments probably increased the odds of bleeding 
• Direct oral anticoagulants probably prevent symptomatic venous thromboembolism better than prophylactic LMWH 
• The authors conclude  

We showed that direct oral anticoagulants and LMWH probably reduce symptomatic venous thromboembolism in major non-cardiac surgery, and that direct oral anticoagulants probably have a relatively greater efficacy than LMWH at the standard prophylactic dose 

Benefits and harms of direct oral anticoagulation and low molecular weight heparin for thromboprophylaxis in patients undergoing non-cardiac surgery: systematic review and network meta-analysis of randomised trials 

Is Chorioamnionitis Associated with Increased Risk for Neurodevelopmental Disorders?

• Tsamantioti et al. (AJOG, 2022) examined the association between chorioamnionitis and neurodevelopmental disorders in offspring 

• Retrospective population-based cohort study 
  • Swedish Medical Birth Register 
  • Between 1998 and 2019  
• Population 
  • Singleton live births and stillbirths 
  • All singleton births ≥22 weeks  
• Exposures 
  • Chorioamnionitis 
• Study design 
  • Multivariable Cox proportional hazards regression was used to estimate associations with adjusted hazard ratios (aHR) 
  • Additional analysis of the relationship between chorioamnionitis and neurodevelopmental disorders with preterm delivery (<37 weeks) was performed 
• Primary outcomes 
  • Cerebral palsy 
  • Autism 
  • Attention deficit hyperactivity disorder 
  • Epilepsy 
  • Intellectual disability 

• 2,228,280 births  
  • Exposed to chorioamnionitis: 0.26%  
• Incidence of neurodevelopmental disorders across all births during study period 
  • Cerebral palsy: 0.21% 
  • Epilepsy: 0.80% 
  • Autism: 2.27% 
  • Attention deficit hyperactivity disorder: 5.12% 
  • Intellectual disability: 0.65% 
• After adjusting for potential confounders, exposure to chorioamnionitis increased risk for the following  
  • Cerebral palsy  
    • aHR 7.43 (95% CI, 5.90 to 9.37) 
  • Autism  
    • aHR 1.43 (95% CI, 1.21 to 1.68) 
  • Attention deficit hyperactivity disorder  
    • aHR 1.17 (95% CI, 1.03 to 1.33) 
  • Intellectual disability  
    • aHR 1.99 (95% CI, 1.53 to 2.58) 
• Chorioamnionitis was not significantly associated with higher rates of epilepsy  
• Associations were mainly explained through preterm delivery, although increased risk was also observed among term infants 

• Exposure to chorioamnionitis in utero is associated with increased risks for cerebral palsy, autism, attention deficit hyperactivity disorder, and intellectual disability 
• These risks are mostly explained through preterm birth 
• The authors state 

Efforts for timely identification and appropriate interventions to treat infections during pregnancy will have sustained benefits in reducing the burden of neurological complications in children at the population level 

Chorioamnionitis and risk of long-term neurodevelopmental disorders in offspring; a population-based cohort study