Chronic HTN & Pregnancy

June 22, 2022 at 8 pm ET

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

Includes CME | Event will be recorded

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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

May 27, 2022 at 10 am ET

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

Includes CME | Event will be recorded

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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 

ALTAR RCT Results: Methenamine Hippurate Prophylaxis for Recurrent UTI 

• Harding et al. (BMJ, 2022) compared the efficacy of methenamine hippurate for prevention of recurrent UTI with the current standard prophylaxis of daily low dose antibiotics 

• Multicenter, open label, randomized, non-inferiority trial 
  • The ALTAR trial (alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women) 
  • 8 centers across the UK  
• Participants 
  • Women ≥18 years  
  • Recurrent UTI requiring prophylactic treatment 
• Interventions 
  • Antibiotic prophylaxis for 12 months (standard treatment) | Oral once daily | Choice of antibiotic dependant on urine culture and history of allergy or intolerance 
    • Nitrofurantoin (50 or 100 mg) or 
    • Timethoprim (100 mg) or 
    • Cefalexin (250 mg)
  • Methenamine hippurate for 12 months 
    • 1 g oral twice daily  
• Study design 
  • Participants were randomly assigned 1:1 
  • Recurrent UTI definition 
    • ≥3 episodes of symptomatic UTI in the previous 12 months or 
    • ≥2 episodes in the past six months 
  • Treatment allocation was not masked and crossover between arms was allowed 
  • A patient and public involvement group predefined the non-inferiority margin as one episode of UTI per person year 
  • Intention-to-treat analyses 
    • All participants observed for at least six months 
• Primary outcome 
  • Absolute difference in incidence of symptomatic UTIs requiring antibiotic treatment 

• Standard treatment: 102 participants | Methenamine hippurate: 103 
• Incidence of UTIs requiring antibiotic treatment during the 12-month study period 
  • Standard treatment: 0.89 episodes per person year (95% CI, 0.65 to 1.12) 
  • Methenamine hippurate: 1.38 episodes per person year (95% CI, 1.05 to 1.72) 
• Methenamine hippurate was confirmed to be non-inferior to the standard treatment of low dose prophylactic antibiotics 
  • Absolute difference in UTI incidence: 0.49 (90% CI, 0.15 to 0.84) 
• Incidence of adverse reactions  
  • Standard treatment: 24% 
  • Methenamine hippurate: 28% 
  • Most reactions were mild 
  • Only 2 serious adverse reactions (severe abdominal pain and raised alanine transaminase), both in antibiotic group

• In this trial, methenamine hippurate was found to be non-inferior to antibiotic prophylaxis for the prevention of recurrent UTI 
• Methenamine hippurate may be appropriate for some women with recurrent UTI 
• Limitations of the study include lack of blinding and heterogeneity of prophylactic antibiotics prescribed 
• The authors state 

The range of a priori outcomes reported confirm clinical utility of methenamine hippurate as a non-antibiotic option for prevention of urinary tract infection in this pragmatic trial, which allows generalisability of results 

Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women: multicentre, open label, randomised, non-inferiority trial 

Diagnosing Hypertension: How Do Clinic, Home and Kiosk BP Measurements Compare?

• Prior to making a new hypertension diagnosis, the USPSTF recommends blood pressure (BP) monitoring outside of a clinic setting 
  • 24 hour ambulatory BP monitoring (ABPM) is one non-clinic option, but its use is infrequent in the US 
  • Home BP monitoring (HBPM) is another possibility, but requires training and the use of validated monitoring systems 
  • BP monitoring at kiosks found in pharmacies or clinic waiting rooms are an alternative, but their use has not been compared to the other monitoring options 
• Green et al. (Journal of General Internal Medicine, 2022) compared clinic-, home-, and kiosk-based BP measurement to ABPM for diagnosing hypertension 

• Randomized diagnostic study 
  • 12 Washington State primary care centers 
• Participants 
  • 18 to 85 years 
  • Elevated BP: ≥138 mmHg systolic or ≥88 mmHg diastolic at last outpatient visit No hypertension diagnosis in the prior 2 years  
  • No prescribed antihypertensive medications in the prior 12 months 
  • Without diagnosed hypertension or prescribed antihypertensive medications 
• Interventions 
  • Clinic: Usual care follow-up BPs 
  • Home: Duplicate BPs twice daily for 5 days 
  • Kiosk (pharmacy or clinic waiting area): Triplicate BPs on 3 separate days 
• Study design 
  • All participants completed ABPM at 3 weeks 
• Primary outcome 
  • Difference between ABPM daytime mean systolic BP and BP measured with intervention 
• Secondary outcomes 
  • Difference in diastolic BP 
  • Sensitivity 
  • Specificity 

• 434 participants 
  • Mean age: 58.7 years 
  • 80.2% White 
• Adjusted mean differences in systolic BP, compared to daytime ABPM 
  • Clinic: −4.7mmHg (95% CI, −7.3 to −2.2); P<0.001 
  • Home: −0.1mmHg (95% CI, −1.6 to 1.5); P=0.92 
  • Kiosk: 9.5mmHg (95% CI, 7.5 to 11.6); P<0.001 
• Adjusted mean differences in diastolic BP, compared to daytime ABPM 
  • Clinic: −7.2mmHg (95% CI, −8.8 to −5.5); P<0.001 
  • Home: −0.4mmHg (95% CI, −1.4 to 0.7); P=0.52 
  • Kiosk: 5.0mmHg (95% CI, 3.8 to 6.2); P<0.001 
• Sensitivity and specificity, compared to ABPM 
  • Clinic 
    • Sensitivity: 31.1% (95% CI, 22.9 to 40.6) 
    • Specificity: 79.5% (95% CI, 64.0 to 89.4) 
  • Home 
    • Sensitivity: 82.2% (95% CI, 73.8 to 88.4) 
    • Specificity: 53.3% (95% CI, 38.9 to 67.2) 
  • Kiosk 
    • Sensitivity: 96.0% (95% CI, 90.0 to 98.5) 
    • Specificity: 28.2% (95% CI, 16.4 to 44.1) 

• Compared to ABPM, clinic BPs that were significantly lower, and kiosk BPs were significantly higher 
  • There was no difference with home BP monitoring 
• Clinic BP measurements have low sensitivity for detecting hypertension | Kiosk BP measurements have low specificity 
• The authors state 

BP is highly variable, particularly among individuals with untreated hypertension, with systolic often varying by 30–40 mmHg or more during daytime hours 

Home provided many more BPs, with average standard deviation smaller than single or duplicate clinic measurements 

Findings support utility of home BP monitoring for making a new diagnosis of hypertension 

Clinic, Home, and Kiosk Blood Pressure Measurements for Diagnosing Hypertension: a Randomized Diagnostic Study 

RCT Results: Relugolix Versus Leuprorelin for the Management of Endometriosis-Associated Pelvic Pain

• Relugolix (REL) is an oral GnRH antagonist medication 
• Leuprorelin (LEU) is a sustained-released GnRH agonist that downregulates the GnRH receptor 
• Harada et al. (Fertility and Sterility 2021) evaluated the efficacy and safety of 40-mg REL vs LEU in women with endometriosis-associated pain 

• Phase 3, multicenter, randomized, double-blind, double-dummy, active-controlled study 
  • 42 centers in Japan  
• Participants 
  • ≥20 years  
  • Regular menstrual cycles (25 to 38 days)  
  • Endometriosis or ovarian endometrioma and pelvic pain 
• Interventions 
  • REL group: 40 mg of REL, orally administered once a day for 24 weeks 
  • LEU group: 3.75 or 1.88 (body weight <50 kg) mg of LEU, subcutaneously injected every 4 weeks for 24 weeks 
• Primary outcome 
  • Change in the maximum visual analog scale (VAS) score for pelvic pain from baseline until the end of treatment period (last 28 days of the treatment period including those who completed treatment up to 24 weeks or discontinued treatment early) 
• Secondary outcomes 
  • Change from baseline to the end of treatment for 
    • Mean VAS score | Menstrual pain | Nonmenstrual pelvic pain (NMPP) | Dyspareunia 

• REL group: 171 participants | LEU group: 164 participants 
• REL was found to be noninferior to LEU at reducing maximum visual analog scale score for pelvic pain  
  • Changes in the mean (±SD) maximum visual analog scale score 
    • REL: −52.6 ± 1.3 
    • LEU: −57.5 ± 1.4 
• Ovarian endometrioma also decreased among both treatment groups 
  • REL: –12.26 ± 17.52 cm³  
  • LEU: –14.10 ± 18.81 cm³ 
• Return of menses 
  • REL: Median, 38 days 
  • LEU: Median 68 days 
  • By approximately 4 months, menstruation had returned to almost all patients 
• Drug-related treatment emergent adverse events (TEAE) with an incidence of >10% for both groups  
  • Hot flushes 
  • Metrorrhagia 
  • Headache 
  • Genital hemorrhage 
• Discontinuations due to TEAE 
  • REL: 2.9% 
  • LEU: 4.3% 

• Relugolix was found to be noninferior to leuprorelin at reducing endometriosis-associated pelvic pain 
• Both treatment groups experienced similar levels of adverse events 
• Women in the relugolix group had their menses return earlier than those in the leuprorelin group 
• The authors state 

The recovery of the serum E2 levels and menstruation after EOT occurred earlier for REL than for LEU, a huge advantage for patients who plan to become pregnant 

In addition, because REL is an oral drug, patients often recover from a TEAE more quickly after stopping treatment 

Relugolix, an oral gonadotropin-releasing hormone receptor antagonist, reduces endometriosis-associated pain compared with leuprorelin in Japanese women: a phase 3, randomized, double-blind, noninferiority study 

Have Stage IV Breast Cancer Diagnoses Increased During the COVID-19 Pandemic?

• The COVID-19 pandemic has disrupted cancer screening programs, such as mammograms and colonoscopies, and this may have led to an increase in late-stage cancer diagnoses during the pandemic 
• Zhou et al. (JAMA Network Open, 2022) compared the incidence of early- and late-stage breast and colorectal cancer diagnoses during vs before the COVID-19 pandemic  

• Quality improvement study  
• Participants 
  • All patients presenting to a cancer center for a new diagnosis of malignant neoplasm or a second opinion  
• Exposures 
  • Presentation in 2019 
  • Presentation in 2020 
• Study design 
  • Fisher exact test used to compare the proportions of stage I or stage IV of cancers between 2019 and 2020 
• Primary outcome 
  • Stage distribution at presentation for  
    • Cancer overall 
    • Colorectal cancer 
    • Breast cancer 

• Men: 55 | Women: 476  
  • Mean age: 58.1 (SD, 13.5) years 
• The total number of new patient visits for malignant neoplasm was similar in 2019 and 2020 
  • In 2019: 1894 visits 
  • In 2020: 1915 visits 

Overall Cancer  

• The overall stage distribution for all patients with cancer was similar 
  • Stage I  
    • In 2019: 31.9% of patients 
    • In 2020: 29.0% of patients 
    • OR 1.15 (95% CI, 1.00 to 1.32); P=0.05 
  • Stage IV 
    • In 2019: 26.0% of patients 
    • In 2020: 26.4% of patients 
    • OR 0.98 (95% CI, 0.84 to 1.13); P=0.77 

Colorectal Cancer  

• After the start of the COVID-19 pandemic, there was no significant decrease in colorectal cancer  
  • Stage I 
    • In 2019: 17.8% 
    • In 2020: 14.6% 
    • OR 1.26 (95% CI, 0.34 to 4.88); P=0.78 
  • Stage IV 
    • In 2019: 6.7% 
    • In 2020: 19.5%  
    • OR 0.3 (95% CI, 0.05 to 1.37); P=0.11 

Breast Cancer  

• Among patients with breast cancer, a lower percentage of patients presented with stage I disease in 2019 vs 2020 
  • In 2019: 63.9% 
  • In 2020: 51.3% 
  • OR 1.67 (95% CI, 1.13 to 2.47); P=0.008 
• There was a significantly higher number of patients presenting with stage IV breast cancer in 2020 
  • In 2019: 1.9% 
  • In 2020: 6.2% 
  • OR 0.33 (95% CI, 0.09 to 0.98); P=0.04 
• Recent data for January through March 2021 demonstrate a continuing trend of a lower percentage of patients with breast cancer presenting with stage I disease and a higher percentage presenting with stage IV disease 
  • Stage I: 41.9% 
  • Stage IV: 8.0% 

• The percentage of patients presenting with stage IV breast cancer increased in 2020, compared to before the COVID-19 pandemic 
• Limitations include a single center study | Study design addresses associations but not causality | Colorectal cancer cases were limited 
• The authors state 

There is increasing concern regarding the effect of the COVID-19 pandemic on cancer mortality, as the evidence suggests that the number of patients presenting at late, incurable stages is increasing. Patients who have delayed preventative care during the pandemic should be encouraged to resume treatment as soon as possible 

Comparison of Early- and Late-Stage Breast and Colorectal Cancer Diagnoses During vs Before the COVID-19 Pandemic 

Is Obesity Linked to Weaker Uterine Contractility During Labor?

• Hautakangas et al. (BJOG, 2022) investigated the impact of severe obesity (BMI ≥35 kg/m2) on uterine contractile activity 

• Exploratory, blinded analysis of a prospective cohort from a previous RCT 
• Primary RCT compared intrauterine and external tocodynamometries and labor outcomes 
• Population 
  • Singleton pregnancies 
  • ≥ 37 weeks 
  • Cephalic presentation 
  • Intrauterine tocodynamometry during labor 
• Exposures 
  • Severe obesity: BMI ≥35 kg/m²  
• Primary outcome 
  • Uterine contractile activity 
    • Assessed as intrauterine pressure, frequency of contractions and basal tonus of uterine muscle 
• Secondary outcomes 
  • Use of oxytocin 
  • Labor outcomes 

• 686 participants 
  • BMI ≥35 kg/m²: 84 participants 
• Participants with obesity reached intrauterine pressure ≥200 MVUs during the first stage of labor more often than those with BMI <35 kg/m² 
  • BMI ≥35 kg/m²: 62% 
  • BMI <35 kg/m²: 49% 
  • OR 1.67 (95% CI, 1.05 to 2.67) 
• Participants with obesity also had a higher basal tone of uterine muscle 
• Women with obesity without a previous vaginal delivery  
  • Were more likely to fail to reach the active stage of labor  
    • OR 2.36 (95% CI, 2.39 to 4.37); P=0.005 
  • Were more likely to require cesarean 
    • OR 1.88 (95% CI, 1.08 to 3.27); P=0.024 
• If a parturient had had previous vaginal delivery 
  • Obesity did not influence uterine activity 
  • There was no increased risk for caesarean 
• Doses and total oxytocin amounts did not significantly differ between BMI groups 

• Women with obesity were less likely to reach the active stage of labor and were more likely to require cesarean 
• However, these outcomes are probably not due to decreased uterine contractile activity as uterine contractility was increased vs leaner participants 
• The authors state 

The uterine contractile activity of obese parturients is equal to or even greater than that of leaner parturients, but obese parturients less often achieve vaginal delivery 

However, if the active stage of labour is reached, obese parturients have labours that are as straightforward as those among leaner parturients 

Impact of obesity on uterine contractile activity during labour: a blinded analysis of a randomised controlled trial cohort 

CDC Surveillance: ART-Related Birth Outcomes in the US

• Pregnancies resulting from assisted reproductive technology (ART) are at higher risk of adverse obstetrical outcomes 

• Sunderam et al. (CDC MMWR, 2022) report on US state-specific ART procedures performed in 2018 and compare ART birth outcomes with outcomes for all infants born in the United States in 2018 

• Population cohort study 
  • Data derived from all fertility clinics in the US that provide and verify information about the outcomes of the ART cycles through the National ART Surveillance System (NASS), a web-based data collection system developed by CDC 
• Population 
  • Live births in the US in 2018 
• Exposures 
  • Conception via ART  
  • State of patient residence 
• Primary outcomes 
  • Number of ART procedures performed 
  • Incidence of adverse obstetrical outcomes (e.g., small for gestational age) 

ART Procedures Performed 

• ART procedures performed in 2018: 203,119 
  • Live birth deliveries: 73,831 
  • Infants born: 81,478 
• Rate of ART procedures performed among women 15 to 44 years old: 3,135 per 1 million women 
  • ART use was 1.5 times higher than the national rate in 7 states and the District of Columbia 
    • Connecticut, Illinois, Maryland, Massachusetts, New Jersey, New York, and Rhode Island 

ART Embryo Transfers 

• Average number of embryos transferred was similar across age groups 
  • Women aged <35 years: 1.3 
  • Women aged 35 to 37 years: 1.3 
  • Women aged >37 years: 1.4 
• Single-embryo transfer (SET) rate among all embryo-transfer procedures 
  • Women aged <35 years: 74.1%  
  • Women aged 35 to 37 years: 72.8% 
  • Women aged >37 years: 66.4% 

ART Conceived Births 

• In 2018, 2.0% of all infants born the US were conceived with ART 
• The majority of infants conceived with ART were singletons: 78.6% 
  • Twins: 20.7% 
  • Triplets and higher order multiples: 0.6% 
• ART contribution to multiple birth 
  • All multiple births attributable to ART: 12.5% 
  • Twins attributable to ART: 12.5% 
  • Triplets and higher order births attributable to ART: 13.3% 
• The percentage of multiple births was higher among infants conceived with ART 
  • ART: 21.4% 
  • Total birth population: 3.3% 

ART Obstetrical Outcomes 

• Low birthweight (<2,500 g) attributable to ART: 4.2% 
• The percentage of low birthweight infants was higher in the ART conceived population 
  • ART: 18.3% 
  • Total birth population: 8.3% 
• Preterm (<37 weeks) births attributable to ART: 5.1% 
• The percentage of preterm births was higher among infants conceived with ART 
  • ART: 26.1% 
  • Total birth population: 10.0% 

• Most infants conceived via ART procedures are singletons, though the percentage of multiple births are higher among those conceived with ART 
• The percentage of low birthweight and preterm births is also higher among infants conceived by ART 
• The authors state 

Since 1995, the number of ART procedures performed and the number of infants born as a result have more than tripled in the United States 

With this increasing use, ART-conceived infants represented approximately 2% of infants born in 2018 in the United States and contributed to approximately 4% and 5% of all low birthweight and preterm births, respectively 

Assisted Reproductive Technology Surveillance — United States, 2018