Do the New Guidelines for Diagnosing Nonprogressing Labor Actually Reduce Cesarean Deliveries?
BACKGROUND AND PURPOSE:
Wood et al. (AJOG, 2023) assessed whether adoption of new guidelines for diagnosing nonprogressing labor reduced cesarean delivery rates
METHODS:
Cluster randomized controlled trial
26 Canadian hospitals
Province of Alberta
REDucing the utilization of CEsarean delivery for dystocia (REDUCED trial)
Participants
Nulliparous
Vertex presentation
In labor at term
Intervention
Intervention sites: 2014 guidelines for nonprogressing labor
Control sites: Operated under usual care
Old guidelines (2012)
First stage arrest: ≥6 cm dilation with rupture and no cervical change for ≥4 hours with adequate contractions or ≥6 hours with inadequate contractions
Second stage arrest: No progress for ≥4 hours in nulliparous with epidural or ≥3 hours in nulliparous without epidural
New guidelines (2014)
First stage: Prolonged latent stage (e.g., ≥20 hours in nulliparous) should not be considered an indication for cesarean | Slow but progressive labor should not be indication for cesarean
Second stage: Specific maximum time at which point women should undergo operative delivery has not been established | Allow at least 3 hours pushing in nulliparous | Longer times may be indicated on individualized basis
Study design
Data from all sites from the baseline (2015–2017) and follow-up (2017–2020) periods
Intention to treat approach
Cesarean delivery rates assessed using repeated measures mixed effects logistic regression applied to individual births
Primary outcome
Rate of cesarean delivery
Secondary outcomes
Spontaneous vaginal birth
Maternal and neonatal safety
RESULTS:
Deliveries at intervention sites: 45,193 | Deliveries at control sites: 43,725
There was no evidence of a decrease in the rate of cesarean delivery when the new 2014 guidelines were implemented
Baseline-adjusted odds ratio 0.94 (95% CI, 0.85 to 1.05) | P=0.259
The rate of spontaneous vaginal delivery increased slightly
Baseline-adjusted odds ratio 1.10 (95% CI, 1.01 to 1.18) | P=0.024
There were no differences in adverse maternal or neonatal outcomes
CONCLUSION:
Randomized implementation of 2014 guidelines for diagnosing nonprogressing labor did not reduce cesarean deliveries
Hospitals that implemented the intervention did experience increased spontaneous vaginal deliveries
Implementation of the guidelines did not have adverse effects
The authors state
Furthermore, this trial was conducted in a setting where midpelvic forceps deliveries are performed more often than cesarean deliveries. Therefore, if the intervention had been tested in a setting where this is rarely done, the cesarean delivery rate may have been more substantially reduced
Secondary Analysis of the ANODE Trial: Does the Benefit of Antibiotics Following Operative Birth Depend on Presence of Episiotomy?
BACKGROUND AND PURPOSE:
The ANODE trial (see ‘Related ObG Topics’ below) showed that prophylactic antibiotics reduced infection burden following operative delivery
However, episiotomy rates were high and infections remained high even in the treatment group
Humphreys et al. (AJOG, 2022) sought to determine whether the effectiveness of the prophylactic antibiotic at reducing infection was independent of perineal trauma
METHODS:
Secondary analysis of ANODE RCT
Population
Forceps or vacuum assisted birth at ≥36 weeks
Exclusion: Missing data or withdrew consent
Primary interventions
IV prophylactic amoxicillin and clavulanic acid
Placebo
Study design
Received intervention/placebo as soon as possible immediately after delivery to ≤6 hours
Primary outcome
Consistency of the prophylactic antibiotics in preventing infection across the exposure subgroups
RESULTS:
3225 women
Episiotomy alone: 66.5%
Episiotomy and a tear: 22.5%
Tear alone: 8.6%
Neither episiotomy nor tear: 2.4%
Among women who experienced perineal trauma, amoxicillin and clavulanic acid administration were protective against infection in all subgroups
The following were associated with higher risk of infection
Episiotomy: Adjusted risk ratio (aRR) 2.94 (95% CI, 1.62 to 5.31)
This study has found no evidence to suggest that prophylactic amoxicillin and clavulanic acid administration is less protective against confirmed or suspected infection after OVB with perineal trauma in the absence of episiotomy, which provides reassurance of the benefit of prophylactic antibiotic in settings where the episiotomy rate is lower
Importantly for clinical practice, the burden of infection may be further reduced by timely administration of the antibiotic to all women irrespective of the state of their perineum
Hysteroscopy can be performed either in the operating room or the office. When planning a hysteroscopic procedure, the joint ACOG/AAGL recommendations include the following
Preoperative consultation
Discuss risks/ benefits/ alternatives
Review medical history
Exclude pregnancy if appropriate
If cervical stenosis is present
Consider misoprostol (off label) 200 to 400 mcg buccal/ sublingual/ intravaginal the night before surgery
Optimize visualization
Perform during follicular phase of cycle, after menses | Secretory phase may mimic polyps: Irregular menses may be scheduled at any time
Actively bleeding “may not undergo the procedure” due to decreased visibility
Pretreatment with progestins or combined OCP may further optimize visualization by thinning the endometrial lining
Antibiotic prophylaxis not recommended
Pain management
Multiple pharmacologic approaches described, but evidence insufficient to recommend any particular analgesic regimen | No regimen has been shown to be superior to placebo
Note: Mannitol 5% is iso-osmolar and while may cause hyponatremia, should not decrease serum osmolality
Electrolyte-containing fluids
Normal saline | Lactated Ringer’s solution
Use for
Diagnostic cases
Laser | Bipolar | Mechanical energy
Less risk of hyponatremia/ decreased osmolality
SYNOPSIS
Polyps, synechiae, Mullerian abnormalities, leiomyomata and retained foreign bodies can often be diagnosed and treated successfully with hysteroscopy. Visualization of the endometrial cavity allows biopsy of abnormal areas and can optimize the diagnosis of hyperplasia or malignancy
KEY POINTS:
Complications
Vasovagal
Signs and symptoms
Hypotention | Bradycardia
Sweating | Pallor | Loss of conciousness | Nausea and vomiting
Management
Assess: Vitals | Airway, Breathing, Circulation
Place patient in Trendelenberg or raise legs
If bradycardia does not resolve
Atropine: Single dose 0.5 mg IV q3 to 5 minutes (total dose 3 mg)
Fluid Overload and Hyponatremia
Prevention
Strictly monitor both IV hydration and hysteroscopic fluid deficit
Electrolyte poor fluids maximal deficit: 1000 mL (in healthy individuals)
Consider stopping procedure at 750 mL deficit
Electrolyte-containing fluids maximal deficit: 2500 mL (in healthy individuals)
Consider stopping procedure at 2000 mL deficit
Consider lower thresholds for elderly, cardiovascular or renal comorbidity or when laboratory services/ acute care options are limited
Management
Hypertonic saline solution and diuretics (e.g., furosemide)
Increase serum sodium levels by 1 to 2 mEq/L/h
Caution: Do not increase by more than 12 mEq/L in the first 24 hours
Transfer to an urgent care facility and further consultation may be required
Hemorrhage
Management
Apply electrosurgical coagulation if bleeding sites identified
Inject vasopressin into the cervix
Use Foley catheter balloon tamponade or manual uterine compression
Surgical approach as a last resort includes
Laparoscopic suturing of perforation
Hysterectomy
Uterine artery embolization
Uterine Perforation
Prevention
Perform careful pelvic exam prior to hysteroscopy
Use ultrasound guidance as needed
If flexible hysteroscope available, insertion may be performed prior to using dilators
Management
Midline perforation is seldom morbid unless laser or electrosurgery is used
Lateral perforations carry risk for retroperitoneal hematomas
Discontinue hysteroscopy if perforation occurs
Consider laparoscopy to
Identify any bowel/ bladder injury
Check for hematomas
Air/CO2 Embolization
Prevention
Purge and flush air from tubing prior to procedure and whenever bags are changed | Avoid repetitive instrument insertions | Limit intrauterine pressure
ACOG has published two committee opinions on carrier screening. Committee Opinion 691 reviews the recommendations based on disorders. Committee Opinion 690 addresses the issues related to use of screening strategies such as expanded gene panel testing.
Key Highlights
Spinal Muscular Atrophy (SMA) has joined cystic fibrosis (CF) as a recommendation for all women who are pregnant or considering pregnancy
Hemoglobinopathies
Test all patients for CBC and RBC indices as part of antepartum care (ideally preconception)
Add Hgb electrophoresis if
Increased risk based on ethnicity: African, Middle Eastern, Southeast Asian, West Indian and Mediterranean ancestry
MCV is less than 80 fL with normal iron studies
Ashkenazi Jewish Testing (central and Eastern Europe descent)
Additional tests to ‘consider’ has been expanded to the following
Usher syndrome, Familial hyperinsulinism, Joubert and Maple syrup urine disease in addition to Bloom/Gaucher/Fanconi anemia/ML4/Neimann-Pick disease
Tay Sachs Disease
In addition to Ashkenazi Jews, offer if either partner is French-Canadian descent or Cajun
Screening can be performed using DNA-based testing (mutation analysis) or hexosaminidase enzyme in serum or leuckocytes (leukocyte only with oral contraceptives)
Enzyme testing picks up approximately 98% of carriers regardless of ethnicity
Mutation analysis is highly effective in at risk populations – detection rate is limited in other populations
Committee Opinion 690 reviews expanded carrier screening, including a discussion on counseling and what disorders should be included | Important summary statements include the following
Ethnic-specific, panethnic, and expanded carrier screening are acceptable strategies for prepregnancy and prenatal carrier screening. Each obstetrician–gynecologist or other health care provider or practice should establish a standard approach that is consistently offered to and discussed with each patient, ideally before pregnancy. After counseling, a patient may decline any or all carrier screening.
Expanded carrier screening does not replace previous risk-based screening recommendations. If obstetrician–gynecologists or other health care providers do not offer expanded carrier screening in their practice, screening recommendations for individual disorders should follow guidelines for carrier screening as outlined in Committee Opinion No. 691, Carrier Screening for Genetic Conditions.
Note: ACMG has published a document on preconception and prenatal carrier screening that includes a tiered approach to the selection of disorders | For the summary and links see ‘Related ObG Topics’ below)
FDA approval for Makena, a drug used to reduce risk for preterm birth, has been formally withdrawn. The withdrawal also includes all generics (17-alpha hydroxyprogesterone caproate [17-OHPC]). Regarding any current medication in distribution, the FDA states that “Patients who have questions should talk to their healthcare provider.” Both ACOG and SMFM have addressed the situation.
ACOG
Intramuscular 17-OHPC is not recommended for the primary prevention of preterm birth in patients with a history of spontaneous preterm birth
In summary, at this time, the body of evidence is equivocal regarding the effectiveness of 17-OHPC, and the referenced FDA action will limit access to 17-OHPC for patients
SMFM
We agree with the FDA determination and discourage continued prescribing of 17-OHPC, including through compounding pharmacies
We agree with the FDA that there is no evidence of benefit with continued treatment
Patients currently receiving 17-OHPC can be counseled that the FDA’s Center for Drug Evaluation and Research (CDER) has not identified evidence of harm from discontinuation prior to 37 weeks of gestation
RESEARCH SUMMARY:
The authors of the PROLONG trial (Progestin’s Role in Optimizing Neonatal Gestation) reported on the use of 17α-hydroxyprogesterone caproate (17-OHPC) for the treatment of preterm birth (PTB)
In this study population, 250 mg 17-OHPC did not decrease recurrent PTB and was not associated with increased fetal/early infant death
On October 29, 2019, the FDA advisory committee recommended that the drug be withdrawn from the market (9 to 7 vote). On October 5, 2020, the Center for Drug Evaluation and Research (CDER) proposed that Makena be withdrawn from the market. At that time, the decision was made to hold further meetings and discussions. Based upon further follow-up, the CDER briefing materials for the Advisory Committee meeting (October 17-19, 2022) states
Makena has not been shown to improve neonatal outcomes from premature birth, is no longer shown to be effective for its approved use, and has known risks
The 1,708-person confirmatory trial designed to verify Makena’s clinical benefit instead failed to show that Makena has any benefit to newborns. Data from this trial, taken together with other evidence, also fail to show that Makena reduces the risk of recurrent preterm birth
For these and other reasons detailed herein, Makena should be withdrawn from the market
Background to PROLONG Trial
A previous study, on behalf of the NICHD, demonstrated success of IM 17-OHPC in preventing PTB (see ‘Learn More – Primary Sources)
Meis et al. (NEJM, 2003): 250 mg IM 17-OHPC reduced recurrent preterm birth (PTB) in women with a prior spontaneous PTB (SPTB)
Relative risk [RR] 0.66 (95% CI, 0.54–0.81)
The current PROLONG study was a ‘confirmatory trial’, performed with FDA input as a requirement for the FDA accelerated approval pathway
PROLONG Methods
Double-blind randomized controlled trial (RCT)
Participants
≥18 years
Singleton pregnancy
Currently 16w0d to 20w6d
Previous history of singleton SPTB (birth between 20w0d and 36w6d following preterm labor or PROM)
Groups (IM injection 1 in upper outer quadrant of the gluteus maximus) weekly until delivery or 36 weeks
17-OHPC (250 mg)
Placebo
Stratified by
Study site
GA at randomization
Primary outcomes
PTB < 35 weeks
Composite neonatal morbidity and mortality index
PROLONG Results
PTB < 35w0d (p=0.72)
17-OHPC: 11.0%
Placebo: 11.5%
Relative risk (RR) 0.95 (95% CI, 0.71–1.26)
Neonatal composite index (p=0.73)
17-OHPC 5.6%
Placebo 5.0%
RR 1.12 (95% CI, 0.70–1.66)
Note: No differences seen in any of the individual components that were part of the composite index
KEY POINTS:
Sibai et al. Obstet Gynecol, 2020
Meis Trial
Well designed and conducted
Highly statistically significant results
Prespecified criterion threshold of alpha=0.015 was met regarding benefit of 17-OHPC
Subgroup analysis: Number of prior preterm birth | Race | Marital status | Smoking or substance use
Confirmed generalizability
Prolong Trial
Population studied was very different from that of the Meis trial (non-US)
Trial is underpowered based on observed event rates
For 90% power, PROLONG required 3,600 women for preterm birth <35 weeks and 6,000 women for neonatal composite outcome
PROLONG not powered for subgroup analysis, but Meis et al. did look at US subgroup and found that while not statistically significant
Direction and magnitude of effect <32 weeks and neonatal composite index were similar to the Meis trial
Authors’ Conclusion
We assert PROLONG was underpowered, based on substantially lower observed preterm birth rates than anticipated, and therefore was a false-negative study, rather than the Meis trial being a false-positive study
Careful assessment of these two trials is critical as removal of 17α-hydroxyprogesterone caproate from the U.S. marketplace may have substantial effects on public health
NOTE: The FDA has addressed the use of bebtelovimab among nonhospitalized patients in light of an increase in subvariants. Due to resistance, bebtelovimab is not currently authorized for emergency use in any US region. Information and guidelines may change rapidly. Check in with listed reference in ‘Learn More – Primary Sources’ to best keep up to date.
SUMMARY:
NIH has released guidance on the diagnosis, management and treatment of COVID-19. A Panel was convened to develop recommendations, with the understanding that there is still much that is unknown and the guidelines will be updated as additional data become available
Infection Control When Caring for Patients with COVID-19
Aerosol-generating procedures
Use fit-tested respirators (N-95 respirators) or powered air-purifying respirators rather than surgical masks
The above masks should be used in addition to other PPE (gloves, gown, and eye protection such as a face shield or safety goggles)
Endotracheal intubation
Should be done by healthcare professionals “with extensive airway management experience, if possible”
Intubation should be done with video laryngoscopy, if possible
Hemodynamic Support
First-choice vasopressor: Norepinephrine
To assess fluid responsiveness
Use dynamic parameters, skin temperature, capillary refilling time, and/or lactate levels vs static parameters
Acute resuscitation of adults with COVID-19 and shock
Use buffered/balanced crystalloids over unbalanced crystalloids
Panel recommends against initial use of albumin
Septic shock and steroids
IV hydrocortisone 200 mg per day administered either as an infusion or in intermittent doses
Duration of hydrocortisone is typically a clinical decision
Patients who are receiving corticosteroids for COVID-19 are receiving sufficient replacement therapy such that they do not require additional hydrocortisone
Ventilatory Support for Patients with COVID-19
Oxygen saturation (SpO2) target
Optimal goal is uncertain
A target SpO2 of 92% to 96% “seems logical”
Experience suggests that SpO2 <92% or >96% may be harmful
Prone position
Appropriate candidate for awake prone positioning: Patients who can adjust their own position independently and tolerate lying prone
Awake proning should not be used as a substitute for intubation and invasive mechanical ventilation in patients with refractory hypoxemia who otherwise meet the indications for these interventions
Pregnancy: Acceptable and can be done in left lateral decubitus or fully prone
Refractory hypoxemia in patients who otherwise require intubation and mechanical ventilation
Panel recommends against using awake prone positioning as a rescue therapy to avoid intubation
Options for providing enhanced respiratory support include high-flow nasal cannula (HFNC), NIPPV, intubation and invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)
Use HFNC oxygen rather than noninvasive positive pressure ventilation (NIPPV)
If HFNC is unavailable and there is no indication of intubation: Use a closely monitored trial of NIPPV
For patients on supplemental oxygen
Monitor closely for worsening of respiratory status
If respiratory status worsens, the Panel recommends early intubation by an experienced practitioner in a controlled setting
For patients mechanically ventilated with ARDS
Use low tidal volume (VT) ventilation (VT 4 to 8 mL/kg of predicted body weight) vs higher tidal volumes (VT >8 mL/kg)
If refractory hypoxemia despite optimized ventilation, the Panel recommends prone ventilation for 12 to 16 hours per day over no prone ventilation
In the setting of hypoxemia and severe ARDS despite optimized ventilation and other rescue strategies, a trial of inhaled pulmonary vasodilators is recommended as a rescue therapy| Taper if there is no rapid improvement in oxygenation
Inpatient Pharmacologic Management
Note: For patients who are hospitalized for reasons other than COVID-19 and who are found to have mild to moderate COVID-19 and a high risk of disease progression, the Panel recommends following its recommendations for treating nonhospitalized patients with COVID-19 (section below)
The following applies to individuals admitted for the treatment of COVID-19
Therapeutic Management of Hospitalized Adults With COVID-19 Based on Disease Severity
Tap picture below to view Therapeutic Management Tables for Hospitalized Adults with Covid-19
Remdesivir
Recommended for use in hospitalized patients who require supplemental oxygen
200 mg IV once, then RDV 100 mg IV once daily for 4 days or until hospital discharge
If the patient progresses to more severe illness, complete course
Dexamethasone
Found to improve survival in hospitalized patients who require supplemental oxygen
Greatest effect observed in patients who require mechanical ventilation
The Panel recommends against using dexamethasone among patients who do not require supplemental oxygen
Primary immunomodulator for all patients who require high-flow nasal canula oxygen, noninvasive ventilation, mechanical ventilation, or ECMO
Dose
6 mg IV or PO once daily for up to 10 days or until hospital discharge
If dexamethasone is not available, an equivalent dose of another corticosteroid may be used
Tocilizumab
Humanized monoclonal antibody against the interleukin-6 receptor (IL-6R)
FDA approved to treat inflammatory diseases
Dose
8 mg/kg actual body weight (up to 800 mg) administered as a single IV dose
In clinical trials, a third of the participants received a second dose of tocilizumab 8 hours after the first dose if no clinical improvement was observed
Avoid tocilizumab for the following
Significant immunosuppression | Alanine transaminase >5 times the upper limit of normal | High risk for gastrointestinal perforation | Uncontrolled, serious bacterial, fungal, or non-SARS-CoV-2 viral infection | Absolute neutrophil count <500 cells/µL | Platelet count <50,000 cells/µL
Baricitinib
Oral Janus kinase (JAK) inhibitor that is selective for JAK1 and JAK2
FDA approved to treat rheumatoid arthritis
Dose
Baricitinib dose is dependent on eGFR; duration of therapy is up to 14 days or until hospital discharge
eGFR ≥60 mL/min/1.73 m2: Baricitinib 4 mg PO once daily
eGFR 30 to <60 mL/min/1.73 m2: Baricitinib 2 mg PO once daily
eGFR 15 to <30 mL/min/1.73 m2: Baricitinib 1 mg PO once daily
eGFR <15 mL/min/1.73 m2: Baricitinib is not recommended
Tofacitinib
Oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis
Dose
10 mg PO twice daily for up to 14 days or until hospital discharge
Use as an alternative immunomodulatory drug if baricitinib is not available or not feasible to use (BIIa)
eGFR <60 mL/min/1.73 m2: Tofacitinib 5 mg PO twice daily
Sarilumab
Humanized monoclonal antibody against the interleukin-6 receptor (IL-6R)
FDA approved to treat rheumatoid arthritis
Dose
Use the single-dose, prefilled syringe (not the prefilled pen) for SQ injection
Reconstitute sarilumab 400 mg in 100 cc 0.9% NaCl and administer as an IV infusion over 1 hour
Use as an alternative immunomodulatory drug if tocilizumab is not available or not feasible to use
Therapeutic Management of Nonhospitalized Adults With COVID-19
Tap picture below to view Therapeutic Management Tables for Nonhospitalized Adults with Covid-19
NIH refers to the CDC guidance to determine at increased risk for progression | See ‘Learn More – Primary Care’ for reference
In Order of Preference
Paxlovid (for more information, see ‘oral antivirals below’)
Orally twice daily for 5 days, initiated as soon as possible and within 5 days of symptom onset in those aged ≥12 years and weighing ≥40 kg
Remdesivir
200 mg IV on Day 1, followed by remdesivir 100 mg IV daily on Days 2 and 3, initiated as soon as possible and within 7 days of symptom onset in those aged ≥12 years and weighing ≥40 kg
Alternative Therapies to be used ONLY if none of the preferred therapies are available, feasible to deliver, or clinically appropriate (listed in alphabetical order)
Molnupiravir
800 mg orally twice daily for 5 days, initiated as soon as possible and within 5 days of symptom onset in those aged ≥18 years ONLY when none of the above options can be used
Note: BQ.1 and BQ.1.1 subvariants appear to be resistant to bebtelovimab and as of 11/30/2022, bebtelovimab is not currently authorized for emergency use in any US region | The Panel continues to recommend Paxlovid, followed by remdesivir for treatment of mild to moderate COVID-19 in nonhospitalized adults who are at high risk for progression
More on Oral Antivirals
Ritonavir-Boosted Nirmatrelvir (Paxlovid)
Nirmatrelvir
Orally bioavailable protease inhibitor
Works by inhibiting viral protease MPRO (protease that plays an essential role in viral replication)
Active against all coronaviruses known to infect humans
Packaged with ritonavir (as Paxlovid)
Ritonavir is a cytochrome P450 (CYP) 3A4 inhibitor and pharmacokinetic boosting agent
Boosts nirmatrelvir concentrations to the target therapeutic ranges
Note: Review other medications to assess drug interactions including OTCs and herbal supplements | University of Liverpool has a site with COVID-19 Drug Interactions (included in the NIH Panel guidelines – see “Learn More – Primary Resources’ below)
Molnupiravir
Oral prodrug of beta-D-N4-hydroxycytidine (NHC)
NHC is a ribonucleoside with antiviral activity against RNA viruses
NHC uptake by viral RNA-dependent RNA-polymerases results in viral mutations and lethal mutagenesis
Note: Pregnancy and COVID-19 Oral Antivirals
Paxlovid
SMFM supports the use of Paxlovid in pregnancy as indicated (see ‘Primary Sources – Learn More’ below)
Molnupiravir
Although FDA concluded that there is a low risk for genotoxicity, due to concern regarding mutagenesis, the FDA EUA recommends against use during pregnancy
The NIH Panel states “However, when other therapies are not available, pregnant people with COVID-19 who are at high risk of progressing to severe disease may reasonably choose molnupiravir therapy after being fully informed of the risks, particularly those who are beyond the time of embryogenesis (i.e., >10 weeks’ gestation). The prescribing clinician should document that a discussion of the risks and benefits occurred and that the patient chose this therapy”
KEY POINTS:
Serologic or Antibody Testing for Diagnosis of SARS-CoV-2 Infection
The Panel does not recommend using serologic testing as the sole basis for diagnosing acute SARS-CoV-2 infection
Serologic or antibody tests can detect recent or prior SARS-CoV-2 infection
It may take ≥21 days after symptoms for seroconversion to occur (i.e., IgM and/or IgG antibodies to SARS-CoV-2)
NAATs and antigen tests for SARS-CoV-2 occasionally yield false negative results
Serologic tests have been used in some settings as an additional diagnostic test for patients who are strongly suspected to have SARS-CoV-2 infection
Using a serologic test in combination with a NAAT to detect IgG or total antibodies 3 to 4 weeks after symptom onset maximizes the sensitivity and specificity to detect past infection
Concomitant Medications in Patients with COVID-19
Angiotensin-Converting Enzyme (ACE) Inhibitors and Angiotensin Receptor Blockers (ARBs) and Statins (HMG-CoA Reductase Inhibitors)
Continue taking these medications as prescribed
The Panel recommends against the use of ACE inhibitors or ARBs for the treatment of COVID-19 outside of the setting of a clinical trial
Chronic Corticosteroids
For patients on oral corticosteroid therapy used prior to COVID-19 diagnosis for another underlying condition (e.g., rheumatological diseases)
Corticosteroids should not be discontinued
Supplemental or stress-dose steroids: Determine use on a case-by-case basis
Asthma and chronic obstructive pulmonary disease for control of airway inflammation (daily use)
Should not be discontinued
Pregnancy Considerations
Betamethasone and dexamethasone cross the placenta and are therefore used for fetal benefit to decrease the risk of RDS in the setting or threatened preterm delivery
The Panel recommends “using dexamethasone in pregnant women with COVID-19 who are mechanically ventilated or who require supplemental oxygen but who are not mechanically ventilated”
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
Continue taking NSAIDs for a co-morbid condition as previously directed by physician
“The Panel recommends that there be no difference in the use of antipyretic strategies (e.g., with acetaminophen or NSAIDs) between patients with or without COVID-19”
Coagulopathy Considerations
Antithrombotic Therapy for Nonhospitalized Patients without VTE
The Panel recommends against the use of anticoagulants and antiplatelet therapy (aspirin or P2Y12 inhibitors) for the prevention of VTE or arterial thrombosis unless the patient has other indications for the therapy or is participating in a clinical trial
The Panel recommends against routinely continuing VTE prophylaxis for patients with COVID-19 after hospital discharge, except in a clinical trial
For patients who are at high risk for VTE and low risk for bleeding, there is insufficient evidence to recommend either for or against continuing anticoagulation after hospital discharge unless another indication for VTE prophylaxis exists
General Considerations for Hospitalized Patients
The Panel recommends against using anticoagulant or antiplatelet therapy to prevent arterial thrombosis outside of the usual standard of care for patients without COVID-19
In hospitalized patients, low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) is preferred over oral anticoagulants, because these 2 types of heparin have shorter half-lives and the effect can be reversed quickly, can be administered intravenously or subcutaneously, and have fewer drug-drug interactions
When heparin is used, LMWH is preferred over UFH
Hospitalized, Nonpregnant Adults Who Require Low-Flow Oxygen and Are Not Receiving Intensive Care Unit Level of Care
Use therapeutic-dose heparin for patients who have a D-dimer above the upper limit of normal and have no increased bleeding risk
LMWH is preferred over unfractionated heparin
Contraindications for therapeutic anticoagulation for COVID-19 due to an increased bleeding risk
Platelet count <50 x 109/L
Hemoglobin <8 g/dL
Need for dual antiplatelet therapy
Known bleeding within the last 30 days requiring an emergency room visit or hospitalization
Known history of a bleeding disorder
Inherited or active acquired bleeding disorder
If no VTE
Continue therapeutic treatment for 14 days or until hospital discharge, whichever comes first
The Panel recommends using prophylactic-dose heparin (LMWH or unfractionated heparin) for patients who are not administered therapeutic heparin unless a contraindication exists
Note:
There is insufficient evidence for the Panel to recommend either for or against the use of a therapeutic dose of apixaban for VTE prophylaxis or the prevention of COVID-19 progression.
The Panel recommends against the use of a therapeutic dose of rivaroxaban for VTE prophylaxis or the prevention of COVID-19 progression
There is insufficient evidence for the Panel to recommend either for or against the use of thrombolytic agents for the treatment of COVID-19
The Panel recommends against the use of antiplatelet therapy to prevent COVID-19 progression or death in noncritically ill patients
Hospitalized, Nonpregnant Adults Who Are Receiving ICU Level of Care (Including Patients Who Are Receiving High-Flow Oxygen)
Use prophylactic-dose heparin as VTE prophylaxis unless a contraindication exists
The Panel recommends against the following except in a clinical trial
Use of intermediate-dose (e.g., enoxaparin 1 mg/kg daily)
Therapeutic-dose anticoagulation for VTE prophylaxis
For patients who start on therapeutic-dose heparin while on low-flow oxygen due to COVID-19 and then transfer to the ICU
Switch from therapeutic to prophylactic-dose heparin unless a VTE is confirmed
There is insufficient evidence for the Panel to recommend either for or against antiplatelet therapy in critically ill patients with COVID-19
Pregnant Adults
The Panel recommends that pregnant patients who are receiving anticoagulant or antiplatelet therapies for underlying conditions continue these medications after they receive a diagnosis of COVID-19
Use prophylactic-dose anticoagulation for pregnant patients hospitalized for manifestations of COVID-19 unless otherwise contraindicated
Because pregnant patients have not been included in most clinical trials evaluating therapeutic anticoagulation in the setting of COVID-19, there is currently insufficient evidence to recommend either for or against therapeutic anticoagulation for pregnant patients with COVID-19 in the absence of a known VTE
Influenza and COVID-19
Vaccine Considerations
It is important to ensure that vaccination programs to protect against influenza continue during the pandemic
Patients with COVID-19 can receive inactivated influenza vaccine
Moderately or Severely Ill with SARS-CoV-2
Consider deferring influenza vaccination until the patients have completed the COVID-19 isolation period and are no longer moderately or severely ill
Asymptomatic or not moderately or severely ill with SARS-CoV-2
Influenza vaccination can be given when infected individual no longer require isolation
Vaccinate sooner if they are in a health care setting for other reasons
Note: Influenza vaccine and a COVID-19 vaccine may be administered concurrently at different injection sites
Testing for Influenza
Test for both viruses in all hospitalized patients with acute respiratory illness
The Panel recommends influenza testing in addition to SARS-CoV-2 testing in outpatients with acute respiratory illness if
Results will change the clinical management strategy for the patient such as initiating antiviral treatment for influenza
Consider testing patients for other pathogens based on their specific clinical circumstances
Additional testing is especially important for patients with influenza who have a high risk of acquiring bacterial superinfections
Treatment for Influenza
Antiviral treatment of influenza is the same in all patients with or without SARS-CoV-2 coinfection
Hospitalized patients with suspected influenza
Start on empiric treatment for influenza with oseltamivir as soon as possible
Do not wait for influenza test results
Stop antiviral treatment for influenza when influenza has been ruled out by nucleic acid detection assay
Nonintubated: Negative report for upper respiratory tract specimens
Intubated: Negative report for both upper and lower respiratory tract specimens
Do Proton Pump Inhibitors Increase the Risk for CVD in Patients with Type 2 Diabetes?
BACKGROUND AND PURPOSE:
Proton pump inhibitors (PPIs), used for treating gastric-acid related diseases, have been linked with cardiovascular disease (CVD)
How PPI use affects type 2 diabetes (T2D) patients, who are more likely to use PPIs and more likely to develop CVD, is unclear
Geng et al. (Journal of Clinical Endocrinology & Metabolism, 2022) evaluate the associations of PPI use with risks of CVD and all-cause mortality in patients with T2D
METHODS:
Secondary analysis of prospective cohort study
Population
Patients in the UK Biobank with preexisting T2D
Exposure
PPI use
Primary outcomes
Coronary artery disease (CAD)
Myocardial infarction (MI)
Heart failure (HF)
Stroke
All-cause mortality
RESULTS:
19,229 adults with T2D
Median follow up: 10.9 to 11.2 years
PPI use was significantly associated with higher risks of
CAD: HR 1.27 (95% CI, 1.15 to 1.40)
MI: HR 1.34 (95% CI, 1.18 to 1.52)
HF: HR 1.35 (95% CI, 1.16 to 1.57)
All-cause mortality: HR 1.30 (95% CI, 1.16 to 1.45)
The results were consistent in the subgroup analyses stratified by factors including
Indications of PPI | Antidiabetic medication use | Antiplatelet drug use
Analyses in a 1:1 propensity score-matched cohort of PPI users vs nonusers yielded similar results
CONCLUSION:
PPI use among patients with T2D is associated with an increased risk of CVD events, compared to non-use
The authors state
The benefits and risks of PPI use should be carefully balanced among patients with T2D, and monitoring of adverse CVD events during PPI therapy should be enhanced
For both ‘vigorous’ term and preterm infants, ACOG recommends waiting at least 30 to 60 seconds after birth before clamping the umbilical cord. The committee opinion provides a comprehensive literature and evidence review. ACOG states
In term infants, delayed umbilical cord clamping increases hemoglobin levels at birth and improves iron stores in the first several months of life, which may have a favorable effect on developmental outcomes
Delayed umbilical cord clamping is associated with significant neonatal benefits in preterm infants, including improved transitional circulation, better establishment of red blood cell volume, decreased need for blood transfusion, and lower incidence of necrotizing enterocolitis and intraventricular hemorrhage
Benefits include
Term infants
Increased hemoglobin levels and iron stores
Preterm infants
Improved transitional circulation
Better establishment of RBC volume
Decreased blood transfusion
Lower risk of NEC and IVH
Note: There was no evidence for increased risk of PPH
Caution: The committee opinion notes that there may be a small risk for jaundice requiring phototherapy in term infants and therefore the delivery center should have the necessary infrastructure to monitor and treat, if necessary
Maternal hemodynamic instability or the need for immediate resuscitation of the newborn on the warmer would be an indication for immediate umbilical cord clamping
Cord Milking
Based on the latest evidence (see ‘Learn More – Primary Sources’ below) that found a higher risk of IVH in preterm infants (23 to 27 weeks) following cord milking, ACOG states
…cord milking should not be used for extremely preterm infants (less than 28 weeks of gestation)
…there is insufficient evidence to either support or refute umbilical cord milking in infants born at 32 weeks of gestation or more, including term infants
Eclampsia is a severe, life-threatening manifestation of preeclampsia. While long-term neurologic damage is rare, there is risk of maternal hypoxia and death. Most women will experience signs such as headaches or visual changes prior to a seizure.
Eclampsia
Defined as convulsions during pregnancy and/or postpartum
Tonic-clonic, focal, or multifocal
New onset
Unexplained by other neurologic pathology
Consider other underlying cerebral conditions when
Seizures occur 2 to 3 days postpartum
Patient on magnesium sulfate
Note: Not all women will demonstrate classic features of preeclampsia (hypertension, proteinuria)
Magnesium Sulfate – Seizure Prophylaxis
Magnesium sulfate is the treatment of choice for seizure prophylaxis (ACOG recommended dosing)
Loading dose of 4–6 g of magnesium sulfate administered per infusion pump over 20–30 minutes (i.e., slowly) followed by a maintenance dose of 1-2 g per hour as a continuous intravenous infusion
Continue 24 hours postpartum
Recurrent seizures
Additional dose of 2-4 g can be infused over 5 minutes
Refractory seizures
Sodium amobarbital: 250 mg IV in 3 minutes
Thiopental or phenytoin: 1,250 mg IV at a rate of 50 mg/minute
Patient should be managed in ICU
Consider neuroimaging
IM option
10 g initially as a loading dose (5 g IM in each buttock) followed by 5 g every 4 hours
Use if IV access limited
Mix with 1 mL xylocaine 2% to alleviate pain
Note: Magnesium sulfate should not be considered an antihypertensive agent
Magnesium Sulfate – When to Use
Severe features of preeclampsia
Administer to all women
No severe features of preeclampsia and systolic BP > 140 and < 160 mm Hg or diastolic BP > 90 and < 110 mm Hg
There is no consensus on this matter as prophylaxis will reduce eclampsia but 1 in 100 to 129 women need to be treated and side effects (although not life threatening) will increase
ACOG states that the decision to use magnesium sulfate when severe features are not present should be the decision of the “physician or institution, considering patient values or preferences, and the unique risk-benefit trade-off of each strategy”
Delivery and Postpartum
Vaginal delivery
Continue infusion 24 hours postpartum
Cesarean
Begin infusion (if not yet running) before surgery and continue 24 hours postpartum
Discontinuing prior to operative vaginal birth or cesarean section to avoid uterine atony or anesthetic drug interactions is not recommended
Prevention of Magnesium Sulfate toxicity
Place Foley to monitor renal function (hourly output)
Confirm normal serum creatinine
Serial evaluation of patellar deep tendon reflexes
Monitor respiratory rate
Serum magnesium levels not routinely required
Monitor serum magnesium levels in setting of renal dysfunction and/or absence of patellar reflexes
Maintain serum concentrations 5 to 9 mg/dL (4–7 mEq/L) range
Predictive symptoms of magnesium sulfate toxicity
Loss of deep tendon reflexes >9 mg/dL (greater than 7 mEq/L)
Respiratory depression >12 mg/dL (greater than 10 mEq/L)
Cardiac arrest >30 mg/dL (greater than 25 mEq/L)
Pending toxicity
Notify appropriate health care provider
Discontinue magnesium infusion
Administer supplemental oxygen
Obtain a serum magnesium level
Reverse magnesium
10 mL of 10% calcium gluconate IV (1 g total) and over 3 min (i.e., slowly) to avoid hypotension and/or bradycardia
Calcium effect (competitively inhibits magnesium at neuromuscular junction) can wear off if magnesium level stays high
Furosemide may help increase urinary excretion
Respiratory arrest: Intubation and assisted ventilation as indicated
Other Prophylactic Agents
Magnesium sulfate is superior to diazepam, phenytoin and lytic cocktail (chlorpromazine, promethazine, pethidine) in reducing significantly the risk of seizure recurrence
Cochrane Review 2010: Magnesium sulfate reduced eclampsia compared to phenytoin (relative risk 0.08, 95% CI 0.01 to 0.60)
Morbidity related to pneumonia, mechanical ventilation and admission to an intensive care unit are significantly reduced with the use of magnesium sulfate compared with phenytoin
Magnesium sulfate does not cause maternal or newborn CNS depression
Diazepam or lorazepam does stop or shorten seizures, but risk of maternal apnea and/or cardiac arrest
HPV Vaccine Recommendations Including Guidance for Ages 27 to 45
SUMMARY:
The most recent evidence-based HPV vaccine recommendations address when to administer the vaccine and dosing. One area that has elicited more recent guidance focuses on whether to offer the HPV vaccine to individuals over the age of 26.
The FDA (October 2018) extended approval of HPV vaccine to individuals age 27 to 45 years
ACIP (June 2019) voted to
Expand routine and catch-up HPV vaccination in males through 26 years of age who are inadequately vaccinated
Offer HPV vaccine to individuals age 27 to 45 years who have not been adequately vaccinated based on shared clinical decision making
ACIP published their final recommendations (August 2019) in the CDC’s Morbidity and Mortality Weekly Report
Children and adults aged 9 through 26 years: HPV vaccination is routinely recommended at age 11 or 12 years; vaccination can be given starting at age 9 years. Catch-up HPV vaccination is recommended for all persons through age 26 years who are not adequately vaccinated.
Adults aged >26 years: Catch-up HPV vaccination is not recommended for all adults aged >26 years. Instead, shared clinical decision-making regarding HPV vaccination is recommended for some adults aged 27 through 45 years who are not adequately vaccinated. HPV vaccines are not licensed for use in adults aged >45 years.
These recommendations for children and adults aged 9 through 26 years and for adults aged >26 years apply to all persons, regardless of behavioral or medical risk factors for HPV infection or disease.
For persons who are pregnant, HPV vaccination should be delayed until after pregnancy; however, pregnancy testing is not needed before vaccination.
Persons who are breastfeeding or lactating can receive HPV vaccine. Recommendations regarding HPV vaccination during pregnancy or lactation have not changed.
ACIP suggests considering the following points for shared-decision making with adults who are 27 to 45 years of age
HPV is very common, usually transient and asymptomatic
Although typically acquired in young adulthood, some adults are at risk for acquiring new HPV infection
A new sex partner is a risk factor, while those in long-term, mutually monogamous partnerships are not likely to acquire a new HPV infection
HPV types: Sexually active adults will likely have been exposed to some HPV types, but not all HPV types are vaccine targets
There is no antibody test to determine immunity
HPV vaccine has high efficacy in young persons not yet exposed to vaccine-type HPV
Lower vaccine effectiveness may be expected in those with HPV risk factors
Multiple lifetime sex partners | Previous infection with vaccine-type HPV | immunocompromising conditions
HPV vaccines are prophylactic only and can’t prevent infection progression, improve time to clearance or treat HPV-related disease
In summary, the CDC states
For adults aged 27 years and older, clinicians can consider discussing HPV vaccination with people who are most likely to benefit. HPV vaccination does not need to be discussed with most adults over age 26 years
CDC Dosing Schedule
<15 years: 2 doses spaced 6 to 12 months apart
≥15 years: 3-dose schedule
Initial dose
Second dose at 1 to 2 months after initial
Third dose at 6 months after initial
Updated ACOG HPV vaccine recommendations
Routine HPV vaccination is recommended for females and males
Target age is 11 to 12 years but can be given through age 26
Can be given from age of 9
Do not test for HPV DNA prior to vaccination
Vaccinate even if patient was tested and is HPV DNA positive
If not vaccinated between 11 to 12 years
Vaccinate between 13 to 26 years (catch up period)
Women 27 to 45 years and not previously unvaccinated
Use shared clinical decision making
ACOG “does not recommend that an individual who received the quadrivalent HPV vaccine be revaccinated with 9-valent HPV vaccine, including those aged 27–45 years who previously completed some, but not all, of the vaccine series when they were younger”
Pregnancy
HPV vaccine is not recommended during pregnancy
Pregnancy testing prior to HPV vaccination not recommended
If vaccination schedule is interrupted by pregnancy, resume postpartum with the next dose
HPV vaccine can and should be given to breastfeeding women ≤26 who have not been vaccinated
Counsel to expect mild local discomfort and that this is not a cause for concern
Watch adolescents for at least 15 minutes following vaccination due to risk of fainting in this population
AAP
The AAP has also endorsed the CDC HPV recommendations
The HPV vaccine should be normalized as a standard of care
Recommendation should be clear and unambiguous
AAP provides multiple strategies (see ‘Learn More – Primary Sources’ below) to engaging with patients including focusing on cancer prevention benefits for all children
ACS
The ACS endorses ACIP CDC guidance regarding HPV guidance except for the approach to take with individuals who are 27 to 45 years and not adequately vaccinated
The ACS does not endorse the 2019 Advisory Committee on Immunization Practices recommendation for shared clinical decision making for some adults aged 27 through 45 years who are not adequately vaccinated because of the low effectiveness and low cancer prevention potential of vaccination in this age group, the burden of decision making on patients and clinicians, and the lack of sufficient guidance on the selection of individuals who might benefit
Adjuvant HPV Vaccine to Prevent CIN Recurrence
ACOG recommends considering adjuvant HPV vaccine for unvaccinated individuals 27 to 45 years who are undergoing treatment for CIN 2+
Transvaginal Ultrasound in the Evaluation of Postmenopausal Bleeding
SUMMARY:
Postmenopausal uterine bleeding needs to be evaluated quickly and transvaginal ultrasound can play an important role in the initial work-up.
Endometrial Thickness
Measure the maximum anterior-posterior thickness on a long-axis transvaginal view
Transvaginal ultrasound is appropriate for the initial evaluation
Thin endometrial echo
Defined as ≤4mm
Endometrial fluid should not be included in measuring endometrial thickness
>99% NPV for endometrial cancer
Cannot exclude all pathology, including endometrial cancers such as uterine papillary serous, mucinous, clear cell
Thickened endometrium is not diagnostic of a particular pathology
Recommended Management
Transvaginal ultrasound
Should only be used as an initial evaluation if there is low prior probability for cancer or hyperplasia
Additional evaluation is required if persistent/recurrent bleeding
Either transvaginal ultrasound or endometrial sampling are ‘reasonable’ alternatives as first line – both not required if low risk
Proceed to endometrial sampling if abnormal endometrium is seen on transvaginal ultrasound
Endometrial sampling
First-line test if clinical risk factors are present (see ‘Endometrial Cancer: The Basics’ in ‘Related ObG Topics’ below) or clinical presentation is suspicious
Outpatient endometrial sampling using disposable device is method of choice
NOTE: Proceed to hysteroscopy with D&C if persistent or recurring bleeding and blind sampling is negative for endometrial hyperplasia or malignancy
KEY POINTS:
If transvaginal ultrasound image inadequate proceed to following options
Transvaginal ultrasound can be used to further evaluate and if a thin echo is seen and bleeding has stopped, no further work-up is necessary
Persistent/recurrent bleeding needs a histologic evaluation even in the presence of a thin echo
Postmenopausal women who are not bleeding
Transvaginal ultrasound should not be used as a screening tool for endometrial cancer in this population
If an endometrial echo >4mm is found incidentally, this is not an automatic ‘trigger’ for further evaluation but rather should be placed in context and “individualized … based on patient characteristics and risk factors”
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
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
