For Physicians. By Physicians.™

NIH COVID-19 Treatment Guidelines

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

Critical Care Treatment

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 
  • Acute hypoxemic respiratory failure despite conventional oxygen therapy
    • 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

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
  • 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

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: Oral anticoagulants for VTE prophylaxis or prevention of COVID-19 progression are not recommended for hospitalized patients, except in a clinical trial 

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

Learn More – Primary Sources:

NIH: Coronavirus Disease 2019 (COVID-19) Treatment Guidelines

Underlying Medical Conditions Associated with Higher Risk for Severe COVID-19: Information for Healthcare Providers (cdc.gov)

Liverpool COVID-19 Interactions (covid19-druginteractions.org)

SMFM: FDA Issues EUA for the Treatment of Mild-to-Moderate COVID-19 (Paxlovid)

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

Learn More – Primary Sources:

Proton Pump Inhibitor Use and Risks of Cardiovascular Disease and Mortality in Patients with Type 2 Diabetes

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) 
    • Forceps (vs vacuum extraction): aRR 1.37 (95% CI, 1.12 to 1.69)  
    • Primiparity: aRR 1.34 (95% CI, 1.05 to 1.70) 
    • Prophylactic antibiotic use: aRR 0.60 (95% CI, 0.51 to 0.72) 
    • BMI of 25.0 to 29.9 kg/m2: aRR 1.21 (95% CI, 1.00 to 1.47) 
    • BMI of ≥30 kg/m2: aRR 1.22 (95% CI, 0.9 to 1.52) 
  • Each 15-minute increment between birth and antibiotic administration was associated with a 3% higher risk of infection
    • aRR 1.03 (95% CI, 1.01 to 1.06)

CONCLUSION:

  • Prophylactic antibiotics reduce the risk of infection after operative birth, regardless of type of perineal trauma 
  • The following were associated with increased risk of infection after operative birth
    • Episiotomy | Forceps birth | Primiparity | Overweight
  • The authors state

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

Learn More – Primary Sources:

Factors associated with infection after operative vaginal birth—a secondary analysis of a randomized controlled trial of prophylactic antibiotics for the prevention of infection following operative vaginal birth

ACOG Committee Opinion on Delayed Cord Clamping

SUMMARY:

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

Immediate Umbilical Cord Clamping

When is delayed cord clamping not appropriate?

  • Maternal reasons
    • Hemorrhage
    • Hemodynamic instability
    • Abnormal placentation (e.g., previa, abruption etc.)
  • Fetal / Neonatal reasons
    • Need for immediate resuscitation
    • Placental circulation not intact
      • abruption
      • previa
      • cord avulsion
      • IUGR with abnormal cord Doppler

NOTE: ACOG states

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

Learn More – Primary Sources:

ACOG Committee Opinion 814: Delayed Umbilical Cord Clamping After Birth

Eclampsia and Role of Magnesium Sulfate

SUMMARY:  

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
  • Diazepam and phenytoin may be considered if
    • Patient on these medications to treat epilepsy
    • Magnesium sulfate is contraindicated
      • Myasthenia gravis | Hypocalcemia | Moderate-to-severe renal failure | Cardiac ischemia | Heart block | Myocarditis

Learn More – Primary Sources:

National Partnership for Maternal Safety: Consensus Bundle on Severe Hypertension During Pregnancy and the Postpartum Period 

ACOG Practice Bulletin 222: Gestational Hypertension and Preeclampsia

Management of pre-eclampsia: issues for anaesthetists 

Acute pulmonary oedema in pregnant women 

Cochrane Review: Magnesium sulphate and other anticonvulsants for women with pre-eclampsia 

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 27-45 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 27-45 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

Updated ACOG HPV vaccine recommendations 

  • Routine HPV vaccination is recommended for females and males 
  • Target age is 11-12 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 11-12 years
    • Vaccinate between 13–26 years (catch up period)
  • Women 27–45 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 HPV Vaccine Implementation Guidance 2017

  • The AAP  has also endorsed the CDC HPV recommendations and provides the following guidance

The AAP and the ACIP of the CDC recommend HPV vaccination with any available vaccine for routine immunization of females at 11 or 12 years of age, and recommend either 9vHPV or 4vHPV** for routine immunization of males 11 or 12 years of age. The vaccination series can be started as young as 9 years of age, and in the case of a child who has been the victim of sexual abuse, HPV vaccination is recommended beginning at 9 years of age.

AAP recommends that physicians frame their HPV discussions with families as an opportunity to prevent HPV-related cancer deaths rather than as an STI vaccine

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

Learn More – Primary Sources:

FDA approves expanded use of Gardasil 9 to include individuals 27 through 45 years old

Human Papillomavirus Vaccination for Adults: Updated Recommendations of the Advisory Committee on Immunization Practices (MMWR)

CDC: HPV Vaccination Schedules & Recommendations

ACOG Committee Opinion 809: Human Papillomavirus Vaccination

CDC Frequently Asked Questions about HPV Vaccine Safety

CDC HPV Vaccine Fact Sheet for Parents

Human papillomavirus vaccination 2020 guideline update: American Cancer Society guideline adaptation

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  
    • Sonohysterography | Office hysteroscopy | Endometrial sampling   
  • If insufficient tissue on endometrial sampling 
    • 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”  


Learn More – Primary Sources:  

ACOG Committee Opinion 734: The Role of Transvaginal Ultrasonography in Evaluating the Endometrium of Women With Postmenopausal Bleeding

ACOG Recommendations on Marijuana Use During Pregnancy and Lactation

SUMMARY:

The US Surgeon General released an advisory regarding marijuana use during pregnancy and the potential for adverse outcomes. This advisory echoes concerns of ACOG and AAP regarding potency and potential harms during pregnancy and adolescence. Use in pregnancy has doubled (3.4 to 7%) and appears to be associated with adverse outcomes including LBW. ACOG’s updated committee opinion on marijuana use in pregnancy and lactation, due to reported association between marijuana use and impaired neurodevelopment in the offspring, recommends that the use of marijuana in the pre-conception, pregnancy, or lactation periods should be discouraged.

KEY POINTS:

Background 

  • Prevalence of marijuana use (self-reported) during pregnancy: 2-5% 
    • May be as high as 28% in young, urban and disadvantaged populations 
  •  Up to 60% of women using marijuana may continue use during pregnancy  
    • Data suggests that women are not aware of risks and consider marijuana to be cheaper and safer than tobacco

Pharmacology 

  • Tetrahydrocannabinol (THC) is the active substance  
    • Distributed rapidly to the brain and fat 
    • Metabolized by the liver 
    • Half-life:  20-36 hours in occasional users and may be up to 4 to 5 days in heavy users 
    • Excretion: Up to 30 days 
  • Fetal THC levels are
    • Approximately 10% of maternal levels (animal models)
    • Found in breast milk (human studies)

Perinatal Risks and Outcomes  

CNS Effects Including Visual and Behavioral Outcomes 

  • Cannabinoid receptors have been detected in humans as early as 14 weeks gestation and endocannabinoids may be important for neurodevelopment
  • Animal models suggest that exogenous cannabinoids may interfere with normal brain development
  • Children exposed to prenatal marijuana may have
    • Lower scores on tests of visual problem solving
    • Visual-motor coordination
    • Decreased attention span
    • Behavioral problems 

Structural malformations 

  • Available evidence does not suggest increased risk for fetal structural malformations 

Perinatal death 

  • Marijuana use does not increase risk of perinatal death
    • Relative risk (RR) 1.09; 95% CI, 0.62 to 1.91
  • Some studies have shown higher risk of stillbirth but may be confounded by cigarette smoking and other factors
    • RR 1.74; 95% CI, 1.03 to 2.93

Birth weight 

  • Some studies have shown an association between marijuana use and lower birth weight (<10th percentile) even after adjusting for tobacco use
  • A meta-analysis with primary outcome of birth weight <2,500 did not show a difference when adjusted for other factors, such as tobacco use, but did identify possible effects when data was stratified by
    • Weekly users
    • Use in the 1st and 2nd trimesters 

Preterm birth

  • A meta-analysis with primary outcome of preterm delivery <37 weeks did not a show a relationship when adjusted for tobacco use
    • Possibility exists that tobacco “may be an important mediator for some “adverse pregnancy outcomes”

Note: For perinatal death/stillbirth, birthweight and preterm birth, data derived from meta-analysis (see ‘Learn More – Primary Sources below) and other more recent studies

Breastfeeding 

  • There are insufficient data on the effects of marijuana use on breastfeeding infants 
  • Bertrand et al. (Pediatrics, 2018) identified significant transfer of cannabinoids into breast milk following marijuana us (see ‘Related ObG Topics’, below)
  • At this time, both ACOG and AAP recommend that marijuana use during lactation should be discouraged

Medical Marijuana Use 

  • The FDA does not evaluate nor regulate medical marijuana use 
  • There are currently no indications for use in pregnancy 
  • ACOG recommends the following
    • Encourage women to discontinue marijuana use
    • Avoid prescribing or suggesting the use of marijuana for medicinal purposes during pre-conception, pregnancy, or lactation periods 
    • Identify alternative therapies with better safety profiles

Other Counseling Notes

  • All pregnant women, or those planning to become pregnant should be asked about their use of alcohol, tobacco, and drugs including marijuana
  • Discuss potential adverse events
    • More research is necessary to determine whether marijuana is an isolated risk factor for adverse outcomes or whether findings are a result of confounding related to other factors (e.g., tobacco use, other substances, socioeconomic factors, nutrition) or recall bias
  • ACOG recommends that patients should be made aware that screening for substance use allows for the provision of treatment when necessary and not to punish
  • In addition, the ACOG guideline states

…patients should also be informed of the potential ramifications of a positive screen result, including any mandatory reporting requirements

Seeking obstetric–gynecologic care should not expose a woman to criminal or civil penalties for marijuana use, such as incarceration, involuntary commitment, loss of custody of her children, or loss of housing

Learn More – Primary Sources:

ACOG Committee Opinion 722: Marijuana use in pregnancy

ACOG Breastfeeding Page

AAP: Marijuana Use During Pregnancy and Breastfeeding – Implications for Neonatal and Childhood Outcomes

Maternal Marijuana Use and Adverse Neonatal Outcomes: A Systematic Review and Meta-analysis

U.S. Surgeon General’s Advisory: Marijuana Use and the Developing Brain

ACOG Recommendations: When to Deliver Medically Complicated Pregnancies

SUMMARY:

ACOG has developed important guidance on the timing of medically indicated late-preterm and early-term deliveries in collaboration with SMFM. The recommendations are based on placental, fetal and maternal complications.

KEY POINTS:

  • Antenatal Corticosteroids 
    • Anticipated late-preterm delivery: Administer single course of antenatal corticosteroids within 7 days of delivery if patient has not received a previous course 
    • Medically indicated late-preterm delivery should not be delayed for administration of corticosteroids 
  • Lung maturity testing 
    • Amniocentesis for determination of fetal lung maturity should not be used to guide timing of delivery (even in poorly dated pregnancies) 
  • Data are lacking for some conditions, such as dehiscence or chronic abruption 
    • In these cases, individualize timing of delivery

Placental Indications  

  • Previa (otherwise uncomplicated): 36w0d – 37w6d  
  • Accreta, increta, percreta (otherwise uncomplicated) : 34w0d – 35w6d  
  • Vasa previa: 34w0d – 37w0d 
  • Prior classical cesarean: 36w0d – 37w0d  
  • Previous uterine rupture: 36w0d – 37w0d  
  • Prior myomectomy requiring cesarean: 37w0d – 38w6d  
    • May require delivery similar to classical section (see above) if surgery was more extensive and complicated
    • With less extensive surgery, delivery may be considered as late as 38w6d
    • ACOG states

Timing of delivery should be individualized based on prior surgical details (if available) and the clinical situation

Fetal Conditions 

  • Oligohydramnios (DVP <2cm) isolated and uncomplicated : 36w0d – 37w6d (or at time of diagnosis if later) 
  • Polyhydramnios (otherwise uncomplicated): 39w0d – 39w6d  
  • Fetal growth restriction (FGR) – singleton
    • Uncomplicated and EFW between 3rd and 10th percentile: 38w0d – 39w0d
    • Uncomplicated and EFW <3rd percentile: 37w0d (or at time of diagnosis if later) 
    • UA Doppler decreased end diastolic flow without absent end diastolic flow: 37w0d (or at time of diagnosis if later) 
    • UA Doppler absent end diastolic flow: 33w0d – 34w0d (or at time of diagnosis if later) 
    • UA Doppler reversed end-diastolic flow: 30w0d – 32w0d (or at time of diagnosis if later) 
    • Note: Concurrent condition (e.g., oligohydramnios, preeclampsia, hypertension): 34w0d – 37w6d 
  • Multiple gestation – uncomplicated  
    • Di-di twins: 38w0d – 38w6d   
    • Mono-di twins: 34w0d – 37w6d   
    • Mono-mono twins: 32w0d – 34w0d   
    • Note: Triplets and higher: Individualize 
  • Alloimmunization 
    • At-risk and not requiring intrauterine transfusion: 37w0d – 38w6d  
    • Note: Requiring intrauterine transfusion: Individualize 

Maternal Conditions 

Chronic hypertension  

  • Uncomplicated, no meds: 38w0d – 39w6d  
  • Uncomplicated, controlled on meds: 37w0d – 39w6d  
  • Difficult to control: 36w0d – 37w6d  

Gestational hypertension 

  • Without severe BP: 37w0d (or at time of diagnosis if later) 
  • With severe BP: 34w0d (or at time of diagnosis if later) 

Preeclampsia 

  • Without severe features: 37w0d (or at time of diagnosis if later) 
  • With severe features 
    • Stable maternal-fetal status: 34w0d (or at time of diagnosis if later)  
    • Unstable or complicated by HELLP: Soon after maternal stabilization (guided by maternal/fetal status and gestational age)
    • Before viability: Soon after maternal stabilization (guided by maternal/fetal status and gestational age) 

Diabetes 

  • Pregestational diabetes 
    • Well-controlled: 39w0d – 39w6d   
    • With vascular complications, poor control, or prior stillbirth: 36w0d – 38w6d   
  • Gestational diabetes 
    • Well-controlled on diet: 39w0d – 40w6d   
    • Well-controlled on meds: 39w0 – 39w6d  
    • Note: Poorly-controlled: Individualize 

HIV 

  • Intact membranes & viral load > 1,000 copies/mL: 38w0d   
  • Viral load <1,000 copies/mL and antiretroviral therapy: ≥39w0d  

Intrahepatic cholestasis of Pregnancy 

  • Bile acids ≥100 micromol/L: 36w0d
  • Bile acids <100 micromol/L: 36w0d to 39w0d | Delivery <36 weeks may be required depending on clinical findings and lab values 

PROM and Stillbirth

  • Ruptured membranes  
    • Preterm PROM (PPROM): 34w0d to 36w6d
    • PROM (≥37w0d): Generally, deliver at time of diagnosis 
  • Previous stillbirth: Individualize
    • Early term birth not routinely recommended
    • “…maternal anxiety with a history of stillbirth should be considered and may warrant an early term delivery (37 0/7 weeks to 38 6/7 weeks) in women who are educated regarding, and accept, the associated neonatal risks”

Learn More – Primary Sources:

ACOG Committee Opinion 831: Medically Indicated Late-Preterm and Early-Term Deliveries

USPSTF Recommends Universal Screening for Hepatitis C

SUMMARY:

  • USPSTF has reviewed available evidence and has updated its hepatitis C screening guidance. HCV is the most common chronic blood-borne pathogen in the US with potential for significant morbidity and mortality if left untreated. The prevalence of chronic HCV infection in the US is approximately 1.0% (2013 to 2016), with 44,700 new HCV infections in 2017. There has been an increase in acute infections over the last decade primarily due to increased injection drug use and better surveillance.
  • The USPSTF recommends screening for HCV infection in adults aged 18 to 79 years
  • Population: All asymptomatic adults aged 18 to 79 years without known liver disease
  • B level recommendation
    • Offer or provide this service
    • There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial

The USPSTF concludes with moderate certainty that screening for HCV infection in adults aged 18 to 79 years has substantial net benefit

Risk Assessment

  • Screen all adults ages 18 to 79 years
  • Risk factors to consider
    • Injection drug use: Consider screening adolescents <18 years or >79 years
      • Young adults (ages 18 to 30): Approximately 30% are infected
      • Older adults: 70% to 90% are infected
  • Pregnancy
    • Screen pregnant adults  

Because of the increasing prevalence of HCV in women aged 15 to 44 years and in infants born to HCV-infected mothers, clinicians may want to consider screening pregnant persons younger than 18 years

Screening Test

  • Anti-HCV antibody testing followed by polymerase chain reaction testing for HCV RNA
    • HCV infection can be detected by anti-HCV screening tests (enzyme immunoassay) 4 to 10 weeks after infection
    • Delayed seroconversion may occur in immunocompromised individuals (e.g., those with HIV infection)

Screening Intervals

  • “Most adults need to be screened only once”
    • Consider more frequent screening for individuals with ongoing risk (e.g., ongoing injection drug use)
    • Data is limited to determine optimal screening interval for those at continued risk or whether pregnancy impacts need for additional screening

KEY POINTS:

Hepatitis C Overview

  • Acute Hepatitis C occurs within the first 6 months after exposure to HCV
  • Many individuals will remain asymptomatic
  • 15% of patients will spontaneously clear the virus within 6 months
  • Signs and symptoms of acute HCV infection
    • Fever | Fatigue | Dark urine | Clay-colored stool | Abdominal pain | Loss of appetite | Nausea and vomiting | Joint pain | Jaundice
    • Most individuals with newly acquired HCV infection will be asymptomatic | 20 to 30% will exhibit symptoms
    • Symptoms will usually appear within 2 to 12 weeks (range: 2–26 weeks) 
  • Signs and of chronic HCV infection
    • Most people are asymptomatic or have non-specific symptoms (e.g., chronic fatigue and depression)
    • Many eventually develop chronic liver disease, which can range from mild to severe, including cirrhosis and liver cancer
    • Chronic HCV infection is typically not recognized until asymptomatic people are identified as HCV-positive when screened for blood donation or liver function tests return an abnormal result (e.g., elevated ALT), often during routine evaluation 

Hepatitis C Treatment

Acute

  • The same regimens recommended for chronic HCV infections are recommended for acute infection

Chronic

  • Current antiviral therapies can result in sustained virologic response (SVR; absence of detectable virus 12 weeks after completion of treatment)
    • SVR is indicative of a cure of HCV infection
    • Over 90% of HCV infected persons can be cured of HCV infection regardless of HCV genotype with 8-12 weeks of oral therapy
    • CDC provides a link to currently approved FDA therapies to treat hepatitis C (see ‘Learn More – Primary Sources’ below)

Other considerations

  • Advise abstinence from alcohol and acetaminophen during acute infection                
  • Evaluate for hepatitis B and HIV infection
  • Vaccinate against Hepatitis A and Hepatitis B
  • Evaluation for advanced hepatic fibrosis with
    • Elastography or liver imaging (US or CT Scan)
    • FIB-4 Score (see ‘Learn More – Primary Sources’ below for calculator)
    • Lab tests: ALT | AST | Albumin | Bilirubin | INR | CBC
  • Provide education on how to prevent HCV transmission to others

Other Professional Recommendations

  • AASLD/IDSA
    • One-time, routine, opt out HCV testing is recommended for all individuals aged 18 years and older
    • One-time HCV testing should be performed for all persons less than 18 years old with behaviors, exposures, or conditions or circumstances associated with an increased risk of HCV infection
    • Periodic repeat HCV testing should be offered to all persons with behaviors, exposures, or conditions or circumstances associated with an increased risk of HCV exposure
    • Annual HCV testing is recommended for all persons who inject drugs and for HIV-infected men who have unprotected sex with men
    • As part of prenatal care, all pregnant women should be tested for HCV infection, ideally at the initial visit
  • CDC
    • All adults 18 years and older (except in settings where the prevalence is <0.1%)
    • All pregnant persons should be screened for HCV during each pregnancy (except in settings where the prevalence of HCV infection is < 0.1%)
    • All persons with risk factors (eg., persons with HIV, prior recipients of blood transfusions, persons who ever injected drugs and shared needles, and persons who are born to an HCV-infected mother) should be tested for HCV, with periodic testing while risk factors persist

Learn More – Primary Sources:

Screening for Hepatitis C Virus Infection in Adolescents and Adults – US Preventive Services Task Force Recommendation Statement

AASLD / IDSA: HCV Testing and Linkage to Care

CDC Recommendations for Hepatitis C Screening Among Adults — United States, 2020

CDC link to FDA therapies to treat hepatitis C

Hepatitis C Questions and Answers for Health Professionals

Reported Prevalence of Maternal Hepatitis C Virus Infection in the United States

SMFM Consult Series #56: Hepatitis C in pregnancy—updated guidelines

Fibrosis-4 (FIB-4) Calculator – Clinical Calculators – Hepatitis C Online (uw.edu)

Updated ACOG Guidance on Gestational Diabetes

SUMMARY:

ACOG released updated guidance on gestational diabetes (GDM), which has become increasingly prevalent worldwide.  Class A1GDM refers to diet-controlled GDM. Class A2GDM refers to the clinical scenario where medications are required. Highlights and changes from the previous practice bulletin include the following:

Screening for GDM – One or Two Step?

  • ACOG (based on NIH consensus panel findings) supports the ‘2 step’ approach (24 to 28 week 1 hour venous glucose measurement following 50g oral glucose solution), followed by a 100g 3 hour oral glucose tolerance test (OGTT) if positive
    • Note: Diagnosis of GDM is based on 2 abnormal values on the 3 hour OGTT
      • ACOG recommends that currently there is insufficient evidence to diagnose GDM based on only one abnormal value
      • Patients with only one elevated value may require additional surveillance
  • 1 step approach (75 g OGTT) on all women will increase the diagnosis of GDM but sufficient prospective studies demonstrating improved outcomes still lacking
  • The USPSTF
    • Recommends screening for gestational diabetes in asymptomatic pregnant persons at ≥24 weeks of gestation or after (B recommendation)
    • Current evidence is insufficient to assess the balance of benefits and harms of screening for gestational diabetes in asymptomatic pregnant persons <24 weeks of gestation (I statement)

Who Should be Screened Early?

Consider early screening in pregnancy if patient is overweight with BMI of 25 (23 in Asian Americans), and one or more of the following

  • Physical inactivity
  • Family history of diabetes – 1st degree relative (parent or sibling)
  • African American, Native American, Asian American, Latino, or Pacific Islander
  • Previous pregnancy history of
    • GDM
    • Macrosomia (≥ 4000 g)
  • Hypertension (140/90 mm Hg or being treated for hypertension) | ADA now uses 130/80 cut-off for prediabetes screening
  • HDL cholesterol ≤ 35 mg/dl (0.90 mmol/L)
  • Fasting triglyceride ≥ 250 mg/dL (2.82 mmol/L)
  • PCOS
  • Conditions associated with insulin resistance (e.g., acanthosis nigricans, morbid obesity)
  • Hgb A1C ≥ 5.7%, impaired glucose tolerance or impaired fasting glucose | If A1C>6.5%, diagnosis of pregestational diabetes is met and GCT/GTT not needed
  • Cardiovascular disease

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