Antenatal Corticosteroids – When to Administer?

The appropriate use of antenatal corticosteroids improves neonatal outcomes, including decreased severity and/or frequency of respiratory distress syndrome (RDS), intracranial hemorrhage, necrotizing enterocolitis and death. Antenatal corticosteroids, when appropriate, are administered in a clinical setting where patients are at risk for preterm delivery within 7 days, irrespective of membrane status and fetal number.

Clinical Actions:

Risk of preterm delivery within 7 days

Between 24w0d to 33w6d – ‘Recommended’

• • Single course of corticosteroids

Between 22w0d and 23w6d – ‘May be Considered’

• 23w0d to 23w6d
  • Single course of corticosteroids
• 22w0d to 22w6d
  • Single course of corticosteroids

Note: ACOG and SMFM revised recommendation states

Antenatal corticosteroids may be considered at 22 0/7 weeks to 22 6/7 weeks of gestation if neonatal resuscitation is planned and after appropriate counseling

Some families may choose to forgo resuscitation and support after appropriate counseling

Between 20w0d and 21w6d – ‘Not Recommended’

• Antenatal corticosteroids are not recommended due to lack of data suggesting benefit

Late preterm (34w0d – 36w6d)

ACOG 

• If no previous corticosteroids
  • Single course of betamethasone
  • Not indicated in women diagnosed with clinical chorioamnionitis

SMFM 

• Single course of betamethasone in specific populations
  • Population included in ALPS trial: Recommended
    • Nonanomalous singleton gestation
    • High risk for preterm delivery (medically indicated or spontaneous)
    • No prior antenatal steroids
  • Select populations not in the original ALPS trial: Suggest consideration for use in the following clinical scenarios
    • Multiple gestations reduced to a singleton gestation ≥14w0d
    • Fetal anomalies
    • Expected to deliver in less than 12 hours
  • Low likelihood of delivery <37 weeks: Recommend against
  • Pregestational diabetes: Recommend against due to risk for worsening neonatal hypoglycemia

Repeat or Rescue Courses

• Regularly scheduled repeat courses or serial (> 2) courses
  • Not recommended
• If a patient has received one prior course of corticosteroids > 14 days ago, is less than 34w0d gestation and is at risk of preterm delivery within 7 days
  • a single repeat course of corticosteroids should be considered (change from previous ‘may’)
  • Rescue course corticosteroids could be provided as early as 7 days from the prior dose, if indicated by the clinical scenario (based on Cochrane meta-analysis)
• Preterm prelabor rupture of membranes (PPROM)
  • There is insufficient evidence to make a recommendation for or against repeat or rescue courses

Dose and Regimen: give first dose even if 2nd dose unlikely

• Betamethasone: 12 mg IM, 2 doses 24 hours apart
• Dexamethasone:  6 mg IM, 4 doses 12 hours apart

Learn More – Primary Sources

ACOG Committee Opinion 713: Antenatal Corticosteroid Therapy for Fetal Maturation

ACOG Practice Advisory: Use of Antenatal Corticosteroids at 22 Weeks of Gestation

ACOG Practice Bulletin No. 171 : Management of Preterm Labor

Society for Maternal-Fetal Medicine (SMFM) Consult #58: Use of Antenatal Corticosteroids for Individuals at Risk for Late Preterm Delivery

Society for Maternal-Fetal Medicine Special Statement: Quality metrics for optimal timing of antenatal corticosteroid administration – American Journal of Obstetrics & Gynecology (ajog.org)

Prediction and Prevention of Preterm Birth

SUMMARY:

Spontaneous preterm birth (PTB) includes preterm labor, preterm rupture of membranes and cervical insufficiency from ≥20w7d to <37w0d of gestation. The PTB rate has significantly increased during the last 2 decades. According to the CDC, PTB rates decreased from 2007 to 2014, partly due to fewer teens and young women giving birth. However, the PTB rate rose for the fifth year in a row in 2019 and sits at approximately 10%. Unfortunately, racial, and ethnic differences in PTB rates remain problematic. The CDC reports that “in 2019, the rate of preterm birth among non-Hispanic black women (14.4%) was about 50% higher than the rate of preterm birth among non-Hispanic white women (9.3%) or Hispanic women (10%).”

Adverse Outcomes and Preterm Birth

• The rate of neonatal adverse outcomes decreases with advancing gestational age
  • While adverse outcomes are therefore greatest <34 weeks (early preterm), higher rates of both short- and long-term complications are seen between 34w0d an 36w6d (late preterm) vs ≥37 weeks
• The CDC reported that in 2018, preterm birth and low birth weight accounted for about 17% of infant deaths <1 year
• Associated adverse outcomes include
  • Respiratory complications | Feeding difficulties | Cerebral palsy | Developmental delay | Vision and hearing impairment

Risk Factors 

• History of prior PTB
  • Number of prior preterm birth deliveries
  • Gestational age at delivery
• Short cervical length (<25 mm) between 16 and 24 weeks
• Behavioral factors
  • Low maternal pre-pregnancy weight (BMI <18.5)
  • Smoking
  • Substance abuse
  • Short interpregnancy interval (<18 months)

Note: Surgical procedures (e.g., cold-knife conization, loop electrosurgical excision, or laser ablation) have been postulated to be associated with preterm birth, but data is inconsistent

Clinical Evaluation and Management

Previous Spontaneous PTB (Singleton)

• Risk assessment
  • Detailed medical history and prior obstetric history
• Management
  • Insufficient data to recommend IM 17-OHPC
  • Serial endovaginal cervical length measurements starting at 16w0d and repeated every 1 to 4 weeks until 24w0d
  • If cervical length ≤25 mm, consider the following
    • Vaginal progesterone (vs cerclage)
    • Cervical cerclage (vs vaginal progesterone if not already on supplementation)
    • Physical exam indicated cerclage
  • Cervical pessary: Not indicated

No Previous History of PTB

• Low risk for PTB
  • Clinical utility of universal cervical length screening “remains unsettled”
  • Cervix should be visualized at the 2nd trimester anatomy exam (18 to 22 weeks) | Transabdominal or endovaginal approach is acceptable
  • If cervix appears short on transabdominal scan, endovaginal ultrasound is recommended to determine whether progesterone may be of benefit
  • Serial endovaginal ultrasonography is not indicated in low risk patients
• Short cervical length (≤25 mm)
  • IM 17-OHPC: Not indicated
  • Vaginal Progesterone: Indicated | “Although most studies used 200 mg progesterone daily from the time of identification of a cervix shorter than 25 mm at 18 0/7–25 6/7 weeks of gestation until 36–37 weeks of gestation, there are no adequate dosing studies or comparative trials, and there are insufficient data to indicate which formulation and which dose are most effective”
  • Cervical cerclage
    • Ultrasound-indicated: Overall, no significant reduction of PTB | May be potential benefit in very short cervix (<10 mm)
    • Physical exam-indicated: Consider if dilated cervix on digital/speculum exam at 16w0d to 23w6d “are candidates” for cerclage | Uncertain if amniocentesis to test for infection impacts outcome
  • Pessary: Not recommended

Multiple gestation with or without history of PTB

• Cervix should be visualized at the 2nd trimester anatomy exam (18 to 22 weeks)
• IM 17-OHPC: Not indicated
• Vaginal progesterone: Insufficient data
• Cerclage if cervix ≤25 mm
  • Ultrasound: Insufficient data
  • Physical exam-indicated: Consider procedure
• Pessary is not recommended

History of a Medically Indicated Preterm Delivery

• May be increased risk for PTB
• “insufficient evidence to support a recommendation that these individuals undergo serial cervical length surveillance in future pregnancies”

KEY POINTS:

• Evidence does not support use of vaginal progesterone to reduce risk of recurrent preterm birth if cervix is not shortened
• Vaginal progesterone is recommended in women without a history of PTB but with short cervix
• Screening for fetal fibronectin, bacterial vaginosis and home contraction monitoring are not recommended
• Universal cervical length with endovaginal remains unclear | However, cervix should be visualized during the second trimester anatomy scan
• Neither progesterone nor cerclage are recommended routinely in multiple gestations
• Activity restriction is not recommended to reduce the risk of preterm birth

Note: SMFM addresses vaginal progesterone and recommends shared decision making in the setting of a previous preterm birth but without input of cervical length or cervical length 25 mm or greater | This approach should especially be considered if the progesterone therapy for PTB prevention was used in a prior pregnancy

Learn More – Primary Sources:

ACOG Practice Bulletin 234: Prediction and Prevention of Preterm Birth

ACOG: Updated Clinical Guidance for the Use of Progesterone Supplementation for the Prevention of Recurrent Preterm Birth

SMFM Special Statement: Response to the Food and Drug Administration’s withdrawal of 17-alpha hydroxyprogesterone caproate

AACC Guidance Document on Laboratory Testing for the Assessment of Preterm Delivery

CDC: Preterm Birth

March of Dimes Report Card

Does fetal fibronectin testing prevent preterm birth?

FINDINGS:

In a systemic review and meta-analysis, the authors assessed 6 high quality randomized clinical trials to determine whether the use of fetal fibronectin (FFN) in the clinical setting actually reduces preterm labor. Berghella and Saccone (AJOG, 2016) compared 546 singleton gestations that were randomized to management based on FFN results (intervention group) or not (comparison group). When comparing the intervention to the control group, the researchers found:

No differences in

• Labor incidence at <37 weeks, <34 weeks <32 weeks and <28 weeks gestation
• Number of women who delivered within 7 days
• Mean gestational age at delivery
• Rate of maternal hospitalization
• Use of tocolysis or antenatal steroids
• Mean time in the triage unit
• Neonatal outcomes, including RDS, admission to the NICU

Statistical difference was identified in

• Cost of hospitalization charges with a mean additional cost of $153 in the intervention group (95% CI, 24.01 – 281.99)

SYNOPSIS:

FFN is an extracellular matrix glycoprotein produced during pregnancy by amniocytes and cytotrophoblasts. Studies have shown that increased levels of FFN in vaginal and cervical secretions are associated with spontaneous preterm birth (SPTB). Obtaining FFN is easy and safe, using a swab, and FFN has been used to help providers determine whether to keep patients with symptoms of SPTB under surveillance. While clinical validity has been determined – increased FFN levels are associated with SPTB – this meta-analysis sought to determine clinical utility and whether outcomes are altered in a positive way.

KEY POINTS:

• Based on the findings of this paper, it appears that there is no clinical benefit but there are increased costs to the use of FFN in the management of singleton pregnancies with symptoms suggestive of SPTB
• An editorial by GA Macones, MD, advocates that based on the findings in this study, the use of FFN testing in treated preterm labor is not justified
• Studies that included the use of ultrasound measurement of cervical lengths were not included
• Strengths of study include rigorous adherence to principles of evidence-based medicine, thereby reducing sources of bias
• Limitations relate to the number of study subjects, and therefore stratification based on more individualized or particular clinical scenarios could not be assessed

Learn More – Primary Sources:

AJOG: Fetal fibronectin testing for prevention of preterm birth in singleton pregnancies with threatened preterm labor: a systematic review and meta-analysis of randomized controlled trials.

AJOG Editorial: Fetal fibronectin testing in threatened preterm labor: time to stop