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
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
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
Progesterone (vaginal or IM) starting at 16w0d to 20w6d “more effective than starting later” | “Although the pharmacokinetic data are reassuring, there are no clinical data on which to make a recommendation regarding use of subcutaneous 17-OHPC in pregnant individuals at risk for preterm birth”
Serial endovaginal cervical length measurements starting at 16w0d and repeated every 1 to 4 weeks until 24w0d
If cervical length ≤25 mm, offer the following
Not on progesterone: Cervical cerclage or vaginal progesterone
On progesterone: Cervical cerclage and continue progesterone
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
Vaginal Progesterone: “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)
Exam-indicated: 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
Progesterone: No reduction of PTB
Cerclage if cervix <25 mm: May increase risk for PTB
“There is a paucity of information about optimal cervical length screening and treatment approaches for individuals with higher-order multiple gestations”
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:
Women with singleton pregnancy and history of PTB should be offered progesterone supplementation staring at 16 weeks
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
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
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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.
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