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
  • 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

Learn More – Primary Sources:

ACOG Practice Bulletin 234: Prediction and Prevention of Preterm Birth

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

CDC: Premature Birth

Cervical Cerclage – Professional Recommendations

CLINICAL ACTIONS:

ACOG defines cervical insufficiency as “the inability of the uterine cervix to retain a pregnancy in the absence of the signs and symptoms of clinical contractions, or labor, or both in the second trimester.” In addition, ACOG separates out indication for cerclage in to 3 categories

• History: ≥1 of the following
  • Second trimester pregnancy losses related to painless cervical dilation and no history of labor or abruption
  • Previous second trimester cerclage for painless cervical dilation
• Physical Examination: Also known as ‘physical examination–indicated cerclage’, ‘rescue cerclage’ and ’emergency cerclage’
  • Patient presents with painless second trimester cervical dilation
• Ultrasound: Cervical length shortening and history of preterm birth
  • Singleton pregnancy
  • Prior spontaneous preterm birth (<34 weeks)
  • Cervical length:  <25 mm (at <24 weeks)

SMFM states that cerclages are effective in woman based on the following indications:

• History indicated: 3 or more PTBs or second-trimester losses.
• Ultrasound indicated: ≥1 early PTB (defined as delivery between 17w to 33w6d), and cervical length (CL) <25 mm on transvaginal ultrasound (TVUS) before 24 weeks

Timing of Cerclage Placement

• History-indicated cerclage
  • Place between 12 and 14 weeks after confirmation of pregnancy viability
• Ultrasound or exam-indicated cerclage
  • May be placed prior to 23 weeks

Risk Factors

• Prior PTB
• Repeated cervical dilation
• Cervical procedures (including cone and LEEP)
• Cervical laceration
• Urogenital abnormalities

SYNOPSIS:

Clinically, cervical insufficiency is painless dilation and recurrent mid-trimester losses without signs of preterm labor (PTL), PPROM, or infection. Patient history may include superimposed symptoms (i.e. bleeding, pressure), therefore a judicious review of records is advised.  Those with a history of prior preterm birth can benefit from cervical length screening to appropriate guide selected patients for cerclage.

KEY POINTS:

Ultrasound Indicated Cerclage with Prior History of Preterm Birth or Second Trimester Losses (SMFM)

• CL surveillance
  • Begin at 16 weeks
  • Perform every 2 weeks
  • CL measurement 25-29 mm: Perform weekly
• Offer cerclage when
  • CL <25 mm prior to 23w0d weeks and
  • History of spontaneous PTB at 17w0d to 33w6d
• 17–alpha hydroxyprogesterone caproate (17-OHPC)
  • Note: Cerclage placement or presence should not alter recommendations
• Evidence from research studies
  • There is no difference in efficacy of McDonald versus Shirodkar techniques

Special Circumstances

• Diagnosis of cervical insufficiency is unclear
  • Consider close screening starting at 16 weeks in place of history indicated cerclage placement
• Very early losses
  • Consider beginning screening <16 weeks if there is a history of very early second trimester losses

‘Emergency’ Cerclage (Exam indicated)

• There is literature, including a meta-analysis (Obstet Gynecol, 2015), to support ’emergency’ or ‘rescue’ cerclage
  • Neonatal survival
    • Cerclage: 71% survival
    • No cerclage: 43% survival
    • Relative risk 1.65 (95% CI 1.19–2.28)
  • Prolongation of pregnancy
    • Mean difference: 33.98 days (95% CI, 17.88 to 50.08)
  • Authors note significant limitations including quality of data and only 1 RCT included

After clinical examination to rule out uterine activity, or intraamniotic infection, or both, physical examination-indicated cerclage placement (if technically feasible) in patients with singleton gestations who have cervical change of the internal os may be beneficial

SMFM Choosing Wisely Campaign

• SMFM recommends the following after cerclage placement
  • Do not perform serial cervical length measurements
  • There is no evidence that cervical length monitoring following a cerclage improves outcomes, despite cervical shortening being associated with increased risk for preterm birth

Learn More – Primary Sources:

SMFM: Cervical cerclage for the woman with prior adverse pregnancy outcome

ACOG Practice Bulletin 142: Cerclage for the Management of Cervical Insufficiency

Physical Examination–Indicated Cerclage: A Systematic Review and Meta-analysis