Can alpha‑lipoic acid (ALA) be used to prevent preterm birth or treat a short cervix in a 18‑ to 24‑week singleton pregnancy with a transvaginal cervical length ≤25 mm and no prior preterm delivery?

Alpha-Lipoic Acid for Short Cervix: Not Recommended

Alpha-lipoic acid (ALA) should not be used for the prevention of preterm birth or treatment of short cervix in singleton pregnancies; vaginal progesterone (90-mg gel or 200-mg micronized capsules daily) is the only evidence-based first-line therapy for this indication.

Evidence-Based Treatment for Short Cervix Without Prior Preterm Birth

Recommended Therapy: Vaginal Progesterone

• Vaginal progesterone is the definitive treatment for singleton pregnancies with transvaginal cervical length ≤25 mm identified at 18–24 weeks, with strong evidence demonstrating reduction in preterm birth and neonatal morbidity 1.

• For cervical length ≤20 mm, vaginal progesterone reduces:

  • Preterm birth before 33 weeks by 45% (RR 0.55) 1
  • Preterm birth before 28 weeks by 50% (RR 0.50) 1
  • Respiratory distress syndrome by 61% (RR 0.39) 1
  • Composite neonatal morbidity and mortality by 43% 1

• For cervical length 21–25 mm, vaginal progesterone should be offered after shared decision-making, reducing preterm birth before 32 weeks by 36% (RR 0.64) 1.

Dosing and Duration

• Start vaginal progesterone at diagnosis (typically 18–24 weeks) and continue until 34–36 weeks of gestation 1, 2.

• Either formulation is acceptable:

  • 90-mg progesterone gel (8% formulation) once daily, OR
  • 200-mg micronized progesterone capsules once daily 1, 2

• Contraindication: Severe peanut allergy contraindicates micronized capsules (contain peanut oil); use gel formulation instead 1, 2.

Why Alpha-Lipoic Acid Is Not Recommended

Absence of Evidence for Preterm Birth Prevention

• No clinical trials or guidelines support the use of alpha-lipoic acid for short cervix or preterm birth prevention in any population 3, 1, 2.

• The 2024 SMFM guideline on short cervix management makes no mention of alpha-lipoic acid as a therapeutic option, listing only vaginal progesterone as the recommended intervention 3.

• The 2012 SMFM progesterone guideline comprehensively reviewed interventions for short cervix and preterm birth prevention without identifying alpha-lipoic acid as an evidence-based therapy 3.

Safety Data Does Not Equal Efficacy

• While one retrospective study of 610 pregnant women demonstrated that oral alpha-lipoic acid 600 mg daily for ≥7 weeks was safe with no adverse maternal or neonatal effects 4, safety alone does not establish therapeutic benefit for preterm birth prevention.

• The study evaluated alpha-lipoic acid's antioxidant and anti-inflammatory properties but did not assess efficacy for short cervix or preterm birth outcomes 4.

Interventions That Are Contraindicated or Not Recommended

Do Not Use These Therapies

• 17-alpha-hydroxyprogesterone caproate (17-OHPC) must not be used for short cervix management in women without prior preterm birth; the FDA withdrew approval in 2023 after trials showed no benefit (preterm birth 25.1% vs 24.2%; RR 1.03) 1, 2.

• Cervical cerclage is not recommended for short cervix (10–25 mm) in women without prior preterm birth and without cervical dilation; it has not shown consistent benefit and carries procedural risks 1, 2.

• Cervical pessary is not recommended; recent large trials showed no benefit and one trial was halted early due to higher perinatal mortality (13.1% vs 6.8%; RR 1.93) 1, 2.

Diagnostic Requirements

Proper Cervical Length Measurement

• Cervical length must be measured by transvaginal ultrasound using standardized protocols (Perinatal Quality Foundation or Fetal Medicine Foundation standards) 3, 1.

• Transabdominal measurements are insufficient for clinical decision-making and may miss 57% of women with short transvaginal cervical length 3.

• The optimal screening window is 18–24 weeks of gestation 3, 1.

Clinical Algorithm for Your Patient

For an 18- to 24-week singleton pregnancy with transvaginal cervical length ≤25 mm and no prior preterm delivery:

1. Confirm diagnosis: Ensure cervical length was measured by transvaginal ultrasound using standardized technique 3, 1

2. Initiate vaginal progesterone immediately:

   • 90-mg gel OR 200-mg capsules daily 1, 2
   • Continue until 34–36 weeks 1, 2

3. Do not use alpha-lipoic acid for preterm birth prevention (no evidence of efficacy)

4. Do not use 17-OHPC, cerclage, or pessary in this population 1, 2

5. Consider physical exam if cervical length ≤11 mm, as this threshold predicts asymptomatic cervical dilation ≥1 cm with 75% sensitivity and 80% specificity 5

Critical Pitfalls to Avoid

• Do not extrapolate antioxidant or anti-inflammatory benefits of alpha-lipoic acid to preterm birth prevention without randomized controlled trial evidence demonstrating efficacy for this specific outcome.

• Do not delay initiation of vaginal progesterone while considering unproven therapies; early treatment (at diagnosis before 24 weeks) is essential for maximal benefit 1, 2.

• Do not use multiple interventions simultaneously without evidence; combining therapies (e.g., progesterone plus cerclage) is only indicated in women with prior spontaneous preterm birth and short cervix 2.