Preterm Labor – Causes, Symptoms, Diagnosis, Treatment and Ongoing care
Contractions occurring between 20 and 36 weeks’ gestation at a rate of 4 in 20 minutes or 8 in 1 h with at least 1 of the following: Cervical change over time or dilation ≥2 cm (1)
Preterm birth is the leading cause of perinatal morbidity and mortality in the US.
10–15% of pregnancies experience at least 1 episode of preterm labor.
∼12% of all births in the US are preterm (9% spontaneous preterm births and 3% indicated preterm births).
- Demographic factors including single parent, poverty, and black race
- Short interpregnancy interval
- No prenatal care
- Prepregnancy weight <45 kg (100 lb), body mass index <20
- Substance abuse (e.g., cocaine, tobacco)
- Prior preterm delivery (common)
- Previous 2nd-trimester dilation and evacuation (D&E)
- Cervical insufficiency
- Abdominal surgery/trauma during pregnancy
- Uterine or cervical anomalies such as large fibroids
- Serious maternal infections/diseases
- Bacterial vaginosis
- Vaginal bleeding during pregnancy
- Multiple gestation
- Fetal abnormalities
- Intrauterine growth restriction
- Placenta previa
- Premature placental separation (abruption)
- Ehler-Danlos syndrome
- Patient education at each visit in 2nd and 3rd trimesters for those at risk and periodically in the last 2 trimesters for the general population
- If previous preterm birth, evaluate if etiology is likely to recur, and target intervention to specific condition:
- Weekly injections of 17α-hydroxyprogesterone (250 mg IM every week) from 16–36 weeks if previous spontaneous preterm birth (2,3)[A]
- Consider cerclage placement before 24 weeks’ gestation for those at high risk because of cervical insufficiency or significant or progressive cervical shortening (4)[A].
- For women with a short cervix in the second trimester (<15 mm on transvaginal ultrasound), progesterone 200 mg/d per vagina × 24–34 weeks may decrease the risk of preterm delivery (5)[A].
- Premature formation and activation of myometrial gap junctions
- Inflammatory mediator–stimulated contractions
- Weakened cervix (structural defect or extracellular matrix defect)
- Abnormal placental implantation
- Systemic inflammation/infections (e.g., urinary tract infection, pyelonephritis, pneumonia)
- Local inflammation/infections (intra-amniotic infections from aerobes, anaerobes, Mycoplasma, Ureaplasma)
- Uterine abnormalities (e.g., cervical insufficiency, leiomyomata, septa, diethylstilbestrol exposure)
- Overdistension (by multiple gestation or polyhydramnios)
- Preterm premature rupture of membranes
- Placental abruption
- Immunopathology (e.g., antiphospholipid antibodies)
- Placental ischemic disease (preeclampsia and fetal growth restriction)
There is no single test that will diagnose or reliably predict true preterm labor. The diagnosis is based on a combination of physical findings and diagnostic tests that are interpreted in the context of the degree of risk to the patient.
- Address risk factors, especially etiologies of previous preterm birth.
- Regular uterine contractions or cramping
- Dull, low backache or pain
- Intermittent lower abdominal pain
- Increased low pelvic pressure
- Change in vaginal discharge
- Vaginal bleeding
- Fluid leakage
- Sterile speculum exam for membrane rupture evaluation, cultures, cervical inspection
- Bimanual cervical exam if intact membranes: Dilation of the cervix >1 cm and/or effacement of the cervix >50%
Avoid bimanual examination when possible if rupture of the membranes is suspected.
Diagnostic Tests & Interpretation
Initial lab tests
- In symptomatic women from 22–34 weeks’ gestation with intact membranes and no intercourse or bleeding in past 24 h, obtain a fetal fibronectin swab (FFN) from the posterior vaginal fornix. FFN must be obtained prior to digital cervical exam:
- If results are positive (≥50 ng/mL), patient is at a modest increased risk of preterm birth [positive predictive value (PPV) 13–30% for delivery within 2 weeks].
- If results are negative, more than 97% of patients will not deliver in 14 days, so can consider avoiding complicated or high-risk interventions (6)[A].
- Urinalysis and urine culture
- Cultures for gonorrhea and chlamydia
- Wet prep for bacterial vaginosis evaluation (although evidence for improved outcomes with treatment is weak)
- Vaginal introitus and rectal culture for group B Streptococcus
- pH and Ferning test of vaginal fluid to evaluate for rupture of membranes
- Complete blood count with differential
- Drug screen when appropriate
Follow-Up & Special Considerations
Repeat FFN as indicated by symptoms.
- Ultrasound to identify number of fetuses and fetal position, confirm gestational age, estimate fetal weight, quantify amniotic fluid, and to look for conditions making tocolysis contraindicated
- Transvaginal ultrasound to evaluate cervical length, funneling, and dynamic changes after obtaining FFN and if clinical assessment of the cervix is uncertain or if the cervix is closed on digital exam (4)[B]
Follow-Up & Special Considerations
Progressive shortening of the cervix on repeat ultrasound (in 1–2 weeks) may indicate need for hospitalization.
- Monitor contractions with external tocodynamometer.
- Consider amniocentesis at any preterm gestational age to evaluate for intra-amniotic infection (cell count with differential, glucose, Gram stain, aerobic, anaerobic, Mycoplasma, Ureaplasma cultures).
- Consider amniocentesis if ≥32 weeks’ gestation for evaluation of fetal lung maturity [e.g., lecithin/sphingomyelin (L:S) ratio and phosphatidylglycerol (PG)]. If L:S ratio >2:1 (nondiabetic) and PG is present, hyaline membrane disease is unlikely, so tocolysis is contraindicated.
- Placental inflammation:
- Acute inflammation usually caused by infection
- Chronic inflammation caused by immunopathology
- Braxton-Hicks contractions/false labor
- Round ligament pain
- Lumbosacral muscular back pain
- Urinary tract or vaginal infections
- Adnexal torsion
- Viral gastroenteritis
Tocolysis may allow time for interventions such as transfer to tertiary care facility and administration of corticosteroids, but may not prolong pregnancy significantly (2)[A].
- Nifedipine: 10 mg p.o. q10min up to 30 mg total; then 10–20 mg q6h × 24 h; then 10–20 mg p.o. q8h (do not use sublingual route); check blood pressure often, and avoid hypotension. Concurrent use with magnesium sulfate should be avoided.
- Indomethacin: 50–100 mg p.o. initial dose; then 50 mg q6–8h × 24 h (or, if available, 100-mg suppository per rectum q12h for 2 doses); then 25 mg q6–8h; use for no longer than 72 h due to risk of premature closure of ductus arteriosus, oligohydramnios, and possibly neonatal necrotizing enterocolitis.
- Contraindications to tocolysis: Severe preeclampsia, hemorrhage, chorioamnionitis, advanced labor, intrauterine growth retardation, fetal distress, or lethal fetal abnormalities
- Antibiotics: Antibiotics for group B Streptococcus prophylaxis if culture positive or unknown
- Steroids: If mother is at 23–34 weeks’ gestation with no evidence of systemic infection, give glucocorticoids to decrease neonatal respiratory distress, intraventricular hemorrhage, necrotizing enterocolitis, and overall perinatal mortality (7)[A]. Betamethasone 12 mg IM × 2 doses 24 h apart (preferred choice)or dexamethasone 6 mg IM q12h for 4 doses.
- Terbutaline 0.25 mg SC q30min for up to 3 doses until contractions stop; then 0.25 mg SC q6h for 4 doses (optional); if contractions persist or pulse >120 beats/min, change to another tocolytic agent (may be poorly tolerated by mothers).
- Terbutaline infusion pumps are potentially useful only in multiples or in selected refractory or symptomatic patients:
- Caution with terbutaline infusion: Palpitations, nausea, intractable vomiting, pulse >140 beats/min, decreased urine output
- Magnesium sulfate by intravenous infusion has been used in the past as a 1st-line tocolytic agent. Recent data are conflicting as to whether it has a benefit for prolongation of pregnancy beyond 48 h and whether it increases the risk for complications. Therefore, this agent should be used cautiously. (Standard dosages for tocolysis start with a 4- to 6-g IV bolus over 20 minutes and then 2–3 g/h until contractions stop.)
- Magnesium may decrease the risk of cerebral palsy when given prior to an anticipated preterm birth (8)[B].
- Relative contraindications to magnesium sulfate include myasthenia gravis, hypocalcemia, renal failure, or concurrent use of calcium channel blockers.
- Significant possible interactions include pulmonary edema from crystalloid fluids and tocolytic agents, especially magnesium sulfate.
- Oral maintenance therapy with any agent is controversial, and its use is limited (9)[A].
Treat underlying risk factors with appropriate measures (e.g., antibiotics for infections, hydration for dehydration). Liquids only or nothing by mouth if delivery imminent; hospitalization is necessary if the patient is on IV tocolysis or if bed rest is impossible at home.
Issues for Referral
If delivery is inevitable but not immediate, consider transport to a tertiary care center or hospital equipped with a neonatal ICU. Consider consultation with maternal-fetal medicine specialist.
- Treating symptomatic bacterial vaginosis in 2nd trimester with metronidazole 250 mg p.o. t.i.d. × 7 days or clindamycin 300 mg p.o. b.i.d. × 7 days might reduce risk of preterm delivery in high-risk symptomatic women.
- Pelvic rest (e.g., no douching or intercourse)
- Discontinue work and strenuous physical activity.
- Strict bed rest is not demonstrated to be effective in most situations.
- For malpresentation or fetal compromise, consider cesarean delivery if labor is progressing.
- If incompetent cervix is suspected, consider cerclage (4)[B].
- Intravenous access
- Continuous fetal and contraction monitoring
- Assess cervix for dilatation and effacement
Suspected/threatened preterm labor
Hydrate with 500 mL 5% dextrose normal saline solution or 5% dextrose lactated Ringer solution for 1st half-hour; then at 125 mL/h.
Monitor for fluid overload, especially with tocolysis and multiple gestations.
- Regular contractions resolved and no progressive cervical change
- If cervix is dilated ≥3 cm or FFN is positive, individualize decision to discharge by gestational age and specific patient circumstances.
- Weekly office visits and cervical checks or cervical ultrasound if at high risk for recurrence
- Routine use of maintenance tocolysis has not been proven beneficial.
Call physician or proceed to hospital whenever contractions last >1 h, low back pain comes and goes, change in vaginal discharge, “menstrual cramping,” or intestinal cramping.
- If membranes are ruptured and no infection is confirmed, delivery often occurs within 3–7 days.
- If membranes are intact, 20–50% deliver preterm.
Labor resistant to tocolysis, pulmonary edema/fluid overload, and infection with preterm rupture of membranes (PROM)
1. Management of Preterm Labor. Summary, Evidence Report/Technology Assessment: Number 18. AHRQ Publication No. 01-E020, October 2000. Agency for Healthcare Research and Quality, Rockville, MD. http://archive.ahrq.gov/clinic/tp/pretermtp.htm.
2. Simhan HN, Caritis SN. Prevention of preterm delivery. N Engl J Med. 2007;357:477–87.
3. Tita AT, Rouse DJ. Progesterone for preterm birth prevention: an evolving intervention. Am J Obstet Gynecol. 2009;200:219–24.
4. Daskalaksis GJ. Prematurity prevention: the role of cerclage. Curr Opin Obstet Gynecol. 2009;21(2):148–52.
5. Fonseca FB, Celik E, Parra M, et al. Progesterone and the risk of preterm birth among women with a short cervix. NEJM. 2007;357(5):462–9.
6. Goldenberg RL, Goepfert AR, Ramsey PS. Biochemical markers for the prediction of preterm birth. Am J Obstet Gynecol. 2005;192(5 Suppl):S36–46.
7. Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database of Systematic Reviews. 2006, Issue 3. Art. No.: CD004454. DOI: 10.1002/14651858.CD004454.pub2.
8. Magnesium sulfate before anticipated preterm birth for neuroprotection. Comm Opin No 455. ACOG. Obstet Gynecol. 2010;115:669–71.
9. Dodd JM, Crowther CA, Dare MR, et al. Oral betamimetics for maintenance therapy after threatened preterm labor. Cochran Database of Systemic Reviews.2006, Issue 1. ArtNo.:CD003927. DOI:10.1002/14651858.CD003927.pub2.
- 644.03 Threatened preterm labor, antepartum
- 644.13 Other threatened labor, antepartum
- 6383007 premature labor (finding)
- 267201003 early or threatened labor (disorder)
- Preterm labor is common and has multiple etiologies.
- Tocolytic therapy allows steroid dosing. Steroids improve neonatal outcomes.
- Progesterone therapy can prevent recurrence of preterm birth in next pregnancy.