Preterm labor

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

The diverse etiology of preterm labor makes it difficult to evaluate the success of any strategy. As most pregnancies succeed, there is a danger that an ineffective intervention is perceived to be successful, and that anecdotal experience filters into practice without proper evaluation. Even women with poor previous history, substantial risk factors, or symptoms of preterm contractions often have a normal pregnancy. This has been confounded by the difficulty in recruiting pregnant women with preterm labor into clinical trials.

Gestational age at delivery is key to the mortality and morbidity of the fetus. Survival is rare below 22 weeks' gestation, and serious morbidity is relatively common before 26 weeks.[1] The principles of management are therefore to extend gestation as long as possible.

However, as infection is common either as a cause of preterm labor or as a consequence of preterm rupture of membranes, prolonging pregnancy may not be advisable in all cases. Chorioamnionitis can cause neurologic damage in the fetus and may increase rates of conditions such as necrotizing enterocolitis and bronchopulmonary dysplasia.[10][11][12][109] The use of antibiotics to treat threatened preterm labor with intact membranes has been linked to the subsequent development of cerebral palsy, as antibiotics may prolong gestation in a hostile in utero environment.[62][110] Once chorioamnionitis is evident, delivery is indicated to prevent morbidity in both mother and fetus.

Threatened preterm labor (TPTL)

Initial assessment in a woman who presents with apparent preterm contractions should include a careful review of all data concerning gestational age, as this is related to prognosis. Fetal monitoring can be carried out by either intermittent auscultation or continuous cardiotocography (CTG), although at very early gestations monitoring may be inappropriate. [ ] Only a small proportion of women who present with TPTL deliver within 1 week. The method of potential delivery should be considered, especially if a cesarean section is likely to be required. There is little evidence to guide these decisions, and they should be made by an experienced obstetrician, in consultation with a neonatologist. If possible, parents should be encouraged to see the neonatal intensive care unit. Bed rest and supplemental hydration are not recommended as useful interventions.[58][59]

The use of antibiotics to treat TPTL with intact membranes has not been shown to reduce the rate of preterm delivery. It has also been linked to the subsequent development of cerebral palsy, as treatment may prolong gestation in a hostile in utero environment.[62][110]

The fibronectin test may reduce preterm birth rates by helping identify women at high risk of delivery, and by influencing subsequent management.[95][111] [ ] Women experiencing uterine contractions but negative for fetal fibronectin are unlikely to deliver in the next week (<1%), and corticosteroid administration and/or in utero transfer may be withheld. Quantification of fetal fibronectin allows a more precise risk stratification.[104] In women at critical gestations (23-26 weeks), admission to the hospital may prevent inadvertent delivery away from neonatal resuscitation facilities.

Preterm prelabor rupture of membranes (PPROM)

After PPROM, women should be closely monitored for signs of infection as an inpatient. These should include monitoring vital signs for maternal tachycardia or pyrexia, uterine tenderness, offensive vaginal discharge, leukocytosis, or elevated C-reactive protein. However, the sensitivity and specificity of these maternal blood tests for clinical chorioamnionitis is rarely more than 50%.[112]

The fetal heart rate should be monitored to detect signs of tachycardia (>160 bpm), which can be a sign of chorioamnionitis. Fetal monitoring using CTG is recommended if fetal surveillance is required, while the use of Doppler or biophysical profile scoring is not recommended for first-line surveillance of the fetus.[113] Women should also be informed there is an increased risk of placental abruption where PPROM has occurred.[114]

Antibiotics should be given for 10 days after a diagnosis of PPROM, or until the woman is in established labor (whichever is sooner).[71][114] Erythromycin or a penicillin may be given. Amoxicillin/clavulanic acid is not recommended because it may increase the risk of necrotizing enterocolitis in the neonate. [ ]

Intrapartum antibiotic prophylaxis may be given for women in preterm labor if there is prelabor rupture of membranes, or suspected/confirmed intrapartum rupture of membranes lasting more than 18 hours.[115][116]

Prenatal corticosteroids should be prescribed as, once membranes have ruptured, preterm delivery is almost inevitable, and corticosteroids are of benefit to the fetus. There is no evidence that they increase the risk of infection.[94][117][118] Magnesium sulfate may also be given for fetal neuroprotection in women who are in established preterm labor or who are having a planned preterm birth within 24 hours.[71][114][119] See ‘High risk of imminent delivery’ section below for further details on prenatal corticosteroids and magnesium sulfate.

Prophylactic tocolysis is not recommended if PPROM is the only presenting feature, but it can be considered if there is uterine activity.[114][120]

In carefully selected patients who have a low risk of cord prolapse, and normal inflammatory markers, outpatient monitoring after 48 to 72 hours of inpatient observation may be considered. These women should continue to measure their temperature twice daily and be aware of the symptoms and signs of possible infection requiring hospital admission. They will require regular follow-up 2 to 3 times a week to check fetal and maternal heart rate and inflammatory markers.

If pregnancy continues following PPROM, expectant management can be considered in cases without overt signs of infection.[121][122][123] The Royal College of Obstetricians and Gynaecologists (RCOG) advises that women with PPROM, after 24 weeks’ gestation, with no contraindications to continuing the pregnancy, should be offered expectant management up to 37 weeks. The exact timing of birth is considered on an individual basis, taking account of the patient’s preferences and clinical features.[114] Evidence on the optimal timing of delivery for PPROM in the late preterm period (34 weeks’ to 36+6 weeks’ gestation) is conflicting, and guideline recommendations vary.[99][123] The American College of Obstetricians and Gynecologists (ACOG) and the UK National Institute for Health and Care Excellence recommend that either expectant management or immediate delivery is reasonable for PPROM between 34 weeks’ and 36+6 weeks’ gestation, suggesting shared decision making with careful consideration of the risks and benefits from both a maternal and neonatal perspective.[119][124]

There is little justification for nonmedically indicated preterm delivery, and assessment of fetal lung maturity should not be used to justify delivery in these circumstances.[125]

Conservative management beyond this is possible and the fetus may gain maturity, but there is an increased risk of infection.[109] Immediate delivery may reduce the incidence of infection but increase the risk of cesarean section. Therefore, more evidence is needed to guide best practice.[122]

High risk of imminent delivery

The two most important interventions that improve outcome in preterm labor are prenatal corticosteroids and in utero transfer to a specialist center when local neonatal services are not adequate.[63][94][126]

Corticosteroids

ACOG and the World Health Organization recommend a single course of corticosteroids for women between 24 weeks' and up to 34 weeks' gestation if they are at risk of preterm delivery within the next 7 days.[33][118][127] RCOG guidelines recommend the use of corticosteroids in women at imminent risk of preterm delivery (due to PPROM, established preterm labor, or planned preterm birth) from 24 to 34+6 weeks’ gestation.[114][128] Betamethasone and dexamethasone have been widely studied, but it is unclear if there is benefit of one over the other.[94][127] [ ] It has been suggested that dexamethasone may result in lower rates of intraventricular hemorrhage.[94][129] Corticosteroids may be considered in women at 22 weeks' gestation who are at risk of preterm delivery within 7 days (dependent on the family’s wishes regarding resuscitation).[127][128][130]

ACOG recommends a single course of betametasone for pregnant women at risk of preterm labor within 7 days, from 34 weeks' and up to 37 weeks' gestation.[127] Corticosteroids have shown benefit when given at 35 or 36 weeks' gestation, with less respiratory distress in the infant after birth, but a potential increase in the likelihood of neonatal hypoglycemia.[127][131][132] Therefore, corticosteroids may be given to these patients at the discretion of the obstetrician depending on the risk of delivery and concerns over treatment.[128]

Optimal clinical benefit of prenatal corticosteroids is likely to be from 24 hours to 7 to 14 days after administration. The use of multiple doses has been linked to intrauterine growth restriction and theoretical concerns of long-term morbidity.[133] However, a single repeat course after 7 days may be beneficial if still at a critical gestation,[Evidence A] and a meta-analysis suggests no evidence of harm at 2 to 3 years (in over 4000 children).[134][135][136] [ ] The use of prenatal corticosteroids in low- and middle-income countries has been associated with an increase in overall neonatal mortality, and care must be taken not to extrapolate clinical trial findings to all populations.[137][118]

Tocolysis

Tocolytic agents may prolong gestation by between 2 and 7 days and are recommended for short-term use to provide time for prenatal corticosteroids to work and to transfer the mother to an appropriate facility with a neonatal unit.[63][64] One Cochrane review reported low- to moderate-certainty evidence that all tocolytic drug classes assessed were effective in delaying preterm birth for 48 hours and 7 days.[138]

The use of tocolytic drugs must be carefully considered, as there is no clear evidence that they improve outcome, and their adverse-effect profile should be taken into account when choosing a particular agent.[58] Nifedipine is a commonly used agent. Nifedipine has adverse effects that are dose dependent.[139] Calcium-channel blockers may be more effective than other tocolytic agents at reducing deliveries before 34 weeks' gestation and at reducing neonatal morbidity. [ ]

Beta agonists no longer seem the best choice as, although they can prolong gestation, they may cause maternal adverse effects that lead to discontinuation of therapy, and the Food and Drug Administration cautions against the off-label use of terbutaline for preterm labor.[138][140] [ ] [ ] [ ] [ ] Atosiban (an oxytocin antagonist) and nifedipine have comparable effectiveness to beta agonists with fewer adverse effects and similar perinatal outcomes.[141][142][143] Prostaglandin inhibitors may be less likely to cause maternal adverse effects. During administration, maternal pulse rate and blood pressure should be monitored every 30 minutes for the first 4 hours, then every 2 hours for the first 24 hours. There is no evidence to show that maintenance therapy with an oxytocin antagonist following acute treatment improves the length of gestation or outcome.[144]

Contraindications to tocolysis include lethal fetal anomaly, chorioamnionitis, fetal compromise, significant vaginal bleeding, or maternal comorbidity.[58]

Antibiotics

All women in active preterm labor with regular uterine contractions and progressive cervical dilation are given intravenous antibiotics for group B streptococcus (GBS) prophylaxis (except in case of negative GBS culture obtained at ≥36+0 weeks’ gestation).[116] In the UK, there is no routine screening for GBS, but intravenous antibiotics are recommended for women in confirmed preterm labor, irrespective of GBS status.[115]

Magnesium sulfate

Magnesium sulfate given prior to delivery may protect the fetus against neurologic damage. One Cochrane review found that prenatal magnesium sulfate significantly reduced the risk of cerebral palsy in babies born under 34 weeks’ gestation (relative risk 0.68, 95% CI 0.54 to 0.87).[145]

Guidelines recommend offering intravenous magnesium sulfate for fetal neuroprotection to women between 24 and 29+6 weeks’ gestation who are in established preterm labor or having a planned preterm birth within 24 hours.[71][114] Magnesium sulfate may also be considered from 23 weeks’ gestation and for gestations below 32 to 34 weeks; it is not recommended before viability.[71][119][146]

Physicians electing to use magnesium sulfate for fetal neuroprotection should develop specific guidelines regarding inclusion criteria, treatment regimens, and concurrent tocolysis.[147]

There is no evidence that magnesium sulfate has any value as a tocolytic agent, and its use should only be for neuroprotection in appropriate groups of women.[148]

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Preterm labor

Approach

Threatened preterm labor (TPTL)

Preterm prelabor rupture of membranes (PPROM)

High risk of imminent delivery