Prevention And Management Of Preterm Labor
- Recommendations
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1. Risk Assessment for Preterm Labor |
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1.1. Assess risk factors preconception and early pregnancy with a comprehensive review of all previous pregnancies because the most important historical risk factor is prior spontaneous PTL. Remark: The cause of spontaneous preterm labor remains unidentified in up to half of all cases. The cause of spontaneous preterm labor remains unidentified in up to half of all cases and although many factors have been associated with an increased risk of spontaneous PTL, there is a relative paucity of high-level research. [12,13] [HQE, STRONG]
1.2. Risk factors, that should be thought of, include maternal characteristics and factors related to medical or obstetric conditions 1.2.1. Maternal Characteristics: o Age of woman: Younger than 20 years and older than 40 years[12,13] o Smoking o Women residing in rural and remote areas[13] o Ethnicity: increased among African women compared to Caucasian or Asian women[14-16] o Late or no antenatal care o Lack of continuity of care o Low socio-economic status o High or low body mass index (BMI) 1.2.2 Medical or Obstetric Conditions o Multiple birth: 66% of twins and 98.2% of all other multiples (triplets and higher order) [13] o Previous PTL: Rational: Approximately 30% of women who give birth between 20 and 31 weeks in a prior pregnancy will give birth before 37 weeks in a subsequent pregnancy and 10% of these will occur at a similar gestational age [11] . Number of prior PTL :15% recurrence risk with single prior PTL, 32% recurrence risk with two prior PTL [17] o Genital tract infections: The risk of PTL doubles with Bacterial vaginosis[18,19] o Urinary tract infections[20] o Vaginal bleeding[20] o Assisted reproduction associated with two-fold risk of PTL[[20] o Preterm prelabor rupture of membranes (PPROM) o Surgical procedures involving the cervix[5] o Uterine anomalies[20] o Polyhydramnios/oligohydramnios o Chronic medical conditions o Acute medical conditions (e.g. preeclampsia, antepartum hemorrhage) |
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2. Risk Reduction |
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2.1 Assessment & Counseling (MQE, GPS) 2.1.1 Assess Risk Factors Preconception [14,15] 2.1.2 Smoking cessation interventions reduce PTL rate by 18%[19] 2.1.3 Optimization of control of underlying chronic diseases reduces risk[21] 2.1.4 Lifestyle modifications (e.g. balanced diet, activity limitations, and stress management |
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2.2 Bacterial Vaginosis (MQE, GPS) 2.2.1 Women with previous PTL may benefit from routine screening and treatment of BV[19] 2.2.2 The following is suggested to treat bacterial vaginosis after the first trimester of pregnancy. All regimens have equal effectiveness: [22,23] i. Local vaginal application of 500–1000 mg metronidazole suppository for 7 days. ii. Oral clindamycin 2 × 300 mg/day for 7 days iii. Intravaginal application of 5 g of 2 % clindamycin vaginal cream for 7 days |
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2.3 Urinary Tract Infections (HQE, STRONG) 2.3.1 Screen and recommend treatment for urinary tract infections (asymptomatic bacteriuria, cystitis, pyelonephritis) 2.3.2 Empirical antimicrobial treatments for asymptomatic bacteriuria will be required using an antibiotic regimen with either Nitrofurantoin (100 mg three times daily), amoxycillin (500 mg three times daily) for a week or Fosfomycin 3 grams orally as a single dose with 3 glasses of water. Treatment should be re-evaluated once culture and sensitivity results are available. [13,24] |
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2.4 Cervical Length Measurement (MQE, GPS) 2.4.1 Recommend routine cervical length measurement to women during the mid-trimester morphology (18–20 weeks) ultrasound scan with the cervical length documented in medical records[25-27] 2.4.2 Consider serial transvaginal cervical length (TVCL) measurement for high-risk women with prior PTL (From 14–24 weeks gestation, serial TVCL every two weeks may be appropriate) [28,29]. |
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2.5 Progesterone Therapy (MQE, STRONG) 2.5.1 For singleton pregnancies recommend vaginal progesterone 200 mg by night from 16–36 weeks gestation for women with: [26]. o An incidentally diagnosed shortened cervix (less than or equal to 25 mm) on TVCL between 16–24 weeks, OR[30]. o A prior spontaneous PTL or mid-trimester miscarriage between 20–36 weeks+6days (with or without preterm prelabor rupture of membranes) [31]. |
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2.1. Cervical Cerclage For Risk Reduction |
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3.1 Cervical cerclage may be indicated (individualize decisions) for women with history of either: (MQE, CONDITIONAL) · One or more prior spontaneous PTL and/or second-trimester loss related to painless cervical dilation and in the absence of labor or abruptio placentae, or[32]. · Prior cerclage due to painless cervical dilation in second trimester[32]. · TVCL less than 25 mm before 24 weeks if: [5]. o Prior spontaneous PTL (or a PPROM) before 34 weeks gestation and o Current singleton pregnancy 3.2 There is limited data about the effectiveness of rescue cerclage particularly beyond 24 weeks of gestation therefore individualize decisions 3.3 Multiple dilation and evacuations or cervical surgery (e.g. cone biopsy, large loop excision of the transformation zone, laser ablation, diathermy) or other abnormalities (e.g. Mullerian anomaly) are not themselves an indication for cerclage 3.4 Cerclage is Not recommended for women with: · Funneling of the cervix in the absence of cervical shortening to 25 mm or less[33]. · An incidentally identified short cervix without a history of spontaneous PTL or second trimester loss [5]. · Multiple pregnancy (and may be detrimental) [34]. 3.5 If prophylactic cervical cerclage is used, ensure that a plan is in place for removal of the suture. [5]. |
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2.2. Diagnosis of PTL in Women with Intact Membranes |
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4.1 Identifying and treating women with symptoms of preterm labor, provides the opportunity to utilize interventions to minimize the impact of PTL. Only around 10% of women who present with symptoms of preterm labor (contractions) will deliver preterm[35] (MQE, GPS) In a patient presenting with symptoms of suspected preterm labor: 4.2. Review history: Medical, Surgical, Obstetric, Psychosocial and Lifestyle (Refer to section 1. Risk Assessment for Preterm Labor) 4.3. Assess Symptoms of uterine contractions: in a single phrase[36]. o Pelvic pressure o Lower abdominal cramping o Lower back pain o Vaginal loss (mucous, blood or fluid) o Regular uterine activity 4.4. Perform Physical examination · Vital signs · Abdominal palpation to assess uterine tone, contractions, fetal size and presentation · Sterile speculum examination to: o Confirm/exclude rupture of membranes o Visualize cervix/membranes o Assess liquor in case of PPROM (e.g. clear, meconium stained, bloody) · Sterile digital vaginal examination o Assess cervical dilatation and effacement by sterile digital vaginal examination unless confirmed by speculum examination or contraindicated due to ruptured membranes or suspected placenta previa · Fetal surveillance o Monitor and document Fetal heart rate (FHR by clinical or electronic monitoring if available) |
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5. Indications Of Admission in Women with Intact Membranes |
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5.1 Admit the patient If: (HQE, STRONG) · Gestational age less than 30 weeks · Membranes ruptured · A cervical cerclage has been performed · Cervical dilation (painless or painful) · Cervical change over 2–4 hours · Contractions are regular and painful · Further observation or investigation indicated · TVCL changes and/or less than 25 mm (if available) · Other maternal or fetal concerns 5.2 If the clinical assessment suggests that the woman is in suspected preterm labor and she is 29+6 weeks pregnant or less, advise treatment as diagnosed preterm labor as described in the sections on tocolysis and maternal corticosteroids. 5.3 If the clinical assessment suggests that the woman is in suspected preterm labor and she is 30+0 weeks pregnant or more, consider transvaginal ultrasound measurement of cervical length as a diagnostic test to determine likelihood of birth within 48 hours. |
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6. Criteria For Discharge in Women With Intact Membranes |
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6.1. A woman with suspected preterm labor may be discharged home If all the following criteria are fulfilled: [5] (HQE, GPS)
6.2. Women should be informed about: · Signs and symptoms of preterm Labor · Risk reduction measures appropriate to the circumstances · Follow-up as indicated |
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7. Management Of Women with Suspected PTL And PPROM |
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7.1. Admission for reassessment and/or therapeutic interventions |
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7.1.1. offer admission for reassessment and/or therapeutic interventions for women with suspected PTL and diagnosed PPROM |
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7.2. Antenatal prophylactic antibiotics for women with PPROM [5]. (HQE, STRONG) |
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7.2.1. Offer women with PPROM oral erythromycin 250 mg 4 times a day for a maximum of 10 days or until the woman is in established labor (whichever is sooner). [5]. |
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7.2.2. For women with PPROM who cannot tolerate erythromycin or in whom erythromycin is contraindicated, or if not available consider one of the oral penicillins for a maximum of 10 days or until the woman is in established labor (whichever is sooner). [5]. |
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7.2.3. Do not offer women with PPROM co-amoxiclav as prophylaxis for intrauterine infection. [5]. |
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7.3. Identifying infection in women with PPROM |
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7.3.1. Use a combination of clinical assessment and tests (C-reactive protein, white blood cell count and measurement of fetal heart rate) to diagnose intrauterine infection in women with PPROM every 48 hours. Do Not use any of these tests in isolation to confirm or exclude intrauterine infection. [5] (HQE, GPS) |
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7.3.2. If the results of the clinical assessment or any of the tests are not consistent with each other, continue to observe the woman and consider repeating the tests. [5] (HQE, GPS) |
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7.4. Chorioamnionitis |
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7.4.1. Suspect Intra-amniotic infection in presence of: [37] (HQE, STRONG) · Maternal fever greater than 38 °C (present in 95–100% of cases) in presence of 2 or more of the following: o Maternal tachycardia greater than 100 beats per minute (bpm) (present in 50–80% of cases) o Fetal tachycardia greater than 160 bpm (present in 40–70% of cases) o Uterine tenderness o Offensive smelling vaginal discharge o Increased white cell count (greater than 15x109/L) Management of Preterm labor with PPROM and suspected infection (HQE, STRONG) 7.4.2. Do not inhibit labor, but consider hastening birth under broad spectrum intravenous antibiotic cover 7.4.3. Suspect chorioamnionitis in women with PPROM if Labor ensues 7.4.4. The optimal antibiotic suggested regimen to cover Gram negative and positive and anaerobic microorganisms is combination of: [38] · Ampicillin (or amoxycillin) 2 g IV every 6 hours AFTER sensitivity testing, and, · Tobramycin 5 mg/kg IV daily (preferred) or gentamicin 1.5-2mg/kg/day in 3 divided doses (every 8 hours) and, · Metronidazole 500 mg IV every 12 hours (rectal may be considered if IV is not available). 7.4.4. Continue oral ampicillin and metronidazole treatment after birth for 7 – 10 days, plus IV tobramycin or IM gentamycin for 5 days maximum. |
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8. Management Of Diagnosed Preterm Labor With Intact Membranes |
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8.1. General Rules[9] (MQE, GPS) |
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8.1.1. Tocolysis and steroids are the main strategies to manage preterm labor. 8.1.2. Consider in-utero transfer to a center with higher neonatal service capabilities. 8.1.3. Discuss with the women and family the conditions of transfer including limited resuscitation if birth occurs in the route. 8.1.4. Adequate assessment of the women should be done before transfer. 8.1.5. Transfer decisions should be coordinated between obstetric and neonatology teams on both sides. |
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8.2. Tocolysis |
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8.2.1. Tocolysis is recommended to give time for a course of corticosteroid therapy or to allow in-utero transfer to an obstetric center with higher-level neonatal care[5] (HQE, STRONG) 8.2.2. Criteria for tocolysis: 1. Woman is in suspected or diagnosed preterm labor with intact membranes 2. No other clinical features that may suggest that stopping labor is contraindicated 3. Gestational age at presentation < 37 weeks 8.2.3. It is NOT recommended to use tocolysis for > 48 hours 8.2.4. Nifedipine is the recommended tocolytic of choice[39,40] (HQE, STRONG) 8.2.5. Nifedipine is administered according to this protocol: [41] (HQE, STRONG) · Nifedipine 20 mg oral (2 of 10 mg capsules) · If contractions persist after 30 minutes repeat Nifedipine 20 mg oral · If contractions persist after a further 30 minutes repeat Nifedipine 20 mg oral · If BP is stable, give Nifedipine 20 mg oral every 6 hours for 48 hours · Further maintenance therapy is ineffective[42] · Maximum dose is 160 mg/day[41] · Do not use sustained release formulation or sublingual route. 8.2.6. On Nifedipine, observe: BP, pulse and respiratory rate every thirty minutes for the first hour, then hourly for four hours (Review frequency in accordance with clinical circumstances), and measure temperature every four hours[41,42] 8.2.7. Nifedipine is contraindicated in: [41] (HQE, STRONG) · Maternal hypotension · Maternal cardiac disease (preload-dependent cardiac lesions) · Previous adverse reaction to calcium channel blockers. · Concomitant use with Magnesium Sulfate may increase effects of nifedipine and the risk of hypotension so use cautiously with Magnesium Sulfate 8.2.8. If there are contraindications to Nifedipine, use an alternative tocolytic as indomethacin 8.2.9. Inhibitors of prostaglandin synthesis (Indomethacin) may be used with the following conditions fulfilled: [43,44] (LQE, STRONG) · There is failure to achieve tocolysis with Nifedipine or Nifedipine is contraindicated · Only before 32 weeks of gestation (indomethacin is a potential option for use in conjunction with magnesium sulfate). · Maximum duration is 48 hours to avoid risks for the fetus and neonate · Ensuring close monitoring of fetal wellbeing 8.2.10. Betamimetics are not recommended for tocolysis[45,46] (HQE, STRONG) 8.2.11. Magnesium Sulfate is not recommended for the sole purpose of tocolysis[47,48] (HQE, STRONG) |
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8.3. Corticosteroids |
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8.3.1. Corticosteroids are administered according to ONE of the following protocols: [49] (HQE, STRONG) · Betamethasone: two 12-mg doses of betamethasone I.M. 24 hours apart OR · Dexamethasone: four 6-mg doses of dexamethasone I.M. at 12 hours intervals Repeat Dose of Corticosteroids 8.3.2. Do not routinely administer scheduled serial or weekly courses of antenatal corticosteroids Rational: Do not routinely administer further repeat courses. Before repeat treatment, consider current gestational age, probability and expected timing of birth, fetal growth, previous cumulative corticosteroid exposure, maternal diabetes or infection, and the balance between reduced neonatal respiratory morbidity and the small adverse effect on fetal growth.(49,5) (HQE, CONDITIONAL) 8.3.3. Consider one repeat course of antenatal corticosteroids for a woman at less than 34+0 weeks of gestation who received an initial course at least seven days previously and who, following renewed clinical assessment, has a high likelihood of preterm birth within the next seven days. (49-52) (HQE, CONDITIONAL) 8.3.4. In women with diabetes mellitus, blood sugar levels should be monitored during the intake of corticosteroids.
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8.4. Antibiotics |
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i. Routine administration of prophylactic antibiotics to women in threatened preterm labor with intact membranes and without evidence of infection is not recommended (53-3) (HQE, GPS) ii. When preterm labor starts, give intrapartum antibiotic prophylaxis for prevention of early onset Group B-streptococcal disease irrespective of GBS status or membrane status: (3) (HQE, STRONG) · Benzylpenicillin (Penicillin G): After a sensitivity test; give 3 gm (5 million units) IV be given as soon as possible after the onset of labor (the first dose should be given at least 4 hours prior to delivery of baby) and then 1.5 gm (2.5- 3 million units) every 4 hours. · Alternatives (any of): o Amoxicillin 2 gm IV initial dose then 1 gm every 4 hours or 2 gm every 6 hours o Ampicillin 2 gm IV initial dose then 1 gm every 4 hours or 2 gm every 6 hours o Cefuroxime 1.5 g loading dose then 750 mg every 8 hours o Cephazolin 2gm IV initial dose then, 1 gm every 8 hours until delivery · If allergic to penicillin ➔ either of: o Vancomycin IV 1 gm every 12 hours, or o Clindamycin 900 mg every 8 hours |
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8.5. Magnesium Sulfate for Neuroprotection (53) (HQE, STRONG) |
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8.5.1. Offer intravenous magnesium sulfate for neuroprotection of the baby to women between 26+0 and 33+6 weeks of pregnancy who are in established preterm labor or having a planned preterm birth within 24 hours 8.5.2. When birth is planned, commence magnesium sulfate administration 4-6 hours prior to birth for best effect. 8.5.3. If birth is expected to occur within four hours, commence MgSO4 immediately, as there may still be benefit from administration. 8.5.4. In situations where urgent birth is necessary, do not delay birth to administer MgSO4 8.5.5. Give 4 gm intravenous bolus of magnesium sulfate over 15 minutes, followed by an intravenous infusion of 1 gm per hour until the birth or for 24 hours (whichever is sooner). 8.5.6. If birth does not occur after giving MgSO4 and PTL (less than 30 weeks’ gestation) again appears imminent (planned or expected within 24 hours), a repeat dose of MgSO4 may be considered. |
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8.6. Observations and fetal surveillance Intrapartum |
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8.6.1. Use of intermittent auscultation is recommended as there is absence of evidence that using cardiotocography improves the outcomes of preterm labor compared with intermittent auscultation. (5) (HQE, GPS) |
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8.7. Mode of Preterm Birth |
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8.7.1. There is insufficient high-quality evidence about whether mode of birth affects neonatal morbidity and outcomes. (55,56) (HQE, STRONG) 8.7.2. For Singleton Vertex presentation: Vaginal birth is recommended unless there are specific contraindications to vaginal birth or maternal conditions necessitating CS. (55) (HQE, STRONG) 8.7.3. For Breech Presentation: (55) o ≥ 26+0 weeks: The evidence regarding optimal mode of birth for preterm breech is conflicting and unclear due to a lack of high-quality studies (LQE, GPS) - Base decisions on individual circumstances and maternal preferences - CS is not generally recommended where vaginal birth is imminent. 8.7.4. Consider that Preterm CS is usually technically more difficult to perform and is not without risks to the baby (57) The lower segment is usually not well formed (upper segment incision) with risks to future pregnancies including scar dehiscence, uterine rupture, placental adherence and maternal death 8.7.5. Timing of cord clamping for preterm babies (born vaginally or by caesarean section): (58) (MQE, GPS) · Delayed cord clamping is recommended for 60 to 120 seconds because it decreases newborn mortality and morbidity and improves hematological outcomes after the newborn period. · Absolute contraindications to delayed cord clamping are § fetal hydrops, § the need for immediate resuscitation of mother or infant § disrupted utero-placental circulation (e.g., bleeding vasa previas), and § known twin-to-twin transfusion syndrome or twin anemia polycythemia sequence (HQE, STRONG) · Relative contraindications to delayed cord clamping are few but include (in term infants) risk factors for significant hyperbilirubinemia (e.g., significant polycythemia, severe intrauterine growth restriction, pregestational diabetes), and cases where maternal antibody titers are high or when the first infant in a pair of monochorionic twins is delivered. In all these circumstances, immediate cord clamping should be considered. (CONDITIONAL, LQE). · Umbilical cord milking: § Umbilical cord milking is not recommended in very preterm infants <32 weeks, due to increased risk for severe intraventricular hemorrhage (HQE, STRONG) § Delayed cord clamping should be performed instead of umbilical cord milking (HQE, STRONG) |
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