Persalinan Preterm

01Pathophysiology

Preterm delivery is defined as birth occurring between 20 and 36 weeks and 6 days of gestation. It is the leading cause of neonatal morbidity and mortality worldwide.

The pathophysiology is driven by several converging mechanisms that ultimately activate the common pathway of parturition: uterine contractility, cervical ripening, and decidual/membrane activation. Under normal conditions, this pathway is suppressed until term by progesterone dominance and relative myometrial quiescence. In preterm labor, this suppression fails prematurely.

Infection and inflammation represent the most well-understood mechanism. Ascending bacterial infection from the lower genital tract (commonly bacterial vaginosis organisms such as Gardnerella vaginalis, Ureaplasma urealyticum, or Mycoplasma hominis) triggers an inflammatory cascade in the decidua and fetal membranes. This leads to release of prostaglandins (particularly PGE2 and PGF2-alpha), which cause cervical ripening and myometrial contractions, and matrix metalloproteinases (MMPs), which degrade the extracellular matrix of the fetal membranes, leading to preterm premature rupture of membranes (PPROM).

Uterine overdistension, seen in multiple gestation and polyhydramnios, mechanically stretches the myometrium. This upregulates gap junction proteins (connexin-43) and oxytocin receptors, shifting the uterus from a quiescent to a contractile state.

Cervical insufficiency results from structural weakness of the cervix, often from prior cervical procedures (cone biopsy, LEEP) or congenital collagen disorders (Ehlers-Danlos syndrome). The cervix shortens and dilates painlessly in the second trimester, typically presenting as painless cervical dilation without contractions, distinguishing it from true preterm labor.

Decidual hemorrhage from placental abruption or retroplacental clot activates thrombin, which directly stimulates myometrial contractions and membrane degradation independently of the prostaglandin pathway.

Stress and the hypothalamic-pituitary-adrenal (HPA) axis also contribute. Maternal or fetal stress increases corticotropin-releasing hormone (CRH) from the placenta. Elevated maternal serum CRH in the second trimester is associated with earlier delivery. CRH stimulates fetal adrenal production of dehydroepiandrosterone sulfate (DHEA-S), which is converted to estrogen in the placenta, shifting the progesterone-to-estrogen ratio in favor of labor.

This explains why prior preterm birth is the strongest risk factor: whatever mechanism caused preterm activation of the parturition pathway in a previous pregnancy is likely to recur. It also explains why progesterone supplementation works as a preventive strategy in women with a history of preterm birth, as it directly opposes the withdrawal of progesterone dominance.

02Classification and Clinical Manifestation

Classification by Gestational Age

Classification by Mechanism

Clinical Manifestations by Presentation

03Diagnostic Workup

When a patient presents with contractions before 37 weeks, the first priority is to determine whether she is in true preterm labor versus false labor (Braxton-Hicks contractions). True preterm labor requires both regular uterine contractions and documented cervical change (dilation or effacement).

Step 1: Confirm gestational age. Accurate dating by first-trimester ultrasound is essential, as all management decisions depend on gestational age.

Step 2: Rule out membrane rupture. Perform a sterile speculum exam to look for pooling of amniotic fluid in the posterior fornix, test with nitrazine paper (turns blue at pH >6.0, since amniotic fluid is alkaline at pH 7.1 to 7.3), and assess for ferning (crystallization pattern on air-dried slide). Do not perform a digital exam if PPROM is suspected, as this increases infection risk and shortens latency. If equivocal, commercially available tests detecting placental alpha-microglobulin-1 (PAMG-1) or insulin-like growth factor binding protein-1 (IGFBP-1) in vaginal fluid can confirm rupture with high sensitivity and specificity.

Step 3: Assess cervical status. Transvaginal ultrasound for cervical length is the best objective measure. A cervix measuring <25 mm in a symptomatic patient significantly increases the probability of preterm delivery. In an asymptomatic high-risk patient (e.g., prior preterm birth), serial cervical length measurements starting at 16 to 24 weeks guide intervention decisions.

Step 4: Fetal fibronectin. This glycoprotein is normally found at the choriodecidual interface and should be absent from cervicovaginal secretions between 22 and 34 weeks. Its greatest clinical utility lies in its negative predictive value: a negative result essentially rules out delivery within the next 2 weeks, which can prevent unnecessary hospitalization and tocolysis. However, fFN is invalidated by recent intercourse, vaginal exam, or vaginal bleeding, so it must be collected before digital cervical examination. A positive result is less helpful, as its positive predictive value is only about 20%.

Step 5: Evaluate for underlying causes. Check urinalysis and culture (UTI can trigger contractions), obtain vaginal/rectal GBS culture, and assess for signs of chorioamnionitis (maternal fever, uterine tenderness, fetal tachycardia, purulent discharge).

04Management and Treatment

Acute stabilization begins with confirmation of preterm labor and assessment of gestational age, fetal presentation, and estimated fetal weight.

For a patient between 24 and 33 weeks in active preterm labor with intact membranes:

1. Administer antenatal corticosteroids immediately. Betamethasone is preferred (12 mg IM, repeated once at 24 hours). This is the single most important intervention for improving neonatal outcomes. Steroids accelerate fetal lung maturity by inducing surfactant production, reduce the incidence of RDS, IVH, NEC, and neonatal death. The benefit window is optimal between 2 and 7 days after the first injection, but some benefit begins within hours.

2. Start tocolysis to buy 48 hours for steroid effect. First-line agents include nifedipine (calcium channel blocker) or indomethacin (cyclooxygenase inhibitor, preferred at <32 weeks). Nifedipine is given as a 20 mg oral loading dose, followed by 10 to 20 mg orally every 4 to 6 hours. Indomethacin is given as 50 mg orally or rectally as a loading dose, then 25 to 50 mg orally every 6 hours for a maximum of 48 hours. Indomethacin must not be used beyond 32 weeks due to the risk of premature closure of the ductus arteriosus and oligohydramnios. Terbutaline (beta-agonist) is no longer recommended for prolonged use (FDA black box warning for serious maternal cardiac events) but may be given as a single subcutaneous dose for acute tocolysis. Tocolytics are contraindicated in chorioamnionitis, significant maternal hemorrhage (abruption), severe preeclampsia, or non-reassuring fetal status, as these situations warrant delivery regardless of gestational age.

3. Administer magnesium sulfate for fetal neuroprotection if gestational age is <32 weeks and delivery is anticipated within 24 hours. The loading dose is 4 g IV over 20 to 30 minutes, followed by a maintenance infusion of 1 to 2 g/hour. This reduces the risk of cerebral palsy by approximately 30 to 40%. Magnesium toxicity must be monitored: loss of patellar reflexes occurs at serum levels of 8 to 12 mEq/L, respiratory depression at 12 to 15 mEq/L, and cardiac arrest at >15 mEq/L. Calcium gluconate (1 g IV over 3 minutes) is the antidote.

4. Obtain GBS culture and begin prophylaxis if GBS status is unknown or positive. Penicillin G is first-line. For penicillin-allergic patients with low anaphylaxis risk, cefazolin 2 g IV loading then 1 g IV every 8 hours is used. For high anaphylaxis risk, check susceptibilities: clindamycin 900 mg IV every 8 hours if susceptible, or vancomycin 20 mg/kg IV every 8 hours (max 2 g per dose) if resistant.

5. Arrange maternal transfer to a facility with an appropriate level NICU if needed.

For PPROM, the management depends on gestational age. Between 24 and 33 weeks with no signs of infection, chorioamnionitis, placental abruption, or non-reassuring fetal status, expectant management is preferred. Administer latency antibiotics (ampicillin + azithromycin regimen), antenatal corticosteroids, and magnesium sulfate if <32 weeks. Avoid digital exams to minimize infection risk. Monitor for signs of chorioamnionitis (maternal fever >38.0 degrees C, uterine tenderness, maternal/fetal tachycardia, purulent discharge). At 34 weeks, delivery is generally recommended for PPROM because the risks of prematurity-related complications become lower than the risks of infection from prolonged membrane rupture.

For late preterm (34 to 36 weeks): A single course of betamethasone is now recommended if steroids have not been given previously during this pregnancy (per current ACOG guidelines). Tocolysis is generally not indicated at this gestational age. If the patient is GBS-positive or status unknown, administer intrapartum prophylaxis.

Prevention in subsequent pregnancies: Women with a prior spontaneous preterm birth should receive 17-alpha hydroxyprogesterone caproate 250 mg IM weekly beginning at 16 to 20 weeks and continuing through 36 weeks. Women found to have a short cervix (<25 mm) on routine ultrasound without prior preterm birth should receive vaginal progesterone (200 mg suppository or 90 mg gel nightly). If a woman has both a prior preterm birth and a short cervix (<25 mm) developing before 24 weeks, a cervical cerclage should be placed in addition to progesterone. An emergency (rescue) cerclage may be considered if the cervix is found to be dilated with bulging membranes in the absence of labor, infection, or bleeding, though outcomes are less favorable.

05Differential Diagnosis and Distractors

06Traps and High-Yield Pearls

The most common way students lose points on preterm labor questions is by confusing the role of tocolytics with definitive treatment. Tocolytics do not improve neonatal outcomes on their own. Their sole purpose is to delay delivery long enough for corticosteroids to take effect (48 hours) and for maternal transfer to an appropriate facility. A vignette describing a patient at 30 weeks in active labor should prompt you to think "corticosteroids and magnesium sulfate" first, not tocolysis alone.

Another frequent trap involves indomethacin use beyond 32 weeks. The question stem may describe a patient at 33 or 34 weeks where indomethacin seems like a reasonable tocolytic. The correct answer is nifedipine or no tocolysis at all, because indomethacin at this gestational age causes premature closure of the ductus arteriosus and oligohydramnios.

Students also commonly miss the distinction between cervical insufficiency and preterm labor. If the vignette describes painless cervical dilation in the second trimester without contractions, the answer is cervical insufficiency (and cerclage if appropriate), not tocolysis. Tocolytics are ineffective when there is no uterine contractile activity driving the dilation.

The negative predictive value of fetal fibronectin is the tested concept, not its positive predictive value. A negative fFN essentially rules out delivery within 2 weeks and can be used to avoid unnecessary intervention. However, fFN is only valid if collected before digital exam and in patients with intact membranes and dilation <3 cm.

For PPROM questions, remember two critical rules: do not perform a digital cervical exam (it shortens latency and increases infection), and deliver at 34 weeks even if the patient is stable, because the infection risk outweighs the benefit of continued expectant management beyond that point. If the vignette adds maternal fever and uterine tenderness to PPROM at any gestational age, the answer is immediate delivery for chorioamnionitis, and tocolysis is absolutely contraindicated.

Finally, know the gestational age cutoffs cold: corticosteroids at 24 to 36 weeks 6 days (with the late preterm steroid course being a single course for those who have not previously received steroids), magnesium sulfate for neuroprotection at <32 weeks, and indomethacin contraindicated at >32 weeks. Exam questions frequently hinge on whether a patient falls just above or just below these thresholds.