Preterm labor is defined as birth occurring between 23+6 and 36 weeks of gestation and is classified into spontaneous, after premature rupture of membranes (pprom), and medically indicated cases. Key risk factors include prior preterm labor, infections, multiple pregnancies, and uterine anomalies, with significant implications for neonatal outcomes. Management strategies involve tocolysis, corticosteroids for lung maturity, and interventions like cervical cerclage in high-risk women.

1. PRETERM LABOR

2. DEFINITION & CLASSIFICATION
• It’s a birth occurs after 23+6 weeks and before 37 weeks , (24-36+6 weeks)
• PROM : premature rupture of membranes : rupture of membranes before contractions
• PPROM : preterm premature rupture of membranes : rupture of membranes before term
• Classified into : A. spontaneous
B. preterm labor after PPROM
C. medically indicated preterm birth

3. EPIDEMIOLOGY
• Human has more PTL (preterm labor )than other species
• Preterm labor with worse outcome of the babies are in less
developed countries
• 50 % of the cases of preterm labor are spontaneous PTL
• 25 % of PTL cases are after PPROM and the other 25 % are
medically indicated
• More in low socioeconomic status ,African , teenagers ,
substance abuse like smoking , cocaine and alcohol
spontaneous PTL after PPROM indicated PTL

4. RISK FACTORS
Non modifiable modifiable
Previous preterm labor ***** and abortions
Family history or personal history being delivered
preterm
Smoking
African race Substance abuse (cocaine – abruptio placenta )
Maternal Age less than 18 and more than 40 Poor prenatal care
Poor pre-pregnancy weight , poor nutrition Short pregnancy interval
Low socioeconomic status Anemia
Uterine and cervical anomalies (incompetence)
(fibroids, septate uterus ….)
Urinary tract infections
Overdistended uterus (polyhydramnios, multiple
pregnancy )
Bacterial vaginosis *****
Unexplained vaginal bleeding in the first trimester Unmarried status
Excessive uterine activity social stress
IVF pregnancy excessive exercise ?

5. The strongest risk factor is a previous PTL
( 1.5-fold to twofold increased risk)
20 % after the first , 40 % after the second preterm labor
• Bacterial vaginosis is associated with a 2X increased risk of spontaneous preterm
birth, the association is stronger when BV is detected early in pregnancy
• Despite the association, antibiotic eradication of BV does not consistently reduce
the risk of preterm birth
• Multifetal gestation is one of the strongest risk factors for preterm birth ( more
than 50% of women with twins deliver before 37 weeks.) more in monochorionic , and
higher order multiple pregnancies

6. ENDOCRINE MECHANISM OF LABOR
• To understand the causes of preterm labor, you should understand the mechanism of
labor on endocrine base .
• The initiation of labor is not well understood (maybe fetal )

8. PRO-PREGNANCY FACTORS
• Keeps the uterus relaxed (quiescent )and the cervix rigid and closed
• These factors are : progesterone, relaxin, human chorionic gonadotrophin (hCG) and
pro-relaxation prostaglandins (PGs), such as prostacyclin, inhibit myometrial
contractility
• It’s the theory we rely on when we use prostaglandin as a prophylaxis for PTL .
• When labor occur progesterone functional withdrawal may occur (level not decreased in
human )

9. ONSET OF LABOR
• greater expression of gap junctions that connect myometrial cells
• Labour onset is diagnosed by the occurrence of painful uterine contractions with changes in the structure of the
cervix, leading to cervical dilatation and effacement
• The changes in the cervix occur through breakdown of collagen, changes in proteoglycan concentrations,
infiltration of leucocytes and macrophages and an increase in water content
• Increased myometrial activity results from the activation of a ‘cassette of contraction-associated proteins’ (CAPs),
which convert the myometrium from a quiescent to a contractile state
• CAPS includes gap junction proteins, oxytocin and prostanoid receptors, enzymes for PG synthesis
• and cell signalling proteins.
• CAPs also activate fetal membrane PG and cytokine production, as well as cervical remodelling and ripening

10. LABOUR AS AN INFLAMMATORY PROCESS
human labour is associated with a global increase in a number of proinflammatory factors including PGs,
cytokines and chemokines.
Elevated levels of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α
(TNFα) have been shown in amnion, myometrium and choriodecidua.
The influx of inflammatory cells such as neutrophils, macrophages and T-lymphocytes into
the labouring uterine tissues may result in the increased levels of proinflammatory
cytokines. In addition, inflammation has been strongly implicated in infectiondriven
preterm labour

11. Prostacyclin (PG12) --- relaxation
PGE2 and PGF2a (contractions of
gravid uterus )
the amnion is the dominant site of
PG synthesis, while the prime site
of PG action is the myometrium.
PG leads to the cervical changes
and uterine contractions
This theory led to the use of anti
prostaglandins (indomethacin) as a
tocolytic agent

12. THE ROLES OF OXYTOCIN AND
PROSTAGLANDINS
• At term, sensitivity of oxytocin receptors increase, but no increase in blood level of
oxytocin
• Oxytocin receptors increased and activated by estrogen produced from the placenta
which is increased by fetal CRH .
• Oxytocin increase Ca influx into myometrial cells leading to contractions
• Oxytocin also, stimulate the production of prostaglandin ----- helps cervical changes and
myometrial contractions

14. THE PRETERM SYNDROME

15. CAUSES OF PRETERM LABOR

16. CAUSES OF PRETERM LABOR
CERVICAL WEAKNESS
• Cervical weakness is classically associated with painless premature cervical dilatation
and is suggested by a history of painless second trimester pregnancy loss.
• Several studies have demonstrated a strong relationship between cervical length and
the risk for PTD, and a previous history of cervical surgery is a common risk factor for
cervical weakness
• Cut off cervical length on screening is 25 mm between 20-24 weeks , and can be done
using transvaginal ultrasound for high risk and symptomatic patients .

17. CAUSES OF PRETERM LABOR
INFECTION
Chorioamnionitis (infection of fetal membrane ) increases the risk of preterm labor 3-4 times and
can occur even in intact membranes .
• Most commonly by ascending infections from vagina
• 33% of all pregnancies delivered after PPROM are complicated by infection
• positive amniotic fluid cultures found in 83% of babies delivered before 28 weeks
(more in earlier gestational age )
Chorioamnionitis increase fetal risk of periventricular leukomalacia, intraventricular hemorrhage , CP and
death .
Bacterial vaginosis is a major risk factor, treatment doesn’t decrease the risk and screening is only
for high risk population, treat only positive ones (no prophylactic antibiotic )

18. CAUSES OF PRETERM LABOR
MULTIPLE PREGNANCY AND UTERINE
DISTENSION
• 56% of multiple births deliver before 37 weeks and 10–15% before 32 weeks
• The risk of PTD rises with fetal number, with triplets delivering on average at 32 weeks
and quadruplets delivering at 28 weeks
• 75 % due to spontaneous PTL and PPROM , less than 25 % is indicated PTL due to
complications that are increased in multiple pregnancies

19. CAUSES OF PRETERM LABOR
UTERINE MÜLLERIAN ANOMALIES
• They are associated with adverse pregnancy outcome in up to 25% of women, including
first and second trimester miscarriage, PPROM, preterm birth, FGR, breech presentation
and caesarean section.

20. • Acute bleeding leads to the release thrombin that directly stimulates myometrial
contractions
• Antepartum haemorrhage and placental abruption may lead to spontaneous PTL.
• The presence of a subchorionic haematoma in early pregnancy increases the risk of
later PPROM
• Abription occur in 1% of pregnancies , increased with hypertensive disorders , trauma ,
thrombophilia , history of abruption , smoking , cocaine , multiple pregnancy and
polyhydramnios .
• When an abruption involves 50% or more of the placenta it is frequently associated with
fetal death.

21. PREDICTION OF PRETERM DELIVERY
• By history (previous preterm labor and the risk factors )
• ultrasound measurement of cervical length
(screening the high risk population at 20-24 weeks with length less than 25 mm increases
the risk of PTL )
• Fibronectin test (22-36 weeks )
The combination of cervical length and obstetric history can predict 80.6% of extremely early
spontaneous PTD

22. TRANSVAGINAL CERVICAL LENGTH

23. PREVENTION OF PRETERM DELIVERY
Progesterone
• promote uterine quiescence and inhibit the production of proinflammatory cytokines and
PGs within the uterus
• Can be used in patients with short cervix or history of preterm labor (vaginal supp or
injectables hydroxyprogesterone caproate )
• no evidence from any study that progesterone can reduce the longer-term adverse
effects of preterm birth, that of neurodevelopmental disability and respiratory morbidity

24. TRANSVAGINAL
CERCLAGE
• In multiple mid-trimester losses or preterm deliveries (history indicated cerclage)
• when the cervix shortens (usually <25 mm) in women with a history of cervical surgery
or previous preterm birth (ultrasound indicated cerclage)
• when the cervix is dilating in the absence of contractions (rescue cerclage)
A transabdominal cerclage is usually inserted following a failed vaginal cerclage or
extensive cervical surgery.

25. MANAGEMENT OF PRETERM LABOR
• According to the case when maternal and fetal condition is good and no indication for
delivery
• Giving tocolytic agents in order to delay the delivery for 48 hours to give corticosteroid for
fetal benefit or to refer the fetus in utero to another central hospital
• First make sure that the mother and the baby are not at any risk , then identify the cause
• Balance between benefit of prolongation of pregnancy vs letting delivery go
(fetal lung maturity , gestational age , presence of any indication for delivery ? )

26. TOCOLYTIC AGENTS
I. Calcium channel blockers (first choice )
II. Oxytocin receptor antagonists (second choice )
III. Beta-sympathomimetics (dangerous )
IV. Non-steroidal anti-inflammatory drugs
V. Magnesium sulphate (not true tocolytic )

27. CALCIUM CHANNEL BLOCKERS
• Nifedipine
• The first choice , effective and relatively safe
• Binding to L-type channels, reducing intracellular levels of calcium and blocking the
transmembrane influx of calcium ions into muscle cells
• Flushing , palpitation , headache , postural hypotension
• Contraindicated in unstable angina and aortic stenosis , heart block , coronary heart
diseases

28. OXYTOCIN ANTAGONIST
• Atosiban
• Inhibition of uterine contractility and oxytocin-mediated PG release
• Headache , tachycardia , hypotension , nausea

29. BETA SYMPATHOMIMETICS
• Beta2-agonists (ritodrine, salbutamol and terbutaline)
• myometrial relaxation by stimulating cyclic adenyl monophospate (AMP) production
• significant maternal side-effects ; hyperglycemia , pulmonary edema , hypokalemia ,
palpitation ,hypertension
• Contraindicated in cardiac disease , uncontrolled DM , uncontrolled HTN , arrythmias ,
thyrotoxicosis

30. NON-STEROIDAL ANTI-INFLAMMATORY
DRUGS
• Indomethacin, It is a reversible, non-specific competitive cyclooxygenase (COX) inhibitor
• Before 32 weeks , limited to less than 72 hours
• Reversible Premature closure of ductus arteriosus
• persistent pulmonary hypertension
• Oligohydramnios
• Necrotizing enterocolitis
• Maternal GIT bleeding
• Contraindicated in asthma , peptic ulcer and platelets disorders

31. MAGNESIUM SULPHATE
• Modulate calcium uptake by smooth muscles inhibiting uterine contractions
• Not effective as tocolytic
• May decrease the risk of CP
• Needs monitoring of respiratory rate , urine output , deep tendon reflexes
• Contraindicated in myasthenia gravis and renal failure
• Flushing , palpitation , low fetal heart variability

32. CONTRAINDICATIONS TO TOCOLYSIS
Any indication for delivery is contraindication to tocolysis
• Chorioamnionitis
• Fetus more than 37 weeks
• Stillbirth
• Maternal or fetal compromise
• Sever PET
• Sever vaginal bleeding
• Abnormal fetal heart trace

33. CORTICOSTEROIDS
• associated with significant reduction in neonatal mortality , RDS , IVH
• Given between 24 – 34+6 weeks
• Dexamethasone 6 mg IM Q 12 hr for (4 doses )
• Betamethasone 12 mg q 24 hrs (2 doses )
• The effect is maximum after 24 hours to 7 days

34. ANTIBIOTICS
in singleton pregnancies with PPROM, erythromycin improved neonatal outcomes(10 days
erythromycin)
but that antibiotic treatment in women with intact membranes had no benefit
Only if PPROM

35. PPROM
• PROM : premature rupture of membranes = rupture of membranes at term but before labor initiated
60 % will go into labor in 24 hours
induction of labor after 24 hours if all normal in absence of signs of infection
• PPROM :
preterm premature rupture of membranes : rupture of membranes without labor before 37 weeks
occur in 2 %
1/3 of preterm labor occur after PPROM

36. PPROM
• 50% of women deliver within 1 week and
• 75% within 2 weeks of PPROM
• Carries a risk of preterm labor , lung hypoplasia , limb deformities , intrauterine
infections
• PPROM is diagnosed through clinical history and the demonstration of a pool of liquor
in the vagina on speculum examination
• In general, conservative management is followed in PPROM before 34 weeks’
gestation unless there is evidence of chorioamnionitis and immediate induction of
labour is advised in women after 37 weeks’ gestation

37. COMPLICATIONS OF PRETERM BIRTH
• PTL is the most important cause of perinatal morbidity and mortality
worldwide, also of infant mortality less than 5 years of age
• Common complications in premature infants include
 respiratory distress syndrome (RDS),
 intraventricular hemorrhage (IVH),
 bronchopulmonary dysplasia (BPD),
 patent ductus arteriosus (PDA),
 necrotizing enterocolitis (NEC),
 sepsis, apnea,
 and retinopathy of prematurity (ROP).

38. LONG TERM OUTCOME
The incidence of long-term morbidity in survivors is especially increased for those born
before 26 weeks including
chronic lung disease,
cerebral palsy,
NEC, and vision and hearing impairment.
neurosensory impairment,
reduced cognition and motor performance,
 academic difficulties,
 and attention-deficit disorders.

39. TAKE HOME MASSAGE
• Preterm labour has multiple causes.
• Worldwide, preterm delivery is the most important cause of infant (<5 years)
• mortality.
• Tocolysis does not improve neonatal outcomes.
• Antenatal steroids reduce the risk of RDS.
• Screening with transvaginal ultrasound can detect women at high risk of
• preterm delivery.
• Progesterone reduces the risk of preterm birth in women with a short cervix.
• Cervical cerclage reduces the risk of preterm birth in high-risk women.