Preterm labor is defined as labor beginning before 37 weeks of gestation. It can be spontaneous or iatrogenic and is a leading cause of neonatal mortality globally. Diagnosis involves assessing cervical dilation, length, and contractions. Risk factors include prior preterm birth, infection, cervical insufficiency, and multiple gestations. Treatment aims to prolong pregnancy through tocolysis to allow for antenatal corticosteroids and magnesium sulfate administration, which reduce neonatal respiratory and neurological complications respectively. Antibiotics may also be given for GBS prophylaxis or infection treatment. The goal of intervention is to delay birth until a gestational age of viability or transfer to a higher level of care is possible.

1. Preterm Labor
Dr Saumya Varshney
Moderator: Dr Rupa Padwalkar

2. Definition
• Onset of labor before 37 completed weeks or 259 days of gestation,
after the gestation of viability (22-28 weeks) dependent on setting.
• Onset of labor refers to regular uterine contractions (at least one in
10 minutes or 8 in one hour) associated with documented cervical
changes or rupture of fetal membranes.
• In the absence of cervical changes or rupture of membranes, it is
termed as threatened preterm labor. (WHO)

3. Introduction
• Gestational age based on first day of last menstrual cycle.
• Most women in TPL do not deliver before term
• Preterm labor can be specified as spontaneous (70%) or iatrogenic
(30%) for maternal or fetal health indications.
• Preterm birth contributes to 50% of all neonatal deaths globally.

4. CRITERION
• Gestational age <37 weeks
• Dilatation >2 cm
• Cervical length <1.5 cm
• Painful uterine contractions
- 1 in 10 minutes
- 4 in 20 minutes
- 8 in 1 hour

5. Classification
• Extreme prematurity ( under 28 weeks)
• Very preterm (28-32 weeks)
• Moderately preterm (32-37 weeks) – (84%)
- late preterm (34-37 weeks)

6. Pathophysiology
• Strongest historic risk factor is previous birth between 16-36 weeks’ of
gestation (1.5 to 2 fold)
• Interplay of infection and inflammation
- Ascending genital tract infections
> Lower genital tract flora commonly found in amniotic fluid in preterm
labor with intact membranes (20-60%) (PCR/culture)
> Most commonly detected bacteria include ureaplasma urealyticum ,
fusobacterium and mycoplasma hominis
- Clinical/ subclinical chorioamnionitis
- Bacteriuria

7. • Maternal systemic infection
• Uterine distension
- Multiple pregnancies (50% twins are born preterm)
- Polyhydramnios
• Cervical insufficiency (<2.5cm at 14-24 wk, 6.5 fold increased risk)
• Maternal obesity/ underweight prior to pregnancy
• PPROM (40% of all spontaneous preterm labor)
• Stressful life events
• Smoking / drug use
• Advanced maternal age ( dm and htn confounding factors for iatrogenic
PTB)

8. Clinical assessment
• History
• Physical examination
• Speculum examination – integrity of membranes/detection leaking
per vagina
• Digital per vaginal examination – dilatation and effacement
• Collect vaginal swab and anal swab prior to digital examination for
culture/sensitivity of Group B streptococcus organism

9. Terminology (NICE guidelines 2019)
Suspected preterm labor
If she has reported symptoms of preterm labor and has had a clinical
assessment (including a speculum or digital vaginal examination) that
confirms the possibility of preterm labor, but rules out established labor.
Established preterm labor
If she has progressive cervical dilatation from 4 cm with regular contractions
Diagnosed preterm labor
If she is in suspected preterm labor and has had a positive diagnostic test for
preterm labor.

10. NICE GUIDELINES 2015 (with 2019 update)
• If patient is 29w6d or lesser in suspected preterm labor treat with tocolysis and
antenatal corticosteroids
• If patient is 30w+ with suspected preterm labor, transvaginal ultrasound as a
diagnostic test to diagnose preterm labor
- if cervical length > 15 mm, unlikely to be preterm labor and think
about alternative diagnoses
- if cervical length <15mm, diagnosed preterm labour treat with
tocolysis and antenatal corticosteroids

11. Cervical assessment
• Trained operator
• Prospective case cohort study (2004,2010) – Positive predictive value for CL
<1.5cm at <32 weeks for delivery was 47%
• Negative predictive value for CL threshold 1.5cm, 2 cm and 2.5cm were 95-97%.
• Better targeting of interventions like corticosteroids for fetal pulmonary
maturation and infusion of magnesium sulfate as neuroprotective agent
• Avoids unnecessary overtreatment of false preterm labor

12. NICE GUIDELINES 2015 (with 2019 update)
• Consider fetal fibronectin testing to determine likelihood of birth within 48 hours
for women who are 30+0 weeks pregnant or more if transvaginal ultrasound
measurement of cervical length is indicated, but is not available or not acceptable
- Negative (concentration 50 ng/ml or less), unlikely to be preterm
labor － think about alternative diagnoses
- Positive (concentration more than 50 ng/ml), view as diagnosed
preterm labor and treat as same.

13. NICE GUIDELINE 2015
• If a woman in suspected preterm labor who is 30+0 weeks pregnant or more does
not have transvaginal ultrasound measurement of cervical length or fetal
fibronectin testing to exclude preterm labor, offer treatment consistent with her
being in diagnosed preterm labor
• Do not use both the diagnostic tests together

14. Other biomarkers
• Phosphorylated insulin like growth factor binding protein -1
• Has high NPV (>95%) for SPTB within 7 days to 2 weeks but poor
sensitivity hence it’s a “rule out” test
• Actim partus - Qualitative immunochromatographic test
• Can be used in presence of semen in vaginal secretion but not active
vaginal bleeding

15. Other biomarkers
• Placental alpha macroglobulin (PAMG-1)
• “PARTOSURE” immunoassay bedside test
• Has a higher positive predictive value of 78% for delivery within 7
days
• The test can be used if vaginal infections, urine, semen and trace
amounts of blood are present.

16. Investigations

17. Antenatal corticosteroid therapy (RCOG)
• Given within the 7 days prior to preterm birth reduces perinatal and neonatal
death and respiratory distress syndrome.
• Should be offered to women between 24+0 and 34+6 weeks’ gestation in whom
imminent preterm birth is anticipated (either due to established preterm labor,
preterm premature rupture of membranes [PPROM] or planned preterm birth)
• Women with twins and triplets should be offered targeted antenatal
corticosteroids for early birth in line with recommendations for singletons

18. • Birth should not be delayed for antenatal corticosteroids if the
indication for birth is impacting the health of the woman or her baby
• If imminent preterm birth is likely, a course of antenatal
corticosteroids should be offered to small-for-gestational-age (SGA)
or to have fetal growth restricted babies
• Benefits are also seen when the first dose is given within 24 hours of
birth and antenatal corticosteroids should still be given if birth is
expected within this time.

19. • Diabetes should not be considered a contraindication to antenatal
corticosteroids for fetal lung maturation
• In women with diabetes who are receiving corticosteroids, additional
insulin should be given according to an agreed protocol and close
monitoring should be undertaken
• Maternal blood glucose levels rise shortly after administration of
corticosteroids and can remain elevated for up to 5 days

20. • In extreme cases, where ACS may jeopardize maternal health, e.g., in
diabetic ketoacidosis or fulminant infection, maternal health should
take precedence over fetal prophylaxis.
• Glucose challenge test/ tolerance test : false positive within 72 hours
of ACS therapy.
• Screening test for GDM should with withheld till one week after ACS
therapy.

21. • Corticosteroid therapy between 35wk to 36w6d shows decrease in
need for respiratory support
• However there is evidence of likely increase in neonatal hypoglycemia
and potential developmental delay (visual and motor function).
• May increase psychiatric and behavioral diagnoses if children born at
term.
• Hence it is not recommended.

22. Experience with corticosteroid therapy
• A 2006 Cochrane review, showed 44% reduction in respiratory
distress syndrome and a reduced incidence of cerebroventricular
hemorrhage
• Long term benefits in preterm - less developmental delay at 3 years
and fewer cases of cerebral palsy.

23. Corticosteroid Therapy
Complication Time period within which therapy is effective
Fetal and neonatal death upto 24-48 hrs
Respiratory distress syndrome Between 24 hr to 7 days
Reduction in birth weight Within 1-7 days and more pronounced if born more
than 7 days of administration

24. Criterion for corticosteroid therapy
• Gestational age accurately undertaken
• Preterm birth is imminent (likely within 7 days)
• No clinical evidence of maternal infection

25. Repeat and rescue dose of corticosteroids
• If more than 7 days have elapsed after the first dose of steroids, and
subsequent clinical assessment demonstrates likelihood of preterm birth in
another 7 days, a single repeat dose or course of steroids is beneficial
• The maximum number of corticosteroid courses given in any one
pregnancy should not exceed three.
• In a meta analysis of 11 RCTs, there was a statistically significant
reduction in the use of respiratory support in babies who had repeat
antenatal corticosteroids compared with infants who received a
single dose.

26. Types of corticosteroid therapies
• Betamethasone 12 mg IM 2 doses 24 hrs apart
• Dexamethasone 6 mg IM 4 doses 12 hrs apart
- Or 2 doses 12 mg 24 hrs apart

27. Comparison
• According to various studies comparing effect of dexamethasone and
betamethasone on AFI, BPP and NST indices, it is observed
dexamethasone has lesser effect on all parameters.
• Recipients of dexamethasone have found to have higher rate of
normal fetal movements and higher BPP scores.
• These effects typically last 48-72 hrs after last dose.

28. Comparison
• Clinical Outcomes
- Betamethasone was more effective in reducing RDS (44% vs 20%),
while reduction in mortality was similar (33% vs 28%)
- However, greater reduction in intraventricular hemorrhage (IVH) for
dexamethasone.
• Cost
- Dexamethasone is cheaper
- More widely available

29. Neurological aspects of preterm birth
• Cerebral palsy – more common in preterm babies
• As higher chances of intraventricular hemorrhage (5%)
• Periventricular leukomalacia – preoligodendrocyte injury followed by
gliotic scarring leading to impaired myelination and maturation
• Preoligodendrocytes have a maturation dependent vulnerability –
hence propensity for cerebral ischemia in preterm. (impaired vascular
autoregulation)

30. • Cerebral ischemia – release of excess glutamate – causes white
matter injury
• Reversal of glutamate transporters in preoligodrocytes and
overexpression of glutamate transporter in premature period.
• EXCITOTOXICITY OF NEURONS IN PRETERM BIRTH

31. Magnesium Sulphate (neuroprotection)
• NMDA (glutamate) receptor antagonist on oligodendroglial progenitor
cells
• Blocks excess release of glutamate (prevents excitatory Calcium
mediated injury)
• Substantially reduces risk of cerebral palsy and gross motor
dysfunction in preterm birth
• Maternal side effects include hypotension and tachycardia

32. Evidence based use of MgSO4
• 4 Meta analysis of 5 international RCTs (MAGPIE, BEAM, PREMAG,
ACTOMgSO4 and MagNET)
CONSISTENT AND CONCLUSIVE RESULTS
- Significantly reduced risk of cerebral palsy (RR 0.6 to 0.7)
- Noted minor maternal side effects such as flushing, sweating
nausea or vomiting )
- No significant effect on serious maternal complication

33. NICE Guidelines 2019 Update
• Offer IV magnesium sulfate for neuroprotection of the baby to
women between 24+0 and 29+6 weeks of pregnancy who are:
• in established preterm labor,
or
• having a planned preterm birth within 24 hours.

34. • Consider intravenous magnesium sulfate for neuroprotection of the
baby for women between 30+0 and 32 weeks of pregnancy who are:
• in established preterm labor,
or
• having a planned preterm birth within 24 hours

35. Dosage
• Give a 4 g (20% 0.9 NS solution) intravenous bolus of magnesium sulfate over 15 minutes
• Followed by an intravenous infusion of 1 g per hour until the birth or for 24 hours
(whichever is sooner). (40g magnesium sulfate added to 1 L 0.9 NS/RL at 50ml/hr)
• Limit IV Fluids at 125ml/hr. Indwelling catheter is recommended. I/O (2-4 hourly)
• Monitor for clinical signs of magnesium toxicity at least every 4 hour by recording
-pulse
-blood pressure
-respiratory rate
-deep tendon (for example, patellar) reflexes.

36. • If a woman has or develops oliguria or other evidence of renal failure:
- monitor more frequently for magnesium toxicity (hourly)
- reduce or stop the dose of magnesium sulfate
• Concurrent use with tocolytics like beta agonists and calcium channel blockers
cause potentially serious maternal complications (hence not recommended)
- pulmonary oedema
- bradycardia
- hypotension
- skeletal muscle blockade
- electrocardiogram changes (i.e., P–Q interval prolongation and
widened QRS complex),
- very high levels, cardiac arrest.
• Use of indomethacin as alternative to CCB along with MgSO4 before 32 weeks is
potential option.

37. Antibiotics (NICE guideline 2021)
• Offer antibiotics during labor to women who:
- are in pre-term labor (regardless of rupture of membranes) or
- have group B streptococcal colonization, bacteriuria or infection
during
the current pregnancy or
- Have had group B streptococcal colonization, bacteriuria or
infection in a
previous pregnancy or
- have had a previous baby with an invasive group B streptococcal
infection or
- have a clinical diagnosis of chorioamnionitis. [2021]

38. • Antibiotic therapy in preterm labor :
- limited to GBS prophylaxis
- In women with PPROM
- Treatment of specific organism ( eg in UTI )
Rationale :
• Antibiotics reduce the number of maternal infections in women in pre-
term labor.
• Pre-term labor and chorioamnionitis are important risk factors for
neonatal infection, so intrapartum antibiotics are very likely to reduce
the risk to the baby.
• Recommendations are made for antibiotic treatment that would
simultaneously treat infection in the mother and prevent early-onset
group B streptococcal infection in the baby to make the best use of
antibiotics.

39. Intrapartum Antibiotics
Allergies Women without chorioamnionitis Women with chorioamnionitis
No penicillin allergy Use benzylpenicillin Benzylpenicillin with gentamicin
and metronidazole
Non severe penicillin allergy Use cephalosporin with activity
against group B streptococcus
(example cefotaxime, cefuroxime)
Cephalosporin with gentamicin and
metronidazole
Severe penicillin allergy Vancomycin or alt antibiotic that
would be expected to active
against group B streptococcus by
local antibiotic susceptibility
surveillance data
Vancomycin plus gentamicin plus
metronidazole

40. Tocolysis
• Take the following factors into account when making a decision about
whether to start tocolysis:
- whether the woman is in suspected or diagnosed preterm labor
- other clinical features (for example, bleeding or infection) that may
suggest that stopping labor is contraindicated
- gestational age at presentation
- likely benefit of maternal corticosteroids
- availability of an appropriate level of neonatal care (if there is need
for transfer to another unit).

41. Aim of tocolysis
• To prolong pregnancy with goal of administering an antenatal therapy
example corticosteroids
• Or for purpose for transfer to a better equipped healthcare facility
NOTE
• It cannot be used as a maintenance therapy
• Avoid using multiple drugs due to associated adverse effects.

42. Tocolytic drugs
Drug Dose Maternal side effects Fetal/ neonatal side
effects
Contraindications
1. Nifedipine
( Calcium channel
blocker )
20 mg stat followed
by 10-20 mg every 6-
8th hrly for 48 hrs.
Tachycardia,
Hypotension,
Headache, Hot
flushes
Tachycardia Cardiac disease
Uncontrolled DM
Hepatic dysfunction
Concurrent use with
beta agonist, Mgso4
ST elevation
Myocardial infarction
Ritodrine
(beta 2 agonist)
IV infusion with
50pg/min, increase
every 20 min to a
maximum of 350
ug/min
Palpitations, tremor,
nausea headache
chest pain, dyspnea,
pulmonary edema,
hypokalemia,
hyperglycemia
Tachycardia,
Hypoglycemia,
hypocalcemia,
hypotension
hyperbilirubinemia,
intraventricular
hemorrhage
Diabetes mellitus,
cardiac diseases,
thyrotoxicosis
Preeclampsia
Terbutaline
(beta 2 agonist)
0.25mg s/c every 20
min x 4-6 doses with
maximum dose 80
mcg/min (increment
of 5-15mcg/min
every 10-15 min
Cardiac arrhythmias
Pulmonary edema
Myocardia ischemia
Hypotension
tachycardia
Hyperinsulinemia
Tachycardia
Hypoglycemia
Myocardial, septal
hypertrophy,
ischemia
Diabetes mellitus
Thyrotoxicosis
Cardiac disease

43. • Drug
• Dose
• Maternal side effects
Drug Dose Maternal Side
effects
Fetal side effects Contraindications
Atosiban Initial bolus of 6.75
mg over one minute
followed by an
infusion of
18mg/hr for 3 hours
then 6mg/hr
nausea, allergic
reaction, chest pain,
head ache
nil significant
known
Hepatic and renal
dysfunction
Indomethacin 50 mg oral loading
dose followed by
25-50mg orally
every 6 hourly up to
48 hours
Use is limited to
prior to 32 weeks of
gestation
gastrointestinal
disturbance,
oligohydramnios
(monitor AFI)
(reversible)
Premature close of
ductus arteriosus
(unlikely if drug is
used for less than
48hr)
Hepatic and renal
dysfunction
Gastric ulcers,
Asthma
Heart disease
Coagulation
dysfunction
Poorly controlled
hypertension

44. NICE Guideline 2015
• Offer nifedipine for tocolysis to women between 24+0 and 33+6
weeks of pregnancy who have intact membranes and are in
suspected or diagnosed preterm labor.
• If nifedipine is contraindicated, offer oxytocin receptor antagonists for
tocolysis
• Do not offer betamimetics for tocolysis

45. Evidence
• Each of these medications has shown to reduce incidence of delivery
within 48hrs up to 7 days
• Nifedipine has greater suppression of uterine contractions and fewer
side effects.
• Side effects requiring cessation of therapy were most with beta
sympathomimetics.
• Use of tocolytic therapy after rupture of membranes may be
associated with increased incidence of chorioamnionitis hence
avoided.

46. Monitoring on tocolysis
• Pulse
• Blood pressure
• No of contractions
• FHS
• Side effects
• Every 15 mins for first 2 hours then every 4 hours.

47. Contraindications to tocolysis (ACOG bulletin)
• A gestational age above 34 weeks
• Intrauterine fetal demise
• Lethal fetal anomaly
• Non reassuring fetal status
• Severe preeclampsia or eclampsia
• Maternal bleeding with hemodynamic instability
• Chorioamnionitis
• Preterm premature rupture of membranes (except when there are no signs of
maternal infection and there is a need for transportation, steroid
administration, or both)
• Abruptio placenta
• IUGR with abnormal doppler changes
• Cardiac Disease

48. Fetal monitoring
• In established preterm labor with no other risk factors, offer a choice
of fetal heart rate monitoring using either:
• cardiotocography using external ultrasound or
• intermittent auscultation.
• Normal cardiotocography trace is reassuring and indicates that the
baby is coping well with labor, but an abnormal trace does not
necessarily indicate that fetal hypoxia or acidosis is present

49. Mode of Delivery
• Explain about the benefits and risks of caesarean birth that are specific to
gestational age.
• In particular, highlight the difficulties associated with performing a
caesarean birth for a preterm birth and the implications of this for future
pregnancies.
• Explain that there are no known benefits or harms for the baby from
caesarean birth, but the evidence is very limited.
• Consider caesarean birth for women in preterm labor between 26+0 and
36+6 weeks of pregnancy with breech presentation.

50. Kangaroo Mother Care
• Kangaroo mother care is a method of care of preterm infants.
The method involves infants being carried, usually by the
mother, with skin-to-skin contact.
• KMC is at least equivalent to conventional care (incubators), in terms
of safety and thermal protection, if measured by mortality.
• KMC, by facilitating breastfeeding, offers noticeable advantages in
cases of severe morbidity.

51. • KMC contributes to the humanization of neonatal care and to better
bonding between mother and baby in both low and high-income
countries.
• KMC is, in this respect, a modern method of care in any setting, even
where expensive technology and adequate care are available for low
birth weight neonates (<2.5kg).

52. Evidence
• Observational studies showed that KMC could help reduce mortality
and morbidity in preterm/LBW infants.
• Rey and Martinez in their early account, reported an increase in
hospital survival from 30% to 70% in infants between 1000g and
1500g.
• Bergman and Jürisoo, in another study with an historical control
group conducted in a remote mission hospital without incubator care
in Zimbabwe,14 reported an increase in hospital survival from 10% to
50% in infants weighing less than 1500g, and from 70% to 90% in
those weighing between 1500 to 1999g.

53. Thank you