This document discusses prediction and prevention of preterm labour. It begins by defining preterm labour as contractions before 37 weeks of gestation. It then discusses the major causes of preterm labour and the pathophysiology. Several predictive variables and tests are examined, including cervical length screening, fetal fibronectin levels, and various biochemical markers. Prophylactic progesterone supplementation and cervical cerclage are explored as prevention methods for women at high risk of preterm labour, such as those with a prior preterm birth or short cervix. However, the document concludes that while research has identified several predictive factors, no single marker can accurately predict preterm labour on its own.

2. 2
Preterm labour
prediction and
prevention
can we do more……..?
Dr.Gowthami Dumpala MS OBG , FMAS
Smile multispeciality hospital
Vijayawada

3. Introduction – Pre-term labour
“Contraction (labour) before 37
weeks gestational age”
World:
• ~15 million preterm births
• Contributes to ~ 1 million
neonatal deaths and is the
leading cause of neonatal
mortality & morbidity
India:
• Largest number of preterm births
• 3.5 million/year of which 10% die
due to direct complications
Top 5 countries:
India: 3,519,100
China: 1,172,300
Nigeria: 773,600
Pakistan: 748,100
Indonesia: 675,700
Incidence 1 in 10
3

4. Major causes of PTL
IDIOPATHIC(50%)
PROM(30%)
MEDICAL INDICATIONS(15-
20%)
SPONTANEOUS IATROGENIC/provi
der initiated
•INFECTION
•GENETIC
•ENVIRONMENTAL
•MATERNAL
•OBSTETRIC
•ART
•IOL for obstetric
indicaion(Hyperten
sion,DM,
,IUGR,Obstetric
cholestasis,Multipl
e pregnancies)
4

5. • Commonest etiological factor world wide is
INFECTION.
• Several genetic, environmental and physiological
factors are associated with preterm birth and
contribute to uterine activation ,labour and
preterm birth
• The diverse etiology of preterm labour makes its
prediction difficult
5

6. Factors associated with increased risk
of PTL
• PPROM
• Previous history of preterm labour/delivery
• Decidual thrombus/hemorrhage(abruption)
• Maternal smoking
• Extremes of maternal age
• Suboptimal weight gain in pregnancy
• Maternal stress
• Mechanical factors-multiple pregnancy, polyhydramnios
• Cervical insufficiency- idiopathic or iatrogenic(trauma or dilatation induced)
• Uterine distortion( fibroids,septate uterus)
• Maternal urogenital infections,systemic infections
• Harmonal changes
• , uteroplacental insufficiency
• Fetal anomalies,IUGR,abnormal lie presentation
• Genetic
• Environmental factors
Causes are
multifactorial and vary
according to gestation
age
6

7. PATHOPHYSIOLOGY
Fetal inflammatory
response syndrome
7

8. Predictive VARIABLES / TESTS
• There are several indicators which have been
proposed for predicting the risk of spontaneous
PTD
• Early identification helps in timely admission, close
supervision, early initiation of appropriate
therapy(Antibiotics,corticosteroids,tocolytics,Magn
esium sulfate) or transferred to higher centres
when required
8

9. Predictors of PTL
1. High risk factors assessment
2 . TVS for cervical parameters
3 . Biochemical markers
• Fetal fibronectin >50ng/ml
• PIGFBP-1>1ng/ml(Actim partus test kit)
• PAMG-1>4ng/ml
• Cytokines and protiens –IL6, IL8
• Salivary estriol>1.8ng/ml
• Salivary progesterone<2575pg/ml
• Proteomic markers
4 Screening for bacterial vaginosis
Vaginal mirobiome
5. HUAM
9

10. 1 Risk factor assessment
Previous history
• The risk of recurrence is – 15-30% after one
spontaneous PTB & furthermore after 2 PTBs
• Conization and LEEP for treatment of CIN
• Congenital uterine malformations
• Women who were born pre-term
Current pregnancy
• Low socioeconomic status, ethnicity, extremes of age,
short interpregnancy interval, smoking ,alcohol,ivf
conception, h/o APH, medical disorders like
CKD,DM,HTN,multifetal gestation,polyhydramnios
10

11. 2 TVS-cervical length
• Short cervical length is the strongest predictor of PTL
• If Cervical length <25mm ( corresponds to 10th centile prior to 34
weeks GA) risk of PTL increases by 6fold
• If dilated internal cervical OS is detected on examination –
chances of PTB increases by 4fold
• Universal screening is controversial not currently recommended
• Screening for cervical assessment may be started in high risk
women at 14-16wks and repeated every 2weeks till 24th week.
• Funneling of cervix is less reproducible hence not a good
predictor of PTL.
• NEW-cervical elastography, Utero cervical angle(>105◦).
• Combination with other markers
11

12. 3 Fetal Fibronectin(FFN)
• FFN is a glycoprotein produced by fetal amnion
• Presence of FFN in cervicovaginal fluids between 24-
34weeks has been linked to PTD within a week from
testing.
• FFN in high concentrations indicates disruption of
uteroplacental interface.
• High NPV ≥95%.
• It’s a qualitative test with detection value of
>50ng/ml(hotgen , quickcheck FFN kits) .
• New-quantitative testing using multiple FFN
threshold(10,50,200,500) increases the PPV of PTB
12

13. 4 PIGFBP-1 & PAMG-1
• These are proteins found in decidual tissues and detectable in
cervicovaginal secretions in case of disruption of choriodecidual
interface
• Commercial kit (Actim partus test kit) for the qualitative detection of
PIGFBP-1 in cervical secretions above the >10ng/ml is available.
• High NPV similar to FFN.
• Results are not affected by seminal fluid unlike FFN
• Further evidence is needed for this test to be widely
accepted
• The presence of PAMG-1 in cervicovaginal secretions indicates that PTD
is likely to occur within a week(80%sensitivity,95%specificity)
• The partosure test kit comprises immunochromatographic assay
designed to identify the presence of human PAMG-1 in cervical
secretions of above 4ng/ml.
• A recent metaanalysis compared PAMG-1,fetal fibronectin,PIGFBP-1 in
symptomatic women & PAMG-1 was reported to have high PPV while
NPV remained similarly high for all 3 biomarkers
13

14. 5 Cytokines & proteins
• Many proinflammatory cytokines including IL6,IL 8
,IL 16 interferon gamma –inducible protein 10
annexin A2(ANXA2),and proinflammatory proteins
like CXCL11,ADAM8,SLPI,sICam1,and vICAMI have
been examined for their diagnostic and prognostic
value for predicting PTL and PTD.
• IL-6 was able to predict PTD in asymptomatic
women with 43% sensitivity and 74%specificity
14

15. 6 Maternal serum markers
• Salivary estradiol have been reported as a sensitive
,timely,and noninvasive marker for PTL
• Salivary estriol level of ≥1.8ng/ml before 34weeks
has a sensitivity of 68% and specificity of 76% for
prediction of PTL
• A low saliva concentration of progesterone predicts
PTL before 34weeks of gestation.
• A single cutoff value for salivary progesterone of
<2575pg/ml can detect more than 80% of PTD
before 34 wks GA with sensitivity of 83% and
specificity of 86% and 95% NPV
15

16. 7 Proteomic markers(serum markers)
• Two dimensional electrophoresis biomarker-
discovery studies identify differentially expressed
proteins that increase or decrease before PTL.
• Protease inhibitors(cystatin A),antiinflammatory
cytokines,antioxidant enzymes(TXN,SOD-1,PRDX-
2,GSTP-1) ,SERPINB1,3,4,IL-1 receptor antagonist
are downregulated
• Epidermal FABP-5,AnnexinA3 and albumin and
other inhibitors of phospholipid metabolism are
upregulated
16

17. Other screening modalities
• Uterocervical angle (>105)
• Placental strain ratio/ elastography
• Measurement of central zone of fetal adrenal gland
Routine screening for BV, assessment of cervical
status or FFN measurement is not indicated in low
risk women
17

18. PREVENTION
• Primary prevention for general population: Lifestyle
modification,cessation of smoking and alcohol,diet
control,weight management,supervised antenatal
care,modifying physical activity
• Secondary prevention for higher risk group:Screening
for cervical parameters,FFN testing,antibiotics for
associated infections,progestreone
supplementation,cervical cerclage
• Tertiary prevention when labour has been
initiated:Tocolytic agents,antenatal steroids,magnesium
sulphate before 32weeks for
neuroprophylaxis,antibiotics
18

19. Prophylactic Progesterones
and
cervical encerclage
19

20. Mechanism of Action –
Progesterone in prevention of PTL
At placenta,
Regulates
timing of
labour via
controlling
stress
hormone –
CRH
In amniotic
fluid,
Limits
prostaglandin
production
At Myometrium &
cervix,
Suppresses
inflammatory
response and
myometrial
contractility
At fetal membrane,
Blocks pro-
inflammatory
cytokines induced
apoptosis,
preventing PPROM
In patients at risk of PTL,
Progesterone Maintains uterine quiescence by acting at
all 4 sites1
1. Norwitz E R et al, Rev Obstet Gynecol.

21. Preparations & doses
21
17-OH Progesterone caproate Micronised progesterone
Synthetic
MOA-inhibits uterine
contractions
•Route –IM
•Dose-250mg IM started in 2nd
trimester continued to
36+6weeks
•Common side effect-local
injection site reaction
•Potential concern – Risk of
hypospadias in male offspring if
given before 11weeks of
gestation
Natural
MOA-inhibits cervical ripening
•Route-Oral/Vaginal
•Dose- 100-400mg
•Advantage-High bioavailability
and less systemic side effects
•Diasdvantage –vaginal
irritation,daily dosage

22. Various clinical scenarios
where progesterone is
recommended
22

23. Previous PTB
• In women with a previous PTB,supplementation
with Hydroxyprogesterone caproate 250mg
intramuscularly weekly or micronised progesterone
100-200mg/day is started in the second
trimester(16-20weeks) and continued through
36+6weeks of gestation.(Cochrane database)
• Serial cervical length ultrasound examinations till
24weeks of gestation should be performed and
cerclage is considered if cervical length ≤25mm.
23

24. Short cervix
• The preferred approach to prevent PTB in
asymptomatic women with a sonographically short
cervix (≤25mm) is to start supplementation with
100mg vaginal progesterone upon diagnosis and to
continue upto 36+6weeks
• Weekly Intramuscular hydroxyprogesterone
caproate(250mg or 500mg) did not reduce the risk
of PTB in some studies.
24

25. • PPROM in current pregnancy- progesterone
supplementation not useful.
• H/O prior PPROM with PTB- benefit from progesterone
in next pregnancy
• Pregnancy with threatened PTL or established PTL –
progesterone did not reduce the risk of PTB
• TWIN PREGNANCY- neither 17 OHPC nor micronised
progesterone decreased the risk of PTB
• Pregnancy after ART or with uterine anomaly-there is
paucity of data on efficacy of progesterone
• The role of progesterone supplementation in women at
high risk of PTB and positive FFN has no supportive
strong evidence.
25

26. CERVICAL ENCERCLAGE
• Prophylactic/elective cerclage should be considered
in women with history of more than two prior
spontaneous preterm births/second trimester
losses
• Short cervix with history of PPROM in prev
pregancy or cervical trauma(NICE)
• Cochrane review concluded that
there is no evidence that cerclage
is an effective intervention in
multiple gestation.
26

27. 27

28. 28

29. Methods of cerclage
• Trans vaginal cerclage-mcdonalds cerclage
• High trans vaginal cerclage-shirodkars
• Transabdominal cerclage
29

30. Tocolytics role?
• Only short term therapy is recommended
• Goal- to buy time for corticosteriod dosage, MgSo4
for neuroprotection or to shift to a teritiary center
for NICU care.
• Tocolysis is indicated for PTL between 24 and 34
wks.
• Maintainance tocolysis is ineffective and not
recommended
30

31. Adjunctive treatments???
• Antibiotics shouldnot be used to prolong gestation
in women with PTL and intact membranes
• Antibiotics are recommended in case of PPROM
• Bedrest for prevention of PTB shouldnot be
routinely recommended
• Abstinence from sexual intercourse doesnot
decrease the incidence of PTL
31

32.  Prediction of PTL is done through risk factor
screening,cervical assessment and other
biochemical genomic and proteomic markers
Despite much research there is currently no single
marker which can accurately predict PTL.
Combination of biochemical markers along with
cervical parameters increases the predictive value
Progesterones and encerclage has proven benefit
in preventing PTL in pts with previous h/o PTB and
short cervix
32

33. 33