Pre-term labour, could it be predicted? Pre-term labour (PTL) is defined as labour less than 37 completed weeks or 259 days. 15 million PT babies are delivered annually worldwide with a global rate of about 11% with rising trends in most countries. This represents a serious health and economic challenge. The objective of early prediction of PTL is to Identify women at risk so, delaying preterm birth by Interventions long enough to optimize the outcome for the fetus. Prediction could be done by: -Pre-conceptual/early prenatal evaluation - Prenatal Ultrasound markers - Biomarker predictors Highlights on diagnosing PTL for women with intact membranes and preterm prelabour rupture of membranes (P-PROM) will be presented plus recommended prophylactic interventions as prophylactic vaginal progesterone, prophylactic cervical cerclage & 'Rescue' cervical cerclage. Treatment essentials of PTL include tocolysis, maternal corticosteroids & Magnesium Sulphate.

1. PRE-TERM LABOUR
COULD IT BE PREDICTED?
Dr Wafaa Benjamin Basta (FRCOG)
Consultant Ob/Gyn Mataria Teaching Hospital
Member of Egyptian Representative Committee of RCOG
Member of the National Council for Human Rights
29th international Conference of Gynaecology & Obstetrics / Arab Society for Gynaecology & Obstetrics
March 31- April 1, 22022 Triumph hotel Cairo – Egypt

2. GOAL OF RELIABLE PREDICTION
Identification of women at risk
Prevention of preterm birth (by
Delaying preterm birth long enough to optimize the
outcome for the fetus

3. DEFINITION OF PRETERM BIRTH
• Less than 37 completed weeks or 259 days
• Preterm birth is further classified as:
 extremely preterm (<28 weeks)
 very preterm (28 to <32 weeks)
 moderate (32 to <34 weeks)
 late preterm (34 to <37 weeks)

4. INCIDENCE OF PRETERM BIRTH
• 15 million PT annually worldwide
• A global PTB rate of about 11%
• PTB rates are rising in most countries.
(Estimates of preterm births for 184 countries using 2010 data)

5. CAUSES OF PRETERM BIRTH
• Iatrogenic: 15–20%
• Spontaneous: 80 %
• 45–50% of it are idiopathic
• 30% are related to PROM

6. PREDICTION OF BTB
- Pre-conceptual/early prenatal evaluation
- Prenatal Ultrasound markers
- Biomarker predictors

7. PRE-CONCEPTUAL/EARLY
PRENATAL EVALUATION

8. PRE-CONCEPTUAL/EARLY PRENATAL
ASSESSMENT OF RISK
• Risk factors :
 Preterm birth history / Mid-trimester loss
 Cervical or uterine abnormalities /
trauma
 Asymptomatic bacteriuria, STD, and BV
 APL / PE
 Social stressors (domestic violence, drug
abuse …,)

9. PRETERM LABOUR /BIRTH HISTORY
PT history Recurrent
PT
- Baseline
10-12%
1 15%
2 30%
3 45%
One of the
strongest predictors
of recurrent preterm
birth

10. CERVICAL TRAUMA
• Elective abortion:
- If multiple 1st -trimester or one or more 2nd -trimester ----
increased risk for PTL
• Cervical dysplasia (CIN).
- The incidence of PTL may be increased 200-300% after surgical
treatment (eg, cold knife , cryo, laser cone, LEEP)
• Obstetric trauma:
- Defects that involve more than 50% of the cervical length may
indicate a higher risk for mid-trimester loss.

11. PRENATAL ULTRASOUND MARKERS
(PREDICTORS)FOR PTL

12. PRENATAL ULTRASOUND MARKERS
FOR PTL
• Cervical length assessment
• Newer tools:
Cervical elastography
Utero- cervical angle
Placental strain ratio
Fetal middle cerebral artery pulsatility index
(MCA-PI)
Central zone of fetal adrenal gland measurement

13. PRENATAL CERVICAL LENGTH
ASSESSMENT
• The most sensitive prenatal
predictor of PTB
• Threshold of cervical length in
24 weeks of gestation for PTL
risk was defined as 25 mm
(10th percentile), with 37.3%
sensitivity and 92.2% specificity

14. PRENATAL CERVICAL LENGTH
ASSESSMENT
• A meta-analysis: the knowledge of cervical
length had a reduced risk for PTB before 37
weeks
• A recent study in an extensive population:
universal cervical screening program during
mid-trimester sonogram in women without a
history of preterm birth was associated with
reduction in the PTB

15. PRENATAL CERVICAL LENGTH
ASSESSMENT
• In mid-trimester asymptomatic twin ---- poor
predictor of PTL
• Screening of cervical length in the first
trimester (11-13 weeks): Conflicting evidence!

16. ASSESSMENT OF CERVICAL
ELASTOGRAPHY
• Strain elastography and shear wave
elastography: promising but limited
implementations
• Cervical elastography, is proposed to be a
possible alternative in the future which may
be combined with cervical length

17. UTERO-CERVICAL ANGLE
 ≥95∘ in second trimester ------increased risk
for PTL> 37
 ≥105∘ -------increased risk for PTL> 34
• In low risk population at 20-24 weeks ;
combination of anterior cervical angle, cervical
length, and maternal characteristics -----
predict approximately 40% of severe PTL

18. LOWER FETAL MIDDLE CEREBRAL
ARTERY PULSATILITY INDEX
• Associated with an earlier onset of labor
• Poor predictor of PTL, unlikely to be useful in
clinical practice

19. MEASUREMENT OF CENTRAL ZONE OF
FETAL ADRENAL GLAND
Effective in predicting PTL within 7 days with a
similar accuracy to cervical length
measurement

20. BIOMARKER PREDICTORS FOR
PRETERM BIRTH

21. BIOMARKERS PREDICTORS OF PTB
Cervical Fluid
• Fetal fibronectin
• IL-6 and IL-8 levels
• Placental alpha macroglobulin-1 (PAMG-1),
• Insulin-like growth factor binding protein-1 (IGFBP-1)
Amniotic Fluid
• amniotic fluid glucose
• Interleukin-6 (IL-6)
• matrix
metalloproteinase-8
(MMP-8)
• vascular endothelial
growth factor (VEGF),
placental growth factor
(PGF), and VEGF
receptor-1 (sFlt-1)
• interleukin-1 (IL-1)
Maternal Serum
• Calponin
• Ratio of maternal serum alpha fetoprotein (AFP)/amniotic fluid AFP
• progesterone-induced blocking factor (PIBF)
• Platelet-crit count
• Maternal salivary estriol

22. FETAL FIBRONECTIN
• Is a glycoprotein, produced by amniocytes and
cytotrophoblasts
• Normally found in cervico-vaginal fluids before 22
weeks
• its presence between 24 and 34 weeks indicates a risk
for PTB
• Pros, it is most accurate in predicting PTB within 7-10
days after testing
• Cons, a recent meta-analysis: fFN was not associated
with prevention of PTB or improved perinatal outcomes,
despite its higher costs. Blood-stained swabs has higher
false positive rates

23. OTHER CERVICO-VAGINAL FLUID
BIOMARKERS
• IL-6 and IL-8 levels were associated with PTB within 7
days
• Combination of IL-8 levels and cervical length had a
high specificity of 92.8% & low sensitivity (56.4%) -
limited clinical use
• Placental alpha macroglobulin-1 (PAMG-1), bedside
test PartoSure, more accurate in predicting PTB
within 7 days compared to fetal fibronectin and
cervical length measurement with 80% sensitivity and
95% specificity

24. OTHER CERVICO-VAGINAL FLUID
BIOMARKERS
• Insulin-like growth factor binding protein-1 (IGFBP-1) positive at
significantly higher rates in PTB
• Premaquick©, developed as a triple biomarker of native and
total IGFBP-1 and IL-6, with 87.1% sensitivity, 92.4% specificity,
84.4% PPV, 100% NPV, and 95% accuracy in predicting PB in 7
days
• Actim Partus test (IGFBP-1) combined with cervical length
more reliable in prediction of PB than fetal fbronectin test

25. AMNIOTIC FLUID BIOMARKERS
(PREDICTORS)
In patients who had undergone amniocentesis at 16-22 weeks for standard indications
• Low amniotic fluid glucose was found associated with preterm delivery
• Interleukin-6 (IL-6) negatively correlated with gestational age at delivery
• matrix metalloproteinase-8 (MMP-8) was reported to predict nearly half of
spontaneous PB
• Increased vascular endothelial growth factor (VEGF), placental growth factor (PGF),
and decreased soluble VEGF receptor-1 (sFlt-1) indicating angiogenesis and
inflammation, were predictive for PB
• Elevated levels of interleukin-1 (IL-1) due to possible infection or inflammation,
potential predictor of PB
• Neutrophil elastase levels Duration of pregnancy was significantly longer when
neutrophil elastase levels were> 180ng/ml
• IL-8 and Annexin-A2 levels sensitivity of 81.25%, specificity of 88.89%, for predicting
PB within 2 weeks

26. MATERNAL SERUM BIOMARKERS
(PREDICTORS)
• Maternal serum calponin 1: significantly high in patients who
delivered preterm within 7 weeks
• Ratio of maternal serum AFP/ amniotic fluid AFP was suggested
as a potential predictor for IUGR & PTL
• Prgesterone-induced blocking factor (PIBF) significantly lower in
patients within 5 days prior to PTL
• Maternal platelet-crit count significantly higher in patients who
delivered preterm
• Maternal salivary estriol, measured in 25-34 weeks, had 82%
negative predictive value on identifying women who will not
deliver preterm, which could be used for avoiding unnecessary
interventions to prevent PB

27. BIOMARKER TESTS TO
HELP DIAGNOSE PTL IN
WOMEN WITH INTACT
MEMBRANES
• There is currently insufficient evidence to
recommend the routine adoption of:
 Actim Partus and PartoSure
 Rapid fetal fibronectin (fFN) 10Q
Cassette Kit
to help diagnose preterm labour in
women with intact membranes when
TVUS measurement of cervical length is
not available or not acceptable.
• Further research is needed on the
accuracy of the tests and their effect on
clinical outcomes
NICE guidance
04 July 2018

28. DIAGNOSING PTL FOR WOMEN
WITH INTACT MEMBRANES
Preterm labour and birth NICE guideline Published: 20 November
2015

29. DIAGNOSING PRETERM LABOUR FOR
WOMEN WITH INTACT MEMBRANES
Clinical assessment
(History,
observations,
Speculum
examination)
suspected preterm
labour 30+0 wks or
more
cervical length is more
than 15 mm---
conservative
cervical length is
or less, diagnosed
preterm labour
suspected preterm
labour 29+6 wks or less
treatment for preterm
labour
TVUS measurement of cervical length ---- likelihood of birth within 48 hours

30. DIAGNOSING PRETERM LABOUR FOR
WOMEN WITH INTACT MEMBRANES
• if TVUS measurement of cervical length is not available or
not acceptable, consider foetal fibronectin testing as a
diagnostic test to determine likelihood of birth within
48 hours ( 30+0 weeks or more).
• if fetal fibronectin testing is negative (50 ng/ml or less),
PTL is unlikely
• if fetal fibronectin testing is positive (more than 50 ng/ml)-
----- PTL
• If suspected PTL 30+0 weeks or more & no TVUS nor fFN
testing , offer treatment as being diagnosed PTL
• TVUS for cervical length and fFN testing not used in
combination to diagnose PTL

31. DIAGNOSING PRETERM PRELABOUR
RUPTURE OF MEMBRANES (P-PROM)
Preterm labour and birth NICE guideline Published: 20 November
2015

32. DIAGNOSING PRETERM PRELABOUR RUPTURE
OF MEMBRANES (P-PROM)
• Sterile speculum examination:
• if pooling of amniotic fluid, no need for other
diagnostic test
• If no pooling ---- insulin-like growth factor binding
protein-1 test or placental alpha-microglobulin-1 test
of vaginal fluid
• Do not use nitrazine to diagnose P-PROM
• Do not perform diagnostic tests for P-PROM if labour
becomes established

33. PROPHYLACTIC INTERVENTIONS
Preterm labour and birth NICE guideline Published: 20 November
2015

34. PROPHYLACTIC INTERVENTIONS
• Prophylactic vaginal progesterone
• Prophylactic cervical cerclage
• 'Rescue' cervical cerclage

35. TVUS between 16+0 and 24+0 weeks, with cervical length of 25 mm or less
Consider prophylactic vaginal
progesterone
+ history of spontaneous PTL (up to 34+0 weeks )
or mid-trimester loss (from 16+0 )
Alone
Offer a choice of prophylactic vaginal
progesterone or prophylactic cervical cerclage
+ P-PROM in a previous
pregnancy or a history
of cervical trauma
Consider prophylactic cervical
cerclage
History of spontaneous PTL (up to 34+0 weeks) or mid-trimester loss (from 16+0) alone,
Consider prophylactic vaginal progesterone

36. PROPHYLACTIC INTERVENTIONS IN
MULTIPLE PREGNANCY
• The optimal method of preventing PTB has yet to be
proven.
• Cervical cerclage, prophylactic bed rest, and empiric
use of tocolytics have not been successful.
• RCT by Lim et al suggests that the use of 17α-
hydroxyprogesterone caproate does not prevent
neonatal morbidity or PTB in multiple pregnancies

37. 'RESCUE' CERVICAL CERCLAGE
• Between 16+0 and 27+6 weeks when dilated cervix and
exposed, un-ruptured foetal membranes
• benefits are greater for earlier gestations and less cervical
dilatation
• Not offered to women with:
• Infection
• active vaginal bleeding
• uterine contractions

38. TREATMENT OF PTL
Preterm labour and birth NICE guideline Published: 20 November
2015

39. TREATMENT OF PTL
• Tocolysis
• Maternal Corticosteroids
• Magnesium Sulphate

40. TOCOLYSIS
• Factors affecting decision to start tocolysis:
 suspected or diagnosed PTL
 other clinical features (bleeding or
infection)
 gestational age
 likely benefit of maternal corticosteroids
 availability of neonatal care
 the preference of the woman

41. TOCOLYSIS IN PTL WITH INTACT
MEMBRANES
• Consider nifedipine between 24+0 and
25+6 weeks
• Offer nifedipine between 26+0 and 33+6 weeks
in
• If nifedipine is contraindicated, offer oxytocin
receptor antagonists (Atosiban)
• Do not offer betamimetics for tocolysis

42. MATERNAL CORTICOSTEROIDS
• Offered----- if 24+0 and 33+6 weeks
• Considered-------between 34+0 and 35+6
weeks
• Do not routinely offer repeat courses

43. MATERNAL CORTICOSTEROIDS
• Significantly lower severity, frequency, or
both, of:
 RDS (RR, 0.66; 95% CI, 0.59–0.73)
 ICH (RR, 0.54; 95% CI, 0.43–0.69)
 NEC (RR, 0.46; 95% CI, 0.29–0.74)
 Death (RR, 0.69; 95% CI, 0.58–0.81)

44. MAGNESIUM SULFATE FOR
NEUROPROTECTION
• MGSO4 prevents CP and reduces the
combined risk of fetal /infant death or CP
• Offer IV MgSO4 between 24+0 and 29+6
weeks in established PTL or planned preterm
birth within 24 hours
• Consider IV MgSO4 between 30+0 and 33+6
weeks in established PTL or planned preterm
birth within 24 hours

45. CONCLUSIONS
• Spontaneous preterm birth is a complex, multifactorial condition
characterized by varying clinical presentation.
• Whereas advances have been made to identify women at
increased risk of SPTB, these practices are best applied to women
with a history of prior preterm birth.
• There remains a lack of consistent and cost-effective screening
modalities for early recognition of low-risk patients who
subsequently develop SPTB.
• As knowledge regarding the pathophysiology of SPTB evolves,
further research must take into consideration the heterogeneity of
this condition.

46. REFERENCES
• Biomarker tests to help diagnose preterm labour in
women with intact membranes, NICE diagnostics
guidance [DG33] Published: 04 July 2018
• Preterm labour and birth, NICE guideline [NG25], Last
updated: 02 August 2019
• Prediction of Preterm Birth: Maternal Characteristics,
Ultrasound Markers, and Biomarkers: An Updated
Overview Zeynep Asli Oskovi Kaplan and A. Seval Ozgu-
Erdinc /Hindawi Journal of Pregnancy Volume 2018,
Article ID 8367571, 8 pages
• Predicting Preterm Labour: Current Status and Future
Prospects Harry M. Georgiou,1,2,3 Megan K. W. Di
Quinzio,1,2 Michael Permezel,1,2 and Shaun P
.
Brennecke1,3 1 2 June 2015/ Disease Markers Volume
2015, Article ID 435014, 9 pages
• Glover, Angelica V, and Tracy A Manuck. “Screening for
spontaneous preterm birth and resultant therapies to
reduce neonatal morbidity and mortality: A
review.” Seminars in fetal & neonatal medicine vol. 23,2
(2018): 126-132. doi:10.1016/j.siny.2017.11.007
• What are the risk factors for preterm labor? Updated:
May 04, 2021 Author: Michael G Ross, MD, MPH; Chief
Editor: Carl V Smith, MD
Dr Wafaa Benjamin Basta (FRCOG)
Consultant Ob/Gyn Mataria Teaching Hospital
Member of Egyptian Representative Committee of
RCOG