DR PUSHPENDRA SINGH PRETERM LABOUR t.pptx

Preterm labour

1. - DR NIHAL SINGH SIR PRETERM LABOUR

2. PRETERM LABOR DEFINITION  Preterm labor is defined as presence of uterine contraction of sufficient frequency and intensity to cause progressive effacement and dilatation of cervix after period of viability before 37 completed weeks of gestation. Lower gestational age limit for preterm labor =20 wk.

3. Based on gestational Age(WHO) Extreme Preterm-<28wk Very Preterm- 28-32 weeks Moderate to Late Preterm-32-36+6 weeks CDC/ACOG criteria Late Preterm- 34-36wks+ 6 days Early Preterm- less than 34 wks Classification

4. INCIDENCE – 5-18% (11%) SPONTANEOUS 40-50%  Preterm labor 20-30%  PPROM Rarely  Cervical incompetence IATROGENIC

5. MATERNAL Socioeconomic status Age : Young primi gravida and elderly gravida Race Genetic factors – Hereditary. Long working hrs Previous history of preterm birth (1) Previous 1 has RR of 15-30% (2) Previous 2 has RR of 60% RISK FACTORS

6. Chronic medical disease like diabetes, renal disease, depression, anxiety, autoimmune diseases Cervical surgery like conization with LLEEP Uterine anomaly like septate, bicornuate, and uterine fibroid. Assisted reproductive technique- independent risk factor. Short interpregnancy interval Multifetal pregnancy Infection

7. PATHOGENESIS OF PRETERM LABOr 1.Premature activation of HPA axis 2.Exaggerated inflammatory response /infection/ altered genital tract microbes 3.Decidual Haemorrhage 4.Pathological overdistention of uterus.

8. 1 . PREMATURE ACTIVATION OF HPA AXIS OF FETUS Maternal stress( chronic d/s, depression, anxiety) Hypothalamus in mother Release CRH Act on pituitary gland. Release ACTH act on adrenal gland release Cortisol the feedback on placenta PLACENTAL CRH (A) Fetal HPA axis (B) Increase fetal adrenal (C) Increase glucocorticoids prematurely activated DHEA-S Increase Prostaglandins Fetal cortisol Functinal withdrawl of progesterone Uterine cont. Cervical maturation

9. (B) Increase fetal adrenal DHEA-S in placenta converted into estrogen estrogen level prematurely increase in case of preterm labour which lead to (a) Increase in GAP jxn (b) Increase in no. of oxytocin receptors (c) Increase activity of prostaglandins (d) Increase enzyme activity = responsible for uterine contraction. eg - calmodulin ,myosin light chain kinase etc

10. 2. EXAGGREATED INFLAMMATORY RESPONSE / INFECTION (A) Asymptomatic bacteriuria – MC (B) Clinical/Subclinical chorioamnionitis (C) Bacterial vaginitis or alteration in vaginal flora (D) Trichomonas (E) Malaria

11. Infection lead to Preterm birth by  1. Direct effect- Bacteria produces phospholipase A2 and endotoxins which cause increase in prostaglandins. Organism like streptococcus and pseudomonas – produce protease which causes degradation of fetal membranes leading to PPROM resulting in Preterm birth.

12. 2. INFLAMMATORY RESPONSE – Bacterial ligand bind to toll like receptors which are present on decidua / present on chorion amnion and leukocytes membrane which release IL-1 and TNF-alpha They activate COX-2 enzymes which lead to increase PG’s and also do physiological withdrawal of progesterone .

13. 3. Release enzymes- like Matrix Metalloprotein which can lead to (a) Degradation of fetal membrane PPROM resulting in Preterm birth (b) Promote uterine contraction

14. 3. DECIDUAL HAEMORRHAGE- Abruption release thrombin which bind to protease activated receptors ( PAR 1 And 3) It has 4 action Increase uterine contraction Increase MMP –which lead to degraded membrane and uterus contraction Functional withdrawal of progesterone Induce IL-8 from decidual cell and fetal membrane which lead to neutrophillic infiltration.

15. 4 Overdistention of uterus Eg - Twin pregnancy / Polyhydramnios / Macrosomia stretching of myometrium causes (a) formation of GAP junctions (b) increase oxytocin receptors (c) release of Prostaglandins. (d) overexpression of gene

16. CLINICAL FEATURES  Menses like cramps Low backache Vaginal discharge Pressure symptoms Fever

17. Diagnosis of PRETERM LABOUR- (1) Uterine Contraction- >=4 / hr (2) Any one of following- (a) Bishop score>=4 (b) Cervical length <25 mm (c) Cervical length 2-3 cm and Positive FFN

18. 1- Speculum examination- to inspect the liquor escaping out through the cervix. 2- Detection of pH- by litmus or Nitrazine paper- Nitrazine paper turns from yellow to blue at pH>6. 3- Fern test 4-Centrifuged cells stained with 0.1% Nile blue sulphate. 5-Amnisure 6-USG CONFIRMATION OF DIAGNOSIS

19. 1-Full blood count 2-CRP 3-Urine routine analysis and culture 4-Vaginal swab for GBS 5-Vaginal pool for estimation of Phosphatidyl glycerol and L:S ratio 6-USG INVESTIGATIONS

20. The principal in management of preterm labor (1) To prevent birth asphyxia and development of RDS (2) To prevent birth trauma >=34 WKS (1) Admit patient = observe for 4-6 hrs (2) Corticosteroids therapy (3) No role of tocolytics (4) Asses fetal well being (5) Rule out abruptio/Chorioamnionitis/PROM (6) Give Group B Streptococci prophylaxis. MANAGEMENT OF PRETERM LABOUR

21. If no progress in labor discharge the patient follow up after 1-2 wks and explain the RED FLAG SIGN = 1. Sign and symptoms of Preterm labor. 2. Bleeding 3. Decrease fetal movement 4. Leaking per vagina

22. Choice of corticosteroids- 1. BETAMETHASONE - Dose- 2 dose of 12 mg given gap of 24 hrs 2. DEXAMETHASONE - Dose- 4 dose 6mg given gap of 12 hrs t 1/2= 35-54 HRS CORTICOSTEROIDS

23. 1. It decrease chance of Transient tachypnea of newborns. 2. Decrease RDS 3. It also improve circulatory stability in preterm neonate 4. It decrease IVH 5. It decrease NEC Benefits of Corticosteroids therapy

24. ACOG recommend single dose of Betamethasone 12 mg in patient with all of following characteristics- (a) <34 wks of gestation + (b) imminent risk of patient delivered within 7 days + (c) a prior course of ACS administration equal or more than 14 days This is recommended if 1 st dose was given at 28 or less than 28 wks. ACOG guideline for ANTENATAL CORTICOSTEROIDS

25. MATERNAL SIDE EFFECTS- 1.Hyperglycemia 2.Slight increase in uterine activity by betamethasone specially in twin pregnancy . FETAL SIDE EFFECTS- 1. FHR Variability 2. Decrease breathing and decrease body weight 3. Associated with neonatal hypoglycemia 4. Associated with neurodevelopmental risk ABSOLUTE C/I IS CHORIOAMNITIS

26. 1. Admit the patient 2 Monitor progress of labor and Fetal well being 3 Steroids 4.TOCOLYTICS for max 48 hrs. 5.Antibiotics for GBS prophylaxis 6.MgSO4 for neuroprotection b/w 24-32 wks Send urine Routine/microscopy Swab for Group B Streptococci GESTATIONAL AGE <34 WKS

27. Purpose : to buy time for corticosteroids CHOICE OF TOCOLYTICS- 1 ST Line- 1. NIFEDIPINE 2.INDOMETHACIN ACOG says 24-32 wks= Indomethacin 32-34 wks = Nifedipine In India DOC is NIFEDIPINE. TOCOLYTICS

28. 2 ND Line are- A.Terbutaline B. Atosiban C. MgSO4 D. NO oxide donor = NTG

29. MOA= Ca Channel blocker Dose = LD – Orally = 20-30 mg for 3-8 hrs maintenance dose = 10-20mg Max period = 48 hrs S/E = it cause vasodilation which lead to nausea/ flushing/headache/dizziness/palpitation. C/I= 1. HEART FAILURE with decrease Ejection Fraction 2.Hypotension < 90/60 mmhg 3. PR > 100 4. Fever> 100 F NIFEDIPINE

30. Known specific COX inhibitor. It prevent formation of Prostaglandins Its safe upto 32 wks of gestational age Its duration not >48 HRS Dose = LD = 50-100mg ( oral/per rectal) 4-6 hrs 25 mg oral. MATERNAL S/E - Nausea/Gastritis/GERD/Platelet dysfunction FETAL S/E – it promote closure of DA and it decrease urine production lead to oligohydramnios. C/I OF Indomethacin - Gastritis/liver dis/kidney dis/any bleeding disorders. INDOMETHACIN

31. REGIMEN - Dose  -loading- 40mg iv infusion( in D5 500 ml) at rate of 8 drops/min increase by 8 drop*15 min till contractions stop. -After 15 min of infusion if contractions stop-  Inj.Isoxsuprine 10mg im * 4 hrly upto 1 st 24 hrs.  For next 24 hrs - cap 40mg retard BD as maintenance therapy and same till time of delivery. ISOXSUPRINE

32. C/I  1.Maternal tachycardia 2.Hypotension 3.Palpitation/chest pain 4.Pulmonary edema 5.Suspected chorioamnionitis 6.Vaginal bleeding 7.Hypokalemia 8.Fetal tachycardia

33. No longer use Only b2 agonist TERBUTALINE Dose – S/C = 0.25 mg I/V = 2.5 to 5 mcg/min Max 25 mcg/min MATERNAL S/E = it cause vasodilation so tachycardia/palpitation/hypotension/hypokalemia/hyperglycemia. FETAL S/E = fetal tachycardia and hypoglycemia. C/I =1. Heart d/s in mother with tachycardia. 2. poorly controlled diabetes/hypothyroidism. B2 AGONIST

34. Its oxytocin vasopressor receptor antagonist. Not FDA approved. MOA= compete with oxytocin to bind with oxytocin receptor in myometrium and decidua. DOSE = 6.75mg i /v over 1 min followed by infusion 18 mg/hr for 3 hr followed by 6mg/hr for 45 hrs. ATOSIBAN

35. The therapeutic range is 9-10 meq /l S/E are more like slurred speech/nausea/ absent DTR. C/I 1. Myasthenia gravis 2. Cardiac conduction defect 3. MI DOSE = LD is 6gm i/v over a period of 20 min and continue infusion of 1gm/hr till 24 hrs or till delivery of baby which ever is sooner. MgSO4

36. 1.Congenital malformation. 2.IUD 3.Maternal Hemorrhage - Hemodynamically unstable. 4.Dilatation of Cervix > 4 cm. 5.PPROM and high chance of cord prolapse 6.Chorioamnionitis. 7.Severe preeclampsia and eclampsia 8. Acute fetal distress. 9. Hyperthyroidism. 10. Gestational age > 34 weeks CONTRAINDICATIONS OF USING TOCOLYTICS

37. 1.PROGESTERONE THERAPY 2.CERVICAL CERCLAGE. PROGESTERONE It decrease the risk of Preterm birth by 20%. It decrease absolute risk by 0.02%. PREVENTION OF PRETERM LABOUR

38. 1. Previous H/o Spontaneous Preterm birth. 2. Short cervix. TYPES OF PROGESTERONE: A. 17 HYDROXYPROGESTERONE CAPROATE= Synthetic progesterone with minimal or no androgenic properties. Dose: 250 mg i/m weekly Indications of using Progesterone

39. B. NATURAL PROGESTERONE/MICRONISED PROGESTERONE  It can be used vaginally.  patient with short cervix and no previous preterm birth :natural progesterone 100mg vaginally daily which is begins at time of diagnosis and continue till 36 wks+6 days.  patient with history of preterm birth and short cervix: serial cervical length monitoring followed by cerclage if needed with progesterone supplementation.

40. Natural progesterone effective in decreasing myometrial contractility and preventing cervical ripening. Vaginal progesterone has high uterine bioavailability due to first pass metabolism. Dose begins with 100 mg daily to 200mg Max Dose = 400 mg OD DIFFERENCE IN HYDROXYPROGESTERONE AND NATURAL PROGESTERONE

41. 1. If Preterm labour/PROM has occurred 2. If H/O Preterm Birth but other risk factors like H/O uterine anomalies. Conception due to Assisted reproductive technique. Obesity 3.Positive fetal fibronectin test 4.If female is undelivered after Preterm labour. NO ROLE OF PROGESTERONE

42. A positive increase in risk of hypospadias in male offspring exposed to exogenous progesterone before 11 wk of gestation. C/I OF PROGESTERONE - 1.Liver d/s 2.Uncontrolled HTN RISK OF TERATOGENICITY

43. DEFINATION  Cervical cerclage defined as a surgical procedure in which synthetic suture or tape is used to reinforce the cervix by mechanically increasing its strength. CONTRAINDICATIONS OF CERVICAL CERCLAGE 1.Prolapse of the fetal membrane into the vagina 2.Intrauterine infection 3.PPROM 4.Preterm labour and birth. CERVICAL CERCLAGE

44. HISTORY INDICATED CERCLAGE 1. H/O 2 or more than 2 2 nd trimester abortions or extremely early Preterm birth associated with no or minimal symptom Cerclage time = 12-14wks Start supplementation progesterone at 16 wks either hydroxyprogesterone caproate weekly or vaginal progesterone daily till 36 wks+6 days INDICATION FOR CERVICAL CERCLAGE

45. USG INDICATED CIRCALAGE H/O 1 second trimester Abortion or extreme Preterm birth in this patient we do serial TVS + start progesterone @ 16 wks , if <25mm before 24 wks do cerclage.

46. ROUTE OF CERCLAGE- 1 Vaginal= MC 2 Abdominal In all cases of cerclage rule out (A) Fetal anomaly incompatible with life. (B) Intrauterine infection. (C) Active preterm labour. (D) PPROM (E) Fetal demise

47. It can be offered to women between 16 to 24 weeks of pregnancy with a dilated cervix and exposed unruptured membranes. C/I  1.Active vaginal bleeding 2.Uterine contraction. RESCUE CERCLAGE

48. 1. H/O indicated preterm birth – Aspirin prophylaxis in next pregnancy it decrease PIH and Preterm birth 2 H/O cervical surgery or transcervical like cold knife conization /LEEP so for this we do single TVS B/W 18-24 wks if short cervix with no h/o previous Preterm birth we give progesterone supplementation. 3. Maternal chronic disease – optimization of disease 4.Multifetal pregnancy- reduce multifetal pregnancy to twin pregnancy 5.adolescent or older female- counselling 6 infection- all female should be screened by urine c/s in first trimester. OTHER INTERVENTION TO DECREASE PRETERM BIRTH

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