Preterm labour

It is a medical educational presentation.

1. Preterm Labour Dr. Poly Begum Assistant Professor Diabetic Association Medical College Faridpur

2. Definition Preterm labour is defined by WHO as Onset of labour prior to the completion of 37 weeks of gestation, in a pregnancy beyond 20 wks of gestation. The period of viability varies in different countries from 20 to 28 wks. Preterm labour is considered to be established if regular uterine contractions can be documented atleast 4 in 20 minutes or 8 in 60 minutes with progressive change in the cervical score in the form of effacement of 80% or more and cervical dialatation >1cm. 30 September 2016 2 Dr. Poly Begum

3. If uterine contractions are perceived in the absence of cervical change, the condition is called Threatened Preterm Labour. This condition tends to be over diagnosed and over treated. Nearly 50-60% of preterm births occur following spontaneous labour. 30% due to preterm premature rupture of membranes Rest are iatrogenic terminations for maternal or fetal benefit. 30 September 2016 3 Dr. Poly Begum

4. I ntroduction Half of all neonatal morbidity occurs in preterm infants. Inspite of all major advances in obstetric and neonatal care, there has been no decrease in incidence of preterm labour over half a century. On the contrary , it has been increasing in the developed countries as more and more high risk mothers dare to get pregnant. 30 September 2016 4 Dr. Poly Begum

5. Incidence Preterm birth occurs in 5-12% of all pregnancies and accounts for majority of neonatal deaths and nearly half of all cases of congenital neurological disability, including cerebral palsy. A neonate weighing 1000- 1500 g today has ten times greater chance of surival then what it had in 1960s. The focus is hence shifting to early preterm births(<32 weeks) which account for 1-2% of all births but contribute to 60% of perinatal mortality and nearly all neurological morbidity. 30 September 2016 5 Dr. Poly Begum

6. One of the major reasons for increase in incidence of premature births is the increase in numbers of multiple pregnancies , particularly higher order pregnancies, resulting from the use of fertility drugs and assisted reproduction. 30 September 2016 6 Dr. Poly Begum

7. Pathogenesis Preterm labour may be: - Physiological or - Pathological The molecular basis of initiation of labour is unclear but a number of theories have been proposed. Of these -Progesterone withdrawl oxytocin stimulation and -Premature decidual activation are important ones. Regardless of the stimulus, the final pathway seems to converge towards a central role of inflammatory mediators, i.e. Cytokines. 30 September 2016 7 Dr. Poly Begum

8. Classification of preterm birth Term 39- 40 wks 6 days Early term – 37- 39 weeks Late preterm birth - 34 - <37 weeks Very preterm birth - 28 -<32 weeks Extremely preterm birth - <28 weeks 30 September 2016 8 Dr. Poly Begum

9. BIRTH WEIGHTS LOW BIRTH WEIGHT – 1500- 2500 gms VERY LOW BIRTH WEIGHT – 500 – 1500 gms EXTREMELY LOW BIRTH WEIGHT – 500 – 1000 gms . 30 September 2016 9 Dr. Poly Begum

10. As parturition nears the fetal adrenal axis becoms more sensitive to ACTH and there is an increased production of cortisol. This simulates 17-hydroxylase in the trophoblast resulting in decreased progesterone secretion. The reversal of oestrogen – progesterone ratio Increase in prostaglandin formation Initiation of labour Progesterone supresses myometrial contractility and inhibits production of prostaglandins by upregulating prostaglandin dehydrogenase 30 September 2016 10 Dr. Poly Begum

11. Role of cytokines Infection (is implicated as the etiological factor in 40-50% of cases of preterm labour at early gestations(<30 weeks).) Infection induces intraamniotic inflammatory response involving the activation of a no. of cytokines and chemokines. Intrauterine bleeding is also an important trigger of cytokine release. Cytokines Action Effect IL-6, IL-8, IL-1, TNF-  Degradation of collagen fibres Cervical ripening IL-1, TNF-  Induce matrix metalloproteinases Membrane rupture IL-1, IL-2, IL-6, TNF-  Increase PGE2, PGF2  Uterine contractions 30 September 2016 11 Dr. Poly Begum

12. Aetiology and Risk Factors A large variety of aetiological factors have been implicated but in majority of cases no definite cause is found . Causes include: Obstetric complications Racial factors Demographic factors Psychosocial factors Past obstetric history Infection Genetic factors 30 September 2016 12 Dr. Poly Begum

13. Obstetric Risk factors Conditions that cause overdistension of uterus: Multiple Pregnancy- carries one of the highest risk. About 50% of twins nearly all higher multiple gestations. Hydramnios Preterm premature rupture of membranes(PPROM) Idiopathic preterm labour Pre eclampsia Antepartum hemorrhage Second trimester bleeding not associated with placental causes Iatrogenic preterm termination for pre-eclamsia, fetal distress, intrauterine growth restriction, abruptio placentae and intra uterine fetal death 30 September 2016 13 Dr. Poly Begum

14. Racial factors Black women have twice the risk as compared to whites. This may be explained by multiple factors like socioeconomic status, medical disorders and genetic predisposition. 30 September 2016 14 Dr. Poly Begum

15. Demographic Factors Women with low BMI and poor maternal weight gain in pregnancy are at increased risk. Age- women younger than 17 and older than 35 yrs. Poor education Women living alone Minimal or no prenatal care Low socioeconomic status Multiple sexual partners 30 September 2016 15 Dr. Poly Begum

16. Psychosocial Factors Anxiety Stress Depression Negative life events Perception of racial discrimination and domestic violence Excessive alchohol intake Smoking 30 September 2016 16 Dr. Poly Begum

17. Past obstetric history Previous h/o preterm birth(17-20% recurrence risk) or second trimester pregnancy loss. 3 or more abortions (may result in cervical incompetence) DES exposure Conceptions following in-vitro fertilization Cervical incompetence- 10-25% of second trimester losses. 30 September 2016 17 Dr. Poly Begum

18. Infection Result in 50% of spontaneous preterm births. Asymptomatic bacterial vaginosis Trichomonas vaginalis Chlamydia trachomatis Ureaplasma urealyticum Mycoplasma hominis Asymptomatic bacteriuria Systemic infections like pyelonephritis, pneumonia, acute appendicitis. 30 September 2016 18 Dr. Poly Begum

19. INFECTION Bacteria can gain access to intrauterine tissues through Transplacental transfer of maternal systemic infection Ascending infection with bacteria from vagina and cervix Retrograde flow of infection from peritoneal cavity via fallopian tubes. 30 September 2016 19 Dr. Poly Begum

20. DEGREES OF INFECTION # Potential degrees of intrauterine infections by Goncalves Stage 1 – bacterial vaginosis Stage 2 - Decidual infection Stage 3 – Amniotic infection Stage 4 – fetal systemic infection 30 September 2016 20 Dr. Poly Begum

21. Genetic Important component of idiopathic group. Single gene polymorphisms of cytokines in both mother and fetus may be responsible Polymorphisms involving TNF -308, IL-1 and IL-6 have been most consistently associated with spontaneous preterm labour and preterm birth. 30 September 2016 21 Dr. Poly Begum

22. Prediction of Preterm labour A number of scoring systems have been proposed combining various risk factors but their clinical utility is poor. The two most promising markers currently available are: fetal fibronectin levels Ultrasound assessment of cervical length. 30 September 2016 22 Dr. Poly Begum

23. Fetal Fibronectin(fFN)- It is an extracellular glycoprotein secreted by the chorionic tissue at maternal-fetal interface. It is present in amniotic fluid, placental tissue and decidua basalis. It acts as a biological glue which binds blastocyst to endometrium. It can be normally present in cervicovaginal secretions upto 20-22 wks. Around 22 wks chorion fuses completely with underlying decidua. This prevents fibronectin to leak into the vaginal secretions any further, until at term, a few wks before labour when cervix dialates or membranes rupture. Therefore presence of fFN between 27 to 34 wks can provide important marker of preterm labour 30 September 2016 23 Dr. Poly Begum

24. Swabs can be taken from ectocervix or post vaginal fornix. ELISA with FDC-6 monoclonal antibody is used to detect fetal fibronectin. A cut-off of 50ng/ml is considered positive. Presence of fibronectin indicates increased risk of preterm labour (89% sensive and 86% specific) A negative fFN indicated very low risk of preterm delivery. 30 September 2016 24 Dr. Poly Begum

25. Length of cervix Cervical insufficency is defined as cervical changes in absence of uterine contractions. Cervix can be assesed digitally or by ultrasound. A reduction in cervical length of >6mm between 2 ultrasounds have higher risk. Funneling( internal os diameter >=5mm) is also independent risk factor. 30 September 2016 25 Dr. Poly Begum

26. Prevention Interventions have been aimed at general improvement in nutrition, rest , hydration and psychological support. Adequate antenatal care Cervical cerclage Nutritional intervention: iron, calcium, vit-C, zinc, proteins Bed rest and hydration Antiboitics: antibiotic therapy at 24 wks and repeated in labour reduced the incidence of bacterial vaginosis and trichomoniasis but did not have significant effect on preterm labour. 30 September 2016 26 Dr. Poly Begum

27. M anagement Includes tocolysis to halt uterine contractions. Administration of steroids to decrease perinatal morbidity 30 September 2016 27 Dr. Poly Begum

28. A. Tocolytics: Aim of tocolysis is to prolong pregnancy and prevent premature births. Beta-agonists: Beta-2 agonists: cause vasodialation, bronchodialation and uterine muscle relaxation Ritodrine Terbutaline Salbutamol Beta-3 agonists: BRL37344 – induce uterine relaxation with similar potency but less cardiovascular side effects compared to ritodrine 30 September 2016 28 Dr. Poly Begum

29. 2. Magnesium Sulphate Cause myorelaxation. It has been used to arrest preterm labour particularly in US. 3.Calcium Channel blockers Act by reducing influx of calcium ions into the cell membrane thereby reducing the tone of smooth muscles Nifedipine is most commonly used . 30 September 2016 29 Dr. Poly Begum

30. 4. Prostaglandin synthetase inhibitors Drugs like indomethacin, asprin, ibuprofen, sulindac belong to this group. Indomethacin has been most commonly used. Fetal complications like oligohydramnios, premature closure of ductus and necritising enterocolitis have restricted their use. 5. atociban Oxytocin antagonists have been evaluated as tocolytics and atociban is now licenced in UK for treatment of preterm labour 30 September 2016 30 Dr. Poly Begum

31. 6.Nitric oxide donors Nitric oxide is a potent endogeneous hormone causing smooth muscle relaxation Nitroglycerine has been used for the treatment of preterm labour 30 September 2016 31 Dr. Poly Begum

32. B. Corticosteroids: Steroids decrease the incidence of respiratory distress syndrome, intraventricular hemorrhage and neonatal mortality. Recommended regimens include: C. Progesterone: Progestational agents and 17-  hydroxy progesterone caproate reduced the incidence of preterm births and low birth weight babies. 30 September 2016 32 Dr. Poly Begum

33. Intrapartum management Monitoring: Fetal hypoxia and acidosis may increase the risk of intraventricular hemorrhage. The preterm fetus should be monitored closely for signs of hypoxia during labour, preferably by continuous electronic fetal monitoring. Antibiotic prophylaxis: In countries with high incidence of group B streptococcal infection. Delivery: Delivery must be conducted in the presence of expert neonatologist capable of dealing with complications of prematurity. Ventouse is contraindicated in preterm deliveries. Caesarian section : only for obstetric indications. 30 September 2016 33 Dr. Poly Begum

34. Burden of Illness: Significance Accounts for over 85% of perinatal morbidity and mortality. Major short term problems in preterm infants include: Respiratory distress syndrome Bronchopulmonary dysplasia Necrotizing enterocolitis Hospital acquired infections Intra ventricular hemorrhage Retinopathy of prematurity Patent ductus arteriosus Hypoglycemia etc. 30 September 2016 34 Dr. Poly Begum

35. Long term problems include : Reactive airway disease Asthma Bronchiolitis Cerebral palsy, Cerebral atrophy Hydrocephalus Neurodevelopmental delay Hearing loss Blindness, Retinal detachment Pulmonary hypertension Hypertension in adulthood Increased insulin resistance etc. 30 September 2016 35 Dr. Poly Begum

36. THANK YOU 30 September 2016 Dr. Poly Begum 36