PRETERM LABOUR Dr.Esraa Al- Maini FICOG,CABOG

1. PRETERM LABOUR Dr.Esraa Al-Maini FICOG,CABOG Assistant professor-Al-Mustansyria Medical College

2. Preterm labour(PTL): • is defined by WHO as the onset of regular uterine contractions associated with cervical effacement and dilatation, between viability and 37 weeks’ gestation, viability of fetus in UK regarded as 24 complete weeks of gestation or birth weight more than 500grams in many developed country • -Mild preterm 32+0 to36+ 6 • -Very Preterm Infants defined as those born between 28 and 32 weeks • -Extremely Preterm Infants defined as those born before 28 weeks.

3. The incidence of preterm birth in the developed world is thought to have increased over the past decade, with an estimated annual incidence of 10–15% of all live births • 2 major clinical subtypes: • 1-1/3 Preterm birth for maternal or fetal reason . • 2-2/3 Spontaneous preterm labor divided in to : PPROM ,PTL.

4. Sequelae of preterm birth: • Rates of perinatal morbidity and mortality increase with decreased gestational age at birth. • Perinatal outcomes between 32 weeks and term are quite similar, whereas those infants born before 32 weeks have poorer outcome.

5. Adverse outcomes in terms of morbidity include: • Neonatal RDS (respiratory distress syndrome) .The cause of RDS is HMD (hyaline membrane disease):- which occur due to inadequate production of surfactant by type II alveolar cells. • Necrotizing enterocolitis. • Intraventricular hemorrhage, periventricularleukomalacia. • Jaundice. • Retinopathy of prematurity, and neonatal hypoglycaemia . • Long-term problems include cerebral palsy, deafness, visual impairment, developmental delay, and bronchopulmonary dysplasia

6. Aetiology of preterm labour:- Genital tract infection:There is a strong correlation between infection within the uterus and the onset of spontaneous preterm labour. bacterial vaginosis and chlamydiatrachomatis have been shown to increase the rates of preterm labour. Ascending infection from the genital tract can result in intrauterine infection and chorioamnionitis. Chorioamnionitis is thought to cause preterm premature rupture of the membranes (pPROM) , itself an antecedent of preterm labour in approximately 40% of babies born preterm.

7. -Chorioamnionitis (( it may exist without fever , leukocytosis , uterine tenderness , fetal tachycardia )) or any of the classical signs of chorioamnionitis. • If amniocentesis is performed in preterm labor with intact membranes 10-15 % of samples result in positive cultures. • Resistant to conventional Rx with beta mimetic agent may be the only clue for infection .

8. It is possible that aggressive Rx of vaginal & endocervical inf. before pregnancy or even in the 1st trimester may be useful for the prevention of preterm labors . • There is inverse relationship with GA earliest births carry the highest risk of an infectious etiology

9. 2- Other maternal infections resulting in a systemic inflammatory response may also be responsible for initiating preterm labor, including pyelonephritis and pneumonia. In the developing world, malaria is an important cause of preterm labor. (either chemical triggers endotoxins or direct spread of blood borne infections to uterine cavity.

10. 3.Placental abnormalities :{ morphology, implantation or function} it is common with (Placenta previa). 4.Anatomical abnormalities of the uterus: 1-3% could be congenital (septate) or acquired like (leiomyoma the effect of it remain controversial ,minimal influence in absence of cervical involvement). cervical surgery such as cone biopsy,large loop excision of transformation zone, no. of previous surgical cervical dilatation 5.Fetal pathology. 6.Uterine over distention: in multiple gestation & Polyhydramnios.

11. 9 7.Cervical weakness(maternal diethylstilbestrol exposure). 8-Vascular increase in membrane haemosidrin deposits thought to reflect deciduual haemorrhage 9.Idiopathic (20-30%). 10.30–40% of cases of preterm birth are iatrogenic due to deliberate induction of labour or prelabour caesarean section for conditions causing maternal(like severe pre-eclmpsia ,eclampsia, antepartumhaemorrhge or fetal compromise like fetal distress or severe IUGR.

12. Social & epidemiological risk factors preterm labour is more in female of 1. Maternal prepregnancy weight <50 kg . 2.Maternal age extremes (<19; >35 years) 3- parity (nulliparous,grandmultiparous) 4.Race (especially African-American) 5-ethncity(black women) 6.Education (<12 grade) 7.Poor socio-economic. 8.Maternal lifestyle (e.g,smoking, drug abuse unemployment, STD) 9.Inter pregnancy interval < 1 year.

13. 8.Obstetric gynecologic history: prior spontaneous PTB(preterm birth); prior STL(second trimester loss); prior cone biopsy. • 9.Certain medical conditions (e.g., DM, HTN) • 10.Limited prenatal care • 11.Vaginal bleeding (Vaginal bleeding in early pregnancy is associated with increased adverse outcomes later. Both light and heavy bleeding were associated with subsequent preterm labor, placental abruption, and subsequent pregnancy loss prior to 24 weeks). • 12.Stress . • 13.Anemia.

14. Management of asymptomatic high risk women Prediction&prevention of preterm labour. Ideally women should be seen postnatally and the event leading to their preterm birth reviewed. There should be a clear management plan for any subsequent pregnancy. Advice to stop smoking, leaving at least 12 months between pregnancy & dietician advice in women with low BMI.

15. Investigation&treatment during pregnancy to prevent pTL 1.Early dating scan (first trimester U/S is essential to time subsequent investigations precise GA). 2.Bacterial vaginosis.diagnose by vaginal swab and gram staining and microscopy. Oral metronidazole significantly lower the risk of preterm birth In high risk women positive for BV60%.(it might reflect systemic infection) ,5-7 days at standard doses seems appropraite) 3.Asymptomatic bacteriuria. this carry an increased risk for preterm labor, the risk reduced by appropriate antibiotic (be a marker of heavy vaginal microbial colonization or increased risk of pyelonephritis

16. 4.Group B streptococcal colonization (GBS) has been linked weakly to prematurity. Preterm infants are more susceptible to early onset GBS infection acquired during the passage through the birth canal. high risk women for preterm labor are tested for GBS antenatally(but treatment with penicillin is not recommended) • Appropriate intrapartum prophylaxis to be planned(pencillin or clindamycin if allergic to pencillin) • If chorioamnionitis is suspected ,broad spectrum antibiotic therapy including an agent active against GBS- specific antibiotic prophylaxis

17. 5.Cervical ultrasound. There is now good evidence that transvaginalsonographic(TVS) measurement of cervical length can be used to predict the risk of preterm labour in both low- and high-risk pregnancies and in women who are symptomatic. • TAUS for measurement of cervical length not reliable. • Serial digital measurement at each visit for assessing cervical length of no benefit.

18. Two strategie are currently in common use :either serial measurement of cervical length through pregnancy or single measurement of cervical length usually at the time routine US between 18-22 weeks. • Serial appear superior to single measurement . • Absolute cervical length rather than the presence or absence of funneling. If single 21-24 weeks • A cervical length of 15 mm or less at 20–24 weeks predicts a 50% risk of preterm delivery prior to 34 weeks in a low-risk population.

19. 6. Fetal fibronectin testing. Fetal fibronectin is a glycoprotein present in amniotic fluid, placenta and the extra cellular substance of the decidua.any disruption at the choriodecidual interface results in detection in the cervico- vaginal secretion. This measurement after23weeks as levels are often high prior to this gestation

20. Rarely present between 23-34 weeks in vaginal secretions may be used to predict a risk of preterm labour. Fibronectin testing may be used to assess risk in asymptomatic women at high risk of preterm labourif+ve at 24 week the risk is 46%for delivery before 30 weeks, if –ve risk of PTLbelow 1% (method:no digital ,sexual intercourse with in 24 hours the swab introduce in the posterior vaginal fornix for15-20 seconds and read with in 15 minute. False +ve if vaginal bleeding , sexual intercourse

21. 6.Cervical Cerclage. There are at least three circumstances when cerclage placement may be used to prevent preterm birth. First, cerclage may be used in women who have a history three and more recurrent mid trimester losses and/ or PTL who are diagnosed with an incompetent cervix . Second, circumstance is in women identified during , sonographicexamination to have a short cervix less than 25mm insertion of ceclage is not recommended with out previous history, if history of previous more than one 2nd trimester or PTLso US indicated cerclage should be offered if cx length below 25mm by TVUS Third indication is "rescue" cerclage, done emergently when cervical incompetence is recognized in the women with threatened preterm labor .Not recommended for twin

22. 7.Progesterone. Progesterone is thought to inhibit the myometrial contractility. Women who were at high risk of preterm delivery were given a 100-mg vaginal suppository daily between 24 and 33 weeks or weekly injections of 17 α hydroxyl progesterone capruate (250 mg) between 16 and 36 weeks. • progesterone does not appear to prevent preterm birth in multiple pregnancies

23. 8.LIFE STYLE MODIFICATION: stop smoking ,psychological support but no clear role for sexual abstinence no clear role. 9.Salivary oestriolsurge 3 weeks prior to preterm labour has not been proven. 10.Home uterine activity monitors:increase painless uterine activity may precede the onset of labor but early detection of increase activity has not been found to reduce the incidences of PTL

24. Management of symptomatic women (Treatment of established case):- • Management of the woman with symptoms of PTL starts with initial assessment of: • History(low backache,cramping are often cyclical ,vague complaints such as pelvic pressure or increase vaginal discharge,presence of vaginal bleeding should always be taken seriously. • Physical examination:the presence of uterine tenderness,suggesting abruption or chorioamnionitis , • Specific laboratory and other screening tests to establish diagnosis and prognosis, so as to obtain an accurate initial assessment and decide the correct interventions.

25. 1).Evaluation should include determination of the following • a)Gestational Age.Gestational age must be between 24 and 37 weeks' estimated gestational age (EGA), which should be calculated based upon the patient's last menstrual period (LMP), if known, or the previous sonographic estimation if these dates are uncertain. • b)Fetal Weight .especialy below 28 weeks,Care must be taken to determine fetal size by ultrasonography. • c)Presenting Part. The presenting part must be noted because abnormal presentation is more common in earlier stages of gestation.

26. d)Fetal Monitoring. fetal monitoring should be performed to ascertain fetal well-being, criteria used at term is inappropriate. some work suggested that the baseline rate is more important than either deceleration or variability. • Intermitantor continuos in moderately preterm is the same • Steriod suppress both fetal activity and variability umbilical artery Doppler studies can also be influence,absent or reversed end diastolic flow is commonly return after short term .

27. (2).Laboratory Studies • 1. Complete blood count with differential. • 2. Urinalysis, culture, and sensitivity testing. • 3. Speculum examination should be performed(pooling of amniotic fluid,blood,discharge) • Cervical cultures should be sent for gonorrhea and chlamydia. • A wet mount should be performed to look for signs of bacterial vaginosis. Group B streptococcus (GBS) cultures should be taken from the vaginal and rectal mucosa. • A visual assessment of cervical dilatation has been shown to be as accurate as digital examination (significant reduction in the latent interval before labor) • Repeated vaginal examinationin 1-4 hours guided by the severity of symptoms.

28. 4. Ultrasound examination for fetal size, position, and placental location &cervical length (by transvaginal U/S). normal cervix measure 35mm in length , cervical shortening is accompanied by dilatation and funneling of the membranes down the cervical canal. • 5. Hematologic work-up in cases associated with vaginal bleeding . • 7.Fetal fibronectin. A cervical swab is taken to look for fetal fibronectin. A negative test is effective at ruling out imminent delivery (within 2 weeks). A positive test result, however, is less sensitive at predicting preterm birth.

29. 8.Amniocentesis may be useful to ascertain fetal lung maturity in instances where EGA is uncertain, the size of the fetus is in conflict with the estimated date of conception (EDC) (too small, suggesting intrauterine growth restriction, IUGR, or too large, suggesting more advanced EGA), or the fetus is more than 34 weeks' EGA. Specifically, the amniotic fluid can be tested for lecithin/sphingomyelin (L/S) ratio, the presence of phosphatidylglycerol,. Amniocentesis should also be performed in instances where chorioamnionitis is suspected; the fluid should be tested for Gram's stain, bacterial culture, glucose levels, cell count.

30. The next step depends on: • Degree of cervical dilatation. • Duration of pregnancy & estimated fetal weight. • The condition of the fetus & mother. • Any associated medical or obstetrical condition.

31. Allow labour & delivery to proceed when the(first group): • Cervix is 4cm or more dilated. • Membranes are ruptured. • Mother has an acute medical or surgical condition such as thyrotoxicosis, heart disease (NY class III, IV) . • Mother has temperature ≥ 38C or other evidence of symptomatic chorioamnionitis. • 5.Fetal demise.

32. 6.Fetal congenital anomalies incompatible with life ,chromosomal abnormality • 7.Severe fetal distress. • 8-fetal compromise (.Severe IUGR). • 9.Maternal hemorrhage (e.g. abruptioplacentae, placenta previa, disseminated intravascular coagulation) • 10.Severe pre-eclampsia (PE). • 11. Estimated fetal weight => 2500 g. • 12.Adequate fetal lung maturity.

33. Inhibiting Preterm Labor when the(second group) :- Membranes are intact. Gestational age is < 34 weeks. There is no overt maternal or fetal infection. Cervix is < 4 cm dilated. There is no evidence of placental insufficiency or maternal disease to justify ending pregnancy

34. In such patient(second group) the treatment will be: Treatment of patient with established pretemlabour include: 1.Maternal steroid. 2.Tocolytics. 3.Antibiotics. 4-Emergency cerclage

35. Maternal steroid: It has been shown that :steroid administration decrease the incidence of:و neonatal respiratory distress intraventricularhemorrhage neonatal mortality reduction in necrotizing enterocolitis respiratory support,intensive care admission systemic infection in the first 24 hours of life

36. Steroids can be given according to 1 of 2 protocols: (1) betamethasone 12 mg IM every 24 hours for a total of 2 doses better in reducing neonatal cystic periventricularleukomalacia than (2) dexamethasone 6 mg IM every 12 hours for a total of 4 doses. The optimal benefits of antenatal corticosteroids are seen 24 hours after administration of 2nd dose, peak at 48 hours, and continue for at least 7 days

37. The administration of single coarse of corticosteroids to accelerate fetal lung maturity has become the standard of care in the United State(should offer)for all women at risk of preterm delivery between 24 and 34 weeks. Can be considered 23+0-23+6at risk of PTL. Should still be given even it delivery is expected with in 24 hours because it reduce risk of neonatal death with in first 24 hours .Single coarse: no significant short term maternal or fetal adverse effect (sepsis) no clear difference on long term for multiple courses on long term (no clear evidence, it may increase risk of birth weight reduction, behavioral disorders at 3 years of age, higher risk of CP compare to single coarse

38. Multiple coarse not recommended in multiple pregnancy not associated with decrease RDS. (attenuated beneficial effect of single coarse steroid) DM ,impaired OGTT not CI for steroid ,patient should monitor and receive additional insulin the effect can last up to 24 hours after second dose of steroid . Steroid should considered in IUGR(24-36+6) Elective delivery after 33 weeks are at increased risk of respiratory difficulties and may benefit from prophylactic steroids

39. Should given with Caution to women with systemic infection including TB ,sepsis (even no evidence that single coarse can cause profound effect ) Senior opinion in case of chorioamnionitis (delay delivery for steroid adminsration)

40. 2.Antibiotic : No evidence of benefit for use of antibiotics in uncomplicated PTL,but in PPROM significant advantage obtained Patients with preterm labor should be started on antibiotics for prevention of neonatal GBS infection weather known or unknown state . (risk factors for early onset GBS disease these are :PTL,prolonged rupture of the membranes more than 18 hours,fever in labor,GBSbacteriuria detected during the current pregnancy).

41. prophylactic treatment not recommended: during pregnancy and for women undergoing planned C.S in the absence of labor and with intact membranes • Penicillin or ampicillin is used as first-line agents; clindamycin, erythromycin, or vancomycin can be used if the patient is allergic to penicillin. • If the patient is successfully tocolyzed and there is no sign of imminent delivery, GBS prophylaxis can be discontinued . • If chorioamnionitis is suspected ,broad spectrum antibiotic therapy including an agent active against GBS should replace GBS-specific antibiotic prophylactaxis.

42. 3.Tocolytic Drugs: use of tocolytic drugs no clear evidence that they improve outcome , But should considered iffew days to completing a coarse of steroid or in uterotransfere ,associated with prolongation of pregnancy 7 days, not associated with a reduction in perinatal or neonatal mortality or morbidity ,may be considered for women who have had other wise uncomplicated pregnancy. The women most likely to benefit from use of tocolytic drugs: Still very preterm ,inuterotransfere ,completed full steroid Women and her partner should involve in the discussion for the use of tocolytic ,senior obstetrician.

43. -β –Sympathomimetics Ritodrine (Yutopar),-Terbutaline (Bricanyl), salbitamol(ventolin). -Magnesium sulphate. -Ca channel blockers (Nifedipine). -Antiprostaglandins (Indomethacin). -Oxytocin receptor antagonists (Atosiban). -Nitricoxide donors (Glyceryltrinitrate)

44. If a tocolytic drug is to be used, ritodrine (β.agonist) no longer seems the best choice decrease risk of birth with in 48 hours . Atosiban or nifedipine appear preferable as they have fewer adverse effects and seem to have comparable effectiveness in terms of delaying delivery for up to seven days.

45. Nefidipineassociated with improvement in neonatal outcome in comparing with beta agonist delay delivery by 48 hours in compare to atosiban non significant. Magnesuimsulphate :ineffective in delaying PTL should not be used,it associatedwith side effects and adverse effect for the women: adult R.D.S Respiratory depression Cardiac arrest& Low therapeutic ratio  Increase risk of fetal or infant death.

46. Indomethacin is cycloxygenase(COX) enzyme inhibitor: inhibit PG production dose not decrease risk of birth before 32 weeks and increase risk after stop treatment if with drawn at 32 weeks . • A common regimen for tocolysis is indomethacin 100 mg per rectum loading dose (or 50 mg by mouth), then 25–50 mg by mouth or rectum every 4–6 hours. Ultrasound should be performed every 48–72 hours to check for oligohydramnios. Because of the potentially serious fetal effects, many centers limit its use to infants less than 32 weeks' EGA and its duration of use to less than 48 hours.

47. Side effect fetal: • Premature closure of ductusarteriosus, • pulmonary hyperplasia • persistant patent ductusarteriosus necrotizing enterocolitis • Intraventricular hemorrhage. • Maternal: peptic ulcer, Bleeding, Thrombocytopenia& Allergic reaction .

48. Nitric oxidenitroglycerine:no clear impact on birth before32-34weeks. Atosiban well tolerated side effect: Nusea,vomiting,headach,chest pain duspnea Dose:6.75mg over 1 minute, infusion18mg /hours for 3 hours ,6mg/hours up to 4 hours(maximum330mg) duration for duration of treatment for 48 hours 

49. Contraindications to β- Sympathomimetics • Symptomatic maternal cardiac disease, especially outflow obstruction. • Arrhythmia. • Hyperthyroidism. • Severe bleeding. • Severe anemia. • Eclampsia & severe pre- eclampsia. • Uncontrolled insulin dependent diabetes. • If patient is taking monoaminoxidase inhibitors. • Asthma & patient is already taking β- sympathomimetics.

50. Side effect:have high frequency of side effects • Tremer, headache n and v, chest pain ,dyspnea, pulmonary odema with aggressive IV hydration, hyperglycemia ,hypokalemia • Ritodrine: may result in severe life threatening adverse effect for the women.