prevention of preterm birth :

1. prevention of preterm birth: Dr. Omondi-Ogutu Department of Obstetrics & Gynaecology SOM-UON

2. declaration • Conflict of interest- none • Funding -none

3. PTB Preterm birth is delivery before 37 completed weeks of gestation in the human species

4. background • PTB is the major determinant of infant mortality in most countries in the developed nations one in 20 births and two in three perinatal deaths, is associated with preterm birth, the magnitude in the developing countries is larger Lumley J. Aust. Paediatr. J. (1988) 24, 101-111

5. PTB • The incidence of preterm birth varies between 5% and 11% of all births • its prevention continues to remain elusive, with many reports indicating an increase in the prevalence of preterm birth over recent years. • Assisted reproductive techniques and the concomitant increase in multiple pregnancies have contributed to the rise Steer P BJOG 2005. Goldberg Lancet 2008

6. PTB • accounts for 70% of the total perinatal mortality in developed countries, excluding deaths related to congenital anomalies. • For surviving infants born preterm, there may be significant health consequences with lasting disabilities, including cerebral palsy, mental retardation, respiratory problems, hearing and vision impairment

7. USE OF PROGESTERONE TO REDUCE PRETERM BIRTHACOG COMMITTEE OPINIONOCTOBER 2008 • Progesterone supplementation for the prevention of recurrent preterm birth should be offered to women with a singleton pregnancy and a prior spontaneous preterm birth due to spontaneous preterm labor or premature rupture of membranes. Current evidence does not support the routine use of progesterone in women with multiple gestations. Progesterone supplementation for asymptomatic women with an incidentally identified very short cervical length (less than 15 mm) may be considered; however, routine cervical length screening is not recommended.

8. “effective therapeutic interventions to decrease spontaneous preterm delivery have not been discovered.” R.L. Goldenberg 2002

9. Classification of PTB • indicated are • hypertensive disorders, • hemorrhage, • acute or chronic fetal compromise (non-reassuring fetal testing or intrauterine growth restriction). • Such iatrogenic preterm births are increasing, particularly at earlier gestations

10. 2 .spontaneous • About two-thirds of preterm births are spontaneous; these births follow spontaneous onset preterm labor and preterm premature ruptured membranes, or related diagnoses, such as cervical insufficiency.(NOT INCOMPETANCE) • There is still an increase in PTB in the low risk groups of up to 51% in the last 10 years, and despite several intervention it has not regressed Shennan BMJ, McCormick New Eng J

11. aetiology of PTB The ‘cause’ of preterm birth is multifactorial, with • social, • psychological, and • Biological factors playing a role Prysak M, ObstetGynecol 1995

12. Prevention of Preterm Birth-GoldenbergNEJM 1998

13. PTB • Increased understanding of the pathophysiology of preterm labour has resulted in increased focus on preventive strategies • In the past, medical efforts focused on ameliorating the consequences of prematurity rather than preventing its occurrence. • This approach resulted in significant advances in neonatal medicine With no effect on the rate of preterm birth • .

14. Primary prevention Is a limited strategy which involves public education, smoking cessation, improved nutritional status and avoidance of late preterm births.

15. Primary prevention • Primary prevention is the strategy directed at all women before or during pregnancy to prevent and reduce the risk of preterm birth. • include weight optimization, nutritional supplementation, smoking cessation and avoidance of late-preterm births

16. BMI <19 kg/m2 have the greatest risk of PTB compared to women with BMI >30 kg/m • serum levels of micronutrients: iron, folateand zinc are highly prevalent among pregnant women in low income settings, and are associated with preterm birth and stillbirth • There is still lots of controversies on the benefits of micronutrient supplementation in preventing preterm births

17. Secondary prevention • Secondary prevention efforts are directed at women who are already at higher risk of preterm birth • The most significant and consistently identified risk factor for preterm birth is a woman’s history of previous PTB • rate of recurrent preterm birth in this group of women is 25% ,2.5-fold increased relative risk when compared to women with no previous spontaneous preterm birth.

18. Secondary prevention • Focuses on recurrent preterm birth which is the most recognizable risk factor. • Other accepted strategies include cervical cerclage, progesterone and dedicated PTB clinics, which we do not have here. • The role of antibiotics and anti-inflammatory treatments in the prevention of PTB needs more work to be done. Karen Flood, Fergal Malone Seminars in Fetal & Neonatal Medicine (2012) 58e63

19. Cervix- cerclage • Has been with us since 1950 from the Lash and Lash, Shirodkar 1955 to McDonald in the early 60’s • The pathophysiology of cervical shortening and the precise mechanism by which cerclageconfers benefit remains largely unknown. • Use of ultrasonography to determine the cervical length vs clinical assesment.in client selection’ • Benefit of Shirodkar in failed McDonald Stich Omondi 0gutu EAMJ

20. progesterone • The administration of progesterone as an agent for the prevention of preterm birth dates to the early 1960s • A recent analysis suggested that almost 10,000 spontaneous preterm births could be averted each year and that the overall preterm birth rate would decline by 2% with administration of progesterone in high risk populations. Armstrong J. Am J ObstetGynecol 2007

21. Actions of Progesterone on the Myometrium • Decreases conduction of contractions • Increases threshold for stimulation • Decreases spontaneous activity • Decreases number of oxytocin receptors • Suppresses the inflammatory cascade

22. Progesterone on the Myometrium contd. • Inhibits T lymphocyte development • Promotes expression of prostaglandin EP2 receptor • Prevents formation of gap junctions • Administration of progesterone antagonists stimulates onset of labor in women at term

23. Omega-3 fish oil • No beneficial effect has been reported

24. COCHRANE : MgSO4 for preventing preterm birth in threatened preterm labour • Authors’ conclusions Magnesium sulphate is ineffective at delaying birth or preventing preterm birth, and its use is may associated with an increased mortality for the infant. Any further trials should be of high quality, large enough to assess serious morbidity and mortality, compare different dose regimens, and provide neurodevelopmental status of the child. • CrowtherCA, Hiller JE, Doyle LW (2009)

25. COCHRANE • Bed rest in singleton pregnancies for preventing preterm birth (Review) Authors’ conclusions • There is no evidence, either supporting or refuting the use of bed rest at home or in hospital, to prevent preterm birth. Sosa C, Althabe F, Belizán JM, BergelE (2010)

26. COCHRANE PROBIOTICS FOR PREVENTION OF PRETERM LABOUR Authors’ conclusions Although the use of probiotics appears to treat vaginal infections in pregnancy, there are currently insufficient data from trials to demonstrate any impact on preterm birth and its complications Mohammad Othman, ZarkoAlfirevic, James P Neilson (2012)

27. In a world where nothing seems to work, Progesterone seems effective in preventing PTD in subsets of high risk patients • This effectiveness, is supported by decades of studies and clinical experience

28. Magnesium Sulfate • First-line tocolytic is due to its familiarity, ease of use, and almost absence of serious maternal AEs • minor side effects- feeling hot/flushed, n/v, blurred/double vision, or lethargic • Lethargy, hypotonicity, and low Apgar scores are the primary side effects in neonates • Stops 96% of PTL without cervical changes and 75-85% with cervical changes • A meta-analysis showed no substantial effect on the proportion of women delivering within 48hrs

29. β-sympathomimetic • Terbutaline is β2-receptor specific which is the receptor causing uterine relaxation and has replaced ritodrine • If contractions continue after 2 treatments, most clinicians switch to Mag. Sulfate • SEs- flushing, tachycardia, palpitations, hypotension, cardiac arrhythmias, chest pain, EKG changes, and myocardial ischemia with the most common serious AE being pulmonary edema • β-agonists are better in prolonging pregnancy 3-7 days and increasing birth weight, but have not shown a significant reduction in perinatal M & M

30. Calcium Channel Blockers • Initial choice in Europe, but remain 2nd line treatment in the U.S. • Appeal- effectiveness, ease of oral administration, rapid onset of action, tolerable SE, & lack of known neonatal AE • Reduced # of women giving birth within 7 days of treatment and before 34wks of gestation, assoc. with a reduction in neonatal RDS, necrotizing enterocolitis, intraventricular hemorrhage, and neonatal jaundice • SE- dizziness, lightheadedness, HA, flushing, nausea, and transient hypotension • MgSO4 and Nifedipine should not be used together

31. Antiprostaglandin synthetase inhibitors • Prostaglandins are key components in the labor process • Indomethacin- nonspecific COX-1 & 2 inhibitor • Reduces the # of deliveries within 48hrs & before 37wks, but due to concern over the SEs, it is typically used only when other therapies fail • Fetus should be monitored for signs of ductal constriction or oligohydramnios and could mask chorioamnionitis and may independently increase the rate of NE and grade III to IV intraventricular hemorrhage • Compared with β-mimetics, MGSO4, and atosiban… indomethacin proved superior in tocolytic efficacy without an increase in neonatal or maternal morbidity

32. Comparison • Pregnancy was prolonged more than 48 hours significantly more frequently in patients receiving nifedipine when compared to β-agonists • When compared to magnesium sulfate, there was no difference in efficacy, but nifedipine was better tolerated • When indirectly compared with atosiban, nifedipine is more effective and is assoc. with a significant reduction in RDS, but when directly compared the efficacy was the same, but the AE of nifedipine were significantly more

33. END