Antenatal Testing – A Review of the current Recommendations

1. Antenatal Testing – A Review of the current Recommendations Sarah Waller, MD MFM Fellow Department of OB/GYN University of Washington Medical Center October 22, 2010

2. Objectives • To review the background for the origin of antenatal testing • Learn the appropriate response for test results based on procedures and policies established • To learn the various indications and recommended surveillance for specific maternal and fetal conditions • Evaluate the benefits of testing

3. Background • In both animals and humans, fetal heart rate pattern, level of activity, and degree of muscular tone are sensitive to hypoxemia and acidemia • Redistribution of fetal blood flow in response to hypoxemia may result in diminished renal perfusion and oligohydramnios

4. Background • In humans, the range of normal umbilical blood gas parameters has been established by cordocentesis performed in pregnancies in which the fetus ultimately proved to be healthy, and ranges vary by gestational age • Manning et al (1993) • Fetuses with a non-reactive nonstress test (NST) were found to have a mean umbilical vein pH of 7.28. • Cessation of fetal movement appears to occur at lower pH levels; fetuses with abnormal movement were found to have an umbilical vein pH of 7.16 ± 0.08

5. Etiology of Antenatal Deaths 33% 66% • Unexplained • Maternal • Acute chorioamnionitis • Diabetes mellitus • Rheumatologic disorders • Placental • Abruption • Large chorioangiomas • Hypertensive disorders of pregnancy • Fetal • Structural defects • Genetic syndromes • Growth restriction

6. When and How often do Babies die? • Fetal Deaths • Incidence: 6.2/1000 total births (2005) • 25-75% of these may be avoided • Early: stillbirth 20-27 weeks per 1000 total births • Late: stillbirth ≥28 weeks per 1000 total births • Neonatal Deaths • Incidence: 4.5% of all live births (2000) • Early: death <7 days of life per 1000 total live births • Late: death 7-27 days of life per 1000 total live births

7. Etiology of Neonatal Deaths

8. NEED FOR ANTENATAL TESTING Adverse Perinatal Outcomes Cerebral Palsy: 2/1000 live born infants Neonatal encephalopathy: 1.9-3.8/1000 live births May result in permanent neurologic disability

9. Implies an inadequate nutritive or respiratory supply to the fetus secondary to inadequate exchange between the maternal-fetal unit as a consequence of maternal, uteroplacental, or fetal disorders UTEROPLACENTAL INSUFFICIENCY

10. What Tests areAvailable?

11. History of Fetal Monitoring 1980s:Continuous fetal monitoring is widely used in labor

12. Antepartum Testing • Any test of fetal well-being typically has a low false-negative rate and a high false-positive rate

13. Antepartum Testing • Electronic fetal monitoring • Contraction stress test • Nonstress test • Ultrasound • Fetal biometry • Biophysical profile • Amniotic fluid index • Doppler velocimetry • Maternal monitoring of fetal activity

14. Nonstress Test (NST) • Reactive • 2 accelerations within 20 min (may be extended to 40 min) • Nonreactive • <2 accelerations in 40 min • False Negative: 0.2-0.65% • False Positive: 55-90%

15. Advantages of a NST as compared to CST • Faster • Simpler • Nursing not required • Less expensive • Easier to interpret • No contraindications

16. Causes of a Nonreactive NST Fetal Maternal • Hypoxia • Sleep cycle • CNS anomalies • Cardiac anomalies • Fever with fetal tachycardia • Administration of narcotics or sedatives

17. Contraction Stress Test (CST) • False Negative: 0.04% • False Positive: 35-65%

18. Amniotic Fluid Volumes

19. Decreased Amniotic Fluid • Uteroplacental insufficiency • PROM • Congenital anomalies • Chromosomal abnormalities • All are associated with adverse perinatal outcomes

20. Measurement of Amniotic Fluid • Direct measurement • Dye-dilution • Aspiration at delivery • Ultrasound • Single deepest pocket • Amniotic fluid index • 2 x 2 cm pocket technique • Subjective assessment

21. Assessment of Amniotic Fluid Measurement by U/S • Sensitivity for detecting: • Normal fluid is high • Oligohydramnios: 10-25% • Polyhydramnios: 30-45% • No technique is significantly better than another in predicting abnormal fluid or adverse outcome • AFI is 2-3 times more likely to diagnose oligohydramnios and lead to intervention

22. Amniotic Fluid Assessment in Twins • Use single deepest vertical pocket for each twin • Membrane must be visible • >2cm is normal • Subjective assessment is just as accurate

23. Biophysical Profile (BPP) • Acute variables: subject to immediate change • Fetal muscle tone • Fetal movements • Fetal breathing • Fetal reactivity • Chronic variable - take several days to change • Amniotic fluid level

24. Biophysical Profile (BPP) • Normal expression requires signals from the central nervous system • Neurons highly sensitive to hypoxemia • Presence of biophysical variables implies the absence of clinically significant CNS hypoxia at the time of testing • Biophysical variables may also be lost with fetal sleep cycles, transplacental passage of maternal sedatives and glucocorticoids

25. Biophysical Profile (BPP) • Variables are lost in the reverse order of their development as hypoxia worsens • Reactivity / breathing • Movement • Tone • Testing may be initiated as early as 26 weeks • More common at 32-34 weeks • Approximately 80% of late stillbirths will demonstrate abnormal biophysical variables

26. Biophysical Profile (BPP) • False negative tests (rare) • NPV = 99.9% • False positive tests (common) • PPV = 50%

27. Biophysical Profile (BPP)

28. BPP and Perinatal Mortality *The perinatal mortality is 0.8/1000 for structurally normal fetuses with a normal test within 7 days.

29. BPP and Risk of Cerebral Palsy

30. Measures placental resistance to fetal perfusion Doppler Ultrasound

31. Dopplers in Pregnancy • 1977: First use of Doppler ultrasonography to study flow velocity in the fetal umbilical artery • Volume of flow in the UAs increases with advancing gestation • Increased vascular impedance detected in the 1st trimester gradually decreases due to: • Growth of placental unit • Increase in the number of the functioning vascular channels

32. Umbilical artery Dopplers

33. Umbilical artery Dopplers

34. Uses for Dopplers • If Doppler is available, it may be used for the following reasons: • To identify a fetus with IUGR who registers later and you are uncertain of the gestational age • Under further investigation to identify patients at risk for pre-eclampsia

35. Fetal movement assessment • Approximately 10% of women complain of decreased fetal movement (DFM) • Near-term fetuses spend approximately 25% of their time in a quiet sleep state and 60-70% in an active sleep state • Longest period without fetal movements in a normal fetus is about 75 minutes • Fetal movement appears to peak between 9pm and 1am • Hypoglycemia is associated with increased fetal movement • 3rd trimester DFM is associated with a 10 fold increase in perinatal mortality • Over 50% of the perinatal mortality in these patients is diagnosed at presentation

36. Fetal Movement • DFM may be a compensatory mechanism with hypoxemia • Fetal paralysis decreases p02 by 30% • Decreased pO2 causes bradycardia and transient hypertension • Other causes of DFM include: • Decreased amniotic fluid • Maternal drug sedation • Uterine anomaly • Placental position • Maternal obesity • Smoking

37. Evidence for Kick Counts • Neldam et al (1983) • Randomized trial conducted in Denmark • Fetal movement counting was associated with a 73% reduction in avoidable stillbirths • RR 0.27, 95% CI 0.08-0.93 • Grant et al (1989) • N = 68,654 • Results: no significant difference in potentially avoidable late fetal deaths between women who were instructed to count routinely and controls • Mangesi et al (2007) • Completed a systematic review which concluded insufficient evidence to recommend routine fetal movement counting to prevent stillbirth

38. Diagnosis of DFM • No standard method of diagnosis • Wide physiologic variation among fetuses • Use as a primary means of fetal surveillance has not been verified in controlled prospective studies

39. Who should we test antenatally?

40. Indications for Testing Maternal Fetal • Diabetes Mellitus • Hypertension • SLE • Renal Disease • AMA • Thrombophilias • Multiples • Oligohydramnios • Growth restriction • Decreased fetal movement

41. Diabetes Mellitus • 1993: Lagrew et al. • Reviewed 13 studies using NST weekly for fetal surveillance • Results: Among the 23 stillbirths reported within a week of a reactive NST which did not result from acute clinical events 10 women had IDDM • Conclusions: Frequency of testing for women with diabetes increased to twice per week • 1995: Kjos et al. • Analyzed 2134 women with GDM who had twice weekly NST and weekly AFI’s • Results: No stillbirths within 4 days of the last test • Overall corrected stillbirth rate for the group was 1.4/1000

42. Hypertension of Pregnancy • Includes: chronic hypertension, pregnancy-induced hypertension and pre-eclampsia • Pathophysiology • Vasoconstriction affecting the uteroplacental circulation, intervillous space blood flow may be compromised and this can result in interruption in the supply of oxygen to the fetus • Chronic fetal compromise resulting from uteroplacental insufficiency caused by these various hypertensive disorders may result in intrauterine growth restriction (IUGR) and abnormal fetal heart rate patterns

43. Hypertension of Pregnancy • 1993: Sibai et al. recommended testing all chronic hypertensives • 2007: Sibai and colleagues recommend testing only those hypertensive patients with pre-eclampsia and/or IUGR • ACOG Practice Bulletin: • Does not recommend antepartum fetal testing in patients with mild to moderate blood pressure abnormalities on no medications and in the absence of preeclampsia and/or IUGR

44. Multiples • NST is the primary method for fetal heart rate testing in twins • Initial reports used independent electronic fetal monitoring systemsfor each fetus and reported failure rates of 2-15% in successfully capturing both fetuses • Studies found that reactive NSTs conferred a good prognosis with no perinatal deaths and rates of growth restriction ranging from 8-28% • Nonreactive NSTs were associated with rates of fetal growth restriction of 55-100% and perinatal mortality rates of 50% or higher

45. Multiples • Knuppel et al assessed the impact of initiating routine NSTs on all twins after 31 weeks gestation. • Compared a historical group of 129 twin pairs not receiving routine NSTs to a subsequent group of 90 twin pairs receiving routine weekly NSTs. • 6/258 fetuses (2.3%) in the control group had perinatal deaths, while there were no deaths in the routine NST group.

46. Growth Restriction • Incidence: Affects 15% of pregnancies • Defined as <10%ile for gestational age in most studies • Pathophysiology: reduction of uterine perfusion decreases fetal glucose and amino acid delivery which leads to down-regulation of both the insulin and the insulin-like growth factor-1 endocrine axis and hepatic glucose metabolism. • Glycogenolysis with a decrease in liver size, redirection of gluconeogenic amino acids from endogenous protein breakdown, and eventually, delayed longitudinal growth

47. Growth Restriction • 2000: McGowan et al. • Pilot trial of 167 woman with U/S identified IUGR were randomized to 2x weekly testing versus every 2 week testing • Results: No different in maternal morbidity if emergent C/S and unable to assess fetal primary outcome of combined morbidity • Women in 2x weekly group had more testing, higher rates of IOL (25%) and earlier deliveries (4 days) • 2004: Odibo et al. constructed a decision analysis model to determine best antenatal testing strategy for IUGR fetuses • Compared with the other options, biophysical profile was the best strategy to guide physicians on the timing of the delivery of the preterm growth-restricted fetus • Individual tests have a limited ability to distinguish between physiologic and pathologic variation in fetal status

48. Postdates • Incidence: 4-19% of pregnancies reach or exceed 42 weeks gestation • Divon et al. evaluated fetal and neonatal mortality rates in 181,524 accurately dated term and prolonged pregnancies • Study showed a small but significant increase in fetal mortality in accurately dated pregnancies that extend beyond 41 weeks gestation and demonstrated that fetal growth restriction is independently associated with a large increase in perinatal mortality in these pregnancies

49. Postdates • 2004: Caughey et al. showed several maternal and fetal complications evaluated in a large (n = 45,673) retrospective, cohort study • Conclusion: risks to both mother and infant increase as pregnancy progresses beyond 40 weeks' gestation, and that antenatal fetal testing should begin sooner than current recommendation of 42 weeks of gestation • 2007 Cochrane Database of Systematic Review • 26 trials of variable quality were included • Routine induction of labor after 41 weeks gestation appears to reduce perinatal mortality • Not enough evidence to evaluate the effects of antenatal testing on fetal wellbeing.

50. History of stillbirth • Women who have suffered one stillbirth are at increased risk for perinatal mortality in subsequent pregnancies • The National Institute of Neurological Diseases and Stroke determined that patients with previous stillbirths had a perinatal mortality rate of 73/1000 in subsequent pregnancies and nearly 2% of their surviving children were neurologically abnormal at 1 year of age • UK study reported that the risk of poor outcomes in subsequent pregnancies was more than doubled among women with previous stillbirths