1. Fetal Growth Restriction Steven R. Allen, MD Scott & White Clinic TAMU-HSC

2. Educational Objectives Review epidemiology and significance of fetal growth restriction (FGR) Know etiologies (= risk factors) Discuss screening strategies for FGR Evaluate the role for Doppler velocimetry in the diagnosis & mgmt of FGR Develop treatment strategies for FGR

3. Arbitrary threshold for “growth restriction” Weight Gest Age, weeks

4. Variables affecting normal fetal growth* Gender Ethnicity Number of fetuses Altitude Parental phenotype * generally not accounted for in growth curves

5. Significance of fetal growth restriction (FGR) 3-10% of newborns are “growth restricted” associated morbidities intrapartum FHR abnormalities cord blood acidemia cesarean delivery neonatal hypoglycemia, hypothermia, and hyperbilirubinemia 1/4 stillbirths are SGA

6. FGR: neonatal morbidities 27-32 wks gestation % NS* NS *RDS: not benefited by FGR AJ Perinat 2000;17:187

7. Long term implications of FGR Outcome related to etiology - worse for aneuploidy, viral infxn Catch-up growth common Adult risks: HTN, hypercholesterolemia Minimal reduction in IQ not predictive of academic achievement IQ J Pediatr 2001;138:87

8. Long term implications of FGR Barker “thrifty phenotype” hypothesis Fetus adapts to malnutrition –Cephalized blood flow –Metabolic programming beneficial to malnourished fetus is detrimental if adequate nutrition later available Unknowns –Molecular basis –Relative roles of genetic & environmental factors RR LBW vs heaviest Ozanne. Online review. 9/12/02. http://tem.trends.com

9. Pathophysiology of FGR Cellular Hyperplasia Cellular Hypertrophy Trimester 13 “symmetric” “asymmetric”

10. Etiology of FGR

11. “Symmetric”: infection (<5%) malformation aneuploidy low mat wt, wt gain multiple gest XR exposure

12. Etiology of FGR “Symmetric”: tobacco alcohol substance abuse teratogens

13. Etiology of FGR “Asymmetric”: HTN renal dis thrombophilia hypoxia anemia advanced DM malnutrition “Constitutionally small” Placental mosaicism (up to 1/4)

14. Prior IUGR as a predictor of subsequent stillbirth OR Wks gest age of prior SGA birth Swedish birth registry 1983-1997 Surkan. NEJM 2004;350;777-85

15. Defects in “classic” model of FGR subsets Many preterm fetuses with growth restriction secondary to maternal HTN have symmetric FGR Many aneuploid fetuses have asymmetric growth (“head sparing”)

16. Classification of FGR symmetric asymmetric

17. Abnormal metabolic parameters seen in some populations with FGR Most FGR fetuses have normal PO 2 & PCO 2 Hct & Hgb usually normal, with high MCV and RDW (erythropoeisis/reticulocytosis) Inconsistent hypoglycemia (& hypo-insulinemia) Increased ratio of non-essential:essential AA Hypertriglyceridemia Thrombocytopenia

18. Screening for FGR Etiologies = risk factors Fetal Maternal-fetal Maternal Idiopathic

19. Screening for FGR Physical exam Serial fundal height: between 18- 30 weeks, FH(+/- 2-3 cm) = EGA in weeks –sensitivity for FGR = 40-67% –false pos rate = 50%

20. Screening for FGR Ultrasonography EFW Abdominal circumference Head:abdomen ratio Serial measurements (rate of growth) Amniotic fluid volume Anatomic survey indicated if FGR detected

21. Screening for FGR Ultrasonography 3rd TM AC sensitivity for FGR = 80% (no different than sensitivity of FH) Reserve US for those pts at risk for FGR: –risk factors –S<D –prior SGA ACOG Prac Bull #12, 1/2000

22. Doppler velocimetry Screening for FGR sensitivity in Low Risk population: 15-30% sensitivity in Hi Risk population: 75-95% commonly associated with FGR, but not diagnositic NOT uniquely helpful

23. Doppler velocimetry: S/D ratio S/D = 3.1

24. Doppler velocimetry Management of FGR Umbilical artery: S/D ratio increases with placental resistance

25. Umbilical artery in FGR

26. Doppler velocimetry Management of FGR Umbilical artery: S/D ratio increases with placental resistance Middle cerebral artery: S/D ratio decreases with cephalization (“head sparing”)

27. Middle cerebral artery in FGR

28. Doppler velocimetry Management of FGR Umbilical artery: S/D ratio increases with placental resistance Middle cerebral artery: S/D ratio decreases with cephalization (“head sparing”) Umbilical vein: becomes pulsatile with heart failure

29. Umbilical vein in extreme FGR

30. Doppler velocimetry Management of FGR Umbilical artery: S/D ratio increases with placental resistance Middle cerebral artery: S/D ratio decreases with cephalization (“head sparing”) Umbilical vein: becomes pulsatile with heart failure Ductus venosus: decreased forward velocity or reversal of “a” wave (atrial kick) Changes typically occur in this sequence prompting a logical screening sequence

31. Ductus venosus in extreme FGR “a” wave

32. FGR example 1 risk factor: tobacco Weight Gest Age, weeks Umb artery S/D nl

33. FGR example 1: mgmt d/c tobacco serial US biophysical testing and FACs delivery plan?

34. Umb art S/D predicts risk of neonatal morbidity % J US Med 2000;19:661

35. FGR example 2 risk factor: CHTN Weight Gest Age, weeks Umb artery S/D elevated

36. FGR example 2: mgmt MCA S/D ratio - minimally decreased; normal umb venous flow pattern R/O PIH serial US biophysical testing and FACs delivery plan?

37. Interventions with UNproven efficacy nutrient treatment zinc supplementation calcium supplementation plasma volume expansion oxygen heparin aspirin

38. FGR example 3 risk factor: AMA Weight Gest Age, weeks Oligohydramnios; umb art AED; MCA S/D low; umb vn pulsatile

39. FGR example 3: mgmt Continuous monitoring Corticosteroids Delivery after 24 hrs if stable

40. Considerations for delivery Non-reassuring acute fetal status Cessation of growth over 2-4 wks Oligohydramnios “When extrauterine survival is likely in the presence of significantly abnormal antenatal testing” ACOG Prac Bull #12, 1/2000

41. FGR: Summary Recommendations (Level A) Umbilical artery velocimetry is useful to reduce perinatal death once FGR is suspected or diagnosed No specific treatments (nutritional supplements, oxygen, heparin, ASA, volume expansion, or antihypertensive agents) effectively prevent or treat FGR ACOG Prac Bull #12, 1/2000

42. FGR: Summary Recommendations (Level C) Antepartum surveillance should be instituted when extrauterine survival is possible No particular form of antenatal testing is superior Screen low-risk pts for FGR using physical exam US is appropriate screen for FGR in hi-risk pts ACOG Prac Bull #12, 1/2000