1. E. Rebecca Pschirrer, MD, MPH Dartmouth Medical School Maternal Fetal Medicine

2. Objectives  Review risks of obesity and congenital anomalies  Impact of BMI on screening  Review screening options  Best choices for obese patients

3. Background  2 – 3% live births affected by structural anomaly 2.25% cardiac defect 1 per 1500 neural tube defect  Majority of birth defects occur in euploid fetuses

4. Obesity Epidemic  2003-2004 National Health and Nutrition Examination Survey (NHANES) Women 20 – 39 years old 28.9 % BMI ≥ 30 kg/m 2 8.0 % BMI ≥ 40 kg/m 2

5. 1999 Obesity Trends* Among U.S. Adults BRFSS, 1990, 1999, 2008 (*BMI 30, or about 30 lbs. overweight for 5’4” person) 2008 1990 No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30% Data from CDC Behavior Risk Factor Surveillance System

6. Congenital Anomalies  Overweight & obesity associated with  risk structural anomalies Neural tube defects Cardiovascular anomalies Orofacial clefting Other congenital anomalies

7. Watkins, Pediatrics, 2003  Population-based case-control study  Pregestational diabetics excluded  Spina bifida OR 3.5, CI 1.2 – 10.3  Omphalocele OR 3.3, CI 1.0 – 10.3  Cardiac defect OR 2.0, CI 1.2 – 3.4  Multiple anomalies OR 1.9, CI 1.1 – 3.4

8. Watkins, Pediatrics, 2003  Population-based case-control study  Pregestational diabetics excluded  Spina bifida OR 3.5, CI 1.2 – 10.3  Omphalocele OR 3.3, CI 1.0 – 10.3  Cardiac defect OR 2.0, CI 1.2 – 3.4  Multiple anomalies OR 1.9, CI 1.1 – 3.4

9. Stothard, JAMA, 2009  Systematic review & meta-analysis  1944 potential articles  39 review; 18 meta-analysis  Pooled OR comparing risks among overweight, obese, & recommended weight women  Anomalies ≥ 150 cases reported in literature

10. Stothard, JAMA, 2009  Spina bifida OR 2.24, CI 1.86 – 2.69  CV anomalies OR 1.30, CI 1.12 – 1.51  Cleft palate OR 1.23, CI 1.03 – 1.47  Cleft lip and palate OR 1.20, CI 1.03 – 1.40  Anorectal atresia OR 1.48, CI 1.12 – 1.97  Hydrocephaly OR 1.68, CI 1.19 – 2.36  Limb reduction anomalies OR 1.34, CI 1.03 – 1.73

11. Stothard, JAMA, 2009  Spina bifida OR 2.24, CI 1.86 – 2.69  CV anomalies OR 1.30, CI 1.12 – 1.51  Cleft palate OR 1.23, CI 1.03 – 1.47  Cleft lip and palate OR 1.20, CI 1.03 – 1.40  Anorectal atresia OR 1.48, CI 1.12 – 1.97  Hydrocephaly OR 1.68, CI 1.19 – 2.36  Limb reduction anomalies OR 1.34, CI 1.03 – 1.73

12. Stothard, JAMA, 2009  Spina bifida OR 2.24, CI 1.86 – 2.69  CV anomalies OR 1.30, CI 1.12 – 1.51  Cleft palate OR 1.23, CI 1.03 – 1.47  Cleft lip and palate OR 1.20, CI 1.03 – 1.40  Anorectal atresia OR 1.48, CI 1.12 – 1.97  Hydrocephaly OR 1.68, CI 1.19 – 2.36  Limb reduction anomalies OR 1.34, CI 1.03 – 1.73

13. Stothard, JAMA, 2009  Congenital anomalies not analyzed in meta-analysis: Risk of omphalocele and risk of multiple congenital anomalies significantly higher among obese women  Not included in meta-analysis due to low power / less than 150 cases reported

14. Malformation Etiology  Undiagnosed or unrecognized diabetes  Altered metabolism (  insulin, triglycerides, uric acid, estrogen) Increased insulin resistance Fuel mediated teratogenesis  Nutritional deficits  Low folate levels Supplementation not found to decrease risk

15. Challenges of Diagnosis  Poor sensitivity of ultrasound  “Ultrasound was limited by maternal habitus”  Spine & heart views particularly challenging in obese patients

16. Hendler, 2004, Intl Jnl Obesity Challenges of Diagnosis

17. Dashe, J Ult Med, 2009 Challenges of Diagnosis  Retrospective cohort, singleton pregnancies, standard second trimester ultrasound exam (AIUM)  18 – 23+6 weeks EGA  10 components analyzed for adequacy of visualization Cerebral ventricles, posterior fossa, midline face, 4-chamber heart, spine, ventral wall, umbilical cord, stomach, kidneys, bladder

18. Dashe, J Ult Med, 2009 Challenges of Diagnosis  Exclusion criteria: indication for targeted ultrasound Pregestational DM, teratogen exposure, family history, increased risk on screening  10,112 women  2676 (26%) obese  Results: decrease in ability to adequately visualize fetal anatomy with increasing maternal BMI Class 1 57%, class 2 41%, class 3 30%

19. Dashe, J Ult Med, 2009 Challenges of Diagnosis

20. Hendler, J Ult Med, 2005 SUV: Repeat the ultrasound?

21. Dashe, Obstet Gyn, 2009  Retrospective cohort, 5 year period 10,112 standard u/s 1,098 targeted u/s  79 fetuses with undiagnosed anomalies, 0.7%  Decreased detection of anomalies with increasing BMI with either standard or targeted ultrasound Detection even less in pregnancies complicated by pregestational diabetes 38% vs. 88%, p < 0.001 Challenges of Diagnosis: Decreased Detection

22. Decreased detection of anomalies Dashe, Ob Gyn, 2009

23. Dashe, Obstet Gyn, 2009  Broad range of anomalies not detected Straight forward: endocardial cushion defect Challenging: micrognathia Not detectable at 18 – 24 wks: GI atresia Not detectable: absent ear canal  Residual risk after normal U/S: 0.4% normal BMI 1% BMI ≥ 30 Challenges of Diagnosis: Residual Risk

24. What to do?  Image enhancing modalities Harmonic imaging Compound imaging Speckle reduction filters  Approach through least SQ adipose Periumbilical, suprapubic, R / L iliac fossae  Endovaginal ultrasound

25. Techniques to Enhance Visualization 4-chamber heartPosterior fossa

26. First trimester anatomy?  11 – 13+6 weeks  Endovaginal & abdominal u/s  Structural malformation detection rates range 16 – 84%  Possible 2 stage process  Not ready for prime time Research re: feasibility, outcomes Cost benefit analysis

27. Aneuploidy Screening Tests  Maternal age  Quad Screen  First Trimester Screen  Integrated Screen  Sequential Screen  Serum Integrated Screen

28. Weight Correction of Serum Analytes  Adjust analyte concentration or MoMs for maternal weight  Placental- or fetal-derived markers more diluted in heavier women due to larger blood volume  Conversely, more concentrated in lighter women because of smaller blood volume

29. Comparing Screening Methods for Down syndrome Quad Marker Screen First Trimester Screen Serum Integrated Screen SequentialScreenIntegratedScreen Detection Rate 81%84%85%89%90% Screen Positive 5%5%3%3%3%

30. Conclusions  Screening for birth defects & aneuploidy is a significant challenge in obese women  Reduction in detection rate of congenital anomalies  Discussion & documentation of limitations with patients  Document BMI in ultrasound reports