1. UOG Journal Club: June 2014 Aortic and carotid arterial wall thickness in term small-for-gestational-age newborns and relationship with prenatal signs of severity I. Stergiotou, F. Crispi, B. Valenzuela-Alcaraz, M. Cruz-Lemini, B. Bijnens, E. Gratacos Volume 43, Issue 6, Date: June 2014, pages 625-631 Journal Club slides prepared by Dr Leona Poon (UOG Editor for Trainees)

2. IUGR may be linked to adverse pregnancy outcome through profound changes in the metabolic and cardiovascular (CV) systems (Hattersley, 1999; Girsen, 2007; Crispi, 2008; Batalle, 2012) Vascular intima-media thickness (IMT) is a standard diagnostic procedure in assessing CV risk in asymptomatic adults (Stein, 2008) There is an inverse relationship among aortic IMT (aIMT), arterial stiffness and low birth weight (BW) (Skilton, 2005; Koklu ,2006; Mori 2006; Tauzin 2006). Recent evidence suggests that late SGA fetuses have worse CV and neurodevelopmental outcomes than initially anticipated (Comas, 2011; Crispi, 2012). Hattersley AT et al. Lancet 1999;353:1789-92. Koklu E et al. Horm Res 2006;65:269-75. Mori A et al. Pediatrics 2006;118:1034-41. Skilton MT et al. Lancet 2005;365:1484-6. Stein et al. J Am Soc Echocardiogr 2008;21:93-111. Tauzin L et al. Pediatr Res 2006;60:592-6. Batalle D et al. Neuroimage 2012;60:1352-66. Comas M et al. Am J Obstet Gynecol 2011;205:57.e1-6 Crispi F et al. Am J Obtet Gynecol 2008;199:254. Crispi F et al. Am J Obstet Gynecol 2012;207:121.e1-9. Girsen A et al. Ultrasound Obstet Gynecol 2007;29:296-303.

3. Aortic and carotid arterial wall thickness in term small-for-gestational-age newborns and relationship with prenatal signs of severity Stergiotou et al., UOG 2014 To assess carotid arterial wall and aortic intima-media thickness (IMT) in term growth-restricted newborns with and without prenatal signs of severity Objective

4. Aortic and carotid arterial wall thickness in term small-for-gestational-age newborns and relationship with prenatal signs of severity Stergiotou et al., UOG 2014 Patients and Methods Prospective cohort study of 201 newborns prenatally diagnosed as SGA or AGA and delivered after 37 weeks, subdivided into: 1. SGA with prenatal signs of severity defined by estimated fetal weight (EFW) and confirmed BW < 3rd percentile or uterine artery mean pulsatility index (mean UtAPI) > 95th percentile or cerebroplacental ratio < 5th percentile; 2. SGA without prenatal signs of severity defined by EFW and BW between 3rd and 10th percentiles with normal mean UtAPI and cerebroplacental ratio; 3. Controls defined by EFW and confirmed BW > 10th percentile, with no pregnancy complications.

5. Patients and Methods Aortic and carotid arterial wall thickness in term small-for-gestational-age newborns and relationship with prenatal signs of severity Stergiotou et al., UOG 2014 Doppler examination before delivery included uterine artery (UtA), umbilical artery (UA) and middle cerebral artery (MCA) Controls were matched 2 to 1 with cases by gender and gestational age at delivery ( 1 week). Exclusion criteria were chromosomal or genetic disorders, monochorionic (MC) twin pregnancy and evidence of infection. Fetal and neonatal weight centile were calculated according to local reference curves. Neonatal blood pressure (BP) was obtained using a validated ambulatory automated device; BP centiles were calculated using local standards.

6. Patients and Methods Aortic and carotid arterial wall thickness in term small-for-gestational-age newborns and relationship with prenatal signs of severity Stergiotou et al., UOG 2014 Longitudinal clips of the far wall of both carotid arteries were obtained ~1cm proximal to the bifurcation using a 13-MHz linear-array transducer Longitudinal clips of the far wall of the proximal abdominal aorta were obtained in the upper abdomen using a 10-MHz linear probe. Carotid artery IMT (cIMT) and aIMT measurements were performed offline according to the standardized trace method protocol (Figure 1). To obtain IMT, the average of 3 end-diastolic frames selected across a length of 10 mm and analyzed for mean and maximal IMT was used Intraobserver and interobserver variability was determined.

7. Patients and Methods Aortic and carotid arterial wall thickness in term small-for-gestational-age newborns and relationship with prenatal signs of severity Stergiotou et al., UOG 2014 Figure 1. Ultrasound assessment of mean cIMT (a, c, e) and aIMT (b, d, f) in controls (a, b) and in SGA without (c, d) and with (e, f) signs of severity

8. Statistical analysis Aortic and carotid arterial wall thickness in term small-for-gestational-age newborns and relationship with prenatal signs of severity Stergiotou et al., UOG 2014 Intraobserver reproducibility was assessed by intraclass correlation coefficients (ICCs) and coefficients of variation (CV). Interobserver reproducibility was assessed by CV for each parameter. An estimated sample size of 32 women per group was achieved for a power > 90% and 5% type 1 error level. Comparisons by one-way ANOVA, based on log-transformed data adjusted with Bonferroni post-hoc test and Pearsons chi-square test. Models for vascular results were adjusted by multiple linear regression by gender, gestational age at birth and age at evaluation. Polynomial orthogonal contrasts were constructed to test for linear trends of parameters across severity groups.

9. Aortic and carotid arterial wall thickness in term small-for-gestational-age newborns and relationship with prenatal signs of severity Stergiotou et al., UOG 2014 Characteristics Controls (n=134) SGA without signs of severity (n=32) SGA with signs of severity (n=35) P Maternal characteristics Smoking 22 (16.4) 8 (25.0) 13 (37.1)* 0.028 Prenatal ultrasound GA at scan (wks) 34.1 (33.2 to 37.2) 37.7 (36.5 to 38.4)* 37.6 (37.1 to 38.5)*