UOG Journal Club: Aortic and carotid arterial wall thickness in term small-for-gestational-age newborns and relationship with prenatal signs of severity
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UOG Journal Club: Aortic and carotid arterial wall thickness in term small-for-gestational-age newborns and relationship with prenatal signs of severity

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Aortic and carotid arterial wall thickness in term small-for-gestational-age newborns and relationship with prenatal signs of severity ...

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
http://onlinelibrary.wiley.com/doi/10.1002/uog.13245/abstract

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UOG Journal Club: Aortic and carotid arterial wall thickness in term small-for-gestational-age newborns and relationship with prenatal signs of severity UOG Journal Club: Aortic and carotid arterial wall thickness in term small-for-gestational-age newborns and relationship with prenatal signs of severity Presentation Transcript

  • 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)
  • • 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.
  • 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 View slide
  • 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. View slide
  • 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.
  • 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.
  • 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
  • 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 Pearson’s 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.
  • 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)* <0.001 UA PI (Z-score) -0.04 (-0.57 to 0.53) 0.06 (-0.31 to 0.39) 0.19 (-0.11 to 0.49)* 0.04 Delivery data GA at delivery (wks) 39.5 (38.5 to 40.2) 38.7 (38.2 to 40.0) 38.5 (38.1 to 39.7)* 0.012 Cesarean Section 22 (16.4) 6 (18.8) 15 (42.9)* 0.006 Cesarean Section for non- reassuring fetal status 4 (3.0) 2 (6.3) 5 (14.3)* 0.033 BW (g) 3350 (3078 to 3622) 2603 (2455 to 2727)* 2200 (2070 to 2400)* <0.001 BW percentile 55 (27 to 80) 4 (2 to 6)* 1 (0 to 2)* <0.001 Days in neonatal intensive care unit 0 (0 to 0) 0 (0 to 0) 4 (3 to 6)* <0.001 Table 1. Significant baseline characteristics and perinatal outcomes of study groups * P<0.05 compared with controls
  • Results 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 Variable Intraobserver Interoberver CV (%)ICC (95% CI) CV (%) Mean right cIMT 0.827 (0.790-0.859) 2.7 1.3 Mean left cIMT 0.870 (0.842-0.895) 2.6 1.5 Max. right cIMT 0.908 (0.887-0.926) 2.8 1.2 Max. Left cIMT 0.921 (0.903-0.937) 2.6 1.0 Mean aIMT 0.861 (0.830-0.887) 2.6 7.6 Max. aIMT 0.934 (0.919-0.947) 2.1 4.5 Table 2. Intra- and interobserver reproducibility of neonatal cIMT and aIMT
  • Results 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 2. Vascular cIMT (a) and aIMT (b) in controls and in late SGA with and without signs of severity. Data given as mean (95% CI). *P<0.05 compared with controls after adjustment according to gender, gestational age at birth, age at evaluation and group
  • • This study demonstrates that term SGA cases, with and without prenatal signs of severity, show increased vascular IMT. • A significant linear trend for higher values of IMT has been demonstrated in relation to growth restriction severity. • SGA neonates without prenatal signs of severity also presented clear changes, suggesting vascular remodeling. • This association challenges the notion of “constitutionally small” SGA and suggests that this group contains a substantial proportion of cases representing forms of true growth restriction. Discussion 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
  • • The observed changes in SGA neonates without prenatal signs of severity suggests that severity markers such as UtA PI, cerebroplacental ratio and EFW < 3rd percentile, fail to predict a normal postnatal CV outcome. • These results are in line with previous studies evaluating postnatal long- term cardiac function in SGA. • Whether vascular IMT could be used as a prognostic imaging biomarker to improve stratification of risk among term SGA newborns needs further investigation. • Long-term pediatric follow up is warranted in order to gain a better understanding of the pathophysiology of CV remodeling in IUGR and subsequently to implement preventive strategies. Discussion 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
  • • This is the first study to evaluate the structural/functional parameters of the carotid arteries and aorta as components of the vascular tree. • Thorough classification of neonates according to prenatal data in stages of severity has allowed the observation of vascular remodeling in growth restricted neonates. • Adjustment of results by both neonatal weight and lumen diameter further confirmed this finding. • Limited sample size could account for the non-significant findings in blood pressure. • Long-term pediatric follow up is not available. Strengths and limitations 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
  • • Term SGA neonates, both with and without prenatal signs of severity, demonstrate similar changes in vascular structure and function. • These results challenge the notion of ‘constitutionally small’ SGA and support that the majority of SGA neonates represent forms of true growth restriction and suffer fetal CV programming. • Identifying those neonates at risk of vascular remodeling could make a significant contribution to screening public health programs, given that SGA occurs in 10% of the general maternity population. Conclusions 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
  • Discussion points • With evidence demonstrating that term SGA neonates, without prenatal signs of severity, undergo vascular remodeling, consider:  Do we need more evidence to support the notion that “constitutional SGA” is potentially at risk of long-term adverse CV outcomes?  Should we continue to “downplay” the significance of “constitutional SGA”? How can we achieve the balance of being informative and yet not causing unnecessary anxiety for the parents to be? • When is the optimal time for delivery of term SGA without prenatal signs of severity? Is earlier delivery likely to improve/reverse the vascular remodeling thus improving long-term outcomes? • Why is long-term pediatric follow up is also warranted? And what sort and length of follow-up would be needed? 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