Edurne Mazarico

Aortic Intima-Media Thickness and Aortic Diameter in Small for Gestational Age and Growth Restricted Fetuses

Objective The objective of this study is to measure aortic intima-media thickness (aIMT) and aortic diameter (AD) in appropriate for gestational age (AGA) fetuses, small for gestational age (SGA) fetuses, and intrauterine growth restricted (IUGR) fetuses. Methods Case-control study performed between June 2011 and June 2012. Forty-nine AGA fetuses, 40 SGA fetuses, and 35 IUGR fetuses underwent concomitant measurement of aIMT and AD at a mean gestational age of 34.4 weeks. Results Median aIMT was higher in fetuses with IUGR (0.504 mm [95%CI: 0.477-0.530 mm]), than in SGA fetuses (0.466 mm [95% CI: 0.447–0.485 mm]), and AGA fetuses (0.471 mm [95% CI: 0.454-0.488 mm]) (p = 0.023). Mean AD was significantly lower in fetuses with IUGR (4.451 mm [95% CI: 4.258–4.655 mm]), than in AGA fetuses (4.74 mm [95% CI: 4.63-4.843 mm]) (p = 0.028). Conclusions Growth restricted fetuses have a thicker aortic wall than AGA and SGA fetuses, which possibly represents preclinical atherosclerosis and a predisposition to later cardiovascular disease.

Use of Placental Growth Factor and Uterine Artery Doppler Pulsatility Index in Pregnancies Involving Intrauterine Fetal Growth Restriction or Preeclampsia to Predict Perinatal Outcomes

Aim: The potential of uterine artery (UA) Doppler pulsatility index (PI) and maternal serum placental growth factor (PlGF) level to predict perinatal outcome was explored in pregnancies complicated by intrauterine fetal growth restriction (IUGR) or preeclampsia (PE). Methods: This longitudinal, prospective, and case-controlled study was conducted over a period of 24 months. At-risk pregnancies involving small-for-gestational-age (SGA) fetuses, IUGR, gestational hypertension (GH), or PE were investigated, analyzing UA Doppler PI findings and maternal PlGF levels determined at the time of diagnosis (third trimester). Results: UA Doppler PI and maternal serum PlGF values differed significantly in pregnancies complicated by IUGR and/or PE (vs. SGA or GH, p < 0.01). In the context of IUGR or PE, both parameters also differed significantly by perinatal outcome (adverse vs. normal, p < 0.01), although no predictive advantage over UA Doppler PI alone was conferred by adding a PlGF assay. Conclusion: UA Doppler PI and maternal serum PlGF determinations in the third trimester help identify pregnancies at the highest risk of adverse perinatal outcomes due to IUGR and/or PE. Although joint testing confers no predictive benefit over UA Doppler PI alone, the two diagnostics are interchangeable for this purpose.

Placental 11B-Hydroxysteroid Dehydrogenase Type 2 mRNA Levels in Intrauterine Growth Restriction versus Small-for-Gestational-Age Fetuses

Introduction: The objective of this study was to evaluate placental 11B-hydroxysteroid dehydrogenase type 2 (11B-HSD-2) mRNA levels in intrauterine growth-restricted fetuses (IUGR) as compared with small-for-gestational-age (SGA) fetuses according to clinical criteria. Material and Methods: Placental levels of 11B-HSD-2 mRNA levels were measured in SGA (birth weight <10th centile) and gestational-age-matched, appropriate-for-gestational-age (AGA) births. SGA was classified as IUGR (birth weight <3rd centile or <10th percentile with abnormal uterine artery Doppler or cerebroplacental ratio) or non-IUGR SGA. After RNA extraction, mRNA levels were determined by reverse transcription and quantitative PCR. Results: A total of 38 placentas were analyzed (20 AGA and 18 SGA). Among the SGA pregnancies, 13 qualified as IUGR. The activity of 11B-HSD-2 in IUGR pregnancies [0.105 (SD 0.328)] was significantly reduced compared to non-IUGR SGA [0.304 (SD 0.261); p = 0.018] and AGA [0.294 (SD 0.328); p = 0.001]. These differences remained significant after adjusting for potential confounders (such as smoking or maternal cortisol levels). Activity levels did not significantly differ between non-IUGR SGA and AGA. Discussion: IUGR fetuses had reduced 11B-HSD-2 activity in comparison with SGA and normally grown fetuses. This finding provides opportunities to develop new placental biomarkers for the phenotypic characterization of fetal smallness.

Differences in dietary and lifestyle habits between pregnant women with small fetuses and appropriate‐for‐gestational‐age fetuses

The purpose of this study was to determine differences in lifestyle and dietary habits between pregnant women with small for gestational age (SGA) fetuses and those appropriate for gestational age (AGA).

Longitudinal growth assessment for the prediction of adverse perinatal outcome in SGA-suspected fetuses

Fetal growth restriction (FGR) is associated with an increased risk of adverse perinatal outcome. However, distinguishing this condition from small‐for‐gestational age (SGA) remains elusive. A set of criteria has been proposed recently for such a purpose, including the degree of smallness, Doppler parameters and growth velocity. The aim of this study was to establish whether the use of growth velocity adds value to Doppler assessment in predicting adverse perinatal outcome among SGA‐suspected fetuses.

Second- to Third-Trimester Longitudinal Growth Assessment for the Prediction of Largeness for Gestational Age and Macrosomia in an Unselected Population

Background: Prenatal detection of excessive growth remains inaccurate. Most strategies rely on a single cross-sectional evaluation of fetal size during the third trimester. Objectives: To compare second- to third-trimester longitudinal growth assessment with cross-sectional evaluation at the third trimester in the prediction of largeness for gestational age (LGA) and macrosomia. Methods: A cohort of 2,696 unselected singleton pregnancies scanned at 21 ± 2 and 32 ± 2 weeks was created. Abdominal circumference (AC) measurements were transformed to z values according to the INTERGROWTH-21st standards. Longitudinal growth assessment was performed by calculation of z velocity and conditional growth. Both methods were compared to cross-sectional assessment at 32 ± 2 weeks. Predictive performance for LGA and macrosomia was determined by receiver operating characteristic curve analysis. Result: A total of 188 (7%) newborns qualified for LGA and 182 (6.8%) for macrosomia. The areas under the curve (AUCs) for 32-week AC z score, AC z velocity, and conditional AC were 0.78, 0.61, and 0.55, respectively, for the prediction of LGA, and 0.75, 0.61, and 0.55, respectively, for the prediction of macrosomia. Both AUCs of AC z velocity and conditional AC were significantly lower (p < 0.001) than the AUC of cross-sectional AC z scores. Conclusions: In the general population, second- to third-trimester longitudinal assessment of fetal growth is inferior to third-trimester cross-sectional evaluation of size in the prediction of LGA and macrosomia.

Genomic Microarray in Fetuses with Early Growth Restriction: A Multicenter Study

Background: Little information is available about the risk of microdeletion and microduplication syndromes in fetal growth restriction (FGR) with a normal karyotype. Objective: To assess the incremental yield of genomic microarray over conventional karyotyping in fetuses with early growth restriction. Study Design: Genomic microarray was prospectively performed in fetuses with early growth restriction defined as a fetal weight below the 3rd percentile estimated before 32 weeks of pregnancy, and a normal quantitative fluorescent polymerase chain reaction result. The incremental yield of genomic microarray was defined by the rate of fetuses presenting with a pathogenic copy number variant below 10 Mb. Results: Among 133 fetuses with early FGR, a 6.8% (95% CI: 2.5-11.0) incremental yield of genomic microarray over karyotyping was observed. This incremental yield was 4.8% (95% CI: 0.2-9.3) in isolated FGR, 10% (95% CI: 0-20.7) in FGR with nonstructural anomalies, and 10.5% (95% CI: 0-24.3) in FGR with structural anomalies. Conclusion: Our multicenter study reveals that 6.8% of fetuses with early growth restriction present with submicroscopic anomalies after common aneuploidies were excluded. Even when FGR is observed as an isolated finding, genomic microarray analysis should be considered after or instead of karyotyping, due to its 4.8% incremental yield.

Longitudinal growth assessment for prediction of adverse perinatal outcome in fetuses suspected to be small‐for‐gestational age

Fetal growth restriction (FGR) is associated with an increased risk of adverse perinatal outcome. However, distinguishing this condition from small‐for‐gestational age (SGA) remains elusive. A set of criteria has been proposed recently for such a purpose, including the degree of smallness, Doppler parameters and growth velocity. The aim of this study was to establish whether the use of growth velocity adds value to Doppler assessment in predicting adverse perinatal outcome among SGA‐suspected fetuses.

Second‐ to third‐trimester longitudinal growth assessment for prediction of small‐for‐gestational age and late fetal growth restriction

Detection of fetal growth restriction (FGR) remains poor and most screening strategies rely on cross‐sectional evaluation of fetal size during the third trimester. A longitudinal and individualized approach has been proposed as an alternative method of evaluation. The aim of this study was to compare second‐ to third‐trimester longitudinal growth assessment to cross‐sectional evaluation in the third trimester for the prediction of small‐for‐gestational age (SGA) and late FGR in low‐risk singleton pregnancy.This article is protected by copyright. All rights reserved. This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/uog.17471 A cc ep te d A rti cl e Background: Detection of fetal growth restriction (FGR) remains poor. Most screening strategies rely on a cross-sectional evaluation of fetal size at one point during the third trimester. A longitudinal and individualized approach may allow a more appropriate evaluation. Objectives: To compare second to third trimester longitudinal growth assessment with cross-sectional evaluation at third trimester in the prediction of SGA and late FGR. Methods: A cohort of 2696 unselected singletons pregnancies scanned at 21±2 and 32±2 weeks was created. Abdominal circumference (AC) measurements were transformed to zvalues according the 21st-INTERGROWTH standards. Longitudinal growth assessment was performed by the calculation of z-velocity and second to third trimester conditional growth centile. Longitudinal assessment was compared to cross-sectional assessment at 32 weeks. Predictive performance for SGA and late FGR was determined by receiver operating characteristic (ROC) curve analysis. Result: A total of 210 (7.8%) newborns were classified as SGA and 103 (3.8%) as late FGR. None of the longitudinal measures (AC z-velocity and conditional AC growth) relevantly improved the association to SGA or late FGR provided by the cross-sectional evaluation of AC z-score at 32 weeks. Both areas under the curve (AUC) of AC z-velocity and conditional AC growth were significantly lower than that of cross-sectional AC z-scores (p<0.001). AC zvelocity performed significantly better than conditional AC growth (p<0.001). Conclusions: Longitudinal assessment of fetal growth from second to third-trimester has a low predictive capacity for SGA and late FGR in the general population.

Relationship between Foetal Growth Restriction and Maternal Nutrition Status Measured by Dual-Energy X-Ray Absorptiometry, Leptin, and Insulin-Like Growth Factor

Aims: The aim of this study was to determine if maternal nutritional status, as defined by body composition, leptin, and insulin-like growth factor (IGF)-I levels, relates to foetal growth. Methods: In this prospective study, mothers of foetuses with foetal growth restriction (FGR; cases; n = 46) and mothers of appropriate-for-gestational-age (AGA) foetuses (controls; n = 81) were consecutively recruited over a 14- month period. A maternal blood sample was obtained during the third trimester (between 32 and 34 weeks of gestation) for the assessment of IGF-I and leptin. Body composition was assessed by dual-energy X-ray absorptiometry within the first 15 days after delivery. The study used the SPSS-PC statistical package, version 19.0, and p < 0.05 was considered statistically significant. Results: Mean serum IGF-I levels were lower in the cases than in the controls (p < 0.05), whereas leptin concentrations were higher in the cases after adjusting for age, body mass index and cigarette consumption (p < 0.05). Cases had less lean and fat tissue than controls (p < 0.05) but a relatively higher fat percentage. Conclusions: The mothers of foetuses with FGR have a body composition pattern characterized by a slightly increased fraction of fat mass, lower IGF-I concentrations, and increased serum leptin levels. Optimization of maternal nutritional status should be considered, as the nutritional status may be involved in the pathogenesis of FGR.