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Objective: To create antenatal gender-specific reference growth charts in uncomplicated monochorionic diamniotic twins., Materials and Methods: This is a prospective longitudinal study in which uncomplicated monochorionic (MC) twin pregnancies were included from 23 + 4 weeks of gestation onwards. Estimated fetal weight (EFW) and biometric parameters (biparietal diameter, head circumference, abdominal circumference, and femur length) were evaluated in both fetuses every 2 weeks using standardized methodology. Maternal and fetal complications were excluded. Charts were fitted for each biometric parameter and EFW in relation to gestational age and fetal gender using multilevel mixed models., Results: The final analysis included a total of 456 ultrasound examinations in 62 MC twins, with a mean of 7 scans per pregnancy (range 5-8). The mean as well as 5th and 95th percentiles of each biometric parameter and EFW were adjusted in relation to gender and gestational age between 24 and 37 weeks of gestation. Male fetuses have higher reference values than females, and the disparity is larger in the upper centiles of the distribution., Discussion: We provide gender-specific reference growth charts for MC twins. We suggest that these charts will improve prenatal MC twin assessment and surveillance, with a more accurate classification of normal or growth-restricted fetuses adjusted per sex., (© 2017 S. Karger AG, Basel.)

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., (© 2017 S. Karger AG, Basel.)

Perinatal maternal smoking exposure (PMSE) is one of the major environmental risk factors encountered by the fetus. PMSE is usually associated with adverse pregnancy outcomes that may manifest at different stages of life. Nevertheless, fetal growth restriction is the most common smoking-induced side effect. PMSE induces changes in the maternal multiple organ systems. These alterations may affect placentation, which subsequently affects fetal growth. It is worthy to note, however, that the extent of maternal smoking-induced changes depends mainly on the maternal level of susceptibility. Hence, the perinatal pregnancy outcomes vary depending on the interaction between the triad: the maternal, fetal, and placental modifications, making it more complex. In this review, we try to unveil the effect of smoking-induced maternal changes on the maternal immune, endocrine, and metabolic pathways and their impact on fetal growth., (© 2017 S. Karger AG, Basel.)

Introduction: Chronic reduction of oxygen and nutrient delivery to the fetus has been related to neurodevelopmental problems. Placental underperfusion induces a significant reduction in oxygen and nutrient delivery, whereas maternal undernutrition causes mainly nutrient deficiency. A comparison of the neurodevelopmental effects of both situations in pregnant rabbits was performed., Materials and Methods: The placental underperfusion model was induced after uteroplacental vessel ligation at 25 days of pregnancy. The undernutrition model was induced after a reduction of 70% of the basal maternal intake at 22 days of pregnancy. Neurobehavioral tests were applied in the derived offspring at the neonatal period and over the long term. Structural brain differences were evaluated by brain networks obtained from diffusion magnetic resonance imaging., Results: Birth weight was significantly lower in both cases. However, stillbirth was only increased in the placental underperfusion model. Cases from both models presented poorer neurobehavioral performance and network infrastructure, being more pronounced in the placental underperfusion model., Discussion: Prenatal insults during the last third of gestation resulted in functional and structural disturbances. The degree of neurodevelopmental impairment and its association with structural brain reorganization seemed to be related to the type of the prenatal insult, showing stronger effects in the placental underperfusion model., (© 2017 S. Karger AG, Basel.)

Objectives To examine perinatal outcomes in pregnancies conceived by different methods: fertile women with spontaneous pregnancies, infertile women who achieved pregnancy without treatment, pregnancies achieved by ovulation induction (OI) and in vitro fertilization or intra-cytoplasmic sperm injection (IVF/ICSI). Methods Retrospective single-center cohort study including 200 fertile and 748 infertile women stratified according to infertility treatment. The outcome measurements were preterm delivery (PTD), small-for-gestational-age (SGA), gestational diabetes, placenta previa or preeclampsia. Results The overall rate of pregnancy complications was significantly increased in all infertility groups regardless of the infertility treatment (adjusted odds ratio (OR): infertile without treatment 2.3 versus OI 2.2 versus IVF/ICSI 3.4). While PTD was mainly associated to IVF/ICSI (adjusted OR: infertile without treatment 1.3 versus OI 1.6 versus IVF/ICSI 3.3), SGA was significantly associated to both OI and IVF/ICSI (adjusted OR: infertile without treatment 1.9 versus OI 2.7 versus IVF/ICSI 2.6). All these associations remained statistically significant after adjusting by maternal age and twin pregnancy. Conclusions This study confirms the higher prevalence of pregnancy complications in infertile women irrespectively of receiving infertility treatment or not, and further describes a preferential association of prematurity with IVF/ICSI, and SGA with treated infertility (OI and IVF/ICSI).

Objective: To evaluate insular cortical morphometry assessed by magnetic resonance imaging (MRI) in late-onset small-for-gestational-age (SGA) fetuses compared with controls, and its association with neurobehavioral outcomes., Methods: MRI was performed in 65 late-onset SGA and 59 normally-grown fetuses at 37 weeks' gestation. T2-weighted half Fourier acquisition single-shot turbo spin echo (HASTE) anatomical and diffusion-weighted images were acquired. Insular cortical thickness, volume and fractional anisotropy values were assessed, and asymmetry indices were constructed. At 42 weeks of age, a Neonatal Behavioral Assessment Scale (NBAS) test was performed on the SGA neonates., Results: Late-onset SGA fetuses had significantly thinner insular cortical thickness and smaller insular cortical volume than did controls. SGA fetuses also presented a more pronounced left asymmetry in the posterior cortex and significantly lower fractional anisotropy values in the left insula. Insular measurements in the SGA group were significantly correlated with neurobehavior as assessed by NBAS scores., Conclusions: Insular cortical morphometry was significantly different in late-onset SGA fetuses and correlated with poorer neurobehavioral performance. These data support the impact of growth restriction on brain development and the potential value of cortical assessment as a biomarker of neurodevelopment in at-risk fetuses., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: The objective of the study was to evaluate cortical development parameters by magnetic resonance imaging (MRI) in late-onset intrauterine growth-restricted (IUGR) fetuses and normally grown fetuses., Study Design: A total of 52 IUGR and 50 control fetuses were imaged using a 3T MRI scanner at 37 weeks of gestational age. T2 half-Fourier acquisition single-shot turbo spin-echo anatomical acquisitions were obtained in 3 planes. Cortical sulcation (fissures depth corrected by biparietal diameter), brain volumetry, and asymmetry indices were assessed by means of manual delineation and compared between cases and controls., Results: Late-onset IUGR fetuses had significantly deeper measurements in the left insula (late-onset IUGR: 0.293 vs control: 0.267; P = .02) and right insula (0.379 vs 0.318; P < .01) and the left cingulate fissure (0.096 vs 0.087; P = .03) and significantly lower intracranial (441.25 cm(3) vs 515.82 cm(3); P < .01), brain (276.47 cm(3) vs 312.07 cm(3); P < .01), and left opercular volumes (2.52 cm(3) vs 3.02 cm(3); P < .01). IUGR fetuses showed significantly higher right insular asymmetry indices., Conclusion: Late-onset IUGR fetuses had a different pattern of cortical development assessed by MRI, supporting the existence of in utero brain reorganization. Cortical development could be useful to define fetal brain imaging-phenotypes characteristic of IUGR., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: To establish normal reference intervals of the fetal left modified myocardial performance index (MPI) with the use of stringent criteria for delimitation of the time periods., Study Design: A cohort of consecutive singleton fetuses was created including at least 20 fetuses for each completed week of gestation between 11 and 41 weeks. The isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT), and ejection time (ET) were calculated using the clicks of the mitral and aortic valves as landmarks, and the MPI was calculated as follows: (ICT + IRT)/ET. Normal reference ranges for the MPI and its individual components were constructed by means of regression analysis of the mean and standard deviation against gestational age (GA)., Results: A total of 730 fetuses were included. After a natural logarithmic transformation, a third degree cubic polynomial model (log(e) mean MPI = 0.0477 × GA - 0.002565 × GA² + 0.000043 × GA³ -1.22, with GA measured in weeks) was selected to fit our data. There was a progressive increase in the mean MPI from 11 weeks (mean, 0.39; 95th centile, 0.51) to 41 weeks (mean, 0.55; 95th centile, 0.78) of gestation. While the mean ICT and IRT values increased with GA from 25 to 32 ms and from 39 to 51 ms, respectively, the ET showed an initial increase until 30 weeks and a progressive decrease thereafter., Conclusion: Normative references of left modified MPI from 11 to 41 weeks of gestation are provided, which could be useful in the assessment of cardiac function in fetuses., (Copyright © 2012 S. Karger AG, Basel.)

Purpose: Assessment of cardiac function in the fetal heart is challenging because of its small size and high heart rate, restricted physical access to the fetus, and impossibility of fetal ECG recording. We aimed to standardize the acquisition and postprocessing of fetal echocardiography for deformation analysis and to assess its feasibility, reproducibility, and correlation for longitudinal strain and strain rate measurements by tissue Doppler imaging (TDI) and 2D speckle tracking (2D-strain) during pregnancy., Methods: Echocardiography was performed in 56 fetuses. 2D and color TDI in apical or basal four-chamber views were recorded for subsequent analysis. Caution was taken to achieve a frame rate >70 Hz for speckle tracking and >150 Hz for TDI analysis. For each acquisition, 7.5 s of noncompressed data were stored in cine loop format and analyzed offline. Since fetal ECG information is by definition not available, aortic valve closure was marked from aortic flow and the onset of each cardiac cycle was manually indicated in the 2D images. Sample volume length was standardized at the minimum size. Two observers measured the left and right ventricular peak systolic longitudinal strain and strain-rate., Results: Strain and strain rate measurements were feasible in 93% of the TDI and 2D-strain acquisitions. The mean time spent on analyzing TDI images was 18 min, with an intraclass agreement coefficient of 0.86 (95% CI 0.77-0.92), 0.83 (95% CI 0.72-0.90), 0.96 (95% CI 0.93-0.98), and 0.86 (95% CI 0.76-0.92) for basal left and right free wall peak systolic strain and strain rate, respectively. Agreement between observers using tissue Doppler also showed high reliability. The mean time spent for 2D-strain analysis was 15 min, with an intraclass agreement coefficient of 0.97 (95% CI 0.95-0.98), 0.94 (95% CI 0.89-0.96), 0.96 (95% CI 0.93-0.98), and 0.84 (95% CI 0.73-0.90) for basal left and right free wall peak systolic strain and strain rate, respectively. Agreement between observers also showed a high reliability that was similar for TDI and 2D-strain. There was a weak correlation between TDI and 2D-strain measurements., Conclusions: A standard protocol with fixed acquisition and processing settings, including manual indication of the timing events of the cardiac cycle to correct for the lack of ECG, was feasible and reproducible for the evaluation of longitudinal ventricular strain and strain rate of the fetal heart by TDI as well as 2D-strain analysis. However, both techniques are not interchangeable as the correlation between them is relatively poor., (Copyright © 2012 S. Karger AG, Basel.)

Objectives: To evaluate the feasibility and reproducibility of volume segmentation of fetal intracranial structures using three-dimensional (3D) ultrasound imaging, and to estimate differences in the volume of intracranial structures between intrauterine growth-restricted (IUGR) and appropriate-for-gestational age (AGA) fetuses., Methods: Total intracranial, frontal, thalamic and cerebellar volumes were measured using 3D ultrasound imaging and Virtual Organ Computer-aided AnaLysis (VOCAL) in 39 IUGR and 39 AGA fetuses matched for gestational age, at 28-34 weeks of gestation. Volumes of, and ratios between, structures were estimated, and differences between IUGR and AGA fetuses were calculated. Volume measurements were performed by two observers, and interobserver and intraobserver intraclass correlation coefficients (ICCs) were calculated for each structure., Results: Volumes were satisfactorily obtained in all fetuses. All net volumes except those for the thalamus (P = 0.23) were significantly smaller (P = 0.001) in IUGR fetuses. After adjusting volumes for biparietal diameter the frontal volume was significantly smaller (P = 0.02) and the thalamic volume significantly greater (P = 0.03) in IUGR fetuses than in AGA fetuses. Significant intergroup differences in the ratios between structures were found only in those involving the frontal region. Interobserver ICCs were as follows: total intracranial 0.97 (95% CI, 0.92-0.98), cerebellar 0.69 (95% CI, 0.44-0.75), frontal 0.66 (95% CI, 0.42-0.79) and thalamic 0.54 (95% CI, 0.37-0.72)., Conclusions: IUGR fetuses show differences in the volume of intracranial structures compared with AGA fetuses, with the largest difference found in the frontal region. These differences might be explained by in-utero processes of neural reorganization induced by chronic hypoxia.

Objective: The purpose of this study was to examine the clinical and placental characteristics of monochorionic diamniotic twin pregnancies with early-onset discordant growth diagnosed at 20 weeks, late-onset discordant growth diagnosed at 26 weeks or later, and concordant growth., Study Design: We studied a prospective cohort that underwent an ultrasound scan in the first trimester, at 16, 20, and 26 weeks. We excluded pregnancies complicated by twin-to-twin transfusion syndrome, miscarriage, fetal death less than 16 weeks, or severe congenital anomalies. Placental sharing and angioarchitecture were assessed by injection of each cord vessel with dyed barium sulphate. The 2 territories were delineated on an X-ray angiogram. The diameter of each intertwin anastomosis was measured on a digital photograph., Results: We included 178 twin pairs. Early onset discordant growth, late-onset discordant growth, and concordant growth occurred in 15, 13, and 150 pregnancies, respectively. Twin pairs with early-onset discordant growth had lower survival rates and were delivered at an earlier gestational age than pairs with late-onset discordant and concordant growth. The degree of birthweight discordance was similar in early- and late-onset discordant growth. Severe intertwin hemoglobin differences at the time of birth occurred in 0%, 38%, and 3% of pairs with early-onset discordant growth, late-onset discordant growth, and concordant growth, respectively. The placentas of pairs with early-onset discordant growth were more unequally shared and had larger arterioarterial anastomoses and a larger total anastomotic diameter as compared with placentas of pairs with late onset-discordant or concordant growth., Conclusion: Unequal placental sharing appears to be involved in the etiology of early-onset discordant growth, whereas a late intertwin transfusion imbalance may be involved in some cases with late-onset discordant growth.

STUDY QUESTION Do spontaneously conceived (SC) fetuses from subfertile couples show the same signs of cardiac remodeling as those observed after IVF treatments? SUMMARY ANSWER As opposed to fetuses from IVF, SC fetuses from subfertile couples do not show cardiac remodeling and present a similar cardiac structure and function to those of SC fetuses from fertile couples. WHAT IS KNOWN ALREADY Subjects conceived by IVF present signs of cardiac remodeling and suboptimal function in utero and during childhood, including larger atria, more globular and thicker ventricles, reduced longitudinal motion, and impaired relaxation as compared to SC individuals from fertile couples. There are no previous publications investigating the independent cardiac programming effects of infertility in SC fetuses from subfertile couples (with time-to-pregnancy (TTP) over 12 months). STUDY DESIGN, SIZE, DURATION A prospective cohort study of 289 singleton pregnancies exposed and not exposed to subfertility recruited from 2019 to 2021, including 96 SC pregnancies from fertile couples (TTP under 12 months), 97 SC from subfertile couples (TTP over 12 months), and 96 from IVF after fresh embryo transfer. Fetal echocardiography was performed in all pregnancies. Epidemiological data and perinatal outcomes were collected in all pregnancies. The overall attrition rate was 15.7%. PARTICIPANTS/MATERIALS, SETTING, METHODS SC from subfertile couples and IVF pregnancies were identified as eligible at pregnancy diagnosis, and eligible SC pregnancies from fertile couples who attended our maternal-fetal unit were invited to participate at third trimester, being matched to the other groups by maternal age. Fetal echocardiography was performed at 29–34 weeks of pregnancy to assess cardiac structure and function, and results were adjusted by parental age, maternal smoking status, child's birth order, birthweight centile, gestational age, and estimated fetal weight at scan. MAIN RESULTS AND THE ROLE OF CHANCE Parental age, ethnicity, BMI, and smoking exposure, median gestational age and estimated fetal weight were similar in all study groups. There were no significant differences in infertility duration or etiology between the subfertile and the IVF populations (TTP: subfertile median 35 months (interquartile range 20–48) versus IVF: 47 (25–61); P -value = 0.051). While both fertile and subfertile SC groups presented similar fetal cardiac results, IVF fetuses showed larger atria (right atria-to-heart ratio: IVF mean 18.9% (SD 3.4) versus subfertile 17.8% (3.5) versus fertile 17.6% (3.3); adjusted P -value < 0.001), more globular ventricles (right ventricular sphericity index: IVF 1.56 (0.25) versus subfertile 1.72 (0.26) versus fertile 1.72 (0.26); <0.001), and thicker myocardial walls (relative wall thickness: IVF 0.86 (0.22) versus subfertile 0.64 (0.13) versus fertile 0.64 (0.18); <0.001). Whereas SC fetuses from fertile and subfertile couples had preserved cardiac function, IVF fetuses showed signs of suboptimal systolic and diastolic function, with reduced tricuspid ring displacement (IVF 7.26 mm (1.07) versus subfertile 8.04 mm (1.18) versus fertile 7.89 mm (1.51); <0.001) and increased left myocardial performance index (IVF 0.49 (0.08) versus subfertile 0.45 (0.09) versus fertile 0.45 (0.10); <0.001). A sub-analysis including only unexplained infertility cases in subfertile SC and IVF groups showed similar results. LIMITATIONS, REASONS FOR CAUTION The fetal cardiac changes reported here are subclinical, and most of the cardiovascular parameters were within normal ranges. Although echocardiographic changes are recognized as potential cardiovascular risk factors, their association with long-term cardiovascular disease remains to be demonstrated. WIDER IMPLICATIONS OF THE FINDINGS Subfertility per se does not seem to be associated to fetal cardiac remodeling, which has been previously described in IVF fetuses. Future studies are warranted to further investigate other factors related to the observed fetal cardiac changes associated with ART. STUDY FUNDING/COMPETING INTEREST(S) This project has been partially funded with support from the Erasmus + Programme of the European Union (Framework Agreement number: 2013-0040). This publication reflects the views only of the author, and the Commission cannot be held responsible for any use, which may be made of the information contained therein. Additionally, the research leading to these results has received funding from 'la Caixa' Foundation under grant agreement LCF/PR/GN18/10310003, the Instituto de Salud Carlos III (PI15/00130, PI16/00861, PI17/00675, PI18/00073, INT21/00027)—co-funded by the European Union, Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK) and AGAUR 2017 SGR grant no 1531. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Objectives: To assess by magnetic resonance imaging (MRI) the cortical maturation pattern in fetuses with cytomegalovirus (CMV) infection with mild or no abnormalities on ultrasound (US) and MRI, and to establish possible differences compared with healthy controls. Methods: This was a retrospective case–control study of consecutive pregnancies with a CMV‐infected fetus undergoing prenatal MRI as a complementary diagnostic tool in two centers, and a control group of singleton low‐risk pregnancies without fetal structural abnormalities, with normal fetal growth and with healthy newborns. CMV infection was confirmed by extraction of CMV‐DNA from fetal and neonatal samples. Only fetuses with mild (mildly affected) or no (unaffected) neuroimaging abnormalities on US and MRI were included. MRI measurements of fetal parieto‐occipital sulcus, cingulate sulcus and calcarine sulcus depth, Sylvian fissure depth and Sylvian fissure angles were performed and cortical development grading of specific cortical areas and sulci were assessed by one operator who was blinded to CMV infection status. Data were compared between controls and fetuses with CMV infection, using linear regression and non‐parametric trend analysis. Results: Twenty‐four CMV‐infected fetuses (seven unaffected and 17 mildly affected) and 24 healthy controls that underwent fetal MRI between 27 and 36 weeks' gestation were included. Compared with controls, CMV‐infected fetuses showed significantly larger median lateral ventricular width (right side, 7.8 (interquartile range (IQR), 5.9–9.9) mm vs 3.9 (IQR, 2.6–5.3) mm; left side, 7.5 (IQR, 6.0–10.9) mm vs 4.2 (IQR, 3.2–5.3) mm), significantly decreased parieto‐occipital sulcus depth (right side, 12.6 (IQR, 11.3–13.5) mm vs 15.9 (IQR, 13.5–17.3) mm; left side, 12.3 (IQR, 10.6–13.5) mm vs 16.0 (IQR, 13.3–17.5) mm) and calcarine sulcus depth (right side, 15.4 (IQR, 14.4–16.3) mm vs 17.5 (IQR, 16.1–18.7) mm; left side, 14.6 (IQR, 14.1–15.6) mm vs 16.7 (IQR, 15.6–18.9) mm) (P < 0.001 for all). Compared with controls, CMV‐infected fetuses also had significantly smaller upper (right side, 42.8° (IQR, 35.8–45.8°) vs 48.9° (IQR, 38.4–64.7°); left side, 40.9° (IQR, 34.2–45.8°) vs 48.2° (IQR, 41.9–60.7°)) and lower (right side, 41.6° (IQR, 34.4–49.2°) vs 48.9° (IQR, 40.6–60.9°); left side, 42.2° (IQR, 38.8–46.9°) vs 48.9° (IQR, 39.5–57.5°)) Sylvian fissure angles (P < 0.05 for all). In addition, the mildly affected CMV‐infected fetuses had a significantly lower cortical development grading in the temporal and parietal areas, and the parieto‐occipital and calcarine sulci compared with healthy fetuses (P < 0.05). These differences persisted when adjusting for gestational age, ipsilateral atrium width, fetal gender and when considering small‐for‐gestational age as a confounding factor. Conclusions: Unaffected and mildly affected CMV‐infected fetuses showed delayed cortical maturation compared with healthy controls. These results suggest that congenital CMV infection, even in non‐severely affected fetuses that are typically considered of good prognosis, could be associated with altered brain cortical structure. Further research is warranted to better elucidate the correlation of these findings with neurodevelopmental outcomes. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: Fetuses conceived by assisted reproductive technology (ART) and those that are small-for-gestational age (SGA) show cardiovascular remodeling in utero; however, these two conditions are often associated. We aimed to evaluate the differential effect of ART and SGA on fetal cardiac remodeling.Methods: This was a prospective cohort study of term singleton pregnancies seen at our department between April 2011 and September 2013. The cohort was divided according to fetal growth and mode of conception into the following four groups: 102 appropriate-for-gestational-age (AGA) fetuses conceived spontaneously (controls), 72 AGA fetuses conceived by ART (ART-AGA), 31 SGA fetuses conceived by ART (ART-SGA) and 28 SGA fetuses conceived naturally (Spont-SGA). SGA was defined as birth weight < 10th centile. Fetal echocardiography was performed at 28-32 weeks to assess cardiac dimensions, geometry and function.Results: ART fetuses had dilated atria (mean left atrium-to-heart area ratio: controls, 15 ± 2.7%; ART-AGA, 18 ± 4.1%; Spont-SGA, 14 ± 3.7%) and more globular ventricles (left ventricular sphericity index: controls, 1.77 ± 0.2; ART-AGA, 1.68 ± 0.2; Spont-SGA, 1.72 ± 0.2), with normally sized hearts. In contrast, SGA fetuses had enlarged hearts (cardiothoracic ratio: controls, 24 ± 3%; ART-AGA, 24 ± 4%; Spont-SGA, 29 ± 6%), preserved atrial size, more globular and concentric hypertrophic ventricles (left ventricle relative wall thickness: controls, 0.48 ± 0.17; ART-AGA, 0.54 ± 0.13; Spont-SGA, 0.63 ± 0.23). Both ART and SGA fetuses had decreased longitudinal motion (tricuspid annular ring displacement: controls, 6.5 ± 0.8 mm; ART-AGA, 5.5 ± 0.7 mm; Spont-SGA, 5.9 ± 0.6 mm) and impaired relaxation (left isovolumetric relaxation time: controls, 47.0 ± 7.3 ms; ART-AGA, 50.0 ± 7.9 ms; Spont-SGA, 49.5 ± 9.3 ms). ART-SGA fetuses presented a combination of features from both ART and SGA groups.Conclusion: SGA and conception with ART were associated with distinct patterns of fetal cardiac remodeling, supporting the concept that they are independent causes of cardiac programming. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

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Objectives: To compare the performance of third-trimester screening, based on estimated fetal weight centile (EFWc) vs a combined model including maternal baseline characteristics, fetoplacental ultrasound and maternal biochemical markers, for the prediction of small-for-gestational-age (SGA) neonates and late-onset fetal growth restriction (FGR).Methods: This was a nested case-control study within a prospective cohort of 1590 singleton gestations undergoing third-trimester (32 + 0 to 36 + 6 weeks' gestation) evaluation. Maternal baseline characteristics, mean arterial pressure, fetoplacental ultrasound and circulating biochemical markers (placental growth factor (PlGF), lipocalin-2, unconjugated estriol and inhibin A) were assessed in all women who subsequently delivered a SGA neonate (n = 175), defined as birth weight < 10th centile according to customized standards, and in a control group (n = 875). Among SGA cases, those with birth weight < 3rd centile and/or abnormal uterine artery pulsatility index (UtA-PI) and/or abnormal cerebroplacental ratio (CPR) were classified as FGR. Logistic regression predictive models were developed for SGA and FGR, and their performance was compared with that obtained using EFWc alone.Results: In SGA cases, EFWc, CPR Z-score and maternal serum concentrations of unconjugated estriol and PlGF were significantly lower, while mean UtA-PI Z-score and lipocalin-2 and inhibin A concentrations were significantly higher, compared with controls. Using EFWc alone, 52% (area under receiver-operating characteristics curve (AUC), 0.82 (95% CI, 0.77-0.85)) of SGA and 64% (AUC, 0.86 (95% CI, 0.81-0.91)) of FGR cases were predicted at a 10% false-positive rate. A combined screening model including a-priori risk (maternal characteristics), EFWc, UtA-PI, PlGF and estriol (with lipocalin-2 for SGA) achieved a detection rate of 61% (AUC, 0.86 (95% CI, 0.83-0.89)) for SGA cases and 77% (AUC, 0.92 (95% CI, 0.88-0.95)) for FGR. The combined model for the prediction of SGA and FGR performed significantly better than did using EFWc alone (P < 0.001 and P = 0.002, respectively).Conclusions: A multivariable integrative model of maternal characteristics, fetoplacental ultrasound and maternal biochemical markers modestly improved the detection of SGA and FGR cases at 32-36 weeks' gestation when compared with screening based on EFWc alone. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To identify different cardiac phenotypes among cases of fetal growth restriction (FGR).Methods: Echocardiography was performed in 126 cases with FGR (birth weight < 10th centile) and 64 appropriate-for-gestational-age (AGA) fetuses. Principal component and cluster analyses were performed to identify different cardiac phenotypes among FGR cases.Results: Three different cardiac phenotypes were identified among the FGR group: globular in 54% of cases, elongated in 29% of cases and hypertrophic in 17% of cases. Those with a globular heart had the lowest median left-ventricular sphericity index (controls, 1.78 (interquartile range (IQR), 1.62-1.97); FGR elongated, 1.92 (IQR, 1.78-2.09); FGR globular, 1.44 (IQR, 1.36-1.52); FGR hypertrophic, 1.65 (IQR, 1.42-1.77); P = 0.001). FGR cases with an elongated left ventricle had nearly normal cardiac dimensions. FGR cases with a hypertrophic phenotype had the highest median left-ventricular wall thickness (controls, 1.22 (IQR, 1.10-1.67) mm/kg; FGR elongated, 1.52 (IQR, 1.28-1.86) mm/kg; FGR globular, 1.65 (IQR, 1.39-1.99) mm/kg; FGR hypertrophic, 3.68 (IQR, 3.45-4.71) mm/kg; P = 0.001) and cardiac dimensions. Globular and elongated phenotypes showed a fetoplacental profile of late-onset FGR, while the hypertrophic phenotype showed signs of early-onset FGR. The hypertrophic group also had the poorest perinatal results, having the lowest birth-weight centile, gestational age at delivery and Apgar score and the highest postnatal blood pressure and aorta intima-media thickness.Conclusions: FGR induces at least three different cardiac phenotypes, with early-onset FGR cases being associated with a hypertrophic response and worse perinatal outcomes. This cardiac phenotypic classification may improve identification of FGR cases with the highest perinatal and long-term cardiovascular risks. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To determine the longitudinal behavior of fetal biometric measures and cerebroplacental hemodynamics throughout gestation in fetuses with congenital heart disease (CHD).Methods: Fetal biometry and Doppler hemodynamics (uterine artery (UtA), umbilical artery (UA) and fetal middle cerebral artery (MCA)) were measured serially in a cohort of consecutive fetuses diagnosed with CHD. Evaluations were made at various time points, from diagnosis (20-25 weeks) to delivery, with at least two measurements per fetus that were at least 2 weeks apart. Fetuses were classified into three groups according to the pattern of blood supply to the brain (placental vs systemic) that would be expected on the basis of the type of CHD. All parameters were transformed into Z-scores. A linear mixed model to analyze repeated measurements was constructed for each parameter to assess its behavior throughout gestation.Results: Four hundred and forty-four ultrasound examinations were performed in 119 CHD fetuses, with a median of two measurements per fetus. The fetuses presented a small head at diagnosis (biparietal diameter (BPD) Z-score, -1.32 ± 0.99; head circumference (HC) Z-score, -0.79 ± 1.02), which remained small throughout gestation. UtA and UA pulsatility indices (PI) showed a significant increase towards the end of pregnancy, whereas no significant changes were observed in MCA-PI or cerebroplacental ratio (CPR) with gestational age. Both MCA and CPR presented significant differences in longitudinal behavior between CHD groups, while BPD and HC did not.Conclusions: CHD fetuses have a relatively small head from the second trimester of pregnancy, regardless of the type of CHD anomaly, and increasing resistance in the UtA and UA as pregnancy progresses, suggestive of increasing degree of placental impairment. Our findings indicate the early onset of mechanisms that could lead to poorer neurodevelopment later in life. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: Among late-onset small fetuses, a combination of estimated fetal weight (EFW), cerebroplacental ratio (CPR) and mean uterine artery (UtA) pulsatility index (PI) can predict a subgroup of fetuses with poor perinatal outcome; however, the association of these criteria with fetal cardiac structure and function is unknown. Our aim was to determine the presence and severity of signs indicating cardiac dysfunction in small fetuses, classified as intrauterine growth-restricted (IUGR) or small-for-gestational age (SGA), according to EFW, CPR and UtA-PI.Methods: A cohort of 209 late-onset small fetuses that were delivered > 34 weeks of gestation was divided in two categories: SGA (n = 59) if EFW was between the 3(rd) and 9(th) centiles with normal CPR and UtA-PI; and IUGR (n = 150) if EFW was < 3(rd) centile, or < 10(th) centile with a CPR < 5(th) centile and/or UtA-PI > 95(th) centile. The small population was compared with 150 appropriately grown fetuses (controls). Fetal cardiac morphometry and function were assessed by echocardiography using two-dimensional M-mode, conventional and tissue Doppler.Results: Compared with controls, both IUGR and SGA fetuses showed larger and more globular hearts (mean left sphericity index ± SD: controls, 1.8 ± 0.3; SGA, 1.5 ± 0.2; and IUGR, 1.6 ± 0.3; P < 0.01) and showed signs of systolic and diastolic dysfunction, including decreased tricuspid annular plane systolic excursion (mean ± SD: controls, 8.2 ± 1.1; SGA, 7.4 ± 1.2; and IUGR, 6.9 ± 1.1; P < 0.001) and increased left myocardial performance index (mean ± SD: controls, 0.45 ± 0.14; SGA, 0.51 ± 0.08; and IUGR, 0.57 ± 0.1; P < 0.001).Conclusions: Despite a perinatal outcome comparable to that of normal fetuses, the population of so-defined SGA fetuses showed signs of prenatal cardiac dysfunction. This supports the concept that at least a proportion of them are not 'constitutionally small' and that further research is needed. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective To elucidate the association between Doppler parameters and histological signs of placental underperfusion in late-onset small-for-gestational-age ( SGA) babies. Methods Umbilical, fetal middle cerebral and uterine artery pulsatility indices and umbilical vein blood flow (UVBF), which had been recorded within 7 days prior to delivery, were analyzed from a cohort of SGA singleton pregnancies delivered after 34 weeks' gestation and confirmed as having a birth weight < 10th percentile by local standards. In each case, the placenta was histologically evaluated for signs of placental underperfusion using a hierarchical and standardized classification system. The independent association of the Doppler parameters with placental underperfusion was evaluated using logistic regression and decision tree analysis. Results In 51 cases (53.7%), there were 61 placental histological findings indicative of placental underperfusion. These cases had a significantly higher incidence of Cesarean section for non-reassuring fetal status (52.1% vs 11.9%; P < 0.001) and neonatal metabolic acidosis at birth (21.6% vs 0%; P = 0.001). Significant and independent contributions to the presence of placental underperfusion lesions were provided by increased mean UtA pulsatility index ( PI) ( P = 0.018; odds ratio ( OR) 2 (95% CI, 1.1-3.7)) and decreased UVBF normalized to estimated fetal weight ( P = 0.027; OR 0.97 (95% CI, 0.95-0.99)). The combination of both parameters revealed three groups with differing risks for placental underperfusion: normalized UVBF > 82 mL/min/kg (risk 31.3%), normalized UVBF ≤ 82 mL/min/kg and mean UtA-PI ≤ 95th percentile (risk 65.5%), and normalized UVBF ≤ 82 mL/min/kg and UtA-PI > 95th percentile (risk 94.4%). Conclusions In late-onset SGA pregnancies, uterine Doppler and UVBF are surrogates for placental underperfusion. These findings facilitate phenotypic profiling of cases of fetal growth restriction among the general population of late-onset SGA babies. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd [ABSTRACT FROM AUTHOR]

The article presents a cohort study which examines the intrauterine growth restriction and changes in aortic isthmus and ductus venosus blood flow of fetuses relative to other arterial Doppler parameters. Longitudinal changes of the fetuses are analyzed to estimate mean point at which the Doppler parameter becomes abnormal. It concludes that aortic isthmus provides management protocols that improve fetal survival.

The article investigates potential differences in the prediction of early- vs. late-onset pre-eclampsia and/or intrauterine growth restriction (PE/IUGR) by second-trimester uterine artery Doppler examination. The measurement of maternal serum placental growth factor and soluble fms-like tyrosine kinase one was described. The results indicate that angiogenic factors and uterine artery Doppler evaluation may be useful second-trimester screening tests for early-onset, but not late-onset PE/IUGR.

Objective To assess the incidence of parenchymal lesions on early and late neonatal brain scans and its association with the presence or absence of intermittent absent or reversed end-diastolic umbilical artery flow velocity (A/REDV) in monochorionic twins complicated by selective intrauterine growth restriction (IUGR), as compared to dichorionic twins and monochorionic twins without selective IUGR. Methods This was a prospective cohort study involving 42 monochorionic twins diagnosed with selective IUGR and managed expectantly. The presence or absence of intermittent A/REDV was recorded in all cases. This study group was compared to dichorionic twins (n = 29) and monochorionic twins without selective IUGR (n = 32) delivered at 26-34 weeks during the study period. All infants underwent an early neonatal brain scan (at or before the fourth day of postnatal life) and at least one follow-up scan during the first 28 days of postnatal life. Perinatal outcome and the incidence of neurological damage were compared between the study groups. Results The incidence of intrauterine fetal death (IUD) and periventricular leukomalacia was significantly increased in monochorionic twins complicated with selective IUGR, as compared with the other study groups. Intermittent A/REDV was observed in 22/42 (52.4%) twin pairs, and was always present in the growth- restricted twin. The incidence of IUD (overall 9/44 (20.5%) vs. 0/40, P < 0.001; smaller twin 6/22 (27.3%) vs. 0/20, P < 0.05) and parenchymal brain damage (overall 7/35 (20.0%) vs. 2/40 (5.0%), P = 0.07; larger twin 7/19(36.8%) vs. 1/20(5.0%), P < 0.05) was significantly higher in pregnancies with intermittent A/REDV than in those without intermittent A/REDV. Brain damage usually occurred in the larger twin, irrespective of whether the smaller twin was liveborn or not. Conclusions The presence of intermittent A/REDV in monochorionic twins with selective IUGR identifies a subgroup with an elevated risk of intrauterine demise of the smaller twin and neurological damage in the larger twin; this latter finding is not restricted to cases with IUD of the cotwin. [ABSTRACT FROM AUTHOR]

The perceived stress scale (PSS) and the state-trait anxiety inventory (STAI) were assessed in mothers of singleton gestations that subsequently delivered a neonate with a birthweight below the 10 SP th sp centile (n = 282) and in a control group of pregnancies with adequate fetal growth who delivered normally grown neonates (n = 279). Importantly, women without antenatal diagnosis of FGR but that delivered a neonate with a birthweight < 10 SP th sp centile have significantly higher PSS than controls (p < 0.05). [Extracted from the article]

The aim of this study was to evaluate the myocardial performance index (MPI) and its time intervals in monochorionic diamniotic (MCDA) twin pairs complicated by selective fetal growth restriction (sFGR) with abnormal umbilical artery (UA) Doppler. In MCDA twin pregnancies complicated by sFGR with abnormal UA Doppler, smaller twins showed signs of systolic dysfunction most probably due to increased afterload, secondary to discordance of placental territories. [Extracted from the article]

Biparietal diameter (BPD), occipitofrontal diameter (OFD) and left Sylvian fissure depth (LSFD) were significantly different when corrected for GA and fetal sex (p respectively < 0.013, < 0.013 and 0.026). Insular depth, parieto-occipital fissure, cingulate fissure and calcarine fissure were not significantly different on either side of the brain. In the visual grading of the fetal brain, the left temporal area (0.0026), the bilateral Sylvian fissure (both < 0.003), the bilateral superior temporal fissure (both < 0.003), bilateral mesial area (both < 0.003) and left cingulate sulcus (0.01) were significantly different between LCDH and normal fetuses. [Extracted from the article]

Fetuses with VM have significantly smaller CC, both in length and in whole area. Fetuses with isolated non-severe VM showed a significant reduction of the CC, mainly affecting all its regions. Furthers studies correlating changes in cortical development and CC would be of help in the understanding of fetal brain development in VM. [Extracted from the article]

The article comments on the study which examines the risks of predicting neurological outcome associated with preterm intrauterine growth restriction (IUGR). The author argues that preterm uterine growth compromises the risks between irreversible neurological damage and risks of prematurity. According to the author, the study will help in the clarification of optimal issues related to delivery.

P18.07: Pattern of cortical development in fetuses with isolated non-severe ventriculomegaly is associated with poorer neurodevelopmental performance at early infancy INSVM fetuses showed significant underdevelopment of the cortex (Global cortical grading score: early onset INSVM 37 ± 10 vs controls 43 ± 10, p=< 0.01; late onset INSVM 75 ± 6 vs controls 82 ± 6, p = 0.02) and poorer performance in Bayley III with lowest scores in adaptive-behavior composite (INSVM 84.5 ± 16.3 controls 94.6 ± 11.6; p = 0.04). Fetuses with INSVM showed underdeveloped cortical sulcation being correlated with poorer neurodevelopmental performance at early infancy. [Extracted from the article]

To evaluate paired maternal and fetal lipidomic profile in pregnancies complicated by pre-eclampsia (PE) and/or fetal growth restriction (FGR) compared to uncomplicated pregnancies by NMR-based lipidomics. H NMR-based lipidomic profiling was applied using the Liposcale test which quantifies the concentrations of the lipoproteins [very-low density lipoprotein (VLDL), low-density lipoprotein (LDL), intermediate-density lipoprotein (IDL) and high-density lipoprotein (HDL)] in conjuction with cholesterol (C) or triglecyrides (TG). Maternal lipidomic profile showed significantly lower concentrations of LDL-TG (-10%) in normotensive FGR whereas in PE with and without FGR there were higher concentrations of VLDL-C (+50%, +70% respectively), IDL-C (+19%, +32% respectively), VLDL-TG (+52%, +62% respectively), IDL-TG (+13%, +25% respectively) and lower concentrations of HDL-C (-15%, -19% respectively). [Extracted from the article]

The objective of this study was to develop a core outcome set for studies evaluating treatments for sFGR. An international meeting of stakeholders used the modified nominal group technique to consider the consensus outcomes and agree a final core outcome set. [Extracted from the article]

Detailed neurosonography with transabdominal and transvaginal approach was performed at 33±2 weeks including measurement of Insula, Sylvian fissure and Parieto-occipital, Cingulate and Calcarine sulci. As previously reported, FGR fetuses showed significant differences in cortical development with reduced Sylvian fissure and parieto-occipital sulcus depth together with larger Insula width. Interestingly, a similar pattern of reduced Sylvian fissures and larger Insula depth were observed in the PE group with normally grown fetuses (table 1). [Extracted from the article]

To assess placental perfusion by magnetic resonance (MR) biexponential intra-voxel incoherent motion (IVIM) model in pregnancies near term complicated by fetal growth restriction (FGR) and to evaluate its correlation with placental volume and feto-placental Doppler. Placental perfusion assessed by IVIM model seems to be a promising technique for assessing placental insufficiency, but further studies with larger sample size are needed. [Extracted from the article]

Intrauterine growth restriction (IUGR) is associated with abnormal neurodevelopment, but the structural correspondence are poorly documented. IUGR animals also showed reduced whole brain area relative to body weight (IUGR 2.91±0.36 vs controls 2.41±0.47, p = 0.049). Regional analyses evidenced an increase corpus callosum thickness relative to brain area in IUGR (IUGR 0.0102±0.005 vs controls 0.0086±0.001, p = 0.035), with no differences in grey matter structures. [Extracted from the article]

Alpha-1-microglobulin (A1M) serves as a scavenger to eliminate circulating free fetal hemoglobin which has been proposed to have a role in placental related disorders such as pre-eclampsia (PE) and fetal growth restriction (FGR). A prospective case control study including 192 singleton pregnancies with a diagnosis of normotensive FGR (n=47), PE with appropriate for gestational age fetus (n=45) and PE with FGR (n=51) as well as uncomplicated pregnancies (n=49). Whereas in fetal blood, A1M was significantly lower in FGR fetuses with and without PE with no differences in PE without FGR (table 1). [Extracted from the article]

To evaluate paired maternal and fetal metabolomic profile in pregnancies complicated by pre-eclampsia (PE) and/or fetal growth restriction (FGR). A prospective case control study including 236 singleton pregnancies with a diagnosis of normotensive FGR (n = 48), PE with appropriate for gestational age fetus (n = 46) and PE+FGR (n = 52) as well as uncomplicated pregnancies (n = 90). Mothers and fetuses from PE pregnancies have an altered metabolomic profile in comparison with normotensive FGR and uncomplicated pregnancies. [Extracted from the article]

OC15.07: Identification of phenotypes of fetal growth restriction using a network-based clustering approach We sought to describe phenotypes of FGR using machine-learning unsupervised network-based analysis. Unsupervised machine-learning models generated three phenotypes that resemble early-, late FGR and late SGA. [Extracted from the article]

To evaluate corpus callosum (CC) development by neurosonography (NSG) in fetuses with isolated cardiac heart defect (CHD). Fetuses with CHD presented smaller CC being this reduction more marked in CHD associated with poor oxygenated brain flow. [Extracted from the article]

Twin-twin transfusion syndrome (TTTS) and selective fetal growth restriction (sFGR) are the most common complications of monochorionic twin pregnancies. Donors were divided into groups according to preoperative EFW (appropriate-for-gestational age (AGA) and sFGR) and umbilical artery (UA) Doppler pattern (positive end-diastolic flow (EDF) and absent-reversed EDF (AREDF)). In our population, the main risk factors for intrauterine donor demise after laser therapy were GA at surgery and the presence of preoperative UA AREDF irrespective of sFGR. [Extracted from the article]

An abstract of the article "Fetal growth restriction induces different phenotypes of cardiac remodelling," by M. Rodriguez-Lopez and colleagues is presented.

An abstract of the article "Prediction of fetal growth restriction using estimated fetal weight versus a combined screening model at 34 weeks of gestation," by J. Miranda and colleagues is presented.

An abstract of the article "Neurobehavioural outcomes in fetal growth restriction versus small-for-gestational age, as defined by estimated fetal weight centile, cerebroplacental ratio and uterine artery Doppler," by C. Paules Tejero and colleagues is presented.

An abstract of the article "Long-term functional impairment and their structural correspondence in an animal model of intrauterine growth restriction," by M. Illa and colleagues is presented.