Objective: The terms early- and late-onset fetal growth restriction (FGR) are commonly used to distinguish two phenotypes characterized by differences in onset, fetoplacental Doppler, association with preeclampsia (PE) and severity. We evaluated the optimal gestational age (GA) cut-off maximizing differences among these two forms. Patients and Methods: A cohort of 656 consecutive singleton pregnancies with FGR was created. We used the decision tree analysis to evaluate the GA cut-off that best discriminated perinatal mortality, association with PE and adverse perinatal outcome (fetal demise, early neonatal death, neonatal acidosis at birth, and 5-min Apgar score <7). Results: We identified 32 weeks at diagnosis as the optimal cut-off, resulting in two groups with 7.1 and 0%, p < 0.001 perinatal mortality, 35.1 and 12.1%, p < 0.001 association with PE, and 13.4 and 4.6%, p < 0.001 composite adverse perinatal outcome. Abnormal versus normal umbilical artery (UA) Doppler classified two groups with 10.6 and 0.2%, p < 0.001 perinatal mortality, 50.0 and 11.8%, p < 0.001 association with PE, and 18.2 and 4.2%, p < 0.001 composite adverse perinatal outcome. Conclusions: UA Doppler discriminated better the two forms of FGR with average early- and late-onset presentation, higher association with PE and poorer outcome. In the absence of UA information, a GA cut-off of 32 weeks at diagnosis maximizes differences between early- and late-onset FGR.

Background—: Assisted reproductive technologies (ARTs) have been shown to be associated with general vascular dysfunction in late childhood. However, it is unknown whether cardiac remodeling is also present and if these changes already manifest in prenatal life. Our aim was to assess fetal and infant (6 months of age) cardiovascular function in ART pregnancies. Methods and Results—: This prospective cohort study included 100 fetuses conceived by ART and 100 control pregnancies. ART fetuses showed signs of cardiovascular remodeling, including a more globular heart with thicker myocardial walls, decreased longitudinal function (tricuspid ring displacement in controls: median, 6.5 mm [interquartile range, 6.1–7.1 mm]; tricuspid ring displacement in ART: 5.5 mm [interquartile range, 5.1–6.1]; P <0.001), impaired relaxation, and dilated atria (atrial area in controls, 1.46 cm ² [interquartile range, 1.2–1.5 cm ² ]; atrial area in ART, 1.6 cm ² [interquartile range, 1.3–1.8 cm ² ]; P <0.001). Additionally, ART infants showed persistence of most cardiac changes and a significant increase in blood pressure and aortic intima-media thickness (systolic blood pressure in controls, 74 mm Hg [interquartile range, 67–83 mm Hg]; systolic blood pressure in ART, 83 mm Hg [interquartile range, 75–94 mm Hg]; P <0.001; aortic intima-media thickness in controls, 0.52 mm [interquartile range, 0.45–0.56 mm]; aortic intima-media thickness in ART, 0.64 mm [interquartile range, 0.62–0.67]; P <0.001). We could not demonstrate that our findings were directly caused by ART because of their association with various confounding factors, including intrauterine growth restriction or factors related to the cause of infertility. Conclusions—: Children conceived by ART manifest cardiac and vascular remodeling that is present in fetal life and persists in postnatal life, suggesting opportunities for early detection and potential intervention. The underlying mechanisms and the effect of potential confounders such as growth restriction or prematurity remain to be elucidated.

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. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Objectives Intrauterine growth restriction is associated with increased cardiovascular risk later in life but the link between fetal disease and postnatal risk is not well-documented. We evaluated longitudinally the association between cardiovascular remodeling in small-for-gestational-age (SGA) fetuses and at 6 months of age. Methods A cohort of 80 SGA fetuses (defined by estimated fetal and birth weights < 10^th centile) delivered > 34 weeks' gestation was compared with 80 normally grown age-matched control fetuses, with follow-up at 6 months of corrected age (i.e. 6 months from estimated date of delivery according to first-trimester crown–rump length). Cardiovascular evaluation included a comprehensive echocardiographic assessment in both fetuses and infants and blood pressure and aortic intima–media thickness (aIMT) measurement in infants. Parameters were adjusted by linear regression analysis for gender, gestational age at delivery, pre-eclampsia, prenatal glucocorticoid exposure, Cesarean delivery, admission to neonatal intensive care unit and body surface area. Results Both pre- and postnatally, when compared with controls, the SGA group showed a more globular cardiac shape (left sphericity index: controls 2.06 vs SGA 1.87 (P = 0.022) prenatally and 1.92 vs 1.67 (P = 0.007) postnatally), as well as signs of systolic longitudinal dysfunction (systolic annular peak velocity (S′): 7.2 vs 6.3 cm/s (P = 0.003) prenatally and 7.9 vs 6.4 cm/s (P < 0.001) postnatally; tricuspid annular plane systolic excursion: 7.2 vs 6.8 mm (P = 0.015) prenatally and 16.0 vs 14.2 mm (P < 0.001) postnatally) and diastolic dysfunction (left isovolumetric relaxation time: 46 vs 52 ms (P < 0.001) prenatally and 50 vs 57 ms (P = 0.034) postnatally). In addition, infants in the SGA group had increased mean blood pressure (mean: 61 vs 70 mmHg, P < 0.001) and maximum aIMT (0.57 vs 0.66 mm; P < 0.001). Conclusions Primary cardiovascular changes are already present in the SGA fetus and persist at 6 months of age. These data support prenatal cardiovascular remodeling as a mechanistic pathway of increased risk later in life in cases of SGA, regardless of Doppler abnormalities. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.