Late-onset Intrauterine Growth Restriction Research Articles

Prediction of Intrauterine Growth Restriction and Preeclampsia Using Machine Learning-Based Algorithms: A Prospective Study.

(1) Background: Prenatal care providers face a continuous challenge in screening for intrauterine growth restriction (IUGR) and preeclampsia (PE). In this study, we aimed to assess and compare the predictive accuracy of four machine learning algorithms in predicting the occurrence of PE, IUGR, and their associations in a group of singleton pregnancies; (2) Methods: This observational prospective study included 210 singleton pregnancies that underwent first trimester screenings at our institution. We computed the predictive performance of four machine learning-based methods, namely decision tree (DT), naïve Bayes (NB), support vector machine (SVM), and random forest (RF), by incorporating clinical and paraclinical data; (3) Results: The RF algorithm showed superior performance for the prediction of PE (accuracy: 96.3%), IUGR (accuracy: 95.9%), and its subtypes (early onset IUGR, accuracy: 96.2%, and late-onset IUGR, accuracy: 95.2%), as well as their association (accuracy: 95.1%). Both SVM and NB similarly predicted IUGR (accuracy: 95.3%), while SVM outperformed NB (accuracy: 95.8 vs. 94.7%) in predicting PE; (4) Conclusions: The integration of machine learning-based algorithms in the first-trimester screening of PE and IUGR could improve the overall detection rate of these disorders, but this hypothesis should be confirmed in larger cohorts of pregnant patients from various geographical areas.

Quantitative Proteomics of Maternal Blood Plasma in Isolated Intrauterine Growth Restriction

Intrauterine growth restriction (IUGR) remains a significant concern in modern obstetrics, linked to high neonatal health problems and even death, as well as childhood disability, affecting adult quality of life. The role of maternal and fetus adaptation during adverse pregnancy is still not completely understood. This study aimed to investigate the disturbance in biological processes associated with isolated IUGR via blood plasma proteomics. The levels of 125 maternal plasma proteins were quantified by liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM MS) with corresponding stable isotope-labeled peptide standards (SIS). Thirteen potential markers of IUGR (Gelsolin, Alpha-2-macroglobulin, Apolipoprotein A-IV, Apolipoprotein B-100, Apolipoprotein(a), Adiponectin, Complement C5, Apolipoprotein D, Alpha-1B-glycoprotein, Serum albumin, Fibronectin, Glutathione peroxidase 3, Lipopolysaccharide-binding protein) were found to be inter-connected in a protein–protein network. These proteins are involved in plasma lipoprotein assembly, remodeling, and clearance; lipid metabolism, especially cholesterol and phospholipids; hemostasis, including platelet degranulation; and immune system regulation. Additionally, 18 proteins were specific to a particular type of IUGR (early or late). Distinct patterns in the coagulation and fibrinolysis systems were observed between isolated early- and late-onset IUGR. Our findings highlight the complex interplay of immune and coagulation factors in IUGR and the differences between early- and late-onset IUGR and other placenta-related conditions like PE. Understanding these mechanisms is crucial for developing targeted interventions and improving outcomes for pregnancies affected by IUGR.

Fetal Cerebroplacental Artery Ratio versus Uterine Artery Doppler Ultrasonography for Prediction of Late Onset Intrauterine Fetal Growth Restriction among High Risk Pregnant Women

Fetal Cerebroplacental Artery Ratio versus Uterine Artery Doppler Ultrasonography for Prediction of Late Onset Intrauterine Fetal Growth Restriction among High Risk Pregnant Women

Intrauterine Growth Restriction-Prediction and Peripartum Data on Hospital Care.

Background and Objectives: We aimed to prospectively obtain data on pregnancies complicated with intrauterine growth restriction (IUGR) in the Prenatal Diagnosis Unit of the Emergency County Hospital of Craiova. We collected the demographic data of mothers, the prenatal ultrasound (US) features, the intrapartum data, and the immediate postnatal data of newborns. We aimed to assess the detection rates of IUGR fetuses (the performance of the US in estimating the actual neonatal birth weight), to describe the prenatal care pattern in our unit, and to establish predictors for the number of total hospitalization days needed postnatally. Materials and Methods: Data were collected from cases diagnosed with IUGR undergoing prenatal care in our hospital. We compared the percentile of estimated fetal weight (EFW) using the Hadlock 4 technique with the percentile of weight at birth. We retrospectively performed a regression analysis to correlate the variables predicting the number of hospitalization days. Results: Data on 111 women were processed during the period of 1 September 2019-1 September 2022. We confirmed the significant differences in US features between early- (Eo) and late-onset (Lo) IUGR cases. The detection rates were higher if the EFW was lower, and Eo-IUGR was associated with a higher number of US scans. We obtained a mathematical formula for estimating the total number of hospitalization days needed postnatally. Conclusion: Early- and late-onset IUGR have different US features prenatally and different postnatal outcomes. If the US EFW percentile is lower, a prenatal diagnosis is more likely to be made, and a closer follow-up is offered in our hospital. The total number of hospitalization days may be predicted using intrapartum and immediate postnatal data in both groups, having the potential to optimize the final financial costs and to organize the neonatal department efficiently.

SLC38A4 Amino Acid Transporter Expression Is Significantly Lower in Early Preterm Intrauterine Growth Restriction Complicated Placentas.

Intrauterine growth restriction (IUGR), predominantly caused by placental insufficiency, affects partitioning of nutrients to the fetus. The system A sodium-coupled transporters (SNAT or SLC38), of types A1, A2, and A4, control non-essential amino acid uptake and supply. Here, we aimed to investigate the expression of these transporters across different placental disease cohorts and cells. To determine disease impact, transporter expressions at the gene (qPCR) and protein (western blots) level were assessed in gestationally matched placental tissues. Early (<34 weeks), and late (34-36 weeks) onset IUGR cases with/out preeclampsia were compared to preterm controls. We also investigated level of transporter expression in primary trophoblasts under glucose deprivation (n = 6) and hypoxia conditions (n = 7). SLC38A4 protein was significantly downregulated in early preterm pregnancies complicated with IUGR with/out preeclampsia. There were no differences in late preterm IUGR cohorts. Furthermore, we demonstrate for the first time in primary trophoblast cells, that gene expression of the transporters was sensitive to and induced by glucose starvation. SLC38A4 mRNA expression was also significantly upregulated in response to hypoxia. Thus, SLC38A4 expression was persistently low in early preterm IUGR pregnancies, regardless of disease aetiology. This suggests that gestational age at delivery, and consequently IUGR severity, may influence loss of its expression.

Fetal Tibial Artery Doppler in Late IUGR Fetuses: A Longitudinal Study

Late-onset intrauterine fetal growth restriction (IUGR) is a common pregnancy complication diagnosed in 5-10% of pregnant women worldwide. Under the impact of hypoxia, the fetus develops a protective mechanism of adaptive changes occurring in the cerebral circulation ("brain-sparing effect"). We conducted detailed longitudinal Doppler examinations and the monitoring of the fetal condition in 53 IUGR fetuses. Doppler measurements of the pulsatility index in the fetal tibial (TA-PI), umbilical (UA-PI), and middle cerebral arteries (MCA-PI) were performed, and the cerebral placental ratio (CPR) was determined on a weekly basis from the 33rd week to the birth. The longitudinal analysis showed a significant increase in the TA-PI. The UA showed a plateau, but no increase was detected near term. The MCA-PI and CPR showed a progressive decrease in values from inclusion to delivery. Our findings indicate that the increase in the TA-PI was the first sign of the aggravating state of the fetus with the changes registered from the 35th week. The parameters of the UA-PI did not show significant changes, while the MCA and CPR became abnormal later from the 37th week. These observations can serve towards the development of guidelines for detecting the deteriorating signs and intervention timing in IUGR during late pregnancies.

OC04.01: Late onset intrauterine growth restriction: from prenatal diagnosis to short‐term neurodevelopment outcomes

OC04.01: Late onset intrauterine growth restriction: from prenatal diagnosis to short‐term neurodevelopment outcomes

Late-onset intrauterine growth restriction and HHV-6 infection: A pilot study.

Late-onset Intrauterine growth restriction (IUGR) refers to impaired growth and development of the fetus, characterized by placental morphological abnormalities that affect the fetus's supply of nutrients. Human leukocyte antigen-G (HLA-G) is physiologically expressed during pregnancy, but decreased in normal placenta during the last weeks of gestation possibly inducing childbirth. Several viruses involved in congenital infection, such as herpesviruses, exploit HLA-G expression as an immune-escape mechanism. To date, despite different congenital herpetic infections havingbeen associated with late IUGR, no direct implication of Human herpesvirus 6 (HHV-6) infection has been reported. We evaluated HLA-G expression and HHV-6 infection in 11 placentas from late-onset IUGR newborns and 11 placentas from uncomplicated pregnancies by histopathological and immunohistochemistry analysis. We found higher levels of HLA-G expression and HHV-6 presence in IUGR placenta samples compared with control placenta samples. We report HHV-6 staining in IUGR placenta samples, characterized by high HLA-G expression. These preliminary data suggest a possible involvement of HHV-6 infection in HLA-G deregulation that might affect vessel remodeling and prevent the correct pregnancy outcome in the IUGR condition.

Standardized healthcare pathway in intrauterine growth restriction and minimum evidence-based care

IntroductionFetal growth restricted fetuses are less likely to receive evidence-based care; a previous work demonstrated an improvement in neonatal prognosis when fetuses with intrauterine growth restriction (IUGR) received minimum evidence based-care. ObjectiveThe objective of the study was to evaluate the impact of a standardized healthcare pathway on the implementation of the recommended clinical practice in the antenatal management of IUGR fetuses, in comparison to a traditional pathway. The quality of the implementation of practice has been defined whether or not minimum evidence-based care (MEC), defined according to the recommendations of the French college of gynecologists and obstetricians (CNGOF), has been implemented. Study designFrom a historical cohort of 31,052 children, born at the Femme Mère Enfant Hospital (Lyon, France) between January 1st, 2011 and December 31st, 2017, we selected the population of IUGR fetuses. We compared the rate of MEC between the IUGR fetuses followed-up in the traditional healthcare pathway versus the IUGR fetuses followed-up in a standardized healthcare pathway between 2015 and 2017. ResultsA total of 245 IUGR were tracked between 2015 and 2017. Over this period, 120 fetuses were followed within the traditional pathway and 125 within the IUGR pathway.The standardized pathway resulted in a higher rate of MEC (86,4%) when compared to IUGR fetuses followed-up in the traditional pathway (27,5% (OR* 20 (95 % CI 10.0−39.7). Among early-onset IUGR: 31 % received MEC in the traditional pathway versus 83 % in the standardized pathway (p<0.001). Among late-onset IUGR: 22 % received MEC in the traditional pathway versus 92 % in the standardized pathway (p<0.001). The provided care in the standardized pathway resulted in an increase of complete antenatal corticosteroid therapy (92,8 %) when compared to the traditional pathway (50.0 %; p<0.001) and a reduction of the rate of caesarean sections before labor for non-reassuring fetal heart rate (15 %) when compared to the traditional pathway (41.3 % p=0.007). ConclusionThe standardized pathway improves the implementation of the local recommendations in the management of early- and late-onset IUGR. This study is the first to suggest a standardized care pathway in prenatal medicine. A medico-economic study could estimate the health care savings that such a pathway would provide by allowing a medical management in accordance with the recommendations.

Placental fibronectin staining is unaffected in pregnancies complicated by late-onset intrauterine growth restriction and small for gestational age fetuses.

To investigate the placental staining pattern of fibronectin, an extracellular matrix protein essential for trophoblastic invasion, in pre-eclampsia and fetal growth restriction. This was a retrospective study conducted at the University of Udine, including the placentas of women with pre-eclampsia and fetal growth restriction collected between January 1, 2001, and December 31, 2010. Fibronectin was evaluated in placental tissue micro-array by immunohistochemistry, describing localization and intensity of staining. The study included the placentas of 36 women with early-onset (delivery <34weeks of gestation) pre-eclampsia; 6 with early-onset HELLP syndrome; 17 with early-onset intrauterine growth restriction (IUGR); 14 with late-onset (delivery ≥34weeks of gestation) pre-eclampsia; 35 with late-onset IUGR; 18 with small for gestational age (SGA) fetuses (birth weight <10th percentile); and 64 controls. Fibronectin was present both at the cell surface and in the cytoplasm. Cytoplasm staining intensity resulted higher in early forms of pregnancy-related complications compared to controls, although this was statistically significant (P<0.05) only for early-onset pre-eclampsia (P=0.085 for HELLP syndrome; P=0.091 for IUGR). Also, late-onset forms of pre-eclampsia had stronger cytoplasmic and pericellular staining compared to controls (P<0.05). Interestingly, staining of both late-onset IUGR and SGA was comparable to controls. Fibronectin appeared to be unaffected in women with late-onset IUGR and SGA fetuses, suggesting a peculiar common pathogenetic pattern in these conditions.

Cardiovascular adaptation to extrauterine life after intrauterine growth restriction

A comprehensive echocardiographic study was performed in 25 neonates with intrauterine growth restriction and 25 adequate-for-gestational-age neonates. Compared with controls, neonates with intrauterine growth restriction had more globular ventricles, lower longitudinal tricuspid annular motion, and higher left stroke volume without differences in the heart rate. Neonates with intrauterine growth restriction also showed subclinical signs of diastolic dysfunction in the tissue Doppler imaging with lower values of early (e') diastolic annular peak velocities in the septal annulus. Finally, the Tei index in the tricuspid annulus was higher in the intrauterine growth restriction group. Neonates with history of intrauterine growth restriction showed cardiac remodelling and signs of systolic and diastolic dysfunction. Overall, there was a significant tendency to worse cardiac function results in the right heart. The adaptation to extrauterine life occurred with more globular hearts, higher stroke volumes but a similar heart rate compared to adequate-for-gestational-age neonates.

Increased placental sFlt-1 but unchanged PlGF expression in late-onset preeclampsia

ABSTRACTObjective: To investigate whether differences between late-onset preeclampsia (PE) and intrauterine growth restriction (IUGR) can be explained by differential placental expression patters of sFlt-1, Flt-1, and placental growth factor (PlGF).Methods: Placental tissues and maternal blood samples from seven patients with PE, five IUGR, and seven age-matched controls were studied for mRNA and protein levels as well as protein localization and expression intensity.Results: Placental PlGF mRNA and protein expression were not altered by placental dysfunction while placental villous trophoblast expression intensity of PlGF was increased.Conclusion: High sFlt-1 concentrations may account for diminished maternal serum PlGF levels.

Ultrasound detection of altered placental vascular morphology based on hemodynamic pulse wave reflection.

Abnormally pulsatile umbilical artery (UA) Doppler ultrasound velocity waveforms are a hallmark of severe or early onset placental-mediated intrauterine growth restriction (IUGR), whereas milder late onset IUGR pregnancies typically have normal UA pulsatility. The diagnostic utility of these waveforms to detect placental pathology is thus limited and hampered by factors outside of the placental circulation, including fetal cardiac output. In view of these limitations, we hypothesized that these Doppler waveforms could be more clearly understood as a reflection phenomenon and that a reflected pulse pressure wave is present in the UA that originates from the placenta and propagates backward along the UA. To investigate this, we developed a new ultrasound approach to isolate that portion of the UA Doppler waveform that arises from a pulse pressure wave propagating backward along the UA. Ultrasound measurements of UA lumen diameter and flow waveforms were used to decompose the observed flow waveform into its forward and reflected components. Evaluation of CD1 and C57BL/6 mice at embryonic day (E)15.5 and E17.5 demonstrated that the reflected waveforms diverged between the strains at E17.5, mirroring known changes in the fractal geometry of fetoplacental arteries at these ages. These experiments demonstrate the feasibility of noninvasively measuring wave reflections that originate from the fetoplacental circulation. The observed reflections were consistent with theoretical predictions based on the area ratio of parent to daughters at bifurcations in fetoplacental arteries suggesting that this approach could be used in the diagnosis of fetoplacental vascular pathology that is prevalent in human IUGR. Given that the proposed measurements represent a subset of those currently used in human fetal surveillance, the adaptation of this technology could extend the diagnostic utility of Doppler ultrasound in the detection of placental vascular pathologies that cause IUGR.NEW & NOTEWORTHY Here, we describe a novel approach to noninvasively detect microvascular changes in the fetoplacental circulation using ultrasound. The technique is based on detecting reflection pulse pressure waves that travel along the umbilical artery. Using a proof-of-principle study, we demonstrate the feasibility of the technique in two strains of experimental mice.

Fetal gender and gestational age differentially affect PCSK9 levels in intrauterine growth restriction.

BackgroundMaternal and fetal Low Density Lipoprotein-Cholesterol (LDL-C) concentrations are compromised in intrauterine growth restriction (IUGR). Generally, LDL-C catabolism is under control of PCSK9 by binding to the LDL-receptor leading to its degradation. Hence, we hypothesized a role for PCSK9 in the modulation of lipid metabolism and placental transport in IUGR.Methods172 women, 70 IUGR and 102 controls were included in the study. Maternal and fetal serum PCSK9 levels and lipid profiles including LDL-C were measured. Placental LDL-receptor and PCSK9 expressions were estimated by tissue microarray immunohistochemistry, and analyzed by two blinded observers using an immunoreactivity score. Non-parametric tests and multivariate regression analyses were used for statistical estimations.ResultsPCSK9 levels in the maternal and fetal compartment independently predicted LDL-C levels (maternal compartment: adjusted R 2 = 0.2526; coefficient b i = 0.0938, standard error sbi =0.0217, rpartial = 0.4420, t-value = 4.323, p < 0.0001; fetal compartment: adjusted R 2 = 0.2929; b i = 0.1156, sbi =0.020, rpartial = 0.5494, t-value = 5.81, p < 0.0001). We did not find significant differences in maternal PCSK9 concentrations between IUGR and controls. However, we found lower fetal serum PCSK9 concentrations in IUGR than in controls (IUGR median 137.1 ng/mL (95% CI 94.8-160.0) vs. controls 176.8 (154.6-202.5), p = 0.0005). When subgrouping according to early onset, late onset IUGR, and fetal gender differences remained consistent only for male neonates born before 34 weeks of gestation. In the placenta we found no correlation between PCSK9 and LDL-receptor expression patterns. However, the LDL-receptor was significantly upregulated in IUGR when compared to controls (p = 0.0063).ConclusionsOur results suggest that PCSK9 play a role in impaired fetal growth by controlling fetal LDL-C metabolism, which seems to be dependent on gestational age and fetal gender. This underlines the need to identify subgroups of IUGR that may benefit from individualized and gender-specific pharmacotherapy in future studies.

Doppler velocimetry and adverse outcome in labor induction for late IUGR

Background: Late onset intrauterine growth restriction (IUGR) represents one of the main causes of perinatal morbidity/mortality. No guidelines are available on labor induction in IUGRs, even if delivery at 37/38 weeks is suggested. This study aims to assess maternal–fetal variables related to adverse outcome in labor induction for late IUGR.Methods: One hundred cases of induction for late IUGR were retrospectively revised on fetal weight, MCA, UA, CPR and uterine artery (utA) Doppler, oligohydramnios, Bishop score, start of induction, augmentation. The variables were matched with the following adverse outcomes: CS or vacuum extractor delivery (IVD); NICU admission; low Apgar score; UA pH < 7.10.Results: Regular vaginal delivery occurred in 65% of cases; the rate of CS and IVD was 32% and 5%. UA, MCA and CPR abnormalities were all significantly related to a higher risk of CS. Bishop score < 3 and start of induction by oxitocin resulted statistically associated to CS, while prostaglandins were related to vaginal delivery. No augmentation and oxitocin in labor were positively related to vaginal delivery. Maternal morbidity and Bishop score < 3 showed a significant association with NICU admission.Discussion: Doppler velocimetry of UA, MCA and CPR are useful tools for the identification and management of the late term IUGRs.

The usefulness of fetal Doppler evaluation in early versus late onset intrauterine growth restriction. Review of the literature.

Intrauterine growth restriction (IUGR) represents a serious condition that can lead to increased perinatal morbidity, mortality and postnatal impaired neurodevelopment. There are two distinct phenotypes of IUGR: early onset and late onset IUGR with different onset, patterns of evolution and fetal Doppler profile. In early onset preeclampsia the main Doppler modifications are at the level of umbilical artery, with progressive augmentation of the pulsatility index to absent or reverse end diastolic flow. The modifications of the cerebral, cardiac and ductus venosus circulation are generally present, but with different sequences. The late onset IUGR is determined by third trimester placental insufficiency that entails fetal hypoxia. The cerebro-placental ratio (CPR) and the pulsatility index of the middle cerebral artery (PI MCA) seems to be the main markers for both diagnosis and obstetrical management while umbilical Doppler PI is frequently normal. Also the sequence of Doppler alterations is neither specific nor complete. New protocols for the diagnosis and management of late onset IUGR need to be implemented.

Early functional and morphological brain disturbances in late-onset intrauterine growth restriction

AimsTo determine whether the brain disturbances develop in late-onset intrauterine growth restriction (IUGR) before blood flow redistribution towards the fetal brain (detected by Doppler measurements in the middle cerebral artery and umbilical artery). Further, to evaluate predictive values of Doppler arterial indices and umbilical cord blood gases and pH for early functional and/or morphological brain disturbances in late-onset IUGR. Study designThis cohort study included 60 singleton term pregnancies with placental insufficiency caused late-onset IUGR (IUGR occurring after 34 gestational weeks). Umbilical artery resistance index (URI), middle cerebral artery resistance index (CRI), and cerebroumbilical (C/U) ratio (CRI/URI) were monitored once weekly. Umbilical blood cord samples (arterial and venous) were collected for the analysis of pO2, pCO2 and pH. Morphological neurological outcome was evaluated by cranial ultrasound (cUS), whereas functional neurological outcome by Amiel-Tison Neurological Assessment at Term (ATNAT). Results50 fetuses had C/U ratio>1, and 10 had C/U ratio≤1; among these 10 fetuses, 9 had abnormal neonatal cUS findings and all 10 had non-optimal ATNAT. However, the total number of abnormal neurological findings was much higher. 32 neonates had abnormal cUS (53.37%), and 42 (70.00%) had non-optimal ATNAT. Furthermore, Doppler indices had higher predictive validity for early brain disturbances than umbilical cord blood gases and pH. C/U ratio had the highest predictive validity with threshold for adverse neurological outcome at value 1.13 (ROC analysis), i.e., 1.18 (party machine learning algorithm). ConclusionAdverse neurological outcome at average values of C/U ratios>1 confirmed that early functional and/or structural brain disturbances in late-onset IUGR develop even before activation of fetal cardiovascular compensatory mechanisms, i.e., before Doppler signs of blood flow redistribution between the fetal brain and the placenta.

Vessels of the umbilical cord: an anatomo-microscopic study in normal and pathological newborns

Intrauterine growth restriction (IUGR) due to placental insufficiency is associated with blood-flow redistribution. Placental insufficiency in late-onset IUGR often goes undetected by umbilical artery Doppler scan. Despite a broad general body of literature referencing placentas of IUGR pregnancies, there are no report on the structural characteristics of the vessels of the umbilical cord in IUGR. Thus, the aim of the present study was to compare the microscopic anatomy of the umbilical arteries and veins in normal, IUGR and small for gestational age (SGA) newborns. Twenty six umbilical cords were taken from 10 IUGR, 5 SGA, and 11 controls newborns. The histological and morphological examination was performed with EE, Azan–Mallory, Sirius Red stains and morphometric evaluation was performed through a computer image analysis approach. In the controls, the umbilical artery shows a muscular tunica, organized by two layers, an outer one with circularly arranged cells, and an inner one, with irregularly arranged cells. In the IUGR longitudinal muscular fibers are observable. In IUGR the percentage of the muscular fibers of the umbilical artery was greater with respect of SGA and controls. In IUGR and SGA the percentage of the muscular fibers was minor with respect to controls. In the umbilical artery in IUGR and SGA the elastic fibers and collagen I was major and collagen III was minor with respect to SGA. In the umbilical vein the collagen III was major in IUGR and SGA with respect to controls. These data agree with those of intrauterine life, in which a major thickness of the abdominal aortic wall was observed in fetuses with abnormalities of Doppler flussimetry. The rearrangement of umbilical artery may affect the mechanical properties of these vessels and disturb fetal blood circulation.

The hemodynamics of late-onset intrauterine growth restriction by MRI

Late-onset intrauterine growth restriction (IUGR) results from a failure of the placenta to supply adequate nutrients and oxygen to the rapidly growing late-gestation fetus. Limitations in current monitoring methods present the need for additional techniques for more accurate diagnosis of IUGR in utero. New magnetic resonance imaging (MRI) technology now provides a noninvasive technique for fetal hemodynamic assessment, which could provide additional information over conventional Doppler methods. The objective of the study was to use new MRI techniques to measure hemodynamic parameters and brain growth in late-onset IUGR fetuses. This was a prospective observational case control study to compare the flow and T2 of blood in the major fetal vessels and brain imaging findings using MRI. Indexed fetal oxygen delivery and consumption were calculated. Middle cerebral artery and umbilical artery pulsatility indexes and cerebroplacental ratio were acquired using ultrasound. A score of ≥ 2 of the 4 following parameters defined IUGR: (1) birthweight the third centile or less or 20% or greater drop in the centile in estimated fetal weight; (2) lowest cerebroplacental ratio after 30 weeks less than the fifth centile; (3) ponderal index < 2.2; and (4) placental histology meets predefined criteria for placental underperfusion. Measurements were compared between the 2 groups (Student t test) and correlations between parameters were analyzed (Pearson's correlation). MRI measurements were compared with Doppler parameters for identifying IUGR defined by postnatal criteria (birthweight, placental histology, ponderal index) using receiver-operating characteristic curves. We studied 14 IUGR and 26 non-IUGR fetuses at 35 weeks' gestation. IUGR fetuses had lower umbilical vein (P = .004) and pulmonary blood flow (P = .01) and higher superior vena caval flow (P < .0001) by MRI. IUGR fetuses had asymmetric growth but smaller brains than normal fetuses (P < .0001). Newborns with IUGR also had smaller brains with otherwise essentially normal findings on MRI. Vessel T2s, oxygen delivery, oxygen consumption, middle cerebral artery pulsatility index, and cerebroplacental ratio were all significantly lower in IUGR fetuses, whereas there was no significant difference in umbilical artery pulsatility index. IUGR score correlated positively with superior vena caval flow and inversely with oxygen delivery, oxygen consumption, umbilical vein T2, and cerebroplacental ratio. Receiver-operating characteristic curves revealed equivalent performance of MRI and Doppler techniques in identifying IUGR that was defined based on postnatal parameters with superior vena caval flow area under the curve of 0.94 (95% confidence interval, 0.87-1.00) vs a cerebroplacental ratio area under the curve of 0.80 (95% confidence interval, 0.64-0.97). MRI revealed the expected circulatory redistribution in response to hypoxia in IUGR fetuses. The reduced oxygen delivery in IUGR fetuses indicated impaired placental oxygen transport, whereas reduced oxygen consumption presumably reflected metabolic adaptation to diminished substrate delivery, resulting in slower fetal growth. Despite brain sparing, placental insufficiency limits fetal brain growth. Superior vena caval flow and umbilical vein T2 by MRI may be useful new markers of late-onset IUGR.

Fetal cardiac function in late-onset intrauterine growth restrictionvssmall-for-gestational age, as defined by estimated fetal weight, cerebroplacental ratio and uterine artery Doppler

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. 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. 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). 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.