Growth Restriction Group Research Articles

Altered Transmission of Cardiac Cycles to Ductus Venosus Blood Flow in Fetal Growth Restriction: Why Ductus Venosus Reflects Fetal Circulatory Changes More Precisely.

We aimed to investigate the relation between the time intervals of the flow velocity waveform of ductus venosus (DV-FVW) and cardiac cycles. We defined Delta A as the difference in the time measurements between DV-FVW and cardiac cycles on the assumption that the second peak of ductus venosus (D-wave) starts simultaneously with the opening of the mitral valve (MV). As well, we defined Delta B as the difference of the time measurements between DV-FVW and cardiac cycles on the assumption that the D-wave starts simultaneously with the closure of the aortic valve (AV). We then compared Delta A and Delta B in the control and fetal growth restriction (FGR) groups. In the control group of healthy fetuses, Delta A was strikingly shorter than Delta B. On the other hand, in all FGR cases, no difference was observed. The acceleration of the D-wave is suggested to be generated by the opening of the MV under normal fetal hemodynamics, whereas it precedes the opening of the MV in FGR. Our results indicate that the time interval of DV analysis might be a more informative parameter than the analysis of cardiac cycles.

The role of oligohydramnios and fetal growth restriction in adverse pregnancy outcomes in preeclamptic patients.

We aimed to compare perinatal outcomes of oligohydramnios or fetal growth restriction with normal amniotic fluid index and fetal growth in preeclampsia and to compare the outcomes of only oligohydramnios, only fetal growth restriction and oligohydramnios with fetal growth restriction preeclamptic groups. A total of 743 preeclamptic patients were evaluated between June 2016 and 2020. Patients were divided into two groups: preeclampsia with oligohydramnios or fetal growth restriction (n = 237) and preeclampsia with normal amniotic fluid index and fetal growth (n = 506). Then, the first group was divided subgroups as only oligohydramnios (n = 55), only fetal growth restriction (n = 125) and oligohydramnios with fetal growth restriction (n = 57). Demographic characteristics and perinatal outcomes were recorded. Gestational age at delivery (p < 0.001), birth weight (p < 0.001), Apgar scores (p < 0.001) and eclampsia (p < 0.001) were lower whereas impaired doppler findings (p < 0.001), cesarean rates (p < 0.001), preterm delivery (p < 0.001), abruptio placenta (p < 0.001), acute fetal distress (p < 0.001), RDS (p < 0.001), NICU requirement (p < 0.001) and neonatal death (p < 0.001) were higher in oligohydramnios or fetal growth restriction preeclamptic group. In subgroup analysis, there were differences between three groups according to the gestational age (p < 0.001), cesarean rates (p = 0.002), preterm delivery (p < 0.001), intensive care unit requirement (p = 0.039), birth weight (p < 0.001), Apgar scores (p < 0.001), RDS (p < 0.001) and NICU requirement (p < 0.001). In pairwise comparison, there was significant difference between only oligohydramnios and only fetal growth restriction group and between only oligohydramnios and oligohydramnios with fetal growth restriction group according to birth weight, Apgar scores, preterm delivery and cesarean rates, presence of RDS, maternal and neonatal intensive care unit requirement. No significant difference was detected between only fetal growth restriction group and oligohydramnios with fetal growth restriction group in terms of all parameters. We suggest that patients with only oligohydramniosis have more favorable pregnancy outcomes than pregnants with only fetal growth restriction and coexistence of two conditions in preeclamptic patients. We claim that it could be appropriate to recommend close monitorization in preeclamptic patients with only fetal growth restriction and oligohydramniosis and fetal growth restriction.

Human placental microperfusion and microstructural assessment by intra-voxel incoherent motion MRI for discriminating intrauterine growth restriction: a pilot study

Objectives To evaluate the potential of Intravoxel Incoherent Motion (IVIM) Imaging in the quantification of placental micro-perfusion and microstructural features to identify and discriminate different forms of intrauterine growth restriction (IUGR) and normal fetuses pregnancies. Methods Small for gestational age SGA (n = 8), fetal growth restriction FGR (n = 10), and normal (n = 49) pregnancies were included in the study. Placental Magnetic Resonance Imaging (MRI) was performed at 1.5 T using a diffusion-weighted sequence with 10 b-values. IVIM fractional perfusion (fp), diffusion (D), and pseudodiffusion (D*) were evaluated on the fetal and maternal placental sides. Correlations between IVIM parameters, Gestational Age (GA), Birth Weight (BW), and the presence or absence of prenatal fetoplacental Doppler abnormalities at the US were investigated in SGA, FGR, and normal placentae. Results fp and D* of the placental fetal side discriminate between SGA and FGR (p = .021; p = .036, respectively), showing lower values in FGR. SGA showed an intermediate perfusion pattern in terms of fp and D* compared to FGR and normal controls. In the intrauterine growth restriction group (SGA + FGR), a significant positive correlation was found between fp and BW (p < .002) in the fetal placenta and a significant negative correlation was found between D and GA in both the fetal (p < .0009) and maternal (p < .006) placentas. Conclusions Perfusion IVIM parameters fp and D* may be useful to discriminate different micro-vascularization patterns in IUGR being helpful to detect microvascular subtle impairment even in fetuses without any sign of US Doppler impairment in utero. Moreover, fp may predict fetuses’ body weight in intrauterine growth restriction pregnancies. The diffusion IVIM parameter D may reflect more rapid microstructural rearrangement of the placenta due to aging processes in the IUGR group than in normal controls.

Comparison of umbilical coiling index in term pregnancies with and without fetal growth restriction

Objective: To investigate pregnancies with and without fetal growth restriction, giving birth after 37 weeks of gestation in terms of umbilical coiling index and neonatal outcomes. Materials and Methods: Twenty-nine patients with fetal growth restriction and 46 patients who have normal pregnancy and delivered after the 37th week of gestation were recruited in this study. The umbilical coiling index was measured by ultrasound, following the patients who were hospitalized for delivery. Results: There were statistically significant differences between the groups regarding to umbilical artery pulsatility index, gestational age at delivery and birth weight of the newborn. The need for a cesarean section because of non-reassuring fetal condition was statistically significantly higher in the fetal growth restriction group. The mean antenatal umbilical coiling index in fetal growth restriction and control patients was 0.29±0.08 and 0.27±0.08, respectively and the difference was not statistically significant. Conclusion: There was no statistically significant difference between the patients diagnosed with and without fetal growth restriction who delivered after the 37th gestational week, regarding the umbilical coiling index and perinatal outcomes, except umbilical artery pulsatility index, gestational age at birth and birth weight of the newborn.

Individualized growth assessment in pregnancies complicated by fetal gastroschisis

Objective Prenatal ultrasound (US) has been shown to overestimate the incidence of suspected fetal growth restriction (FGR) in gastroschisis cases. This is largely because of altered sonographic abdominal circumference (AC) measurements when comparing gastroschisis cases with population nomograms. Individualized Growth Assessment (IGA) evaluates fetal growth using serial US measurements that allow consideration of the growth potential for a given case. Our goal was to assess the utility of IGA for distinguishing normal and pathological fetal growth in gastroschisis cases. Study design Pregnancies with prenatally diagnosed fetal gastroschisis were managed and delivered at a single academic medical center. US fetal biometry including head circumference (HC), abdominal circumference (AC), and femur diaphysis length (FDL), and neonatal measurements including birthweight and HC were collected and analyzed for 32 consecutive fetal gastroschisis cases with at least two 2nd and two 3rd trimester measurements. Second trimester growth velocities were compared to a group of 118 non-anomalous fetuses with normal neonatal growth outcomes. Gastroschisis cases were classified into groups based on fetal growth pathology score (FGPS9) patterns. Agreement between IGA (FGPS9) and serial conventional estimated fetal weight (EFW) measurements for determining growth pathology was evaluated. Neonatal size outcomes were compared between conventional birthweight classifications for determining small for gestational age (SGA) and IGA Growth Potential Realization Index (GPRI) for weight and head circumference measurements. Results Fetal growth pathology score (FGPS9) measurements identified three in-utero growth patterns: no growth pathology, growth restriction and recovery, and progressive growth restriction. In the no growth pathology group (n = 19), there was 84% agreement between IGA and conventional methods in determining pathological growth in both the 3rd trimester and at birth. In the growth restriction and recovery group (n = 7), there was 71% agreement both in the 3rd trimester and at birth between IGA and conventional methods. In the progressive growth restriction group (n = 5), there was 100% agreement in the 3rd trimester and 60% agreement at birth between IGA and conventional methods. Conclusion We present the first study using IGA to evaluate normal and pathological fetal growth in prenatally diagnosed gastroschisis cases. IGA was able to delineate two 3rd trimester growth pathology patterns – one with persistent growth restriction and another with in-utero growth recovery. Further validation of these initial findings with larger cohorts is warranted.

"Aggressive" Feeding of Very Preterm Neonates and Body Mass Index at School Age.

Introduction: The effects of “aggressive” neonatal feeding policies of very preterm neonates (VPN) and the risk of metabolic syndrome later in life remain questionable. We aimed to evaluate the effect of our “aggressive” nutrition policies of VPN during hospitalisation on body mass index (BMI) at ages 2 and 8 years. Materials and Methods: Eighty four VPN, who received “aggressive” nutrition during hospitalisation in an effort to minimise postnatal growth restriction (PGR) (group A), and 62 term neonates, as controls (group B), were enrolled in the study. Group A was further divided in four subgroups depending on the type (A1: fortified expressed breast milk and preterm formula; A2: exclusively preterm formula) and quantity of milk received (A3: maximum feeds 180–210 mL/kg/day; A4: maximum feeds 210 and up to 260 mL/kg/day). BMI was calculated at ages 2 and 8 years and plotted on the centile charts. Results: There was no significant difference in BMI between groups A and B at 2 and 8 years, respectively, in both absolute BMI values and their centile chart distribution. There was no significant difference in BMI at 2 and 8 years either between subgroups A1 and A2 or between subgroups A3 and A4. Conclusions: “Aggressive” and individualised feeding policy for VPN did not affect the BMI and obesity rates at ages of 2 and 8 years in our study population. The type and quantity of milk feeds had no impact on their BMI at school age. Further larger studies are needed to confirm our results.

Ultrasound Doppler fetal heart rate detection algorithm analyzes the correlation between twin selective fetal growth restriction and cord blood SFass fasL level.

Objective:The paper uses ultrasound Doppler fetal heart rate detection algorithm to explore the placental characteristics of monochorionic twin pregnancy with selective fetal growth restriction, and discuss the correlation between selective fetal growth restriction and cord blood SFass FasL level.Methods:From June 1, 2019 to June 1, 2020 in our hospital, 23 cases of selective fetal growth restriction and 32 cases of uncomplicated cases were included in the monochorionic twin pregnancies whose pregnancy was terminated in our hospital (control group) research. Perfusion was completed within 24 hours after delivery of the placenta. The umbilical arteries and veins of the two fetuses were respectively perfused with four different colors of pigments. The type of anastomoses was judged according to the color of the blood vessels on the placenta surface.Results:The selective fetal growth restriction group was higher than the control group. In the selective fetal growth restriction group and the control group, the number of anastomoses of the placental superficial arterial artery, arterial vein and venous vein were 1.0 and 1.0, 3.0 and 2.0, 0.0 and 0.0, respectively; the placental superficial arterial artery, arterial vein and venous vein. The total diameters of the anastomosed blood vessels were 2.7 and 2.2, 4.0 and 3.4, 0.0 and 0.0 mm, respectively; the total number of superficial placental anastomosed blood vessels in the selective fetal growth restriction group and the control group were 3.5 and 3.5, respectively.The total diameters were 6.9 and 6.9, respectively 5.9mm.Conclusion:Uneven placental share and non-central attachment of the umbilical cord may be risk factors for selective fetal growth restriction in monochorionic twin pregnancy.

HIGHER FREQUENCY OF GERMINAL MATRIX-INTRAVENTRICULAR HEMORRHAGE IN MODERATE AND LATE PRETERM AND EARLY TERM NEONATES WITH INTRAUTERINE GROWTH RESTRICTION COMPARED TO HEALTHY ONES.

SUMMARYGerminal matrix-intraventricular brain hemorrhage is mostly found in preterm neonates, but may also occur in term neonates. The aim of this study was to analyze the prevalence and severity of this type of hemorrhage in moderate and late preterm and early term neonates with intrauterine growth restriction. In the prospective analysis, 100 newborns were examined, i.e. 70 with intrauterine growth restriction and 30 as a control group. Study subjects were neonates from 32 0/7 to 38 6/7 gestational weeks. Body weight, body length, head circumference and ponderal index at birth were analyzed. Hemorrhage was assessed by cranial ultrasound using Papile classification. Out of 70 neonates with intrauterine growth restriction, germinal matrix-intraventricular hemorrhage was not found in 36 (51.43%) neonates, 31 (44.29%) had hemorrhage grade 1, and three (4.29%) had hemorrhage grade 2, which was statistically significant (p<0.001) in relation to the control group. There were no neonates with hemorrhage grade 3 or 4. The predominant type of germinal matrix-intraventricular hemorrhage in the intrauterine growth restriction group was hemorrhage grade 1. Germinal matrix-intraventricular hemorrhage was more often present in the intrauterine growth restricted neonates than in the control group.

The Relationship of Intrauterine Growth Restriction with Placental Pathologic Changes in Newborns

Introduction: Intrauterine growth restriction is a multifaceted problem and is associated with a significant increase in the level of morbidity and perinatal mortality. According to some studies, failure of the placenta is responsible for the most cases of intrauterine growth restriction. The aim of this study was to evaluate the placental pathologic changes in the intrauterine growth restriction (IUGR) samples and compare them with normal cases. Methods: A study population consisted of 60 intrauterine growth restriction neonates and 60 normalized neonates born at Tehran Imam Khomeini Hospital between June 2016 and July 2017. The placenta was weighed, immediately after delivery, and the umbilical cord was separated, then stored in 10% formalin and sent for pathological examination as soon as possible. Data collection was performed according to the following items: the pathologist's report, the results of the infants' examination, and the data in the neonatal cases. Results: The intrauterine growth restriction group showed a high frequency of placenta infarction (P &lt; 0.001), inflammation of the villous (P &lt; 0.001), villous fibrosis (P = 0.044), villous vascularization disorder (P = 0.001), prevalence of chorioamnionitis (P = 0.027), prevalence of Syncytiotrophoblastic knots (P &lt; 0.001) and placental necrosis (P = 0.048) than normal group. However, the mean weight of the placenta (P &lt; 0.001), the length and width of the macroscopic placenta changes was less (P &lt; 0.001). Conclusion: The results of the current study showed that a major part of the macroscopic and histological changes are detectable in the intrauterine growth restriction samples, which are considerably more common than normal, although they are not pathognomonic, but in the future, more accurate results can be obtained from more extensive studies.

Clinical application for pregnacy outcomes of radiofrequency ablation in complex multiple pregnancies

Objective: To investigate the safety and effectiveness of radiofrequency ablation (RFA) for selective fetal reduction in complex multiple pregnancies and analyze factors affecting perinatal outcomes. Methods: This was a retrospective case series of 156 patients undergoing selective fetal reduction by RFA in Provincial Hospital Affiliated to Shandong University from July 22th, 2011 to September 12th, 2018. They were divided into five groups according to surgical indications, including 46 cases in the monochorionic twins discordant for fetal anomalies group, 42 cases in the multiple pregnancies for reducing fetal numbers group, 40 cases in the twin to twin transfusion syndrome (TTTS) group, 24 cases in the selective intrauterine growth restriction (sIUGR) group and 4 cases in the twin reversed arterial perfusion sequence (TRAPS) group. According to the gestational age at surgery, patients were divided into two groups: the gestational age at surgery <20 weeks group (75 cases) and the gestational age at surgery≥20 weeks group (81 cases). According to the cycles of RFA required for surgery, patients were divided into two groups: one cycle group (124 cases) and ≥2 cycles group (32 cases). Basic information of patients, surgical process, postoperative complications and pregnancy outcomes were recorded. The growth and development of survival newborns were also followed up. Factors affecting perinatal outcomes were analyzed. Results: (1) The median gestational age at procedure of 156 patients was 20 weeks (14(+5)- 29(+1) weeks). The median cycles of RFA was 1 cycle (1-3 cycles), of which one cycle accounted for 79.5% (124/156). (2) Eleven (7.1%, 11/156) patients experienced intrauterine fetal death, 27 (17.3%, 27/156) patients miscarried, and the overall survival rate was 75.6% (118/156). Premature birth rate before 34 weeks was 19.5% (23/118). There were 129 neonates. The median gestational age at delivery was 37(+3) weeks (28(+2)- 41(+1) weeks) with a mean birth weight of (2 657±700) g. (3) Analysis of pregnancy outcomes based on surgical indications found that, the gestational age at delivery [38 weeks (30(+1)-41(+1) weeks), 36(+4) weeks (29- 39 weeks), 36(+4) weeks (28(+2)-39(+5) weeks), 38 weeks (31-39(+6) weeks), 38(+3) weeks (30(+4)-38(+4) weeks)] and neonatal birth weight [(2 820±671), (2 435±416), (2 497±843), (2 998±718), (2 517±1 087) g] were significantly different among fetal anomalies group, reducing fetal numbers group, TTTS group, sIUGR group and TRAPS group, respectively (all P<0.05). There were no significant differences in the pregnancy outcomes between gestational age at surgery <20 weeks group and gestational age at surgery ≥20 weeks group, or between one cycle group and ≥2 cycles group, respectively (all P>0.05). Conclusions: RFA is a safe and effective procedure in treating complex monochorionic multiple pregnancies. Surgical indications would affect the gestational age at delivery and neonatal outcomes.

Predictive value of first-trimester ultrasound markers for complicated monochorionic diamniotic twins

Objective To investigate the value of first-trimester ultrasound parameters in predicting complicated monochorionic diamniotic (MCDA) twins. Methods In this retrospective study, pregnant women diagnosed as MCDA twins by ultrasound in the First Affiliated Hospital of Sun Yat-sen University from January 2013 to January 2018 were recruited and divided into the following four groups: non-complicated MCDA twins group, twin-twin transfusion syndrome (TTTS) group, selective intrauterine growth restriction (sIUGR) group and twin anemia-polycythemia sequence (TAPS) group. Thickness of nuchal translucency (NT), crown-rump length (CRL), umbilical cord insertion (UCI) and ductus venosus (DV) flow at 11-14 weeks of gestation were recorded. The predictive value for complicated MCDA twins was analyzed using t-test, Chi-square (or Fisher's exact) test, multivariate logistic regression analysis and receiver operating characteristic (ROC) curve. Results (1) A total of 430 MCDA twin pregnancies were included in this study with 152 in the TTTS group, 142 in the sIUGR group, seven in the TAPS group and 129 in the normal MCDA twins group. No further analysis was performed on the TAPS group due to the small sample size. (2) NT discordance in twins of the TTTS group was significantly greater than that in the normal MCDA twins group[(21.5±16.0)% vs (14.6±13.5)%, t=-3.533, P<0.001]. The area under ROC curve (AUC) of TTTS predicted by NT discordance was 0.649. Stratified analysis showed that TTTS was best predicted when NT discordance was 20% with the sensitivity of 57.9% and specificity of 70.6%. (3) The sIUGR group had greater discordance in CRL and NT and higher UCI discordance than the normal MCDA twins group [NT: (27.8±21.3)% vs (14.6±13.5)%, t=-5.556, P<0.001; CRL: (8.6±6.9)% vs (5.4±4.4)%, t=-3.144, P=0.002; UCI: 47.9% (68/142) vs 13.9% (18/129), χ2=35.929, P<0.001]. The AUC of sIUGR was 0.675 predicted by NT discordance and 0.649 by CRL discordance. Stratified analysis showed that NT discordance of 20% and CRL discordance of 10% were the best prediction for sIUGR with the sensitivity of 53.1% and 34.7% and specificity of 72.1% and 83.8%, respectively. Multivariate logistic regression analysis suggested that UCI discordance was the risk factor for sIUGR (OR=7.165, 95%CI: 2.637-19.472). Conclusions MCDA twins with NT discordance greater than 20% during early pregnancy are at increased risk for TTTS. CRL discordance greater than 10%, NT discordance greater than 20% and abnormal UCI are risk factors for sIUGR. Key words: Twins, monozygotic; Pregnancy trimester, first; Ultrasonography, prenatal; Nuchal translucency measurement; Fetofetal transfusion; Fetal growth retardation; Forecasting

Utility of the modified myocardial performance index in growth-restricted fetuses.

The modified myocardial performance index (Mod-MPI) can be used to assess myocardial function. Fetal growth restriction can affect fetal myocardial function, thereby altering the Mod-MPI. The results of previous studies on the utility of the Mod-MPI in growth-restricted fetuses are conflicting. The aim of this study was to calculate the left modified-MPI in growth-restricted fetuses and to compare the results with those of healthy fetuses. This was a prospective cross-sectional case-control study. In total, 40 women with growth-restricted fetuses and 40 women with fetuses of normal weight (controls) at 29-39 gestational weeks were enrolled in the study. An experienced obstetrician calculated the Mod-MPI for each fetus. Women with systemic diseases or fetuses with chromosomal/structural abnormalities were excluded from the study. The results of Mod-MPI measurements of the two groups were compared. The mean single deepest vertical pocket (SDVP) of amniotic fluid, estimated fetal weight (EFW), and isovolumetric relaxation time (IRT) was significantly lower in the fetal growth restriction (FGR) group as compared with these parameters in the control group (P<.05). The uterine artery (UtA) pulsatility index (PI) was significantly higher in the FGR group as compared with that in the control group (P<.05). There were six cases of absent end-diastolic flow (AED) in the FGR group. There were no statistically significant between-group differences in the Mod-MPI, isovolumetric contraction time (ICT), and ejection time (ET) (P>.05). There was also no statistically significant correlation between the Mod-MPI in the fetuses with AED and the control group for Mod-MPI (P>.05). The utility of the Mod-MPI in FGR remains unclear. Future studies with larger populations are needed to determine the utility of the Mod-MPI as a predictor of cardiac compromise in FGR.

An abnormal cerebroplacental ratio (CPR) is predictive of early childhood delayed neurodevelopment in the setting of fetal growth restriction

Fetal growth restriction accounts for a significant proportion of perinatal morbidity and death. The cerebroplacental ratio is gaining much interest as a useful tool in differentiating the "at-risk" fetus in both fetal growth restriction and appropriate-for-gestational-age pregnancies. The Prospective Observational Trial to Optimize Pediatric Health in Fetal Growth Restriction group has demonstrated previously that the presence of this "brain-sparing" effect is associated significantly with adverse perinatal outcomes in the fetal growth restriction cohort. However, data about neurodevelopment in children from pregnancies that are complicated by fetal growth restriction are sparse and conflicting. The aim of the Prospective Observational Trial to Optimize Pediatric Health in Fetal Growth Restriction NeuroDevelopmental Assessment Study was to determine whether children born after fetal growth-restricted pregnancies are at additional risk of adverse early childhood developmental outcomes compared with children born small for gestational age. The objective of this secondary analysis was to describe the role of cerebroplacental ratio in the prediction of adverse early childhood neurodevelopmental outcome. Participants were recruited prospectively from the Perinatal Ireland multicenter observational Prospective Observational Trial to Optimize Pediatric Health in Fetal Growth Restriction study cohort. Fetal growth restriction was defined as birthweight <10th percentile with abnormal antenatal umbilical artery Doppler indices. Small for gestational age was defined similarly in the absence of abnormal Doppler indices. Cerebroplacental ratio was calculated with the pulsatility indices of the middle cerebral artery and divided by umbilical artery with an abnormal value <1. Children (n=375) were assessed at 3 years with the use of the Ages and Stages Questionnaire and the Bayley Scales of Infant and Toddler Development, 3rd edition. Small-for-gestational-age pregnancies with normal Doppler indices were compared with (1) fetal growth-restricted cases with abnormal umbilical artery Doppler and normal cerebroplacental ratio or (2) fetal growth restriction cases with both abnormal umbilical artery and cerebroplacental ratio. Statistical analysis was performed with statistical software via 2-sample t-test with Bonferroni adjustment, and a probability value of .00625 was considered significant. Assessments were performed on 198 small-for-gestational-age children, 136 fetal growth-restricted children with abnormal umbilical artery Doppler images and normal cerebroplacental ratio, and 41 fetal growth-restricted children with both abnormal umbilical artery Doppler and cerebroplacental ratio. At 3 years of age, although there were no differences in head circumference, children who also had an abnormal cerebroplacental ratio had persistently shorter stature (P=.005) and lower weight (P=.18). Children from fetal growth restriction-affected pregnancies demonstrated poorer neurodevelopmental outcome than their small-for-gestational-age counterparts. Fetal growth-restricted pregnancies with an abnormal cerebroplacental ratio had significantly poorer neurologic outcome at 3 years of age across all measured variables. We have demonstrated that growth-restricted pregnancies with a cerebroplacental ratio <1 have a significantly increased risk of delayed neurodevelopment at 3 years of age when compared with pregnancies with abnormal umbilical artery Doppler evidence alone. This study further substantiates the benefit of routine assessment of cerebroplacental ratio in fetal growth-restricted pregnancies and for counseling parents regarding the long-term outcome of affected infants.

Characteristics of the Intestinal Microbiota in Very Low Birth Weight Infants With Extrauterine Growth Restriction.

Objective: Very low birth weight (VLBW) infants, which experience significant postnatal growth restriction at the time of discharge, are at high risk of later growth failure and long-term consequences. This study aims to characterize the structure of intestinal microbiome community in VLBW infants with extrauterine growth restriction (EUGR).Methods: Twenty-three VLBW infants appropriate for gestational age (GA) hospitalized at the neonatal intensive care unit of the BaoAn Maternal and Child Care Hospital (Shenzhen, China) were enrolled in this study, which were divided into the growth restriction group (EUGR; n = 12) and the normal growth group (AGA; n = 11). Meconium and fecal samples at postnatal day 28 were collected respectively during hospitalization. Total bacterial DNA was extracted and sequenced using the Illumina MiSeq Sequencing System based on the V3–V4 hyper-variable regions of the 16S rRNA gene.Results: The intestinal bacterial communities of preterm infants were dominated by the phylum Proteobacteria. Compared with the AGA group, the relative abundances of the genera Aeromicrobium and Serratia in meconium samples significantly decreased, whereas genera Parabacteroides, Ruminococcus, Blautia, and Aeromonas were more prevalent in the EUGR group. On postnatal day 28, the relative abundances of the genera Parabacteroides, Bacteroides, Eubacterium, Granulicatella, and Salinivibrio were significantly different between the two groups, where genus Salinivibrio decreased significantly in the EUGR samples. Among them, genus Parabacteroides was more abundant on both postnatal day 1 and 28. Further KEGG prediction analysis showed that there were many differences in functional genes and pathways between the two groups on postnatal day 28, but not on day 1, the majority of which were related to energy metabolism. And no statistical differences were observed in the clinical characteristics of infants.Conclusions: Overall, these findings showed that a distinct gut microbiota profile presented in preterm infants with EUGR. The role of intestinal microbiome in the extrauterine growth of preterm infants during hospitalization should be further investigated.

Correlation of Maternal and Cord Blood Leptin Concentrations with Neonatal Birth Weight in Term, Preterm and Growth-Restricted Fetuses

Background: To determine the association of cord blood and maternal leptin levels with neonatal birth weight in preterm deliveries, intrauterine growth retarded neonates, and term neonates. Materials and Methods: Sixty parturients were enrolled in this prospective observational study and data of fifty-one parturients were analyzed. There were nine dropouts. Of these patients 20 had intrauterine growth restriction (Group I), 15 had moderate preterm labor (Group II), and 16 had labor with normal term pregnancies (Group III). Obstetric and demographic data were recorded for the mothers and neonates. Cord blood sampling was done just before clamping of the cord and maternal venous blood was sampled within five minutes after parturition. Results: Mean cord blood leptin levels in Groups I, Group II, and Group III were 2.29±2.92, 0.93±0.64, and 2.26±1.78 respectively. Maternal leptin levels in Group I, Group II, and Group III were 8.79±5.92, 4.91±3.76, and 5.83±4.36. Mean birth weights were 2395±461g in Group I, 2142±464 g in Group II, and 3472±419 g in Group III. There was no statistically significant difference in neonatal birth weight between Group I and Group II (p=0.487), whereas the difference was significant for both Group I and Group II compared to Group III (p

Calreticulin Regulates Syncytialization Through Control of the Synthesis and Transportation of E-Cadherin in BeWo Cells.

During placental development, mononuclear cytotrophoblasts differentiate and fuse to syncytiotrophoblasts (STBs) to form syncytia, which secrete human chorionic gonadotropin (hCG). Decreased maternal perfusion of the placenta, which leads to placental dysfunction, induces changes in trophoblast syncytialization. Our previous study showed that calreticulin (CRT), a Ca2+-binding molecular chaperone found in the endoplasmic reticulum, is expressed in the human placenta and is involved in regulating extravillous trophoblast invasion, although its role in villous trophoblasts remains unclear. In this study, we investigated the functional role of CRT in trophoblast differentiation using the human trophoblast-like cell line BeWo, in which CRT gene expression was knocked down. We found that CRT was highly expressed in human third-trimester placentas and mainly localized in STBs. The fetal growth restriction group exhibited significantly lower CRT expression levels than did the control group. In BeWo cells, CRT knockdown markedly suppressed forskolin-induced cell fusion and β-hCG secretion. As for the mechanism responsible for these effects, the cell surface expression of E-cadherin, a key adhesion molecule related to syncytialization, was decreased, and E-cadherin accumulated adjacent to the Golgi apparatus in the CRT-knockdown cells, which led to dysfunctional cell-to-cell adhesion. Additionally, metabolic labeling and a pulse-chase study revealed that the protein expression of E-cadherin was suppressed at the translational level in the CRT-knockdown cells. Collectively, these results demonstrate that CRT regulates syncytialization by ensuring appropriate control of both the synthesis and transportation of E-cadherin, suggesting that CRT expression is important for placental development during pregnancy.

Expression of von Willebrand factor and caldesmon in the placental tissues of pregnancies complicated with intrauterine growth restriction

Purpose: The decreased placental perfusion is the underlying reason for intrauterine growth restriction that in turn leads to reduced placental perfusion and ischemia. However, there are several issues to be understood in the pathophysiology of intrauterine growth restriction. We aimed to study whether any compensatory response in placental vascular bed occur in pregnancies complicated with intrauterine growth restriction by the immunohistochemical staining of von Willebrand factor and caldesmon in placental tissues.Materials and methods: A total of 103 pregnant women was enrolled in the study including 50 patients who were complicated with IUGR and 50 uncomplicated control patients. The study was designed in a prospective manner. All placentas were also stained with von Willebrand factor and caldesmon monoclonal kits.Results: The immunohistochemical staining of von Willebrand factor and caldesmon expressions in placental tissues were different between normal and intrauterine growth restriction group. The percentages of 2+ and 3+ von Willebrand factor expression were higher in the intrauterine growth restriction group comparing with the normal group, although the difference was not statistically significant. The intensity of caldesmon expression was significantly lower in the intrauterine growth restriction group in comparison with the normal group (p < .001).Conclusion: Angiogenesis occurs as a placental response to intrauterine growth restriction which is a hypoxic condition. But newly formed vessels are immature and not strong enough. Our study is important to clarify the pathophysiology and placental compensatory responses in intrauterine growth restriction.

EP16.13: The correlation of nuchal translucency and maternal serum aneuploidy markers with placental dysfunction

To evaluate the association of nuchal translucency (NT) at 11-13 weeks, maternal serum aneuploidy marker and placental dysfunction. The data were collected on 678 women delivered in single tertiary hospital between February 2011 and May 2016. NT and maternal serum aneuploidy markers during 1st and early 2nd trimester were measured respectively. Afterwards, pregnant women were subdivided into 4 groups: normal controls (487), pre-eclampsia (PE) group (74), intra-uterine growth restriction (IUGR) group (74) and PE with IUGR group (42). Statistical correlations between each of the parameters evaluated and incidence of placental dysfunction were investigated. PAPP-A was significantly lower in placental dysfunction groups than normal controls, and the lowest value was shown in PE with IUGR pregnancies (p<0.05). NT was elevated in IUGR and PE groups, but it was not statistically significant. Second trimester aneuploidy markers presented αFP and hCG were significantly higher in placental dysfunction groups than normal controls, while uE3 and inhibin-A were lower in these patients. The maternal serum aneuploidy markers were significantly associated with placental dysfunction disorder. However, these markers alone are not effective as screening methods due to low sensitivity and positive predictive value. Further research including uterine artery Doppler, additional serum markers and combination of such makers should be warranted.

Effect of L-arginine supplementation on the hepatic phosphatidylinositol 3-kinase signaling pathway and gluconeogenic enzymes in early intrauterine growth-restricted rats.

The present study aimed to investigate the response of the phosphatidylinositol 3-kinase (PI3K) signaling pathway and gluconeogenic enzymes in intrauterine growth-restricted rats to dietary L-arginine (L-Arg) supplementation during the lactation period early in life. Pregnant Sprague-Dawley rats were randomly divided into a control group (CON), an intrauterine growth restriction group (IUGR) and an L-Arg group (LA). The pregnant rats in the CON group were fed a 21% protein diet, and those in the IUGR and LA groups were fed a 10% low protein diet, and all rats were fed a 21% protein diet after delivery. Water was available ad libitum to the pregnant rats during the 21-day lactation period, and the water provided to the LA group included 200 mg/kg/day L-Arg. Blood glucose, serum insulin, homeostasis model of assessment for insulin resistance (HOMA-IR), PI3K and protein kinase B (PKB) protein expression, and phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase) mRNA expression in the offspring rats were measured postnatally at 1, 3 and 8 weeks. No significant difference in blood glucose, serum insulin and HOMA-IR were identified at any time point among the three groups. PI3K and PKB expression was lower in the IUGR group offspring compared with that in the CON group offspring, but both were increased by dietary L-Arg supplementation. PEPCK mRNA and G-6-Pase mRNA expression levels in the offspring of the IUGR group were higher compared with those in the CON group but were downregulated following L-Arg supplementation. These results suggest that dietary L-Arg supplementation during the early lactation period promoted catch-up growth and reversed abnormalities in hepatic insulin signaling and gene expression of gluconeogenic enzymes in IUGR offspring rats.

Association of maternal and umbilical cord blood leptin concentrations and abnormal color Doppler indices of umbilical artery with fetal growth restriction

Fetal growth restriction (FGR) is a condition with heterogeneous pathophysiology which characterized by fetal weight less than the tenth percentile for gestational age. Several factors have impact on maternal, placental and fetal due to growth restriction. The aim of this study was to investigate the relationship between levels of leptin in the cord, and serum leptin of mothers also abnormal color Doppler indices of umbilical artery with fetal growth restriction. This is a cross sectional study conducted in Isfahan, Iran, 2015-2016. We recruited 40 women with singleton pregnancies complicated by fetal growth restriction (Group I) and 40 pregnant women with normal fetal growth (Group II) with matched age. Maternal serum and umbilical artery leptin levels were determined with Enzyme-Linked immunosorben method. Also, color Doppler ultrasound of umbilical artery was performed. Mean maternal and fetal leptin levels were lower in the FGR group compared to the normal group (36.58±(20.99) and 7.42 ±(4.08)vs. 47.32±(22.50) and 30.49±(14.50) respectively). Also, mean fetal leptin level was lower in the group with abnormal color Doppler sonographic indices compared to the normal group (7. 40 ±(4.10)vs 27.06±(15.80), respectively). This study indicated that maternal and fetal leptin levels are correlated with FGR originating from damaged placental function; also fetal leptin level can indicate changes in color Doppler sonographic indices.