Late-onset Fetal Growth Restriction Research Articles

Modified Myocardial Performance Index in Fetal Growth Disturbances as Diagnostic and Prognostic Adjunct.

Fetal growth disturbance can be associated with cardiac dysfunction. This study aimed to assess the modified myocardial performance index in growth-restricted and appropriate for gestational age fetuses and evaluate both its prognostic value in perinatal period and also its association with adverse perinatal outcomes. Totally 131 pregnant women were included in this prospective study. Of these, 56 cases were in study group with a diagnosis of small fetus and 75 cases were in control group with a diagnosis appropriately grown fetus. Fetal echocardiography was performed in all pregnant women to measure modified myocardial performance index. Umbilical, middle cerebral and uterine artery Doppler ultrasound parameters were measured in the study group. Small fetuses were categorized into 2 subgroups of late-onset fetal growth restriction and small for gestational age. Modified myocardial performance index was significantly higher in small fetuses compared to controls (0.45 vs. 0.37, P <.001). Newborn intensive care unit admission rates were significantly higher in small fetuses than in controls (chi-square test, P <.001). The highest mean modified myocardial performance index was recorded in the late-onset fetal growth restriction subgroup (0.45 vs. 0.41 vs. 0.37). The sensitivity and specificity of modified myocardial performance index in predicting adverse outcomes at a cut-off value of 0.41 were 63% and 75%, respectively. There was a significant negative correlation between modified myocardial performance index values and birth weights. We found higher left fetal heart modified myocardial performance index values in small fetuses indicating the presence of prenatal cardiac dysfunction. Fetal myocardial performance deteriorates in concordance with severity of growth restriction. Modified myocardial performance index can also be used to predict adverse perinatal outcomes among growth-restricted fetuses.

Antenatal characteristics and perinatal outcomes of late-onset fetal growth restriction (FGR) diagnosed in diabetic pregnancies: a retrospective study

Antenatal characteristics and perinatal outcomes of late-onset fetal growth restriction (FGR) diagnosed in diabetic pregnancies: a retrospective study

Uteroplacental-Cerebral Ratio: A Doppler Parameter for Prognostic Prediction of Late-Onset Fetal Growth Restriction: Single Center Prospective Cohort Study.

Purpose: This study aimed to elucidate the accuracy of Doppler parameters in predicting the prognosis of late-onset fetal growth restriction (FGR). Methods: This was a prospective study of 114 pregnancies. Doppler parameters, including the cerebroplacental ratio and pulsatility index (PI) in the middle cerebral, umbilical, uterine artery, were recorded. The new uteroplacental−cerebro ratio (UPCR) was constructed as the ratio of (umbilical artery + mean of the left and right uterine artery) to middle cerebral artery PI. Logistic regression analyses and receiver operating characteristic curves were performed. Results: Adverse outcomes occurred in 37 (32%) neonates. The z values of the middle cerebral artery PI and cerebroplacental ratio were lower (p < 0.001), while the z values of the umbilical artery PI, mean uterine artery PI, and UPCR (p < 0.001) were higher in late-onset FGR in those with compared to those without adverse outcomes. Multivariate logistic regression revealed that only UPCR was independently associated with adverse outcomes (p < 0.001). For predicting the prognosis of late-onset FGR, UPCR showed a fair degree of accuracy (area under the curve [AUC], 0.824). Conclusion: The new UPCR, reflecting the impact of placental impedance from both fetal and maternal sides on fetal well-being, improves the accuracy of prognostic prediction for late-onset FGR.

Interrelation between miRNAs Expression Associated with Redox State Fluctuations, Immune and Inflammatory Response Activation, and Neonatal Outcomes in Complicated Pregnancy, Accompanied by Placental Insufficiency.

Redox disbalance in placental cells leads to the hyperproduction of reactive oxygen species (ROS), it mediates the dysregulation of the maternal immune tolerance to a semi-allogenic fetus, inducing pro-inflammatory reactions, and it plays a central role in perinatal complications and neonatal disease programming. Microvesicles, which provide transplacental communication between a mother and fetus, contain microRNAs (miRNAs) that are sensitive to oxidative stress (OS) mediators and can control the balance of ROS production and utilization in target cells. In the context of this paradigm, we evaluated the markers of redox balance-MDA and 4-HNE for OS and GPx, and SOD, CAT, and GSH for the antioxidant system in the cord blood plasma of newborns diagnosed with fetal growth restriction (FGR)-by using polarography, spectrophotometry, and Western blotting. The expression of miRNAs associated with OS, immune and inflammatory responses in the blood plasma of newborns with intrauterine pneumonia (IP), neonatal sepsis (NS) and respiratory distress syndrome (RDS) was evaluated by a quantitative RT-PCR. Significant differences in the MDA level and reduced GPx and CAT activity were co-found for early-onset FGR (i.e., &lt;34 gestational age). Significant correlations were found with a low birth weight by Apgar scores with reduced levels of antioxidant enzymes. Indeed, the level of OS markers increased in early-onset FGR in newborns with an extremely low body weight and high echogenicity of the periventricular zones, and reduced in late-onset FGR in newborns with IP, hyperbilirubinemia, intraventricular hemorrhage (IVH) and cerebral cysts. A prognostic model (AUC = 1; cutoff-0.5) was developed to assess the risk of IVH in newborns diagnosed with FGR based on the assessment of the OS markers (i.e., MDA + 4 HNE + CAT + GSH). A significant increase in the miR-127-3p expression was found in the plasma of newborns with NS (&lt;32 GA; p ≤ 0.03 and &gt;32 GA; p ≤ 0.009), IP (&gt;32 GA; p ≤ 0.0001), and RDS (&gt;32 GA; p ≤ 0.03). At the same time, the expression of miR-25-3p (p ≤ 0.03) was increased only in newborns with NS (&gt;32 GA; p ≤ 0.03). The risk of developing IVH for premature newborns with IP (AUC = 0.8; cutoff-0.6) and NS (AUC = 0.68; cutoff-0.49) was assessed based on the miR-25-3p and miR-127-3p expression. Several key transcription factors were identified as the targets of studied miRNA since they are involved in the regulation of OS (NRF2), signaling and activation of the immune response (PRDM1, CCL26) and, also, inflammatory responses (NFKB1). The study of these miRNAs showed that they are involved in the modulation of processes leading to perinatal complications. Moreover, miR-127-3p is related to pro-inflammatory reactions and the formation of the macrophage phenotype in newborns with IP, NS, and RDS, while miR-25-3p is associated with an inhibition of macrophage migration and activation of antioxidant enzymes, which may prevent the development of oxidative damage in newborns with NS.

Assessment of fetal cardiac morphology and functional changes in early-onset and late-onset fetal growth restriction.

To compare the fetal cardiac morphology and functions of early-onset fetal growth restriction (EO-FGR) and late-onset fetal growth restriction (LO-FGR) groups with gestational weeks-matched controls. A total of 164 pregnant women were included, 28 of whom were in the EO-FGR group, 54 in the LO-FGR group, and 82 in the control group. Fetal echocardiographic evaluation was performed with two-dimensional, M-mode, tissue Doppler imaging (TDI), and pulsed wave Doppler. Fetal cardiac morphologic measurements and diastolic and systolic functions changed in EO-FGR and LO-FGR fetuses compared with controls. The EO- and LO-FGR fetuses had reduced right and left cardiac output, increased myocardial performance index, and significantly higher mitral and tricuspid E/E' ratios compared with controls. The EO-FGR fetuses had lower mitral and tricuspid E and E' values. In LO-FGR fetuses, mitral and tricuspid E' values were lower than in their controls (P= 0.001 and P< 0.001). On the other hand, the mitral and tricuspid E values were not significantly changed (P= 0.107 and P= 0.196). We hypothesized that EO-FGR and LO-FGR fetuses had insufficient myocardial maturation. Especially in the LO-FGR fetuses, TDI is the earliest and most sensitive technique to show subtle changes in fetal cardiac functions.

Late-onset fetal growth restriction management: a national survey.

Fetal growth restriction (FGR) is an obstetric condition that increases the risk of adverse neonatal outcomes. FGR antenatal care aims to decrease fetal morbidity and mortality through optimal fetal monitoring. However, no univocal strategies for late-onset FGR outpatient management are available, and this survey investigated gynaecologists' attitudes concerning outpatient frequency tests. We mailed a survey to 429 Italian gynaecologists. The primary purpose was the ambulatory care of late-onset FGR without doppler alterations evaluation. The queries estimated the self-reported medical practice regarding cardiotocography (CTG) and obstetric ultrasound exams before hospitalization. Statistical analysis was performed with Stata 14.1 (Stata corp., College Station, TX, USA) for symmetrically distributed continuous variables, and the mean differences were analyzed using the t-test. Where appropriate, the proportions between the groups were evaluated using Fisher's exact or χ2 test. All P value <0.05 were considered statistically significant. 128 responses (29.8%) from the 429 SCCAL members were available for the survey. 39.9% of respondents had a late FGR standardized protocol. Regarding non-severe FGR with normal fetal doppler, 70.8% suggested a fetal doppler study after one week (92/128), 13.8% (18/128) and 6.9% (9/128) proposed the exam, respectively, two and three times for a week. 0.8% (1/128) of respondents had a daily doppler exam, 7.7% (10/128) did not answer, and 3.1% (4/128) repeated the ultrasound exam to time for a week. The antenatal CTG was offered: 70.8% (92/128) of gynaecologists recommended one weekly CTG, whereas 13.8% (18/128) suggested two. 6.9% (9/128) recommended three weekly tests and 0.8% a daily test. 7.7% (10/128) of gynaecologists did not respond. At least, we investigated the gynaecologist's recommendations for outpatient EFW evaluation: 59.4% (76/128) repeated EFW after two weeks, 31.3% (40/128) after one week. 3.9% (4/128) and 3.1 (4/128) recommended EFW after three weeks and twice a week. Gynaecologists recommend unnecessary cardiotocography and ultrasound Doppler exams for non-severe late-onset FGR with normal doppler. However, additional studies and comprehensive surveys are needed to support a standardized protocol and assess the feto-maternal outcomes impact.

The effect of middle cerebral artery peak systolic velocity on prognosis in early and late-onset fetal growth restriction.

We aim to investigate the utility of middle cerebral artery peak systolic velocity (MCA PSV) Doppler in determining the perinatal mortality and morbidity in serial Doppler measurements from the time of diagnosis to the delivery of complicated cases with fetal growth restriction (FGR). At 24-38weeks of gestation, 65 pregnant women diagnosed with FGR were included in the study. The fetal biometry measurements, MCA pulsatility index (PI), and MCA PSV Doppler evaluation of the cases formed at the diagnosis and the delivery were recorded. Gestational weeks, birth weights, APGAR scores, cord pH values, NICU (neonatal intensive care unit) admission, NICU duration of stay, and perinatal morbidity parameters such as RDS (respiratory distress syndrome), BPD (bronchopulmonary dysplasia), NEC (necrotizing enterocolitis), sepsis and perinatal mortality were compared. The patients were divided into two groups: early and late-onset fetal growth restriction. Perinatal morbidity and mortality were accepted as adverse perinatal outcomes. MCA PSV above the 95th percentile at the diagnosis and delivery time was seen at a significantly higher rate with adverse perinatal outcomes. This study shows that evaluating MCA PSV with Doppler can be a helpful diagnostic method for early diagnosis of restriction and hypoxic fetuses. Also, it may be used in clinics as a noninvasive method to predict neonatal prognosis.

Patterns of Brain Sparing in a Fetal Growth Restriction Cohort.

Objective: Our objective was to compare differences in Doppler blood flow in four fetal intracranial blood vessels in fetuses with late-onset fetal growth restriction (FGR) vs. those with small for gestational age (SGA). Methods: Fetuses with estimated fetal weight (EFW) <10th percentile were divided into SGA (n = 30) and FGR (n = 51) via Delphi criteria and had Doppler waveforms obtained from the middle cerebral artery (MCA), anterior cerebral artery (ACA), posterior cerebral artery (PCA), and vertebral artery (VA). A pulsatility index (PI) <5th centile was considered “abnormal”. Outcomes included birth metrics and neonatal intensive care unit (NICU) admission. Results: There were more abnormal cerebral vessel PIs in the FGR group versus the SGA group (36 vs. 4; p = 0.055). In FGR, ACA + MCA vessel abnormalities outnumbered PCA + VA abnormalities. All 8 fetuses with abnormal VA PIs had at least one other abnormal vessel. Fetuses with abnormal VA PIs had lower BW (1712 vs. 2500 g; p < 0.0001), delivered earlier (35.22 vs. 37.89 wks; p = 0.0052), and had more admissions to the NICU (71.43% vs. 24.44%; p = 0.023). Conclusions: There were more anterior vessels showing vasodilation than posterior vessels, but when the VA was abnormal, the fetuses were more severely affected clinically than those showing normal VA PIs.

Prediction of late-onset fetal growth restriction by umbilical artery velocities at 37 weeks of gestation: a cross-sectional study

ObjectiveTo explore the predictive capacity of umbilical artery (UA) velocities at 37 weeks of gestation in identifying fetal growth restriction (FGR).DesignCross-sectional study.Setting and participantsWe retrospectively recruited 569 fetuses in the...

Non-invasive Maternal Hemodynamic Assessment to Classify High-Risk Pregnancies Complicated by Fetal Growth Restriction.

To verify whether the use of the temporal criterion of 32 weeks' gestation is effective in identifying maternal hemodynamic differences between early- and late-onset fetal growth restriction (FGR), and to test the statistical performance of a classificatory algorithm for FGR. A prospective multicenter study conducted at three centers over 17 months. Singleton pregnant women with a diagnosis of FGR based on the international Delphi survey consensus at ≥ 20 weeks of gestation were included. FGR was classified as early-onset if diagnosed <32 weeks' gestation and as late-onset if ≥32 weeks. Hemodynamic assessment was performed by USCOM-1A at the time of FGR diagnosis. Comparisons between early- and late-onset FGR among the entire study cohort, FGR associated with hypertensive disorders of pregnancy (HDP-FGR), and isolated FGR (i-FGR) were performed. In addition, HDP-FGR cases were compared to i-FGR, regardless of the temporal cut-off of 32 weeks' gestation. Finally, a classificatory analysis based on the Random Forest model was performed to identify significant variables with the ability to differentiate FGR phenotypes. During the study period, 146 pregnant women fulfilled the inclusion criteria. In 44 cases, FGR was not confirmed at birth, thus limiting the final study population to 102 patients. In 49 (48.1%) women, FGR was associated to HDP. Fifty-nine (57.8%) cases were classified as early-onset. Comparison of the maternal hemodynamics between early- and late-onset FGR did not show any difference. Similarly, non-significant findings were observed in sensitivity analyses performed for HDP-FGR and for i-FGR. In turn, comparison between pregnant women with FGR and hypertension and women with i-FGR, independently of the gestational age at FGR diagnosis, revealed substantial differences, with the former showing higher vascular peripheral resistances and lower cardiac output, among other significant parameters. The classificatory analysis identified both phenotypic and hemodynamic variables as relevant in distinguishing HDP-FGR from i-FGR (p=0.009). Our data show that HDP, rather than gestational age at FGR diagnosis, allows to appreciate specific maternal hemodynamic patterns and to accurately distinguish two different FGR phenotypes. In addition, maternal hemodynamics, alongside phenotypic characteristics, play a central role in classifying these high-risk pregnancies.

The Genetic and Clinical Outcomes in Fetuses With Isolated Fetal Growth Restriction: A Chinese Single-Center Retrospective Study.

Objective: To evaluate the utility of a chromosomal microarray (CMA) in fetuses with isolated fetal growth restriction (FGR) and explore risk factors for the prediction of chromosomal aberration and perinatal adverse outcomes. Method: This study included 271 fetuses of estimated fetal weight less than the 3rd percentile without other structural malformation. Early-onset and late-onset FGR were defined as gestational weeks less than 32 weeks and more than 32 weeks respectively. These patients underwent quantitative fluorescent polymerase chain reaction (QF-PCR) and CMA as the first-line genetic detection strategy. Chromosomal anomalies were compared after stratified analysis by the early-onset and the late-onset FGR, including the absence or presence of ultrasound soft markers, abnormal amniotic fluid, abnormal umbilical Doppler, and gestational disorders. The follow-up time was within 1 year after birth. Logistic regression was used to seek risk predictors of chromosomal aberration and perinatal adverse outcomes for isolated FGR. Results: The CMA identified clinically significant variants in 18/271 (6.6%) fetuses, and variants of unknown significance (VOUS) in 15/271 (5.5%) fetuses. Stratified analysis showed that there was a higher incidence of clinically significant variants in fetuses with the early-onset FGR compared with late-onset FGR (8.7%, 17/195 vs. 1.3%, 1/76, p < 0.05). Regression analysis showed that early gestational age (GA) at diagnosis of FGR was the major risk factor for chromosomal aberration (OR = 0.846). By variable regression analysis, early GA at diagnosis and decreased estimated fetal weight (EFW) percentile of suspicion of FGR, asymmetrical FGR, abnormal amniotic fluid, and severe preeclampsia could all increase the risk of adverse outcomes of isolated FGR including intra-uterine fetal death (IUFD), termination of pregnancy (TOP), and preterm birth in pregnancies with FGR. Conclusion: This study emphasized the value of microarrays for unbalanced genomic variants in fetuses with isolated FGR, especially since the gestational age of nullipara was less than 32 weeks. Perinatal adverse outcomes of isolated FGR were influenced by multiple factors including GA and estimated fetal weight (EFW) percentile of suspicion of FGR, asymmetrical FGR, abnormal amniotic fluid, and severe preeclampsia.

Predictive role of Doppler indices of cerebral–placental–uterine ratio and umbilico-cerebral ratio for late-onset fetal growth restriction: a prospective cohort study

Predicting late-onset foetal growth restriction (FGR) has proven to be rather challenging. In this study, we propose a new parameter, cerebral–placental–uterine (CPU) ratio and umbilico-cerebral (UC) ratio for this matter. Results of this study which included a total of 227 nulliparous women showed that an increase in CPU ratio (OR = 0.45; 95% CI: 0.23–0.88; p=.020) was associated with lower odds of foetal weight above the 10th percentile at birth. CPU ratio measured at 35–37 weeks of gestation had an AUC of 0.78 (95% CI: 0.58, 0.98), sensitivity of 0.62 (95% CI: 0.24, 0.91) and specificity of 0.90 (95% CI: 0.79, 0.96) for prediction of late-onset FGR, which showed higher accuracy than UC ratio. As some cases of the late-onset FGR are not diagnosed by foetal biometry, it is important to find Doppler parameters that can help us predict these cases and CPU ratio may help physicians in detection of high-risk foetuses that will benefit from earlier intervention. Impact Statement What is already known on this subject? Late-onset foetal growth restriction (FGR) defined by an FGR diagnosis after 32 weeks of gestational age, can lead to short- and long-term morbidities and early diagnosis is the key to prevent these complications. What do the results of this study add? Results showed that each unit increase in numeric variables including CP ratio (OR = 0.29, p=.006), and CPU ratio (OR = 0.40, p=.006) was associated with lower odds of the foetal weight above the 10th percentile in the second ultrasound at 35–37 weeks. In other words, CPU ratio can prove to be useful marker in prediction of late-onset FGR. What are the implications of these findings for clinical practice and/or further research? Our prospective cohort study confirms the added value of low CPU ratio, with higher predictive accuracy than UC ratio, in predicting late-onset FGR. Detection of late FGR remains poor, but it is important to prevent stillbirth so further studies on the role of CPU ratio in predicting FGR and perinatal outcomes are needed.

Umbilical Venous Volume Flow in Late-Onset Fetal Growth Restriction.

Umbilical vein flow (UVF) is reduced in fetal growth restriction (FGR). We compared absolute and size-adjusted UVF (estimated fetal weight [EFW] and abdominal circumference [AC]) and rates of abnormal UVF parameters (<10th percentile) among FGR fetuses meeting Delphi criteria (FGR-D) against small for gestational age (SGA) fetuses and appropriate for gestational age (AGA) controls. Absolute UVF, UVF/EFW, and UVF/AC were compared between 73 FGR pregnancies (35 FGR-D, 38 SGA) and 108 AGA controls. Rates of abnormal UVF were compared to abnormal umbilical artery pulsatility index (UAPI). Independent samples t-tests, Mann-Whitney U, odds ratio (OR), chi-squared, and Fisher's exact tests were used as appropriate. Mean absolute UVF was significantly decreased in FGR-D compared to AGA (P=.0147), but not between SGA and AGA fetuses. The incidence of both abnormal absolute UVF and UVF/AC values (<10th centile) was higher among late-onset FGR fetuses versus AGA fetuses (UVF: OR 2.7, confidence interval [CI] 1.37-5.4; UVF/AC: OR 2.73, CI 1.37-5.4). UVF was more frequently abnormal than UAPI and in only two fetuses were both Doppler values abnormal. Absolute UVF is altered in late-onset FGR, and most pronounced among FGR-D. UVF may provide additional insight into fetal compromise in those affected by growth restriction.

Rs868058 in the Homeobox Gene HLX Contributes to Early-Onset Fetal Growth Restriction.

Simple SummaryFetuses with hypotrophy (FGR, fetal growth restriction) are too small for their gestational age and may be prone to various diseases and loss of life. This study aimed to determine the role of single nucleotide polymorphisms (SNPs), located in two homeotic and two angiogenesis-related genes, in the occurrence of FGR, by analyzing blood samples from 380 women in singleton pregnancies. We found that the AT heterozygotes in HLX rs868058 were significantly associated with an approximately two-fold increased risk of FGR, diagnosed before 32 weeks of gestation (early-onset FGR). AT heterozygotes were significantly more frequent in women with early-onset FGR than in those with late-onset FGR (diagnosed from 32 weeks of gestation) and compared with healthy subjects. In conclusion, the AT genotype in HLX rs868058 may be a significant risk factor for the development of early-onset FGR. So far, the only therapeutic strategy for the management of early-onset FGR is to monitor and terminate pregnancy when the risk of fetal immaturity is lower than the risk of intrauterine death. Therefore, the disclosure of the mechanisms of action of the heterozygous AT state in HLX rs868058 would be important to identify plausible targets for new therapeutic approaches to treat the condition.Fetal growth restriction (FGR) is a condition that characterizes fetuses as too small for their gestational age, with an estimated fetal weight (EFW) below the 10th percentile and abnormal Doppler parameters and/or with EFW below the 3rd percentile. We designed our study to demonstrate the contribution of single nucleotide polymorphisms (SNPs) from DLX3 (rs11656951, rs2278163, and rs10459948), HLX (rs2184658, and 868058), ANGPT2 (−35 G > C), and ITGAV (rs3911238, and rs3768777) genes in maternal blood in FGR. A cohort of 380 women with singleton pregnancies consisted of 190 pregnancies with FGR and 190 healthy full-term controls. A comparison of the pregnancies with an early-onset FGR and healthy subjects showed that the AT heterozygotes in HLX rs868058 were significantly associated with an approximately two-fold increase in disease risk (p ≤ 0.050). The AT heterozygotes in rs868058 were significantly more frequent in the cases with early-onset FGR than in late-onset FGR in the overdominant model (OR 2.08 95% CI 1.11–3.89, p = 0.022), and after being adjusted by anemia, in the codominant model (OR 2.45 95% CI 1.23–4.90, p = 0.034). In conclusion, the heterozygous AT genotype in HLX rs868058 can be considered a significant risk factor for the development of early-onset FGR, regardless of adverse pregnancy outcomes in women.

Impact of suspected late-onset fetal growth restriction on obstetrical interventions and perinatal outcomes at term; a retrospective cohort study

ObjectivesFirst, assess accuracy of late third trimester universal fetal growth screening in high risk nulliparous women with a singleton in vertex presentation at term. Second, assess instrumental delivery rates and perinatal outcomes in this population. Study designSingle centre retrospective cohort study in a teaching hospital, The Netherlands. ResultsIn a cohort of 1902 pregnancies, growth ultrasound after 33 weeks was moderately accurate in detecting children with a birthweight below the 10th centile with a sensitivity of 46.2% and a false positive rate of 4.7%. Induction of labour followed an antenatal suspicion of FGR more often than in the group with normal expected fetal weight (73.4% vs 52.6% OR 2.49 (1.88–3.3)) as could be expected from application of guidelines. The caesarean section rates was lowest in the group with suspected FGR compared to the group with expected normal fetal weight (15.2% vs 22.1% OR 0.63 (0.45–0.9)). There were no differences between both groups in rates of composite severe adverse perinatal outcome (0.7% vs 0.8% OR 0.87 (0.2–3.93)). ConclusionsThe detection of growth restriction using universal screening in term high risk nulliparous women with a singleton in vertex position is moderate. Despite this, caesarean section rates were not increased and perinatal outcomes were similar when compared to that found in the randomized controlled trial on which the recommendation for induction of labour for suspected term FGR is based. This supports universal late third trimester fetal growth screening in pregnancies under consultant-led care in the two tiers Dutch obstetrical system.

96 Early versus late-onset fetal growth restriction (FGR): Analysis of soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (plgf) levels and sFlt-1/PLGF Ratio

Introduction: FGR affects 5-10% pregnancies and is a risk factor for perinatal mortality. Ultrasound remains the gold standard in detection and monitoring of FGR, however its accuracy is limited. sFlt-1, PLGF together with sFlt-1/PLGF ratio are valuable tools in predicting risk of preeclampsia (PET). The common etiology of inadequate trophoblast invasion in both conditions affords the opportunity to use the above markers to improve detection and management of FGR pregnancies. Aim: To evaluate sFlt-1, PLGF and sFlt-1/PLGF ratio in pregnancies affected FGR compared to AGA fetuses.

Ultrasound prediction of adverse perinatal outcome at diagnosis of late-onset fetal growth restriction.

ABSTRACTObjectiveTo evaluate the relationship between Doppler and biometric ultrasound parameters measured at diagnosis and perinatal adverse outcome in a cohort of late‐onset growth‐restricted (FGR) fetuses.MethodsThis was a multicenter retrospective study of data obtained between 2014 and 2019 including non‐anomalous singleton pregnancies complicated by late‐onset FGR (≥ 32 weeks), which was defined either as abdominal circumference (AC) or estimated fetal weight (EFW) < 10th percentile for gestational age or as reduction of the longitudinal growth of AC by over 50 percentiles compared to ultrasound scan performed between 18 and 32 weeks of gestation. We evaluated the association between sonographic findings at diagnosis of FGR and composite adverse perinatal outcome (CAPO), defined as stillbirth or at least two of the following: obstetric intervention due to intrapartum fetal distress, neonatal acidemia, birth weight < 3rd percentile and transfer to the neonatal intensive care unit (NICU).ResultsOverall, 468 cases with complete biometric and umbilical, fetal middle cerebral and uterine artery (UtA) Doppler data were included, of which 53 (11.3%) had CAPO. On logistic regression analysis, only EFW percentile was associated independently with CAPO (P = 0.01) and NICU admission (P < 0.01), while the mean UtA pulsatility index (PI) multiples of the median (MoM) > 95th percentile at diagnosis was associated independently with obstetric intervention due to intrapartum fetal distress (P = 0.01). The model including baseline pregnancy characteristics and the EFW percentile was associated with an area under the receiver‐operating‐characteristics curve of 0.889 (95% CI, 0.813–0.966) for CAPO (P < 0.001). A cut‐off value for EFW corresponding to the 3.95th percentile was found to discriminate between cases with and those without CAPO, yielding a sensitivity of 58.5% (95% CI, 44.1–71.9%), specificity of 69.6% (95% CI, 65.0–74.0%), positive predictive value of 19.8% (95% CI, 13.8–26.8%) and negative predictive value of 92.9% (95% CI, 89.5–95.5%).ConclusionsRetrospective data from a large cohort of late‐onset FGR fetuses showed that EFW at diagnosis is the only sonographic parameter associated independently with the occurrence of CAPO, while mean UtA‐PI MoM > 95th percentile at diagnosis is associated independently with intrapartum distress leading to obstetric intervention. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

PERINATAL OUTCOMES AND PROGNOSTIC FACTORS IN EARLY AND LATE-ONSET FETAL GROWTH RESTRICTION

Objective: To evaluate the obstetric and perinatal outcomes of fetuses with early (EO) and late-onset (LO) fetal growth restriction (FGR), and to explore the prognostic factors on perinatal survival and adverse perinatal outcome. Materials and Methods: We retrospectively reviewed 105 EO and 55 LO-FGR singleton pregnancies. Umbilical artery (UA), middle cerebral artery (MCA) and ductus venosus (DV) Doppler parameters and cerebroplacental ratio (CPR) were assessed. Prognostic significance of gestational age at delivery, birth weight and Doppler parameters were evaluated. Results: Gestational age at delivery greater than 27 weeks (sensitivity 87.5%, specificity 76%) and birth weight of 665 g (sensitivity 88.8%, specificity 92%) provided the best prediction of survival in EO-FGR. Logistic regression analysis of UA absent or reversed end diastolic flow (EDF), abnormal DV Doppler, and absent/reversed DV a-wave revealed Odds Ratios of 2.57, 6.97, 4.51 and 8.75 respectively for perinatal mortality in EO-FGR. The incidence of CPR below the 5th percentile was significantly higher in LO-FGR pregnancies with the composite adverse outcome than normal outcome (p&lt;0.001). Conclusion: Gestational age at delivery and birth weight are the strongest predictors of perinatal mortality in EO-FGR. In LOFGR, CPR &lt;5th percentile is associated with an increased risk of delivery complications.

Морфологические особенности плацент при хронической плацентарной недостаточности и задержке роста плода

The most reliable criterion for differential diagnosis between small-for-gestational-age fetus and fetal growth restriction (FGR) is chronic placental insufficiency (CPI) verified by morphological analysis. CPI is associated with abnormal development of the placental villous tree and is traditionally divided into primary, which develops during implantation, early embryogenesis, and placentation, and secondary, which develops after the completion of trophoblast invasion. CPI is morphologically manifested by abnormal development of the placental villous tree, changes in its vascular structure, increased number of syncytial knots, as well as the presence of infarctions and sometimes inflammatory changes. At the same time, it is noted that the differences in placental histology between early-onset and late-onset FGR are more quantitative than qualitative. Key words: intrauterine development, chronic placental insufficiency, fetal growth restriction

Overexpression of microRNAs miR-25-3p, miR-185-5p and miR-132-3p in Late Onset Fetal Growth Restriction, Validation of Results and Study of the Biochemical Pathways Involved.

In a prospective study, 48 fetuses were evaluated with Doppler ultrasound after 34 weeks and classified, according to the cerebroplacental ratio (CPR) and estimated fetal weight (EFW), into fetuses with normal growth and fetuses with late-onset fetal growth restriction (LO-FGR). Overexpression of miRNAs from neonatal cord blood belonging to LO-FGR fetuses, was validated by real-time PCR. In addition, functional characterization of overexpressed miRNAs was performed by analyzing overrepresented pathways, gene ontologies, and prioritization of synergistically working miRNAs. Three miRNAs: miR-25-3p, miR-185-5p and miR-132-3p, were significantly overexpressed in cord blood of LO-FGR fetuses. Pathway and gene ontology analysis revealed over-representation of certain molecular pathways associated with cardiac development and neuron death. In addition, prioritization of synergistically working miRNAs highlighted the importance of miR-185-5p and miR-25-3p in cholesterol efflux and starvation responses associated with LO-FGR phenotypes. Evaluation of miR-25-3p; miR-132-3p and miR-185-5p might serve as molecular biomarkers for the diagnosis and management of LO-FGR; improving the understanding of its influence on adult disease.