Severe Fetal Growth Restriction Research Articles

FRI416 Primary Hyperaldosteronism in Pregnancy

Abstract Disclosure: S.M. Seav: None. M. Basina: None. Background: Primary hyperaldosteronism is extremely rare in pregnancy. Since 1962, only approximately 30 cases have been reported in the literature.1 Clinical Case: A 40-year-old female was referred for work-up of primary hyperaldosteronism (PHA). She was first diagnosed with hypertension (HTN) at age 29 during her first pregnancy. Laboratory work-up was consistent with PHA: serum aldosterone 22.6 ng/dL, renin activity 0.1 ng/mL/hr, aldosterone:renin ratio of 226. Post-saline infusion aldosterone level was 10.7 ng/dL. Adrenal CT scan showed a 6mm left-sided adenoma. Surgery was not recommended because adrenal vein sampling did not show lateralization. She was started on Spironolactone 25 mg/day. Despite the significant pregnancy risks, patient continued to desire conception and was switched to Labetolol. She was lost to follow-up and returned to the emergency room for dizziness at 26 weeks pregnant with twins with BP 180/109 mmHg. She had not been taking any anti-hypertensives and there was evidence of severe fetal growth restriction in both babies. After a goals of care discussion, patient deferred emergent C-section and suffered intrauterine fetal demise on hospital day 9. Conclusion: PHA in pregnancy is rare and difficult to diagnose and manage. Newer studies estimate that > 5-10% of patients with HTN have PHA.2 Hence, maintaining high vigilance of this disease in pregnant patients is even more imperative, including screening for PHA during pre-conception period in hypertensive women. A systematic review of 38 cases of PHA in pregnancy showed that 19% of cases were diagnosed with HTN prior to pregnancy without PHA screening.1 The average age of women in this study was 29.8 years. Additionally, there is a correlation in women with younger age at diagnosis and having unilateral PHA, in which case adrenalectomy should be performed prior to conception.3 In pregnancy, first line anti-hypertensive therapies include alpha methyl dopa, labetolol, and nifedipine. In PHA, diuretics such as amiloride and mineralocorticoid receptors should also be considered if BP is not at goal. Spironolactone and eplerenone have been safely used in pregnancy with both male and female fetuses.1,4 If surgery is not an option and medical therapy is ineffective, then physicians should have a low threshold to admit patients for close BP monitoring. 1Landau, et al. Primary Aldosteronism and Pregnancy. Annales d’Endocrinologie. 2016;77:148–160 2Funder, et al. Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(5):1889–1916 3Akasaka, et al. Sex Difference in the Association Between Subtype Distribution and Age at Diagnosis in Patients With Primary Aldosteronism. Hypertension. 2019;74(2):368-374 4Cabassi, et al. Eplerenone Use in Primary Aldosteronism in Pregnancy. Hypertension. 2012;59:e18-e19 Presentation: Friday, June 16, 2023

Angiogenic Function of Human Placental Endothelial Cells in Severe Fetal Growth Restriction Is Not Rescued by Individual Extracellular Matrix Proteins.

Severe fetal growth restriction (FGR) is characterized by increased placental vascular resistance resulting from aberrant angiogenesis. Interactions between endothelial cells (ECs) and the extracellular matrix (ECM) are critical to the complex process of angiogenesis. We have previously found that placental stromal abnormalities contribute to impaired angiogenesis in severe FGR. The objective of this research is to better characterize the effect of individual ECM proteins on placental angiogenic properties in the setting of severe FGR. ECs were isolated from human placentae, either control or affected by severe FGR, and subjected to a series of experiments to interrogate the role of ECM proteins on adhesion, proliferation, migration, and apoptosis. We found impaired proliferation and migration of growth-restricted ECs. Although individual substrates did not substantially impact migratory capacity, collagens I, III, and IV partially mitigated proliferative defects seen in FGR ECs. Differences in adhesion and apoptosis between control and FGR ECs were not evident. Our findings demonstrate that placental angiogenic defects that characterize severe FGR cannot be explained by a singular ECM protein, but rather, the placental stroma as a whole. Further investigation of the effects of stromal composition, architecture, stiffness, growth factor sequestration, and capacity for remodeling is essential to better understand the role of ECM in impaired angiogenesis in severe FGR.

Management of catecholaminergic polymorphic ventricular tachycardia in pregnancy: a case report

Objective To report the case of a successful pregnancy in a patient with catecholaminergic polymorphic ventricular tachycardia with a history of cardiac arrest and placement of an implantable cardioverter defibrillator (ICD). Case(s) A 29-year-old Caucasian G1P0 presented to the maternal fetal medicine service at seven weeks gestation with known CPVT. She was medically managed with nadolol and experienced no arrhythmias or ICD shocks during her pregnancy. Her pregnancy was complicated by severe fetal growth restriction. She ultimately delivered by urgent cesarean section due to fetal intolerance of labor. Conclusion Episodes of catecholaminergic polymorphic ventricular tachycardia during pregnancy can be life-threatening for both mother and baby, though successful management is possible with care from a multidisciplinary team.

Comparison of Adverse Maternal Outcomes between Early- and Late-Onset Superimposed Preeclampsia.

Superimposed preeclampsia (SIPE), defined as preeclampsia in individuals with chronic hypertension, is one of the most common complications, accounting for 13 to 40% of pregnancies with chronic hypertension. However, there are limited data regarding maternal outcomes of early- and late-onset SIPE in individuals with chronic hypertension. We hypothesized that early-onset SIPE was associated with increased odds of adverse maternal outcomes compared with late-onset SIPE. Therefore, we aimed to compare adverse maternal outcomes between individuals with early-onset SIPE and those with late-onset SIPE. This was a retrospective cohort study of pregnant individuals with SIPE who delivered at 22 weeks' gestation or greater at an academic institution. Early-onset SIPE was defined as the onset of SIPE before 34 weeks' gestation. Late-onset SIPE was defined as the onset of SIPE at or after 34 weeks' gestation. Our primary outcome was a composite of eclampsia, hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome, maternal death, placental abruption, pulmonary edema, SIPE with severe features, and thromboembolic disease. Maternal outcomes were compared between early- and late-onset SIPE. We used simple and multivariate logistic regression models to calculate crude and adjusted odds ratios (aOR) with 95% confidence intervals (95% CI). Of 311 individuals, 157 (50.5%) had early-onset SIPE, 154 (49.5%) had late-onset SIPE. There were significant differences in the proportions of obstetric complications, including the primary outcome, HELLP syndrome, SIPE with severe features, fetal growth restriction (FGR), and cesarean delivery between early- and late-onset SIPE. Compared with individuals with late-onset SIPE, those with early-onset SIPE had increased odds of the primary outcome (aOR: 3.28; 95% CI: 1.42-7.59), SIPE with severe features (aOR: 2.72; 95% CI: 1.25-5.90), FGR (aOR: 6.07; 95% CI: 3.25-11.36), and cesarean delivery (aOR 3.42; 95% CI: 2.03-5.75). Individuals with early-onset SIPE had higher odds of adverse maternal outcomes compared with those with late-onset SIPE. · We revealed the incidence of maternal outcomes in early- and late-onset SIPE.. · Severe features were common in individuals with SIPE.. · Early-onset SIPE was associated with increased adverse maternal outcomes compared with late-onset SIPE..

#4764 NEPHROTIC SYNDROME IN PREGNANT DIABETIC WOMEN: MATERNAL AND PERINATAL OUTCOMES AT A TERTIARY CENTER

Abstract Background and Aims Management of pregnant women with diabetic kidney disease and nephrotic range proteinuria or nephrotic syndrome constitute a challenge to clinicians. Maternal and perinatal outcomes, especially in patients with chronic kidney disease, remain poor. The authors describe the multidisciplinary approach and the outcomes of diabetic pregnant patients with nephrotic range proteinuria. Method Retrospective observational study in which the authors reviewed maternal, obstetric and perinatal outcomes in pregnant diabetic woman with nephrotic range proteinuria or nephrotic syndrome surveilled at our nephro-obstetric unit from 2011 until 2021. Results We evaluated 7 gestations in 6 patients. Mean age was 31.7±4.7 years (26-38), 5 were caucasian and 1 was black African, and 4 were nuliparas. They all had type 1 diabetes, with mean disease diagnosis at 9.9±5.9 years of age. All patients had chronic hypertension and 5/6 patients had poor glycemic control before pregnancy (mean HbA1c of 11.9%). Mean baseline SCr was 1.1±0.5 mg/dl (0.51-2.8) and mean baseline proteinuria was 3697.2±2301.4 mg/day (75-6326), with 1/1/3/2 patients being on CKD stage 1/2/3/4, before pregnancy, respectively. Exposure to teratogenic therapy during the first trimester occurred in 5/7 gestations with a mean exposure of 7.4 ± 3.1 weeks. Proteinuria increased in all patients and renal function deteriorated in 5/7 gestations (mean SCr of 2.5±1.2; 0.67-4.07 mg/dl) in association with pre-eclampsia in 2 patients and with pregnancy hyperfiltratrion and nephrotic syndrome in all gestations. One patient started dialysis at week 28, due to urea levels >100mg/dL. Partial renal recovery occurred in 2 patients. To date, 3/6 patients initiated PD 15 months (6-29 months) after gestation, 1 of which received a kidney-pancreas transplant. Hypertension aggravated in 6 gestations. Aspirin and low molecular weight heparin were initiated in 6 gestations and they were all treated with furosemide to control volume overload. Regarding fetal outcomes, severe fetal growth restriction was responsible for 1 still birth and 1 medical termination of pregnancy, both at 24 weeks. Cesarean was performed in 4/5 gestations (one is still undergoing) due to pre-eclampsia, renal function deterioration and/or fetal growth restriction. Mean gestation age at delivery was 29.5±4.7 weeks, mean birth weight was 1389 ±203.3 mg (1190-1665) and mean apgar scores at 1/5/10 minutes were 9/10/10 respectively. Neonatal intensive care was needed in 4 newborns. Conclusion This study reinforces the idea that diabetic women with nephrotic range proteinuria have an increased risk of complications and worse outcomes during pregnancy, namely pre-eclampsia, fetal growth restriction, preterm delivery and renal function deterioration. As such, glycemic and proteinuric control should be optimized and careful counseling regarding outcomes should be discussed before pregnancy. Management during gestation should involve an experienced multidisciplinary team including endocrinologist, nutritionist, nephrologist and obstetrician.

Perinatal mortality rate and adverse perinatal outcomes presumably attributable to placental dysfunction in (near) term gestation: A nationwide 5-year cohort study.

Placental dysfunction can lead to perinatal hypoxic events including stillbirth. Unless there is overt severe fetal growth restriction, placental dysfunction is frequently not identified in (near) term pregnancy, particularly because fetal size is not necessarily small. This study aimed to evaluate, among (near) term births, the burden of hypoxia-related adverse perinatal outcomes reflected in an association with birth weight centiles as a proxy for placental function. A nationwide 5-year cohort of the Dutch national birth registry (PeriNed) including 684,938 singleton pregnancies between 36+0 and 41+6 weeks of gestation. Diabetes, congenital anomalies, chromosomal abnormalities and non-cephalic presentations at delivery were excluded. The main outcome was antenatal mortality rate according to birthweight centiles and gestational age. Secondary outcomes included perinatal hypoxia-related outcomes, including perinatal death and neonatal morbidity, analyzed according to birthweight centiles. Between 2015 and 2019, 1,074 perinatal deaths (0.16%) occurred in the study population (n = 684,938), of which 727 (0.10%) antenatally. Of all antenatal- and perinatal deaths, 29.4% and 27.9% occurred in birthweights below the 10th centile. The incidence of perinatal hypoxia-related outcomes was highest in fetuses with lowest birthweight centiles (18.0%), falling gradually up to the 50th and 90th centile where the lowest rates of hypoxia-related outcomes (5.4%) were observed. Perinatal hypoxia-related events have the highest incidence in the lowest birthweight centiles but are identifiable throughout the entire spectrum. In fact, the majority of the adverse outcome burden in absolute numbers occurs in the group with a birthweight above the 10th centile. We hypothesize that in most cases these events are attributable to reduced placental function. Additional diagnostic modalities that indicate placental dysfunction at (near) term gestation throughout all birth weight centiles are eagerly wanted.

Mode of delivery and neonatal outcomes with early preterm severe preeclampsia: does fetal growth restriction matter?

Objective Severe preeclampsia diagnosed at or prior to 34 weeks is an indication for preterm delivery. Many patients with severe preeclampsia develop fetal growth restriction as a result of the placental dysfunction associated with both conditions. The ideal mode of delivery in cases of preterm severe preeclampsia with fetal growth restriction remains controversial, with providers often proceeding directly to cesarean delivery rather than attempting a trial of labor due to theoretic concerns about the harms of labor in the face of placental dysfunction. There are limited data supporting this approach. This study evaluates whether the presence of fetal growth restriction affects the ultimate mode of delivery or neonatal outcomes among pregnancies with severe preeclampsia undergoing induction of labor at or before 34 weeks. Methods This was a retrospective cohort study of singletons with severe preeclampsia undergoing induction of labor ≤ 34 weeks at a single center between January 2015 and April 2022. The primary predictor was fetal growth restriction, defined as estimated fetal weight < 10th percentile for gestational age on ultrasound. Mode of delivery and neonatal outcomes were compared between those with and without fetal growth restriction using Fisher’s exact and Kruskal-Wallis tests, and multivariate logistic regression was used to obtain adjusted odds ratios. Results 159 patients were included (N = 117 without fetal growth restriction, N = 42 with fetal growth restriction). There was no difference in vaginal delivery between the groups (70% vs 67%, p = .70). While those with fetal growth restriction had a higher incidence of respiratory distress syndrome and longer neonatal hospital stay, these differences were not statistically significant after adjusting for gestational age at delivery. There were no significant differences in other neonatal outcomes, including Apgar score, cord blood gases, intraventricular hemorrhage, necrotizing enterocolitis, neonatal sepsis, and neonatal demise. Conclusion For pregnancies complicated by severe preeclampsia that require delivery ≤ 34 weeks, the likelihood of successful vaginal delivery following induction of labor does not differ based on presence of fetal growth restriction. Furthermore, fetal growth restriction is not an independent risk factor for adverse neonatal outcomes in this population. Induction of labor should be considered a reasonable approach and should be routinely offered to patients with concurrent preterm severe preeclampsia and fetal growth restriction.

Late-Onset Severe Fetal Growth Restriction and Isolated Severely Small Abdominal Circumference: Do Neonatal Outcomes Differ? [ID: 1377666

INTRODUCTION: Updated guidelines from the Society for Maternal-Fetal Medicine (SMFM) define severe fetal growth restriction (sFGR), or an estimated fetal weight (EFW) less than 3rd percentile, as a distinct entity due to higher perinatal morbidity in this group. Whether an isolated abdominal circumference (AC) less than 3rd percentile similarly portends adverse outcomes remains unclear. METHODS: This is a single-institution, retrospective cohort study of singleton gestations with late-onset FGR and normal Doppler studies from 2012 to 2022. Pregnancies affected by AC less than 3rd percentile (but EFW≥3rd percentile) and EFW less than 3rd percentile were compared using univariable analysis and multivariable logistic regression. The primary outcome was neonatal intensive care unit (NICU) admission. RESULTS: Among eligible participants, 78 (63%) had an isolated AC less than 3rd percentile and 45 (37%) had sFGR. Neonates prenatally diagnosed with sFGR were more likely to be admitted to the NICU than those with isolated AC less than 3rd percentile (68.9% versus 23.1%, P&lt;.001). After adjusting for gestational age, birth weight, race, maternal age, and medical comorbidities, sFGR was still associated with an increased odds of NICU admission (adjusted odds ratio 4.9, 95% CI 1.37–17.48, P=.014). Rates of cesarean delivery (46.7% versus 26.9%; P=.03), small for gestational age (86.7% versus 67.9%, P=.02), and 5-minute Apgar score less than 7 (6.7% versus 0.0%, P=.02) were also higher in the sFGR group. There were no significant differences in NICU length of stay or perinatal death between groups. CONCLUSION: Adverse neonatal outcomes were more prevalent in pregnancies affected by sFGR compared with isolated AC less than 3rd percentile, providing support for the updated SMFM guidelines.

The Natural History of Fetal Triploidy in an Era of Limited Abortion Access: A Case Series [ID: 1380133

INTRODUCTION: Triploidy is a chromosomal abnormality that occurs in 1–3% of all conceptions and often results in early spontaneous miscarriage. It is exceedingly rare for a triploid fetus to survive to birth. Neonates usually die within hours to days after delivery. After the Dobbs v Jackson Women's Health Organization ruling in July 2022, access to abortion is becoming increasingly limited, and therefore providers should consider the adverse maternal health outcomes that can be associated with triploidy. METHODS: In this case series, we describe three cases of confirmed fetal triploidy that we encountered in our center within 1 year (2021–2022). All three cases were referred to us after House Bill 1259 was passed on July 1, 2020, in Mississippi banning termination of pregnancy based on race, sex, or genetic abnormality. RESULTS: Our first case is a 21-year-old patient referred at 19 weeks 2 days for abnormal second-trimester serum screen. Ultrasound showed an enlarged multicystic placenta and multiple fetal anomalies. Amniocentesis showed a 69,XXY karyotype. Patient was managed expectantly. At 21 week 5 days, patient was diagnosed with superimposed preeclampsia with severe features. Patient underwent medical termination of pregnancy. The second case is a 25-year-old referred at 30 weeks 0 days for concerns of fetal anomalies. Ultrasound confirmed multiple fetal anomalies. Amniocentesis showed a 69,XXY karyotype. Patient was diagnosed with preeclampsia and pulmonary edema and was delivered at 30 weeks 1 day. The neonate passed away at 22 days of life. Our third case is a 20-year-old referred at 24 weeks 0 days for abnormal aneuploidy screening. Ultrasound showed a major cardiac defect and severe fetal growth restriction. Amniocentesis showed a 69,XXY karyotype. Patient was managed expectantly. At 29 weeks 0 days, intrauterine fetal demise was diagnosed. Patient was diagnosed with peripartum depression. CONCLUSION: Women with pregnancies affected by fetal triploidy are at risk of developing preeclampsia. Restricting access to abortion will lead to increased maternal morbidity and mortality rates.

Neonatal outcomes following early fetal growth restriction: a subgroup analysis of the EVERREST study

ObjectiveTo quantify the risks of mortality, morbidity and postnatal characteristics associated with extreme preterm fetal growth restriction (EP-FGR).DesignThe EVERREST (Does vascular endothelial growth factor gene therapy safely improve outcome in...

Early differentiation and gene expression characteristics of trophoblast lineages.

With the development of the embryo, the totipotent blastomere undergoes the first lineage decision to the inner cell mass (ICM) and the trophectoderm (TE). The ICM forms the fetus while the TE forms the placenta, which is one of the most unique organs in mammals serving as the interface between maternal and fetal. Proper trophoblast lineage differentiation is crucial for correct placental and fetal development, including the TE progenitor self-renewal and its differentiation toward mononuclear cytotrophoblast (CTB), which later either develops into invasive extravillous trophoblast (EVT), remodeling the uterine vascular, or fuses into multinuclear syncytiotrophoblast (STB), secreting pregnancy-sustaining hormone. Aberrant differentiation and gene expression of trophoblast lineage is associated with severe pregnancy disorders and fetal growth restriction. This review focuses on the early differentiation and key regulatory factors of trophoblast lineage, which have been poorly elucidated. Meanwhile, the recent development of trophoblast stem cells (TSC), trophectoderm stem cells (TESC), and blastoids derived from pluripotent stem cells bring the accessible model to investigate the profound mystery of embryo implantation and placentation were also summarized.

O1-2 - A case of severe fetal growth restriction with oligohydramnios was successfully treated with antithrombotic therapy

O1-2 - A case of severe fetal growth restriction with oligohydramnios was successfully treated with antithrombotic therapy

ISUOG Practice Guidelines (updated): performance of fetal magnetic resonance imaging.

ISUOG Practice Guidelines (updated): performance of fetal magnetic resonance imaging.

Genetic causes of isolated and severe fetal growth restriction in normal chromosomal microarray analysis.

To investigate the genetic burden in fetuses with isolated and severe fetal growth restriction (FGR) using Trio whole-exome sequencing (WES) with a normal chromosomal microarray. This retrospective study analyzed WES results of singleton fetuses with isolated and severe FGR, whose estimated fetal weight (EFW) was less than the third percentile by Hadlock formula, in a tertiary center between March 2016 and March 2022. Cases with abnormal chromosomal microarray analysis (CMA) and TORCH results were excluded. Fifty-one fetuses with isolated and severe FGR and negative CMA results underwent Trio-WES. Of all patients, eight (15.7%) were diagnosed with FGR at its early onset (<32 weeks) and showed pathogenic or likely pathogenic variants involving Nipped-B-like protein gene (NIPBL) (n= 3), fibroblast growth factor receptor 3 (n= 1), pyruvate dehydrogenase E1 subunit alpha 1 (n= 1), collagen, type I, alpha 1 (n= 1), superkiller viralicidic activity 2-like (n= 1), and chloride voltage-gated channel (CLCN5) (n= 1). De novo-generated variants were identified in five fetuses, of which two were novel, including c.6983C>A (p. Thr2328Lys) in NIPBL and c.934-1G>T in CLCN5. Genetic disorders involved Cornelia de Lange syndrome and metabolic and skeletal genetic diseases. The present study indicates that Trio-WES can improve effectivity of prenatal diagnoses for isolated and severe FGR in cases with normal CMA results, aiding prenatal genetic counseling and pregnancy management for FGR fetuses.

The role of extracellular matrix proteins on placental angiogenesis in severe fetal growth restriction

Impaired vascular development is a central finding in severe fetal growth restriction (FGR) with abnormal Doppler velocimetry. Angiogenesis involves complex interactions between endothelial cells (ECs) and extracellular matrix (ECM). Our laboratory previously found that FGR ECs exhibit deficient angiogenic properties, a deficit that is further worsened in the presence of ECM generated from FGR placentae but partially rescued by control ECM. Our objective was to identify the effects of individual ECM substrates on EC function to better characterize the impaired angiogenic pathway characteristic of FGR. ECs were isolated from term control (n=8) or severe FGR (n=8) human placentae and plated on six individual ECM proteins: fibronectin; collagens I, III, and IV; laminin; and thrombospondin. Adhesion was assessed by colorimetric staining. Live cell microscopy was used to determine proliferation. Migration was analyzed via relative wound density following wound scratch. Apoptosis was evaluated by immunoblotting for cleaved caspase 3. T tests, ANOVAs, and nonlinear regressions were performed. There was no difference between adhesion of control and FGR ECs to individual ECM substrates. Control ECs proliferated more rapidly than FGR ECs (p< 0.01; figure 1). Deficient growth of FGR ECs was not rescued by any ECM substrate. Migration of FGR ECs was impaired relative to control ECs when accounting for all substrates (p=0.02). This finding persisted specifically in the presence of collagen I (p=0.03; figure 2) but not other substrates. Apoptosis was not detected for either type of ECs on any substrate. ECs from placentae affected by severe FGR display impaired proliferation and migration. This growth deficit appears to be independent of individual ECM substrates. FGR migratory defects persist on collagen I but not other substrates. Our data suggest that no singular ECM protein is responsible for the aberrant angiogenesis seen in severe FGR and rather there are likely multiple mechanisms underlying this pathology.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Прогнозирование риска неблагоприятных перинатальных исходов у беременных с задержкой роста плода

Objective. Development of additional Doppler criteria for predicting the risk of adverse perinatal outcomes in pregnant women with fetal growth restriction (FGR) Patients and methods. 161 patients with singleton pregnancies were examined: 100 women were diagnosed with АПК, and 31 women had fetuses that were low in weight by gestational age; The control group consisted of 30 patients with normal fetal growth. Ultrasound, in addition to fetometry, included Doppler sonography of blood flow in the uterine arteries, umbilical arteries and the fetal middle cerebral artery. The cerebroplacental ratio (CPR) and cerebro-placental-uterine ratio (CPUR) were determined. Reference values of CPUR in patients with FGR have been developed. Results. The ROC analysis in 100 patients with FGR showed that using of CPUR predict a high risk of adverse perinatal outcomes with a sensitivity of 60% and a specificity of 82%. The positive predictive value of CPUR was 91% (83% for CPR). In pregnant women with severe FGR (&lt;3rd centile), the positive prognostic value was – 97%, the highest values were founded in patients with an early phenotype – 100% (with late – 93%). Conclusion. CPUR has a high prognostic significance in relation to the risk of adverse perinatal outcomes in patients with FGR, which indicates the using this indicator along with CPR in the examination of patients with low fetal weight. Key words: fetal growth restriction, early phenotype, late phenotype, cerebro-placental ratio, cerebro-placental-uterine

Should abdominal circumference

Should abdominal circumference <3rd percentile be included in the definition of severe fetal growth restriction?

Role of sFLT-1/PlGF ratio in predicting severe adverse materno-fetal outcome in high risk women.

To evaluate the role of angiogenic biomarkers in predicting severe adverse materno-fetal outcome (SAO) among women at high risk of preeclampsia (PE). All antenatal women at high risk of PE underwent MAP estimation, sFlt-1/PlGF ratio, uterine artery evaluation at 20-22, 28-30 and 34-36weeks of gestation and were followed until delivery. The severe adverse outcome included severe PE, severe fetal growth restriction with Doppler changes and intrauterine death or early neonatal death. Those who developed SAO were cases and rest were controls, the cases and controls were compared using univariate and multivariate logistic regression analysis. In 54/287(18.8%) SAO was observed, and they comprised of severe PE (21/287, 7.3%), FGR with absent or reverse diastolic flow on Doppler (23/287, 8.0%) and intrauterine death or early neonatal death (10/287, 3.5%). For detecting complications up to 30weeks, the sFLT-1/PlGF ratio at 20weeks (cut off≥38) was the best test (accuracy- 97.6%) followed by MAP and uterine artery Doppler PI. For detecting complications up to 34weeks, prediction was good (accuracy -80.4%) when sFLT-1/PlGF ratio was combined with uterine artery PI. The predictive value of the complications before 34weeks was far superior to that after 34weeks. Combining the sFLT-1/PlGF ratio with the uterine artery PI improved the accuracy of the test (79% to 87%). Increased sFlt-1/PlGF ratio, was a good predictive marker for SAO in the study population. The accuracy of prediction was better for those who developed the complications before 34weeks.

Prenatal differential diagnosis of placental mesenchymal dysplasia and molar disease with coexistent live twin fetuses

Background: Numerous hypoechoic cysts in the placenta on prenatal ultrasonography with a live fetus may indicate twin pregnancy with a complete hydatidiform mole with a coexistent fetus, partial mole, confined placental mosaicism, or placental mesenchymal dysplasia (PMD). Ultrasonographic appearances of these are similar; however, the differential diagnosis should be made because maternal and fetal prognoses differ. Cases: We present two cases of twin pregnancies with numerous placental cystic lesions. The first case was a partial hydatidiform mole in monochorionic diamniotic twins with a diploid karyotype that underwent a spontaneous abortion at 20 gestational weeks. The second case was PMD in dichorionic diamniotic twins; live twin neonates were delivered at 34 gestational weeks. Emergency cesarean section delivery was performed due to severe preeclampsia and fetal growth restriction in twin A at 34 weeks of gestation. Conclusions: Numerous hypoechoic cysts in the placenta on prenatal ultrasonography with a normal live fetus warrants chromosomal analysis and serial ultrasonographic examination to differentiate between PMD and molar pregnancy with a coexisting normal fetus to avoid unnecessary termination.

Dysregulation of integrin αvβ3 and α5β1 impedes migration of placental endothelial cells in fetal growth restriction.

Placentas from pregnancies complicated by severe early-onset fetal growth restriction (FGR) exhibit diminished vascular development mediated by impaired angiogenesis, but underlying mechanisms remain unknown. In this study, we show that FGR endothelial cells demonstrate inherently reduced migratory capacity despite the presence of fibronectin, a matrix protein abundant in placental stroma that displays abnormal organization in FGR placentas. Thus, we hypothesized that aberrant endothelial-fibronectin interactions in FGR are a key mechanism underlying impaired FGR endothelial migration. Using human fetoplacental endothelial cells isolated from uncomplicated term control and FGR pregnancies, we assessed integrin α5β1 and αvβ3 regulation during cell migration. We show that endothelial integrin α5β1 and αvβ3 interactions with fibronectin are required for migration and that FGR endothelial cells responded differentially to integrin inhibition, indicating integrin dysregulation in FGR. Whole-cell expression was not different between groups. However, there were significantly more integrins in focal adhesions and reduced intracellular trafficking in FGR. These newly identified changes in FGR endothelial cellular processes represent previously unidentified mechanisms contributing to persistent angiogenic deficiencies in FGR.