Stillbirth Associated With Anomalous Origin and Course of the Left Coronary Artery: A Report of 2 Cases.

Coronary artery anomalies and their potential sequelae are not well studied in association with stillbirth. Herein, we report the autopsy findings in two term stillborn fetuses with coronary artery anomalies. Both fetuses showed identical findings consisting of an abnormal origin of the left coronary artery from the right sinus of Valsalva and an interarterial course of the left coronary artery. Histologic vascular and myocardial changes were also present. These coronary artery findings are associated with sudden death in adults and neonates, and therefore, their potential to be a cause and/or contributor to fetal death is suspected.

Placental inflammation in a fetal demise of a SARS-CoV-2-asymptomatic, COVID-19-unvaccinated pregnant woman: a case-report.

BACKGROUND: Intrauterine fetal demise is a recognized complication of coronavirus disease 2019 in pregnant women and is associated with histopathological placental lesions. The pathological mechanism and virus-induced immune response in the placenta are not fully understood. A detailed description of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced inflammation in the placenta during fetal demise is crucial for improved clinical management. CASE PRESENTATION: We report the case of a 27-week gestation SARS-CoV-2-asymptomatic unvaccinated pregnant woman without comorbidities or other risk factors for negative pregnancy outcomes with a diagnosis of intrauterine fetal demise. Histopathological findings corresponded to patterns of subacute inflammation throughout the anatomic compartments of the placenta, showing severe chorioamnionitis, chronic villitis and deciduitis, accompanied by maternal and fetal vascular malperfusion. Our immunohistochemistry results revealed infiltration of CD68+ macrophages, CD56+ Natural Killer cells and scarce CD8+ T cytotoxic lymphocytes at the site of placental inflammation, with the SARS-CoV-2 nucleocapsid located in stromal cells of the chorion and chorionic villi, and in decidual cells. CONCLUSION: This case describes novel histopathological lesions of inflammation with infiltration of plasma cells, neutrophils, macrophages, and natural killer cells associated with malperfusion in the placenta of a SARS-CoV-2-infected asymptomatic woman with intrauterine fetal demise. A better understanding of the inflammatory effects exerted by SARS-CoV-2 in the placenta will enable strategies for better clinical management of pregnant women unvaccinated for SARS-CoV-2 to avoid fatal fetal outcomes during future transmission waves.

Pregnancy following assisted reproductive technology in morbidly obese patients: assessment of feto-maternal outcomes.

PURPOSE: To examine feto-maternal characteristics and outcomes of morbidly obese pregnant patients who conceived with assisted reproductive technology (ART). METHODS: This cross-sectional study queried the Healthcare Cost and Utilization Project's National Inpatient Sample. Study population was 48,365 patients with ART pregnancy from January 2012 to September 2015, including non-obesity (n = 45,125, 93.3%), class I-II obesity (n = 2445, 5.1%), and class III obesity (n = 795, 1.6%). Severe maternal morbidity at delivery per the Centers for Disease and Control Prevention definition was assessed with multivariable binary logistic regression model. RESULTS: Patients in the class III obesity group were more likely to have a hypertensive disorder (adjusted-odds ratio (aOR) 3.03, 95% confidence interval (CI) 2.61-3.52), diabetes mellitus (aOR 3.08, 95%CI 2.64-3.60), large for gestational age neonate (aOR 3.57, 95%CI 2.77-4.60), and intrauterine fetal demise (aOR 2.03, 95%CI 1.05-3.94) compared to those in the non-obesity group. Increased risks of hypertensive disease (aOR 1.35, 95%CI 1.14-1.60) and diabetes mellitus (aOR 1.39, 95%CI 1.17-1.66) in the class III obesity group remained robust even compared to the class I-II obesity group. After controlling for priori selected clinical, pregnancy, and delivery factors, patients with class III obesity were 70% more likely to have severe maternal morbidity at delivery compared to non-obese patients (8.2% vs 4.4%, aOR 1.70, 95%CI 1.30-2.22) whereas those with class I-II obesity were not (4.1% vs 4.4%, aOR 0.87, 95%CI 0.70-1.08). CONCLUSIONS: The results of this national-level analysis in the United States suggested that morbidly obese pregnant patients conceived with ART have increased risks of adverse fetal and maternal outcomes.

Temporal ultrasound findings in the first trimester of a dual fetal demise occurring in a monochorionic diamniotic twin gestation.

Single fetal demise in monochorionic gestations in the 2nd and 3rd trimester is associated with adverse outcomes for the co-twin. We present a case of single demise in a monochorionic gestation in the 1st trimester with evidence of subsequent hemodynamic aberrations in the co-twin, supportive of feto-fetal hemorrhage occurring early in gestation.

Fetal Supraventricular Tachycardia: Histologic Evidence of Accessory Pathways Due to Incomplete Annulus Fibrosus Formation.

BACKGROUND: Atrioventricular (AV) reentrant tachycardia is a common type of supraventricular tachycardia (SVT) that occurs in the fetus and neonate. Although many tachycardias resolve within several weeks of birth or respond to medical management, disruptions in the cardiac annulus fibrosus and development of additional accessory pathways may lead to refractory dysrhythmia resulting in fetal hydrops and ultimately, fetal death. OBJECTIVES: While accessory pathways have been well documented anatomically in adult and childhood tachyarrhythmias, there are no reports of the histology of these pathways in human fetuses with SVT. RESEARCH DESIGN, SUBJECTS, MEASURES: This is a small case series of 2 fetuses with a history of SVT that resulted in fetal hydrops. RESULTS: In both cases, examination of the cardiac conduction system was unremarkable and examination of the atrioventricular junction revealed a focally thinned and/or discontinuous annulus fibrosus with documented direct continuity between the atrial and ventricular myocardium in 1 case. CONCLUSIONS: This case series demonstrates that thinning or absence of the annulus fibrosus is a feature seen in fetal SVT, and the development of subsequent aberrant AV connections due to defective formation of the annulus fibrosus suggests a possible cause for these arrhythmias.

Comparison of the Autopsy and Placental Findings in Second vs Third Trimester Stillbirth.

BACKGROUND: The pathology of second trimester fetal loss is not well-characterized due to lack of comprehensive autopsy studies. The purpose of this study is to compare autopsy pathology of second trimester and third trimester stillbirth. METHODS: In this retrospective cohort study, fetal autopsies performed in-house with complete placental examination were included. From autopsy reports, maternal demographics, gestational age, sex, body and placental weight, congenital anomalies, and cause of death (COD) were obtained. Immediate COD was coded "probable" or "possible" according to Initial Causes of Fetal Death (INCODE). RESULTS: Among 68 second trimester and 54 third trimester fetal autopsies, at least 1 probable COD was identified in 59/68 (87%) second trimester and 44/54 (81%) third trimester cases. 42/68 (62%) second trimester and 28/54 (52%) third trimester fetuses had probable COD secondary to placental pathology. Among placental causes, 29/42 (69%) second trimester and 14/28 (50%) third trimester stillbirths were related to compromised fetal microcirculation with umbilical cord abnormality. CONCLUSIONS: Among stillborn first and second trimester fetuses who undergo autopsy, the most prevalent COD is pathologic placental conditions, particularly those associated with umbilical cord obstruction. This study stresses the importance of placenta examination for establishing COD in both second and third trimester fetuses.

Microfocus computed tomography for fetal postmortem imaging: an overview.

Over the last few years, fetal postmortem microfocus computed tomography (micro-CT) imaging has increased in popularity for both diagnostic and research purposes. Micro-CT imaging could be a substitute for autopsy, particularly in very early gestation fetuses for whom autopsy can be technically challenging and is often unaccepted by parents. This article provides an overview of the latest research in fetal postmortem micro-CT imaging with a focus on diagnostic accuracy, endovascular staining approaches, placental studies and the reversibility of staining. It also discusses new methods that could prove helpful for micro-CT of larger fetuses. While more research is needed, contrast-enhanced micro-CT has the potential to become a suitable alternative to fetal autopsy. Further research using this novel imaging tool could yield wider applications, such as its practise in imaging rare museum specimens.

Intrauterine Fetal Demise Associated with Vascular Malperfusion and Multiple Uterine Leiomyomata: A Report of Two Cases.

BACKGROUND: Uterine leiomyomata have been loosely associated with intrauterine fetal demise (IUFD), largely attributed to fetal growth restriction from cavitary distortion. We present two cases of IUFD in patients with non-distorting leiomyomata and pathologic placental findings of maternal vascular malperfusion (MVM) and fetal vascular malperfusion (FVM). CASE REPORT: Case 1 details a 28w3d IUFD associated with large leiomyomata (largest 11.9 × 7.6 × 9.7 cm), post-partum deep vein thrombosis, and severe pre-eclampsia histologic features. Case 2 details a 25w2d IUFD associated with smaller leiomyomata (largest 3.1 × 3.0 × 3.3 cm). Both placentas demonstrated MVM, including parenchymal thrombi and accelerated villous maturity, and FVM, including avascular stem villi. DISCUSSION: As the placentas in both cases demonstrated findings consistent with altered placental perfusion, we posit that leiomyomata in these cases may have been associated with both maternal and fetal vascular malperfusion, ultimately contributing to fetal demise.

Assessing Intrauterine Retention according to Microscopic Stillbirth Features: A Cluster Analysis Approach.

Background: Previous studies identified microscopic changes associated with intrauterine retention of stillbirths based on clinical time of death. The objective of this study was to utilize unsupervised machine learning (not reliant on subjective measures) to identify features associated with time from death to delivery. Methods: Data were derived from the Stillbirth Collaborative Research Network. Features were chosen a priori for entry into hierarchical cluster analysis, including fetal and placental changes. Results: A four-cluster solution (coefficient = 0.983) correlated with relative time periods of "no retention," "mild retention," "moderate retention," and "severe retention." Loss of nuclear basophilia within fetal organs were found at varying rates among these clusters. Conclusions: Hierarchical cluster analysis is able to classify stillbirths based on histopathological changes, roughly correlating to length of intrauterine retention. Such clusters, which rely solely on objective fetal and placental findings, can help clinicians more accurately assess the interval from death to delivery.

Recurrent Second Trimester Fetal Demise Caused by Hypercoiled Umbilical Cords.

BACKGROUND: Umbilical cord flow impairment accounts for a majority of fetal vascular malperfusion (FVM). Hypercoiled umbilical cords are one cause of impaired fetal blood flow that may, in severe cases, result in intrauterine fetal demise (IUFD). Although the factors involved in umbilical cord patterning are incompletely understood, a limited number of reports have described recurrent intra-familial hypercoiling leading to death in the second trimester, suggesting a subset may have a genetic etiology. CASE REPORTS: Herein, we report two additional cases of recurrent second trimester IUFD secondary to FVM due to umbilical cord hypercoiling and briefly discuss all published cases. CONCLUSION: Our cases add to a small, but growing, body of literature that suggests a genetic etiology to a subset of hypercoiled umbilical cords.

Intrauterine Fetal Demise in the Third Trimester of Pregnancy Associated With Mild Infection With the SARS-CoV-2 Delta Variant Without Protection From Vaccination.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a higher infection rate in pregnant women than age-matched adults. With increased infectivity and transmissibility, the Delta variant is predominant worldwide. METHODS: In this study, we describe intrauterine fetal demise in unvaccinated women with mild symptoms of SARS-CoV-2 Delta variant infection. RESULTS: Histology and elevated proinflammatory responses of the placenta suggest that fetal demise was associated with placental malperfusion due to Delta variant infection. CONCLUSIONS: This study suggests that the Delta variant can cause severe morbidity and mortality to fetuses. Vaccination should continue to be advocated and will likely continue to reduce SARS-CoV-2 infection risks for pregnant women and their fetuses.

Beyond stillbirth: association of intrahepatic cholestasis of pregnancy severity and adverse outcomes.

BACKGROUND: Intrahepatic cholestasis of pregnancy is associated with adverse pregnancy outcomes, including sudden fetal cardiac arrhythmias, resulting in stillbirth. This association has been correlated with the total bile acid levels, which are a marker for disease severity. Studies are yet to determine if intrahepatic cholestasis of pregnancy severity is also associated with increased rates of other adverse neonatal outcomes. OBJECTIVE: This study aimed to determine whether pregnancies complicated by intrahepatic cholestasis of pregnancy show a bile acid severity-based relationship with other adverse obstetrical outcomes beyond stillbirth alone. STUDY DESIGN: This was a retrospective cohort study of singleton, nonanomalous gestations complicated by intrahepatic cholestasis of pregnancy at the Elmhurst Hospital Center from 2005 to 2019. Severity was defined by the peak total bile acid levels (µmol/L): mild (10-19), low moderate (20-39), high moderate (40-99), and severe (>100). We examined the rates of spontaneous preterm labor, fetal growth restriction, preterm prelabor rupture of membranes, iatrogenic preterm birth, meconium-stained amniotic fluid, cesarean delivery for nonreassuring fetal heart tracing, umbilical artery pH, neonatal intensive care unit admission, and neonatal birthweight. The chi-square, Fisher exact, Student t, Mann-Whitney, and multivariate regression tests were used to determine the association of intrahepatic cholestasis of pregnancy severity and adverse neonatal outcomes. In all analyses, mild severity was used as the base comparator. A P value of <.05 and 95% confidence interval not crossing 1.00 indicated statistical significance. RESULTS: Of the 1202 pregnancies complicated by intrahepatic cholestasis of pregnancy, 306 (25.5%) were mild, 449 were low moderate (37.4%), 327 were high moderate (27.2%), and 120 were severe (10.0%). After adjusting for confounders, progressive intrahepatic cholestasis of pregnancy severity was associated with an increased risk of spontaneous preterm labor (low moderate adjusted odds ratio, 1.60; 95% confidence interval, 0.76-3.38; high moderate adjusted odds ratio, 3.49; 95% confidence interval, 1.69-7.22; severe adjusted odds ratio, 6.58; 95% confidence interval, 2.97-14.55), iatrogenic preterm birth (low moderate adjusted odds ratio, 1.54; 95% confidence interval, 0.95-2.52; high moderate adjusted odds ratio, 3.11; 95% confidence interval, 1.91-5.06; severe adjusted odds ratio, 4.94; 95% confidence interval, 2.81-8.71), and meconium-stained amniotic fluid (low moderate adjusted odds ratio, 1.33; 95% confidence interval, 0.75-2.36; high moderate adjusted odds ratio, 2.63; 95% confidence interval, 1.48-4.65; severe adjusted odds ratio, 3.91; 95% confidence interval, 1.98-7.69). There was no significant association between intrahepatic cholestasis of pregnancy severity and other adverse outcomes. CONCLUSION: The findings suggest that intrahepatic cholestasis of pregnancy disease severity is associated with an increased risk of spontaneous preterm labor, iatrogenic preterm birth, and meconium-stained amniotic fluid. These findings provide valuable insight toward patient anticipatory counseling.

Unique Case of Congenital Langerhans Cell Histiocytosis Presenting as Intrauterine Fetal Demise.

Congenital Langerhans cell histiocytosis (LCH) (formerly called Letterer-Siwe disease) is characterized by a clonal proliferation of Langerhans cells occurring in children at birth and manifests typically with multifocal cutaneous lesions, hepatosplenomegaly, lymphadenopathy, pulmonary lesions, and destructive osteolytic bone lesions. We present a case of LCH involving multiple systems high-risk organs (LCH MS-RO+), in a 32-week stillborn from a 20-year-old G2A1. The fetus was mildly hydropic and pale. Apart from maceration, the skin showed multiple targetoid lesions over the face, trunk, and limbs. There was hepatosplenomegaly and a pale brain. The placenta was large and bulky. Despite severe autolysis, histological examination showed disseminated histiocytes with multinucleated giant cells in the skin, lungs, thymus, mesenteric lymph nodes, spleen, and brain. By immunohistochemistry, the histiocytes were positive for S100, CD1a, and Langerin (CD207), confirming the diagnosis of LCH. There was extramedullary hematopoiesis in the spleen, brain, and placenta. Targeted next-generation sequencing performed on thymic DNA did not show the BRAF p.V600E variant but did show the MAP2K1 p.F53_Q58delinsL. Infants with LCH pose a diagnostic challenge due to their heterogeneous presentations. Our case is unusual in that the newborn presented with severe multiorgan involvement including brain and intrauterine death. LCH is still poorly understood requiring further genetic and molecular studies.

Placental mesenchymal dysplasia complicated with sudden fetal demise and amniotic fluid embolism: a case report.

BACKGROUND: Placenta mesenchymal dysplasia (PMD) is a rare placental anomaly associated with various fetal and maternal complications. Whether close ultrasound surveillance can prevent intrauterine fetal demise (IUFD) in patients with PMD is still under investigation. Amniotic fluid embolism (AFE) is a rare, lethal, and unpredictable maternal complication that has never been described in association with PMD. Here, we report a case of PMD, in which the fetus eventually demised in utero despite weekly color Doppler monitoring, and the mother subsequently encountered AFE during delivery. CASE PRESENTATION: A 43-year-old woman who had received three frozen embryo transfer, was found to have a singleton pregnancy with an enlarged multi-cystic placenta at 8 weeks' gestation. Fetal growth restriction (FGR) was noted since the 21stweek. The fetus eventually demised in-utero at 25 weeks despite weekly color Doppler surveillance. Cesarean section was performed under general anesthesia due to placenta previa totalis and antepartum hemorrhage. During surgery, the patient experienced a sudden blood pressure drop and desaturation followed by profound coagulopathy. AFE was suspected. After administration of inotropic agents and massive blood transfusion, the patient eventually survived AFE. PMD was confirmed after pathological examination of the placenta. CONCLUSIONS: While FGR can be monitored by color Doppler, our case echoed previous reports that IUFD may be unpreventable even under intensive surveillance in PMD cases. Although AFE is usually considered unpredictable, PMD can result in cumulative risk factors contributing to AFE. Whether a specific link exists between the pathophysiology of PMD and AFE requires further investigation.

Fetomaternal hemorrhage: evaluation of recurrence within a large integrated healthcare system.

BACKGROUND: Fetomaternal hemorrhage is associated with severe fetal morbidity and mortality. The recurrence risk of fetomaternal hemorrhage is unknown. OBJECTIVE: We sought to establish the recurrence rate of fetomaternal hemorrhage in a large integrated healthcare system over a 10-year period. STUDY DESIGN: In this retrospective study within the Kaiser Permanente Northern California medical system, cases of fetomaternal hemorrhage were defined by either an elevated fetal hemoglobin level as determined by flow cytometry for a concerning pregnancy outcome (preterm delivery, perinatal demise, neonatal anemia, or transfusion within the first 2 days of life) or by perinatal demise with autopsy findings suggestive of fetomaternal hemorrhage. The outcomes of subsequent pregnancies were reviewed for features of recurrence. RESULTS: Within the 2008 to 2018 birth cohort of 375,864 pregnancies, flow cytometry testing for fetal hemoglobin levels was performed in 20,582 pregnancies. We identified 340 cases of fetomaternal hemorrhage (approximately 1 in 1100 births). Within the cohort of 340 affected pregnancies, perinatal loss was recorded for 80 (23.5%) pregnancies and 50 (14.7%) pregnancies delivered neonates who required transfusion. The affected patients had 225 subsequent pregnancies of which 210 were included in the analysis. Of these, 174 (82.9%) advanced beyond the threshold of viability and were delivered within our healthcare system. There was 1 case of recurrent fetomaternal hemorrhage identified. The recurrent case involved a spontaneous preterm delivery of an infant who was noted to have an elevated reticulocyte count but was clinically well. CONCLUSION: Within our large integrated healthcare system, approximately 1 in 1100 pregnancies was affected by fetomaternal hemorrhage within a 10-year period, which is comparable with previous studies. We identified 1 case of recurrence, yielding a recurrence rate of 0.5%. This infant did not have features of clinically important fetomaternal hemorrhage. This information can inform counseling of patients with affected pregnancies.

Heterotopic Liver Nodule Compressing a Two-Vessel Umbilical Cord: An Unusual Cause of Intrauterine Fetal Demise.

Heterotopic liver tissue in the umbilical cord is rare, and the outcome is quite unpredictable based on the few reported cases. We present a case of heterotopic liver nodule in the umbilical cord of a midtrimester fetus who died in utero. Although such association has only been reported once, heterotopic nodular tissue in the umbilical cord must be regarded as a potential cause of fetal demise by a mechanism analogous to the more common umbilical cord abnormalities resulting in umbilical vessel compromise.

Chronic non-infectious inflammations of the placenta.

In addition to the well-known group of inflammations of infectious etiology, placental inflammations arising on immunological basis are also encountered. The incidence of the latter far exceeds the group of infectious lesions of the placenta caused mainly by microorganisms of the TORCH group. Given the current knowledge of the possible complications of these inflammations, their precise diagnosis becomes more important not only from the clinicopathological point of view, but also because of potential forensic consequences. The aim of this article is to provide readers with a basic overview of the morphology, classification, presumed pathogenesis and clinical aspects of these entities.

Brucellosis in pregnancy: results of multicenter ID-IRI study.

Brucellosis in pregnant women is reported to be associated with obstetric complications (OCs), and adequate data for human brucellosis during pregnancy are largely lacking. We performed this multicenter retrospective cross-sectional study to evaluate the epidemiology, clinical course, treatment responses, and outcomes of brucellosis among pregnant women. The study period comprised a 14-year period from January 2002 to December 2015. All consecutive pregnant women diagnosed with brucellosis in 23 participating hospitals were included. Epidemiological, clinical, laboratory, therapeutic, and outcome data along with the assessment data of the neonate were collected using a standardized questionnaire. Data of 242 patients were analyzed. The OC rate was 14.0% (34/242) in the cohort. Of the 242 women, 219 (90.5%) delivered at term, 3 (1.2%) had preterm delivery, 15 (6.2%) aborted, and 5 (2.1%) had intrauterine fetal demise. Seventeen (7.0%) of the newborns were considered as low birth weight. Spontaneous abortion (6.1%) was the commonest complication. There were no maternal or neonatal deaths and pertinent sequelae or complications were not detected in the newborns. Splenomegaly (p = 0.019), nausea and/or vomiting (p < 0.001), vaginal bleeding (p < 0.001), anemia (blood hemoglobin < 11 g/dL; p < 0.001), high level of serum aspartate aminotransferase (> 41 IU/L; p = 0.025), oligohydramnios on ultrasonography (p = 0.0002), history of taking medication other than Brucella treatment during pregnancy (p = 0.027), and Brucella bacteremia (p = 0.029) were the significant factors associated with OCs. We recommend that pregnant women with OC or with fever should be investigated for brucellosis if they live in or have traveled to an endemic area.

Streptococcus pneumoniae - An Uncommon but Noteworthy Cause of Intrauterine Fetal Demise and Acute Necrotizing Funisitis.

Background: Streptococcus pneumoniae (S. pneumoniae) is an uncommon cause of amniotic fluid infection and intrauterine fetal demise. Case report: A 39-year-old G8P2052 presented with preterm premature rupture of membrane at 22 weeks gestation and had a spontaneous vaginal delivery of a neonate who soon expired. Placental examination revealed retroplacental hematoma, acute necrotizing chorioamnionitis, acute three-vessel vasculitis and necrotizing funisitis of the umbilical cord. Postmortem examination demonstrated features of amniotic fluid infection syndrome with blood culture growing S. pneumoniae. Antenatal screening does not typically quantify S. pneumoniae infection, but small series have found vaginal colonization in fewer than 1% of women. Intrauterine or peritoneal infection derives primarily from ascending infection although other routes are hypothetically possible. Intra-amniotic and neonatal infections by S. pneumoniae are associated with high morbidity and mortality. Conclusion: S. pneumoniae should be considered in perinatal death of immature fetus with severe amniotic fluid infection syndrome and acute necrotizing funisitis.

Increased levels of serum serglycin and agrin is associated with adverse perinatal outcome in early onset preeclampsia.

Goal: Our aim was to determine whether alterations in serum serglycin and agrin levels in early-onset preeclampsia (EOPE) are useful in predicting adverse perinatal outcomes such as fetal growth restriction (FGR), intrauterine fetal demise (IUFD), preterm delivery and/or neonatal unit admission. Materials and Methods: A prospective case-controlled study enrolled 88 pregnant patients (44 EOPE and 44 controls). Maternal serum serglycin and agrin levels were determined before the 34th gestational week by enzyme-linked immunosorbent assay. Results: Compared with controls, women with EOPE had significantly higher serglycin and agrin levels (p = .018; p = .048). Multivariable logistic regression analysis revealed serglycin was independently associated with FGR in EOPE (OR 0.866; 95% CI 0.779-0.953). Agrin was independently associated with IUFD in EOPE (OR 0.757, 95% CI 0.636-0.879). Conclusions: The current study suggests that increased maternal serum serglycin is associated with FGR, and increased maternal serum agrin is associated with IUFD in EOPE.