Keratan sulfate proteoglycan: putative template for neuroblast migratory and axonal fascicular pathways and fetal expression in globus pallidus, thalamus, and olfactory bulb.

Keratan sulfate (KS) is a proteoglycan secreted in the fetal brain astrocytes and radial glia into extracellular parenchyma as granulofilamentous deposits. KS surrounds neurons except dendritic spines, repelling glutamatergic and facilitating GABAergic axons. The same genes are expressed in both neuroblast migration and axonal growth. This study examines timing of KS during morphogenesis of some normally developing human fetal forebrain structures. Twenty normal human fetal brains from 9-41 weeks gestational age were studied at autopsy. KS was examined by immunoreactivity in formalin-fixed paraffin sections, plus other markers including synaptophysin, S-100ß protein, vimentin and nestin. Radial and tangential neuroblast migratory pathways from subventricular zone to cortical plate were marked by KS deposits as early as 9wk GA, shortly after neuroblast migration initiated. During later gestation this reactivity gradually diminished and disappeared by term. Long axonal fascicles of the internal capsule and short fascicles of intrinsic bundles of globus pallidus and corpus striatum also appeared as early as 9-12wk, as fascicular sleeves before axons even entered. Intense KS occurs in astrocytic cytoplasm and extracellular parenchyma at 9wk in globus pallidus, 15wk thalamus, 18wk corpus striatum, 22wk cortical plate, and hippocampus postnatally. Corpus callosum and anterior commissure do not exhibit KS at any age. Optic chiasm shows reactivity at the periphery but not around intrinsic subfasciculi. We postulate that KS forms a chemical template for many long and short axonal fascicles before axons enter and neuroblast migratory pathways at initiation of migration. Cross-immunoreactivity with aggrecan may render difficult molecular distinction.

Antidepressants and fetal death: A systematic review and disproportionality analysis in the WHO safety database (VigiBaseⓇ).

Recent research suggests that fetal exposure to antidepressants (ADs) is significantly associated with fetal death, including stillbirth. However, there has been limited investigation into the timing of AD exposure during pregnancy, the specific effect of each drug, and the possibility of indication bias. To address these gaps in knowledge, we conducted a systematic review of literature and disproportionality analyses using the WHO Safety Database (VigiBaseⓇ). The systematic review provided evidence for increased risks of fetal death with exposure to any selective serotonin reuptake inhibitor (SSRI) at any time of pregnancy, stillbirth with exposure to any AD during the first trimester, and stillbirth with exposure to any SSRI during the first trimester. Disproportionality analyses revealed significant associations with citalopram, clomipramine, paroxetine, sertraline, and venlafaxine. Combining both sets of results, we conclude that exposure to ADs, especially during the first trimester of pregnancy, seems to be associated with fetal mortality, and that ADs with highest placental transfer may be particularly involved. Further research should investigate the links between ADs during early pregnancy and fetal mortality.

Anti-Jk-b Antibodies and Hemolytic Disease of the Fetus and Newborn: Case-Based Learning.

The Kidd blood group is clinically significant as Kidd antibodies have the potential to trigger both acute and delayed transfusion reactions, along with hemolytic disease of the fetus and newborn (HDFN). Here, we have reported a case of HDFN due to Jk-b antibodies. A 31-year-old pregnant female was found to have Jk-b antibodies on screening with the Bio­Rad ID Dia 11-cell panel (Bio-Rad Laboratories, Inc., CA) after her cross-matching results were incompatible. Emergency lower segment caesarian section was done; the baby was non-hydropic at birth with an increase in bilirubin that required high-intensity phototherapy. HDFN resulting from anti-Jk-b incompatibility is rare and tends to present with mild clinical symptoms and a favorable prognosis. However, monitoring of antibody titers is essential to prevent potentially fatal complications. Additionally, antenatal antibody screening should be mandatory for all pregnant women, regardless of their Rh-(D) antigen status, to detect red cell alloimmunization to other clinically significant blood group antigens.

Advancing prenatal diagnosis: Echocardiographic detection of Scimitar syndrome in China - A case series.

Objective: To investigate the clinical value of echocardiographic detection in the prenatal early diagnosis of Scimitar syndrome (SS) in fetuses, and to develop better and more accurate management strategies for improved prognosis. Methods: A retrospective analysis was conducted on medical records and fetal echocardiographic findings of all cases diagnosed as SS between April 1, 2016 and June 1, 2021. To summarize its echocardiographic features and distinguishing points, comprehensive clinical data and prognostic information were gathered. Results: Six patients were diagnosed with SS during the study period. Major associated abnormalities included atrial septal defect (n = 3), right inferior pulmonary vein anomalies (n = 2), ventricular septal defect (n = 1), and right aortic arch (n = 1). Post-surgery, all patients exhibited unobstructed pulmonary vein flow and absence of pulmonary hypertension. The average follow-up duration was 24 months, during which five infants underwent surgical intervention for SS. Conclusion: Comprehensive prenatal screening, particularly combined coronal and sagittal views of the fetal thorax, enables accurate diagnosis of right SS. This approach not only aids in timely intervention but also provides crucial prognostic insights for the child's future well-being.

Fetal Gas Gangrene: A Rare and Critical Case.

Gas gangrene is a lethal necrotic infection resulting in gas production within tissue. It is typically associated with trauma and is especially lethal during pregnancy, resulting in severe maternal infection and fetal death. We report the case of a 31-year-old G3P2 female who presented to the emergency department with abdominal bloating, vaginal cramping, and brown vaginal discharge. Physical examination showed that the patient was hypertensive, tachycardic, and tachypneic, and laboratory examination showed a downtrending beta-human chorionic gonadotropin and leukocytosis, with elevated inflammatory markers. Ultrasound showed copious gas located within the lower abdomen and the fetus was not visualized. Computed tomography (CT) of the abdomen and pelvis showed a gravid uterus with a single fetus and extensive air locules in the fetus, amniotic cavity, and placenta. The findings were consistent with gas gangrene of a mature fetus in the third trimester. Fetal gas gangrene is a potentially lethal condition during pregnancy, and early diagnosis is imperative in management. CT was utilized in this case to outline the increased gas production within the amniotic cavity and fetal organs and proved crucial in determining the next steps of management.

Bilateral renal agenesis: fetal intervention and outcomes.

Bilateral renal agenesis (BRA) is a fetal anomaly which leads to anhydramnios and resultant pulmonary hypoplasia. Historically, this anomaly was universally fatal early in the neonatal period due to the severity of the associated lung disease. Over the last 30 years, innovations in fetal therapies-specifically, serial amnioinfusions-have led to instances of infant pulmonary survival and initiation of postnatal dialysis, raising the possibility that early neonatal death may not be inevitable. Amnioinfusions are not without risk, and maternal complications can include prelabor rupture of membranes, preterm labor, infection, and bleeding. The data detailing neonatal outcomes are still limited and actively being collected. Two case series and one non-randomized clinical trial have supplied most of the known outcome data for infants with BRA after prenatal amnioinfusion. Although there are survivors reported in the literature, mortality remains high, with many deaths in infancy due to dialysis-associated sepsis. In addition, previously unknown morbidities have been documented in these infants, including neurologic injury. These challenges, in addition to the mechanical difficulties of providing dialysis to extremely small infants, can result in significant burdens for patients and their caregivers and moral distress for the health care team. The present review aims to explain the pathophysiology of BRA, detail the historical context and rationale for serial amnioinfusions to treat the pulmonary insufficiency associated with BRA, describe the available data regarding outcomes of infants born following prenatal amnioinfusions, discuss ethical issues surrounding this fetal intervention, and describe critical aspects of prenatal counseling for patients considering the intervention.

Prenatal diagnosis of ectopic kidney: Evaluation of characteristics, additional anomalies and urinary complications.

OBJECTIVE: To assess the characteristics, additional structural anomalies and postnatal urinary outcome of the cases diagnosed with fetal ectopic kidneys in the prenatal period. STUDY DESIGN: Cases having fetal ectopic kidneys, detected from a total of 14,617 pregnant women examined by routine detailed (Group 1) or indicated (Group 2) obstetric ultrasonography (USG) in a tertiary perinatology unit were analyzed. The prevalence of the cases, time of the diagnosis, sidedness of the affected kidney, anatomical location, origins of blood supply, additional urinary or extraurinary anomalies, and urinary complications during the postnatal follow-up period were investigated. RESULTS: We have detected 33 fetuses with ectopic kidneys in our cohort. The prevalence of fetal ectopic kidney was 0.22 %, with a median (min.-max.) diagnosis time of 21.3 (17.6-34) weeks. In the group in whom indicated USG was performed, the time of diagnosis was later compared to routine detailed USG (p = 0.04) group. There was no difference in terms of gender [male, (n = 14), female (n = 19), p = 0.38] and the sidedness of the ectopic kidneys (p = 0.38). The location of ectopic kidneys was most frequent in the iliac fossa (n = 20, 60.6 %) and in the lateral pelvic areas (n = 13, 39.3 %). The blood supply origin of ectopic kidneys was the common iliac artery in 22 (66.6 %), whereas the aorta in 11 cases (33.3 %). There was an additional urinary anomaly in 8 cases (24 %), an extraurinary structural anomaly, most commonly cardiac, and/or a soft marker for aneuploidy were presented in 16 cases (48 %). The most common urinary complication in the postpartum period was vesicoureteral reflux (n = 5). CONCLUSION: Ectopic kidney in the prenatal period is a rare structural anomaly that can equally affect both genders and both kidneys. Prenatal diagnosis is important for the diagnosis of additional anomalies and follow-up of postnatal complications.

Maternal infection with hepatitis B virus before pregnancy and risk of congenital malformations in offspring: a record-linkage study of a large national sample from China.

Background: Whether hepatitis B virus (HBV) infection of women prior to pregnancy can influence risk of congenital malformations in offspring remains controversial. We assessed the association between them by considering congenital malformations in the aggregate as well as risk of organs systems using a large national sample of Chinese women. Methods: We performed a record-linkage cohort study of women who participated in National Free Preconception Health Examination Project, between January 1, 2010, and December 31, 2019 for whom data on congenital malformations in their offspring were available from the National Population-Based Birth Defects Surveillance Network. A total of 498,968 linked records were obtained, of which 127,371 were excluded because HBV status before pregnancy was unknown, the records involved multiple pregnancies, or pre-pregnancy examinations were conducted after conception. Based on pre-pregnancy status, mothers were assigned to two categories of HBsAg- or HBsAg+ and, in certain analyses, to three categories of HBsAg-, HBsAg+/HBeAg- or HBsAg+/HBeAg+. Potential associations of serological status with risk of congenital malformations, considered separately or in aggregate, were explored using multilevel logistic regression. Factors that might influence such associations were also explored. Findings: Among the 371,597 women analyzed, 21,482 (5.78%) were HBsAg+ before pregnancy, and 8333 (2.24%) had a fetus or child diagnosed with congenital malformations, composed of 7744 HBsAg- women and 589 HBsAg+ women. HBsAg+ status was associated with increased risk of congenital malformations in the aggregate (OR 1.14, 95% CI 1.03-1.25) and of cardiovascular malformations specifically (OR 1.18, 95% CI 1.03-1.35). HBsAg+/HBeAg- status was associated with significantly higher risk of cardiovascular malformations (OR 1.19, 95% CI 1.01-1.39) as well as reproductive malformations (OR 1.51, 95% CI 1.02-2.23). Associations between HBsAg+ status before pregnancy and risk of congenital malformations was modified by alanine aminotransferase activity (P interaction < 0.05). Interpretation: Prepregnancy HBV infection might be associated with fetal malformations. This association needs further investigation to confirm whether it is a causal association, and assess whether antiviral therapy of women with HBsAg+ planning to conceive might reduce the risk of fetal malformations. Funding: The National Health Commission of the People's Republic of China, China; Science and Technology Department of Sichuan Province, China; and the Ministry of Science and Technology of the People's Republic of China.

Evaluation of fetal cerebral microvascular status and its relationship with fetal growth and development using microvascular imaging technique.

The study conducted retrospective analysis design, aiming to explore the use of Microvascular Imaging Technique (MVFI) to assess fetal cerebral microcirculation and analyze the relationship between Microvascular Index (MVI) and fetal growth and development. 100 pregnant women who met the criteria for fetal growth restriction (FGR) provided in the Expert Consensus on Fetal Growth Restriction (2019 Edition) and underwent routine prenatal examinations at the Obstetrics and Gynecology Department of Peking University Third Hospital from January 2021 to June 2023 were selected as the study subjects. A normal fetus with a fetal weight less than 10 % can be classified as FGR, Pregnant women with fetal umbilical artery (UA) systolic and diastolic (S/D) values ≥3 were included in the observation group, while 200 pregnant women with normal fetuses were selected as the control group during the same period. The fetuses' change in both groups were measured using color Doppler ultrasound, including bi-parietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL). The cerebral microcirculation of the fetuses in both groups was evaluated using MVFI, and the MVI values were compared. The clinical characteristics of FGR fetuses with umbilical artery S/D ratio ≥ 3 were summarized, and the correlation between fetal cerebral microvascular status and fetal growth and development was analyzed using Pearson correlation analysis. The outcomes told that the BPD, HC, AC, and FL values of the fetuses in the control group were lower the other's value (P < 0.05), and the MVI and peak systolic velocity of the middle cerebral artery (MCA-PSV) values were also lower in the control group (P < 0.05). Pearson correlation analysis revealed a positive correlation between fetal growth and development and MVI and MCA-PSV values in FGR fetuses. In conclusion, MVFI can monitor and quantitatively analyze fetal intracranial microcirculation, visualize slow blood flow in microvascular structures, and this study provides preliminary evidence of the close relationship between fetal cerebral microcirculation and intrauterine growth and development.

Gastric cancer in pregnancy: a review.

Malignant tumors including gastric cancer (GC) are the leading cause of deaths among reproductive women. Physiological morning sickness can mask the clinical manifestations of GC, whereas the clinical presence of metastatic tumors in the abdominal cavity may be easily mistaken for abdominal swelling caused by fetal growth. Pregnancy and delivery processes in young females could accelerate the growth of GC, leading to its rapid development and grave prognosis. Therefore, early diagnosis is critical and gastrointestinal endoscopy is recommended for any suspected pregnant woman with long-term morning sickness. Treatment strategies, including chemotherapy, resection surgery and radiotherapy, will be determined based on a comprehensive consideration of the status of both the fetus and the mother. Rational management, especially clinical multidisciplinary collaboration may significantly benefit such patients.

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Cardiac programming in the placentally restricted sheep fetus in early gestation.

Fetal growth restriction (FGR) occurs in 8% of human pregnancies, and the growth restricted newborn is at a greater risk of developing heart disease in later adult life. In sheep, experimental restriction of placental growth (PR) from conception results in FGR, a decrease in cardiomyocyte endowment and an upregulation of pathological hypertrophic signalling in the fetal heart in late gestation. However, there is no change in the expression of markers of cellular proliferation nor in the level of cardiomyocyte apoptosis in the heart of the PR fetus in late gestation. This suggests that FGR arises early in gestation and programs a decrease in cardiomyocyte endowment in early, rather than late, gestation. Here, control and PR fetal sheep were humanely killed at 55 days' gestation (term, 150 days). Fetal body and heart weight were lower in PR compared with control fetuses and there was evidence of sparing of fetal brain growth. While there was no change in the proportion of cardiomyocytes that were proliferating in the early gestation PR heart, there was an increase in measures of apoptosis, and markers of autophagy and pathological hypertrophy in the PR fetal heart. These changes in early gestation highlight that FGR is associated with evidence of early cell death and compensatory hypertrophic responses of cardiomyocytes in the fetal heart. The data suggest that early placental restriction results in a decrease in the pool of proliferative cardiomyocytes in early gestation, which would limit cardiomyocyte endowment in the heart of the PR fetus in late gestation. KEY POINTS: Placental restriction leading to fetal growth restriction (FGR) and chronic fetal hypoxaemia in sheep results in a decrease in cardiomyocyte endowment in late gestation. FGR did not change cardiomyocyte proliferation during early gestation but did result in increased apoptosis and markers of autophagy in the fetal heart, which may result in the decreased endowment of cardiomyocytes observed in late gestation. FGR in early gestation also results in increased hypoxia inducible factor signalling in the fetal heart, which in turn may result in the altered expression of epigenetic regulators, increased expression of insulin-like growth factor 2 and cardiomyocyte hypertrophy during late gestation and after birth.

Meconium Proteins Involved in Iron Metabolism.

The lack of specific biological materials and biomarkers limits our knowledge of the mechanisms underlying intrauterine regulation of iron supply to the fetus. Determining the meconium content of proteins commonly used in the laboratory to assess the transport, storage, and distribution of iron in the body may elucidate their roles in fetal development. Ferritin, transferrin, haptoglobin, ceruloplasmin, lactoferrin, myeloperoxidase (MPO), neutrophil gelatinase-associated lipocalin (NGAL), and calprotectin were determined by ELISA in meconium samples obtained from 122 neonates. There were strong correlations between the meconium concentrations of haptoglobin, transferrin, and NGAL (p < 0.05). Meconium concentrations of ferritin were several-fold higher than the concentrations of the other proteins, with the exception of calprotectin whose concentration was approximately three-fold higher than that of ferritin. Meconium ceruloplasmin concentration significantly correlated with the concentrations of MPO, NGAL, lactoferrin, and calprotectin. Correlations between the meconium concentrations of haptoglobin, transferrin, and NGAL may reflect their collaborative involvement in the storage and transport of iron in the intrauterine environment in line with their recognized biological properties. High meconium concentrations of ferritin may provide information about the demand for iron and its utilization by the fetus. The associations between ceruloplasmin and neutrophil proteins may indicate the involvement of ceruloplasmin in the regulation of neutrophil activity in the intrauterine environment.

Resveratrol as modulator of PSA-NCAM expression in the hippocampus of diazinon-injured rat fetuses.

Polysialylated neural cell adhesion molecule (PSA-NCAM) is expressed in the developing central nervous system (CNS) and plays an important role in neurogenesis. Organophosphorus (OP) toxins, including diazinon (DZN), cause oxidative stress (OS) and damage the CNS. Resveratrol (RV), with its antioxidant effect, leads to the reduction of OS. Therefore, this research was conducted with the aim of the effect of RVon the expression of PSA-NCAM in the hippocampus (HPC) of rat fetuses treated with DZN. In this study, 24 female Wistar rats were divided into 4 groups (n = 6): Control, DZN (40 mg/kg), RV(10 mg/kg), and DZN + RV(40 mg/kg + 10 mg/kg) after confirming they were pregnant. On the 21st day of pregnancy, the mother mice were anesthetized with ketamine and xylazine, and the fetuses were removed; after anesthesia, their brains were removed for immunohistochemistry and western blot (WB) technique. The results of the study showed that in the group receiving DZN, the level of PSA-NCAM protein expression decreased significantly compared to the control group, and the group receiving RV with its antioxidant property increased the expression of PSA-NCAM protein compared to the DZN group. All in all, the exposure of pregnant mice to DZN causes disorders in the CNS, especially the level of PSA-NCAM protein expression in the HPC of fetuses, and the use of RV as an antioxidant by pregnant mothers neutralizes the effects of DZN in the HPC of their fetuses.

Moral parenthood: not gestational.

Parenting our biological children is a centrally important matter, but how, if it all, can it be justified? According to a contemporary influential line of thinking, the acquisition by parents of a moral right to parent their biological children should be grounded by appeal to the value of the intimate emotional relationship that gestation facilitates between a newborn and a gestational procreator. I evaluate two arguments in defence of this proposal and argue that both are unconvincing.

A case report of hepatic fetus-in-fetu: Approach to diagnosis.

Multiple theories have been proposed about the pathophysiology of Fetus-in-fetu (FIF). The most widely accepted theory is abnormal embryogenesis in diamniotic monochorionic pregnancies, in which a malformed parasitic fetus is found within the body of a twin host. Hepatic FIF has been reported in almost 1% of FIF cases, with only 2 case reports being published in the literature. This article presents the third case report of intrahepatic FIF. Additionally, we review the role of radiology in diagnosing these cases and guiding their proper management. This case report supports the monozygotic twin theory of FIF and the diagnostic dilemma of FIF vs. teratoma can be solved through collaborative work between radiologists and pathologists.

A systematic review of prenatally diagnosed vein of Galen malformations: prenatal predictive markers and management from fetal life to childhood.

Introduction: Vein of Galen malformations (VGMs) account for less than 1% of all intracranial vascular malformations. However, in fetal and pediatric populations, they represent the most common vascular malformation of the brain. For the effective management of this condition, an optimal knowledge of its prenatal and postnatal clinical features is mandatory. Methods: Articles published between 1 January 2003 and 31 January 2024, reported in PubMed and EMBASE, were evaluated for a systematic review analyzing the prenatal and postnatal features and management of fetal VGMs. Results: Thirty-one papers reporting information on 51 prenatally diagnosed VGMs were included. The most common prenatal features were fetal hydrocephalus (39%) and cardiomegaly (56%). Postnatal data for 43 VGM cases are described. The overall mortality was 58.14%. In total, 77.78% of the survivors had normal development. Conclusions: Close follow-up and a multidisciplinary approach are mandatory to manage this condition. Our study aimed to provide a guide for gynecologists, neonatologists, cardiologists, and neuroradiologists.

Overdose of angiotensin II receptor blocker in the third trimester of pregnancy: A case report.

Angiotensin II receptor blockers (ARBs) are contraindicated during pregnancy because of fetal toxicity. All previous reports on adverse fetal outcomes involved women who continued to take low-dose ARBs for hypertension and were unaware of the adverse effects. Herein, we report the case of a 23-year-old pregnant woman in her third trimester who experienced an ARB overdose after an argument with her partner. Pregnancy was complicated by transient oligohydramnios, and fetal magnetic resonance imaging suggested renal failure. Despite these concerns, the newborn had no morphological abnormalities or abnormal neurological findings. Renal impairment improved over time, and the infant grew well. A single overdose of ARBs in the third trimester can lead to fetal renal failure, similar to long-term low-dose ARB administration; however, favorable outcomes are possible. An overdose of ARBs may transiently cause renal failure, which may improve. The study findings may inform counseling for women who are unexpectedly exposed to an overdose of ARBs.

Growth patterns of facial muscles at the angle of the mouth: A histological study using midterm and near-term human fetuses.

At the angle of the mouth, spoke-like muscle bundles converge at the "modiolus," which is believed to appear in utero. The aim of this study was to investigate the growth of the modiolus histologically. We studied frontal histological sections of the face from 12 midterm and six near-term fetuses. At midterm, a convergence of the levator anguli oris (LAOM) and depressor anguli oris (DAOM) was frequently present, and another convergence of the LAOM with the platysma (PM) or orbicularis oris (OOM) was also often evident. At near-term, muscle fiber merging or interdigitation was classified into nine combinations, five of which were frequently seen: LAOM-PM, LAOM-DAOM, zygomaticus major (ZMM)-orbicularis oris (OOM), buccinator (BM)-LAOM, and BM-PM. These combinations existed at slightly different depths and/or sites, thus allowing the angle of the mouth to receive multiple muscles. Notably, tissues interposed between the muscle fibers were limited to a thin epimysium at each crossing or interdigitation. Therefore, the LAOM, DAOM, OOM, BM, and PM appear to form a basic configuration at birth, but the development and growth were much delayed than the classical description. The modiolus is not a specific fibromuscular structure but simply represents a cluster of muscle convergence sites. Even at meeting between an elevator and depressor, a specific fibrous structure seems unlikely to connect the epimysium for the muscle convergence. Instead, the central nervous system appears to regulate the activity of related muscles to minimize tension or friction stress at the meeting site.