Reply to Onkenhout et al. Comment on "van Gemert et al. Child Abuse, Misdiagnosed by an Expertise Center-Part II-Misuse of Bayes' Theorem. 2023, , 843".

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A Deep Intronic Splice Variant in COL1A1 Causing Osteogenesis Imperfecta Type II.

Osteogenesis imperfecta (OI) is a rare disease, hallmarked by bone fragility, multiple fractures, and deformities, and is commonly caused by pathogenic variants in the genes encoding type I collagen. Type II OI is the most severe form and is lethal in the perinatal period. Here, we report recurrence of perinatal lethal OI in two fetuses due to parental mosaicism for a deep intronic pathogenic variant at c.

Uneven Distribution of Purkinje Cell Injury in the Cerebellar Vermis of Term Neonates with Hypoxic-Ischemic Encephalopathy.

In term neonates with hypoxic-ischemic encephalopathy (HIE), cerebellar injury is becoming more and more acknowledged. Animal studies demonstrated that Purkinje cells (PCs) are especially vulnerable for hypoxic-ischemic injury. In neonates, however, the extent and pattern of PC injury has not been investigated.

Timing of cerebral damage in molybdenum cofactor deficiency: A meta-analysis of case reports.

Purpose: Molybdenum cofactor deficiency (MoCD) classically presents shortly after birth, with neurological symptoms ascribed to postnatal toxicity of accumulating sulphite. Case reports suggest that cerebral damage associated with MoCD may have a prenatal onset.

Methods: A meta-analysis of case reports was performed on individuals with genetically proven MoCD retrieved through a systematic review and in-house search.

Prevalence of placental bed spiral artery pathology in preeclampsia and fetal growth restriction: A prospective cohort study.

Background: Preeclampsia and fetal growth restriction (PE/FGR) are pregnancy complications known to be associated with poor utero-placental function due to abnormal "physiological" remodeling of spiral arteries and unfavorable maternal cardiovascular health. However, the prevalence and degree of impaired spiral artery remodeling has not been clearly established.

Method: Prospective, multi-center observational cohort study to assess the prevalence of lesions associated with abnormal development of spiral arteries in placental bed biopsies systematically obtained from 121 women undergoing Caesarian section for PE/FGR compared with a reference group of 149 healthy controls.

Direct correlation of MR-DWI and histopathology of Wilms' tumours through a patient-specific 3D-printed cutting guide.

Objectives: The International Society of Paediatric Oncology-Renal Tumour Study Group (SIOP-RTSG) discourages invasive procedures to determine the histology of paediatric renal neoplasms at diagnosis. Therefore, the histological subtype of Wilms' tumours (WT) is unknown at the start of neoadjuvant chemotherapy. MR-DWI shows potential value as a non-invasive biomarker through apparent diffusion coefficients (ADCs).

Multipotent adult progenitor cells prevent functional impairment and improve development in inflammation driven detriment of preterm ovine lungs.

Background: Perinatal inflammation increases the risk for bronchopulmonary dysplasia in preterm neonates, but the underlying pathophysiological mechanisms remain largely unknown. Given their anti-inflammatory and regenerative capacity, multipotent adult progenitor cells (MAPC) are a promising cell-based therapy to prevent and/or treat the negative pulmonary consequences of perinatal inflammation in the preterm neonate. Therefore, the pathophysiology underlying adverse preterm lung outcomes following perinatal inflammation and pulmonary benefits of MAPC treatment at the interface of prenatal inflammatory and postnatal ventilation exposures were elucidated.

Placental Pathology Contributes to Impaired Volumetric Brain Development in Neonates With Congenital Heart Disease.

Background: Neonates with congenital heart disease are at risk for impaired brain development in utero, predisposing children to postnatal brain injury and adverse long-term neurodevelopmental outcomes. Given the vital role of the placenta in fetal growth, we assessed the incidence of placental pathology in fetal congenital heart disease and explored its association with total and regional brain volumes, gyrification, and brain injury after birth.

Methods And Results: Placentas from 96 term singleton pregnancies with severe fetal congenital heart disease were prospectively analyzed for macroscopic and microscopic pathology.

First-trimester 3D power Doppler imaging markers of utero-placental vascular development are associated with placental weight and diameter at birth: The Rotterdam Periconception Cohort.

Introduction: Early utero-placental vascular development impacts placental development and function throughout pregnancy. We investigated whether impaired first-trimester utero-placental vascular development is associated with pathologic features of the postpartum placenta.

Methods: In this prospective observational study of 65 ongoing pregnancies, we obtained three-dimensional power Doppler ultrasounds of the placenta at 7, 9 and 11 weeks of gestation.

The Radiological and Histological Phenotype of Skeletal Abnormalities in Fetal -Related Syndrome.

Mutations in give rise to a syndromic disorder with rhizomelic short stature with microretrognathia and developmental delay. encodes the delta subunit of the coat protein I complex, which is required for intracellular trafficking of collagen 1 and which may also be involved in the endoplasmic reticulum (ER) stress response. In this paper we describe for the first time the skeletal histological abnormalities in an 18-week-old fetus with an mutation, and we suggest that the skeletal phenotype in -related syndrome has more resemblance with ER stress than with a defect in collagen 1 metabolism.

Asymptomatic Infant Rib Fractures Are Primarily Non-abuse-Related and Should Not Be Used to Assess Physical Child Abuse.

Finding infant rib fractures was for many years an almost undisputed proof that physical child abuse took place. Yet, these rib fractures are virtually always occult and asymptomatic and are only identified when looked for, usually with X-rays, from physical child abuse accusations related to, e.g.

Maturation and Function of the Intercalated Disc: Report of Two Pediatric Cases Focusing on Cardiac Development and Myocardial Hyperplasia.

The development of the normal human heart, ranging from gestational age to the mature adult heart, relies on a very delicate and timely orchestrated order of processes. One of the most striking alterations in time is the gradual extinction of the ability for cardiomyocytes to proliferate. Once passing this event, cardiomyocytes grow and increase in contractile strength by means of physiological hypertrophy.

Identification of a unique intervillous cellular signature in chronic histiocytic intervillositis.

Introduction: Chronic histiocytic intervillositis (CHI) is a rare histopathological lesion in the placenta characterized by an infiltrate of CD68 cells in the intervillous space. CHI is associated with adverse pregnancy outcomes such as miscarriage, fetal growth restriction, and (late) intrauterine fetal death. The adverse pregnancy outcomes and a variable recurrence rate of 25-100% underline its clinical relevance.

Clinical and Molecular Diagnosis of Osteocraniostenosis in Fetuses and Newborns: Prenatal Ultrasound, Clinical, Radiological and Pathological Features.

Osteocraniostenosis (OCS, OMIM #602361) is a severe, usually lethal condition characterized by gracile bones with thin diaphyses, a cloverleaf-shaped skull and splenic hypo/aplasia. The condition is caused by heterozygous mutations in the gene and is allelic to the non-lethal, dominant disorder Kenny-Caffey syndrome (KCS, OMIM #127000). Here we report two new cases of OCS, including one with a detailed pathological examination.

Hypothesized pathogenesis of acardius acephalus, acormus, amorphus, anceps, acardiac edema, single umbilical artery, and pump twin risk prediction.

Background: Acardiac twinning complicates monochorionic twin pregnancies in ≈2.6%, in which arterioarterial (AA) and venovenous placental anastomoses cause a reverse circulation between prepump and preacardiac embryos and cessation of cardiac function in the preacardiac. Literature suggested four acardiac body morphologies in which select (groups of) organs fail to develop, deteriorate, or become abnormal: acephalus (≈64%, [almost] no head, part of body, legs), amorphus (≈22%, amorphous tissue lump), anceps (≈10%, cranial bones, well-developed), and acormus (≈4%, head only).

Age-Related Variation in Sympathetic Nerve Distribution in the Human Spleen.

The cholinergic anti-inflammatory pathway (CAIP) has been proposed as an efferent neural pathway dampening the systemic inflammatory response via the spleen. The CAIP activates the splenic neural plexus and a subsequent series of intrasplenic events, which at least require a close association between sympathetic nerves and T cells. Knowledge on this pathway has mostly been derived from rodent studies and only scarce information is available on the innervation of the human spleen.

Fetal akinesia deformation sequence and massive perivillous fibrin deposition resulting in fetal death in six fetuses from one consanguineous couple, including literature review.

Background: Massive perivillous fibrin deposition (MPFD) is associated with adverse pregnancy outcomes and is mainly caused by maternal factors with limited involvement of fetal or genetic causes. We present one consanguineous couple with six fetuses developing Fetal Akinesia Deformation Sequence (FADS) and MPFD, with a possible underlying genetic cause. This prompted a literature review on prevalence of FADS and MPFD.

Placental Complement Activation in Fetal and Neonatal Alloimmune Thrombocytopenia: An Observational Study.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease that causes thrombocytopenia and a risk of bleeding in the (unborn) child that result from maternal alloantibodies directed against fetal, paternally inherited, human platelet antigens (HPA). It is hypothesized that these alloantibodies can also bind to the placenta, causing placental damage. This study aims to explore signs of antibody-mediated placental damage in FNAIT.

Why does second trimester demise of a monochorionic twin not result in acardiac twinning?

Background: We previously explained why acardiac twinning occurs in the first trimester. We raised the question why a sudden demised monochorionic twin beyond the first trimester does not lead to acardiac twinning. We argued that exsanguinated blood from the live twin would strongly increase the demised twins' vascular resistance, preventing its perfusion and acardiac onset.

One-Sided Chronic Intervillositis of Unknown Etiology in Dizygotic Twins: A Description of 3 Cases.

Chronic intervillositis of unknown etiology (CIUE) is a rare, poorly understood, histopathological diagnosis of the placenta that is frequently accompanied by adverse pregnancy outcomes including miscarriage, fetal growth restriction, and intrauterine fetal death. CIUE is thought to have an immunologically driven pathophysiology and may be related to human leukocyte antigen mismatches between the mother and the fetus. Dizygotic twins with one-sided CIUE provide an interesting context to study the influence of immunogenetic differences in such cases.

Sequential Exposure to Antenatal Microbial Triggers Attenuates Alveolar Growth and Pulmonary Vascular Development and Impacts Pulmonary Epithelial Stem/Progenitor Cells.

Perinatal inflammatory stress is strongly associated with adverse pulmonary outcomes after preterm birth. Antenatal infections are an essential perinatal stress factor and contribute to preterm delivery, induction of lung inflammation and injury, pre-disposing preterm infants to bronchopulmonary dysplasia. Considering the polymicrobial nature of antenatal infection, which was reported to result in diverse effects and outcomes in preterm lungs, the aim was to examine the consequences of sequential inflammatory stimuli on endogenous epithelial stem/progenitor cells and vascular maturation, which are crucial drivers of lung development.

Acardiac twin pregnancies part VI: Why does acardiac twinning occur only in the first trimester?

Background: Clinical observation suggests that acardiac twinning occurs only in the first trimester. In part, this contradicts our previous analysis (part IV) of Benirschke's concept that unequal embryonic splitting causes unequal embryo/fetal blood volumes and pressures. Our aim is to explain why acardiac onset is restricted to the first trimester.