Vitomics: A novel paradigm for examining the role of vitamins in human biology.

The conventional view of vitamins reflects a diverse group of small molecules that facilitate critical aspects of metabolism and prevent potentially fatal deficiency syndromes. However, vitamins also contribute to the shaping and maintenance of the human phenome over lifecycle and evolutionary timescales, enabling a degree of phenotypic plasticity that operates to allow adaptive responses that are appropriate to key periods of sensitivity (i.e., epigenetic response during prenatal development within the lifecycle or as an evolved response to environmental challenge over a great many lifecycles). Individually, vitamins are important, but their effect is often based on nutrient-nutrient (vitamin-vitamin), nutrient-gene (vitamin-gene), and gene-gene interactions, and the environmental influence of shifting geophysical cycles, as well as evolving cultural practices. These ideas will be explored within what I refer to as the "adaptive vitome (vitomics)" paradigm.

The use of parent-completed questionnaires to investigate developmental outcomes in large populations of children exposed to antiseizure medications in pregnancy.

OBJECTIVE: This study was undertaken to assess the utility of the Ages and Stages Questionnaire-3rd Edition (ASQ-3) and the Vineland Adaptive Behavior Scales-2nd Edition (VABS-II) as neurodevelopmental screening tools for infants exposed to antiseizure medications in utero, and to examine their suitability for use in large-population signal generation initiatives. METHODS: Participants were women with epilepsy who were recruited from 21 hospitals in England and Northern Ireland during pregnancy between 2014 and 2016. Offspring were assessed at 24 months old using the Bayley Scales of Infant Development-3rd Edition (BSID-III), the VABS-II, and the ASQ-3 (n = 223). The sensitivity and specificity of the ASQ-3 and VABS-II to identify developmental delay at 24 months were examined, using the BSID-III to define cases. RESULTS: The ASQ-3 identified 65 children (29.1%) as at risk of developmental delay at 24 months using standard referral criteria. Using a categorical approach and standard referral criteria to identify delay in the ASQ-3 and BSID-III at 24 months, the ASQ-3 showed excellent sensitivity (90.9%) and moderate specificity (74.1%). Utilizing different cut-points resulted in improved properties and may be preferred in certain contexts. The VABS-II exhibited the strongest psychometric properties when borderline impairment (>1 SD below the mean) was compared to BSID-III referral data (sensitivity = 100.0%, specificity = 96.6%). SIGNIFICANCE: Both the ASQ-3 and VABS-II have good psychometric properties in a sample of children exposed to antiseizure medications when the purpose is the identification of at-risk groups. These findings identify the ASQ-3 as a measure that could be used effectively as part of a tiered surveillance system for teratogenic exposure by identifying a subset of individuals for more detailed investigations. Although the VABS-II has excellent psychometric properties, it is more labor-intensive for both the research team and participants and is available in fewer languages than the ASQ-3.

The lived experience of young adults with Fetal Valproate Spectrum Disorder, and the perspective of their parents: A qualitative study.

BACKGROUND: While research has investigated the physical and neurodevelopmental consequences following prenatal exposure to valproate, our understanding of individuals with a formal diagnosis of Fetal Valproate Spectrum Disorder (FVSD), particularly in the context of adulthood, remains limited. AIM: To investigate how symptoms and challenges of FVSD present in adulthood. METHODS: 30 people took part in the study, including 13 young adults aged between 21 and 37 years, 15 mothers, and 2 fathers. In all cases, valproate had been used for the treatment of maternal epilepsy. Data were collected using semi-structured interviews and analysed using thematic analysis. RESULTS: Six broad themes were identified: 1. Health and development, 2. Employment, 3. Daily living and independence, 4. Social skills and relationships, 5. Access to services, and 6. Impact on families. Individuals with FVSD live with an array of physical, mental, and developmental challenges that extend well beyond childhood, significantly altering their life course and that of their families. Challenges in obtaining employment, achieving independent living, and navigating social and romantic relationships become increasingly significant as individuals with FVSD age. Despite their persistent need for support, services for adults with FVSD are either limited or entirely absent. Recommendations from families were provided regarding optimized support systems. CONCLUSION: This study highlights the lifelong physical, cognitive, emotional, social and behavioural symptoms associated with FVSD. Young adults and their parents desire further research regarding the condition along with improved support and health services in adulthood.

Better communication between experts is needed to solve the environmental origins of birth defects.

More than 6% of babies are born with a structural or functional defect, and many of these need special care and treatment to survive and thrive. Such defects can be inherited, arise through exposure to altered conditions or compounds in the womb, or result from a combination of genetic and environmental factors. Since the 1940s, animal experiments and epidemiological studies have identified many environmental factors that can cause particular birth defects. More recently, advances in genomics have allowed a simple genetic diagnosis in ∼ 30% of birth defects. However, the cause of the remainder is a mystery. I believe that a key limiter to successful identification of new environmental factors is that clinicians, epidemiologists and developmental biologists all approach the topic from different angles. I propose that better communication between such experts will further increase our understanding of the environmental causes of birth defects, and potentially reduce their global burden.

ZeBraInspector, a platform for the automated segmentation and analysis of body and brain volumes in whole 5 days post-fertilization zebrafish following simultaneous visualization with identical orientations.

In recent years, the zebrafish has become a well-established laboratory model. We describe here the ZeBraInspector (ZBI) platform for high-content 3D imaging (HCI) of 5 days post-fertilization zebrafish eleuthero-embryos (EEs). This platform includes a mounting method based on 3D-printed stamps to create a grid of wells in an agarose cast, facilitating batch acquisitions with a fast-confocal laser scanning microscope. We describe reference labeling in cleared fish with a fluorescent lipophilic dye. Based on this labeling, the ZBI software registers. EE 3D images, making it possible to visualize numerous identically oriented EEs on a single screen, and to compare their morphologies and any fluorescent patterns at a glance. High-resolution 2D snapshots can be extracted. ZBI software is therefore useful for diverse high-content analyses (HCAs). Following automated segmentation of the lipophilic dye signal, the ZBI software performs volumetric analyses on whole EEs and their nervous system white matter. Through two examples, we illustrate the power of these analyses for obtaining statistically significant results from a small number of samples: the characterization of a phenotype associated with a neurodevelopmental mutation, and of the defects caused by treatments with a toxic anti-cancer compound.

Gamma secretase inhibition: Effects on fertility and embryo-fetal development in rats.

Avagacestat inhibits γ-secretase, a protease that cleaves the amyloid precursor protein (APP) to produce amyloid beta (Aß). Aß plaques, a predominant lesion in Alzheimer's patient's brain, is considered a mechanism driving neurodegeneration. As part of the nonclinical reproductive safety assessment, avagacestat effects on fertility and early embryonic development and embryo-fetal development were evaluated in rats. In the embryo-fetal development study, avagacestat was a selective developmental toxicant with dose-related increased fetal mortality, decreased fetal growth, and increased fetal malformations and variations (primarily affecting the axial and appendicular skeletal system) at ≥3 mg/kg/day. In the female fertility and early embryonic development study, avagacestat-related reductions in female fecundity at ≥5 mg/kg/day were attributed to impaired ovarian follicular development that was reflected in dose-dependent reductions in implantation sites, litter size, and gravid uterine weights. In the male fertility and early embryonic development study, avagacestat-related effects on reproduction could not be fully assessed because of low systemic exposures achieved due to extensive metabolism and clearance of the drug. The results obtained in these studies were consistent with pharmacologically mediated inhibition of γ-secretase and resulting inhibition of Notch processing and signaling that are key for embryonic development and ovary folliculogenesis. These findings are not considered a risk for late-onset AD where the patient population is ≥65 years old most with women who are post-menopausal. However, for treatment of early onset AD with a younger patient population, there are risks for reproductive or developmental toxicities with treatment with gamma secretase inhibitors like avagacestat.

History and highlights of the teratological collection in the Narrenturm, Vienna (Austria).

The collection of the Narrenturm in Vienna houses and maintains more than 50,000 objects including approximately 1200 teratological specimens; making it one of the biggest collections of specimens from human origin in Europe. The existence of this magnificent collection-representing an important resource for dysmorphology research, mostly awaiting contemporary diagnoses-is not widely known in the scientific community. Here, we show that the Narrenturm harbors a wealth of specimens with (exceptionally) rare congenital anomalies. These museums can be seen as physical repositories of human malformation, covering hundreds of years of dedicated collecting and preserving, thereby creating unique settings that can be used to expand our knowledge of developmental conditions that have to be preserved for future generations of scientists.

Adverse effects of maternal retinyl palmitate, a vitamin A compound, on the fetal liver.

Background: Consuming high doses of vitamin A during pregnancy may lead to malformations in the offspring. Some reports state that low doses that do not cause macroscopic abnormalities may result in mental and behavioral disorders. However, there are few studies on the microscopic effects of these doses on the organism. Objective: The aim was to investigate the effects of early prenatal exposure to different doses of oral vitamin A on the fetal liver. Materials and methods: Twenty-five pregnant rats, divided into five groups, received oral vitamin A at doses of 10,000, 50,000, 100,000, and 200,000 IU/kg between days 10 and 12 of gestation. The fetuses were collected on day 19 of gestation, their livers were dissected, and histology, apoptosis, and proliferation were examined by hematoxylin-eosin, TUNEL assay, and Ki67 immunolabeling using stereological methods. Results: Vitamin A decreased fetal liver volume, the number of Ki67-positive cells per unit volume, and the total number of hepatocytes at all doses except 10,000 IU/kg (p<0.001). Consequently, apoptosis was significantly higher in the groups receiving 100,000 and 200,000 IU/kg vitamin A (p<0.001). Conclusion: Our study shows that vitamin A administered during gestation days 10-12 has a suppressive effect on the developing rat liver when the dose exceeds 10,000 IU/kg, probably due to increased apoptosis and suppressed cell division.

Alternatives to Monkey Reproductive Toxicology Testing for Biotherapeutics.

Embryofetal toxicity studies are conducted to support inclusion of women of childbearing potential in clinical trials and to support labeling for the marketed pharmaceutical product. For biopharmaceuticals, which frequently lack activity in the rodent or rabbit, the nonhuman primate is the standard model to evaluate embryofetal toxicity. These studies have become increasingly challenging to conduct due to the small number of facilities capable of performing them and a shortage of sexually mature monkeys. The low number of animals per group and the high rate of spontaneous abortion in cynomolgus monkeys further complicate interpretation of the data. Recent FDA guidance has proposed a weight of evidence (WoE) approach to support product labeling for reproductive toxicity of products intended to be used for the treatment of cancer (Oncology Pharmaceuticals: Reproductive Toxicity Testing and Labeling Recommendations), an approach that has also supported the approval of biotherapeutics for non-cancer indications. Considerations to determine the appropriateness and content of a WoE approach to support product labeling for embryofetal risk include known class effects in humans; findings from genetically modified animals with or without drug administration; information from surrogate compounds; literature-based assessments about the developmental role of the pharmaceutical target; and the anticipated exposure during embryofetal development. This paper summarizes the content of a session presented at the 42nd annual meeting at the American College of Toxicology, which explored the conditions under which alternative approaches may be appropriate to support product labeling for reproductive risk, and how sponsors can best justify the use of this approach.

The role of the University of Padua medical school in the study of conjoined twins between 18th and early 19th century.

The Medical School of Padua (Italy) contributed profoundly to the study of teratology. Many famous physicians and professors of medicine, such as Liceti, Vallisneri, Morgagni, and Malacarne, have studied and investigated these anomalies to better understand the causes and to find a potential explanation, often preserving the specimens for future studies. The present study highlights some historical cases of conjoined twins and a conjoined triplet preserved at the Morgagni Museum of Human Anatomy to show the development of medical theories in the teratological field between the 18th and early 19th century. This approach will provide insights into different study methods and ideas of some of the most famous scholars working in Padua at that time. The current article focuses on rare cases, both human and animal, that were encountered by physicians who worked in the Veneto area in the late 18th and early 19th century. Their detailed descriptions are not only of historical but also of contemporary dysmorphological value.

Neuropsychological effects in children exposed to anticonvulsant monotherapy during gestation: Phenobarbital, carbamazepine, and phenytoin.

OBJECTIVE: Usage during pregnancy of the antiseizure medication (ASM), phenobarbital (PB), carbamazepine (CBZ), and phenytoin (PHT), has been associated with adverse pregnancy outcomes. While morphological effects on offspring are well-documented, inconsistent findings have been reported on neuropsychological development, possibly due to differences in attention to maternal demographics, and other design characteristics. Herein, we report the results of a carefully designed protocol used to examine the effects of gestational monotherapy with PB, CBZ, or PHT upon children's general mental abilities, when compared to age- and gender- matched children born to unexposed women of similar age, education, and socioeconomic status. METHODS: For each ASM, we selected qualifying cases from children born to PB, CBZ, or PHT monotherapy-exposed and unexposed women. Following the application of inclusion, exclusion, and matching criteria, our sample included 34 PB-exposed, 40 PHT-exposed, and 41 CBZ-exposed children along with matched unexposed children for each drug group. Criteria were applied through examination of maternal medical and educational histories, parental socioeconomic characteristics, and child's age and gender. Each child's physical and neuropsychological characteristics were examined, using standardized protocols. We report on the cognitive performance of the children as assessed by the Wechsler Intelligence Scale for Children - III (WISC-III), the leading measure of mental ability in the U.S. RESULTS: An overall mixed model ANOVA of the adjusted performance of the children across all groups controlling for maternal IQ revealed significant effects on verbal IQ, but not full-scale IQ or performance IQ. In the individual drug and unexposed group comparisons, only reduced verbal and full-scale IQ scores in PB-exposed versus matched unexposed children were found. Comparisons between drug groups revealed a significant reduction in verbal IQ and full-scale IQ in PB-exposed versus PHT-exposed children, but not in other drug-drug comparisons. SIGNIFICANCE: These results demonstrate effects on children's mental ability due to prenatal PB exposure, such that analyses adjusted for maternal IQ scores, revealed reduced verbal mental abilities and reduced full-scale IQ scores when scores in exposed children were compared to scores from children of the same age and sex born to demographically similar, healthy unexposed women. When comparisons were made between drug groups, children exposed prenatally to PB performed significantly worse than prenatally PHT-exposed children, but CBZ-exposed children's scores were not significantly different from those of PB or PHT-exposed groups. In light of shared effects on structural teratogenicity, these findings suggest that use of PB monotherapy for the management of seizures during pregnancy may be associated with increased risk in comparison to PHT when neurobehavioral functioning is considered, and that only PB-exposed children have reduced performance compared to matched controls. Attention to these effects is critical in the developing world where use of these older medications remains predominant, and prudent choices can be made to reduce impact on cognitive development.

Identifying target areas of medicines information efforts to pregnant and breastfeeding women by reviewing questions to SafeMotherMedicine: A Norwegian web-based public medicines information service.

BACKGROUND: Online information about safety of medications during pregnancy and breastfeeding is shown to be conflicting, resulting in anxiety and abstaining from use. The aim of this study was to characterize questions to SafeMotherMedicine, a web-based medicines information service for pregnant and breastfeeding women, to identify target areas that could guide subsequent development of medicines information directed at pregnant and breastfeeding women. METHODS: The SafeMotherMedicine database contains all questions received through the web-based service and their corresponding answers. A retrospective database analysis of questions received from January 2016 to September 2018 was performed, using descriptive statistics. RESULTS: A total of 11 618 questions were received including 5 985 questions (51.5%) concerning pregnancy, 4 878 questions (42.0%) concerning breastfeeding, and 755 questions (6.5%) concerning both conditions. The medications in question represented all therapeutic groups with paracetamol (7.0%), ibuprofen (4.1%), cetirizine (3.3%), desloratadine (3.2%) and meclizine (2.8%) being the top five. The 20 medications most frequently asked about for either pregnancy, breastfeeding or both pregnancy and breastfeeding, constituted half of all questions and were used to identify target areas. These included both symptomatic relief of common complaints, such as pain, nausea, and rhinitis, as well as treatment of chronic conditions such as allergy, psychiatric disorders, and asthma. Analysis of a subset of questions showed that most of these questions were asked before use of medications in a current pregnancy (49%) or during breastfeeding (72%). The questions concerned use of medications in all stages of pregnancy and breastfeeding. For 81.6% of the questions concerning pregnancy, and for 84.2% of the questions concerning breastfeeding, information of no or low risk for the foetus or the breastfed infant was provided by SafeMotherMedicine. CONCLUSIONS: We found that target areas for medicines information directed at pregnant and breastfeeding women included both symptomatic relief of common complaints as well as treatment of chronic conditions. The questions concerned a wide range of medications and involved use in all stages of pregnancy and breastfeeding. Our findings indicate that developing medicines information addressing the identified target areas will meet the information need for a large proportion of this patient group.

From Monsters to Malformations: Anatomical Preparations as Objects of Evidence for a Developmental Paradigm of Embryology, 1770-1850.

A common object found within medical museums is the developmental series: an arrangement of embryos depicting the transformation of an unremarkable blob into an anatomically organized and recognizable organism. The developmental series depicts a normative process, one where bodies emerge in reliable sequential stages to reveal anatomically perfect beings. Yet a century before the developmental series would become a visual model of embryological development, the very process of development itself was discerned through the comparative study of preserved human fetuses-specifically, those deemed "monstrous" or characterized as "malformations." This article examines how anatomically diverse fetal bodies were reformulated from singular curiosities into alternative developmental pathways whose characteristics testified to the laws of nature and to the primordial, physical relationship between humans and other species. In early nineteenth century Amsterdam, the father-son team of physicians Gerard and Willem Vrolik built up an internationally renowned anatomical museum famous especially for Willem's collection of fetal malformations. Physical preparations of fetal malformations play a central role in Willem's monumental handbook on developmental embryology: comparing human embryos against one another and the embryos of other species, Willem plots out a sequence of embryological development in which a body's form marks its place within the ever-unfolding natural order. In conversation with the literature on model organisms, this article explores how the "monstrous" gets standardized and, in doing so, contributes to the scientific production of a normative physiological process.

Effect of salinity on valves morphology in freshwater diatoms.

Increased salt concentration is one of the most widespread problems affecting freshwater worldwide. Aquatic communities, and in particular periphytic diatoms, react to this alteration in water quality by modifying their structural parameters and physiology at the individual level, which is commonly manifested by the appearance of teratological forms. The present work presents the results of an experimental laboratory study in which a biofilm grown on artificial substrates was subjected to a gradient of water conductivities for 4 weeks. The results show an increase in the number of deformed valves over time proportionally to the increase in conductivity for each experimental treatment. These effects are also verified by analyzing the concentration of chlorophyll-a in the experimental biofilms, which demonstrate a metabolic response to the induced osmotic stress. No changes were recorded; however, in species richness or diversity of taxa present in the treatments. Our results, therefore, confirm at the experimental level numerous previous field observations about the harmful effect of salinity on periphytic diatoms, and also their ability to reintegrate with the new stress conditions.

The environments of reproductive and birth defects research in the U.S. and West Germany (c. 1955-1975).

Most historiographies of the crossroads of environmental and reproductive health in 20th century start and end with the case of thalidomide. Despite its global scope, thalidomide today stands for sharp contrasts: in the numbers of victims, in institutional responses to the disaster, and also-more generally-in regulatory approaches to potential risks and national cultures of reproductive justice and disability rights. This paper takes a closer look at two countries that have been seen as emblematic of this divide in regulatory frameworks, despite similarities and interconnections in other areas, such as (pharma)industrial production, science, and robust feminist environmental health movements: the U.S. and West Germany. It argues that thalidomide needs to be historically contextualized within a broad framework of concepts and models of environment from research on exogenous reproductive effects. To do so, it reconstructs what counted as environment in research on reproductive health and birth defects in these two national settings in the postwar decades. It looks at transformations made across multifaceted initiatives, studying collective landscapes and workplaces as potentially dangerous "outer worlds," as well as smaller scale and more individualized environments, i.e., the maternal metabolism, uterus, lifestyle, or social interactions. The article thereby aims to explicate concepts and debates about the environment that influenced later national divisions in politics of science and technology, hinting of the democratic challenges these posed.

Implications of a cheliceral axial duplication in Tetragnatha versicolor (Araneae: Tetragnathidae) for arachnid deuterocerebral appendage development.

The homology of the arachnid chelicera with respect to other head appendages in Panarthropoda has long been debated. Gene expression data and the re-interpretation of early transitional fossils have supported the homology of the deutocerebrum and its associated appendages, implying a homology between primary antennae (mandibulates), chelicerae (euchelicerates), and chelifores (sea spiders). Nevertheless, comparatively little is known about the mechanistic basis of proximo-distal (PD) axis induction in chelicerates, much less the basis for cheliceral fate specification. Here, we describe a new cheliceral teratology in the spider Tetragnatha versicolor Walckenaer, 1841, which consists on a duplication of the PD axis of the left chelicera associated with a terminal secondary schistomely on the fang of the lower axis. This duplication offers clues as to potential shared mechanisms of PD axis formation in the chelicera. We review the state of knowledge on PD axis induction mechanisms in arthropods and identify elements of gene regulatory networks that are key for future functional experiments of appendage development in non-insect model systems. Such investigations would allow a better understanding of PD axis induction of modified and poorly studied arthropod limbs (e.g., chelicerae, chelifores, and ovigers).

Dutch teratological collections and their artistic portrayals.

Several teratologic collections containing specimens with malformations and syndromes are maintained in a number of Dutch anatomical museums. Technically, these are not works of art or antiquities. However, many have been depicted in illustrations of such high quality that they merit discussion here. We review a selection of specimens and their artistic portrayals which find their origin in four Dutch teratological collections. These museum specimens are more than just intriguing objects for the inquisitive museum visitor. As we will substantiate, these specimens-and their artistic depictions-can be used to find and describe rarely occurring birth defects, provide etiopathogenetic information and are a source of novel diagnosis. Additionally, we briefly discuss the ethical aspects and motivations of exhibiting these specimens, as these collections have to be protected meticulously by the new generation of museum professionals, who eventually determine what kind of past our future will have. It is therefore imperative that these collections of antique specimens are treasured as their importance is easily overlooked.

Pregnancy outcomes following gestational exposure to papaverine: An observational comparative study.

AIMS: Papaverine is indicated for abdominal pain of various aetiologies. However, data on maternal and foetal safety following gestational exposure are lacking. The aim was to examine whether first trimester exposure to papaverine is associated with increased risk for major malformation and whether gestational exposure at any stage is associated with increased risk for preterm delivery, lower birthweight, small for gestational age, caesarean section (CS), lower Apgar score and perinatal death. METHODS: A retrospective comparative study consisted of pregnant women treated with papaverine between February 2010 and October 2019 at a large tertiary center. The control group comprised of livebirth deliveries randomly selected from the institutional obstetric database. RESULTS: The study group consisted of 498 pregnancies, which resulted in 537/544 (98.7%) live births, of whom 46/537 (8.6%) were exposed during the first trimester. The control group consisted of 498 pregnancies and 514 live births. Rate of major malformations did not differ between study group (2/46, 4.3%) and control (25/315, 4.9%, P = .67). Papaverine exposure was associated with higher rate of preterm delivery (22.3 vs. 10.3%, P < .001), CS (35.9 vs. 24.1%, P < .001) and lower birth weight (3207 vs. 3246 g, P = .02). Adjustment for treatment indication demonstrated that these remained significant only when given for obstetrical/surgical aetiologies. Comparable rates were observed for the remaining outcomes. CONCLUSIONS: Short-term gestational exposure to papaverine adjusted for indication was not associated with preterm deliveries, CS, lower birthweight, small for gestational age or perinatal death. Rate of major malformations among 46 first trimester exposures was comparable to controls.

Teratological trilobites from the Silurian (Wenlock and Ludlow) of Australia.

Documentation of malformed trilobites has presented invaluable insight into the palaeobiology of a wholly extinct euarthropod group. Although the northern hemisphere record is relatively well documented, examples of abnormal trilobites from Australia are limited. Furthermore, most recorded specimens are from Cambrian-aged rocks. To extend this limited record, we document five new examples of malformed Australian trilobites from the Middle and Late Silurian (Wenlock and Ludlow) deposits of the Yarralumla Formation of the Australian Capital Territory and Yarwood Siltstone Member, Black Bog Shale in New South Wales. We record the first examples of abnormal pygidial and thoracic nodes and present new evidence for bifurcating pygidial ribs. These abnormal features are considered teratological morphologies. The aberrant nodes likely arose through developmental malfunctions, while the bifurcating ribs represent either similar defects, or an injury that developed into a teratological feature. Explanations for the limited record of malformed Australian trilobites and for the decrease in injured trilobites after the end-Ordovician are presented. Further documentation of malformed Australian trilobites from the middle-to-late Paleozoic will undoubtedly paint a more complete picture of how Gondwanan taxa recovered from injuries or unfortunate developmental complications.

Examining the Relationship Between Gastroschisis and Placental Fetal Vascular Malperfusion.

INTRODUCTION: Gastroschisis is a congenital malformation characterized by intestinal herniation through an abdominal wall defect. Despite its unknown pathogenesis, known risk factors include maternal smoking, alcohol use, and young maternal age. Previous work has shown that gastroschisis is associated with placental delayed villous maturation, and the goal of this study was to assess for additional associated placental pathologies that may help clarify the pathogenesis of gastroschisis. METHODS: We conducted a retrospective slide review of 29 placentas of neonates with gastroschisis. Additionally, we reviewed pathology reports from one control group of 30 placentas with other congenital malformations. Gross and histological data were collected based on a standardized rubric. RESULTS: Gastroschisis was associated with increased placental fetal vascular malperfusion (FVM) in 62% of cases (versus 0% of controls, p < 0.0001). It was also associated with increased placental villous maldevelopment in 76% of cases (versus 3% of controls, p < 0.0001). CONCLUSION: Our study demonstrates an association between gastroschisis and FVM. While FVM could be the consequence of vascular disruption due to the ventral location of gastroschisis, it could also reflect estrogen-induced thrombosis in early pregnancy. Further research is needed to separate these possibilities and determine the cause of the placental FVM observed in gastroschisis.