Amelioration potential of Moringa oleifera extracts against sodium arsenate induced embryotoxicity and genotoxicity in mouse (Mus musculus) / Potencial de melhoria de extratos de Moringa oleifera contra embriotoxicidade e genotoxicidade induzida por arseniato de sódio em camundongos (Mus musculus)

Previous studies have suggested that arsenic crosses the placenta and affects the fetus development. The study under consideration aims to show comparative ameliorative effect of Moringa oleifera leaf and flower extracts against sodium arsenate induced fetus toxicity of mice. Pregnant mice (N=44) were kept in lab and divided into eleven group from (A to K) and were orally administered the doses 6 mg/kg, 12 mg/kg for sodium arsenate, 150 mg/kg and 300 mg/kg for Moringa oleifera leaf extracts (MOLE) and 150 mg/kg and 300 mg/kg for Moringa oleifera flower extracts (MOFE) comparing with control. The investigation revealed evident reduction in the fetuses weight, hind limb, fore limb, tail and snout length, crown rump and head circumferences well as malformations in tail, feet, arms, legs, skin and eyes in the negative control group (only administered with sodium arsenate). Co-administration of sodium arsenate with MOLE and MOFE ameliorate the reversed effect of sodium arsenate on the shape, length, body weight and DNA damage of fetus significantly at 95% confidence interval. However, Moringa oleifera leaf extract showed more significant results in comparison to Moringa oleifera flower extract. Hence concluded that Moringa oleifera leaf extract ameliorated the embryo toxic effects of sodium arsenate and can be used against environmental teratogens.

Estudos anteriores sugeriram que o arsênio atravessa a placenta e afeta o desenvolvimento do feto. O estudo em consideração visa mostrar o efeito melhorador comparativo de extratos de folhas e flores de Moringa oleifera contra a toxicidade fetal induzida por arseniato de sódio em camundongos. Camundongos grávidas (N = 44) foram mantidos em laboratório e divididos em 11 grupos (de A a K) e foram administrados por via oral nas doses de 6 mg/kg, 12 mg/kg para arseniato de sódio, 150 mg/kg e 300 mg/kg para extratos de folhas de Moringa oleifera (MOLE) e 150 mg/kg e 300 mg/kg para extratos de flores de Moringa oleifera (MOFE) em comparação com o controle. A investigação revelou redução evidente no peso do feto, membro posterior, membro anterior, comprimento da cauda e focinho, coroa, nádega e circunferência da cabeça, bem como malformações na cauda, pés, braços, pernas, pele e olhos no grupo de controle negativo (apenas administrado com arseniato de sódio). A coadministração de arseniato de sódio com MOLE e MOFE melhora significativamente o efeito reverso do arseniato de sódio na forma, comprimento, peso corporal e dano ao DNA do feto, com intervalo de confiança de 95%. No entanto, o extrato da folha da Moringa oleifera apresentou resultados mais significativos em comparação ao extrato da flor da Moringa oleifera. Portanto, concluiu que o extrato da folha de Moringa oleifera melhorou os efeitos tóxicos do arseniato de sódio para o embrião e pode ser usado contra teratógenos ambientais.

Percepção sobre o cuidado à perda gestacional: estudo qualitativo com casais brasileiros / Perceptions on pregnancy loss care: a qualitative study with brazilian couples / Percepción sobre la atención a la pérdida del embarazo: estudio cualitativo con parejas brasileñas

Este artigo analisou a percepção e os sentimentos de casais sobre o atendimento recebido nos serviços de saúde acessados em função de perda gestacional (óbito fetal ante e intraparto). O convite para a pesquisa foi divulgado em mídias sociais (Instagram e Facebook). Dos 66 casais que contataram a equipe, 12 participaram do estudo, cuja coleta de dados ocorreu em 2018. Os casais responderam conjuntamente a uma ficha de dados sociodemográficos e uma entrevista semiestruturada, realizada presencialmente (n=4) ou por videochamada (n=8). Os dados foram gravados em áudio e posteriormente transcritos. A Análise Temática indutiva das entrevistas identificou cinco temas: sentimento de impotência, iatrogenia vivida nos serviços, falta de cuidado em saúde mental, não reconhecimento da perda como evento com consequências emocionais negativas, e características do bom atendimento. Os achados demonstraram situações de violência, comunicação deficitária, desvalorização das perdas precoces, falta de suporte para contato com o bebê falecido e rotinas pouco humanizadas, especialmente durante a internação após a perda. Para aprimorar a assistência às famílias enlutadas, sugere-se qualificação profissional, ampliação da visibilidade do tema entre diferentes atores e reorganização dos serviços, considerando uma diretriz clínica para atenção ao luto perinatal, com destaque para o fortalecimento da inserção de equipes de saúde mental no contexto hospitalar.(AU)

This study analyzed couples' perceptions and feelings about pregnancy loss care (ante and intrapartum fetal death). A research invitation was published on social media (Instagram and Facebook) and data collection took place in 2018. Of the 66 couples who contacted the research team, 12 participated in the study by filling a sociodemographic questionnaire and answering a semi-structured interview in person (n=04) or by video call (n=08). All interviews were audio recorded, transcribed, and examined by Inductive Thematic Analysis, which identified five themes: feelings of impotence, iatrogenic experiences in health services, lack of mental health care, not recognizing pregnancy loss as an emotionally overwhelming event, and aspects of good healthcare. Analysis showed experiences of violence, poor communication, devaluation of early losses, lack of support for contact with the deceased baby, and dehumanizing routines, especially during hospitalization after loss. Professional qualification, extended pregnancy loss visibility among different stakeholders, and reorganization of health services are needed to improve the care offered to grieving families, considering a clinical guideline for perinatal grief care with emphasis on strengthening the insertion of mental health teams in the hospital context.(AU)

Este estudio analizó las percepciones y sentimientos de parejas sobre la atención recibida en los servicios de salud a los que accedieron debido a la pérdida del embarazo (muerte fetal ante e intraparto). La invitación al estudio se publicó en las redes sociales (Instagram y Facebook). De las 66 parejas que se contactaron con el equipo, 12 participaron en el estudio, cuya recolección de datos se realizó en 2018. Las parejas respondieron un formulario de datos sociodemográficos y realizaron una entrevista semiestructurada presencialmente (n=4) o por videollamada (n=08). Los datos se grabaron en audio para su posterior transcripción. El análisis temático inductivo identificó cinco temas: Sentimiento de impotencia, experiencias iatrogénicas en los servicios, falta de atención a la salud mental, falta de reconocimiento de la pérdida como un evento con consecuencias emocionales negativas y características de buena atención. Los hallazgos evidenciaron situaciones de violencia, comunicación deficiente, desvalorización de las pérdidas tempranas, falta de apoyo para el contacto con el bebé fallecido y rutinas poco humanizadas, especialmente durante la hospitalización tras la pérdida. Para mejorar la atención a las familias en duelo, se sugiere capacitación profesional, ampliación de la visibilidad del tema entre los diferentes actores y reorganización de los servicios, teniendo en cuenta una guía clínica para la atención del duelo perinatal, enfocada en fortalecer la inserción de los equipos de salud mental en el contexto hospitalario.(AU)

Early pregnancy exposure to beta-cypermethrin compromises endometrial decidualisation in mice via downregulation of cyclin D3, CDK4/6, and p21.

Beta-cypermethrin (ß-CYP) is a highly effective broad-spectrum insecticide that can potentially affect female reproduction. However, little is known about the effect of ß-CYP on uterine decidualisation, which is a vital process by which the uterus provides a suitable microenvironment for pregnancy maintenance. Therefore, we focused on the effect and mechanism of ß-CYP on endometrial decidualisation during early pregnancy in mice. The results indicated that the expression levels of HOXA10, BMP2, and IGFBP1 was significantly downregulated in the decidual tissue and primary endometrial stromal cells of pregnant and pseudopregnant mice following ß-CYP treatment. Serum E2 concentration was significantly increased, whereas P4 concentration and oestrogen receptor (ERα) and progesterone receptor (PRA) expression were significantly downregulated following ß-CYP exposure. The number of polyploid decidual cells was lower in the ß-CYP-treated group. Furthermore, ß-CYP significantly downregulated the protein expression levels of CDK4 and CDK6, and the mRNA expression levels of cyclin D3 and p21. The number of foetuses per female in the first litter was markedly reduced following exposure to ß-CYP. In summary, early pregnancy exposure to ß-CYP may result in defective endometrial decidualisation via compromised proliferation of uterine stromal cells and reduced expressions of cyclin D3, CDK4/6, and p21 in mice.

Novel agents for the treatment of lymphomas during pregnancy: A comprehensive literature review.

Lymphoproliferative diseases occurring during pregnancy present unique diagnostic and therapeutic challenges aiming to achieve maternal cure without impairing fetal health, growth, and survival. These goals are further complicated by the fast-paced emergence of novel therapies and their introduction as standard of care, even in newly diagnosed patients. Due to the rarity of hematological malignancies in pregnancy and the exclusion of pregnancy in almost all clinical trials, available data on the fetal effects of novel drugs are limited to animal models and case reports. The current review addresses the entire multidisciplinary team involved in treating pregnant patients with lymphoproliferative diseases. We describe novel agents according to their mechanism of action, and summarize our knowledge of their effects during the gestational period, particularly those associated with fetotoxicity. Therapeutic dilemmas associated with the employment of these new agents are also discussed.

Concentrations of organochlorine pesticides in placental tissue are not associated with risk for fetal orofacial clefts.

Previous epidemiological studies have shown that prenatal exposure to organochlorine pesticides (OCPs) entails a variety of adverse impacts on fetal health, but it is not yet known whether it is associated with risk for orofacial clefts (OFCs). This study of 103 fetuses or newborns with a diagnosis of OFCs (cases) and 103 healthy newborns without malformations (controls) examined whether prenatal exposure to OCPs, as indicated by their concentrations in placental tissue, is a risk factor for OFCs. No differences were found in the median concentrations of OCPs between cases and controls, with exception of o,p'-dichlorodiphenyldichloroethylene, o,p'-dichlorodiphenyldichloroethane, and total o,p'-dichlorodiphenyltrichloroethane (DDTs), whose concentrations were higher in controls than in cases (Ps < 0.05). Although higher concentrations of placental δhexachlorocyclohexane and isodrin were found to be associated with decreased risk for OFCs in logistic regression, no association was observed in the Bayesian kernel machine regression, a novel statistical model in analyzing exposure mixtures. Women who reported periconceptional folic acid supplementation had lower placental concentrations of DDTs than women who did not. In conclusion, no association between levels of OCPs in placental tissue and risk for OFCs was observed in this population. Supplementation with folic acid may help decrease the levels of DDTs in placental tissue, but further studies are needed to confirm this unexpected finding.

Implementation of a multidisciplinary perinatal emergency response team improves time to definitive obstetrical evaluation and fetal assessment.

BACKGROUND: Trauma is the leading cause of nonobstetric death during pregnancy and is associated with an increased risk of maternal and fetal mortality. In an effort to improve the delivery of care to pregnant trauma patients, we developed an institutional multidisciplinary quality initiative designed to improve response times of nontrauma specialists and ensure immediate availability of resources. We hypothesized that implementation of a perinatal emergency response team (PERT) would improve time to patient and fetal evaluation and monitoring by the obstetrics (OB) team and improve both maternal and fetal outcomes. METHODS: We performed a 6-year (2012-2018) retrospective cohort analysis of consecutive pregnant trauma patients presenting to our university-affiliated, level I trauma center. Patients in the pre-PERT cohort (before April 2015) were compared with a post-PERT cohort. Variables analyzed included patient demographics, mechanism of injury, Injury Severity Score, and level of trauma activation. The main outcome measure was time to OB evaluation. Secondary outcomes included time to cardiotocometry, and mortality. RESULTS: Of 92 pregnant trauma patients, there were 50 patients (54.3%) in the pre-PERT cohort and 42 (45.7%) in the post-PERT group. Blunt injuries predominated (98.9%), with the most common mechanism being motor vehicle collisions (76.1%), followed by assaults (13%) and falls (6.5%). The mean time to obstetrical evaluation was 44 minutes in the pre-PERT cohort compared with 14 minutes in the post-PERT cohort (p = 0.001). There was a significant decrease in level I (highest acuity) trauma activations pre-PERT and post-PERT (46% vs. 21%, p = 0.01), and the time to cardiotocography was significantly decreased post-PERT implementation (72 vs. .37 min, p = 0.01) CONCLUSION: Implementation of a multidisciplinary PERT improves time to evaluation by the OB team and time to cardiotocometry in the pregnant trauma patient. LEVEL OF EVIDENCE: Retrospective review, level IV.

Myelomeningocele sac associated with worse lower-extremity neurological sequelae: evidence for prenatal neural stretch injury?

OBJECTIVE: To determine whether the presence of a myelomeningocele (MMC) sac and sac size correlate with compromised lower-extremity function in fetuses with open spinal dysraphism. METHODS: A radiology database search was performed to identify cases of MMC and myeloschisis (MS) diagnosed prenatally in a single center from 2013 to 2017. All cases were evaluated between 18 and 25 weeks. Ultrasound reports were reviewed for talipes and impaired lower-extremity motion. In MMC cases, sac volume was calculated from ultrasound measurements. Magnetic resonance imaging reports were reviewed for hindbrain herniation. The association of presence of a MMC sac and sac size with talipes and impaired lower-extremity motion was assessed. Post-hoc analysis of data from the multicenter Management of Myelomeningocele Study (MOMS) randomized controlled trial was performed to confirm the study findings. RESULTS: In total, 283 MMC and 121 MS cases were identified. MMC was associated with a lower incidence of hindbrain herniation than was MS (80.9% vs 100%; P < 0.001). Compared with MS cases, MMC cases with hindbrain herniation had a higher rate of talipes (28.4% vs 16.5%, P = 0.02) and of talipes or lower-extremity impairment (34.9% vs 19.0%, P = 0.002). Although there was a higher rate of impaired lower-extremity motion alone in MMC cases with hindbrain herniation than in MS cases, the difference was not statistically significant (6.6% vs 2.5%; P = 0.13). Among MMC cases with hindbrain herniation, mean sac volume was higher in those associated with talipes compared with those without talipes (4.7 ± 4.2 vs 3.0 ± 2.6 mL; P = 0.002). Review of the MOMS data demonstrated similar findings; cases with a sac on baseline imaging had a higher incidence of talipes than did those without a sac (28.2% vs 7.5%; P = 0.007). CONCLUSIONS: In fetuses with open spinal dysraphism, the presence of a MMC sac was associated with fetal talipes, and this effect was correlated with sac size. The presence of a larger sac in fetuses with open spinal dysraphism may result in additional injury through mechanical stretching of the nerves, suggesting another acquired mechanism of injury to the exposed spinal tissue. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Prenatal influences on bone health in children.

INTRODUCTION: Optimising bone health might reduce the burden of both fractures in childhood and fragility fractures in later life. A number of maternal dietary and non-dietary factors have been identified that might influence offspring bone health and represent targets for intervention. AREAS COVERED: This article will outline the accrual of bone mineral throughout the life course and how observational and intervention studies have shown that maternal diet, in particular maternal calcium and 25-hydroxyvitamin D [25(OH)D] status, and lifestyle are associated with offspring bone mineralization. Studies examining the effects of maternal micronutrient supplementation on offspring bone mineral density (BMD) will also be discussed. EXPERT COMMENTARY: There is a wealth of observational evidence relating maternal diet to offspring BMD. However, high quality randomized controlled trials, such as the ongoing MAVIDOS study, are needed before these findings can be definitively translated into public health advice.

Effects of Maternal Sildenafil Treatment on Vascular Function in Growth-Restricted Fetal Sheep.

Objective- The objective of this study was to investigate the effect of intravenous maternal sildenafil citrate (SC) administration on vascular function in growth-restricted fetal sheep. Approach and Results- Fetal growth restriction (FGR) results in cardiovascular adaptations that redistribute cardiac output to optimize suboptimal intrauterine conditions. These adaptations result in structural and functional cardiovascular changes, which may underlie postnatal neurological and cardiovascular sequelae. Evidence suggests SC, a potent vasodilator, may improve FGR. In contrast, recent clinical evidence suggests potential for adverse fetal consequence. Currently, there is limited data on SC effects in the developing fetus. We hypothesized that SC in utero would improve vascular development and function in an ovine model of FGR. Preterm lambs (0.6 gestation) underwent sterile surgery for single umbilical artery ligation or sham (control, appropriately grown) surgery to replicate FGR. Ewes received continuous intravenous SC (36 mg/24 h) or saline from surgery until 0.83 gestation. Fetuses were delivered and immediately euthanized for collection of femoral and middle cerebral artery vessels. Vessel function was assessed via in vitro wire myography. SC exacerbated growth restriction in growth-restricted fetuses and resulted in endothelial dysfunction in the cerebral and femoral vasculature, irrespective of growth status. Dysfunction in the cerebral circulation is endothelial, whereas smooth muscle in the periphery is the origin of the deficit. Conclusions- SC crosses the placenta and alters key fetal vascular development. Extensive studies are required to investigate the effects of SC on fetal development to address safety before additional use of SC as a treatment.

Exosomes derived from umbilical cord mesenchymal stem cells reduce microglia-mediated neuroinflammation in perinatal brain injury.

BACKGROUND: Preterm newborns are at high risk of developing neurodevelopmental deficits caused by neuroinflammation leading to perinatal brain injury. Human Wharton's jelly mesenchymal stem cells (hWJ-MSC) derived from the umbilical cord have been suggested to reduce neuroinflammation, in part through the release of extracellular vesicle-like exosomes. Here, we studied whether exosomes derived from hWJ-MSC have anti-inflammatory effects on microglia-mediated neuroinflammation in perinatal brain injury. METHODS: Using ultracentrifugation, we isolated exosomes from hWJ-MSC culture supernatants. In an in vitro model of neuroinflammation, we stimulated immortalized BV-2 microglia and primary mixed glial cells with lipopolysaccharide (LPS) in the presence or absence of exosomes. In vivo, we introduced brain damage in 3-day-old rat pups and treated them intranasally with hWJ-MSC-derived exosomes. RESULTS: hWJ-MSC-derived exosomes dampened the LPS-induced expression of inflammation-related genes by BV-2 microglia and primary mixed glial cells. The secretion of pro-inflammatory cytokines by LPS-stimulated primary mixed glial was inhibited by exosomes as well. Exosomes interfered within the Toll-like receptor 4 signaling of BV-2 microglia, as they prevented the degradation of the NFκB inhibitor IκBα and the phosphorylation of molecules of the mitogen-activated protein kinase family in response to LPS stimulation. Finally, intranasally administered exosomes reached the brain and reduced microglia-mediated neuroinflammation in rats with perinatal brain injury. CONCLUSIONS: Our data suggest that the administration of hWJ-MSC-derived exosomes represents a promising therapy to prevent and treat perinatal brain injury.

Prenatal exposure to pyrrolizidine alkaloids induced hepatotoxicity and pulmonary injury in fetal rats.

Hepatic and pulmonary toxicity in fetal rats induced by pyrrolizidine alkaloids (PAs) was investigated. Retrorsine (RTS) or monocrotaline (MCT) was intragastrically administered during pregnancy. The reduction of body and tail lengths was consistent with body weight loss in PA-exposed fetuses, and pathological lesions in liver and lung were observed only in fetuses. Both PAs reduced fetal serum transaminase activities. The GSH/GSSG ratio, GSH peroxidase and superoxide dismutase activities also decreased but glutathione S-transferase activity increased in fetal lung, especially for MCT. The pyrrole-protein adducts in fetal liver and lung could be detected, and those adducts in RTS fetal lungs were about 65% of those in MCT group. In conclusion, prenatal PAs exposure induced fetal hepatic and pulmonary toxicities through the generation of pyrrole metabolites and oxidative injury. The difference on fetal pulmonary redox homeostasis between two PAs groups might be associated with the content of PAs migrated to fetal lungs.

Traumatic injuries to the pregnant patient: a critical literature review.

INTRODUCTION: Trauma during pregnancy is the leading non-obstetrical cause of maternal death and a significant public health burden. This study reviews the most common causes of trauma during pregnancy, morbidity, and mortality, and the impact upon perinatal outcomes associated with trauma, providing a management approach to pregnant trauma patients. MATERIALS AND METHODS: A systematic review of the current literature from January 2006 to July 2016 was performed. RESULTS: Fifty-one articles were identified, including a total of 95,949 patients. Motor vehicle crash was the most frequent cause of blunt trauma, followed by falls, assault both domestic and interpersonal violence, and penetrating injuries (gunshot and stab wounds). CONCLUSIONS: Trauma in pregnant women is associated with high rates of adverse maternal and neonatal outcomes. Knowledge of the mechanism of injury is important to identify the potential injuries and the complexity of the management of these patients. As in all traumatic events, prevention is of paramount importance.

Early recognition and management of fetal head trauma with massive subgaleal hemorrhage.

Non-obstetrical fetal head injury is an unusual clinical event. While multiple case reports describe motor vehicle collisions resulting in intrauterine fetal skull fractures, management of these injuries has not been emphasized. We report a case of a depressed fetal skull fracture with massive subgaleal and subperiosteal hemorrhage requiring neurosurgical intervention with good clinical outcomes for both mother and infant dyad.

Role for Cystathionine γ Lyase (CSE) in an Ethanol (E)-Induced Lesion in Fetal Brain GSH Homeostasis.

Earlier, we reported that gestational ethanol (E) can dysregulate neuron glutathione (GSH) homeostasis partially via impairing the EAAC1-mediated inward transport of Cysteine (Cys) and this can affect fetal brain development. In this study, we investigated if there is a role for the transulfuration pathway (TSP), a critical bio-synthetic point to supply Cys in E-induced dysregulation of GSH homeostasis. These studies utilized an in utero E binge model where the pregnant Sprague⁻Dawley (SD) rat dams received five doses of E at 3.5 g/kg by gastric intubation beginning embryonic day (ED) 17 until ED19 separated by 12 h. The postnatal day 7 (PN7) alcohol model employed an oral dosing of 4 g/kg body weight split into 2 feedings at 2 h interval and an iso-caloric and iso-volumic equivalent maltose-dextrin milk solution served as controls. The in vitro model consisted of cerebral cortical neuron cultures from embryonic day (ED) 16⁻17 fetus from SD rats and differentiated neurons from ED18 rat cerebral cortical neuroblasts. E concentrations were 4 mg/mL. E induced an accumulation of cystathionine in primary cortical neurons (PCNs), 2nd trimester equivalent in utero binge, and 3rd trimester equivalent PN7 model suggesting that breakdown of cystathionine, a required process for Cys supply is impaired. This was associated with a significant reduction in cystathionine γ-lyase (CSE) protein expression in PCN (p < 0.05) and in fetal cerebral cortex in utero (53%, p < 0.05) without a change in the expression of cystathionine ß-synthase (CBS). Concomitantly, E decreased Cse mRNA expression in PCNs (by 32% within 6 h of exposure, p < 0.05) and in fetal brain (33%, p < 0.05). In parallel, knock down of CSE in differentiated rat cortical neuroblasts exaggerated the E-induced ROS, GSH loss with a pronounced caspase-3 activation and cell death. These studies illustrate the importance of TSP in CSE-related maintenance of GSH and the downstream events via Cys synthesis in neurons and fetal brain.

Fetal brain imaging following laser surgery in twin-to-twin surgery.

OBJECTIVE: To describe the incidence and nature of prenatal brain damage following fetoscopic laser selective coagulation (FLSC) of placental vessels for twin-to-twin transfusion syndrome (TTTS). DESIGN: Retrospective observational study. SETTING: Single center cohort. POPULATION: All consecutive cases referred for TTTS treated by FLSC between 2003 and 2015. METHODS: After the FLSC, patients were followed weekly by ultrasound. Fetal magnetic resonance imaging (MRI) scans were systematically planned at 30-32 weeks of gestation. MAIN OUTCOME MEASURES: Brain damage diagnosed prenatally by ultrasound or MRI. RESULTS: In total, 1023 cases were reviewed. Brain damage was diagnosed prenatally in 22/1023 (2.1%) cases. Diagnosis was performed by ultrasound prior to MRI in 18 (82%) cases. All lesions were within the spectrum of ischaemic haemorrhagic lesions. Postoperative twin anaemia polycythaemia sequence and recurrence of TTTS were significantly associated with brain damage. CONCLUSION: The incidence of prenatal brain damage is low following FSLC, and is strongly associated with incomplete surgery. TWEETABLE ABSTRACT: Following FSLC for TTTS, prenatal brain damage occurs in 2% of cases and is associated with incomplete surgery.

Fetal liver injury ameliorated by migration inhibitory factor inhibition in a rat model of acute pancreatitis in pregnancy.

AIM: This study was designed to investigate and assess fetal liver injury in a rat model of acute pancreatitis in pregnancy (APIP) as well as its possible mechanisms and potential therapeutic targets. METHODS: The APIP model was induced by sodium taurocholate in Sprague-Dawley rats during the third trimester. ISO-1, a macrophage migration inhibitory factor (MIF) antagonist, was given before the induction of APIP. In addition, sham-operated rats at later gestation were set as controls. Histological changes in the fetal liver and maternal pancreas were assessed. Amylase and lipase activity as well as the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß were examined. The expression of MIF in fetal liver was determined by immunochemistry and the expression of NF-κB, IκBα, high mobility group box-1 protein (HMGB1), TNF-α, and IL-1ß in fetal liver was determined by Western blot analysis. Ultrastructures of hepatic cells in fetal rats were observed under transmission electron microscopy. RESULTS: ISO-1 ameliorated the following: (i) pathological injuries in maternal pancreas and fetal liver; (ii) levels of TNF-α and IL-1ß in maternal serum; and (iii) levels of MIF, myeloperoxidase, NF-κB, HMGB1, TNF-α, and IL-1ß in fetal liver. CONCLUSION: Pathological damage and an inflammatory response in fetal liver were induced by APIP, and MIF inhibition ameliorated fetal liver injury by inhibiting the inflammatory cascade.

A Rare Fetal Firearm Injury.

Firearm injury (FAI) in pregnant women is reported in the literature; however, no reference to date was found to address the neonatal abdominal surgery performed after maternal FAI. FAI during fetal life is extremely rare and very few cases have been reported. We present a report of a 37-week gestation newborn whose mother had an accidental FAI. The neonate was delivered by emergency caesarian section along with emergency laparotomy of the newborn. The baby presented at eight hours of life, who was managed surgically in emergency for multiple small and large bowel perforations and a piece of bullet was recovered from anterior part of thigh.

MRI Patterns of brain injury and neurodevelopmental outcomes in neonates with severe anaemia at birth.

AIMS: To define patterns of brain injury and associated neurodevelopmental outcomes in infants with severe neonatal anaemia. METHODS: We studied 20 infants with severe anaemia at birth (haemoglobin<7g/dL). Clinical details were analysed for causes of anaemia and co-morbidities. All had early brain magnetic resonance imaging (MRI) scans, which were reviewed for injury pattern. Neurodevelopmental outcomes were assessed at a median age of 24months. RESULTS: The aetiology of the anaemia was feto-maternal haemorrhage in 17 and antepartum haemorrhage in 3 infants. The predominant site of injury was the white matter, which was affected in all infants, with differing grades of severity and with cystic evolution in 45%. Only one infant showed an injury pattern typical of an acute severe hypoxic-ischaemic insult. Outcomes correlated closely to the severity of MRI findings. Cerebral palsy was seen only with the most severe neuroimaging patterns (n=6). Global developmental delay, learning or behavioural problems and seizures were common with moderate injury. Visual impairment occurred, particularly with posterior injury. Microcephaly developed in 45%. INTERPRETATION: Severe neonatal anaemia at birth was associated with a white matter predominant pattern of injury, the severity of which was related to neurodevelopmental outcomes. Early MRI and long-term follow-up are advisable following severe neonatal anaemia.