The incidence of heterotopic pancreas (HP) is relatively rare and mainly found in the upper gastrointestinal tract, and no case of HP cyst in the adrenal gland has been reported. Informed consent has been obtained from the patient for the publication of the case details.A 21-year-old woman who presented with chronic lower back pain for a week without urinary disturbance or gastrointestinal discomfortable.Ultrasound (US) revealed a left renal cyst, and computed tomography (CT) showed a cyst in the area of the adrenal gland.Cystectomy was successfully performed laparoscopically. Histopathologic examination of the removed cyst wall showed heterotopic pancreatic cyst accompanied by cystic degeneration.No unusual drainage or abdominal signs were observed during the 6-month follow-up.Despite of its rarity, HP accompanied by cyst formation in the adrenal gland area can present with waist pain. Therefore, the possibility of such disease needs to be considered. For thorough evaluation, in addition to abdominal US, CT, and/or magnetic resonance imaging, histopathological examination should sometimes be performed to make a definite diagnosis. Total excision and regular follow-up is necessary for such cases due to the potential risk of complications or recurrent cyst formation. To date, no case of HP cyst in the adrenal gland has been reported previously. This paper reports the first case of a 21-year-old woman with a cystic formation of the ectopic pancreas in the area of adrenal gland.Heterotopic pancreas (HP) is a rare congenital anomaly defined as pancreatic tissue that has no contact with the orthotopic pancreas and has its own duct system and vascular supply. It is believed that the pancreatic primordium adhered to original intestine or penetrated the intestinal wall during embryonic development. These primitive bases gradually separated with the changes of the original bowel movement and the pancreas was developed in the gastric, intestinal wall, or mesenteric.2A 21-year-old woman visited our hospital due to a week of chronic lower back pain without radiation. She had no complaints about urinary disturbances or gastrointestinal discomfort. The pain was not aggravated after excessive meat or alcohol consumption. There was nothing significant about her past personal history and family history.On physical examination, the patient was well built, her abdomen was soft and nontender, with no palpable mass or percussion pain on either kidney area. The results of routine blood tests and urinalysis were unremarkable. Ultrasound (US) revealed a left renal cyst, and computed tomography (CT) showed a cyst in the adrenal gland area, measuring approximately 5 × 5 cm without reinforcement by contrast-enhanced CT Figs.  and 2. FThe cystectomy was successfully performed laparoscopically. The cyst wall was carefully isolated. The volume of postoperative drainage was below 2 mL on the 3rd postoperative day and tube was removed. Histopathologic examination of the removed cyst wall tissue showed cystic degeneration of HP in the left adrenal area Figs. . She rec3,6 HP is usually asymptomatic and found during imaging, endoscopy, or upper abdominal operations, but may become clinically evident depending on its size and the pathological changes . Most ectopic pancreases measure less than 2 cm in size and the diagnosis of HP is difficult as there are no specific diagnostic methods, leading to be misdiagnosed preoperatively in most of the patient.HP has a genetic alteration, physiologic function, and local environmental exposure similar to that of the pancreas. It is often an incidental finding, with a reported incidence of approximately 0.2% at laparotomy and 13.0% at autopsy, and most commonly found in the stomach (25%–38%), duodenum (17%–21%), and proximal jejunum (15%–21%).,9 Therefore, the levels detection of hormone secreted by adrenal glands and enhanced CT scanning was performed accordingly. The normal hormone levels and no reinforcement effect were observed. A diagnosis of adrenal cyst was preliminarily made based on the clinical presentations and imaging. The cyst with a diameter of 5 cm has made the patient feel pain at waist and was then treated by retroperitoneoscopic.In this case, US showed a left renal cyst, CT, coronal and sagittal imaging demonstrated the cyst was located at the superomedial side of kidney, closely connected with adrenal gland without abnormal renal morphology. Some research reports have reported that pheochromocytoma or neoplasm can present as adrenal cystic lesion. In this case, the presence of abnormal pancreatic ducts, in addition to the epithelial component on the cystic wall, was further indicative of a congenital heterotopic true pancreatic cyst.Surprisingly, HP accompanied by cyst formation was confirmed by pathology in this case and possessed acini, duct, and islets similar to those seen in normal pancreas. Furthermore, the typical surface epithelium of pancreas cyst was found and indicated the cyst should be congenital, in contrast to the walls of pancreatic pseudocyst, which do not contain epithelial components. True cysts are commonly classified into congenital–developmental cysts, retention cysts, or duplication cysts. It is accepted that true cysts occur as a result of developmental anomalies related to the sequestration of primitive pancreatic ducts. Enzymatic activity detection of cystic fluid of this patient was not carried out since we considered the cyst origin from adrenal gland before the pathological result. Fortunately, complete resection and adequate drainage were performed for this patient and the recovery was successful without complications caused by trypsin. If the detection was examined, it would be helpful for understanding the exact cause of this true cyst.In congenital cystic fluid, low enzymatic activity is generally observed, whereas enzymatic activity of retention cysts is considerably high.,13 Laparoscopic surgery is thought to be technically feasible and safe. In this case, since the cyst is large and adjacent to pancreas, careful isolation was performed to avoid pancreatic injury. The cyst was completely resected with a small part of adrenal gland removed for obvious adhesion between them, which was further confirmed by pathology (Fig. At present, surgical resection should be performed if HP is symptomatic or when the lesion is larger than 3 cm in size, in order to prevent complications.ogy Fig. . There w,15 Postoperative follow-up is necessary for these patients. In our case, no similar pain occurred in the patient's left waist again after discharge. US and CT scan showed no cystic structure in lesion area during 6-month follow-up.Malignant transformation of HP has been reported, although it is difficult to determine its true incidence.In conclusion, despite of its rarity, HP accompanied by cyst formation in the adrenal gland area can present with waist pain. Therefore, the possibility of such disease needs to be considered. Thorough evaluation, abdominal US, CT, and/or magnetic resonance imaging should be performed. Intraoperative biopsy may sometimes be considered and total excision with such cyst is preferred to avoid some complications. Regular follow-up is necessary due to the potential risk of recurrent cyst formation and malignant transformation.


Purpose To research the origins of the 2500 g cutoff for low birth weight and the evolution of indicators to identify newborns at high mortality risk. Description Early research concluded “prematurity”, measured mainly through birth weight, was responsible for increased health risks. The World Health Organization’s original prematurity definition was birth weight ≤2500 g. 1960s research clarified the difference between gestational age and birth weight leading to questions of the causal role of birth weight for health outcomes. Focus turned to two etiologies of low birth weight, preterm births and intrauterine growth restriction, which were both causally associated with morbidity and mortality but through different pathways; a standard cutoff based on gestational age or customized cutoff was debated. Assessment While low birth weight can be due to preterm or intrauterine growth restriction (or both), the historic 2500 g cutoff remains the standard by which the majority of policy makers define low birth weight and use it to predict perinatal and infant adverse outcomes. Conclusion Current efforts to refocus research on preterm births and poor intrauterine growth are important to understanding the direct causes of mortality rather than low birth weight as a convenient surrogate. Such distinctions also allow researchers and practitioners to test and target interventions outcomes more effectively. What is already known on this subject? 2500 g is the standard cutoff used to identify low birth weight infants at high mortality risk.What this study adds? This study provides the historical context for this low birthweight standard and more recent trends to link early morbidity and mortality to their etiological causes of birth size.Public health and medical professionals have categorized infants as low birth weight for almost a century. These infants have 20 times greater likelihood of dying compared to infants of normal birth weight  in 1935, summarized the problem as follows:Later in the meeting a standard criterion of prematurity (≤2500 g regardless of period of gestation) to facilitate comparison across studies was proposed. This meeting codified the 2500 g division first proposed by Ylppö in 1919.Subsequent papers began to use definitions in publications with some exceptions. A 1938 review of over 15,000 deliveries focused on the attributes of premature births  emerged  associated with birth weight that also increase mortality risk. Increasing birth weight is a health target for many countries to reduce infant mortality. However, these efforts may be misguided if birth weight is not a causal factor, although it may be a reasonable surrogate measure of a successful policy. More recent work has focused on the epidemiology of preterm and SGA as these are causal factors in neonatal morbidity and mortality (Katz et al. While WHO provides one low birth weight standard for the world it acknowledges “it has also become increasingly evident that the cut-off value of 2500 g may not be appropriate for all settings. Some countries, with high incidence of low birthweight do not necessarily have high mortality rates, as for example in Sri Lanka” Wardlaw . In addiGardosi developed a custom fetal growth weight standard that could be adjusted based on maternal factors and fetal sex (Gardosi et al. Lancet paper described a global reference for fetal-weight and birth weight percentiles (Mikolajczyk et al. Despite evidence against Gardosi’s model its momentum continued with the British Royal College of Obstetricians and Gynaecologists and other professional associations supporting customized birth weight percentiles (Hutcheon et al. INTERGROWTH-21 sought to develop a universal global standard for normal fetal growth (Uauy et al. Low birth weight continues to be an accessible measure of mortality risk in resource limited settings (World Health Organization


P=0.008) and 3% lower for those born in winter . When considering the month of birth, the risk of n-AMD was 5.9% lower for people born in January . The factors causing such differences should be determined.In order to investigate the influence of season and month of birth on the risk of neovascular age-related macular degeneration (n-AMD) in Italy, we evaluated the month birth and sex of all patients, recorded in the anti-vascular endothelial growth factor (VEGF) monitoring registry of the Italian Medicines Agency, born between 1925–1944, who received intravitreal anti-VEGF injections for n-AMD between January 1, 2013 and July 29, 2015. The numbers of all births in Italy in the same years, extracted from the Italian National Institute of Statistics, were used to calculate the expected number of n-AMD cases. Overall, 45,845 patients  received intravitreal anti-VEGF for n-AMD; in the same years, 20,140,426 people  were born in Italy. Comparing the observed number of n-AMD cases with the expected number of n- AMD cases in each season, we found that the season-specific risk for n-AMD was 2.5% higher for those born in summer (OR=1.03, Bonferroni-corrected  Age-related macular degeneration (AMD), a progressive chronic disease of the central retina, is a major cause of blindness worldwide . The preThe precise pathogenesis is still poorly understood. It is generally accepted that AMD is the result of a complex interaction between genetic and environmental factors .Several risk factors involved in the pathogenesis of AMD have been described, including genetic predisposition, age, and other modifiable factors such as smoking, light and ultraviolet (UV) exposure, dietary factors, and hypertension, which may influence the molecular mechanisms or cellular processes involved in development of the disease.It is well established that the prevalence and incidence of many diseases are related to the month or season of birth -8. ThereNo study has investigated whether there is an association between the season or month of birth and the risk of AMD. The aim of this study was to examine whether the month or season of birth is related to the risk of neovascular AMD (n-AMD) in Italy.Overall, in Italy, 60,818 patients received intravitreal injections of anti- vascular endothelial growth factor (VEGF) for n-AMD from January 1, 2013 to July 29, 2015. Consecutive years having at least 1000 individuals treated were found during the span 1925 to 1944 (included). A total of 46,826 patients born in these years were treated with anti-VEGF; after excluding 981 patients born outside Italy, a final sample of 45,845 patients  who were born in Italy and treated with intravitreal anti-VEGF for n-AMD was obtained. In the same years, 20,140,426 people were born in Italy  and were included in the analysis.2 = 3.057, P = 0.002; Bonferroni corrected P = 0.008) and 3% lower for those born in winter    and 3.2% lower for those born in winter ; χ2 = 3.29, P = 0.001, Bonferroni corrected P = 0.004). In women, no significant differences were found between different months after Bonferroni correction. In men, no significant differences were found between seasons or months.When we considered the month of birth, the risk of n-AMD was 5.9% lower for people born in January ; χIn this study, we analyzed the month of birth in the years 1925 to 1944 of patients with n- AMD who were treated with intravitreal anti-VEGF injections in Italy. We found a seasonal variation: the number of people who developed n-AMD was higher than expected in summer, and lower in winter.Several diseases exhibit an effect of birth month or birth season on the incidence.-8 A metaA national study in the UK showed that the distribution of births of patients who developed an immune-mediated disease  differed significantly from that of the general population. The peak of births for those who developed one of these diseases occurred in April and a trough in October, and the risk correlated inversely with predicted second-trimester UVB exposure and third-trimester vitamin D status .Several seasonal factors acting during pregnancy and the perinatal period have been proposed to explain these data, including infections, dietary factors , and vitamin D deficiency through lack of sun exposure during pregnancy.. This laThe biologically active form of vitamin D is generated in the skin during exposure to UV radiation from sunlight, and its levels follow a seasonal distribution. In the Unites States, a study of more than 3 million people reported a peak of 25-hydroxyvitamin D (25(OH)D) level in August and lowest level in February . In younGestational vitamin D concentration is considered important for the development of the immune system. The vitamin D acts as an immunomodulator by inhibiting the proliferation of the T cells, shifting the T-cell population toward noninflammatory T helper 2 (Th2) and T-regulatory cells, and suppressing the transcription of genes encoding key Th1 pro-inflammatory cytokines . Genes a2/day compared with those with insolation >3 kWh/m2/day (P < 0.001) [In animal models, gestational vitamin D deficiency affects brain development , and the< 0.001) .An effect of the month of birth has also been reported for ocular conditions such as myopia. In Israel, a study found increased rates of moderate and severe myopia in people born in summer and lower rates in those born in winter . These differences correlated with the number of daylight hours, which is thought to relate to the melatonin level, or an imbalance in the melatonin–dopamine relationship.. SimilarStudies of the effect of birth month or birth season have observed significant variability in birth month in the general population. This factor, combined with the inevitable heterogeneity in region of origin and year of birth, can lead to false-positive associations . In thisThis study has several limitations. Although season of birth is a well-defined variable, it is only one possible factor in the pathogenesis of the n-AMD. It is associated with various other environmental factors, such as meteorological factors, daily sunlight exposure, and alterations in air pollution and food supply, as well as behavioral variables, including dietary habits and physical activity levels. Personal factors, such as smoking, urban or rural residency, alimentary habits, and migration  could have caused different levels of exposure to risk factors and had an effect on the development of n-AMD.In conclusion, this study shows that there is seasonal variation in the risk of developing neovascular AMD in Italy. The factors causing such changes should be determined.In this study, all consecutive patients recorded in the anti-VEGF monitoring registry of the Italian Medicines Agency (AIFA) who received intravitreal injections of anti-VEGF for n-AMD between January 1, 2013 and July 29, 2015 were included. The system monitors the registration process throughout the country and uploading of clinical data, and allows access to data about reimbursement by the National Health Service ,34.The inclusion criteria were patients born in Italy and treated with intravitreal anti-VEGF injection for n-AMD. Patients born outside Italy were excluded. The data obtained from the AIFA database for each patient were year and month of birth, region of birth, and sex. Other parameters allowing personal identification  were not provided. The drugs used for intravitreal injections of anti-VEGF recorded in the AIFA registry included in this study were pegaptanib sodium , bevacizumab , ranibizumab , and aflibercept .From the initial cohort of patients, to ensure a sufficient sample size across all 12 months, as previously described , we inclInstitutional review board approval was obtained.The n-AMD incidence rate was calculated per 100,000 residents per year. The distribution of season of birth was compared between the study population (with n-AMD) and the corresponding Italian population. We compared the observed number of n- AMD cases with the expected number of n-AMD cases in each season, and we analyzed the season-specific risk of n-AMD compared with the other 3 seasons using the odds ratios (ORs) and 95% confidence intervals (CIs) and a 2 × 2 chi-square test. Significant (P ≤ 0.05) values for a single season were corrected for the 4 comparisons using the Bonferroni correction.We also compared the observed number of n-AMD cases with the expected number of n-AMD cases in each month, and we analyzed the month-specific risk of n-AMD compared with the other 11 months using ORs and 95% CIs and a 2 × 2 chi-square test. Significant (P ≤ 0.05) values for single months were corrected for the 12 comparisons using the Bonferroni correction.Subgroup analyses were performed for women and men. We calculated 95% CIs based on the Poisson distribution for describing the variation in the number of events during a period of time.Data were analyzed using IBM SPSS Software 22 version . All P-values were 2-sided, and P ≤ 0.05 was considered to be significant.


Although vitamin D (vitD) deficiency is a common problem in pregnant women, in China, few studies have focused on the relationship between maternal vitD deficiency throughout the three trimesters and subsequent neonatal outcomes in China.Between 2015 and 2016, maternal serum and neonate cord blood samples were collected from 1978 mother-neonate pairs from Liuzhou city.P = 0.026). A relatively lower risk of vitD deficiency was observed in the third trimester than in the first and second trimester . VitD-calcium cosupplementation during pregnancy improves the vitD deficiency in both the maternal and neonatal groups . Maternal vitD deficiency significantly increased the risk of neonatal low birth weight (LBW)  and small-for-gestational-age (SGA) . There was a positive correlation between maternal and neonatal vitD deficiency . VitD supplementation during pregnancy significantly reduced the risk of giving birth to LBW infants .The mean concentrations of 25-hydroxy vitD (25(OH)D) were 16.17±6.27 and 15.23±5.43 ng/ml in the mother and neonate groups, respectively, and the prevalence values of vitD deficiency in the two groups were 78.18% and 83.27%, respectively. Logistic regression showed that maternal vitD deficiency independently increased the risk of gestational diabetes mellitus (GDM) (adjust OR, aOR 1.08; Further research focusing on the consumption of vitD with calcium during pregnancy and the consequential clinical outcomes in Chinese pregnant women is warranted. Vitamin D (vitD) is a well-known secosteroid hormone for its classical functions, such as skeletal health and bone metabolism. RecentlAn abundance of epidemiological evidence links vitD deficiency and insufficiency to a variety of adverse maternal and neonatal outcomes including preeclampsia, hypertension, gestational diabetes mellitus (GDM), spontaneous abortion, intrauterine growth restriction (IUGR), small size for gestational age (SGA), low birth weight (LBW) and premature birth–13. It wAlthough there is growing evidence that vitD deficiency and insufficiency are associated with negative pregnancy and infant outcomes, evidence for the correlation of hypovitaminosis D with the potential risk to maternal-neonatal pairs is limited. The objective of the present study was to explore the correlation of maternal-neonatal pairs with vitD status and determine whether maternal vitD deficiency may increase the risk of adverse neonatal outcomes.The Liuzhou Birth Cohort Study was a prospective population-based study with a birth cohort that recruited 2000 pregnant women between 2015 and 2016 at Liuzhou Maternity and Child Health Care Hospital. The inclusion criteria were mother-singleton-offspring pairs for whom serum samples from mothers and umbilical cord blood samples from neonates were obtained. Because there were reports,15 descrThe study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Ethics Committee of Liuzhou Maternity and Child Health Care hospital. In addition, all the participants were given written informed consent in the study. All procedures and methods involving human samples were in accordance with approved guidelines.Blood samples were collected and sent to the clinical laboratory for the vitD measurement. Serum 25(OH)D levels were measured using an electrochemiluminescence immunoassay (ECLIA) kit  according to manufacturer’s instructions as described previously .Season was defined by the following groups: spring (March to May), summer (June to August), autumn (September to November), winter (December to February).th percentile for gestational age[SGA was calculated as birth weight below the 10ional age.IUGR was defined as a failure of the fetus to achieve its optimal growth potential according to the criteria adopted by the American College of Obstetricians and Gynecologists (ACOG).Preeclampsia was defined as the presence of hypertension (systolic blood pressure ≥140mmHg and/or diastolic blood pressure ≥90mmHg) after 20 weeks of gestation with the presence of proteinuria (≥0.3g/24h or ≥1+ on dipstick) in previously normotensive women, according to the criteria adopted by ACOG[A 75g oral glucose tolerance test (75g OGTT) was performed between 24–48 weeks of gestation. GDM was defined as the fasting plasma glucose ≥92mg/dl (5.1mmol/L) or 1h plasma glucose ≥180mg/dl (10.0mmol/L), or 2h plasma glucose ≥153mg/dl (8.5mmol/L), according to the recommendations of reference.Weight of birth was measured within 15 minutes after birth. Low birth weight was defined as those newborns with birth weight less than 2500g.Minority ethnic group: There are 56 different ethnic groups in China. Han and Zhuang are the two major ethnic groups in Guangxi, which consist of about 90% of the population in Guangxi. The minority ethnic group is defined as any other ethnic groups except Han and Zhuang.VitD status based on laboratory and clinical records from two electronic databases was reviewed. The following data were extracted: maternal age, pre-pregnancy BMI, gestational age, season of blood draw, trimester, GDM, preeclampsia, vitD supplemental during pregnancy, vitD-calcium cosupplementation during pregnancy, birth weight, infant gender, preterm delivery, IUGR, SGA, neonatal/maternal serum 25(OH)D levelshttp://www.R-project.org) were used for data analyses. Nonparametric methods were used to compared variables of which were not normally distributed. The Kruskal-Wallis rank test was used to compare the differences between trimesters, seasons of maternal blood draw, birth season, and of 25(OH)D measurements. Comparisons of associations of the 25(OH)D level with different groups of related factors were performed using univariate analysis methods. The following variables were entered as predictors in the model: maternal age, pre-pregnancy BMI, gestational age, season of blood draw, trimester, GDM, preeclampsia, vitD supplemental during pregnancy, vitD-calcium cosupplementation during pregnancy, birth weight, infant gender, preterm delivery, IUGR, SGA, neonatal/maternal vitD deficiency. All variables with P<0.10 were selected for inclusion in the multivariate logistic regression model to identify predisposing risk factors that are associated with maternal and neonatal vitD deficiency. P values of <0.05 were considered significant. All P values were corrected by Bonferroni’s method for multiple testing.SPSS software version 20.0  and R (P = 0.026) (P = 0.004). Maternal 25(OH)D concentration was inversely associated with SGA risk, the OR (95% CI) was 1.17 (1.03–1.32) (P = 0.015).Evaluation of the potential risk factors explored in this study revealed that season was a determinant of maternal vitD status. Compared to spring, a significant increase in maternal 25(OH)D concentrations was observed in the summer, autumn and winter seasons; the odds ratio (OR) and 95% confidential interval (95% CI) were 0.31 (0.22–0.44), 0.33 (0.23–0.48), and 0.60 (0.40–0.90), respectively , Fig 1. = 0.026) . A relatP = <0.001)  and 0.15  for vitD supplementation ≤6 times/week and ≥1 time/day, respectively. The same result was observed for vitD-calcium cosupplementation; for supplementation ≤6 times/week, the OR (95% CI) was 0.43 (0.33–0.56). For supplementation ≥1 time/day, this risk was reduced to 0.29  compared to the group that did not take supplements. In the multivariate regression analysis, vitD-calcium cosupplementation during pregnancy increased the maternal vitD status; the OR (95% CI) was 0.56 (0.48–0.65) ( <0.001) .r = 0.522, P<0.001) (P<0.001).There was a positive correlation between the maternal vitD concentrations and neonatal birth weight (P<0.001) . MaternaP trend <0.001) (P = 0.021) D was lower in birth seasons of spring and winter ( <0.001) , Fig 4,  <0.001) . In the = 0.021) .P = 0.005) (P<0.001). There was a positive correlation between maternal and neonatal vitD deficiency . The maternal vitD deficiency was a predictor for neonatal vitD deficiency, and the predictive model is shown in P<0.001).One hundred and thirty (6.57%) neonates had a LBW. The risk of vitD deficiency was much higher in neonates who had LBW than those who had a normal birth weight; the OR (95% CI) was 2.83 (1.36–5.89) (= 0.005) . The matThe recent establishment of a causal relationship between maternal vitD deficiency and adverse pregnancy outcomes is a matter of great public health concern–25. The GDM was the most common maternal complication with the prevalence of 4.1%-27.5% globally. We obseMost of the recently published randomized controlled trials (RCTs) have focused on whether maternal vitD supplementation may influence maternal or neonatal vitD deficiency,34. Few 2+ homeostasis and parathyroid hormones. A significantly increased risk of low neonatal birth weight among populations with vitD deficiency during pregnancy is anticipated and consistent with existing trends in the literature[VitD plays an important role in fetal growth due to its key interaction with Caiterature. Growingiterature–16. VitDiterature. Our stuiterature, which wP<0.001). Meanwhile, severe maternal vitD deficiency was associated with a higher risk of LBW neonates[Our study reported that maternal vitD deficiency has a positive correlation with neonatal vitD deficiency, and maternal vitD deficiency significantly increased the risk for neonatal vitD deficiency, while the relative risk was nearly 2-fold. Reports from another Chinese population demonstrated similar results. A study conducted in Beijing indicated that neither mothers nor newborns had normal levels of 25(OH)D (>30 ng/ml) and that a significantly positive correlation between maternal and neonatal 25(OH)D concentrations has been demonstrated Click here for additional data file.


Echinococcus humans are an accidental host. Liver and lungsare the most frequently involved organs. Herein a unique case of intramyocardialhydatid cyst of left ventricle along with pulmonary hydatid cyst in a38-year-old lady is reported. Surgical removal of the cardiac hydatid cyst wasdone with the aid of cardiopulmonary bypass followed by removal of pulmonaryhydatid cyst.Cardiac hydatid cyst is an uncommon but potentially fatal disease. In cystic Echinococcus granulosus. It is endemic in countries where farmanimals are raised. Cardiachydatidosis has been reported infrequently even in countries where hydatid diseaseis endemic: 0.5-2% in comparison with liver (65%) and lungs (25%),3. The diagnosis is difficult because of long latency betweeninfection and manifestation of disease. Hence we report a case of a young lady withintramyocardial and pulmonary hydatid cyst, which was surgically removed.Hydatid cyst is a human parasitic disease caused by larval stage ofEchinococcus granulosus, which was positive.A 38-year-old lady was admitted to our hospital with hemoptysis followed by chestpain, breathlessness and lowgrade fever. There was history of rearing pet animals.On clinical evaluation, no abnormal findings were detected. Her hematological andbiochemical parameters were within normal limits except ELISA test forElectrocardiogram (ECG) showed T-wave inversion in V2, V3, V4, and V6. The chestradiography showed well defined lesion in the right lower zone of the lung with airfluid level, and normal cardiac silhouette . UltrasoMedian sternotomy was done for removal of both cardiac and lung hydatid cyst.Cystectomy was performed under aortobicaval cardiopulmonary bypass with arrestedheart. Cystic lesion of size 2x 2 cm was found to be encapsulated by a well-formedmyocardium at the apex of left ventricle. The entire pericardial cavity was coveredwith mops soaked in hypertonic saline. The cystic cavity was sterilized with 5%cetrimide and fluid was aspirated. The cyst cavity was then opened and the daughtercyst was removed in Toto . The edgEchinococcusgranulosus. The life cycle of this tapeworm involves dogs and othercanids as definitive hosts, and domestic and wild ungulates, usually sheep, asintermediate hosts. Human beings are only incidental intermediate hosts. Theinfection, often acquired in childhood during play with infected dogs, is mostcommon in sheep-raising areas of the world. Hydatid cyst of the heart is an uncommon lesion. The mostfrequent locations of hydatid cysts in humans are the liver 65% and lungs 25%, withonly 0.5-2% of cases located in the heart,3. The commonlocation of cardiac hydatid cysts are the left ventricle (55-60%), right ventricle(15%), interventricular septum (9%), left atrium (8%), right atrium (4%) andinteratrial septum (2%)-4.Hydatidosis is a parasitic infection caused by . Clinicalpresentation of cardiac hydatid cyst is variable; the usual manifestations reportedare dyspnea, chest pain and palpitations. The most dangerous and potentially lethal complication ofcysts is their intracardiac or intrapericardial rupture, which may result inanaphylactic shock, embolization, or cardiac tamponade, acute pericarditis, andchronic constrictive pericarditis. Cysts growing toward the epicardium can compress the smallcoronaries, presenting with features of coronary artery disease. Involvement ofinterventricular septum may lead to conduction defects.After infection, the embryo usually reaches the myocardium via the coronarycirculation from the left side of the heart. The cyst is then formed within a periodof one to five years. Pulmonary cyststypically increase in diameter at 1-5 cm/yr. Most lung cysts are incidentallydiagnosed on chest radiographs. Occasionally, patients present with cough,hemoptysis, or chest pain.Complication of pulmonary hydatid cysts are mainly due to the release of antigenicmaterial and secondary immunological reactions that develop cyst rupture.Pulmonary hydatid disease affects the right lung in around 60% of cases, 30% exhibitmultiple pulmonary cysts, 20% bilateral cysts and 60% are located in lowerlobes. ECGmay show T-wave inversion, premature ventricular beats. Hematological profile mayreveal eosinophilia of varying degree. Serological tests are positive in only about50% of patients and thus limited diagnostic accuracy. Echocardiography remains the most reliablediagnostic measure for cardiac hydatid cyst. Computed tomography and magnetic resonance imaging areother valuable diagnostic tools.The diagnosis is difficult because of long latency between infection andmanifestation of disease. The chest radiograph may reveal cardiomegaly, and meniscussign for pulmonary hydatid-4. The operative management for concomitant pulmonary hydatidcyst can be done in the same setting or different setting. In our case, it was donein the same setting via separate right posterolateral thoracotomy.The recommended treatment is enucleation, pericystectomy or cystectomy withcappitonage of the cyst under cardiopulmonary bypass via median sternotomy withtopical scolicidal agents in the surrounding operative field-4. Though cardiac hydatid cysts be very uncommon, the possibilityof this disease should be kept in mind especially in endemic areas. In order toprevent fatal cardiac complications, cardiac hydatid cyst should be removed even inasymptomatic patients.During surgery, it is important to minimize spillage of the cystic contents in orderto prevent intraoperative dissemination and eventual recurrence. This may beaccomplished by delivery of intact cyst or by cystic fluid aspiration with use ofscolicidal agent and preoperative therapy with Albendazole. As a rule, the heartshould not be manipulated before application of cross clamp and cardiopulmonarybypass. Prior to enucleation, a hydatid cyst is usually sterilized by instillationof scolicidal agents such as 2% formalin, 0.5% silver nitrate solution, 20%hypertonic saline solution, 1% iodine solution or 5% cetrimide solution. We used 5%cetrimide for instillation and soaked mops around the cyst cavity


This study assesses the whole brain microstructural integrity of white matter tracts (WMT) among older individuals with a history of falls compared to non-fallers.85 participants  were evaluated with conventional MRI and diffusion tensor imaging (DTI) sequences of the brain. DTI metrics were obtained from selected WMT using tract-based spatial statistics (TBSS) method. This was followed by binary logistic regression to investigate the clinical variables that could act as confounding elements on the outcomes. The TBSS analysis was then repeated, but this time including all significant predictor variables from the regression analysis as TBSS covariates.The mean diffusivity (MD) and axial diffusivity (AD) and to a lesser extent radial diffusivity (RD) values of the projection fibers and commissural bundles were significantly different in fallers (p < 0.05) compared to non-fallers. However, the final logistic regression model obtained showed that only functional reach, white matter lesion volume, hypertension and orthostatic hypotension demonstrated statistical significant differences between fallers and non-fallers. No significant differences were found in the DTI metrics when taking into account age and the four variables as covariates in the repeated analysis.This DTI study of 85 subjects, do not support DTI metrics as a singular factor that contributes independently to the fall outcomes. Other clinical and imaging factors have to be taken into account. Falls are common in the older population. The annual incidence of falls is nearly 30% in individuals 65 years and above and the number is expected to increase further as the population ages . Falls iIn the LADIS study, Baezner et al 2008) concluded that a strong association exists between the severity of age-related white matter (WM) changes with gait and motor compromise . Blahak  concludeAn additional advantage of DTI is the ability to study the integrity of individual white matter tracts (WMT) , therefoStudies determining the integrity of the WMT among older fallers remain limited, with many studies evaluating surrogate balance and gait outcomes rather than comparing WMT changes with actual fall outcomes. To our knowledge, there has been no similar whole-brain analysis study in an Asian population. We, therefore, conducted a case-control comparison of WMT changes between older fallers with recurrent or injurious falls and non-fallers in an urban Malaysian population consisting of various racial backgrounds. We also took into account the various confounding factors contributing to falls to assess the importance of DTI as an independent diagnostic measure.A total of 85 subjects were recruited for the study over a period of 2 years which included 43 patients with falls and 42 healthy non-fallers. Fallers were recruited from among participants of a separate randomised controlled trial—the Malaysian Falls Assessment and Intervention Trial (MyFAIT) . These pAll participants received a baseline clinical assessment conducted by trained researchers and a consultant geriatrician. Gait and balance performance were assessed using Functional Reach (FR) and Timed Up-and-Go (TUG) tests . FR was b = 700 s/mm2 and image scan time of 7mins 22s.All MR examinations were performed on a clinical 3.0 Tesla Signa® HDx MR System  equipped with a dedicated 8-channel high definition head coil. The imaging protocols included: (i) Axial T1-weighted 3D fast spoiled gradient echo (3D FSPGR) with imaging parameters of TR = minimum 6.7ms, TE = minimum 1.9ms, range 1.9–11.0ms, FOV = 31mm, matrix = 256 x 256, isovoxel, thickness = 1.2mm and image scan time of 3mins 47s; (ii) Coronal T2-weighted fluid-attenuated inversion recovery sequence (FLAIR) with TR = 1600ms, TE = minimum 9.9ms, range 9.8–68.5mms, TI = 920ms, FOV = 24mm, matrix = 512 x 320, thickness = 5.0mm, spacing = 2mm and image scan time of 2mins 57s; and (iii) DTI datasets using single-shot spin-echo echo-planar imaging (EPI) with TR = 13000ms, TE = 81.2ms, FOV = 24mm, matrix = 128 x 128, thickness = 3.0 mm, gradient encoding along 32 non-collinear directions and diffusion-weighted factor, Voxel-wise, whole brain tract-based spatial statistics (TBSS) were carried out to identify tracts of interest that showed significant differences between fallers and non-fallers  . StandarAxial T1-weighted 3D FSPGR images were used for whole brain volume measurement. Voxel-based morphometry (VBM) analysis was computed using Christian Gaser's VBM8 toolbox  with defIndividual statistical analysis for demographic, clinical and imaging characteristics was performed using computerized statistic software SPSS version 22.0 . Mann-Whitney and Chi-square tests were used for numerical and categorical variables respectively. A p-value of < 0.05 was considered to be statistically significant.Multiple binary logistic regression analysis was carried out using fallers or non-fallers as the dependent variable, and demographic, clinical, and imaging characteristics as independent variables. Known risk factors for falls which showed significant differences in the univariate analysis were selected for the regression analysis. These factors included age, TUG, FR, WMLV, hypertension, orthostatic hypotension, and syncopal events . The reg3; SD 20.66 vs mean, 4.85 cm 3; SD 4.68).The demographic characteristics of fallers and non-fallers are presented in Tested individually, clinical variables that demonstrated statistical significances were hypertension, orthostatic hypotension and syncopal events. All the clinical variables with significant differences showed higher fractional values in the fallers group compared to the non-fallers. Using TBSS, significant differences in the white matter tracts are seen between the fallers versus non-fallers in the MD and AD values genu/body/splenium of corpus callosum, fornix, anterior /posterior/ retrolenticular part of the internal capsules, external capsule, anterior/posterior/superior corona radiata, posterior thalamic radiation, superior longitudinal fasciculus, superior fronto-occipital fasciculus and tapetum Figs . The RD To take into account all the confounding factors that may contribute towards falls, we then performed a multiple logistic regression analysis. Clinical variables known to be related to falls which demonstrated significant differences in univariate analysis  were entered for stepwise backward elimination of the non-significant variables. The final logistic regression model obtained showed that only functional reach (FR), white matter lesion volume, hypertension and orthostatic hypotension demonstrated statistical significant differences between fallers and non-fallers, with age retained in the model although no significance is shown . Age andThis is the first study utilising DTI for whole brain white matter tract analysis while taking into account confounding factors of fallers in an ageing multi-racial Asian population. DTI has been shown to be a reliable technique to detect microstructural abnormalities in the individual white matter tracts . Using wPrevious studies evaluated the relationship between motor disturbances, grades and DTI metrics in Parkinson’s patients and found association between motor disturbances and the DTI abnormalities in the body of the corpus callosum , 24. SevThe microstructural changes in major WM tracts are associated with age-related changes in adults older than 50 years . WM degeAside from the clinical parameters such as FR, hypertension and orthostatic hypotension, the imaging parameter of significant values is total WML volume in fallers. WML affect the information processing speed and executive function . WML hadTo understand the confounding effects of the clinical and imaging variables towards the outcomes , a multiple binary logistic regression analysis was performed, which identified functional reach, WML volume, hypertension, and orthostatic hypotension as independent predictors of falls. Repeated TBSS analysis accounting for age and these four variables demonstrated that DTI metrics did not contribute significantly to the outcomes independent of the covariates, which identifies that the difference in DTI metrics between fallers and non-fallers were mediated by the differences in dynamic balance, WML volume and blood pressure drop with posture change between the two groups .Hemodynamic changes related to orthostatic hypotension were reported to be associated with white matter changes and white matter hyperintensities volume in patients with neurodegenerative disorder , 41. AnoSeveral limitations were apparent in our study. Due to the presence of susceptibility artefacts at the brainstem and cerebellum in our DTI datasets, the white matter tracts assessment for a number of subjects had been eliminated from our analyses. Our study was limited by its relatively small sample size and cross-sectional design, therefore limiting any causal inference. The assessment of falls was retrospective based on patient history that may be inaccurate. A larger, prospective study should now be conducted to evaluate WM integrity and their correlation with new falls or new motor disturbances in older adults.Overall DTI data suggests that there are changes in the white matter micro-structural integrity in projection fibers and commissural bundles in fallers. However, DTI is not a singular factor that contributes independently to the fall outcomes in the presence of functional reach, WML volume, hypertension, and orthostatic hypotension. This novel finding importantly highlights the potentially synergistic relationship between postural blood pressure fluctuations, balance disorders and structural abnormalities observed among fallers. Prospective evaluation of this relationship is required to establish the potential causal relationship between these factors.S1 TableThe tract-based spatial statistics (TBSS) of the DTI metrics.(XLSX)Click here for additional data file.


Health informatics projects combining statewide birth populations with child welfare records have emerged as a valuable approach to conducting longitudinal research of child maltreatment. The potential bias resulting from linkage misspecification, partial cohort follow-up, and outcome misclassification in these studies has been largely unexplored. This study integrated epidemiological survey and novel administrative data sources to establish the Alaska Longitudinal Child Abuse and Neglect Linkage (ALCANLink) project. Using these data we evaluated and quantified the impact of non-linkage misspecification and single source maltreatment ascertainment use on reported maltreatment risk and effect estimates.The ALCANLink project integrates the 2009–2011 Alaska Pregnancy Risk Assessment Monitoring System (PRAMS) sample with multiple administrative databases through 2014, including one novel administrative source to track out-of-state emigration. For this project we limited our analysis to the 2009 PRAMS sample. We report on the impact of linkage quality, cohort follow-up, and multisource outcome ascertainment on the incidence proportion of reported maltreatment before age 6 and hazard ratios of selected characteristics that are often available in birth cohort linkage studies of maltreatment.w to 25.2%w), and the hazard ratio (HR) by as much as 33% for some risk factors. Overly restrictive linkage parameters biased the incidence proportion downwards by 43% and the HR by as much as 27% for some factors. Multi-source linkages, on the other hand, were of little benefit for improving reported maltreatment ascertainment.Failure to account for out-of-state emigration biased the incidence proportion by 12%  contains supplementary material, which is available to authorized users. Child maltreatment, which includes all forms of abuse, neglect, and mental injury of a child by a parent or other caregiver, is under-studied relative to its public health significance, impact on children, and contribution to adult health outcomes  records have emerged as a health informatics approach  project that integrates epidemiologic survey and multi-sector administrative data  with a core set of sources to follow the PRAMS cohort prospectively, which include vital records, child death review, and Alaska Permanent Fund Dividend (PFD) records  infants for reasons of statistical precision. Oversampling and nonresponse are reflected in post-stratification sample weights. Alaska PRAMS samples approximately 1 in every 6 live births occurring to resident mothers, and maintains about a 65% weighted response rate. Complete PRAMS methodology is described in detail elsewhere  of these eligible mothers of newborns, with 1235 (64.7%) responding to the survey (69% weighted response rate).We used the PRAMS cohort as the basis of ALCANLink opposed to the full birth cohort for the following reasons: a) PRAMS provides population-representative exposure measures that are extensively more comprehensive and detailed than those available only on birth records, b) PRAMS respondents provide consent to have their responses linked to other information the department has about them facilitating data linkages with multiple administrative databases, c) PRAMS is conducted in nearly all other states potentially allowing for standardization and expansion of these methods, and d) The complex sampling enables population estimation while reducing the resources required for exhaustive data linkages which can ultimately make additional administrative data linkages unfeasible.n = 1235) were followed prospectively by linking PRAMS birth children to death certificates, Alaska Child Death Review (CDR) program records, and the Alaska Permanent Fund Dividend database with the most recent complete and available year (2014) at the time of this analysis. We used these follow-up sources to censor subjects for competing cause mortality and out-of-state emigration from Alaska.The 2009 PRAMS respondent births . All PRAMS births were subsequently linked to the annual PFD database. Adopted by constitutional amendment in 1976, Alaska established the Permanent Fund to invest a portion of the revenue earnings generated from petroleum production  were followed and censored at the date of death. To detect out-of-state emigration, the PFD data was used. This source only allows for annual interval censoring, which required us to develop a set of rules for systematic classification Table . For a va priori definition captured all outcomes within our observation window and censored for out-of-state emigration using a conservative rule to maximize accrual of person-time and was thus utilized as a reasonable expectation. Finally, we scrutinized, using the manual review process described above, a subset of cases that responded to the three-year follow-up survey but had a survey date greater than the last PFD linkage date (n = 23). Among these 23 cases, 18 had either moved or died, 3 were either adoptions or had substantial name changes and missed as initial linkages, and 2 had no documented history with PFD but remained in the state. Based on our censoring rule for these 23 cases we estimated a contribution of 126 person-months compared to 120 person-months calculated when using the most probable departure dates identified through manual review.The PFD provides only a crude annual estimation of censorship and even with manual review we are unable to identify exact dates, we examined multiple different censoring rules and compared the: 1) person-time estimation, 2) number of outcomes  excluded based on the rule specification (recognizing that such exclusions may reflect lack of precision in the PFD and CPS dates), and 3) impact on the incidence estimate, crudely approximated as the number of events divided by the total person-time at risk  we reduced the amount of suspected matches requiring manual review. For probabilistic linkages we developed comparison patterns based on a Joarowinkler distance metric to account for typos, spelling errors, transpositions, and other edits or deletions between two strings or set of strings and dates. The probabilistic linkage approach automatically accepted matches when the first, last, and alias names, date of birth and sex were identical. Suspected matches that returned a probability match score between 0.85 and 0.99 were manually reviewed, while those below 0.85 were automatically rejected. For complete linkage details and methods on establishment of these thresholds for review please see Data linkages in the Additional file w.We calculated the incidence proportion (“cumulative risk”) of first multi-source report of maltreatment before age six years. We estimated the survivorship function S(t) using a weighted Aalen hazard-based estimation (Klein and Moeschberger We created a dichotomous variable for censorship (yes or no) to assess the probability of censorship for a limited number of selected covariates obtained from both the birth certificate and PRAMS responses using logistic regression. The limited set of covariates selected for investigation to assess this potential bias included: as a proxy for military families if the birth was paid by Tricare ; sex of the child ; years of maternal education completed at delivery of child ; marital status at birth ; any maternal alcohol use during pregnancy as indicated on the birth certificate or PRAMS ; any maternal smoking during pregnancy as indicated on the birth certificate or PRAMS ; maternal race ; birth defect indicated on the birth certificate ; mother or child on Medicaid at birth ; fathers name listed on birth certificate ; maternal age at birth (continuous); multi-agency maltreatment report ; mother reported being divorced/separated 12 months before pregnancy ; mother reported moving 12 months before pregnancy ; mother reported losing a job 12 months before pregnancy ; mother reported partner/husband losing a job 12 months before pregnancy . These covariates were selected due to either being previously documented in the literature to be associated with maltreatment and hypothesized to potentially have differential population movement  of the 1235 PRAMS births to at least one PFD record with an Alaska residence before the age of 6 years. Among the 73 non-matching births, 15 were deaths occurring during the first year of life. On average, deterministic linkages captured 93.7% of all correct matches with annual PFD data. The PRAMS sample consistently linked with between 9% and 10% of PFD, CPS, APD, and CAC records  had at least one multi-source report of maltreatment during the follow-up period. Of the 327 multi-source reports detected, CPS captured the overwhelming majority , CAC captured 43 (13%), APD captured 33 (10%), and the CDR captured five (2%) fatalities , and monotonically decreased to 10.6% through age 5 years. Among the 1235 PRAMS births and considering only documented reports by CPS, 2.7%w  were reported for alleged sexual abuse, 5.1%w  were reported for alleged physical abuse, 9.1%w  were reported for alleged mental injury, and 21.0%w  were reported for alleged neglect among the birth population. The majority reported to CPS were due to neglect (88.7%w), followed by mental injury (38.5%w), physical abuse (21.4%w), and sexual abuse .Among the 1235 PRAMS births, 327 (24.2%The cohort was followed for 5812.7 (86.9%) of the 6690.9 total potential person-years. Among the 1235 PRAMS births, 930 (75.3%) had complete cohort follow-up through the first 5 years of life. Approximately 4% of the births were lost-to-follow up annually. Among the 305 births lost-to-follow up during the project period regardless of outcome, 32% were lost prior to age 1 year and 49% prior to age 3 years. There were 23 total deaths, with 78% occurring prior to age 1 year. Cohort follow-up details are available in Table w) PRAMS births were paid by TRICARE (crude proxy for military births). Military paid births had substantially more out-of-state emigration before age six , to such an extent that military paid births accounted for 42.5%w of all emigration movements. Among military paid births only 54.6%w of total potential person time was captured, compared with 91.9%w among non-military births before age six. The proportion of first reported multi-agency events was slightly lower among military paid births compared to non-military births .A total of 162 , birth or pregnancy not being covered by Medicaid as indicated on the birth certificate, and maternal self-reporting husband or partner losing a job or reporting moving to a new address during the 12 months before the child’s birth. The odds of out-of-state emigration censorship was lower among children of Alaska Native mothers (relative to White) Table .Table 3Uw  of the 2009 births to Alaska residents were the subject of at least one multi-source maltreatment report. Under the non-linkage assumption for out-of-state emigration  the incidence proportion calculated attenuated from 28.3%w to 25.2%w, an absolute difference of 3.1%. When we restricted our analysis to deterministic linkages only, the incidence proportion calculated attenuated from 28.3%w to 20.1%w, an absolute difference of 8.2%. Combining both sources of non-linkage error, the incidence proportion further attenuated to 18.5%w, an absolute difference of 9.8%. Finally, the incidence proportion calculated when restricted to using only child welfare reports  was nearly equivalent to the multi-source maltreatment report outcome .We observed that before the age of 6 years 28.3%The hazard ratios for multiple risk and demographic factors were also influenced by failing to correctly account for censoring and/or restrictive data linkage Table . FailingWe documented that failing to account for out-of-state emigration and/or using restrictive linkage methods in longitudinal birth linkage studies will bias both the incidence proportion and effect estimates. Integrating unique data resources in the state of Alaska enabled us to examine these sources of bias. The manageable sample size facilitated comprehensive high confidence data linkages and total cohort follow-up using the PFD. Furthermore, we demonstrated the utility of linking the PRAMS sampled child of a respondent mother with administrative data to effectively measure the incidence proportion of reported maltreatment over time in a representative birth population.All administrative studies using official reports of maltreatment (reports to CPS) are affected by potential detection bias  . Three quarters (75%) of the 2009 PRAMS births, representing 86% of the person-time of follow-up, had complete follow-up from birth to administrative censoring. High completeness of follow-up on the entire baseline population minimizes the potential for bias in estimating incidence proportion and effect estimates over time Rothman . Using tBy limiting to the PRAMS population-based subsample (as opposed to the entire Alaskan 2009 birth cohort) we were able to set liberal manual review ranges and only automatically accept linkages with perfect matches on all linkage elements . This resulted in high overall linkage success between sources with minimal effort, resources, and time. Studies linking entire birth cohorts may limit manual review and rely heavily on probabilistic cut points as a product of limited resources and data size resulting in unquantified sensitivity and specificity . The direction and magnitude of the error associated with the bias depends on the three-way association between the exposure, outcome, and factor influencing linkage and therefore can produce estimates that over or underestimate the true effect. We detected that the bias associated with linkage method can be strong enough to “pull” the effect across the null (as in the case for military paid births). Because the direction and magnitude of the bias is not readily predictable, results produced without addressing these forms of bias could result in erroneous conclusions, especially when comparing subgroups.w  were reported to child welfare before age 5 years. This crude estimate is 1.7 times that of California. Similarly to California however, we observed that relative to White children, Alaska Native/American Indian (AN/AI) children had 2.8  times the hazard of being reported before age five, with similar stratum specific estimates  for AN/AI children vs 15.8% w  for White children. Although Alaska indicated a crude elevated estimate relative to California, variations in population movement between these states could impact any direct comparison. Further, the observed similarity in the stratum specific estimates indicate confounding by race and that race standardization may be needed to account for large differences in underlying population distributions to facilitate state-by-state comparisons.No national estimate is available for comparison of the incidence proportion estimate generated in the ALCANLink study and bias estimates measured. Researchers in California however, did observe that 14.8% of children born during 2006–2007 in the state were reported to child welfare before age 5 years  PRAMS respondents may be differential from the total sampled population resulting in selection bias. We conducted a post-hoc comparison with the full 2009 birth cohort and found a similar raw percentage of births reported to CPS suggesting a minimal impact on overall estimates. 2) This study accounted for censorship using the PFD based on a crude mid-year interval specification which may have led to erroneous or imprecise exclusions which could result in an overestimation of out-of-state emigration. The impact of this on our person-time estimation is unknown but could in theory result in an overestimation. However, we feel that the overall impact is likely minimal as we conducted extensive data mining from all available systems for respondents that failed to match with the PFD. Further, for those that had “breaks in PFD applications” for example applied in 2010 and again in 2011 but not in 2009 we assumed they remained in the state even though we were able to document for some cases intermittent movement (e.g. attendance at out-of-state school). Thus our conservative censoring rule may in fact still overestimate actual eligible person-time in the state for the population and would likely lead to attenuated results. 3) The multi-agency outcome measure was limited due to incomplete law enforcement and CAC data.Child maltreatment is a substantial public health problem; however, etiologic analyses are needed to inform public health prevention efforts. Comprehensive population-representative data linkage studies are essential to detangling the multifaceted etiologies and interplay of factors that contribute to child maltreatment. Further, our confidence in assessing the impact of public health prevention efforts and policy over time relies on reliable, consistent estimates. PRAMS provide a rich set of measures for prospective cohort studies and when linked with administrative sources  can efficiently increase the breadth of information available for longitudinal analysis. Other PRAMS states should consider the utility of the ALCANLink methodology for studying reported child maltreatment longitudinally. This study underscores the importance of manual review of data linkages to monitor linkage quality and suggests the need for increased transparency and standardizations in linkage studies. We also highlight the importance of adjustment for out-of-state emigration, especially for states like Alaska that may have large population movements among population subsets. Data linkage did not substantially improve the detection of reported maltreatment in this study; additional research is needed to develop methods to improve the identification and classification of maltreatment.


Electroconvulsive therapy (ECT) is an effective treatment option for severe mental illness during pregnancy. However, there is little knowledge about the amount of electric field produced inside the foetus, which is important to understand the effects of ECT on the foetal excitable tissues. Thus, in this paper, the electric field strength inside the foetus was computed and compared to the basic restriction of the International Commission for Non-Ionizing Radiation Protection (ICNIRP). A computational human phantom representing a 30-weeks pregnant female, four types of electrode placements and a range of stimulus pulse width (0.25 ms–2 ms) and frequency (10 Hz–140 Hz) were used to compute the electric field inside the foetus. A linear relationship between the maximum electric field inside the foetal brain and the electrode current was derived. The results suggest that, considering the maximum current output, pulse width, and frequency range of constant-current ECT devices, the electric field produced inside the foetal brain is most likely below the ICNIRP basic restriction. This is based on the practical scenario of a 30-weeks foetus with a bottom-up and head-down foetal position and the mother taller than 1.62 m. It is also an effective treatment option for several psychiatric disorders in pregnant patients2. An extensive review of the reported cases of ECT performed on pregnant patients shows, out of the 339 collected reports, 11 cases represented foetal complications likely related to ECT3. The reported foetal complications include transient foetal arrhythmia, a foetal death secondary to status epilepticus, and a miscarriage. In another review, nearly one third of the cases reported adverse events, such as, foetal heart rate reduction, uterine contraction, and premature labor, from the total cases of 169 pregnant patients who received ECT4.Electroconvulsive therapy (ECT) is a psychiatric treatment in which electric currents are applied through scalp electrodes to induce seizures in anesthetized patients. ECT is often used as a last line of intervention for major depressive disorder, mania, and catatonia5, which are limits defined to protect from the effects of low frequency electromagnetic fields, such as, stimulation of excitable tissues.Despite the increasing interest in understanding the adverse effects of ECT during pregnancy, there is little knowledge about the amount of electric field produced inside the foetus. The knowledge of the electric field inside the foetus is crucial to understand the effect of ECT on the foetal excitable tissues, such as, the muscular tissue or tissues in the central and peripheral nervous system. Within this context, for the first time, we numerically computed the electric field inside the foetal tissues by utilizing the computational model of a 30-weeks pregnant female. The computed electric field was also compared to the basic restriction of the International Commission for Non-Ionizing Radiation Protection (ICNIRP)In this paper, the electric field from ECT was numerically computed inside the computational model of a 30-weeks pregnant female that was developed by merging the mesh model of a non-pregnant female and a 30 weeks old foetus. The computed electric field was related to the amplitude of rectangular biphasic stimulation current waveforms, which were used to compare the electric field inside the foetal brain to the ICNIRP basic restriction.14. Moreover, the development of most of such models required the manual translation and deformation of the maternal organs to place the utero-foetal unit. Similarly, we built the pregnant female computational model by merging the mesh model of a non-pregnant female (obtained from http://www.nevaelectromagnetics.com) and a foetus (obtained from http://femonum.telecom-paristech.fr/). The non-pregnant female mesh model (VHP Base 3.0), which has 26 individual tissues, was constructed from a cryosection image dataset of a female cadaver of height 162 cm. The VHP Base 3.0 was modified by stretching the skin, fat and muscle tissues at the abdomen by referring to the anatomical atlas of a pregnant female15. Also, other body parts, such as the intestine, liver, stomach, and blood vessels were deformed to place the uterus. The triangular surface meshes were made not to have non-manifold faces, non-manifold vertices and self-intersections. The development of the utero-foetal mesh model is discussed in16. The model consists of brain, lungs, skeleton, soft tissues, uterus and uterus content. The uterus content consists of uterus wall, placenta and amniotic fluid. The placenta was modeled with location and shape similar to that of the anatomical atlas used. Figures The problem of computing the electric field distribution inside the foetus requires a full-body pregnant computational model since the ECT current is applied on the mother’s scalp. However, the whole-body medical image datasets of a pregnant patient, which are needed to develop a full-body computational model, are not available since it is unethical to unnecessarily expose the foetus to imaging radiation. Consequently, most of the pregnant female computational models available in the world are hybrid models that were built by combining a full-body non-pregnant female model with the model of foetus or utero-foetal unit that was built from obstetric imageshttp://femonum.telecom-paristech.fr/projects.html), which were made available to the scientific community after passing an evaluation by an obstetrician and a group of paediatric radiologists16. The models obtained from the FEMONUM project are voxel based that consist of homogeneous pregnant woman envelopes (generated from a 3D model provided by DAZ 3D http://www.daz3d.com), pelvis bone with some vertebrae, and utero-foetal units representing 28 and 32 weeks of gestation. The pelvis bone was used as a visual landmark to correctly place the utero-foetal unit inside the woman envelope. Therefore, we also used the voxel pelvis bone as a landmark by overlying it on the mesh based pelvis bone of our model to compare the positions of the utero-foetal units. Figure The computational model was validated by comparing it to the pregnant computational models developed by the FEMONUM project . Also, ECT electrodes are isolated from the mains ground; thus, the capacitive effect of the bed frame can also be neglected. Therefore, the boundary of the problem was limited to the skin surface. The expression in (1) was solved by imposing a Dirichlet boundary condition on the skin surface underlying the electrodes and a Neumann boundary condition on the rest of the skin surface. The computational domain was discretized into tetrahedral volumetric meshes that are suitable to solve the expression in (1) using finite element analysis. It was assumed that the electrode current has a rectangular biphasic waveform so that its amplitude was used to compute the potential ϕ. The computed potential was used to calculate the electric field E = −∇ϕ that has similar waveform to the electrode current. The stationary current solver of CST Studio  was used to solve (1), which allows the use of the electrode current amplitude (electrode current density) as the initial condition.In the spectral content of ECT pulses, the tissue conduction current density is much larger than the displacement current density; thus, the electric potential distribution https://www.itis.ethz.ch/virtual-population/tissue-properties/downloads/database-v3-1/). The anisotropic conductivities of muscle, cortical bone, cerebellum, grey matter, and white matter provided in the database were also used. However, the data for the dielectric properties of foetal tissues is rare. Therefore, foetal tissue conductivity values obtained from the relationship between tissue water content and aging was used. It is known that tissue water content decreases with age, which also causes a general decrease in the conductivity of tissues17. Dimbylow6 proposed a formula that relates the ratio of foetal conductivity, σF, to the adult, σA based on the volume fraction of water in foetal, pF, and adult, pA, body tissues asThe conductivity of the maternal tissues was obtained from the online IT’IS database (18 (pF = 0.807 for a 30 weeks foetus) and the total body water for the reference adult female (pA = 0.5) from ICRP report 2319. Accordingly, for a 30 weeks foetus, the conductivity of the foetal tissue is 1.84 times more than that of the adult female. Since the foetal brain in our model was considered as a single tissue and was not segmented to different parts, its conductivity was related to the average of the conductivities of the adult’s isotropic grey matter and white matter. Moreover, since the foetal lungs are not filled with air, their conductivity was related to the adult’s deflated lungs. Also, the conductivity of the other tissues was related to the conductivity of similar tissues of the adult, such as, the foetal skeleton to the adult’s cortical bone, and the foetal soft tissues to the adult’s muscle. The conductivity of the placenta was assumed to be equal to the conductivity of blood due to the similarity of their composition20. The conductivity of the amniotic fluid was taken as 1.27 S/m21.The water fraction in the foetal body tissues was taken from the reference values in the ICRP 8922. One of the causes of such changes is the mechanism of electroporation of the skin, which is the phenomenon where the membrane permeability to ions and macromolecules is increased when exposed to a high electric field23. In other words, the skin conductivity changes with the applied electric field or the stimulation voltage. Experimental data suggest that the conductivity is linearly related to the current density24. Thus, the conductivity of the skin in contact with the electrode surface σes can be expressed asσe = kJes is the increased conductivity due to the current density Jes; k is a proportionality constant; and σs is the conductivity when the applied current is very small. In other words, σe is responsible for the reduced dynamic impedance and σs is responsible for the large static impedance. The conductivity relation (3) was applied to the expression in (1) and the resulting nonlinear equation was solved using the stationary current solver of CST Studio®.An accurate representation of the skin impedance is crucial for the computation of the dynamic impedance encountered during ECT. It is well known that the dynamic impedance decreases when the stimulation voltage of ECT increases. In other types of electrical transcutaneous stimulations, similar nonlinear impedance variations were attributed to the changes in the characteristics of the stratum corneum underneath the electrode interfaceJes is uniform on an area A of the skin underlying the electrodes that has a thickness of d, the expression in (3) can be written in terms of the skin conductance Gs and the current I asa and b are constants that are used to calculate k and σs. Luna et al.25 discussed the technique of estimating the subject specific coefficients a and b from transcutaneous stimulation measurement data. We used a = 25.9 mS/A and b = 37.8 μS, which was estimated for a single subject in their study25, to calculate the conductivity of the skin in contact with the electrodes. In the computational model, the skin underlying the stimulus electrodes was separated, meshed at higher resolution, and assigned a current density dependent conductivity as shown in Fig. Assuming the current density We simulated the four electrode placements shown in Fig. In order to represent the maximum current output of constant-current ECT devices, electrode current of 0.9 A was used to compute the electric field and the corresponding current density inside the tissue for each electrode placement. Figure a and b (see (4)) that were estimated for a single subject25. The contribution of the static component of the conductivity (b) is negligible at the electrode current amplitude used in ECT, such as, 0.9 A. The values of a and b depend on the subjects and they determine the accuracy of the computed dynamic impedance and the voltage drop across the skin. In other words, the values of a and b are important when an electrode voltage is used as the initial condition in (1) since the dynamic impedance determines the electrode current. However, when an electrode current is used as the initial condition, the computed electric field in the other tissues (excluding the skin underlying the electrodes) is independent of the value of a and b. This implies that for constant-current ECT devices, the electric field in the other tissues remains unchanged irrespective of the fluctuation in the dynamic impedance of the underlying skin. Therefore, a simple linear relation was derived for the maximum electric field in the foetal brain Ea (V/m) and the electrode current I (A) as Ea = γI, where γ is the constant of proportionality and its value is 0.055 for BL, 0.0152 for BF, 0.0227 for RUL, and 0.0356 for LART. Figure Ea versus the electrode current I for the four electrode placements.The conductivity of the skin underlying the electrodes was calculated based on the values of 5. The ICNIRP guideline states that the evidences for the neurobehavioural, developmental or reproductive effects due to low frequency electromagnetic field exposure are much less clear or very weak. ICNIRP recommends basic restrictions of the electric field in the brain not exceeding 0.1/f V/m for 1 Hz–10 Hz, 0.01 V/m for 10 Hz–25 Hz, 4 × 10−4f V/m for 25 Hz–1000 Hz, and 1.35 × 10−4f V/m for 3 kHz–10 MHz, where f is electric field frequency in Hz.The maximum electric field in the foetal brain was compared to the basic restriction set by the ICNIRP. The basic restrictions of ICNIRP in the frequency range of 1 Hz–100 kHz were defined based on the well-known effects of the low frequency electric and magnetic fields, which are, the stimulation of electrically excitable nerve and muscle tissues, the perception of surface charges, and the induction of retinal phosphenesτ was varied from 0.25 ms–2 ms; the pulse frequency (f = 1/T) from 10 Hz–140 Hz; and the amplitude Ea was set to the maximum electric field in the foetal brain. The maximum electric field inside the foetal brain was compared to the ICNIRP basic restriction by converting it to the frequency domain via Fourier Transform and applying the spectral method outlined in the ICNIRP guideline5. For the electric field in the foetal brain to be below the ICNIRP basic restriction, the following equation should be satisfiedt is time and ELi is the exposure limit at the ith harmonic frequency fi, where Ei, θi, φi, are the amplitude of the electric field, its phase angles and phase angles of the filter (given in5) at the harmonic frequencies.Since the capacitive effects were neglected when computing the electric potential in (1), the waveform of the electric field is similar to that of the electrode current. Thus, we considered the biphasic waveform shown in Fig. M(t) calculated for the electric field in the foetal brain for BL electrode placement when the electrode current is 0.9 A. Different waveforms were generated that have pulse widths in the range of 0.25 ms–2 ms and pulse frequency between 10 Hz–140 Hz. The electric field with waveforms of τ ≤ 1.75 ms was below the ICNIRP basic restriction for the whole pulse frequency range. Similarly, for BF, RUL, and LART electrode placement, the electric field obtained from all pulse widths and pulse frequencies is below the ICNIRP basic restriction. Moreover, the maximum electrode current that produces an electric field in the foetal brain below the ICNIRP basic restriction is 0.8 A for the range of pulse width and frequency considered. Given the specifications of ECT devices, the electric field produced inside the foetal brain is most likely below the ICNIRP basic restriction. For example, the MECTA devices (http://www.mectacorp.com) have a maximum current output of 0.8 A and pulse width of 0.3 ms–2 ms for the frequency range of 20 Hz–120 Hz. And the Somatics devices (http://www.thymatron.com) have a maximum current output of 0.9 A and pulse width 0.25 ms–1.5 ms for the frequency range of 10 Hz –140 Hz.Figure The electric field computed in this paper is for the specific case of a 30 weeks-old foetus that is in the bottom-up and head-down position and using the a computational model representing a pregnant female of height 1.62 m. It should be noted that the results do not represent the general case of different developmental stages of the foetus, different foetal positions, and the anatomical variations of the mother. Therefore, the readers should be cautious when using the results. The results serve to initiate further studies to establish more accurate and comprehensive assessments. The accuracy of the results can be improved by using a more anatomically realistic phantom of the pregnant female at different stages of pregnancy and more accurate conductivity values of tissues.et al.26. The study compares the ICNIRP basic restriction and the electric current density produced inside the foetal brain when a uniform electric field (5 kV/m) and magnetic field (100 μT) irradiate the whole-body of a 30-weeks pregnant voxel computational model. The electric and magnetic fields considered are the ICNIRP reference levels at 50 Hz. For the specific scenario considered, the study concluded that the current density produced inside the foetal brain exceeds the ICNIRP basic restriction. Our study focuses on a different scenario where the stimulus is an ECT pulse applied on the scalp (not a uniform electric or magnetic field irradiating the whole body); thus, naturally, the resulting conclusions are different.It might be worth mentioning the study conducted by Cech The electric field inside a 30 weeks-old foetus was computed using the computational model of a pregnant female. The dynamic impedance during ECT was represented by defining a current-dependent conductivity of the skin underlying the electrodes. Four types of electrode placement were simulated for electrode current of 0.9 A. Rectangular biphasic waveforms were considered with a range of pulse width (0.25 ms–2 ms) and frequency (10 Hz–140 Hz) that are commonly used in ECT devices. A linear relationship between the electric field inside the foetal brain and the electrode current was derived. The computed maximum electric field inside the foetal brain was compared to the basic restriction of ICNIRP. The results suggest that the electric field in the foetal brain from constant-current ECT devices is most likely below the ICNIRP basic restriction.


Placental histologic examination can assist in revealing the mechanism leading to preterm birth. Accumulating evidence suggests an association between intrauterine pathological processes, morbidity and mortality of premature infants, and their long term outcome. Neonatal brain activity is increasingly monitored in neonatal intensive care units by amplitude integrated EEG (aEEG) and indices of background activity and sleep cycling patterns were correlated with long term outcome. We hypothesized an association between types of placental lesions and abnormal neonatal aEEG patterns.To determine the association between the placental lesions observed in extreme preterm deliveries, and their neonatal aEEG patterns and survival.This prospective cohort study included extreme premature infants, who were born ≤ 28 weeks of gestation, their placentas were available for histologic examination, and had a continues aEEG, soon after birth)n = 34). Infants and maternal clinical data were collected. aEEG data was assessed for percentage of depressed daily activity in the first 3 days of life and for sleep cycling. Associations of placental histology with clinical findings and aEEG activity were explored using parametric and non-parametric statistics.st day of life. Fetal-vascular-thrombo-occlusive lesions of inflammatory type were negatively associated with depressed cerebral activity during the 1st day of life, and with aEEG cycling during the 2nd day of life (P<0.05). Placental lesions associated with MUP were associated with depressed neonatal cerebral activity during the first 3 days of life (P = 0.007).Twenty two out of the 34 newborns survived to discharge. Preterm prelabor rupture of membranes (PPROM) or chorioamnionitis were associated with placental lesions consistent with fetal amniotic fluid infection (AFI) or maternal under perfusion (MUP) (P < 0.05). Lesions consistent with fetal response to AFI were associated with absence of SWC pattern during the 1Depressed neonatal aEEG patterns are associated with placental lesions consistent with maternal under perfusion, and amniotic fluid infection of fetal type, but not with fetal thrombo-oclusive vascular disease of inflammatory type. Our findings highlight the association between the intrauterine mechanisms leading to preterm parturition and subsequent depressed neonatal cerebral function early after birth, which eventually may put premature infants at risk for abnormal neurodevelopmental outcome. Spontaneous preterm parturition has been the concern of obstetricians and neonatologist in the past decades. Efforts of primary and secondary preventions of this syndrome with progesterone–6, cerclThe vast majority of early preterm deliveries are due to spontaneous premature parturition,a syndroThe lack of success to decrease the rate of preterm delivery prior to 28 weeks of gestation may result from insufficient understanding of the underlying mechanisms leading to these severe obstetrical complications, hampering the ability to develop effective treatment modalities. The placenta reflects the underlying pathologies leading to very early premature delivery, and the study of these lesions may assist in the effort to prevent such early premature birth and in the treatment of theses neonates. Several studies in the recent years demonstrated correlations between premature parturition and histologic placental features of vascular and inflammatory lesions –31. MoreNeonates delivered prior to 28 weeks of gestation have a substantially higher rate of short  and long term complications of prematurity  and abnormal neurocognitive development). The rate of these complications is inversely related to the gestational age at delivery.–40In light of the association between prematurity, especially the early one, and long term neurodevelopmental sequela, neonatal brain activity monitoring was introduced to the Neonatal Intensive Care Units (NICUs). Indeed, in the last two decades, amplitude-integrated EEG (aEEG), a technique with graphics-based visual display of electric cerebral activity is increasingly used in NICU in order to monitor neonates at high risk for brain injury, especially extremely premature ones–44. MoreThe objective of this study was to determine the association between very early preterm birth, placental histopathologic lesions and aEEG patterns in premature infants born before 28 weeks of gestation.This prospective cohort study was conducted in the NICU and the department of Obstetrics and Gynecology of Soroka University Medical Center  between 2008 and 2010 with retrospectively collected maternal data.Newborn included in the study:1) Were born ≤ 28 weeks of gestation; 2) survived resuscitation after delivery and had an aEEG monitoring that was initiated prior to 6 hours of age; and 3) had a placental specimen available for histologic examination. Excluded from the study were newborns with major central nervous system anomalies or chromosomal abnormalities. The study protocol was approved by the Soroka Medical Center ethics committee and informed consent forms were signed by guardians of recruited infants. Maternal data were collected retrospectively from medical records of labor and delivery admissions and prospectively from newborns' files. Maternal information included demographic data , risk factors for preterm birth (assisted reproductive treatment (ART), multiple gestation, amniotic fluid amount disorders, pre-eclampsia), information regarding the course of delivery , and bacterial cultures data from maternal blood, urine, vagina, cervix, uterine cavity and from the placenta).Parity groups were defined as follows: nulliparous (1st delivery) multipara(deliveries ≥ 2). Amniotic fluid volume was estimated with a real time scanner equipped with a 3.5/5 MHz transducer of appropriate focal length. Oligohydramnios was defined as AFI < 5  while poSlides from placental paraffin blocks were retrieved from the pathology department. From each placenta, five tissue samples were used for histopathologic examination as follows: a slide from the free membranes (chorion and amnion with attached decidua capsularis), a slide from a section of the umbilical cord and three full thickness disc samples. In addition, any abnormal area was sampled. All samples stained with hematoxylin and eosin. Slides were analyzed by a single pathologist using a light microscope and classified into one of four groups according to Redline at al.: Normal Data were collected prospectively and included demographic data, delivery data , clinical hospitalization data . Small for gestational age (SGA) was defined if newborn birthweight was below the 10th percentile, according to the revised Fenton growth curves. Apgar sBrain ultrasound scans were carried out daily in the first three days of life, at one week of age, 30 and 34 weeks post conception. Short and long term outcome data were collected and included cerebral pathologies, presence of bronchopulmonary dysplasia and if the infant survived hospitalization, whether his neurological examination was within normal limits or not at discharge. Long term outcome at 2 years of age included a neurological examination –58 and Bth weeks of gestation are monitored with aEEG as soon as possible, and continued as clinically necessary. Informed consent for the incorporation of the information obtained from the aEEG in the study was sought from guardians of infants as soon as possible following the delivery. Enrolled infants were monitored for at least 72 hours after birth or until neonatal death.As part of our local protocol, infants born at ≤28aEEG was recorded with the CFM 6000 recorder . In this method EEG signals are sampled from two parietal electrodes located at P3 and P4 areas according to the international 10/20 EEG system. FrequenContinuous data were presented as mean ± standard deviation (SD). Ordinary data were presented as median and inter-quartile range. Categorical data were presented as proportions. The normality of the aEEG activity was investigated by normal distribution attributes, skewness, kurtosis and inverse normal plot. Due to abnormal distribution, we have examined the associations of placental histology with maternal or neonatal clinical findings and aEEG activity by Mann-Whitney test for continuous variables. Chi Square or Fisher's exact test were used to assess categorical variables as appropriate.In order to assess the first three days of life as a block, we divided our study group into three equal sub-groups (thirtiles) based on rate of depressed aEEG activity during the first days of life. Then we examined the associations between placental pathologies and depressed brain activity using the Mann Whitney test.Differences were considered statistically significant when p<0.05. Data were analyzed using the Statistical Package for Social Sciences (IBM SPSS version 21).During the study period 132 newborns were born at or prior to28 weeks of gestation. aEEG recording was initiated prior to 6 hours of age in 54 infants and 34 placental samples were available for histologic examination and consisted the study cohort.The maternal and neonatal clinical characteristics are summarized in Placental lesions were identified in all the 34 samples . In one Women with PPROM or with chorioamnionitis had a significantly higher prevalence of placental lesions associated with AFI (p = 0.001), and significantly lower rates of MUP(p = 0.038). None of the neonatal clinical variables including Apgar score, cord pH, rates of RDS, IVH, NEC, BPD and mortality were associated with a specific placental lesion..On the first day of life while cycling was not detected in 50% of infants with placental lesions consistent with AFI of the fetal side, it was recorded in all infants who had placental lesions consistent with FVTOD and with villous type MUP (p = 0.037). On the second day of life cycling was not detected in46%of infants with placental lesion consistent with AFI of the maternal side, 62.5% of those with AFI of the fetal side, 62% of those with MUP of vascular type and 57% of those with MUP of villous type, in contrast to lack of cycling in 20% of infants who had placental lesions with FVTOD of inflammatory type(p = 0.024) .Infants with placental lesions consistent with MUP had a higher percentage of depressed cerebral activity in the first two days of life  in comparison to those without these lesions. In addition, infants with placental lesions consistent with vascular MUP were more likely to be in the highest thirtile of depressed cerebral activity in regards to the overall percentage of depressed activity during the first three days of life, (p<0.05). NeonateAmong early premature infants (≤28 weeks of gestation) platacental lesions consistent with intrauterine infection with fetal involvement were associated with absent aEEG cycling in the first day of life. In addition, placental lesions consistent with vascularMUPwere associated with depressed cerebral activity during the first two days of life and an overall lower cerebral activity during the first three days of life. In contrast, placental lesions consistent with FVTOD of inflammatory type wereless likely to be associated with abnormal cerebral activity.The current paradigm supports the concept that pathological processes leading to early premature delivery affect the fetus and the neonate,33–35,40Prior reports suggested associations between specific placental lesions and short, as well as long, term neonatal neuro-developmental outcome ,63,67–71In our cohort, unlike other reports ,73 the mPlacental vascular MUP was the most common lesion in our study, and was associated with depressed aEEG recording during the first three days of life. This type of placental lesion is derived from implantation disorders and vascular remodeling, and is classically associated with pre-eclampsia and IUGR. Earlier reports found this lesion as more common among late preterm deliveries. However MUP is associated with subsequent development of CP in infants with extremely low birth weight.Indeed, early onset preeclampsia, and IUGR are associated with increased risk for CP. Nevertheless, even in absence of these obstetrical complications placental vascular lesions that are associated with such early premature delivery may represent a higher degree of severity of the placental vascular disease that is usually observed later on during gestation when these lesions are more prevalent. Moreover, such severity of vascular disease can also affect the fetus and the neonate. Our novel finding that depressed aEEG recording during the first 3 days of life of extremely premature neonates are more prevalent in infants who had placentas with vascular MUP, support this view.Placental lesions consistent with AFI of the fetal side of the placenta (i.e. funisitis) were associated in our population with absence of aEEG cycling on the first day of life. Previous reports found an association between the absence of neonatal aEEG cycling and abnormal neurodevelopmental outcome ,46. ImpaThis small prospective cohort bring forth for the first time a possible link between specific placental lesion and abnormal infant brain function recording during the first three days of life. This suggests that the placenta may mirror the process leading to early prematurity and may assist to identify the newborns at risk for subsequent abnormal neurocognitive development and even CP. This information is important since it may have a role in early identification of neonates who will benefit from specific intervention to ameliorate the cerebral damage associated with early premature delivery.The major strength of our study is its prospective nature and our ability to demonstrate the association between clinical obstetrical conditions related to extreme prematurity, specific placental lesions and abnormal infant cerebral activity in the first days of life.The small sample size and limited availability of placentas for histopathological evaluation restrained us from performing a multivariable analysis to strengthen the validity of our findings. Furthermore, though short and long term outcome of this cohort are available, we were not able to assess the associations between placental findings, cerebral activity and outcome.The association between abnormal neonatal cerebral activity and placental lesions in early premature neonates is novel; highlighting a possible association between intra uterine processes leading to extreme preterm parturition and depressed cerebral function early after birth which eventually put premature infants at risk of subsequent abnormal neuro-developmental outcome.