Birth weight is a major determinant of infant morbidity and mortality. Fetal undernourishment means an increased risk of dying during a baby’s early months and years. Birth weight has emerged as the leading indicator of infant health and welfare and the central focus of infant health policy. The issues have not been comprehensively evaluated in part due to lack of or limited empirical data. To this end, this study is aimed to evaluate the effects of maternal determinants on the birth weights of neonates in two major hospitals.p < 0.001) associated with low gestation at birth (34.8 ± 3.8) while mothers of low birth weight neonates had significantly (p = 0.034) lower body mass index (27.3 ± 5.4) than their normal birth weight counterparts (29.0 ± 6.3). Gestation at birth (p < 0.001), diastolic blood pressure (p = 0.008) was the only significant determinant of birth weight.Low birth weight neonates were significantly (An increase in gestation at birth by 1 week results in over twice more likelihood of a normal birth weight while a rise in diastolic blood pressure is less likely to give rise to a normal birth weight neonate. Low birth weight (infants born weighing less than 2500 g) is a very important phenomenon with respect to birth outcomes in the developing world . Birth wMany studies have been conducted all over the world and a wide range of risk factors for LBW recorded over the years . These rA major determinant of birth outcomes is the nutritional status of mothers during pregnancy . Other iStudies have demonstrated a linear relationship between maternal weight gain and birth weight. Thus a weight gain is popularly associated with normal birth weight whereas a maternal weight loss is associated with low birth weight, among others . Some stIn the light of the afore-stated, this cross-sectional study was designed to evaluate the associations, if any, between the effect of maternal anthropometric measurements, other maternal factors of expectant women and birth weight of neonates, and to also assess the effect of these same factors on the birth weight of the neonates.Korle-Bu Teaching Hospital is a flagship urban teaching hospital that serves Accra and other nearby towns and villages. It is the largest hospital in the country with obstetric care at all levels. It registers approximately 10,000 pregnancies annually. It receives referrals from polyclinics and other maternity centers within Accra and surrounding towns and villages and indeed throughout the country.Ridge Hospital serves as a regional medical centre. Catchment area extends to Winneba, Kasoa, Nsawam, including neighbourhood polyclinics in Accra. There is an open door policy, no cases are turned away.Women with singleton pregnancies comprised the study population. Nine-hundred and sixty-six singleton pregnant women were randomly sampled in two health facilities  in the Greater Accra Region with singleton pregnancies above 28 weeks at delivery and at attendance of antenatal clinics were studied. Systematic Random Sampling, specifically, was employed in this regard. Knowing, on average, the number of women within our inclusion criteria who visited each facility per day, on a daily basis, we picked a random start and thereafter, we picked successive participants, based on the sampling interval till they were all been sampled for the day. Mothers with twin or multiple births, as well as those seriously sick or had physical incapacitation, were excluded from the study.Ethical review was granted by the Ethical Review Committee of the Ghana Health Services. Participants provided written informed consent to share data and participation was completely voluntary.Information about the maternal, demographic and anthropometric measurements were recorded on fully structured questionnaire. The questionnaire was first pre-tested, in a facility different from the two study-facilities, to ascertain the validity of questions enshrined in it and its potential to capture required information for the study adequately well. Questions were finally modified to reflect language simplicity, clarity and ease in comprehension.Weight was taken with the Seca scale. The scale was calibrated each time it was moved. A participant stood still in the middle of the scale’s platform without touching anything and with the body weight equally distributed on both feet. The weight was read to the nearest 100 g (0.1 kg) and recorded immediately (two measurements taken in immediate succession should agree to within 0.1 kg).Each participant was bare footed with heels together, arms to the sides, legs straight, shoulders relaxed. Heels, buttocks, scapulae (shoulder blades), and back of the head were against the vertical board of the stadiometer. The measurement was read to the nearest 0.1 cm and the eye level with the headboard to avoid errors. Since there is no data on pre-pregnancy weight, first registration weight was used. For maternal height measurement reference, 145 cm was used as cut-off for short stature, which is considered a risk criteria for birth weight.Neonatal measurements were obtained within 72 h of delivery. Birth weight was obtained using a calibrated electronic scale. Length was measured using a standardized plastic length board. The newborns were weighed on a paediatric Seca scale that was accurate to within 10 g by research nurses. Adjustments were made to zero for any cushion, a towel or diaper that was in place. The weight of the cushion was subtracted from the newborn’s weight. Infants were weighed nude or with minimum clothing. The average of two weighing was recorded in the infant’s record to the nearest 10 g (0.01 kg). Weight at delivery was used to determine birth weight >90th percentile. Weight at the anthropometric assessment was used to determine total and percent body fat . Sex of the neonate was also established.After at least 10 min rest, after a woman walked in, blood pressure was measured on two occasions with a mercury sphygmomanometer with an interval of 5 min between measurements with a pressure monitor. Two readings were taken–the “systolic” pressure was recorded as the heart beats, and the second “diastolic” reading was taken during the “rest” between beats. The mean of the last two measurements was used. If BP was above 140/90 on at least two occasions within a week, a diagnosis of elevated blood pressure was made. This was followed by a referral to a competent professional for further evaluation.A separate consent statement was read to the eligible participants. This statement explained the purpose of the test and requested permission for the test to be carried out. It required just a small sample of easily obtained blood. Before the blood was taken, the finger was wiped with an alcohol prep swab and allowed to air-dry. Then the palm side of the end of a finger was pricked with a sterile, non-reusable, self-retractable lancet and a drop of blood collected. It measured the concentration of hemoglobin in the blood. The results were recorded in the maternal health book, and the book was returned to each mother as per hospital policy. For each participant whose hemoglobin level was lower than the cut-off point of 11 g/dl a referral was made for further evaluation. It is normal for hemoglobin levels to go down somewhat in the second half of pregnancy, when the amount of blood in the body is expanding dramatically. Follow-up hemoglobin (Hb) tests were given in late second trimester or early third trimester for monitoring. Consent was given for blood work.The questionnaire was reviewed for completeness and consistency before data was entered. To ensure that sample selection procedures were complied with, the author worked closely with the field supervisors and interviewers throughout the data collection period. Effective management of fieldwork was emphasized. Participants were screened based on inclusion criteria and sampling procedures were adhered to. The study questionnaire was pretested to provide face validity in wording and interpretation.The general characteristics of the study population were examined using mean and standard deviation for continuous variables and frequencies for categorical variables. Cross tabulations were used to establish the relationship between two or more categorical variables. Bivariate analysis was performed by cross tabulation to determine the predictors associated with birth weight which was coded as 1 = normal, 0 = low. Wald statistics was used to test the significance of individual coefficients in the model.P-values obtained through both chi-square analysis and binary logistic regression analysis was employed to assess any associations between BW and maternal demographic and anthropometric variables. These predictor variables in the bivariate model included sex of baby, blood pressure status, meal intake frequency, hemoglobin concentration, gestational age at the time of birth urine protein levels, age of the respondent, employment status, marital status and antenatal care visits. The basis for building the multivariate model was using the Enter approach, in SPSS. Gestational age, in weeks, was calculated from the first day of the last menstrual period (LMP), as ultrasound and sonogram systems were not available. Significance level was defined as p < 0.05. The strength of these associations was established using odds ratio and their 95 % Confidence Intervals (CI). Statistical analysis was performed using SPSS software version 20.0  [n, 2011) .Almost all of the respondents were on health insurance 99.1 %). Over half of the respondents (56.3 %) earned less than GH¢100.00 per month while only 2.5 % earned GH¢1000.00 or more, Table  %. Over r = 0.216, p = 0.001), diastolic blood pressure and baby’s weight at birth , and parity and baby’s weight at birth  and between mother’s age and baby’s weight at birth . The mean gestation at birth was almost 39 weeks, the mean BMI of mother at birth was 28.8 kg/m2, and the mean systolic blood pressure at birth was 114.5 mmHg while that of the diastolic blood pressure at birth was 70.3 mmHg. The hemoglobin at birth was 11.3. The anthropometric measurements were re-grouped in Table 2 group.Table Whereas majority of the low birth weights were recorded among the female neonates, 60.3 %), the opposite was the case for the recorded normal birth weights , Table  %, the op < 0.001) lower gestation (34.8 ± 3.8 weeks) than the normal birth weights (37.3 ± 3.3). It is also the case, per the underlying data, that mothers of normal weight neonates (29.0 ± 6.3) have a significantly (p = 0.034) higher BMI than their low birth weight counterparts (27.3 ± 5.4). However, the systolic blood pressure of mothers of normal birth weight neonates (113.3 ± 17.0) are significantly lower (p < 0.001) than that of the mothers of low birth weight neonates (122.2 ± 30.0). A similar picture can be seen with the case of diastolic blood pressure . However, mothers’ hemoglobin levels had no significant association with birth weights of neonates, Table In Table One of the areas of interest in this study was how the mean birth weights of the neonates were affected by the various levels of the socio-demographic and anthropometric parameters of mothers, Table For the binary logistic regression, the Nagelkerke R Square =0.236) shows that about 23.6 % of the variation in the outcome variable (Birth Weight) is explained by this logistic model. In the Wald statistics  column of Table  shows thDiastolic-blood-pressure-at-birth (0.008) was the only significant factor that predicted baby’s weight at birth. The Exp (B) and 95 % C.I. columns of Table The overall accuracy of this model to predict subjects having normal birth weight (with a predicted probability of 0.5 or greater) is 93.7 % Table . The senThe bulk of incidents of low birth weight are found in developing countries, the major cause of which is preterm birth (<37 weeks) . One keyMeanwhile, several studies across the world have shown that, education affects neonatal birth weight , 19, 21,There was no significant association between gestation at birth and birth weight of neonates, mother’s BMI and birth weight of neonates, systolic blood pressure and birth weight of neonates, as well as diastolic blood pressure and birth weight of neonates. Though the gestation at birth, mothers’ height and weight at birth were lower for LBW neonates than their NBW counterparts, that difference was not statistically significant. Whereas the systolic and diastolic blood pressures and were higher for mothers of LBW neonates than their NBW counterparts, only the diastolic blood pressure showed a statistically significant difference. These findings in the current study run through several studies over the world , 27, 28.Anthropometric assessment of nutritional status of Bangladeshi pregnant women and weight of their newborns, conducted in Bangladesh. In their study they found a positive association between the weight of mothers and that of their neonates. Similarly, these findings in the current study also run through the studies of Hassan et al., titled relationship between maternal characteristics and neonatal birth size in Egypt, in which correlation tests between maternal and neonatal anthropometric measurements revealed that for both sexes combined maternal weight had a significant positive correlation with neonatal weight [There was a significant positive association between the BMI of mothers, on one side, and the weights of their neonates. Thus mothers of normal birth weight neonates were also significantly taller and heavier than their low birth weight counterparts . This isl weight . The rell weight . The saml weight . On the Mothers’ hemoglobin levels had no association with birth weights of their neonates in this current study. Other studies have however shown the contrary –32.In several other studies, factors such as birth order, antenatal care and mother’s health status were found to also be significant predictors of birth weight of neonates , 23–35. It is evident from this study that among mothers’ characteristics, Diastolic Blood Pressure was the only important determinant of birth weight of neonates. Mothers’ Systolic Blood Pressure, Haemoglobin at birth and mother’s height were not significant per the binary logistics regression. However among the socio-demographic characteristics of mothers, Age of mother, level of education, occupation and monthly income were not significant in determining the birth-weight of neonates’.Mothers of neonates with low birth weight were found to have significantly higher systolic and diastolic blood pressures, lower weight and shorter in terms of height as well as lower gestation at birth than their normal birth-weight counterparts. There was no significant difference between the haemoglobin level of mothers of normal birth weight and their low birth weight counterparts.Ethical review was granted by the Ethical Review Committee of the Ghana Health Services. Informed written consent was requested from study participants. The participation by any person in the study was voluntary. A separate consent was obtained for blood work including hemoglobin. They were informed that upon completion of the work the results would be shared with them and the community. This will help inform interventions on maternal child health services.


SLC6A4 have been associated with early adverse experiences in infants. The main aim of the present work was to investigate the association between level of exposure to pain-related stress during hospitalization and changes in SLC6A4 DNA methylation at NICU discharge in VPT infants. In order to exclude the potential effect of birth status  on SLC6A4 methylation, we preliminarily assessed SLC6A4 epigenetic differences between VPT and full-term (FT) infants at birth. Fifty-six VPT and thirty-two FT infants participated in the study. The level of exposure to pain-related stress was quantified on the basis of the amount of skin-breaking procedures to which they were exposed. VPT infants were divided in two sub-groups: low-pain exposure  and high-pain exposure . DNA methylation was evaluated at birth for both VPT and FT infants, assessing 20 CpG sites within the SLC6A4 promoter region. The same CpG sites were re-evaluated for variations in DNA methylation at NICU discharge in LPE and HPE VPT infants. No differences in SLC6A4 CpG sites' methylation emerged between FT and VPT infants at birth. Methylation at CpG sites 5 and 6 significantly increased from birth to NICU discharge only for HPE VPT infants. Findings show that preterm birth per se is not associated with epigenetic alterations of the SLC6A4, whereas higher levels of pain-related stress exposure during NICU stay might alter the transcriptional functionality of the serotonin transporter gene.Very preterm (VPT) infants need long-lasting hospitalization in the Neonatal Intensive Care Unit (NICU) during which they are daily exposed to pain-related stress. Alterations of DNA methylation at the promoter region of the  Preterm birth represents a major health care issue worldwide with the rate of preterm birth ranging from about 5% in some European countries to 18% in several African countries  : a short and a long allelic variant. The short variant results in a two-fold reduction of serotonin reuptake compared to the long one  on the basis of the amount of skin-breaking procedures to which they were exposed during NICU stay. We examined if different levels of pain-related stress were associated with changes of SLC6A4 methylation status  from birth to NICU discharge. In order to control for the potential effect of birth status , we first compared epigenetic differences in the SLC6A4 methylation status between low-pain exposure, high-pain exposure and a group of full-term infants at birth. As no previous research directly assessed the association between levels of pain-related stress and SLC6A4 methylation status at NICU discharge in VPT infants, no specific hypotheses were formulated. Nonetheless, consistently with previous literature on epigenetic correlates of early adverse experiences in infancy  were enrolled at the NICU of the Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milan. Inclusion criteria for preterm infants were: gestational age < 32 weeks and/or birth weight ≤ 1500 g. Exclusion criteria included: major brain lesions as documented by cerebral ultra-sound ; neuro-sensorial deficits (rethinopathy of prematurity ≥ stage 2); genetic syndromes and/or major malformations. A group of 32 full-term infants  was recruited at the Pediatric Unit of the Sacra Famiglia Hospital, Erba (CO). Full-term (FT) infants were healthy, with no neonatal morbidities or prenatal/perinatal-risk factors. To obtain a homogenous group of mothers for both groups, we applied the following inclusion criteria: age over 18 years, good comprehension of Italian language, no obvious cognitive impairments, no manifest psychiatric disorders, no psychotropic medication during pregnancy, no prenatal depression or anxiety symptomatology, no drug addiction and no single-parent families. All parents of infants enrolled in the study signed a written informed consent form. The study was approved by the Ethics Committees of the Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini (LC) and of the participating hospitals.Adopting procedures from previous research in preterm behavioral epigenetics  were obtained from medical records. Neonatal clinical condition was assessed with the Vermont Oxford Network Risk Adjustment index (VON-RA) . The gene-specific forward 5′-GYGGGTTTTTATATGGTTTGATTTTTAG-3′ and reverse 5′-CRAAAATCCCTCCCCTCCTAACTCTAAAATC-3′ primers correspond to the boxed sequences in Figure We analyzed a CpG-rich region of the low pain-exposure (LPE) group, whereas 25 VPT infants were included in the high pain-exposure (HPE) group. This approach had the advantage of avoiding bias from extreme scores.To distinguish levels of pain exposure, VPT infants were divided through median split of the number of skin-breaking procedures : 31 VPT infants were included in the delta methylation value was obtained for each CpG site subtracting methylation percentage at birth from methylation percentage at NICU discharge. The delta methylation value allowed to adjust for possible between-subjects variations in CpG methylation at birth. Delta methylation values higher than zero indicated increases in methylation from birth to NICU discharge, whereas delta methylation values lower than or equal to zero indicated decreases or no variation.In order to assess the variation in methylation percentages from birth to NICU discharge in the VPT group, a post-hoc. LPE and HPE VPT infants were compared for the length of stay in the NICU and for the neonatal clinical condition  through independent-samples t-test and for the presence or absence of assisted ventilation through chi-squared test. To evaluate differences at birth in SLC6A4 DNA methylation between LPE VPT, HPE VPT, and FT infants a multivariate analysis of variance (MANOVA) was used, with Group as between-subject variable  and percentage of methylation of the 20 CpG sites within the promoter region as dependent variables. To test for SLC6A4 DNA methylation differences from birth to NICU discharge in the VPT group, a MANOVA was adopted, with Group as between-subject variable (2 levels: LPE VPTs vs. HPE VPTs) and the methylation delta values for the 20 CpG sites as dependent variables. To control for confounders, any socio-demographic and clinical variable for which significant differences emerged between LPE and HPE VPT infants were included as covariate in a MANCOVA with Group as between-subject variable (2 levels: LPE VPTs vs. HPE VPTs) and the methylation delta values for the 20 CpG sites as dependent variables. For all analyses, Bonferroni adjusted post-hoc tests were used to qualify significant effects as appropriate. Statistical analyses were carried using SPSS 21 for Windows 7 with alpha set at p < 0.05.LPE VPT, HPE VPT, and FT infants were compared for socio-demographic and neonatal variables as well as maternal self-reports through univariate analyses of variance (ANOVAs) and Bonferroni-adjusted F = 287.55, p < 0.001, η2p = 0.87, and birth weight, F = 298.15, p < 0.001, η2p = 0.88. Post-hoc tests revealed that full-term infants had higher birth weight than LPE (ps < 0.001) and HPE (ps < 0.001) VPT infants, whereas LPE and HPE VPT infants did not differ for gestational age and birth weight. Length of stay in the NICU was similar in LPE VPT and HPE VPT infants. No differences in need for invasive mechanical ventilation were observed between LPE and HPE VPT infants. Significant differences emerged between the two groups of VPT infants for the number of skin-breaking procedures, t(54) = 3.57, p = 0.001 and for VON-RA, t(54) = 2.40, p = 0.01.Neonatal variables for infants and socio-demographic variables for mothers are reported in Table SLC6A4 gene are reported in Figure DNA methylation percentages at birth for the 20 CpG sites included in the promoter region of the SLC6A4 methylation delta values between LPE and HPE VPT infants, F = 1.91, p < 0.05, η2p = 0.52. Significant differences emerged for CpG site 5, F = 4.66, p < 0.05, η2p = 0.08, and site 6, F = 8.81, p < 0.01, η2p = 0.14. A significant increase in DNA methylation was found for these sites in the HPE VPT infants, but not in LPE VPT counterpart  = 2.04, p < 0.05, η2p = 0.55. HPE VPT infants reported significantly higher delta methylation values for site 5, F = 5.14, p < 0.05, η2p = 0.09, and site 6, F = 8.92, p < 0.01, η2p = 0.14. No significant effect emerged for VON-RA covariate.As LPE and HPE VPT infants showed significantly differences in the VON-RA index, a MANCOVA was used to account for potential confounder effect of this variable on the association between levels of pain-related stress and CpG methylation. When adjusting for VON-RA index, the effect of Group remained significant, SLC6A4 gene in relation to different levels of pain-related stress during NICU stay in VPT infants. Also, we controlled for methylation levels at birth comparing FT and VPT infants.The current study aimed at assessing DNA methylation at 20 CpG sites within the promoter region of the SLC6A4 methylation at birth between VPT and FT infants, suggesting a lack of significant relationship between birth status  and epigenetic markers in the stress-related gene encoding for serotonin transporter. These findings are consistent with previous research on the epigenetic correlates of preterm birth, which documented no differences in the methylation status of imprinted genes between preterm and full-term infants at birth  between preterm infants and full-term infants at birth  only for infants exposed to high levels of pain-related stress during NICU stay. This result is consistent with a recent retrospective study which has documented that the exposure to pain-related stress during NICU stay was associated with changes in specific CpG sites of the u et al.  controllSLC6A4 gene have recently, been linked with similar developmental outcomes. Altered SLC6A4 methylation has been associated with reduced hippocampal gray matter  did not apply to subjects enrolled in the present work. Future studies are warranted to account for differential epigenetic effects of diverse stressors among populations of preterm infants at different clinical and developmental risk. Finally it should be noted that bisulfite conversion analysis does not differentiate between 5 mC and 5 hmC residues. As 5 mC and 5 hmC have different implications for early biological development and gene transcription regulation, future studies are suggested to adopt tools capable to unequivocally distinguish 5 mC and 5 hmC, such as digestion of in vitro synthesized double-stranded oligonucleotides  and at NICU discharge for preterm infants . Cord blood sampling has been already used in newborn epigenetic studies (Oberlander et al., With the ongoing reduction of mortality in preterm neonates, the focus of neonatal health care systems is shifting from granting survival to sustaining functional outcomes through improved developmental care (Als et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Preterm birth rate is increasing and is currently a worldwide concern. The purpose of this study was to estimate the prevalence of preterm birth in a sample of health facilities in Brazil and to identify the main risk factors associated with spontaneous preterm births.adj = 3.19, 2.30–4.43), multiple pregnancy , cervical insufficiency , foetal malformation , polyhydramnios , vaginal bleeding , and previous abortion . High BMI  and weight gain during gestation  were found to be protective factors.This was a multicentre cross sectional study on preterm births in 20 referral obstetric hospitals with a case-control component to identify factors associated with spontaneous preterm birth. Surveillance was implemented at all centres to identify preterm births. For eligible consenting women, data were collected through a post-delivery questionnaire completed with information from all mother-newborn medical records until death or discharge or at a maximum of 60 days post-delivery, whichever came first. The risk of spontaneous preterm birth was estimated with OR and 95%CI for several predictors. A non-conditional logistic regression analysis was then performed to identify independently associated factors. The overall prevalence of preterm birth was 12.3%. Among them, 64.6% were spontaneous and 35.4% therapeutic. In the case-control component, 2,682 spontaneous preterm births were compared to a sample of 1,146 term births. Multivariate analyses identified the following as risk factors for spontaneous preterm birth among women with at least one previous birth: a previous preterm birth (ORThe preterm birth rate in these health facilities in Brazil is high and spontaneous preterm births account for two thirds of them. A better understanding of the factors associated with spontaneous preterm birth is of utmost importance for planning effective measures to reduce the burden of its increasing rates. The risk factors associated with spontaneous preterm births (SPB) seem to vary by gestational age, and social and environment factors abruptio placentae, and placental insufficiency Approximately 25% of preterm births are caused by an intentional interruption of pregnancy. Of those, more than half are related to pre-eclampsia, chronic foetal distress, intrauterine growth restriction, 1 In the United States, nearly 12% of newborns in 2010 were preterm, and this rate has increased by 30% since 1981 Preterm birth rates are increasing in almost every country with reliable data.The purposes of the Brazilian Multicentre Study on Preterm Birth (EMIP) The proposal for this study has been reviewed and approved by the National Council for Ethics in Research and by the Institutional Review Board of each site. Before enrolment, an individual Informed Consent form was signed by each subject after understanding and accepting the study conditions. The confidentiality of identity was ensured regardless of whether the women participated in the study or not. The study totally complies with The Declaration of Helsinki.The Review Boards of the following institutions reviewed and approved this study: Maternidade Climeério de Oliveira , Maternidade Escola Assis Chateaubriand , Hospital Universitaário da Universidade Federal do Maranhao , Instituto de Sauúde Elıdio de Almeida , Hospital Universitaário Lauro Wanderley da Universidade Federal da Paraiba , Instituto de Medicina Integral Prof. Fernando Figueira , Hospital das Clınicas da Universidade Federal de Pernambuco , Hospital das Clınicas da Universidade Federal do Paranaá , Instituto Fernandes Figueira , Hospital das Clinicas da Universidade Federal do Rio Grande do Sul , Faculdade de Medicina de Botucatu da Universidade Estadual Paulista , Hospital da Mulher da Universidade Estadual de Campinas , Maternidade Escola de Vila Nova Cachoeirinha , Hospital Estadual de Sumaré , Faculdade de Medicina de Jundiaí , Hospital das Clınicas da Faculdade de Medicina de Ribeirão Preto da Universidade de Saão Paulo , Santa Casa de Limeira , Santa Casa de São Carlos , Casa Maternal Leonor Mendes de Barros , and Hospital São Paulo da Universidade Federal de São Paulo .This is a multicentre cross-sectional study plus a nested case-control component implemented in a research network of 20 referral obstetrical hospitals in different geographical regions of Brazil  [17]. RaSample size was calculated using the official prevalence of preterm birth in Brazil in 2006 of 6.5% This study included women with preterm birth and their newborns admitted during the data collection period, and a random sample of women who delivered at term immediately after the first 1,146 preterm births included (for the case-control component), who agreed to participate in the study. After a preterm birth was identified and enrolled in the study, electronic files and log books of each health facility were checked to identify the term birth that occurred immediately after that specific case of preterm birth. This term birth was then eligible as control if the woman agreed to participate; otherwise the next term birth was approached.The main dependent variable was preterm birth either spontaneous or therapeutic. The independent variables evaluated were related to some socio demographic characteristics, working status, weight assessment, reproductive and obstetrical history, prenatal care  immediately after each preterm birth and the same procedures were followed until the estimated number of controls was achieved.All information was gathered in a post-delivery interview using a questionnaire designed for the study. Additional relevant information was retrieved from medical records before discharge from the hospital. Data on the newborn was collected at a maximum of sixty days after birth.A meeting was held with all the participating centres before the start of data collection, in order to standardise the process and procedures for enrolment, data collection and management. Data collection was performed by local researchers who also received an electronic feedback during the study period to remind important points and to address specific questions arising. After completion of each questionnaire, the data were double checked to assess completeness and consistency, and only then introduced in the electronic system database.For data entry, a clinical research form (CRF) was developed into the electronic system for the management of clinical studies OpenClinica. Each collaborator received a username and password allowing different types of access to the database depending on their hierarchy in the study. For instance, local researchers had access only to their site information and data entry. Full access was allowed only to those from the coordinating centre. The CRF had an internal consistency checking with a pre-specified range of possible values for each variable in order to avoid data entry errors.Several procedures were performed to guarantee high quality and reliable information, including preparatory meetings for training, availability of detailed manuals of interviewer and of operation, technical visits to participating centres, and monitoring of data collection and electronic entry. Auditing and monitoring of collected information were implemented and data changes were provided whenever pertinent after cross-checking.For data analysis we considered a cluster cross-sectional design where each centre corresponded to one cluster. The heterogeneity among clusters was previously checked and considered satisfactory, with very low values of intra-class correlation coefficients for the great majority of variables. Therefore, the reported effect measure was adjusted for the cluster design The prevalence of preterm birth for the whole sample of the study was estimated as the rate among all births occurring in the participating centres during the data collection period. However not all cases of preterm births were in fact enrolled due to several causes, mainly hospital discharge during weekends before the woman could be approached by research interviewers, and some few cases of refusal to consent. During the study period in the participating facilities there were 4579 preterm births among 37228 births occurred. Considering 4150 preterm births were enrolled (9.37% of eligible women not enrolled), we considered 33740 births to keep the same proportion, also for the regions of the country. Prevalence was then estimated according to the geographical region, gestational age and main determining factor. A bivariate analysis was performed with risk estimates for SPB using OR with 95% confidence intervals (CI) for each predictor.adj) with 95%CI. Two models were run, one including all women and the other only for women with at least one previous pregnancy. The forward selection method was used and only predictors with a p-value <0.10 in the bivariate analysis entered the multivariate model. The software SPSS version 20.0 , and Stata version 7.0  were used for data analysis.Then, a multivariate analysis using non-conditional multiple logistic regression was applied to jointly assess the risk factors for SPB, reporting the estimated adjusted odds ratio , pre-labour premature rupture of membranes , and provider-initiated or therapeutic , as shown in In the case-control component 2,682 SPB were compared to 1,146 term births. Among the socio-demographic characteristics , maternaThe assessment of other several aspects of pregnancy conditions is shown in EMIP represented an innovative and fundamental step of a planned comprehensive assessment of preterm birth in Brazil in order to provide information to support health policies, the implementation of clinical trials, and prevention and treatment strategies. The results showed a higher prevalence of preterm birth than found in other studies. Additionally, this study indicated that multiple pregnancy, previous preterm birth, cervical insufficiency, vaginal bleeding, fetal malformation, polyhydramnios, inadequate prenatal care, previous abortion and urinary tract infection are all factors independently associated with SPB.The major strengths of EMIP were the expressive number of subjects evaluated and distributed among the three most populous regions of the country and the large number of variables prospectively collected in detail, which allowed for the analysis of several aspects of preterm births. There are, however some limitations in the study that we need to highlight as well. First we were not able to enrol all the eligible women as previously stated. We had a 9.37% rate of loss mainly due to logistic constraints, but we believe this did not represent a selection bias. These losses were similarly distributed among facilities and without a specific pattern of occurrence. In addition, we considered this same rate for having the correspondent number of births in the denominator in order to avoid distortions in the estimates. Additionally some recall bias could also be argued regarding some habits or previous conditions, but we hypothesize that this would be equally distributed between cases and controls. Lastly, the subjects were enrolled mainly from tertiary centres and therefore the results could not be generalized to the whole Brazilian population, but only for those attending centres like the ones from the study for having their deliveries.The global prevalence rate of preterm birth of 12.3% found in this study was slightly higher than those recently available, ranging from 9.9% to 11.7% Focusing on a large number of predictors, the results of EMIP showed that factors identified as associated with SPB are in accordance with most similar studies. The factor found to have the highest odds ratio was multiple pregnancies, both in parous and nulliparous women. In fact, a previous Brazilian study found an adjusted estimated risk of preterm birth that was almost five times higher among twin pregnancies Modifications of the uterine cervix and their relation with preterm birth have been largely studied. In EMIP, cervical insufficiency was clearly associated with an increased odds ratio of preterm births, even for first pregnancies. Cervical shortening and the cerclage procedure were associated with a 4- to 6-times higher odds ratio of preterm births in the bivariate analysis. In an international prospective cohort of nulliparous healthy women with a singleton pregnancy, a 4% increased risk of preterm birth was estimated per millimetre decrease in cervical length Prenatal care in Brazil is currently widely available and the number of visits is no longer seen as a real standard of quality. However, one third of women who delivered prematurely had fewer visits than recommended for gestational age During pregnancy, some conditions such as urinary tract infection and vaginal bleeding were considered risk factors for preterm births; these findings have already been well described in the literature There seems to be an interaction between genetic and environmental individual risk factors. The history of a previous SPB was the second strongest condition associated with prematurity in women with at least one previous pregnancy. This is known to be the single most important marker to screen women for in order to select those at higher risk of preterm birth. These findings are in accordance with the literature Finally, socio-demographic and behavioural characteristics of women were not significantly associated with SPB. Some other factors such as paid work during pregnancy and housework appeared only in the bivariate analysis as protective. We believe that they are confounded by the common bias that women at higher risk of preterm birth have been removed from these activities and those at lower risk remained working until later in pregnancy. In conclusion, although advances in high-risk obstetric and neonatal care have resulted in the improved survival of infants born prematurely, preterm rates are increasing in Brazil as in other countries. Moreover, this study identified some risk factors for SPB related to pregnancy conditions and maternal care for the Brazilian population that may help to implement health policies. Improving access to and the quality of prenatal care, in order to adequately screen and diagnose conditions and identify risk factors amenable to interventions seem to be worthwhile in order to effectively reduce the burden of preterm birth.


Ionic-based dielectrophoretic microchips have attracted significant attention due to their wide-ranging applications in electro kinetic and biological experiments. In this work, a numerical method is used to simulate the dynamic behaviors of ionic droplets in a microchannel under the effect of dielectrophoresis. When a discrete liquid dielectric is encompassed within a continuous fluid dielectric placed in an electric field, an electric force is produced due to the dielectrophoresis effect. If either or both of the fluids are ionic liquids, the magnitude and even the direction of the force will be changed because the net ionic charge induced by an electric field can affect the polarization degree of the dielectrics. However, using a dielectrophoresis model, assuming ideal dielectrics, results in significant errors. To avoid the inaccuracy caused by the model, this work incorporates the electrode kinetic equation and defines a relationship between the polarization charge and the net ionic charge. According to the simulation conditions presented herein, the electric force obtained in this work has an error exceeding 70% of the actual value if the false effect of net ionic charge is not accounted for, which would result in significant issues in the design and optimization of experimental parameters. Therefore, there is a clear motivation for developing a model adapted to ionic liquids to provide precise control for the dielectrophoresis of multi-phase ionic liquids. Dielectrophoresis (DEP) is an efficient and precise technique that is widely applied to manipulate droplets or particles in electrolyte based microsystems –8. DEP mIonic liquids are widely used in electro kinetic experiments and biological experiments because of their conductivity and biocompatibility. Plecis et al studied the ionic fluid transport process in microfluidic systems for the application for a simultaneous preconcentration and separation of biomolecules within simple straight channels . The ion2PO4), the local electric field, and the gradient of the squared electric field and found that these factors influenced the dielectrophoresis force exerted on polystyrene microspheres. Jung, Y. M. et al [The dielectrophoresis manipulation of ionic droplets has been investigated comprehensively using experimental and numerical methods. The microdroplet shape and size, the ion concentration and the frequency of the electric field can influence the dielectrophoresis force to some extent. Gallo-Villanueva, R. C. et al  investigM. et al  investigM. et al . The comM. et al ,21 and nM. et al ,23 studiM. et al ,23, the Numerical simulations regarding dielectrophoresis phenomena have provided significant contribution to the analysis of dynamic behaviors and major influences of the fluids. Luo J. et al  simulateIn this work, a numerical method is used to simulate the dynamic behavior of ionic droplets in a microchannel under the effect of dielectrophoresis; the model was developed with the Comsol multiphysics software. The ion concentration of the sodium chloride solution (NaCl) is considered to form a more accurate model. The Navier-Stokes equations are solved using the level set method, which considers the deformable interface between the water droplets and oil. Both the polarization Coulomb force and the dielectrophoresis force are considered the force sources of the Navier-Stokes equations. Using these sources, the Navier-Stokes equations are coupled and solved using the finite element method. In addition, the ion migration and the electrophoretic migration are considered in the dielectrophoresis force calculation. The electric field force of the droplet and the deformation of the droplet are investigated, and the effect of the net charge on the electric field force is considered. The goal of this work is to further develop means for the precise manipulation of microdroplets and microparticles.V, as follows [E is the electric field intensity, ε is the permittivity and ρe is the free charge density. According to dielectrophoresis theory, when a dielectric drop is polarized by an electric field in a continuous dielectric fluid, electric stress is generated by the electric dipole moment and is given by the Maxwell stress tensor [Generally, for spherical droplets suspended in a medium in either an AC or DC electric field, there are three types of forces that can affect the dynamic behaviors of the droplets: the Coulomb force, the DEP force, and the interfacial tension force. The DEP force and electric field force are generated by the non-uniform electric field and the permittivity of the two-phase flow. Modeling the electric field is performed using the electric potential  follows :E=−∇V, m is mobility, u is the fluid velocity, z is the ion valency. The diffusion coefficient, D, isR is the gas constant and T is the absolute temperature. The net charge density is defined asρe in equ.). The temperature is 20°C, and the diffusion coefficient is 1.3×10-9 m2/s. The conductivity of this model is 10-3 S/m[3,0.01 mol/m3 and 0.1 mol/m3 are designed. The conductivities of these models are 0 S/m, 10-4 S/m and 10-3 S/m respectively. The frequency is set as 104 Hz and the voltage applied on the electrode is The density and viscosity of the solution and the oil are 1000 kg/m 10-3 S/m. In ordeoperties . This reAs shown in φ. Both the velocity and the potential feature second-order accuracy, but a linear element for the pressure is used for the sake of calculation stabilization. The curvature of the interface domain is calculated using the finite difference method. The second-order implicit backward differencing method is used for the time integration. The solution domain is meshed with a non-uniform triangle mesh using the advancing front method, and a higher resolution is applied at the droplet domain, particularly at the initial interface region. Due to the requirement of level set method, the maximum mesh size is less than or equal to the defined thickness to ensure at least one layer of mesh in the transition region. The minimum size of the element is 1.2×10-7m and the number of the mesh elements is 103367. It takes about 7670s for one calculation model on the compute server . The reinitialization parameter, γ, is a time-varying function, and its approximate value can be represented by the fluid speed. However, the speed could not be known in advance, so the proper value is determined during an initial calculation with a time period of 10-8 s; γ is subsequently modified using the calculated speed in the subsequent time steps. The absolute tolerance for the variables is set to 1×10-6.To achieve precise solutions but avoid an overly large number of meshes from exhausting the computation time, the axisymmetric geometry model is adopted. FEM is used to simultaneously solve the time-dependent, second-order partial differential equations in two dimensions, as expressed in their weak  forms, using the weighted residual approach. The electric field equations, the flow field equations and the electrokinetic flow equations are coupled by the function variable, Generally, the ion concentration influences both the electric field force and the dielectrophoresis force. If the electric field is not considered, the positive and negative ions uniformly distribute in the solution, and the solution does not show an electrical property. However, when introducing an alternating electric field, the ions move towards the electrodes. Therefore, the local concentration of the solution is altered and results in net charge. With variations in the electric field, the direction of the charge transmission and the electrical property of the net charge change. The local electric field distribution is also altered.th hour. The calculation subsequently considers the electric field force.To study the characteristics of the charge, the role of the electric field force at the interface is not considered during the first two periods, so there is no deformation of the interface area, and the ions outside the interface region achieve a dynamic equilibrium state under the influence of the electric field force. This method also avoids the influence of an initial state of electrically neutral ions in a comparative analysis of the results. This state is then regarded as the initial value to be marked as the 0+ and Cl- ions, the droplet is a weak conductive solution. It is known that the net charge moves to the surface such that the electric field of the internal part is 0, according to the physical properties of a conductor in an electric field. In this model, Na+ and Cl- ions move toward the respective poles under the effect of electric field. Although the positive and negative ions move in opposite directions, the balance of the internal charge is unaffected. In fact, the net charge is only distributed within the interface domain. Due to the rate of ion transmission related to the ion nature and the strength of the electric field, the distribution of net charge contains the relaxation process. With an AC field, positive and negative net charge appear alternately and coexistent within the local area. Based on the results, it is concluded that the net charge strength reduced and that the peak value of the net charge decreased with a decrease in the electric field. Alternatively, the net charge with an opposite electric property appeared, and the contribution of the net charge to increasing and transforming the electric field gradually increased.Due to the existence of NaIn There were two sodium chloride droplets suspended in the microchannel, which was embedded with electrodes. Under the non-uniform AC electric field, the droplets were simultaneously deformed and moved. As displayed in Under the influence of an AC electric field, the average velocities of the droplet changed with the time. In 2014, Gallo-Villanueva, R. C. et al. determined that the ion distribution influenced the dielectrophoresis force and that the dielectrophoresis force may decrease under certain conditions. As shown in The velocity and polarization of the microdroplets with different ion concentration are shown in Because of the relaxation process of the positive and negative ions that occurred when exposed to an AC electric field, the net charges can coexist with each other on the interfacial area. The net charges moved toward the wall alternatively and ultimately disappeared. The net charges changed according to the intensity of the electric field. The frequency of this process is consistent with the electric field. The emergence of net charge ions weakened the polarization strength of fluid medium and the dielectrophoresis force. When the droplets in the electric field stretched, the distance was reduced and the curvature of the poles was increased. As a result, the electric field strength increased rapidly, as did the polarization charge density. Furthermore, both the Coulomb and dielectrophoresis forces increased. The density of the ion net charge remained almost the same, although there was an increase in the electric field strength and changes to the local droplet boundary curvature. Although the dielectrophoresis force appears due to a gradient within the medium, it is produced by the polar moment of the medium and is closely related to the polarization strength. The density of polarization charge increases when the droplets stretch such that they are in close proximity. Accordingly, the medium polarization is strengthened, and the interface electrophoresis force also increases rapidly.This study investigated in detail the distribution state of an ion solution medium and the influence of droplet dynamic behaviors under the effects of an AC electric field. Ions are transmitted when exposed to the electric field, and net charges are produced. The net charges not only affect the polarization strength of the medium but also influence the electric field force. The directional migration of positive and negative ions change the charge balance of the solution. Net charges position themselves in accordance with the concentration difference between positive and negative ions. Because the net charge is equivalent to polarization charge in terms of its impact on the electric field, it will enhance or weaken the polarization according to its location. Furthermore, because the impact of net charge and polarization charge are essentially equivalent, there is little influence on the electric field strength and the Coulomb force; however, the effect on the dielectrophoresis force is significant because the dielectrophoresis force is produced by the polarization dipole moment. According to the results, an increase in ion concentration leads to a small dielectrophoresis force, and the droplet motion slows.Dielectrophoresis in ionic-based microdevices was investigated via numerical simulation. The influence of ion concentration on droplet dynamic behavior was analyzed to determine how to control ionic droplets under the influence of a non-uniform AC electric field. The dynamic behaviors of the microdroplets can be controlled more precisely with the help of an ionic fluid. Dielectrophoresis is a precise and efficient method to control the droplets or particles in microfluidic devices. This simulation work considered the effect of an ionic fluid that is commonly used in biological or chemical experiments, which may contribute to the design of more precise and efficient microchip operation.


In laboratory research and clinical practice, externally-applied electric fields have been widely used to control neuronal activity. It is generally accepted that neuronal excitability is controlled by electric current that depolarizes or hyperpolarizes the excitable cell membrane. What determines the amount of polarization? Research on the mechanisms of electric stimulation focus on the optimal control of the field properties  to improve stimulation outcomes. Emerging evidence from modeling and experimental studies support the existence of interactions between the targeted neurons and the externally-applied electric fields. With cell-field interaction, we suggest a two-way process. When a neuron is positioned inside an electric field, the electric field will induce a change in the resting membrane potential by superimposing an electrically-induced transmembrane potential (ITP). At the same time, the electric field can be perturbed and re-distributed by the cell. This cell-field interaction may play a significant role in the overall effects of stimulation. The redistributed field can cause secondary effects to neighboring cells by altering their geometrical pattern and amount of membrane polarization. Neurons excited by the externally-applied electric field can also affect neighboring cells by ephaptic interaction. Both aspects of the cell-field interaction depend on the biophysical properties of the neuronal tissue, including geometric  and electric  attributes of the cells. The biophysical basis of the cell-field interaction can be explained by the electromagnetism theory. Further experimental and simulation studies on electric stimulation of neuronal tissue should consider the prospect of a cell-field interaction, and a better understanding of tissue inhomogeneity and anisotropy is needed to fully appreciate the neural basis of cell-field interaction as well as the biological effects of electric stimulation. In such, deep brain stimulation (DBS) with inserted electrodes is rendered effective for the treatment of Parkinson’s, essential tremor, and dystonia . Transcractivity , 7. Highactivity , 9 for eactivity .th century through the pioneering works of Jacques d’Arsonval (1896) and Silvanus P. Thompson (1910) in human visual sensations, i.e., magnetophosphenes. In 1982, Polson and Barker applied the first successful stimulation of peripheral nerves through the use of magnetic fields [Aside from direct application via stimulating electrodes, electric current can also be delivered by electromagnetic induction with time-varying magnetic field inside the biological tissue, activating the cells and providing non-invasive stimulation . The effc fields . In 1985c fields . Today, c fields , epilepsc fields  and Parkc fields . Magnetic fields , and in Effects of an electric field on neuronal tissue are caused by an establishment of a transmembrane potential. When a neuron is positioned inside an electric field, the electric field will induce a change in the resting transmembrane potential by superimposing an electrically-induced transmembrane potential (ITP). When the electric current penetrates the membrane, the neuronal membrane may be depolarized and/or hyperpolarized from its resting value , which causes excitation or inhibition of the cell. The depolarization may reach the threshold to generate an action potential, which involves the opening of voltage-gated ion channels such as sodium and potassium channels . Under eIn this review, we focus our questions on 1. How is ITP measured and calculated during electric or magnetic stimulation? 2. What might be the impact factors on the establishment of the ITP across the neuronal membrane? We show that interactions between the targeted neurons and the externally-applied electric fields play significant roles in generating ITP. We argue that a better understanding of tissue inhomogeneity and anisotropy is crucial for the full appreciation of neural basis of cell-field interaction, as well as the biological effects of electric stimulation.http://www.neuron.yale.edu/neuron/) capable of stimulating active ion-channel mechanisms.Both modeling and experimental approaches have been used to estimate the ITP during electric stimulation. The mathematical basis of modeling work is to solve Maxwell equations , which dIn parallel to theoretical studies, direct measurements of ITP were reported ranging from hippocampal neurons with sharp electrodes  to neuraEstimations on ITP during magnetic stimulation have been equally successful with a primary focus on axonal responses to the fields . In examAlthough the electric and magnetic stimulations share the same biophysical mechanisms in activating the neurons, they are not interchangeable in neither clinical nor experimental practices. At a macroscopic tissue level, the electric field further from the stimulating electrodes may be significantly dispersed by the non-homogenous tissue conductivity during electric stimulation. In contrast, the induced electric field may be less dispersed during magnetic stimulation because the magnetic field may penetrate through the tissue without significant attenuation. Therefore, with careful coil design and placement around the head, the magnetic field can achieve good stimulation in the brain region such as the motor cortex , 37. At direction, intensity, frequency, and waveform of the field. Amplitude and frequency of the stimulation current are the key parameters in deep brain stimulation [What determines the amount and pattern of cellular polarization in electric stimulation? First, the properties of the externally-applied electric field play significant roles in membrane polarization; these include mulation , 40. Orimulation . Similarmulation , 43. Celmulation , 44.frequency of the externally-applied magnetic field determines the strength of the induced field by the law of electromagnetic induction [magnitude of the magnetic field determines the intensity of the induced electric field. Both these quantities, in turn, affect the extent of polarization in a single cell [orientation of the magnetic field in relationship to the neurons determines the direction of the induced electric field and the geometric pattern of polarization in the neuronal tissue [Similarly, the characteristics of the magnetic field have been tightly related to the effects of stimulation as they define the properties of the induced electric current in the tissue. Among these parameters, three stand out and dictate the bulk of the overall outcomes. The nduction . The maggle cell . Lastly,l tissue , 46. Conl tissue , 47–50.Evidence presented thus far suggests a one-way process in electric stimulation of neuronal tissues, i.e. the cell membrane is passively polarized by the external field. We, however, hereby argue that a two-way interactive process exists between the neuron and the field: the cell - field interaction. We agree that the cell is directly polarized by the external field, but we propose that the electric field is perturbed and re-distributed by the neuronal tissue Fig. . The folWe first define the electric field around a cell. An electric field around a single cell is separated into three major areas: the field in the extracellular medium (extracellular field), the field within the membrane (transmembrane electric field), and the field in the cytoplasm (intracellular field).Electric fields in these distinct regions all possess important physiological significance. Extracellular electric field has been recorded and analyzed in the study of cellular communication and synchronized excitability. Direct measurement and computation of this field has been a focus for research interested in electric stimulation on neuronal tissue. Equally important, the transmembrane electric field maintains the meta-stable membrane structure , and is Initial evidence of the counter-effect of the neuron to the externally-applied field is seen in the significant disruption and redistribution of the local field when the field is sensed by the cell in question. Models with both analytical and numerical methods support this notion. For example, in an evenly distributed DC field, the electric field could be greatly augmented inside the cell membrane . Jerry eA direct consequence of the counter-effects of the cell to the electric field is that electric field alteration by one individual cell may cause secondary effects on neighboring cells during electric stimulation, particularly in the scenario that two or more cells are located in close proximity and in a high-density cell medium. Evidence demonstrated that the presence of a single cell affects ITP in its neighboring cells without direct physical contact between the two cells . Though Since an externally-applied electric field can activate neurons and the presence of neurons can alter extracellular electric field distribution, it is likely that neurons excited by the externally-applied electric field can also affect neighboring cells via ephaptic interaction. The functional significance of direct electric (ephaptic) interaction was largely ignored until the 1960s when an inhibitory action on Mauthner cells in goldfish was discovered . A singlWhat may affect the cell-field interaction during electric stimulation? In the following sections we will present evidence that both aspects of the interaction (the ITP and the re-distributed electric field around the polarized cell) depend on the inhomogeneous properties of the target tissue.At a microscopic level, cell property falls under two categories of measurement: the geometric and the electric parameters of the cell. Geometrical properties include the shape and size of the cell, as well as its orientation and location in the field. Electrical properties include tissue conductivity and dielectricity in the microscopic cellular environment, including the properties of the extracellular media, the cell membrane, and the internal cellular environment.Shape of the target neurons plays a significant role in determining the amplitude and pattern of distribution of ITP during electric and magnetic stimulations. By comparing different ITPs in a spherical cell  versus aCell radius is also important in determining the amplitude of the ITP . Larger Orientation of the cell to the externally-applied field determines both the amplitude and pattern of ITP within the cell , 24. ForIn addition to the geometrical properties of the cell, growing evidence supports that electric properties of the cellular environment affect ITP. For example, ITP induced by a microelectrode on a spherical cell is dependent on extracellular and intracellular media conductance . In a spThe other half of the cell-field interaction, redistribution of the field by the tissue, is also largely reliant on the properties of the tissue.The geometrical property of the cell causes external field redistribution. Numerical modeling results  have shoField distribution in the neuronal tissue also depends heavily on the electrical properties of the target tissue under electric stimulation. At a single cell level, membrane conductance affects the field distribution around and within a single cell during electric stimulation , 58, 72.The existence of cell-field interaction is rooted in the fact that most biological tissue is composed of abundant non-homogenous, anisotropic components such as the cellular/axonal membrane, the internal organelles, and the extracellular medium. The electrical properties  of the tissue vary with its geometrical location within the tissue, even at a subcellular level, causing local accumulation of induced electric charges  that aff2V = 0 in charge-free regions [As charge accumulation is a process that depends on microscopic cellular properties across the interface of two media, ITP and field re-distribution around a cell depend on both the geometrical and electrical properties of the neuron. Many works, including ours, have focused on understanding the neuronal excitation by electromagnetic field with low frequency (including DC). Under electric stimulation, the electric field distributions can be calculated by  regions , 24. Of  regions , which c regions , 23.In magnetic stimulation, two sources contribute to the magnetically-induced transmembrane electric field : \documemponent” , \documee . The tee  has significant experimental implications. Currently, many researchers use invasive methods (patch or microelectrodes) to measure electric field distributions during electric stimulation. Unfortunately, the presence of these electrodes may further perturb the applied field in the tissue. To accurately quantify field distributions and transmembrane potential changes during electric stimulation, less invasive methods should be considered, such as voltage-sensitive dyes, which provide high temporal and spatial resolutions to measure potential changes in the single cells , 83, 84.Parallel to the intensive experimental efforts, many mathematical modeling works have explored the mechanisms underlying the biological effects of electric stimulation. At least two distinguished types of approaches have been taken, and the discrepancy between these approaches has not been fully resolved.The “biophysical modeling” approach simplifies the neuronal tissue with the use of basic geometrical shapes “Engineering modeling” relies on powerful computerized simulation tools to replicate biologically authentic neurons that possess complicated morphologies and active ion channels. Extracellular stimulation of target neurons is a three-step process . FiThese simplifications could potentially cause underestimation of the field generated by the electrode, and introduce potential certain inaccuracy in the modeling. Some investigators have acknowledged this problem in previous studies. Among them, Kotnik  suggesteFuture modeling approaches should encapsulate the biophysical concept of cell-field interaction. This is even more important for the modeling works focusing on the mechanisms of neural control by modern technologies, such as TMS and tDCS, in the treatment of neurological diseases.Preliminary modeling studies that include some aspects of cell-field interaction have yielded a better description of the system and provided more acute simulation results that better represent biological authenticity. In the modeling of DBS of the subthalamic nucleus (STN) and its neighboring regions, Sotiropoulos and Steinmetz  includedWe propose a hybrid method in modeling electric effects by combining “biophysics modeling” and “engineering modeling”. The core of the hereby proposed approach relies on the consideration of cell-field interactions and its dependency on tissue properties, as argued in this review. The following offers several insights into our approach: 1. Because ITP depends on tissue non-homogeneity, a detailed morphological description of the cell geometry and electrical properties at a microscopic cellular level should be implemented in the model to calculate the electric field. 2. ITP depends on the “instant” conductivities in the intracellular space, the membrane, and the extracellular space. In addition, activation of the membrane will change these conductivities through mechanisms such as voltage-gated channel opening and influx/efflux of ions. Therefore, an “instant” update of the tissue conductivities is necessary during simulations. 3. If more than one cell is modeled, as in a high-density cell medium, the interactions between the cells/axons through extracellular electric field coupling must also be considered, as the electric field generated by a polarized neuron may have “secondary” effects on its neighboring neurons/axons and vice versa.Several lines of converging experimental and modeling substantiations have suggested a broader frame of reference in which the interaction between the cells and the electric field might play significant roles in determining the ultimate polarization of the neuronal tissue under electric and magnetic stimulation. The inhomogeneous tissue property seems to affect this interaction and cellular polarization. The emerging methodology of combined physics modeling and engineering modeling, which takes into account the cell-field interaction, will provide a more accurate quantitative understanding of the neuronal activation by electric current. A joint effort of modeling and experimental research can further illustrate the significance of cell-field interaction and its biological effects during electric stimulation.


Myocardial architectural abnormalities, have been identified in hypertrophic cardiomyopathy(HCM) gene mutation carriers without hypertrophy(G+LVH-). Some of these changes may be related to the underlying mutation, but whether they can predict gene carriage in relatives of HCM probands is unknown. Cardiac trabeculae may be prominent in overt HCM, suggesting they could form part of this constellation of abnormalities but previous techniques have not permitted more detailed study. We developed a fractal method for quantitation of trabeculae, tracked their development in embryonic mice and applied it to humans imaged by CMR. We hypothesize that fractal analysis may detect abnormal trabeculae in HCM mutation carriers before development of LVH and that a combination of cardiac architectural abnormalities could be used to predict gene carriage in HCM.TRABECULAE IN MOUSE EMBRYONIC DEVELOPMENT-63 Murine hearts were examined from the time of ventricular septation(E14.5) till just before birth(E18.5). Trabeculae ware charted by fractal analysis of high-resolution episcopic microscopy images using a box-counting method. HUMAN MORPHOLOGY-74 G+LVH- sarcomere mutation carriers(29 ± 13 yr[SD]|51%M) were identified in 12 US-centers(HCMNet|n = 35) and UCL(n = 39). Subjects underwent CMR and fractal analysis. Results were compared with 111 overt HCM patients and 136 matched controls(36 ± 16 yr|63%M). We analyzed a single-center(UCL) G+LVH- case-control cohort to identify factors associated with gene carriage, evaluating anterior mitral valve leaflets(AMVL), wall thickness, clefts, trabeculae and other variables. We validated identified associations in the multi-center HCMNet cohort, and combined significant parameters into a model for predicting genetic carriage.In mice a fractal atlas of trabecular development showed decreasing complexity across the basal LV while complexity in the mid/apical LV rose again just before birth and by the European Union (Science and Technology Research Grant). Her work on HCMNet in Bethesda (NIH) and Boston (BWH) was funded by the UCL Charlotte and Yule Bogue Research Fellowship. Murine HREM Experiments are funded by the The Wellcome Trust .


Objective: Although numerous studies have found higher rates of abortion and still births following consanguinity , the question of whether consanguinity significantly increases the risk of neonatal death has inadequately been addressed.This study aims to evaluate familial marriage effects on neonatal death in rural areas in Iran. Materials and methods: In this nested case-control study, 6900 newbornswho were born in rural areas of Kohgiluyeh and Boyerahmad Province (South-West of Iran)were followed till the end of neonatal period, and neonatal death was the outcome of interest. Subsequently 97 cases and 97 controls were selected in study cohort by using risk set sampling model. Crude and adjusted odds ratios (OR) were estimated by usinga conditional logistic regression model.Results: In the final model, prematurity (OR = 5.57), low birthweight (LBW) (OR = 7.68), consanguinity (first cousins) (OR = 5.23), C-section (OR = 7.27), birth rank more than 3 (OR = 6.95) and birthsinterval less than 24 months (OR = 4.65) showed significant statistical association with neonatal mortality (p < 0.05).Conclusion: According to our findings, after adjusting the effects of other significant risk factors, familial marriageto first cousins is considered asan important risk factor for neonatal death. Neonatal mortality rate is one of the most important indicators forthe evaluation of children health status and improvement of this health indicator is quite gradual in rural areas of Iran . ConsangIn assessing the effects of consanguinity on neonatal and infant death, it is clearly accepted that variables such as maternal education, maternal age, birth intervals, gestational age and birth weight need to be adequately controlled .Altough numerous studies have found higher rates of abortion and still births following consanguineous marriages, for countries such as Iran the question of whether consanguinity significantly increased the risk of neonatal death is inadequately addressed.This study was done to give an evidence-based answer to this question and to provide a better evaluation of familial marriage effects on neonatal death in rural areas in Iran. To achieve this aim, we tried to use a sophisticated design as well as modern analytic techniques.This research was carried out as a nested case-control study and the study cohort included all of the neonates bornduring 12 months in rural areas of Kohgiluyeh and Boyrahmad province which is located in South-West of Iran. All of the cohort subjects were followed during the first 28 days of life and the outcome of interest was the neonatal death.For each case at the time of death, one control was randomly selected among all newborns with same birth date. According to the risk set sampling method, 97 controls were selected due to occurrenceof 97 cases of neonatal death in the 6900 studied cohort.The sample size was enoughto establish regression method analysis, based ongeneral rule of 5-10 subjects per variable in each comparison group.The dependent variable was neonatal death andtheindependent variables were parents relation , gender , gestational age (<37 weeksvs. ≥37 weeks), birth weight (<2500gr vs. ≥2500gr), maternal age (<18 or > 35 vs. ≥18 or ≤ 35), birth rank (>3 vs. ≤3), delivery route ) and birth spacing (<24 months vs. ≥ 24 months). The data were analyzed using univariate and multivariate conditional logistic regression methods in Stata software  version 10.Based on descriptive results, there are moderate discrepancies in frequencies of consanguineous marriages between the two groups . CompariIn the next step, each risk factor with marked association  was selected for multivariate analysis. Thus, conditional logistic regression model included thebirth weight , gestational age , parents relation , births spacing , delivery route  and birth rank .Final model includes following variables with significant statistical association : close consanguinity (adjusted odds ratio (AOR = 5.23), prematurity (AOR = 5.57), LBW (AOR = 7.68), C-section (AOR = 7.27), birth rank more than 3 (AOR = 6.95) and births spacing less than 24 months (AOR = 4.65) .This studyshows that first cousin marriages, prematurity, LBW,C-section, birth spacing less than 24 months and birth rank more than 3were potential risk factors for neonatal death.In this study, an increased risk of neonatal death was found in the consanguineous group and this finding is consistent with previous similar studies in Iran ,15. AlsoIn thisstudy, gender of neonate was not a risk factor which is consistent with resultsof a study done in Kurdistan Province of Iran. But delivery route (C-section) which did not have a significant effect in the above-mentioned study, revealed higher OR with significant statistical association in present study .Our observations are similar to a case-control study which was conducted in Brazil and the results indicated that prematurity and LBWwere risk factors for neonatal death. They did not estimate significant OR for delivery route but we identified C-section as an important risk factor. Neither of the studies showed significant correlation between maternal age and neonatal death . In thisNumerousinvestigations have shown that LBW with or without prematurity plays in a complex causal framework of neonatal death, involving genetic and environmental factors related to socioeconomic status - 23. ThuThe key findings of the present study is a significant positive association between close consanguinity and neonatal death, after controlling the effects of prematurity, LBW, C-section, birth spacing less than 24 months and birth rank more than 3.


January is National Birth Defects Prevention Month. Each year, birth defects affect approximately one in 33 newborns in the United States . Birth dμg of folic acid daily   . Health-