Preterm birth (PTB), a leading cause of infant mortality and morbidity, has a complex etiology with a multitude of interacting causes and risk factors. The role of environmental contaminants, particularly bisphenol A (BPA), is understudied with regard to PTB.In the present study we examined the relationship between longitudinally measured BPA exposure during gestation and PTB.A nested case–control study was performed from women enrolled in a prospective birth cohort study at Brigham and Women’s Hospital in Boston, Massachusetts, during 2006–2008. Urine samples were analyzed for BPA concentrations at a minimum of three time points during pregnancy on 130 cases of PTB and 352 randomly assigned controls. Clinical classifications of PTB were defined as “spontaneous,” which was preceded by spontaneous preterm labor or preterm premature rupture of membranes, or “placental,” which was preceded by preeclampsia or intrauterine growth restriction.Geometric mean concentrations of BPA did not differ significantly between cases and controls. In adjusted models, urinary BPA averaged across pregnancy was not significantly associated with PTB. When examining clinical classifications of PTB, urinary BPA late in pregnancy was significantly associated with increased odds of delivering a spontaneous PTB. After stratification on infant’s sex, averaged BPA exposure during pregnancy was associated with significantly increased odds of being delivered preterm among females, but not males.These results provide little evidence of a relationship between BPA and prematurity, though further research may be warranted given the generalizability of participant recruitment from a tertiary teaching hospital, limited sample size, and significant associations among females and within the clinical subcategories of PTB.http://dx.doi.org/10.1289/ehp.1408126Cantonwine DE, Ferguson KK, Mukherjee B, McElrath TF, Meeker JD. 2015. Urinary bisphenol A levels during pregnancy and risk of preterm birth. Environ Health Perspect 123:895–901;  Preterm birth (PTB), defined as delivery before 37 weeks completed gestation, is a leading cause of infant mortality and significant precursor to future morbidity. Overall rates of PTB in the United States are significantly higher than several decades ago, with persistent racial and economic disparity . The etiBisphenol A (BPA) is a high production–volume chemical most commonly used in the manufacturing of epoxy resins and polycarbonate polymers. Downstream applications include, but are not limited to, a variety of consumer products such as food can linings, water bottles, dental sealants, thermal receipts, medical equipment, flooring, reusable food and drink containers, and water supply pipes. As these products age or are exposed to high heat or acidic/basic conditions, monomers can be released to the environment . Because2) in some of its effects  of PTB in Mexico City, researchers found that the adjusted odds ratio of delivering at < 37 weeks in relation to a 1-log increase in specific gravity–adjusted third-trimester BPA concentration was 2.5  . Written informed consent was obtained from all participating women, and the study protocol was approved by each institutional review board. In 2011, a nested case–control study of singleton PTBs was selected from the Brigham and Women’s Hospital participant pool , who were originally enrolled as part of this larger prospective birth cohort. These women were originally recruited at two Brigham and Women’s Hospital clinical facilities and one private practice facility. This nested case–control study consisted of 130 women who delivered before 37 weeks of gestation and 352 randomly selected women who delivered at or after 37 weeks. The study was approved by the institutional review boards of Brigham and Women’s Hospital and the University of Michigan.Maternal urine samples were obtained at four visits during pregnancy. Initial visit samples were collected at median 9.7 weeks gestation , visit 2 at median 17.9 weeks , visit 3 at median 26.0 weeks , and visit 4 at median 35.1 weeks . All specimens were stored at –80°C until analysis. Demographic information was collected at the initial visit. Clinically relevant pregnancy characteristics were collected at the initial visit and subsequently at three additional time points throughout pregnancy. Gestational age was confirmed by ultrasound scanning at < 15 weeks gestation if inconsistent with last menstrual period dating.We further classified preterm birth by clinical presentation . In thisUrinary BPA concentrations. Total BPA (free + conjugated) was measured in all available urine samples  by NSF International in Ann Arbor, Michigan, based on methods developed by the Centers for Disease Control and Prevention (CDC) (c = PP[(1.015 – 1)/(SG – 1)], where cP represents the SG-corrected BPA concentration (nanograms per milliliter), P represents the measured concentration in urine, 1.015 is the median SG of all samples measured, and SG represents the specific gravity of the individual sample (on (CDC) . Levels on (CDC) . Urinaryl sample . Both unStatistical analysis. Analysis was performed using SAS version 9.2  and R version 2.15.2 , prepregnancy body mass index (BMI), smoking status during pregnancy (yes/no), parity (nulliparous/parous), prior history of preterm birth (yes/no), and use of assisted reproductive technology (ART) (yes/no). As a sensitivity analysis, we explored whether addition of either time point specific summed di(2-ethyheyxl) phthalate (ΣDEHP) or average urinary ΣDEHP, which were shown earlier in this population to be associated with an increased odds of PTB, altered any effect estimates , mono(2-ethylhexyl) phthalate (MEHP), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) was also explored, but results were not included because separate adjustment did not alter the results seen with adjustment for ΣDEHP. ΣDEHP, MEHP, MECPP, and MBP metabolites were associated with preterm birth in a previous study , and education level were included stimates . Adjustmus study  in this Windows of vulnerability to BPA exposure were then assessed by fitting separate logistic regression models with preterm birth as the outcome to calculate odds ratios (ORs) corresponding to BPA levels from each individual visit and, due to low correlation between time points, together in the same model. We did not control for multiple comparisons.To explore the longitudinal nature of the relationship between BPA exposure and risk of PTB, we initially used linear mixed-effects models to generate random slopes and intercepts for BPA exposure over time. Random intercepts and slopes were then used as predictors in the adjusted logistic regression models. We also fit generalized additive mixed models (GAMMs) and linear mixed-effects models using BPA concentrations as the response variable, and preterm birth, gestational age at sample collection, and other covariates as the explanatory variables, to explore the interaction between preterm birth and gestational age at time of urine sample collection.For additional secondary analyses, we repeated the above steps for subtypes of preterm birth, including placental and spontaneous preterm birth. PTB cases that did not fit into the subtype were excluded from analysis instead of being recoded as controls. We additionally recreated models of overall preterm birth stratified by infant sex. Covariates from full models were kept the same for sensitivity analyses for comparison.2 BMI) or obese (> 30 kg/m2 BMI). These population characteristics did not differ significantly between PTB cases and controls . Spearman correlations between study visits for BPA were low and ranged from 0.17 to 0.26 . ICC for SG-corrected BPA indicated low temporal reliability , and ICCs were slightly higher in cases of PTB compared with controls  of overall preterm birth in association with averaged and cross-sectional  urinary BPA levels are presented in p = 0.67). n = 25). This relationship persisted even after additional adjustment for ΣDEHP metabolites. No significant relationships were observed between BPA concentrations and the medical protocol–driven PTBs (data not shown).Generally, in both crude and adjusted models no significant relationships were observed between overall preterm birth and either averaged  or individual-visit urinary BPA levels, although, except for visit 3, ORs tended to be > 1.0 . In our After stratifying by sex, we observed significantly elevated odds of overall PTB for female infants in relation to averaged BPA concentrations , though statistical significance did not persist after additional adjustment for phthalate concentrations . We obseWithin our nested case–control study of mothers giving birth in the Boston area, we found no significant associations between averaged or cross-sectional urinary BPA levels and PTB when treating PTB as a single, homogeneous outcome. After further classifying PTB by either spontaneous or placental etiology, no significant relationships with BPA exposure developed, except for significantly elevated odds of spontaneous preterm birth in association with levels measured at visit 4 . However, these associations should be interpreted cautiously because of the low number of cases in each subgroup. After additional stratification on infant sex, we observed significantly elevated odds of overall PTB for female but not male infants in association with averaged BPA exposure. As far as we are aware, this is the first study to use a more clinical and biological classification of PTB, and to assess BPA exposure at multiple time points during pregnancy with regards to the risk of PTB.n = 30 cases, n = 30 controls) of PTB in Mexico City, the unadjusted OR of delivering at < 37 weeks in relation to specific gravity–corrected third-trimester urinary BPA concentration was 2.5   . It is iOther studies have found inconsistent evidence between BPA and gestational length. In a small study of 40 pregnant women living in southeastern Michigan, there were no differences in gestational length between women with plasma BPA concentrations > 5 and ≤ 5 ng/mL . Wolff eIn our secondary analysis, we further analyzed preterm birth by differing clinical presentation. Our intention was not only to explore potential mechanistic links between BPA exposure and PTB but also to address potential bias that could arise from including medically indicated protocol-driven PTBs. These preterm births, usually after 36 weeks, are commonly delivered for reasons associated with obstetrical practice rather than actual underlying pathobiology, and without intervention they would have likely proceeded to term. By excluding certain types of protocol-driven PTBs in our data set, we observed a strengthening of our overall associations , suggesting that inclusion of these PTBs biases our results toward the null.in vitro that BPA exposure at environmentally relevant concentrations can affect the proliferative process in trophoblastic cells through the ERRγ1. Additionally, that study demonstrated the presence of ERRγ1 in several trophoblastic cell lines and isolated extravillous and villous cytotrophoblasts from first-trimester placenta, further suggesting another potential mechanistic link to disruption of normal placental development by exposure to BPA (n = 35) placental preterm births in our population, and calculated odds ratios, though not statistically significant, were somewhat elevated.Placental preterm birth comprised preterm birth following preeclampsia or intrauterine growth restriction (IUGR), which can result from impaired placentation early in pregnancy. The intrauterine environment in early stages of placentation is highly sensitive, and increases in oxidative stress can lead to apoptosis and altered cytotrophoblast turnover rate in the developing placenta . Mechanie to BPA . Even thSpontaneous preterm birth was clinically defined as resulting from spontaneous preterm labor or preterm premature rupture of membranes, both of which primarily arise from inappropriate initiation of an intrauterine inflammatory cascade . BPA hasOur results suggest that female infants may be more sensitive to being delivered preterm in relation to gestational BPA exposure than males. Endocrine-disrupting effects of BPA are well studied, and multiple animal and human studies have reported evidence of sex-specific adverse health effects resulting from BPA exposure . Only onOur study had several strengths, including a repeated time point assessment of BPA exposure, ultrasound dating of gestational age, physician-validated clinical outcomes, and a large number of subjects and preterm cases, which allowed for exploring the heterogeneous nature of PTB. Still, results from our secondary analyses of subtypes of PTB and stratification on infant sex should be interpreted cautiously, given that we were limited in our number of placental and spontaneous PTB cases and are likely to be underpowered to detect subtle relationships. There was also no control for multiple comparisons, which may lead to an inflated type 1 error rate. We acknowledge that the few significant associations found in our analysis may be attributable to chance alone, and larger follow-up studies to replicate the findings are warranted. We substituted BPA values below the LOD with LOD divided by the square root of two in the present study. Although several authors have shown that using a maximum-likelihood estimate for LOD can reduce the inherent bias in using a substitution method for LOD, the improvements are minimal (1–2% reduction in bias) .Additionally, this study was limited in our understanding of other residual confounders, such as diet, which may be associated with BPA levels and PTB. It is worth noting that the generalizability of our population may be restricted because Brigham and Women’s Hospital is a major referral center for high-risk pregnancies; thus, our population might have a higher than normal proportion of women with prior conditions that could lead to medically indicated protocol-driven PTB . Regardless, this population was originally collected in a prospective fashion from a major regional hospital in a large urban center whose overall demographic breakdown of delivery patients is reflective of the general U.S. population. Our choice of a nested case–control design stemmed from financial considerations for exposure assessment and may have some inherent limitations. Analyzing continuous gestational age in a time-to-event framework in the entire cohort would yield more informative inference if we could obtain exposure measures on a larger cohort; however, given the resources, the case–control design maximizes our power to detect exposure–outcome associations. Although, to our knowledge, this was the first study of preterm birth or gestation length to use multiple urinary BPA concentrations from each woman, the low temporal reliability of BPA concentrations across pregnancy may indicate that even with three to four repeated measures, there may still be substantial nondifferential exposure measurement error, which would further limit statistical power to detect associations.In conclusion, although we found no consistently significant associations between urinary BPA concentrations and prematurity, further research may be warranted given our significant adverse findings with spontaneous PTB and late-pregnancy urinary BPA concentrations and stratified analysis effects in females. Additionally, this study highlights the need to model PTB by underlying causes in population studies not only to help inform potential mechanistic links, but also to reduce potential bias from inclusion of medically indicated protocol driven PTBs.(201 KB) PDFClick here for additional data file.


Dentigerous Cyst/developmental cyst of benign odontogenic origin are ones that surround the crown of impacted, embedded, unerupted or developing teeth. Dentigerous cyst is second most common cyst of the oral cavity after radicular cyst. They are usually solitary in occurrence and mostly associated with the mandibular third molars. Dentigerous cysts involving impacted second premolars are rarely reported in the literatures. We present a rare case of dentigerous cyst in a 12-year-old female patient associated with an impacted mandibular second premolar.How to cite this article: Mishra R, Tripathi AM, Rathore M. Dentigerous Cyst associated with Horizontally Impacted Mandibular Second Premolar. Int J Clin Pediatr Dent 2014;7(1): 54-57. Dentigerous Cyst/developmental cyst of odontogenic origin are ones that surround the crown of impacted, embedded, unerupted or developing teeth. Dentigerous cyst is second most common cyst of the oral cavity after radicular cyst.Incidence of dentigerous cyst is 20 to 24% of the entire epithelial lined jaw cyst. Frequency of 1.44% cyst for every 100 unerupted teeth in general population with more frequently occurs during 2nd – 3rd decades of life. Also occurs in children and adolescence during mixed dentition period. Affects males more frequently than females and is seen most commonly around the crowns of mandibular third molars, maxillary canines and maxillary third molars.A 12-year-old girl reported to the Department of Pedo-dontics and Preventive Dentistry, Babu Banarasi Das College of Dental Sciences, Lucknow with a chief complaint of a painful swelling in the lower left back region of jaw. On general examination, no abnormality detected.On extraoral examination, asymmetrical face with swelling on lower left side of face and palpable and tender left submandibular lymph node .see On intraoral examination, grossly carious mandibular left deciduous second molar with circumscribed swelling. Swelling extended from distal side of deciduous first molar to mesial side of permanent first molar along the vestibule. On palpation swelling was painful and firm see .see On radiographic examination, OPG reveals a well defined unilocular radiolucent area characterized by sclerotic boarder in the region of deciduous second molar surrounding the crown of horizontally impacted left second premolar. The dentigerous cyst in OPG is of central variety because the crown is enveloped symmetrically. The follicular space is 19.0 mm that shows dentigerous cyst when the space is more than 5 mm see .see On histopathologic examination of the aspiration biopsy showed a cystic lesion, and presumptive diagnosis of the dentigerous cyst was made see .Surgical enucleation of the cyst to marsupialization with decompression of cyst via fenestration may be treatment of choice. In the present case, extraction of mandibular left deciduous second molar followed by surgical enucleation of the cyst was done and fragment was given for biopsy. Cystic sac enclosed the second premolar tooth firmly at the cervical margin  and 3.12 Since cysts can attain considerable size with minimal or no symptoms, early detection and removal of the cysts is important to reduce morbidity. Although evidence in the literature suggests that dentigerous cysts occur more frequently during the second decade of life,34these lesions can also be found in children and adolescents. The incidence of dentigerous cysts is twice as high in male patients compared to female counterparts in contrast to the present case.56 Whites are more affected than blacks.7Dentigerous cysts are developmental cyst of odontogenic origin and the most prevalent, comprising 14 to 24% of the entire jaw cyst.710Occasionally these cysts become painful when infected causing swelling and erythema. The cyst is usually small but when large, results in the expansion and thinning of the cortex leading to pathological fracture.79 Although the clinical presentations are classical of a dentigerous cyst, in our case it is associated with horizontally impacted mandibular second premolar which has not been reported.Dentigerous cysts are usually solitary, slow growing, asymptomatic lesions that are incidentally found during routine radiographs taken to identify a missing tooth. They can occur at any location of the jaw but frequently seen in relation to impacted mandibular third molars followed by the maxillary canines and maxillary third molars.89 Although they mimic a normal tooth follicle, literatures suggest any follicular space of more than 4 mm to be a dentigerous cyst.7 Radiographically the cyst is classified according to its relation with the involve tooth crown as central, lateral and circumferential type. The central type is the most common and presents surrounding the crown. The lateral dentigerous cyst is that, which partially surrounds the crown and extends along the side of the root. The circumferential variant surrounds both the crown and the root of the involved tooth.8Radiographic features are specific to the lesion characterized by a well defined radiolucency circumscribed by a sclerotic border, associated with the crown of an impacted or unerupted tooth. The borders may be ill-defined when infected. Rarely may they be found with odontoma or a supernumerary tooth.11 The epithelium may be hyperplastic with the presence of hyaline bodies associated with inflammation. The connective tissue is more collagenous when infamed and contain varying degree of chronic infammatory cell infltration.79 Occasionally the cyst lining may contain ciliated and mucous secreting cells.7 Dentigerous cysts are treated most commonly by Enucleation,2 Marsupialization13 and decompression of cyst by fenestration.4 Motamedi et al suggested the criteria for selecting the treatment modality based on the age, size, location, stage of root development, position of the involved tooth and relation of the lesion to the adjacent tooth and vital structure.12 The most preferred treatment is enucleation with the removal of unerupted or impacted tooth. If the cyst is associated with the canine or premolar with favorable eruptive position, then extraction of the associated tooth is deferred. Large dentigerous cyst may be treated with marsupialization followed by enucleation. The prognosis is excellent when the cyst is enucleated in toto and recurrence is rare. As the lining epithelium has the pluripotential capacity, these lesions may progress to ameloblastoma, mucoepidermoid carcinoma and squamous cell carcinoma.7Histologically, the lumen is lined by 2 to 4 cell layers of cuboidal to flattened nonkeratinized epithelial cells but may form keratin by metaplasia.Dentigerous cyst associated with an impacted mandibular second premolar is extremely rare. As the clinical finding of unerupted tooth may be the only presenting symptom of a dentigerous cyst, a thorough radiographic evaluation is mandatory for all unerupted teeth that have well past their expected eruption date. Serial panoramic flms are a common and reliable tool for the diagnosis and assessment of progress in healing of space occupying lesions of jaw bones.Why this paper is important to pediatric dentists Healing and bone regeneration is excellent in pediatric patients. Serial panoramic flms is a common and reliable tool for the diagnosis and assessment of progress in healing of space occupying lesions of jaw bones. Early diagnosis and being able to differentiate a developmental cyst from infammatory cyst is crucial in pediatric patients for subsequent treatment planning to reduce potential morbidity.


Recognition that ascending infection leads to preterm birth has led to a number of studies that have evaluated the treatment of vaginal infections in pregnancy to reduce preterm birth rates. However, the role of candidiasis is relatively unexplored. Our aim was to undertake a systematic review and meta-analysis to assess whether treatment of pregnant women with vulvovaginal candidiasis reduces preterm birth rates and other adverse birth outcomes.We undertook a systematic review and meta-analysis of published randomised controlled trials (RCTs) in which pregnant women were treated for vulvovaginal candidiasis (compared to placebo or no treatment) and where preterm birth was reported as an outcome. Trials were identified by searching the Cochrane Central Register of Controlled Trials, Medline and Embase databases to January 2014. Trial eligibility and outcomes were pre-specified. Two reviewers independently assessed the studies against the agreed criteria and extracted relevant data using a standard data extraction form. Meta-analysis was used to calculate pooled rate ratios (RR) and 95% confidence intervals (CI) using a fixed-effects model.asymptomatic candidiasis, with a total of 685 women randomised. Both trials compared treatment with usual care . Data from one trial involved a post-hoc subgroup analysis (n = 586) of a larger trial of treatment of 4,429 women with asymptomatic infections in pregnancy and the other was a pilot study (n = 99). There was a significant reduction in spontaneous preterm births in treated compared with untreated women . Other outcomes were reported by one or neither trial.There were two eligible RCTs both among women with This systematic review found two trials comparing the treatment of asymptomatic vaginal candidiasis in pregnancy for the outcome of preterm birth. Although the effect estimate suggests that treatment of asymptomatic candidiasis may reduce the risk of preterm birth, the result needs to be interpreted with caution as the primary driver for the pooled estimate comes from a post-hoc (unplanned) subgroup analysis. A prospective trial with sufficient power to answer the clinical question ‘does treatment of asymptomatic candidiasis in early pregnancy prevent preterm birth’ is warranted.CRD42014009241PROSPERO  Preterm birth is a major pregnancy complication affecting 5% to 18% of births worldwide . InfantsPreterm birth (birth before 37 completed weeks of gestation) results from either spontaneous onset of labour (including preterm prelabour rupture of the membranes) or a clinical decision that planned birth should occur because of pregnancy complications. The cause of spontaneous preterm birth is often unknown, but intrauterine infection is implicated in up to 40% ,7. The lThe role of infection in preterm birth is thought to be a chronic process, with early pregnancy a period of vulnerability to establishment of inflammatory responses that may be the trigger for preterm parturition ,9,11. OrCandida colonization [Candida colonisation may disrupt normal vaginal flora so that there is a decrease in lactobacilli and an increase in proinflammatory organisms [Pregnancy increases the frequency of vaginal nization . This isnization . Candidarganisms ,13. Howerganisms .Candida species among women at 22 to 30 weeks gestation [Studies utilising population-based data from Hungary reported that vaginal clotrimazole treatment of candidiasis during pregnancy was associated with a 34% to 64% reduction in the prevalence of preterm birth -17. In cestation ,19. TherThe study procedure and outcomes were pre-specified . We idenRandomised controlled trials (RCT) in which pregnant women were treated for symptomatic or asymptomatic vulvovaginal candidiasis and where preterm birth was reported as an outcome were the pre-specified eligibility criteria . Only RCThe titles and abstracts of all potential studies identified for inclusion as a result of the search strategy were independently assessed for inclusion by two reviewers. The two reviewers also assessed the full papers of potentially eligible studies or where eligibility was unclear. Discrepancies at both stages of study selection were resolved through discussion.The two review authors also independently assessed the risk of bias  for each study using the following pre-specified criteria: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment and completeness of outcome data . Again, Preterm birth (<37 completed weeks of gestation) following spontaneous onset of labour or following preterm prelabour rupture of membranes.Any birth before 37 weeksMedically indicated birth (by labour induction or prelabour caesarean section) before <37 weeksBirth before 32 weeksBirth weight less than the tenth percentile for gestational ageBirth weight <2,500 gApgar score of less than 7 at 5 minRespiratory distress syndromeUse of mechanical ventilationDuration of mechanical ventilationIntraventricular haemorrhageRetinopathy of prematurityChronic lung diseaseNecrotising enterocolitisPerinatal mortality Admission to neonatal intensive care unitNeonatal length of hospital stayBreastfeedingPreterm prelabour rupture of the membranesSpontaneous pregnancy loss <20 weeks gestation,Mode of birthDuration of maternal hospitalisation at the time of birthMaternal views/satisfaction with the therapyMaternal anxietyData were extracted independently by the two reviewers, and disagreements were resolved by discussion. A standard data extraction form was used to extract data on study characteristics, methods and study results. All data on study results were entered into an Excel Spreadsheet.2 test. Meta-analysis was used to calculate pooled risk ratios (RR) and 95% confidence intervals (CI) using a fixed-effects model (Mantel-Haenszel), unless the assumption of homogeneity was rejected (P < 0.1) when a random effects model would be used. Statistical analyses were performed using the ‘metan’ command in STATA .Characteristics, main findings and risk of bias assessment were tabulated for each study. The raw data presented in the included studies were used to determine the outcome rates for intervention and control groups of each study. Where data were missing , the results reported in the studies as the numerator (no information on those lost to follow-up) and denominator  were used; no imputation of outcomes was made. There were two pre-specified subgroup analyses for the primary outcome: symptomatic and asymptomatic candidiasis, and commencing treatment before 20 weeks gestation versus after 20 weeks gestation. For each dichotomous outcome of interest within individual studies, relative risks (RR) and 95% confidence intervals (CIs) were calculated according to the intention to treat. The assumption of homogeneity of treatment effect between studies was assessed using Cochran’s Q test statistic and the IA total of 1,014 unique articles were identified  were randomised to treatment  or to usual care . There was no pre-specified subgroup analysis by infection type so the information on treatment of asymptomatic candidiasis from this trial was extracted from the published paper post-hoc.The aim of the study by Kiss and colleagues was to assess whether general screening for, and treatment of, asymptomatic vaginal infections  was effective in reducing the rate of preterm birth and late miscarriage . Women wDrawing on post-hoc subgroup analyses of the Kiss trial, Roberts and colleagues undertook a pilot study with the specific aim of assessing treatment of asymptomatic candidiasis to prevent preterm birth . The stuCandida colonisation rate was 14.1% (15 to 19 weeks gestation) in the Kiss et al. study and 19.6% (12 to 19 weeks gestation) in the Roberts et al. study. Kiss et al. reported that women were to be retested, and if necessary retreated, at 24 to 27 weeks. However, overall, only 22% of women in the entire treatment arm had a follow-up gram stain and of these 27% still had a vaginal infection present, including 78 (27%) with candidiasis, all of whom were retreated. Roberts et al. report a posttreatment colonisation rate of 48% on average 10 weeks after recruitment but asymptomatic women were not offered further treatment.The asymptomatic Both studies utilised computer random number generation and central randomisation procedures. In the Kiss et al. study, women who were randomised to clotrimazole treatment (and their obstetricians) were not blinded to their treatment allocation. However, the untreated group (93% of women screened) included both women without infections and those with asymptomatic infections who were randomised to usual care. Clinicians and women were blinded to the colonisation-status within this group. Roberts et al. used a similar method but women allocated to clotrimazole treatment were notified and treated by the study personnel. So, although the women in the treatment arm were not blinded, clinicians were blinded to treatment allocation unless it was revealed during the subsequent pregnancy management. Like the Kiss et al. study, the untreated group (90% of participants) included women with and without asymptomatic candidiasis and the clinicians and women were blinded to this information. This partial blinding of participants and personnel to exposure status was considered unlikely to affect results. Furthermore, the assessment of outcomes from medical records was blinded and gestational age determination is not subjective (based on ultrasound dating and date of birth). The candidiasis subgroup analysis in the Kiss et al. study was not pre-specified but extracted post-hoc from the published paper. Furthermore, Kiss et al. did not report loss to follow-up and exclusions by treatment arm or infection subgroups so the number of women with candidiasis for whom outcome data were missing could not be determined. However, overall 3.2% women were lost to follow-up and there were 3.0% post-randomisation exclusions . The follow-up rate was 99% in the Roberts et al. study (outcome information was missing for one woman) with no post-randomisation exclusions.For both studies, the risk of bias was considered low for all aspects assessed: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment and completeness of outcome data. However, neither study had a published protocol so it is possible that there was selective choice for reporting of secondary outcomes. Acknowledged funding for the trials was from government sources, and there is no suggestion  that the trial treatment was provided by a pharmaceutical company Table .The only outcome available from both studies was spontaneous preterm birth. Meta-analysis showed an overall reduction in spontaneous preterm birth  with similar point estimates from both studies but little contribution  around the estimate from the pilot study by Roberts et al. Figure . While RThis systematic review found two trials comparing the treatment of asymptomatic vaginal candidiasis in pregnancy with usual care  for the outcome of preterm birth. The findings provide support for the hypothesis that treatment of asymptomatic candidiasis may reduce the risk of preterm birth. Although the two studies had similar methods, treatment regimens and findings among general maternity populations in different countries, the result needs to be interpreted with caution as the primary driver for the pooled estimate is a post-hoc subgroup analysis of the Kiss trial. We believe that the meta-analysis result supports the need for a larger trial that specifically addresses the question of whether the treatment of asymptomatic candidiasis early in pregnancy can reduce the risk of spontaneous preterm birth. If a simple, inexpensive intervention is demonstrated to reduce spontaneous preterm birth, this would change current maternity care internationally. A significant reduction in preterm birth would not only reduce perinatal mortality and morbidity, but also have major resource implications, such as reduced need for neonatal intensive care and childhood hospitalisations.The two trials reported different colonisation rates of asymptomatic candidiasis (14.1% and 19.6%) ,35. ThisBoth trials included in the meta-analysis used a similar design, described by Roberts et al. as a Prospective, Randomised, Open-label, Blinded-Endpoint (PROBE) design. PROBE designs have been used in cardiovascular disease trials -46, and Candida from the vagina. Furthermore, the susceptibility of both Candida albicans and non-albicans Candida vaginal isolates to azole antifungal agents, such as clotrimazole, supports the continued practice of azole antifungal agents for empirical therapy of Candida vaginitis [Clotrimazole, the treatment used in both the included studies, is classified as a category A drug meaning it has been used by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed . Large paginitis .Candida is considered a vaginal commensal organism [Despite the interest in infection as a risk factor for preterm birth, we found only two trials  to contribute to this review. Perhaps as organism , the rolorganism ,50-53. HCandida colonisation in pregnant women with symptomatic candidiasis. The availability of only two trials precludes the opportunity to explore issues like heterogeneity and any impact of reporting biases in sensitivity and subgroup analyses. Only one outcome (spontaneous preterm birth) was available from both studies, and future trials should consider other potential pregnancy outcomes and treatment side effects [Candida eradication [Rather than pregnancy outcomes, previous research has mostly focussed on the question of best treatment for eradicating  effects . Althougdication ,37,55-62dication ,58,60,62Inclusion in the meta-analysis of some women with missing outcome information is unlikely to change the conclusions. From the Kiss et al. trial, the extent of missing data on the outcome of preterm birth for women with candidiasis could not be determined but was approximately 3% among all women with asymptomatic infections. One woman (of 99) in the Roberts et al. trial was missing information on birth outcome. Only Roberts et al. reported other birth outcomes for the treated and untreated groups of women but this was limited by small event numbers: any preterm birth , spontaneous vaginal birth , instrumental vaginal birth , caesarean section , birth weight <2,500 g  and nursery admission . The remaining pre-specified outcomes were not reported in either of the included studies.Candida in all women nor prevent recolonisation. Posttreatment ‘Candida eradication rates’ (assessed at 3 to 6 weeks) for symptomatic candidiasis in pregnancy range from 69% to 100%  [asymptomatic candidiasis was 73% (assessed at 4 to 5 weeks) in the Kiss trial [The rationale of the two included trials is that early treatment of vaginal infections is necessary for effective prevention of infection-related preterm birth, as early pregnancy is the period of greatest risk for the establishment of inflammatory responses to low virulence organisms that increase the risk of preterm birth -9. Treatian 88%)  and for ss trial  and 52% ss trial . HoweverThe findings of this review, that treating asymptomatic candidiasis in early pregnancy may reduce spontaneous preterm birth rates, need to be interpreted with caution. The findings are based on only two published trials  both using clotrimazole and both in asymptomatic women, and the post-hoc subgroup analysis was the primary driver for the pooled estimate. Furthermore, there were insufficient data on other important infant and maternal outcomes. This systematic review suggests that a trial with sufficient power to answer the clinical question ‘does treatment of asymptomatic candidiasis in early pregnancy prevent preterm birth’ is warranted.


Method of Study. Four neonates underwent surgery for vallecular cyst by using Arthrocare ENT coblator system. Results Obtained. All the four cases presented in stridor and difficult intubation was also a concern which necessitated a swift, high precision instrument with almost immediate results. Coblation excision includes direct contact with vallecular cyst, improved targeting of the cyst, and preservation of normal tissue. All the four cases had an uneventful postoperative period and smooth recovery and had an early discharge from the hospital. Conclusions. Early diagnosis and intervention hold the key for an early recovery and for minimizing nutritional disturbances secondary to poor feeding in cases of neonatal vallecular cysts.The objective of the case series is to understand the clinical and surgical aspects of new minimally invasive technique of coblation in cases of vallecular cysts in neonates.  Congenital vallecular cyst is a rare but potentially dangerous cause of stridor in neonates and young infants. Without recognition and proper therapy, the resulting airway obstruction can lead to serious morbidity and mortality –9. When A 2-month-old term female baby was referred to us for noisy breathing and progressive respiratory distress. Earlier, the child developed respiratory distress with failure to thrive and noisy breathing. On examination, vitals were stable and there were no dysmorphic features. She had marked inspiratory stridor with suprasternal and subcostal recession and tachypnoea. A provisional diagnosis of severe laryngomalacia was made. A flexible fiberoptic bronchoscopy was done which revealed a cystic mass at the base of the tongue which was obstructing the laryngeal inlet and was pushing the epiglottis. Computed tomography scan showed well-defined nonenhancing fluid filled lesion located at base of tongue 12.2 × 13.4 mm in size  causing 99 m technetium (Tc) pertechnetate scan was performed. Both lobes of thyroid gland were normal in size, shape, and placement. No abnormal tracer uptake was seen in the swelling at the base of the tongue .T3, T4, and TSH levels were also found to be within normal limits.The child was taken up for coblation assisted ablation of the cystic mass of the tongue mass under endoscopic guidance . An EVacThe child had an uneventful recovery with extubation at 24 hours after procedure and thriving well at 3-month follow-up.A term 3-month-old male baby was referred to our centre for progressive difficulty in breathing. He was asymptomatic until 1 month of age when he gradually developed stridor and progressive respiratory stress. He was then referred to our centre, where the child again had an apneic spell requiring resuscitation and was subsequently intubated.Flexible fiberoptic bronchoscopy was done which revealed a large swelling at the base of tongue obscuring the view of laryngeal inlet. Contrast enhanced computed tomographic scan of neck was performed, which showed a well-defined, nonenhancing cystic lesion located at the base of the tongue measuring 12.7 mm × 13.5 mm . The diaA 40-day-old term male child was referred to our center for respiratory distress. The child developed noisy breathing about 10 days after birth which continued to worsen. On examination, child was tachypnoeic with mild dehydration. He was having inspiratory stridor and was using accessory respiratory muscles. A flexible fiberoptic bronchoscopy was done which showed a large mass in the base of tongue close to valleculae, thus causing epiglottis to obstruct the laryngeal inlet.A contrast enhanced computed tomography scan was done which revealed a cystic lesion at base of tongue of 11.7 × 10.3 mm causing significant airway compromise. Thyroid scan revealed that there was no tracer uptake in the region of thyroid gland. No functioning thyroid tissue was appreciated on thyroid scan. A low TSH of 4.7 U/mL was present. The child was started on levothyroxine. The child was taken up for coblation assisted removal of the cyst and was extubated uneventfully 24 hours later.A 4-month-old male was referred with complaints of failure to thrive, noisy breathing, and occasional respiratory distress. The child was a full term normal vaginal delivery; he developed noisy breathing at 15 days of age. The child had frequent episodes of vomiting with features of failure to thrive. The child was treated as a case of laryngobronchomalacia with reflux disease. A contrast enhanced computed tomography scan imaging revealed cystic mass lesion of 10.3 × 8.9 mm in base of tongue compromising the airway due to mass effect on epiglottis.The child was taken up for removal of cyst using coblation. Endoscopic visualization of the cyst was done. The cyst was ablated using coblation.Vallecular cyst although rare is a potentially life threatening condition causing sudden airway obstruction by its location –5. 12–45Vallecular cysts have been reported in various case studies under differential names . Terms uVallecular cyst is a unilocular cystic mass of variable size which arises from lingual surface of epiglottis and contains clear and noninfected fluid . Two majThe infants with vallecular cysts usually present with symptoms during the first few weeks of life , 4. ClinInfants with vallecular cysts may present with a secondary form of laryngomalacia which can be explained by altered airway dynamics caused by progressively enlarging cyst which cause increased inspiratory negative pressures, contributing to supraglottic prolapse .Flexible laryngoscopy or bronchoscopy is usually performed to diagnose the vallecular cyst , 6. TherIn our case series, all cases underwent contrast enhanced computed tomographic scan to see the extent and nature of the mass. A thyroid screening was also performed to rule out the lingual thyroid and thyroglossal cyst and was supplemented by a thyroid scan. In one of the cases, there was total absence of any functioning thyroid tissue which was detected by the thyroid scan.The smallest child was of 40 days old and inspiratory stridor indicated that nature of lesion was arising from supraglottic and/or glottis region. So, the underlying “ball valve” effect should be kept in mind. However, laryngomalacia should also be excluded –14.Haemangioma, cystic hygroma, teratoma, hamartoma, dermoid cyst, lymphangioma, thyroglossal duct cyst, and thyroid remnant cyst should be considered in the differential diagnosis of vallecular cyst –4.Coblation assisted ablation of the vallecular cyst in our case series was a novel technique for the management of the condition. Coblation is a unique modality that can ablate tissue by generating a field of ionized sodium molecules. During the procedure, conductive saline solution is converted to an ionized plasma layer in the gap between the device tip and the tissue. At the tissue plasma interface, there is generation of adequate energy. This energy breaks the molecular bonds resulting in molecular dissociation. This effect is achieved at temperatures of approximately 40–70°C; so, thermal damage is minimal as compared to radiofrequency. This minimally invasive technology resulted in less tissue trauma, minimal bleeding, and reduced postoperative recovery time, thus effectively resolving the problem of hemorrhage and postoperative decannulation.The four cases that we described illustrate how a benign, self-limiting swelling can be potentially life threatening to airway and the superior postoperative outcome secondary to coblation assisted intervention. All the four cases presented in stridor and difficult intubation was also a concern which necessitated a swift, high precision instrument with almost immediate results.The advantages of coblation excision include direct contact with epiglottic cyst, improved targeting of the cyst and preservation of normal tissue, and lower temperatures to prevent excessive burning, thus improving recovery time and minimizing surgical and postsurgical complications; so, it is a simple, safe, and effective method.


Bronchogenic cyst is a congenital malformation, rarely located in the cervical region and almost never involved in a neonate with acute respiratory distress in the delivery room.A female newborn with respiratory distress syndrome caused by a large left cervical mass. Intubation was difficult due to tracheal deviation. Magnetic resonance imaging confirmed a left cervical cyst displacing the trachea and esophagus laterally. Surgical excision was performed via a cervical approach on the 5th day, and pathological examination revealed a bronchogenic cyst. The patient's course was complicated by left vocal cord paralysis and necrotic lesions in the glottic and subglottic regions; she required a tracheostomy on the 13th day. Inflammatory stenosis in the subglottic region required balloon dilation once, 20 days later. Proximal esophageal stenosis induced transient upper airway obstruction with salivary stasis. Decannulation was performed at 2 months and the patient was discharged 10 days later.A bronchogenic cyst can exceptionally obstruct the airways in the neonatal period. Surgical excision is necessary, but postoperative complications may occur if the cyst is in close contact with the trachea and esophagus, including necrotic and stenotic lesions of the upper aerodigestive tract. In those situations, tracheostomy may be necessary for mechanical ventilation weaning and the initiation of oral feeding. Bronchogenic cyst is a congenital malformation of the tracheobronchial tree. It is usually located in the mediastinum or lung parenchyma, though rarely can be seen in extrathoracic locations such as the neck. In 2004, Mehta et al. reported a series of 4 cases of cervical bronchogenic cysts over a 22-year period, with the age of discovery ranging from 3 weeks to 6 years . In 2008+4 gestational weeks in a type 2a maternity ward and delivery was by cesarean section because of abnormal fetal heart rate. The newborn was female with a birth weight of 3045 g. The newborn showed ineffective ventilation from the first postnatal minute, and positive pressure ventilation with a bag and mask was immediately started. A left cervical swelling was also observed. Respiratory distress, with suprasternal tugging and stridor, occurred at every attempt to withdraw ventilatory support. Furthermore, FiO2 of 90 % was required to maintain SpO2 above 90 %. Two attempts of orotracheal intubation failed because the larynx could not be visualized. A more experienced pediatrician was called for help. Standard direct laryngoscopy found a right laryngeal deviation with a restricted laryngeal orifice. After sedation with midazolam , tracheal intubation was achieved at the 3rd attempt, with a 2.5-mm endotracheal tube, at 1 h 30 min after birth. The newborn was then transferred to a type 3 neonatal unit.The patient’s mother received prenatal care during pregnancy, with 3 antenatal US exams showing normal fetal development. Labor was induced at 412 set at 21 %. Clinical examination confirmed a noninflammatory cervical swelling that was soft on palpation. Chest x-ray revealed the endotracheal tube deflected to the right with respect to the spinal axis. Cervical US showed a thin-walled cystic mass measuring 24 × 28 × 37 mm displacing the trachea and the left thyroid lobe medially and forward, and the carotid and jugular vessels laterally and posteriorly. MRI identified a large cystic mass with well-defined walls that laterally displaced the aerodigestive tract  and the use of permissive hypercapnia . On the assumption that the cyst might be squeezing the endotracheal tube, we performed fine needle aspiration of the cyst in the operating room, under general anesthesia, on postnatal day 3. Twenty milliliters of clear liquid was removed for cytological analysis, which revealed both respiratory-type epithelium and squamous epithelium. Rigid bronchoscopy performed at the same time confirmed tracheal compression and no laryngeal fistula. A 3-mm endotracheal tube was put into place to secure the airway. On day 5, surgery using a cervical approach isolated a unilocular cystic structure measuring 25 × 23 × 6 mm in close contact with the trachea and esophagus. Dissection was not possible from the trachea or the esophagus, and limited resection of trachea and esophagus was therefore mandatory, resulting in an opening of both structures. Both were then sutured. Histological examination showed that the cyst wall was composed of fibrous and smooth fibromuscular tissue, with some seromucinous bronchial gland cells. The wall was lined by a layer of respiratory-type ciliated cells. These findings suggested the diagnosis of bronchogenic cyst.In the first 48 h of management, peak inspiratory pressures > 25 cm HAfter the first attempt at extubation on the day after surgery, the infant had respiratory distress due to laryngotracheal edema and left vocal fold paresis that was refractory to treatment with nebulized epinephrine and corticosteroids and required reintubation. The second attempt at 8 days postsurgery was equally unsuccessful. The upper respiratory tract was explored under general anesthesia at a postnatal age of 13 days. We observed edema of the left laryngeal ventricle and the anterior third of the glottis, associated with the necrotic appearance of the mucosa in the left lateral subglottis Fig. . Such leSedation was gradually reduced over 48 h postsurgery, and mechanical ventilation was ended 2 weeks later with the infant ventilating effectively with the tracheal cannula.Laryngotracheobronchoscopy under general anesthesia on day 33 revealed a subglottic stenosis treated with a 6-mm diameter balloon dilation. Proximal esophageal stenosis was also observed and not treated. Videographic exploration of swallowing confirmed the images of a very proximal partial esophageal stenosis, from C3 to C4., the cannula was withdrawn. The infant was then discharged 10 days later. She was exclusively breastfed and weight and height gains were satisfactory, with respective gains of 915 g and 7 cm since birth, with absence of swallowing difficulty in relation to the partial esophageal stenosis.After a final endoscopic assessment at 2 months showing the absence of airway stenosisThe respiratory bud develops from the ventral side of the primitive foregut from the 4th week of development. Cervical bronchogenic cyst may result from an abnormal division of the bud and migration to an ectopic localization in the neck region ,5,6. OthAntenatal discovery of a bronchogenic cyst is rare and localization is generally intrathoracic ,10. One The immediate neonatal respiratory distress of our patient was explained by direct compression of the trachea, causing major difficulties for intubation because the larynx could not be visualized. The use of a video-laryngoscope for intubation can improve the viewing conditions of the upper airways, making it easier to identify the laryngeal inlet. Rigid bronchoscopy or a flexometallic tube can also relieve glottic-subglottic compression, although great caution is required while advancing the scope or the tube. The ex utero intrapartum treatment (EXIT) procedure can also be done if prenatal diagnosis suggests fetal airway obstruction by a neck mass. Its use in this context has mainly been reported for cervical lymphatic malformations and cervical teratomas ,14.The main differential diagnosis is cystic hygroma, which is more likely in the setting of a multilocular cyst, and more unlikely in the setting of a unilocular cyst. Other differential diagnoses include thymic cyst, branchial cyst and thyroglossal duct cyst, but they are rarely responsible for neonatal respiratory distress. Only histological examination of the resected specimen confirms the diagnosis.MRI is essential before surgery, as it provides the surgeon with precise information on the anatomical relationships with adjacent organs . Rigid bThe only treatment is surgical excision, even for an asymptomatic cyst, given the risks of infection, hemorrhage and, rarely, malignant transformation . The parSeveral factors probably contributed to the alterations in the glottic and subglottic regions observed after the intervention, including intubation and the repeated attempts to intubate, the inflammation associated with laryngeal surgery, and the prolonged mechanical ventilation. In a newborn, edemic and necrotic lesions further narrow an already physiologically narrow larynx, which is an additional motivation to perform tracheostomy.In addition to the vocal cord paralysis, persistent airway obstruction after laryngeal surgery should always raise the suspicion of a local cause, such as stenosis. In our patient, a proximal esophageal stenosis was also present after surgery. The damage to the esophageal mucosa was probably caused by the surgery, secondary to cyst resection and the suturing of borders. This stenosis, however, had only transient and moderate clinical consequences and did not preclude satisfactory breastfeeding, even with the tracheal cannula.Cervical bronchogenic cyst is rare and diagnosis is most often made in childhood. However, it should be systematically considered in all cases of neonatal cervical tumor, especially if respiratory distress is present. Prenatal diagnosis may be guided by an unexplained polyhydramnios and/or direct visualization of a cyst, in which case delivery should be performed in a maternity hospital with a type 3 neonatal unit. The EXIT procedure, with a multidisciplinary team approach, should also be planned for fetuses with evidence of airway obstruction on prenatal images.Written informed consent was obtained from the parents of the patient for publication of this case report and the accompanying images. A copy of the written consent is available for review by the Editor of this journal.


Individual differences in the temperamental dimension of effortful control are constitutionally based and have been associated with an adverse prenatal developmental environment, with structural brain alterations presenting a potential mechanism. We investigated this hypothesis for anatomically defined brain regions implicated in cognitive and inhibitory motor control.Twenty-seven 15–16 year old participants with low, medium, or high fetal growth were selected from a longitudinal birth cohort to maximize variation and represent the full normal spectrum of fetal growth. Outcome measures were parent ratings of attention and inhibitory control, thickness and surface area of the orbitofrontal cortex  and medial (MOFC)) and right inferior frontal gyrus (rIFG), and volumetric measures of the striatum and amygdala.Lower birth weight was associated with lower inhibitory control, smaller surface area of LOFC, MOFC and rIFG, lower caudate volume, and thicker MOFC. A mediation model found a significant indirect effect of birth weight on inhibitory control via caudate volume.Our findings support a neuroanatomical mechanism underlying potential long-term consequences of an adverse fetal developmental environment for behavioral inhibitory control in adolescence and have implications for understanding putative prenatal developmental origins of externalizing behavioral problems and self-control. Effortful control (EC) is a temperamental dimension that describes individual differences in self-regulation, or the ability to exert behavioral control, including attentional focusing and inhibitory control Differences in EC are thought to be constitutionally based, which implies a biological basis. It has been suggested that genetic factors as well as maturation and experience are the primary factors affecting individual differences in EC However, the mechanisms underlying the association between birth weight and EC are unknown. A number of studies recently demonstrated associations between birth weight and global and regional brain morphology across the full normal range of birth weight in broad age samples including children, adolescents and adults It has been suggested that EC is based on the executive attention network, which is involved in resolving conflict between other brain networks and is thought to underlie cognitive and emotional self-regulation However, as mentioned above, EC is a heterogeneous construct including lower order facets, particularly attention and inhibitory control. Akin to this heterogeneity it has been suggested that executive attention functions, reflected in anterior cingulate activation, should be distinguished from executive motor control In addition, a number of studies suggested a neural basis for impulse control based on a circuit including ventromedial prefrontal cortex (VMPFC), anterior cingulate cortex (ACC) and amygdala Based on these findings we hypothesized that an adverse prenatal developmental environment might lead to deficits in attention and inhibitory control in adolescence, and that such associations would be based on effects of prenatal adversity on brain development resulting in specific structural changes. The aim of our study was to investigate in a longitudinal birth cohort (1) whether birth weight across the normal spectrum  is associated with attention and inhibitory control in adolescence, and (2) if structural characteristics of OFC, rIFG, ACC, striatum and amygdala statistically mediate such associations.This is a follow-up study of children of mothers recruited for a longitudinal birth cohort study at 17 or less weeks of gestation at the Princess Anne Maternity Hospital in Southampton, UK lowFG = 8; nmediumFG = 12; nhighFG = 7). The 27 participants included in the study did not differ from the 53 excluded in terms of age, sex, birth weight, and gestational age .Data on birth weight and gestational age were used to generate groups of participants to be recruited for the MRI study with the aim of having the full normal spectrum of fetal growth represented by the sample. In a first step, five participants born before the 37th week of gestation were excluded to prevent any confounding effect of preterm birth. The remaining 134 participants were then allocated to five groups based on sex-specific fetal growth  by regressing birth weight on gestational age and using quintiles of the residuals for group allocation separately for males and females. This resulted in equally sized groups of low FG (n = 27), low-medium FG (n = 27), medium FG (n = 27), medium-high FG (n = 27) and high FG (n = 26). To represent the full normal spectrum of FG and increase power of the hypothesis tests only those 80 participants in the low, medium and high FG groups were included in the study. Of those, addresses of 27 were not traceable; the remaining participants were contacted by telephone and screened for exclusion criteria. Twenty-four participants were excluded because they wore dental braces (n = 6), did not want to participate (n = 12), reported symptoms of claustrophobia (n = 2), had metal implants (n = 2) or suffered from epilepsy (n = 1), and one participant was surplus to requirements. Thus, 29 adolescents were recruited into the MRI study. After MRI scanning, one participant was excluded due to poor image quality, and one participant had a very small total brain volume at 2.5 SD below the sample mean and therefore was excluded from all brain analyses. Thus, the resulting total sample size was n = 27  3 with an acquisition matrix of 174×192×192 and the following parameters: TR = 2040 ms; TE = 4.7 ms; inversion time (TI)  = 900 ms; flip angle  = 8°. Acquisition duration for this sequence was 5 min and 56 s. The sequence was acquired twice during the same session for each adolescent.Imaging data were acquired at the Oxford Centre for Clinical Magnetic Resonance Research, John Radcliffe Hospital, Oxford, UK, on a 3.0 Tesla TIM Trio scanner . T1-weighted structural images for the structural analysis were acquired using a 3D magnetization prepared rapid gradient echo (MPRAGE) sequence. The voxel resolution was 1×1×1 mmhttps://surfer.nmr.mgh.harvard.edu). This process included motion correction and averaging of the two T1-weighted images acquired for each subject, removal of non-brain tissue, and segmentation of white matter and subcortical grey matter volumetric structures Cortical reconstruction and volumetric segmentation was performed with the FreeSurfer v5.1.0 imaging analysis suite , lateral orbitofrontal cortex (LOFC), ACC  and rIFG . Exact anatomical boundaries and reliability of the parcellation are described elsewhere The main analysis focused on a potential mediating effect of structural brain characteristics for associations between fetal adversity and behavioral measures of attention and inhibitory control. Indicators of average CT, SA and volume were exported from FreeSurfer into Stata v12.1 . We used birth weight as a continuous predictor of brain structure and behaviour in hierarchical least squares multiple linear regression models. Potential mediation effects were tested by estimating path models including indirect effects using Mplus v6.11 . Tests were conducted in the following order. First, associations between birth weight and behavioral measures  were tested. Second, associations between fetal adversity and brain structure in adolescence were tested by regressing structural brain characteristics of the ROIs defined above on birth weight. Third, behavioral measures were regressed on those structural brain indicators that showed significant associations with birth weight in the step before. All three association tests should reveal statistically significant associations for a mediating effect to be plausible. Therefore, mediation models were tested only for those behavioral measures and brain structures that fulfilled these criteria. To control for potential sex differences in birth weight and brain structure, all analyses were adjusted for sex. Brain analyses were additionally adjusted for intracranial volume (ICV) by including ICV as a covariate into the regression. To explore potential prenatal and postnatal confounding variables, we also included maternal smoking and drinking alcohol during pregnancy, parity and social class as covariates in additional models. All hypotheses were tested using a significance level of p<.05.2 = .15), but not attention . Thus, consistent with our hypothesis, adolescents born at higher birth weight showed more behavior indicative of higher inhibitory control as reported by their parents, with birth weight explaining 15% of the variance in inhibitory control. In contrast, attention was not significantly related to fetal growth. Adjusting the models for maternal smoking, drinking alcohol, parity and social class did not change the results , total gray matter  and white matter volume .Birth weight was positively associated with total brain volume . In contrast, caudate volume was significantly and positively associated with inhibitory control, explaining 20% of variance , thus qualifying as a potential mediator of the relationship between birth weight and inhibitory control.Results so far suggest SA of rIFG, LOFC and MOFC, CT of MOFC, and caudate volume as potential mediators of the relationship between birth weight and inhibitory control. To establish a potential mediational path, we next tested for associations between these structural indices and inhibitory control scores. Regression models showed no significant relationship for any of the cortical structures, all explaining almost no variance in inhibitory control , or reflects specificity in long-term consequences of fetal adversity in adolescence is not clear. For inhibitory control we were able to detect a significant indirect effect of birth weight via caudate volume, suggesting that fetal adversity might be linked to behavior in adolescence via alterations in brain development.We found that birth weight was positively associated with total brain, gray and white matter volume, as well as cortical surface area in both LOFC and MOFC, and in rIFG. With regards to subcortical structures, birth weight was positively associated with caudate volume, but not with other striatal areas or the amygdala. These findings are largely consistent with recent studies in larger samples that found birth weight effects for surface areas similar to our frontal cortical ROIs In contrast to cortical surface area, a significant association with cortical thickness was found only for the MOFC. Adolescents with lower fetal growth had a thicker MOFC averaged across hemispheres. This finding is consistent with earlier studies of samples covering childhood to young adult age groups showing that cortical thickness was not or only very weakly associated with indicators of fetal growth in both monozygotic and dizygotic twins It has been suggested that the striatum is particularly vulnerable to perinatal hypoxic-ischemic events The finding of a positive association between caudate volume and inhibitory control in daily life is consistent with neuroscience models that postulate a major involvement of striatal areas in inhibitory motor control The main limitations of our study were the relatively low internal consistency of the Inhibitory Control scale and limited statistical power due to a relatively small sample. The internal consistency of a scale is dependent on the number of items and the observed scale score variance. For a short scale of five items and a relatively homogenous and small sample the internal consistency observed in this study can be considered acceptable for a group study. Nevertheless, both limitations mean that some relevant associations might have been missed.In summary, this study demonstrated that an adverse fetal developmental environment might lead to reduced inhibitory control in adolescence, and that reduced caudate volume might mediate this association. As inhibitory control is an integral part of self-control, identifying such pathways originating in prenatal life might in the future help to improve well-being through targeted early preventative action such as educational or nutritional intervention File S1Combined supporting information, containing results of vertex-wise analyses  and results of adjustment for potentially confounding covariates (Table S1).(DOCX)Click here for additional data file.


The low utilization of skilled birth attendants sustained high maternal mortality. The aim of this study was to assess its magnitude and correlates in Northwest Ethiopia. A study was conducted on 373 randomly selected women who gave birth in the 12 months preceding the survey. Correlates were identified using binary logistic regression. Skilled birth attendance was 18.8%. Inability to perform cultural practices in health facilities (65.5%), expecting smooth delivery (63.4%), and far distance (62%) were the main barriers. Women with urban residence (AOR = 5.46: 95% CI [2.21–13.49]), primary (AOR = 2.10: 95% CI [0.71–6.16]) and secondary-plus (AOR = 6.12: [1.39–26.92]) educational level, four-plus ANC visits (AOR = 17.33: 95% CI [4.22–71.29]), and proximity to health centers (AOR = 5.67: 95% CI [1.47–25.67]) had higher odds of using skilled birth attendants though women with no labor complications had lower odds (AOR = 0.02: 95% CI [0.01–0.05]). Skilled birth attendance use was low. Urban residence, primary-plus level of education, frequent ANC visits, living nearby the health centers, and a problem during labor were positively correlated with skilled birth attendance utilization. Stakeholders should enhance girls' education beyond primary level and ANC services and shorten distances to health facilities. Though pregnancy and childbirth are a natural phenomenon and is often an eventful process which most women aspire to have at some point in their lives, this normal life affirming process carries its own risk and complications to both the mother and the newborn , 2. GlobMany researchers documented that more than three-fourths of maternal deaths are related to direct obstetric causes, such as haemorrhage, sepsis, abortion, ruptured uterus, and hypertensive diseases of pregnancy which are easily preventable and treatable, and 77% of deaths occur during or soon after childbirth within 24 hours) , 5. Eigh4 hours ,World leaders started to join their efforts together at the dawn of the millennium by the MDG through the safe motherhood initiative to decrease maternal morbidity and mortality globally . TargetsStudies from both industrialized and developing countries indicated that maternal mortality has been generally low when a higher proportion of deliveries are attended by skilled birth attendants –16. HoweIn Ethiopia, only 6% of births were delivered in health facilities at 2000 and there is no significant increase in the proportions of health facility delivery service utilization as evidenced from the series of Ethiopian Demographic and Health Surveys (EDHS) conducted in 2000, 2005, and 2011 which was found to be 6%, 8%, and 10% respectively , 20.Institutional delivery service utilization in Amhara Region was only 10.1% according to the EDHS 2011 which is equivalent to the national level of 10% . HoweverTherefore, this study was very crucial to measuring the prevalence of skilled birth attendance utilization and its correlates in remote areas of the second populous country in Africa to enhance maternal health to thereby reduce maternal morbidity and mortality in Ethiopia. The result will also be very important for policy makers as documented in the reproductive health road map to improve maternal health in general and increase level of skilled birth attendance by promoting quality antenatal care, make mothers have skilled assistance during their delivery, strengthen capacity of community health workers and community development army to perform emergency obstetric care (EmOC). Woreda (district) in Awi zone, Amhara Regional State of Ethiopia. The main town of the study district was located at a distance of 450 kilometers northwest of Addis Ababa. The Woreda was administratively divided into seven clusters, 29 rural and 4 urban kebeles (the lowest administrative units). Clusters were established according to availability of health center. The area coverage of the study is 79881.75 square kilometers and was inhabited by about 221,796 persons [This study was conducted in Akansha Guagusa Woreda Health Department report there were seven health centres and five private clinics. With regard to health professionals employed in the woreda, there were nine health officers, five B. Sc. nurses, 46 clinical nurses, 16 midwifery nurses, one pharmacy technologist, nine pharmacy technicians, two laboratory technologists, 11 laboratory technicians, and 80 health service extension workers  making a total of 179 health professionals. The same source indicated that 28.4% mothers had four or more ANC visits and 74% of children had taken Penta three immunization. The average number of expected deliveries per annum in the Woreda was 6520, that is, 2.9% of the total population [According to thepulation .A community based cross-sectional study was conducted in February 2014 among 373 women who had delivered in 12 months prior to the study.The sample size was calculated using single population proportion formula considering the Amhara Region skilled birth attendance utilization level of 10.1% , a 95% cAn interviewer-administered pretested and close ended questionnaire developed in the local language was used. Mothers were briefed about the purpose of the study and data were collected after a verbal informed consent. The data collection was done by 12 female nurses supervised by two senior supervisors with public health background. Data quality was assured through careful design of the questionnaire and training of the field staffs. Moreover, data were checked for completeness and consistency.p value less than 0.05 at the bivariate level were included in a multivariate logistic regression model to control for potential confounding variables.Data were entered in Epi Info and exported to SPSS for analysis. Bivariate and multivariate models using binary logistic regression were run to assess any relationship between independent variables and skilled birth attendant utilization. Crude and adjusted odds ratios were used to ascertain effect sizes for any association between the dependent and predictor variables while significance was determined using 95% confidence intervals. Independent variables found to be significant with  Woreda Administration Council. The purpose of the study was explained to mothers and the survey was commenced after obtaining verbal consent. Confidentiality of information was maintained by omitting any personal identifier from the questionnaires.Ethical approval was obtained from the Research Ethics Committee of the School of Public Health, Addis Ababa University, and approval letter was obtained from theAltogether, 373 mothers participated in the survey. Of these, more than three-fourths, 282 (75.6%), of them were from rural areas and almost all, 367 (98.39%), of them were Orthodox Christians. The main ethnic group was Agew, 290 (77.75%), and nearly one-third, 115 (30.83%), of them were in the age range of 25–29 years with a mean age of 30.41 (±5.56) years. With regard to educational status of respondents', nearly two-thirds, 233 (62.47%), of them could not read and write whereas only 54 (14.48%) of them had attained secondary educational level and above. Majority, 347 (93.03%), of them were currently married. Among married, 19 (5.5%) of respondents' husband were polygamous. Three quarters, 278 (74.53%), of the mothers were housewives and nearly half, 186 (49.87%), of them had five to seven household members. Concerning respondents' monthly income, majority, 124 (33.24%), of mothers were found in 701–1249 Ethiopian birrs income group which is less than two dollars per day (a dollar is approximately 20 ETB during our study period) .Analysis of the obstetric characteristics of study women showed that 165 (44.24%) of respondents were married before celebrating their 16th birthday and the mean age at first marriage was 16.38 (±3.77) years. More than a third, 138 (37.00%), got their first pregnancy before the age of 19 years with the mean age of 19.73 (±3.00). About 101 (27.08%) gave their first birth before celebrating their 19th year of age with the mean age at first childbirth of 20.52 (±2.99) years. Moreover, 145 (38.87%) of them had more than four children and 285 (76.41%) of them who recently gave birth to a child had received antenatal care visits. Among 285 mothers who had ANC visit, about 89 (31%) of them had only one visit while 45 (16%) had four and more antenatal visits . Out of In addition, this study revealed that only 78 (20.91%) of the mothers gave birth to their last babies at health facilities including health posts where health extension workers (who do not have education and training about basic obstetric skills) are working, whereas only 70 (18.77%) of them were attended by skilled birth attendants with basic obstetric skills (with nursing and above level of training). Among institutional deliveries assisted by skilled birth attendants, 43 (61.43%) of them delivered by spontaneous vaginal deliveries while 21 (30.00%) and 6 (8.57%) of them were assisted to give birth using instruments and through caesarean section, respectively. On the other hand, 71 (19.0%) of women who gave birth 12 months preceding the survey had history of labor complications, mainly prolonged labor, vaginal bleeding, and severe headache.Nevertheless, from mothers who were not attended by skilled birth attendants, 219 (58.71%) were assisted by family members and relatives, 60 (16.08%) by health extension workers, and 12 (3.22%) by traditional birth attendants, and 12 (3.22%) had to do it by themselves without any assistance. About 295 (79.09%) mothers gave a variety of reasons for delivering at home; of these, 193 (65.42%) felt more comfortable to deliver at home since they will perform variety of cultural practices, 187 (63.39%) assumed no problem during home delivery as it is natural, 183 (62.03%) considered that health facilities are located far from their places of residences, and for 148 (50.17%) of the mothers their parents decided where they should have a baby and preferred home as their place of delivery .Binary logistic regression models were fitted to identify correlates of skilled birth attendant utilization. The first model which attempted to calibrate sociodemographic correlates revealed that residence type has been found to be strongly and significantly associated with skilled birth attendance at both bivariate and multivariate levels.Skilled birth attendance was COR = 7.15: 95% CI (4.07–12.28) times more likely to be utilized among urbanites compared with rural residents whereas when other confounding sociodemographic variables were controlled, the odds of skilled birth attendance utilization were AOR = 5.46: 95% CI (2.21–13.49) times higher among urban residents compared with their rural counterparts. On the other hand, skilled birth attendance was COR = 2.59: 95% CI (1.33–5.05) and COR = 9.83: 95% CI (4.95–19.52) times more likely to be utilized among mothers who completed primary and secondary and above level of education, respectively, compared with those who had never been into formal schooling. However, the significance of association vanishes at multivariate level for primary level of education. When all the other sociodemographic variables are controlled, the odds of skilled birth attendance were AOR = 6.12: 95% CI  times higher among those mothers whose educational level was secondary and above compared with those with no education .The focus of the second model was to identify the reproductive health related correlates of skilled birth attendance utilization. Skilled birth attendant utilization among women who had four or more antenatal care visits was AOR = 17.33: 95% CI (4.22–71.29) times higher compared to those mothers with three and lower antenatal care visits . On the This study showed that about one-third of the women in Akansha Guagusa Woreda had completed three visits of antenatal care services. However, institutional delivery and skilled birth attendant utilization were low, especially among women from rural areas, who had three and less antenatal care visits and were uneducated.In this study less than one-fifth of the mothers 18.77%) were assisted by skilled birth attendants during their recent deliveries. Moreover, the study documented women who were not attended by anyone during delivery. The prevalence of skilled birth attendant utilization for the study district was somewhat similar to the findings of other studies done in Ethiopia, that is, Ephrtanagidim district, Kembata-Tembaro zone, and Raya Alamata district –25. Howe7% were aThis study also showed the association of place of residence with skilled birth attendant utilization. In particular, mothers who resided in urban areas were more likely to get skilled birth attendance compared to their counterparts which is consistent with the findings of similar studies done in Ethiopia and other countries , 29–35. Educational status of mothers was also significantly associated with the utilization of skilled birth attendants. Mothers who had attained primary and secondary and above educational level were more likely to utilize skilled birth attendant than those mothers who were unable to read and write. This finding was in line with other studies that were done in Ethiopia and other developing countries , 36, 37.Controlling other variables, frequency of antenatal care visits during their last pregnancy was also found to be a strong predictor of utilization of skilled birth attendants. Those mothers who had four antenatal care visits and above were more likely to deliver through the assistance of skilled birth attendants than those mothers who had three and less antenatal care visits. This finding was consistent with studies done in developing countries including Arsi, Alamata, Tigray, Dabat, Woldia, Mekelle, Fogera in Ethiopia, Nepal, Tanzania, and Cambodia , 29–35. Another important finding of this study was that mothers who did not face any labour complications during recent labour and delivery were 98% less likely to get skilled attendant during their delivery compared to those mothers who faced maternal complications. This implies that labouring mothers decide to give birth in health facilities and require the assistance of skilled birth attendants when they faced difficulties and when repeated trials at home failed. Similar findings were documented by other studies done in Sekela, North Shewa, Agemssa, Wollega, and Metekel zone , 38, 39.Utilization of skilled birth attendant is still very low with a high number of deliveries being attended by unqualified persons at home. There are still women who deliver by themselves. Women's higher education, urban residence type, higher frequency of antenatal care visits, proximity of living to a health center, and encountering complications during current labour were found to be positively correlated with skilled birth attendant utilization. Therefore, the government should enhance secondary and above level of educational attainment among females, promote universal antenatal care follow-up service, and encourage mothers to utilize skilled birth attendants during pregnancy and delivery. Good referral linkages should be established, health facilities should be staffed by professionals with basic obstetric skills and with necessary supplies and medicines, and different means of behavioral changing communication should be designed to improve the demand.