This retrospective study determined for the first time the role of baseline antral follicle count (AFC) and serum anti-Mullerian hormone (AMH) level in the first in-vitro fertilisation (IVF) cycle in predicting cumulative live birth from one stimulation cycle.We studied 1,156 women (median age 35 years) undergoing the first IVF cycle. Baseline AFC and AMH level on the day before ovarian stimulation were analysed. The main outcome measure was cumulative live birth in the fresh plus all the frozen embryo transfers after the same stimulation cycle.Serum AMH was significantly correlated with AFC. Both AMH and AFC showed significant correlation with age and ovarian response in the stimulated cycle and total number of transferrable embryos. Baseline AFC and serum AMH were significantly higher in subjects attaining a live birth than those who did not in the fresh stimulated cycle, as well as those attaining cumulative live birth. There was a significant trend of higher cumulative live birth rate in women with higher AMH or AFC. However, logistic regression revealed that both AMH and AFC were not significant predictors of cumulative live birth after adjusting for age and number of embryos available for transfer. Considering only one single predictor, the areas under the ROC curves for AMH  and age  were slightly higher than that for AFC  in predicting cumulative live birth. However, a model combining AMH (with or without AFC) and age of the women only classified an addition of less than 2% of subjects correctly compared to the model with age alone.Baseline AFC and serum AMH have only modest predictive performance on the occurrence of cumulative live birth, and may not give additional value on top of the women's age. In assisted reproduction programmes, a number of parameters known as ovarian reserve markers, such as serum follicle stimulating hormone (FSH) concentration, antral follicle count (AFC) and serum anti-Mullerian hormone (AMH) concentration, are widely used to predict ovarian responses to gonadotrophin stimulation during in-vitro fertilization (IVF) treatment. These markers may help to decide on the initial dose and regimen of stimulation AMH, also known as Mullerian-inhibiting substance, is a dimeric glycoprotein that belongs to the transforming growth factor-beta family. It is involved in the regression of the Mullerian ducts during development of the male fetus In modern-day assisted reproduction programmes, embryo cryopreservation has become an integral component. It allows the storage and subsequent usage of surplus good quality embryos in frozen-thawed embryo transfer (FET) cycles. Hence, to evaluate the outcome of an IVF cycle, it would be more logical to consider the cumulative live birth rate from the fresh and all FET cycles combined, instead of merely looking at the single fresh cycle outcome.There have been limited data on the role of these ovarian reserve markers in predicting cumulative pregnancy or live birth rates in IVF programmes. A study looked at the use of AMH on Day 6 of ovarian stimulation in predicting cumulative ongoing pregnancy outcome Therefore, we conducted this retrospective analysis to evaluate the role of baseline AFC and AMH in the first stimulated IVF cycle in predicting the cumulative live birth from the stimulated cycle and all subsequent FET cycles derived from that stimulated cycle.We reviewed all first IVF cycles carried out between January 2007 and December 2009 at the Centre of Assisted Reproduction and Embryology, The University of Hong Kong – Queen Mary Hospital, Hong Kong. Cycles carried out for pre-implantation genetic diagnosis or those using donor oocytes were excluded from this analysis. Clinical details of all treatment cycles were prospectively entered into a computerized database, which were retrieved for analysis.An ethics approval was obtained from the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster for this retrospective study to be carried out using existing patient data in an anonymous manner without requiring written consent from individual patients. The project did not involve any additional intervention or modification from the standard treatment.All patients attended the clinic for blood test and pelvic ultrasound examination at the beginning of the IVF treatment cycle before commencing ovarian stimulation. Transvaginal scanning was performed using a 5 MHz vaginal probe  to determine AFC (2–9 mm) in both ovaries. Blood was taken for routine oestradiol (E2) assay, and residual serum samples were stored at −20°C. For the current study, these archived serum samples were retrieved and assayed for AMH using the AMH Gen II ELISA kit . The assay has a sensitivity of 0.08 ng/ml (0.6 pmol/l), and intra- and inter-assay coefficients of variation of less than 5.4 and 5.6%.All subjects were treated either with the long GnRH agonist protocol or the GnRH antagonist protocol for pituitary down-regulation, with the latter mostly for selected patients with poor ovarian reserve. In the long GnRH agonist protocol, the women received buserelin  nasal spray 150 µg four times a day starting from the mid-luteal phase of the cycle preceding the treatment cycle, and received human menopausal gonadotrophin (HMG) or recombinant FSH for ovarian stimulation after return of a period. In the GnRH antagonist protocol, after confirming a basal serum oestradiol level, ovarian stimulation was started. The women received ganirelix or cetrorelix 250 µg daily starting from the sixth day of stimulation. The initial dose of stimulation was determined according to the baseline AFC . Human chorionic gonadotrophin (hCG) (Pregnyl® 5000 or 10000 units or Ovidrel® 250 µg) was given when the mean diameter of the leading follicle reached 18 mm and there were at least 3 follicles reaching a mean diameter of 16 mm or above, followed by transvaginal ultrasound-guided oocyte retrieval 36 hours later. Fertilisation was carried out in-vitro either by conventional insemination or intracytoplasmic sperm injection (ICSI) depending on semen parameters.Subjects were allowed to have replacement of at most two embryos two days post-fertilisation. Embryo transfer (ET) was performed under transabdominal ultrasound guidance using a soft catheter . Fresh embryo transfer would be cancelled and all the embryos with good quality were cryopreserved on day 2 after the retrieval if the subject had symptoms suggestive of ovarian hyperstimulation syndrome (OHSS) or serum E2 concentration on the day of hCG injection was >20,000 pmol/L.Embryos were graded based on the number/regularity of blastomeres and the degree of fragmentation A urine pregnancy test was done 16 days after embryo transfer. Pregnant women were offered an ultrasound examination 10–14 days later to confirm intrauterine pregnancy and the number of gestational sacs present. Pregnancy outcome was traced from all pregnant women by postal questionnaire or by phone.The primary outcome measure was the cumulative live birth in the fresh and all FET cycles combined following the same index stimulation cycle. The age of the women used in analysis referred to the time of starting ovarian stimulation. Non-normally distributed continuous variables were expressed as median (interquartile range) unless otherwise stated. Continuous and categorical variables were compared between groups using Mann-Whitney test and Fisher's Exact test respectively. Logistic regression analysis was used to examine factors predicting cumulative live birth, and receiver-operator characteristic (ROC) curves were compared for different ovarian reserve markers in predicting cumulative live birth. Statistical analysis was carried out using the Statistical Program for Social Sciences  and MedCalc . The two-tailed value of P <0.05 was considered statistically significant.2 respectively. The cause of subfertility included male factor , tubo-peritoneal factor , endometriosis , anovulation , unexplained  and mixed causes .Of the 1,156 subjects who underwent the first IVF cycle during the study period, 1,050 (90.8%) were treated on the long GnRH agonist protocol, and the remaining 106 (9.2%) on the GnRH antagonist protocol. The age and body mass index (BMI) [median (interquartile range)] of our subjects were 35 (33–38) years and 21.2 (19.6–23.1) kg/mThere was a significant correlation between serum AMH and AFC . As shown in Table I, both serum AMH and AFC were significantly correlated with the women's age, duration of stimulation, total dose of gonadotrophin used, number of mature-sized follicles (≥16 mm), peak serum E2 concentration, number of oocytes retrieved and transferrable embryos obtained (for fresh transfer and/or freezing) and number of top quality embryos . There was no significant correlation between serum AMH or AFC with BMI.There were 1,026 subjects (88.8%) who had fresh ET. Among them, 510 (49.7%) had a positive pregnancy test in the fresh cycle, and 383 (37.3%) attained live birth. Among those who were pregnant, there was no significant difference (p>0.05) in AFC and serum AMH between those who miscarried and those who had live birth. The clinical and demographic characteristics of subjects with or without a live birth in the fresh cycle are compared in Table II. Subjects who attained a live birth were significantly younger (median 34.0 vs 36.0 years), had significantly higher AFC (median 10.0 vs 9.0) and serum AMH [median 3.27 ng/ml (23.3 pmol/l) vs 2.64 ng/ml (18.8 pmol/l)], and more of them had double embryo transfer (94.3% vs 82.0%). There were no statistically significant differences in BMI between subjects who had live birth in the fresh cycle or not, nor in the distribution of the cause of subfertility.Binary logistic regression using the enter method was used to analyse the prediction on live birth in the fresh IVF cycle by the women's age, AFC, serum AMH and number of embryos replaced. The women's age and the number of embryos replaced, but not AFC or serum AMH, were the significant factors which independently predicted the likelihood of a live birth in the fresh cycle (Table IIIa).Among the subjects included in this study, 1,038 (89.8%) had completed replacement of all available embryos and with a live birth outcome available. Of them, 558 (53.8%) attained live birth cumulatively from the fresh plus all FET cycles after the same index IVF cycle.Table IV depicts the demographic and clinical characteristics of subjects who had a cumulative live birth and those who did not. Subjects who attained a cumulative live birth were significantly younger (median 34.0 vs 36.0 years), had significantly higher AFC (median 11.0 vs 8.0) and serum AMH [median 3.7 ng/ml (26.4 pmol/l) vs 2.3 ng/ml (16.4 pmol/l), and had significantly higher number of transferrable embryos (median 5 vs 2). The minimum values of AFC and serum AMH in subjects who attained a cumulative live birth were 0 and 0.15 ng/ml (1.1 pmol/l) respectively (vs 0 and <0.08 ng/ml (<0.6 pmol/l) respectively in those without a cumulative live birth).2 test for trend).When the women's age, AFC, serum AMH and total number of transferrable embryos derived from the index IVF cycle were entered into the binary logistic regression model using the enter method, the women's age and total number of transferrable embryos, but not AFC or AMH, were significant independent factors in predicting a cumulative live birth (Table IIIb).We further analysed the predictive performance of AFC and AMH in additional to age of the women versus age alone on cumulative live birth. (Table V). The addition of AMH, but not AFC, to age provided additional predictive value compared to using age alone. However, although statistically significant , the model combining the women's age and AMH, with or without AFC, only respectively classified an additional 1.7% or 1.9% of subjects correctly compared to the model with age alone.In assisted reproduction programmes, ovarian reserve markers such as FSH, AFC, and more recently AMH, have been widely used for predicting ovarian response and prognostic counseling. Recent systematic reviews have suggested that AFC and AMH were the best predictors of excessive and suboptimal ovarian response and both had comparable performance in this regard Nonetheless, most of the reported studies evaluated the pregnancy or live birth outcome in the fresh IVF cycle only. In modern assisted reproduction programmes, cryopreservation of surplus embryos with subsequent transfers in thawed cycles has become an integral part. It has been estimated that in programmes which incorporate embryo cryopreservation, up to 42% of all conceptions could be derived from FET Our results demonstrated that women who attained a cumulative live birth had significantly higher serum AMH and AFC at baseline before ovarian stimulation. However, the predictive performance of both parameters on the absolute occurrence of cumulative live birth was only modest and not better than age as demonstrated in the ROC curves. This is obviously comprehensible by observing the trend of cumulative live birth rate over serial increase in serum AMH or AFC as shown in Hypothetically, women with higher AMH or AFC have better ovarian reserve and hence higher oocyte yield and a larger potential pool of good quality embryos to be selected for transfer. This was supported by our findings that subjects who attained cumulative live birth had higher number of transferable embryos, and that the latter was an independent factor predicting cumulative live birth in logistic regression analysis. This is in line with a recent study which suggested that the total number of good-quality embryos and total number of transferable embryos were the two most important predictors of cumulative clinical pregnancy, particularly in women aged below 40 years With regard to endometrial receptivity, women with high AFC and/or serum AMH levels are at increased risk of ovarian hyperstimulation, and the resultant higher peak E2 levels could have detrimental effects on endometrial receptivity We also analysed the value of adding AFC and AMH on top of the women's age in the prediction model for cumulative live birth. Although statistically significant, the combined model with the women's age and AMH (with or without AFC) classified an addition of less than 2% of subjects correctly compared to the model with age alone. This very modest improvement in the prediction may not be very meaningful clinically.Based on our results, we would recommend that it is not worthwhile to use any of the ovarian reserve markers including serum AMH or AFC as the basis to exclude subjects from attempting assisted reproduction treatments, and when used for prognostic counselling the women should understand the limitations and imprecision of these indices in anticipating the treatment outcome.Inherent to the retrospective design, our results might have been subjected to verification bias, as the gonadotrophin dosing regimen has been preselected based on AFC in our protocol. We have repeated the analysis on the subgroup of subjects stimulated with an average daily dose of 225 IU or more, which presumably gave maximal stimuation. There was no significant difference in the areas under the ROC curve for AMH, AFC and age in predicting cumulative live birth (data not shown).The strength of our study was the inclusion of a large cohort of subjects over a wide age range from 22 to 45 years with diversified ovarian reserve to enhance generalisability. Although some of the subjects had not completed replacement of all available frozen embryos and were hence excluded from the cumulative live birth analysis, they did not differ significantly from the included subjects in sociodemographic parameters.In conclusion, our results confirmed a good correlation of baseline serum AMH and AFC with ovarian response parameters in IVF treatment. Baseline AFC and serum AMH were significantly higher in subjects attaining cumulative live birth, and there was a significant trend of increase in cumulative live birth rate in women with higher AMH or AFC. However, the predictive role of AFC and AMH on absolute occurrence of cumulative live birth was only modest and may not give much additional value on top of the women's age.


Genital prolapse is commonly observed in postmenopausal and multiparous women, However, nulliparous women contribute to 2% of prevalence. We report a case of 21-year-old female who presented with a large nabothian cyst contributing to prolapse. This is the first case reported in the literature. Pelvic organ prolapse is an issue of major health concern. Genital prolapse is commonly observed in postmenopausal and multiparous women. However, nulliparous women contribute to 2% of prevalence . The etiA 21-years-old unmarried nulliparous female presented with complaints of something coming out of vagina for 8 years associated with discharge per vaginum. Menstruation was normal. There were no urinary or bowel complaints, chronic cough, constipation, heavy weight lifting, and no family history of similar problem. General physical and systemic examination including nervous system and vertebral column examination were unremarkable. Local genital examination revealed third-degree cervical descent manifesting as a cystic swelling protruding through the introitus. External os was compressed and deviated to one side due to swelling . SwellinPatient was planned for cystectomy and sling surgery. A large 4 × 5 cm cyst filled with white mucinous substance was removed from the cervix which was 35 grams in weight . After tA nabothian cyst is a mucus-filled cyst on the surface of the cervix. They are most often caused when squamous epithelium blocks the opening of nabothian glands trapping mucosal secretion in small (2–10 mm diameter) subdermal pockets. They appear as firm bumps on the surface of cervix which may be single or in groups. Nabothian cysts are usually associated with chronic cervicitis, an inflammatory condition of cervix, and are harmless and usually disappear on their own. Nabothian cysts are not problematic unless they are sizeable and present secondary symptoms like in this case. Intraabdominal giant nabothian cyst has been reported ; however


To identify perinatal clinical antecedents of white matter microstructural abnormalities in extremely preterm infants.A prospective cohort of extremely preterm infants (N = 86) and healthy term controls (N = 16) underwent diffusion tensor imaging (DTI) at term equivalent age. Region of interest-based measures of white matter microstructure - fractional anisotropy and mean diffusivity - were quantified in seven vulnerable cerebral regions and group differences assessed. In the preterm cohort, multivariable linear regression analyses were conducted to identify independent clinical factors associated with microstructural abnormalities.Preterm infants had a mean (standard deviation) gestational age of 26.1 (1.7) weeks and birth weight of 824 (182) grams. Compared to term controls, the preterm cohort exhibited widespread microstructural abnormalities in 9 of 14 regional measures. Chorioamnionitis, necrotizing enterocolitis, white matter injury on cranial ultrasound, and increasing duration of mechanical ventilation were adversely correlated with regional microstructure. Conversely, antenatal steroids, female sex, longer duration of caffeine therapy, and greater duration of human milk use were independent favorable factors. White matter injury on cranial ultrasound was associated with a five weeks or greater delayed maturation of the corpus callosum; every additional 10 days of human milk use were associated with a three weeks or greater advanced maturation of the corpus callosum.Diffusion tensor imaging is sensitive in detecting the widespread cerebral delayed maturation and/or damage increasingly observed in extremely preterm infants. In our cohort, it also aided identification of several previously known or suspected perinatal clinical antecedents of brain injury, aberrant development, and neurodevelopmental impairments. The prevalence of neurodevelopmental impairments (NDI) may be increasing as a consequence of improved survival in extremely preterm infants (EPI) in vivo using diffusion tensor imaging (DTI) have facilitated sensitive detection of microstructural injury and aberrant brain development in very preterm infants Recent MRI advances that permit quantification of water diffusion and anisotropy Institutional IRB approval was obtained from the University of Texas Health Science Center Houston IRB prior to study initiation. Written informed consent for each infant (preterm and term) was obtained prior to enrollment in the study. The consent was approved by IRB and signed by each subject's parents or guardians prior to enrollment and participation in the study.Extremely preterm infants cared for in the Children's Memorial Hermann Hospital NICU between May 2007 and October 2010 were eligible for enrollment after 34 weeks post-menstrual age (PMA). Enrolled infants (N = 86) underwent brain MRI with DTI at 38 weeks PMA or prior to discharge, whichever occurred earlier. A control group of 16 healthy term newborns from the Children's Memorial Hermann Hospital Well Baby Nursery were enrolled between July 2008 and January 2010 to undergo DTI within the first 2 weeks after birth.2O, and high frequency oscillator or requiring sedation  at the time of enrollment. Main exclusion criteria for term infants were ≥42 weeks gestation or history of perinatal distress or complications To be eligible for the study, preterm infants had to be ≤1000 g birth weight and/or ≤29 weeks gestational age; term infants had to be ≥37 weeks gestational age and with weight appropriate for gestational age. Main exclusion criteria for preterm infants were known congenital CNS anomalies; mechanically ventilated with supplemental oxygen >50%, mean airway pressure >15 cm H2, field of view 180 mm2; 112×112 matrix; and 2-mm contiguous slices. 15 directions of diffusion gradients were used with a b value of 800 s/mm2; additional image with no diffusion gradient was obtained (b = 0 s/mm2).Brain MRI scans were performed on a 3T Philips Achieva scanner, equipped with a 32 channel receiver system and a gradient system capable of producing gradient amplitudes of 80 mT/m with a slew rate of 200 T/m/s. An 8-channel phased array head coil was used for data acquisition. The DTI protocol consisted of a single-shot, spin-echo planar sequence with TR/TE, 6000/61; in plane resolution 1.6×1.6 mmPrior to scanning, patients were fed, swaddled, and restrained in a MedVac Infant Vacuum Splint . Noise was reduced using Insta-Puffy Silicone Earplugs  and Natus MiniMuffs . All scans were completed without sedation and were supervised by an experienced neonatologist and a neonatal research nurse.http://cmrm.med.jhmi.edu) http://imagej.nih.gov/ij) was utilized for development and placement of ROI templates (one for each ROI) in the native space for fractional anisotropy (FA) and mean diffusivity (MD) measurements  were prospectively collected. Clinical variable selection was based on current knowledge, supporting literature, and biological plausibility. Each of the chosen variables had previously been suspected antecedents or previously reported association with early brain injury and/or NDI. All data were entered into a secure database with error checks by qualified neonatal research nurses. All unique identifiers were removed to protect privacy and to blind investigators to clinical history.Stata 11/12 IC  was used for all data analyses. Two sample t-test, Chi-square and Fisher's exact tests were used as appropriate to describe and compare demographic characteristics among the groups . Two samFor the preterm cohort, the selected clinical factors were correlated with FA in bivariate analyses (controlling for PMA at MRI) for each significant ROI. All variables with P<0.25 in bivariate analyses were entered in multiple linear regression analyses with elimination of factors with the highest P values one at a time manually, retaining variables with P<0.1 only 75 of the 86 preterm infants and 15 of 16 term infants had high quality DTI scans free of motion artifact and were included in the analyses. Their demographic and clinical characteristics are summarized in Intra-rater intra-class correlation coefficient for ROI placements was 0.93. FA and MD comparisons between preterm and term infants are shown in Multiple independent clinical antecedents of FA and MD were identified in the preterm cohort . Of anteSeveral postnatal factors were significant independent adverse antecedents for FA and MD abnormalities in multiple regions . White mDiffuse non-cystic white matter abnormalities are more commonly encountered in preterm infants than destructive cystic lesions Investigation of adverse and favorable antecedents for microstructural WM abnormalities is crucial for advancing our understanding of preterm brain injury/development and validating the use of diffusion measures as robust imaging biomarkers. Although important steps have been taken to identify risk factors for white matter abnormalities utilizing DTI, many important antecedents remain unexamined We uncovered several novel antecedents for regional microstructural abnormalities in our extremely preterm cohort. Chorioamnionitis was a strong adverse predictor for abnormalities in the corpus callosum. This association was stronger than previously reported Several favorable factors were identified in our cohort: maternal private medical insurance, use of antenatal steroids, increasing birth weight, female gender, Caucasian race, increasing duration of caffeine therapy, and longer duration of human milk use. More mature white matter microstructure following increasing duration of human milk use is a novel imaging finding that is consistent with prior evidence of improved cognition in EPI and larger white matter volume in preterm boys Several important and novel postnatal factors are associated with microstructural cerebral injury and/or aberrant development as assessed using DTI. Although many of these factors have also been linked with later NDI, external validation of our results will be important. DTI is emerging as an early imaging biomarker and a sensitive tool to advance our understanding of perinatal brain injury and development. Correlation of DTI measures at term with neurodevelopmental outcomes during early childhood are important next steps.


Objective. To examine the relationships between birth weight and body mass index, percent body fat, blood lipids, glycemia, insulin resistance, adipokines, blood pressure, and endothelial function in a cohort of obese adolescents. Design and Methods. Ninety-five subjects aged 10–16 years (mean age 13.5 years) with a body mass index >95th centile (mean [±SEM] 33.0 ± 0.6) were utilized from two prospective studies for obesity prevention prior to any interventions. The mean term birth weight was 3527 ± 64 g . Results. Body mass index z-score correlated positively with birth weight , but not percent body fat. Insulin resistance negatively correlated with birth weight , as did fasting plasma insulin ; both being significantly greater for subjects of small versus large birth weight (Δ Homeostasis Model Assessment = 2.5 and Δ insulin = 10 pmol/L for birth weight <2.5 kg versus >4.5 kg). Adiponectin, but not leptin, blood pressure z-scores or peripheral arterial tomography values positively correlated with birth weight . Conclusions. Excess body mass index in obese adolescents was positively related to birth weight. Birth weight was not associated with cardiovascular risk factors but represented a significant determinant of insulin resistance. Childhood obesity in Canada, as in other developed countries, has increased dramatically with 29% of children being overweight or obese in 2007 compared to 15% in 1978 . The futThe association between LGA, often with macrosomia, and adolescent and adult obesity, as well as the associated increased risk of T2D and cardiovascular disease, is most apparent when accompanied by maternal diabetes, both gestational and pregestational , 9. Mateβ cells, insulin release, and insulin resistance from animal models and of glucose intolerance and insulin resistance in the human offspring resulting in an increased risk of diabetes in the adult [In comparison with LGA, SGA infants have been shown to be at greater risk of hypertension and cardiovascular disease as adults . While She adult , 17. In he adult . Howeverhe adult . The SGAhe adult .Park  showed aNCT00934570) will assess the effects of a structured lifestyle intervention and metformin (or placebo) on BMI and other risk factors for T2D and cardiovascular disease in obese adolescents. Both studies were approved by the Western University Research Ethics Board, London, ON, Canada, in addition to Health Canada. Informed consent was obtained from all study subjects.  Entry data were utilized from 2 prospective cohort studies of obese adolescents. Twenty-six subjects were recruited for an obesity intervention which was completed in 2007, and 69 subjects were screened between 2008 and 2010 for entry to the REACH trial. Both groups were evaluated by the same clinical team and lead physician Cheril Clarson as the initial obesity prevention cohort was used as a pilot group to assess interest and feasibility for a more intensive clinical study. The REACH study  of ≥6% (≥7 mmol/L). Pubertal staging was assessed using the method of Tanner. At study entry, potential risk factors for development of T2D in addition to obesity were assessed, including pregestational maternal type 1 or 2 diabetes or gestational diabetes, birth weight, ethnicity, and the presence of acanthosis nigricans, hirsutism, or acne in adolescent girls. All subjects were asked to fast from 10 p.m. of the evening prior to study and to avoid caffeine for the preceding 24 h period. Blood was sampled for measurement of glucose, insulin, LDL and HDL cholesterol, triglycerides, and the adipocytokines, leptin, and high molecular weight adiponectin. Subjects (69) entering the REACH study also had an oral glucose tolerance test (2 h GTT) with measurement of 2 h plasma glucose and A1C. Glucose was measured by the glucose oxidase technique and plasma insulin levels determined by a double antibody radioimmunoassay using a recombinant human insulin standard and the minimum detection level of <2 pmol/L. Within- and between-assay coefficients of variation were 5.8% and 6.5%, respectively. Insulin resistance was estimated by the measurement of Homeostasis Model Assessment (HOMA), calculated as fasting plasma insulin (mU/L) × fasting plasma glucose (mmol/L)/22.5. HOMA values greater than 3.0 in adolescents are indicative of insulin resistance [z-scores were calculated from the US Centers for Disease Control and Prevention reference data [Weight was measured with subjects wearing minimal clothing using an electronic scale to the nearest 0.1 kg. Height was measured without shoes using a wall mounted stadiometer to the nearest 0.1 cm. BMI nce data . The perz-scores were calculated using the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents [Diastolic and systolic blood pressure was measured in the right arm using an appropriately sized cuff using a Dynamap machine. Age and sex-adjusted lescents . A measulescents .z-score, percent body fat, blood pressure z-scores, plasma insulin, leptin, adiponectin (and leptin/adiponectin ratio), HOMA, fasting and 2 h GTT plasma glucose, circulating lipids (HDL and LDL cholesterol and triglycerides), A1C, and RH-PAT. Stepwise regression with forward entry was also used to investigate the relevance of possible confounding variables such as maternal age, ethnicity, and stage of puberty. Details for other possible confounders such as maternal smoking during pregnancy and socioeconomic status were not available. The cohort was further separated into quintiles based on birth weight and the above parameters analyzed by analysis of variance using Fisher's PLSD post hoc test for significance of differences between quintiles. Statistical analyses were performed using GraphPad PRISM software .Measured values were obtained from 95 individuals, except for values for A1C, 2 h GTT, and percent body fat, which were obtained from a subgroup of 69 subjects. The normality of variables was confirmed using the Kolgomorov-Smirnov test. Values are expressed as mean ± SEM. The relationships between BMI and diabetes and cardiovascular risk factor variables at study entry were examined by univariate linear regression, as were the associations between birth weight and the following factors: BMI z-score was 2.22 ± 0.04  aged between 10 and 16 years with a mean age of 13.5 ± 0.2 years and selected as having an age-adjusted BMI >95th percentile, a fasting plasma glucose of ≤6 mmol/L, and an A1C of ≤6% (≤7 mmol/L). The mean BMI was 33.0 ± 0.6 and the mean BMI 2 ± 0.04 . Stage oz-scores were 0.30 ± 0.08 for systolic and 0.33 ± 0.10 for diastolic, and they indicated only a slight elevation above normal. Only 2 subjects had a blood pressure greater than 130/85 mm. These characteristics did not significantly differ with gender. Subject characteristics are depicted in z-score and the percent body fat, serum triglyceride levels, leptin levels and the leptin/adiponectin ratio, HOMA, and fasting plasma insulin , the mean length of gestation was 39.9 ± 0.1 weeks, and the mean maternal age was 28.8 ± 0.9 years. Linear regression analysis showed a significant positive relationship between birth weight and BMI lescents . Stepwislescents . Fastingn = 7) to those who were large for gestational age (LGA) . Obese adolescents were significantly more likely to have higher fasting insulin levels and greater insulin resistance (HOMA) if they were SGA   demonstrated a positive correlation between BMI and percent body fat, circulating triglycerides, and leptin. Thirty-five percent of subjects had an HOMA value >4.0, indicating insulin resistance [z-scores were only slightly elevated in the obese subjects. We previously demonstrated a significant inverse relationship between PAT ratio and BMI z-score in a cohort of adolescents that included both nonobese and obese individuals, indicating the association of endothelial dysfunction with obesity [As expected, adolescents with a BMI >95th centile (mean BMI sistance . In our  obesity . In the  obesity , and indz-score in obese adolescents but was not related to percent body fat or circulating leptin levels. Similarly, there were no differences in mean percent body fat or leptin when birth size was arranged by quintiles. Birth weight has a positive correlation with both lean body mass and percent body fat at age 9 or 10 [z-score is related, in part, to birth weight, but not percent body fat which may be determined more by postnatal growth patterns.In a population of over 1,000 9-year-olds not selected by weight the prevalence of SGA was 7% and LGA 9% . In our  9 or 10 . However 9 or 10 . Postnat 9 or 10 , 32. We in utero environment, SGA infants whose mothers were subjected to nutritional restriction as in the Dutch hunger famine of 1944 demonstrated a statistically greater risk of becoming obese as young adults and had a higher rate of T2D [We noted a strong inverse relationship between birth weight and both HOMA and fasting circulating insulin levels, indicating a relatively greater insulin resistance in obese adolescents who were of smaller birth size. Although fasting glucose and glucose tolerance were not statistically different, glycemic status was worse in these individuals because A1C levels were also significantly higher for those of smaller birth weight. Adolescents who were born SGA had, on average, a HOMA value 2.5 units greater than those born LGA. There is strong evidence that infants born to mothers who were diabetic have increased risks of obesity and T2D as young adults , but thee of T2D . When 34e of T2D . Similare of T2D  showed aWe found a strong inverse relationship between circulating adiponectin levels and the adiponectin/leptin ratio, with birth size. Adiponectin increases hepatic triglyceride accumulation, enhances pancreatic beta cell function, and improves insulin sensitivity in peripheral tissues . A decrez-scores in childhood did not correlate with birth weight but were related to maternal prepregnancy BMI. Our findings suggest that for obese adolescents, birth size does not confer a detectable risk of future cardiovascular problems.While this cohort of obese adolescents had relatively decreased mean PAT ratios and slightly elevated mean blood pressure compared to a nonobese population, these measurements showed no relation to birth weight. Several studies found that birth size was inversely related to systolic and diastolic blood pressure in children or adults and to risk of cardiovascular disease , 39. HowIn summary, this study shows that the individual BMI, but not the percent body fat, in obese adolescents was positively related to birth weight. While no differential risk for development of cardiovascular disease was found that could be related to birth weight, there was significantly worse glycemic status and insulin resistance in obese adolescents of lower birth weight. This represents an additional risk factor for future T2D in obese adolescents and may be relevant to the intensity of lifestyle or pharmaceutical intervention necessary within an obesity prevention program.


Weakly electric fish generate an electric field with their electric organ and detect the potential perturbation caused by a target object. There have been many studies of electrolocation in weakly electric fish, but the electrolocation rules have been suggested to reflect the biological experiments ,2. ModelWe can theoretically derive an electrolocation rule that the sensor locations with maximum and minimum peak amplitude in the bimodal electric image, or the distance between the point with minimum peak amplitude and zero crossing point can determine the lateral distance of a target object. The maximum peak position approximately matches the rostrocaudal position of the object. This result matches with the result of other electrolocation rules ,3. Also


Paediatric and Perinatal Epidemiology 2012; 26: 236–249.Matijasevich A, Howe LD, Tilling K, Santos IS, Barros AJD, Lawlor DA. Maternal education inequalities in height growth rates in early childhood: 2004 Pelotas birth cohort study. Socio-economic inequalities in attained height have been reported in many countries. The aim of this study was to explore the age at which maternal education inequalities in child height emerge among children from a middle-income country. Using data from the 2004 Pelotas cohort study from Brazil we modelled individual height growth trajectories in 2106 boys and 1947 girls from birth to 4 years using a linear spline mixed-effects model. We examined the associations of maternal education with birth length and trajectories of growth in length/height, and explored the effect of adjusting for a number of potential confounder or mediator factors.P < 0.001). Among girls the mean height was 100.02 cm (SE = 0.27) and 103.03 cm (SE = 0.15) in the lowest and highest education categories, respectively . For both boys and girls there was on average a 3-cm difference between the extreme education categories. Adjusting for maternal height reduced the observed birth length differences across maternal education categories, but differences in postnatal growth rates persisted.We showed linear and positive associations of maternal education with birth length and length/height growth rates at 0–3 months and 12–29/32 months with very little association at 3–12 months, particularly in boys. By age 4 years the mean height of boys was 101.06 cm (SE = 0.28) in the lowest and 104.20 cm (SE = 0.15) in the highest education category (mean difference 3.14 cm, SE = 0.32, Our data demonstrate an increase in the absolute and relative inequality in height after birth; inequality increases from approximately 0.2 standard deviations of birth length to approximately 0.7 standard deviations of height at age 4, indicating that height inequality, which was already present at birth, widened through differential growth rates to age 2 years. As such, height is considered not a causal factor that directly influences later health and other outcomes, but rather a marker of genetic and intergenerational/intrauterine factors and of childhood environmental exposures, and the timing of puberty.Childhood height is an important marker of health and living conditions in childhood, and secular trends in height have been shown to correlate with trends in economic development.Several prenatal and postnatal factors influence childhood height, including parents' height, genetics, and environmental factors such as parental social class and employment status, dietary intake and infectious diseases.The age at which socio-economic differentials in height appear and the patterns such differentials follow during childhood are less well known. Understanding whether these differentials are largely driven by intrauterine factors  or by postnatal factors  is important for understanding how to reduce height differentials. Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) from the UK showed that the socio-economic differential in height during childhood arises largely through inequalities in birth length, with negligible increases in the inequality from differences in growth after infancy.The aim of the present study was to investigate the age at which socio-economic inequalities in child height emerge among children from a middle-income country birth cohort study, the 2004 Pelotas cohort study from Brazil. The patterning of maternal education on individual growth trajectories was modelled, and potential factors that influence the maternal education–early childhood height growth association were examined.During the whole of 2004, a population-based birth cohort study attempted to enrol all births from mothers resident in the urban area of the city of Pelotas, southern Brazil. Births were identified by daily visits to the five maternity hospitals. Mothers were interviewed soon after delivery. Information was obtained on demographic, environmental and socio-economic variables and on the characteristics of pregnancy, labour, delivery and health care service utilisation. In the city of Pelotas more than 99% of all deliveries take place in hospitals. In 2004, of the 4263 livebirths born to mothers living in the urban area of the city of Pelotas, 4231 were included in the perinatal study (0.8% loss) and were enrolled in the cohort study. Follow-ups were performed at home at mean (SD) ages 3.0 (0.1), 11.9 (0.2), 23.9 (0.4) and 49.5 (1.7) months. On each occasion, mothers were interviewed by trained fieldworkers and information about mother's and children's health was collected. A total of 3985, 3907, 3869 and 3799 children were visited at home at 3, 12, 24 and 48 months of age, respectively. Response rates were 95.7%, 94.3%, 93.5% and 92.0% for the 3-, 12-, 24- and 48-month follow-up, respectively. Further information about the methodology of the 2004 Pelotas birth cohort study is described in detail elsewhere.Birth length was measured within 24 h of delivery by trained research fieldworkers following a standardised procedure using AHRTAG infantometers with 1-mm precision .n = 303 participants), we used the clinical maturity estimate based on the Dubowitz method,Infant sex was recorded at birth. Estimates of gestational age were based on the last menstrual period (LMP), providing they were consistent with predicted birthweight, length and head circumference, based on the normal curves for these parameters for each week of gestational age. When LMP-based gestational age was unknown or inconsistent  was collected at each follow-up. The earliest available information on stopping breast feeding was used to reduce recall bias.Information on maternal variables was gathered from the perinatal interview. Maternal schooling at the time of delivery was collected as a continuous variable and categorised according to the Brazilian Education System. The System is divided into three levels: fundamental (grades 1–8), intermediate (9–11) and higher education . Because of the small numbers of women without any formal education (0 years) and those with higher education, we opted to combine these women with the nearest category available. In addition, we decided to split the 1–8 category because it is very common in the city for women to start the fundamental level and only complete 4 years. Finally, maternal education was categorised as 0–4, 5–8 and ≥9 complete school years of formal education.Family income in the month prior to delivery was expressed as multiples of the minimum wage per month (one minimum wage was worth approximately $80 in 2004). Maternal smoking behaviour during pregnancy was assessed retrospectively at birth and was self-reported. Regular smokers were those women who smoked at least one cigarette per day on an everyday basis in any trimester of pregnancy. Mother's skin colour was self-reported and categorised as white or black/mixed. Women who were single, widowed, divorced or lived without a partner were classified as single mothers. Maternal age in complete years was categorised as ≤19, 20–34 and ≥35 years. Parity was defined as the number of previous viable pregnancies and categorised as 0, 1 and ≥2. Maternal height was measured using a stadiometer manufactured in aluminium with 1-mm precision at the third-month follow-up. Information on paternal height was not available.http://www.cmm.bristol.ac.uk/MLwiN/index.shtml). Such models allow for the change in scale and variance of height over time (i.e. they account for the fact that the mean height and the standard deviation of height increase as children get older) and use all available data from all eligible children under a missing-at-random assumption. They also allow for individual variation in growth trajectories, as random effects allow each individual to have different intercepts and slopes. Models for growth between birth and 48 months were constructed separately for boys and girls, for all individuals with data on maternal education and at least two measurements of length/height (n = 2106 boys and 1947 girls). The methodology identified spline points that defined periods of approximately linear growth based on the data. Based on previous work in the ALSPAC cohort,We estimated individual growth trajectories using a linear spline mixed-effects model , fitted using the statistical package MLwiN version 2.20 .Maternal education inequality in the growth trajectories was estimated by fitting interaction terms in the random-effects model between maternal education and the constant term (representing birth length) and each of the slopes for the four different growth periods. The parameters for these interaction terms demonstrate whether there are differences in birth length or growth in length/height in each period between groups of maternal education  adjusting for family income, (2) adjusting for marital status, maternal age, parity and maternal skin colour, (3) adjusting for maternal height, (4) adjusting for maternal smoking during pregnancy, (5) adjusting for gestational age and duration of breast feeding, and (6) adjusting for all significant confounders. To be included in the last model, variables had to be associated with maternal education and at least one of the outcomes (birth length and growth in length/height), with a a priori conceptualisation of how these covariables might influence the associations we have examined. These are based on previous studies of the associations of each covariable with exposure  and outcome (birth length and childhood growth). In the analytical model we considered maternal skin colour as a potential confounding factor of the maternal education–birth length and growth association. Maternal age at birth, maternal parity, smoking during pregnancy, gestational age and breast feeding were considered to be mediators. Family income, marital status and maternal height could possibly act as either confounder or mediator in this association.Several of the covariables considered in the current analyses could act through different pathways to confound or mediate the associations of maternal education with birth length and early childhood growth. Table S1 summarises our The perinatal study and each follow-up were approved by the Research Ethics Committee of the Federal University of Pelotas School of Medicine. After being informed of the details of the study, mothers signed a form of informed consent for participation.P = 0.888), marital status (P = 0.155), maternal skin colour (P = 0.309), parity (P = 0.352), maternal smoking during pregnancy (P = 0.393), child's sex (P = 0.750), gestational age (P = 0.563) or duration of breast feeding (P = 0.652). However, missing information for length/height was more frequent among the richest group of women (P < 0.001) and among those ≥35 years old (P = 0.022).Data on growth and maternal education were available for 2106 boys and 1947 girls, representing 90% of the original 2004 Pelotas cohort. More than 86% of boys and girls had both data on birth length and measurements of length/height for all follow-ups . Missing information for length/height was not associated with maternal education . There was a mean difference in birth length between the highest and lowest maternal education categories of 0.59 cm (0.23 standard deviations of birth length) and 0.43 cm (0.18 standard deviations of birth length) for boys and girls, respectively. These differences represent 1.2% and 0.9% of the average birth length of a son or a daughter, respectively, of a woman in the highest education category  (Table S4). The equivalent predicted heights at age 4 for girls were 100.02 cm (SE = 0.27) and 103.03 cm (SE = 0.15) in the lowest and highest education categories respectively . Thus for both boys and girls there was, on average, a 3-cm difference between the extreme maternal education categories, representing 2.9% of the average height of a son or a daughter of a woman in the highest education category.Final predicted heights displayed in Table S4 were derived from the results of the multilevel linear spline model and were used to build In a middle-income country, we have shown linear and positive associations of maternal education with birth length and growth rates in length/height at 0–3 months and 12–29/32 months with very little association between 3 and 12 months, particularly in boys.Our data demonstrate an increase in the absolute and relative inequality in height after birth; inequality increases from approximately 0.2 standard deviations of birth length to approximately 0.7 standard deviations of height at age 4. This indicates that height inequality, which was already present at birth, widened as a result of differences in growth rates to age 2 years. Even though adjusting for maternal height reduced the observed birth length differences across maternal education categories, differences in postnatal growth rates among some, but not all, growth periods persisted. Other factors considered as potential confounders or mediators of the maternal education–growth associations  explained little of the observed associations with growth, although family income did reduce maternal education differences in birth length in girls.A major strength of the present study was the mode of data collection; prospective information was obtained among a large unselected population combined with the use of standardised anthropometric measurements performed by trained fieldworkers, with high follow-up rates and low levels of missing data for most variables. However, some methodological difficulties of the study need to be discussed. First, children for whom we have complete information on growth were of lower-income and younger mothers compared with those with missing information for anthropometric variables. It is possible that the magnitude of maternal education inequalities in birth length and growth in length/height could have been higher if all cohort members had been considered. Second, measures for early childhood illness and malnutrition were not included in the present analyses and their effect on maternal education inequalities in height could not be explored. We believe that this is an area for further work. Third, we did not include time-varying covariates in the analyses, although it is possible that baseline levels of maternal variables  could have changed throughout the 4-year follow-up. However, we wished to avoid the possibility of reverse causality of child health influencing parental socio-economic position, so we chose maternal education and family income variables that were measured at the birth of the child. Finally, many other methods are available for modelling growth. Conditional growth modelling has been used to investigate patterns of child growth in length/height in early childhood and final attained stature in the COHORTS  collaboration.–et al.z-score higher by nearly 0.031 and that a child whose mother has completed 7 years of primary schooling has a height-for-age z-score 0.22 higher than a child whose mother has never attended school.et al.z-score higher by 0.024 standard deviations; in other words, a child of a mother with a college degree was, on average, 1.02 cm taller than a child whose mother had only a high school degree.Socio-economic inequalities in height among children have been previously described among high-incomeOur study showed, by the age of 4 years, higher inequalities in height between children in the lowest and highest maternal education categories than in the other two studies previously mentioned (mean height difference of 3 cm in Pelotas and 1 cm in the US and ALSPAC study). Although in the ALSPAC study most of the educational inequality in height during childhood was driven by differences in birth length, this pattern was observed neither in the US study, nor in the Pelotas cohort, where height inequality remained or widened during early childhood.Maternal education in the Pelotas study was measured as complete years of schooling, while in the ALSPAC study it was measured as educational achievement, with all mothers in the ALSPAC cohort having at least 12 years of compulsory schooling . Schooling and educational achievement do not mean exactly the same thing,et al.Many studies have demonstrated a strong correlation between maternal education and child health. However, some investigators disagree with the idea of a causal effect of maternal education on child health and survival.Our results showed that the association of maternal education with birth length and growth rates during early childhood does not appear to operate through income as birth length and growth rate differentials across maternal education categories remained almost the same after adjusting for family income, with the exception of the association with birth length in girls. The relationship between family income and disposable material resources could be influenced by mean family size and sources of unofficial income, which were not accounted for in this study. Other measures which are commonly used to describe socio-economic status, like parental employment and ownership of domestic appliances that were not used in the present study, could have shown different associations with birth length and growth.Leg length is a key component of early height. While in long-term industrialised populations it has been shown that leg length is particularly sensitive to postnatal environmental influences,In our study maternal education was consistently associated with differences in growth rates at age 0–3 months and 12–29/32 months, but not at all after 29/32 months. A possible explanation could be that paternal influences are stronger at older ages. One study from France suggested that mother's height influenced child's height velocity in the first months, but paternal height was more important in the second year of life.The maternal contribution to her offspring's length reflects both genetic and intergenerational/intrauterine factors (see Table S1). Maternal height represents a highly complex combination of genes and environment in the mother's own intrauterine period and childhood. Maternal height could be linked to childhood length via genetic variants; however, it could also represent a perpetuation of a programming influence through several generations.et al.,et al.,Even though shorter people, like the Japanese, have a greater longevity potential than many other taller populations, within populations child height is considered to be a strong predictor of human capital and the health of future generations. Evidence to date suggests that socio-economic inequalities in childhood height have been reduced in magnitude in some settings in the last decades. Li Even though we cannot deduce exactly the reason why higher formal education would make such a difference in child height, our findings accentuate the importance of reducing socio-economic inequalities in child outcomes in low- and middle-income populations like Brazil. Improving educational standards may be one way of reducing inequalities. Much progress has been made in Brazil in the last decades to ensure universal access to primary education and to improve the quality of schools around the country. However, data from the 2004 Pelotas cohort study indicated that almost one in 10 mothers did not complete primary education. The second Millennium Development Goal states that boys and girls everywhere will be able to complete a full course of primary schooling. This measure should help to reduce inequalities in childhood height, among other aspects of child health, and thence to avoid possible long-term consequences of impaired linear growth to adult life in future generations.A. M. identified the research question, conducted the analyses and wrote the first draft of the article. LDH contributed with the analyses, the interpretation of the findings and the writing of the article. KT, DAL, ISS and AJDB contributed to developing the research question, the interpretation of the analysis and assisted with the editing of the article.


Social deprivation is associated with higher rates of preterm birth and subsequent infant mortality. Our objective was to identify risk factors for preterm birth in the UK's largest maternity unit, with a particular focus on social deprivation, and related factors.+0 weeks). In the low risk group, preterm birth rates increased with deprivation, reaching 1.6% (CI95 1.4 to 1.8) in the most deprived quintile; the unadjusted odds ratio comparing an individual in the most deprived quintile, to one in the least deprived quintile was 1.5 (CI95 1.2 to 1.9). Being underweight and smoking were both independently associated with preterm birth in the low risk group, and adjusting for these factors explained the association between deprivation and preterm birth. Preterm birth was five times more likely in the high risk group (RR 4.8 CI95 4.3 to 5.4), and there was no significant relationship with deprivation.Retrospective cohort study of 39,873 women in Liverpool, UK, from 2002–2008. Singleton pregnancies were stratified into uncomplicated low risk pregnancies and a high risk group complicated by medical problems. Multiple logistic regression, and generalized additive models were used to explore the effect of covariates including area deprivation, smoking status, BMI, parity and ethnicity on the risk of preterm birth (34Deprivation has significant impact on preterm birth rates in low risk women. The relationship between low socio-economic status and preterm births appears to be related to low maternal weight and smoking in more deprived groups. ENREF6. Understanding the relationship of these factors is central to designing effective prevention strategies Preterm birth is an important public health issue in the UK and internationally, since prematurity is a major contributor to infant mortality and inequalities in health There is increasing interest in the UK in publishing and comparing clinical outcomes across centres Since the aetiology of preterm birth is significantly different in multiple pregnancies, women with a previous history of preterm birth, and following intrauterine transfers to tertiary obstetric units, we aimed to explore the effect of SES in singleton, booked pregnancies regarded clinically as either high or low risk. Our a priori hypothesis was that there would be differential rates of preterm birth by socioeconomic status, and that these might be related to individual level risk factors. We show that deprivation is indeed an important risk factor in low risk pregnancies, and that this is related to maternal smoking and underweight.Ethical approval for this study was sought and granted by the Sefton Research Ethics Committee. We used routinely collected data from electronic hospital records, analysed anonymously, and individual patient consent was not required.To quantify the effect of social deprivation and other risk factors on preterm delivery in high and low risk pregnancies.+0 weeks gestation over a seven year period from 2002–2008. In order to avoid clustering of risk factors, subsequent pregnancies of women who had more than one pregnancy during the data collection period were excluded from the analysis. The data extracted contained detailed information on demographics, previous and current obstetric history and details of medical conditions.We undertook a retrospective cohort study using routinely collected data from the Liverpool Women's NHS Foundation Trust (LWH). This is the single largest maternity unit in the UK, delivering around 8,000 babies and caring for around 1,000 preterm infants in the neonatal unit annually. We accessed data from the LWH Meditech hospital information system on all women delivering after 24We excluded intrauterine transfers (IUTs), multiple pregnancies, and pregnancies in women with a previous history of preterm delivery <34 weeks from this analysis. The remaining pregnancies were allocated to the high-risk group if they had significant medical conditions. Two obstetricians reviewed all the coded data on co-morbidity in pregnancy, and identified all medical disorders of potential relevance to preterm birth. These included problems identified at booking  and problems developed during pregnancy . The group remaining was our low risk population of interest, and represents uncomplicated singleton pregnancies with no identifiable major clinical risk factors for preterm birth.+0 gestational weeks (<238 days: PTB<34) calculated on the basis of first trimester scan. We included both spontaneous and obstetrically induced births less than 34 weeks gestation in this outcome as this group is likely to have significant morbidity, both short and long term, with important resource implications for health services +1 and 36+6 weeks (PTB 34–37) was also considered, because the public health burden of late preterm birth is substantial The primary outcome was preterm birth before 34We aimed to explore the following covariates: maternal age, parity (nulliparous or not), smoking status , and current smoker>10 cpd, and ), BMI at booking  and ethnicity (self-reported categories coded to white and other). BMI was consistently collected from 2004 onwards in MEDITECH. Before 2004. BMI was calculated from height and weight where available. Postcodes were used to derive Index of Multiple Deprivation (IMD) scores for all of the pregnancies. The IMD combines a number of indicators, chosen to cover a range of economic, social and housing issues, into a single deprivation score for small areas in the UK ENREF18 eneralized additive models (GAMs) were used to explore the univariate relationship between the log-odds of preterm birth and deprivation score Although IMD is measured on a continuous scale, for descriptive summaries, we have followed the common practice of grouping IMD into quintiles. However, reducing IMD to a categorical variable looses information. For formal analysis of the association between deprivation and pre-term birth we therefore retained IMD as a continuous variable. G51,857 pregnancies were recorded in the Meditech system. We excluded 431 intrauterine transfers, 940 multiple pregnancies and 732 pregnancies in women with a history of previous preterm birth, leaving 39,404 low risk pregnancies, and 10,351 high risk pregnancies. Selecting the first pregnancy for each woman during the data collection period resulted in the final sample of 31,785 low risk and 8,130 high-risk pregnancies. A valid postcode was available on all but 42 women leaving 39,873 pregnancies in the final analysis.95 4.3 to 5.4) comparing the high risk group to the low risk group. Out of these preterm live births there were 53 neonatal deaths before hospital discharge (5.1%) with no difference in the proportion of deaths within the preterm birth subgroups.Overall, 2.6%  of pregnancies resulted in preterm birth before 34 weeks, significantly more than 1.9% nationally in 2005 95 2.7 to 3.2) comparing the high risk group to the low risk group.There were 1148 (3.6%) late preterm births in the low risk group, and 871 (10.7%) in the high risk group, equating to a late preterm birth relative risk of 2.97 (CI95 1.4 to 1.8) with a significant trend towards a higher proportion of preterm births as deprivation increases (Chi square for trend p<0.01). By contrast, there was no significant trend in preterm births in the high risk group by deprivation quintile. The numbers of deaths was small in both groups with no significant trend detected when these deaths were stratified by deprivation quintile. 95 1.003 to 1.0114), which equates to an OR of 1.47 (CI95 1.16 to 1.86) comparing an individual in the most deprived quintile to one in the least deprived quintile . Age<18, being underweight and smoking were also highly significantly associated with an increased risk of preterm birth.95 1.05 to 1.51), as did smokers, being underweight, and non-white women.For low risk late preterm births there was a similar relationship with deprivation, smoking and being underweight, but age<18 was not significant. For high risk late preterm births the most deprived quintile had an increased risk of preterm birth (OR 1.26 CI95 0.90 to 1.73). Smoking and being underweight remained highly significant, both approximately doubling the risk of preterm birth<34. For late preterm births smoking had a similar effect, but underweight was not significant, and the adjusted OR for the effect of deprivation was reduced, but remained significant (1.32 CI95 1.12 to 1.64). In high risk women, smoking was associated with both preterm subgroups, but being underweight was only significant for preterm births between 34–37 weeks.Using routinely collected obstetric data from a retrospective cohort of 39,873 women with a singleton pregnancy, we were able to define a high risk group with a five fold greater risk of preterm birth before 34 weeks compared with the women without obvious risk factors. In otherwise low risk pregnant women deprivation, age <18, underweight and smoking were associated with preterm birth<34.Our data, therefore, suggest that reducing the burden of disease due to very preterm birth will have to involve targeted, disease specific preventative interventions in high risk pregnancies, but for low risk groups, population level public health action is needed to address risk factors for preterm birth associated with social deprivation.In women who gave birth between 34 and 37 weeks the distinction between low and high groups was less distinct – smoking was important, but age and obesity were not. Interestingly, being underweight was significant in high risk, but not in low risk. The opposite was found in very preterm births. The reasons for this pattern are unclear. Despite the large number of pregnancies analyzed, it is likely that our analysis was underpowered to detect a statistically significant association with being underweight in some of our subgroups. All of the point estimates for underweight are in the same direction, however, suggesting that underweight women are at increased risk of preterm birth.We have demonstrated that it is possible to identify distinct clinically important groups, with markedly different preterm birth rates, on the basis of medical information collected during pregnancy. In-utero transfers, multiple pregnancies and women with a history of previous preterm birth have very different risks of preterm birth (results not reported here) and should be analysed separately. We suggest that stratification of birth outcomes in terms of these groups provides a more meaningful method to report preterm birth outcomes from maternity units for auditing and benchmarking purposes. So for example, rates of preterm birth in multiple pregnancies would provide an additional useful metric.ENREF19 Furthermore, addressing inequalities in infant mortality rate has been a political imperative in the UK over the last 10 years. The UK government's latest report on health inequalities suggests that one quarter of infant deaths would potentially be avoided if all births had the same level of risk as those to women with the lowest level of deprivation Reducing infant mortality, which is accounted for to a great extent by preterm birth, is a key focus of both the recent NHS white paper, and the Public Health white paper It has been hypothesised that the relationship between low socioeconomic status and preterm birth may be explained by the clustering of demographic and ‘lifestyle’ risk factors in women from more disadvantaged backgrounds In our cohort, being underweight (BMI<18.5) emerged as a clear risk factor in the low risk group, approximately doubling the risk of preterm birth<34. This is in line with a recent meta-analysis A strength of our analysis is that we have a large sample, with individual level clinical data, and were able to stratify pregnancies in terms of major obstetric risk factors. The main purpose of this stratification was to allow a ‘cleaner’ view of the relationship between SES and preterm births, without the risk of confounding, particularly by medical problems. For this reason, we stratified the pregnancies based on a combination of characteristics that may or may not be present in early pregnancy. A different analytical approach would be required to quantify the risk of preterm birth for counselling purposes in early pregnancy. These methods and our findings are likely to be generalizable to other large tertiary maternity units in the UK, serving deprived populations.This study is hospital based, rather than population based, but our cohort is likely to be similar to a population based cohort, since LWH is the main maternity unit in the Liverpool area, and there are no private providers. We have limited selection bias by excluding transfers in to LWH, who have a different risk profile. We had to rely on retrospective, routinely collected data, and there is scope for response bias in the self-reported smoking status covariate. We have used a standard small area based measure of deprivation. It was therefore not possible to separate effects of SES operating at the individual and area level, which may be distinct, as suggested in other studies of preterm births Our results have a number of implications. Social deprivation is an important risk factor for preterm birth, and the effect of deprivation is related to maternal smoking and underweight, providing clear targets for public health action to reduce inequalities in preterm birth and subsequent infant mortality. At the individual level smoking is recognised as one of the most important “lifestyle” factors in the pathway to health inequalities, and persistent social gradients remain in the UK The social distribution of preterm birth suggests that social factors – the “social determinants of health” – are having an important effect on outcomes. These are the “conditions in which we are born, grow up, work and live” Further attempts to explore the pathways from low SES to preterm births need to take into account individual and area level mediators to identify further targets for preventative interventions. As a way forward, maternity units should produce preterm birth rates stratified by clinical risk factors and deprivation quintiles. Given the influence of SES, the proportion of preterm and term births to women in the most deprived normative English quintile should be used as a metric in comparing quality of maternity care across centers. Targeted analysis of outliers will provide important insights into possible preventative interventions and resource allocation by newly established GP consortia in the UK


A brachial artery pseudoaneurysm is a rare but serious condition that can be limb threatening. A number of reports have found that it may be the result of damage to the blood vessels around the brachial artery, either directly or indirectly, due to trauma or systemic diseases. We present our experience of delayed pseudoaneurysm rupture of the brachial artery in a rehabilitation patient with burns of the upper extremity who underwent fasciotomy and musculocutaneous flap coverage. We also provide a review of the brachial artery pseudoaneurysm. A pseudoaneurysm of the peripheral artery is very rare and is generally a late sequela of trauma, iatrogenic injury, and general illness. It is more infrequent in the upper limb vasculature than in the lower limb vasculature. Although there are many reported causes of brachial artery pseudoaneurysms, to our knowledge, this is the first report of delayed rupture of a brachial artery pseudoaneurysm during the rehabilitation of a patient with burns of the upper extremity who underwent fasciotomy and musculocutaneous flap coverage. We also present a review of the brachial artery pseudoaneurysm.A 26-year old male patient presented to the hospital with wound dehiscence and oozing of the left axilla that had commenced two days earlier while undergoing rehabilitative therapy for postburn joint ankylosis and brachial plexus palsy of the upper extremity Figure . AccordiAn aneurysm is defined as a permanent localized dilatation of an artery with at least a 50% increase in its diameter compared with the expected normal diameter . AneurysA brachial artery aneurysm usually presents as a pseudoaneurysm and rarely as a true aneurysm . Its etiThe brachial artery pseudoaneurysm usually develop slowly. It took days to months, even years to develop symptoms or be detected clinically. A brachial artery pseudoaneurysm often presents with erythema and induration, together with an expanding, painful mass. It is sometimes accompanied by a thrill or an audible bruit, decreased temperature, cyanosis, loss of pulsation, and paresthesia upon nerve compression of the distal extremity . VariousVery rarely, the presence of a thromboembolism in the aneurysm can result in terminal ischemia, gangrene, and amputation . In suchThis case did not show the generally observed symptoms of a pseudoaneurysm: swelling, thrill, and a mass-like lesion. A brachial artery pseudoaneurysm was not suspected at first because the patient had visited the hospital with wound dehiscence, accompanied by oozing as the main complaint. It is difficult to perform an accurate physical examination after burn wound reconstruction because the surrounding tissue hardens as a result of fibrosis. This fibrosis of the surrounding tissues also helped to prevent continuous enlargement of the pseudoaneurysm in the present case. The pseudoaneurysm in this patient is likely to have formed gradually due to partial damage of the brachial artery wall during burn rehabilitation when the soft tissues adhered to the blood vessel tract, and due to burn-induced blood vessel injuries. As shown in Figure Delayed rupture of a brachial artery pseudoaneurysm during rehabilitation therapy in a patient with postburn wound reconstruction of the upper extremity is very rare. Nerve-vessel damage may occur in such cases due to adhesion of neurovascular bundle to the surrounding tissues during burn rehabilitation. The exposed neurovascular bundle after fasciotomy in a severe burn patient should be covered with well vascularized soft tissue padding to prevent scarring to the surrounding tissue to prevent scar tethering-induced pseudoaneurysm formation. Although it is hard to observe symptoms of a pseudoaneurysm due to the fibrotic, hard reconstructed tissues, early diagnosis and immediate treatment of the pseudoaneurysm are needed to prevent serious complications, such as distal necrosis.Written informed consent was obtained from the patient for publication of this case report and accompanying images.The authors declare that they have no competing interests.All of the authors were involved in the preparation of this manuscript. JYL wrote the manuscript and reviewed the literatures. HKim was an assistant surgeon and helped in literature search. HKwon participated in the clinical and surgical management. S-NJ participated in the conception, design of the study, and operated the patient. All authors read and approved the final manuscript.


The goal of this study was to assess the relationship between Aβ deposition and white matter pathology  on microstructural integrity of the white matter. Fifty-seven participants (mean age: 78±7 years) from an ongoing multi-site research program who spanned the spectrum of normal to mild cognitive impairment  and low to high risk factors for arteriosclerosis and WMH pathology  were assessed with positron emission tomography (PET) with Pittsburg compound B (PiB) and magnetic resonance and diffusion tensor imaging (DTI). Multivariate analysis of covariance were used to investigate the relationship between Aβ deposition and WMH pathology on fractional anisotropy (FA) from 9 tracts of interest . WMH pathology was associated with reduced FA in projection  and association  fiber tracts. Aβ deposition  was associated with reduced FA in the fornix and splenium of the corpus callosum. There were interactions between PiB and WMH pathology in the internal capsule and parahippocampal white matter, where Aβ deposition reduced FA more among subjects with WMH pathology than those without. However, accounting for apoE ε4 genotype rendered these interactions insignificant. Although this finding suggests that apoE4 may increase amyloid deposition, both in the parenchyma (resulting in PiB positivity) and in blood vessels (resulting in amyloid angiopathy and WMH pathology), and that these two factors together may be associated with compromised white matter microstructural integrity in multiple brain regions, additional studies with a longitudinal design will be necessary to resolve this issue. Focal and diffuse lesions in the white matter, seen as hyperintensities on T2-weighted magnetic resonance images (MRI)  are the most ubiquitous age-related alteration seen in the brain Diffusion tensor imaging (DTI) measures the organization of fibers within specific white matter tracts Recent epidemiologic studies have noted that risk factors for atherosclerosis  are also associated with increased risk of incident AD Subjects were older adults from the ongoing multi-site Aging Brain research program designed to recruit individuals with substantial risk factors for arteriosclerosis and vascular brain injury This study focused on a subset of 57 individuals who had PiB PET and DTI data. The mean time between acquisition of the PiB and DTI imaging data was 3.9±4.9 months (range: 0–19 months). The subjects received clinical diagnostic evaluations at the Alzheimer’s Disease Centers at the University of California at Davis and San Francisco. For purposes of analyses, the participants were classified by their Clinical Dementia Rating CDR  scores. The study was approved by the University of California  and Lawrence Berkeley National Laboratory institutional review boards (IRB) for human research. Written informed consent was obtained from all participants or their legally authorized representatives following IRB-approved protocols. If there was an indication of cognitive impairment , the study personnel obtaining consent would first assess whether or not the potential participant understood key elements of the protocol, including that participation is voluntary, that it is a research study, the procedures, the risks and benefits. If the potential participant lacked the capacity to provide informed consent, then informed consent was obtained from the participant’s legally authorized representative in accordance with California law and the policy of the IRB of all participating institutions. The majority of participants with CDRs of 0.5 had the capacity to provide informed consent.3 isotropic resolution), a Fluid-Attenuated Inversion Recovery (FLAIR) scan , a T2-weighted turbospin echo sequence for intracrinal volume (ICV) determination , and DTI scans obtained with a dual spin-echo EPI sequence, augmented by diffusion weighting gradients (b = 800 s/mm2) along six collinear directions and the acquisition of a reference image (b = 0). Other parameters of DTI were TR/TE = 10,000/101 ms, 60 slices 2×2×2 mm3 resolution. Twofold parallel imaging acceleration was used for DTI to reduce geometrical distortions MRI images were collected on Siemens 3 T MRI systems. Eight participants were scanned using a 3 T Siemens Magnetom Trio Syngo System with an 8-channel head coil at the University of California, Davis (UCD) research center. Acquired images included a T1-weighted volumetric MP-RAGE , a FLAIR scan , a T2-weighted turbospin echo sequence , and DTI scans obtained with a dual spin-echo EPI sequence supplemented with GRAPPA to reduce susceptibility distortions .Forty-three participants were scanned at UCD using a 3 T Siemens Magnetom TrioTim system with an 8-channel head coil. Six participants were scanned at the University of California, San Francisco (UCSF) Neuroscience Imaging Center using a 3 T Siemens Magnetom TrioTim system with a 12-channel head coil. Acquired images for the participants scanned on the 3 T Siemens Magnetom TrioTim system at UCD and UCSF included a T1-weighted volumetric MP-RAGE  blind to any other participant data using the T1 and FLAIR MRIs, were identified on 22 of the 57 participants (39%). Infarcts were categorized according to affected vascular territory, structures involved, size , severity , and number. Blood was drawn with the subject’s consent for apolipoprotein E (apoE) genotyping, available for 48 of the 57 participants. Subjects with 3/4 or 4/4 combined alleles were classified as apoE ε4 positive, and those with 3/3 alleles as apoE ε4 negative. Because the 2/4 combined allele is associated with a lower risk of AD WMH were segmented from skull-stripped, intensity inhomogeneity corrected FLAIR images 3). Next, the ‘JHU ICBM-DTI-81’ atlas package Preprocessing of the DTI data involved skull-stripping, motion and eddy-current correction with FSL package, geometric distortion correction Based on the literature and a priori hypotheses, FA were extracted from 9 tracts of interest that included the corona radiata and internal capsule (projection fibers), cingulum gyrus and parahippocampal white matter, and fornix (limbic fibers), superior longitudinal fasciculus, inferior and superior fronto-occipital fasciculi (association fibers), and corpus callosum. PiB-PET imaging was conducted at Lawrence Berkeley National Laboratory using a Siemens ECAT EXACT HR PET scanner in 3D acquisition mode. The PiB radiotracer was synthesized using a previously published protocol http://www.fil.ion.ucl.ac.uk/spm). Region of Interest (ROI) labeling, including the cerebellum gray matter masked, was implemented using the FreeSurfer v5.1 software package (http://surfer.nmr.mgh.harvard.edu/). Distribution volume ratio (DVR) images were created using Logan graphical analysis with PiB frames corresponding to 35–90 minutes post-injection and a gray matter cerebellar mask as the reference region PiB-PET data was preprocessed using the Statistical Parametric Mapping software package . Associations among dichotomous variables were assessed using Pearson Chi-Square test. We used multivariate analysis of covariance (MANCOVA) to evaluate the effects of WMH pathology and PiB status on FA from the 9 a priori tracts of interest, controlling for age, CDR, and presence of infarct. Because we had no a priori hypotheses about laterality, FA from homologous parcels was averaged across hemispheres to reduce the number of comparisons. To further protect against type I error, we combined several of the ‘JHU ICBM-DTI-81’ white matter parcels . We examined the 3 subregions of the corpus callosum  separately because we wanted to test the patho-anatomic model for regional disruption of callosal FA proposed by Lee et al 2 = 3.93, df = 1, p<0.05) than PiB negative. There were no significant age, sex, education, MMSE, GDS, CDR, apoE, global PiB index, or frequency of brain infarct among participants with (N = 27) or without (N = 30) WMH pathology. As expected, WMH volume was larger among participants with than without WMH pathology . Twenty-two participants  had radiologic evidence infarct(s). A summary of the description of the participants’ infarcts is presented in 1,50 = 6.69, p = 0.01) and the splenium of the corpus callosum . WMH pathology was associated with lower FA in the corona radiata , internal capsule , superior longitudinal fasciculus , superior fronto-occipital fasciculus , inferior fronto-occipital fasciculus , and body of the corpus callosum . There was a positive interaction between PiB and WMH pathology in the internal capsule  and parahippocampal white matter , where PiB-related reductions in FA was greater among participants with WMH pathology.1,29 = 3.29, p = 0.08) after controlling for age and CDR. WMH pathology was associated with lower FA in the corona radiata , internal capsule , superior longitudinal fasciculus , and inferior fronto-occipital fasciculus , and marginally lower FA in the superior fronto-occipital fasciculus  and body of the corpus callosum . There was a positive interaction between PiB and WMH pathology on FA in the internal capsule  and a marginally significant interaction in the parahippocampal white matter .Similar to the analysis in the entire study population, secondary analysis in the subset of subjects without infarct(s) revealed a marginal effect of PiB positivity on FA in the fornix  and in the splenium of the corpus callosum ; a main effect of WMH pathology on FA in the corona radiata , internal capsule , superior longitudinal fasciculus , superior fronto-occipital fasciculus , inferior fronto-occipital fasciculus , and body of the corpus callosum ; and interactions between PiB and WMH pathology on FA in the internal capsule  and parahippocampal white matter . In a second MANCOVA that controlled for apoE ε4 status in addition to age, CDR, and presence of infarcts, there was a main effect of PiB on fornix  and splenium  FA and a main effect of WMH pathology on FA in the corona radiata , internal capsule , superior longitudinal fasciculus , superior fronto-occipital fasciculus , inferior fronto-occipital fasciculus , and body of the corpus callosum . However, the interaction between PiB and WMH pathology in the internal capsule  and parahippocampal white matter  were no longer significant.In our examination of the effects of WMH pathology and Aβ deposition on white matter microstructural integrity, we found that (1) WMH pathology was significantly associated with reduced FA in projection and association fibers. (2) Aβ deposition was significantly associated with reduced FA in the fornix and splenium of the corpus callosum. (3) Although there were positive interactions between WMH pathology and Aβ deposition on FA in the internal capsule and parahippocampal white matter, accounting for apoE genotype rendered these interactions only marginally significant. Possible mechanisms and interpretations of the interaction are discussed below.As hypothesized, WMH pathology was associated with reduced FA in projection and association fibers. This finding is consistent with earlier reports of an inverse relationship between FA and WMH volume As hypothesized, Aβ deposition was significantly associated with reduced FA in the fornix and selenium of the corpus callosum. Several studies have demonstrated that Aβ deposition can lead to DTI changes in mice There is evidence suggesting that vascular brain injury exerts subtle deleterious effects on brain structure and function beyond frank infarction or hemorrhage One possible mechanism by which WMH pathology and Aβ deposition might interact positively to degrade white matter microstructure is through the reduction of brain reserve. Reserve is the concept that there are characteristics of the brain that buffer the impact of pathology on brain performance ow angular resolution of DTI (6 directions), the fact that we did not account for the location of vascular lesions in our analyses of FA values obtained from 9 white matter tracts that covered most of the supratentorial white matter, and the cross-sectional nature of the study design. Future studies with a longitudinal design will be able to better resolve the nature of the relationship between WMH pathology and PiB positivity on white matter microstructural integrity in different regions of the brain.The current findings should be considered in the context of several study limitations: First, the study sample was the small and heterogeneous. Second, apoE genotyping was only available in a subset of subjects. Therefore, our interpretation of the role of apoE in the interaction between PiB positivity and WMH pathology on FA are speculative at best and should be regarded with caution. Other study limitations include the l