In addition, telomere lengths were not significantly different between preterm infants sampled at birth and those sampled at term equivalent age. These results indicate that other, as yet undetermined, factors may influence telomere length in the preterm born infant and raise the intriguing hypothesis that as preterm gestation declines, telomere attrition rate increases.There are well-established morbidities associated with preterm birth including respiratory, neurocognitive and developmental disorders. However several others have recently emerged that characterise an ‘aged’ phenotype in the preterm infant by term-equivalent age. These include hypertension, insulin resistance and altered body fat distribution. Evidence shows that these morbidities persist into adult life, posing a significant public health concern. In this study, we measured relative telomere length in leukocytes as an indicator of biological ageing in 25 preterm infants at term equivalent age. Comparing our measurements with those from 22 preterm infants sampled at birth and from 31 term-born infants, we tested the hypothesis that by term equivalent age, preterm infants have significantly shorter telomeres (thus suggesting that they are prematurely aged). Our results demonstrate that relative telomere length is highly variable in newborn infants and is significantly negatively correlated with gestational age and birth weight in preterm infants. Further, longitudinal assessment in preterm infants who had telomere length measurements available at both birth and term age (n = 5) suggests that telomere attrition rate is negatively correlated with increasing gestational age. Contrary to our initial hypothesis however, relative telomere length was significantly  Preterm birth, defined by the World Health Organisation as birth at less than 37 weeks completed gestation, is estimated to account for 14.9 million or 11.1% of all births worldwide. Although survival rates are improving, recent data suggests that preterm birth is a risk factor in half of all neonatal deaths and that 1 million deaths each year are a direct result of complications associated with preterm birth . FurtherBy term age, preterm babies display a phenotype that is different from that of the term born infant. Specifically, these babies have altered adipose tissue partitioning , 8, ectoTelomeres are repetitive DNA sequences at the end of chromosomes that become shorter with each cell cycle , 20. Wheex utero, since age matched foetuses do not conform to this trend [Despite recent academic focus on telomere biology in newborns –49, littis trend . Furtheris trend , 53.ex utero environment of the neonatal intensive care unit differs fundamentally from both the in utero environment and the postnatal environment experienced by the term infant. For example, exposure of preterm infants to elevated levels of oxygen may potentially lead to increased reactive oxygen species and induce DNA damage (to which the G-rich telomere sequence is particularly susceptible) [ex utero factors might act to modulate telomere length in the preterm infant, resulting in a phenotype reminiscent of premature ageing.The eptible) , 55. In eptible) –59. Therex utero environment may be relevant, we sought to test the hypothesis that by term equivalent age, telomere length is shortened in preterm infants in comparison to term born infants.Therefore, the aim of this study was to conduct a prospective observational study to compare telomere lengths of preterm infants sampled at birth and at term equivalent age with that of term infants. Although a small number of studies have compared telomere lengths in preterm infants with that of those born at term, none have assessed telomere length in preterm infants at term equivalent age (i.e. 37–42 weeks). Given that the evidence available demonstrate a reduction in telomere length with advancing gestational maturity in preterm infants and that the With institutional research ethics committee approval 10/H1109/51) and informed parental consent we conducted a prospective observational study over a four year period (June 2011 to June 2015). A total of 47 preterm infants with a birth gestational age of < 32 completed weeks gestation were recruited from the level 3  neonatal unit at the William Harvey Hospital in Ashford, Kent and the level 1 neonatal unit at the Queen Elizabeth the Queen Mother Hospital in Margate, Kent. We chose to include preterm infants born < 32 weeks completed gestation in light of previous data, which showed a rapid and significant decline in telomere length with advancing gestational age in infants born at < 32 weeks [ and info°C. Samples were collected by a member of the research team who was blinded to the group allocation of the blood sample and transported to the School of Biosciences, University of Kent under dry ice. Samples were thawed and equilibrated to room temperature prior to genomic DNA extraction using a DNA isolation from mammalian blood kit (Roche). Isolated DNA was dissolved in Tris-EDTA pH8.0 and assessed for DNA concentration and purity using a Nanodrop spectrophotometer. All samples were stored at -20°C until telomere length analysis by a single observer, using multiplex quantitative real time polymerase chain reaction (qRT-PCR). Primer design for telomere and a single copy reference gene (haemoglobin B) amplification was as previously described by Cawthon et al 2009 [TM SYBR No-ROX Kit (Bioline), 50nM each primer and 25ng of standard or unknown sample DNA. The reaction was carried out using a Rotor-gene Q 2 plex HRM platform under the following cycling conditions: 95°C for 10 mins, two cycles of 94°C for 15 secs and 49°C for 15 secs, 37 cycles 94°C for 15 secs, 62°C for 10 secs, 74°C for 15 secs, 84°C for 10 secs and 88°C for 10 secs. Each unknown and standard DNA sample was assayed in triplicate. Relative telomere length expressed as telomere to single copy gene ratio (T/S ratio) was calculated using a standard comparative method (delta delta Ct) [1ml of additional blood was collected by venepuncture in a paediatric lithium heparin bottle taken at the time of routine blood sampling in study recruits. In preterm infants, we aimed to collect a sample within 48 hours of life or at term equivalent age . Term born infants underwent blood sampling at the time of routine blood sampling within the first 48 hours of life. Each blood sample was assigned a 2 digit numerical code and frozen at -80 al 2009 . Simultaelta Ct)  . The primary outcome, T/S, ratio was normally distributed and therefore parametric methods (univariate ANOVA) were used for analysis. Cohen’s d was used to determine effect size  for mean T/S ratio between the groups.p = <0.01) when compared to term infants (p = 0.28 and 0.18 respectively). There were no significant differences between the groups with respect to maternal age . The characteristics of recruited term and preterm infants recorded at the time of sampling are displayed in  infants . Birth g infants  and pret infants  were notrnal age . In eachrnal age . The PreMean T/S ratio and T/S variability for preterm infants sampled at birth, preterm infants sampled at term and term born infants are shown in p = 0.001, p = 0.006 respectively) and that maternal age was positively correlated with T/S ratio (p = 0.011). Moreover, our data demonstrate a gradient effect with T/S ratios being highest in preterm infants sampled at birth and lowest in term infants, with term infant T/S ratios being significantly shorter than those of both preterm infants sampled at term (p = 0.04) and preterm infants sampled at birth (p = 0.004) (p = 0.42).We did not observe any difference in T/S ratios in males compared to female infants either overall, or within each cohort. However, our results show that both gestational age and birth weight were negatively correlated with T/S ratio (= 0.004) . Cohen’sFor reasons highlighted in the discussion section, we were only able to obtain longitudinal telomere length samples  in five preterm infants. A post hoc analysis of this longitudinal data enabled calculation of telomere attrition rate (Equation 2) between birth and term age.p = 0.07) for these 5 babies . These data are shown in longer telomere lengths than term born infants. However, in keeping with other published data, our results indicate a significant decline in telomere length with advancing gestational age at birth [In this study we assessed whole blood leukocyte telomere length in a cohort of preterm and term born infants shortly after birth, and for the first time, we also assessed telomere length in preterm infants at term equivalent age. Our data do not support our initial hypothesis that telomere length is significantly shortened by term equivalent age in preterm infants and in comparison to term infants. On the contrary, our results show that preterm infants at term equivalent age have significantly at birth –52. We ain comparison to term born babies: Friedrich et al. found no significant difference between the two groups when they assessed cord blood leukocyte telomere length [et al. and Ferrari et al. found significantly shortened leukocyte and placental telomere lengths respectively in term born infants compared to preterm infants born with intact membranes [et al. provided data to support the hypothesis that unexplained stillbirths are associated with placental telomere attrition by demonstrating a reduction in placental telomere length between stillbirths and term born infants [et al. noted failed karyotype analysis in 15/42 stillborn cases.Telomere length in preterm infants is a largely understudied area and to the best of our knowledge, only three other studies have assessed telomere length in preterm infants e length , howeverembranes , 51, 53. infants . Indeed While these findings . Nonetheless, given the high variability in telomere lengths shown by our own and others’ data , 64, 65,et al. who found a significant shortening of telomeres in the weeks following preterm birth [In light of previous observations by Holmes rm birth , the finrm birth , 75. Altrm birth –78. In orm birth . Should et al demonstrated a similar association, albeit using a telomere restriction fragment (TRF) methodology to measure newborn telomere length [To further investigate these areas of uncertainty, it would have been beneficial to assess preterm infant telomere length longitudinally in all preterm babies recruited to our own study. This would additionally unmask any potential hidden effects attributable to a large spread in data as a result of variable genetic and epigenetic influences. Despite this being our original intention, obtaining samples for telomere length analysis at birth and at term equivalent age proved difficult as a number of preterm babies were either discharged from hospital or transferred back to their local neonatal unit prior to term age. From the five preterm infants in whom we were able to collect longitudinal data , we demoe length . This fie length . Howevere length , 82. TheIt may be that analysis of average telomere length in the preterm infant at term equivalent age cannot act as a suitable marker of the aged phenotype observed. Perhaps rather than measuring telomere length at term equivalent age in preterm infants, it may be more prudent to measure them further downstream e.g. during later childhood or adolescence. This has proved to be informative in previous studies where shortened telomere length was shown to be associated with respiratory morbidity in the ex-preterm infant , 83. HowIn conclusion, our data indicate that preterm infants assessed at term equivalent age manifest longer telomere lengths than term born infants. In addition, our data and that of other groups , 84, 89 S1 FileAnonymised patient data collected for the study.(XLSX)Click here for additional data file.


The relationship between maternal body compositions and birth weight was not definite. Fat Mass (FM) and Fat Free Mass (FFM) can accurately reflect the maternal body fat compositions and have been considered as better predictors of birth weight. Despite its potential role, no studies have been described the maternal compositions during pregnancy in East Asian women previously. We investigated the correlation between birth weight and Maternal body composition including fat mass (FM) and fat free mass (FFM). To determine whether birth weight is associated with maternal body fat FM and FFM during pregnancy and, if so, which trimester and parameter is more critical in determining birth weight.A longitudinal prospective observational study performed, 348, 481 and 321 non-diabetics Han Chinese women with a singleton live birth attending a routine visit in their first, second and third trimesters were recruited. Maternal body composition was measured using segmental multi-frequency bioelectrical impedance analysis. Data of the pre-pregnancy body mass index (BMI), maternal BMI, the gestational weight gain (GWG), and placental and birth weight were collected.P < 0.05). On stepwise multiple linear regression analysis, material’s FFM was the most important factor associated with the birth weight. After adjustment, there was significantly associated with 2.47-fold increase in risk for birth weight more than 4 kg when FFM ≥ 40.76 kg (Upper quartile of participants). The increased maternal age became a protective factor (OR = 0.69) while the increased pre-pregnancy BMI (OR = 1.50) remained predictors to birth weight more than 4 kg.A significant correlation exists between maternal FFM in the process of pregnancy, placental weight, GWG at delivery, and birth weight (The change of maternal FFM during pregnancy is independently affected the birth weight. The relationship between maternal body compositions and birth weight was not definite. Fat Mass (FM) and Fat Free Mass (FFM) can accurately reflect the maternal body fat compositions and have been considered as better predictors of birth weight. Despite its potential role, no studies have been described the maternal compositions during pregnancy in East Asian women previously. We investigated the correlation between birth weight and Maternal body composition including fat mass (FM) and fat free mass (FFM).A longitudinal prospective observational study was performed. 348, 481 and 321 non-diabetics Han Chinese women with a singleton live birth attending a routine visit in their first, second and third trimesters were recruited respectively at the Gansu Provincial Maternity & Child Care Hospital, China. Maternal body composition (including FM and FFM) was measured using segmental multi-frequency bioelectrical impedance analysis.The prenatal testing records of the pre-pregnancy body mass index (BMI) and maternal BMI at the tested time were collected. At delivery the gestational weight gain (GWG), placental and birth weight were weighed. Pearson correlation and multiple linear regressions were used to identify the strongest predictors of birth weight.In conclusion, the change of maternal FFM during pregnancy is independently affected the birth weight.There has been a growing concern in respect to birth weight because of the fetal origin hypothesis of adulthood chronic diseases . Birth wMaternal increased body mass index (BMI) and gestational weight gain (GWG) reflect pregnancy nutritional status. Excess GWG has been proved to be associated with an increasing risk of large for gestational age (LGA) . MaternaSeveral epidemiologic studies have investigated the relationship between maternal body compositions and birth weight; however, results were in consistent. Some of them reported that maternal TBW associated with birth weight ; some foIn this longitudinal prospective observational study, the participants were randomly selected, pregnant Han Chinese women with a singleton live birth, attending a routine visit at the Center of Prenatal Care of the Gansu Provincial Maternity & Child Care Hospital (GPMCCH), the largest maternity and child care hospital in Lanzhou of China from 2012 Jun to 2014 July.n = 41), a preterm birth (≤36 Weeks) (n = 76), GDM (n = 26), pregnancy-induced hypertension (n = 60), and other diseases which affecting maternal body weight (n = 19). We lost to follow-up 88 women because they changed contact information.Within the 1500 participates enrolled in their search group, 1150 women who gave birth to full-term babies completed the study. 217 women were excluded because they had a multiple pregnancies  were excluded from further analysis presented for oral glucose tolerance test (OGTT) at 28All participates had an early pregnancy ultrasound scan to confirm gestational age. At the first antenatal visit height and weight were measured digitally in a standardized way, BMI was calculated. Simultaneously, maternal body fat composition parameters were measured and recorded by foot-to-foot BIA system, which was conducted using a Body Composition Analyzer  with 4-point contact electrodes. The test current was 800μAand at a frequency of 50 KHz. The inter-observer coefficients for FM, FFM were 0.99 and 0.98, respectively. To ensure accurate test results, each participant was measured under the following conditions: no alcohol consumption within 24 h and no exercise or food intake during the 4 h preceding the test. All measurements were performed in the morning. Each women, wearing light clothing and without jewelry, shoes or socks, stood 1 min on the squared surface of the scale, putting the heels one per electrode and the metatarsal-phalangeal joints of each foot, one per electrode, respectively. The percentage of body fat (PBF), FM, and FFM were estimated with instrument computer software. Fat free mass index (FFMI) was analyzed by using the standard formula of FFM divided by height in meters squared.st, 2nd and 3rd trimesters. At delivery the GWG, placental and birth weight were weighed. The antenatal and postpartum details were obtained from the hospital’s computerized database. Maternal BMI was categorized in four groups according to the Asia-Pacific standard: the underweight group (<18.5kgm−2), normal weight group (18.5–22.9 kgm−2), overweight group (23.0–24.9 kgm−2) and obese group (≥25.0 kgm−2).We measured 348, 481 and 321 women in their first, second and third trimesters respectively. Based on different antenatal visit and BIA measurement time, eligible women were assigned to three study groups according to 1Pearson correlations of birth weight with maternal demographic, pre-pregnancy BMI, mid-pregnancy BMI, GWG, maternal body FM and FFM, and placental weight were analyzed indifferent trimester groups. Explanatory variables identified as significant in bivariate analysis were subsequently entered into a multiple liner regression model in different trimester groups respectively, with birth weight as the dependent variable.P < 0.05 was considered for entry and removal of variables into the model.Multiple logistic regression analysis was then used to generate odds ratios for birth weight greater than 4 kg per BIA–measured FFM quartile, with the lowest quartile serving as the reference group. Models incorporated maternal age, gestational age, BMI, along with BIA–measured FM. P < 0.05 was considered to indicate statistical significance. Analyses were performed using statistical software package SPSS 20.0 .A nominal −2. Most of them were urban residents (92.1%) and primiparous (74.2%). Amongst the Han Chinese women studied, 13.5% were underweight, 64.6% were normal weight, 12.3% were overweight and 9.6% was obese according to the Asia-Pacific classification. The maternal BMI, FM and FFM all increased with the pregnancy process development. Among the first, second and third groups, there were no significant differences in maternal age, pre-pregnancy BMI, gestational age at delivery, and weight gain during pregnancy (P > 0.05).A total of 1150 women were enrolled into the study. Among them, 348 had measured body fat composition during the first trimester, 481 during the second trimester, and 321 during the third trimester. The characteristics of the study population were presented in Table r = 0.52), GWG (r = 0.15), maternal FM (r = 0.27), FFM (r = 0.35), pre-pregnancy BMI (r = 0.23), mid-pregnancy BMI (r = 0.23) in 1st trimesters. The significance correlations were found between birth weight and placental weight (r = 0.55), GWG (r = 0.18), maternal FM (r = 0.28), FFM (r = 0.28), pre-pregnancy BMI (r = 0.24), mid-pregnancy BMI (r = 0.25) in 2nd trimesters. There were significance correlations between birth weight and placental weight (r = 0.61), GWG (r = 0.15), FFM (r = 0.38), pre-pregnancy BMI (r = 0.09) in 3rd trimesters.The Pearson correlation between birth weight and placental weight, maternal FM, FFM, pre-pregnancy BMI, mid-pregnancy BMI, and GWG was evaluated at different trimester respectively Table . The sigst trimester, 19% was by FFM, pre-pregnancy BMI and gestational age in the 2nd trimester. The associations for birth weight at the 3rd trimester were weaker, with only 12% of the variation explained by FFM (Table P > 0.05).In multiple liner regression analysis, it was found that approximately 24% of the variation in birth weight was explained by FFM in the 1We divided maternal FFM of participants into four quartiles: the lower quartile was 36.68 kg; the upper quartile was 40.76 kg. Maternal FM was also divided into four quartiles: the lower quartile was 14.88 kg; the upper quartile was 21.65 kg. After adjustment for age and gestational age, pre-pregnancy and mid-pregnancy BMI and FM, the maternal age , FFM of the upper quartile , and pre-pregnancy BMI  remained predictors of birth weight more than 4 kg , all major structures are already formed in the fetus, and they begin to grow rapidly. The growth of muscle tissue and bones plays a decisive role in birth weight. Thirteen to twenty-two weeks of gestation is a critical period: more muscle tissue and bones of fetus are developed, and the bones become harder [After adjustment for age and gestational age, pre-pregnancy and mid-pregnancy BMI and FM, the increased maternal age became a protective factor (OR = 0.69) but the increased pre-pregnancy BMI (OR = 1.50) remained predictors of birth weight more than 4 kg. There was significantly associated with 2.47-fold increase in risk for birth weight more than 4 kg when FFM ≥ 40.76 kg (Upper quartile of FFM). Limited previous large-scale epidemiologic studies have examined the association between birth weight and maternal body fat composition. It is unclear why increased FFM and pre-pregnancy BMI were associated with higher birth weight. This could be due to the obesity status before pregnancy, rapid growth of the fetus in early second trimester and the increase of TBW in third trimester. From the 10e harder . In the e harder . These iOur findings must be interpreted in the context of the study design and ethnicity. One of the strengths was that the information on both anthropometry measurements and pregnancy outcome collected through medical records rather than recall, which minimized potential recall bias. It is notable that women with pre-existing and emerging diseases which could influence birth weight were all excluded in our study. Nevertheless, our study does have some limitations. We used a foot-to-foot BIA instrument to analyze maternal body composition. Due to limited instrument, there is no way to acquire the data of TBW. Therefore we do not know whether or how this factor contributed to birth weight. Additionally, our findings showed the relationships among maternal body component indices and neonatal birth weight might vary among ethnic groups. The East Asians had lower BMI than other ethnic , 24. We Our key findings confirm the complex relationship between birth weight and maternal factors. The fact is that maternal FFM in whole pregnancy process was independently associated with increased offspring birth weight after controlling for other explanatory variables. These findings provide further evidence that maternal FFM but not FM may be important in programming intrauterine fetal weight growth. The interventions intended to reduce FM during pregnancy for non-diabetic women may not prevent LGA. The conclusion would highlight the feasibility of interventions to improve birth weight and decreasing obstetric complications.


Echinococcosis is a multisystem disease and has propensity to involve any organ, an unusual anatomical site, and can mimic any disease process. The hydatid cyst of the mesenteries known to occur secondary to hepatic involvement but occasional cases of his primitive form has also been reported. We report here one such case of primitive mesenteric hydatid cyst herniated through inguinal canal in a 5-yr-old boy, admitted to our Pediatric Surgery Department of Children’s Hospital in Tunis, Tunisia in 2015. Echinococcus granulosus. It affects almost every region of the body. In children, the lungs are the most common site (64%) of hydatid cyst followed by liver (28%) (Hydatid disease (HD) is a parasitic infection caused by the larvae of er 28%) . The hyd8% . The A 5-yr-old boy was admitted to the Pediatric Surgery Department of our Children’s Hospital in Tunis on Sep 2015. Informed consent and University approval were taken.He presented to the clinic with abdominal mass. He had a history of left recurrent hydrocele operated on twice. On examination, a mass approximately 6 × 8, 5 cm in diameter was identified in hypogastric region. External genitalia examination was suggestive of recurrent communicating left vaginal hydrocele . AbdominIts anterior wall filled the left inguinal ring. As for liver hydatid cyst, we performed PAIR  technique. Saline pads were packed beneath the cyst, elevating it to a fixed position, and the intestines were protected with these pads. Hydatid fluid and protoscolices were aspirated with needle aspirator. A 20% hypertonic saline solution was used to deactivate the cyst content. The solution was left inside the cyst about 10 min to kill the protoscolices. After evacuating the cystic contents, cystotomy was performed.The typical germinative membrane of a hydatid cyst was identified and removed. The cavity was explored, revealing a communication with internal inguinal ring. The inguinal approach showed the extension of the pericystic layer through inguinal canal. A very careful dissection of the structures of the cord was performed to isolate the processus. The communication was ligated at the internal ring. After dissection of the inguinal part of the cyst, total excision was performed. Given the risk of injuring major vessels passing just outside the posterior pericystic layer of the mesenteric cyst, we opted for a partial cystectomy. A drain was then placed into the residual cavity. The examination of the fluid aspirated from the cyst demonstrated free protoscolices showed hooklets. On histopathological examinations, the cyst wall had a laminated membrane with inner germinal layer containing degenerated eosinophilic protoplasmic mass. The inguinal part of the cyst revealed similar histopathological findings of the hydatid cyst. The postoperative course was uneventful and the child had a full recovery.The patient received albendazole, 10 mg kg−1 d−1 for 3 months postoperatively. No recurrence was encountered during the 8-month follow-up period.Echinococcus granulosus. It is still a considerable health problem in the world (Hydatid cyst is a parasitic disease that caused by the larval stage of he world , 2. Hydahe world . Therefohe world . Rupturehe world . In conthe world , 5. The he world .Inguinal herniation of mesenteric hydatid cyst has not been reported yet, however, it should be considered especially in countries where echinococcosis is endemic, such as South East Asia, Mediterranean countries, the Middle East, and the Far East .There are no specific signs or symptoms attributed to hydatid disease with uncommon localization . BecauseOnly two cases with herniation of intraperitoneal hydatid cyst by inguinal canal have been reported in English literature and they were one case of primary hydatid cysts and another case of secondary hydatid cysts of the female genitaliain adults . This caHD should be remembered in the differential diagnosis of cystic pelvic masses whatever the age of the patient. Recurrent vaginal hydrocele, when it is combined with an intraabdominal palpable mass, should be a reminder of HD in endemic regions.


To investigate the mechanisms that link maternal haemoglobin concentration with stillbirth.A retrospective cohort analysis using anonymised maternity data from two hospitals in England.The Royal Wolverhampton NHS Trust and Guy’s and St Thomas’ NHS Foundation Trust.12 636 women with singleton pregnancies ≥24 weeks of gestation giving birth in the two hospitals during 2013–2015.A conceptual framework of hypothesised pathways through birth weight-for-gestational age and maternal infection including potential confounders and other risk factors was developed and examined using path-analysis. Path-analysis was performed by fitting a set of regression equations using weighted least squares adjusted for mean and variance. Goodness-of-fit indices were estimated.Coefficient of association (β) for relationship between each parameter, and direct, indirect and total effects via the postulated pathways.The path-model showed a significant adjusted indirect negative effect of maternal haemoglobin on stillbirth mediated via birth weight-for-gestational age (standardised estimate (SE)=−0.01; 95% CI=−0.01 to −0.001; P=0.028). The effect through maternal infection was not significant at P<0.05 . There was a residual direct negative effect of maternal haemoglobin on stillbirth  after accounting for the two pathways. Total indirect SE=−0.004; 95% CI −0.01 to 0.003; P=0.267; total direct and indirect SE=−0.13; 95% CI −0.23 to −0.02; P=0.016. The goodness-of-fit indices showed a good fit between the model and the data.While some of the influence on risk of stillbirth acts through low birth weight-for-gestational age, the majority does not. Several new mechanisms have been suggested for how haemoglobin may be exerting its influence on the risk of stillbirth possibly involving genetic, epigenetic and/or alternative obstetric and nutritional pathologies, but much more research is needed. While a number of studies have demonstrated low maternal haemoglobin to be a risk factor for stillbirth, this study advances the knowledge about the relationship between maternal haemoglobin and stillbirth by delineating the pathways using a statistical modelling technique called path-analysis.Path-models are not causal models and therefore the findings of this study are hypothesis-generating rather than demonstrating causal pathways.Inability to adjust for socioeconomic status in the main model was a limitation, but sensitivity analysis did not materially change the results.Information about the causes of stillbirth in the study population was not available and it is possible that the mechanisms through which haemoglobin affects stillbirth vary by cause.Stillbirth is a global problem, and while the rate has been gradually falling it is difficult to discern the impact of different initiatives. In high-income countries, the rates have only marginally improved. Many of the risk factors associated with stillbirth are known and include maternal obesity, advanced maternal age, smoking, small-for-gestational age (SGA) fetuses, placental abruptions, placental pathology, pre-existing diabetes and hypertension.4We recently studied the association between maternal anaemia and stillbirth in a cohort of 14 001 pregnant women.We conducted a retrospective cohort analysis using anonymised maternity data from 14 001 women with singleton pregnancies ≥24 weeks of gestation giving birth in two hospitals between 2013 and 2015 . Information on maternal haemoglobin concentration at the first visit, usually between 9 and 12 weeks’ gestation was extracted from the hospital laboratory databases and then paired with maternity data. The datasets were then anonymised and analysis was restricted to 12 636 singleton babies born after 24 weeks of gestation and for whom information about haemoglobin at first visit and infant outcomes was available. The outcome ‘stillbirth’ was defined as ‘the death of a baby occurring before or during birth once a pregnancy has reached 24 weeks'.It has been shown that causal pathways for stillbirth involve fetal growth restriction.Sociodemographic characteristics, BMI, obstetric history, current pregnancy problems and medical comorbidities were used to generate the study variables. Based on reported ethnic background, women were divided into ‘white’ and ‘non-white’ groups. Information on ethnicity was not available for about 16% of the study sample. Women with unknown ethnicity were included in the ‘white group’, as has been performed previouslyWe calculated the z-scores for birth weight-for-gestational age using the LMS-Growth tool that uses Microsoft Excel add-in written using Excel 2000 with Visual Basic for Applications based on LMS method and the 1990 British reference cohort. This method adjusts for sex and gestational age while calculating the z-scores. The z-scores were converted to centiles using a standard formula in Excel.We conducted an initial examination of the relationships between the key individual components of the hypothesised pathways  using unadjusted linear and logistic regression analysis. Test for deviations from linearity using fractional polynomials did not suggest the presence of significant non-linear associations between haemoglobin at first visit and birth weight-for-gestational age centiles or between maternal infection and haemoglobin concentration. We tested the correlation between the other factors included in the conceptual framework. The calculated pairwise correlation coefficients did not show any statistically significant moderate or strong correlations among the factors. We tested for plausible interactions between haemoglobin concentration and mother’s ethnicity, haemoglobin and BMI, and birth weight-for-gestational age and ethnicity by fitting interaction terms into each of the univariable models that tested the crude associations between the individual pathway components followed by likelihood ratio testing. No significant interactions were observed.We conducted path-analysisData on index of multiple deprivation (IMD) quintiles, a measure of socioeconomic status, were available only in the Wolverhampton dataset, hence path-analysis was repeated using these data to measure the effect of IMD quintiles on the hypothesised pathways by testing two models, one with IMD quintiles in addition to the other 11 variables and one without. The results did not vary with the inclusion and exclusion of the variable.This is not applicable since the study was a secondary analysis of anonymous hospital data.2 (range 10–74 kg/m2). Nearly half of the women were multiparous (48%), 13% smoked during pregnancy and 30% belonged to ethnic minority groups. A quarter of the women had one or more pre-existing medical problems, 0.4% had antepartum haemorrhage, 5% were diagnosed with gestational diabetes, 5% had hypertensive disorders of pregnancy and about 7% had other problems during the index pregnancy.In total, 76 babies were stillborn in the study population. Details of the characteristics of the study population and their comparison with that of the general population of pregnant women in England are described in a previous paper.As shown in The results of the path-analysis are shown in The causal pathways for stillbirth are complex often with multiple risk factors interacting to influence the eventual outcome. We postulated that two pathways were most likely to mediate the effect of maternal haemoglobin during the first trimester on stillbirth: birth weight-for-gestational age and maternal infection. Of these, only birth weight-for-gestational age was found to be statistically significantly mediating the effect. Neither pathway completely explained the effect of haemoglobin on stillbirth as there was a significant residual direct effect of haemoglobin in the first trimester on stillbirth. This suggests that there are other unidentified factors involved in the pathway(s).While a number of studies have demonstrated low maternal haemoglobin or maternal anaemia to be a risk factor for stillbirth,2) affecting placental circulation leading to fetal growth restriction resulting in stillbirth in some cases.The observed pathway of effect of maternal haemoglobin on stillbirth mediated via low birth weight-for-gestational age could be explained by a number of factors. In addition to the possibility of haemoglobin exerting its influence through a reduced oxygen tension, there could be other plausible mechanisms through its interaction with nitric oxide (NO), carbon monoxide (CO) and carbon dioxide  influencing cell signalling and cellular interactions and 2) neural function.An altogether more prosaic explanation is that the mother’s concentration of haemoglobin, or more specifically low haemoglobin, could be a marker for another ‘abnormality’ . Iron itself plays a pivotal role in several metabolic processes and a deficiency at any time during a pregnancy may confer a disadvantage on the woman and/or the fetus. Low iron stores, leading to iron-deficient anaemia, may be an indicator of poor nutrition and deficiencies in other micronutrients, which either alone or in concert may play a role in the increased risk of stillbirth.28While the antecedents of stillbirth are well-known, the mechanisms through which they exert their effect on this outcome still remain unclear. Our findings clearly show that while some of the influence from haemoglobin concentration on risk of stillbirth acts through low birth weight-for-gestational age possibly as an adjunct to vascular pathology in the placenta, the majority does not. Haemoglobin may be exerting its influence on the risk of stillbirth involving genetic, epigenetic and/or alternative obstetric and nutritional pathologies, but more research needs to be undertaken to understand these relationships. Our findings suggest that prevention of anaemia will also have a beneficial impact on birth weight which in turn could influence favourably the intergenerational risk of stillbirth. However, more research needs to be performed on causal mechanisms, if we are to understand in depth the pathologies through which maternal haemoglobin affects pregnancies and fetal outcomes.


Weight gain during pregnancy has an important impact on maternal and neonatal health. Unlike the Institute of Medicine (IOM) recommendations for weight gain in singleton pregnancies, those for twin gestations are termed “provisional”, as they are based on limited data. The objectives of this study were to determine the neonatal and maternal outcomes associated with gaining weight below, within and above the IOM provisional guidelines on gestational weight gain in twin pregnancies, and additionally, to explore ranges of gestational weight gain among women who delivered twins at the recommended gestational age and birth weight, and those who did not.A retrospective cohort study of women who gave birth to twins at ≥20 weeks gestation, with a birth weight ≥ 500 g was conducted in Nova Scotia, Canada (2003–2014). Our primary outcome of interest was small for gestational age (<10th percentile). In order to account for gestational age at delivery, weekly rates of 2nd and 3rd trimester weight gain were used to categorize women as gaining below, within, or above guidelines. We performed traditional regression analyses for maternal outcomes, and to account for the correlated nature of the neonatal outcomes in twins, we used generalized estimating equations (GEE).A total of 1482 twins and 741 mothers were included, of whom 27%, 43%, and 30% gained below, within, and above guidelines, respectively. The incidence of small for gestational age in these three groups was 30%, 21%, and 20%, respectively, and relative to gaining within guidelines, the adjusted odds ratios were 1.44 (95% CI 1.01–2.06) for gaining below and 0.92 (95% CI 0.62–1.36) for gaining above. The gestational weight gain in women who delivered twins at 37–42 weeks with average birth weight ≥ 2500 g and those who delivered twins outside of the recommend ranges were comparable to each other and the IOM recommendations.While gestational weight gain below guidelines for twins was associated with some adverse neonatal outcomes, additional research exploring alternate ranges of gestational weight gain in twin pregnancies is warranted, in order to optimize neonatal and maternal outcomes.The online version of this article (10.1186/s12884-017-1530-2) contains supplementary material, which is available to authorized users. Weight gain during pregnancy is increasingly recognized as being a key, modifiable perinatal factor with an important impact on a number of maternal and infant outcomes . RecogniDespite accounting for only 3% of births –6. SmallWhile some raise caution at the fact that excessive weight gain during pregnancy may be detrimental to the mother and her baby , others Although several studies have since attempted to explore the adequacy of the provisional IOM GWG guidelines for twins, no consensus has yet been reached. Due to this, more current, robust research to guide optimal GWG in twin pregnancies has been called for .The objectives of this study were two-fold: 1) to examine the association between the existing provisional IOM GWG guidelines for twin pregnancies and SGA , and 2) to determine the GWG in women who delivered twins at the recommended gestational age and birth weight, using a large cohort separate from that in which the provisional guidelines were estimated, in order to explore similarities and/ or differences in optimal GWG.A retrospective cohort study was conducted of all women who gave birth to twins between January 1, 2003 and December 31, 2014 in Nova Scotia, which is an eastern province of Canada. Data for this study were obtained from the Nova Scotia Atlee Perinatal Database (NSAPD), a validated population–based database that captures information on all births within the province –19.The NSAPD contains maternal and neonatal information on demographics, procedures/ interventions, diagnoses, morbidities and mortality for all pregnancies and births, which is extracted from antenatal and medical charts by trained personnel, using standardized forms. The NSAPD is a valid and reliable database, as confirmed by an ongoing quality assurance program, which carries out periodic abstraction studies.2) were excluded since the current IOM guidelines do not provide GWG recommendations for underweight women with twin pregnancies [Women who were between 18 and 45 years of age and gave birth to twins at ≥20 weeks were eligible for study inclusion. Women were excluded if one or both of their infants had a birth weight < 500 g, major congenital anomalies, twin-to-twin transfusion syndrome, or if they were conjoined or monoamniotic. Additionally, mothers of single infants with a co-twin loss, mothers of co-twins of infants lost presumably from pregnancies that started with >2 fetuses, and mothers of infants with undetermined, unknown, or missing chorionicity were also excluded. Records with missing data on gestational age at delivery, BMI, or maternal weight at the time of delivery were excluded. Women who were underweight . Women’s total GWG was calculated by subtracting their self-reported pre-pregnancy weight, or if unavailable, their first measured weight, from their last measured weight closest to delivery. The measure of pre-pregnancy weight as reported in the NSAPD is based on the value that is written by the physician on the Nova Scotia Prenatal Record (field: “Pre-Pregnancy Weight”). The NSAPD does not record the specific source of this information, however it is known that the physician can use a pre-pregnancy weight as reported by the mother or a weight at the first prenatal visit .The primary exposure was maternal GWG, categorized as below, within, or above the IOM provisional guidelines for twin pregnancies, according to the woman’s pre-pregnancy BMI group  in the NSAPD have an early-pregnancy ultrasound. In women with both gestational age estimates, 87.2% of the last menstrual period-based estimates are within the ultrasound-based estimates by +/− 1 completed week. The total GWG recommendations for twin pregnancies for normal weight, overweight and obese women are: 16.8–24.5 kg, 14.1–22.7 kg and 11.4–19.1 kg, respectively. According to the IOM, the average cumulative weight gains for the first trimester (up to 13 weeks of gestation) in women who deliver twins at the recommended gestational age and birth weight  are: 3.6 kg, 2.1 kg and 2.0 kg, respectively, for the three BMI categories. The optimal length of gestation was not defined by the IOM, although they considered a gestational age of 37–42 weeks in their recommendations of total GWG. Since that time practice has shifted to twin delivery during the earlier portion of that range in most instances , 21. ForOur primary outcome was SGA, defined as birth weight < 10th percentile for gestational age and sex based on singleton growth curves . SingletSecondary neonatal outcomes included: birth weight (continuous outcome), LBW <2500 g, SGA more strictly defined as birth weight < 5th percentile for gestational age and sex, large for gestational age (LGA) defined as birth weight > 90th percentile for gestational age and sex, Apgar score < 7 at 5 min, umbilical cord pH <7.10, respiratory distress, hypoglycaemia, NICU admission, and NICU length of stay.Secondary maternal outcomes included: gestational age at delivery (continuous outcome), PTB <37 weeks , labour induction, mode of delivery , postpartum haemorrhage, and length of postpartum hospital stay.Important covariates included: maternal age, ethnicity, marital status, smoking status and drug use during pregnancy, pre-existing diabetes mellitus, pre-existing hypertension, other physical health problems, mental health problems, prenatal class attendance, chorionicity, and babies’ sex. In addition to a woman’s level of education, a neighborhood-level measure of socioeconomic status was also included – the Quintile of Adjusted Income Per Person Equivalent (QAIPPE), where 1 corresponds to the lowest and 5 corresponds to the highest income quintiles . Obstetr2 or Fisher’s exact test. To address our primary objective, to determine the effects of gaining below, within, or above the IOM GWG guidelines on each of the individual outcomes, linear regression was used for continuous outcomes and logistic regression was used for binary outcomes, with generalized estimating equations (GEE) used for the neonatal outcomes in order to adjust for the correlation between twins in a set. In order to assess the independent effect of GWG on neonatal and maternal outcomes, multivariable analyses were performed, adjusting for baseline maternal and pregnancy characteristics that may confound the associations of interest. The multivariable analyses adjusted for relevant a priori determined variables, which included maternal age, maternal pre-pregnancy BMI, smoking, socioeconomic status, parity, and chorionicity, as well as any additional baseline characteristics significant with a p-value <0.2 in the univariate analyses. All effect estimates from the models using GEE for the neonatal outcomes and the regression models for the maternal outcomes were reported as mean differences  or odds ratios , with their accompanying 95% confidence intervals (CI).Baseline characteristics were compared across the three GWG groups – women who gained below, within, or above the IOM GWG guidelines. Continuous variables were compared with the analysis of variance (ANOVA) or Kruskal-Wallis test. Categorical data were compared with a χAdditionally, in order to explore potential GWG effect measure modification by parity or chorionicity, the multivariable models for all maternal and neonatal outcomes were also reanalyzed with an additional interaction term between parity and GWG, and separately chorionicity and GWG. The Wald test was used to test the significance of the interaction terms.6/7 weeks as the upper limit of gestational age at birth, and further amending the definition of the recommended birth weight, such that both twins individually weighed ≥2500 g. We also determined ranges of GWG in women who delivered twins outside of the recommended gestational age and birth weight, based on both definitions for comparison.In order to address our second objective and determine the GWG in women who delivered twins at the recommended gestational age and birth weight, we followed the calculations outlined in the IOM guidelines in our study population. The recommended gestational age was defined as birth at 37–42 weeks of gestation. The recommended birth weight was defined as an average twin birth weight ≥ 2500 g. The interquartile range (IQR: 25th and 75th percentiles of the 2nd and 3rd trimester weekly rates of GWG) was determined. To reflect more recent clinical practice, we repeated the calculations after replacing 42 with 38 Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline [Prior to study commencement, a sample size calculation was performed. Analyses were performed using SAS . We followed the uideline . InstituN = 445), and those who had missing information on gestational age, maternal pre-pregnancy height or weight, or maternal weight at delivery (N = 461), 741 women and 1482 infants were included.There were 3294 twin hospital births to 1647 women between January 1, 2003 and December 31, 2014 in Nova Scotia , with the majority of women being married or common-law (77.8%), overweight or obese according to their pre-pregnancy BMI classification , multiparous (52.5%), and residing in the top two highest neighborhood-level income quintiles . Approximately one-fifth of the infants were monochorionic (19.4%), and 47.2% were male (with the sex of one baby being ambiguous). Additional baseline characteristics of all study participants are reported in Table N = 461) had similar baseline characteristics as those included  or excess maternal weight gain .Gestational age, PTB <37 weeks, instrumental delivery, or postpartum hemorrhage did not differ by groups of GWG. The low incidence of LGA >90th percentile, Apgar score < 7 at 5 min, and umbilical cord pH <7.10, prohibited their exploration with multivariable regression. We did not find evidence of interaction between the classification of GWG and either parity or chorionicity (i.e., all average twin birth weight ≥ 2500 g, while 31% of the women delivered twins between 37 and 38 6/7weeks, with each twin individually having a birth weight ≥ 2500 g. The rates of 2nd and 3rd trimester weight gain appeared to be fairly comparable between women who delivered within the recommend gestational age and birth weight ranges and those who did not, regardless of which definition was used, and were also similar to the provisional recommendations from the IOM, regardless of pre-pregnancy BMI (Table Forty-four percent of the women in our study population delivered twins between 37 and 42 weeks, with an within the recommended gestational age and birth weight ranges, of all pre-pregnancy BMI classes, were fairly comparable to the rates computed based on current recommendations by the IOM, but they were not very different from the rates in women who delivered outside of the recommended gestational age and birth weight ranges.In this large retrospective cohort study, we determined that relative to gaining within the provisional IOM guidelines for twins, gaining above the guidelines was associated with higher odds of labour induction, while gaining below was associated with higher odds of SGA, LBW, and longer NICU stay. Additionally, we determined that the rates of 2nd and 3rd trimester weight gain for women who delivered twins averaging ≥ 2500 g, thereby precluding the ability to truly examine the association between GWG and individual small infant size [The original 1990 IOM guidelines recommended 6–20 kg of GWG for women carrying twins, regardless of their BMI . Given tant size . The guiSeveral studies have attempted to examine the 2009 recommendations for twin gestations, with conflicting results. Only a few studies considered SGA <10th percentile specifically, and of those that did, one did not find a significant difference between women , while aStrengths of this study include the methodology used to classify GWG as below, within, or above guidelines which took into account the length of gestation as recommended by the IOM. Unlike numerous previous studies that restricted their study population to 37 weeks or more, excluding up to 50% of the population of interest , 34 and We maintained three BMI groups, rather than grouping together women gaining within and above the guidelines to compare them to women gaining below, which dismisses differences in the incidence of adverse outcomes between the first two groups, and could therefore result in biased effect estimates –32. The Limitations of this study include some missing data as sometimes occurs with large databases, for some variables of interest, including GWG. However, a comparison of the baseline characteristics of the women who were included in the study and those who were excluded due to missing information did not reveal any significant differences. Furthermore, missing data does not necessarily bias our associations, although our study findings should not be over-generalized to be representative of all pregnant women. Additionally, while our sample size was large enough for us to control for a number of key confounding variables, we were unable to perform analyses stratified by pre-pregnancy BMI, as such analyses would have been underpowered.Limitations of the method used to develop the provisional guidelines  should aFuture research is required to examine different patterns of GWG throughout pregnancy on maternal and neonatal outcomes, using a longitudinal approach with serial antenatal weight measurements. Determining the optimal GWG for underweight women, and further refining and narrowing the recommended ranges of GWG for normal weight, overweight and obese women is also key. Studying the effects of GWG on SGA defined according to twin growth charts will also be important, if standardized, validated twin growth charts that are based on rigorous data are developed and recommended in clinical practice guidelines.In summary, while GWG below the provisional guidelines for twins was associated with SGA and other adverse neonatal outcomes, GWG above the guidelines did not reduce the odds of SGA, and was further associated with adverse maternal outcomes, such as labour induction. As such, GWG recommendations outside of the provisional IOM guidelines may not be advisable, and further research is required to confirm the robustness of the provisional guidelines.


Most simple renal cysts rarely require therapy. When it grows to such a large size, regardless of the presence of symptomatology, surgical intervention is required. In this study, we explored a new approach called percutaneous ureteroscopy laser unroofing for treatment renal cysts and evaluated its safety and efficacy. 71 simple renal cyst patients with surgical indications were enrolled, including 6 patients with a peripelvic cyst and 5 patients coexisting ipsilateral calculi. Under ultrasound guidance, an eighteen-gauge needle was placed inside the cyst cavity, and a guidewire was introduced followed by sequential dilation up to 28 F. The extra-parenchymal portion of cyst wall was dissociated and incised using either a Thulium or Holmium laser, and a pathological examination was performed. Renal calculi were treated simultaneously. For peripelvic cyst patients, one end of a double-J stent was inserted into the cyst cavity to prevent auto-closure. Mean of 11.7 months follow-up, the results showed that the cyst was completely resolved in 53 patients, its size was reduced to less than 50% in 15 patients, and treatment failed in only 3 anterior cyst patients, suggesting that percutaneous ureteroscopy laser unroofing is an effective and less invasive alternative for treatment of renal cysts in selected patients. Most renal cysts are simple cysts and are asymptomatic, and many of them are found incidentally through routine physical examinations and rarely require therapy3. However, when the diameter of the cyst is >5 cm and renal parenchyma (collection system) compression is present, regardless of the presence of flank or abdominal pain, surgical intervention is required4.Renal cysts are simple benign lesions with an unknown etiology that are either inherited or acquired. The kidney is one of the most common sites of cyst formation in the human body; the estimated prevalence of renal cysts is approximately 10% of the general population, and the incidence increases with age5, surgical resection7, and sclerotherapy with a variety of different agents9. Although none of these approaches appear to be better than the others described, aspiration and sclerotherapy are associated with a higher incidence of cyst recurrence, fever, and ureteropelvic junction obstruction regarding the treatment of peripelvic cysts, given their proximity to the renal vessels and collecting system. These techniques may also require multiple treatments to satisfactorily ablate the cystic lesion10.A variety of therapeutic interventions have been described for benign symptomatic cystic lesions of the kidney. These include cyst aspiration12. However, this approach requires general anesthesia, which causes an increase in hospitalization expenses and an extension of the postoperative hospital stay. In addition, three ports are needed for the procedure, which makes it controversial as an ideal minimally invasive treatment.A laparoscopic approach for renal cyst unroofing was the first described in 1992 and has since become the gold standard of treatment. Laparoscopy may be associated with a higher safety margin and better efficacy, especially for peripelvic cyst treatmentRecently, we have explored a new approach for the treatment of symptomatic renal cystic lesions that merges the merits of both of the abovementioned methods and is referred to as percutaneous ureteroscopy renal cyst laser unroofing. This significantly less invasive approach needs only one port, is more comfortable for patients, and requires less expensive anesthesia than a laparoscopic procedure. Moreover, this approach is more attractive if there are coexisting calculi that also require treatment. In this study, we sought to assess the efficacy and safety of this procedure in the management of patients with symptomatic renal cysts or cysts complicated with ipsilateral renal calculi.The operations were performed successfully in all patients and their characteristics are given in Table The mean operative time was 35.3 minutes ; the operative times were obtained from the anesthesia record and were recorded as the time from the initial ultrasound-guided puncture or cystoscopy to the placement of the ureter stent until the placement of the nephrostomy tube. The cyst fluid cytology was negative for malignancy, and the histopathologic diagnosis of all cyst walls was consistent with a simple renal cyst. Some patients with peripheral or peripelvic cysts were usually discharged 1–2 days after the surgery, while others required the pathological results before discharge, so the postoperative hospital stay would be exceeded. In addition, Patients with renal cysts complicated with ipsilateral renal calculi were hospitalized for a relatively long time, usually 2–4 days after the surgery. Therefore, the mean postoperative hospital stay was 3.1 days.The patients were followed up at least every 3 months for the first year and annually thereafter. With a mean follow-up of 11.7 months , all patients underwent an abdominal CT scan or bilateral ultrasonography of the kidneys. It was slightly difficult to persuade the patient to return for a follow-up due to the benign nature of the disease. Some patients came after two years, but others managed to come after 6 or 9 months postoperatively. Of the 71 cyst units, 53 cyst units (74.7%) were completely resolved with almost 100% disappearance of the cyst, and 15 cyst units (21.1%) were reduced in size by more than 50% compared to the preoperative size  are likely to represent benign lesions and require either no therapy or just continued radiographic follow-up in patients with a diagnosis of class IIF lesions16. However, benign cystic lesions of the kidney can grow to such a large size (diameter >5 cm) that they may cause flank  pain and constrict the nephrons; in these cases, an intervention will become necessary17.Renal cysts remain the most common types of benign renal lesions, and represent more than 70% of asymptomatic renal masses19. The recurrence rate associated with percutaneous aspiration and sclerotherapy was up to 82%20.The use of antegrade percutaneous ureteroscopy laser unroofing to treat simple renal cysts is a novel technique that has been explored by clinicians at our center. With this approach, surgery was performed on 71 patients, and the mid-term follow-up results showed that the cyst volume shrank in 68 patients and the recurrence rate was only 4.2%. That relatively low recurrence rate is similar to the rates reported by several groups using a laparoscopic approach, which were approximately 4.5–5.6%21, whereas the latter possess two characteristics: cutting and lithotrity.One of the strengths of this technique is that it requires just a single incision. This technique was associated with a similar recurrence rate as a traditional laparoscopic approach, it was minimally invasive and showed superior cosmetic results. The established 28F work channel can accomplish most of the cyst wall dissociation, as seen with a laparoscopic approach. When the sheath and ureteroscope both returned to the exterior cyst during the operation, perirenal adipose tissue that adhered to the exterior cyst wall was identified. Then, by using a ureteroscope and a hydro-dissection technique, the extra-parenchymal portion of the cyst wall could be separated from the surrounding perirenal adipose tissue. The tensility was maintained, and the collapsed cyst wall was grasped and resected in the Amplazt sheath interior, which can ensure a safe incisal margin and avoid injury to the normal renal parenchyma. One deficiency of the technique was that once the cyst is grasped, the size of cyst wall is limited, and good effects can be achieved by repeating the grasp and resection procedure. The Thulium and Holmium laser are most commonly used lasers in our center for cyst wall resection. The Thulium laser has a higher cutting efficiency than does the Holmium laseret al., who described percutaneous intrarenal marsupialization and concomitant nephrolithotomy for the treatment patients with a renal cyst and ipsilateral calculi and follow-up results have confirmed the safety and efficacy of the procedure22. Gelet A et al. first reported in 1980 that the use of antegrade percutaneous resection offers an excellent surgical alternative for renal cysts and is associated with a 9% recurrence rate according to follow-up studies24. First, a 30F work channel was established, a standard transurethral resectoscope was used to resect the exophytic portion of the cyst wall and the parenchyma portion of the cyst was subsequently cauterized. However, this approach cannot simultaneously treat patients with a renal cyst that coexists with ipsilateral calculi. In addition, it used distilled water, not saline used in our approach as an intraoperative irrigation fluid, which may increase the potential incidence of dilutional hyponatremia in patients.Another attractive advantage of this approach is the simultaneous treatment of renal cysts and ipsilateral calculi for selected patients. Our experience is that the optimal patient is one who has a solitary, posterior, large-sized renal cyst and ipsilateral calculi, and our priority is to achieve stone clearance. If the renal cyst was not on the optimal puncture route, we would choose an additional route to reach the cyst after the percutaneous nephrolithotomy (PCNL). In our study, 5 renal cyst patients with coexisting ipsilateral calculi showed a good therapeutic effect, which could decrease the costs and the risks associated with a potential second operation. This viewpoint is further supported by a recent study by Chen 25. We also performed it to offer anesthetic cover for percutaneous ureteroscopy renal cyst laser unroofing, which could theoretically become a daytime operation. Compared to general anesthesia, PVB anesthesia can decrease both the costs and the incidence of postoperative malignant vomiting attributed to a reduced use of opioids26 and can retain the patient’s muscular strength in the lower limbs, which accelerates their recovery25.It is worth noting that we are the first to demonstrate that ultrasound-guided paravertebral block (PVB) is an attractive option for anesthetic management during PCNLet al. initially described the transurethral management of a peripelvic renal cyst27. The incision in the cyst wall created a permanent channel between the renal collecting system and the cyst, which forces the cyst fluid to continuously drain into the pelvis. Other colleagues have reported on the safety and efficacy of this approach29. Admittedly, the natural orifice transluminal endoscopic surgery (NOTES) is the least invasive approach. Unfortunately, this technique is limited in the treatment of peripelvic cysts that coexist with ipsilateral calculi and does not enable the collection of enough tissue specimens for histopathologic analysis.A retrograde approach with flexible ureteroscopy laser marsupialization is another novel technique with which to manage renal cysts. Kavoussi et al.24 and Chen et al.22. Other limitations to the study include the single-center retrospective analysis, the relatively small sample size and the short-term follow-up period. Moreover, the prolonged placement time of the nephrostomy tube and the double-J stent in patients with a peripelvic cyst may slightly increase the degree of stent-related symptoms.Some limitations of our report need to be acknowledged. Patients with a solitary, larger posterior or parapelvic renal cyst that has an appropriate puncture route are ideally suited for the surgery. However, it is not recommended for patients with an anterior cyst. Due to the limited dissociation range, the extra-parenchymal portion of the cyst wall is very difficult to manipulate, which can cause incomplete resection and high recurrence rates , as seen during the intermediate follow-up in our study. This viewpoint is supported by studies by Hamedanchi, S To sum up, percutaneous ureteroscopy laser unroofing offers several advantages over a laparoscopic approach for treating patients with a solitary, larger posterior or parapelvic renal cyst; this technique is minimally invasive, can simultaneously address ipsilateral calculi, possibly lower the costs and result in a shorter hospital stay. In addition, the instruments that are used are familiar to the urologist, and the technique can be performed in any endourological center. However, the few limitations of this study still merit consideration. A multi-center, randomized, prospective, control study with a large sample and a long follow-up time is needed to validate the results of this exploratory study in the future.2 (3.4–9.8 cm2). Three patients had a history of ipsilateral renal cyst operation . The operative procedure was carefully explained to each patient, and the possible complications and the invasiveness of the procedure were detailed. Patients were also informed of and offered alternative treatment methods, including the laparoscopic unroofing procedure. Patients were actively involved in the decision-making process, and their preferred treatment option was chosen. This manuscript are not contains information or images that could lead to identification of the study participant. Characteristics of the patients are given in Supplementary Table This present study was approved by the Ethical (Helsinki) Committee of Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology. All study participants provided written informed consent. All the methods performed in patients were carried out in accordance with the relevant guidelines and regulations. From November 2014 to October 2016, patients who had surgical indications and simple renal cysts were evaluated via abdominal ultrasonography and contrast-enhanced computer tomography CT. According to the Bosniak Classification system of renal cyst lesions, 71 patients with a class I and II cyst lesions were enrolled in the study. In addition, patients with calcification, septation or enhancement of their renal mass and coagulation disorders were excluded from the study. In regards to the 71 patients, 46 complained of flank and abdominal pain, and 25 patients exhibited a renal cyst by routine imaging examination. Of all 71 patients, 19 had cysts that were in the upper pole, 23 had cysts that were in the middle pole, 22 had cysts in the lower pole and 6 patients had peripelvic cysts. The mean diameter of the cysts was 6.5 cm (4.9–9.6 cm) and 5 patients had a renal cyst that was complicated with ipsilateral renal calculi. The mean stone surface area was 5.7 cmAll patients underwent continuous epidural anesthesia or ultrasound-guided paravertebral block anesthesia. The procedures for the latter were as follows:The patient was firstly placed in a supine position. Hydromorphone 1 to 2 mg was administered intravenously 10 minutes prior to the nerve block for patient’s comfort during puncture. The patients were then turned to lateral position with the side to be operated upward. The level of nerve block was T10/T11, T11/T12, and T12/L1. Ultrasound-guided PVB was performed using a linear array US 5- to 10-MHz probe. The probe was positioned parallel to the rib through the lumbar back. With the probe being moved cephalad or caudad, the transverse process of T 10, T11, T12 or L1 was identified. After infiltration of 2% lidocaine, a 100-mm, 21-gauge Tuohy needle  was respectively introduced into the T10/T11, T11/T12, and T12/L1 paravertebral spaces under direct visualization of the needle tip. 7 ml to 10 mL of 0.5% ropivacaine was injected at each segment.Surgical instruments are similar to those used in percutaneous ureteroscopy laser lithotripsy Fig. . The surPatients in this group were then placed in the prone position for percutaneous puncture and tract dilation. Under ultrasound guidance, the cyst was identified and an eighteen-gauge access needle  was placed inside the cyst cavity Fig. . The conPatients with peripelvic renal cysts were first placed in the dorsal lithotomy position, where the cystoscope was then used to identify the target ureter orifice, an open-ended 6 F ureter stent was then placed through the cystoscope and into the renal pelvis . Patients were then placed in a prone position as in the first group. Under ultrasound guidance, the peripelvic cyst was identified, and then an eighteen-gauge needle cyst puncture was made. Tract dilation was started and was dilated up to 24F; excessive tract dilation was thought unnecessary and was avoided to prevent possible bleeds due to its closeness to a highly vascular area compared to peripheral cysts. After effective dilation, an ureteroscope was used to visualize the cyst cavity and to identify the interior wall adjacent to the renal pelvis Fig. . Then, tPCNL and cyst unroofing were performed simultaneously on all of the five patients with renal cysts that coexisted with ipsilateral renal calculi. The puncture procedure and tract dilation targeting the stone through the cyst was created and dilated up to 28F. After fragmenting and extracting the stone, the same unroofing procedure described above was used to treat the cyst. Of the five patients, one required an additional puncture route to reach the cyst after the PCNL due to the far distance between the cyst and the stone. In the other patients, all of the procedures were performed with a single puncture route.Supplementary video 1Supplementary table 1


The continued rise in caesarean section (c-section) deliveries raises a major public health concern worldwide. This study assessed the trend of c-section deliveries and examined factors associated with a rise in c-section deliveries among the Egyptian mothers, from 2005 to 2014, by place of delivery.P-value for the trend was assessed by entering the year of the survey as a continuous variable. The study followed STROBE statement in reporting observational studies.This study utilized the 2005, 2008, and 2014 Egypt Demographic and Health Surveys (EDHS). The EDHS reported on the mode of delivery for the last birth occurred within five years preceding each survey including place of delivery and sociodemographic information for a total sample of over 29,000 mothers in the three surveys. To document trend of c-section, the EDHS-2005 was set as a reference in two binary logistic regression models; among all mothers together and for mothers stratified by place of delivery (public or private). Ptrend < 0.001). Compared to mothers with low socioeconomic status (SES), mothers with high SES had higher odds  for c-section, but only in EDHS-2005. The adjusted trend of c-sections was found to be 4.19-time  higher in private sector while that in public sector it was 2.67-time  higher, in EDHS-2014 relative to EDHS-2005. This increase in the private sector is explained by significant increases among mothers who are potentially at low risk for c-sections; mothers aged 19-24 years vs. ≥35 years ; primigravida mothers vs. mothers with ≥4 children ; and among normal compared to high risk birth weight babies .Institutional-based c-sections increased by 40.7 points from EDHS-2005 to EDHS-2014  contains supplementary material, which is available to authorized users. Caesarean section (c-section) delivery is a major surgical operation aimed at saving lives . GloballThe WHO has considered a population-based rate of c-sections between 10 and 15%, as an ideal rate that was associated with a notable decline in maternal mortality ratio (MMR) and neonatal mortality rate (NMR) . In 23 oHealth services in Egypt are provided by three sectors based on the financing source: the public, the parastatal, and the private sector. The public sector covers the government and quasi-governmental hospitals . Public hospitals receive funding from the Ministry of Finance while the government ministries have a controlling share of decision making in parastatal hospitals . Public In the past two decades, there were significant achievements in matters related to maternal health in Egypt. Home-based deliveries declined by over 60% , medicalThe last study tracking changes in c-sections in Egypt was reported in 2004 . AccordiThe EDHS survey aimed at providing national estimates with special emphasis on maternal and child health . EmployiHas your last baby born in the past five years, including this year, was delivered by a c-section or normal/vaginal delivery?” were included in the analysis, leaving a final sample of 29,489 mothers  after excluding five women with missing data and 28,269 women who did not report giving birth within the prior five years  was calculated as the ratio of the weight in kilograms divided by height squared (m2) data that were collected at the time of survey. Mother’s BMI was trichotomized into normal (BMI = 18.5–24.9 kg/m2), underweight (BMI <18.5 kg/m2), or overweight/obese (BMI ≥25 kg/m2) [Mothers were categorized according to their lifetime parity into primigravida, multipara with 2–3, or multipara with ≥4 births. Female genital mutilation (FGM) status was reported in a binary variable (yes or no). Body mass index (BMI) (kg/mese BMI ≥ kg/m2 [25 kg/m2)  while ov5 kg/m2) –30.Spatial characteristics included place of residence  and geographical region .Mothers were categorized according to the birth weight as mother with: normal , low , or high  birth weight baby. According to the birth multiplicity of the last birth born within the 5 years prior to the EDHS survey, mothers were categorized into two groups (singleton or multiple births). Mothers reported singleton or normal birth weight  babies were categorized as “low risk” while multiple or low/high birth weight  babies were categorized as a “high risk” group for c-section , 23. LowAccording to the number of ANC visits made by mother during her last pregnancy, mothers were categorized into four groups . Place of birth delivery was categorized into: home, public sector including parastatal health care facilities, or private sector.Frequency of mothers for each survey and their percentage distribution per each measured characteristic for all births and for institutional-based births were calculated, by survey round. Also, the proportion of institutional-based c-sections for each measured characteristic by survey round were recorded and assessed the over time trend of c-sections for each measured category’s item by chi-square tests for trend.P-value for the trend was assessed for each model by entering the year of the survey as a continuous variable.The crude and adjusted trend of c-sections utilizing the EDHS-2005 as a reference in binary and multivariable logistic regression models for all institutional-based deliveries, and stratified by place of delivery, after merging the datasets were subsequently investigated. This stratification was done to examine the role of place of delivery on the over time trend of c-sections in Egypt. In the binary logistic regression models, The quantitative association between institutional-based c-sections and each measured characteristic for each survey separately was also investigated. The crude (ORs) and adjusted odds ratios (aORs) and their respective 95% confidence intervals (CIs) were reported. To adjust for any potential confounding effect, all covariates were entered under analysis simultaneously in multivariable models.A place of delivery-stratified multivariable logistic regression analysis was performed to quantify the association between institutional-based c-sections and the measured characteristics for each survey round. This was performed to understand which factors were associated with increased trend of c-sections in Egypt, stratified by place of delivery.P-values <0.05 were considered statistically significant.The sampling weights available in the EDHS databases were applied in all of performed statistical calculations. The data were analyzed using IBM SPSS version 22.0  . P-valueThe three EDHSs were based on a nationally representative sample of 57,763 ever-married women aged 15 to 49 years, of which, 29,107 mothers reported on the mode of delivery of their last birth born within five years preceding each survey  increase in trend of c-sections in EDHS-2014 relative to EDHS-2005. The further place of delivery-stratified multivariate analysis showed that this increase in trend of c-sections was higher in private sector  than in public sector  (Table P = 0.001) were more likely to undergo c-section relative to those with low SES, but in EDHS-2014 this observed significant difference disappeared. Among primigravida, trend of c-sections in EDHS-2014  was higher than that in EDHS-2005 . Normal birth weight babies had higher odds undergoing c-section delivery in EDHS-2014  compared to EDHS-2005 .Table Furthermore, place of delivery-stratified multivariable logistic regression demonstrated that in private sector, mothers aged ≤18 years had less likelihood to undergo c-sections in EDHS-2005  compared to EDHS-2014 . However, in EDHS-2014 same age group of mothers was 84% less likely to undergo c-sections in the public sector. In public sector, SES was not associated with c-section delivery in all survey rounds, but in private sector, the significant association of SES with c-section observed in EDHS-2005 disappeared in EDHS-2014. The likelihood of primigravida mothers to undergo c-section in public sector declined from 2.21-time (95% CI: 1.37–3.58) to 1.72-time (95% CI: 1.18–2.50) whereas it increased in private sector from 1.62-times (95% CI: 1.12–2.34) to 3.76-times (95% CI: 2.94–4.80), in EDHS-2005 to EDHS-2014, respectively. Normal birth weight babies were significantly at lower risk to undergo c-section in EDHS-2005, but in EDHS-2014 they had an equal likelihood with high-risk birth weight babies in both public and private sectors , vaginal birth after a previous c-section, and one-on-one trained support during labor were effective psychosocial and structural strategies at reducing the likelihood of c-sections, even among those who may have a medical indication . MoreoveThe strengths of this study are that the data were from large, randomly selected population-based three datasets collected by accredited and reliable official entities using comparable methodology. The larger sample size and high response rates provided in the study with good statistical power and objective outcome measures. However, in population-based survey, the probability of recall bias is low since mothers who had a c-section delivery would not easily forget the mode of delivery given its surgical nature, particularly for the last birth . EstimatFindings from this study should be interpreted in light of the following limitations. The cross-sectional design of the EDHS limits the causality pathway with regard to the factors found associated with increased c-sections. Given the nature of the household-based survey where medical records are usually unavailable, collected data did not include information about whether the c-sections were performed under medical indications such as fetal mal-presentation or based solely on maternal demand, except for the birth weight and birth multiplicity that served as the only obstetric indicators could potentially at medically necessary c-section. Despite of these limitations, this study provided evidence-based estimates on trend of c-section deliveries in Egypt and associated factors to fine-tune strategies necessary to halt the rising c-sections in Egypt.Obtained results demonstrated that the proportion of c-sections in Egypt has been increasing steadily in recent years and has reached an alarming level. The proportion of c-sections documented in the last EDHS conducted in 2014 quadrupled the maximum threshold recommended by the WHO. The increase in number of birth deliveries occurred in the private sector appears to be associated with a shift towards delivery in private facilities. This increase in the private sector, particularly among mothers who were potentially at low risk of c-sections requires an urgent need to adopt critical policies and strategies that able to halt the steady rise in c-sections in Egypt and improve reproductive health and mothers and babies health outcomes. In the meantime, an in-depth institutional-based study collecting data on the exact indications associated with c-sections in Egypt is also necessary.


Preterm infants present an immature neurobehavioral profile at birth, even in absence of severe brain injuries and perinatal complications. As such, they require a long-lasting hospitalization in the Neonatal Intensive Care Unit (NICU), which is thought to grant at-risk newborns’ survival, but still entails a number of physical, painful, and socio-emotional stressors. Hence, preterm birth and NICU stay represent an early adverse experience, which has been linked to detrimental consequences for neurological, neuro-endocrinal, behavioral, and socio-emotional development, as well as to disease later in life. Recent advances in the behavioral epigenetic field are helping us to unveil the potential mechanisms through which early NICU-related stress may lead to negative developmental outcomes. From this perspective, telomere regulation might be a key programming mechanism. Telomeres are the terminal portion of chromosomes and are known to get shorter with age. Moreover, telomere length (TL) is affected by the exposure to stress during early development. As such, TL might be an innovative biomarker of early adverse exposures in young infants and children. Unfortunately, there is paucity of studies investigating TL in populations of preterm infants and its association with known NICU-related stressors remains unexplored. In the present paper, the potential relevance of TL for research and clinical work with preterm infants will be underlined in the light of recent contributions linking progressive telomere shortening and early exposure to adverse experiences and stressful environments in humans. Finally, insights will be provided to guide clinically relevant translational research on TL in the field of VPT birth and NICU stay. Preterm birth  is estimated to account for about 11% of all live births worldwide . NotablyTelomeres are repeat sequences at the ends of chromosome arms, known to shorten because of cellular aging and in relation to disease conditions . Recent Preterm infants need long-term hospitalization and specialized multi-disciplinary interventions in NICU. During this time, they are exposed to painful procedures , 8 and hThe NICU environment is far from being a surrogate of the maternal womb and represents a source of distress in newborns due to three main aspects: (1) sensorial adverse stimulation, (2) invasive and painful procedures, and (3) limited opportunities for parental caregiving and alteration of parent–infant bonding.First, infants are exposed to physical and sensorial stimulations  characterized by levels of intensity and length of exposure which easily exceed the average recommended exposure standard for newborns . As suchAdditionally, invasive and painful clinical procedures  are needed to improve the health status of preterm infants. Due to their immature neurobehavioral profile, preterm infants present lower threshold and higher sensitization to external perturbations, so that even routine handling  might be responded to with a heightened physiological response . InterveNotably, preterm newborns are suddenly separated from the mother after birth, which may disrupt the biological routes to caregiving and parental bonding  and alteDuring the last decades, DC strategies have been developed to minimize the negative effects of preterm birth, optimize infants’ neurobehavioral development, and improve interactions between parents and infants , 27. DC The quality of DC is critical to counterbalance the effect of NICU-related stressors on preterm infants’ developmental trajectories. Preterm infants hospitalized in NICUs characterized by high quality of DC practices exhibit better neurobehavioral development during the first month of life , less inNR3C1, encoding for cortisol receptors and SLC6A4, encoding for the serotonin transporter  current evidence pertaining to TL analysis and prematurity; (2) methodological issues; and (3) implications for research and clinical practice.To best of our knowledge, only few studies have investigated TL in the preterm infants. One study reported no significant differences between mean leukocyte TLs of preterm infants compared with their full-term counterparts at birth . HoweverN = 5). Vasu and colleagues , socio-demographic , and contextual factors . This implies that researchers need to pay attention to different conditions that interact in a complex manner in affecting TL in preterm infants. For instance, preterm infants born at lower gestational age might have longer telomeres at birth but greater stress-related erosion due to cumulative NICU-related stress and pain. Consistently, careful selections of preterm infants in terms of inclusion criteria should be pursued to avoid mixed samples of subjects, which might affect the quality of life, developmental trajectories, and number of stressful intervention to which they are exposed during the NICU stay.Differences in DC practices among diverse NICUs and countries represent another source of variation . DespiteFinally, the context and timing of early adversity exposure might be critical in setting a TL-related biomarker of later-in-life health and disease , 66. As Figure Future investigation could also consider the protective effects of DC practices in reducing or slowing the rate of telomere erosion. Studies in adult human subjects have demonstrated that positive changes in life-style have the possibility to result in significantly increased telomerase activity and improved telomere maintenance capacity in human immune-system cells . SimilarThe study of TL in preterm infants is an intriguing area of research and a potential source of scientifically sound beneficial information for NICU staff. Although now it remains a hypothetical scenario, it is possible to speculate that TL measure might have some clinical implications for NICU-related stress and infant DC. For example, given the evidence for association between TL and pain , one couLP conceived the work, wrote the first draft of the manuscript, and approved the final version of the paper. GSM contributed to literature review, revised English language, and approved the final version of the paper. RG supervised the work, by providing unique expertise in relation to biological sections, and he approved the final version of the paper. RM contributed to the conception of the work, supervised the writing, and approved the final version of the paper. All authors agree to be accountable for all aspects of the work.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Congenital Zika virus infection can cause microcephaly and other severe fetal neurological anomalies  codes, which allows more specific categorization of defects than that permitted by ICD-CM codes alone. To increase completeness of case ascertainment, the Registry conducts hospital audits and links to the Statewide Planning and Research Cooperative System (SPARCS) administrative discharge database. SPARCS is an administrative all-payer data-reporting system that collects information on hospital discharges, services, and treatments using ICD-CM codes. SPARCS requires monthly submission of billing data, which is beneficial for timely prospective surveillance; however, it does not collect narrative descriptions of birth defects , a surveillance system that receives reports from hospitals on major birth defects in infants and children diagnosed before the age of 2 years. The Registry requires a narrative description of birth defects along with Toxoplasma gondii, rubella virus, cytomegalovirus, herpes simplex virus, human immunodeficiency virus, Treponema pallidum, and varicella, dengue, and lymphocytic choriomeningitis viruses), maternal consumption of alcohol, tobacco, illicit drugs and certain teratogenic medications , and environmental exposures . Information also was abstracted on any documented genetic anomalies such as trisomy, gene deletions or duplications, and genomic imprinting, and on family history of birth defects, and parental consanguinity.Although congenital microcephaly is a reportable birth defect and should be included in hospital reports to the Registry, because of concerns about timeliness and completeness of routine reporting, a query was sent to all 154 New York birth hospitals. Hospitals were asked to report all newborns who had a diagnosis code specifying microcephaly (ICD-9-CM code 742.1 or ICD-10-CM code Q02), born during 2013–2015 to women who resided in New York at the time of delivery. All birth hospitals responded, and 83 (54%) identified suspected cases of microcephaly. The SPARCS database was also queried for ICD-9-CM code 742.1 or ICD-10-CM code Q02. Charts were obtained for all newborns with suspected microcephaly and were reviewed by trained clinicians who abstracted birth measurements , demographic information, and prespecified infant clinical characteristics, maternal conditions, and maternal/fetal exposures that might have associations with birth defects. Maternal conditions included preeclampsia, eclampsia, hypertension, and gestational diabetes. Prenatal exposures included in utero and perinatal infections  and Finger Lakes (5.9) health service areas . The majApproximately equal proportions of newborns with severe congenital microcephaly were Hispanic (31%), non-Hispanic white (30%), and non-Hispanic black (30%) . The majBefore evidence of importation of Zika virus infections, the overall prevalence of microcephaly in New York was 7.4 per 10,000 live births, similar to national estimates for the period 2009–2013 reported recently  identified in this analysis did not have any known maternal conditions or maternal/fetal exposures documented in the newborn hospital record. When the race/ethnicity of mothers of infants with severe congenital microcephaly was compared with the race/ethnicity of live births statewide in New York during 2013–2015, a higher proportion of infants with severe congenital microcephaly were born to Hispanic (31% compared with 23%) and non-Hispanic black mothers (30% compared with 15%) and a lower proportion to non-Hispanic white mothers (30% compared with 48%).** Further investigation is needed to better understand risk factors for microcephaly and disparities in microcephaly prevalence  has not been known.During 2013–2015, before documentation of widespread introduction of imported Zika virus infection in the continental United States, the prevalence of severe congenital microcephaly in New York was 4.2 per 10,000 live births. Requests to birth hospitals identified 93% of cases, and statewide administrative discharge data identified 90% of cases.Administrative data can enhance microcephaly case finding for birth defects surveillance programs. Cases of congenital microcephaly must be clinically confirmed using anthropometric measurements to determine whether they meet the case definition for severe congenital microcephaly. A baseline prevalence estimate of severe congenital microcephaly can enable estimation of risk attributable to Zika virus infection.


Our approach facilitates whole-heart coverage with scan time under 15 minutes, leading to reproducible DTI measurements, and enabling 3D tractography.Currently diffusion tensor MRI (DTI) of the heart can be performed ated STE  or gatedated STE . Both arated STE . Simultaated STE  has emerated STE . Here, w2, resolution 2.5 × 2.5 mm2, thickness = 8 mm, in-plane GRAPPA rate 2, TE = 34 ms, b-values = 0 and 500s/mm2, 10 diffusion-encoding directions, 8 averages, and 12 contiguous short-axis slices. Rate 2 SMS excitation was followed by a blipped-CAIPI readout. A sequential acquisition of diffusion-encoding directions evenly distributes the rejections across all directions ensuring that we can select enough samples of each direction. STR was applied to reduce the misregistration resulting from respiratory motion [DTI was performed in healthy volunteers (n = 7) on a clinical 3T scanner (Siemens Skyra), with an ECG-gated STE sequence. Acquisition parameters were: FOV = 360 × 200 mmAccelerated FB DTI using SMS was performed in all 7 volunteers with the proposed sequential gradient acquisition order. Figure We introduce a clinically feasible whole-heart accelerated FB DTI with scan time under 15 minutes. The results compare favorably with those previously acquired and validated using BH. Future improvements could include increased SMS acceleration resulting from advanced purpose-built RF coils. The integration of DTI into clinical protocols may enable the reliable characterization of myocardial structure in patients with cardiac diseases.