Men were 2.36 times more likely to be preterm  among LBW neonates. Outcomes of LBW neonates who were delivered by SVD were not significant compared to preterm delivered by CS . Sixty percent (60%) of the mothers had Prolonged Rupture of Membranes (PROM). Morbidities such as hypothermia (72.2%), apnoea (63.6%), haemorrhagic disease of the newborn (HDN) (66.7%), and respiratory distress syndrome (RDS) (66.7%) were more observed with preterm LBW neonates. Importance of qualitative antenatal care (ANC) should be emphasized; anticipation and prevention of LBW births can help mitigate some of the problems they are prone to.Globally, 30 million low birth weight (LBW) babies are born every year and 95% of them are from developing countries. LBW neonates are at a high risk of mortality, morbidity, and long-term disability. The objective of this study is to investigate outcomes and disease spectrum among low birth weight neonates. This is a prospective, observational study conducted on 540 neonates admitted in the Mother and Child Hospital, Akure, Ondo State, Nigeria, from 2017 to 2018. Questionnaire, interview, clinical, and diagnostic procedures were used as research tools. There were 137 low birth weight (LBW) neonates, with the mean mothers' age of 31.92 ± 6.60. Of the 540 neonates, 69 (50.4%) and 68 (49.6%) were term and preterm, respectively. There were 64 female neonates (46.7%) and 73 male neonates (53.3%). The mean weight of the neonates was 1.82 ± 0.44 kg, and mean number of days on admission was 6.42 ± 6.75 days. Neonatal sepsis (NNS) was the highest morbidity 51 (37.2%) among the LBW neonates, followed by prematurity 47 (34.4%) and neonatal jaundice (NNJ) 18 (13.1%). Sex ( Neonate's birth weight can be categorized to be low birth weight <2,500 g), normal birth weight 2,500 to 4,000 g), and high birth weight  . Low bir,500 g, n,000 g, aGlobally, 30 million of low birth weight (LBW) occurs every year and 95% of them are from developing countries , 7. Low Several factors have been associated with low birth weight though not necessarily in isolation. Maternal factors could be responsible for this, such as congenital malformations of the uterus, prenatal malnutrition and lifestyle, maternal illnesses such as hypertension or diabetes in pregnancy, infection with bacterial vaginosis, malaria, and flu. Race, maternal age, socioeconomic factors, and parity are also contributory factors –16. Incird trimesters [Obstetric factors such as previous stillbirth, short birth interval, inadequate prenatal care, placenta previa, and abruption  could alimesters .The outcomes of low birth weight are also dependent on other factors such as an enabling environment with adequate and effective perinatal and neonatal care, skilled birth attendants, and appropriate equipment and technological advancement in the care of such special cohort of newborns. In developed countries, survival rates of LBWs have improved due to the requisite skills and availability of appropriate equipment to support the low birth baby. Though the requisite skills and equipment might be lacking in the developing countries, the introduction of Kangaroo Mother Care has improved the survival rates in LBWs with comparable significantly better rates with the conventional methods .In Africa, 5.7 million of LBW neonates are recorded every year . In 2018The study was carried out at the Mother and Child Hospital, Akure (MCHA), a modern secondary public health facility providing specialized free health services to the state capital and surrounding communities. It also serves as a referral care center for other government, private, and missionary hospitals. The Mother and Child Hospital Akure is located in the city of Akure, the capital city of Ondo State. Ondo State lies between latitudes 5°45' and 7°52'N and longitudes 4°20' and 6°5'E. Its land area is about 15,500 square kilometers. Ondo State has an estimated population of 5,372,477, with over 1,715,820 female inhabitants base on projection from the 2006 Nigeria national population.This is an observational prospective study conducted on 540 neonatal admission for one year (May 2017 to April 2018). All the births were studied till either discharged from the hospital or inadvertent death.A well-structured questionnaire was used for the collection of the socio-demography data of the baby's father and mother. Before applying the questionnaire to the target population, pretesting was carried out with twenty (20) women who are not part of the study group; this was to ascertain simplicity and the objective accuracy. A well-trained nurse and medical assistants were recruited to assist in administering the questionnaires and to conduct interviews for the parents and also in taking clinical and diagnostic data. Information collected included mother and father's age, educational level, occupation, marital status, antenatal visit, gestational age, neonate's birth weight, place of delivery, and days on admission was also monitored.RGZ-20 weighing scale. The scale records weights in grams to the nearest 25 g. It was adjusted for zero error before each reading. Other measures taken to ensure reliability of results included weekly standardization of the weighing scale, using known weights.Each baby was weighed using the Apnoea defined as cessation of breathing lasting for 20 seconds or more, associated with bradycardia or cyanosis and needing resuscitationNeonatal sepsis defined as clinical signs and symptoms suggestive of neonatal infections positive laboratory indices and multiple organ involvementNeonatal jaundice is a yellowish discoloration of the sclera and skin and serum bilirubin up to 5 mg/dlSevere birth asphyxia defined as an APGAR score of 5 or less at 5 minutes and with neurological manifestations or babies with multiple organ involvementHypoglycemia defined as random blood glucose of <50 mg/dlAnemia defined as hemoglobin level <10 g/dlHypothermia defined as a rectal temperature of <35°CFailure-to-thrive (FTT) was used to describe inadequate growth, failure to gain weight or height, and the inability of the baby to maintain growth according to the standard growth chart; it is a sign of multiple problems as well as undernutritionPhysical examination and laboratory findings as well as clinical history were done to ascertain complications and it was carried out by the attending neonatologist. Some of the conditions were defined as follows:The enrollment was based on any live birth <2,500 g in MCHA and neonates transferred in.The excluded were children whose parents did not give their consent, babies with congenital abnormalities, and stillbirths.Ethical procedures were followed obtaining permission for the study from the Research and Ethics Committee in the MCHA. Informed consent was obtained from parents of participants.p < 0.05.Statistical analysis was carried on the collected data, using SPSS (version 21.0), and graphs were generated using Microsoft Excel. The chi-squared test was done to determine if gestational age and outcome of admission depend on mother's sociodemographic variables. The logistic regression procedure was used to determine the risk factors of LBW neonates in the studied area. Level of significance for this study is put at The disease spectrum of LBW neonates is shown in χ2 = 3.584, p=0.310), method of delivery , and gestational age  are not a significant determinant of outcome among LBW neonates, except neonate's weight  (p=0.048) among LBW neonates. Also, the neonates' gestational age  significantly determined their weight.Sex (p=0.002) . In TablPROM (60%), hypothermia (72.2%), apnoea (63.6%), haemorrhagic disease-HDN (66.7%), and respiratory distress syndrome-RDS (66.7%) were more observed with preterm LBW neonates . In FiguWithin the period of study, 540 neonates were admitted and majority of the neonates (75.9%) were referred from other government hospitals to MCHA. The incidence of low birth weight (LBW) among the neonates in the current study was 25.37%. This figure is higher than the reports of 2.6% in the 45 months of study from Enugu, southeast, and Nigeria , 6.3% frIn 2019, Melkamu et al.  reportedMothers with secondary and tertiary education were 0.88 and 0.66 time, respectively, less likely to experience low birth weight delivery than mothers with lower educational levels. In accordance with this study, reports by Maznah et al.  on 2013 Also, in the current study, majority of the mothers of the low birth weight babies had ANC; this is contrary to a study by Yaya et al.  where paFurthermore, working mothers were 5 times more likely prone to have a low birth weight infant than the housekeeper and self-employed mothers , 44. In Extreme low birth weight (ELBW) neonates recorded in this study were 100% preterm, while the very low birth weight (VLBW) was 95.7% preterm. This shows that the low birth weight is strongly associated with gestational age. Several other researchers have also affirmed it , 46, 47.There was a slightly higher number (53.3%) of a male LBW neonate in this study. The binary logistic analysis further revealed that male babies were 2.36 times preterm than their female counterpart. Several researchers have corroborated this finding –50. RepoThe immediate outcomes of the LBWs showed that 80.6% of babies in the range of 1500–2499 g were discharged alive from the hospital and are in keeping with the study done in National Institute of Child Health by the American Association of Pediatricians where it was proven that outcomes improved significantly with birth weights. In addition to this, Lemons et al.  recordedIn the current study, 6.6% of the studied LBW neonates were later referred to the surgical unit for surgical interventions. Overall, there was 14.6% mortality. Neonatal death recorded in this study is very low compared to 30% death reported by Chidiebere et al.  from a hAmong the disease spectrum associated with LBW babies, neonatal sepsis ranked highest at 57.7% in the current study. This is not surprising; many of the babies were born in unusual places such as Church, home, and farm. Essential newborn care  as well as basic care for feeding support, infection control, and breathing support which can make the difference between life and death for small babies cannot be found in these places. The current study also reported morbidities such as hypoglycemia (7.3%), hypothermia (13.1%), and apnoea (16.1%). LBW newborns are particularly susceptible to heat loss immediately after birth as a result of a high body surface area–to–body weight ratio, decreased brown fat stores, nonkeratinized skin, and decreased glycogen store . All theThe number of dead neonates in this study is still of concern, and amelioration of survival rate of low birth weight babies is important in our society. More emphasis should be placed on the importance of qualitative antenatal care (ANC) for the pregnant women. This will foster education among women for early prevention, detection, and better management and consequently better outcomes of LBW neonates.


To investigate risk factor associated with hospitalisation of infants with a congenital anomaly in Wales, UK.A population-based cohort study.Data from the Welsh Congenital Anomaly Register and Information Service linked to the Patient Episode Database for Wales and livebirths and deaths from the Office for National Statistics.All livebirths between 1999 and 2015 with a diagnosis of a congenital anomaly, which was defined as a structural, metabolic, endocrine or genetic defect, as well as rare diseases of hereditary origin.Adjusted OR (aOR) associated with 1 or 2+ hospital admissions in infancy versus no admissions were estimated for sociodemographic, maternal and infant factors using multinomial logistic regression for the subgroups of all, isolated, multiple and cardiovascular anomalies.25 523 infants affected by congenital anomalies experienced a total of 50 705 admissions in infancy. Risk factors for ≥2 admissions were younger maternal age ≤24 years , maternal smoking , preterm birth  and moderately severe congenital heart defects . Girls had an overall decreased risk of 2+ admissions . Preterm birth was a significant risk factor for admissions in all anomaly subgroups but the effect of the other characteristics varied according to anomaly subgroup.Over two-thirds of infants with an anomaly are admitted to hospital during infancy. Our findings identified sociodemographic and clinical characteristics contributing to an increased risk of hospitalisation of infants with congenital anomalies. Congenital anomalies are a leading cause of infant morbidity and hospitalisation.Evidence about the risk factors contributing to the hospitalisation of infants with congenital anomalies is limited.Infants who had ≥2 admissions were more likely to be boys, born preterm, born with a moderately severe congenital heart defect, or have mothers who were younger and smokers, compared to those with ≤1 admission.Preterm birth is the strongest risk factor for hospitalisation in infants with congenital anomalies or rare diseases of congenital origin.The mechanisms by which maternal age, smoking and infant sex are risk factors for hospitalisation are similar for anomaly-specific admissions and admissions due to other causes.Congenital anomalies are a leading cause of infant morbidity and hospitalisation.There is some evidence that infant characteristics can influence hospitalisation of children affected by specific anomalies. For example, previous studies have shown that preterm birth, low birth weight, disease severity and comorbidity are significantly associated with an increased risk of excess hospitalisation of infants with spina bifida, choanal atresia, congenital heart defects, orofacial clefts, congenital diaphragmatic hernia, biliary atresia, gastroschisis and Down syndromeWe aimed to investigate risk factors for hospitalisation in the first year after birth among infants with congenital anomalies.A national population-based cohort study was established using registry data from the Congenital Anomaly Register and Information Service (CARIS) for Wales, linked to Patient Episode Database for Wales (PEDW), and births and deaths registration data from the Office for National Statistics (ONS),Deterministic and probabilistic linkage between datasets were performed using an unique Anonymised Linkage Field (ALF) encrypted code provided by NHS Wales Informatics Service, based on infant’s NHS number, name, date of birth and address. All infants in the CARIS and PEDW datasets have a validated ALF and hence each infant was matched with hospital admissions using one to multiple merge; unmatched infants were treated as zero admissions. The outputs of linkage were validated by the Secure Anonymised Information Linkage (SAIL) team.The inclusion criteria for this study were:+0 weeks, with a confirmed or probable diagnosis of a congenital anomaly reported to CARIS. CARIS defines congenital anomalies as structural, metabolic, endocrine or genetic defects, as well as rare diseases of hereditary origin present in the child or fetus at the end of pregnancy, even if not detected until after birth.All livebirths between 1999 and 2015 with birth weight ≥500 g, gestational age ≥22All hospital admissions  of infants with a congenital anomaly. An admission is defined as a hospital stay of a patient using a bed on premises controlled by the one healthcare provider.Exclusion criteria:Admissions solely for the birth of babies  were excluded.Congenital anomalies were categorised according to the European Surveillance of Congenital Anomalies (EUROCAT) subgroup classification10.1136/bmjpo-2021-001238.supp1Supplementary dataInfants were considered as having an isolated congenital anomaly (or disease) if a single anomaly (or disease) was diagnosed and reported to CARIS. Infants were considered as having multiple anomalies (or diseases) if more than one anomaly (or diseases) was diagnosed, either within the same body system or involving different body systems. Infants who were diagnosed with a syndrome involving more than one anomaly (or disease) were considered as having multiple anomalies (or diseases).The outcome was total hospital admissions for any cause in infancy (period from birth up to the first birthday) and infants were categorised as having 0, 1 or 2+ admissions.Multinomial logistic regression was conducted to estimate the adjusted OR (aOR) of hospital admission and the corresponding 95% CI according to the categories of sociodemographic, maternal and infant factors, comparing infants who had 1 or 2+ admissions versus those who had no admission (the comparison group). Any hospital transfers were treated as separate admissions in order to assess the full burden and utilisation of hospitalisation.The modelling strategy aimed to identify the strongest risk factors for hospital admission. Variables included a priori in the multivariable models were infant sex, gestational age at birth and disease severity for cardiovascular anomalies as these are known determinants of infant morbidity and hospitalisation,A further subgroup analysis was conducted for those babies who had at least one admission to investigate whether risk factors were different between infants with anomaly-specific admissions and those whose admissions were for ‘other-causes’. Here, anomaly-specific admissions were defined as hospitalisation of infants due to ‘congenital anomalies, deformations and chromosomal abnormalities’ (ICD-10 codes: Q00-Q99/chapter XVII) as the primary reason for admission. Crude ORs with corresponding 95% CIs were estimated for each explanatory variable comparing these two groups of infants. Significant variables from the univariable analysis (p<0.1) were included in the multivariable analysis. P<0.05 was considered as statistically significant in all final models.A sensitivity analysis was conducted by adding year of birth to the final model for each subgroup to investigate if the effect of the key risk factors changed.Missing data for the majority of variables were few and they are not shown due to the risk of statistical disclosure. All analyses were performed using complete case analysis. All statistical analyses were performed using Stata V.13.19All proposals to use data within the SAIL Databank are subject to review by an independent Information Governance Review Panel (IGRP) for privacy risk, data governance and public benefit assessment. The IGRP is made up of a range of independent experts as well as members of the public.Between 1999 and 2015, 25 523 babies were born alive and affected by congenital anomalies or rare disease of congenital origin, and required a total of 50 705 admissions in infancy. Overall, approximately a quarter of infants had only one admission, over 40% had two or more admissions and more than one-third had no admission in infancy. Among infants with isolated anomalies, the largest number of admissions occurred in infants with a cardiovascular anomaly .In the univariable analysis, social deprivation, maternal age, parity, maternal smoking and preterm birth were significantly associated with an increased or decreased risk for repeated admissions for ‘all’, ‘all isolated’ and ‘all multiple’ anomaly subgroups . Except Among infants who had at least one admission, maternal age, parity, maternal smoking and infant sex were not associated with having admissions for causes related to the anomaly as opposed to admissions for other causes . HoweverUsing linked deidentified data from CARIS, PEDW and ONS, we investigated a comprehensive range of risk factors associated with hospital admissions during infancy in babies born with congenital anomalies or rare diseases of congenital origin. Preterm birth was the strongest risk factor associated with an increased risk of one and two or more infant hospitalisation across all anomaly or rare disease of congenital origin subgroups. In addition, infants with two or more admissions had a higher risk profile than those with only one or no admission. Infants who had two or more admissions were more likely to be boys, born preterm, or to have mothers who were younger and smokers or for those who were born with a moderately severe CHD anomaly, compared with those with one or no admission.Previous studies have shown that infants with a congenital anomaly were associated with a significantly high risk of hospitalisation compared with infants without an anomaly in the general population due to anomaly-related comorbidities and complications, which require ongoing inpatient treatment and investigations.6 20–22Maternal and infant factors have an impact on hospitalisation in infant with congenital anomalies through different potential mechanisms. For example, previous studies have shown that teenage mothers may have an increased risk of adverse neonatal outcomes due to inadequate antenatal care and social support, and other behavioural determinants such as maternal smoking, alcohol and recreational drug misuse compared with older mothers.Preterm birth has consistently been shown to be associated with an increased risk of infant morbidity and hospitalisation; preterm infants generally have a lower physiological reserve and a higher susceptibility to comorbidities and infections compared with term infants.Infants born with the most severe CHD  often experience life-threatening events at birth and hence the mortality risk among these infants is considerably higher during their first admission compared with infants with less severe CHD.The risk factors for increased hospitalisation in infants with congenital anomalies found in this study are similar to known risk factors for hospitalisation in the general paediatric population, in which previous studies have found that being a boy and maternal smoking are associated with preterm birth leading to increased risk of hospitalisation.The main strengths of this study include the national study population, robust study design and data collection. Infants with congenital anomalies or rare diseases of congenital origin were identified from CARIS, an active surveillance and multiple source reporting system covering all livebirths in Wales which maximises case finding and internal validity. The use of routinely collected data from PEDW is particularly advantageous for this hospitalisation study due to the large size of the dataset and long period of data collection. A further strength relates to the broad definition of congenital anomalies, which includes structural and chromosomal defects, as well as rare diseases of congenital origin such as metabolic, endocrine and congenital blood disorders. Consequently, we were able to investigate risk factors associated with hospitalisation of infants with a wide range of congenital anomalies and rare diseases of congenital origin.There are several limitations. As PEDW is a hospital administrative dataset, data on admissions was not always complete which can be due to infants being treated in a specialist centre outside the catchment area of NHS Wales. In addition, the number of variables explored in this study was restricted by what was available in the dataset. It is possible that institutional factors such as outpatient follow-ups which were not available in this dataset are also important determinants of hospitalisation of infants with congenital anomalies.Infants with congenital anomalies and rare diseases of congenital origin have a high risk of hospitalisation in infancy. Our findings can help clinicians to identify infants who are likely to require hospitalisation according to their sociodemographic and clinical characteristics. Public health interventions such as promoting good prenatal care and smoking cessation may have an important role in reducing the need for hospitalisation in infants with a congenital anomaly.


No new method of assisting vaginal birth has been introduced into clinical practice since the development of the vacuum extractor in the 1950s. The Odon Device is a new device that employs a circumferential air cuff over the fetal head to assist birth. In this study, the Odon Device has been used to assist vaginal birth for standard clinical indications.This study aimed to investigate the clinical impact, safety, and acceptability of the Odon Device to women, their babies, and clinicians and to assess the feasibility of recruiting women to an interventional intrapartum research study.This is a nonrandomized, single-arm interventional feasibility study of the Odon Device for operative vaginal birth undertaken in a single maternity unit: Southmead Hospital, Bristol, United Kingdom. The Odon Device was used to assist birth in 40 women who required the birth to be assisted for suspected fetal compromise and/or prolonged second stage of labor. The primary clinical outcome was the proportion of births successfully assisted with the Odon Device, and the primary feasibility outcome was the proportion of eligible women who were approached and who agreed to participate. Neonatal outcome data were reviewed at day 28, and maternal outcomes were investigated up to day 90.Between October 2018 and January 2019, 298 of 384 approached, eligible women (77.6%) consented to participate. Of these women, 40 received the intervention—the use of the Odon Device. Birth was assisted in all cephalic  fetal positions, at all stations at or below the ischial spine and with or without regional analgesia. The Odon Device was effective in 19 of 40 cases (48%). Of the 40 births, 21 (52.5%) required additional assistance: 18 of 40 births (45%) were completed using nonrotational forceps, 1 of 40 births (3%) required rotational forceps, and 2 of 40 births (5%) required an emergency cesarean delivery. There was no serious maternal or neonatal adverse event related to the use of the device, and there was no serious adverse device effect. There were 4 devices (10%) that were ineffective because of a manufacturing fault. Furthermore, 39 of 40 women (98%) reported a high birth perception score. All practitioners were able to use the device as intended, although some steps in using the device were reported to be easier to perform (setup and deflation of air chamber) than others .Recruitment to an interventional study of a new device for operative vaginal birth was feasible; 78% of eligible women were willing to participate, often expressing an aspiration for an alternative to forceps and vacuum. The success rate of the Odon Device was lower than reported success rates of vacuum and forceps; however, in this study, the device had been used to assist birth for standard clinical indications. There was no significant maternal or neonatal safety concern associated with the use of the device, although the number of births studied was small. Further feasibility study to establish iterative changes to the device, technique, and clinical indications is necessary. No new method of operative vaginal birth has been introduced since the development of the vacuum extractor in the 1950s. The Odon Device is a new type of instrument that uses a circumferential air cuff over the fetal head and offers an alternative to vacuum and forceps.There was no serious maternal or neonatal adverse event related to the use of the Odon Device. In the first 40 clinically indicated cases ever to be conducted, the Odon Device was successful in 19 (48%), and there was a high maternal birth perception score.The Odon Device currently has a lower success rate than current devices, but this should improve with technique refinements. High recruitment rates to studies of novel devices to assist birth are feasible.,The optimal duration of the second stage of labor is contentious,The Odon Device is a new device that can be used for operative vaginal birth  consisti9The ASSIST Study used the Odon Device to assist birth for routine clinical indications: suspected fetal compromise and/or failure to progress in the second stage of labor. The study aimed to investigate the feasibility of recruitment and to investigate the efficacy, safety, and acceptability of the Odon Device to women and their babies, midwives, obstetricians, and neonatologists.This is a nonrandomized, single-arm feasibility study of the Odon Device for 40 women who required an operative vaginal birth for a recognized clinical indication. Qualitative work that explored the experience and views of women and clinicians will be published in full, separately.Potential participants were approached at Southmead Hospital, Bristol, United Kingdom. Odon Device–assisted births were conducted by 1 of 5 obstetricians who had undergone specialized training . If the The primary feasibility outcome was the proportion of approached and eligible women agreeing to participate. The primary clinical outcome was the proportion of births successfully assisted with the Odon Device. A birth was defined as “successful” if all of the following 6 criteria were met: (1) vaginal birth assisted with the Odon Device, (2) no serious maternal adverse reactionThe PPS has been previously validated for operative vaginal birth.,Sample sizes between 24 and 50 have been recommended for feasibility studies.Data were entered and stored on a bespoke study database (GeneSYS) designed and managed by the Clinical Trial and Evaluation Unit, University of Bristol, Bristol, United Kingdom. Data were analyzed using Stata . Continuous variables were reported as mean and standard deviation or median and interquartile range; categorical variables were reported as frequency and percentages. Relationships among characteristics that affect the success of the Odon Device were explored using nonparametric tests, the Fisher exact test for categorical variables, and the Mann-Whitney test for continuous variables.This study was approved by South Central–Berkshire REC, United Kingdom, on September 3, 2018 (18/SC/0344), the Medicines and Healthcare Products Regulatory Agency on August 9, 2018, and the Health Research Authority on September 3, 2018.Women were recruited between October 2018 and January 2019 . PregnanOf the 298 women who had consented, 224 (75.2%) did not have an operative vaginal birth: 139 (62.1%) had a spontaneous vaginal birth, 76 (33.9%) had a cesarean delivery, and 9 (4.0%) were not yet in labor when the recruitment target was reached. In addition, 72 women (24.2%) who had provided consent required an operative vaginal birth; the Odon Device was used in 40 cases (55.6%).There were minimal missing data: body mass index at 36 weeks’ gestation ; umbilical artery pH and base excess ; umbilical vein pH and base excess ; Neonatal Infant Pain Score (NIPS)The Odon Device was the only device required to assist birth in 19 of 40 cases (48%). There was no serious maternal or neonatal adverse reaction related to the use of the device during birth, and there was no serious adverse device effect. All practitioners found the device easy to use; however, 1 woman (3%) whose birth was assisted using the Odon Device reported her perception of the operative birth as poor. Therefore, by our a priori definition, the proportion of births that were “successfully” assisted with the Odon Device was 18 of 40 (45%).Additional assistance was required to complete the birth in 21 of 40 cases (52%). Of the 40 cases, 18 (45%) were completed using nonrotational forceps, 1 (3%) required rotational forceps, and 2 (5%) required an emergency cesarean delivery . The fetal vertex was at the level of the ischial spines in all cases requiring rotational forceps or cesarean delivery.In addition, 39 of 40 devices (98%) were inspected after use, and 4 of 40 devices (10%) had a fault in the bulb pump mechanism, unable to inflate the air cuff. None of the faulty device had been successful, and in each case, the operator had raised concerns that the air chamber had not inflated adequately during use.P=.014) and degree of molding (P=.022) were strongly related to the success of the device; higher fetal station and/or increased molding was associated with lower device success rates. Caput (P=.057) may also affect the success of the device; greater degrees of caput were associated with a higher likelihood of failure. There was no evidence to support any relationship among device success and onset of labor (P=.650), head circumference (P=.368), primary indication for operative vaginal birth (P=1.000), position of the fetal head (P=.843), birthweight (P=.272), length of the second stage of labor (P=.814), and length of the first stage of labor (P=.178).Most neonatal events (16 of 17) were attributed to soft tissue trauma  . There wFurthermore, 11 infants (28%) experienced a serious adverse event (SAE) defined as an event that required hospitalization or prolongation of hospital stay or further intervention: 3 cases of jaundice requiring phototherapy not contributed to by bruising; 2 cases of respiratory difficulties requiring NICU admission; 1 prolonged neonatal stay for intravenous antibiotics secondary to maternal sepsis in labor; 1 hospitalization for weight loss; and 1 readmission for bronchiolitis aged 10 days. None of the cases were directly attributable to the use of the Odon Device.The median weighed blood loss was 499 mL . Furthermore, 2 women (5%) received a postnatal red blood cell transfusion. In both cases, the Odon Device had been unsuccessful, and nonrotational forceps were used, resulting in hemorrhage from perineal trauma.In addition, 7 women (18%) experienced an SAE: 3 third-degree tears, 2 postpartum hemorrhages required blood transfusion, 1 postnatal infection, 1 complication from a known neurologic condition, and 1 case of fecal incontinence at 28 days after birth.Women reported a better health score  at day 28  compared with antenatally  and on day 1 postnatal .In the 19 cases in which the Odon Device assisted the birth of the baby, the median time between the application of the device and time of birth was 5 minutes , with a median “decision-to-delivery” interval of 11 minutes . There were 21 births where the Odon Device did not assisted the birth of the baby: a manufacturing error affecting 4 devices accounted for 19% of the failed births; 3 failures (14%) occurred when the vertex was at the level of the ischial spines; further failures were attributed to (1) failure to reach “0” during the application of the device , (2) operator learning curve , and (3) no reason identified .The operator reported that the device was “easy” or “very easy” to “set up” and “deflate the air chamber” in 38 (95%) and 35 (88%) of 40 cases, respectively. The application of the device and the withdrawal of the applicator were more challenging: only 21 (53%) and 20 (50%) cases were reported as “easy” or “very easy,” respectively.The 5 operators joined the study in stages. The number of births and success rates per operator were variable . Operato,It is feasible to recruit women to a study investigating a novel device for operative vaginal birth. A recruitment rate of 78% is high and appears to be related to a general maternal aspiration for an alternative to forceps and vacuum . The success rate of the Odon Device was lower than the reported success rates of both vacuum and forcepsFactors that are likely to affect the efficacy of the device assisted the clinical context, technique of application and traction, the initial uncertainty of the optimal technique in inserting and using the device , and the design and functionality of the device itself. For example, it became clear after 3 births that the device is most effectively placed during a uterine contraction, in contrast to forceps and vacuum.Although the study was not powered to look at predictors, births were more likely to be successful if the fetal vertex was lower in the birth canal or if there was minimal molding of the fetal skull or similar other assisted births.There was no significant maternal or neonatal safety concern associated with the use of the device, although the number of births is small. There seem to be some neonatal benefits associated with the use of the device, consistent with the findings from simulation,Maternal outcomes were also acceptable. No woman required a blood transfusion after a successful Odon Device–assisted birth compared with 10% of women in unsuccessful cases. Clearly, this may reflect the use of 2 instrumentsThis study routinely collected maternal birth perceptions as part of the assessment of operative vaginal birth. It is encouraging that 98% of women in the study rated their birth very positively.https://www.nbt.nhs.uk/research-innovation/our-research/current-research/women-childrens-health-research-unit/women-4), and Besançon, France, and the success rate has markedly improved in this second phase; an interim analysis of the current ongoing studies demonstrated a success rate of 78% (66 of 85 cases).A future randomized controlled trial will be required to objectively compare outcomes among the Odon Device, forceps, and vacuum. However, this would require equipoise among the options for operative vaginal birth. We are confident that the success rates of the Odon Device can be improved with iterative improvements to the insertion technique, refinement of participant selection, and a more reliable device design. Further feasibility studies are currently underway in Bristol, United Kingdom  merit further iterative exploration and investigation of the device in larger studies.•The Odon Device may offer women an alternative instrumental birth.•There was no maternal or neonatal safety concerns in the births.•Recruitment rate was higher than expected.


Conclusions: Women aged 35 and over were more likely to have children born with Down syndrome. In addition, there is an association of Down syndrome with premature birth, low birth weight, and the number of prenatal consultations (≥6).Background: Down syndrome is the most frequent genetic cause of intellectual disability, with an estimated birth prevalence of 14 per 10,000 live births. In Brazil, statistical data on the occurrence of babies born with Down syndrome remain unclear. We aimed to estimate the occurrence of Down syndrome between 2012 and 2018, and to observe its association with maternal, gestational, paternal characteristics, and newborn vitality. Methods: A retrospective study was carried out using secondary data included in the Certificate of Live Birth in a state located in the southeastern region of Brazil. Data analysis was performed in the software Stata 14.1. Pearson’s chi-square test for bivariate analysis, and logistic regression for multivariate analysis were performed, with a 95% confidence interval (CI) and a significance of 5%. Results: We observed that 157 cases of Down syndrome were reported among 386,571 live births, representing an incidence of 4 in 10,000 live births. Down syndrome was associated with maternal age ≥ 35 years, paternal age ≥ 30 years, the performance of six or more prenatal consultations, prematurity, and low birth weight ( Down syndrome (DS) is a genetic disorder resulting from trisomy of chromosome 21 (whole or part), which occurs due to the failure of chromosome 21 to separate during gametogenesis, resulting in an extra chromosome in all body cells . There aDS is the most frequent genetic cause of intellectual disability, with an estimated birth prevalence of 14 per 10,000 live births ,12. AddiPatients with DS have several degrees of impairment mainly of cognitive functions, such as learning, memory, language, and executive function ,3,17,18,Additionally, children with DS have an increased risk of comorbidities, such as hypotonia and orofacial dysfunction, which can affect the child’s feeding ability, and hypothyroidism , which cIt has been identified that DS is the commonest known medical cause of intellectual disability , occurriAn observational retrospective study was undertaken, using secondary data, generated by the Certificate of Live Birth in the Southeastern region of Brazil, between 2012 and 2018. In this study, the diagnosis of DS was described in the Certificate of Live Birth . It is noteworthy that, through the Certificate of Live Birth, there is no possibility of knowing whether the diagnosis was made during the gestational period or after birth; thus, it may have happened by karyotype examination or phenotypic assessment. In Block VI of the Certificate of Live Birth, entitled Congenital Anomaly, field 41 indicates that all anomalies or congenital defects observed by the person responsible for the birth or by the neonatologist must be reported, without hierarchy or attempt to group them into syndromes, prioritizing the description contained in the list of codes of the International Classification of Diseases (ICD-10). Furthermore, the screening for DS made in Brazil in the first trimester is mainly the “nuchal translucency” measurement. Termination of pregnancy only due to DS diagnosis is illegal in Brazil and rates of illegal procedures are unknown. Ethical approval was obtained by the Institutional Review Board (Protocol Number 3.572.276/2019).p < 0.20 and permanence with a p-value less than 0.05.The primary outcome of the study was the prevalence of DS. The prevalence rate was calculated considering the number of live births with DS between 2012 and 2018, divided by the total number of live births in that same period, with the rate being expressed per 1000 births. The independent variables analyzed included: (i) “newborn”: sex , birth weight (<2500 g or ≥2500 g), and Apgar score at the first (1st) minute and fifth (5th) minute (<7 or ≥7); (ii) “mother”: maternal age (up to 34 y.o. or ≥35 y.o.), marital status (without a partner or with a partner), and education ; and (iii) “father”: age (up to 29 y.o. or ≥30 y.o); (iv) “pregnancy and childbirth”: number of prenatal consultations (<6 or ≥6), weeks of pregnancy (<37 or ≥37 weeks), type of delivery . Data were analyzed using the software Statistic Data Analysis (STATA) 14.1 and presented descriptively using tables with raw frequencies (N) and relative (%) and confidence intervals (95%CI). Pearson’s chi-square test was performed for bivariate analysis. Regarding the multivariate analysis, logistic regression was performed, with entry into the model when the variables presented We note that between 2012 and 2018, there were 386,571 live births, of which 157 were born with DS, representing a birth rate of 4 cases of children with DS for every 10,000 live births. Regarding the characterization of the population of cases with DS, among the 157 births, a greater proportion of newborn babies was observed, and most mothers had six or more prenatal consultations. More than half of the mothers were ≥35 years old, had incomplete higher education, and had a partner. About 84% of parents were 30 years old or older. Regarding the weeks of gestation, for 72%, they were ≥37, and in more than 90% the Apgar at the 1st minute and 5th minute was ≥7. We found that one in four births with DS weighed less than 2500 g (25.5%). Cesarean delivery was the most prevalent (68.1%) .p < 0.05).p < 0.05).We observed that pregnant women of babies with DS are 2.45 (95%CI: 1.12–5.34) more likely to have six or more prenatal consultations, when compared to the group of pregnant women with babies without DS. Likewise, women aged 35 years or older have an odds 6.0 times higher for newborns with DS. Regarding the association between DS and gestational age and birth weight, we observed that there is an approximately 2.4 times greater chance of premature births and low birth weight in the group of pregnant women whose fetus has DS, when compared to the group without this condition. In addition, older parents (30 years or older) were twice as likely to have a newborn with DS.We observed a prevalence of 4/10,000 cases of live births with DS through the Certificate of Live Birth, in the period between 2012 and 2018, in Brazil. A study carried out in Mexico  found siA study showed that there are significant geographic inequalities in both the total and live birth prevalence of DS . For insDifferences in total prevalence are mainly due to the large variation in the maternal age profile of European countries an also due to the pregnancy termination rate after prenatal diagnosis of DS . In addiResearch carried out in the State of Bahia, located in the Northeast region of Brazil, showed a lower percentage compared to our study, with a DS rate of 1.81 to 10,000 live births . In ValeTwo studies ,48 have In Brazil, in 2012, Law Number 12.662  transforThe Certificate of Live Birth is a document of great importance, which in addition to being a source of the Information System on Live Births (Sistema de Informação sobre Nascidos Vivos—SINASC), serves as basis for civil registration. The Certificate of Live Birth consists of eight blocks of information on the occurrence of births, with data related to the mother, pregnancy, delivery, and the newborn, which allows identification of the profile of live births, such as the birth weight, vitality conditions, prematurity, in addition to maternal and paternal age, among others. It should be noted that block VI, which adds only field 41, of a descriptive nature, requests that all anomalies or congenital defects observed by the person responsible for delivery or by the neonatologist who receives the child be recorded, without attempting to group them into syndromes . In thisRegarding the association of DS with maternal characteristics, it appears that women aged ≥ 35 y.o. are 6.0 times more likely to have children born with the syndrome. This data corroborates the results from Mexico and Argentina, which show that, from the age of 35, the chance of women having a child with DS increases progressively ,42. MateThe average maternal age has also increased in Europe since the late 1970s. An increasing number of newborn infants with DS is expected, since the prevalence of DS is associated with maternal age. Prenatal screening and termination of affected pregnancies could counteract this effect, although this varies among countries depending on the policy, provision, and uptake of prenatal screening ,40,54,55With regards to the weight, newborns with DS were 2.37 times more likely to be born with low weight than typical newborns. In line with this finding, a study published by Morris  presentsConsidering 38 weeks of gestation, the average weight of newborns with DS was lower than that of normal newborns . It is wRegarding the gestational age, babies with DS were 2.34 times more likely to be born premature. In typical babies, the decrease in intrauterine growth is on average at 40 weeks; however, in babies with DS, the retraction of intrauterine growth can occur in the 38th week of gestation, which may be related to the higher probability of premature birth of babies with DS .Prenatal diagnosis of DS can be suspected from the first trimester of pregnancy, through tests that indicate an increased risk of the fetus having congenital diseases and even accurate tests to confirm the syndrome. Nuchal translucency, an ultrasound image that assesses the accumulation of fluid in the posterior neck, performed between the 10th and 14th week of gestation, has predictive results for DS, when greater than or equal to 2.5 mm ,60. HoweIt should be noted that an invasive prenatal diagnosis, such as, CVS as well as amniocentesis, is not a feasible option for all low-risk mothers, as these procedures carry a small but finite risk and would ultimately cause more miscarriages than they would detect aneuploidy. Therefore, a number of noninvasive tests have been developed, including first-trimester risk assessment at 11 to 14 weeks, maternal serum analyte screening at 15 to 20 weeks, and sonographic fetal structural survey at 18 to 22 weeks, all of which are designed to give a woman an adjusted estimate of having an aneuploid fetus using her a priori age-related risk as a baseline. The ability to isolate fetal cells and fetal DNA from maternal blood during pregnancy has opened up exciting opportunities for improved noninvasive prenatal testing (NIPT). Direct analysis of fetal cells from maternal circulation has been challenging, given the scarcity of fetal cells in maternal blood . Currently, the use of cell-free DNA (cfDNA) for NIPT for chromosomal aneuploidies has been frequently reported, especially for trisomy or monosomy. Moreover, a number of commercial products are already being marketed for this indication .Our study showed that mothers carrying fetuses affected with DS were more likely to have frequent prenatal consultations  secondary to the associated congenital anomalies. In contrast, a study carried out in the Northeastern region of Brazil revealed a slight difference between the group of mothers of newborns with DS and mothers of newborns without DS, in which the variable did not remain associated with the occurrence of DS .The Brazilian Ministry of Health recommends that at least six prenatal consultations be carried out, preferably one in the first trimester, two in the second trimester, and three in the last trimester of pregnancy . A possiA study held in Europe has found that the prevalence of newborn infants with DS should decrease because of prenatal screening, diagnostic tests, and pregnancy termination . The expRegarding the paternal age, it appears that men aged ≥ 30 y.o. are 2.0 times more likely to have children born with DS. In line with this finding is a study  that shoWe recognize the limitations of our study. The main issue faced in this research was the possibility of underreporting events and the variability in the quality of data and information related to congenital anomalies in the Certificate of Live Birth, a fact that is often related to the lack of training and supervision of the professional in filling out the Certificate of Live Birth and entering this data into the system. It is also noteworthy that the scarcity of studies addressing only the profile of live births with DS makes it difficult to expand the discussion, reinforcing the present research and its findings.In summary, between 2012 and 2018, there was a Down syndrome birth rate of 4 for every 10,000 live births in Brazil.Women aged 35 and over were more likely to have children born with DS. In addition, there was an association of DS with premature birth, low birth weight, and the number of prenatal consultations (≥6). This study draws attention to the proper completion of data from the Certificate of Live Birth, attributing its real importance in the context of public health surveillance, in addition to giving visibility to the factors associated with DS. Taken together, these aspects may qualify the care delivered to the family and the newborn with DS.


Bladder cancer (BLCA) is a common genitourinary cancer in patients, and tumour angiogenesis is indispensable for its occurrence and development. However, the indepth mechanism of tumour angiogenesis in BLCA remains elusive. According to recent studies, the tight junction protein family member occludin (OCLN) is expressed at high levels in BLCA tissues and correlates with a poor prognosis. Downregulation of OCLN inhibits tumour angiogenesis in BLCA cells and murine xenografts, whereas OCLN overexpression exerts the opposite effect. Mechanistically, the RT‐qPCR analysis and Western blotting results showed that OCLN increased interleukin‐8 (IL8) and p‐signal transducer and activator of transcription 3 (STAT3) levels to promote BLCA angiogenesis. RNA sequencing analysis and dual‐luciferase reporter assays indicated that OCLN regulated IL8 transcriptional activity via the transcription factor STAT4. In summary, our results provide new perspectives on OCLN, as this protein participates in the development of BLCA angiogenesis by activating the IL8/STAT3 pathway via STAT4 and may serve as a novel and unique therapeutic target. The incidence rate of BLCA in males is 3–4 times that in women, and it is the fourth most common malignancy in men.Occludin (OCLN) is an important tight junction protein that regulates cytoskeletal remodeling,Signal transducers and activators of transcription signalling (STATs) have been proven to be molecules that connect cytokine signalling with the regulation of important cellular mechanisms such as tumour cell survival and infiltration, inflammation and immunity.Here, we observed markedly upregulated OLCN expression in BLCA that was significantly associated with tumour angiogenesis in both patients with BLCA and murine xenograft models. Furthermore, OCLN overexpression enhanced the activity of the IL8/STAT3 signalling pathway by activating STAT4, ultimately contributing to tumour vascular remodelling and metastasis. Therefore, this study focused on the biological mechanism of OCLN in BLCA angiogenesis and provides potential targets for tumour treatment.22.12 at 37°C.BLCA cell lines, namely T24 (ATCC HTB‐4), 5637 (ATCC HTB‐9) were derived from laboratory retained cells.2.2Cells were lysed in RIPA buffer on ice for 30 min, shaken 3 times every 10 min, and then centrifuged at 12 000 rpm for 15 min. The proteins in the cell supernatant (protein lysates) were separated on 8% to 12% SDS‐PAGE and then transferred to PVDF membranes . After blocking with 5% skim milk at room temperature for 1 h, the PVDF membranes were incubated with the primary antibody at 4°C overnight. The following antibodies were used: β‐Actin , OCLN , p‐STAT3 , STAT3  and HSP90 . The corresponding secondary antibodies were as follows: HRP‐conjugated horse anti‐mouse  and goat anti‐rabbit  secondary antibodies. β‐Actin and HSP90 were used as the internal controls.2.3n = 5 mice/group), and 2 × 106 tumour cells were injected subcutaneously into the backs of mice. The cell suspension and 150 µl of Matrigel  were mixed at a ratio of 1:3. After two weeks, the Matrigel plugs were collected and photographed, followed by IHC staining and a pathological examination. All animal experimental procedures were approved by the Animal Experimental Ethics Committee of Sun Yat‐Sen University.BALB/c nude mice  were randomly divided into 4 groups ‐containing selection media (0.5 μg/ml) for 24 h. OCLN knockdown efficiency was measured by Western blotting and RT‐qPCR assays. The following shRNA sequences were used: shOCLN‐1 forward: 5′‐CCGGGCACCAAGCAATGACATATATCTCGAGATATATGTCATTGCTTGGTGCTTTTTG‐3′, reverse: 5′‐AATTCAAAAAGCACCAAGCAATGACATATATCTCGAGATATATGTCATTGCTTGGTGC‐3′; shOCLN‐2 forward: 5′‐CCGGGGATGACTATAGAGAAGAAAGCTCGAGCTTTCTTCTCTATAGTCATCCTTTTTG‐3′, reverse: 5′‐AATTCAAAAAGGATGACTATAGAGAAGAAAGCTCGAGCTTTCTTCTCTATAGTCATCC‐3′; and scrambled shRNA forward: 5′‐CCGGGCTAAACTCGTAATTCAACTTCTCGAGAAGTTGAATTACGAGTTTAGCTTTTTG‐3′, reverse: 5′‐AATTCAAAAAGCTAAACTCTAATTCAACTTCTCGAGAAGTTGAATTACGAGTTTAGC‐3′.2.5The primer sequences for the Flag‐OCLN (NCBI Gene ID: 100506658) plasmid were as follows: forward: 5′‐TTTAAACTTAAGCTTGGTACCATGTCATCCAGGCCTCTTGA‐3′ and reverse: 5′‐GTCATCCTTGTAATCGAATTCTGTTTTCTGTCTATCATAGT‐3′. The HA‐STAT4 (NCBI Gene ID:6775) plasmid primer sequences were as follows: forward: 5′‐TTTAAACTTAAGCTTGGTACCGCCACCATGTCTCAGTGGAATCAAGTCCAAC‐3′ and reverse: 5′‐GACGTCGTATGGGTAGAATTCTTCAGCAGAATAAGGAGACTTCATT‐3′. Genes were amplified by reverse transcription PCR and cloned into the pcDNA3.1(+) vector. All sequences were verified to be correct. The relevant plasmids were transiently transfected into 5637, T24 and 293T cells using Lipofectamine™ 3000  according to the manufacturer’s instructions.2.6All OCLN‐specific RNAs (siRNAs) and the negative control siRNA were designed by and purchased from RiboBio . The siRNAs were transfected into 293T cells using Lipofectamine™ 3000. 24 hours after the transfection of siRNAs, the cells were lysed for Western blotting or RT‐qPCR assays.2.74 cells/well) were resuspended in 100 μl of conditioned medium (CM), seeded on Matrigel and incubated at 37°C for 6–8 h. The cells were then stained with 1 μM Calcein‐AM  for 30 min and imaged with a fluorescence microscope . The number of tubes was quantified in each image, and the total number of meshes and segments was calculated using ImageJ software.Matrigel (50 μl/well) was coated in each well of a 96‐well plate and incubated at 37°C for 30 min. After the polymerization of Matrigel, EA.hy926 cells  was used to detect the IL8 concentration in CM according to the manufacturer’s instructions. Levels of the secreted protein were measured from a standard curve.2.9n = 120) were collected from the Fifth Affiliated Hospital of Sun Yat‐Sen University and were used after obtaining written consent from the patients. The collected tissues were first embedded in paraffin and cut into 4‐μm‐thick slices before the IHC assay. Sections were baked at 65°C for 3 h and then deparaffinized in xylene and alcohol. After dewaxing, the samples were washed with water and incubated with a citrate buffer solution (pH 9.0) in a pressure cooker for 2.5 min for antigen retrieval. Sections were treated with 3% hydrogen peroxide in methanol to block endogenous peroxidase activity and then incubated with goat serum for 30 min to block nonspecific staining. The sections were incubated with OCLN  and CD31  primary antibodies followed by secondary antibodies. A biotinylated secondary antibody  was applied, followed by an incubation with 3,3‐diaminobenzidine tetrahydrochloride (DAB). Finally, sections were counterstained with haematoxylin and sealed with neutral gum. Five fields were randomly selected from each sample to calculate expression. Scale bar = 100 µm. Staining/expression was scored as described in a previous study.All BLCA specimens  according to the manufacturer’s instructions. The IL8 promoter was cloned into the pGL3 vector with the following primers:pGL3‐IL8 forward: ATTTCTCTATCGATA GGTACC TTCATTGTCCTGTACTTCCTGT and;pGL3‐IL8 reverse: ACTTAGATCGCAGAT CTCGAG GTTTACACACAGTGAGATGGTT.The firefly and Renilla luciferase activities were detected with a microplate reader. Firefly luciferase activity was normalized to Renilla luciferase activity.2.11−4 g/L; Peprotech, CI6217, Princeton Business Park, NJ, USA) and human antibody IL8  for 24 h separately, they were switched to fresh RPMI‐1640 medium containing 10% FBS, and the supernatant was collected after 24 h.5637 and T24 cells were seeded in 6‐well plates with RPMI‐1640 medium supplemented with 10% FBS. When cells reached confluence, they were washed with 1× PBS and cultured in serum‐free medium (1 ml/well). After an incubation for 4–6 h, the supernatant was replaced with fresh RPMI‐1640 medium containing 25% FBS and the STAT3 inhibitor Stattic . After 24 h, the medium was replaced with fresh RPMI‐1640 medium containing 10% FBS, and then the supernatant was collected after 24 h. After the cells were cultured with recombinant human IL8 , and then reverse transcribed into cDNAs using the Evo M‐MLV RT Kit . Subsequently, cDNAs were amplified using a CFX96 real‐time PCR system  and quantified with SYBR‐Green Pro Tap HS premix . The sequences of the gene‐specific primers were as follows: h‐β‐Actin forward: 5′‐TCAAGATCATTGCTCCTCCTG‐3′, reverse: 5′‐CTGCTTGCTGATCCACATCTG‐3′; h‐OCLN forward: 5′‐ACTTCAGGCAGCCTCGTTAC‐3′, reverse: 5′‐CCTGATCCAGTCCTCCTCCA‐3′; h‐IL8 forward: 5′‐CACCGGAAGGAACCATCTCAC‐3′, reverse: 5′‐TGGTCCACTCTCAATCACTCTCAG‐3′; h‐STAT4 forward: 5′‐GGAAATTCGGCATCTGTTGGCC‐3′, reverse: 5′‐TTCTCTTTGGAAACACGACCTAACTGT‐3′; h‐ANG forward: ACTGTGTCCTCTTCCACCAC, reverse: GGATGTTTAGGGTCTTGCTTT; h‐MMP9 forward 5′‐AAGGCGCAGATGGTGGAT‐3′, reverse 5′‐TCAACTCACTCCGGGAACTC‐3′; and h‐IL18 forward: ATCAACCTCAGACCTTCCAG, reverse: GCATTATCTCTACAGTCAG. h‐β‐Actin was used as an internal control. The cycling conditions were 95°C for 30 s, followed by 40 cycles of 95°C for 5 s and 60°C for 30 s. The fold change in gene expression was calculated using the 22.13p < .05; **.001< p < .01; ***p < .001. Student’s t‐test was used for comparisons of two independent datasets.SPSS Standard version 25.0  was applied for statistical analyses. All data were analysed and are expressed as the mean ± SD. Deviation from at least three independent experiments. *.01< 33.1We analysed the relationship of OCLN expression with the overall survival rate of patients with BLCA to determine whether OCLN is clinically associated with BLCA progression. The Kaplan–Meier plot indicated that patients in the Cancer Genome Atlas (TCGA)‐BLCA cohort with high OCLN expression had a lower survival rate than those with low OCLN expression Figure . Moreove3.2BLCA is a highly vascularized tumour, and we investigated whether OCLN was involved in the development of BLCA by regulating tumour angiogenesis. We constructed stable 5637 and T24 OCLN knockdown BLCA cell lines using lentiviruses to verify this hypothesis, and the knockdown efficiency was confirmed by Western blotting and RT‐qPCR assays Figure . CM from3.3We performed RNA sequencing to identify changes in gene expression in T24 OCLN‐silenced cells and to further investigate the mechanism by which OCLN regulates angiogenesis. The two T24 OCLN‐shRNA groups presented 1547 and 172 downregulated genes, respectively, and 190 genes were common to the two groups Figure . We perf3.4We next explored the detailed mechanism by which OCLN regulates IL8 expression in BLCA angiogenesis. Previous studies have shown that STAT3 is involved in vascular remodelling and progression in breast cancer3.5In the enrichment analysis of proangiogenic genes in OCLN knockdown cells shown in Figure 4BLCA is the most common urothelial tumour, accounting for approximately 430 000 newly diagnosed cases and 170 000 deaths worldwide annually.Tumour neovascularization is essential for the metastasis of some malignant tumours, and various proangiogenic factors are involved in tumour progression, including angiopoietin (Ang), platelet‐derived growth factor (PDGF), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), IL8 and matrix metalloproteinases (MMPs).According to a previous study, IL8 is involved in transcriptional regulation by activated NFκB,In summary, we discovered that OCLN expression is strongly correlated with the TNM stage and survival rate of patients with BLCA. In pathological samples and mouse xenograft models, OCLN was positively correlated with tumour angiogenesis. Importantly, OCLN regulated vascular remodelling in BLCA by regulating the IL8/STAT3 pathway through the induction of STAT4 expression. Collectively, these results indicate great potential for OCLN as a multipotent therapeutic target to inhibit tumour angiogenesis and progression in BLCA. As tumour angiogenesis plays an important role in the occurrence, development and metastasis of many tumours, our study expands the in‐depth knowledge of the possible effects of OCLN and proposes the basic principle of targeting OCLN to suppress angiogenesis in the treatment of metastatic tumours.All authors agree to submit the article and have no conflict of interest.Fan Yang: Data curation ; Investigation ; Writing – original draft . Xue‐Qi Liu: Investigation ; Writing – original draft . Jian‐Zhong He: Software . Shi‐Ping Xian: Software . Peng‐Fei Yang: Software . Zhi‐Ying Mai: Software . Miao Li: Funding acquisition ; Supervision . Ye Liu: Funding acquisition ; Supervision . Xing‐Ding Zhang: Funding acquisition ; Supervision .Fig S1Click here for additional data file.


Preterm birth (PTB) is a syndrome resulting from a complex list of underlying causes and factors, and whether these risk factors differ in the context of prior PTB history is less understood. The aim of this study was to explore whether PTB risk factors in a second pregnancy were different in women with versus without previous PTB.We conducted a population-based cohort study using data from the birth cohort of the Center for Data and Knowledge Integration for Health (CIDACS) for the period 2001 to 2015. We used longitudinal transition models with multivariate logistic regression to investigate whether risk factors varied between incident and recurrent PTB.Pdifference <0.05) between incident and recurrent PTB. The following were associated with an increased chance for PTB incidence, but not recurrent: household overcrowding (OR 1.09), maternal race/ethnicity [(Black/mixed—OR 1.04) and (indigenous—OR 1.34)], young maternal age (14 to 19 years—OR 1.16), and cesarean delivery (OR 1.09). The following were associated with both incident and recurrent PTB, respectively: single marital status (OR 0.85 vs 0.90), reduced number of prenatal visits [(no visit—OR 2.56 vs OR 2.16) and (1 to 3 visits—OR 2.44 vs OR 2.24)], short interbirth interval [(12 to 23 months—OR 1.04 vs OR 1.22) and ], and advanced maternal age (35–49 years—OR 1.42 vs OR 1.45). For most risk factors, the point estimates were higher for incident PTB than recurrent PTB.A total of 3,528,050 live births from 1,764,025 multiparous women were analyzed. We identified different risk factors (The risk factors for PTB in the second pregnancy differed according to women’s first pregnancy PTB status. The findings give the basis for the development of specific prevention strategies for PTB in a subsequent pregnancy.The online version contains supplementary material available at 10.1186/s12916-022-02313-4. Preterm birth (PTB) is one of the main causes of death among children under 5 years of age . PTB is PTB is a syndrome resulting from a complex list of underlying causes and factors including sociodemographic, psychosocial, nutritional, behavioral, and biological factors . Higher Despite this knowledge, whether these risk factors differ in the context of prior preterm birth history is less understood. Also, only one study has distinguished between risk factors for premature birth between women with a previous PTB compared with women without a previous PTB . HoweverThis population-based cohort study used data from the CIDACS Birth Cohort. This cohort was created by linking data from Brazil’s National Live Birth System (SINASC) and the 100 Million Brazilian Cohort baseline from Jan 1, 2001, to Dec 31, 2015. This study adhered to the RECORD  statement.The SINASC gathers information on birth notifications across the country, including information about the mother, pregnancy, newborn, and gestational age at birth, which allows the estimation of the prematurity rate for the country. The live birth declaration forms that provide information to SINASC adopt the last menstrual period (LMP) as the standard method for estimating the gestational age in weeks. Results of physical examinations and other methods are alternatively accepted . The 100The linkage process used CIDACS-RL (Record Linkage), a novel record linkage tool developed to link large-scale administrative datasets at CIDACS . The linIn this study, we included live births of multiparous women, aged 14–49 years, who entered the CIDACS Birth Cohort as nulliparous women. We excluded (a) all multiple births and live births with congenital anomalies as these conditions are known to be strongly associated with premature birth , 6, (b) The study outcome was the occurrence of PTB in the second pregnancy. Incident PTB was defined as a live birth with a gestational age less than 37 weeks preceded by a term delivery. Recurrent PTB was defined as a live birth with a gestational age less than 37 weeks preceded by a previous PTB.The following covariates were considered in the analyses: (i) sociodemographic characteristics of the mother: residence area , household overcrowding , self-declared race/ethnicity , level of education , marital status ; (ii) prenatal assistance: the number of visits ; (iii) maternal, delivery, and newborn-related variables: maternal age , type of delivery , and sex of the newborn , and interbirth interval . Household overcrowding was calculated by dividing the number of individuals living in the house and the number of rooms. The interbirth interval was estimated (in months) by the difference between the second child's birth date and the previous child’s birth date.α=0.05). However, the interaction test does not explicitly test whether the risk factor is significant for the incident and recurrent PTB, and thus the odds ratio (OR) and 95% confidence intervals (95% CI) for each risk factor were reported separately according to the first pregnancy PTB status. All models were adjusted for the complete set of risk factors considered to be relevant and plausible in the literature on preterm birth , single marital status , reduced number of prenatal visits [ and ], maternal age at birth between 14 and 19 years , and cesarean delivery . For these risk factors, point estimates were higher in magnitude for incident PTB compared to recurrent PTB. Inverse results were observed for short interbirth interval [ and ] and maternal age between 35 and 49 years . The univariate analyses are presented in Additional file We first investigated whether the factors associated with PTB in a second pregnancy differed between women whose first pregnancy was delivered at term or preterm Table . We idenincident 2.57, 95% CI 2.52–2.62; ORrecurrent 2.25, 95% CI 2.14–2.37). The chance of incident PTB was 14% higher in the live births from mothers without at least four prenatal visits in the first pregnancy who had this number of visits in the second pregnancy ; however, there was no significant increased chance among those recurrent PTB and the reference group. When mothers had an inadequate number of prenatal visits  in both pregnancies, there was a similar increased risk of incident PTB  and recurrent PTB . Table S2. Frequency and factors associated with incident and recurrent preterm birth in the second pregnancy, 2012-2015 . 1Analysis adjusted for all model variables. 2 Pdifference represents the interaction between incident and recurrent preterm birth for the respective characteristic. The equation for this model is as follows: Logit [ Pr (PTB2=1/Risk factors)] = β0 + β1 (PTB1) + β2 (risk factor X2) + β3 (PTB1) × (risk factor X2), where PTB1 and PTB2 are indicators of a preterm birth in the first and second pregnancy, respectively. Table S3. Incident and recurrent preterm birth in the second pregnancy according to change in the number of prenatal visits between the first and the second pregnancies, 2012-2015 . 1Adjusted analysis by mother’s residence area, family density, mother’s self-declared race/skin color, mother’s level of education, mother’s marital status, maternal age, type of delivery in the second birth. 2Pdifference represents the interaction between incident and recurrent preterm delivery for the respective characteristic. The equation for this model is as follows: Logit [ Pr (PTB2=1/Risk factors)] = β0 + β1 (PTB1) + β2 (risk factor X2) + β3 (PTB1) × (risk factor X2), where PTB1 and PTB2 are indicators of a preterm birth in the first and second pregnancy, respectively. Table S4. Factors associated with incident and recurrent preterm birth in the second pregnancy, using cross-validation technique, 2001-2015. 1Analysis adjusted for all model variables. Figure S1. ROC curve for logistic regression model of incident preterm birth in cross-validation analysis. (A) Empirical ROC curve; (B) Binomial ROC curve. Non-parametric ROC curve not generated due to database size. Figure S2. ROC curve for logistic regression model of recurrent preterm birth in cross-validation analysis. (A) Empirical ROC curve; (B) Binomial ROC curve; (C) Non-parametric ROC curve.


Immediate clamping and cutting of the umbilical cord have been associated with death and/or neurodisability ,2,3,4,5.There are several resuscitation trolleys that are available for research use. Two are commercially available in Europe (CONCORD and LifeStart Trolley) and others are under research protocols (INSPIRE and NOOMA). No matter which is used, all should have some of the basic features as shown in Neonatal resuscitation equipment needs to be designed to allow for routine resuscitation with an intact placental circulation. At the same time the obstetric team needs to have access to provide any necessary care to for the mother. A stable platform which can be brought right up to the mother close enough for an intact cord may require modification and integration with the various designs of birthing tables. The practice of delayed clamping with resuscitation remains mostly as part of research protocols. This may be because concerns remain about the need for immediate resuscitation, or situations where there may be an imminent delivery without adequate time to setup equipment or space for extra personnel. Currently, two specially designed neonatal resuscitation trollies are available for resuscitation with an intact cord. While resuscitation with an intact cord can be achieved with standard equipment some of the above previously stated challenges may continue ,24.The precise requirements will vary between the two main modes of birth, assisted vaginal birth and caesarean section. While neonates born naturally sometimes need resuscitation this is infrequent and the equipment and procedure can be more readily dealt with. The equipment at assisted births needs specific requirements. A major consideration at caesarean section is maintaining the integrity of the sterile field. This needs the neonatal resuscitation team to be part of the sterile field. Provided nothing passes from the neonatal team to the obstetric team after the neonate is delivered, some compromise to the equipment used by the neonatal team may be acceptable.The surface of the platform should be flat to provide an optimal position for an open airway (“sniffing position”). It should be at a height which allows the neonatal team to provide the care necessary. The surface should be soft and firm. It must be stable so that the neonate can be placed on the surface without any risk of the platform moving or risk of the neonate falling off the platform. The platform should be of a sufficient size to accommodate also large term neonates and must be capable of getting as close as possible to the vaginal introitus or caesarean incision, as the cord must not be under tension for it to remain functional. In case of caesarean section, it can be covered with sterile drapes as is normal for the Mayo table.With a specialized resuscitation trolley, three sides of the trolley can be easily accessed by a member of the resuscitation team. Position 1, over the mother’s thighs seems the most straightforward position. Provided the platform is relatively thin, the surface can be virtually at the level of the uterus/placenta. It needs to be supported and not resting on the mother’s thighs. Only one person can have ready access to the neonate.Position 2, at the side of the operating table is the normal position for the operating obstetrician, so this position requires the obstetrician to move away during the resuscitation. This position gives access for two or possibly three people around the resuscitation platform. The platform can be lowered to be significantly below the level of the placenta provided there is sufficient cord length. The surgical assistant remains to deal with the surgical wound and delivery of the placenta if necessary. Rarely will there be any significant problem during the few minutes after a birth. After about three minutes or earlier delivery of the placenta there is no physiological advantage for the resuscitation procedure to remain at the side of the mother.Position 3 is likely to place the neonate significantly above the placental level and may also require the obstetrician to move slightly if there is more than one person providing resuscitation. A sterile screen can be used to separate off the surgical field immediately after delivery of the baby. It is close to the face of the mother, who potentially could see, speak to and touch her baby.Position 4 is similar to position 1 but probably permit to manage newborn with a shorter cord. This position gives access for two people around the resuscitation platform but requires the obstetrician to move apart during the resuscitation.In all four positions there needs to be an independent support for the platform which provides sufficient stability as well as mobility to get into position immediately after the birth and away again three to five minutes later. It needs to be able to accommodate height differences especially if it is also used at assisted vaginal birth. If the trolley is customised for caesarean birth only then the range of height adjustment is significantly reduced. The height of the operating table could be adjusted to meet the requirements of the resuscitation platform.The resuscitation platform has significantly different height requirements for caesarean section as for assisted vaginal birth. Enterprising design is required to make the specialized equipment provide the same standards as routine resuscitation beds. At assisted vaginal birth it is inevitable that the platform to place the baby will be lower than the height of the standard resuscitation equipment. Raising the birthing table may help to reduce this compromise. The mother’s legs, in the lithotomy poles may also limit access and require the obstetrician to move away for a short time to allow the neonatal team access.A specialized trolley which provides the facility for resuscitation with intact placental circulation at both caesarean births and assisted vaginal births may compromise the facility for both modes of birth, and separate designs may be preferable. Most assisted vaginal births do not take place in the caesarean room, so equipment customised for an assisted vaginal birth can remain in the labour ward delivery room, while equipment customised for caesarean births can remain in the operating room.The cost of the equipment is obviously a serious consideration, but, given the enormous cost of the lifelong care of an individual with hypoxic birth injury , and theA standard resuscitation bed is equipped by an overhead radiant heater. The resuscitation platform of the trolley can also be warmed if the heater is switched on for a short time before the equipment is required, however this may be ineffective compared to radiant heat. The preterm neonate’s body is enclosed in polythene, a cap is placed on the neonatal head and warmed towels placed around its body. Chemical heating mattresses can be used to provide additional heating. Some types of mattress seem to be efficacious in maintaining normothermia (36.5–37.5 °C) even without an overhead radiant heater, but body temperature should be accurately checked in the delivery room. Instead, if such mattresses are used in combination with a radiant heater, hyperthermia (>38 °C) should be checked and avoided. The ambient temperature of the delivery room  is important to reduce the risk of hypothermia even with all the above measures. The ambient temperature should be checked in the delivery room and promptly increased while assisting a very preterm delivery.Providing the equipment for warming during these first few minutes after birth at motherside is a significant challenge. The possibility of the traditional radiant heater is limited at both caesarean section and vaginal births due to limited access immediately above the resuscitation platform. A temporary radiant heater could be used in positions 1 and 3, possibly attached to the operating light and only turned on immediately before the birth.A warming mattress is available on one of the commercially available trollies, but, for preterm neonates, it may not be sufficient and supplementary chemical heating units have been effectively used. The ambient temperature of the air is extremely important and a warm theatre temperature is required for the safety of these neonates.The use of a sterile polythene bag, covering also the head of the infant, presents no additional problem at caesarean section.Newborns who do not start breathing efficaciously after proper stimulation should be supported by nCPAP or positive pressure ventilation (PPV) within 1 min of life. In high-resource settings the initial provision of PPV is with a T-piece ventilator providing PEEP, (positive end expiratory pressure) with carefully controlled PIP (peak inspiratory pressure). A number of items of equipment are commercially available which provide PEEP and PIP with visible gauges showing the set pressure levels . A suctiThe equipment to provide ventilation and suction can be remote or within the structure supporting the platform. International guidelines for neonatal resuscitation do not recommend routine oral, nasal, or oropharyngeal suctioning of the newborn at birth , and equIncreasingly, more sophisticated monitoring is being used routinely. The minimal requirement is for heart rate and lung air entry via a stethoscope and also pulse oximetry. Electronic equipment for monitoring the neonatal parameters such as heart rate and oxygen saturation at birth are rapidly developing. In terms of size, weight, and sterility, none of these should present any difficulty in having them available on a mobile resuscitation trolley, but still they have not. Wireless transmission of signals makes it possible to include the equipment within the caesarean section sterile field if this can be contained within a sterile container.Roomside neonatal resuscitation trollies are generally stable and mobile enough so that if extended care is required the neonate can be moved to the special care nursery on the trolley. This is provided there is an independent gas supply on the machine. However, a transport incubator is frequently used to move the newborn from delivery room to neonatal intensive care unit.Motherside neonatal resuscitation trolley is not intended to be used to move the neonate, but being mobile, it must also be capable of having a safe and stable platform for resuscitation of the neonate. Stability normally requires a large base but a large base limits mobility and proximity to the operating table.Although the intervention of early cord clamping has no advantage for the mother or the baby, it is a reality that neonatal resuscitation was introduced while the practice was already established. Current practice and guidelines are based on the premise that there is unrestricted access to the neonate. The World Health Organisation (WHO) suggests that resuscitation with the cord intact is dependent upon the skill of the neonatologist . A chang


Objective: This study aims to explore the occurrence of extrauterine growth retardation (EUGR) in preterm infants with a gestational age of <34 weeks, at discharge, and the factors influencing the occurrence of EUGR.Method: A retrospective analysis of 691 preterm infants with a gestational age of less than 34 weeks, born in our hospital over the past 3 years. At discharge, the growth indicators head circumference, weight, and length were used to divide the infants into an EUGR group (n = 255) and the non-EUGR group (n = 436). The occurrence of EUGR and its influencing factors were then analyzed.Results: Of the 691 preterm infants evaluated for inclusion in the study, 255 cases (36.9%) met the requirements of EUGR at discharge. The different growth indicators used, i.e., weight, length, and head circumference, classified the infants differently. The incidence of EUGR using these measures was 30.2% (209), 27.9% (193), and 23.2% (161), respectively. The results of a univariate analysis showed that gestational age, birth weight, intrauterine growth retardation (IUGR), maternal gestational hypertension, age at which the infant commenced feeding, duration of the application of an invasive ventilator, length of hospital stay, nosocomial infection, respiratory and gastrointestinal diseases, symptomatic patent ductus arteriosus, and the early onset of neonatal sepsis were correlated with the occurrence of EUGR. Further logistic multivariate regression analysis revealed that low gestational age, low birth weight, complicated IUGR, respiratory distress syndrome, and necrotizing enterocolitis were independent risk factors for EUGR in preterm infants with a gestational age <34 weeks.Conclusion: In preterm infants with a gestational age <34 weeks in our hospital, there is a high incidence of EUGR, which is affected by factors such as the gestational age, birth weight, IUGR, respiratory distress syndrome, necrotizing enterocolitis, and other factors. American researchers, Clark et al., first proposed the definition for extrauterine growth restriction (EUGR) in preterm infants in 2003, i.e., newborns with the growth indicators  less than the 10th percentile of the average growth indicators in infants of the same gestational age . TherefoPreterm infants with a gestational age of <34 weeks, who had been admitted to the neonatal intensive care unit (NICU) of the First Affiliated Hospital of Xinjiang Medical University within the past 3 years, were enrolled as study subjects. The inclusion criteria were as follows: (1) neonates born in our hospital or transferred to our department within 24 h of birth with gestational age <34 weeks, who survived for more than 7 days and (2) neonates with complete medical records. The exclusion criteria were as follows: (1) neonates who died during hospitalization or were discharged abnormally or (2) neonates with diseases of the surgical system, severe developmental abnormalities or chromosomal abnormalities, or genetic metabolic diseases.Data were collected and placed in a clinical database for preterm infants for a research project undertaken by the Children's Hospital of Fundan University. These data were used for a cluster randomized controlled trial named “Reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality” . The datInfants with a weight, length, or head circumference below the 10th percentile of the average growth parameters, adjusted by the gestational age at discharge, were defined as having EUGR  at the time of discharge. Of these subjects, 53.3% (136) had measurements less than the 10th percentile of neonates of the same gestational age in all three areas, i.e., weight, head circumference, and length. When considering each measurement criterion separately, i.e., weight, length, and head circumference, the incidence of EUGR was 30.2% (209), 27.9% (193), and 23.2% (161), respectively, as shown in P < 0.05). Preterm infants with a gestational age of <30 weeks had the highest incidence of EUGR (78.2%), and those with a gestational age of 32–34 weeks had the lowest incidence of EUGR (21.2%). The details are shown in The 691 cases were classified according to their gestational age, and the difference in the incidence of EUGR was statistically significant between the age groups (P < 0.05). Preterm infants with a weight <1,500 g had the highest incidence of EUGR (97.6%), and those with a weight of more than 2,500 g had the lowest incidence of EUGR (7.1%). The details are shown in The 691 cases of the preterm infants were also classified by weight, and the difference in the incidence of EUGR between the weight groups was statistically significant (P < 0.05). The incidence of complicated IUGR, gestational hypertension, age of commencement of feeding, duration of the application of traumatic ventilator, length of hospital stay, and nosocomial infection in the EUGR group were all higher than those in the non-EUGR group (P < 0.05), as shown in The average gestational age and average birth weight in the EUGR group were lower than those in the non-EUGR group (P < 0.05) than in the non-EUGR group, as shown in This study suggests that the incidence of complicated respiratory system diseases , gastrointestinal diseases , symptomatic patent ductus arteriosus, and the early onset of neonatal sepsis in the EUGR group was significantly higher (The statistically significant variables from the univariate analysis were introduced into the logistic multivariate regression analysis and the results revealed that low gestational age, low birth weight, IUGR, respiratory distress syndrome, and necrotizing enterocolitis were independent risk factors for EUGR. The results are shown in www.growthcalculator.org is recommended to assess weight gain. It provides an accurate graphic display of the current weight percentile, target weight and its deviation. Fenton 2013 charts may be an alternative to monitor linear and head growth while in the neonatal unit (Preterm infants account for the highest percentage of inpatients in the NICU in our hospital. In this hospital, in accordance with national trends in the national neonatal specialty, the ability to treat preterm infants has improved rapidly in recent years, and many very preterm infants and infants with very low birth weight survive. However, there are more complications in preterm than in full-term infants, most notably the high incidence of EUGR , 11. Thetal unit  (Figure tal unit . When astal unit . This suIt was also found in this study that the prenatal factors related to EUGR in preterm infants were gestational hypertension and IUGR. Complicated IUGR was also found to be an independent risk factor for EUGR. This supports the results of Cai Yueju and Lee et al. , 16. AmoThe present study suggested that low gestational age and low birth weight are independent risk factors for EUGR on discharge. Preterm infants with a low gestational age still have inadequate nutritional status after large quantities of nutritional intake. This results in a significant decrease in weight, a long time to return to the birth weight, and slow weight gain, all of which lead to a long stay in hospital and a greater probability of EUGR . PretermIn summary, to reduce the incidence of EUGR in preterm infants, the focus should be on preterm infants with a low gestational age and a very low birth weight. Clinical management must focus on nutritional supply, which includes starting breastfeeding as soon as possible in combination with active parenteral nutritional support, actively preventing complications, and decreasing the duration of invasive respiratory support, with the aim of closing the gap in extrauterine growth and development.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by Ethics Committee of The First Affiliated Hospital of Xinjiang Medical University. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.TZ and H-MF: conception and design of the research and writing of the manuscript. TZ and BC: acquisition of data. H-MF: analysis and interpretation of the data. Y-PZ: statistical analysis. Y-PZ and BC: critical revision of the manuscript for intellectual content. All authors contributed to the article and approved the submitted version.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.