For preterm birth, mean serum concentration for selenium was 79.7, SD 21.6 μg/L; for copper was 2.61, SD 0.57 mg/L; and for zinc was 0.81, SD 0.20 mg/L compared to that for term births: selenium , copper , and zinc , respectively. In an adjusted analysis, every unit increase in maternal selenium concentrations gave increased odds of being a case OR 1.01 , p = 0.234; copper OR 1.62 , p = 0.184; zinc OR 6.88 , p = 0.032. Results show that there was no deficiency of selenium and zinc and there were high serum concentrations of copper in pregnancy. Preterm birth was associated with higher maternal serum concentrations of copper and zinc.Preterm birth is delivery before 37 completed weeks. A study was conducted to evaluate the association of maternal serum concentrations of selenium, copper, and zinc and preterm birth. There were 181 women in this nested case-control study, 90/181 (49.7%) term and 91/181 (50.3%) preterm pregnant women. The overall mean serum concentration of selenium was 77.0, SD 19.4  Preterm birth occurs before 37 completed weeks 259 days) after the first day of the last menstrual period preceding the pregnancy . Globall59 days aPreterm birth is a condition with many pathological processes and no precise mechanism. A common pathway involving a cellular apoptosis-transmitting inflammatory signal, senescent placental cells, and its changes in the placental membrane was hypothesised to stimulate parturition both term and preterm . This coMicronutrients, though required in minute quantities, are necessary inorganic constituents of human health. Their concentration status could lead to adverse pregnancy outcomes. Selenium is integrated into proteins to make selenoproteins which include glutathione peroxidase, thioredoxin reductases, and selenoprotein-P . ReducedHaematological concentrations of micronutrients are influenced by diet, lifestyle, and environmental conditions. Whether maternal concentrations of selenium, copper, and zinc during pregnancy have an effect on preterm birth in sub-Saharan Africa needs to be further determined. Subsequently, this study was conducted to evaluate the status of selenium, copper, and zinc in pregnancy and whether their concentrations are different between term and preterm pregnancies in a Malawian population. The knowledge gained on the exact role these micronutrients play in pregnancy would assist in improving nutrition in pregnancy to reduce the incidence of pregnancy complications specifically preterm birth.This nested case control study was conducted between June 2016 and March 2017 at Kamuzu Central Hospital and Bwaila Hospital, tertiary and general hospitals, respectively. The two hospitals are public and government funded and both located within the city of Lilongwe, the capital of Malawi in the central region. Spontaneous preterm birth patients within the district can be managed at either hospital. The early preterm births (gestation of <34 weeks) are referred to Kamuzu Central Hospital because of the availability of neonatal services while the late preterm births (>34–<37weeks) are managed at Bwaila Hospital. Therefore, the two hospitals were chosen in order to capture both early and late spontaneous preterm births. Our main outcome was to determine the concentrations of selenium, copper, and zinc in term and spontaneous preterm births. The secondary outcome was to determine the association of spontaneous preterm birth and maternal serum concentrations of selenium, copper, and zinc.The target populations were all pregnant women presenting with spontaneous preterm birth at these sites. Gestational age was based on prior-dating ultrasound. For women coming without ultrasound-dated gestation, ultrasound was done at presentation prior to recruitment, and a Ballard score was done after delivery to exclude small for gestation age babies . The casSoon after the delivery process, the trained midwife proceeded to withdraw 5 mL of venous blood using a regular vacutainer technique into a royal blue top vacutainer tube (lot no. BD368380). The blood samples were immediately transported to a Baylor project laboratory within the hospital premises where centrifugation at 3000 g for 10 minutes was done. Serum was transferred into a screw-top vial and stored in the freezer at -80°C. Metal-free vessels were used throughout the process. When the required number of specimens was reached, the serum samples were shipped in the frozen state to the University Hospital of North Norway (UNN), Tromsø, Norway, for chemical analysis.A structured questionnaire was administered in the vernacular language (Chichewa)—a local language which study participants were conversant with—by the trained midwife. Quantitative data were captured on demographic characteristics of the participants: age, gravidity, marital status, educational level, and previous history of preterm birth. Information on antenatal care package including gestation age, serology test results for human immunodeficiency virus (HIV), and syphilis was collected from the patient's health passport. Self-reported information on herbal medicine ingestion defined by the World Health Organization (WHO) as “any medicinal product based on herbs, herbal materials, herbal preparations and finished products that contain as active ingredients parts of plants, other than plant materials, or combinations thereof” and a bedside laboratory test of haemoglobin using HemoCue were documented in the questionnaire.μL serum was diluted with a solution consisting of Milli-Q water  with 0.08% v/v Triton X-100 , 10% v/v ammonium , isopropanol , and 0.25 μg/L gold  and mixed in the bioshaker for 2 minutes. The instrumental analysis was performed on a NEXION 300D ICP-MS system  equipped with an ESI-Fast SC2DX auto sampler. An internal standard solution was introduced online via a T-piece containing 20 μg/L rhodium . For the MS analysis, the kinetic-energy-discrimination (KED) mode was applied. Measurements were conducted in triplicates. All concentrations were obtained by the internal standard method together with a blank subtraction using the Nexion software (version 1.5). The trace element concentrations within the samples were determined based on a 3-point external matrix matched calibration curve using the ClinCal serum calibration material from Recipe , which was diluted together with each batch of 32 samples by 1 : 100, 1 : 40, and 1 : 20. For quality assurance and quality control, two sets of ClinCheck control materials L-1 and L-2 from Recipe  and Seronorm L-1 and L-2 , as well as 4 Milli-Q water blanks, were run together with each batch of samples. Diluent blanks for control of the background and instrumental carryover were also included. Additionally, the Laboratory for Analysis of Environmental Pollutants, UNN, Norway, participates successfully in the international quality control programme: Quebec Multielement External Quality Assessment Scheme (QMEQAS) organized by the Centre de toxicologie du Quebec, Quebec, Canada.The chemical analyses were conducted at the Norwegian laboratory in Tromsø, using inductively coupled plasma mass spectrometry (ICP-MS) for analysis of the trace elements selenium (Se), copper (Cu), and zinc (Zn). For sample preparation, an automated liquid handler Tecan Freedom Evo 200  equipped with an 8-channel liquid handler arm (LiHa) for conductive disposable tips, a robotic manipulator arm (RoMa) for transport of microtiter plates, and a shaker  were used. 100 The study was reviewed and approved by the College of Medicine Research Committee (COMREC) P.05/15/1738. In addition, the Directors of Kamuzu Central and Bwaila Hospitals approved that the study can take place at their respective hospitals. Written informed consent was obtained from all study participants.Quantitative data from the questionnaires and laboratory reports were entered into IBM SPSS version 14.0 software by a data entry clerk and verified by the principal investigator. Data cleaning was performed involving a range of consistency checks, and all outliers were rectified.Data analysis was done using R . A binary variable was generated for the primary outcome based on gestation: 26–<37 weeks (preterm birth as cases) coded as 1 and ≥37–41 weeks (term birth as controls) as 0. One-way frequencies were computed for categorical variables while mean and standard deviation (SD) or median and interquartile range (IQR) were computed for continuous variables that were normally distributed or skewed, respectively. Log transformation was done where necessary for positively skewed continuous variables.p values from all tests of less than 0.05 were considered statistically significant. Logistic regression models were fitted, addressing each covariate with the outcome variable. Variables were included in the multiple logistic regression model based on the best fit regression model from stepwise regression analysis using the R software based on the observed association in the unadjusted analysis at the p < 0.05 test level of significance. Odds ratios and associated 95% confidence intervals (CI) were computed from the logistic regression models.Two-way associations between independent variables and the outcome variable of the preterm birth were investigated using Pearson's correlation for continuous independent variables and the chi-squared test for categorical variables. There were 181 mothers with an overall mean maternal age of 25.2 years (SD: 6.1) and 181 babies participating in the present study . The majp = 0.011, for women who had preterm births. Women who had spontaneous preterm births were more likely to have low gravidity than those who had a term birth (p = 0.048). Use of herbal medications was significantly higher among women with spontaneous preterm birth  than among those with term birth , p = 0.035. Syphilis was significantly associated with preterm birth, p = 048.There were 90/181 (49.7%) term and 91/181 (50.3%) spontaneous preterm births in the present study . Women dμg/L; SD 19.4 μg/L) and zinc  were within the normal laboratory reference values of 47-142 μg/L and 0.59-1.11 mg/L, respectively. The overall mean concentration value of copper  was above normal laboratory reference value (0.76-1.59 mg/L). All concentrations of trace elements were higher among the cases compared to the controls. Selenium concentrations were marginally increased for women with spontaneous preterm birth  compared to those with term births , p = 0.058. Copper and zinc concentrations were significantly higher for women with spontaneous preterm births than for those with term births with a mean of 2.61 mg/L (SD: 0.57 mg/L) vs. 2.39 mg/L (SD: 0.43 mg/L), p = 0.004, for copper and a mean of 0.81 mg/L (SD: 0.20 mg/L) vs. 0.73 mg/L (SD: 0.19 mg/L), p = 0.006, for zinc.Two-way analyses were also investigated for a number of trace elements . The ovep = 0.234). Although there was an association between a unit increase in copper and the increased odds of being a spontaneous preterm birth in the unadjusted analysis , this association was no longer significant in the adjusted analysis, OR 1.62 . However, there was an association between a unit increase in zinc and an increased risk for being a preterm birth in both unadjusted, OR 8.56 , and adjusted analyses, OR6.88 . Women who had taken herbal medication had increased odds of having a spontaneous preterm birth compared to those who did not take the herbal medication; however this was not significant, OR2.44 .In an adjusted analysis, similar results to those for the unadjusted analysis were observed for the metals . There wThe current study found that the overall serum concentrations for selenium and zinc were within normal reference values while that of copper was above normal reference values. Concentrations of selenium, copper, and zinc were higher in women who had spontaneous preterm birth compared to those who delivered at term, with copper and zinc concentrations being significant. After adjusting for other variables, increase in zinc concentration was associated with increased risk of spontaneous preterm birth.p < 0001 [Very little information was found in the literature on the maternal serum concentrations of the trace elements selenium, copper, and zinc in pregnancy and their associations with spontaneous preterm birth in the African region. Comparing with researches from other regions, some studies have found maternal concentrations of these trace elements to be associated with preterm birth, while others have reported no associations , 35–39. p < 0001 . HoweverThis study finding of increased maternal serum concentrations of selenium, copper, and zinc in women with preterm birth is not surprising. As pregnancy progresses, the fetus takes up selenium, copper, and zinc with maximum concentrations reached at the end of the third trimester when the fetal liver is mature enough to store these trace elements –42. SponThe mechanism for the association of maternal serum concentration and increased risk of preterm birth could be explained due to the dual function of zinc, as an antioxidant as well as a prooxidant, and the cytotoxicity of copper. The placenta is the main source for ROS . NonetheThe finding of maternal serum copper concentrations above the normal limit in both preterm and term deliveries also needs further investigation. Considering that excess copper ingestion has negative health effects on humans, the study recommends looking at the social habits, diet, and water as sources of exposure for excess copper ingestion.Women who had taken herbal medication had almost 2.5 times increased risk of having spontaneous preterm birth compared to those who did not. It is possible that herbal medicine increased the intake of zinc and copper ion in women which resulted in increased production of ROS. Further research is required to establish this link.Some limitations should be considered when interpreting these study results. Firstly, the sample size was relatively small which reduced the power to 34% for detecting the effect. Recruitment was also only done when the research assistants were on duty, and this may have affected the randomisation. Increased sample size and purposely recruited research assistants working in shifts to recruit day and night for the seven days of the week should be considered for future studies. Secondly, the study population diet information was not available; as such, it was difficult to ascertain the daily dietary intake of these trace elements. Thirdly, data on body mass index (BMI) was not captured in this study. This made the findings of this study not comparable with the findings by van den Broek et al. which noted the association of very low BMI with preterm birth . IrrespeNo selenium, copper, or zinc micronutrient deficiencies were found in the study population. Preterm births were associated with higher maternal serum concentrations of the micronutrients copper and zinc which play a role in prooxidation and antioxidation as well as an anti-inflammatory mechanism. Copper maternal serum concentrations were above the upper normal limit in both term and preterm birth groups. As such, further assessments are recommended to determine the excess source of copper. This study is a first assessment of these trace elements in mothers of term and preterm pregnancies in Malawian women. Further assessments in first and second trimesters with dietary information are recommended to establish local reference values as well as causal relationship.


BackgroundEvidence suggests that neonates born at 34-36 weeks should not be considered full-term neonates, given the magnitude of morbidities they experience compared with term infants. Neonates born at 34 to 36 weeks are at increased risk for early illness such as hypoglycemia and hyperbilirubinemia compared to term infants.ObjectiveThis study's objective was to determine the frequency of immediate neonatal complications  in late preterm and term neonates.Subjects and methodsA serial descriptive case study was conducted at the private tertiary care hospital. Random samplings were taken, and the sample size was calculated on Epi Info software . All the eligible samples were taken into confidence following approval by the College of Physicians and Surgeons Pakistan's institutional review board. A structured questionnaire was used in which demographic information of the patient was collected, and all neonates were closely observed for early targeted morbidities ResultsA total of 215 neonates were born during the study period, of whom 108 (50.2%) were term babies and 107 (49.8%) late preterm babies. There were 122 (56.7%) male infants and 93 (43.3%) female infants. Jaundice was observed in 6.5% (n=7) of term neonates and 22.4% (n=24) of late preterm neonates (p<0.0). Similarly, hypoglycemia was observed in only 4.6% (n=5) of term neonates and 15.9% (n=17) of late preterm neonates (p<0.01).ConclusionThere is a significant association between gestational age and immediate neonatal complications of jaundice and hypoglycemia. Compared with term neonates, late preterm neonates are at a higher risk of neonatal jaundice and hypoglycemia. Gender and mode of delivery did not correlate to complications rate. Late preterm births account for 74% of premature births and 10% of all live births . The incNeonatal jaundice is also a well-known immediate complication in newborn babies. Approximately 55% of late preterm and 24.8% of term neonates develop jaundice (p<0.001) .To our knowledge, there is no study done in Pakistan on the frequency of hypoglycemia and neonatal jaundice in late preterm and term neonates. Therefore, the goal of this study was to determine the frequency of immediate neonatal complications  in neonates born in Pakistan at 34 to 40 weeks plus six days compared to those born late preterm  and term .We conducted a descriptive, serial case study at the private tertiary care hospital. We used nonprobability consecutive samplings, and the sample size was calculated on Epi Info software  by using a prevalence of 5.3% and the estimated sample size of 215 neonates with a bound of error of 3% with 95% confidence interval [After approval from the Ethical Review Committee, all subjects fulfilling the eligibility criteria were enrolled after providing informed verbal and written consent from the mother or father. Neonates born late preterm and term were monitored for up to 72 hours. The patient data confidentiality was maintained by assigning a number for each patient's data, electronic data were password-protected, and data on hard copies were kept in locked storage. All study data were stored for five years. After completion of the study, results can be shared with the patient's parents upon request. The primary investigator did not have control over the management of the study patients.Data were collected on a proforma and included necessary demographic information. Gestational age, birth weight, gender, mode of delivery, and complications such as hypoglycemia and neonatal jaundice were recorded. Data were analyzed using IBM SPSS Statistics for Windows, Version 20.0 . Descriptive statistics were analyzed for demographic, gestational age, birth weight, sex, mode of delivery, neonatal hypoglycemia, and neonatal jaundice. Continuous variables were presented as mean ± standard deviation. Frequency and percentages were calculated for sex, mode of delivery, gestational age category, hypoglycemia, and neonatal hyperbilirubinemia requiring phototherapy. Complications were evaluated for both term and late preterm neonates using the Chi-square test. A p-value of <0.05 was considered significant. Confounders had been restricted in eligibility criteria. All possible confounders such as clinical sepsis and metabolic disorders were filtered at recruitment. However, if any complications occur in recruited infants, those cases were excluded from the analysis.Stratification to gestational age, weight at birth, sex of the neonate, and mode of delivery was done. Post-stratification chi-square test was applied, and p <0.05 was considered significant.A total of 215 neonates were born during the study period, of whom 108 (50.2%) were term babies and 107 (49.8%) late preterm babies Figure .One hundred fifty neonates (69.8%) were delivered by cesarean section while 65 30.2%) were delivered by spontaneous vaginal delivery  of term neonates and 22.4% (n=24) of late preterm neonates (p<0.01). Similarly, hypoglycemia was observed in only 4.6% (n=5) of term neonates and 15.9% (n=17) of late preterm neonates (p<0.01).We found no sex predominance for any complications (p>0.05), nor did we find an association between complications and mode of delivery (p>0.05). However, complications declined with increased birth weight, but the association was not statistically significant  are at higher risk for early morbidities. Several important differences in clinical outcomes appear when comparing the late-term neonates' hospital courses with term neonates. Despite their appropriate size and favorable Apgar scores, late preterm infants had significant complications such as jaundice and hypoglycemia when compared with term neonates. A study conducted in the Division of Neonatology at Hacettepe University in Turkey from 2001 and 2002 evaluated 365 neonates (219 term and 146 late preterm neonates) for jaundice . Twenty-Jaiswal et al. reported that 70.8% of late preterm neonates and 29.1% of term neonates had at least one neonatal morbidity like neonatal jaundice, hypoglycemia, respiratory morbidities, and sepsis that may need observation in hospital . They obWang et al. noted significant differences in the rate of hypoglycemia for the term 5.3%) and late preterm (15.6%) infants (p=0.028) [% and latOur study was limited in that we were unable to assess feeding difficulty and breastfeeding status due to hospital policy to supplement feeding to all neonates. Also, the study did not address other early complications and long-term complications. Finally, the study used a relatively short monitoring period, and we did not conduct a long-term follow-up to monitor outcomes.There is a significant association between gestational age and immediate neonatal complications of jaundice and hypoglycemia. Compared with term neonates, late preterm neonates are at a higher risk of neonatal jaundice and hypoglycemia, and gender and mode of delivery did not correlate to complications rate. Therefore, to prevent early neonatal jaundice and hypoglycemia, efforts should encourage proper gestation age, good birth weight, and proper antenatal care to reduce neonatal mortality and morbidity. Strong communication between patients, hospital staff, and obstetricians can help ensure the proper time of induction of labor and Caesarean section and improve care at birth and afterward for optimal outcomes for all neonates.


To investigate the effect of pathological staging of chorioamnionitis (CA) on complications in preterm infants;A single-center, retrospective study was conducted to choose singleton preterm infants  from the Department of Obstetrics and Gynecology in our hospital from December 2016 to December 2017. The basic data and placental pathological results were retrospectively collected. According to the placental pathological results of whether inflammation infiltrating amnion, CA 0/I phase was classified into non-amnionitis group, CA II/III phase was classified into amnionitis group, the incidence of common complications in preterm infants was compared. Further, logistic regression was used to analyze the effects of amnionitis on complications after being adjusted to gestational age, birth weight and thrombocytopenia.P < 0.05). The incidence of intraventricular hemorrhage (IVH) in amnionitis group (37.14%) was significantly higher than that in non-amnionitis group (13.98%) (P = 0.002), and the risk of IVH was significantly increased by amnionitis ; after correction of gestational age, birth weight and thrombocytopenia, the risk of IVH was still significantly increased . And the late-onset IVH was more common (P = 0.009).A total of 221 preterm infants were enrolled, including 186 cases in non-amnionitis group and 35 cases in amnionitis group. The gestational age of amnionitis group (32.00 ± 2.71 weeks) was significantly lower than non-amnionitis group (34.14 ± 2.06 weeks), birth weight (1.93 ± 0.64 kg) was significantly lower than that of non-amnionitis group (2.26 ± 0.58 kg), and the hospital stay in amnionitis group was significantly longer (25.71 ± 19.23 days), all of the difference above was statistically significant(Amnionitis leads to a significant reduction in gestational age and birth weight in preterm infants, and it is an independent risk factor for IVH. Chorioamnionitis, an inflammatory status of the intrauterine or fetal membrane, were divided into histological chorioamnionitis and clinical chorioamnionitis . It is wIn summary, Chorioamnionitis is associated with adverse outcomes in preterm birth. Although, the effect of chorioamnionitis on complications in preterm infants has been widely studied, the pathological staging on them has been rarely published. Therefore, this study aimed to investigate the effect of pathological staging of chorioamnionitis on complications in preterm infants.A single-center, retrospective study was conducted. Singleton infants  who were given birth in our hospital from December 2016 to December 2017 were selected as study population, cases of genetic metabolic diseases, nervous system malformations, and stillbirth were eliminated. The inclusion criteria for sending placenta for pathology investigation in our center are one of the following situations: 1. Mother with gestational diabetes or preeclampsia; 2. Mother had fever a week before or during delivery; 3. Macroscopic abnormity during delivery. In addition, informed consent for pathology analysis should be obtained. The protocol was approved by Ethics Committee of Guangdong Women and Children’s Hospital (201801053).After delivery, the whole placenta, fetal membrane and umbilical cord were fixed in 4% formaldehyde for 48 h, the quality of the placenta, the length and the attachment of umbilical cord, the number of blood vessels were evaluated, and the placenta was cut at intervals of 1 cm. All specimens were embedded in paraffin, sectioned, and routine Hematoxylin-Eosin Staining (HE staining).The criteria for histological chorioamnionitis: Stage 0 (CA0): Normal placenta; Stage 1 (CAI): acute inflammation of the chorioamniotic membranes, in which neutrophilic infiltration is limited to the chorion; Stage 2 (CAII): acute inflammation of the chorioamniotic membranes, showing neutrophilic migration into the amniotic connective tissue (asterisk); Stage 3 (CAIII): acute inflammation of the chorioamniotic membranes, whose characteristic is the amnion epithelial necrosis (arrows) .According to the placental pathological results of whether inflammation infiltrating amnion, CA 0/I phase was classified into non-amnionitis group, CA II/III phase was classified into amnionitis group.The gestational age , Apgar score, birth weight, blood routine, C-reactive protein, procalcitonin and blood culture results of each premature infant were collected, and the disease of each system during hospitalization was observed. The relevant complications were as follows :Intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL) are common complications in preterm infants, which can be detected by serial head ultrasound and MRI, the first is recommended between 5 and 8 days, 21 and 28 days, between 34 and 36 weeks of corrected gestational age . Those wThe sepsis in this study requires positive clinical or laboratory screen and positive culture. Early-onset sepsis (EOS) occurred during the first 72 h of life, Late-onset sepsis (LOS) refers to sepsis that occurred between day of 4 and 120 .Bronchopulmonary dysplasia (BPD) is defined as oxygen dependency at 36 weeks of corrected gestational age, the main causes including damage of alveolar, vascular structural and stagnation of alveolarization.NEC is a syndrome manifested as abdominal distension, vomiting, diarrhea and Bloody stools, severe cases even develop shock and multiple systemic organ failure, can be diagnosed by abdominal piece, usually characterized by gas accumulation in the intestinal wall.Retinopathy of prematurity (ROP) refers to retinal vasoconstriction, obstruction and retinal vascular hypoxia, leading to a large number of angiogenic factors, stimulating neovascularization form.9/L in all healthy newborn infants, regardless of gestational age [Neonatal thrombocytopenia: The platelet count ≤150*10onal age .2 and t tests as appropriate. Variables with statistical significance after univariate analysis and factors which could affect neonatal complications were further adjusted by multivariate logistic regression, the effect size is expressed in OR and 95% CI. Significance was accepted at p < 0.05. All analyses were performed by using SPSS version 19.0 software.One Sample Kolmogorov—Smirnov test was performed for normality of distributions, and the normal distribution data was represented as the mean ± standard deviation (SD). Dichotomous data was expressed by the frequency and relevant percentage. Maternal and neonates’ characteristics were compared using χP < 0.05). However, there were no significant difference in maternal age, placental weight, use of antenatal glucocorticoids, premature rupture of membranes, mode of delivery, gender, thrombocytopenia, and Apgar scores (P > 0.05).  was significantly lower than non-amnionitis group (34.14 ± 2.06 weeks), birth weight (1.93 ± 0.64 kg) was significantly lower than that of non-amnionitis group (2.26 ± 0.58 kg), and the hospital stay in amnionitis group (25.71 ± 19.23 days) was significantly longer than that in non-amnionitis group (18.84 ± 16.80 days), the difference was statistically significant; After correction of gestational age, birth weight and thrombocytopenia-the three factor that are regarded to affect the IVH incidence, the risk of IVH was still significantly increased , and it more likely to cause late-onset IVH (P = 0.009) (as shown as in Table P > 0.05) (as shown as in Table P < 0.05).Among the 221 patients, the incidence of intraventricular hemorrhage (IVH) in amnionitis group 37.14%) was significantly higher than that in non-amnionitis group (13.98%), the difference was statistically significant , and multi-organ fetal involvement , 18. In The study has three strengths. First, we divided the studying population into non-amnionitis and amnionitis groups, the classification was not reported previously and it could highlight the effect of severe intrauterine inflammation on birth outcomes and complications of preterm compared with other previous studies. The placental tissue inflammation continues to progress and the intensity of the inflammation increases, which can cause severe amniotic inflammation and fetal inflammatory response syndrome, it is believed that the latter is closely related to the occurrence of premature delivery and fetal complications , 20. SecP<0.05), which was the same with Lou. Chorioamnionitis leads to the release of vasoactive inflammatory cytokines which can mediate blood–brain barrier alterations, intra-vascular cells adhesion, coagulation, and thrombosis, conversely, this can lead to endothelial damage. If the severity of systemic and local hemodynamic changes increased in infants accompanied by cerebral endothelial damage, the enhanced late neonatal inflammatory response syndrome leads to the development of late onset IVH [The placenta functions are important for development of fetal multiple organs and systems. Placental dysfunction would affect the fetus, resulting in fetal growth restriction, premature and neurodevelopmental abnormalities , 23. A snset IVH .Earlier studies have focused mainly on the respiratory and neurological outcomes, chorioamnionitis have more recently been described in several other organs and systems. Watterberg et al. were the first to show that exposure to placental inflammation decreased the risk of RDS, but a subsequent increase in chronic lung injury (BPD) . But a fAntenatal factors are also important to chorioamnionitis and neonatal morbidity. Antenatal steroids were reported to reduce negative effects of CA, such as IVH and RDS, as well as mortality by suppression of inflammation . In thisThis study revealed the adverse birth outcomes caused by severe intrauterine inflammation exposure, which could help to highlight the importance of placental pathology examinations, therefore guiding clinical management and reducing the devastating burden of adverse birth outcomes.In this study, there is a lack of the underlying mechanisms of stage of chorioamnionitis on neonatal adverse outcomes. For example, how the chemotactic signals in the amniotic cavity induced the amniotic inflammation, the relationship of FIRS and IVH. Therefore, additional preclinical studies are needed to explore these problems, and the number of included amnionitis cases needs to be enlarged.Histological chorioamnionitis is closed to various complications of premature infants, especially intraventricular hemorrhage IVH associated with a fetal inflammatory response syndrome . Clinica


Almost all cases of renal hydatid cysts need surgical intervention for treatment. We report a case of isolated renal hydatid cyst treated successfully only with medical therapy.This case is a 79-year-old veterinarian presented with right flank pain, hydatiduria and positive echinococcus granulosus serology. A 70*50 mm cyst with daughter cysts in mid-portion of right kidney on presentation was changed into a 60*40 mm cyst without daughter cysts at last follow-up. Due to patient’s refusal of surgery, our patient received medical treatment including praziquantel and albendazole. After completion of first round of treatment, recurrence occurred and the same treatment was repeated. At last, the cyst became inactive and calcified with negative serology and no clinical symptoms under medical treatment.The treatment of choice in renal hydatid cyst is surgery; although there are some reports about the efficacy of medical treatments for hydatid cysts but lower rates of recurrence and higher efficacy put surgery in a superior position compared to medical approaches. Our case showed relative success of medical treatment, despite the presence of a large multilocular renal involvement. Thus, medical therapy without surgery can be considered in very particular cases with isolated renal hydatid cysts. Hydatid cysts are caused by echinococcus species. Echinococcus is a flat worm with three evolutionary stages during its life cycle. The structure of this cyst is usually composed of three components. A component is a “pericyst” which is produced by the inflammatory tissues of the host. The other two elements are “exocysts” and “endocysts” , 2. IranRisk factors of development of hydatid cysts include direct contact with animals such as sheep and dogs, as well as geographic region and consumption of contaminated water and raw vegetables. This infection can affect different organs of the body. The most common involved parts of the body are liver (~ 50–70% of cases) and lung . InvolveRenal involvement in hydatid cysts can be symptomatic or asymptomatic. The diagnosis is based on history, imaging, pathological and serological findings. The enzyme-linked immunosorbent assay (ELISA) test has an 80% sensitivity at initial diagnosis for hydatid cyst . LaboratOn imaging evaluations, a thin calcification rim can suggest hydatid cyst. In ultrasound examinations, the presence of daughter cysts can be a key for diagnosis of hydatid cyst but CT scans are more sensitive for detection of hydatid cysts .Treatment of choice for renal hydatid cyst is surgical removal. Although medical therapy has been reported in treatment of a few cases but high rates of recurrence with medical therapy prompt the need for longer follow-up duration in patients . SuccessA 79-year-old male retired veteranarian from Semnan province, living in Tehran, was referred to a non-academic private nephrology clinic due to slightly elevated creatinine levels and flank pain at 2012. He had hypertension and coronary artery stenting. He was under treatment with aspirin and metoprolol.In 2005, he had presented with generalized itching and a skin lesion on his left leg, which was non-significant on biopsy and resolved without any special treatment. He was totally asymptomatic until 2012, when he was admitted at a private clinic hospital in Tehran, for intermittent right flank pain without urinary symptoms.Ultrasonography revealed cysts in the kidneys. Four cysts with the largest diameter of < 3 cm and one cyst of 36*49 mm size with multiple septa in right kidney were visualizied. There were four cortical cysts in the left kidney with a maximum diameter of 28 mm. The patient had been discharged with the wrong diagnosis of bilateral simple cysts and was advised for continuation of follow-up.After 3 years, the patient presented at our hospital for the first time with acute-onset severe right flank pain radiating to groin which lasted for 6 h. He also complained of nausea, vomiting, hematuria and passage of small, white, balloon-like, and grape-size structures in urine. Laboratory findings were listed in Table The kidneys were examined by ultrasonography and there were some cortical cysts in the left kidney with a maximal diameter of 33 mm and fine calcified septa in one cyst. There was also a solid mass containing small cystic regions with the size of 60*74 mm in lower pole of right kidney with external extension and no vascular flow on color Doppler ultrasonography. The bladder was reported to be normal. Since a complicated cyst was suspected, further investigations were performed. In CT scan, a 70*50 mm multiloculated cystic lesion with multiple non- enhancing internal septa resembeling walls of doughter cysts in mid portion of right kidney was reported Figs.  and 2.FThe pathological assessment of balloon-like structures in urine revealed that they were highly suggestive of hydatid cyst. Pathological evaluation showed a laminated cyst wall, partially lined up by a layer of germinal cells. In serological assessment, there were weakly positive results in two laboratory assays by ELISA with a five-month interval.Due to the diagnosis of active hydatid cyst, surgery was recommended but the patient refused surgical treatment. The reason for refusal was the patients’ severe fear of undergoing surgery. Then praziquantel 800 mg three times a day and albendazole 400 mg three times a day were initiated for the patient. Follow-up was recommended.Fourteen months later, while under treatment, he was presented with hydatiduria. Pathology again confirmed the diagnosis of hydatid cyst. With recurrence of hydatiduria, surgical treatment was offered to the patient again, but he refused and medical treatment was continued. Around 12 months later, the hydatid cyst serology turned negative and after 3 months, he was recommended to stop the medications. The concurrent complete blood count, liver function tests and urinalysis were normal.Nine months after cessation of medical treatment, ultrasonography showed a hetero-echo exophytic mass in the right kidney with a size of 58*42 mm. There were cortical cysts in the left kidney in the middle-lower region with the maximum diameter of 26 mm. The bladder wall was thickened. In CT scan a 60*44*42 mm cystic lesion without obvious internal septa and no enhancement was seen. Calcification in the cyst was observed. Follow-up sonography at the last visit 3 years after discontinuation of medications, demonstrated a 60*40*45 solid-appearance lesion without daughter cyst in mid portion of the right kidney (Fig. Hydatid disease is a parasitic infection, which can be transmitted from animals to humans. The disease is prevalent all over the world and some areas such as Iran are considered endemic for this disease, as traditional animal husbandry is prevalent in Iran .Other countries such as Greece, Australia, and Turkey  are invoEarly diagnosis and treatment of the disease are the key steps in preventing complications. The patient may be asymptomatic for many years or present with flank pain, hematuria and hydatiduria. Sometimes it can manifest as a cortical cyst. According to Gharbi sonographic classification of hydatid cysts, type I is a simple cyst without internal architecture . Thus, cPatient first presented at 2012 with flank pain. Back then, he was diagnosed with simple cyst labelled as Bosniak class I renal cyst. If more careful history was taken, more advanced evaluations such as serology, repeat ultrasonography and CT scan could be ordered and the delay in diagnosis and consequent complications could be prevented. History of the patients can give the clinicians valuable clues for the diagnosis. As in our case, being a veterinarian increases the likelihood of presence of hydatid cysts. In patients with high-exposure backgrounds, additional evaluations could prompt the appropriate diagnosis .If the cyst invades the urinary tract, it causes hydatiduria, which is a pathogenomonic finding for hydatid cyst. Hydatiduria occurs in 10–20% of cases, which is usually microscopic. Gross passage is relatively uncommon, although it has high diagnostic value . EosinopSimple abdominal radiography reveals nonspecific findings which are mostly not useful for establishing the exact diagnosis. Ultrasound performed by an expert radiologist who can detect daughter cysts and other features of hydatid cyst can be useful but in majority of cases, these findings are missed on ultrasonography. CT-scan is the modality of choice for imaging in hydatid cyst which has high diagnostic yield as high as 98% specificity .In renal hydatid cysts, parenchymal preservation surgeries such as cyst removal or partial nephrectomy are the main treatment options. Nephrectomy is also indicated in cases where the cyst is ruptured into the cavity and is complicated by a kidney infection ultimately leading to sequels in kidney . HoweverRamteke et al. reported a 50-year-old female patient with 6-month history of lower abdominal pain presenting with hematuria. Hematuria as the presenting complaint was the same as our case but the difference is the location of pain. In this case abdominal pain was reported but in our case, flank pain was notable. She had right renal hydatid cyst on imaging which was treated with right nephrectomy and albendazole treatment regimen before and after operation . Kumar eSurgery is the treatment of choice in renal hydatid cyst. According to cyst size, location and staff expertise, it could be managed by total or radical nephrectomy. In some cases, conservative surgical excision and drainage are also recommended; although medical treatment is needed to prevent dishydatosis as well as spillage. The medical treatment usually includes albendazole before and after surgery .In very rare studies, only medical therapy has been used to treat renal hydatid cysts- particularly in younger patients . In the According to the case we reported, medical therapy with the combination of albendazole and praziquantel can be used with comparable outcomes for patients who can not undergo surgery or refuse the surgical procedure. In these cases closer monitoring and follow-up must be conducted due to higher probability of recurrence of cyst.


The majority of studies linking exposure to metals with certain health outcomes focus on known toxic metals. Alternatively, this study assesses the extent to which exposure to a wider range of metals during gestation is associated with childhood morbidity.We analyzed the concentrations of 25 metals found in urine samples of 111 pregnant women of Arab-Bedouin origin collected prior to birth. In addition, we collected medical records on their offspring for six years following birth, including every interaction with HMOs, local hospitals, and pharmacies.The main types of morbidities diagnosed and treated during this period were preterm births, malformations, asthma-like morbidity, cardiovascular and behavioral problems, and obesity. Multivariable analysis showed that offspring born before term were more likely to have been exposed to elevated maternal concentrations of zinc, thallium, aluminum, manganese, and uranium, all with adjusted relative risk above 1.40 for an increase by each quintile. Likewise, children with asthma had been exposed to higher levels of magnesium, strontium, and barium at gestation, while behavioral outcomes were associated with elevated biometals, i.e., sodium, magnesium, calcium, selenium, and zinc, as well as higher levels of lithium, cobalt, nickel, strontium, cadmium, vanadium, arsenic, and molybdenum. A heatmap of adjusted relative risk estimates indicates the considerable implications that exposure to metals may have for preterm birth and developmental outcomes.The current study shows that perinatal exposure to metals is adversely associated with pediatric morbidity. Further such analyses on additional samples are warranted.The online version contains supplementary material available at 10.1186/s12199-021-00963-z. Exposure to heavy metals, the majority of which are highly toxic, can result in severe human morbidities. Lead (Pb), arsenic (As), and mercury (Hg) head the list, followed by aluminum (Al), cadmium (Cd), chromium (Cr), nickel (Ni), titanium (Ti), and others, whose presence is not essential to the human body. As a result, exposure to high concentrations is likely to be adversely associated with health outcomes. At the same time, other metals, including calcium (Ca), cobalt (Co), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), molybdenum (Mo), selenium (Se), sodium (Na), and zinc (Zn), are considered essential for human physiology . There iSince toxic metals are known to cross the placenta and blood-brain barrier and deposit in fetal tissues, children are likely to be susceptible to metal exposure early, starting from the time of gestation. For this reason, maternal metal concentration is frequently used as a proxy for that of a fetus when studying health outcomes.congenital defects at birth [Small-for-gestational age (SGA) status at birth has been adversely linked to Cd [preterm birth was reported associated with Cd [Maternal elevated concentrations of Al, As, Cd, Hg, Ni, and Mn have been reported in relation to newborn at birth –7. Smalled to Cd  and As [ed to Cd , 9. Like with Cd , 11 and  with Cd . Neverth with Cd , 14.neurological and cognitive impairment [A recent review by Allen provided an evidence of an association between prenatal Pb exposure and pairment . The finpairment , 17, as pairment , 19, Hg pairment , 21. Howpairment –24. The pairment  as well pairment , and thePulmonary function indices and asthma in children were linked with Pb [elevated blood pressure in 5-year-old children [obesity at the age of five [ with Pb , 28, Mn, with Pb , 30, as  with Pb . Likewischildren  and pren of five .The Bedouin-Arab population of southern Israel is known for elevated rates of childhood morbidity  usually Because of the vulnerability of the Bedouin-Arab community, the extensive monitoring of hazardous exposures, in an attempt to identify and eliminate modifiable factors related to morbidity, is required. In the current analysis, we aim to explore the possible links between maternal exposure to a wide range of heavy metals at gestation with birth outcomes and the health conditions of 5 to 6-year-old offspring.We investigated the subset of a cohort of mothers and their newborns of Bedouin-Arab origin enrolled in our study between Dec 2011 and Mar 2013. Enrollment procedures and characteristics of the study population are described in a previous study . BrieflyIn order to be included in the current analysis, the women had to be the members of “Clalit” health maintenance organization (HMO), 18 years and older, and to have an available urine sample collected prior to birth and the newborns had to survive their birth hospitalization. The membership in Clalit HMO allowed the researchers an access to the subjects’ medical records besides the information in the hospital system. This additional information was especially important for retrieval of pediatric diagnoses for morbidities not requiring hospitalization. Since members of the Clalit HMO represent close to 70% of the local population, this restriction is not expected to affect the generalizability of the study conclusions. In all, 1437 of the initial cohort had Clalit HMO membership.The study hospital (SUMC) is located in Beer-Sheva, a metropolis city in the Negev desert, in southern Israel. This is the only hospital providing tertiary and outpatient services in the Negev region to a population of 1 million residents   was used to assess the metal content of each sample. The list of metals included Na, K, Mg, Ca, Zn, Se, Cu, Li, Co, Ni, Tl, Al, Cr, strontium (Sr), Cd, barium (Ba), beryllium (Be), vanadium (V), Fe, As, molybdenium (Mo), Pb, silver (Ag), Mn, and uranium (U). Testing was performed in a trace metal clean room, a laboratory in the Institute of Earth Sciences at the Hebrew University of Jerusalem. Values that fell below the level of quantification (LOQ) were imputed by LOQ = 0.01 divided by the square root of two . A more We obtained access to all medical records prepared by local hospital and/or HMO personnel. These hospitalization records relied on the admission-transfer-discharge (ATD) database and included details concerning children’s complications and diagnoses during birth, subsequent hospitalizations, and emergency room and outpatient clinic visits. HMO records included visits to primary physicians, specialists’ clinics, and records on all medications purchased for a child through an HMO pharmacy. It should be noted that pharmacies in Israel sell all the chronic and the majority of over-the-counter (OTC) medications, both with a substantial discount when bought with an HMO membership. For that reason, the HMO pharmacy records are expected to almost fully cover the medication purchases. The data platforms listed above represent the comprehensive list of medical records collected for each child in the analysis. Based on these sources, we were able to retrieve the complete information on diagnoses, medications, and types of clinics visited by children during the follow-up.The following categories of morbidities were verified: preterm delivery and small-for-gestational age (SGA), malformations, asthma and cardiovascular morbidity, behavioral/developmental disorders, obesity, and malignancies.preterm delivery as delivery at a gestational age equal to or less than 37.0 weeks [Malformations’ diagnosis in an International Classification of Diseases 9th revision (ICD-9) system is based on the neonatologist’s evaluation shortly following delivery together with diagnoses received throughout a child’s encounters with the medical system, as recorded in the ATD and HMO databases . Concentrations were ranked into quintiles, and their associations with health outcomes were explored visually.Metal concentrations in urine were reported as a geometric means along with a 95% confidence interval (CI) and compared by subjects’ morbidity status using a ratio We adjusted for individual risk factors using a Poisson regression model with a health outcome as a dependent variable and metal concentration in quintiles and other factors as independent parameters. We used the same list of covariates for models exploring associations with all health outcomes, and they included maternal age, parity, newborn gender, and preterm birth. Covariates in the model of preterm birth included only maternal age, parity, and newborn gender. The detailed information on the models is presented in Table SThe point estimates of an association were expressed as relative risk (RR). In order to ensure the robustness of the model inference, we conservatively chose the sandwich estimator approach for standard error calculation. Adjusted point estimates of RR are presented in a heatmap reflecting a potential range of an effect of metals on health outcomes.In view of the explorative nature of this analysis, performed on SAS 9.4 and R software, and a relatively small sample size, we did not correct for multiple comparisons. The code for the main analysis is provided .In all, 111 of women and their 111 newborns had a stored maternal urine sample available for chemical analysis. There were no twins in the sub-sample. Mothers were on average (mean ± SD) 28.1 ± 6.3 years old, with more than half of them giving birth to their fourth child  and with comparable point estimates. Asthma was linked to high concentrations of Mg, Sr, and Ba, all featured by a relatively small effect of RR close to 1.1. The behavioral and developmental group of disorders was the one most frequently associated with elevated metals, with the majority of them biometals, as well as Li, Co, Ni, Sr, Cd, V, As, and Mo. All point estimates were greater than PR = 1.42 and were different in their majority from the metals linked to preterm birth in this study.Women who delivered preterm were more likely to have elevated concentrations of Zn, Tl, Al, Mn, and U with an RR of 1.40–1.64 times higher compared to in term deliveries  for the lowest or highest quintiles of Ca.Finally, as part of a sensitivity analysis, we investigated the possibility of a U-shape association linked to biometals and morbidities. For this purpose, we defined the exposure to a metal as a concentration in the lowest and highest quintiles (data not shown). This U-shape association was supported only in the case of Ca and specifically in its association with behavioral and developmental morbidities, with RR = 5.62 .Cardiovascular outcomes and obesity were not associated with the metals, independent of other risk factors. Malformations were associated with Ag with PR = 1.33, but at a borderline significance  when adjusted for other factors. The current study adds to the findings of a relatively short list of studies on the association of metal with birth defects: one shows an adverse effect of As, Pb, Cd, and Cu on neural tube defects in infants [Despite the fact that an asthma-like illness outcome was not associated with exposure to metals with the exception of Mg, Sr, and Ba, this outcome occurred so commonly as to produce a valid analysis specific to the cause. Malformations were found to be related only to Ag, but at a borderline significance  of metals that to date have not been explored for their relation to pediatric morbidity. Behavioral and developmental disorders and preterm delivery were associated with heavy metals detected in maternal urine at pregnancy, independent of other factors.Our analysis provides many hypotheses-generating findings that warrant further exploration on a larger sample.Additional file 1: Table S1: Demographic characteristics and clinical outcomes in the study population and the initial cohort, Clalit HMO membersAdditional file 2: Table S2: ICD-9 codes used for health outcome definitionsAdditional file 3: Table S3: Association between maternal and newborn clinical background and presence of a clinical outcome at birthAdditional file 4: Figure S1: Study area map and geographical distribution of the study population. Figure legend: the blue dots in the map represent the subjects' residence location. (JPEG 45 kb)Additional file 5: Figure S2: Graphical presentation of the metal concentrations by outcomesAdditional file 6.


Flexoelectric materials have played an increasingly vital role in nanoscale sensors, actuators, and energy harvesters due to their scaling effects. In this paper, the nonlocal effects on flexoelectric nanosensors are considered in order to investigate the coupling responses of beam structures. This nonlocal elasticity theory involves the nonlocal stress, which captures the effects of nonlocal and long-range interactions, as well as the strain gradient stress. Based on the electric Gibbs free energy, the governing equations and related boundary conditions are deduced via the generalized variational principle for flexoelectric nanobeams subjected to several typical external loads. The closed-form expressions of the deflection and induced electric potential (voltage) values of flexoelectric sensors are obtained. The numerical results show that the nonlocal effects have a considerable influence on the induced electric potential of flexoelectric sensors subjected to general transverse forces. Moreover, the induced electric potential values of flexoelectric sensors calculated by the nonlocal model may be smaller or larger than those calculated by the classical model, depending on the category of applied loads. The present research indicates that nonlocal effects should be considered in order to understand or design basic nano-electromechanical components subjected to various external loads. The nanoscale cantilever beam has been widely utilized as a basic element in nano-electromechanical systems, such as nanoactuators, nanosensors, and nano energy harvesters. At the nanoscale, the mechanical and electrical properties of nanostructures have significant differences from their bulk structures, which are size effects. In a few decades, flexoelectric, nonlocal, coupled stress, and strain gradient theories have been developed to capture the size effects for cases where the classical theories cannot describe the real electromechanical responses of the nanostructures.Flexoelectricity, which is related to the electromechanical coupling between the polarization and the strain gradient, exists in a wide variety of dielectric materials and may lead to strong size-dependent properties at the nanoscale ,2,3. RecIn recent years, the nonlocal elastic field theory proposed by Eringen , which oIn this paper, the objective is to deal with the nonlocal effect on the induced electric potential of flexoelectric sensors subjected to various mechanical loads. Introducing the nonlocal elasticity theory into the linear piezo-flexoelectric model, the equilibrium equations of nanosensors and the corresponding general mechanical boundary conditions are derived using the generalized variational method. The influences of structural sizes, nonlocal parameters, and types of external loads on the normalized deflection and induced electric potential are presented graphically and discussed.Taking the nonlocal elasticity theory into account, the linear piezo-flexoelectric theory is employed to analyze the electromechanical coupling responses of flexoelectric nanostructures. In the nonlocal elasticity model, which contains a wide range interaction, the stress at a point is a function of the strains of all neighboring points ,33. Hence theory  is used.jklmn is ,20:(4)giThe total electrical enthalpy of flexoelectric solids can then be written as ,15:(5)Π=L are the thickness, width, and length, respectively, is depicted in x1-axis is coincident with the neutral surface and the x3-axis runs along the thickness direction of the beam. The bottom surface electrode undergoes a change of electric potential as a result of mechanical deformation and the top electrode is grounded.In this paper, a cantilever beam, in which As the beam is slender  along the thickness of the beam, the constitutive equation can be rewritten as:ctricity . Applyinasticity . Using ESubstituting Equation (18) into Equation (13), the mechanical equilibrium of the flexoelectric beam with the nonlocal effect can be rewritten as:Equation (19) can describe the electromechanical responses of flexoelectric beams with different electrical boundary conditions. We have discussed these electrical boundary conditions in detail . The OpeIn the present case, the flexoelectric sensors would be considered. We note that the top and bottom surfaces of the flexoelectric beam are covered with electrodes perfectly, meaning the electric potential −ϖb)dA=0 . MoreoveThe induced electric potential as a result of mechanical deformation due to the flexoelectric effect is proportional to the deviation between two rotational angles at the ends. Applying Equations (15), (17), (19), and (20), the nonlocal equilibrium equation and the corresponding general mechanical boundary conditions for the cantilever beams can be expressed as:Equation (21) can be easily simplified into equations of the nonlocal strain gradient theory for elastic materials ,29 by se3 and the corresponding material parameters are −6 C/m, and L/h = 20 and the width b = h, unless otherwise stated.In order to assess nonlocal and flexoelectric effects, we discuss bending beams subjected to distributed loads and a concentrated force. In this simulation, the material is BaTiO=1.92 nm . The sleSolving the general nonlocal equilibrium and boundary conditions (Equation (21)), the deflection l effect ,27,28 anEquation (23) shows that the induced electric potential is entirely dependent on the nonlocal effect when only uniformly distributed loads exist. No nonlocal effect arises for the induced electric potential of flexoelectric sensors subjected to a concentrated force only.3 under the OCI condition increased as the normalized thickness decreased.In The boundary condition in Equation (21) indicates that nonlocal and flexoelectric effects act as a concentrated bending moment at the free end, which would change the shape of the deflection curve, especially near the free end. Hence, ic beams . When τ= sensors . It can The induced electric potential, which is very important for sensors and energy harvesters, has a significant scaling effect. A maximum value exists for the intrinsic thickness l effect ,20. Figu sensors ) of the n et al.  theoretiF without the nonlocal effect, as a function of the nonlocal parameter. It is observable from F have a great influence on the induced electric potential of the flexoelectric sensors due to the nonlocal effect. When From Equation (23), it can be clearly found that neglecting the nonlocal effect causes the induced electric potential to disappear as When the uniformly distributed load The rotational angle at the free end can be written as:When By taking Flexoelectric sensors were investigated in the present paper considering the nonlocal effect. The governing equations and corresponding boundary conditions were developed based on the generalized variational principle of the flexoelectric nanobeams. Further, the expression of the induced electric potential, which is fully dependent on the rotational angles at the ends, was obtained. The numerical examples revealed that the induced electric potential of the flexoelectric sensors has a significant nonlocal effect with distributed loads only or with a combination of distributed loads and a concentrated force. Specifically, the nonlocal effect affects the induced electric potential of flexoelectric sensors with some combinations of external mechanical loads. Hence, the optimal induced electric potential of flexoelectric sensors can be obtained by choosing appropriate structural sizes, material parameters, and external mechanical loads. The results show that the electromechanical responses of flexoelectric sensors are sensitive to the nonlocal effect, which cannot be ignored. The present research could, thus, inspire theoretical and experimental work on new flexoelectric structures at the nanoscale.


In 2014, the EU funded a four-year European Cooperation in Science and Technology (COST) Action to address the topic of childbirth. The COST Birth Action was a cross-European network, that brought together over 120 scientists, practitioners, activists and policy makers from 34 countries to work on intrapartum care. The central aim was to advance the state of research and practice in a specific area of great clinical and social importance, intrapartum care. The Action used inter and trans-disciplinary approaches to address birth from multiple perspectives and drew on complexity theory and the concept of salutogenesis (wellbeing). This special collection presents six papers produced from the Action and gives a sense of the range and depth of the work conducted. The Collection illustrates the knowledge that can be generated when a diverse group of people come together with a similar goals and perspectives. The underpinning scientific framework of the Action  was compThe promise of classical enlightenment science has been that scientific method based on the idea that A causes B, (a linear hypothesis) can be used to uncover what is true. The belief underpinning this hypothesis is through scientific progress, we will eventually know everything there is to know about the world . The acaNew ideas, insights, and phenomenon that emerge unexpectedly are fundamental to this new approach. The parts of all kinds of different systems  interact, and organise themselves spontaneously into new, unpredictable patterns and characteristics. The consequence is that the overall system cannot be predicted or described based only its component parts. Emergence arises when self-organising components of a complex adaptive system interact. These generate new unpredictable pathways as a consequence of this interactivity . Often tEvidence-based medicine (EBM) has become central to modern healthcare policy and practice. This is often interpreted through protocols and guidelines derived from systematic reviews of population level data, and then applied to all those with particular conditions/clinical needs . David SEvidence-based medicine (EBM) is the integration of best research evidence with clinical expertise and patient value… when these three elements are integrated, clinicians and patients form (an)…alliance which optimises clinical outcomes and quality of life…’The theory of salutogenesis was developed by Aaron Antonovsky . It concThere are hundreds of thousands of published studies in the area of pregnancy, labour and birth. The vast majority of these are focused on pathologies and the interventions designed to prevent them. This would be an uninteresting observation, if the field of investigation was a particular disease, illness, or adverse state. Indeed, for women and babies who do have diseases or complications, this type of research is critical. For example, the evidence on the efficacy of magnesium sulphate to prevent pre-eclampsia and to treat eclampsia  and the In 1978, the Alma Alta agreement stated:Health is…a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity"In terms of childbirth, this has been reinforced by the following statements from an obstetrician (Montgomery 1958) and from the UK NICE guidelines (2020). The NICE guidelines were written 60 years after Montgomery made the following comment:I have stated on numerous occasions that there is no more need to interfere with the course of normally progressing labor than there is to tamper with good digestion, normal respiration, and adequate circulationDo not offer or advise clinical intervention if labour is progressing normally and the woman and baby are well. In all stages of labour, women who have left the normal care pathway because of the development of complications can return to it if/when the complication is resolved.(NICE) [(NICE) th 2020 using the term ‘childbirth physiology’ to capture all articles on the physiology of childbirth only generated 17,131 hits. In contrast, searching for studies of a specific procedure ‘caesarean section’, generated 62,945 hits. This suggests that there is four times as much research taking place on one single surgical childbirth intervention than for the whole field of straightforward, uncomplicated labour and birth.Despite this, a search of PubMed undertaken on February 15‘too little too late’ for many marginalised, poor and/or rural women and babies, and ‘too much too soon’ for many urban women and neonates. In even the poorest economies, the inverse care law operates. More marginalised women who need lifesaving interventions for them or for their babies are not getting them. Whereas, wealthier women who do not need such interventions are getting too many of them. This can lead to iatrogenic harm for them and their babies in the short and longer term [Rates of routine intervention in childbirth, such as induction and augmentation of labour, surgical birth, and widespread routine use of antibiotics for mother and baby , are higger term . For exager term , and caeger term . Howeverger term . There iger term . In Euroger term . Pretermger term , 28.These data suggest that, while the current way of doing birth around the world has brought benefits to some women and babies, it is also associated with harms for others. This is particularly prevalent in privately funded health care systems, or in countries where access to good health care, education, housing and women’s rights are restricted . The driAn illustration of this is the assumption that universal hospitalisation for giving birth will inevitably reduce maternal and infant mortality and morbidity, and will improve long term physical and psychological thriving. This assumption has been only partially evident in practice. Indeed, there is evidence from a number of high-income countries that hospitalisation of healthy women and babies without complications can increase iatrogenic damage for women and does not benefit their babies. The increased use of induction, augmentation, and caesarean section contribute to these iatrogenic harms –32. Somedilemmas in political and social planning that resist clear definitions, defy traditional analysis approaches, and refuse definitive resolution through predetermined solutions [Balancing the benefits of non-intervention for physiologically normal childbirth with the need to intervene appropriately when pathology arises in the complex, dynamic, highly individual situation of labour could be termed a ‘wicked’ problem. Such problems are defined as olutions .Intriguingly, as an exemplar of the way in which wicked problems do not have simple right or wrong solutions, a recent study of 64 facilities in Ghana showed a complex set of relationships between maternal and neonatal mortality and factors such as geographic distance from facilities, wealth, and education. These factors influence maternal and neonatal mortality in unexpected directions . WealthiHospitalization  may affect the microbiota of the vagina… and… initial colonization during labor and birth, with effects that could persist in the intestinal microbiota of infants 1 month after birth.This suggests that physiological birth in a home/community environment is a critical contextual mediator of the biological adaptive processes of labour and birth. The consequences of this, both in the short and long-term are not yet fully understood.In recognition of the potential intrinsic value of physiological labour and birth as a catalyst for long-term wellbeing, those collaborating on the COST Birth Action set out to re-imagine the kinds of questions and investigations that could be asked and undertaken in the future. The mix of academic and clinical disciplines, policy makers, service users, and activists who were invited to join the Action at the outset, and who joined it subsequently, worked to unsettle current scientific and normative ways of understanding and investigating this topic area. The salutogenic approach taken by the Action entailed examining how things go right, as well as how they go wrong, with an aim of increasing research on physiology as well as pathology.The papers in this Special Collection are indicative not only of the inter and trans-disciplinary insights that emerged from the interaction and multiple perspectives of over 120 people from 34 countries over the four years of working on the EU COST Action. They also illustrate the new kinds of questions that can be asked once those from different disciplines and perspectives spend time listening to each other. The Action worked across disciplines, challenging assumptions and incorporating service users and activists’ experiences and knowledges. The papers in this Collection on neurophysiology  address some of the basic science questions that still remain to be explored in the delicate neurohormonal-psycho-social dance that labour has evolved to be , 40. TheMembers of the EU COST Birth Action engaged with childbirth from the perspectives of both complexity theory and salutogenesis. The networks formed by the scientists, academics, clinicians, service users, activists and policy makers that were included in the programme have generated unexpected, emergent insights, that have led to new areas of enquiry that are ongoing. The intention of this Collection is to summarise and synthesis some of the research in this area and contribute to growing the evidence base in this critical, but relatively neglected, field of physiological labour and birth.


Objective: To evaluate the nutrition-related effects of prophylactic Lactobacillus acidophilus/Bifidobacterium infantis probiotics on the outcomes of preterm infants <29 weeks of gestation that receive human milk and/or formula nutrition. We hypothesize that human-milk-fed infants benefit from probiotics in terms of sepsis prevention and growth. Methods: We performed an observational study of the German Neonatal Network (GNN) over a period of six years, between 1 January, 2013 and 31 December, 2018. Prophylactic probiotic use of L. acidophilus/B. infantis was evaluated in preterm infants <29 weeks of gestation (n = 7516) in subgroups stratified to feeding type: (I) Exclusively human milk (HM) of own mother and/or donors , (II) HM of own mother and/or donor and formula , and (III) exclusive exposure to formula . The effect of probiotics on general outcomes and growth was tested in univariate models and adjusted in linear/logistic regression models. Results: 5954 (76.5%) infants received L. acidophilus/B. infantis prophylactically for the prevention of necrotizing enterocolitis (NEC). Probiotic use was associated with improved growth measures in the HM group  but not in the F group . The HM group had the lowest incidence of clinical sepsis (34.0%) as compared to the Mix group (35.5%) and the F group (40.0%). Only in the Mix group, probiotic supplementation proved to be protective against clinical sepsis . Conclusion: Our observational data indicate that the exposure to L. acidophilus/B. infantis probiotics may promote growth in exclusively HM-fed infants as compared to formula-fed infants. To exert a sepsis-preventive effect, probiotics seem to require human milk. Bifidobacterium longum and Bifidobacterium infantis/Lactobacillus acidophilus has been adopted into clinical routine by many European neonatal intensive care units (NICUs), for example in Austria [Probiotics that act as gut colonizers of human-milk-fed infants  have a h Austria , the Net Austria , and Ger Austria . In hosp Austria . Despite Austria . To prom Austria ,7. In li Austria . Human m Austria , whereas Austria .Herein we hypothesize that human milk as a nutritional source is required for probiotics to provide a sepsis-preventive and growth-promoting effect. Accordingly, we performed an observational study in a large GNN cohort of extremely preterm infants <29 weeks of gestation discharged after the year 2012 and evaluated the impact of probiotics in the context of feeding strategies.www.vlbw.de) is a population-based observational multicenter cohort study enrolling Very low birth weight infants (VLBWI) at 64 neonatal intensive care units (NICUs) in Germany. Within the study period, data were collected from infants discharged between 1 January, 2013 and 31 December, 2018. Preterm infants of a birth weight <1500 g and/or a gestational age between 22 + 0 and 28 + 6 weeks, who were actively managed with intensive care, met the inclusion criteria. Infants with lethal malformations or those treated with comfort  care were excluded from the study. In the analysis of this study, only cases with complete documentation for feeding type were included.The German Neonatal Network . Data quality was evaluated by a physician trained in neonatology via annual on-site monitoring of completed record files. After monitoring, data were coded and evaluated. B. infantis. and L. acidophilus corresponds to the formulation that has been most commonly used among the participating study sites in the past [9 CFU (Colony forming units) L. acidophilus and 1–1.5 × 109B. infantis.The probiotic formulation consisting of the past . ProbiotThe preparation  of human milk (own mother’s and donor’s milk) before use was carried out according to local standards  at the study site. In all centers providing donor milk, the samples were pasteurized before use for feeding. Three “human milk feeding” strata were applied:I HM (HM group): Infants who were exclusively fed with own mother‘s and/or donor‘s milk.II Mix (Mix group): Infants who were fed with HM and formula at any time during the primary stay in hospital.III Formula (F group): Infants who were exclusively fed with formula.Gestational age was calculated from the “best obstetric estimate”. This is defined as the estimate of the infant’s gestation based on the birth attendant’s final estimate by using early prenatal ultrasound and obstetric examination .Small-for-gestational age (SGA) was defined as a birth weight less than the 10th percentile for gestational age according to gender-specific standards for birth weight by gestational age in Germany .Full enteral feeding was defined as enteral nutrition at a minimum of 150 mL/kg body weight per day.Z-scores are numerical measurements of the value’s relationship to the mean of the group values measured in terms of standard deviations from the mean (between −3.0 and 3.0). Z-scores were calculated for birth weight according to the 2003 Fenton preterm growth chart [Weight gain velocity was defined as gain in body weight, calculated as g/day . Growth velocity of body length was defined as gain in body length, calculated as mm/day . Head growth velocity was defined as gain in head circumference, calculated as mm/day . th chart ,16.Staphylococcus (CoNS) was isolated as a single pathogen in one peripheral blood culture, two clinical signs and one laboratory sign were required for classification of CoNS sepsis [Clinical sepsis was defined as condition with at least two signs of systemic inflammatory response , one laboratory sign , and the neonatologist’s decision to treat with anti-infective drugs for at least 5 days but no proof of causative agent in blood culture . Blood cS sepsis .Bronchopulmonary dysplasia (BPD) was diagnosed when needing supplemental oxygen or ventilatory support at 36 weeks of postmenstrual age. Necrotizing enterocolitis (NEC) was defined as necrotizing intestinal inflammation requiring surgery, and focal intestinal perforation (FIP) was FIP requiring surgical treatment classified by the attending surgeon. Retinopathy of prematurity (ROP) was defined as typical retinal changes  requiring interventions such as laser therapy, cryotherapy, or intraocular vascular endothelial growth factor inhibitors.p-value of <0.05 was considered as statistically significant for single tests. Data analyses were performed using the SPSS 24.0 data analysis package . Hypotheses in the univariate analysis were evaluated with Fisher’s exact test and Mann–Whitney U test. Only two-sided tests were used. A p-value < 0.1 in multivariate logistic regression models and known confounders as independent variables: gestational age per week, gender, multiples, and SGA status. Odd ratios and 95% confidence intervals were calculated in order to identify the influence of probiotic prophylaxis on outcomes independent of the abovementioned confounders. The following outcome parameters were tested in multivariate models: necrotizing enterocolitis, retinopathy of prematurity requiring intervention, bronchopulmonary dysplasia, clinical sepsis, and blood culture confirmed sepsis. To address the problem of multiple comparisons, we performed Bonferroni corrections for multivariate analyses in order to protect from statistical Type I errors. Additional information derived from Bonferroni correction is indicated in Subsequent to univariate analyses, we included parameters with a Z-score-based body weight at discharge according the 2003 Fenton growth chart for preterm infants, z-score-based weight gain, growth velocity of body weight (g/day), body length (mm/day) and head circumference (mm/day). A p-value of <0.05 was considered statistically significant. For primary and subgroup analyses, we used a uniform dataset with available data for all metric parameters. Infants with incomplete data for variables that were used in our analyses were not included.In order to evaluate the influence of probiotic prophylaxis on growth parameters, we conducted linear regression models using known/probable confounders as independent variables: gestational age per week, birth weight, gender, multiple birth, and maternal descent. Effect size and 95% confidence intervals (CI) were calculated. The following outcome parameters were tested in linear models: Graphical analysis was carried out using GraphPad Prism .All study parts were ethically approved by the University of Lübeck Ethical Committee and the committees of the participating centers (vote no. 08-022). Informed consent was obtained from all subjects. All methods were carried out in accordance with relevant guidelines and regulations, specifically: the Declaration of Helsinki, the current revision of ICH  Topic E6, the Guidelines for Good Clinical Practice, and the Guidelines of the Council for International Organization of Medical Sciences, the WHO  .From 1 January, 2013 until 31 December, 2018, 7516 extremely low gestational age neonates (ELGANs) were discharged in 64 GNN centers. The study cohort had a mean gestational age at birth of 26.5 weeks  and a mean birth weight of 855 g , mix, or exclusively formula according to the year of the infant’s discharge. There has been an increasing rate of ELGANs that receive HM  infants, with a frequency of 74.8% for infants receiving HM (HM group) and 74.9% for those with formula . Notably univariate analyses revealed that the F group had significantly higher rates of NEC , clinical sepsis , and severe ROP  as compared to the HM group. Exclusively formula-fed infants (F group) had a higher body weight at discharge and weight gain/day, head circumference, and body length than infants receiving HM in univariate analyses , z-score-based weight gain , and growth rates of body weight, body length, and head circumference (p < 0.001) and z-score-based weight gain. Notably probiotic treatment was associated with increased weight gain velocity , body length, and head circumference. This (probiotic) effect was observed to a lesser extent in the Mix group , while Formula infants were not affected by probiotics in that aspect  that han sepsis . Hence, n sepsis . Both, hn sepsis , which nThe major strengths of our study design are the large sample size and high quality of the clinical data that are monitored on-site by a study team trained in neonatology. The main limitations are the observational design, the lack of information on the daily type of feeding in the Mix group, indication for supplementation, and timing with bovine and individual fortification of human milk or formula. Furthermore, we did not have exact data on the timing of probiotics, the number of pasteurized milk portions, and the bacterial load of human own-mother milk (if not pasteurized) in the individual infants. Whether probiotics or the probiotic/prebiotic load of human milk is causal for the observed effects, needs to be addressed in future studies including extensive sequencing of human milk microbiome and the gut microbiome of the milk (+probiotic)-fed infants.L. acidophilus/B. infantis and feeding strategies interact and have the potential of improving outcomes and growth in preterm infants. Our data demonstrates sepsis-preventive and growth-promoting effects exclusively in infants receiving human milk, supporting usage of human milk (including human milk from donors) in preterm infants whenever possible. Randomized, placebo-controlled trials as the PRIMAL clinical study [Evidence of nutrition-related effects of probiotic prophylaxis in preterm infants is scarce. In a large cohort of VLBWI, we conclude that supplementation of al study  are pend


To evaluate if women with a history of myomectomy have a modified preterm birth risk compared to women with myomas during pregnancy.Retrospective cohort study including all women with a history of myomectomy (operated group) or uterine myomas during pregnancy (unoperated group) who delivered in a tertiary center between January, 2011 and December, 2017. The operated group included women who had a myomectomy history with or without myomas during the ongoing pregnancy. The unoperated group included women with uterine myoma(s) seen on at least one ultrasound during pregnancy without history of myomectomy. The primary outcome was preterm birth < 37 weeks, and the secondary outcome spontaneous preterm birth < 37 weeks. To control for confounding factors, a propensity score approach was used. Two sensitivity analysis were performed, one repeating the analysis using the propensity score after excluding operated women with persistent myomas and one using a classical multivariable logistic regression model.p = 0.82). No difference in preterm birth risk was shown between unoperated and operated women in the cohort matched on the propensity score: OR 0.86; 95%CI [0.47–1.59]. These results were consistent for spontaneous preterm birth  and for the sensitivity analyses.The cohort included 576 women: 283 operated women and 293 unoperated women. The rate of preterm birth was similar in the two groups: 12.6% in the unoperated group and 12.0% in the operated group (In women with a leiomyomatous uterus, a history of myomectomy is not associated with a reduced preterm birth risk.The online version contains supplementary material available at 10.1186/s12884-020-03413-w. Myomas are benign uterine smooth muscle tumors affecting 1.5 to 11% of reproductive-aged women . Their pPrevious studies have shown associations between both preterm birth and myomas , 6–8 andTo our knowledge, the preterm birth risk of unoperated women with myomas during pregnancy was never compared to that of women with a history of myomectomy. Therefore, the question of whether myomectomy reduces the preterm birth risk has never been addressed. Yet, the fact that the risk of preterm birth is modified or not by myomectomy is an important information for both surgeons and women with myomas. How myomectomy could reduce the preterm birth risk could depend on the location, the number or the size of myomas –17.Thus, the main objective of this study is to evaluate if women with a history of myomectomy have a modified preterm birth risk compared to women with myomas during pregnancy.We performed a retrospective monocentric cohort using hospital data from January 1st, 2011, to December, 31st, 2017, in a tertiary university hospital maternity unit .+ 0 weeks during this period were eligible. Multiple pregnancy and women referred from other hospitals after 22 weeks were excluded. Women with myomas or a history of myomectomy were identified using a computer query with a multiple combination of key words: “myoma”, “fibroids”, “myomectomy”, “scared uterus of gynecological origin” and “surgical history”. All medical paper files were reviewed to obtain detailed information from ultrasound and surgical reports.All singleton pregnancy delivered > 22We included all women with uterine myomas during pregnancy or a history of myomectomy. This study was approved by the National Data Protection Authority . Under French regulations, this study is exempt from Institutional Review Board (IRB) review because it was an observational study using anonymized data from medical records. Women were informed that their records can be used for the evaluation of medical practices and were allowed to opt out of these studies. The study’s exempt status was confirmed by the Institutional Review Board Ile-de-France.+ 0 and 13+ 6 weeks. All ultrasound examinations were performed by licensed sonographers and as recommended in France, at least three ultrasounds were performed during pregnancy. Women with history of myomectomy were managed as women with a history of cesarean delivery i.e. attempted vaginal birth at term or cesarean delivery at 39 weeks if indicated.Gestational age was confirmed during the 1st trimester ultrasound by measurement of the craniocaudal length between 11We created two groups: “unoperated women”, which included all women with uterine myomas without a history of myomectomy; and “operated women”, which included women with a history of myomectomy, with or without myomas during the ongoing pregnancy. Women could have been operated by either laparotomy, laparoscopy or hysteroscopy. In both groups myomas were considered if there was at least one myoma (operated or not) measuring at least 20 mm or multiple myomas (≥2) whatever the size. The myomas present during the ongoing pregnancy had to be visualized on at least one prenatal ultrasound.The primary outcome was preterm birth < 37 weeks. The secondary outcome was spontaneous preterm birth < 37 weeks. Spontaneous preterm birth was defined as preterm labor with intact membranes or preterm premature rupture of membranes (PPROM) regardless of labor onset.We collected the following maternal characteristics: maternal age, body mass index (BMI), geographic origin, socioeconomic status, parity and history of cesarean delivery, previous preterm birth, medical history (preexisting diabetes and hypertensive disorders), and use of Assisted Reproductive Technology (ART). We also collected obstetrical characteristics and outcomes: high blood pressure or preeclampsia, gestational diabetes, small for gestational age, and gestational age at delivery. Myomas’ characteristics were collected from ultrasound and surgical reports: myomas’ location, number of myomas, and size of the largest myoma. If several myomas were present, we reported the location of the closest to the cavity myoma. For example, if a woman presented with a submucosal and serosal myoma it was reported as submucosal.2 tests or Fisher’s tests for qualitative variables and Student t test for quantitative variables.We compared the baseline clinical and demographic characteristics, the pregnancy characteristics and the myomas’ characteristics between the unoperated and operated women. These comparisons were performed using Pearson χTo identify the variables associated with preterm birth, we performed a bivariate analysis comparing the association between preterm birth and women and myoma characteristics.Supplementary information S1.To control for confounding factors that might influence both the indication of myomectomy and the occurrence of preterm birth, we used a propensity score approach. A propensity score was estimated for all women by a logistic regression model with myomectomy as the dependent variable. The variables included in the propensity score were variables known in literature as associated with preterm birth  or indicThe analyses were repeated for our secondary outcome.p < 0.10) was performed on the whole population. This model did not include the myomas’ characteristics as in the operated group these myomas had been removed. The adjusted odds ratio (aOR) and their 95% confidence intervals (95% CI) reflecting the association between preterm birth and history of myomectomy adjusted on the selected variables: maternal age, BMI, geographic origin, socioeconomic status, parity and history of preterm birth and use of ART, were assessed through multivariable logistic regression.Two sensitivity analysis were performed. First, the analysis in the matched cohort was repeated after excluding operated women with diagnosed myomas during the ongoing pregnancy. Then, a multivariable model including the variables known in literature as associated with preterm birth  and the P values were two-tailed, and values of P < .05 were considered significant. All statistical analyses were performed using Stata .All Among the 32,812 women delivered at Port-Royal hospital between January, 1st, 2011 and December, 31st, 2017, 576 (1.7%) women met the inclusion criteria: 293 unoperated women and 283 operated women. In the operated group, 93 (33%) women had persistent myomas during the ongoing pregnancy, with a median number of persistent myoma of 2 IQR [1–3], 183 (64.7%) women had been operated by laparotomy, 49 (17.3%) women by laparoscopy and 51 (18.0%) women by hysteroscopy.p = 0.04), more frequently multiparous (p < 0.01), had had more frequently a previous preterm birth (p = 0.02) than the unoperated women (Table p < 0.01). Before surgery, the operated women had significantly more submucosal myomas, more numerous myomas (p < 0.01) and a larger mean size of the largest myoma (p < 0.01) than unoperated women . These results were consistent for spontaneous preterm birth  and preterm birth < 34 weeks .The crude preterm birth rate was not significantly different between the two groups: 12.6% in the unoperated group and 12.0% in the operated group (p = 0.48). Bivariate analyses comparing the association between preterm birth and women’s preexisting, obstetrical and myoma characteristics are detailed in Table SIn the operated group, there were no significant differences in preterm birth rates between women with and without myomas during the ongoing pregnancy  showed no differences in preterm birth risk or spontaneous preterm birth risk between the two groups, respectively OR 0.78; 95%CI [0.38–1.59]; p = 0.67.Analysis by multivariable logistic regression models in the whole population provided similar results to propensity score estimates, aOR 0.89; 95%CI [0.52–1.51]; In this cohort, the risk of preterm birth did not differ between women with a history of myomectomy and unoperated women with myomas during pregnancy. These results were consistent when studying spontaneous preterm birth and when restricting the analysis to women with a history of myomectomy and with no myomas during the ongoing pregnancy.Most physicians consider the association between preterm birth and myomas to be due to a lack of uterine distension caused by the presence of myomas in the uterine cavity. Because myomectomy, does not improve the rate of preterm birth or spontaneous preterm birth, even when no residual myomas are present during the ongoing pregnancy, we can hypothesize that lack of uterine distension caused by the presence of myomas in the uterine cavity is not the only mechanism impairing pregnancy course.n = 35,983 women), a 2-fold increased risk of preterm birth was reported in women with a history of cesarean section  [To explain the persistence of preterm birth risk after myomectomy we can formulate two hypotheses. First, uterine fibrous scars due to myomectomy could restrict the ability of the uterine cavity to distend. Indeed, it has been showed that history of cesarean section increases the risk of preterm birth. In a case control study evaluating the risk factors of preterm birth < 37 weeks during women’s second pregnancy (< 0.001) . This coA second hypothesis to explain the absence of differences in preterm birth rates in our two groups is the role of hormonal and inflammatory processes. Myomas are indeed hormonal-dependent tumors growing under the influence of both estrogen and progesterone, they are also known to secrete inflammatory factors such as TGF-β3 and other pro-inflammatory cytokines . DeregulTo our knowledge, this is the first study comparing the risk of preterm birth between women with history of myomectomy and unoperated women with myomas during pregnancy. The analyses were performed on a large cohort of 576 women during a 6 years period in a single tertiary maternity center. The number of women with and without a history of myomectomy was similar for each year of our study period, and no significant change in in perinatal care was noted during the study period.One of the main strengths of this study is the use of the propensity score approach. Indeed, the use of the matched propensity score enabled us to reduce bias due to confounding variables influencing our exposition (myomectomy) but also our outcome (preterm birth). The sensitivity analyses allow us to show that the preterm birth risk in women with history of myomectomy was not only due to the presence of persistent myomas during pregnancy.Another strength of our study is the available data on risk factors of preterm birth such as previous preterm birth. To avoid a selection bias, as we are a tertiary university maternity unit receiving women with a risk of preterm birth (induced or spontaneous) from surrounding hospitals, we excluded all referred women.The main limitation of our study is its retrospective design. The myomas’ characteristics were insufficiently reported on ultrasound and surgical reports which affected the rate of missing data. Nonetheless, the myoma characteristics were imputed using multiple imputation-chained equations enabling us to match 67% of our initial population. The propensity score matching allowed us to compare women with similar characteristics, but cannot balance unmeasured characteristics. No data on women delivering before 22 weeks were available, therefore we cannot conclude on the risk of delivery before term of viability.In our cohort, there was no difference in preterm birth risk between women with myomas during pregnancy and women who had been operated of their myomas even when no persistent myomas were present during the ongoing pregnancy. Our findings raise questions about the physio-pathological processes resulting in preterm birth in these women. Nevertheless, prevention of preterm birth risk should not in itself be an indication for surgery.Additional file 1:Table S1. Bivariate analysis comparing women’s preexisting characteristics, pregnancy characteristics and myoma characteristics between women with a preterm birth < 37 weeks and women with a term birth, n = 576. Table S2. Association between history of myomectomy and spontaneous preterm birth < 37 weeks (reference = unoperated women); bivariate analysis, logistic regression model in the propensity matched cohort, and sensitivity analyses. Supplementary Information S1. Construction of Propensity score. Figure S1. Standardized differences between unoperated and operated women, for the variables included in the propensity score, before  and after matching (propensity score-matched population).