Preterm birth continues to be an important problem in modern obstetrics and a large public health concern and is related to increased risk for neonatal morbidity and mortality. The aim of this study was to evaluate the data in the literature to determine the relationships between mode of delivery  in the first pregnancy and the risk of subsequent preterm birth from a multi-year population based cohorts (PROSPERO registration number: 42018090788). Five electronic databases were searched. Observational studies that provided mode of delivery and subsequent preterm birth were eligible. Ten cohort studies, involving 10333501 women, were included in this study. Compared with vaginal delivery, women delivering by previous cesarean section had a significantly higher risk of preterm birth in subsequent births . After adjusting confounding factors, there was still statistical significance . However, both before and after adjustment, there was no difference among very preterm birth . To the best of our knowledge, this is the first systematic review and meta-analysis that suggests previous cesarean section could increase the risk of preterm birth in subsequent pregnancies. The result could provide policy makers, clinicians, and expectant parents to reduce the occurrence of unnecessary cesarean section. Preterm birth, defined as iatrogenic or spontaneous delivery before 37 completed gestational weeks, continues to be an important problem in modern obstetrics and remains a large public health concern. It affects 7.2% and 9.6% of pregnancies in China and United States, respectively , 2, and Over the past two decades, several cohort studies have investigated the association between previous mode of delivery and preterm birth in subsequent births. The positive association between cesarean section in the first pregnancy and subsequent preterm birth has been well documented –19. HoweThrough a systematic review and meta-analysis, our aim of this study was to evaluate the data in the literature to determine the relationships between mode of delivery  in the first pregnancy and the risk of subsequent preterm birth from a multi-year population based retrospective cohort. Understanding the intertwined relationship between mode of delivery  in the first pregnancy and the risk of subsequent preterm birth may remind policy makers, gynecologists and obstetricians, and expectant parents to reduce the occurrence of unnecessary cesarean section.We reported this systematic review and meta-analysis following the Preferred Reporting Item for Systematic Reviews and Meta-analyses statement . Before In this systematic review and meta-analysis, published articles were searched with no language restrictions by two independent reviewers (LL and YM) in PubMed, Web of Science, Embase, Elsevier ScienceDirect and the Cochrane Library . The search terms were “mode of delivery”, “cesarean delivery”, “cesarean section” “vaginal delivery”, “preterm birth”, and “preterm delivery”. A detailed search processes used for the PubMed was shown in Observational studies (including cohort and case-control) assessing previous mode of delivery  and preterm birth in subsequent births were included. Only single pregnancy in our analyses was included, and twin pregnancy was excluded. First, based on the predetermined eligibility criteria, titles and abstracts of the potentially eligible articles were independently screened by YM and LL. Any duplicates were excluded. Then, potentially eligible studies were assessed and appraised full texts. Two authors (YM and LL) independently read the full text of the included studies and extracted the relevant data via a recognized data extraction form in Microsoft Excel software. Study characteristics, such as published journal and year, and first author’s name, study setting, such as period of enrollment and country, study design, study population characteristics, such as number of participants, gestational week, and outcomes such as risk estimates with corresponding confidence intervals, and confounding factors were extracted in each included study. Diagnosis and confirmation of preterm birth  and very preterm birth  were done according to the criteria of each study. If there were disagreement or uncertainty, consensus with the team members was used to resolve it.To assess the risk of bias of observational studies, two authors (LL and QX) used the Newcastle Ottawa Scale (NOS) , 26 to aI2 statistics was used. According to I2-value, the statistical heterogeneity was divided into three categories: mild (< 25%), moderate (25–50%), and large (> 50%) [P-value of 0.05 was considered statistically significant. Data analysis was completed using Stata 12.0 .Relative risk (RR) with 95% confidence intervals (CI) was collected from the included articles. To examine the statistical heterogeneity, Higgins  (> 50%) , 29. Mea (> 50%) , 31. To The flow diagram, detailed process of inclusion and exclusion criteria (PRISMA template), was shown in I2 = 98.8%; I2-value indicated that there was a high heterogeneity after pooling together. However, Begg’s and Egger’s tests showed there was no small-study effects  in the publication bias. Sensitivity analysis showed each single study did not influence the stability of the overall result.In the quantitative meta-analysis, ten retrospective cohort studies, involving 10333501 women, were included. Compared with vaginal group, women delivering by cesarean section in the last pregnancy had a significantly higher risk of preterm birth in subsequent births . There were no existing publication bias before and after adjustment was performed  using Begg’s and Egger’s tests.Four studies, including 764741 women, involved very preterm birth. However, both before and after adjustment, there were no found to be statistically significant in the risk of subsequent very preterm birth for women who had delivered by cesarean section in the last pregnancy  in the first pregnancy and the risk of subsequent preterm birth. With published data from ten retrospective cohort studies, for more than ten million women, our pooled analysis revealed that, compared with primary vaginal birth, cesarean section in the first pregnancy increased the risk of preterm birth  in subsequent pregnancies.The uterine structure and/or intrauterine microenvironment may be changed by previous cesarean section . These cOne possible risk factor that cervical trauma in the second stage of labor or unintentional incision into the uterine cervix during the previous cesarean section could disrupt the cervical integrity. This damage can affect the function of the cervix, and further increase the risk of preterm birth in future pregnancies. This phenomenon has been described in pregnant women by a Japanese obstetrician Koyama S . MeanwhiAnother possible explanation for the subsequent increase in preterm birth may be the formation of uterine scar after previous cesarean section. It has been found that adhesions created by the previous cesarean section could reduce utero-placental function and disturb the position of blastocyst implantation. These could further create sub-optimal conditions for fetal development . A retroAlternatively, underlying reasons, such as higher body mass index, advanced maternal age, or other maternal medical characteristics , which are indications for the cesarean section in the first pregnancy can also be an important cause of preterm birth in the next pregnancies –44. FromIn this study, our results indicate that previous cesarean section could increase the risk of preterm birth  in subsequent birth, but we showed that previous cesarean section was not associated with very preterm birth  in subsequent birth. Although other confounders may be related to very preterm birth which are not known or addressed here, an important explanation could be that too few articles (only four articles) included very preterm birth. After all, small individual studies might be underpowered and easy to cause false negative to identify the risk of results in the analysis.Interpregnancy interval can affect the outcome of the subsequent pregnancy. A previous study reported that a short interpregnancy interval may increase the risk for abnormally invasive placenta in subsequent pregnancy , which mStrength of our systematic review is the access to a relatively large sample size, including more than ten million women, and the consistent results of both before and after adjustments factors are provided in the preterm birth in subsequent pregnancies. However, some limitations of the study merit attention. Firstly, only developed cohort studies, including data from multicenter and national registries, were included in this meta-analysis, and the differences in the reporting of preterm birth rate could have affected the quality of the reported data. We would hope that future studies would also consider the previous mode of delivery and preterm birth in subsequent pregnancies in developing countries. Secondly, there was a high heterogeneity among the studies evaluating the risk of preterm birth in the combined analysis. However, Begg’s test and Egger’s test for each site-specific analysis showed no publication bias or small-study effects. Third, although including more than ten million women included, there are only ten published articles that are suitable to include in this review. The number of articles included seems too small. Fourth, while the RR-value reached statistical significance, it is should also note that the small size suggest that the clinical significance is not very strong.In conclusion, this is the first systematic review and meta-analysis to our knowledge that showed that previous cesarean section could increase the risk of preterm birth in subsequent pregnancies. The result could provide policy makers, clinicians, and expectant parents to reduce the occurrence of unnecessary cesarean section.S1 Table(DOC)Click here for additional data file.S1 Text(DOCX)Click here for additional data file.


Duplication cyst of the alimentary tract is a rare congenital anomaly. Duodenal duplication cyst accounts for less than 5% overall. These entities rarely present in adults. They are often mistaken as choledochoceles. Management is most often complete excision, but it is individualized to the particular case.A 22-year-old woman was admitted to our hospital with a history of intermittent colicky right hypochondrial pain not relieved by any medications for the past 3 months. Initially, she was given proton pump inhibitors, but her pain was not relieved. Further evaluation was done, and preoperative imaging showed a cyst in the second part of the duodenum. Magnetic resonance imaging revealed it as a choledochocele, but duodenal duplication cyst was kept in the differential diagnosis. Further ultrasound identified it to be a duplication cyst. After failed endotreatment, the patient was successfully managed with partial excision and marsupialization.Duodenal duplication cyst is uncommon and rarely diagnosed in adults. Duplications in the duodenum should always be a part of the differential diagnosis, especially in cystic lesions. Ultrasonogram of the cyst might lead to the proper diagnosis. Surgery is the treatment of choice if endotherapy is not successful. Alimentary tract duplications are a rare congenital anomaly that can occur anywhere from the oropharynx to the anus. Duplication cyst is a spherical or tube-shaped structure lined by luminal epithelial cells. Duodenal duplications account for about 6% of alimentary tract duplications. Prevalence of duplications is about 1 in 100,000 live births. Duplication cyst in the duodenum often was mistaken as choledochocele, which was the initial diagnosis in our patient. Further workup with a multidisciplinary team led to the correct diagnosis and management.A 22-year-old woman was admitted to our hospital with a history of intermittent colicky right hypochondrial pain not relieved by any medications for the past 3 months. Initially, she was given proton pump inhibitors, but her pain was not relieved. She had no other symptoms. Her past medical and family histories were not significant. The result of her clinical examination was normal. Upper gastrointestinal (GI) endoscopy showed globular swelling at the medial wall of D2 Fig. . The ampComputed tomography (CT) with oral contrast agent showed dilation of the intramural part of the common bile duct (CBD). A cyst of size 2.4 × 2.3 cm was noted in the second part of the duodenum  the presence of smooth muscle coat, (2) an epithelial lining representing some type of intestinal tract mucosa, and (3) intimate anatomic association with some portion of the alimentary tract [The duplication cyst is confirmed by a smooth-muscle coat, an alimentary epithelial lining, and an intimate attachment to the GI tract. It presents as a cystic or tubular communicating or noncommunicating structure to the adjacent alimentary tract. In 1937, William E. Ladd coined the term “duplications of alimentary tract.” Gross Duplication cysts are usually located at the first and second parts of the duodenum, and the mesenteric side of the anterior wall is becoming more common. Submucosal and intermuscular sites are also described , 5. TheyIdeal treatment for duplication cysts is a complete surgical resection. Patients may require pancreaticoduodenectomy when the cyst is close to the ampulla of Vater. Therapeutic endoscopy , such asDuodenal duplication cyst is extremely rare, and it is rarely diagnosed in adults. Duplications in the duodenum should always be a part of the differential diagnosis in cystic lesions. Choledochocele is frequently encountered and should be differentiated from duplications. Endotherapy is the preferred treatment and first line in management. Failed endoscopic treatment necessitates surgery.


Quantitative validation studies alone may not be able to distinguish between instances when participants did not accurately report an event vs when participants did not understand a question. We used an explanatory qualitative study design to acquire an in-depth understanding of why some mothers in rural Nepal overestimate birth size of their newborn and their length of pregnancy.We conducted two focus group discussions (FGDs) with study staff who administered a quantitative questionnaire and 12 in-depth interviews (IDIs) with mothers who had participated in a quantitative validation study. Transcripts were coded and analyzed for themes in patterns of meaning within and across FGDs and IDIs. Using this thematic map, we synthesized our data into common and divergent responses from participants to facilitate our interpretation of the quantitative findings.We identified five themes specific to this analysis: difficulties with the length of pregnancy question, challenges in administering the birth size question, the perceived effect of time since birth on mothers’ ability to remember information, the language and style differences specific to this setting, and the study context shaping the relationship between study staff and mothers who participated and how this may have influenced mothers’ responses. Visual aids may help to scale the question about birth size within a cultural frame of reference for maternal reports to be more interpretable. Among both study staff and mothers, a longer period of time since the birth of a child was thought to be associated with diminished accuracy of maternal reports, a perception not supported by our previously published quantitative findings.Poor validity of low birth weight (LBW) and preterm birth indicators based on maternal reports may be partly attributed to challenges in maternal understanding of questions assessing birth size and length of pregnancy. Additional research is needed to confirm these findings regarding maternal comprehension and to further evaluate the utility of visual aids developed for this study. Low birthweight LBW, <2500g) and preterm birth <37 weeks) are associated with increased risk of child mortality, severe disability, cognitive impairment, and other long-term health problems -3. World7 weeks a500g and Maternally-reported information collected as part of national household surveys, like the Demographic and Health Surveys (DHS) and the Multiple Indicator Cluster Surveys (MICS), are often the only source of population-based data available on birthweight and preterm birth indicators in low-income countries . Under tWe conducted both the validation and qualitative studies in the rural Sarlahi District of Nepal, where only about half of its predominantly Hindu residents are able to read and write . Over a The studies were nested within a community-randomized trial that aimed to assess the impact of using sunflower seed oil in full-body newborn massage on neonatal morbidity and mortality ). The goal of the validation study was to validate postpartum reports of birthweight, birth size and length of pregnancy, by comparing maternal reports directly with data on birthweight and gestational age collected as part of the parent trial. Detailed descriptions of participant selection and analysis for the substudy of the trial can be found in a prior publication . In brieIn the validation study, we concluded that maternal reports underestimated LBW and preterm birth, particularly in a setting with relatively high prevalence of both . Our resOur explanatory qualitative approach incorporated perspectives from both study staff who had administered questionnaires and participants in the validation study. In August 2016, during the last month of data collection for the validation study, we conducted focus group discussions (FGD) with the study staff who had administered the quantitative form. To ensure only study staff who wanted to participate were recruited and others did not feel coerced, we limited the number of FGDs to two. The study staff were relatively homogeneous in terms of socioeconomic status, all were local residents, female, and all received standardized training on administration of the quantitative questionnaire. For these reasons, we felt that two FGDs were sufficient to capture the information of interest. A discussion guide was created to cover the following themes: reflection on experiences with administering the quantitative form, identification of questions mothers had difficulty answering, discussion of reasons difficulties were encountered, description of probes used for clarification, and suggestions for how questions could be improved for better understanding. FGDs included a more focused discussion about the birth size and length of pregnancy questions but also allowed for study staff to discuss other questions of the quantitative survey they thought were difficult for mothers to answer. FGDs were conducted by locally-resident, female qualitative interviewers who were fluent in Nepali and Maithili, from the same community as our study staff, and in non-supervisory roles in an attempt to allow study staff to more openly share their experiences working on the study. We conducted the FGDs in a private room at one of the field offices.Based on information from the FGDs, we identified and developed visual aids for use during in-depth interviews (IDI). Because the explanatory design of this qualitative study aimed to better understand why some mothers may have overestimated the birthweight or gestational age of their newborn, those who provided discordant responses in the quantitative validation study were selected for IDIs. Mothers residing in these areas who responded discordantly to at least three of the survey questions of interest relative to gold standard data from the parent trial were eligible to participate in IDIs. From September to November 2016, qualitatively-trained, local female interviewers (literate with no more than a high school level education), who were different from those who conducted the quantitative questionnaires of the validation study, administered oral consent in Nepali or Maithili and obtained a signature or thumbprint for mothers who agreed to participate. IDIs were conducted one-on-one in a private area in households of participants. An interview guide was created to cover the following topics: willingness to discuss labor and delivery and newborn health, attitudes about newborn health checks, views about whether time since birth affects mothers’ ability to remember what happened, and reflection on questions that generated discordant responses and methods to improve the accuracy of maternal responses.Discussion and interview guides were created in English and translated into Nepali and Maithili by local staff. Debrief sessions were conducted with qualitative interviewers following FGDs and IDIs to reflect on the quality of the discussion/interview, summarize content, edit questions for understanding, and discuss challenges. FGD and IDIs were audio recorded and transcribed from Maithili to Nepali by the interviewers. Supervisory staff fluent in Maithili and Nepali in Sarlahi reviewed the first transcript completed for each translator for quality control. The Nepali transcripts were then sent to translators in Kathmandu for translation to English. Supervisory staff fluent in Nepali and English in Kathmandu also reviewed the first transcript completed for each translator to check for quality. For any additional clarifications that were needed in the English versions of transcripts, another native Nepali speaker fluent in English reviewed Nepali versions and re-translated sections as needed. Recordings, transcripts, and translations were all de-identified.The parent trial and the substudy, including the qualitative component, both received ethical approval from the Johns Hopkins Bloomberg School of Public Health Institutional Review Board, Baltimore, MD, USA. Local approval was received from the Tribhuvan University Institute of Medicine, Kathmandu, Nepal for the parent trial and from the Nepal Health Research Council, Kathmandu, Nepal for the substudy.This analysis focused on questions related to birth size and length of pregnancy and the effect of time since birth on mothers’ memory. We analyzed transcripts using Atlas.ti Scientific Software. We generated hypotheses based on preliminary analyses of quantitative data from the validation study focusing on birth size and length of pregnancy and the interview guides, which deductively informed the development of codes in an initial codebook. In a first round of coding, we both applied initial codes and inductively added new codes based on additional themes that arose. In a second stage of the coding process, all codes were grouped into overarching axes and refined to create a final codebook, which was applied to a second review of transcripts. We used thematic analysis to search for patterns of meaning within and across FGDs and IDIs ,18. UsinWe first conducted two FGDs, each with 6 study staff, who had administered the quantitative form. All study staff were female, had at least a high school diploma and ranged from 20 to 50 years of age. In the first FGD, four of our study staff were of the Madhesi ethnicity and two were Pahadi. In the second FGD, two were Madhesi and four were Pahadi. Study staff reported encountering difficulties in maternal understanding of the length of pregnancy question during both FGDs. Citing that the question was too long and the phrasing of the question was confusing, staff in an FGD also suggested that mothers might require more context to understand what the word “time” referred to as the word was used repeatedly in Nepali and Maithili translations of the question. From staff experiences, mothers occasionally misunderstood the question as asking about the time of day the child was born or the length of time they were in labor, as described below:Participant 2: When we ask about the time, they think we mean morning, afternoon, or night.Participant 3: That’s what happened when we asked this question. (Laughing)Participant 2: Yeah, some say it happened in the morning, others at night.Participant 4: That’s what they immediately understand by time.Participant 2: They specify that evening is a time, too, and that it didn’t happen at night.Participant 3: Like Participant 1 said (pointing at Participant 1) actually, women remember the bits starting from their labor pain, and their attention is stuck there.Moderator: Hmm…Participant 3: And that’s probably the reason why it’s difficult for the mothers to answer the question- (Participant 2 interrupting)Participant 2: When we went for training, we were instructed what the phrase “before time” means in the question. But usually, the mothers don’t know what the phrase “before time” means. They don’t know what ‘time’ is referring to. They don’t know which “time.” Maybe that’s why they get confused.When asked about how the question could be rephrased for better comprehension and what additional probes study staff would use to help mothers understand, FGD participants suggested specifying ‘preterm’ or ‘due date’ in the following discussion:Participant 3: When the child was born, was he born at term or preterm… I don’t think it is right. (Laughing)Participant 4: But this is how we explained in the field. We ask them if the child was born at term or prematurely and explain to take the difference between months and days.Participant 6: If the baby was born prematurely- (Participant 1 interrupted)Participant 1: Was your baby born after the time or before it?Participant 6: We asked like that.Participant 4: They don’t understand like that. (Speaking to Participant 1) Was the baby born right at the due date or before it? Or was the baby born way before the due date or past the due date? Or way past the due date or right on time? That’s how we asked and they understand it easily.Data from IDIs with mothers supported these findings. When asked about the length of pregnancy using the original phrasing of the question, one mother described the time of day her child was born and made reference to the possibility of requiring a caesarean-section had her child not been born within a specified time since labor:Participant: The doctor said that if [I] deliver the baby at 8 o’clock, then it is okay.... The baby was not born at 8 o’clock; she was delivered at 7 o’clock. (21 year old mother)When asking this same mother the question specifying ‘preterm’ as an example of ‘early and specifying ‘overdue’ as an example of ‘late,’ the mother responded, her “baby was born at nine months.”Study staff were instructed to ask the birth size question exactly as phrased in the Nepali DHS and MICS surveys. Some difficulties encountered in administering this question included unfamiliarity with the Maithili word for “average” (“ausat”) and using the Maithili word for “normal” (“samanya”) size in clarifying probes.Participant 3: Maybe because they don’t understand the word “ausat” that they don’t get the rest. Instead of the word “ausat,” when we asked them how was the baby, big, small, average, in their way, they understood it.Participant 2: Yes. When we said smaller or bigger than average, they’d understand immediately. When asked whether [the baby] was bigger or smaller than was supposed to be, they said that it was average [“samanya”- the Nepali word for normal]. The answer comes that way…Moderator: Yeah… In Participant 2’s (pointing at Participant 2) opinion, they wonder what the word means and how they should respond. Similarly, are there any other- (Participant 4 interrupts)Participant 4: When we say ‘ausat’ means average, they don’t understand but when we just say “average” [“samanya”- the Nepali word for normal] they understand.In another FGD, staff explained that the question was sometimes misunderstood as asking about the height or length of the child, rather than the weight.Participant 6: When we ask how big was the baby then the first thing that comes to their mind is the height of the child and not the weight and therefore it becomes necessary to repeat the question indicating that it is related to weight.When asked how mothers’ understanding of this question could be improved, study staff suggested using colored photos of newborns of different sizes to show to mothers for a frame of reference.Participant 6: One picture/photo will not do anything. (P6 and P3 agreeing to the statement). Rather a picture of a fat child and a picture of a thin child might have been helpful. It might be helpful if the pictures were in color.Moderator: So you think that the photo of a fat or thin child will be helpful in understanding this question?(Participant 3 and Participant 6 speaking together) The photo of newly born children in color will be better for understanding of the mothers.Based on this suggestion from the study staff, we created the visual aids in Some of the study staff thought the length of time since birth did affect the accuracy of mothers’ responses in some cases.Participant 6: The women who have a five- or six-month old child would remember. But at the beginning of data collection, there were women who had thirteen-month old children, and it was hard for them. They had even forgotten the answers to some of the questions. Others were all right.Other staff pointed out that maternal accuracy depended more on the individual ability of the mother to remember things.Participant 3: So some of the women remember things even after two years while some others do not remember the things that happen within a month or so.Participant 2: Yes, they do not remember.Participant 6: This is problem of some women. All the women do not have the same memory power.Participant 5: All people do not have same type of brain.This question was also posed to mothers during IDIs, and many mothers noted that their memory of events may fade with time. One mother said that day-to-day obligations and worries prevent her from remembering events at birth.Participant: If the mothers are free from other things and keep on thinking the same thing again and again then they can remember it. Therefore if the mothers have time to think on the time of their delivery and the baby conditions at that time then there is every chance that they can remember for longer time. But they have to engage themselves in so many other domestic chores like how to get baby educated, how to earn both times meal for family, looking after the animals and small children etc. So, most of the time their mind is occupied with these things. Don’t you think that these are more important to spend time on rather than just thinking over and over about their delivery time? (19 year old mother)A frequent theme that emerged from our FGDs with study staff was the distinction between the Nepali and Maithili language and styles. In discussions related to the length of pregnancy question, one staff member referred to using the Maithili language to aid mothers’ understanding, saying “Only some [mothers] won’t [understand]. The mothers will understand if we explain in their language.” Another staff member in a different FGD said, “As long as we explained the question in their style (Maithili), they understood it at once, and we didn’t have to probe a lot.” In discussions related to misunderstanding of the birth size question, one of our staff explained that in “Maithili society,” mothers frequently thought the question was asking about height or length rather than weight.In both FGDs, there was a perception that literacy and education levels of mothers were linked to the ability to understand questions. In reference to the birth size question, one of the staff explained, “When we meet literate women, when we say bigger than average and smaller than average, they understand it right away. But when we meet others, they don’t know what it means.” Later in this same discussion, another staff member shared her experience during household visits, “In fact when we go [to their houses], mothers are a bit intimidated and feel shy to talk to us.” While providing suggestions for props and pictures to use as visual aids with mothers during IDIs, study staff made a distinction between mothers who are “smart” vs “silent.”Moderator: Let’s say (showing a doll) this one here. If you question the mothers showing this doll… If you use this doll to question the mothers, what do you think will happen?Participant 3: You have to show this to silent mothers and question.Participant 4: (Using the doll) This is how the navel was examined for any signs of danger in the body of the child- (P2 interrupting)Participant 2: If that’s the case, they won’t understand our questions at all. And if she’s silent there will be no interview. (Laughing and P4 joins)Moderator: Yeah…Participant 2: You have to show it to a mother who is smart rather than a mother who is silent.The theme of being educated vs uneducated was also reflected in IDIs in responses from mothers related to the effect of time since birth on maternal recall.Participant: Sometimes the things are remembered.Interviewer: They are remembered?Participant: No, it is not all remembered. It is not written down like how the educated people do it. Nobody can remember everything. (21 year old mother)When asked to explain how one mother understood the question about length of pregnancy, she pointed out the difference in literacy and education between herself and the qualitative interviewer.Interviewer: How do you understand this question? What do you think this question is trying to ask?Participant: What you asked me is… See, you are educated and I am illiterate. Despite that I have to use whatever wits I can gather to work. Say, I have to think about what is good and what is bad. I have to find a good path. (24 year old mother)We previously reported low accuracy in maternal reports used to calculate LBW and preterm birth indicators as compared to birthweight and gestational age data collected as part of a community randomized trial in rural Nepal . In thisTo aid maternal understanding of the birth size question, we asked mothers during IDIs to refer to photos of newborns of varying weights and identify one that most resembled the size of her child at birth. We observed that while mothers with LBW babies frequently described their child as being of ‘average’ or ‘normal’ size at birth without the visual aid, mothers often selected the photo of the smallest child. Channon describes the influence of various community and regional factors within a societal context on mothers’ perception of birth size that shape a point of reference for how they assess their child’s size . RelativInterestingly, both study staff and mothers believed accuracy of maternal report would diminish over time, consistent with our initial hypothesis; however, our quantitative findings do not support this theory in the context of generally poor maternal accuracy, even at one month after birth. Previous research has found greater accuracy and agreement between maternal reports of birthweight and gestational age and medical records associated with shorter periods of recall -27 whileWe reflect on the relationships between the study staff of the quantitative validation study and mothers who participated in quantitative interviews. Study staff had been recruited from the same local community in an effort to facilitate more open communication with participants. However, we observed a consistent thread in both our FGDs and IDIs that suggested a power dynamic existed between the study staff and the participant that likely influenced the types of responses collected in our study . OverallFinally, there were several limitations in this study. Although we identified repeat concepts and ideas related to difficulties with the length of pregnancy question, difficulties with the birth size question, the effect of time since birth on mothers’ memory, the language and style differences specific to this setting, and the relationship between staff and mothers in the quantitative interviews, logistical circumstances precluded data collection to continue until saturation; therefore, other contributing factors for the discordant maternal responses may exist. However, we believe that the combination of results from the FGDs and the IDIs do contribute to an understanding of further work to explore how some of these DHS questions may be altered in the future for increased fidelity. Transcripts were subjected to several layers of translation. Qualitative interviewers listened to audio recordings of the interviews that were primarily conducted in Maithili and directly translated these into Nepali, which may have resulted in a loss of emic terms. Transcripts were subjected to quality control procedures, where supervisory staff fluent in both Nepali and Maithili checked the first transcript completed for each translator. Although clarifications were sought from a native Nepali speaker during analysis of English transcripts, the author is a non-native Nepali speaker, further limiting our findings from this analysis.Poor validity of LBW and preterm birth indicators based on maternal response may be partly attributed to challenges in maternal understanding of questions assessing birth size and length of pregnancy. Findings from this qualitative study suggest specific terms in Maithili translation and sentence structure affected maternal comprehension. Visual aids, like pictures of newborns of varying sizes, may help to scale maternal perception of birth size in specific settings. In addition, relationships and dynamics between interviewers and participants may affect the nature of responses. More work is required to further explore maternal comprehension of these questions in similar rural and low-income settings as a prelude to improving content and context in DHS/MICS surveys.


The relationship between birth weight and blood pressure has not been well explored in Chinese children and adolescents. The aim of this study was to investigate the relationship between birth weight and childhood blood pressure in China.A total of 15324 children and adolescents (7919 boys and 7405 girls) aged 7–17 years were stratified into six birth weight groups. Analysis of covariance and binary logistic regression were used to analyse the relationship between birth weight and blood pressure while controlling for potential confounding factors, including age, gestational age, season of birth and area of residence.P = 0.017), and children with heavier birth weights also had higher SBP . No significant relationship was found between birth weight and diastolic blood pressure (DBP). The overall rate of hypertension was 10.8% (12.1% in boys and 9.4% in girls). The median weight group (2500–2999 g) had the lowest rate of hypertension (8.9%). Compared with children in the median weight group, children with lower birth weight had a higher prevalence of hypertension , and groups with higher birth weights also had higher risks of hypertension .The group with birth weights from 2500 to 2999 g had the lowest prevalence of hypertension (8.9%). Lower birth weight children (< 2000 g) had significantly higher systolic blood pressure (SBP) (106.00 ± 0.72, Excluding the confounding effect of obesity, a U-shaped relationship between birth weight and risk of hypertension was found in children and adolescents in Chinese cities. Birth weight significantly influences SBP but has a minimal effect on DBP. Further basic research on foetal development and programming may shed light on this phenomenon. There is a consensus that cardiovascular function and blood pressure are determined during childhood and continue into adulthood . ChildhoChildhood blood pressure is affected both by genetic and environmental factors, including factors at birth (birth weight) and factors after birth  –6. Poor The developmental origins of health and disease (DOHaD) theory and the life course theory (LCT) lead to the hypothesis that nutritional status in utero may permanently change the body’s structure, function and metabolism in ways that cause chronic diseases in later life –12. TherIn the present study, we analysed data from a metabolic syndrome investigation among children and adolescents in six cities across China and adjusted for the influence of BMI and other confounders. We finally demonstrated the potential influence of birth weight on childhood blood pressure. The purpose of the current study was first to investigate the prevalence of hypertension in children and adolescents in China. Second and more importantly, we aimed to reveal the association between birth weight and childhood hypertension.Subjects were recruited from a school-based cluster investigation of metabolic syndrome among children and adolescents in six provincial capitals in China in September 2010 . The iniWell-trained investigators measured anthropometric indices, including weight and height, following a standard protocol, referring to a previous study . Informa2). The BMI reference material issued by the World Health Organization (WHO) in 2007  was adopted to establish the BMI Z-scores (BAZ) [Body mass index (BMI) was calculated as body weight in kilograms divided by height in metres squared . Because BMI or BAZ have long been recognized as core and volatile factors influencing blood pressure, a two-step adjustment was conducted. Confounding factors excluding BAZ were first adjusted , and BAZ was subsequently adjusted for along with the other factors . The quadratic and cubic models were used as simulators of curve estimation. All tests were two-sided, and the results were considered significant when the p-value was ≤0.05. Statistical analyses were performed using SPSS for Windows .Normally distributed variables are expressed as the mean ± standard deviation (SD) and were compared by Student’s t test. Categorical variables are expressed by frequencies (percentages) and were compared by χP < .001). The prevalence of hypertension in boys was significantly higher than in girls .The demographic data and anthropometric variables of the subjects were stratified by sex and are listed in Table P = .017), while children with birth weights over 3500 g also had higher SBP . The additional adjustment for BAZ did not change the association between birth weight and blood pressure. The quadratic or cubic model estimated a U-shaped association between birth weight and SBP, even after the adjustment for BAZ . Girls with birth weights over 3500 g also had higher SBP . Boys or girls with extremely low birth weight did not show significant SBP differences when compared with the reference group. However, the adjusted mean was higher than that of the normal group, suggesting that the statistical insignificance might be due to the small sample size.Table P = .075), while those with a birth weight over 3500 g also had a higher DBP . When stratified by sex, the association became nonsignificant. Girls with birth weights over 3500 g had higher DBP .The association between birth weight and DBP was also U-shaped among the different birth weight groups when BAZ was controlled Fig. . The lowThe prevalence of hypertension in different birth weight groups is shown in Table The current study examined the association between birth weight and childhood blood pressure by collecting school-based data from six Chinese cities. This study is also the first, to the best of our knowledge, to investigate the relationship between birth weight and childhood hypertension using a large census from urban areas in China. In summary, birth weight had a profound impact on childhood blood pressure and the prevalence of primary hypertension in Chinese children and adolescents. Moreover, the association between birth weight and blood pressure remained U-shaped after adjusting for various confounding factors, including BAZ, season of birth and area of residence. Children with birth weights from 2500 to 2999 g had the lowest blood pressure and lowest risk for childhood hypertension. Birth weight significantly influenced systolic blood pressure. However, its effect on diastolic blood pressure remains unknown.Some of the previous studies suggested an inverse relationship between birth weight and childhood blood pressure, while others showed a positive relationship or no association at all. In 2012, Edvardsson et al. reviewed the existing studies and listed several reasons that might drive the results apart. They believed that inadequate adjustment for potential confounders, failure to use standard blood pressure values, and disparities in the target populations together contributed to the discrepant results . The resThe proposed mechanisms linking birth weight and childhood hypertension have been widely studied. As has been shown in animal models and partly in humans, the hyperfiltration theory suggests that the reduction in nephron number, a decreased kidney mass and a reduction in renal reserve in low birth weight children enhance salt sensitivity and increase the risk of hypertension –24. The As even small increases in blood pressure are known to increase the long-term risk of cardiovascular diseases and hypertensive nephropathy, it is crucial to understand the aetiology of primary childhood hypertension and to look for potential precautions. Li et al. reported that the prevalence of abnormal blood pressure, together with obesity, dramatically increased from 1993 to 2013 in China . PaediatIn this work, the study population was well defined, and we used Chinese-specific standardized methods to collect data. The effects of main potential confounders, especially BAZ, were controlled in the analysis of covariance. However, the present study had limitations. This was a cross-sectional study, and there might be some recall bias in the interview results. Second, information on growth patterns was not collected. An increasing amount of evidence is available showing that birth weight can influence childhood growth velocity and influence blood pressure , 32. ThiThis study revealed that birth weight was associated with blood pressure levels and the risk of hypertension in Chinese children and adolescents. Both low and high birth weight increased the risk of hypertension. Birth weight influenced SBP but had a minimal effect on DBP.


The objectives of this study were to 1) evaluate the influence of treatment with praziquantel on the inflammatory milieu in maternal, placental, and cord blood, 2) assess the extent to which proinflammatory signatures in placental and cord blood impacts birth outcomes, and 3) evaluate the impact of other helminths on the inflammatory micro environment.This was a secondary analysis of samples from 369 mother-infant pairs participating in a randomized controlled trial of praziquantel given at 12–16 weeks’ gestation. We performed regression analysis to address our study objectives. In maternal peripheral blood, the concentrations of CXCL8, and TNF receptor I and II decreased from 12 to 32 weeks’ gestation, while IL-13 increased. Praziquantel treatment did not significantly alter the trajectory of the concentration of any of the cytokines examined. Hookworm infection was associated with elevated placental IL-1, CXCL8 and IFN-γ. The risk of small-for-gestational age increased with elevated IL-6, IL-10, and CXCL8 in cord blood. The risk of prematurity was increased when cord blood sTNFRI and placental IL-5 were elevated.Our study suggests that fetal cytokines, which may be related to infectious disease exposures, contribute to poor intrauterine growth. Additionally, hookworm infection influences cytokine concentrations at the maternal-fetal interface.NCT00486863).ClinicalTrials.gov . Hookworm coinfection at 12 weeks’ gestation was, however, related to elevated levels of certain cytokines in the placenta . Adverse perinatal outcomes account for a substantial proportion of the global burden of disease  and lay Schistosoma japonicum endemic area, Kurtis and colleagues found increased concentrations of pro-inflammatory cytokines including interleukin-1 (IL-1β) and tumor necrosis factor (TNF) in placental and cord blood among women with S. japonicum infection [With respect to helminthiasis, less is known with regard to treatment strategies for pregnant women. In a non-interventional study conducted in a nfection . Furthernfection . This raHealthy pregnancies are characterized by a placental microenvironment that is biased toward a T-helper 2 (Th2) cytokine milieu , 13, andAs part of the aforementioned RCT conducted in Leyte, The Philippines, we investigated whether treatment for schistosomiasis at 12–16 weeks’ gestation and the presence of other helminth infections would influence the cytokine micro-environment. Specifically, the objectives of this study were to 1) examine the impact of treatment with praziquantel on the inflammatory milieu in maternal, placental, and cord blood, 2) assess the extent to which proinflammatory signatures in placental and cord blood impacts the risk for LBW, SGA, and prematurity, and 3) evaluate the impact of other helminths on the inflammatory micro environment.S. japonicum and soil transmitted helminths (STHs) eggs using the Kato-Katz method [S. japonicum, age 18 or older, otherwise healthy as determined by physician history, physical examination and laboratory studies, and pregnant at 12–16 weeks’ gestation with a live, singleton, intrauterine fetus. Women who met eligibility criteria (n = 370) were randomly assigned (1:1) to receive either over-encapsulated praziquantel (30 mg/kg × 2) or over-encapsulated placebo (dextrose), as a split dose over three hours in a double-blind fashion.This was a secondary analysis of data from a double blind placebo-controlled RCT examining the effects of praziquantel given at 12–16 weeks’ gestation for the treatment of schistosomiasis on pregnancy outcomes . The RCTz method , 24. TheAt 12–16 weeks’ gestation, a detailed demographic and medical history was collected and physical examination (including anthropometric measures) conducted. Weight, height and other anthropometric measures were made as described , 26. AntS. japonicum, low, moderate and heavy intensity infections were defined as 1–99, 100–399 and ≥400 eggs per gram (epg), respectively; Ascaris lumbricoides, low, moderate and heavy intensity infections were defined as 1–4,999, 5,000–49,999 and ≥50,000 epg, respectively; Trichuris trichuria, low, moderate and heavy intensity infections were defined as 1–999, 1,000–9,999 and ≥10,000 epg, respectively; hookworm, low, moderate, and heavy intensity were defined as 1–1,999, 2,000–3,999 and ≥4,000 epg, respectively [Stool samples were collected and intensity of helminth infection was determined as the mean of the three samples, and categorized using WHO criteria as follows: ectively , 24.th percentile for gestational age based on the INTERGROWTH standard [Following initial stabilization of the newborn and mother, placental samples (wedge biopsy and pooled blood) and cord blood were collected. Newborns were examined and weighed within 48 hours of delivery on a Tanita model BD 585 portable scale . LBW was defined as birthweight below 2500g, and SGA as birthweight below the 10standard . PretermMaternal 12-week, 32-week, placental, and cord blood serum samples were aliquoted and stored at -80°C prior to testing. All available samples at each timepoint were used for comprehensive biomarker testing–only 238 cord blood samples were available. Assessment of biomarkers in the blood samples was conducted at the Center for International Health Research Laboratory in Providence, RI, USA. Biomarkers measured include IL-1, 2, 4, 5, 6, 8, 10, 12 and 13, interferon gamma (IFN-γ), TNF, chemokine ligand-9 (CXCL9) and soluble TNF receptors I and II (sTNFRI and sTNFRII). Analytes were quantified using a multiplex bead-based platform  as described previously . The lowIn analyses examining the impact of praziquantel treatment and helminth infections on cytokine production in maternal, placental and cord blood, these biomarkers were outcome measures. These biomarkers were separately evaluated as predictors of adverse pregnancy outcomes. Cytokine production was considered as exposure or outcome in this analysis. Three different measures of cytokine production were also employed: (i) cytokine concentration in ng/L, (ii) the proportion of those with an 'elevated' cytokine concentration, and (iii) the proportion with cytokine present at a level above the assay detection limit. The means (±SE) of maternal cytokine concentrations at 12- and 32-weeks’ gestation were also estimated and the mean difference and 95% confidence interval (CI) estimated.P-values obtained from Fisher’s exact tests. Further, the means (±SE) of cytokine concentrations at 32-weeks’ gestation (with 95% CI) were estimated within treatment subgroups and compared using linear regression. The extent to which the ratios of placental blood cytokines to maternal 12-week cytokines, and placental blood cytokines to maternal 32-week cytokines differed by treatment was also evaluated using Wilcoxon rank-sum tests.To investigate the effect of praziquantel treatment on cytokine production, the proportions of participants with cytokine concentrations above detection limits in maternal 32 weeks’, placental, and cord blood samples were compared across treatment groups, and Generalized estimating equation regression models were used to assess the impact of each helminth infection at 12 weeks’ gestation on the proportion of participants with cytokines at a level above the assay detection limits in maternal 12- and 32-weeks’ gestation, placental and cord blood samples. Log-binomial models were used to evaluate the relationship between elevated maternal 32-week peripheral cytokines and placental and cord blood cytokines, and risk ratios (RRs) with 95% CI obtained. Log-binomial models were also used to examine the influence of elevated placental and cord blood cytokines on the risk of LBW, SGA, and prematurity. Log-binomial models provide RR estimates, which are intuitive and more appropriate for non-case control studies. The log-binomial model is however numerically unstable, and often fails to converge, and in those instances, log-Poisson models, which provide consistent but not fully efficient estimates of the RR and its CIs were employed .P-value <0.15, with no variables forced into the model. Regression models were adjusted for predictors as specified in the footnotes of the respective tables and figures. Variables included in the models were praziquantel treatment, maternal age , newborn sex , maternal height (cm), maternal weight at 12 weeks (kg), maternal underweight (body mass index <18.5kg/m2), parity (number), socioeconomic status (quartiles), reported smoking status , alcohol use , and detection of S. japonicum, A. lumbricoides, T. trichuria, and hookworm, at 12 and 32 weeks’ gestation .Potential confounders known to be related to cytokines and/or perinatal outcomes were considered for inclusion in multivariable models. In addition, potential confounders were identified through stepwise regression techniques, significant at P-values for effect modification were obtained by introducing an interaction term to the log-binomial regression model, in which praziquantel treatment status was multiplied by the biomarker category, and the model compared to the model without the interaction term using the likelihood ratio test. Possible effect modification by hookworm infection at 12 weeks’ gestation was also explored.P-values were 2-sided and statistical significance was defined as P-value <0.001, based on the Bonferroni correction for the familywise error rate , to account for multiple comparisons [α level. All data in our study were de-identified. Analyses were conducted using SAS 9.4 .parisons . CIs werThe study was approved by both the Rhode Island Hospital Institutional Review Board in Providence, RI, USA and the Ethics Review Board of the Research Institute of Tropical Medicine in Manila, The Philippines. This trial was registered with ClinicalTrials.gov, number NCT00486863.Participants included in this analysis were 369. Detailed information on the cohort’s participant characteristics have been previously presented . Most ofFig 1 details the selection of samples for cytokine quantification. Maternal cytokine concentrations significantly decreased from 12 to 32 weeks’ gestation (S2 Supporting Information) for sTNFRI . The concentration of sTNFRII , IL-6  and CXCL8  decreased while the concentration of IL-13  increased from 12 to 32 weeks’ gestation but the Bonferroni corrected P-values were not significant.Fig 2). Praziquantel treatment lowered the concentration of anti-inflammatory IL-10 by 32-weeks’ gestation ), though the difference was not significant after Bonferroni’s correction . Praziquantel treatment did not alter the concentration of other cytokines considerably. There was also no evidence that praziquantel significantly altered the likelihood of detecting cytokines in maternal serum at 12 and 32 weeks, or in placental or cord blood (Table 2).The proportion of participants with detectable cytokines varied widely from 1–100% but tended to be highest in cord blood. To examine the impact of praziquantel treatment on cytokine concentrations, the concentration of cytokines in maternal blood at 32 weeks’ gestation was compared by treatment group , most were of light intensity . Hookworm infection was associated with a 1.42 to 2.58-fold increased risk of elevated placental levels above detection limits for some cytokines : IL-1 , IL-5 , CXCL8  and IFN-γ  in multivariable models. Hookworm infection was not associated with an increased risk of detectable cytokines in maternal peripheral or cord blood . S7 Supporting Information reports the concentration of each cytokine at which the 90th percentile level was reached. Participants with elevated maternal 32-week IL-4 , IL-12 , and IFN-γ  were more likely to have elevated placental levels of the same cytokines. There were no significant associations in the level of maternal cytokines with the levels of the same cytokines in the cord blood.We investigated the extent to which cytokine levels in maternal peripheral blood was related to cytokine levels in placental and cord blood in multivariable log-binomial regression models (Tables  were associated with 2-fold increased risk of SGA: IL-10 (Th2)–RR = 1.80 , IL-6 –RR = 1.84 , and CXCL8 –RR = 1.84  . Elevated sTNFRI  and IL-5 in placenta  were associated with increased risk of prematurity . These associations were not significant following Bonferroni correction. There was no evidence that levels of other placental and cord blood cytokines were related to the occurrence of prematurity, LBW and SGA.The prevalence of LBW, prematurity and SGA were 14% (n = 52), 9% (n = 33) and 23% (n = 84), respectively. Elevated levels of certain cytokines in the cord blood Click here for additional data file.S2 Supporting Information(DOCX)Click here for additional data file.S3 Supporting Information(DOCX)Click here for additional data file.S4 Supporting Information(DOCX)Click here for additional data file.S5 Supporting Information(DOCX)Click here for additional data file.S6 Supporting Information(DOCX)Click here for additional data file.S7 Supporting Information(DOCX)Click here for additional data file.S8 Supporting Information(DOCX)Click here for additional data file.


A 72-year-old woman was referred to our hospital for a persistent right upper abdominal pain after a fall three weeks prior. An ultrasound was performed. This exam demonstrated a heterogeneous cystic mass in the right hepatic lobe, just under the right hemidiaphragm, measuring 11 cm in diameter, with multiple mobile septa , neoplastic or tumorous , and others .During physiological clot lysis the presence of multiple septa and vegetations, mural nodules, and thickened cyst wall may be observed . A liquiContrast-enhanced US improve the sensibility showing microbubbles oozing from the cyst wall into the cyst cavity when there is intracystic bleeding and revealing no enhancement of the intracystic structures, then suggesting intracystic clot. Signal intensities and the MRI characteristic on follow-up examinations may be also helpful to demonstrate the hemorrhagic nature of a cystic lesion and to differentiate it from other mucinous cyst on MRI.Imaging may fail to differentiate hepatic simple cysts from malignant or premalignant mucinous cystic lesions such as biliary cystadenomas. Hepatic simple cysts can be treated conservatively, whereas malignant or premalignant cysts require complete resection. The concentration of TAG-72 in cyst fluid accurately differentiate simple cyst from mucinous cysts requiring complete resection [The therapeutic approach for HHC has varied from simple observation to more invasive approaches. HHC that are mildly symptomatic or asymptomatic can be initially treated by conservative approach with a series of imaging control to monitor the evolution. If there is a deterioration or persistence of symptoms, a laparoscopic or open de-roofing with cyst wall biopsy or enuclation is indicated. When there is spontaneous resolution, a follow-up by US is sufficient.In conclusion, hemorrhagic hepatic simple cyst represent a difficult diagnosis because of its imaging similarities with other cystic or mucinous hepatic lesions. The mobility of septa on US imaging, when not found on CT images, is suggestive of an hemorrhagic content. Enhancement of thick septa, mural nodules or thickened wall are typically found in malignant lesions. MRI signal intensities help to differentiate hemorrhagic content of a cyst from other mucinous cyst. All these elements may lead to the accurate diagnosis and guide appropriate therapeutic decisions.


The increase in ambient temperatures (Ta) and emissions of greenhouse gases over the last century has focused attention on the effects of ambient temperatures on health outcomes. We aimed to investigate the association between Ta and the clinical measures of term low birth weight (tLBW) and small for gestational age (SGA) in singleton term infants using a decade of regional hospital data in southern Israel.We linked all births in Soroka University Medical Center in the southern district of Israel insured by Clalit Health Services with pregnancy Ta estimated by our novel hybrid spatio-temporally resolved prediction model. Logistic regression generalized additive models and general linear models were used, with either tLBW or SGA as the dependent variable, modeling entire pregnancy and trimester-specific Ta adjusting for seasonality, time trend, particulate matter, maternal age, gravidity, parity, ethnicity, sex, poverty index and population density.. The average and the median Ta across the entire pregnancy were 19.9  degrees centigrade. The lowest Ta quartile (Ta = < 18.5) was associated with higher risk of tLBW  while the highest Ta quartile (Ta > =21.3) was not significantly associated with tLBW , in comparison to the two intermediate quartiles. When analyzing SGA as the dependent variable, the lowest Ta quartile was associated with significantly higher risk of SGA  while the highest quartile was associated with significantly lower risk of SGA  in comparison to the two intermediate quartiles.The study population included 56,141 singleton term newborns, with 1716 (3.1%) cases of tLBW and 8634 (15.4%) cases of SGAOur findings suggest that lower pregnancy Ta may increase the risk of tLBW and SGA, and higher pregnancy Ta may decrease the risk of SGA in singleton term infants in southern Israel. The rise in temperatures over the last century and emissions of greenhouse gases has focused attention on the effects of increasing heat . The effMany studies have shown that heat is related to various health outcomes including an increase in total and cause specific mortality , 7–12 asAmong many susceptible groups, pregnant women, fetuses and children are particularly vulnerable to the physiologic stress of extreme temperatures and sudden temperature variation , 18. YetLi and colleagues , examineExtremes of both high –29 and lThese conflicting results published to date on the relationship of Ta with birth outcomes may be due to several reasons. There could be differences between local climatic and geographical conditions of the study areas as well as different levels of acclimatization among the pregnant women across the populations . One estWhile preterm birth and multiple births pregnancy are the major reasons for low birth weight (LBW), approximately 90% of newborns are singleton term infants. tLBW and small for gestational age (SGA) are two main clinical measure that define fetal growth restriction in term infants, a phenomenon that predicts various complications in early childhood and beyond, including perinatal mortality, impaired immune system, respiratory morbidity and neurobehavioral disorders , 39. In The research area is the Southern district of Israel see Fig. . The resThe study population included all singleton term births in Soroka University Medical Center (SUMC) during October 2004 – December 2013, residing in the southern district of Israel and insured by Clalit Health Services, the largest health care provider in Israel, covering approximately 70% of a population of 730,000 residents in the area , 45. TheN = 23) or birth weight (N = 9) and subjects with very extreme Ta , leaving 56,141 subjects for analysis. tLBW was defined as birth weight < 2500 g, and SGA was defined as birth weight < 10th percentile (in Israel), according to newborn sex and gestational age at delivery [Maternal and birth data were routinely collected in the Admission-Transfer-Discharge SUMC computerized database. The study population contained 56,184 singleton term births, from which we excluded subjects with missing Ta (delivery .2 results: 0.966–0.986). To estimate 24 h mean Ta exposure at each mother’s residence during pregnancy, we spatially joined each mother’s residence to the corresponding Ta grid cell centroid (1 km*1 km resolution) into which it fell  exposure data were generated by a novel hybrid spatio-temporally resolved prediction model . Briefly2.5) concentrations were assessed using a hybrid satellite based model incorporating daily satellite remote sensing data at 1 × 1 km spatial resolution [2.5 mass concentration from the Ministry of Environmental Protection monitoring sites against AOD, traditional land use regression temporal and spatial predictors to generate daily high resolution PM2.5 estimations. More in depth details can be found in Kloog 2015 [Air pollution: Daily average particulate matter < 2.5 μm , gravidity, parity, ethnicity (Jewish / non-Jewish), newborn sex, census-level poverty index  and population density . The two latter variables were defined and calculated by the Israel Central Bureau of Statistics [For initial analyses, we used logistic regression generalized additive models with either tLBW or SGA as the dependent variable, modeling entire pregnancy Ta using a thin plate regression spline . The analysis was adjusted for seasonality and time trend using categorical variables for calendar month and year, PMatistics .Further analyses used logistic regression generalized linear models with either tLBW or SGA as the dependent variable, modeling entire pregnancy Ta using a categorical variable and each of the two extreme Ta quartiles with the two middle quartiles, adjusting for the same covariates as described above. Possible effect modification by ethnicity or urbanity were tested by adding interaction terms to these models. Trimester-specific Ta exposures were modeled similarly, in a mutually adjusted model that included the exposure in each trimester as a separate variable, in order to avoid bias from auto-correlation among Ta trimester values .N = 18,412). Statistical analyses were performed in R statistical software version 3.3.2  with general additive models using package mgcv [In a sensitivity analysis, we fit a model that included only those newborns for whom addresses were geocoded at the house or street level , nonlinear (estimated degrees of freedom = 3.2), non-monotonic association between entire pregnancy average Ta and tLBW, with both low and high temperatures associated with higher risk in comparison to intermediate temperatures, although only on low Ta was the association significant  and the highest Ta quartile Ta > =21.3) to the two intermediate quartiles (18.5 < Ta < 21.3) using logistic regression models adjusted for the same covariates as above. The lowest Ta quartile was associated with higher risk of tLBW  while the highest Ta quartile was not significantly associated with tLBW , in comparison to the two intermediate quartiles. When analyzing SGA as the dependent variable, the lowest Ta quartile was associated with significantly higher risk of SGA  while the highest quartile was associated with significantly lower risk of SGA  in comparison to the two intermediate quartiles , and increased risk for SGA with low Ta quartile during the 3rd trimester , while all other associations were not statistically significant , the lowest Ta quartile showed a stronger association , and the highest Ta quartile was still not associated  with tLBW, in comparison with the two intermediate quartiles. When examining Ta quartiles association with SGA in this sub-population, the associations were similar to the primary analyses but not statistically significant . When adding an interaction term to the main models to test for possible effect modification by ethnicity, we did not find any significant interaction between Ta and ethnicity . Similarly, no significant interaction with urbanity was found .In a sensitivity analysis for the entire pregnancy average Ta, including only those newborns whose addresses were geocoded at the building or the street level  which are known predictors of health and disease. From the studies that did examine LBW we found 3 ecological studies –56 and oAnother thing to note is that there are clear and significant changes in average Ta in Israel in recent decades. Since the 1970s, average annual temperature increased by close to 1 °C . These tThere are several limitations in the present study. First, the spatial resolution of the exposure was 1 × 1 km and exposures were assigned based on best-available residential address geolocation. We are planning to improve our hybrid models using new available satellites and machine learning methodologies to generate higher spatial resolution data reaching 100 m, which will further reduce exposure error. Other limitations with the SUMC database include the lack of some health and personal level data such as maternal weight and height, chronic hypertension, preeclampsia or gestational hypertension, maternal smoking and physical activity, which were not available. On the other hand, we do not have a reason to think that these characteristics are a common cause for both ambient Ta and tLBW or SGA, and therefore they should not be a source of concerns of residual confounding.Our findings suggest that lower pregnancy Ta may increase the risk of tLBW and SGA, and higher pregnancy Ta may decrease the risk of SGA in singleton term infants in southern Israel. Future studies may examine associations of Ta with birth weight in preterm infants and examine possible mechanisms of effects of Ta on fetal growth.


To determine the relationship between plaque composition and low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (Apo-B), and Apo-A1 using virtual-histology intravascular ultrasound (VH-IVUS).We assessed plaque composition in patients with stable coronary artery disease (SCD) admitted to our hospital for percutaneous coronary intervention (PCI) between November 1, 2012, and March 10, 2015. Before PCI, fibrous (FI), fibrofatty (FF), necrotic core (NC), and dense calcium (DC) regions were evaluated using VH-IVUS, and the contributions of each to the culprit lesion volume were recorded. Plasma LDL-C, HDL-C, Apo-B, and Apo-A1 levels were assessed before PCI. The relationship between the regions on VH-IVUS and plasma lipid levels was assessed. Patients were categorized into low Apo-B (LAB) and high Apo-B (HAB) groups, based on the overall cohort median Apo-B level.We enrolled 115 patients  with 57 and 58 patients in the LAB (Apo-B ≤ 90 mg/dL) and HAB (Apo-B ≥ 91 mg/dL) groups, respectively. Vessel, plaque, and %NC volumes were significantly greater in the HAB group than in the LAB group. The %FI, %FF, and %DC volumes were similar in both groups. In all 115 patients, the %NC volume correlated with LDL-C  and Apo-B  but not with HDL-C and Apo A-1. The high-sensitivity C-reactive protein level tended to be higher in the HAB group than in the LAB group. Multiple regression analysis showed that being male, Apo-A1, and Apo-B were significant predictors of %NC volume extent.Elevated Apo-B level was related to the %NC in target coronary artery lesions in SCD patients, suggesting a role of Apo-B as a biomarker of unstable plaque in this population. Low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) are standard biomarkers used to predict adverse cardiovascular events in patients with ischemic heart disease. , 2 HowevUsing virtual-histology intravascular ultrasound (VH-IVUS), the PROSPECT study demonstrated that the necrotic cores (NCs) of thin-cap fibroatheromas are sites at which processes associated with adverse cardiovascular events occur.  IntensivTherefore, we used VH-IVUS to investigate the relationship between Apo-B and atheroma composition in patients with SCD. Our hypothesis was that Apo-B could be a potential biomarker for acute coronary syndrome.The Fukushima Red Cross Hospital Ethics Committee approved this study, and all study participants provided written informed consent for participation before enrollment.We prospectively evaluated 334 consecutive patients with SCD that visited our hospital for percutaneous coronary intervention (PCI) between November 1, 2012 and March 10, 2015, for study eligibility. Forty patients selected medical therapy. A total of 294 patients who underwent diagnostic coronary angiography (CAG) and had coronary artery stenosis greater than 75% were eligible for the study. PCI indications were evaluated according to the Japanese Society of Cardiology guidelines for elective PCI in patients with SCD. [IVUS examinations of the culprit lesions were performed before PCI. A phased-array, 20-MHz, 3.2-F IVUS catheter  was placed in the distal coronary artery and pulled back to the aorto-ostial junction using a motorized catheter pull-back system set at 0.5 mm/s . The gray-scale IVUS and captured radiofrequency data were written onto a DVD-R.Off-line gray-scale and VH-IVUS analyses were performed using echoPlaque 4.0 software . Corresponding proximal and distal reference IVUS images were identified for each culprit lesion. These were analyzed to determine the plaque volume within the involved arterial segment. Gray-scale IVUS analysis was performed according to the American College of Cardiology Clinical Expert Consensus Document on Standards for Acquisition, Measurement and Reporting of Intravascular Ultrasound Studies.  In the gLaboratory evaluations of plasma lipid and apolipoprotein levels were performed within two days before PCI. Commercial reagent kits  were used to analyze plasma TC, LDL-C, HDL-C, and triglyceride (TG) levels, and lipid concentrations were measured using an automated chemical analyzer . Apo-B and Apo-A1 were measured by immunonephelometry, and high-sensitivity C-reactive protein (hs-CRP) levels were measured by nephelometry. Apolipoprotein levels were measured at a central clinical laboratory .t-test, and Wilcoxon’s signed rank test. All statistical assessments were two-sided and evaluated at a significance level of 0.05. To investigate the relationship between the NC and each lipid in all patients (not divided into LAB and HAB groups), Pearson’s correlations between %NC and Apo-B, %NC and LDL-C, and %NC and Apo-A1 were also evaluated. To detect the amount of shared variance and the strength of the relationship between the variables of interest, multiple least square regression analysis was performed. The statistical analysis indicated a significant relationship between %NC and the 1st model (model 1), which comprised seven predictive variables including Apo-B ; and the 2nd model (model 2), which comprised seven predictive variables including LDL-C . All statistical analyses were performed using Ekuseru-Toukei for Windows, version 1.02 .Data are presented as means ± standard error. Categorical data are presented as numbers (n) and percentages (%). Categorical and continuous variables were compared between the LAB and HAB groups using the chi-square test, Welch’s The median Apo-B level in the 115 study patients was 91 mg/dL. There were 57 and 58 patients in the LAB (Apo-B ≤90 mg/dL) and HAB (Apo-B ≥ 91 mg/dL) groups, respectively. Antiplatelet and statin treatments were more frequent in the LAB group than in the HAB group . CompareRepresentative VH-IVUS images are shown in In the present study, we demonstrated that the lesion length and vessel, plaque, and %NC volumes were higher in patients with high plasma Apo-B levels than in those with low plasma Apo-B levels. Interestingly, the Apo-B (r = 0.2483) and LDL-C (r = 0.2105) levels were positively correlated with %NC volume in the VH-IVUS volumetric analyses. In this study, Apo-B and %NC appeared to be more closely correlated than were LDL-C and %NC. However, we found no correlation between Apo-A1 and %NC. Furthermore, although hs-CRP tended to be higher in the HAB group than in the LAB group, this difference was not statistically significant. On the other hand, multiple regression analysis (model 1) revealed that the male sex, Apo-A1, and Apo-B were significant predictors of %NC volume. It is interesting that Apo-A1 was not correlated with %NC volume on Pearson’s correlation analysis but affected it on the regression analysis. This can be explained by the fact that the significance of Apo-A1 in the model is dependent upon all the factors being in the model. Male sex and Apo-B were acting as a sort of mediator of the relationship between Apo-A1 and %NC volume. Moreover, these results showed that Apo-B induces plaque progression, vascular remodeling, and, especially, NC progression, the latter of which is also affected by male sex and Apo-A1. Additionally, Apo-B might be involved in plaque vulnerability. Furthermore, in model 2 of the regression analysis, age and LDL-C were significant predictors of %NC volume although the value of the correlation coefficient adjusted R-square (0.0846) was very low. On the other hand, the value of the correlation coefficient adjusted R-square (0.9110) of model 1 including Apo-B was very high, and %NC in the lesion plaque of SCD patients could be predicted by this model.A previous study demonstrated that the accuracy of VH-IVUS for ex vivo tissue characterization exceeds 93.5%. When notNumerous previous studies have evaluated the use of plasma biomarkers for the identification of high-risk lesions or vulnerable plaques in patients with SCD. Furthermore, VH-IVUS has frequently been used to obtain detailed information about the composition and characteristics of coronary atherosclerotic plaques. Consequently, several plasma biomarkers and the Compared with LDL-C, non-HDL-C and Apo-B more successfully predict cardiovascular disease (CVD) risk.  The AMOROf note, Moss et al.  reportedMcGill et al.  were theElevated hs-CRP is a surrogate marker of the inflammatory process that is reportedly related to the plaque burden in non-culprit coronary arteries  and the Fluorescein angioscopy and microscopy images of human coronary artery plaques  showed tThe present study has some limitations worth noting. First, this was a single-center study, and the study sample was relatively small. Therefore, our results need to be validated by larger studies. Second, follow-up data were not available. Therefore, we could not assess the prognostic implications of an elevated Apo-B level in patients with SCD. Despite these limitations, our study identified a correlation between the Apo-B level and plaque composition of the target coronary artery lesion in patients with SCD.In conclusion, an elevated Apo-B level was related to the %NC of the target coronary artery lesion in patients with SCD. Our findings suggest a potential role for Apo-B as a biomarker of unstable plaques in this patient population. Moreover, our study showed the Apo-B more strongly related to plaque advancement, and therefore is a more important contributing factor to the development of acute coronary syndrome than LDL-C. Therefore, future studies should further evaluate the role of Apo-B in cardiovascular disease pathogenesis.S1 File(XLSX)Click here for additional data file.


P-value < 0.05.Improving short birth interval practice is a key strategy to reduce maternal mortality, neonatal mortality, adverse pregnancy outcomes, high fertility rate and undermining economic development efforts. However, there were limited evidences on short birth interval practice and its determinant factors in Ethiopia. This study aimed to determine the prevalence of short birth interval practice and associated factors among pregnant women. Institutional based cross-sectional study was conducted among 418 pregnant mothers using stratified sampling technique. Multivariable logistic regression analysis was performed at the level of significance of Short birth interval practice was found to be 40.9%. Child death , female child , younger maternal age , contraceptive non-use , increase duration of breastfeeding  and home delivery  were found to be significantly associated with short birth interval practice. The prevalence of short birth interval practice is high. Multi disciplinary approach through improving maternal and child health care are recommended to prevent short birth interval practice. Birth interval is the length of time between two successive live births . EvidencGlobally, there were 287, 000 maternal deaths and 3.1 million neonatal deaths in 2013 and most of these occurred in south Asia and in sub-Saharan Africa , 6. EDHSStudies done in USA, DHS from 66 low and middle-income countries and in Bangladesh showed; neonatal, infant, child mortality and stillbirth are high when the women practice short birth interval –12. EvidIn Ethiopia, Short birth interval affects fertility as well as neonatal, infant and Childhood mortality . PromotiBeyond the health implications, close birth intervals increase population growth, makes women to be less productive and the family will invest more of their limited resources to child care .According to researches; maternal age, level of education, marital status, residence, loss of child, sex of child, contraceptive use, breast feeding, and age of pregnancy are contributing factors , 21–28. The study was conducted at Debremarkos governmental health institutions from April 1 to July 30, 2016. The town has 101,582 populations . The numSingle population proportion formula was used to calculate the total required sample size of the study considering the assumption of 95% confidence level, 5% margin of error, 57.6%(P) the proportion of short birth interval practice which is taken from previous study  and consSystematic random sampling techniques were used to select the required sample size then through distributing the required sample size to each governmental health institution allocated in the town based on proportional number of multigravida pregnant women who had ANC visit during study period. For procedure, we used sampling interval approach. Sampling interval (K) was calculated using the summation of 4 months multigravida pregnant women who had ANC visit in all governmental health institutions, which were 920. Then K = N/n, 920/418 = 2.201 ≈ 2. Every 2nd pregnant women were interviewed. To start with the first interview we used lottery method.Short birth interval: if the interval between last birth and current pregnancy expected date of delivery is < 33 months.The data was collected using Amharic questionnaire which is translated from English language. Before the actual data collection; pre-test was done on 5% of total sample size out of the study area which has similar socio demographic context. To collect all the required data we used four diploma midwives.SPSS version 20 software was used to analyze the data. Variables having P-value of < 0.20 in bivariate analysis were entered into multiple logistic regressions for further analysis. Finally, variables with P-value < 0.05 in multivariable logistic analysis were considered as statistically significant.A total of 418 pregnant women who came for ANC follow-up in Debremarkos governmental health institutions were interviewed with a response rate of 98.3%. The mean age was 30 years (SD ± 5.14), 405 (96.1%) mothers were Orthodox Christians, 261 (63.5%) mothers lived in urban area (Table Two hundred sixty-three (63.9%) mothers had 1 or 2 alive children, 96 (23.4) had 3 or 4 alive birth and 52 (12.7%) had ≥ 5 alive children. One hundred fifty-one (36.7%) and 139 (33.8%) women had no alive male and female child respectively. Two hundred four (49.6%) mother`s last child were male. Eighty-eight (21.4%) mother`s last child were not alive. 385 (96.7%) mothers had designer for more child. Among these; 236 (63.1%) mothers needs 1 to 2 more children, 120 (32.1%) mothers needs 3–4 more children and 18 (4.8%) mothers needs more than 4 children. 100 women`s (24.3%) current pregnancy was unplanned.Two hundred eighty (68.1%) of the respondent gave their last live birth in the age group of 20–29 years. 352 (85.6%) women had breastfed their last child. 242 (59%) pregnant women had breastfed their last child for 24 months and more. 357 (86.9%) respondents were ever used contraceptives and 257 (72%) were used contraceptives before this pregnancy. Nearly one-third (32.4%) of study participants gave their last live birth at home. Forty-two (10.2%) respondents gave their last birth through cesarean Sect. 243 (59%), 66 (16%), 25 (6%) and 78 (19%) mothers had breastfed their last child for ≥ 24, 13–23, 7–12 and 1–6 months respectively.One hundred sixty-eight (40.9%) of the study participants had practiced short birth interval. The median duration of birth interval practice was 37 months SD ± 16.7) . Those pregnant women who were in the age group of 15–24 years had 4 times more likely to have short birth interval practice as compared to those who are in the age group of 25–29  and women who were in the age group 35–39 years and 40–49 years had 27 and 23 times less likely to have short birth interval practice as compared to those women who were at the age of 25–29 years  respectively. Women whose last child died were 3.6 times more likely to have short birth interval practice as compared with women whose child were alive . Women who breastfed their last child for 13–23 months were 4.7 times more likely to have short birth interval as compared to those who breastfed for < 6 months . Mothers who were not using contraceptives between their last birth and this pregnancy had 8 times more likely to have short birth interval as compared to those women who used it . Mothers who gave their last birth at home were 4.7 times more likely to have short birth interval as compared to women who gave birth at health institution  . This finding is in line with EDHS report, 41.5% , 24. ThiPregnant mothers whose last child died were 3.6 times more likely to have short birth interval than who had live child. . This finding is in line with studies done in northwest Ethiopia and in Bangladesh , 26, 27.Women who were in the age group 15–24 were 4 times  more likely to have short birth interval compared to 25–29 age group. Women who were in the age group 35–39 and 40–49 had 27 times  and 23 times  less likely to have short birth interval as compared to those age 25–29. This is in consistent with the finding of EDHS, southern Ethiopia and Tanzania .Mothers who were not utilized contraceptive methods between their last birth and this pregnancy were 8 times more likely to practiced short birth interval as compared to users . This finding is in line with study done in southern Ethiopia , 25. ThiPregnant mothers whose last child were female had 2 times more likely to have short birth interval as compared to mothers who had male last child . This finding is consistent with study done in southern Ethiopia and in Saudi Arabia , 28. ThiThose women who were breastfed for 13–23 months had 4.7 times more likely to have short birth interval as compared to those who breastfed for < 6 months . This finding is in line with study done in southern Ethiopia .Women might believe in, breast feeding can prevent pregnancy for long period of time and they may not use contraceptive methods which might expose them to be pregnant .Mothers who gave their last birth at home were 4.75 times more likely to have short birth interval as compare to women who gave birth at health institution . This is in line with the study conducted in Tanzania and Dabat district , 26. ThiShort birth interval practice was high in the study area. Last child survival status, sex of last child, maternal age, contraceptive use, duration of breast feeding, and place of birth were determinant factors for short birth interval practice. Promoting institutional birth in collaboration with health extension workers, Creating awareness for parents through community based health education program to avoid child`s sex based birth interval practice and advice on advantage of using contraceptives while breast feeding to delay pregnancy might decrease short birth interval practice.Measuring birth interval with the women’s memory and duration of breast feeding might result recall bias. Though birth interval can be explained by social and cultural issues, the questionnaire did not extend to investigate such issue in depth.


Preterm birth is a major cause of prenatal and postnatal mortality particularly in developing countries. This study investigated the maternal risk factors associated with the risk of preterm birth.P values < 0.05 were considered to be statistically significant.A population-based case-control study was conducted in several provinces of Iran on 2463 mothers referred to health care centers. Appropriate descriptive and analytical statistical methods were used to evaluate the association between maternal risk factors and the risk of preterm birth. All tests were two-sided, and The mean gestational age was 31.5 ± 4.03 vs. 38.8 ± 1.06 weeks in the case and control groups, respectively. Multivariate regression analysis showed a statistically significant association between preterm birth and mother’s age and ethnicity. Women of Balooch ethnicity and age ≥ 35 years were significantly more likely to develop preterm birth . However, no statistically significant association was observed between preterm birth and mother’s place of residence, level of education, past history of cesarean section, and BMI.Despite technological advances in the health care system, preterm birth still remains a major concern for health officials. Providing appropriate perinatal health care services as well as raising the awareness of pregnant women, especially for high-risk groups, can reduce the proportion of preventable preterm births. Preterm birth is defined as delivery before the gestational week 37 or day 259 –3. It haPreterm birth is a multifactorial phenomenon, partially in association with immunologic, genetic, and environmental factors; however, its attributing factors have not yet been well studied , 8. PrevThis population-based case-control study was conducted on 2463 mothers, including 668 cases and 1795 controls, referred to a health care center in several provinces of Iran, namely, Fars, Hormozgan, Kermanshah, Hamadan, Kohgiloyeh, and Boyerahmad, Yazd, Southern Khorasan, Golestan, and city of Mashhad  were randomly selected. In the second stage, in each of the nine clusters (provinces), four clusters (cities) were randomly selected from the north, south, east, west, and central areas. In each city, two health care centers  were randomly selected. In each health care center, 10 check lists were filled in by well-trained interviewers according to a protocol. In each center, data collection process was conducted simultaneously on the same day for cases and controls. Data of the control group were collected from a random sample of mothers referring to the health care center. If < 10 cases were available in each health care center, the remaining check lists were filled in the nearest center, and if there were > 10 cases, the check lists were filled in for a random sample of mothers. We tried to maintain the same size for the case and control groups.0 = 0.3, p1 = 0.44, z0.95 = 2, z(1-β) = 0.8, design effect = 2) [According to literature review, considering mother’s age > 35 years as a risk factor (pect = 2)  and usinSociodemographic information included mother’s age (age < 35 or ≥ 35 years), place of residence , occupation (housewife/employee/cowhand/farmer/carpet weaver), level of education (illiterate/primary school/intermediate school/high school/academic gradation), ethnicity , and marriage (consanguineous vs. nonconsanguineous).This included history of abortion, stillbirth or cesarean section (yes/no), interpregnancy interval (the first pregnancy/< 1 year/1–3 years/> 3 years), BMI , and cycles of menstruation period (regular/irregular).Preterm birth was the outcome variable, which was ascertained through questioning the exact gestational age at the time of birth.p value < 0.3 in the multivariate model to control for confounding effects [p ≤ 0.05 level of significance.Descriptive statistical tests were performed for socio-demographic and pregnancy-related variables. Bivariate analysis was performed to identify the association of dependent and independent variables. Odds ratio was computed to see the strength of association between preterm birth and each of categorical variables. Adjusted odds ratio and their 95% confident interval were calculated by including all exposures with  effects . Data weThis study was conducted on 2463 mothers referred to health care centers (668 cases with a history of preterm birth and 1795 controls without a history of preterm birth). The mean gestational age at the time of birth was 31.5.” 4.03 vs. 38.8 ± 1.06 weeks for the case and control groups, respectively.Our analysis revealed that 88.8% of cases and 94.0% of controls were 35 years of age. Regarding the ethnicity, 76.8% of cases and 64.1% of controls were Fars. Village dwellers comprised 51.9% of cases and 60.3% of controls. Regarding previous pregnancies, 5.8% of controls reported a history of stillbirth, 12.9% of cases and 11.4% of controls reported a history of cesarean section, and 15.3% of cases and 8.6% of controls had a history of abortion. Birth interval was longer than 3 years in 28.9% of cases and 30.4% of controls , those with a history of abortion were 1.57 times more likely to develop preterm birth , and those with a history of stillbirth were approximately 4 times more likely to develop preterm birth  . Regarding ethnicity, Balooch mothers compared to Turkish mothers were 9.27 times more likely to develop preterm birth . Mothers with irregular cycles of menstruation period compared to those with regular cycles were 1.77 times more likely to develop preterm birth . Regarding the interpregnancy interval, mothers with < 1-year interpregnancy interval compared to those with > 3 years were 1.85 times more liable to develop preterm birth . However, no statistically significant association was observed regarding mother’s place of residence, level of education, supplement consumption, history of cesarean section, and BMI (Table The etiology of preterm birth has been a major concern in obstetrics worldwide. The cause of 50% of preterm births is unknown . HoweverWe observed an increased risk of preterm birth associated with consanguineous marriage, which was consistent with the results of other studies examining the genetic risk factors . In addiConsistent with other studies, the present study demonstrated that a history of abortion and stillbirth is associated with an increased risk of preterm birth. Recent studies suggested an association between history of abortion and increased risk of preterm birth in subsequent pregnancies , 18, 31.We found that mothers with irregular cycles of menstruation period compared to those with regular cycles were more likely to develop preterm birth. Bonessen et al. also showed that regular cycles of menstruation period are associated with lower risk of prolonged pregnancy. In women with regular cycles of menstruation, the exact gestational age is clear and health care providers are not concerned with induction of pain .Consistent with the results of other studies, our study results suggest an increased risk of preterm birth in mothers with < 1-year interpregnancy interval , 40. AdaPreterm birth is a multifactorial issue in obstetrics. Despite technological improvements in the health care system, it still remains a major concern for health officials. In the present study, ethnicity, history of abortion and stillbirth, irregular cycles of menstruation period, consanguineous marriage, and narrow interpregnancy intervals were found to be risk factors for preterm birth. Regarding preventive strategies, it is recommended that mothers be provided with reproductive health care before and during pregnancy, particularly in the high-risk groups, to reduce the proportion of preventable cases of preterm birth.The large sample size of the present study selected from several provinces includes different ethnic groups and socioeconomic status and increases the generalizability of results to the general population. In addition, data were collected by well-trained interviewers according to a predetermined protocol. However, the results of the present study should be interpreted with caution due to potentially uncontrolled confounding effects, recall bias related to history of abortion, and reporting bias due to self-report nature of data collection method. In addition, the time interval between the last abortion and current pregnancy was not recorded in the mother’s profile.