Background: Respiratory syncytial virus (RSV) is the leading cause of acute respiratory infection- related hospitalisations in infants (RSVh). Most of these infants are younger than 6 months old with no known risk factors. An efficient RSVh prevention program should address both mothers and infants, relying on Non-Pharmaceutical (NPI) and Pharmaceutical Interventions (PI). This study aimed at identifying the target population for these two interventions. Methods: Laboratory-confirmed RSV-infected infants hospitalised during the first 6 months of life were enrolled from the Hospices Civils de Lyon birth cohort (2014 to 2018). Clinical variables related to pregnancy and birth  were used for descriptive epidemiology, multivariate logistic regression, and predictive score development. Results: Overall, 616 cases of RSVh in 45,648 infants were identified. Being born before the epidemic season, prematurity, and multiparity were independent predictors of RSVh. Infants born in January or June to August with prematurity and multiparity, and those born in September or December with only one other risk factor (prematurity or multiparity) were identified as moderate-risk, identifying the mothers as candidates for a first-level NPI prevention program. Infants born in September or December with prematurity and multiparity, and those born in October or November were identified as high-risk, identifying the mothers and infants as candidates for a second-level (NPI and PI) intervention. Conclusions: It is possible to determine predictors of RSVh at birth, allowing early enrollment of the target population in a two-level RSV prevention intervention. Respiratory syncytial virus (RSV) infection is the predominant cause of lower respiratory tract infection (LRTI) in infants ,2. In deAlthough RSV is now recognised as a major health burden worldwide, preventive approaches remain limited. Non-Pharmaceutical Interventions (NPI) such as hand hygiene, breastfeeding, and avoiding exposure to smoke or persons with acute respiratory illness are effective in reducing the risk of infection with respiratory viruses in infants ,10. The Nevertheless, successful implementation of the future prevention programs largely relies on their capacity to target the mothers of infants with the higher risk. Recently, it has been reported that prophylaxis regimens, adjusted for regional variations in terms of RSV seasonality, may improve protection compared to the implementation of nationally recommended regimens ,16. Predictive models can help adjust the preventive action to the target population . RegardiThe Normative Outcome of Hospitalisation Assessment for Newborns (NOHAN) strategy proposed herein aimed to adjust multi-level mother-infant interventions according to the risk of RSVh at the general population level. The cut-off values can be adapted to balance the resources available and the effectiveness of the preventive approach. Demographic and laboratory data were collected retrospectively. First, the administrative registry of all infants born in the University Hospitals of Lyon  was used. Stillborn children or those living outside the region were excluded. This database includes the following variables of interest: gender , month of birth, gestational age (WG), maternal parity (primiparity/multiparity), plurality (single/multiple gestation), childbirth type , birth weight, and geographical living area (postcode). Patients with at least one missing piece of data for any studied variable were excluded. The virology laboratory database was then used to identify, among all infants born in the HCL and hospitalised during the RSV season with acute respiratory infection symptoms, those with a respiratory sample positive for RSV . Cases were defined as a new admission, during the first 6 months of life, to one of the conventional paediatric hospital departments of the HCL with an RSV positive sample during hospital stay. This 6-month follow-up period is in line with the preventive approaches proposed herein  which are mostly protective over the first 6 months of life . PresumeA term delivery was defined as a baby born >37 weeks of gestation (WG) measured in weeks of amenorrhoea (WA). Moderate and very preterm deliveries were defined as a baby born ≥32 WG and ≤37 WG and a baby born ˂32 WG, respectively. Birth weight was categorised as either low or high when the value was outside two standard deviations of the weight cohort distribution per WG. Month of birth was categorised into four groups with increased incidence of RSVh during the first 6 months of life. The choice to aggregate these two variables was made to match the categories used in guidelines and clinical practice and to further facilitate the implementation of . n = 8709 infants born between January 2018 and December 2018). The remaining cohort (2014 to 2017) was then randomly divided, with equal-sized month of birth proportion, into a training cohort  and a testing cohort . The validating cohort was exposed to the 2018/2019 RSV season, which was similar to the previous epidemics . To. To26]. pidemics  . The odds ratio (OR) values obtained from the final model were rounded to the nearest integer and used to determine the score. The model was adjusted with the year of birth and the hospital of birth   and the Brier score in the testing and validating cohorts. A k-fold (with k = 4) cross-validation approach was used to estimate the model’s variance on the training cohort. The distribution of month of birth was preserved in the split training sets obtained using the k-fold cross validation. The validating cohort corresponds to a new set of infants exposed to a new RSV epidemic and was used as an external control. p value was lower than 0.05.In the absence of any similar predictive model but based on references from research on other medical predictive models, and given the potential cost-effectiveness of the preventive program, an AUROCC ≥ 0.70 was considered as evidence for good discrimination ,29. A teThe optimal cut-off value for the first level of intervention  was defined a priori with minimal sensitivity and specificity values of 80% and 20%, respectively. This cut-off assumed a lower cost and effectiveness for NPI compared to PI. However, an NPI preventive program may not be maintained year-round if the perceived risk is too low. This assumption was informed by results showing that the application of NPI measures by French parents decreased over time during the COVID-19 crisis (CoviPrev survey) . The optimal cut-off value for the second level of intervention (NPI and PI) was defined a priori with a minimal specificity value of 80%. This cut-off assumed a higher cost and effectiveness for PI that would be then more suitable for a timely seasonal administration than a year-round administration . p values were derived using the chi-squared test for qualitative variables and the Student’s t-test or ANOVA tests for quantitative variables.Statistical analyses were performed using R software version 4.1.0 with the following packages . The caret library was used for data splitting. For the comparison of cohorts, Parents of infants for whom hospitalisation data were used were informed of the study  by postal mail. After this first contact, data were anonymised. Authorisation from Scientific and Ethical Committee of Hospices Civils de Lyon  was obtained on 28 September 2021.There was no funding source for this study. The corresponding author had full access to all the data in the study and had the final responsibility for the decision to submit for publication.Several patients were missing data for gestational age and were excluded . The population studied comprised 45,648 infants: 50.7%  were boys, 16.1% (7354) were born preterm (≤37 WG), 5.8% (2641) from multiple births, 20.8% (9497) were born by caesarean section, and 43.7%  from multiparous mothers. The median (Interquartile Range [IQR]) birth weight was 3207 [2920–3580] g. Among them, 616 were hospitalised in their first 6 months of life with a laboratory-confirmed RSV infection, 53.7% (331) were boys, 22.8% (140) were born preterm (≤37 WG), 7.3% (45) from multiple births, and 73.4% (452) from multiparous mothers . Among aMonth of birth was categorised into four groups with increased incidence of RSVh during the first 6 months of life. In the population studied 95.1% (586/616) of the cases were detected from November to February with a peak during December . Mean  ). The incidence of RSVh in the first 6 months of life was higher for those born just before the seasonal epidemic, from October to November  compared to those born in September and December , as well as to those born in January and June to August , and those born February to May . Considering the gestational age, being born ˂32 WG was associated with a higher risk of RSVh . Considering parity, multiparity was associated with a higher risk of RSVh  score was 16.98 (±16.42) in the testing cohort and 18.41 (±19.64) in the validating cohort . The k-fold validation approach used in the training cohort to estimate the model’s variance found a mean AUROC value of 0.791  for the four split training cohorts compared with a mean AUROC value of 0.821  for the validating cohort. The overlap between the two confidence intervals indicates a low variance.p value < 0.001) and the Brier score measured  in the validating cohort both indicated a good performance of the predictive model.The Hosmer–Lemehow chi-squared test used to assess the goodness of fit  of intervention was defined as a low-risk group . It encoThe maternal population with an RSVh predictive score above the first cut-off value (>14) and below the second cut-off value (<28) of intervention was defined as a moderate-risk group. It encompasses the deliveries occurring during the months of January or June to August with prematurity and multiparity and the deliveries in September or December with only one other risk factor (prematurity or multiparity).The maternal population with an RSVh predictive score above the second cut-off value (>28) was defined as a high-risk group. It encompasses the deliveries in September or December with prematurity and multiparity and all deliveries in October or November .When applied to the validating cohort, the predictive score identified 53% of infants as low-risk (incidence 1.72 cases/1000 infants), 32% of infants as moderate-risk (incidence 18.92/1000 infants), and 15% of infants as high-risk  ,38 were Using a hospital birth cohort, the NOHAN strategy allowed to determine strong maternal and newborn predictors of RSVh risk. By using this strategy, future parents could be enrolled early during pregnancy follow-up in a health-related BCP. The pregnant women could then be proposed a vaccine boost, or neutralizing monoclonal antibodies could be administered to the newborns. As demonstrated herein, the thresholds for triggering each level of intervention can be adjusted to the local epidemiology, the resources available, and the evolving evidence concerning the cost-efficiency of the future interventions. Stakeholders, healthcare professionals, and policy makers should acknowledge this opportunity when designing the future of RSV prevention programs.


Juvenile idiopathic arthritis (JIA) is one of the common rheumatic diseases in pediatrics. Persistent synovitis and joint pain cause reduced range of motion, deformity and gait interruption, which are important reasons for children's disability and a decline in their quality of life. Rheumatology experts have explored good treatment strategies, among which intra-articular corticosteroid injections (IACIs) targeting joints can greatly reduce these systemic adverse reactions while still obtaining local anti-inflammatory effects. Local inhibition of synovitis by the use of steroid hormones in a joint cavity can avoid or reduce adverse reactions of systemic therapy, prevent or treat leg length variance and joint contracture, solve Baker's cyst, improve tenosynovitis, promote physical therapy and rehabilitation, make gait change smoothly, relieve pain, and restore joint function. Given the importance of IACIs in treating JIA, this paper reviewed the case selection, drug injection, dose selection, current anesthesia and injection techniques, the efficacy, recurrence, and influencing factors of IACIs, the management of physiotherapy intervention post-injection, the application of ultrasound guidance and the safety and complications of IACIs in children with JIA. This study aims to guide the use of IACIs for the best approach throughout the review. Intra-articular corticosteroid injections (IACIs) are mainly applicable to chronic rheumatoid arthritis and osteoarthritis of the knee . StudiesIn this study, MEDLINE, PubMed, EMBASE, the web of science and Cochrane libraries were used for comprehensive literature retrieval. The inclusion criteria were: meta-analysis, RCT, cohort study, observational study, case series (prospective/retrospective), and its outcome variables evaluated the clinical case selection dose and efficacy, safety, adverse reactions and/or puncture technology, anesthesia technology, and radiologic effects of IAGs on patients.Depot corticosteroids are most suitable for intra-articular injection therapy. The solubility of these drugs is low, and they can continue to play a role at the injection site of the joint. The duration of efficacy is inversely proportional to the solubility of the drug; the lower the solubility, the longer the duration of efficacy. At present, commonly used drugs include methylprednisolone (MP), triamcinolone acetonide (TA), triamcinolone hexanoate (TH), where the solubility is MP > TA > TH . For preLiterature shows that, although triamcinolone is the best glucocorticoid for IACIs, more soluble glucocorticoids (such as MP) are recommended for use at the facet joints , 9 to avBefore performing joint cavity punctures, the main concern is the anxiety and pain related to the operation. Many factors interact with and affect children's painful experiences, including environmental, cognitive, behavioral and biological factors. Children's anxiety before undergoing painful medical procedures is directly related to the pain experienced. Nieto-González and Monteagudo strongly recommends the use of local anesthesia before or during surgery and the use of conscious sedatives in specific cases for evaluation . The pur2O) and oxygen inhalation mixture to help with children's painful operations, including IACIs. This procedure has the advantages of short-term hospitalization and avoiding the risks caused by intravenous sedation or general anesthesia  can provide safe and effective analgesics for some adolescent patients with idiopathic arthritis and pediatric arthritis. The use of IACIs provides a low-cost alternative to general anesthesia  is used at the same time and whether uveitis is accompanied result in different curative effects. Breit's research showed that the median duration of curative effect varies with joints and disease subtypes. Patients with oligoarthritis before the age of five had the longest median duration, while patients with systemic arthritis had the shortest duration . RavelliIn a study involving 220 patients with JIA with 1,096 IACIs, the strongest predictor of synovitis recurrence after the IACIs was positive for CRP, negative ANA, lack of simultaneous administration of MTX, and the occurrence of multiple joints (as opposed to fewer joints) diseases . RavelliAt present, the benefit of specific physical therapy in patients with JIA after IACIs is still inconclusive. In 2003, Cleary et al. reported that the problems of rest, splint and physical therapy post-injection were still controversial and had not been studied in children's controlled trials. In adults, the evidence is confusing and inconclusive, according to Cleary. There are persistent and significant differences in the improvement of clinical and laboratory functions among patients who have been on strict bed rest for 24 h post-injection, though some studies suggest that strict bed rest is beneficial but unnecessary for IACIs . McKay'sIn the pediatric population, there is not enough scientific evidence to recommend the use of ultrasound scanning guidance in all IACI procedures . There aThere are many studies on the safety of IACIs, and most of them think IACIs are a safe and effective treatment for patients with JIA , 54, 55.Although systemic and local adverse reactions have also been reported, they are significantly less than those of systemic medication, with an incidence of only 2% reported in the literature .Local atrophy (skin or subcutaneous) is the most common adverse event , which iAlthough systemic absorption of corticosteroids may lead to obvious adrenal suppression and transient clinical manifestations from slight cosmetic changes to obvious Cushing's syndrome, it has nothing to do with long-term adverse reactions and is transient. The use of IACIs may cause systemic adverse events, such as Cushingoid habitus, transient adrenal suppression, acne-like rash, and insomnia , 56–58.Another known complication of IACIs is the development of periarticular calcifications. The majority of these abnormalities are asymptomatic and are detected coincidentally on radiological follow-up. Nicolau syndrome has even been reported after IACIs . AbnormaThe use of IACIs for JIA is a safe and effective method for treating synovitis. It can be performed under local anesthesia with or without conscious sedation or under general anesthesia, and is an important treatment choice for children with JIA. This treatment, the so-called “bridge” effect, is an alternative to the use of systemic corticosteroids. However, due to the lack of controlled studies, the current position of IACI treatment in the management of children with JIA is still uncertain. Systematic, controlled and prospective research is needed to determine the best role of IACIs in children with JIA. In addition, it is necessary to support the training of pediatric rheumatologists in IACI technology and further explore the value of physiotherapy and ultrasound guidance.SL and YL conceived the study and participated in its design and coordination. WZ helped to draft the manuscript. All authors have read and approved the final manuscript.This work was supported by 2020 Sichuan Maternal and Child Health Association Maternal and Child Medicine Science and Technology Innovation Project (Key Project) 2020ZD06, Chen Xiaoping Foundation for the Development of Science and Technology for Hubei Province CXPJJH121002-202149, 2020 Sichuan Health Research Project (Key Research Project) 20ZD019, and Chengdu High-Level Key Clinical Specialty Construction Project.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


There are limited studies on the long-term effects of natural/environmental disasters, especially nuclear disasters, on obstetric outcomes. This study aimed to review the results of perinatal outcomes immediately after the Great East Japan Earthquake (GEJE) and the Fukushima Daiichi Nuclear Power Plant accident, as well as their long-term trends over 8 years, in the Fukushima Health Management Survey. The annual population-based Pregnancy and Birth Survey is conducted as part of the Fukushima Health Management Survey. The Fukushima Prefecture government launched it to assess the health conditions of pregnant women and their neonates after the GEJE. The self-reported questionnaire was sent to 115,976 pregnant women by mail from January 2012, with 58,344 women responding to the questionnaire (50.3% response rate). Pregnancy complications, such as gestational hypertension, respiratory diseases, and mental disorders, increased in some women who were pregnant at the time of the earthquake and immediately after the earthquake. However, the direct effects on newborns, such as preterm birth, low birth weight, and congenital anomalies, were not immediately clear after the earthquake. Although there were significant differences in the occurrence of preterm birth and low birth weight among the districts, there was no change in the occurrences of preterm birth, low birth weight, or anomalies in newborns in Fukushima Prefecture from the fiscal year 2011 to the fiscal year 2018. Therefore, the long-term effects of the post-disaster radiation accident on perinatal outcomes are considered to be very small. Although several studies reported the association between disaster and perinatal health, only a few studies examined perinatal health in disasters, such as Fukushima, where the earthquake, tsunami, and radiation exposure occurred in combination.3 Few studies reported chronological trends in perinatal outcomes after the disaster. In particular, due to the concerns about radiation exposure in Fukushima, the chronological trends in pregnancy outcomes after the GEJE are of worldwide interest; the FHMS has maintained data from the investigation on the effects of this disaster on pregnancy and infant care.The most devastating event in recent Japanese history is the Great East Japan Earthquake (GEJE), which occurred on Mar 11, 2011, along with the subsequent tsunami and nuclear accident at the Fukushima Daiichi Nuclear Power Plant. In the Fukushima Prefecture, thousands of deaths occurred due to the tsunami. The devastation affected many people living in the coastal areas of the Soso and Iwaki districts. After the power plant accidents, many people (including pregnant women) living in coastal areas were suddenly forced to evacuate by government order. The Aizu district, located in a mountainous region in Fukushima Prefecture far from the power plant, was hardly affected by the nuclear accident compared to the coastal regions  2011.5The self-reported questionnaire was sent to 115,976 pregnant women by mail between January 2012 and December 2019 . The mothers were asked to complete the questionnaire while referring to their maternal and child health handbooks described above. In total, 58,344 women (50.3% response rate) responded to the questionnaire. The number of cases from 2011 to 2018 was 9,316, 7,181, 7,260, 7,132, 7,031, 7,326, 6,449, and 6,649, respectively.6,7 The Aizu region is mountainous and far from the nuclear power plant, and radiation levels are the lowest in the Prefecture. Deliveries before 37 gestational weeks were defined as preterm birth, and birth weights less than 2,500 g were defined as low birth weight.8 The mode of pregnancy was categorized as natural pregnancy or fertility treatment, such as ovulation induction, artificial insemination, and in vitro fertilization. The mode of delivery was categorized as vaginal delivery or caesarian section. The following major anomalies were reported in the newborns: cataracts, cardiac malformation, kidney, and urinary tract malformation, spina bifida, microcephaly, hydrocephalous, cleft lip and palate, intestinal atresia , imperforate anus, polydactylism, and syndactylism. Every anomaly reported on the questionnaire was defined as a major anomaly.The self-reported questionnaire included maternal information, such as the geographic district where the pregnant women received their maternal and child health handbook, delivery date, maternal age at delivery, single or multiple gestational pregnancies, gestational weeks at delivery, mode of pregnancy, and mode of delivery. It also included neonatal information, such as neonatal birth weight, sex of the newborn, and the presence of anomalies in the newborn. There were six classifications for the geographic district: Kenpoku, Kenchu, Kennan, Soso, Iwaki, and Aizu Figure . Soso anThe local ethics review committee of the author’s institution approved this study , and all participants provided written informed consent.9We report pregnancy complications among pregnant women during the disaster using the results of the FHMS, which targeted women who gave birth during 2011–2012. Pregnant women were divided into four groups according to pregnancy trimester during the disaster . As a result, the third trimester of pregnancy at the time of the disaster was associated with hypertensive pregnancy disorder for the women living in the areas most exposed to the disaster.10 The results showed no obstetric-related adverse events among the women who became pregnant in the 9 months before the disaster.10 In contrast, there was an increased incidence of medical complications, such as respiratory diseases and mental disorders, among the women who became pregnant within 6 months of the earthquake  and Kenpoku was the lowest (7.6%).4 There were no significant differences in the incidence rate of all congenital anomalies among the regional area (P for difference = 0.275), although the rate of Kennan was somewhat higher than other regional areas , preterm birth, low birth weight, and congenital anomalies were 0.25%, 4.4%, 8.7%, and 2.72%, respectively.s Figure .410 We also evaluated the incidence and obstetric outcomes of women who became pregnant using assisted reproductive technology procedures in Fukushima Prefecture and reported that the impact of the disaster was minimal. The proportion of women who became pregnant using in vitro fertilization and embryo transfer decreased during the first 2 months after the earthquake. It returned to pre-disaster levels in the third month after the earthquake. For women who became pregnant without in vitro fertilization and embryo transfer, the incidence of preterm birth and low birth weight increased after the earthquake.12The analysis of the same 12,300 participants as above showed an increased incidence of low birth weight  and preterm birth among women who became pregnant within 6 months of the earthquake  was higher in the SGA group and was an independent risk factor for SGA.13The incidence rate for small for gestational age (SGA) status among newborns delivered by women who were pregnant at the time of the disaster in Fukushima Prefecture was 5.6% .5 There was no change in incidence rate of preterm birth, low birth weight, and congenital anomalies during the survey period. The incidence of preterm births and low birth weight ranged from 4.8% to 5.8% and from 8.9% to 10.1%, respectively, during the survey period. Meanwhile, 5.7% and 9.4% of births nationwide were reported as preterm births and low birth weight, respectively, according to the 2017 Vital Statistics, and the survey results in Fukushima were similar to the national results. The incidence of congenital anomalies ranged from 2.19% to 2.85% during the survey period. Since the general incidence of congenital anomalies is reported to be 3% to 5%, the incidence in Fukushima was considered to be equal to or lower than these values.Figure 14 Therefore, we can conclude that there is no evidence of a direct effect of radiation exposure on perinatal outcomes due to the radiation accident of Fukushima Prefecture.The Pregnancy and Birth Survey of the Fukushima Health Management Survey is the first population-based survey to examine the long-term trends of perinatal outcomes among pregnant women in Fukushima Prefecture after the disaster. This survey revealed that pregnancy complications, such as gestational hypertension, respiratory diseases, and mental disorders, increased in some women who were pregnant at the time of the earthquake and immediately after the earthquake. However, the direct effects on newborns, such as preterm birth, low birth weight, and congenital anomalies, were unclear, either immediately after the earthquake or for several years after the earthquake. Furthermore, there is no association between radiation exposure dose and perinatal outcomes.15 Numerous studies examined the effects of exposure to disasters on pregnancy outcomes, such as the World Trade Center Disaster, the bombing attacks in Serbia, and the Madrid train bombing; environmental and chemical disasters, such as the Bhopal gas release in India, the Three Mile Island accident, and the Chernobyl accident; and natural disasters, such as earthquakes, hurricanes, floods, and ice streams.3 The GEJE and Fukushima Daiichi nuclear accidents formed a complex disaster because they included the natural disaster of the Great Earthquake and tsunami and the environmental/technical disaster of the nuclear power plant accident. However, the Japan Environment and Children’s Study conducted in Fukushima Prefecture examined perinatal outcomes using the results of 12,804 births in the prefecture between 2011 and 2014.16 The prevalence of preterm birth, low birth weight, and neonatal anomalies were 5.6%, 9.5%, and 1.7%, respectively,16 which were not so different from the results of our study.Disasters potentially influence a range of reproductive outcomes.17 However, Levi et al reported that the Chernobyl accident affected gestational age and maternal anxiety among 88 Swedish women early in their pregnancy at the time of the disaster.18 In contrast to our study, an earthquake disaster in China increased the risk of preterm birth. Tan et al compared the incidence of preterm birth between 6,638 pregnant women before the disaster and 6,365 pregnant women after.19 The incidence of preterm birth was 5.6% and 7.4%, respectively, which was significantly higher after the disaster (P < 0.01). In Japan, the incidence of high-risk pregnancies has increased due to advanced maternal age and complicated pregnancies20,21; the post-disaster incidence rates of preterm birth <37 gestational weeks (5.7%) and low birth weight <2,500 g (9.4%)22 have been almost stable.There are conflicting findings on the association between environmental/chemical disasters and gestational age and birth weight. Goldman et al reported that the Love Canal disaster in the United States showed no significant association with gestational age among 227 residents.23–25 However, several studies have reported no effect of these disasters on birth weight.17,26 With regard to the GEJE and Fukushima Daiichi nuclear accident, we reported that there was no evidence that the disaster increased the incidence of SGA births in Fukushima Prefecture during the 8 years after the disaster. Using an institutional investigation in a coastal area where the maximum catastrophic damage had occurred in the GEJE,27 Leppold et al reported no marked increase in the proportion of preterm birth and low birth weight in any year after the disaster .27 In Japan, pregnant women could have better access to relief programs or might receive adequate support from their family, society, and the government during disasters.28 Although the effects on newborns are unclear, it has been reported that the proportion of pregnant women with depressive symptoms increased after the GEJE due to the sudden evacuation of numerous pregnant women and the drastic changes in their living environment.28–30 Therefore, we need to continue examining the direct effects of the earthquake and radiation accident and the indirect effects, such as long-term evacuation.Several studies have reported that environmental and natural disasters increase the risk of low birth weight.31–33 However, the incidence of most congenital disabilities did not increase in most European countries.34–36 It was widely reported that 2–3% of all newborns have a major congenital abnormality that is detectable at birth.37,38 From 2011 to 2016, the incidence of congenital disabilities in Japan was 2.43–2.59%, according to a report of the International Clearinghouse for Birth Defects Surveillance and Research Japan Center,39 although this has not increased since the GEJE. Using the Japanese birth cohort study that included 12,804 pregnant women in Fukushima Prefecture, Kyozuka et al reported that the prevalence of major congenital anomalies at delivery between 2011 and 2014 in the prefecture was 1.6% to 3.2%, depending on maternal age,16 and these rates were similar to the national rates.The association between disasters and congenital anomalies is a major public concern. Several major environmental and technical disasters have been related to congenital anomalies, including the nuclear reactor accidents at Chernobyl in 1986 and Three Mile Island in 1979. The accident at Chernobyl involved a much larger radiation dose exposure and affected more people than the Three Mile Island and Fukushima incidents. Reviews on the effect of the Chernobyl disaster indicated increased microcephaly and neural tube defects.40 However, Kojima et al reported that it is difficult to clarify cryptorchidism prevalence because of complexities in design settings for epidemiological surveys of this disease. They rejected the hypothesis that cryptorchidism increased in Japan due to the Fukushima Daiichi Nuclear Power Plant accident.41 Hirai et al, employing the All Japanese Cardiovascular Surgery Database, revealed no increase in the number of patients with congenital heart disease from 2010 to 2013.42Nevertheless, a survey of hospital discharge records for cryptorchidism showed an increased discharge rate for cryptorchidism nationwide after the GEJE.The Pregnancy and Birth Survey has several strengths. In Japan, few epidemiological studies involve pregnant women in a community. Large-scale studies and data supported by the government are considered valuable. In addition, we obtained relatively accurate data on gestational ages and birth weights from the participants from their maternal and child health handbook. Nevertheless, the survey has potential limitations. First, the response rate was only approximately 50–60% throughout the study period. Therefore, the actual incidence of negative outcomes could have been overestimated if there was an overrepresentation of women affected the most by the disasters, especially those who were pregnant between 2011 and 2012. Second, given that this study used a self-administered questionnaire, we assume that the mothers answered correctly, especially regarding fetal anomalies.In conclusion, the results of the Pregnancy and Birth Survey indicate that the effects of GEJE and the subsequent nuclear accident on pregnant women are negligible in the long term. Improving the understanding of the adverse reproductive effects of disasters requires as much preparedness as required for the emergency response to prevent mortality and morbidity. Further studies should examine whether the disaster caused psychological complications or early pregnancy loss, such as miscarriage and abortion. Due to the relatively high incidence of anxiety and potential long-lasting negative effects on the mental and physical health of mothers, their children, and even other family members, the findings of the Pregnancy and Birth Survey could have significant public health implications.


Preterm birth remains the commonest cause of neonatal mortality, and morbidity represents one of the principal targets of neonatal healthcare. Ethiopia is one of the countries which accounts for the highest burden of preterm birth. Therefore, this study aimed to assess factors associated with preterm birth at public hospitals in Sidama regional state.via chart review. Data were entered using EpiData version 3.1 and exported to R software version 4.0 for analysis. Then, factors associated with preterm birth among mothers were assessed based on the Bayesian statistical approach.A facility-based cross-sectional study was conducted at public hospitals in Southeast Ethiopia from 1 June to 1 September 2020. To recruit the study participants, systematic random sampling techniques were used. Data were collected using pretested structured interviewer-administered questionnaire and a checklist The study showed that the prevalence of preterm birth was 20.6%. Being a rural resident , having no antenatal care service utilization , hypertensive disorder of pregnancy , birth space less than 2 years , having premature rupture of membrane , and physical intimate violence  were risk factors of preterm birth. Whereas, women who had primary, secondary, and higher education levels , respectively, were preventive factors.Most of the risk factors of preterm birth were found to be modifiable. Community mobilization on physical violence during pregnancy and antenatal care follow-up are the ground for the prevention of preterm birth because attentive and critical antenatal care screening practices could early identify risk factors. In addition, information communication education about preterm birth prevention was recommended. According to the World Health Organization, preterm birth is defined as a delivery that occurs before 37 completed weeks of gestation , 2. Out Preterm birth is a major healthcare problem causing over 1 million deaths of neonates annually, and high rates of morbidity and disability among survivors . PretermEthiopia is one of the top eight countries that account for the high prevalence of preterm birth in 2014 and the top six countries that contribute nearly two-thirds of all deaths from preterm birth complications worldwide in 2016 . In EthiTarget 3.2 of Sustainable Development Goal (SDG) 3 is used to reduce global neonatal mortality to at least as low as 12 per 1,000 live births by 2030 . Also, tAn institution-based cross-sectional study was conducted at public hospitals in the southeastern part of Ethiopia  from 1 June to 1 September 2020. Mothers who gave birth at public hospitals in Southeast Ethiopia  were the source population, and mothers who gave birth in the selected public hospitals during the study period were the study population. Mothers who gave live birth to singleton preterm neonate and their index neonates were included. But, mothers without a confirmed diagnosis of preterm birth due to did not remember their LNMP or have not had an early ultrasound record were excluded from the study. Similarly, medically induced preterm births are also excluded from this study.P = 29.6%) (The sample size was determined using the single population proportion formula ]*P(1-p)  by consi= 29.6%) , 95% conA multistage sampling technique was employed. Out of three general and 14 primary hospitals, one general and three primary hospitals, respectively, were randomly selected. In addition, there was only one comprehensive hospital located in the region and it was included in the study. The total sample size was proportionally distributed to each hospital based on an average number of deliveries recorded in the most recent quarterly report of each health facility before the study period. Finally, the study participants were recruited using a systematic random sampling technique.Early ultrasound record: Ultrasound result is taken until 22 weeks of gestational age  of 140 mmHg or more or diastolic blood pressure (DBP) of 90 mmHg or more on 2 or more consecutive occasions during pregnancy  date and/or early pregnancy ultrasound determined date (up to and including 22 completed weeks of gestation). When the LMP and U/S dates had not been correlated, U/S for gestational age assessment was taken in accordance with the recommendation of the American College of Obstetricians and Gynecologists (ACOG) , 18, 22.The questionnaire was prepared first in English and translated into the local language Amharic and Sidaamu Afoo, and finally, retranslated back to English by a language expert to increase accuracy. Before conducting the study, the questionnaire was pretested on 10% of the sample. Based on the pretest, an appropriate modification was made. The 1-day training was provided for data collectors and supervisors.Yi = Brms R-package. Since we do not have prior information, we used vague prior distribution to determine the posterior distribution. To estimate regression coefficients, we used beta distribution , and to estimate the variance, we used gamma distribution . We also used chains = 2, initials  = 0, iteration = 10,000, cores  = 2, warmup (number of iterations that was discarded) = 1,000, and adapt delta (controls divergent transition) = 0.95 to estimate the estimates of the parameters from the posterior distribution.The collected data were checked for completeness, entered into EpiData version 3.1, coded, cleaned, and exported to R software version 4.0 for further analysis. After the data were cleaned and coded, descriptive measures, such as frequency, percentage, graphs, and tables, were used to characterize the study population. The relationship between the dependent and independent variables was assessed using the binary logistic regression model based on the Bayesian statistical analysis approach. The dependent variable (preterm birth) is represented by Then, Hamiltonians Monte Carlo (HMC) method was performed to simulate direct draws from the complex posterior distribution. Therefore, since the iteration convergence is fast, we used No-U-Turn Sampler (NUTS). Finally, summary statistics were carried out from the posterior distribution after the model was converged, and the 95% credible interval was used for the test of significance. The empirical results obtained from a given HMC analysis are not reliable until the chain has reached its stationary distribution. Therefore, to monitor the convergence of the algorithm, we used the most popular assessment methods in which Rhat = 1, Bulk_ESS and Tail_ESS were greater than 1,000, density plots were smooth, and chains of the time series plots were mixed well.The prevalence of preterm birth among women delivered in the Sidama region of Southeast Ethiopia public hospitals was 20.4%.A total of 47.6% of women who experienced hypertensive disorder during pregnancy had a preterm birth. In addition, 19.3% of women who had premature rupture of the membrane experienced preterm birth see .As shown in Even though there have been advancements in perinatal medicine and feto maternal units, preterm birth remains the leading cause of neonatal mortality and morbidity, leading to the first place for neonatal intensive care unit admission and longer hospital stay , 24. ThiThe magnitude of preterm birth in this study was consistent with the previous findings conducted in Bangladesh at 22.3% , NigeriaOf all the factors included in the model, being a rural resident, educational status of the mother, birth interval, ANC follow-up, hypertensive disorders of pregnancy, the premature rupture of membrane, and physical intimate violence were significantly associated with preterm birth in southern Ethiopia . The odds of delivering preterm babies among mothers who lived in rural areas were more likely than among urban residents. This finding is similar to the study conducted in the Amhara region , and AxuThis study depicts that the odds of preterm delivery among mothers who experienced hypertensive disorders of pregnancy were more likely than mothers who have not experienced hypertensive disorders of pregnancy. This finding is in line with a study conducted in Tigray , Jimma , and KenThe odds of preterm delivery among mothers who experienced birth spacing <2 years were more likely as compared to those who spaced more than 2 years. This finding is in line with a study conducted in Jimma , NortherThe odds of mothers who experienced physical intimate violence during pregnancy were more likely to deliver preterm babies than mothers who did not experience physical intimate violence. This finding is in agreement with a study conducted in Iran , VietnamThis study identified several factors associated with preterm birth using an appropriate method of statistical analysis. But, there were some limitations to this study. The study participants might not remember  their exact LNMP. So, to solve this problem, we used ultrasound records. The other limitation of the study was the prevalence of preterm birth in the Sidama regional state might be biased by referrals from the neighboring southwest Arusi and Oromia regional state hospitals. Thus, to alleviate this problem, we excluded women who have referral papers in their chart from the study.Preterm birth had been a major public health problem in the study area for perinatal care, and thus deserves priority attention. There were many factors interwoven to affect the occurrence of preterm birth. Preterm birth is more likely to occur in women living in rural areas, with no ANC follow-up, narrow birth spacing, and suffering from physical violence during pregnancy. Whereas, women who attend primary education and above were preventive factors. Thus, efforts should be intensified to alleviate the identified risk factors to minimize the burden of preterm birth in the study setting, Southeast Ethiopia. Community mobilization on physical violence during pregnancy and ANC follow-up are the ground for the prevention of preterm birth because attentive and critical ANC screening practices could early identify the risk factors. Further community-based longitudinal (cohort) studies might explore additional determinants of preterm birth.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.Ethical clearance was obtained from the Institutional Review Board (IRB/202/12) at the College of Medicine and Health Sciences of Hawassa University. An official letter of cooperation was obtained from the Department of Midwifery to respective hospital administrators. Informed written permission was obtained from each hospital administrator. After the purpose and objective of the study have been explained, written consent was obtained from each study participant. Participants were informed that participation was on a voluntary basis and can withdraw from the study at any time if they were not comfortable with the questionnaire. In order to keep confidentiality, information was maintained throughout by excluding names or personal identifiers in the questionnaire.YN conceived the study, analyzed the data, and wrote the first draft of the manuscript. GA supervised the study, methods, and proofread the manuscript. All the authors read and approved the final version of the manuscript.


Birth injury is harm that a baby suffers during the entire birth process. It includes both birth asphyxia and birth trauma. In Ethiopia, birth injury has become the leading cause of neonatal morbidity and mortality, accounting around 28%-31.6% of neonatal mortality. The study aimed to assess the prevalence and factors associated with birth injuries among newborns delivered in public hospitals Addis Ababa, Ethiopia, 2021.th to April 20th, 2021 in selected public hospitals of Addis Ababa, Ethiopia. Random sampling and systematic random sampling were used. Data was entered by using Epi data version 4.0.2 and exported in to SPSS Software version 25 for analysis. Both bivariate and multivariable logistic regressions analyses were used. Finally P-value <0.05 was used to claim statistically significant.Institution based cross-sectional study was conducted from February 15The prevalence of birth injury was 24.7%. In the final model, birth asphyxia was significantly associated with the short height of the mothers , intrapartal fetal distress , cord prolapse (AOR = 7.7. 95% CI: 1.45–34.0), tight nuchal cord (AOR = 9.2. 95% CI: 4.9–35.3), birth attended by residents , male sex  and low birth weight . Whereas, birth trauma was significantly associated with gestational diabetic mellitus , prolonged duration of labor , instrumental delivery  and night time birth .The prevalence of birth injury among newborns has continued to increases and become life-threatening issue in the delivery and neonatal intensive care unit in the study area. Therefore, considering the prevailing factors, robust effort has to be made to optimize the quality obstetric care and follow up and emergency obstetrics team has to be strengthened to reduce the prevalence of birth injury. The process of birth, whether spontaneous or assisted, is naturally traumatic for the newborns. Birth injury is the structural destruction or functional deterioration of the neonate’s body due to a traumatic event at birth . Birth rth minutes, arterial cord pH < 7 and base deficit >12, neonate did not cry at birth or needed resuscitation, acidosis, seizure and hypotonia  taken in account the study […] with CI 95%).3) The main problem in the method section and subsequently in the reported results was related to the variables considered and their definition. In the statistical analysis the authors used the total length of the labour but it would be desirable to report first and second stage separately. In fact, labor and birth is a dynamic process and each stage of labor is characterized by different aspects, risks, obstetrical management and impact on fetal and maternal wellbeing. The total duration of the labor does not represent an adequate parameter and statistical analysis loses of significance.4) Moreover, a definition of intrapartum fetal distress is not adequately provided: “When the fetal heart rate is either <100 or >180 beat/minutes or if there is non reassurance fetal heart rate pattern” but instant measurement of fetal heart rate does not provide a definition of fetal distress and proper international guidelines need to be considered to define non-reassurance fetal heart.5) The threshold of 1 hour for the premature rupture of membrane is totally arbitrary, add references if available6) Apgar score is a subjective evaluation especially in non adequate trained health workers, I suggest to specify who made the evaluation .7) In the results I suggest to avoid description of sociodemographic features and to refer to Table 18) Provide the list of abbreviations under each table to a better comprehension9) In my opinion was essential to report the number of elective, urgent and emergency cesarean section because they were burdened of different level of birth injury risk. A subgroup analysis is desirable to understand the association with birth injury in the univariate and multivariate analysis.10) I advice to provide a unique paragraph for the Discussion11) The Discussion lacks a decent literature review, and it is unclear what the study adds to what is already known on the subject.12) I suggest to provide a more deep analysis of the literature evidence and to analyze, moreover, the possible impact of healthcare personnel training ( See this paper: 10.11604/pamj.2022.42.169.32816 ).13) In relation to the findings on the role of maternal height, fetal head circumference and pelvic-fetal disproportion consider this paper for the discussion 10.1371/journal.pone.0275400.**********  6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). 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Please note that Supporting Information files do not need this step.While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool,  12 Jan 2023Manuscript PONE-D-22-05977 Rebuttal LetterWe really thank the academic editor and two reviewers for their thoughtful inputs and valuable comments on our manuscript. The feedback provided by them has been help full to improve this manuscript and we are grateful for their input. Please kindly find below our response to point by point raised by the academic editor and reviewers.We hope that we clearly addressed all of them, and that the manuscript will be now suited for publication.Sincerely,On behalf of all the four authors,Esubalew Amsalu Tibebu.Academic editorJournal requirement1. Plos one templatesWe have checked the Plos one templates and made the adjustment to meet the journal requirements.2. Copyedit your manuscript for language usage, spelling, and grammar.We have tried to check for any error in language usage, spelling and grammar and make adjustment 1. Is the manuscript technically sound, and do the data support the conclusions?Reviewer #1: YesReviewer #2: Partly2. Has the statistical analysis been performed appropriately and rigorously?Reviewer #1: YesReviewer #2: NoWe thank the reviewer for this assessment, during statistical analysis we used bivariate logistic regression analysis to check the association between each independent variable with dependent variable and were tried to do the statistical analysis appropriately. Multivariable logistic regression model analysis also used for those variables with p-value ≤ 0.25 in order to control the confounding factors. To check the correlation between independent variables, multi-colinearity (colinearity diagnostic taste) was done by using the value of variance inflation factors and tolerance. Hosmer and Lemeshow goodness of fit test and omnibus tests of model coefficients were done to test the fitness of the logistic regression in the final model.3. Have the authors made all data underlying the findings in their manuscript fully available?Reviewer #1: NoReviewer #2: NoWe thank the reviewer for this assessment and we made amendments as follows All relevant data are within the manuscript and its Supporting information files. 4. Is the manuscript presented in an intelligible fashion and written in standard English?Reviewer #1: YesReviewer #2: YesReview Comments to the AuthorReviewer #1Comment 1Your outcome variable is not clear so you should specify whether Birth injuries or Birth trauma better to focus on over all Birth injuries.Response 1: Thank you for your comment and as we mentioned in operational definition, birth injuries is defined as injury to newborns that occur during labor and delivery who has diagnosis either of birth trauma, birth asphyxia or both. We defined birth trauma as any physical injury to newborns during the entire birth process. Birth asphyxia is failure to initiate, sustain breathing and not crying at birth and diagnosed based on Apgar score <7 at 5th minutes. To assess factors independently associated with birth asphyxia and birth trauma, it’s better to make our outcome variables are two i.e. birth asphyxia and birth trauma.Comment 2One of your variables was pre pregnancy BMI, do you think the participant remember pre pregnancy BMI? Response 2: We are grateful to respond to your constructive comments and here are the responses. The variable pre-pregnancy BMI was obtained by measuring maternal height and taking maternal pre-pregnancy weight (Kg/m²). The maternal pre-pregnancy weight was taken in two ways. The first one was by asking maternal pre-pregnancy weight if she remembers and the second way was taken from chart review during first trimester weight record (<12 wks) if she didn’t remember her weight. Since our Exclusion criteria were those who have incomplete documentation . So that, if the mother didn’t remember her Prepregnancy weight and didn’t have first trimester antenatal follow up weight record, she had excluded from the study participant.Comment 3How do you asses quality of birth attendant?Response 3: Thank you for your observation. It was not our objective to assess the quality of birth attendant; rather we were concerned on qualification of birth attendants. That is assessed by checklist of asking whether the birth attendant is Midwife, general practitioner, residents or gynecologist.Comment 4: Ethical clearance section needs further elaboration especially how did you maintain confidentiality, privacy and linking cases to the specific services and so on?Response 4: We thank the reviewer for this questionStudy participants were asked for their willingness to participate in the study after explaining the purpose of the study. Then written informed consent was obtained from each participant. The privacy and confidentiality of information was strictly maintained by not writing the name of study participants on data collection tool. Comment 5How do you assess the data of intra-partum and early neonatal variables using checklist?Response 5: We thank the reviewer for this question The checklist was consists of a total of 23 questions that used to assess data on intra-partum variables , and early neonatal variables  were taken from chart review of pregnant women who delivered during data collection period by using structured checklist.Comment 6What are others in HIV status result other than positive and negative result?Response 6: Thank you again for your observation.# On table 2, Medical and obstetrics characteristics of the mother, the word ‘Others’ refers not to HIV status, rather it refers to Anemia, congestive heart failure, thrombocytopenia, asthma and hydronephrosis.Comment 7You mentioned that night time delivery is associated with birth trauma and the justification seems not scientific i.e. cases are referred during night time and duty issue what if the pregnant referred at the day time and deliver during night? Response 7: This very important observation is highly appreciatedThe justification may not be scientific and it needs further study. However, when we come to our hospital set up in Addis Ababa, Ethiopia, night time hospital environment is absolutely different from day time due to the following reason.1. The number of staff available during the night time is almost half of the day time b/c of duty payment issue of the government.2. Majority of the mother give birth in our setup is during the night time.3. Most of the staffs are tired, fatigued and give less attention to the mother.Comment 8The medical service provided to the mothers and newborns during delivery is important to reduce the overall prevalence of birth injury and its burden. Is it recommendation or discussion?Response 8: Thank you for this comment and we have moved this paragraph to recommendation part.Reviewer # 2Comment 1I suggest shortening the introduction, to avoid repetition and to move to discussion the passage from line 80 to 94.Response 1: We understand and agree with your comment and we thank the reviewer for suggestion. We made correction based on your comment.Comment 2In the method section i advice to not provide as a separated paragraph the simple size and the procedure removing mathematical formula and summarizing in a single sentence.Response 2: We thank the reviewer for constructive comment and we edited the paragraph as belowThe single population proportion formula was used to determine the sample size with the following assumptions: Where; n=Sample size, Z= 95 % confidence level (Z α/2 = 1.96), α = Level of significance 5% (α= 0.05) and d= Margin of error 5% (d = 0.05).The prevalence of birth trauma was (P) = 8.1% taken from the previous study done in Jimma University Specialized Hospital, South Western Ethiopia, and sample size was 125. The prevalence of birth asphyxia was (P) = 32.9 % taken from the previous study conducted in Jimma zone public Hospitals, South West Ethiopia, after comparing with other studies done in Ethiopia , After considering 10% non-response rate, the total sample size was 373. Finally, from the calculated sample size for the first and second dependent variables, the largest sample size was 373Comment 3 The main problem in the method section and subsequently in the reported results was related to the variables considered and their definition. In the statistical analysis the authors used the total length of the labour but it would be desirable to report first and second stage separately. In fact, labor and birth is a dynamic process and each stage of labor is characterized by different aspects, risks, obstetrical management and impact on fetal and maternal wellbeing. The total duration of the labor does not represent an adequate parameter and statistical analysis loses of significance.Response 3: These is very important comment, However, during data collection we have only taken the total duration of true labor, it would be better if we were take the data by categorizing first and second stage of labor. Comment 4 Definition of intrapartum fetal distressResponse 4: Fetal distress, defined as progressive fetal hypoxia and/or academia secondary to inadequate fetal oxygenation, is a term that is used to indicate changes in fetal heart patterns, reduced fetal movement, fetal growth restriction, and presence of meconium stained fluid.Comment 5 The threshold of 1 hour for the premature rupture of membrane is totally arbitrary, add references if availableResponse 5: We admit that and tried to correct it.Premature rupture of memberane is rupture of membrane of the amniotic sac and chorion occurred before onset of true labor.Comment 6Apgar score is a subjective evaluation especially in non-adequate trained health workers, I suggest to specify who made the evaluation Response 6: This is very important comment and we need to appreciate to thisThe APGAR score was evaluated by trained health worker like resident and gynacologist.Comment 7 In the results I suggest to avoid description of socio-demographic features and to refer to Table 1.Response 7: This is also very important comment; therefor it is corrected based on your suggestion with in the manuscript.Comment 8Provide the list of abbreviations under each table to a better comprehension.Response 8: Thank you very much for this observation; we have written the abbreviations under each table.Comment 9: In my opinion was essential to report the number of elective, urgent and emergency cesarean section because they were burdened of different level of birth injury risk. A subgroup analysis is desirable to understand the association with birth injury in the univariate and multivariate analysis.Response 9: We would like to appreciate your point of view and thank the reviewer for this comment. The number of either elective or emergency cesarean section was burdened for different level of birth injury risk. However, during analysis time bivariate logistic regression was done to check the association b/n mode of delivery (c/s) with birth asphyxia and we found that no association b/n mode of delivery with that of birth asphyxia . Due to this reason we could not able to do multivariate analysis for this variable.Comment 10: I advise to provide a unique paragraph for the discussion.Response 10: We thank and accept the reviewer for this comment. The following paragraph was added on the discussion part. In this study the burdens and associated factors of birth injury among live birth newborns at Addis Ababa Public Hospital are reported. Short height of the mothers, intrapartal fetal distress, cord prolapse, tight nuchal cord, birth attended by residents, male sex and low birth weight where found to be a significant predictors of birth asphyxia. Whereas, birth trauma was significantly associated with gestational diabetic mellitus, prolonged duration of labor, instrumental delivery and night time birth.Comment 11: The Discussion lacks a decent literature review, and it is unclear what the study adds to what is already known on the subject.Response 11: Thank you. We were tried to look all the available literature related to our research, know some literature review are incorporated.Comment 12: I suggest to provide a more deep analysis of the literature evidence and to analyze, moreover, the possible impact of healthcare personnel training (See this paper: 10.11604/pamj.2022.42.169.32816).Response 12: Thank you the reviewer for this suggestion. We have seen those above paper and they are majorly focused on the effect of healthcare personnel training on neonatal resuscitation, on the other hand in our study when we collect data we take only the qualification of birth attendant i.e. General practitioner, Gyni resident or midwifery.Comment 13: In relation to the findings on the role of maternal height, fetal head circumference and pelvic-fetal disproportion consider this paper for the discussion 10.1371/journal.pone.0275400.Response 13: Thank you reviewer for giving us this direction, we have seen and considered this paper in our discussion.AttachmentResponse to Reviewers.docxSubmitted filename: Click here for additional data file. 16 Jan 2023Prevalence of birth injuries and associated factors among newborns delivered in public hospitals Addis Ababa, Ethiopia, 2021. Crossectional StudyPONE-D-22-05977R1  Esubalew Amsalu Tibebu  Dear Dr. We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.An invoice for payment will follow shortly after the formal acceptance. 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A 28-year-old female patient presented to our hospital with cough, fever, and a salty, watery expectoration. She was diagnosed with a pulmonary hydatid cyst based on thorax computed tomography and flexible bronchoscopy findings. Surgical treatment of the hydatid cyst was recommended for the patient. However, the patient did not consent to undergo surgery and medical treatment until 3 months later. Follow-up examinations revealed that the hydatid cyst cavity had completely healed . ,The lung is the second most common organ in which hydatid cysts are seen. Although a hydatid cyst is a benign lesion, it can lead to asphyxia and anaphylaxis when the cyst is ruptured. Moreover, the cyst cavity is often infected during the bronchial or pleural rupture of hydatid cysts


Adverse birth outcomes are a common cause of health problems in developing nations and have a significant negative impact on infant health as well as financial costs to families, communities, and the world. Mothers with HIV may be at increased risk of adverse birth outcomes. However, there is a limited study about adverse birth outcomes among mothers with HIV around the world including in Ethiopia. Therefore this study aimed to assess adverse birth outcomes and associated factors among mothers with HIV Facility based cross-sectional study was conducted among mothers with HIV who gave birth in northwest Amhara region referral hospitals from September 2016 to September 2019. Simple random sampling was used to select 590 mothers. Bivariable and multivariable logistic regressions were carried out to identify factors. Statistical significance was declared by using a p-value < 0.05. An adjusted odds ratio was used to show the magnitude of the association. Out of a total of 590 mothers, the prevalence of adverse birth outcomes among HIV-positive mothers was 21% (95% CI 17.8–24.6%). History of spontaneous abortion , PROM , opportunistic infection , pre-pregnancy BMI of < 18.5 , MUAC < 23 cm , and ANC visit of < 4 times  were significantly associated with Adverse birth outcome. The prevalence of adverse birth outcomes was high. Abortion history, MUAC, BMI, Opportunistic infection, PROM, and a number of ANC visits were associated with adverse birth outcomes. This study suggests to increase number of antenatal care follow-ups, prevent and treat opportunistic infections, and focus on early detection and treatment of pregnancy-related complication In 2019, 37.9 million people were living with HIV2. The sub-Saharan region is the most affected place in the world with 25.6 million people living with HIV3. In Ethiopia by 2018, nearly 690,000 people were living with HIV/AIDS and 11,000 people have died from AIDS4. Although HIV infection has been reported to have little effect on pregnancy outcomes in the developed world, early studies from sub-Saharan Africa suggest that infants of mothers with HIV may be at increased risk of adverse pregnancy outcomes such as lower birth weight, prematurity, and perinatal and neonatal death6.HIV continues to be a burden on women and children worldwide7 and preterm birth is the leading cause of neonatal deaths which is contributing to 35% of the world’s neonatal mortality8. Globally 20.5 million live births is suffered from LBW in 2015 almost half of them in Southern Asia which is 9.8 million and about one-quarter of all LBW newborns are in sub-Saharan Africa9. Worldwide, over 2.6 million deliveries are stillbirths 98% of which occur in low and middle-income countries; 77% in South Asia and sub-Saharan Africa10.Each year, 15 million babies are preterm birth around the world11. Children born with low birth weight and preterm are more likely to die prematurely compared to infants of normal birth weight and gestational age12. Likewise, these children experience more morbidity, both in the short and long term. Among these respiratory distress, heart problems, chronic lung disorders, growth impairment, blindness or low vision, deafness, cognitive impairment, and cerebral palsy are the problems associated with low birth weight and preterm babies14. There is also a greater vulnerability to infectious diseases due to a poorer immune response15.Adverse birth outcomes are a common cause of health problems in developing nations and have a significant negative impact on infant health as well as emotional and financial costs to families, communities, and the world, especially in resource-constrained settings with underdeveloped health systems and weak access to and use of health services21.Studies conducted in different areas reported risk factors for Adverse birth outcomes: low socio-economic status, MUAC < 23 cm, pregnancy-related complications and history of preterm birth, age less than 20, PROM, UTI, multiple pregnancies, preeclampsia, fetal malformation, polyhydramnios, antepartum hemorrhage, previous abortion, residence, lack of antenatal care, maternal disease, null parity, The presence of chronic illness, the absence of antenatal follow-up, HIV status of the mother, CD4 count, Viral load, WHO clinical stage, and anemia were found to be significantly associated with Adverse birth outcomesIn Ethiopia, globally recommended effective strategies have been implemented for a newborn with an adverse birth outcome with given emphasis on the packages of care provided at the prenatal, ante-natal, intrapartum, and postnatal periods. However, the outcome during pregnancy and delivery periods is a major challenge in realizing the seated goal of Sustainable Development Goals. While the effect of HIV infection on maternal morbidity, mortality, and vertical transmission to her offspring is well established. But there is a limited study about adverse birth outcomes among mothers with HIV in Ethiopia. Therefore, this study aims to assess adverse birth outcomes and associated factors among HIV-positive mothers.An institutional-based cross-sectional study was conducted among mothers delivered from September 2016 to September 2019 in northwest Amhara region referral hospitals and the data was extracted from March 3 to May 18/2020.Amhara national region is one of the ten national states in Ethiopia which is found in the Northern part of Ethiopia. The region has 80 hospitals, 847 health centers, and 3342 health posts. there are 6 referral hospitals—namely Gondar University Comprehensive Specialized Hospital (GUCSH), Felegehiwot Comprehensive Specialized Hospital (FCSH), Dessie Referral Hospital (DRH), Debre-Markos Referral Hospital (DMRH), Debre-Birhan Referral Hospital (DBRH) and Debre tabor referral hospitals. Three out of six referral hospitals were found in the Northwest part of the Amhara region. These include: —the University of Gondar comprehensive and specialized Hospital (UoGCSH), Felege Hiwot comprehensive, and specialized hospital (FHCS), and Debre Markos referral hospital. Each referral hospital’s catchment population is estimated to be 5–7 million people. The annual average number of births in each hospital is 6000 per year. according to the hospital report. All three hospitals are providing full ANC/PMTCT, ART, delivery services, and ultrasound-guided obstetric care.All mothers with HIV delivered from September 2016–September 2019 in northwest Amhara region referral hospitals with a gestational age of 28 weeks and above were included in the study. However, mothers who had unknown or unreliable last normal menstrual period (LNMP) with the absence of ultrasound evidence and a mother with unrecorded birth outcome were excluded from the study.The dependent variable in this study was the adverse birth outcome. Whereas Socio-demographic, obstetric, medical, nutritional, and HIV-related variables were the independent variables. This includes age, residence, educational status, marital status history of substance use, including alcohol drinking and smoking, nutritional counseling during ANC, iron and folic acid supplementation during pregnancy, pre-pregnancy BMI, MUAC, CD4 count, viral load, WHO clinical stage of the disease, initiation of ART, time of initiation of ART, time of diagnosis with HIV, types of ARV, anemia, chronic medical disease, Urinary tract infection (UTI), pregnancy-induced hypertension (PIH), Antepartum hemorrhage (APH), the premature rapture of the membrane (PROM), previous history of abortion, previous history of stillbirth, parity, and gravidity.22.Adverse birth outcomes: A woman who had at least one of the following stillbirth, low birth weight, preterm birth23.Preterm birth: Preterm is defined as babies born alive before 37 weeks of gestation but after viability (28 weeks of gestation) and gestational age was calculated based on LNMP or first-trimester ultrasound result24.Low birth weight: a birth weight < 2500 g irrespective of gestational age: dead birth after the 28th week of gestation and before the expulsion from the uterus25.Stillbirth26.APH: defined as any vaginal bleeding in the mother after 28 weeks of gestation as documented in the records by the attending clinician26.PIH: defined clinically as a blood pressure of > 140/90 mmHg after 20 weeks of gestation with or without proteinuria and/or edema as diagnosed and documented by the attending clinician26.Anemia: documented Hgb level below 11gm/dl laboratory diagnosis26.UTI: Defined as a documented clinical/laboratory diagnosis of UTI at any time during the pregnancy2/2p(1 − p)/d2 by considering the prevalence PTB among mothers with HIV was 16.6%16, 95% confidence interval (CI), 3% margin of error to yield a total of 590 study participants. The total sample size was proportionally allocated for the three Hospitals depending on their load of delivery. A simple random sampling technique was employed to select the study participant’s medical records. The delivery registration logbooks were used as a sampling frame and selected each record for our study used a computer-generated random number. Whenever the selected chart did not fulfill the inclusion criteria, the next medical record was considered  Midwives collected the data, while 3 midwives who have a second degree in clinical midwifery supervised the data collection process. Data quality was maintained by the following data quality control mechanisms; A 5% preliminary chart review was conducted in the Gondar university comprehensive and specialized hospital before the actual data collection and amendments were considered based on the result of a preliminary chart review. One day of training was given to data collectors and supervisors. Strict supervision of the data collection was carried out throughout the data collection period. The collected data was checked for its consistency and completeness before any attempt to enter, code, and analyze it.Data were coded and then entered using EPI data version 4.6 and exported to SPSS. The final statistical analysis was done by SPSS version 25. Before analysis, data were cleaned using frequency; listing, and sorting to identify any missed values, and then corrections were made by revising the original questionnaire. There are different techniques of missing data management. Deletion, replacement using the mean or mode of the data (mean substitution/replacement) or predicted values from a regression to substitute the missing values. So for this study, we had used replacement by mean for continuous and Mode for categorical variable if less than 20% of values are missed in one variable, but if more than 20% of values are missed in one variable, we discard the variables. Descriptive statistics were made for categorical variables using frequencies. The result was presented using texts and tables. a multivariable binary logistic regression model was used to assess the association between dependent and independent variables. P-value < 0.05 and Adjusted Odds Ratio (AOR) with 95% CI was used to declare statistically significant predictors in multivariable analysis.Ethical approval was obtained and the need for informed consent was waived by the ethical review committee of the Institute of public health on behalf of the Institutional Review Board (IRB) of the University of Gondar. Permission was obtained from the clinical director of each hospital. Since this study uses secondary data to ensure confidentiality Personal Identifiers Were not used on the data collection form, and all data were kept strictly confidential and used only for the study purposes. The research was conducted according to the Helsinki declarations.Regarding sociodemographic variable such as: educational status and occupational status had missing values of 30 and 43 respectively. These missing values replaced by their Modal value. The study result showed that the majority 564 (95.6%) of respondents were from an urban area and the rest were from a rural area. Regarding the religion of respondents; the majority 553 (93.7%) were orthodox followers and the rest were Muslim and protestant followers. Almost all 584 (99%) mothers with HIV received ARV intervention. Most (84.4%) mothers started their HAART before pregnancy. Regarding their adherence, almost all 578 (98%) have good adherence Table .Table 1SRegarding nutrition variable such as: pre pregnancy BMI and MUAC had missing values of 25 and 14 respectively. These missing values replaced by the mean value. Almost all 583 (98.81%) respondents had taken iron/folate during pregnancy Among those who took iron/folate during pregnancy, 359 (61.58%) of mothers taken with a duration of fewer than 3 months. Almost all 583 (98.81%) respondents received nutritional counseling during their ANC visit. A majority, 524 (88.81%) and 547 (92.71%), of mothers, had MUAC ≥ 23 cm and pre-pregnancy BMI of ≥ 18.5 respectively. A few proportions 36 (6.10%) of mothers are anemic and the rest/majority 554 (93.90%) of them had no anemia. Regarding medical conditions, about 31 (5.25%) had STI and 43 (7.29%) had UTI.Almost all 585 (99.15) mothers with HIV have ANC follow-ups. Only 27 (4.58%) of mothers had prolonged labor the rest/majority of them don’t have prolonged labor . Out of 590 births 10 (1.7%) were stillbirth, 98 (16.6%) were LBW, 74 (12.5%) were preterm, 5 (0.8%) were both stillbirth and LBW, 50 (8.5%) LBW and preterm, 4 (0.68%) Still birth and preterm, and 4 (0.68%) were Still birth, LBW and preterm.In multivariable analysis; history of spontaneous abortion, PROM, presence of opportunistic infection, BMI, MUAC, and ANC visit was significantly associated with adverse birth outcome. This study result showed that having a history of spontaneous abortion increases the risk of adverse birth outcomes by 1.9 times . The odds of adverse birth outcomes among mothers who had PROM during current pregnancy were 3.55 times  higher as compared with their counterparts and other variables kept constant. Regarding opportunistic infection; HIV positive mothers with opportunistic infection were 3.38 times  more likely to develop adverse birth outcomes as compared to those who don’t have an opportunistic infection and the effect of other variables remained constant. Those HIV-positive mothers with pre-pregnancy BMI of < 18.5 were 5.61 times  more likely to have an adverse birth outcome as compared with their counterparts.The study result showed that a mother with MUAC < 23 cm increases the risk of adverse birth outcome by 2.56 times  as compared to those with MUAC ≥ 23 cm and other variables remained constant. Regarding ANC visits; mothers with ANC visits of < 4 times were 3.85 times  more likely to have adverse birth outcomes as compared to mothers with ≥ 4 ANC visits , Tanzania (18%), and Ghana (19%) of mothers who experienced adverse birth outcomes28.The finding of the study showed that the prevalence of adverse birth outcomes was 126 (21.4% 95% CI 18–25%) among which 10 (1.7%) were stillbirth, 74 (12.5%) were preterm and 98(16.6%) were low birth weight. These figures were comparable with findings from studies conducted in Hosanna (24.5%)24 The discrepancy might be due to a difference in the study area and study participant's residents and age group. the study conducted in Dessie used 30–40% of rural resident participants and rural resident mothers are highly prone to adverse birth outcome than those living in urban29 and 15% of study participants in Dessie was Age group < 20 years and this age group is highly prone adverse birth outcome30.The overall prevalence of adverse birth outcomes in this study was slightly lower than in studies conducted in Ethiopia, Dessie, 32.5%25 this might be due to the difference in the study area, this study is done in referral hospitals whereas a study done in Kembata were in a health center and primary hospital. This may be because most normal deliveries take place in health centers while more complicated ones are referred to the tertiary hospital contributing to higher rates of adverse birth outcomes at referral hospitals20 and study participants in this study were HIV positive and HIV increases the risk of having adverse birth outcome31 or it might be due to compromised immune system of HIV positive mothers increase the risk of opportunistic infection, which contributes to the occurrence of adverse birth outcome.The overall prevalence of adverse birth outcomes in this study is slightly higher than in a study done in Kembata (13.9%)32. This might be due to opportunistic infections compromising the nutritional status of the mother and fetal growth, for instance, infants from mothers with syphilis are often premature33.Mothers who had opportunistic infections during pregnancy were found to be more than 3 times more likely to have Adverse birth outcomes than mothers who did not have Opportunistic infections. this finding is consistent with studies done in Nigeria16. Moreover, In these findings mothers with MUAC, less than 23 cm were also found to experience adverse birth outcomes when compared with those with MUAC greater than 23 cm this result is in agreement with the study done in Dessie referral hospital20 This might be due to intergenerational effect of malnutrition that leads to LBW29 or poor nutritional status of the mother compromised the immune system and increase the risk of opportunistic infections that leads to preterm birth.In HIV-positive women the risk of having adverse birth outcomes were more than fourfold higher in a mother who had pre-pregnancy BMI less than 18.5 when compared with mothers having pre-pregnancy BMI ≥ 18.5. This result was similar to a study done in northwest Ethiopia public hospitals30 Debre tabor23, Jima34, Dodola town35, and Metu36. This might be due to the lack of adequate ANC visits decreases the chance of identifying risks factors of Adverse birth outcome early and providing appropriate interventions23.In this study, mothers with less than four times ANC visits were 3.5 times at high risk to have Adverse birth outcomes than those with four and more visits. This result was similar with study done in Mekell Hospital23, East Africa37, Ghana and Kenyatta national hospital39, Axum and Adwa public hospitals40, and Hosanna13. This might be due to that labor will spontaneously initiate within a week after preterm PROM23, or this might be due to -provider-initiated early termination of pregnancy to manage pregnancy-related complications20.Pregnancy-related complication during the current pregnancy was significantly associated with Adverse birth outcome, according to the finding of this research the risk of having adverse birth outcome among mothers who had PROM during the current pregnancy were more than 3 times higher than those mothers who had no PROM. This finding is consistent with a study done Debre taborSince this study is hospital-based, it doesn’t include mothers who gave birth at home, which makes it difficult to conclude the general population. In addition, the data used were secondary there may be bias and incomplete information or missing variables.


Background: This study uses machine learning with large-scale population data to assess the associations of preterm birth (PTB) with dental and gastrointestinal diseases. Methods: Population-based retrospective cohort data came from Korea National Health Insurance claims for 124,606 primiparous women aged 25–40 and delivered in 2017. The 186 independent variables included demographic/socioeconomic determinants, disease information, and medication history. Machine learning analysis was used to establish the prediction model of PTB. Random forest variable importance was used for identifying major determinants of PTB and testing its associations with dental and gastrointestinal diseases, medication history, and socioeconomic status. Results: The random forest with oversampling data registered an accuracy of 84.03, and the areas under the receiver-operating-characteristic curves with the range of 84.03–84.04. Based on random forest variable importance with oversampling data, PTB has strong associations with socioeconomic status (0.284), age (0.214), year 2014 gastroesophageal reflux disease (GERD) (0.026), year 2015 GERD (0.026), year 2013 GERD (0.024), progesterone (0.024), year 2012 GERD (0.023), year 2011 GERD (0.021), tricyclic antidepressant (0.020) and year 2016 infertility (0.019). For example, the accuracy of the model will decrease by 28.4%, 2.6%, or 1.9% if the values of socioeconomic status, year 2014 GERD, or year 2016 infertility are randomly permutated (or shuffled). Conclusion: By using machine learning, we established a valid prediction model for PTB. PTB has strong associations with GERD and infertility. Pregnant women need close surveillance for gastrointestinal and obstetric risks at the same time. PTB is a main cause of serious neonatal morbidity and mortality, which leads to heavy socioeconomic and public health costs [Preterm birth (PTB), a delivery occurring between 20th costs ,2. The eth costs . In Koreth costs . Even wiTo fully identify the pathophysiology of PTB is challenging because it is a complex syndrome in which many factors are involved. Studies have reported various risk factors for PTB, including sociodemographic, lifestyle, genetic, medical, and obstetrics factors. Periodontal disease, such as gingivitis, which more than 40% of the population in the United States suffer from, is one of the contributing factors of PTB ,8,9. TheTo overcome those limitations, we aimed to establish a high-performance prediction model with machine learning and large-scale population data. Furthermore, we assessed the association of PTB with more various dental diseases than in previous studies.Population-based retrospective cohort data came from Korea National Health Insurance claims for 172,462 primiparous women aged 25–40 and delivered in 2017. This retrospective cohort study was approved by the Institutional Review Board (IRB) of Korea University Anam Hospital on 5 November 2018 (2018AN0365). Informed consent was waived by the IRB.The dependent variable was PTB (birth before 37 weeks of gestation) in 2017. Four categories of PTB were introduced according to the ICD-10 Code: (1) PTB 1—PTB with premature rupture of membranes (PROM) only; (2) PTB 2—preterm labor and birth without PROM; (3) PTB 3—PTB 1 or PTB 2; (4) PTB 4—PTB 3 or other indicated PTB . The 188Logistic regression and the random forest were used for the prediction of PTB ,17. A rap-value < 0.01). The proportions of those with GERD during 2011–2016 were higher for preterm birth than for term birth, and these differences were statistically significant: 7.7% vs. 6.6% (2011 GERD), 8.2% vs. 7.6% (2012 GERD), 8.9% vs. 8.0% (2013 GERD), 9.8% vs. 9.1% (2014 GERD), 10.5% vs. 9.6% (2015 GERD), and 11.7% vs. 10.0% (2016 GERD). Likewise, the proportions of those with progesterone, tricyclic antidepressant, and infertility in 2016 were higher for preterm birth compared to term birth, and these differences were statistically significant: 19.0% vs. 15.8% (2016 progesterone), 10.8% vs. 9.6% (2016 tricyclic antidepressant), and 27.7% vs. 18.1% (2016 infertility). The findings of the univariate analysis above confirm the positive associations of preterm birth with GERD during 2011–2016, as well as age, progesterone, tricyclic antidepressant, and infertility in 2016.Descriptive statistics for the 124,606 participants are presented in In The random forest with oversampling data registered an accuracy of 84.03, and the areas under the receiver-operating-characteristic curves with the range of 84.03–84.04. Based on random forest variable importance with oversampling data, PTB has strong associations with socioeconomic status, age, year 2014 GERD, year 2015 GERD, year 2013 GERD, progesterone, year 2012 GERD, year 2011 GERD, tricyclic antidepressant, and year 2016 infertility.This study presents the most comprehensive analysis of the determinants of PTB, using a population-based cohort of 124,606 participants and the richest collection of 186 predictors, including demographic/socioeconomic determinants, dental and gastrointestinal diseases, and medication history. We established a valid prediction model for PTB and investigated its associations with dental and gastrointestinal diseases. Moreover, this study made the following clinical and policy implications. Firstly, the findings of this study agree with those of previous studies on the positive associations of preterm birth with low socioeconomic status ,28. The Thirdly, the findings of this study affirm those of existing literature on the positive associations of preterm birth with GERD ,17,24. IThis study had some limitations. Firstly, indicated PTB  and spontaneous PTB (preterm birth due to spontaneous preterm labor) have different etiology, but this study could not separate them based on the ICD-10 code. Secondly, this study did not examine possible mediating effects among variables . Thirdly, a recent review suggests that different machine learning approaches would be optimal for different types of data regarding the prediction of preterm birth: the artificial neural network, logistic regression, and/or the random forest for numeric data; the support vector machine for electrohysterogram data; the recurrent neural network for text data; and the convolutional neural network for image data . UnitingIn conclusion, this study demonstrated that GERD and infertility are significantly associated with PTB through a valid prediction model for PTB by using machine learning with large-scale population data. Through this study, the need for close surveillance of the obstetric risks as well as the gastrointestinal risk for PTB, which has been overlooked, is ascertained. Further prospective studies to elucidate the pathophysiology of GERD increasing the risk of PTB are needed.