Lower birth weight is associated with diabetes although the underlying mechanisms are unclear. Muscle mass could be a modifiable link and hence a target of intervention. We assessed the associations of birth weight with muscle and fat mass observationally in a population with little socio-economic patterning of birth weight and using Mendelian randomization (MR) for validation.In the population-representative “Children of 1997” birth cohort , we used multivariable linear regression to assess the adjusted associations of birth weight (kg) with muscle mass (kg) and body fat (%) at ~17.5 years. Genetically predicted birth weight (effect size) was applied to summary genetic associations with fat-free mass and fat mass (kg) from the UK Biobank  to obtain unconfounded estimates using inverse-variance weighting.Observationally, birth weight was positively associated with muscle mass  2.83 to 3.75) and body fat . Stronger associations with muscle mass were observed in boys than in girls (p for interaction 0.004). Using MR, birth weight was positively associated with fat-free mass  and fat mass . No difference by sex was evident.Higher birth weight increasing muscle mass may be relevant to lower birth weight increasing the risk of diabetes and suggests post-natal muscle mass as a potential target of intervention. Observationally, lower birth weight is associated with higher risk of many chronic diseases including cardiovascular disease, diabetes and poor liver function,–4 but isObservationally, birth weight is positively associated with muscle mass in both teenagers and adults., 11 RandTo clarify the role of birth weight in body composition, we conducted two analyses with different assumptions and study designs . First, Ethical approval for the study, including comprehensive health related analyses, was obtained from Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster (HKU/HA HKW IRB). Informed written consent was obtained from the parents/guardians, or from the participant if 18 years or older, before participation in the Biobank Clinical Follow-up.The MR study only uses published or publicly-available data. No original data were collected for the MR study. Ethical approval for each of the studies included in the investigation can be found in the original publications (including informed consent from each participant).“Children of 1997” is a population-representative Chinese birth cohort (n = 8327), based on 88% of births in Hong Kong in April and May 1997. The origBirth weight recorded in grams was considered in kilograms and as internally generated gestational age-specific birth weight z-scores. Gestational age recorded in days was considered in weeks. Gestational age was calculated from the actual and expected dates of delivery reported by the mothers or primary caregivers at the initial MCHCs visit. The reported expected date of delivery is based on the date of the last menstrual period and any dating scans.Muscle was assessed from whole-body muscle mass (kg), and dominant hand grip strength (kg). Fat mass was assessed from body fat percentage.−8) adjusted for gestational age where available (only available in <15% of the sample) and study-specific covariates were obtained from a GWAS consisting of two components, the Early Growth Genetics (EGG) Consortium  and the UK Biobank . A structural equation model was used to decompose the contributions of maternal genetic and fetal effects on birth weight .Reviewers' comments:Reviewer's Responses to QuestionsComments to the Author1. Is the manuscript technically sound, and do the data support the conclusions?The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: YesReviewer #2: Partly**********2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: YesReviewer #2: No**********3. Have the authors made all data underlying the findings in their manuscript fully available?PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.The Reviewer #1: YesReviewer #2: Yes**********4. Is the manuscript presented in an intelligible fashion and written in standard English?PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #1: YesReviewer #2: Yes**********5. Review Comments to the AuthorPlease use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. Reviewer #1: It was a pleasure to review this comprehensive study performed by Liu and colleagues, investigating the effect of birth weight on consequent body composition. The authors are experienced with the applied methods and have taken care in the performing appropriate analyses.The work is already close to a standard suitable for publication. My main suggestion for improvement would be some clarification regarding the interpretation of causality. I think it is important that the authors discuss the potential implications of a shared (genetic) aetiology between birth weight and consequent body composition. Keeping this in mind, is it justified that the authors should imply in their conclusion that birth weight has a causal effect on consequent body composition?In any case, I think that the authors should also be more clear about whether they are genuinely suggesting birth weight as a target for clinical intervention - although they do state this in the last line of the conclusion, I must admit that I'm struggling to take it seriously. The practicalities of modifying birth weight is another consideration. How might this be achieved? If the authors prefer not to answer this, then they should probably remove this suggestion.Some discussion about the range of birth weights for which these findings might apply is also warranted. Can these estimates be extrapolated to the extremes of birth weight, for example?Finally, I wonder whether the authors might also consider replacing (or supplementing) some of the existing results tables with figures . The current format used for presenting the data is a little overwhelming in places and therefore difficult to follow. Figures might make things easier to digest.Reviewer #2: The authors examined the associations of birth weight (BW) with muscle and fat mass in an observational study. They also performed a Mendelian Randomisation (MR) of BW on these measures in the UK Biobank study. I have several major concerns relating to the MR section of the paper.https://doi.org/10.1038/s41588-019-0403-1). Further papers discussing this issue are https://doi.org/10.12688/wellcomeopenres.10567.1 and https://doi.org/10.1093/ije/dyz019. Alternatively, the authors might be asking about whether the genetic variation underlying birth weight is shared with the underlying muscle and fat mass, in which case, the fetal genotype is more important. Could the authors please clarify this.The authors do not clearly state the question that they are seeking to answer with the BW-fat/muscle MR analysis. It would be helpful if the authors could provide a diagram (eg. a DAG) explaining the causal question which they seek to answer. For example, are the authors using birth weight as a proxy for intrauterine exposures which might influence muscle and fat mass? If so, the maternal birth weight-associated alleles that are not passed to the child are the appropriate instrumental variables to use. The issue of MR in this context was discussed in the latest BW GWAS paper  is over 50mb from the nearest signal suggesting that the correlation here doesn’t reflect real LD. The signal rs1011939 (GPR139) also is the only SNP on chromosome 16 but seems to have been dropped as “not independent” although there can be no real LD with the other signals.Other commentsIn the limitations section, point 6 leaves me confused. They state “no age-specific genetic predictors of BW are available”, but birth weight is by definition the weight at birth, there is no age variation in BW. Point 8 also leaves me a little confused. It talks about lifetime exposure, but birth weight is again defined only at birth. I suggest the authors rephrase this point as I’m not entirely sure from what they have written what they are trying to say here.**********what does this mean?). If published, this will include your full peer review and any attached files.6. PLOS authors have the option to publish the peer review history of their article  digital diagnostic tool,  22 Aug 2019Thank you so much indeed for these very helpful comments. We have responded all the reviewers' comments respectively and updated the manuscript and other related documents accordingly. Further details could be checked in the Response to Reviewers file and the Manuscript with Track Changes file.AttachmentResponse to Reviewers_Finalized.docxSubmitted filename: Click here for additional data file. 23 Aug 2019The effect of birth weight on body composition: Evidence from a birth cohort and a Mendelian randomization studyPONE-D-19-16847R1Dear Dr. Schooling,We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at onepress@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact With kind regards,David MeyreAcademic EditorPLOS ONEAdditional Editor Comments :Reviewers' comments: 28 Aug 2019PONE-D-19-16847R1 The effect of birth weight on body composition: Evidence from a birth cohort and a Mendelian randomization study Dear Dr. Schooling:I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. onepress@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact plosone@plos.org. For any other questions or concerns, please email Thank you for submitting your work to PLOS ONE.With kind regards,PLOS ONE Editorial Office Staffon behalf ofDr David Meyre Academic EditorPLOS ONE


Classic congenital adrenal hyperplasia (CAH) secondary to 21-hydroxylase deficiency is characterized by increased prenatal adrenal androgen secretion. There are a small number of reports in the literature showing higher birth weight and length in CAH newborns.CYP21A2 gene. Birth data were calculated as standard deviation (SD) scores according to German reference values.We analyzed birth weight and length data of 116 German newborns  with classic CAH who were born during the period from 1990 to 2017. All children have been followed or are currently treated as outpatients in our clinic. All children were born at term. The mothers were healthy and their pregnancies were uneventful. The diagnosis of CAH was confirmed by molecular analyses of the Weight and length in male CAH newborns (mean ± SD)  were significantly higher than in female CAH newborns , but male-female differences in the CAH cohort were lost when the data were converted into SD scores. The birth sizes of the CAH newborns did not differ from the reference group. The birth sizes also did not differ between the different CAH genotypes. Maternal age, mode of delivery and maternal parity had no influence on birth size.Our data show that prenatal hyperandrogenism does not affect fetal growth. What is already known on this topic?Prenatal weight gain and birth weight are partially influenced by androgen action. Some reports in the literature mention higher birth weight and length in congenital adrenal hyperplasia newborns. However data on this topic are inconsistent.What this study adds?We studied birth size in term newborns with classic congenital adrenal hyperplasia who were followed in our hospital. Our data support the assumption that prenatal hyperandrogenism has no effect on fetal growth.CYP21A2 causing varying degrees of impairment of 21-hydroxylase deficiency (21-OHD) activity. Classical CAH with 21-OHD occurs in two forms, namely, a three-times more frequent form with salt wasting  and a simple virilizing form without aldosterone deficiency  is the most common form of inherited disorders of cortisol biosynthesis in the adrenal cortex. It is due to mutations in the active gene ficiency . Both foSince term-born male newborns are heavier than females, it has been speculated that prenatal weight gain and birth weight are also at least partially influenced by androgen action . In contSome reports in the literature show higher birth weight and length in CAH newborns. According to data from Finland, both girls and boys with classical CAH are significantly longer at birth than healthy newborns of the same ethnic origin . ItalianThe objective of our study was to analyse birth weight and length of children with classical CAH who were treated in the outpatient department of our hospital. The severity of the CAH phenotype was determined by molecular genetic classification of the common mutations ,9,10,11.Birth weight and length data of 116 German newborns  with classical CAH who were born during the period from 1990 to 2017 were analyzed. All children have been followed or are currently treated as outpatients in our endocrinology clinic. All children were born at term  either by spontaneous vaginal delivery (n=95) or by caesarean section (n=21). The mothers (age: 20 to 42 years) were healthy primipara (n=77) or multipara (n=39), and the pregnancies were uneventful. Data on maternal body mass index at delivery were not available. CYP21A2 gene. Molecular genetic classification of the severity of CAH was performed according to Krone et al  and length (cm) data were obtained from the patient records (“Vorsorgeheft”). As birth weight we used the weight measured at birth and for length we used the data obtained between three and seven days after birth. The length measurement at that age is part of the clinical examination of the newborn, usually before discharge from the hospital and the value obtained is more reliable than the length measured at birth. Birth data were calculated as SDS according to German reference values as follows : SDS = . We defiThe study design  was approved by the Ethical Committee of our Hospital without an approval number. Informed consent has been obtained from the parents after full explanation of the purpose and nature of all procedures used.Statistical analysis was performed using SPSS, Version 21 . Data are expressed as mean ± SD and median. Kruskal Wallis test was used to compare values between different genetic groups. Student t-test for unpaired samples was used to compare weight and length values between status of maternal parity and mode of delivery.Birth size (weight and length) in term newborns with classic CAH are shown in Androgen action on birth size is implicated by the fact that healthy male newborns are longer and weigh more than female newborns . ChildreIn 1971, a study from Canada compared the birth weights of CAH newborns with their unaffected siblings and normal newborns and found that only females with CAH were heavier than the female controls and female siblings . JaaskelIn addition Italian authors reported that the mean birth length in both boys and girls with classical CAH was significantly greater than the mean birth length in healthy Italian children and speculated that the birth data correlated with the severity of the phenotype . In contFurthermore, in a large retrospective observational cohort study from France, heavier male than female CAH newborns, but overall normal mean birth weight and birth length were reported . Our datIt is not surprising that the results in the literature are inconsistent. Most reports on birth size in CAH newborns do not provide data on the course of pregnancy, maternal age, maternal parity status, or mode of delivery. The somatic classification of neonates is primarily based on birth weight. Birth weight is affected by a multitude of different factors such as socio-economic status, maternal age and concomitant diseases of the mother in pregnancy, as well as placental, fetal and environmental conditions ,19,20,21There were some limitations to our study. The sample size is too small to exclude a type 2 statistical error. The study is retrospective. The data analyzed cover a period from 1990 to 2017. It was not possible to exclude all the different factors which might affect birth size of newborns with CAH.In general data on birth size of newborns with CAH secondary to 21-OHD are scarce. We tried to clarify existing conflicting published data on this topic. Our data support the assumption that prenatal hyperandrogenism has no effect on fetal growth.


Small for gestational age and preeclampsia have both been described as risk factors for bronchopulmonary dysplasia in preterm neonates, but their respective role in the occurrence of bronchopulmonary dysplasia is debated. We evaluated the relation between small for gestational age and bronchopulmonary dysplasia in neonates born to mothers with preeclampsia. We hypothesized that low birth weight is still associated with bronchopulmonary dysplasia in this homogeneous population.th percentile on the AUDIPOG curves) were compared to those with appropriate birthweight for gestational age by bivariable analyses and logistic regression models, estimating odds ratios (ORs) and 95% confidence intervals (CIs).Retrospective single-center cohort study including 141 neonates born between 24 and 30 weeks’ gestation to mothers with preeclampsia. The main outcome measure was moderate to severe bronchopulmonary dysplasia at 36 weeks’ postmenstrual age. Neonates born small for gestational age (birthweight < 10Bronchopulmonary dysplasia rates were 61.5% (32/52) and 27.4% (20/73) for small for gestational age and appropriate birthweight for gestational age neonates (p < .001). On adjustment for gestational age and other confounding factors, the risk of moderate to severe bronchopulmonary dysplasia was greater for small for gestational age than appropriate birthweight for gestational age neonates , as was the composite outcome death or moderate to severe bronchopulmonary dysplasia .Small for gestational age was associated with bronchopulmonary dysplasia in very preterm neonates born to mothers with preeclampsia.CNIL no. 1747084. Bronchopulmonary dysplasia (BPD) is the main respiratory sequelae of preterm birth; it is characterized by arrested alveolar development with reduced number but increased size of alveoli and impaired capillaries . Its incSmall for GA (SGA) has been described as a risk factor for BPD. Several studies found the risk of BPD two- to six-fold higher for SGA preterm infants than AGA newborns ,4,5. OneTo help disentangle the respective role of preeclampsia and SGA in the development of BPD, we evaluated the impact of SGA on the occurrence of BPD in neonates born to mothers with preeclampsia. We hypothesized that low birth weight is still associated with BPD in this homogeneous population.This retrospective cohort study included preterm infants born between 24 and 30 weeks’ gestation and hospitalized between January 1, 2009 and December 31, 2013 in a level III neonatal intensive care unit at Port Royal Maternity . Infants were included if their mothers had preeclampsia  with proteinuria ≥ 0.3 g/24 h, or eclampsia . We excluded mothers with preexisting or gestational hypertension and isolated Hemolysis, Elevated Liver enzymes, Low Platelet count syndrome (HELLP syndrome) not associated with preeclampsia and infants with severe birth defects and chromosomal aberrations. Data were retrospectively collected by using the computer database Perinat Collection, PremUp. The collection of perinatal data was authorized by the National Data Protection Authority (CNIL no. 1747084) and the study was approved by the ethics committee of the French Neonatal Society. The CNIL authorizations allow us to collect and use data retrospectively from patients hospitalized in the unit. There was no consent specifically requested from families but they receive information about clinical research upon admission to the unit and their non-opposition is collected. All data were fully anonymized.The primary outcome was moderate to severe BPD defined as oxygen requirement for at least 28 days and persistent need for oxygen or ventilatory support at 36 weeks’ postmenstrual age (PMA) . The secth percentile according to the sex-specific AUDIPOG curves [Maternal and neonatal data were collected from medical records. Abnormal Doppler findings during pregnancy mean reduced, absent, or reversed umbilical artery end-diastolic flow; increased middle cerebral artery end-diastolic flow or cerebral redistribution process; reduced, absent, or reversed atrial flow in the ductus venosus; diastolic notch or abnormal pulsatility index on uterine artery. The antenatal corticosteroid course was considered complete if betamethasone was administered twice at 24-h intervals, incomplete if only one injection was administered, or absent. GA was estimated by the first trimester ultrasound if available and otherwise with the last menstrual date. SGA was classified as birth weight below the 10G curves  and AGA G curves . NeonataG curves .Ventilation protocols, fluid intake and PDA management were unchanged throughout the study. High-frequency oscillation ventilation (HFO) was used if hypercarbia or hypoxia persisted despite high pressure with conventional ventilation and in cases of pulmonary hemorrhage. Inhaled corticosteroids were used for extubating infants with continuous assisted-ventilation dependency. Systemic corticosteroids were used in rescue for infants with severe respiratory disease, repeated extubation failure and continuous assisted-ventilation dependency.Categorical variables are described with number (%) and were compared by chi-square or Fisher exact test. Continuous variables are described with median and interquartile range (IQR) and were compared by Wilcoxon test. We compared the main maternal, obstetrical and neonatal characteristics between SGA and AGA newborns. The associations between SGA and neonatal outcomes were analyzed by bivariable analyses, then adjusted on GA. The associations between SGA and moderate or severe BPD and death or moderate to severe BPD were further adjusted on potential confounding factors selected among characteristics associated with BPD in our sample and relevant factors from the literature. Results from logistic regression models were quantified by odds ratios (ORs) and 95% confidence intervals (95% CIs). Significance was set at p≤.05. Analyses involved use of SAS v9.3 .We screened 778 infants born between 24 and 30 weeks’ gestation and hospitalized between January 1, 2009 and December 31, 2013 . We analSGA newborns more frequently required HFO ventilation and final extubation occurred later than did AGA newborns . They alOverall, 61.5% (32/52) and 27.4% (20/73) of SGA and AGA newborns showed moderate or severe BPD , lower median birth weight , higher lactate level at birth , and higher rate of PDA  and more frequently received more than 2 doses of surfactant . Male sex and antenatal corticosteroids use were not significantly associated with moderate or severe BPD in our population. However, because these variables are frequently described in the BPD literature, they were selected as potential confounding factors. On multivariate regression, risk of moderate to severe BPD was greater for SGA than AGA infants , as was death or moderate to severe BPD  . Except A second analysis using birthweight z-score as a continuous variable and adjusted on the same potential confounding factors than the previous multivariate analysis was performed, and similar results were found: higher adjusted risk of moderate to severe BPD with decreasing birthweight z-score , and higher risk of death or moderate to severe BPD with decreasing birthweight z-score .Among very preterm infants born between 24 and 30 weeks’ gestation to mothers with preeclampsia, SGA was associated with increased frequency of moderate or severe BPD and death or moderate to severe BPD at 36 weeks’ PMA.et al., including 4525 infants born between 24 and 30 weeks’ gestation in nine European countries, BPD rate significantly increased with decreasing birth weight for GA; the adjusted OR for BPD was 6.4 with birth weight below the 10th percentile versus birth weight between the 50th and 74th percentile [et al. showed that injection of sFlt-1 in amniotic fluid impaired the lung growth of rat pups [The link between SGA and BPD has already been highlighted in several studies ,20,21,22rcentile , and somrcentile . Tang etth percentile but no differences for the other neonatal outcomes [et al., in a large retrospective cohort study in Sweden, including preterm infants born before 37 weeks’ gestation, found a strong association between preeclampsia-related disorders and BPD but did not adjust the analyses for GA [th percentile in the MOSAIC cohort study [et al. [et al. found preeclampsia as a risk factor for DBP with an OR at 2.96 in a population of premature newborns with an average GA 29 week’s gestation [et al. in 2013 found a negative association between preeclampsia and the risk of developing DBP [et al. didn’t find any association between preeclampsia and BPD development in a Canadian population of premature less than 32 week’s gestation [To our knowledge, studies about mortality and morbidity after premature birth often include together several contexts of premature birth or include preeclampsia in vascular disorders of pregnancy without studying separately preeclampsia. Only few studies specifically analyzed neonatal outcomes of newborns born to mothers with preeclampsia. None studied the outcome BPD at 36 weeks’ PMA. One study found increased risk of fetal and neonatal mortality with birth weight below the 10outcomes . A seconoutcomes . Some cos for GA . An Itals for GA . Howeverrt study  but high [et al. , pretermestation , while Yestation .In our study, we focused on a homogenous population of neonates born to mothers with preeclampsia. Moreover, our population concerned more immature infants than those in several already published studies. Moderate or severe BPD and death or moderate to severe BPD were more frequent for SGA than AGA preterm infants and this difference persisted after adjustment for GA. As SGA is frequently the consequence of fetal growth restriction, this result is consistent with Torchin’s study which showed that vascular pregnancy disorders, such as preeclampsia, HELLP syndrome or eclampsia, were factors involved in BPD development only if associated with fetal growth restriction .Besides the main result, we detailed the respiratory management in our population, which indicated more prevalent respiratory morbidity in SGA than AGA infants: the need for endotracheal ventilation including HFO and for non-invasive ventilation was more frequent, and final extubation occurred later. Also, use of inhaled corticosteroids was more frequent for SGA than AGA newborns, although the association was not significant. They were used only to allow weaning of invasive ventilatory support.We conducted this study to help us distinguish the respective role of preeclampsia and small for gestational age in bronchopulmonary dysplasia. In this study, we confirm that low birth weight for GA is a major factor in BPD development. On the other hand, several studies focused on the role of anti-angiogenic factors in this disease, referring to the “vascular hypothesis of BPD”, which implies a modified balance between pro and anti-angiogenic factors leading to an impaired vascular and alveolar development ,33. HoweOur study presents several limitations: it was a retrospective, single-center cohort. The small sample size reduced the statistical power. We used birth weight as a proxy to identify growth-restricted preterm newborns. BPD status and severity were defined at 36 weeks PMA according to the National Institute of Child Health and Human Development definition , which hIn conclusion, in a homogeneous population of babies born to mothers with preeclampsia, we highlight the importance of birth weight for GA in the development of BPD. SGA in a context of preeclampsia multiplied by 5.9 in extremely preterm babies the risk of BPD development. These results encourage us to target this population for futures therapeutics studies. Indeed, SGA preterm infants are often excluded in therapeutics studies because of increased risk of complications or deaths in this population of premature children . At pres


The use of Web-based forms and data analysis can improve the collection and visualization of data in clinical research. In Italy, no register exists that collects clinical data concerning home births.The purpose of this study was (1) to develop a Web portal to collect, through a Web-based form, data on home births in Italy and (2) to provide those interested with a graphic visualization of the analyses and data collected.Following the World Health Organization’s guidelines, and adding questions based on scientific evidence, the case report form (CRF) on the online form was drafted by midwives of the National Association of Out-of-Hospital Birth Midwives. During an initial phase, a group of midwives (n=10) tested the CRF, leading to improvements and adding the necessary questions to achieve a CRF that would allow a more complete collection of data. After the test phase, the entire group of midwives (n=166) registered themselves on the system and began filling out birth questionnaires. In a subsequent phase, the administrators of the portal were able to view the completed forms in a graphic format through the use of interactive maps and graphs.From 2014 to 2016, 58 midwives included 599 birth questionnaires via the Web portal; of these, 443 were home-based, 76% (321/424) of which were performed at home and 24% (103/424) at a midwifery unit. Most of the births assisted  were in northern Italy, and the average ages of the mother and father were 33.6 (SD 4.7) years and 37.0 (SD 5.6) years, respectively.We developed an innovative Web-based form that allows, for the first time in Italy, the collection of data on home births and births in the midwifery unit. Furthermore, the data collected are viewable online by the midwives through interactive maps and graphs that allow them to have a general and continuously updated view of the situation of out-of-hospital births performed by the National Association of Out-of-Hospital Birth Midwives. The future goal is to be able to expand this data collection to all out-of-hospital births throughout the national territory. With an increase in the number of enrolled midwives, it would be possible to use the portal as a Web-based form and also as a portal for sharing resources that would help midwives in their clinical practice. From the mid-20th century, giving birth moved from the home into the hospital in most well-resourced countries. This change was related to the decreased rates of perinatal, neonatal, and maternal mortality observed in the same period. In-hospital birthing was one of the possible explanatory causes, perhaps the most important, as even living conditions, in general, began to change at that time. The rapid improvement of medical technologies and the availability of more knowledge and resources led to the over-medicalization of procedures once considered natural and physiological events, such as childbirth, which needs few obstetrical interventions when of low risk . Thus, aRates of planned out-of-hospital births  are low in high-income countries, although they vary widely. The highest rate is in the Netherlands; in the past, almost 30% of all babies born here were born at home, and home birth had always been an integrated part of the maternity system. Women in the Netherlands also currently have the option of giving birth in a birth center (a home-like setting); 11.4% of births occur in this setting and 16.3% at home ,6. In WaThe Certificate of Delivery Assistance (CeDAP) is the nationwide mandatory questionnaire, completed by the midwife or physician attending the delivery, which collects information about the parents, the pregnancy, and the newborn baby. The CeDAP constitutes the richest source of health, epidemiological, and sociodemographic information concerning the birth event. This certificate is not always complete for out-of-hospital births and therefore does not contain all the information necessary to better assess the quality of births performed at home or in a midwifery unit.To obtain more information on and to evaluate out-of-hospital births, it was necessary to provide the birth assistance certificate with additional questions; for this reason, a few years ago we began to collect paper data sheets and PDF forms. However, problems were found during collection. In fact, to be processed, the data collected had to be sent by mail to the processing site, which involved a waste of resources. In the last few years, the paper data collection questionnaires have been joined by increasingly advanced digital data collection systems: Web pages allow users to enter data collected in their studies and share it immediately with other users or simply analyze it for their own purposes .The continuous development of information technology has allowed us to improve the computerized data collection questionnaires further, making them increasingly user-friendly for those entering the data collected during clinical practice.With this information and with the help of the National Association of Out-of-Hospital Birth Midwives , we decided to develop a portal  that wouThe association is a national network of qualified midwives providing care and support to pregnant women and their babies before, during, and after childbirth. The association, founded in 1981, covers almost all midwives who attend out-of-hospital births. All qualified midwives who adhere to the association assist women who meet the eligibility criteria for out-of-hospital birth defined by national and international guidelines [The portal was developed using ASP.NET WebForms, an open source Web framework for building modern Web apps and services with .Net. For data management, it used Microsoft SQL SERVER 2008 R2, a relational database management system with which all information was saved, loaded, and managed. In the database, the data from the forms were saved in JSON (JavaScript Object Notation) format.Case report form (CRF) variables were defined in an eXtensible Markup Language (XML), then automatically transformed into an HTML page using XSLT transformation; the HTML page contains tags and attributes managed by AngularJS, a framework JavaScript client-side compatible with both desktop and mobile browsers . All datThe XML, which contains the CRF variables, can be changed at any time and according to need  without having to rewrite other files or change the database structure. All the architecture described is downloadable from GitLab .Following the World Health Organization’s guidelines, and adding questions based on scientific evidence, the CRF was created by the midwives of the association. The CRF records every moment of pregnancy from the first visit to the end of each birth, including the weeks immediately following the birth . The maiInformation person completing form: information regarding the midwife filling out the form. It is not necessarily the same person who followed the birth, but the general information is required.First part: to be completed at the beginning of the visit. Some information on the mother is collected .Last third-trimester exams: a report of the tests performed .Second part: subsequent checks . This part collects data on whether the exclusion from home care took place before labor. If the answer is affirmative, a series of questions must be filled out regarding the outcome of the childbirth and the motivations that led to exclusion.Third part: essential data concerning the childbirth .Fourth part: information regarding the weeks following childbirth, type of breastfeeding, and whether the child has had any problems.Lotus: asks if lotus birth has been carried out. Lotus birth is the practice of leaving the umbilical cord uncut so that the baby remains attached to the placenta until the cord naturally separates at the navel as a cut cord does 3 to 10 days after birth. If a lotus birth was carried out, information on type of lotus and related information is collected, including the parent’s experience.The compilation of the questionnaires by midwives has made it possible to obtain a source of useful information not only for the group of clinicians involved in the processing of data but also for the midwives of the association. To facilitate the reading of the data, we created an area of the portal dedicated to the graphic visualization of the collected data. This area was created using Highcharts, a scalable vector graphics-based, multiplatform charting library, which makes it easy to add interactive charts .On one page, for example, a map of Italy is divided into provinces, which are colored differently based on the number of questionnaires. By selecting a single province, information about the births in that area can be visualized by month and by place of birth as seen in The results presented compare women who gave birth at home to those who gave birth in a freestanding midwifery unit.t test was used to test differences of means for normally distributed continuous variables; the Mann-Whitney U test was used for skewed continuous variables.Categorical variables were summarized using proportions and associations tested using chi square or Fisher exact tests, where applicable. Continuous variables were summarized using means and standard deviations for normally distributed data, whereas skewed data were summarized using medians. A two-tailed independent P value of <.05.To identify risk factors, we computed relative risks (RRs) using a multivariate log-binomial regression model, considering the significance of the confidence intervals. Statistical significance was evaluated using 95% confidence intervals and a two-tailed All data management and analyses were performed using SAS software.Data were collected on 424 Italian women who delivered out-of-hospital, 321 (75.7%) of whom delivered at home and 103 (24.3%) at a freestanding midwifery unit. The majority of recruited deliveries  took place in northern Italy. The mean ages of the mothers and fathers were 33.6 (SD 4.7) years and mean 37.0 (SD 5.6) years, respectively . The motOf the 247 multiparas, the majority  had previously given birth in a hospital, and most had a normal vaginal birth . The majority of multiparas who delivered at home  had previously given birth in a hospital, whereas about half of the multiparas who delivered in a freestanding midwifery unit  had previously given birth at home.A quarter of the mothers reported desire for intimacy as a reason for delivering out-of-hospital. Positive previous experience at home and a desire for a new experience were the other frequent reasons for justifying the choice of delivering at home, whereas naturalness and a trusting relationship with midwives were the main reasons for choosing to deliver in a freestanding midwifery unit.The position most frequently used by women for delivering at home was on all fours; for delivering in a freestanding midwifery unit, it was squatting . DeliverThe population enrolled in this first Italian study corresponded to 47% of the expected national deliveries over the study period and for all causes of out-of-hospital births. Considering that the investigated population was selected and only low-risk, planned out-of-hospital births were the target population, the findings are representative and support the choice of out-of-hospital planned births in Italy.Being older than 35 years and being a primipara increased the probability of the delivery occurring in a freestanding midwifery unit compared to at home. Findings are in line with previous studies performed in different European countries, as well as in the United States and Canada -18. AmonThis study had limited power to detect small differences in variables with low incidence. As in similar countries , the ratThis study made it possible, for the first time, to obtain a large amount of information about out-of-hospital births in Italy. The tools used for data collection and visualization have allowed us to optimize the acquisition and monitor the information. The future goal is to be able to expand this data collection to all out-of-hospital births in the national territory. This would also allow midwives to have a more complete and detailed view of the work they perform and help monitor and improve the clinical practice of out-of-hospital births. Moreover, with an increase in the number of enrolled midwives, it would be possible to use the portal not only as a Web-based form but also as a portal for sharing resources that would help midwives in their clinical practice. The interactive graphs and maps  used for


Hepatitis B is a major health concern in Ghana, where prevalence of the virus remains high and most chronic patients are infected during childhood or at birth. This study aimed to determine the prevalence and main factors associated with mother-to-child transmission of hepatitis B in the context of Ghana.In this cross-sectional pilot study, we tested infants born to hepatitis B positive mothers at a hospital in the Eastern Region of Ghana to determine the prevalence of mother-to-child transmission. A questionnaire was completed by hepatitis B positive mothers to investigate the association between factors surrounding the birth of the child and whether transmission had occurred. These factors were analyzed independently using Fisher's exact test. To investigate the relationship between mother's age at the time of delivery and viral transmission, a univariate logistic regression analysis was performed.The prevalence of mother-to-child transmission was 5.9%, with 51 hepatitis B positive mothers included in the study and three infants testing positive. A majority of infants received the standard hepatitis B vaccination schedule (96.1%) while two-thirds received the birth dose. There was no significant association observed between the clinical interventions reported in the study and mother-to-child transmission. No significant association was observed between the age of the mother at the time of delivery and viral transmission . Viral marker testing during pregnancy was absent in the population and could not be reliably assessed.There was a low prevalence of HBV mother-to-child transmission observed despite a clear absence of viral marker and viral load testing. It is recommended that viral profile analysis is performed for hepatitis B positive pregnancies to identify high risk cases. Accordias 12.9% . Ghana ias 12.9% .In addition to the birth dose vaccine, it is crucial to identify infants who are at higher risk of perinatal transmission to administer hepatitis B immune globulin (HBIG), which has previously been shown to be an effective form of post-exposure prophylaxis , 15. HepThe study was conducted at St Dominic's Hospital, Akwatia in the Eastern Region of Ghana. There are roughly 2200 babies born at St Dominic's hospital each year and this site was selected based on the availability of accessible maternal health records and contact details for the mothers. The hospital is funded by donor and government contributions and does not have any specific protocols for handling cases of HBsAg positive pregnancies. They follow the national policy regarding birth dose vaccine and HBIG, both of which must be paid for out-of-pocket.Convenience sampling of maternal health records was used to retrospectively identify mothers who were HBsAg positive during pregnancy, with a child aged between 6-24 months at the time of recruitment. At St. Dominic's Hospital, HBsAg positive cases are recorded within the first days of visiting the antenatal care clinic until birth. Using these records, a list was compiled which consisted of 51 eligible mothers who gave birth within the specified time period, with their child aged 6-24 months. Cases were excluded where infants were outside of the study age range at the time of testing, as well as mothers who declined to provide consent. Study participants were enrolled from February 2018 to April 2018.Hepatitis B tests were performed by a physician using InTec HBsAg Rapid Test Strips of whole blood. According to the manufacturer, test strips have a sensitivity of 99.4% and specificity of 99.8%. The InTec HBsAg Rapid Test Strips were manufactured by Intec Products Inc. in Xiamen, China. Whole blood from a finger prick was placed on the test strip, and the result was read after 15 minutes according to the manufacturer's instructions. The test works on the principle of lateral diffusion, where the formation of an antibody-antigen complex results in visible bands which are considered positive. Positive test results in infants were confirmed by laboratory analysis. The results from prospective HBsAg testing were compared with responses from a questionnaire completed by the mother, which included questions relating to the birth context and interventions.A one-page questionnaire was completed by the mothers and responses were a combination of personal recollection and information retrieved from government issued maternal and child health records. The variables included in the questionnaire were selected based on evidence from previous studies in different settings. These included mother's age at the time of delivery, the birth location, the birth type, the infant's vaccination status, HBIG administration, mother's HBeAg status, viral load measurements, PVST and whether antiviral treatment was administered during pregnancy , 13-18.Questionnaire responses and test results from hepatitis B positive mothers and their children (n = 51) were entered into Microsoft Excel 2007 and imported into Statistical Package for Social Sciences (SPSS) version 25 for analysis. Descriptive analysis was performed to assess the questionnaire response rates. This analysis was also intended to measure the scope of viral marker testing and interventions in HBsAg positive pregnancies to evaluate how cases are managed in the clinic. Categorical data was expressed here as a number and percentage.Aside from mother's age, infant's age and viral load, all of the responses collected from the questionnaire were categorical variables and analyzed independently as unpaired data. The outcome used in the analysis of questionnaire responses was whether the child was HBsAg positive, i.e. whether mother-to-child transmission had occurred. The outcome was binary categorical. The data was cross-tabulated and analyzed using Fisher's exact test for independence. All p-values for this test were two-tailed with p < 0.05 considered significant.To investigate the relationship between incremental change in mother's age at time of delivery and viral transmission, a univariate (unadjusted) logistic regression analysis was performed. The outcome used was whether the infant tested positive for HBsAg. Odds ratio (OR) with 95% confidence intervals (CI) are presented. The p-values for the univariate logistic regression were two-tailed with p < 0.05 considered significant. In order to obtain a valid analysis for multivariate logistic regression, we would need to observe approximately 10 outcome events per variable included . As a reThe study was approved by the Institutional Ethical Review Board at St Dominic's Hospital and local permission was obtained prior to recruitment. The details and reasons for the study were clearly explained in a language that was understood by participants. Information was provided including risks, benefits and any possible complications. Consenting mothers were asked to visit the clinic with their child for HBsAg testing and to complete the study questionnaire.A total of 51 hepatitis B positive mothers were included in the study. Mother's age in the sample population ranged from 23 to 40 years. The average age was 31.2 years and only two mothers recruited into the study were under the age of 25. The age of their infants who were tested for HBsAg ranged from 6 to 22 months, with an average age of 13.5 months. All deliveries took place within a hospital setting with no home births observed. The percentage of caesarean sections was 37.3% and a majority of births were vaginal deliveries (62.7%) .There was a high vaccination rate observed (96.1%), with only two of the infants receiving no HBV vaccine at all. Two-thirds of infants received the WHO recommended birth dose administered within the first 24 hours. Moreover, a majority of infants who were vaccinated received the pentavalent EPI three dose vaccine schedule at 6, 10 and To investigate mother's age at the time of delivery as a potential factor for transmission, a univariate logistic regression was performed with no covariates included in the model. This showed no significant association . The remaining binary study variables were analyzed using Fisher's exact test of independence. Prevention of MTCT through administration of HBIG at birth was not significant (p = 0.06), despite no transmission observed in any of the 30 cases that received the prophylaxis. None of the other study variables, including birth type, any vaccination, birth dose vaccine or antiviral therapy during pregnancy demonstrated significance using this statistical method. Data collected from the study questionnaire was insufficient to test for an association between HBeAg status or DNA viral load and risk of transmission .et al. in Kumasi [et al. in the nearby Ashanti region [This formative study aimed to determine the prevalence of HBV mother-to-child transmission at a single site in the Eastern Region of Ghana as a pre-trial for a larger study. The main factors associated with MTCT were investigated quantitatively, while the responses from the questionnaires were used to evaluate how HBsAg positive pregnancies were managed in the clinic. Given that the estimated national prevalence of individuals with CHB is approximately 12.3% in Ghana , the finn Kumasi  and the i region . In mosti region . If the i region , 25, 26.Although this pilot study was unable to demonstrate significant protection against HBV mother-to-child transmission with HBIG (p = 0.06), this intervention has been previously shown to be an effective form of prevention , 15. TheThe vaccination rates observed at St. Dominic's Hospital were encouraging, at 96.1% in total. A further 66.7% of all infants received the WHO recommended birth dose and only two received no HBV vaccine at all. The study was unable to demonstrate a significant association between vaccination and MTCT. Although speculative given the limited sample size, there is reason to hypothesise that sustained seroprotection may play a role in transmission risk, particularly with a potential lack of cross protection towards the endemic HBV genotype E , 28. ThiOne of the most important observations in this study was the absence of HBeAg and viral load testing. HBV viral profile testing can be performed locally to determine HBeAg status of infected mothers and may be used as a surrogate marker for high viral load. It has been consistently demonstrated in previous studies conducted in different settings that a positive HBeAg status and high viral load during pregnancy are strongly associated with elevated risk of MTCT -18. In fThere was a low prevalence of HBV mother-to-child transmission observed despite a clear absence of viral marker testing and subsequent intervention. Nevertheless, it is strongly recommended that positive HBsAg tests in Ghana are followed up with a viral profile analysis as an effective method of identifying high risk cases.In Ghana, chronic hepatitis B is considered highly endemic, with an estimated HBsAg seroprevalence of 12.3% across all 10 regions;High viral load and positive HBeAg status during pregnancy are associated with an increased risk of mother-to-child transmission;In addition to birth dose vaccination, the risk of HBV mother-to-child transmission from a HBsAg positive mother to infant can be effectively reduced through post-exposure prophylaxis in the form of HBIG.The prevalence of mother-to-child transmission was 5.9%;In this setting, HBeAg and viral load testing are not routinely performed on mothers who test positive for HBsAg during pregnancy;More than half of the families (60%) in this study opted for single dose HBIG at birth to provide further protection against transmission.The authors declare no competing interests.


Low birth weight is defined as a live born infant weighs less than 2 500 g regardless of gestational age. Globally, the prevalence of low birth weight ranges from 3% to 15%. Birth weight plays an important role in infant mortality, morbidity, development, and future health. The prevalence of low birth weight in Ethiopia was estimated to be 14% which is one of the highest percentages in the world. So, the aim of this study is to assess magnitude and associated factors of low birth weight among newborns delivered at Dangla Primary Hospital, Amhara Region, Ethiopia. An institution-based cross-sectional study was conducted at Dangla Primary Hospital from September 27 to June 10, 2017. Systematic random sampling technique was used to select the 232 study participants. A structured and pretested questionnaire was used to collect data. Data quality was assured by pretesting, training, and frequent supervision. Descriptive statistics were performed for the descriptive part of the study. Binary and multiple logistic regression analyses were conducted to identify independent predictors of low birth weight. Those variables and p-value < 0.25 were included in the multivariable logistic regression for controlling the possible effect of confounders. Finally, variables which had significant association were identified on the basis of AOR, with 95%CI and with P-value <0.05. Magnitude of low birth weight was 10.3 %. Previous history of low birth weight , additional food intake during the last pregnancy , and preterm delivery  were independent predictors of low birth weight. Magnitude of low birth weight in Dangla Primary Hospital was high. So, strengthening counseling systems for women through quality antenatal care on advantage of additional food intake and previous bad obstetric outcome is necessary to alleviate the delivery of low birth weight neonates in the study area. Low birth weight is defined as birth weight of a live born infant less than 2500g irrespective of gestational age. It is a public health problem in developing countries especially in sub-Saharan Africa . Around Reasons of low birth weight are mainly linked with either infant/their mothers' side. In developed countries, predominant cause of LBW is preterm birth, whereas in developing countries, Intrauterine Growth Restriction (IUGR) is predominant cause of LBW . MothersConcertinaing outcomes of low birth weight, the odds of developing chronic diseases such as hypertension, cardiovascular diseases, type II diabetes, metabolic syndrome, ischemic heart disease, decreased lung capacity, behavioral disorders, impaired physical, cognitive, and psychological function, and having long-term financial burden and chronic lung disease are higher among newborns weight <1500gm –12.In general, birth weight is an important health status indicator of an infant and is a principal factor that determines the infant's physical, survival, and mental growth. It also indicates past and present health status of the mother , 14. ButThe study was conducted at Dangla Primary Hospital, which is found in Awi Zone, Amhara region, Northwest Ethiopia. It is located in 72 km from South of Bahir Dar regional city. The hospital was established in 2015 as District hospital in Dangla Woreda, Awi Zone. It provides promotive, preventive, curative, and rehabilitative services for about 100,000 catchment population. At the time of its establishment, about 120 staffs were recruited, of them 66 were health professionals and the remaining were supportive staffs. Now the hospital has five wards, namely, medical (19 bed), surgical (21 beds), obstetrics, and gynecology ward (24 beds) and pediatrics (10 beds). Obstetrics and gynecology wards have separate labor, delivery, and postnatal care services and also have family planning, high risk maternity, antenatal care (ANC), and gynecological outpatient department (OPD) . CurrentAn institutional-based cross-sectional study was conducted among sampled mothers who delivered in Dangla Primary Hospital during the study period and fulfill the inclusion criteria.Sample size was calculated by using Single population proportion formula by taking 17.4% from similar recent research performed in Gondar Referral Hospital, Northern Ethiopia . Those pregnant women who did not have additional food intake had 5.0 times higher odds ratio of delivered low birth weight neonates than those who had additional food intake during the current pregnancy  and pregnant women who delivered before 37 weeks of gestational age had 2.14 times higher odds ratio of delivered LBW neonates than those delivered at term  .This study was aimed at determining the magnitude of low birth weight and associated factors in Dangla Primary Hospital. The finding of this study indicated that 10.3% of neonates were born with low birth weight. The finding is in line with the studies conducted in India (11 %)  and instThis study did not find any significant association between low birth weight and sociodemographic factors including maternal age, residence, educational status, monthly income, religion, marital status, and ethnicity. Several studies have shown that sociodemographic factors can influence low birth weight either directly or indirectly .In this study, previous history of low birth weight explained a significant association with low birth weight. Those women having previous history of LBW had higher odds to have delivery of LBW neonates than women who did not have previous history. This result is similar to the study conducted in Nigeria  and JapaThe present study revealed that there is a statistically significant association between additional food intake during last pregnancy and occurrence of LBW. The odds of women who did not have additional food intake in their last pregnancy had get more chance of delivering LBW neonates compared to those mothers who had balanced diet. Again the study conducted in Pakistan , Japan , and AddIn addition, this study showed that LBW was significantly associated with gestational age. The odds of women who gave birth before 37 weeks of gestational age in their last pregnancy had get increased chance of LBW neonates compared to those mothers who delivered at term pregnancy.The finding is similar to studies conducted in Mekele p-value=0.0001 , Gondar The magnitude of low birth weight in Dangla primary hospital was high. Low birth weight in the previous pregnancy, gestational age<37 weeks, and women having no additional food intake during the current pregnancy showed significant association with LBW neonates. Based on the results the following recommendations are forwarded:(I) Health Institutions. To reduce LBW neonate health care providers need to work to early detect and manage risk factors that cause preterm delivery of the newborn. It is advisable that those health care providers need to work in the community on the importance of balanced diet during pregnancy and the consequence of previous pregnancy bad outcomes to the current pregnancy through focused antenatal care on the prevention of LBW newborns.(II) Couples. As pregnancy suspected, it is better to early come to health institutions and get counseling about importance of nutrition and the factors which lead to preterm birth to prevent LBW newborns.(III) Researchers. It is better to do further community based studies.


Birth weight is an important predictor of early neonatal mortality, morbidity, and long-term health outcomes. Annually, approximately 20 million babies are born globally with weights less than 2.5kg. In sub-Saharan Africa, the prevalence of LBW is around 13 to 15 percent. In Ghana, 10% of babies born in 2014 were with LBW. The aim of this study was to identify maternal socio-demographic and obstetric risk factors associated with the birth weight of newborns in the Sunyani Municipality of Ghana.This retrospective cross-sectional study analysed data from 931 birth records of all deliveries between January 1 and December 31, 2017, at the Sunyani Municipal Hospital in the Brong-Ahafo Region of Ghana. Univariate and multivariable logistic regression models were fitted to estimate the effect of maternal factors on low birth weight.We found that the mean age of the participants and the mean gestational age at birth were 27.21(SD = 5.50) years and 37.95(SD = 1.85) weeks respectively. Nearly 10% of the infants born within the study period had birth weights below 2.5kg. The findings revealed that the odds of delivering LBW baby were significantly high  among urban dwellers. However, mothers who attended or completed secondary or higher education were 63% (95% CI 0.20–0.78) less likely to give birth to a LBW baby when compared with uneducated mothers. We found that the odds of LBW significantly decreased with every one-week increase in gestational age (OR 0.67 95%CI 0.59-0.76) and significantly increased with increasing parity (OR 1.43 95%CI 1.21-1.70). Further, the likelihood of delivering LBW baby decreased with every additional ANC visit (OR 0.78 95%CI 0.67-0.90) and with every additional gram of haemoglobin (OR 0.78 95%CI 0.63-0.95).The evidence from this study suggests that maternal educational level, residence, haemoglobin level, parity, number of ANC visits, and gestational age are independent predictors of low birth weight. The current findings add substantially to the growing literature on the influence of maternal socio-demographic and obstetric factors on LBW in resource-constrained settings and provide empirical data for clinical and public health interventions aimed at reducing low birth weight and its associated complications. At birth, most term newborns weigh between 2.5 kg and 4.0 kg. Those with an abnormally low or abnormally high birth weight require special attention and care to prevent neonatal death. According to the World Health Organization, the risk of neonatal death is much higher among neonates with low birth weight (LBW) than those with normal birth weight since LBW babies are more susceptible to birth asphyxia, trauma, hypothermia, hypoglycaemia, respiratory disorders, and infections . NotwithBirth weight is the first weight of a newborn after delivery. It is an important predictor of early neonatal mortality, morbidity, and long-term health outcomes . At birtEvidence have demonstrated that LBW has significant consequences for the health and survival of neonates and is an underlying factor in neonatal deaths . AccordiIn many low-income countries, LBW is associated with lower socioeconomic status, female sex, increasing parity, young maternal age, low level of maternal education, low caloric intake, malaria, and general morbidity –10. Furt2. Six hospitals, 12 clinics, seven chips compound, three maternity homes, and three health centres provide health care services to the municipal population of 123,224  [A retrospective cross-sectional study was conducted in Sunyani Municipal Hospital in the Brong-Ahafo Region of Ghana. The hospital was established in 1927 and upgraded to the status of a municipal hospital in 2004. It is located in the Sunyani Municipal Assembly, one of the 27 districts in the Brong Ahafo Region. The Sunyani Municipal Assembly has a total land area of 506.7 Kmfemales) .The Sunyani Municipal Hospital provides 24 h uninterrupted healthcare services, including specialised services for both insured and uninsured patients from diverse ethnic and socioeconomic backgrounds. It serves as one of the referral centres for the primary level health care facilities in rural and urban communities of the municipality. In 2017, 63,043 outpatients reported at the OPD of the hospital of which 6821 were admitted. Antenatal care attendance in the hospital declined from 10,813 in 2016 to 9966 in 2017 with a similar decline in the number of women who made four or more visits (1889 in 2016 to 1249 in 2017). Professional nurses and midwives in the maternity unit of the hospital record pregnancy history of mother’s, newborn characteristics, delivery information, and socio-demographic characteristics of all mothers in a birth register. We examined birth records of all mothers who delivered live babies in the Sunyani Municipal Hospital between January 1 and December 31, 2017, to determine the influence of maternal socio-demographic and obstetric factors on the birth weight of newborns.Data for the study were extracted from birth registers containing information about maternal and newborn characteristics using a structured data-capturing sheet. The data-capturing sheet was pretested on birth records for March 2018 and appropriate amendments made. Three Registered Nurses (RN) extracted the data from the registers. They were trained on how to extract data from the records and orientated on the eligibility criteria of the study. The second author (IB) supervised the data collectors on daily basis to ensure completeness and consistency of data extraction and allowed frequent scheduled breaks to prevent errors. Permission to use the birth records was granted by the medical superintendent of the hospital. Newborn deliveries recorded in the maternity unit of the hospital between January 1 and December 31, 2017, were 1756. All the newborn deliveries within this period were considered in this study. However, we analysed data from 931 records after excluding records with multiple births, stillbirths, babies with congenital abnormalities, and entries with missing birth weight information. Stillbirths were excluded because the birth weights of the few cases of stillbirths that were recorded within the study period were missing. We excluded records of multiple births and congenital abnormalities because they have a different aetiology and risk profile for LBW .The outcome variable in this study was birth weight. Newborn records with birth weight less than 2.5 kg were considered LBW while those with a birth weight of 2.5 kg or more were considered as normal birth weight, irrespective of gestational age. Based on these criteria the outcome variable was extracted and coded as a dichotomous variable: 0 “LBW (< 2.5 kg)” and 1 “normal birth weight (≥2.5kg)”.Explanatory variables of this study were maternal socio-demographic characteristics and obstetric factors that may influence the birth weight of newborns, given the results of similar previous studies , 20–24. Maternal factors that were extracted were gravida, parity, number of ANC visits, gestational age, intake of Intermittent Preventive Treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP), haemoglobin level (Hb), and blood group. Gravida was categorised as primigravida, gravida 2–4 and gravida 5 or more. Parity did not include current birth and was categorised as first-time mothers, 1–3 previous deliveries, and ≥ 4 previous deliveries. The total number of antenatal care visits for the pregnancy was classified as ≤4 visits and > 4 visits. Gestational age was calculated based on the last menstrual period (LMP) or antenatal ultrasound assessment if the LMP was not known. According to WHO, half of babies born at or below 32 weeks in low-income settings die . In thisData capture sheets were checked for completeness and accuracy. Data were then coded, entered into Microsoft Excel spreadsheet, and imported into STATA Version 14.0  for cleaning and analysis. Frequencies, percentages, means, or standard deviations were used to describe maternal socio-demographic and obstetric characteristics. Univariate logistic regression models were fitted to estimate the effect of maternal socio-demographic characteristics and maternal obstetric factors (independent variables) on LBW (dependent variable). Parameters that were significant (< 0.05) at the univariate level were included in the final multivariable logistic regression models to determine the independent predictors of LBW. Variables were retained in the final model if they were still significant (< 0.05) after adjustment. Statistical significance for all the statistical test was considered at < 0.05.Table n = 797; 85.6%) gave birth between 37 and 42 weeks gestation. Preterm birth was prevalent in one hundred and thirty-four (14.4%) mothers. The majority of the women (75.4%) were para 1–3; 15.4% (n = 143) were primiparous. Nearly three-quarters (73.4%) of the women had had 2 to 4 pregnancies and 84.9% of the women had more than four ANC visits during pregnancy. Most (71.9%) of the mothers received 1 to 3 doses of Intermittent Preventive Treatment with sulfadoxine-pyrimethamine (IPTp-SP) during pregnancy to prevent malaria. Less than half (40.1%) of the women were anaemic and blood group AB (41.6%) was the most common blood group among the mothers. The mean birth weight was 2.89(SD = 0.43) kg. The majority of the children born within the study period had normal birth weight . Only 89(9.6%) children born within the study period had LBW.As shown in Table p = 0.008) predictor of birth weight and mothers who attained this level of education were 63% (95% CI 0.20–0.78) less likely to have LBW infants. As shown in Table The association between birth weight and age of mother, education, occupation, and residence of mothers is shown in Table Table We found that nearly 10% of the infants born within the study period had birth weights below 2.5kg (LBW). Further analysis revealed that the odds LBW were higher among babies born to teenage mothers (age less than 20 years) and low among babies of mothers older than 30 years albeit not significant, which agrees well with several other studies , 27–33 iMothers who attended or completed basic education and secondary or higher education were less likely to give birth to a low weight baby when compared with those with no formal schooling. Indeed, after adjusting for the residence of mothers, secondary or higher education remained a significant predictor of birth weight and mothers who attained this level of education were 63% less likely to have LBW infants. This finding is congruent with several studies which link LBW to the educational level of mothers , 31, 39.In this study, the likelihood of delivering a LBW baby was significantly high among urban dwellers, which is consistent with studies in Ethiopia  and BangWe found that with every one-week increase in gestational age, the odds of LBW significantly decreased. As observed in previous studies, pre-term babies are usually underweight, therefore, once delivery occurs at term the likelihood of a baby weighing above 2.5 kg is high . Our finAnother significant finding from this study was that the probability of a woman delivering a LBW baby decreased with every additional ANC visit, IPTp-SP dose and a gram of haemoglobin. The significance of ANC in maternal and child health cannot be overemphasised. There is strong evidence to suggest that quality ANC during pregnancy is important for the health of the expectant mother and the developing foetus. This is ensured through essential interventions such as the identification and management of obstetric complications including preeclampsia, tetanus toxoid immunisation, intermittent preventive treatment for malaria during pregnancy (IPTp), and identification and management of infections including HIV, syphilis and other sexually transmitted infections (STIs) at the ANC . HoweverThe most important limitation of the current study lies in the fact that the data used for the analyses were primarily collected for routine healthcare services and not for research purposes or for a specific intervention. Errors may have occurred during the documentation of the records. Notwithstanding this limitation, routine collection of health data may allow for the monitoring and evaluation of public health interventions. Finally, the study analysed data from one hospital and findings may not be generalizable to mothers who attended other hospitals and those who delivered at home.The evidence from this study suggests that maternal educational level, residence, haemoglobin level, parity, number of ANC visits, and gestational age are independent predictors of LBW. These findings contribute to the growing literature on the influence of maternal socio-demographic and obstetric factors on LBW in resource-constrained settings. This could guide the development of clinical and public health interventions aimed at reducing LBW and its associated complications.


Birth asphyxia is a leading cause of infant morbidity and mortality in developing nations, such as Ethiopia. Though Ethiopia has made considerable achievement in the reduction of under-five mortality rate, the neonatal mortality burden has not experienced the same reduction, which may be attributed to birth asphyxia. Thus, this study attempts to assess the prevalence and associated factors of birth asphyxia among newborns in public hospitals in the northeastern Amhara region, Ethiopia.st April to 2nd May 2018. The sample size was proportionally allocated to randomly selected three public hospitals namely, Dessie referral hospital, Debre Berhan referral hospital, and Woldia general hospital. The allocation was made by taking the average number of deliveries given in each hospital six months before the data collection period. Using the delivery registration of hospitals a systematic random sampling technique was used to get all study participants. The diagnosis of birth asphyxia was confirmed based on the physician’s diagnosis of an APGAR score < 7 in the 1st and 5th minutes of birth. A pretested and structured questionnaire was used to collect data. Variables with p-values < 0.25 in the bivariable analysis were entered into a multivariable logistic regression analysis. A statistical significant level was declared at a p-value of <0.05.An institution-based cross-sectional study was conducted on 357 births from 1The prevalence of birth asphyxia was found to occur 22.6% of the time [95% CI 19.2% - 26.4%] in the first minute of birth. In the multivariable logistic regression being primipara , presented with complicated labor , premature rupture of membrane  were the independent predictors of birth asphyxia.The study revealed that birth asphyxia is a common newborn complication in the Amhara region. Integrated mitigation measure to reduce neonatal mortality in the Amahar region should give due attention to primipara women and for these high-risk pregnancies in order for the region to achieve national and global commitment to have sustainable change in women and neonatal health. The World Health Organization (WHO) defines birth asphyxia as inadequate oxygen perfusion to vital organs, generally, caused by a failure to initiate and sustain breathing at birth . AdditioGlobally 2.5 million children died in the first month of life which contributed 47% of all child deaths under the age of 5-years and 54 percent of all under-five deaths occur during the neonatal period among African babies . In EthiFurthermore, the prevalence of birth asphyxia varies across the globe and Africa contributes nearly 50% of the total –12; its Presently, the Sustainable Development Goals of 2030, which combine multisystem strategies at global and national levels, have three main focuses to ensure healthy lives and promote wellbeing for all at all ages. Of these goals, one main objective is to reduce the neonatal mortality rate to lower than 12 per 1,000 live births .Despite the implementation of various strategies and interventions at combating under-five children, infant and neonatal mortality rates , 23, 24,st April to 2nd May2018 in order to assess the prevalence and associated factors of birth asphyxia among newborns in public hospitals found in the northeastern part of Amhara regional state namely: Dessie referral hospital, Debre Birhan referral hospital and Woldia District Hospital. The hospitals are located 130kms, 401kms, and 421kms away from the capital city, Addis Ababa, respectively. Combined, these hospitals serve more than two million people living in the catchment areas.An institution-based cross-sectional study was conducted from 1In this study, all neonates with mothers, born with a gestational age ≥ 28 weeks, and delivered live births in selected hospitals during the pre-determined period of study were included in the research. However, mothers who were seriously ill during the study period, neonates who were suffering from major congenital anomalies or syndromes, and those neonates immediately transferred to advanced care before the five-minute APGAR score evaluation were excluded from this study.×0.05 + 340) = 357.The sample size was calculated using a single population proportion formula. The prevalence of perinatal asphyxia was taken as 33% from the previous study conducted in Jimma, Southwest Ethiopia  with theWhere: n = the required sample size, Z α/2 = the standardized normal distribution curve value for the 95% confidence level, P = the proportion of birth asphyxia among the general population, and d = degree of precision (the margin of error between the sample and population).rd interval was used to enroll study participants in each delivery unit of the hospitals.There are eight hospitals in the northeastern Amhara region. Of those, three hospitals were randomly selected for this study, namely, Dessie referral hospital, Debre Berhan referral hospital, and Woldia general Hospital. The number of study participants for each hospital was proportionally allocated based on the monthly average number of delivery in each hospital. A systematic sampling technique with every 3The data collection tool, which this survey used, was adapted and modified from various studies conducted in developing countries , 15, 19 Data was collected by trained midwives using a structured interviewer-administered questionnaire and chart audit. Data collection commenced during the second stage of labor and ended by the fifth minute of the postpartum period for newborn related data. However, the mothers were interviewed within 4 hours of giving birth since mothers who had given normal births were discharged home after six hours of stay in the three hospitals.st and 5th minutes of birth and ending with an APGAR score < 7.. Mothers with premature rupture membranes had 3.8 times greater risk of birth asphyxia compared to their counterparts [AOR = 3.85: 95% CI 1.76–8.45]. The odds of birth asphyxia among mothers which experienced complicated labor was more than threefold compared to those mothers who gave birth without any complications [AOR = 3.45: 95% CI 1.58–7.49]. Mothers with blood-stained amniotic fluid at birth were 5 times more likely to have a baby who experienced birth asphyxia compared to mothers who had clear amniotic fluid at birth [AOR = 5.02: 95% CI 1.69–14.87]  [In this study, the prevalence of birth asphyxia was 22.6% in the 1 29.9%) , Nigeria (29.9%)  and a st.9% , Nig (29.9%) . The stu (29.9%)  showed lThe prevalence of birth asphyxia was found to be higher compared to a five year review study conducted in DilChora referral hospital, Dire Dawa, Ethiopia, which examined causes of admission (12.5%) . SimilarIn this study, primipara mothers were found to have four times greater risk of birth asphyxia compared to multiparous women. This finding agrees with a study done in Rio Grande do Norte which identify being primipara is one of the risk factor at birth , and anoIn addition, the majority (80%) of cases of perinatal asphyxia occur intrapartum or during labor . TherefoAdditionally, the pathophysiology of birth asphyxia centers on the interruption of placental blood flow . In thisFinally, in this study, the likelihood of birth asphyxia among babies born with blood stained amniotic fluid was found to be fivefold higher than compared to those born with clear amniotic fluid. An unmatched case control study conducted among live births at the Gondar, Ethiopia teaching hospital to identify the determinants of birth asphyxia confirmed that meconium stained amniotic fluid at birth is the independent predictor of birth asphyxia . The stuThe first limitation of this study may be that samples were collected at institution-based health care centers, which may not truly represent neonates delivered at home, health centers and other lower level health facilities. Thus, this may underestimate the prevalence depicted in the study. Secondly, the study did not use design effect. As a result, these conditions may affect the precision of the study and this may maximizing the standard error of the study. Finally, the study also shared the limitations of cross-sectional studies.In conclusion, the prevalence of birth asphyxia is comparable with previous studies conducted in developing countries, including Ethiopia. The multivariable logistic regression showed that being a primipara, having premature rupture of membranes, blood-stained amniotic fluid and/or labor complications were all independent predictors for birth asphyxia.Therefore, health care providers, especially those working in labor and delivery wards, must give increased attention to complicated labors, to anticipate and take early action in order to avoid birth asphyxia. Additionally, mothers should be counseled regarding the health impact of premature rupture of membranes during antenatal care service delivery to reduce the burden of birth asphyxia. Lastly, government bodies should be urged to commit to the promotion and education about enhanced antenatal care services and their utilization among the community.Further analytical studies supplemented by qualitative methods are recommended to establish causal relationship.Ethical approval was obtained from the institutional ethical review board (IERB) of Wollo University, College of Health Sciences to ensure the potential benefit and scientific sound of the study. Permission letters were obtained from the administrative body of the hospitals. Finally, informed verbal consent was obtained from each participants including those mothers aged 15 years of age before interviewing them. In Ethiopian context, there was no need of assent for those women already married, as they have the right to decide on their own issues without parents’ interference. Thus, the ethical approval committee has taken into account the lower limit of marital age in the country. In addition, the respondents’ right to refuse or withdraw from participation was fully assured. The confidentiality and anonymity of the data was maintained by avoiding personal identifiers and using a locked personal computer.S1 File(DOCX)Click here for additional data file.


Gestational age and birth weight are strong predictors of infant morbidity and mortality. Understanding spatial variation can inform policies to reduce health inequalities. We examined small-area variation in gestational age and birth weight in Switzerland.All singleton live births recorded in the Swiss Live Birth Register 2011 to 2014 were eligible. We deterministically linked the Live Birth Register with census and survey data to create data sets including neonatal and pregnancy-related variables, parental characteristics and geographical variables. We produced maps of 705 areas and fitted linear mixed-effect models to assess to what extent spatial variation was explained by these variables.We analysed all 315 177 eligible live births. Area-level averages of gestational age varied between 272 and 279 days, and between 3138 and 3467 g for birth weight. The fully adjusted models explained 31% and 87% of spatial variation of gestational age and birth weight, respectively. Language region accounted for most of the explained variation , with shorter gestational age (−0.6 days and −0.9 days) and lower birth weight (−1.1% and −1.8%) in French-speaking and Italian-speaking areas, respectively, compared with German-speaking areas. Other variables explaining variation were, for gestational age, the level of urbanisation (10%) and parental nationality (3%). For birth weight, they were gestational age (27%), parental nationality (27%), civil status (10%) and altitude (10%). In a random sample of 81 968 live births with data on parental education, levels of education were only weakly associated with gestational age  or birth weight .In Switzerland, small area variation in birth weight is largely explained, and variation in gestational age partially explained, by geocultural, sociodemographic and pregnancy factors. This study was based on a large sample with national coverage and routinely collected data on neonatal and pregnancy-related predictors of gestational age and birth weight.Precise location data allowed for detailed geographical maps of spatial distribution and assessment of spatial variation in the two birth outcomes.No data were available on the mode of delivery, health-related behaviours such as maternal smoking or gestational diabetes.Parental nationality served as crude proxy for parental height and weight, and language region as a proxy for a range of cultural, social and behavioural factors.Gestational age and birth weight are important indicators of prenatal development and predictors of infant morbidity, mortality and long-term health.Variation across small areas in pregnancy outcomes have not been studied widely. In Scotland, small-area crime rates were associated with lower birth weight and with the risk of both small for gestational age babies and preterm birth.In Switzerland, studies of pregnancy outcomes have focused on specific groups such as migrants or HIV-infected women,We used deterministic methods to link three data sources using encrypted national identification numbers: the Live Birth Register, the Swiss National Cohort and the Structural Surveys. Registration of live births is compulsory by law in Switzerland and coverage is near 100%. The Swiss National Cohort (SNC) is a long-term, national study of mortality in Switzerland,We defined three sets of variables. The first set, neonatal and pregnancy-related variables come from the Live Birth Register; date of birth, birth weight, gestational age, sex and birth rank. Birth weight is measured after initial mother–child bonding, usually by the midwife using a calibrated hospital scale. Gestational age is based on the last menstrual period, with or without additional information from ultrasound scans. Birth rank was determined from the list of all live births by the same mother recorded in the Live Birth Register, and is hence restricted to the births that occurred in Switzerland. It was classified as 1, 2, 3 and ≥4 live births, including the current birth. The second set includes parental variables. The Structural Surveys provide information about the highest level of completed maternal and paternal education, classified as ‘tertiary’, ‘secondary’ or ‘compulsory or less’. The Swiss National Cohort provides data about parental nationality categorised as ‘Swiss’, ‘Southern Europe’, ‘Western Europe’, ‘Northern Europe’, ‘Eastern Europe’, ‘Other’ (non-European) or missing  to examine the associations between the two outcomes and the neonatal and pregnancy, parental and environmental factors. In the model for birth weight, we log-transformed the outcome and used a cubic spline function with three knots at weeks 25, 30 and 35 to capture the relationship between gestational age and log birth weight. Log transforming the birth weight results in a multiplicative model. Except for gestational age, maternal age and altitude, all predictors were modelled categorically. Maternal age was modelled by a piece-wise linear function, with age group 20 to 30 years as the reference group and separate linear trends for age groups 30–40 years, over 40 years and less than 20 years. Altitude was centred at 500 m and modelled linearly. The random effects in the mixed-effect model captured area-level differences between observed and expected mean outcome, based on the 705 statistical areas.We displayed mean gestational age and birth weight at area level on maps and assessed to what extent spatial variation was accounted for by the explanatory variables. Values were categorised into seven intervals symmetric around the mean and color-coded. Spatial autocorrelation of the gestational age and birth weight across regions was tested by global and local Moran’s I tests.We performed three sensitivity analyses. First, we accounted for spatial autocorrelation using the Besag-York-Mollier (BYM) modelAll analyses and maps were done in R V.3.3.2This analysis was based on routine registry data and no patients were involved in developing the research question, outcome measures and overall design of the study. Due to the anonymous nature of the data, we were unable to disseminate the results of the research directly to study participants.A total of 328 349 live births were recorded in Switzerland between 1 January 2011 and 31 December 2014. We excluded non-singleton live births (n=11 835) and those with missing gestational age, birth weight or maternal nationality. The eligible study population therefore included 315 177 singleton live births. The complete case population consisted of 81 968 singleton live births with values available for all predictors including parental education, for which complete data were only available in the Structural Surveys .The fully adjusted model (model 3) for gestational age explained 31% and 39% of the spatial variation across the 705 areas for eligible and complete case populations, respectively. The corresponding figures for birth weight were 87% and 88%. When assessing each factor separately , languag=0.19, with p<10–14. After adjusting for all the predictors in model 3, there was still some residual autocorrelation . For birth weight, the corresponding Moran’s I statistic was I=0.28, with p<10–15. After adjusting for all predictors in model 3 there was little residual autocorrelation . For gestational age, the global Moran’s I statistic, based on the complete case data set and model 0, was IOur study assessed factors associated with gestational age and birth weight in Switzerland and their contribution to spatial variation, based on routinely collected data. Gestational age at birth was strongly associated with maternal age, missing information on the father and language region. Birth weight was associated with sex, birth rank, missing information on the father, parental education, altitude and language region. The variables included in the fully adjusted model explained more than 80% of the regional variation in birth weight and about 30% of the regional variation in gestational age. Strengths of this study include a large sample with national coverage of the Swiss resident population, as well as the availability of data on several relevant predictors, either on all births or on a large random sample of eligible births. Precise spatial data and spatial statistics allowed us to assess the proportion of area-level variation explained, spatial autocorrelation and gauge the likelihood of bias due to residual autocorrelation.This study found important spatial variation in both gestational age and birth weight in Switzerland. Language region in Switzerland was the single factor that explained the greatest proportion of spatial variation in gestational age and birth weight. In the French-speaking and Italian-speaking regions, gestational age was shorter and birth weight lower than in the German speaking part. Language region is a proxy for a wide range of cultural, social and behavioural factors, including diet, smoking and alcohol consumptionOther factors that could not be measured directly, such as healthcare provision, might have accounted for some of the unexplained variation. In particular, data at the individual or small area level on the mode of delivery  were not available. The proportion of live births with Caesarian section as the mode of delivery varies across regions in Switzerland, and it is reasonable to expect that it would explain some of the remaining variation, both in gestational age and birth weight. Specifically, we would expect regions with higher proportions of Caesarian section to have lower mean gestational age (and consequently birth weight). However, the regional rates of Caesarian section published by the Federal Office of Statistics do not match this expectation,While young and old maternal age are well-known predictors of shorter gestation,There are several limitations to our study. We did not have data about maternal health-related behaviours such as smoking,Our study also showed associations between mean gestational age and the proportion of preterm births (<37 weeks), as well as mean birth weight and proportion of low birth weight newborns (<2500 g) across the 705 small areas, that is, associations with conditions that are clinically relevant . HoweverIn conclusion, our study identified important differences in mean gestational age and birth weight across Switzerland. Small area variation in birth weight is largely, and gestational age partially, explained by pregnancy-related, parental and environmental factors.