Low birth weight (Birth weight < 2500 g) is a leading cause of prenatal and neonatal deaths. The early identification of Low birth weight (LBW) neonates is essential for any comprehensive initiative to improve their chance of survival. However, a large proportion of births in developing countries take place at home and birth weight statistics are not available. Therefore, there is a need to develop simple, inexpensive and practical methods to identify low birth weight (LBW) neonates soon after birth.This is a hospital based cross sectional study. Four hundred twenty two (422) live born neonates were included and anthropometric measurements were carried out within 24 h of birth by three trained nurses. Birth weight was measured by digital scale. Head and chest circumference were measured by using non extendable measuring tape and foot length with hard transparent plastic ruler. Data was entered into SPSS version 20 for analysis. Characteristics of study participants were analyzed using descriptive statistics such as frequency and percentage for categorical data and mean and standard deviation for continuous data. Correlation with birth weight using Pearson’s correlation coefficient and linear regression were used to identify the association between dependent and independent variables. Receiver operating characteristic (ROC) curve was used to evaluate accuracy of the anthropometric measurements to predict LBW.r = 0.85) and foot length had the weakest correlation (r = 0.74). Head circumference had the highest predictive value for birth weight (AUC = 0.93) followed by Chest circumference (AUC = 0.91). A cut off point of chest circumference 30.15 cm had 84.2% sensitivity, 85.4% specificity and diagnostic accuracy (P < 0.001). A cut off point of head circumference 33.25 had the highest positive predictive value (77%).The prevalence of low birth weight was found to be 27%. All anthropometric measurements had a positive correlation with birth weight, chest circumference attaining the highest correlation with birth weight (Chest circumference and head circumference were found to be better surrogate measurements to identify low birth weight neonates. According to the World Health Organization (WHO) definition, neonates with birth weights of less than 2500g are classified as low birth weight (LBW) regardless of gestational age. Subcategories include Very low birth weight, which is less than 1500 g and extremely low birth weight, which is less than 1000 g [A significant progress has been made in the reduction of child mortality in the past decades worldwide. Though the under five mortality rate has decreased globally by about 50% (from 90 to 48 deaths per 1000 live births) in the year 1990 and 2012 respectively, the neonatal mortality rate decreased only 36%, from 33 deaths/1000 live births to 21 deaths/1000 live births over the same period [The WHO country cooperation strategy 2008–2011 showed that the prevalence of low birth weight in Ethiopia was estimated to be 14%. It is one of the highest in the world [LBW is a leading cause of perinatal deaths and remains a worldwide issue and one of the most important public health problems particularly in developing countries .The risk of death increases as the birth weight is lower; neonates born with weight between 2000 and 2499g are 4 times more likely to die during their first 28 days of life than neonates born with weight between 2500 and 2999g, and 10 times more likely to die than those weighing 3000–3499g . Thus eaWeighing scale was, is and will be the appropriate, accurate and standard for detection of neonates’ birth weight. In this study finding a surrogate is particularly intended targeting the disadvantaged communities where the access to health facilities might be difficult and where neonates are not weighed routinely due to paucity of a suitable weighing scale at the health facilities. These surrogates will help in the detection of LBW neonates and bring them to medical attention. The measurements can be done by health extension worker whose responsibilities are to do home visits and detect health problems in the community and get the people come to medical attention.Though the baseline population in Ethiopia is similar with WHO standard (uses WHO growth charts), for the aforementioned reasons there is a need to develop simple to use and carry, inexpensive and practical methods to identify LBW neonates soon after birth. This will be useful in early identification and prompt referral. Efforts should be made to find an effective method for identification of these high-risk neonates in the community.A number of alternative anthropometric measurements have been proposed as surrogate for birth-weight. These include the circumferences of the neonates’ head, chest, and mid arm –14. In mChest and head circumference were used to identify LBW preterm neonates in Ethiopia, and the cut-off points with the best sensitivity and specificity identified were 30 cm and 31 cm for chest and head circumference respectively .Though in most of the previous studies chest circumference has a good sensitivity, the cut off points varies among the studies. This study aims to find a better surrogate anthropometric measurement to detect LBW neonates and will be a supplement to the previously done studies.The study was conducted in Ayder Referral hospital (ARH), which is located in Mekelle city, Tigray region, north Ethiopia which is found at 783 km from Addis Ababa, the capital city of Ethiopia. The Hospital provides a broad range of medical services to both in and out patients of all age groups. It stands as the second largest hospital in the nation with a total capacity of about 500 inpatient beds in four major departments and other specialty units. Pediatrics and child health is one of the departments in the hospital, care for neonates being one of the services it provides. There is fairly equipped neonatal intensive care unit (NICU) and provides a tertiary level of care. About 40% of the admissions to NICU are from other health facilities in the region and the remainder 60% being from obstetrics ward in the hospital which was also the second study area. The annual rate of delivery in the hospital is 2800.Ethical clearance was obtained from the Ethical Review Board of Mekelle University, College of Health Science. Letter of permission was presented to Ayder referral hospital. Verbal informed consent was obtained from mothers/guardian of the newborns after the purpose of the study is explained. Verbal informed consent was done for most of the participants were illiterates.This was a hospital based quantitative cross sectional study design. Data was collected by using data collection format by nurses who work at the NICU after being given one day training on how to measure the neonates’ head and chest circumferences by using non extendable measuring tape, with a width of 1.0 cm and subdivisions of 0.1 cm and foot length using hard transparent plastic ruler. Reliability of measurements was checked by doing repeat measurements for each test intermittently by the supervisor.Four hundred twenty two (422) live born babies were included which was calculated using single population proportion formula. Anthropometric measurements were carried out within 24 h of birth by the trained nurses. Head circumference (HC) was measured between glabellas anteriorly and along the occipital prominence posteriorly. Chest circumference (CC) was measured at the level of nipple at the end phase of expiration. Foot length was measured from the heel to tip of the big toe using hard transparent plastic ruler. Babies were weighed naked on digital weighing scale. Weight scale was calibrated before every measurement using a material of standard weight of 1000g (bag of 1000 ml IV fluid). Gestational age of the newborns was taken from mothers’ medical record.After the collected data was edited and checked for completeness and consistency; it was directly entered into SPSS version 20. Characteristics of study participants were analyzed using descriptive statistics such as frequency and percentage for categorical data and mean and standard deviation (SD) for continuous data.Pearson’s correlation coefficient and linear regression analyses were done to examine linear relationship between two or more continuous variables.Using the chi square analyses, the accuracy of all the variables in identifying LBW neonates were compared. Statistical significance was declared at probability (P) value of < 0.05 and 95% confidence interval (CI) was used to show the strength of association between independent and dependent variables.Non-parametric receiver operating characteristic (ROC) curve analysis was carried out to calculate 95% confidence intervals of areas under the curve (AUC) that is to determine the overall accuracy and the sensitivity of the cut off points to identify best surrogate anthropometric measurement. Finally the predictive performances of the cut off points were calculated.The total number of study participants enrolled in this study was 422, of which 50.24% of them were males Table . The birTable Table p < 0.001). CC attained the highest correlation with birth weight (r = 0.85) while FL attained the lowest (r = 0.746).Table 2) were associated with CC followed by head circumferences and then foot length. All the correlations were significant at p < 0.001. CC had the lowest standard error of the estimate (SEE) and it had a higher coefficient of determination (R2) when compared with HC (0.722 vs. 0.680). FL gave a coefficient of determination (R2) of 0.557 which is the least.Three linear regression models for CC, HC and FL as independent variables and birth weight as dependent variable were created. The highest coefficient of correlation (R) and coefficient of determination (R2) being associated with CC.Three scatter plot graphs were created, each representing CC, HC, and FL for the newborns Fig. . The posThe corresponding ROC curves for CC, HC and FL as surrogates for birth weight less than 2500 g are shown in Fig. For CC, the identified cut-off point was 30.15 cm with a sensitivity of 84.2% and 85.4% specificity. The optimal cutoff point for HC was 33.25 cm with a sensitivity of 80.7% and 90% specificity. With respect to FL the optimal cutoff point was 7.35 cm with 72.8% sensitivity and 91.6% specificity. With this CC is the most sensitive measurement followed by HC which has the highest positive predictive value  of the enrolled neonates. The LBW prevalence is a lot higher than the estimated national average which is 14%  and in tBirth weight has been and is still an important screening tool for detecting newborns with LBW. Because of unavailability or inaccurate weighing scales and higher incidence of home deliveries measuring weight and detecting LBW neonates in developing countries is difficult . This har = 0.85 and AUC = 0.91) and (r = 0.82 and AUC = 0.93) respectively. Other analyses  also indicate that they are the two most appropriate measurements for identifying LBW in the study area. Though HC is not found to be the best surrogate anthropometric tool in most of the studies reviewed, the current finding is similar with a study done in Pokhara among Nepalese newborns. The study found the optimal cut-points for head circumference and chest circumference to identify LBW newborns to be 33.5 cm and 30.8 cm respectively [In the current study involving babies admitted to NICU and those born in Ayder Referral Hospital, birth weight correlated very strongly with the anthropometric variables of CC and HC. CC and HC demonstrated the best correlation with birth weight (ectively .r = 0.74) and was found to be less sensitive as well (72.8%). But in a study done in Uganda it correlated strongly with birth weight (r = 0.76 and AUC = 0.97) and had 94% sensitivity and 83% specificity in detecting LBW [Foot length had the least correlation among all the parameters analyzed in the current study  working at remote areas where weighing scales might not be readily available.The fact that more than one data collectors were used may have an effect on the quality of data collected due to inter observer difference. But this was minimized by training the data collectors. In this study the measurements were done by health professionals but the tool will be used by health extension workers and their skill is likely to be different.Chest circumference and head circumference with cut off points 30.15 cm and 33.25 cm respectively are better surrogates for detecting LBW neonates. Of the two tools this study suggests that chest circumference is the most appropriate predictor given its high correlation and sensitivity in detecting LBW babies.Neonates who fall below the stated cut off point should be considered as high risk and referred to health institutions where they can get better service and chance of survival.


Evidence suggests that home birth is as safe as hospital birth for low risk multiparous women, and is associated with reduced intervention rates and increased rates of normal birth. However the home birth rate in the UK is low, and few women choose this option. The aims of this study were to identify what influences multiparous women’s choice of birth place, and to explore their views of home birth.n = 28) attending mother and baby groups in a city in the UK with a diverse multi-ethnic population. Data were analysed thematically using the Framework Method, combining deductive and inductive approaches to the data.Five focus groups were conducted with multiparous women  contains supplementary material, which is available to authorized users. Recent evidence suggests that home birth is as safe as hospital birth for low risk multiparous women, and that planned birth at home is associated with reduced intervention rates and increased rates of normal birth –5. In adThe birth rate in England has increased dramatically in recent years: between 2001 and 2012 the number of live births increased by 23% . This, aThe aims of this qualitative study were to identify the factors that influence women’s choice of place of birth, and to explore their views of home birth. The study was designed to examine these issues specifically from the perspective of low risk multiparous women, as this group is likely to experience the most benefit from home birth.A qualitative focus group study was conducted between May and June 2014 in a specific geographical area of a large multi-ethnic city in the UK served by a maternity service provider. Ethical approval was obtained from the NHS Research Ethics South Central Committee B (reference 14/SC/1007). We took a broadly interpretive approach which involved seeking culturally derived and historically situated interpretations of the social life-world . Five foJNS identified and recruited ‘gate keepers’ responsible for running the mother and baby groups who distributed study information a week before the focus groups were planned. While selection of the groups was purposive, a convenience sampling approach was taken for individual participants, with women attending the mother and baby groups invited to participate . Data reThe focus groups lasted around one hour, were facilitated by JNS, and moderated by KS and BT. The focus group questions were developed by the research team using the findings from a supporting literature review exploring women’s perceptions. This is provided as a Additional file Management and analysis of the data was conducted using the Framework Method , involviThe initial coding framework was agreed by JNS, KS and SK, based on the research aims and previous literature. This was applied to data from each of the focus groups by JNS according to its meaning and content. The results of this deductive coding strategy were then discussed with KS and SK (who had familiarised themselves with the data). Data that did not fit within this framework was discussed and a final coding framework agreed that was then applied across the whole data set by JNS. Related codes were grouped together and labelled to form descriptive themes, with a summary written for each. The final ‘interpretative’ step of analysis involved all members of the team working together to understand how participants attached meaning to home-birth. This involved generating analytical themes which inferred implications for service provision from participants’ descriptions of their lived experience. Service users were not involved in the interpretation of the findings.Several strategies were employed to maintain trustworthiness in the analysis, including keeping a clear and transparent audit trail, writing a reflexive diary, and discussing emerging understandings within the research team. We also reflected on how our positions as health service researchers with a background in maternity care and social sciences could influence the analysis and challenged preconceptions in our discussions in an effort to remain open to unexpected discoveries.JNS was a clinical research student and midwife at the time of the research. All other authors are experienced qualitative health services researchers. SK, AH and BT are clinical academics .n = 4), and Black or Black British (n = 3). Of the 26 women who disclosed their age, 15 were aged between 16 and 29 yrs., and 13 were over 30 yrs. old, with a mean age of 29 years and 9 months. At two groups fathers were present (but not as research participants), and one father translated for his wife who had limited English language skills.Data was gathered from 28 participants who attended 5 focus groups with between 2 and 8 members . Twenty one (75%) having a single child, and the remaining 7 (25%) having 2 children or more , trust and confidence in the maternity system, and perceptions of birth as a ‘natural’ event, . Two themes emerged regarding the influences on women’s choices: clear information provision, and the role of health care professionals. A final theme concerned women’s responses to the offer of choice. Data extracts are presented alongside participant details. In some extracts it was not possible to identify which participant was speaking, due to background noise in a busy environment where children and babies were present.For many participants, home birth was an unfamiliar concept. If they did consider it as an option it appeared they had little knowledge on which to base an informed choice:‘I don’t even know if you have a home birth where do you give birth? Do you choose a room; do you…in a bed? I’ve got absolutely no idea’ Participant 4, 32, LR’A few women wanted a water-birth, but this was not perceived as practical or affordable at home:‘I always wanted a water-birth, so I knew a home birth wouldn’t be feasible. I know you can but it’s a lot of hassle’ Participant 8, 32 HRThere were some women who were concerned about the mess and responsibility for cleaning up following birth:I wouldn’t want to be sitting in a pile of guts on my living room carpet and then cleaning it up’ Participant 9, 35 HR‘There was a difference of opinion between 2 women about the memories having a baby in their house would leave:‘My husband was born at home, it’s always been talked about in a positive way. I think there’s something quite nice about the fact he was born at home’ Participant 8, 32, HRI didn’t want a home birth because I didn’t want to walk into a room and think I had my baby there…the reality is it wasn’t a pleasant experience to remember and I’m really glad I didn’t have that experience at home’ Participant 10, 32, LR‘Some of the women from minority ethnic backgrounds questioned the practicality of home birth because of the lack of availability or willingness of relatives to support the mothers during and immediately after birth:And what happens with the mother-in-law, does she have to get involved with the birth and clear up afterwards?’ Participant 5, 28, LR.‘Immediate postnatal care was also something that concerned many of the participants, as they were unsure about what would be provided:‘Is there a dedicated length of time that people spend with you before they leave you for their next customer? The last thing you want is …you’ve got this baby and you’re at home sitting in the mess and they say ‘Right okay, well, I’ll see you in community in a weeks’ time’ Participant 9, 35, HR‘When you’re having a home birth you’ve got that attention haven’t you, they don’t have to rush out of the room to go to someone else’ Participant 11, 23, LRSeveral women welcomed the prospect of one-to-one care from the Midwife at home births, although this was usually related to a poor experience in an OU:Some of the women suggested that perhaps more could be done to provide information about the reality of home birth, including the use of television documentaries, and placing televisions in antenatal clinics which could feature information films. However overall there were mixed perceptions concerning the nature of home birth.It was assumed by everybody like myself and my loved ones that it would be in hospital… it wasn’t really discussed’ Participant 1,29,LR (Low-risk)‘Strong cultural norms also played a part:Most women talked about their ‘assumption’ that they would give birth in an OU, often recalling that no other option was mentioned:I’ve never heard of it (home birth) it’s not common, none of my family or my sister have had that experience or anyone I know has needed to consider it’ Participant 2 24, LR‘Many women felt that birth carries significant risk and is safest when it takes place in an OU, identifying their main concern being an ‘emergency’ or ‘something going wrong’. There was a strong desire to have specialist medical support nearby, regardless of risk status.‘if all goes wrong I’m a trolley away from a C-Section if necessary’ Participant 3,40,HRWomen reported that they only considered the hospital for their first baby, because of the associated risk:As a first time mum I would never have had a home birth because I didn’t know what was coming, I wouldn’t have felt safe enough’‘Participant unidentified, Focus Group 1.While most participants were aware that they had a choice, they interpreted this as deciding ‘which hospital’ to give birth in and considered locality, familiarity, reputation and where their friends/family had received care, when making their choice:‘My husband did some research on google and found Trust A had a good reputation’ Participant 3, 40, HR.Choice appeared to be influenced by ethnicity, with women who classed themselves as white being more aware of the choices available to them than women from ethnic minorities (42.9% of participants) who reported they were not offered a choice of location for birth, for example the following quote was from a Bangladeshi participant.‘I didn’t think you were allowed that, they didn’t mention that’ Participant 5, 28, LRWomen from ethnic minorities were most likely to shift their perception of the practicality and desirability of homebirth by the end of the session, illustrated in the quote below from an Egyptian participant, while this was not observed in many women from a white background:‘Only in critical cases should go to hospital. It is the nature of people. Nature is best’ Participant 6, 25, HR (Egyptian).Several participants indicated they had doubts that maternity services could support a safe and responsive home birth. In many cases this related to a perception that the resources necessary to provide such a service were lacking.‘I just don’t think there’s enough money. I don’t think it would happen. It’s just so underfunded and not enough staff. I just couldn’t trust it I wouldn’t’ Participant 4, 32, LRA few women, some with experience of home birth, and others who were contemplating it, reported how women were asked to come into hospital during labour because no midwives were available, which made them reluctant to choose home birth again:‘Obviously we’re often told “Oh yeah, it’ll be available.” And often they say to you, “You’ve got to come into the hospital I’m afraid”’ Participant 14, 28, HRSome women also reported hearing stories about babies being born before the Midwife arrived:‘That’s the only anecdotal stories I’ve heard about home birth, the gas and air hasn’t turned up, the Midwife hasn’t turned up….’ Participant 15, 39, HRThe majority of women reported that the aftercare provided in the hospital was good, and suggested that this would not be replicated at home. This included breastfeeding support, and a constant professional presence for reassurance and help if needed:‘But then what do I do with his first nappy, because it was just like tar. They were brilliant. So if you have that level of support in the home who’s available, who’s on the end of the phone, but more importantly who’s staying there while you get those questions done? Participant 3, 40, HRThe majority of women who participated in this study considered birth to be a ‘risky’ event. Women who had given birth vaginally suggested that that they would have confidence in their ability to achieve a ‘natural’ birth in the future.The women shared different definitions of ‘natural’ depending on their preference of birth setting. The overwhelming majority felt that the availability of medical technology secured a ‘safe and clean’ birth.Hospital is the natural thing’ Participant 5, 28, LR.‘The fact that this participant saw the hospital as the ‘natural’ thing, suggests that the notion of hospital birth is inculcated so completely that she was unaware of the inherent contradiction of this comment, as hospitals are places where technology and medicine prevail. Women, who believed in their ability to give birth outside of the OU, used the term ‘natural’ in a way that reflected an awareness of this:‘More natural not having machines…constantly beeping’ Participant 6, 25, LR.The participants reported a range of ways they had obtained information about home birth. It was generally by informal means, and through involvement in antenatal classes and meeting with groups of ‘like-minded people’.They took us round delivery suite and the birth centre, but I don’t remember anything about home birth’ Participant 11, 23, LR‘The importance of having ‘like-minded’ sources of support, with whom women can identify is illustrated in this extract:‘I went to some of those pregnancy yoga classes – ‘hippy dippy ones’ and probably it wasn’t for me, but I know a lot of them were either considering or having home births. And I just didn’t feel it was for me. Participant 12, 33, LRMany women stated that, after friends and family, antenatal classes were the main source of information, although the ‘hospital tour’ was highlighted as a rich source of knowledge to support decisions:Some participants’ described how place of birth was simply one of many pieces of information shared, and that it was not detailed or prioritised:‘My Midwife did have a vague discussion about place of birth towards the end of my pregnancy’ Participant 12, 33, LR.It was reported that leaflets were not well-regarded or used, except for two participants who did not have friends or family to advise them:‘I was given a leaflet by somebody, but I confess I didn’t really read it’ Participant 12, 36, LRThe need for information to be conveyed by people with the necessary experience was also identified:‘I think it would be nice to meet someone who did home birth, not just a person who gave birth but someone who also was there and delivered because you get a little information’ Participant 16, HR.The data suggest that professionals, including midwives, have little influence on women’s choices, with friends, family, antenatal classes  and the media identified as being the main sources of information:‘I think I was aware of home birth as an option, but certainly not from a health care professional’ Participant 12, 36, LR.They didn’t really want me to have one (home birth) …There was quite a lot of negativity. And in fact even though my husband phoned to say I was in labour they said ‘we haven’t got the staff. Can you get into hospital’….I just felt no-one approved’ Participant 14, 28, HR‘There was, however some evidence of hostility from HCPs if their expectation of control was challenged:There were many reported examples of midwives restricting women’s choice by not presenting all the alternatives:‘They just gave us directions how to get there, we weren’t given any options’ Participant 17, 29, HRThere was one example of a midwife presenting home birth differently to other options suggesting non-verbally that it was not an option she would recommend:We knew each other anyway as I had the same Midwife she said I could have delivery suite or birth centre, or you can have home birth…then she looked at me and smiled  and said ‘Yes well…..’ Participant 9, 35, HR.‘‘They did give me the option of a home birth because we were fine all the way through. I remember talking to her (midwife) about it and she seemed to want me to do it but I didn’t fancy it at the time.’ Participant unidentified, Focus Group 2Two women reported seeking advice and guidance from a midwife but in the end taking the decision not to pursue a home birth.A few women reported changing their choice of birth place in order to access particular birth options, however this active choice was only reported by white British participants:‘Trust A doesn’t allow you to labour in water (after previous caesarean section) so I switched to Trust B’ Participant 15, 39, HROther participants reported how their preferred options were not available, and while they expressed some frustration, they described how they accepted what was on offer:I chose hospital birth and to have a waterbirth but couldn’t the first time as my blood pressure was too high and the second time it (the birthing pool) was being used’, Participant 16, HR‘One woman acknowledged that although she had been offered a choice and exercised it, she felt the weight of responsibility this placed on her:‘It felt quite a strange process to be the person controlling it…it’s quite complicated actually, being given the choice was almost something you didn’t want as a pregnant woman. Because the last thing you want is to make a choice to the detriment of your child’ Participant 15, 39, HRMany of the themes identified in this study confirm findings from earlier work. For example, most women in this study assumed they would give birth in an OU, which has been observed elsewhere. , 21–24 TSome women in our study actively sought to access particular options, while others were frustrated at having to accept the options offered. This is consistent with the ‘active chooser’ and ‘adaptor’ categories identified by Pitchforth et al. . It was Our study is consistent with others’ work which found some women construct a narrative around place of birth choice, synthesising advice and guidance from professionals with their own knowledge. , 29 The Midwives have been found to be much more supportive of home birth than medical staff, , 37 and There was little confidence in the ability of maternity services to provide home birth among a number of participants in our study. As discussed earlier in relation to professional influence, previous work has also identified staffing pressures as a barrier to midwives promoting home birth to women, due to concerns about ability to provide equitable maternity care in a pressurised system,  and womeWhat does a home birth look like?’ And the ‘Trust and confidence in the maternity system’ themes reveal some new insights on women’s perceptions of home birth. An important new finding from our study was that women reported that they did not know what home birth looked like. They often had little knowledge, and were concerned about mess, cleaning, the responsibility of relatives, and what level and type of support would be provided, and for how long. Women had particular concerns about the availability and quality of postnatal care. Some women did not like the idea of giving birth to a baby in their home, while others welcomed the one-to-one care a home birth offers. A lack of exposure and information, plus misinformation and uncertainty about home birth was evident, and the findings suggest that whatever services are doing at present to inform women about their birth place options is not meeting all of women’s information needs. This reflects the complex challenges involved in determining the type of service provision required by women, even in a specific, albeit diverse, area.The data in the ‘In all of the focus groups, when home birth was first discussed, predominantly negative views were expressed. However women from ethnic minorities, whether in homogenous or heterogeneous focus groups, reported an increased awareness of the practicality and desirability of home birth by the end of the session, which was not the case with many women from a white background. This suggests that the opportunity to discuss home birth may specifically encourage more women in minority ethnic groups to consider it as a realistic option for them, and that a disparity in knowledge and access to information about home birth may be a particularly important restriction of choice for women from minority ethnic backgrounds. There are parallels here with evidence from the United States, where women of colour are much less likely to choose home birth , more liCoxon et al. developed a conceptual model of the experiences of choosing, preferring or deciding where to give birth from their evidence synthesis, which describes influences on birth place choice arising from women, and from services . While oA key challenge in informing women about home birth and increasing choice is the lack of exposure to home birth in day-to-day life, as it is so rare . CompareWhen planning the study the intention was to explore the accounts of women designated as low-and high-risk women’s and compare them. However during the conduct of the focus groups, the researchers were not definitively aware of the risk status of the women, as a demographics form was completed anonymously at the end of the session. Although the risk status of some women became obvious during the group as the women referred to their birth experiences, these did not appear to define the women’s views or their ability to consider all places of birth, whether or not they were appropriate to them. It became clear that the risk status of the women was largely irrelevant to the majority of the participants’ views, as women who were low-risk up until they gave birth, and then, for instance, had a caesarean section, could clearly and articulately recall their decision making processes during their pregnancy concerning place of birth choice. The themes encompass the accounts of women deemed to be high and low risk.Individual interviews with women may have provided richer data, though the use of focus groups was particularly beneficial in revealing that women’s perspectives are shaped and changed by meeting and discussing options in a group setting. Although the characteristics of the sample may limit the transferability of the findings to other populations, the diverse membership suggests the findings are likely to reflect key concerns of women in this situation. As all the women in the study had given birth before, it was difficult to determine whether they, or nulliparous women were most open to the idea of alternative places of birth as identified by Coxon et al.  The studThe presence of babies and children in the groups interrupted the discussions at times, but we feel conducting the groups in this natural, comfortable environment with no need for childcare increased participation and generated rich insights in their experience. Some of the women in the one focus group where men were present as interpreters contributed less to the discussion once men joined the group. It is possible that this limited the data collected. However, it also highlighted important cultural issues that need to be factored into approaches to support women with home birth. Two of the researchers are midwives, which may have affected the approach to gathering and interpreting the data, though the team actively reflected upon the impact of professional experience and perspectives on the data collection and analysis. All members of the research team are white British, and the team acknowledged and reflected on this in the interpretation of specific findings relating to ethnicity and minority groups.Despite these limitations this study provided new detailed information about women’s perspectives on home birth. Accounts from a wide range of women in a large multi-ethnic city were collected and the qualitative approach provided rich, in-depth data. It was informed by prior literature review to locate findings within, and build upon existing knowledge in this area. It appeared that the findings approached saturation (i.e. no new themes)  suggestiWhilst consistent with earlier work , 39, 40,Additional file 1:Focus group topic guide. (DOCX 392 kb)


We argue that reproductive suppression has clinical implications beyond its contribution to the burden of spontaneous abortion. We theorize that the incidence of births before the 28th week of gestation, which contribute disproportionately to infant morbidity and mortality, varies over time in part due to reproductive suppression in the form of selection in utero. We further theorize that the prevalence of structural birth defects among survivors to birth from conception cohorts gauges selection in utero. We based these theories on literature positing that natural selection conserved mechanisms that spontaneously abort “risky” pregnancies including those otherwise likely to yield infants with structural birth defects or small‐for‐gestational age males. We test our theory using high‐quality birth defect surveillance data. We identify 479,885 male infants exposed to strong selection defined as membership in conception cohorts ranked in the lowest quartile of odds of a birth defect among live‐born females. We estimate the risk of periviable birth among these infants as a function of selective pressure as well as of mother's race/ethnicity and age. We find that male infants from exposed conception cohorts exhibited 10% lower odds of periviable birth than males from other conception cohorts. Our findings support the argument that selection in utero has implications beyond its contribution to the burden of spontaneous abortion. This approach uses the natural variation among conception cohorts in birth defects among females to estimate the average strength of selection on both male and female fetuses in those cohorts. We cannot use the odds of a birth defect among male infants to measure strength of selection because fetuses with birth defects also exhibit elevated risk of early birth  that together include numerous structural birth defect phenotypes (corresponding to ICD9 codes 740–758) diagnosed before age 1 from a broad mix of urban and rural populations. These high‐quality surveillance data, described in detail elsewhere  and used non‐Hispanic white as the referent group. We further characterized them by maternal age grouped as 13–19, 20–24, 30–34, and 35 or more years, with age 25–29 as the excluded referent group.t subtracted from that at month t + 1) because the raw odds exhibited a downward trend that violates the assumption of a constant mean. The monthly differences vary around a constant mean  and gauge the degree to which a cohort exhibits higher or lower odds than expected from trend. We identified conception cohorts “exposed” to strong selection as those in the lowest quartile of difference scores. We, therefore, created an exposure variable scored 1 for infants from cohorts with difference scores in the lowest quartile and 0 otherwise.We also characterized male infants by whether their conception cohort experienced strong selection. For the reasons described above, we used the odds of a live‐born female in a cohort exhibiting a birth defect as the indicator of selective pressure. We transformed these odds to their monthly differences  of periviable birth among males as a function of exposure to strong selection in utero adjusting for maternal age, maternal race/ethnicity, and the expected value of a male periviable birth contingent only on time . We estimated the test equation using SAS, version 9.4.3The 478,385 male infants in the study included 3,094 born before the 28th week of gestation. Table t predicted the value at month t + 12 better than simply the mean of all values. The best fitting model for the series, therefore, included the mean  and an autoregressive parameter at month t − 12 .Box–Jenkins methods detected seasonality in the logit of male periviable births such that the value observed at month Table The coefficient for propensity for periviable birth contingent on time exceeded 1 . Seasonality detected by the Box–Jenkins modeling, described above, of the odds of periviable birth among males implies this association. The fact that the association remains significant in the test model implies that seasonality in the likelihood of a male periviable birth does not arise from seasonality in the other predictors in the equation.Males born to non‐Hispanic white mothers exhibit the lowest risk of periviable birth while those born to African American mothers exhibit the highest risk . Epidemiologic literature describing periviable birth in the United States predicts this association .The fraction of pregnant women informed by prenatal screening increased during our test period. The State of California made such screening available by law in 1986. Approximately 65% of infants born in the State had been screened in utero during our test period  ascertainment of the periviable births and of birth defects. This coverage permits stable estimation of population rates for relatively rare events and provides sufficient statistical power to detect small but important associations. Assignment of more than 470,000 males to conception cohorts improves upon previous work that relied on date of live birth to infer temporal ordering of selection processes during pregnancy  if interested in obtaining the data and code for replication.Data used in these analyses contain protected health information and therefore require human subjects’ approval from the State of California before dissemination and analysis. Please contact Gary M Shaw (


Small-for-gestational-age in infancy is a known risk factor not only for short-term prognosis but also for several long-term outcomes, such as neurological and metabolic disorders in adulthood. Previous research has shown that severe nausea and vomiting in early pregnancy (NVP) and hyperemesis gravidarum, which is an extreme form of NVP, represent risk factors for small-for-gestational-age birth. However, there is no clear consensus on this association. Thus, in the present study, we investigated the correlation between hyperemesis gravidarum and NVP on the one hand, and infant birth weight on the other, using data from the Japan Environment and Children’s Study (JECS).The data utilized in the present study were obtained from the JECS, an ongoing cohort study that began in January 2011. Our sample size was 8635 parent–child pairs. The presence or absence of severe NVP, hyperemesis gravidarum, and potential confounding factors were noted. A multivariable regression analysis was used to estimate risks for small-for-gestational-age birth, and the results were expressed as risk ratios and 95 % confidence intervals.The risk ratios of small-for-gestational-age birth  for mothers with severe NVP and those with hyperemesis gravidarum were 0.86 (0.62–1.19) and 0.81 (0.39–1.66), respectively, which represents a non-significant result.In our analysis of JECS data, neither severe NVP nor hyperemesis gravidarum was associated with increased risk for small-for-gestational-age birth. There is a high incidence of nausea and vomiting in early pregnancy (NVP), reported at 35–91 % . NVP canth percentile for birth weight as the cutoff value [The condition known as small-for-gestational-age (SGA) is a concern in infants, as it carries with it a multitude of risks, including a poorer life prognosis, neurological disorders, and metabolic diseases during adulthood , 6. SGA ff value , 8.There are many risk factors for SGA, but most of these are not well understood. Extreme NVP may result in poor health during pregnancy, which can influence the prognosis of fetuses , 10, posRecent systematic reviews suggest that HG increases the risk of low birth weight and SGA by 42 and 28 %, respectively . FurtherIn the present study, we investigated the effect of severe NVP and HG (extreme NVP), with respect to the risk for SGA birth in the Japanese population.The data used in this study were obtained from The Japan Environment and Children’s Study (JECS), which is an ongoing cohort study that began in January 2011. The objective of the JECS is to determine the effect of environmental factors on children’s health.More than 100,000 pregnant women were recruited over a period of approximately 3 years. The recruitment period ended in March 2014.The pregnant women lived in one of the 15 study regions included in the JECS. The 15 regions were selected to cover wide geographical areas in Japan. We made contact with as many of these expecting mothers as possible. Either or both of the following two recruitment protocols were applied: 1) recruitment at the time of the first prenatal examination at cooperating health care providers, i.e., obstetric facilities (provider-mediated community-based recruitment), and/or 2) recruitment at local government offices issuing pregnancy journals, namely the Mother-Child Health Handbook, which is an official complimentary booklet that all expecting mothers in Japan are given when they become pregnant in order to receive municipal services for pregnancy, delivery, and childcare.The JECS protocol was approved by the Review Board on epidemiological studies of the Ministry of the Environment, and by the Ethics Committees of all participating institutions. The JECS is conducted in accordance with the Helsinki Declaration and other nationally valid regulations, and with written informed consent from all participants. However, those who had difficulty filling out the questionnaire in Japanese or had other unavoidable circumstances preventing them from participating in the survey, such as being in their hometown at the time of childbirth, were excluded from the analysis , 20.As of the end of 2011, a total of 9646 participants had successful childbirths. After excluding cases with missing data and preterm births, we analyzed the records of the remaining 8631 women who had single, full-term (37–42 weeks) pregnancies . We thus defined the following groups for analysis: the “food intake group”, which included the women who answered 1, 2, or 3; the “no food” or severe NVP group, which included the women who answered 4; and the HG group, which was a subset of participants from the NVP group that included women with severe NVP and weight loss of >5 % from pre-pregnant weight in the first trimester.th percentile according to primiparous and multiparous birth size standards for both genders by gestational age in Japanese neonates [The participants underwent ultrasound examinations during the first trimester, and these results were used to determine the expected date of delivery if there was more than a 7-day difference between this date and the date calculated from the last menstrual period. Birth weight was transferred from medical records, and SGA was concluded if the weight was below the 10neonates .The following covariates were included in the questionnaire for the first trimester: maternal age, pre-pregnancy body mass index (BMI), parity, smoking status, and alcohol consumption; the covariates of education and income were included in the questionnaire for the second trimester; the covariates of weight gain during pregnancy were calculated based on information from medical records.Based on the records of mothers of singletons delivered at full term, we evaluated the relationship between SGA and NVP, HG, factors related to the patient’s background, and social factors. Continuous variables were expressed as mean ± standard deviation (SD). We calculated crude relative risk ratios (RRs) and 95 % confidence intervals (CIs) using the chi-squared test. The interrelationship between patient background, social factors, and birth weight was evaluated by univariate analysis. Covariates of maternal age, pre-pregnancy BMI, weight gain during pregnancy, gestational age at birth, smoking, alcohol consumption, education, and income were included in the calculation of adjusted risk ratios. The adjusted relative RR was calculated using a log-binomial regression model. All statistical analyses were performed using SAS version 9.3 .2, mothers with a weight gain of <7 kg during pregnancy, and those who smoked were 1.58 , 1.28 , and 1.48 , respectively, indicating a slightly higher risk of SGA birth. Moreover, the risk ratio was 0.60  for mothers with a pre-pregnancy BMI of >25 kg/m2, and 0.52  for mothers with a weight gain of >12 kg during pregnancy, indicating a lower risk of SGA birth.There were 880 patients 10.2 %) who experienced severe NVP, and 136 patients (1.6 %) who experienced HG. The mean age of participants, weeks of pregnancy at birth, and birth weight were 30.6 ± 5.02 years, 39.0 ± 1.14 weeks, and 3050.0 ± 371.32 g, respectively. The results of the univariate analysis are shown in Table 0.2 % whoTables In our analysis of JECS data, neither NVP nor HG was associated with the risk for SGA birth. The incidence of HG was 1.6 %, which is lower than the 3.6 % incidence reported by the latest study in the general Japanese population , but witOur study has a methodological limitation, because data regarding the severity of NVP were collected via a self-response questionnaire, while data regarding maternal weight loss were collected from the Mother-Child Health Handbooks and hospital records, and it is unknown whether participants required hospitalization for severe HG, how long severe NVP or HG persisted, and whether the condition reflected in the biochemical parameters.Another limitation is the fact that the questionnaire was applied in the second trimester, but the questions themselves referred to early pregnancy; thus, there might be the risk of recall bias, resulting in an overestimation of the severity of NVP. However, we do not believe that this effect was significant, because the questionnaire was applied during the pregnancy period; moreover, the definition of HG was based on independent records of maternal weight loss.A further limitation is related to the fact that our results were obtained based on the data regarding 136 cases of HG, which may be considered a small number in the context of an epidemiologic study. Nonetheless, given that the incidence of HG is expected to be under 2 %, and there is yet no consensus regarding the influence of HG on the risk for SGA birth, we believe that a sample size of 136 cases can ensure sufficient power to detect relevant trends, as some reports indicate that HG may increase the risk for SGA birth by up to 40 %; moreover, even if the power is low, the potential tendencies should be recognizable, because the confidence interval for our results is narrow.Finally, another limitation of the study is related to the fact that the incidence of SGA birth in the group of mothers for whom weight gain information was missing was relatively high. Unfortunately, the reason for this higher incidence of SGA births cannot be assessed based on the data available to us. While it is possible that the characteristics of the mothers excluded from the study because of missing information on weight gain may have an influence on the results, we do not expect this influence to extend to the conclusions of our study.Previous research demonstrating HG as a risk factor for SGA includes a study by Bailit et al., which showed that neonates born from mothers requiring hospitalization for HG were 125 g smaller compared to those born from mothers without such symptoms . HoweverThe recent Norwegian Mother and Child Cohort Study reported that HG-exposed babies had slightly reduced birthweight, but there were no association between HG and SGA birth , 23, altIt is important to note that both sets of studies  studied patients who required hospitalization. Even under these conditions, there is no conclusive evidence regarding the effect of HG on birth weight. Therefore, precise diagnostic criteria for HG should be developed for use in future investigations.Our results suggest that neither NVP nor HG affect birth weight. Despite the methodological limitations of the study, we believe that these results indicate that pregnant women need not be concerned about potential risk for SGA birth due to NVP or HG.


Birth weight is a strong predictor of infant mortality, morbidity and later disease risk. Previous work from the 1980s indicated a shift in the UK towards heavier births; this descriptive analysis looks at more recent trends.Office for National Statistics (ONS) registration data on 17.2 million live, single births from 1986 to 2012 were investigated for temporal trends in mean birth weight, potential years of birth weight change and changes in the proportions of very low (<1500 g), low (<2500 g) and high (≥4000 g) birth weight. Analysis used multiple linear and logistic regression adjusted for maternal age, marital status, area-level deprivation and ethnicity. Additional analyses used the ONS NHS Numbers for Babies data set for 2006–2012, which has information on individual ethnicity and gestational age.Over 27 years there was an increase in birth weight of 43 g (95% CI 42 to 44) in females and 44 g (95% CI 43 to 45) in males, driven by birth weight increases between 1986–1990 and 2007–2012. There was a concurrent decreased risk of having low birth weight but an 8% increased risk in males and 10% increased risk in females of having high birth weight. For 2006–2012 the birth weight increase was greater in preterm as compared with term births.Since 1986 the birth weight distribution of live, single births in England and Wales has shifted towards heavier births, partly explained by increases in maternal age and non-white ethnicity, as well as changes in deprivation levels. Other potential influences include increases in maternal obesity and reductions in smoking prevalence particularly following the introduction of legislation restricting smoking in public places in 2007. Birth weight is a strong predictor of infant mortality, morbidity and later disease risk.Work in the UK, Europe and America indicated a shift towards heavier births, it is unknown if this trend has continued in England and Wales.Analysis of 17 million births using national birth statistics data 1986–2012 shows that babies in England and Wales have become heavier over the past three decades.We found an adjusted 4% decrease in risk of low birth weight with a corresponding 8%–10% increase risk of high birth weight.Increases in birth weight plateaued in 1993–2006 but increased again from 2007, coincident with the introduction of legislation banning smoking in public places.Birth weight is a strong predictor of infant mortalityPrevious analyses indicate that the distribution of birth weight in Britain shifted towards heavier births during the 1980stemporal trends in the mean birth weightpotential years of change in the mean birth weightchanges in proportions of births that are low or high birth weight.Analysing live singleton births for England and Wales from 1986 to 2012, the aims of this paper are to investigate:Analyses used England and Wales data from the Office for National Statistics (ONS) births data set (1986–2012) and the NHS Numbers for Babies (NN4B) data set (2006–2012) supplied by ONS. All births must be registered at a local register office and the information is compiled nationally by the General Register Office.2 test or t-test. From 1986 to 2012, 247 435 (1.4%) records were excluded from ONS births due to missing data  <1500 glow birth weight (LBW) <2500 ghigh birth weight (HBW) ≥4000 gproportion of infants born with a:NN4B only (2006–2012) — all outcomes split by preterm and term (≥37 weeks gestation) births.Low birth weight categories were based on definitions set by the WHO,Temporal trends in birth weight and in birth weight groups were assessed yearly using multiple linear and logistic regression. Analyses were stratified by sex and adjusted for maternal age, marital status, area-level deprivation and ethnicity. Potential temporal points of change in the average yearly birth weight were identified with a change point analysis using binary segmentation algorithm allowing for multiple change points.All analyses were performed using R V.3.2.3 and Stata V.13.0.From 1986 to 2012, 17 254 624 live, singleton ONS births had complete data and were included. Excluded births had a 38 g lower mean birth weight and lived in more deprived areas with a higher proportion of non-white ethnic groups online .From 1986 to 2012, the mean birth weight increased by 58 g from 3258 g to 3316 g for females, and from 3376 g to 3436 g (60 g) for males . There wThe proportion of births with a very low birth weight remained stable over the study period for both sexes online . The proFrom 1986 to 2012, there was a 1%–2% decrease in the adjusted risk of being born a very low birth weight and 4% decrease in the risk of being born a low birth weight, but an 8%–10% increased risk of being born a high birth weight . For 200We observed a ~40 g increase in the average birth weight of live, singleton births in England and Wales between 1986 and 2012, mainly driven by increases in the late 1980s and 2000s. During the same period the risk of a low birth weight decreased and the risk of a high birth weight increased. Data for the most recent period (2006–2012) with information on gestational age showed that the increase in the average birth weight was greater in preterm births and there was a slight decrease in the risk of being born preterm over the same time period.The increase in birth weight found in this study 1986–2012) is consistent with trends from the early 1970s to the mid-1990s in Norway,86–2012 iThis study uses >98% of all live, singleton records in England and Wales and spans nearly three decades. Excluded births had a lower mean birth weight, a higher area-level percentage of non-white ethnicity and greater area-level deprivation, which may have led to an overestimate of the birth weight increase. There was evidence that the risk of being born preterm was reduced between 2006 and 2012 online , which wDecreases in maternal smoking have been linked to increases in birth weight in DenmarkYounger mothers (<30 years) had lighter babies and showed less increase in birth weight compared with older mothers (≥30 years). Between 1986 and 2012 there was a marked shift in maternal age away from younger mothers (<20 years) online , and by Ethnicity and deprivation both had the largest relative importance in the regression model ~35%). The mean percentage of area-level non-white ethnicity increased from 10.7% to 12.0% from 1986 to 2012. Data on individual-level ethnicity were only available from 2006 onwards and area-level information from the census prior to this. Adjusting for individual-level rather than area-level ethnicity in NN4B increased the observed annual increase in birth weight online , suggest%. The meTo determine the concurrent effects of maternal obesity, ethnicity and socioeconomic status on birth weight, different data sources would need to be used, for example nationally representative cohort studies or linked routine birth data sets.The rise in being overweight or obese is likely to have influenced birth weight as an increasing maternal BMI has been strongly linked with increased birth weight and risk of a high birth weight.2.5, PM10 and nitrogen oxides between 1986 and 2012.2.5 and PM10 during pregnancy is associated with restricted fetal growth, and a higher risk of a low birth weight.Other potential contributory factors to the increase in birth weight are a decrease in the levels of ambient air pollution and changes in antenatal care. UK surveillance data show a decline of more than 60% in the emission of particulate matter PMThe reduction seen in the proportion of births that are low birth weight is a beneficial trend as low birth weight is a major risk factor for infant mortality and infant mortality. Rates for the same time period have decreased from 9.6 deaths per 1000 live births in 1986 to 4.0 per 1000 live births in 2012.This study found an increase in mean birth weight among live, singleton births in England and Wales between 1986 and 2012. The concurrent decrease in the risk of low birth weight births and the increase in the risk high birth weight births suggest that overall the birth weight distribution of live, singleton births has shifted towards heavier births. Some of the observed increase is explainable by increases in maternal age, reductions in smoking and the introduction of smoke-free legislation, and increases in maternal obesity. Given the recognised strong association between birth weight and disease in both infancy and adulthood, improved understanding of the trends and determinants of birth weight in England and Wales is important to plan, implement and evaluate birth weight interventions.


The calculated results indicate that, (002) and (211) orientations exhibit different electric field dependence of band-gap and carrier concentration. The small band gap and more sensitive electric field modulation of band gap were found in (002) orientation. Moreover, the electric field modulation of the resistivity up to 3–4 orders of magnitude is also observed in (002) slab, which reveals that origin of colossal electroresistance. Lastly, electric field modulation of band gap is well explained. This work should be significant for repeating the colossal electroresistance.The Electronic structure of PbPdO In comparison with other half semimetals such as toxic Hg-based IV–VI compounds, uninjurious PbPdO2-based half semimetals seemed to be more compatible to oxide spintronics devices because they were very sensitive to external pressure, magnetic field and electric field as well. Since PbPdO2 half semimetal was predicted by local density approximation (LDA) calculations2, magnetic and electric behaviors of PbPdO2-based semiconductors had been extensively investigated both theoretically and experimentally12. Wang et al.6 reported the colossal electroresistance of PbPd0.75Co0.25O2 film, whose resistivity decreased as the operating current increased. Lee et al.7 reported the positive magnetoresistance of PbPd0.9Cu0.1O2 and negative magnetoresistance of PbPd0.9Zn0.1O2 samples, which might be attributed to the local structural disorder such as Pd/O deficiencies. Tang et al.8 explained the observed coexistence of the ferromagnetism, paramagnetism and antiferromagnetism in Co-doped PbPdO2 film using a carrier-mediated bound magnetic polaron (BMP) model. Chen et al.9 found that Pd deficiency in PbPdO2 would cause increased O 2p-Pb 6p and decreased O 2p-Pd 4d hybridizations, which induces a small band gap and hence reducing conductivity. Srivastava et al.10 reported theoretically that the couplings between Co spins were mediated through the Pd and O atoms rather than Pb atoms. Moreover, the colossal electroresistance should be associated with the external electric field modulation of the band gap for PbPdO2. To agree with this view, the electric field modulation of the band gap in two-dimensional materials had recently been studied17. Zheng et al.13 reported that applied electric field along different direction would weaken or enhance the equivalent field in zigzag BN nanoribbons, resulting in the band gap decrease or increase due to the Stark effect. Liu et al.15 found that MoS2 displayed different band gap modulation for different conformations of MoS2 bilayer due to the Stark effect. However, up to now, there was no convincing explanation for different magnetic behaviors and electronic transportation in PbPdO2-based semiconductors. Especially, the colossal electroresistance of PbPdO2–based semiconductors had hardly been repeated experimentally well, which was worth studying in theory.In recent years, spin-gapless semiconductors(SGS)2 films with (002) and (211) preferred orientations have about 0.03 eV and 0.20 eV18, (002) and (211) orientation slabs of PbPdO2 were selected and the corresponding band-gap modulations under electric field were investigated using first principle calculation. It was found that band-gap modulations of (002) orientation was different from that of (211) orientation. The calculated results could be consistent with the reported experimental measurements. At last, the charge polarization theory was applied to address the potential mechanism of electronic behaviors in PbPdO2–based semiconductors.In this paper, based on the fact that PbPdO2. In our work, the thickness of (002) and (211) slab is 3.57 Å and 4.22 Å, respectively. There are four possible terminations of (002) orientation slab, but they have the same value of band gap. As shown in Fig. 2. The (211) orientation slab presents a symmetric configuration of the center inversion consisting of 12 atoms . In the case of (211) orientation slab, there is only one termination on the surface due to its inversion symmetry along b-axis direction.Figure 02) and 21 slab is18. DOSs from Fig. 9. Furthermore, different contribution of Pd-4d and O-2p states below and above Fermi energy level (EF) are also observed in (002) and (211) orientation slabs. In the case of (002) orientation slab, O-2p states contribution is larger than that of Pd-4d states below Fermi energy level while there is no distinct difference between O-2p and Pd-4d states above Fermi energy level. In contrast, (211) orientation slab exhibits the opposite behavior of O-2p and Pd-4d states above Fermi energy level. Thus, it is reasonably expected that Pd-O bonding in the configuration would play an important role in peculiar electric and magnetic performances in PbPdO2-base semiconductors.Figure Eg and the dipole shift ΔP  on external electric field Eext for PbPdO2 with (002) and (211) orientations, respectively. Here the external electric fields are all perpendicular to the stacking layers. As shown in Fig. Eext = −0.3 V/Å to Eext = 0.3 V/Å. However, in contrast, (211) orientation slab has quite different band gap as a function of electric field. The band gap of (211) orientation slab decreases with increasing value of |Eext|, which displays a symmetrical electric field dependence of band gap, as shown in Fig. 19,T is temperature, KB is Boltzmann constant. At Eext = 0, let n = n0; Eext ≠ 0, let n = nE. Figure nE/n0 as a function of the external electric field Eext for PbPdO2 with (002) and (211) orientations at T = 10 K, 50 K, 100 K, 200 K and 300 K, respectively. Here, the band gap data are taken from Fig. ρT = 10 K, Eext = 0.3 V/Å, the band gap reaches minimum value (0.015 eV) and the value of nE/n0 could be calculated up to 2000. Since resistivity (ρ) is in inverse proportion to carrier concentration (n), the resistivity is correspondingly decreases (1/2000) at Eext = 0.3 V/Å when T = 10 K, which means that the electric field modulation of the resistivity might reach up to 3–4 orders of magnitude. The calculated results could well explain the origin of the observed colossal electroresistance in Wang’s work6. Therefore, it is suggested that the appearing of the colossal electroresistance of PbPdO2–based semiconductors may closely be associated with preferred orientation films with small band gap and sensitive electric field modulationof band gap.Figure 20,2 slab; ρPb(z), ρPd(z) and ρO(z) are the average charge density of Pb, Pd and O atom at z, respectively. In the case of Pd-O bonding, when Eext = 0, the electron cloud is mainly distributing around O atom due to polar covalent bonding of Pd-O. Because of the quantum-confined Stark effect23, the electrons would transfer from one side to the other side of atomic layers against the direction of the electric field, leading an overall net shifting in energy. Due to the asymmetry of Pd-O bonding, a spontaneous electric polarization exists along c-axis direction in (002) orientation slab. Thus, the equivalent field in slab is enhanced as the electric field is along c-axis direction, while it is weakened as the electric field is against c-axis direction, which results in the band gap increases or decreases due to Stark effect21. For (211) orientation slab, there does not exist spontaneous electric polarization along b-axis direction because of the inversion symmetry. A potential difference (U = −d E * e) between the two layer of slab is induced by the external electric field15, where E* is the total electric field (applied electric field plus inner electric field induced from redistribution of the charge), d represents the distance between neighboring layers, and e does the electron charge. As a result, the energy bands belonging to different atom layers will be separated from each other. The larger the applied electric field is, the larger the splitting value of the band is, and the narrower the band gap of the film is.The re-distribution of charge in slabs is proposed to explain the potential mechanism of band gap modulation under electric filed. The charge density difference is usually to elucidate charge transition information, bonding structure and bonding strength during the bonding process of atom in slabs. Figure 24. Figure ρind) caused by charge redistribution of (002) and (211) orientation slabs under the external electric field. It is suggested that field-induced plane-averaged charge density (Δρind) would be responsible for the band gap variations, which induces additional energy barrier due to the electron transfer of CBM and VBM26. The dipole change (ΔP) in slab along the external field could be calculated as following equations28,D) of the system is proportional to the dipole-moments change (ΔP), namely ΔD ∝ −ΔP, which results in the energy-level shifting of CBM and VBM26. As shown in Fig. P as a function of the external electric field (Eext) is just inversely proportional to the change of band gap, which means that the band gap modulation results mainly from the change of ΔP (ΔD) induced by the charge transfer. Moreover, the electron accumulation and depletion could clearly be observed in Fig. It was reported that the external electric field would induce the charge transfer in slab and the electrostatic potential felt by electrons correspondingly changes, resulting in the energy-level shifting of CBM and VBM2 are investigated by first-principles calculations. A different band-gap as a function of the external electric field is found in (002) and (211) orientation slabs. The band gap of (002) orientation slab shows a monotonous decrease with increasing electric field when the electric field is along c-axis direction of (002) orientation slab, while the band gap increases with increasing electric field as the electric field is against c-axis direction. The band gap of (211) orientation slab displays a monotonous decrease with increasing absolute electric field. Moreover, the electric field modulation of the resistivity up to 3–4 orders of magnitude is found, which reveals the origin of the colossal electroresistance. Therefore, it is suggested that the appearing of the colossal electroresistance of PbPdO2–based semiconductors may closely be associated with preferred orientation films with small band gap and sensitive electric field modulation of band gap. At last, the band-gap modulations under electric field could be well explained by charge polarization theory, which might be significant for preparing PbPdO2-based half semimetals.In summary, the electric field modulations of band-gap for (002) and (211) orientation slabs in PbPdOab initio simulation package (VASP), and projector augmented wave method (named as PAW) was used in the electron-ion interactions30. The exchange-correlation energy was considered according to Perdew-Burke-Ernzerhof (PBE) formulation of generalized gradient approximation (GGA)31. The cut-off energy was chosen to be 550 eV. Optimizations of the structures were implemented by relaxing the positions of all the atoms in the cell until the convergence tolerance of force on each atom is less than 0.001 eV/Å with the Gaussians smearing method. In order to simulate the two-dimensional infinite sheet, periodic boundary condition was used. 23 × 15 × 1 and 23 × 1 × 17 Monkhorst-Pack’s meshes were used in calculation of density of states (DOS) for the (002) and (211) orientation slabs, respectively. The slab  with around 35 Å vacuum layer was adopted.In this work, the first-principle calculations were carried out by using Vienna


This study aimed to examine whether (a) exposure to universal newborn hearing screening (UNHS) and b) early confirmation of hearing loss were associated with benefits to expressive and receptive language outcomes in the teenage years for a cohort of spoken language users. It also aimed to determine whether either of these two variables was associated with benefits to relative language gain from middle childhood to adolescence within this cohort.The participants were drawn from a prospective cohort study of a population sample of children with bilateral permanent childhood hearing loss, who varied in their exposure to UNHS and who had previously had their language skills assessed at 6–10 years. Sixty deaf or hard of hearing teenagers who were spoken language users and a comparison group of 38 teenagers with normal hearing completed standardized measures of their receptive and expressive language ability at 13–19 years.2 change = 0.08, p = 0.03).Teenagers exposed to UNHS did not show significantly better expressive  or receptive  language skills than those who were not. Those who had their hearing loss confirmed by 9 months of age did not show significantly better expressive  or receptive  language skills than those who had it confirmed later. In all cases, effect sizes were of small size and in favor of those exposed to UNHS or confirmed by 9 months. Subgroup analysis indicated larger beneficial effects of early confirmation for those deaf or hard of hearing teenagers without cochlear implants , and these benefits were significant in the case of receptive language outcomes . Exposure to UNHS did not account for significant unique variance in any of the three language scores at 13–19 years beyond that accounted for by existing language scores at 6–10 years. Early confirmation accounted for significant unique variance in the expressive language information score at 13–19 years after adjusting for the corresponding score at 6–10 years (RThis study found that while adolescent language scores were higher for deaf or hard of hearing teenagers exposed to UNHS and those who had their hearing loss confirmed by 9 months, these group differences were not significant within the whole sample. There was some evidence of a beneficial effect of early confirmation of hearing loss on relative expressive language gain from childhood to adolescence. Further examination of the effect of these variables on adolescent language outcomes in other cohorts would be valuable. Approximately 1 in 1000 babies is born with bilateral permanent childhood hearing loss (PCHL) of at least moderate severity (>40 dB HL) . The impA significant body of evidence from around the world has demonstrated the efficacy of UNHS in increasing rates of early identification of babies born with PCHL see , 2005. TTo determine whether UNHS, and the resulting early identification of PCHL, is associated with the predicted benefits to language outcomes, studies have compared these outcomes between groups of D/HH children who were exposed and not exposed to a program of UNHS and between groups of early- and late-identified children see . D/HH chMost recently, Other studies have also been conducted to look at the effects of UNHS exposure on language outcomes. From 2003 onwards, UNHS has been implemented as national or regional policy in numerous countries around the world, including the United States, where in 2009, an estimated 5073 cases of PCHL were detected by UNHS . This fiIn the present article, we focus on a subset of the cohort who were spoken language users and, therefore, able to provide data to address the question of whether exposure to UNHS and confirmation of PCHL by ≤9 months brings benefits to spoken receptive and expressive language outcomes in the teenage years. Consistent with the argument of Following this sample of D/HH participants from middle childhood through to adolescence also provided us with a unique opportunity to address the question of whether exposure to UNHS and early confirmation were associated with superior spoken language development during this period. To address this, we examined whether UNHS or early confirmation were associated with variation in language outcomes at 13–19 years  while adjusting for the level of preexisting language skills, as assessed at 6–10 years.To summarize, this article addressed two key questions:Are (a) UNHS and (b) early confirmation of PCHL associated with benefits to adolescent language outcomes in spoken language users?Are (a) UNHS and (b) early confirmation of PCHL associated with benefits to relative language gain from middle childhood to adolescence in spoken language users?The eligible sample for this follow-up study (T2) comprised 120 D/HH teenagers and a comparison group of 63 teenagers with NH who had taken part in the previous phase of this research at primary school at the age of 6–10 years  teenagers with NH who had participated at T1 took part in the present study  between the two ratings for all three scores .The Expression, Reception and Recall of Narrative Instrument ERRNI; , standarThe measure used to assess expressive language skills at primary school age (T1), the Renfrew Bus Story Test , was desA 20-minute timed version  of RavenOther characteristics of the teenager and their family, including maternal education level and languages used in the home, were also documented. The most recently available audiological data were documented from audiology and CI center records. Severity of hearing loss was categorized from the most recent audiological records as moderate (40–69 dB HL), severe (70–94 dB HL), or profound (≥95 dB HL) according to four-frequency averaging of the pure-tone thresholds from 500 to 4000 Hz for the better ear. For participants with CIs, we collected unaided pure-tone thresholds obtained during assessment for implantation.z scores for the D/HH teenagers on that measure. When language outcomes were examined in this cohort at 6–10 years, the BPVS and TROG z scores were averaged into a receptive language composite, and the information and sentence length scores from the ERRNI were averaged into an expressive language composite (p < 0.001), and in the principal component analysis, both loaded highly (0.92) on the first component. They were, therefore, combined into a single receptive language composite for analysis purposes. Of the three expressive language scores, the two information scores  showed strong positive correlations with each other  but weaker relationships with the MLU score . A principal component analysis on these expressive score identified a single component with an eigenvalue greater than 1. On this component, the two information scores had loadings greater than 0.5 . The MLU had a loading of 0.49. The two information scores were, therefore, combined into an expressive information composite, and the MLU score was reported separately for analysis purposes. Thus, the three language outcomes examined in this study were a receptive language composite (BPVS and TROG scores), an expressive information composite , and expressive MLU score.For the purpose of comparisons within the group of D/HH teenagers, we used norms obtained from the participating children with NH . The groomposite . To checWe prespecified the definition of “early” confirmation of PCHL as confirmation at ≤9 months of age, consistent with the definition used in our previous trial of UNHS  and our p values are 2-sided, and 95% confidence intervals (95% CIs) are given.Normality and homogeneity of the residual variance were examined for all measures to ensure that the regression models were appropriate. All reported z scores for the D/HH participants using the norms only from those participants with NH who provided the norms for the T2 phase of the research (N = 38) and used these in the analysis.To examine whether (a) exposure to UNHS and (b) early age at confirmation were associated with variability in relative language gains from middle childhood to adolescence, a hierarchical multiple regression analysis was conducted, which assessed whether UNHS exposure or age at confirmation predicted significant unique variance in T2 language  when adjusted for T1 language , as well as the confounding variables . The analysis was run separately for receptive and the two expressive language measures. Normality and homogeneity of the residual variance were examined for all measures to ensure that the regression models were appropriate. This analysis necessarily included only D/HH participants who had provided spoken language data at both time points . For this longitudinal element of the analysis, it was important to directly compare the same D/HH participants relative to the same NH control group at both time points (T1 and T2). We, therefore, recalculated the T1 language p’s >0.10), but there was a nonsignificant tendency for those who did provide spoken language data to be more likely to have English as the main language at home . The teenagers with NH who provided data in the present study did not differ significantly from those who were lost to follow-up in terms of age, sex, and use of English as a first language at home  but compared to those who were lost, those who were retained showed higher maternal education levels . Both the D/HH and NH groups who provided T2 spoken language data showed higher receptive language z scores at T1 than their counterparts who did not .Table p’s >0.10). The teenagers with NH were significantly younger than the D/HH teenagers , and there was a nonsignificant tendency for them to have higher maternal education levels . Scores were age-adjusted before analysis, and maternal education was adjusted for in the group comparisons.Table p’s > 0.10; Table 2  = 3.51, p = 0.06]. This variable was adjusted for in the group comparisons. Those exposed to UNHS did not differ significantly from those not exposed to UNHS with respect to age, gender, severity of hearing loss, use of a CI, nonverbal ability, etiology . There was a nonsignificant tendency for lower maternal education in the group exposed to UNHS . This variable was adjusted for in the group comparisons.The D/HH participants confirmed at ≤9 months did not differ significantly from those who were confirmed at >9 months with respect to age, gender, severity of hearing loss, use of a CI, nonverbal ability, etiology, and maternal education level , the expressive deficits for both MLU  and information score  were much reduced.The teenagers with NH showed significantly higher adjusted mean receptive language es Table . This co with NH . When weTo examine whether the patterns of language deficits shown by the D/HH group in this study were a function of the NH reference group used, we also examined standard scores on the receptive and expressive language measures to assess their performance relative to the larger hearing samples on which the tests were standardized. Standard scores  were available for all participants who completed the ERRNI. The D/HH group did not show evidence of substantial deficits on this task when examining their scores relative to the standardization sample; their standard scores were close to or above the mean of the standardization sample and were similar to those obtained by the NH reference group who participated in this study Table .Standard scores  were available for all participants on the TROG. For the BPVS, standard scores  were available for participants up to 16;11 years. For all participants in our sample over this age, we allocated them the standard score for the highest available age bracket . For participants whose raw score placed them below the basal standard score of 70 , we allocated them a score of 69. This limited the capacity of these standard scores to reflect variability in raw scores for these lower scoring participants. The mean receptive standard score (TROG standard score + BPVS standard score/2) for the D/HH group was around 1 SD below the standardization mean of 100, while the mean standard score for the NH group was very close to the standardization mean Table .z scores .The additional interaction term reflecting the interaction between the presence of a CI and the effects of UNHS versus no UNHS on overall language was not significant  suggesting that age at confirmation may be differentially affecting the language outcomes of those D/HH participants without CIs (N = 48) compared to those with CIs (N = 12); therefore, results were also examined separately for the CI versus no CI groups.The additional interaction term reflecting the interaction between the presence of a CI and the effects of early versus late confirmation of PCHL on overall language was significant (For the D/HH participants without CIs (N = 48), confirmation of PCHL at ≤9 months was associated with significantly higher receptive, but not expressive, language scores after adjustment for the effects of severity of hearing loss, maternal education level, nonverbal ability, and the presence of English as an additional language in the home (see Table For the D/HH participants with CIs (N = 12), numbers were too small to carry out parallel regression analyses but descriptive statistics comprising unadjusted means (SDs) and mean differences are reported Table  and indiz score at T1 was entered at Step 1 of the hierarchical linear regression analysis predicting receptive language z score at T2. Severity of hearing loss, nonverbal ability, maternal education level, and English as a main language at home were entered at Step 2, and finally, exposure to UNHS (in model 1) or age at confirmation (in model 2) was entered as a dichotomous predictor variable at Step 3. In both models, adding group membership  at Step 3 did not predict significant additional unique variance in T2 receptive language outcomes , receptive language Parallel regression analyses were run predicting the two T2 expressive language outcomes (information and MLU) for all D/HH participants who provided expressive language data at both time points (N = 54), with the equivalent expressive language score from T1 entered at Step 1. The regression models for expressive language accounted for much lower proportions of the variance in T2 expressive language than was the case for receptive language because the relationship between T1 and T2 expressive language scores was much weaker than that between T1 and T2 receptive language scores. Exposure to UNHS entered at Step 3 of the model did not account for significant unique variance in either of the T2 expressive language outcomes. Age at confirmation entered at Step 3 accounted for significant unique variance in expressive information score but not in expressive MLU  = 8.42, p = 0.01] but not T2 expressive MLU [5%; F = 2.38, p = 0.13) scores or T2 receptive scores  = 3.75, p = 0.06). The number of D/HH participants with CIs who had provided language data at both time points  was too small to run these hierarchical multiple linear regression analyses for that subgroup.Running the same set of analyses for the D/HH participants without CIs who had provided language data at both time points  produced the same pattern of significant effects of age at confirmation as in the whole sample, though in all cases, the percentage of unique variance explained by age at confirmation was higher than it was for the whole D/HH group; age at confirmation entered at Step 3 in the model predicted significant unique variance in T2 expressive information [16%; d’s 0.22–0.43), and the differences between groups were not significant. The lack of significant effects of UNHS and early confirmation on teenage language outcomes within the whole sample differs from earlier findings with this cohort in middle childhood  than they were for the whole sample, and confirmation of PCHL at ≤9 months of age was associated with significant benefits to receptive language. By contrast, benefits of confirmation of PCHL at ≤9 months of age were not apparent in the small group of participants with CIs. This is consistent with the suggestion of Subgroup analysis indicated a differential benefit of early confirmation for those in the D/HH sample with and without CIs. Caution must be taken in interpreting the results of subgroup analyses and, particularly, in this case where numbers of participants with CIs were small; however, these results indicate that early confirmation was not bringing the same benefits to the language outcomes of those D/HH teenagers in the study with CIs as it did to those without CI. For the participants in the D/HH sample who did not have a CI , the effects of UNHS and confirmation of PCHL at ≤9 months of age were larger  may havAs with the influence of age at implantation on language outcomes of D/HH teenagers with CIs, it is important to emphasize that UNHS and early confirmation of PCHL is likely to be just one of a multitude of variables that influence spoken language outcomes for D/HH teenagers without CIs. A recent large-scale, longitudinal study of children with mild to severe hearing loss identified variables associated with individual differences in their language outcomes . These vz scores in middle childhood with those in adolescence was much weaker than was the case for receptive language, and consequently, the longitudinal expressive language models were a less good fit to the data; indeed, for expressive information, T1 scores did not account for any variance in T2 scores. This much greater stability in receptive language skills may have contributed to the lack of a significant effect of early confirmation on relative growth in receptive language skills from T1 to T2. The lack of stability for expressive language may also indicate that the T1 and T2 expressive language measures are not necessarily measuring the same sets of skills at both time points, a possibility considered further at the end of the discussion.When examining the effects of UNHS and early confirmation on relative language gain from middle childhood to adolescence, exposure to UNHS did not account for significant unique variance in language scores at 13–19 years (T2) beyond that accounted for by existing language scores at 6–10 years (T1). Early confirmation of PCHL accounted for significant unique variance in T2 expressive information score after adjusting for T1 expressive information score but not for T2 expressive MLU or receptive scores after adjusting for corresponding T1 scores. The same pattern of significant effects of early confirmation was evidenced in the subgroup of participants without CIs; early confirmation of PCHL predicted significant unique variance in T2 expressive information but not in expressive MLU or receptive. These findings suggest that the D/HH teenagers who had their hearing loss confirmed early had made greater relative progress in one element of their expressive language skills over the years subsequent to middle childhood, raising the possibility that earlier exposure to language leading to better language skills in middle childhood may bring lasting benefits to later language development. The relationship between expressive language were exposed to UNHS: 70% of the early-confirmed participants and 36% of the late-confirmed participants in this study had been exposed to UNHS at birth. UNHS is designed to take effect by allowing early confirmation of PCHL and, consequently, early intervention to optimize the child’s early communicative environment. If a child is exposed to a UNHS program but not screened, or is screened but not early confirmed, then they are unable to access early intervention, and the intended benefits of UNHS cannot be realized. This emphasizes the importance of ensuring that effective pathways are in place to follow-up children picked up by UNHS, confirm the presence of PCHL, and initiate intervention within the shortest possible timeframe  differed from that used at 13–19 years  because the ERRNI is a more age-appropriate assessment for a teenage sample. The ERRNI was, nevertheless, selected as a measure that was as comparable as possible to the Bus Story: both tests involve the participant viewing a series of pictures that tell a story and producing a narrative based on the pictures. They differ, however, in that the Bus Story test administrator gives the children a model spoken narrative, whereas in the ERRNI, they must produce their own narrative solely based on the pictures. Skills related to the reception and retention of the model story in the Bus Story assessment may, therefore, have given the hearing children an advantage at the earlier assessment time point, which was not the case with the ERRNI at the second assessment time point. Indeed, this differential dependence of the receptive and expressive language tasks on auditory access may have been a contributing factor to the discrepancy we observed at the present time point in terms of D/HH deficits relative to the NH group on these tasks. This would be in addition to the factor discussed earlier regarding the differential sensitivity of the receptive and expressive language measures to the aspects of language that are most challenging for D/HH individuals .quality of expressive language as it measures only the length of the utterances. Two participants could score identically on mean length of utterance, but the complexity and variety of the language used in their utterances could be different . Again, a strategy focused on producing a high volume of language is likely to inflate MLU scores.It is also possible that some of the D/HH participants have learnt, as they have got older, to use compensatory language strategies that can be successfully deployed on the expressive narrative task, but not on the receptive language tasks where there is simply a right or wrong answer. One strategy, for example, might be to produce a lengthy response to the request for a narrative, which would be more likely to cover the key information points from the story and, hence, increase the information score. Similarly, the mean length of utterance score does not reflect The longitudinal design and population-based sample are strengths of this cohort study. However, the duration of the study, in which children have been followed up over many years, inevitably led to attrition of the study sample. The reduced sample of D/HH teenagers that provided spoken language data at the present assessment time point was similar to those that did not in terms of many key demographic characteristics, though there was some evidence of selective attrition of those participants who did not have English as a first language in the home, so caution should be exercised when generalizing these results to that population. The teenagers who provided spoken language data in this phase of the study showed higher T1 receptive language scores than those who did not. However, it is important to note that because this phase of the study collected spoken language data only from spoken language users, this meant that sign language users who were retained in this phase of the study were counted as nonparticipants for this examination of spoken language outcomes, despite some having provided receptive language data as children. This inflated the T1 receptive language difference between the participants and nonparticipants because these teenagers were more likely to have had low receptive language scores at T1; comparison of the overall retained and non-retained samples for this phase of the study which included these sign language users did not show higher receptive language skills in those who were retained.Ideally, we would have been able to include both the spoken and sign language users within the same language analyses, but the lack of directly comparable standardized tests for speech and sign language users means it is difficult to make comparisons between the language skills of these two groups. As mentioned previously, the inclusion of only those participants who used spoken language reduced the sample size for these spoken language analyses; our work on reading comprehension outcomes in this cohort as teenagers  did inclIn summary, significant benefits of UNHS exposure on teenage spoken language outcomes were not demonstrated within the context of this study. Long-term significant benefits of early confirmation of PCHL to spoken language outcomes were only detectable for those D/HH teenagers who did not have CIs within this cohort and were not present for all language outcomes. High within-group variability, a sample size reduced by attrition, and a lack of sensitivity of some measures may have limited the power of this study to detect significant effects of early confirmation and of UNHS exposure; further examination of the effect of UNHS on spoken language outcomes when larger cohorts reach adolescence, including individual participant meta-analysis combining data across studies, would be valuable.We thank the research assistants Eleanore Coulthard, Joanne Pickersgill, Lisa Shipway, and Zahra Taghizadeh; the audiologists Margaret Baldwin, Alyson Bumby, Adrian Dighe, Harpreet Nijar, David Reed, Joy Roberts, Sue Robinson, Salim Suleman, Rosbin Syed, and Huw Thomas; and the other medical and educational professionals who supported this study. We thank particularly the participating teenagers and their families. H. P. oversaw the conduct of the study, undertook statistical analysis, drafted the initial manuscript, and approved the final manuscript. J. K., M. M., J. S., and S. W. assisted in the design and supervision of the study, assisted with article preparation, and approved the final article. E. T. assisted in the supervision of the study and approved the final article. H. M. Y. undertook statistical analysis and approved the final manuscript. C. R. K. designed and supervised the study and the statistical analysis, assisted in manuscript preparation, and approved the final manuscript.