Overwhelmingly, women in Middle Eastern countries experience birth as dehumanising and disrespectful. Women’s stories can be a very powerful way of informing health services about the impact of the care they receive and can promote practice change. The aim of this study is to examine Jordanian women’s experiences and constructions of labour and birth in different settings , over time and across generations.A qualitative interpretive design was used. Data were collected by face-to-face semi-structured interviews with 27 Jordanian women. Of these women, 20 were living in Jordan (12 had given birth in the last five years and eight had birthed over 15 years ago) while seven were living in Australia . Interview data were transcribed verbatim and analysed thematically.Pain, Privacy, the Personal and to a lesser extent, Purity (cleanliness), were present but experienced in different ways depending on the setting  and the country.Women’s birth experiences differed across settings and generations and were represented in the four themes: ‘Birth at home: a place of comfort and control’; ‘Public Hospital: you should not have to suffer’; ‘Private Hospital: buying control’ and ‘Australian maternity care: a mixed experience’. In each theme, the concepts: The findings demonstrate how meanings attributed to labour and birth, particularly the experience of pain, are produced in different settings, providing insights into the institutional management and social context of birth in Jordan and other Middle Eastern countries. In the public hospital environment in Jordan, women had no support and were treated disrespectfully. This was in stark contrast to women birthing at home only one generation before. Change is urgently needed to offer humanised birth in the Jordanian maternity system, Overwhelmingly, women in Jordan and other Middle Eastern countries experience birth as dehumanising and disrespectful –4. StudiThis phenomenon of mistreatment by health professionals is not isolated to the Arab world –10. IncrThe move to hospitalised birth took place in high income Western countries at the end of the 19th and early twentieth century, arguably for the safety of mother and infant , 21. AltIt was not until the late 70s and 80s that birth in Jordan and other Middle Eastern countries moved into hospital settings. Prior to this, giving birth at home was considered normal for Middle Eastern women , 24. ChiThe increasing evidence of mistreatment during labour and birth has garnered the attention of the World Health Organization (WHO) and Safer Motherhood . The WHOIt is possible that the increasing dehumanisation of birth reported in Jordan, and other Middle Eastern countries, has coincided with the move from birth at home to birth in hospital facilities, and the increasing medicalisation of birth , 6. PrevTogether with the WHO, authors suggest that significant change in maternity systems is needed to improve the care and the experience of women in Jordan and the Middle East , 3, thouTherefore, this study aims to examine Jordanian women’s experiences and constructions of labour and birth in different settings , over time and across generations. Women’s stories can be a very powerful way of informing health professionals and services about the impact of the care they receive and how this can be used to promote practice change. In this study, we draw on the theory of “Birth Territory” developed by Fahy and Parratt . Birth TThis was a qualitative interpretive study  and was Fahy and Parratt  drew on Fahy and Parratt  also desFeminist concerns about patriarchy, hegemony and domination are fundamental to Fahy and Parratt’s work. Research informed by feminism prioritises women’s experiences in the context of their lives and focuses on addressing violations against women . The aimThis study was undertaken in Irbid, Jordan, and in Sydney, Australia. Jordan has a total population of 10,407,793 . Irbid iMany Jordanian people have migrated to Australia and three-quarters of these reside in New South Wales . JordaniTo capture a diversity of Jordanian women’s voices, we sought the experiences of three groups of women. Recent mothers (RM), that is women who had become mothers in the past five years and experienced mothers (EM), being women who had given birth at least 15 years previously. In addition, to enhance understanding of the meaning of childbirth experiences for Jordanian women, we also sought women who had given birth to at least one child in Jordan and Australia. There was no restriction on how long ago women had birthed in Australia. These women are referred to as Australian Jordanian (experienced or recent mothers (AJEM or AJRM). This diversity of participants was selected to facilitate the exploration of the changes in perceptions of birth and birthing practices over generations and in different settings and countries.To be included in the study, women had to have experienced a normal or instrumental birth. Women who had a caesarean section were excluded. This was because we were specifically interested in women’s experience, not only of labour, but of birth and the immediate postnatal period in different settings. Primiparous and multiparous women were both included in this study.Ethical approval for the study was obtained from the University Human Research Ethics Committee (HREC)  in February 2017. Formal written approval was also obtained from the Jordanian Ministry of Health. Participants were recruited between March–May and September–October 2017 and December–February 2018.Women were recruited through two major primary health care centres  in Irbid in Jordan. An information flyer about the study was placed on walls in both primary health care centres. The participant information sheet was distributed by administrative staff in the health care centres. This information was offered to both younger (RM) and older women (EM) who were mothers. The researcher (SH) was available to speak with interested women about the study in the waiting room of the health care centres and provided potential participants with the translated information sheet. The participants were reminded that participation was voluntary and those that provided written consent took part in the study. Some women, particularly the EM, were also recruited in the Jordanian community through word of mouth and women’s groups. In Sydney, information about the study was distributed through the Jordanian Women’s Association. Snowball sampling also occurred, with participants telling others about the study. Women who were interested in participating, were asked to contact the lead researcher either by email or phone to discuss the study. Written informed consent was obtained from all the participants.Data were collected by face-to-face semi-structured interviews with the women. Open-ended questions and prompts were used to enable the participants to talk freely about their childbirth experience  for validation purposes.The transcriptions were read and re-read and the researchers engaged in a process of reflection to discover the meanings and experiences. Data were entered into the program, Quirkos, and coded . PrelimiThe first author (SH), is a Jordanian trained midwife and mother with a strong interest in improving women’s childbirth experiences in Middle Eastern countries. SH has experienced birth in different health settings in both Jordan and Australia. In most interviews the first author (SH) also shared her own birth experiences as appropriate with the participants. Using a feminist approach, it is important to share the experience of the researcher with the participants to encourage them to talk freely about their own experiences, but SH remained conscious to not dominate the conversation with her story or not take away from the story being told by the participant. As a member of the community, SH is embedded in the culture and shares the dominant language of the participant group. During data collection, SH had regular meetings via zoom with her co-researchers and supervision team to discuss the data collection and any challenges encountered in the field. These reflections were recorded in field notes. The co-researchers are not from the same cultural background and acted as a sounding board for SH, checking interpretations and explanations of the data and findings.A total of 27 Jordanian women participated in the study, 12 participants were RM and eight were EM who were living in Jordan. In addition, seven Jordanian women living in Australia were interviewed. These seven women had given birth to at least one child in Jordan and one child in Australia. The RM and the EM were not related.Recent mothers ages ranged between 18 and 37 years, (mean = 30 years). Experienced mothers ranged in age between 51 and 66 years (mean = 56 years). All the EM who lived in Jordan had given birth to at least one baby at home. In contrast, none of the EM who had given birth in Australia had given birth at home in Jordan or in Australia. None of the RM had experienced a home birth as this is now a rare event for Jordanian women. All of the EM, had also experienced birth in a public hospital with subsequent children, except one EM, and the contrasts or comparisons they offered during their interviews, have informed this analysis. In addition, four out of 11 EM had experienced birth in private hospitals. In contrast, 14 out of 16 RM had experienced birth in a public hospital and nine out of 16 RM had given birth in a private hospital in Jordan.All of the EM and most of the RM were multiparous, just three of the RM were primiparous. The EM had between two and 10 children and the RM had between one and five children. Three out of 27 women had one child, four out of 27 women had two children, and four out of the 27 women had more than five children. Seven women had given birth in both Australia and Jordan. For some, their first birth was in Jordan, followed by a birth in Australia, and for others, their first birth occurred in Australia with a subsequent birth in Jordan. See Table The analysis revealed four major themes that reflected place of birth: ‘Birth at home: a place of comfort and control’; ‘Public hospital: you should not have to suffer’; ‘Private hospital: buying control’ and the fourth theme, ‘Australian maternity care: a mixed experience’, was a cross-cutting theme. There were also four common concepts across the women’s narratives - pain, privacy, the personal, and to a lesser extent, purity (cleanliness). These four concepts were present in women’s narratives over time, through generations and across cultures and in the different birthplaces – at home, in public hospitals and private hospitals in Jordan and in public hospitals in Australia. Each of these themes emphasises women’s desire to be in control over her labour and birth. Each of the themes is discussed separately, however, the experience of Jordanian women birthing in Australia is integrated across the first three themes as it provides a point of comparison to birth in Jordan. This is illustrated in Fig. Only the EM in this study had birthed at home, and they talked about home being a place of comfort, where they had the midwife and family around them, providing support. The women who gave birth at home viewed pain during labour as normal, something all women experience and they saw the way they tolerated it as representative of being a ‘good’ mother. Privacy and purity, or cleanliness, were also important and were consistently offered in the home environment.. The following statements reflect this view: “It is something women do, I am not the only woman that gives birth we all do. Everyone is the same” (EM3) and “It was the norm to go through that pain” (EM 8). The following story from one EM suggests that women’s families also viewed birth as an everyday event:At the time I started having labour pain, my family in law were occupied as they were going to visit a girl and to offer a marriage proposal for my brother in law. I told them I had started labour and had pain, and I asked them to postpone it. But they called the midwife for me, and they left me alone in the home with the midwife and went to the girl’s house  (EM 1).For the EM, the dominant discourse around labour and birth and pain, was that birth was a normal, everyday event. It was seen as a part of life, occurring at home, where a woman recovers quickly and gets on with things“The next day after giving birth I was up and running, cooking and vacuuming” (EM 5). For these mothers, home was an accepted place for birth, “I would prefer (to birth) at home more than hospital because there is no need to go to the hospital” (EM 4).The women who gave birth at home expected a speedy recovery: I am the type. I do not feel a lot of pain. I was surprised at that time because I had a mild pain, not really pain and within half an hour I gave birth (EM 1).Most of the EM interviewed did not feel or remember the pain of labour and birth:It is labour pain so no one can help you in relieving that pain, and I think to be a good mother you have to feel the pain of birth (EM 8).Some of the EM believed it was important to handle the pain of childbirth to be a good mother. One mother stated:In the private hospital they gave me some painkillers in the end, but I did not really need it and I think I can handle the pain and I should feel the pain to be a good mother (EM 3).One EM who gave birth to her last child in a private hospital, where pain medication seemed to be an assumed part of the service, appeared to regret having pain relief, as she also linked labour pain with being a good mother:“I had a hot shower and had some home hot herbs to increase my contractions and finish it quickly” (EM 3), and “The midwife helped me by doing perineal massage with olive oil; it helped me a lot” (EM 7). Some of the strategies they used were spiritual in nature, “This (the pain) scared me, but I prayed a lot” (EM 5). One woman expressed her appreciation for the midwife who placed the Quran next to her in labour “that made me relax” (EM 4).The EM also talked about alternative, non-medicated approaches to pain relief, She did not let anyone (family members) see me. She (midwife) asked them to stay in the same room but in a place where they could not see my body, to sit beside my head (EM 7).Birth at home was also preferred by the EM because their privacy was protected and they did not have to share a room, as was often the case in the public, and sometimes the private hospitals. At home the midwife was viewed as guarding women’s privacy:The midwife at home gives me more privacy and care, I was in the room just with the midwife and my family members stayed in a room beside my room (EM 3).To offer greater privacy, some midwives preferred family members to wait outside the room, only allowing them permission for brief visits with the woman:“The home is cleaner , you are more comfortable in your own house and its environment” (EM 1).The EM also preferred giving birth in their own home as it was their domain and they knew it was clean, “She (midwife) stayed with me the whole time until I gave birth” (EM 8) and another stated, “Yes I had my mum and my mother in law” (EM 6). When describing the people, they had around them at birth, only one EM mentioned her husband. She was clear that she liked the idea of having her family nearby, but not necessarily in the same room. At that time in Jordan, having men present at birth was considered unacceptable:My whole family is around me, my husband, and the other children, but they stayed in the other room. I just feel more comfortable that way (EM 8).While privacy was protected at home, women were not left alone. They either had support from the midwife or family; for example, participants described, She (the midwife) was really good and very kind woman (EM 4). One EM contrasted their experience with birth in a public hospital:She used to be patient with me, not like in the (public) hospital; they leave you alone in the room. Staying with one person the whole time during birth is better (EM 2).The EM described the kindness and compassion of the midwives who were with them. They help you, they make food and they stay around you most of the time and because of this help, you do not get depressed (EM 1).The women also stated that it was important to have practical support at home after the birth. EM 11 emphasised support was important because it could prevent postnatal depression,“It is what you do, you go to the hospital for the birth,” represented the meaning that the RM gave to birthing in a hospital. It was also the place where RM expected to have their baby and where they expected to have a pain free birth, “There is no need for the pain when you can take it away” (RM 6). The RM did not believe that a woman had to suffer when giving birth:I did not want to experience the pain that’s why I went to the hospital to give birth… you should not have to suffer to be a mother (RM 9).Most of the RM and some of the EM interviewed had given birth in a public hospital in Jordan. The statement, However, this was not their experience, and in contrast to birth at home, women birthing in the public sector spoke vividly about the pain they experienced during labour and birth. In the context of a public hospital in Jordan, women’s needs for privacy, personal care and support and for purity or cleanliness were not met. In the public sector, women had no option to request what they wanted.was unbearable” (RM 4); “It was a nightmare, and I really do not want to get pregnant anymore” (RM 2). The RM were particularly aggrieved that they were denied pain relief in the public hospital. Even if they asked the midwives for pain relief, the women stated they were not listened to, “I asked for painkillers, they refused and told me ‘it is not good for me’” (RM 6); and RM 11 stated, “At least give the woman painkillers to help with the pain; they do not give it at all even if it is your first baby”. Recent mother 2 described the response from midwives to her request for pain relief, “Go to a private hospital if you need painkillers”. The negative experiences of labour pain continued, particularly for first-time mothers, if they had an episiotomy during birth:It was very hard. Especially with my first baby because I had an episiotomy, it was very painful and hard to move around (RM 7).Statements from the RM reflect their distress at the pain they experienced during labour and birth, “it “I would not have asked for painkillers as I see no need for it” (EM 5). This was also the view of the A-JEM who had given birth in Australia. Even though in Australia, they had more options for medicated pain management, they maintained their opinion that pain was just part of labour and birth:I want to feel that feeling when the baby’s head comes out of my body. At that time, I felt that I was doing something extraordinary (A-JEM 7).In contrast, the EM who also had at least one baby in a Jordanian public hospital continued to view labour pain as ‘normal’, and they tended to respond negatively to the idea of medicated pain relief, The midwife at the antenatal clinic explained to me what was available for pain relief in labour and I decided to choose the gas, I was happy about this (A-JRM 5).Again, however, the perspective of RM birthing in Australia differed from the A-JEM, with the A-JRM appreciating the options for medicated pain relief:“I just do not like things that make me dizzy and that’s what these painkillers do” (A-JRM 2).Yet, the use of medication was not necessarily a positive experience for those who accepted pain medication, My sister told the midwife to give me the gas, she (the midwife) said she does not need it. My sister told her just give it to her. She gave me the gas mask and we later noticed that she did not turn the gas on (A-JRM 1).Some of the RM birthing in Australia were also critical of midwives, noting that at times, the midwives refused to give them pain relief or had “tricked” the mothers into thinking they were receiving gas when the gas had not been turned on:“I am telling her I am in pain with no screaming but she refused. So, I pretty much gave birth on my own with no painkillers at all” (A-JRM 4). Alternatively, A-JRM 2 believed that midwives used medication because they were busy, “I felt the midwives gave the gas to me just so I keep busy with it and they can help others”.The participants thought midwives sometimes withheld medicated pain relief, “There are like six women in the same room, so no privacy” (RM 6); and another woman stated, “It was very easy for others to see me during labour and birth and that was very distressing for me” (RM 10).In the public hospital in Jordan there was no privacy. Experienced and recent mothers described the settings where they birthed in Jordan public hospitals, “No, everyone has to have their own room, but at least to have curtains closed all the time” (EM 4).Some women did not voice concerns about privacy as it was what they expected. For example, one EM who had birthed in a public hospital considered sharing the same room with other women during birth as normal, but she insisted that the curtains should be drawn between the beds, “They were very respectful and always covered me with the sheets” (RM 7), while not for others: “There was a sheet only covering the lower part of my body, but this is quite embarrassing, no privacy” (RM 3).The description ‘covered with a simple sheet’ represented a level of privacy that was acceptable to some women, It is embarrassing and makes you very uncomfortable” (RM 4) and another stated:Yes, every time there was someone different examining me. That’s the problem. It was annoying and frustrating, and it hurts a lot (RM 9).This lack of privacy was intensified by the invasive approach of some health professionals during labour and birth. For example, women talked of being examined vaginally by many different people: “Only the midwife and the doctor were present in the labour room at that time, and this was a kind of privacy for me (EM 1).The EM who birthed in public hospitals 20 years ago in Jordan, talked about being able to demand more privacy where no medical students were attending the birth:“I had a really big room, very clean and a bathroom for myself, it was very comfortable” (A-JRM 5). They also appreciated the care that health staff took to maintain their privacy, “Not one of my family is allowed to be in the labour room when the doctor is present for an internal checkup” (A-JRM 5). These women also noted that mostly they were only cared for by one midwife and this, offered more privacy in contrast to Jordanian public hospitals, “You have your own room and you have one midwife and she introduced herself to me” (A-JRM 4).In contrast, the women who had birthed in a public hospital in Australia described the privacy they were afforded and they appreciated having their own room during labour and birth, “They do not allow anyone to come in with me in the labour room” (RM 7). Their request for support in public Jordanian hospitals was often met with the same response as when they asked for pain relief:When I told them to let my mum to come in with me in labour they said ‘go to private hospital if you want to let anyone to come in with you in labour’ (RM 9).The RM and EM who birthed in a public hospital in Jordan, reported that they were not allowed to have a support person with them during labour, They do not know how to treat the patient and the family. Maybe they do not want families to interfere in their business; that’s why they do not let people come in with their families (A-JEM 3).The women were critical of the Jordanian maternity service for not allowing them to have support people with them. One A-JEM was somewhat suspicious of this, and thought that the maternity staff in Jordan did not want to have outsiders interfering or observing what they do:Probably my mum and my husband. That would be nice because they will help me and are there for me and support me (RM 6).Women were asked who they would like to have with them during labour and birth. In contrast to the EM birthing at home, most RM wanted to have either their husband and or their mother with them:“It was lovely to have your family around you when you are in that much pain” (A-JRM 4). However, women’s views on whether their husband should be present or not varied. One RM stated, “I appreciated having my husband to stay with me the whole time in the labour room” (A-JRM 2). Others preferred to have their mothers or female relatives instead of involving the husband for example, “I do not mind my mum but my husband was not much help” (A-J RM 4) and “I do not recommend the husband to come in as he had a hard time dealing with what he saw.” (A-J RM 5).When birthing in Australia, the A-JEM and A-JRM appreciated that the hospitals allowed support people to stay with them during labour and birth, “I did not really feel I needed anyone as the midwives were good to me” (A-JRM 1).Only one of the RMs who had birthed in both Jordan and in Australia stated that she did not really want a support person at all in labour, “The cleanliness in the hospitals is very poor, there were cockroaches on the floor moving between beds in the hospital” (RM 11) and EM 8 stated, “The bathroom was very dirty, it was so unclean, blood and dirt everywhere in the bathroom”. While some RM considered cleanliness as sanitizing things in the hospital:One thing hospitals do not do is sanitise the cupboards, the beds that previous patients had been on. They should sanitize the beds, cupboards, and things around you (RM 6).Not unexpectedly, it was also important to the participants that they birthed in a clean environment. Some of the mothers, both RM and EM, were shocked at how dirty the public hospital was in Jordan, “It was always clean but really it is the visitors and the women that dirtied the hospital, not that the hospital itself is dirty or unclean” (EM 1).One EM chose to give birth in a public hospital in Jordan rather than at home, because she thought it was cleaner, “Everything around is clean and tidy, so you do not need to worry” (A-JRM 4), and,I can smell the cleaning products all around the hospital, so I can tell that this place is very clean and sanitized” (A-JRM 1).All of the women who gave birth in Australia appreciated the cleanliness of the hospitals. As some of them stated that, In the past 30 years there has been a dramatic increase in the number of births that occur in private hospitals in Jordan. In 2016, 58,019 babies were born in the private hospitals in Jordan. Thirteen participants in this study had given birth to at least one baby in a private hospital. This included nine RM and four EM. See table two for more information. All of the participants choosing a private hospital appeared to be seeking control over their birth experience. The prime reason that women gave for choosing to birth in a private hospital was for pain relief. Private hospitals were also described as cleaner, offering privacy through a private room, and with the possibility of having family with you.“You do not need to suffer as a mum” and that they, “Like(d) the idea of pain free birth” and they preferred to pay to buy their comfort, privacy, and care in the private hospital:I preferred to pay money as long as I was in a comfortable place. So if I needed something they would give me (RM 8).The RM who chose to birth in a private hospital reiterated their perspective that, “The injection. It calmed you and put you to sleep. That was right when the baby’s head was crowning” and RM 12 also stated, “I liked the painkillers I had it in the private hospital, I woke up after the baby was born”. In the interviews, the women were asked how they felt when they not see their baby immediately at birth. This did not appear to worry the women. Recent mother 1 stated, “No, it did not bother me at all, I just wanted to finish the pain”, and another RM 4 said, “I wanted that needle, my doctor gave it to me and I asked for that needle once I was admitted to the hospital”.In the Jordanian private hospitals, there are two options of pain relief in labour - epidural or ‘Dormicum and Valium’ which sedates women during labour and birth, much like ‘twilight sleep’ used in the past. Some RM liked the idea that they could be virtually asleep during the birth. Recent mother 8 stated, “It disturbs the skin to skin bonding. I could not see my baby until three hours of giving birth” and one EM 4 added:No I do not like the idea of being asleep when I gave birth. I did not see my daughter straight away and when I woke up I was confused and very tired to even hold my baby (EM 4).In contrast however, the few EM who birthed in a private hospital did not favour being asleep during birth. As EM 3 stated, I was not going there  again” (EM 8). They also commented that the private hospital was cleaner, “Big difference between the two , with cleanliness” (EM 4). Following this birth, the EM questioned their decision, “There was no need to go to a private hospital and pay a lot of money to only give birth there, it was just a few hours of labour pain” (EM 3).Four of the eight EM, had also birthed in a private hospital. In the interviews, these EM were asked about their decision to go to a private hospital. All four indicated this was because they could now not birth at home and they had not liked their experience in a public hospital, ““I had my own room at least, and I was in the same room the whole time, I was not moved to another room like public hospital”, and RM 7 stated, “They examined me vaginally every half an hour in the public hospitals but in the private hospitals it was only now and then”.Private hospitals offered privacy by not sharing the same room with other women, RM 5 stated, I gave birth, there was no bed for me in the maternity ward, they put me in the corridor for two hours waiting for a bed in a private hospital, with people coming and going, and men also (A-JEM 6).Privacy however, was not always available in a private hospital. Two women living in Australia, who also had their first children in Australia, were surprised at the ‘practices in Jordan, even in a private hospital:If I was to get pregnant again I would go to a private hospital because I want a female doctor who would be with me the whole time (RM 12).Some of the RM and EM preferred giving birth in a private hospital in Jordan, not just for the privacy, but because they believed they choose a female doctor:They do not let any male doctors inside the room without your permission” (A-JRM 4) and A-JEM 3 stated:They ask you if you want a male doctor from your monthly visits during pregnancy. They see you wearing a scarf and they know you would prefer a female. So, they respect you and your religion.The Jordanian women who birthed in Australia, also reported that they had the choice of a female or male doctor while giving birth in Australia, ““Yes, they allowed my mum to come in with me the whole time during labour” (RM 5), and “The family members help and support me. It is good to have someone with you; it eases the pain on you” (EM 4). Again, this was not always the case, and women reported that some private hospitals refused their request to have someone with them, “No, they did not allow anyone to come in with me in labour” (RM 8).When birthing in a private hospital in Jordan, women had anticipated they would have someone with them. Most indicated that they were allowed one support person, “There were two or more midwives, often more. I had not the same midwife the whole time during the birth” (RM 1).In the Jordanian private hospitals, women were also unlikely to have the same health professional during labour and birth, This study aimed to examine Jordanian women’s experiences and constructions of labour and birth in different settings , over time and across generations. The women who participated had given birth either at home, or in a public or private Jordanian hospital or an Australian hospital between 1979 and 2016. The key concepts that emerged from the analysis were; Pain, Privacy, the Personal, and to a lesser extent, Purity (cleanliness). Each concept was evident across the different generations of birthing women and in the different places  and countries they birthed in. Importantly, the experiences reported by participants demonstrate how meanings attributed to labour and birth, particularly the experience of pain, are produced and reproduced providing insights, not only into the medical and institutional management of birth but also the social context influencing decision-making around birth in Jordan and other Middle Eastern countries.Perceptions and experiences of labour and labour pain differed between the EM and RM. All of the EM believed that women’s bodies were designed for labour and birth and that medicated pain relief was not necessary. Feeling the pain of labour was associated with being a good mother. Alternatively, the RM argued that there is no reason why women should suffer pain in labour, that it was not the mark of a good mother and they were amenable to both technological and medicated approaches to birth. It appears in one generation we are seeing changes that occurred in many Western countries over two or even three generations of women.Leap  suggestsIn contrast, Leap  argues tIn Jordan and other Middle Eastern countries, the move from birth at home to hospital has disrupted factors such as one to one support and privacy known to assist the birth process and to support women to work with pain in labour , 24. As In contrast, in both the public and private hospitals in Jordan, and even in some instances in Australia, it was evident that women had no control over what happened to them during labour and birth. Fahy and Parratt  would exIn this study, some women demonstrated their intention to seize control over their birthing experience by seeking care in a private hospital. In making this choice, the participants appeared to want to reclaim control over their birth experience, to control their labour pain, to ensure their privacy, and to assert the right to be accompanied by a trusted family member. In the private hospital environment, women reported being in control of some things such as privacy (own room) and pain where they can ask to be ‘knocked out’ using a form of twilight sleep . They weResearch has demonstrated that a birth environment that provides women with privacy supports the hormonal processes of labour and birth , 54. NumThe findings of this study revealed that at home women were not left alone. They either had support from the midwife or family. The lack of support from someone familiar and caring was a major concern for the women birthing in Jordanian public hospitals. It appeared that some women turned to a private hospital in Jordan, hoping they would have someone with them but were disappointed. In contrast, the Australian - Jordanian EM and RM appreciated that the hospitals in Australia allowed some people to stay with them during labour and birth. The importance of an environment with familiar and caring people, is also advocated clearly in the Birth Territory model . There iThe EM in this study preferred giving birth in their own home as it was their domain and they knew it was clean. Some of the mothers, both recent and experienced, described public hospitals as being unclean. However, all of the recent and experienced mothers who gave birth in Australia appreciated the cleanliness of the hospitals in Australia. A good, physical birth environment influences women’s positive assessment of the childbirth services , 63. CleThere are immediate implications of this study for the training of midwifery and medical students as well as for professional development for trained staff. Staff and students require training to learn about women’s needs, the impact of birth trauma and to understand the effect that they have on women during one-to-one interactions. They also need to learn how the birth environment can affect birth outcomes and to understand how the health service shapes women’s experiences as well as the way in which they provide care. El-Nemer et al.  suggesteMaternity services in Jordan also need to consider how the birth room environment might change. Research shows that birth environment, such as the layout of the rooms in hospitals, the sound levels, the light and cleanliness level and the presence of other people contribute both positively and negatively to the women’s experiences of labour and birth , 69.Jordanian women may also benefit from educational opportunities, for example increasing the opportunity for prenatal education classes that are focused on women’s need with opportunities to explore options for non-medicated pain relief as well as discussing the purpose of pain in labour and birth , 70, 71.Ultimately, change needs to occur at all levels of policy and practice, from the Ministry of Health, through to senior management in health services, maternity service leaders and those providing direct clinical care in birth units. Using the voice of women, such as those voices presented in this study, may be one way to shift attitudes. Change is urgently needed. The first author is now leading a participatory action research study bringing women together with health professionals to identify strategies for change. Further research is also needed to explore the impact of all these four concepts  on women’s birth narratives and stories.This study offers an in-depth exploration of the concepts of pain, privacy, the personal  and purity or cleanliness relating to labour and birth reported by Jordanian women across different generations. It was unique in taking an intergenerational and cross country perspective which demonstrates how the birth environment impacts on women’s experiences. The study offered an opportunity to explore the hegemonic nature of women’s birthing experience in Jordan.This study has several limitations that should be noted. First, the study was conducted in Irbid, Jordan where the EM and RM either birthed in the same public or private hospital and therefore the findings may not be generalisable to other women in Jordan and the Middle East. While the invitation to participate in the study was open to all, only 27 Jordanian women agreed to be interviewed in this study. This is a small number of women from one country and may not represent the views of other women. In addition, while we had set the criteria for RM to have had their last child in the past 5 years, we found some women were very keen to participate who had their last child between six to 8 years previously. We agreed to include these women in the study. However, gaining insight from 27 participants provides a platform to understand Jordanian women’s experience of labour and birth pain. Another limitation was that the participating women self-selected, so they agreed to be interviewed and women who did not agree may have had different stories to tell. Finally, women may not necessarily have felt comfortable discussing everything they had experienced.This study aimed to examine Jordanian women’s experiences and constructions of labour and birth in different settings , over time and across generations. The theory of “Birth Territory” was used to explicate the relationship between the birth environment, issues of power and control and women’s birth experiences and use of medicated pain relief. This study showed how women’s perceptions and experiences of birth in Jordan have changed rapidly across one to two generations of women. Despite the benefits of more highly trained maternity staff and access to technology, it appears that in general, Jordanian women are unhappy with the way they are treated in birth and many report traumatic experiences. This study exposes the high level of disregard for women and their need for pain relief, privacy, and support during birth in public and private hospitals in Jordan. This disregard is deeply embedded in a maternity system dominated by medicine and associated patriarchal cultural practices and beliefs.Action is needed at all levels from policy, education and practice, however, in this context, making change will not easy. In the short-term, training about compassionate care and human rights in childbirth should be provided to midwifery and medical students at university and professional development for maternity staff. Hearing Jordanian women’s stories may be a very powerful way of informing health professionals and services about the impact of the care they receive and how this can be used to promote practice change. In the longer-term, it is likely that women themselves will need to demand the change.


Sepsis is a common and severe complication in premature neonates, particularly those born with low birth weights (<2500 g). Neonatal sepsis is steadily emerging as a leading cause of neonatal mortality in Pakistan. Lactoferrin is a natural product with broad-spectrum antimicrobial properties and glycoprotein that is actively involved in innate immune host responses. Clinical trials have revealed its protective effect on sepsis, but lactoferrin dosage, duration, and role in the prevention of sepsis are still uncertain.We aimed to establish the efficacy of bovine lactoferrin in the prevention of late-onset sepsis and to determine the optimal dose and method of administering bovine lactoferrin that may contribute to improvement in overall survival of low birth weight infants.We will implement the study in 2 phases at the Aga Khan University Hospital. The first phase, which we have completed, was formative research. This phase mainly focused on a qualitative exploration of perceptions about feeding and caring practices of low birth weight newborns and a trial of improved practices for the preparation and administration of bovine lactoferrin to newborns. The second phase is a 3-arm double-blind randomized controlled trial. In this phase, we randomly allocated 2 different daily oral prophylactic doses of bovine lactoferrin (150 mg or 300 mg) and placebo to 300 low–birth weight neonates starting within the first 72 hours of birth and continuing for the first 28 days of life.The study protocol was approved by the Ethics Review Committee of Aga Khan University on August 16, 2017. Data collection began in April 2018 and was completed in September 2020. Data analyses are yet to be completed. We expect the results to be published in peer-reviewed journals by autumn of 2021.This intervention, if effective, has the potential to be translated into a safe, affordable, and widely utilized treatment to prevent sepsis and, subsequently, may improve the survival outcomes of low birth weight neonates in Pakistan and other low- and middle-income countries.ClinicalTrials.gov NCT03431558; https://clinicaltrials.gov/ct2/show/NCT03431558PRR1-10.2196/23994 Globally, 15.5% of newborns are born with low birth weight, with 96.5% of these births occurring in low-income countries . An estiThe incidence of sepsis in neonates is inversely proportional to gestational age and birth weight . Late-onLactoferrin is a whey protein in mammalian milk. It has a multifunctional role in host defense via a myriad of antimicrobial and anti-inflammatory functions. The concentration of lactoferrin is highest in colostrum, decreasing as milk matures, and the decrease is slower in the milk of mothers of preterm infants . Bovine Despite promising experimental data, clinical information on bovine lactoferrin in infants is scarce, with minimal data from low- and middle-income countries . We sougThe primary objective of this study is to evaluate bovine lactoferrin efficacy in reducing the incidence of late-onset sepsis and to define the optimal daily dose and administration method of bovine lactoferrin to prevent late-onset neonatal sepsis in low-birth-weight and preterm neonates. The secondary objective of this study is to evaluate the effectiveness of bovine lactoferrin in reducing the incidence of necrotizing enterocolitis in low-birth-weight and preterm neonates, and the effectiveness of bovine lactoferrin in improving neonatal survival during the first 28 days of life.This study consists of 2 phases. The first phase was a qualitative component with formative research and a trial of improved practices. The second phase was a 3-arm double-blind individually randomized controlled trial.In the first phase, we conducted formative research before the initiation of the clinical trial to explore the acceptability of the delivery of the intervention. We used qualitative research methods, such as in-depth interviews, focus group discussions, and direct observations at the household level, to ascertain the practices and perceptions around feeding and care of low-birth-weight newborns. Based on the information from themes related to adherence, feasibility, and acceptability of bovine lactoferrin use, we carried out an additional trial of improved practices of preparation and administering of bovine lactoferrin to the low-birth-weight newborn by the caregivers at home.In the second phase, we conducted a 3-arm randomized controlled trial to compare 2 different prophylactic oral doses of bovine lactoferrin (150 mg or 300 mg) and placebo, given daily over the first 28 days of life. We initiated the treatment within the first 72 hours following birth.This study was conducted at the Aga Khan University Hospital in Karachi, Pakistan, in collaboration with researchers from the School of Public Health, the University of Sydney, Australia. The Aga Khan University Hospital is a state-of-the-art Joint Commission International accredited tertiary care hospital and has 2 postnatal wards with a fully equipped 24-bed neonatal intensive care unit with an extensive clinical support unit. Annually, approximately 5500 deliveries take place with a known prevalence of 15% to 18% for low-birth-weight neonates. The hospital also has a clinical trial unit, laboratory, and pharmacy, along with other essential hospital services to conduct clinical trials.For the formative research, we recruited women, their husbands, and mothers or mothers-in-law from Aga Khan University Hospital, and the qualitative researcher made an appointment to interview them at the hospital using a standard structured questionnaire. The trial participants, parents with low-birth-weight neonates (birth weight <2500 g and ≥ 1000 g) in each treatment group, were recruited from the Aga Khan University Hospital. All low-birth-weight neonates with gestational age from 28 weeks to 36 weeks 5 days, with no sign of sepsis, and on oral feeding within 72 hours of birth were eligible. We obtained written informed consent from parents or caregivers after assurance that the family planned to stay in the study area for at least 1 month.Exclusion criteria were neonates with congenital anomalies, culture-proven early-onset sepsis, history of severe maternal chorioamnionitis, or group B streptococcus colonization during pregnancy, gestational age less than 27 weeks 6 days, birth weight less than 1000 g, and parental refusal to consent.Following the inclusion criteria, 10-15 low-birth-weight neonates’ parents or caregivers were recruited purposively for the trial of improved practices. We conducted 30 in-depth interviews.A total of 100 low-birth-weight neonates were enrolled in each group, leading to an aggregate of 300 neonates. We estimate that the sample size with a 2-sided α of 5%, power of 80%, and 10% lost to follow up. Based on current hospital data, the incidence of neonatal sepsis in the placebo group is 25%. We conducted 30 in-depth interviews with parents and caregivers of low-birth-weight infants. We enrolled 15 low-birth-weight infants for trial of improved practices. Based on these assumptions, the required sample size in each trial arm was calculated as 95 low-birth-weight neonates (rounded to 100 low-birth-weight neonates), leading to a total of 300 low-birth-weight neonates.An independent statistician from the University of Sydney produced a computer-generated random allocation sequence using Stata  software with a 1:1:1 ratio for the 3 arms of the trial  and a block size of 9 for approximately anticipated number of newborns recruited each day.Once an infant met the eligibility criteria, we provided an information sheet to the parents, in English and the local language, explaining (1) the benefits of lactoferrin as a nutritional supplement along with the method of administration and (2) the placebo and its ingredients. Informed consent was obtained from the parents, after which we enrolled the neonates in the study. We blinded the participants and study teams to the group allocation. We delivered the treatment kits to the study site before initiation of the study.We will evaluate 2 different strengths (150 mg and 300 mg) of bovine lactoferrin as the intervention treatment. The color of bovine lactoferrin powder in each intervention and placebo (D–Glucose) are identical in appearance. The study staff administered the first oral dose of the trial supplement to the neonate at the hospital in the presence of the mother or the caregiver on the third day of life with a single daily dose mixed with milk  and the mother or caregiver continued to administer the supplement/placebo for 28 days. We stored the supplement sachets at room temperature and maintained an inventory at the clinical trial unit at the Aga Khan University Hospital. We monitored adherence by weekly collection of used empty sachets from the parents before providing them with the next set of sachets for the subsequent week.We followed the newborns weekly (for 28 ± 2 days) for general well-being, recognition of danger signs, and adherence to supplementation. Daily follow-ups were completed during the hospital stay until discharge. At the time of discharge, we provided the participants with 1 week’s supply of supplements. A telephone follow-up was conducted midweek, and a home visit was conducted once a week. The study investigators conducted the first follow-up visit after discharge from the neonatal care unit.The research team captured data electronically using tablets equipped with special-purpose programs. We ran a pilot before the implementation of the trial to avoid technical errors. The tablets transferred the captured data to a secured database on the server at Aga Khan University with a secure copy at the University of Sydney.3/uL), hypoglycemia (<40 mg/dL), or positive blood culture.At each follow-up visit, at home or at the hospital, a questionnaire was administered about the history of illnesses and feeding practices during the previous week. The criteria for identifying a baby with presumed clinical sepsis included any signs or symptoms such as lethargy, apnea, tachypnea, respiratory distress, reluctance to feed, temperature instability, feed intolerance, vomiting, aspirates, abdominal distention, and seizures. We define sepsis as a baby with any of the criteria of presumed sepsis in addition to either increased C-reactive protein level (>1 mg/dL) or an increased or decreased white blood cell count  according to the standard protocol of the hospital, which includes complete blood count, C-reactive protein level, blood culture, and admission.t tests. To assess the outcome variable, incident neonatal sepsis, we will use applied logistic regression and report odds ratios and 95% confidence intervals for all predictor variables. Initially, we will conduct bivariate logistic regression analyses to estimate an unadjusted odds ratio for each variable. We will examine the predictors that demonstrate an association with the outcome  in multiple logistic regression models. We will consider a P value ≤.05 as significant.We will use SPSS software  for statistical analysis. For continuous data, we will report the mean and standard deviation or median and interquartile range. We will report the baseline characteristics of the study population with frequencies and percentages. To compare categorical variables, we will use chi-square tests, and to compare continuous variables, we will use paired Previously published evidence shows that orally administered lactoferrin decreases sepsis and necrotizing enterocolitis in preterm neonates without any adverse effects ,16; howeSerious adverse events will be any untoward medical occurrence that at any dose results in death, is life-threatening , requires inpatient hospitalization or prolongation of existing hospitalization, or other important medical events which, in the opinion of the investigator, are likely to become serious if untreated.A suspected unexpected serious adverse reaction will be defined as an serious adverse event that is related to the drug or device and is unexpected .The Ethics Review Committee of the Aga Khan University approved the study (ID 4873-Ped-ERC-17). The National Bioethics Committee of Pakistan granted approval for the study to be conducted on human participants. The study was also approved by the Research Integrity & Ethics Administration, Human Research Ethics Committee, The University of Sydney (ID 2017/420).Written informed consent was obtained from all study participants prior to enrollment in the study. We will take special care to ensure the confidentiality and privacy of the study participants’ medical histories and personal information. We will store all sources of information in a password-protected predefined program, using tablets (at the time of enrollment and subsequent follow-up visits) at the Data Management Unit (The Aga Khan University). All source documents will be maintained in locked files and will only be available to people directly involved in the study.The study protocol was approved on August 16, 2017. Data collection began in April 2018 and was completed in September 2020. Data analyses are yet to be completed. We expect the results to be published in peer-reviewed journals by autumn 2021.This study will provide information on the effectiveness of bovine lactoferrin in preventing late-onset neonatal sepsis in low-birth-weight neonates and will be used to identify the optimal dosage and administration method. Our study approach aims to prevent neonatal infections; current treatment approaches involve treating neonatal infections when they occur. The current approach, which focuses on early detection of infections in newborns through postnatal care and treatment with antibiotics, runs the risk of worsening antimicrobial resistance, which is already an emerging crisis. Our approach, through the use of prophylactic bovine lactoferrin supplements, will be cost-effective, greatly reduce the risk of microbial resistance to antibiotics, and can be implemented in all settings through various health care providers who would initiate the treatment.P=.008; from 6 trials with 886 participants) and the rate of necrotizing enterocolitis  in preterm neonates. The review [A review  of clinie review  also conThis intervention, if effective, has the potential to be translated into a safe, affordable, and widely utilized intervention to prevent sepsis and subsequently improve survival in low-birth-weight neonates in Pakistan and other low-and middle-income countries. Following the achievement of conclusive results, we plan to scale up the intervention. Our long-term vision is to produce lactoferrin within Pakistan as a byproduct of the dairy industry, for use as part of the standard neonatal care package for the support of low-birth-weight babies, delivered both in hospital and at home.The results of this trial will be disseminated to the government, academic, and policy-making communities, as well as to the wider public in a peer-reviewed journal and at relevant national and international conferences.


This article has been corrected.In the Original Investigation, “Association of Air Pollution and Heat Exposure With Preterm Birth, Low Birth Weight, and Stillbirth in the US: A Systematic Review,”


Cognitive impairment is a well-defined complication of chronic kidney disease (CKD), but the neural mechanisms are largely unknown.The study aimed to assess white matter (WM) microstructure changes and their relationship with cognitive impairment development during CKD progression.Diffusion tensor imaging (DTI) datasets were acquired from 38 patients with CKD  and 22 healthy controls (HCs). Tract-based spatial statistics (TBSS) was implemented to assess the differences in WM integrity among the three groups. The associations between abnormal WM integrity and clinical indicators  were also computed.r = -0.61, p = 0.01), and the FA in the left anterior thalamic radiation was positively associated with the level of serum calcium .Compared with patients with CKD at stage 3 and HCs, patients with CKD at stage 4 showed significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD) in the corpus callosum (CC), anterior thalamic radiation, inferior fronto-occipital fasciculus, and inferior longitudinal fasciculus. Correlation analysis showed that the MD in the genu of CC was negatively associated with the digit symbol test scores (Patients with non-end-stage CKD have multiple abnormalities in WM regions. DTI metrics change with the progression of CKD and are primarily associated with cognitive impairment. The reduced integrity of WM tracts may be related to a low level of blood calcium. The current study suggests that one in 10 people will develop CKD at some point in their life (Chronic kidney disease (CKD) is defined as a glomerular filtration rate of less than 60 ml/min/1.73 meir life . Cognitieir life . Impaireeir life . By usineir life , which seir life , but it DTI is a non-invasive neuroimaging technique that has been used to detect changes in white matter (WM) microstructural properties in recent years . Tract-bOur hypothesis is that the WM structure changes are already present in non-end-stage CKD and that these changes are associated with cognitive impairments.2 classified as stage 3 and 4 CKD, respectively, and estimated glomerular filtration rate was calculated using Tc-99mDTPA-based single-photon emission computed tomography . The stage of CKD was defined based on the K/DOQI classification for CKD, with 30–59 and 15–29 ml/min/1.73 mmography . EligiblAll patients underwent multiple neuropsychological tests before MR data acquisition, including the digit symbol test based on Webster’s Adult Intelligence Scale, the type A number connection test , the Chinese revision of the Folstein version of the Mini-Mental State Examination, and Beijing revised version of Montreal Cognitive Assessment (MoCA). MoCA is a fast cognitive assessment tool that has proven to be effective in the CKD population. MMSE is a comprehensive assessment of cognitive function. NCT-A and digit symbol test mainly reflect information processing speed and attention.Several biochemical tests  were measured before MR data acquisition. No blood laboratory test was performed on the participants in the control group.b = 1,000 s/mm2) and one reference image (b = 0 s/mm2). A total of 66 axial slices were collected, covering the whole brain, and the duration of the DTI scan was 4 m and 20 s.All MRI scans were performed using a Philips Ingenia 3.0T scanner with a 32-channel phased-array head coil. DTI data were acquired using a sensitivity-encoding parallel single-shot echo-planar imaging  sequence; the parameters were as follows: TR/TE = 3,870/86 ms, voxel size = 2 mm × 2 mm × 2 mm, matrix = 112 × 109, FOV = 224 mm × 224 mm, slice thickness = 2 mm, without a slice gap. The DTI scheme included 64 non-collinear diffusion gradient directions  and mean diffusivity (MD) maps were calculated using TBSS automatically after all DTI data were corrected for image distortions due to eddy current artifacts and subject motion effects. Voxel-wise analysis was performed using TBSS. The FA maps of all participants were placed into a standard space for non-linear registration, and then the most representative FA image was identified as the common space. The mean FA image was then created and thinned to create a mean FA skeleton that represented the centers of all tracts common to all participants (FA threshold > 0.2). Next, the aligned FA data from each subject were mapped onto this skeleton. MD maps were also mapped onto the mean FA skeleton using the non-linear registrations of the FA images. ANOVA was performed on the differences in FA and MD among the three groups using the randomized statistical analysis panel implemented in FMRIB Software Library. Five thousand random permutation-based non-parametric permutation inference and threshold-free cluster enhancement (TFCE) correction method were used to perform voxel analysis on multiple comparisons. The TFCE results were corrected to a t-test or one-way ANOVA, expressed as mean ± standard deviation, and the categorical data were analyzed by χ2 test; non-normal distribution data were analyzed by Kruskal–Wallis H test, expressed as the median and the interquartile range. Partial correlation analysis was used to assess correlations between the mean FA, MD values from clusters with significant group differences, and the clinical indicators , with age and education level as covariates. A p-value less than 0.05 was defined as a significant difference.All statistical calculations were performed with IBM SPSS software, version 20.0. The sample mean comparisons were performed using a two-sample The demographic characteristics and the clinical data of the CKD patients and HCs are provided in p corrected < 0.05) in the CC, superior longitudinal fasciculus, and inferior fronto-occipital fasciculus than the CKD3 group  was found in the superior longitudinal fasciculus, the body and genu of the CC, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and anterior thalamic radiation compared with the control group. Moreover, increased MD (p corrected < 0.05) was found in the CC, anterior thalamic radiation, inferior fronto-occipital fasciculus, and inferior longitudinal fasciculus in the CKD4 group (Decreased FA in CKD4 (D4 group .p < 0.05), but differences between CKD3 and HCs were found at a liberal threshold .The differences between CKD3 and HCs did not meet the stringent statistical threshold of our study    . In the  = 0.01) . CorrelaOur study used the TBSS method to characterize the WM microstructure changes on cognitive impairment in patients with non-end-stage CKD. Compared to HCs, the CKD 4 group showed decreased FA and increased MD in the body and genu of the CC, anterior thalamic radiation, inferior fronto-occipital fasciculus, and inferior longitudinal fasciculus. Decreased FA values in the CC, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, and inferior longitudinal fasciculus were also found in the CKD4 group compared with the CKD3 group. The MoCA, Mini-Mental State Examination, and digit symbol test of the CKD4 group were lower than HCs. The MD value in the genu of the corpus callosum was significant negatively correlated with the scores of digit symbol test in the CKD4 group. These results indicate associations between WM microstructure changes and specific cognitive functions, supporting the hypothesis that brain microstructure abnormalities affect cognitive impairment during the progression of CKD. In addition, the FA value in the left anterior thalamic radiation was positively associated with the level of serum calcium. Because only stages 3 and 4 CKD patients were included in our study, we ruled out the effects of hemodialysis and kidney transplantation on the results. Our study reveals the impact of CKD itself on WM microstructure changes; this is the first batch of studies on WM neurobiological changes in non-end-stage CKD with TBSS analysis.In this study, WM abnormalities were most significant in patients with CKD at stage 4, mainly located in the CC, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and superior longitudinal fasciculus. By comparison, a recent TBSS study investigated the association between cognitive impairment and WM integrity in patients with end-stage CKD and found decreased FA values in the corona radiata, the anterior thalamic radiation, the inferior fronto-occipital fasciculus, the body and genu of the CC, the superior longitudinal fasciculus, and the inferior longitudinal fasciculus in patients with end-stage CKD . InconsiWhile DTI research on patients with non-end-stage CKD remains sparse, many abnormalities in the WM region reported in this study have previously been reported in DTI studies using end-stage kidney disease samples. For example, most DTI studies on end-stage kidney disease have found decreased FA in the CC . The CC via a neuropathological mechanism, including that of CKD.Our findings also showed degeneration of the inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and superior longitudinal fasciculus in the CKD4 group compared to the CKD3 group and HCs. The inferior fronto-occipital fasciculus is an important association pathway between the frontal, temporal, and occipital lobes and affects neuromotor function and visual and auditory processing . The infOur results supported our hypothesis that the effects of more severe CKD may lead to more serious WM damage, and WM damage is associated with cognitive impairment. This finding is supported by a previous study using a six-item cognitive impairment test, which found that CKD4 patients had significantly worse cognitive abilities than CKD3 patients, almost double the memory and attention deficits . This suOur study has several limitations. The small size of our research sample may limit the universality of the results. Further longitudinal studies of larger samples are needed to determine the effect of CKD on WM. The neurocognitive test scale used in our research is insufficient, resulting in low sensitivity to cognitive function assessment in different areas of CKD patients. Additionally, we did not rule out the effects of blood pressure, which may affect the reversibility of cognitive function. Future research should include more relevant clinical indicators and neurocognitive assessments to clarify their correlation with microstructural changes.In conclusion, we found that patients with CKD4 showed significant WM deterioration, compared to patients with CKD3 and HCs, by means of fractional anisotropy and mean diffusivity. This finding confirms the relationship between abnormalities of WM microstructure and cognitive impairment in CKD; this anomaly may be related to low blood calcium. WM deterioration appears in patients with CKD as the diseases progress. These findings provide valuable insights into the relationship between WM microstructural changes and cognitive impairment as well as the possible neurophysiological mechanisms in patients with non-end-stage CKD.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of Guangdong Second Provincial General Hospital. The patients/participants provided their written informed consent to participate in this study.ML designed the experiment. ML, YW, and XW carried out the experiment. XM and YY collected and sorted out the data. HF, SH, and HS helped on data management and processing. ML, YW, XW, and GJ wrote the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The high proportion of birth weight in Ethiopia is hypothesized to be due to inadequate maternal diet which is associated with poor nutrition education during pregnancy. There was no study that evaluated the effect of nutrition education on birth weight in the study area. This study aimed to assess the effects  of guided counseling on the birth weight of neonates.A two-arm parallel cluster randomized controlled community trial was conducted from May 1, 2018, to April 30, 2019, in West Gojjam Zone, Northwest Ethiopia. At the baseline, 346 pregnant women in the 11 intervention clusters and 348 pregnant women in the 11 control clusters were recruited. However, birth weight was measured from 258 and 272 newborns in the intervention and control groups, respectively.In the intervention group, counseling was given monthly for four consecutive months in the participant’s homes. Besides, leaflets with key counseling messages were distributed to each woman in the intervention arm. Pregnant women who attended routine nutrition education given by the health system were recruited as control. Dietary practice, nutritional status, and birth weight were the primary, secondary and tertiary outcomes of this intervention. Data were collected using a structured data collection tool. Birth weight was measured within 48 h after birth. Independent sample t-test, linear mixed-effects model, and path analysis were fitted to assess effects of the intervention.P < 0.001). The direct effect of this intervention on birth weight was 0.17  whereas the indirect effect of this intervention was 0.08 .The intra-cluster correlation coefficient was 0.095. The average birth weight of newborns in the intervention group was 0.257 kg higher compared with their counterparts in the control arm (β = 0.257, Counseling using the health belief model and the theory of planned behavior has a positive effect on improving birth weight. The findings suggest the need for enhancing nutrition education of pregnant women through the application of theories to improve birth weight.NCT03627156, “Retrospectively registered Jun, 13, 2018”.Clinical Trials.gov  According to the World Health Organization (WHO), low birth weight (LBW) is weight at birth less than 2500 g irrespective of the gestational age of the neonate. Whereas macrosomic babies weigh more than 4000 g at birth , 2. LBW The magnitude of LBW is high throughout the globe affecting 20.5 million neonates in 2015 with 91% from middle and low-income countries [In Ethiopia, the prevalence of LBW ranged from 7.8%  in JimmaLBW is a known underlying cause of neonatal morbidity and mortality. From all neonatal deaths, over 80% occurred in LBW newborns . AccordiMoreover, survivors also have a higher probability of being stunted and having impaired cognitive function  which inFactors associated with low birth weight were having unemployed mother, lack of antenatal care visit, having unintended pregnancy, rural residence, birth interval less than 2 years, previous history of having low birth weight baby, maternal undernutrition, lack of nutrition counseling, not taking an additional meal during pregnancy, pregnancy complication, not taking an iron supplement and preterm delivery , 15–17.Poor maternal diet is one of the several contributing factors to LBW –18. WomeHigh prevalence of LBW related to inadequate nutrient intakes of pregnant women warrant the importance of implementing preventive strategies to reduce low birth weight. Moreover, previous researchers in Ethiopia suggested enhancing nutrition education during pregnancy , 17 as hIn Ethiopia, nutrition education is given during antenatal care visits and at the community level  by healtIn this intervention, education was given based on the trimester of pregnancy, dietary habits, and socioeconomic status of pregnant women. A full description of the intervention can be found in the methods session.Since multiple theories and models are needed to fully explain dietary behavior , in thisThe TPB suggests that the probability of an individual performing a specific behavior is determined by the strength of his or her intention towards a specific behavior. Attitude, subjective norms, and behavioral control regarding a specific behavior are determinants of intention to bring behavioral change . The objThe intervention was implemented in West Gojjam Zone, Ethiopia, considering the principles of the Helsinki Declaration and the requirements of Good Clinical Practice . The totPregnant women within the first 4 months of pregnancy who had planned to give birth in the study area were included in this study. As hypertensive’s and cases of diabetes mellitus have different meal plans from normal cases, they were excluded from this study. Full details regarding the study participants and their enrollment are described elsewhere .G power 3.1.9.2 software was used to estimate the sample size , 37. TheTrials.gov NCT03627156 “Retrospectively registered”. The CONSORT extension flow chart and CONSORT checklist of the trial were prepared based on the Consolidated Standards of Reporting Trials (CONSORT) statement  to conduct the trial. The literate woman signed informed consent, and women who couldn’t sign gave fingerprints prior to conducting the study. The trial was registered in the Clinical 8–04 to cWoredas were selected using a simple random sampling (SRS) method from the seven eligible Woredas. First, a list of noncontiguous Kebeles was prepared using a map in different colors in consultation with a mapping office. Non-selected kebeles (buffer zone) were found between the intervention and control Kebeles to prevent the probability of message communication [West Gojjam Zone has fifteen Woredas, of which eight had nutrition education intervention on infant feeding practices. These eight Woredas were excluded from this study since women in these Woredas may not be representative of women in the nonintervention area. Three nication .Then the Kebeles (clusters) were randomly allocated to intervention and control arms using the lottery method in a 1:1 ratio. All eligible pregnant women within the first 4 months of gestation in the selected Kebeles were included in the study after screening through a home-to-home visit.Full details of the intervention and fidelity check are found elsewhere . CommuniThe core contents of the counseling protocol were increasing the amount and frequency of meals with gestational age, and diversity of meals. Iron/folic acid supplement and iodized salt utilization were also included in the counseling protocol. Moreover, reducing workload, taking day time rest, infection prevention methods, and health care services utilization were the contents of the counseling protocol.The result of taking insufficient nutrients, susceptibility to, and severity of the effects of inadequate nutrient intakes were also discussed during counseling. The benefits and barriers of eating sufficient amount and balanced diet were included in the counseling protocol. Attitude, subjective norms, self-efficacy, perceived control, intention, knowledge, and dietary practice were assessed during each counseling session, and counseling was given accordingly.Individual nutrition counseling was given monthly at women’s homes on religious holidays and weekends, using the counseling protocol. Pregnant women in the intervention arm were counseled four times; each counseling session took 40 to 60 min. During counseling, women had an active role in discussing and choosing from locally available, affordable, and acceptable foodstuffs.The first counseling was implemented within the first 4 months of gestation. It included the importance of taking a balanced diet, selection, preparation, amount, diversity, and frequency of meals. The next two consecutive counseling sessions were delivered during the second trimester of pregnancy and covered the full contents of the counseling protocol. The fourth counseling was delivered during the early third trimester of pregnancy to fill the identified gaps during counseling.Counseled women were provided leaflets with the core messages of the trial in Amharic  language and appropriate pictures. For women who couldn’t read, someone at home or in the neighborhood who could read was recommended to read the leaflet to the woman and other family members. Women in the control arm received nutrition education given by the health care system. The routine practice by the health care system is advising pregnant women to eat one additional meal from foods available at home compared to their meals before pregnancy. The education was given during ANC visit and at the community through a home visit and women’s conference. Nutrition counseling was given in the health system guide on key nutrition practices during pregnancy which was attached as Additional file Counselors and supervisors of the counseling process were BSc nurses and MSc nutritionists, respectively. The counseling team was trained for 3 days using a training manual. Furthermore, they were given a one-day supplementary training after 60 days of the trial to keep up their proficiency in counseling.Fidelity of the intervention was evaluated using criteria for best practice recommendations developed by the National Institutes of Health Behavioral Change Consortium , 46. TheThe intervention was guided by theory and counseling guide. The counseling process was pretested before the implementation. The frequencies and the duration of counseling were approximately similar for all women to make the counseling process standardized. Counselors were trained together and pre- and post-training tests were given. One process evaluator assessed the counseling process using a ‘yes/no’ rating system on items related to counseling.Maternal knowledge on diet during pregnancy was also assessed through enquiring about their understanding of intervention messages. Moreover, women’s skill was determined by observing a demonstration of preparing and taking diversified meals. Women’s practices of increasing frequency of meal, portion size, iodized salt and iron/folic acid use were also assessed using a checklist.Counselors and their supervisors met monthly to discuss and propose possible solutions to the challenges encountered during counseling. Participants, counselors, and data collectors were not aware of the study hypotheses. Furthermore, the data entry clerk was blinded by coding the groups until analysis. The supervisors and the investigators closely supervised the counseling process.Structured questionnaires on socio-demographic variables, obstetric characteristics, and dietary practices were prepared based on literature , 47. DatData collectors and supervisors were employed and trained for 3 days. Supervisors and the principal investigator followed the data collection process closely. The data collection team met daily to discuss and solve difficulties. Dietary practice and nutritional status of pregnant women were primary and secondary outcomes whereas birth weight was the third outcome of this intervention.Birth weight was measured within 48 h of life using balanced digital Seca scales, read to the nearest 100 g [0. The midpoint was marked, and measuring tape was placed snugly around the arm at the midpoint mark while hanging arm freely.To assess the Mid Upper Arm Circumference (MUAC) of the respondents, the distance from the acromion to olecranon processes was measured while the respondents’ elbows were flexed to 90Dietary data were collected using the food frequency questionnaire (FFQ) that contained 54 food items. Food items of the FFQ were categorized into nine food groups  . The conCount of each food items the women ate within a week was used to compute the mean food variety score (FVS). Respondents who consumed above the mean food variety were labeled as having good FVS, or else having poor FVS . Count oThe sums of FVS, ASF consumption, DDS, and frequency of meals were used to assess the dietary practice of pregnant women. The Principal Component Analysis (PCA) was used to generate the wealth index. The availability of a latrine, source of water, household resources, livestock, and farmland ownership were variables included in the PCA. The responses of all non-dummy variables were categorized into three parts. The highest score was labeled as one and the two lower values were coded as zero. Factor scores were produced using variables having a commonality value of above 0.5. The wealth indexes of households were produced using the scores of the first principal component. The wealth index was categorized into five as the poorest, poor, medium, rich, and richest .The sums of composite questions were used to assess each HBM and TPB constructs such as perceived susceptibility, perceived severity, perceived benefits, perceived barriers, attitude, subjective norms, intention, and knowledge on maternal diet.Level one variables were intervention, crop production, and source of drinking water whereas MUAC at the baseline, maternal age, educational status, source of drinking water, sex of the child, pre-intervention dietary practice, wealth index, and decision making on monetary resources were level one variables.Multiple births, preterm deliveries, and stillbirths were excluded from the analysis. A chi-square test was used to compare the baseline characteristics of the two groups. The birth weight difference between the two groups was compared using independent samples t-tests.Since the cluster sampling technique was used, birth weights were nested within the clusters. Taking this into consideration the linear mixed-effects model was used to analyze the effect of the intervention on birth weight. First, the empty model was fitted to determine the need for assessing random effects at the cluster level. Next, the full model which included both level one and level two variables in addition to cluster-specific random effects were fitted. Due to the fact that similar counselor counseled women in the same cluster; the intervention was included as a level two variable. This study was conducted among women in the rural area where the source of drinking water and crop production is similar to women in the same cluster. Due to this crop production and source of drinking water were also considered as a level two variables. The model was adjusted for level one variables such as MUAC at baseline, maternal age, educational status, sex of the child, pre-intervention dietary practice, wealth index, and decision making on monetary resources.Moreover, the intervention was given about dietary practice, iron/folic acid supplement use, infection prevention measures, and health service utilization. This type of counseling has both direct and indirect effects on birth weight. Taking this into consideration, path analysis was also performed to evaluate the direct and indirect effects of guided counseling on birth weight . Birth wp > 0.05) showed that birth weight was approximately normally distributed. Durbin-Watson < 4 and scatter plots also showed that observations are independent and linear, respectively. The variance inflation factor (VIF) was less than five. Before path analysis, a linear regression model was fitted to examine the association between predictors and birth weight.This regression-based path analysis was implemented using the PROCESS macro version 3.4 for SPSS, developed by Andrew F Hayes . The preP-value < 0.05 and 95% CI were used to assess statistical significance. All statistical analyses were performed using SPSS package version 23.Then, the mediation effects of dietary practice and gestational weight gain were assessed in serial multiple mediation analysis. This model also adjusted for the abovementioned predictors. Birth weight of 530 neonates was measured within 48 h. The two groups have comparable baseline socio-demographic and obstetric characteristics Table .Table 1At the endline survey, the mean birth weight of babies born in the intervention group was 3.18 kg (±0.44), while it was 2.92 kg (±0.42) for the control arm showing higher birth weight in the intervention group by 0.26 kg. Mean gestational weight gain was 8.12 kg in the intervention group and 7.17 kg in the control arm (Table p = 0.002). There were 1.2% of macrosomic babies in the intervention group, whereas, there was no macrosomic baby in the control group. There was a significant difference in the mean gestational age at birth .A higher proportion of the newborns in the control group had low birth weight than the intervention arm . At the end of the trial, counseled women had higher MUAC than their counterparts. More women in the intervention group gave birth in the health institution than women in the control group (P = 0.001) (Table MUAC of the study participants was comparable before the implementation of the intervention (1) Table .Table 3p = 0.02). The intra-cluster correlation coefficient was 0.095. According to the Linear mixed-effects model, the average birth weight in the intervention group increased by 0.257 kg compared with birth weight in the control group   (Table The first model (empty model) showed significant variability of the average birth weight across clusters   Table .Table 4, the average birth weight in the intervention group increased by 0.26 kg compared with birth weight in the control group . The direct effect of this intervention on birth weight was 0.17  . Whereas, the indirect effect of this intervention was 0.08   Table .Table 5The findings of this study confirmed the effectiveness of guided counseling using the health belief model and the theory of planned behavior in improving gestational weight gain and birth weight. Women who got counseling on the maternal diet had better gestational weight gain than women who didn’t get counseling.A similar finding was reported by the previous study in Bangladesh . This poNeonates in the intervention group were heavier than newborns in the control group. The mean birth weight of newborns in the intervention group was 0.26 kg greater than the mean birth weight of neonates in the control group. This result is similar to the study finding in Kenya .After the model was adjusted for potential confounders, the linear mixed-effects model and process model results also revealed higher birth weight in the intervention group compared with the control group. This result is consistent with previous studies reported by different scholars , 53.This difference might be due to the difference between counseling given for the intervention and control groups. In this study, counseling was given based on the health belief model and the theory of planned behavior. Counselors used a counseling guide with the core messages of the intervention. Counseling gave emphasis to increasing portion size, frequency, and diversity of meals with increasing gestational age. Moreover, in the intervention group counselors follow a client-centered approach. They assess women’s, knowledge on diet during pregnancy, availability, and accessibility of foodstuffs and counseled them based on the need of individual pregnant woman. All these have significant contributions in improving the dietary practices of pregnant women. Taking an adequate amount of good quality diet plays a crucial role in improving the birth weight of neonates.Whereas, health professionals and health extension workers counsel women to take foods available at home by adding one extra meal compared with women’s usual diet. One extra meal may not be enough for all pregnant women during the third trimester. Foods available at home may not be diversified to meet the nutrient demand of all pregnant women. This type of general non-tailored education may not bring positive results.The direct effect of the intervention on birth weight was 0.18. The possible explanation for the direct positive effect of this intervention could be the core contents of counseling. In addition to the maternal diet, women in the intervention group got counseling about disease prevention and health service utilization. This increased women’s knowledge and disease prevention practices , 55. TheThe intervention effect on birth weight was mediated by women’s dietary practice and gestational weight gain. The indirect effect through path1 (intervention effect through dietary practice) was significant. Previous studies also reported the positive effect of nutrition counseling in improving the dietary practice of pregnant women , 56 whicAnother indirect effect of the intervention was through gestational weight gain (path2). A systematic review of studies about the effect of nutrition interventions on birth weight also reported the indirect effect of nutrition intervention on birth weight . AccordiThe possible explanation could be that women in the intervention group got counseling about maternal diet and the importance of gestational weight gain using the HBM and the TPB. This type of counseling increased women’s knowledge about the consequences of poor diet, the benefits of taking a balanced diet, food preparation, and weight gain , 55. ThiThe prevalence of low birth weight in the control group was higher than in the intervention group. The 2016 Ethiopian demographic and health survey also reported a 13% prevalence of low birth weight  and BangThe results have practical implications in preventing low birth weight. The fact that significantly lower numbers of newborns have LBW in the intervention group implies the need for enacting the community level education through health extension workers using theory enhanced approaches.Although this study was a large and well-organized randomized controlled trial with good data management, increasing the reliability of the data, it is not free from limitations. The findings couldn’t be generalized to urban dwellers as this study was done among rural residents. The high rate of loss to follow up is also a limitation of this study. Though a loss to follow up is high, the baseline characteristics of the study participants were similar between the two groups.Counseling using the health belief model and the theory of planned behavior has a positive effect on improving birth weight. Dietary practice and gestational weight gain were mediators of intervention effect on birth weight. The findings suggest the need for enhancing the nutrition education of pregnant women through the application of the health belief model and the theory of planned behavior to improve birth weight. This study suggests future research to determine the effect of guided counseling starting before conception.Additional file 1.Additional file 2.Additional file 3.