An evidence-based practice suggests that the birth position adopted by women during labour has a significant impact on the maternal and neonatal birth outcomes. The birth positions are endorsed by guidelines of maternity care in South Africa, which documented that women in labour should be allowed to select the birth position of their choice, preferably alternative birth positions  during labour. Thus, the lithotomy birth position should be avoided. However, despite available literature, midwives routinely position women in the lithotomy position during normal vertex births, which causes several adverse maternal outcomes  and adverse neonatal outcomes .The aim was to explore and describe factors hindering midwives’ utilisation of alternative birth positions during labour in a selected public hospital.A public hospital in the Tshwane district, Pretoria were used in the study.This study used the qualitative, exploratory and descriptive research design. This design gathered quality information on factors hindering midwives’ utilisation of alternative birth positions during labour in a selected public hospital.The study revealed the following themes: (1) midwives’ perceptions on alternative use of birth positions and (2) barriers to utilisation of alternative birth positions. The themes were discussed and validated through the use of a literature review.The lack of skills and training during the midwifery undergraduate and postgraduate programme contributes to the midwives being incompetent to utilise alternative birth positions during clinical practice. Within the South African context, the guidelines for maternity care in South Africa supported by the National Department of Health endorse the use of alternative birth positions during labour.4 The guidelines stipulated that women should be positioned in a birth position of their choice, preferably in alternative birth positions; the lithotomy birth position should be avoided in the first and second stages of labour.4 However within the South African context, midwives are still utilising the lithotomy birth position irrespective of the available evidence-based literature.Before colonisation in Africa, it is evident that women were giving birth in various alternative birth positions, such as sitting, upright position, squatting, kneeling, using hands and knees and the left lateral birth positions. These positions were common birth practices that usually occurred in a home setting.6 Secondly, as the woman is flat on her back, trying to bear down against the force of gravity, foetal head descent is inhibited, therefore further exposing the woman to other envisaged obstetric complications such as the prolonged duration of labour that increases the chance of her being booked for emergency caesarean section or instrumental delivery to take place (vacuum delivery).6 Lastly, the woman might sustain perineal injuries involving anal sphincter, perineal tears, episiotomy and the increased rate of analgesia request associated with birth on lithotomy.6 Neonates born with the lithotomy position are at risk of reduced Apgar scores, birth asphyxia and increased intensive care admissions.The use of the lithotomy birth position during labour is associated with negative maternal and neonatal outcomes. During labour in the lithotomy birth position, a woman lies flat on her back, with hips and knees flexed, thighs apart and legs supported in raised stirrups. The gravid uterus compresses the abdominal aorta vessels, thus obstructing blood flow to the uterus, resulting in the detrimental effects of maternal hypotension and reduced foetal oxygenation.7 These positions facilitate labour through normal physiological functioning that utilises the force of nature and gravity and are associated with optimal maternal and neonatal outcomes.7 A systematic review conducted found x-ray results showing the actual increase in pelvic diameters (antero-posterior and transverse pelvic outlet diameters) when a woman adopts alternative birth positions such as upright, squatting and kneeling during childbirth compared to the lithotomy position. Increase in pelvic diameter assists with the facilitation of labour and childbirth.8 During labour on alternative birth position, the women experiences an increase in the frequency and intensity of uterine contractions, resulting in foetal descent and cervical dilation resulting in birth of the foetus.9 In addition, the utilisation of these positions enhances progression and prevents prolonged duration of labour, thus reducing complications such as postpartum haemorrhage.1 Furthermore, alternative birth positions are associated with lower incidence rates of performing episiotomy, less perineal tears and less use of instrumental deliveries.10In contrast, evidence supports the use of alternative birth positions during the first and second stages of labour.11 The statistics indicated that over 39% of all maternal deaths are from avoidable causes, consequently as a result of midwives’ lack of knowledge and skills in assisting women during labour and childbirth. Maternal deaths during pregnancy, childbirth and the puerperium seem to be a significant public health issue in South Africa. A global strategy was implemented, in essence to reach the primary target of 2030 sustainable goal agenda; and the global reduction of maternal mortality ratio to less than 70 per 100 000 live births in South Africa. The strategy indicates that it is mandatory for midwives to be skilful in managing labour and contribute to the reduction of maternal mortality rate.12 The National Committee on the Confidential Enquiries into Maternal Deaths11 indicates that reduction in maternal mortality will be achieved by increasing the proportion of skilled birth attendants, for instance, midwives in labour units. The proposed solution is alternative birth positions, which can be used to address the avoidable causes to maternal mortality. These positions are evidence-based and are associated with optimal maternal and neonatal outcomes.Midwives’ lack of skills in assisting women during labour has been associated with the cause of ‘avoidable causes’ to maternal mortality in South Africa. The mortality rates are supported by recent statistics of the National Committee on the Confidential Enquiries into Maternal Deaths.15 Apart from that, Niewenhuijze14 demonstrates that women who are given a sense of control on the birth position of their choice develop self-esteem and a feeling of competence. Therefore, it means women need to be given a chance of having their sense of control and being involved in decision-making, especially on the type of birth position they would want to adopt during labour. There are also negative birth experiences that are likely to affect women’s emotional well-being. Some of the women are likely to present with depression, which is likely to affect the bond between the mother and the baby. Consequently, this leads to the avoidance of subsequent pregnancies and electing caesarean section/s without any apparent reason in the future.14Studies by Nieuwenhuijze reveal that women’s birth experience is associated with short- and long-term implications on women’s health and well-being.13 However, regardless of the benefits of alternative birth positions, women are not aware of a variety of alternative birth positions available to them.15 Therefore, this paper is about the factors hindering midwives’ utilisation of alternative positions during labour.Despite this, midwives should always play a significant role, which might be used to prevent the identified negative experiences associated with birth outcomes. Based on this, one of the roles of the midwives is to provide women-centred care that enables women to adopt birth positions they are comfortable with, and that are likely to contribute to their self-esteem and their well-being.16 A study found an association between women who are positioned in the supine/lithotomy position during pregnancy and increased stillbirth rates.16The current practice within the South African context condones the use of the lithotomy birth position during labour. Midwives are routinely positioning pregnant women in the lithotomy position during the first and second stages of labour as noted by the researcher. Women are restricted in lithotomy or supine positions during foetal monitoring for a prolonged duration. During the second stage of labour, women bear down flat on their backs exposing themselves to several negative outcomes including perineal injury and postpartum haemorrhage as evident in the maternity case records. Most significantly midwives lack skill in the utilisation of alternative birth positions. Literature highlights the associated several negative maternal birth outcomes to the lithotomy birth position, including prolonged labour, perineal injuries and postpartum haemorrhage.4 Allowing a woman to adopt alternative birth positions during the first and second stages of labour facilitates the descent of the foetus through gravity and is associated with optimal maternal and neonatal outcomes.5 These positions are also known to reduce the risk of maternal postpartum complications such as postpartum haemorrhage and perineal injury.17That said, guidelines for maternity care in South Africa endorse alternative birth positions that women in labour are allowed to select. Preferably women should be allowed to birth in alternative birth positions  during the first and second stages of labour.Irrespective of available evidence-based guidelines on alternative birth positions, midwives continue utilising the lithotomy position during labour. Furthermore, the midwives do not seem to be aware of the effects associated with the lithotomy position as they continue and vouch for the practice. Therefore, the researcher intends to explore and describe the reasons why midwives continue to position women in the lithotomy birth position and disregard alternative birth positions during the management of the first and second stages of labour.To explore and describe factors hindering midwives’ utilisation of alternative birth positions during labour at a selected public hospital.The study used qualitative, exploratory, descriptive and contextual design. This design was used purposively to explore and describe factors hindering midwives’ utilisation of alternative birth positions during labour at a selected public hospital.The study was conducted at a specific public hospital located in the Central Tshwane sub-district with an estimated population of more than 400 000 people. This hospital is a level-one district hospital that provides 24-hours low risk and emergency services to urban and rural areas surrounding the hospital. The hospital also serves as a referral hospital for other level hospitals and the clinics nearby. The bed occupancy in the labour ward is 20. Staffing in the labour ward consists of three categories of nurses registered by the South African Nursing Council. These are advanced midwives, professional nurses and staff nurses. The average number of nurses in each shift for both day and night ranges between four midwives and two staff nurses. The target population was the midwives who conduct normal vaginal births in the hospital. The ward birth statistics were approximately more than 300 birthing women per month.The study population included professional nurses with midwifery training who completed either the four-year degree or 3-year diploma course and advanced midwives with a speciality in midwifery registered by the South African Nursing Council. This equated to 30 midwives working in the labour ward.Purposive sampling was used to select midwives who met the inclusion criteria. The criteria included qualified midwives currently working in the labour ward and responsible for conducting normal vertex deliveries with a minimum experience of 1 year working in the labour ward. The midwives who participated in the study were recruited based on availability and eligibility to participate. Data saturation occurred after conducting 20 interviews with the midwives who were willing to partake in the study based on the inclusion criteria.Data were collected in a private room at the selected hospital in Tshwane. Face-to-face semi-structured interviews were conducted. The interview had one central question and probing follow-up questions. The central question asked was:What are the factors hindering midwives’ utilisation of alternative birth positions during labour in a selected public hospital?Interviews were digitally recorded, and the researcher took field notes. Permission to use a tape recorder was obtained from the participants to enable the extraction researcher and the research assistant to transcribe the information word for word to ensure accuracy. Each interview lasted between 30 and 50 minutes. The researcher probed participants until no new information emerged and stopped interviews when participants indicated that there were no further inputs. At the end, the participants were thanked for their participation.18 Data were transcribed verbatim and then coded by the researcher, and assisted by the supervisor. The research supervisor was provided with printed transcripts and voice recordings. Then consensus was reached between the researcher and research supervisor regarding the emerging two themes.The data were analysed using Tesch’s method of data analysis. The eight steps of Tesch’s method enabled the researcher to analyse the data using open coding systematically to analyse and code the data. This method of data analysis was chosen due to its ability to convert raw written and audiotaped data into a more narrative form.19 The following criteria of trustworthiness were applied in this study: credibility, conformability, transferability and dependability.Trustworthiness is a way of ensuring data quality and is enhanced as explained according to a model by Lincoln and Guba (1985).19 A dependability audit was conducted with the assistance of an experienced researcher (supervisor) in qualitative research, who followed the entire progression of the study to confirm the findings. After data were collected, the supervisor was given transcripts to read through and provide input on interpretations already formulated by the researcher.19 Confirmability was presented through strategies of member checking.19 The researcher provided feedback to the participants about emerging interpretations, for the participants to confirm the accuracy of the collected data. Lastly, transferability was maintained through thick description, and the researcher searched extensive literature to support the phenomena being studied, as already highlighted in the background section of the study.19Credibility was ensured through prolonged engagement between the researcher and participants to build trust and rapport, allocating adequate time to collect data and stay in the field until data saturation was reached.Ethical clearance was obtained from the Research Ethics Committee at the University of Pretoria (ethics number-133/2018). Permission to conduct the study was sought from the Chief Executive Officers of the respective hospital. Informed consent was obtained from the participants. Ethical principles that were considered included beneficence, justice and respect for human dignity. These were maintained throughout the study.Twenty midwives participated in the study. The majority of the participants were females aged 23–60 years. Participants with a postgraduate qualification in advanced midwifery were 7, compared to 13 professional nurses with midwifery training who were interviewed. The participants’ work experience varied from 1 year to 18 years in labour wards. Midwives’ perception of alternative birth positions is the first identified theme. The perception of midwives refers to the preconceived psychological perception and thoughts that midwives possess in relation to alternative birth positions. Two sub-themes were explained under this theme: midwives’ personal convenience and comfortability and women’s choice of birth position.The midwives in this study preferred the lithotomy position as compared to alternative birth positions. Alternative birth positions, also known as non-supine positions of side lying, kneeling and squatting, were preferred to a lesser extent by the midwives. The reason given for their preference of the supine/lithotomy when assisting a delivery was that the position provides a good view of the perineum, ease of labour monitoring and minimising the midwives’ physical strain during the birth. These views depicted the lithotomy position as appropriate and comfortable for the midwives. Most of the midwives were aware of the disadvantages of the lithotomy birth position but still prefer utilising the position because they find it comfortable and familiar to themselves:‘I would like to think what hinders the midwives from using alternative birth positions is convenience; it is more convenient for the midwife to have the woman on lithotomy position, although it is not the best position to use. If you become too controlling as the midwife to patient, then a lot of women get perineal tears. We need to position women on positions that come to them naturally …’ ‘We utilise the lithotomy position because it favours the midwife most of the time, it is easier for me and has no benefit to the birthing woman. My view on alternative birth positions it can be done only if the midwife is comfortable with it …’ Another midwife states procedural reasons for using lithotomy:more] comfortable for us; if she is in squatting how are you going to perform episiotomy. We as midwives we are in control of the labour when we do what is comfortable for us …’ ‘I place woman on lithotomy because when I need to perform episiotomy it is much  in depth. As students, we were allocated in a different hospital and what I observed in the labour ward alternative birth positions are not practised. Therefore all we have been exposed to from undergraduate study is [the] lithotomy position. As midwives, we have built skill in mastering the lithotomy position, and we do not have confidence to offer alternative birth positions to women because we lack skill.’ ‘Yes, we were taught about alternative birth positions, but we do not have the skill to use alternative birth positions. When I attended my undergraduate training at learning institutions, lecturers did not teach alternative birth position[Another participant mentioned the lack of practice as a barrier to utilisation:‘The midwives do not practice what they learnt in theory if we don’t practice what we learnt in undergraduate class the skill fades away. We all know that […] if we learn and practice, we become competent and become comfortable to use other birthing positions. I think many midwives do not practice alternative birth positions because they are not confident in utilising those positions …’ The midwives differed in their views of equipment and facilities needed to utilise alternative birth positions. Some midwives complained that there is a shortage of necessary equipment in assisting birthing women, such as a birthing stool, birthing ball and birthing pool in the labour ward. However, other midwives mentioned that currently in the ward there were electronic beds, which also allow the midwives to position the mother in other positions. In contrast, the midwives did not know how to utilise the bed for alternative birth positions:‘We do not have facilities to use alternative birth positions. I only saw equipment for lithotomy position the lithotomy poles on the beds. I think the main problem is facilities and to buy them can be expensive, and that’s a problem …’ and] doesn’t accommodate birth stools …’ ‘The facilities are not available and the planning of the unit does not anywhere involve the midwives. The hospital needs to buy convenient birthing chairs, but there is no space in the unit as its already built this way [Another participant differed in opinion regarding the availability of facilities:to] use alternative positions as the admission beds are not electronic …’ ‘I think the alternative positions can be done, but it depends on the delivery beds sometimes we do not get time to transfer the mother as labour is fast to the delivery beds, and they sometimes deliver on the admission bed. Therefore it becomes difficult [The midwives identified the leading cause of communication difficulty as the language barrier that exists among them and the labouring women. The midwives experience difficulty in instructing women to adopt various positions due to the language barrier:the] language barrier, then it would be easier for us to communicate with them …’ ‘It is difficult for us to offer alternative birth positions because most of the times the patients we assist do not know how to communicate in our South African languages or even in English. So it is difficult for women to follow instructions during labour and that hinders us from allowing them to take preferred birth position. If we did not have the problem of [the] language barrier …’ ‘We get a lot of women coming from Africa who do not understand English to deliver in our unit. You can’t instruct someone who doesn’t understand you. So with lithotomy position it’s safe because, once they look up maybe you the midwife can look at woman during birth and use sign language to instruct her. With other birth positions like squatting they might be looking down and not hearing what you are saying. So it becomes difficult delivering the woman because of [The colonisation of midwifery training on alternative birth position differed for each midwife. Most of the midwives did not grasp the skill of utilisation of alternative birth positions during undergraduate studies. Thus, the midwives’ preference for lithotomy is underpinned by the lack of correlation of theory and practice of evidence-based positions.13 The better birth initiative is one of the guidelines used in midwifery practice to guide the best evidence-based labour practices.20 It also challenges health care providers to critical thinking and question the standard practices. The better birth initiative encourages health care providers to change the known practices. The initiative also highlights the theme of avoiding harm and respect to women who are being cared for. The midwives should not position women in the lithotomy/supine position because when a woman is placed in this position, there may be reduced blood flow to the uterus, and this interferes with the progress of the second stage of labour. The practice is also degrading and painful; therefore, no matter what the personal preference of the midwives is, the lithotomy birth position needs to be avoided.20Most midwives prefer to use the lithotomy position because they believe it is easy to manage and is what they are confident using. Limited research has been conducted on reasons midwives prefer the lithotomy position. Literature indicates that midwives should allow women to decide on their birth position of choice irrespective of their own perceived preferences. A study highlighted that women’s involvement in decision-making regarding their labouring process is crucial; it has a profound effect on their birth experiences and satisfaction of the care provided.21 For midwifery practice to be functionally embedded within the healthcare system, it needs to be available, accessible, acceptable (organisation of care), respectful, understanding and woman-centred  and focus on the promotion of physiological processes, strengthening resources and taking a non-interventional stance (philosophy). Midwives and other healthcare providers need to be interpersonally and culturally competent and maintain clarity of roles and responsibilities in their inter-professional relationships.21Quality maternal and new-born care as highlighted illustrates the three practice categories for all childbearing women and infants within a framework. Firstly, education, information and health promotion should be rendered by midwives. In relation to the study, the midwives need to provide education to birthing women on different alternative birth positions available to them. Secondly, the midwives need to assess, screen and plan the care to be rendered. Lastly, the midwives need to promote normal processes of labour to prevent complications. These categories are most effective when integrated into the health system in the context of effective teamwork, referral mechanisms and sufficient resources.22 This model provides an overview description on the women’s experiences of childbirth, and that of attending midwives for managing women during childbirth. The women-centred care model integrates the Batho Pele principles within this model. One of the principles integrated is the Consultation principle, which helps foster more participative decision-making and co-operative relationships between providers and users of public services. The shared decision-making and more active involvement of consumers in their health care could increase consumers’ perceptions of control, which in turn could improve health outcomes.22A model that describes the importance of involving women in their birthing experience is called a women-centred model. The women-centred childbirth model was developed by Maputle.22One of the strategies to enhance mutual participation concerns autonomy; mothers displayed limited information, understanding and awareness of what should be attained during childbirth. This contributed to their inability to make informed choices during childbirth. When limited opportunities were created, mothers become powerless, as evidenced by limited participation, responsibility-sharing, decision-making ability and dependency. When there is an exchange of information and knowledge between the mother and a midwife about childbirth issues and available childbirth options, mothers will become empowered.23 The model highlights measures for monitoring different aspects of care quality. It primarily addresses disrespect and abuse; their approach also highlights the interrelationships between the personal experiences of care and the health system. This supports a contextual approach to the quality of care with the focus starting with the woman’s perception and experience of care. This is seen as a central rather than a peripheral component of the quality of care. It was found in this study that midwives, hospital managers and policy-makers diminished women’s choices, due to having a common view that women in labour are unable to make the right decisions and need to be told what to do.23The women-centred model promotes women’s informed consent and choice.3 A limited number of midwives in the study encouraged the notion of giving women a choice of birth position. Therefore, a clinical decision should be based on available evidence-based literature to enhance women’s positive birthing experiences.Women value support as suggested by Nieuwenhuijze when highlighting the importance of women valuing the support that maternity care providers can offer. However, they also want to have an influence on the decisions regarding birthing positions in conjunction with maternity care providers. The World Health Organization recommends that women’s birth position choices should be supported during the first and second stages of labour.24 In support, two significant strategies that recommend the reduction of maternal mortality: skilled staff in childbirth health facilities and timely access to emergency maternal obstetric care in cases of complications. It has been estimated that Africa needs about one million doctors, nurses and midwives to provide the necessary services needed to achieve the Millennium Developmental Goals, now called Sustainable Developmental Goals.25Barriers to the utilisation of alternative birth positions are lack of necessary skills and training, lack of facilities and equipment, and communication difficulties between midwives and women. Most of the midwives expressed that they have no skill to conduct birth in an alternative birth position. Literature suggests that skilled birth attendants including midwives need to be placed in labour units to ensure the survival and safety of pregnant women and infants. The allocation of skilled attendants (midwives) in the labour ward will assist in the reduction of maternal and new born mortality rates.12Consequently, unqualified personnel often provide care, and this affects the quality of services rendered. Therefore, research stipulates the necessity of having skilful birth attendants in labour wards to ensure the achievement of Sustainable Developmental Goal number 3: dealing with ensuring healthy lives and promoting the well-being for all at all ages. The target is to reduce the global maternal mortality ratio to less than 70 per 100 000 live births by 2030. It is important to note that this can be achieved by increasing the number of skilled birth attendants.26 It has been identified that the ‘bed’ remains a dominant and central feature of most Australian birth rooms, as applicable in the hospital under study. The shortage of necessary equipment leads to the following implications such as staff members being overworked, risk of infections for the midwives, inadequate monitoring and delays in treatment, thus resulting in unnecessary obstetrical complications to women.27 Therefore, the labour ward under study possesses the necessary equipment to utilise alternative birth positions.In contrast, the midwives varied in their perception of equipment needed in the labour ward. Some midwives verbalised that the environment is already equipped with the necessary apparatus to utilise alternative birth positions such as the beds. A study conducted alludes to that the birth environment (or space) and a woman’s hormone response to her labour affect childbearing.29 The non-English speaking population utilises a growing volume of healthcare services and thus comes into contact with nurses daily. Literature alluded to that some of the adverse events that occur within the maternity units, may be related to the language barrier as a result of communication difficulty between midwife and patient, adverse events reported were associated with language barriers. For example, it was found that the ward personnel end up causing medication errors in those patients who had a language barrier compared to those who did not.30Another highlighted barrier that coexists is the language barrier. The language barrier was emphasised as a communication difficulty resulting from the parties speaking different languages. Studies indicate that the existence of the language barrier has shown to be a threat to the quality of hospital care.The source of the data was mostly dependent on the midwives of the specific hospital in Tshwane. As such, the findings cannot be transferable as the study is not representative of the entire population.This study aimed at exploring factors affecting midwives’ utilisation of alternative birth positions. It is evident that midwives lack skills related to the utilisation of alternative birth positions excluding the lithotomy birth position. The following recommendations emerged:It is recommended that midwifery practice be intensified through provision and implementation of evidence-based alternative birth positions. Midwives currently training need to be trained by an advanced skilled expert midwife. Alternative birth positions are the cornerstone to the implementation of evidence-based birth positions that enhance optimal maternal and neonatal outcomes.Nursing education institutions should revise the midwifery programme. The programme curriculum should capacitate midwives to teach midwives on the available alternative birth positions and incorporate theory into practice on provision of alternative birth positions.Midwives will be capacitated to promote midwifery care that renders women-centred care, which ensures that a woman’s choice and decision during childbirth are enhanced.Midwives should provide health education to the birthing women on all birth positions, by using posters and leaflets.Hospital management, along with the unit manager and the midwives, should form a team. Team collaboration to formulate a ward protocol on alternative birth positions, based on the evidence-based literature in the guidelines for maternity care in South Africa.Lastly, midwives should learn other South African languages and make use of a family companion or interpreter for translation in situations of language barriers.Evidence is provided in this study that midwifery practice in the hospital still follows a workplace culture that routinely positions all women in the lithotomy position during labour. Irrespective of the knowledge midwives have on the negative maternal and neonatal outcomes associated with the lithotomy position, they continued utilising this position for their own convenience and overlooked other birthing positions and the women’s preferences. Therefore, the study strongly recommends that midwifery programmes should be designed in such a way that they equip midwives with the necessary skills to utilise alternative birth positions. Furthermore, midwives are encouraged to keep abreast with developments on the provision of alternative birth positions.


Pregnancy among adolescent girls in Niger contributes to 34% of all deaths among females ages 15–19, but there is a dearth of research as to the specific contextual causes. In Zinder region, an area that is especially impoverished and where girls are at heightened risk, there is very little information on the main obstacles to improving adolescents’ health and well-being. This qualitative study examines the underlying social, individual and structural factors influencing married girls’ early first birth and participation in alternative opportunities (such as education or economic pursuits) in Niger.n = 107) included adolescent girls, husbands of adolescent girls, influential adults, community leaders, health providers, and positive deviants. All interviews were transcribed, coded and analyzed using Dedoose software.In July of 2017, researchers conducted in-depth interviews with a non-probability sample of community members in three communes of Zinder Region, Niger. Participants , influential local leaders and members of the community at large. Rapid pregnancy among newly married adolescents in Niger is a major cause of death among young girls in the country. Especially in poor, rural areas such as the Zinder region of the country, these girls have limited access to resources that would allow them to prevent pregnancy or to pursue any life opportunities beyond motherhood. CARE International sought to understand the social, cultural and structural reasons why girls continue to get pregnant at such early ages, in order to design a targeted intervention to help girls pursue better futures. CARE researchers carried out in-depth interviews with 107 people in this region including adolescent girls, husbands of adolescent girls, family members, community leaders and health providers. Respondents recognized the health and economic benefits of delaying first birth among young girls. However, newly married couples feel pressure from their communities to get pregnant right away and many individuals believe that pregnancy timing is up to “God’s will”. Moreover, girls in this region are isolated, have low education and lack access to health care and economic opportunities, making it difficult for them to envision or pursue a more prosperous life. The findings from this study suggest that a multi-faceted intervention is needed which includes training adolescent girls in education or economic activities, reducing barriers to reproductive health care and increasing overall community support for delaying rapid first birth among newly married girls.La grossesse rapide chez les adolescentes nouvellement mariées au Niger est. une cause majeure de décès chez les jeunes filles du pays. Dans les zones rurales pauvres telles que la région de Zinder, ces filles ont un accès limité aux ressources qui leur permettrait d’empêcher une grossesse ou de poursuivre toutes les opportunités de la vie au-delà de la maternité. CARE International s’est. efforcée de comprendre les raisons sociales, culturelles et structurelles pour lesquelles les filles continuent de tomber enceintes à un âge aussi précoce, afin de concevoir une intervention ciblée visant à les aider à améliorer leur avenir. Les chercheurs de CARE ont mené des entretiens approfondis avec 107 personnes dans cette région, notamment des adolescentes, des maris d’adolescentes, des membres de leur famille, des dirigeants communautaires et des prestataires de soins de santé. Les répondants ont reconnu les avantages pour la santé et l’économie de retarder la première naissance des jeunes filles. Cependant, les couples nouvellement mariés ressentent la pression de leurs communautés pour tomber enceinte tout de suite et beaucoup de personnes pensent que le moment de la grossesse dépend de la “volonté de Dieu”. De plus, les filles de cette région sont isolées, ont un faible niveau d’éducation et n’ont pas accès aux soins de santé ni aux opportunités économiques, ce qui les empêche d’envisager ou de mener une vie plus prospère. Les résultats de cette étude suggèrent qu’une intervention à multiples facettes comprenant la formation des filles à l’éducation ou aux activités économiques, la réduction des obstacles aux soins de santé en matière de procréation et l’augmentation du soutien de la communauté pour retarder la première naissance rapide chez les filles nouvellement mariées.Niger has among the poorest sexual and reproductive health outcomes of any country in the world, including the highest fertility rate (7.6 children per woman) and a maternal mortality rate of 590 deaths per 100,000 births . AdolescA host of factors drive early childbirth among adolescents. Family planning among young married adolescents can be impeded by inadequate knowledge of contraceptives and partner dynamics which limit their individual ability to make decisions about preventing early pregnancy –7. FamilIn Zinder region, where adolescent girls face a host of barriers to sexual and reproductive health and choice, over 52% of adult women experience their first pregnancy by age 19. Average fertility in Zinder is 8.5 children and knowledge of modern methods of contraception is lower than the country average  . ExtremeThe current evidence base on the reproductive health and lives of adolescent married girls in Niger is sparse. Particularly in the Zinder region, there is little research on the most important drivers of early birth among married adolescents and potential strategies to support girls in delaying birth. The purpose of this research is to understand the obstacles to and supports for delaying early first birth among adolescent girls in the Zinder region of Niger. Furthermore, we aim to investigate the barriers that married adolescent girls face when opting to pursue alternatives opportunities (such as education or employment) in lieu of immediate childbirth. The findings from this formative research study can be used to inform development of interventions targeted towards improving the health and well-being of adolescent girls in this context.In July of 2017, researchers conducted in-depth interviews with a non-probability sample of community members in three districts of Zinder Region, Niger: Dogo, Droum and Koleram. These sites were selected in consultation with the CARE Niger team and local stakeholders on the basis of both accessibility and suitability for intervention. The CARE team also targeted areas of Zinder where other partners were not already implementing programs aimed at delaying childbirth among adolescent girls .n = 21, unmarried n = 20) as well as husbands of adolescent girls (n = 21), influential adults (n = 15), community leaders (n = 15), health providers, (n = 13), and positive deviants . Both married and unmarried girls were included to understand the continuum of support needed for young adolescents as they transition from their natal homes into life as a married woman. Health providers included both physicians, nurses and midwives based at facilities as well as community health workers operating within target villages.Researchers targeted a non-probability sample of adolescent girls under the age of 20 years  informed consent was collected from all participants prior to their interview. This study was reviewed and received ethical approval by the Niger Ministry of Public Health. Adolescents were recruited on the basis of these recommendations, and given informed consent procedures directly (if they were married and considered emancipated) or given assent procedures and asked for parental consent (if they were single and under the age of 18). Only a very small proportion of the candidates we approached refused participation.Interviewers from the local population who were fluent in the local language were selected to minimize bias and increase comfort among participants. Female and male participants were also matched to interviewers of the corresponding gender. All interviews were held in a private area within the village and audio-recorded with the consent of participants, and each participant was interviewed individually. Each interview involved two data collectors: one conducting the interview using a pre-tested semi-structured interview guide, and one taking notes. At the end of each data collection day, recordings and notes were collated by the research team leader and transported to the CARE Niger office for storage in a locked cabinet. Only relevant members of the research team and program staff had access to these materials throughout the course of the study. No individual names or identifiers of participants were recorded.Data from the interviews were transcribed and translated from Hausa into French and analyzed for content. Analysis involved coding the data, developing a list of emerging themes, categorizing the themes within a hierarchical framework of main and sub-themes, using a grounded theory approach. A sample of interviews were double-coded for inter-rater reliability and quality assurance purposes. Where there were discrepancies or disagreements with coding or interpretation, the data analysis team reflected on the text together to determine meaning. All coding was done using Dedoose software.1Table Her husband will not have a problem since his wife will not have problems with childbirth. The family members will also have no problems because they will then think that she has become mature. Thus, she will not have problems with childbirth or a vaginal tear. The family will not have to worry about the problems she may have in childbirth or about her future. – female community leaderSome respondents, notably the adolescent girls themselves, expressed understanding of or interest in benefits such as income-earning opportunities or pursuit of education if an adolescent she delayed the birth of her first child. Some respondents noted that these benefits may extend beyond the adolescent girl, to her husband and parents.When I'm married I will opt for birth spacing and study during this time. Because children prevent a woman from studying. – unmarried adolescentA young woman who does not have a child has many advantages, for example, can move freely, go to the field, find cooking wood and even visit people. The parents can benefit from the help of this woman if she does business. The most important benefit is to her husband. – married adolescent with childrenRespondents reported several benefits to delaying childbirth, including the adolescent’s health and well-being, as well as the well-being of existing or future children. In particular, there was acknowledgment that some married adolescents’ bodies are not physically mature enough to safely carry and bear children.The marriage can be done at the age of 14 or 15 but the first pregnancy does not occur until 17 years. The advantage is to be mature before giving birth. Young people can be up to two years before childbirth, but it all depends on the age at which the daughter is married, the younger she is, the longer the pregnancy takes. – female community leaderSome delay for two years. This is really the ideal age to avoid the risks of complications during childbirth. From a health point of view, they mostly face problems during childbirth, some require assistance to give birth and even caesarean delivery for others. If they are study[ing], having a child will hamper their studies. They cannot do anything to make money. – influential femaleSome of the older, female participants also emphasized the importance of delaying pregnancy until the girl has reached physical maturity and even suggested that delaying pregnancy for 2 years after marriage is ideal.Two years without a child? They will think that she is sick, they will say that she must be treated so that she can get pregnant. – married adolescent w/o childPeople will consider her a fool because how a woman can stay up to 2 years without giving birth? Here the brides give birth at the first chance. She may also be considered as a barren woman, a woman who cannot bear a child. The other parents will say they should give birth each year and that their daughter made the exception so we must look for medicines [for her]. The other members of the community will say that she is barren and will laugh at her. – unmarried adolescentParticipants named a number of obstacles to delaying childbirth among newly married adolescents, mainly stigma and reprisal from family and community members. Adolescents who choose to delay birth can be perceived as infertile or disobedient. The specter of infertility can bring shame upon the girl as well as her family, and she can be rejected by her husband or ostracized by the community.They will see [the adolescent] as one who is mad because not following the divine prescriptions. They will see the husband as someone who is mad for not following the divine prescriptions … The parents will be frowned upon because they did not intervene in the face of the couple's decision. – unmarried adolescentAmong my relatives, no one is going to support me in order to delay the birth because for them it goes against the religious prescriptions – married adolescent with childrenHow can I support delaying pregnancy when it is a thing that depends on God? – influential femaleAnother key obstacle to delaying birth is the risk of being seen as going against God’s will. In these communities, pregnancy and childbirth are viewed both as part of one’s divine duty, as well as an event that is left to God’s choice. Interfering with the process of conception and birth can be interpreted as rebuking one’s religious duty, putting the couple at additional risk of stigma from the community..I think it's not normal for a childless married teenager to use contraceptives. For those with first or second children, they can use them to give their children the chance to grow in the best conditions–influential female.People in the community will take you for crazy. Looks like she's [mentally] sick. Spacing or delay is only allowed after the first pregnancy– married adolescent without childrenAlthough knowledge of modern methods was high among adolescent participants, there is strong stigma against nulliparous married adolescents using any methods to delay their first pregnancy. For many participants, contraceptives are seen as a way to space birth, but not to delay first birth. Particularly for a newly married adolescent, the idea of using contraceptives to delay is judged negatively by community members.Yes, she can delay her pregnancy and take contraceptive methods when she has her first child. – physicianNo, me I will not give her, how could a teenage girl who is married take products? – community health workerProviders will advise her to wait until she has her first child before considering contraceptives. If the bride has a child, it is not a problem in that she seeks to space births. – nurseIn addition to general stigma against contraceptive use, there are some myths and misconceptions about contraceptive products that complicate delaying birth. Some, including health providers, believe that using contraceptive methods prior to the first birth may cause infertility or future miscarriages..If she asked me permission I would not let her do it unless she did so without my knowledge, and if she did, I would divorce her. For me, why is she going to take a product that will make her sick, which can make her sterile? Any product that will deprive you of pregnancy for three years will surely prevent her from being pregnant her whole life– husband of adolescent w/ children.For me [using contraceptives before first birth] is not good because if you start with contraceptive products it could harm her procreation– community health workerEven health providers are subject to the same community and social norms associated with contraceptive use, sometimes exhibiting bias against delaying birth or method use among adolescents. Of the health care providers interviewed, several noted that they would not recommend or prescribe contraceptive methods for married adolescent girls who had not yet had their first birth.after the arrival of the first child had more appeal than deferring the initial pregnancy. Respondents noted that spacing births can benefit the well-being of the woman, child and family overall. Contraceptive method use is also seen as an appropriate means to space birth, but not to prevent or delay the first birth.People will disapprove because she never gave birth and she tries to delay [first birth]. It is after a first pregnancy that one normally tries to delay the following pregnancy – married adolescent without childrenWhen you have too many children, you will face poverty … For the woman, the spacing or the delay of the births will allow her to always be in a good state of health. Otherwise, if she does not, she will get tired quickly. For the husband, the advantage lies in the fact that his money will not be depleted. – husband without childrenNo there is no problem [using contraception] as long as it is for spacing birth and not for delaying birth. – husband with childrenWhile delaying birth was largely condemned in this context, the concept of spacing births .She would be happy, even the members of her family would be happy. Because she continued her studies to the point of having a job and helping her family members– husband of adolescent with childrenI can delay my first birth so that I can achieve my goals (studies). This will allow me to help my parents depending on what I earn. –unmarried adolescentParticipants were asked to relay the potential benefits that could stem from an adolescent girl pursuing other activities while she delayed motherhood. Her potential economic contribution to the family was seen as desirable for both her husband and her parents and in-laws..With economic activities the earnings will allow her to have an autonomy so that she can have everything she needs without expecting me although I have an obligation to her. And in some measure it can even help me in many things. For her parents or her in-laws, she can help them; for the children she will have in the future, they will have everything they desire. For the community, it can serve as a relief for any needy person– husband w/o childrenAny economic activity is beneficial. In 1 year or 2 years she finds, she can do her own activities. She can buy livestock for breeding because we will have to breed. The advantage of the husband, by virtue of this activity, she will not frequently ask him for money, and will provide for her wants without the assistance of the husband. Too much request in a couple kills the marriage. She can help her parents too. If a woman works, before the husband satisfies a need for the children, she can do it. –husband with childrenParticipation in education or income-generating activities could also be a means of increasing adolescent girls’ autonomy. Respondents cited a girl’s ability to provide for herself and her family as means of being less dependent on the husband, seen as something positive in this case.I will support it because I have seen its importance and that our children can grow up healthy and have what they want. – husband without childrenChildren were also mentioned as potential beneficiaries of an adolescent girl’s better future:The most difficult obstacle for her is her husband because if he says no, even if her parents allow it she cannot do otherwise than to follow the husband's decision. –husband of adolescent with childI can have problems if my husband forbids me [to work]. Even if my parents encourage me. If he says no, I will obey his orders.– married adolescent w/o childrenThe biggest potential obstacle to an adolescent pursuing opportunities is the disapproval of the husband. The husband’s consent is essential for a married adolescent girl to be able to pursue education, skills training or labor participation..No, you don’t have to delay the first pregnancy for any reason. Pregnancy is also an opportunity, why pursue other opportunities if we have one right in front of us. It is unimaginable for a young woman to delay her pregnancy for business, it is not done here– husband of adolescent with children.[If she delays birth to pursue an alternative opportunity] the community can make gossip and stigmatize it– husband with childrenFor some participants, delaying birth to pursue work was seen as an inappropriate choice, implying that the adolescent girl’s primary duty is to be a mother and wife. Furthermore, pursuing educational and economic activity is not considered entirely incompatible with childbearing, and earning money is not seen as a good enough reason to go against social and religious norms of immediate childbearing.Her husband can support her. It is only he who can support it because it is the only one who has power over it. – influential femaleIt is an agreement between the spouses. The husband consulted his wife and they found an agreement. It’s an agreement that we sign. She will confer with her husband; the biggest support is his support. – male community leader[She needs] knowledge about reproductive health because if she has knowledge herself, she can sensitize or encourage her husband. – health care providerRespondents were asked to explain what types of support a married adolescent girl would need in order to be able to delay birth. Three main elements emerged as being essential. First, husbands are seen as having ultimate power of decision-making over the adolescent. The next most important source of support comes from the immediate family, namely parents and in-laws. Finally, participants felt that adolescent girls need access to family planning knowledge and services in order to be able to effectively delay birth.Even if by chance the villagers learn that the youngster has had the support of his family they will say that they are not thinking correctly. The in-laws of the girl will also be condemned by the villagers. - unmarried adolescentIn some cases, even the support of husband and family is not enough to avoid reproach by the community and individuals may put direct pressure or judgment on the family or husband to discourage their support for delaying birth.This study fills a significant gap in our understanding of the context-specific drivers of early birth among married adolescent girls in Niger. Our findings suggest a myriad of influences that lead to early childbearing among married adolescent girls in this environment. Despite acknowledging the health and economic benefits to delaying birth, girls are pressured by stigma of infertility, barriers to accessing contraceptives and family influence to get pregnant shortly after marriage. The prospect of economic advancement is not so great as to overtake the barriers to delaying first birth.Numerous other findings echo the results of this study, particularly as relates to the influence of the husband on decision-making, the stigma associated perceived infertility and lack of access to sexual and reproductive health services. A husband’s dominance in fertility decision-making is well established in other similar settings, and is an oft-cited reason for inclusion of husbands in interventions aimed at delaying or spacing births among women , 17. FurAmong the most salient influences on childbirth among married adolescent girls in Niger is a fatalistic belief in the will of God to dictate the timing of first birth. Even participants who supported delaying birth or acknowledged benefits thereof ultimately put the outcome of a couple’s fertility in divine hands. This reliance on God’s will to determine the timing of birth may discourage the use of contraceptives or other attempts to delay birth. A recent study of family planning acceptability in Niger showed that religion may play a role in fertility decision-making, but that the opinion of husbands and influential leaders in the community ultimately takes precedence when it comes to contraceptive use and limiting or spacing births . ReligioThe majority of respondents were in favor of providing married adolescent girls with opportunities for advancing their educational or employment outcomes. However, the promise of economic advancement may not be powerful enough to overtake social pressure for rapid first birth following marriage. These findings indicate the need for effective communication campaigns to demonstrate the long-term health and economic well-being of the girl and her family when she is allowed to delay birth and pursue alternative opportunities. Such a campaign would serve not only to directly educate young brides and their husbands on benefits of delaying birth, but could also help dampen the community stigma around delaying birth that so clearly influence couples’ fertility decisions.spacing as a way to protect a woman’s health and ensure the well-being of her children and family. The fact that Nigerien communities are familiar with and approving of birth spacing suggests a foundation upon which more learning and acceptance for delaying birth may be built. Religious leaders may also be employed to correct misconceptions around religious edicts on contraceptive use, and to encourage protection of girls’ health through delayed first birth. Many respondents, particularly husbands and girls themselves, were also supportive of providing girls with educational and employment opportunities.Despite the barriers to delaying first birth, there were a number of encouraging findings that present opportunities for successful intervention. Study participants displayed knowledge of and support for birth These findings should be viewed in light of the study limitations. Although we sampled a substantial number of different participants in multiple villages, the findings are not generalizable due to the purposive nature of the sampling and total number of participants. Furthermore, these contextual barriers are specific to the Zinder region in which the data collection was focused, and may not apply to other parts of Niger. Finally, due to the highly sensitive topic of sexual and reproductive health in this context, there may be the presence of response bias.Findings from this research suggest the need for a holistic approach to both addressing the barriers to pregnancy prevention and stimulating girls’ participation in economic and educational pursuits. While many participants understood the importance of delaying birth for protecting girls’ health and were encouraging of educational and employment opportunities for girls, there was still a great deal of reticence to back the idea of delaying first birth even in order to advance girls’ economic outcomes. These contradictions highlight the complexity of the issue of childbearing in this setting and suggest the need for a multi-faceted approach to intervention which targets socio-behavioral, structural, community level and individual level barriers to delaying rapid first birth among married adolescents.Promising areas for intervention include addressing mitigating health system barriers to reproductive health care; training adolescent girls on viable economic activities; and providing literacy and educational opportunities for girls. Effective interventions should also include or target immediate members of the girls’ families , influential local leaders and members of the community at large.


An increased risk of adverse conditions related to in vitro fertilization (IVF) pregnancies has been repeatedly reported. Our study aimed to summarize outcome differences between pregnancies after IVF and after spontaneous conception (SC) in Estonia.Data on all liveborn singletons to primiparas women aged 25–40 years during the period 2005–2014 were obtained from the Estonian Medical Birth Registry. There were 1778 and 33,555 newborns in the IVF and SC cohort, respectively. The relative risk of pregnancy-related complications and adverse pregnancy outcomes in the IVF cohort in comparison with the SC cohort was quantified by prevalence proportion ratios (RR) with 95% confidence intervals (CI) using modified Poisson regression models adjusted for maternal age, education, ethnicity, marital status and study period.The cohort of IVF singletons experienced a higher risk of preterm birth , iatrogenic preterm birth , very preterm birth , low birthweight , congenital anomalies , and admission to a neonatal intensive care unit . Somewhat elevated risk of spontaneous preterm birth did not reach statistical significance . IVF mothers were at increased risk of placenta previa , placental abruption  and cesarean section . The risk of pre-eclampsia was borderline . Adjustment for maternal age attenuated the associations between IVF and adverse outcomes. Maternal education, ethnicity and marital status had no effect on the magnitude of the risk estimates.The increased risk of pregnancy-related complications and adverse pregnancy outcomes was observed in the Estonian cohort of IVF singletons in comparison with the cohort of SC singletons. The relative risk estimates grew with maternal age but were not influenced by the maternal education, ethnicity and marital status. To monitor the efficacy and safety of the used assisted reproductive technology, a specialized country-wide register should be created in Estonia. In vitro fertilization (IVF) as an effective infertility treatment procedure was introduced in Estonia in 1997. According to the Artificial Insemination and Embryo Protection Act, women aged 18–50 years and with active legal capacity can undergo artificial insemination by transferring maximally three embryos per cycle . EHIF coBy the Estonian Medical Birth Registry (EMBR) data, 1.2% of newborns in 2005 were conceived by IVF, including 0.7% of singletons and 19.4% of multiples. The respective figures in 2014 were 3.5, 2.6 and 32.9%. The proportion of multiple births among births after IVF declined from 26.1% in 2005 to 16.9% in 2014. One embryo was transferred in 32.5%, two embryos in 58.5% and three embryos in 8.9% of cycles in 2014 [The health of IVF children and their mothers has been monitored since the first IVF baby was born in 1978 . The majPrevious studies have shown that IVF pregnancies are more common among women aged ≥35 years, married or cohabiting, or with higher socioeconomic status , 20, 21.Given the higher risk of PTB and lower mean birthweight among SC singletons born to unmarried, non-Estonian or less educated mothers in Estonia , and relWe used data from the EMBR, which collects information on maternal socio-demographic background, reproductive history, pregnancy risk factors, pregnancy and delivery complications, and on perinatal outcomes for each birth (≥22 weeks of gestation) with unique personal identification numbers for mothers and newborns . IVF staThe study period was split into two sub-periods: 2005–2009 and 2010–2014. The maternal socio-demographic background was described using the following characteristics: age, stratified into three age groups of 25–29, 30–34 and 35–40 years; education, categorized as higher , secondary  and basic (9 years or less); ethnicity, categorized as Estonian, Russian and other; and marital status, categorized as married, cohabiting and single . Births with unknown maternal socio-demographic characteristics were excluded before the analysis .The adverse pregnancy outcomes of interest were selected as preterm birth , very preterm birth , low birthweight , very low birthweight , small for gestational age , low Apgar score at 5 min (< 7), congenital anomalies , and admission to a neonatal intensive care unit (NICU). PTB was separated to iatrogenic PTB, defined as birth after induction of labor or pre-labor cesarean section, and to spontaneous PTB otherwise. Maternal pregnancy-related complications included pre-eclampsia , placenta previa (O44), placental abruption (O45), and cesarean section (planned or emergency). Occurrence of congenital anomalies, admission to a NICU, pre-eclampsia, placenta previa and placental abruption were marked in the birth notification form using tick boxes, where checked meant “yes” and not checked meant “no” or “unknown”. Gestational age was determined by the best clinical estimate . Deaths in the IVF and SC cohort were obtained via linkage with the national causes of death registry. The number of early neonatal deaths (two cases), late neonatal deaths (one case) and infant deaths after the neonatal period (none) in the IVF cohort was too small for quantitative analysis.The proportion of the IVF births in each category of maternal background characteristics and pregnancy outcomes was calculated. The relative risks of pregnancy-related complications and adverse pregnancy outcomes in the IVF cohort in comparison with the SC cohort was quantified by prevalence proportion ratios (RR) using modified Poisson regression models with a robust error variance . In addiStatistical analyses were performed using Stata 14 .We compared data on liveborn singletons to primiparas after IVF (1778 newborns) and SC pregnancies  , VPTB, LBW, VLBW, SGA, congenital anomalies and admission to a NICU among the IVF singletons compared with their SC counterparts. The risk of low Apgar score (< 7) had somewhat increased, but not statistically significant point estimate. IVF mothers were at a higher risk of pre-eclampsia, placental complications and cesarean section Table .Table 2RAdjustment for maternal age markedly attenuated the associations between IVF and adverse outcomes, and the risks for spontaneous PTB, VPTB, VLBW, SGA and pre-eclampsia lost their statistical significance. Further adjustments for study period, maternal education, ethnicity and marital status barely altered the risk estimates. The highest risks were seen for placenta previa , placental abruption  and planned cesarean section . The risks remained stable in the two study periods, with the exception of decreasing rates of planned cesarean section  and congenital anomalies . The risk of having at least one of the pregnancy-related complications  or at least one of the adverse pregnancy outcomes  was significantly higher in the IVF cohort  that are partly determined by the socio-demographic characteristics –39. The Comparing the results from the multiple Poisson regression models for each adverse condition, it appeared that adjustment for maternal age reduced the RRs considerably, indicating that age was a strong confounder of the association between IVF and outcome. Further adjustments for maternal education, ethnicity, marital status and study period had virtually no impact on the risk estimates. This result is consistent to that found by Räisänen et al.  where moThe average maternal age at first birth rose from 25 to 27 years in Estonia during 2005–2014 . It is w-conceived children [The major strength of our study is that it analyzes a relatively large dataset from the EMBR database with prior assessment of the validity of the IVF status registration. Using the whole cohort of liveborn singletons to primiparas in Estonia from 2005 to 2014 increased the study power. The EMBR provided a good opportunity to measure the risk of pregnancy-related complications and adverse pregnancy outcomes after IVF in relation to the maternal socio-demographic background. However, relying only on the birth registry data also has some weaknesses. The EMBR is not designed to contain neither details of the IVF treatment , causes of infertility, nor the complex of lifestyle factors that can influence reproductive health. For these reasons, more efficient control of confounding was not possible to do. Similarly, the EMBR database does not include data on specific congenital anomalies and some interesting topics like increased risk of congenital heart defects in IVFchildren  left untSince tick boxes are used on the birth notification form for the pregnancy-related complications, “no” and “unknown” answers cannot be separately identified. This possible underreporting of some outcomes is likely non-differential that reduces observed risk estimates. In addition, we were not able to exclude pregnancies after ovulation induction or intrauterine insemination from the comparison SC cohort, which could slightly underestimate the associations .The increased risk of pregnancy-related complications and adverse pregnancy outcomes was observed in the Estonian cohort of IVF singletons in comparison with the cohort of SC singletons. The relative risk estimates grew with maternal age, but were not influenced by the maternal education, ethnicity and marital status. To monitor the efficacy and safety of the used assisted reproductive technology, a specialized country-wide register should be created in Estonia.


The aim of this study was to discuss the advantages of GQI reconstruction in the imaging of nerve fibers at crossing regions. Compared with DTI, the paper also discussed the advantages of GQI in imaging principles.3-T MRI data from five normal participants were reconstructed using GQI and DTI. After adjusting the parameters, we compared the differences in reconstructed nerve fibers at the crossing regions between the two methods. To complete this study, we chose four obvious examples  and the anterior part of arcuate fasciculus) to illustrate.By reconstructing nerve fibers in three regions, we can find that crossing-area images of nerve fibers significantly differed between DTI and GQI reconstruction. Although crossing fibers could be clearly and completely visualized after GQI reconstruction, they showed artifacts, incompleteness, deletions, and fractures after DTI reconstruction. After GQI reconstruction, we can find that there were two or more nerve fibers in each voxel. However, only one nerve fiber was present in each voxel after DTI reconstruction.The imaging of crossing fibers is more complete, consistent, and accurate when they are reconstructed by GQI than when they are reconstructed by DTI. Thirty years ago, Crick and Jones said, “If you want to clarify the principles of brain activity, you must clearly present the anatomy of your brain.” . As earlFrom September 2017 to September 2018, we openly recruited 5 adult volunteers from the public  who had no relevant clinical disease, no history of genetic diseases in related family members. Volunteers underwent nuclear magnetic scanning at the First Affiliated Hospital of China Medical University.There are thousands of nerve fibers in a person’s brain. Although some nerve fibers intersect with other nerve fibers’ ending and a lot of fibers occupy this area, artifacts and other factors will affect the imaging of nerve fibers. All nerve fibers we have chosen have a clear anatomy, which make it less controversial and convincing Table . In this2, voxel size = 0.5 × 0.5 × 1.0 mm3, and acquisition time = 215 s.MRI data were acquired with a 3.0 T whole-body MRI scanner . Participants were required to remain in a fixed position in the scanner and were not allowed to move. We placed a foam pad on either side of the head to reduce head movement and used a cotton plug to reduce noise. The three-dimensional T1-weighted image obtained from the brain volume imaging (Bravo) sequence had the following imaging parameters: repetition time = 8.5 ms, echo time = 3.332 ms, inversion time = 450 ms, layer thickness = 1 mm, flip angle = 13°, excitation time = 1 ms, field of view = 240 × 240 mmb-value = 1000 s/m2, field of view = 240 × 240 mm2, voxel size = 1 × 1 × 2.4 mm3, number of excitations = 1, 42 consecutive slices, and acquisition time = 216 s.Diffusion imaging was obtained with a single-shot spin-echo planar imaging sequence with a 25-direction scan, a layer thickness of 2.4 mm, and no interlaminar gap. The coverage of the brain regions were as follows: repetition time = 8000 ms, echo time = 108 ms, flip angle = 90°, http://dsistudio.labsolver.org/) was used to reconstruct diffusion imaging data using the DTI and GQI methods. TRACKVIS software (http://trackvis.org/) was used to track the fibers, in which the commissural tracts are shown in red and the associated fibers are shown in green. The super-to-inferior projection fibers are shown in blue.DSI-STUDIO software . Taking these factors into account and to make our comparison more convincing, we first used the two reconstruction methods to track non-intersecting pyramidal tract fibers on one side of the brain. Knowing the performance in uncrossed areas allowed us to better explain the tracking differences in crossed areas.We chose the pyramidal tract as the region of interest (ROI) and selected it by hand. Because the final shape, fiber number, and other aspects of the tract analysis are affected by factors such as ROI placement, DTI index, FA threshold, GQI index, QA threshold, and total number of fibers in the brain, to objectively compare DTI and GQI for crossing-fiber tracking, we use the “non-cross-fiber correction” approach to rule out the effects of other unrelated factors.First, we loaded the Digital Imaging and Communications in Medicine DICOM data from each of the five patients into DSI Studio, renamed them, and opened them to create the “.src” file. Then we open the “.src” file to rebuild using either DTI or GQI to get the “.fib” data files. Finally, we opened the “.fib” files to track the fibers and get the DTI and GQI reconstructions. We fixed multiple parameters such as maximum angle (50°) and step size (1.2) for both DTI and GQI tracking. The pyramidal tract ROI was placed in the anterior third of the posterior limb of the internal capsule and in 3 out of the 5 mid-lateral bases of the cerebral pedunculus. The remaining factors that can affect the comparison between DTI and GQI fiber tracking are the FA and QA thresholds. We continuously adjusted the FA and QA thresholds when obtaining the DTI and GQI data so that the number of pyramidal fibers on the side of the trace was the same, the shapes were consistent, and the outcome matched the known anatomy. We found that when the FA threshold was 0.040 and the QA threshold was 0.025, the total number of fibers reconstructed by each group was 1500, and the groups had the same shape and conformed to the known anatomy. Then, under these same thresholds, we used DTI and GQI to track and reconstruct the fibers in the intracranial intersection, such as the optic chiasm, etc.One ROI is placed at the region of the optic chiasm, and the other is placed in the lateral geniculate body Fig. a. ROIs fThe ROI was placed at the level between the midbrain peduncles and the superior cerebellar peduncles in the axial phase. Specifically, the ROI included the junction of the two superior cerebellar peduncles at the level of the lower part of the midbrain, at the level of the cerebral peduncle, in the midbrain, and in front of the mesencephalic aqueduct Fig. c.We placed the seeding area on the superior temporal gyrus, middle temporal gyrus, and Inferior temporal gyrus, and then placed a mask ROI on the coronal view at the central posterior position Fig. d, e.We placed the ROI in the posterior limb of the internal capsule and tracked the fibers Fig. f.Using the ‘Select’ command on the median sagittal plane, we selected the entire corpus callosum as the ROI.ROI was placed in the Broca area, we selected nerve fibers on the path of the supplementary motor area manually.DSI-STUDIO software was used to perform GQI and DTI reconstruction on each patient’s raw data then we compared the results of the reconstructions. In general, the fiber structure based on DTI imaging of the crossing areas was missing, broken, incomplete, and had artifacts. However, the fibers visualized by GQI were relatively complete, accurate, and conformed to the anatomical structure. Additionally, the GQI imaging was relatively smooth. Here, we describe our most significant findings when applying DTI and GQI to reconstruct the nerve fibers Table .Table 2CWe performed the FA maps at the level of the superior cerebellar peduncles. It can be seen that although only a single bundle of fibers can be traced in a voxel after DTI reconstruction Fig. a, two orReconstructions of the optic chiasm fibers can be seen in Fig. After reconstruction, according to the anatomy of the superior cerebellar peduncle, we labeled the left and right axons in different colors to observe the fibers in the crossing area. The nerve fibers running on the right side are shown in blue and those on the left side are shown in red Fig. . We presWe performed GQI and DTI reconstruction on the pyramidal tract, arcuate bundle, and corpus callosum of the five participants. The corpus callosum is shown in blue, the pyramidal tract is shown in green, and the arcuate fasciculus is shown in red Fig. . We focuAfter reconstruction, we can get two different results in two reconstruction methods. Red shows the movement of the anterior part of arcuate fasciculus, blue shows the movement of the supplementary motor area (SMA) Fig. . We presThere are thousands of nerve fibers in the human brain, which can be divided into two groups based on whether they cross other fibers or not. This paper focuses on the crossing fibers present in the brain. There are five major fiber intersections in the brain, including the optic nerve, the superior cerebellar peduncle, the pyramidal tract, the corpus callosum, and the arcuate fasciculus. In clinical cases, patient data is often reconstructed using DTI. However, our results clearly show that DTI imaging at fiber intersections is far from perfect. Because DTI was developed from diffusion-weighted imaging (DWI) , it usesWe present our results applying GQI to investigate the structure of the normal human brain. GQI represents a significant improvement in MR-based fiber tracking techniques. The resolution of the crossing problems is illustrated here with the accurate replication of known neuroanatomical features such as the optic chiasm, the superior cerebellar peduncles, the pyramidal tract, the corpus callosum, and the arcuate fasciculus.Wang et al. used GQI and DTI reconstruction in 5 patients with brain tumors . The patIn this study, we confirmed that GQI can visualize nerve fibers in crossing areas more completely and continuously than DTI by comparing reconstructions of four intersections in five healthy volunteers. Moreover, GQI can better determine the location of intracranial nerve-fiber intersections. It is particularly important to determine the anatomical structure of some nerve fibers by defining the structure of nerve fibers in the cross region. When the anatomical structure of the nerve fibers is clear, we can judge the severity of the disease and the choice of surgical methods by preoperatively identifying the relationship between the tumor and brain structure. Looking at the optic chiasm and the crossing region of the superior cerebellar peduncles, it can be clearly seen that when DTI is used, there is a pseudo-crossing phenomenon in the crossing region, and there are artifacts of fiber fracture. In Crossing Region 3, imaging the pyramidal tract, the arcuate fasciculus, and the corpus callosum by GQI allowed all three intersections to be clearly located. In contrast, DTI could not determine whether there were any common intersections between the three fiber bundles in their respective paths. This study used these four aspects to confirm the superiority of GQI imaging in fiber-intersection regions. Although DTI is widely used in clinic, the advantages of GQI are clearly shown in this article. Therefore, we believe that GQI can better display the fibers in intracranial intersections and is a promising technique for disease assessment, especially when it occurs in the vicinity of fiber- crossing regions.Although GQI is better than DTI at quantifying and displaying fibers in the crossing areas, there are still some obvious limitations in this reconstruction method. These limitations are found in almost all MRI methods. First, the process of track reconstruction is determined by researchers and the reconstruction result is closely related to FA value, QA value, angle threshold, slice thickness, and sample number . becauseThis study was also limited by the type of nerve fibers being tracked and the location and extent of the intersections. First, the numbers of some types of fibers were relatively small, which led to an even fewer number of fibers in the crossing areas. Second, the crossing areas for many nerve fibers are obviously larger than those of others. Therefore, in the process of ROI selection, whether the ROI can be accurately set determines the accuracy of the results. Finally, fibers different among people to some extent, which leads to deviations in the tracking process. For further research, more samples are required to confirm the ability of GQI to image nerve fibers in all crossing regions of the brain.The GQI-reconstruction method is still new, and there are many limitations in its ability to visualize nerve fibers in crossing areas. However, compared with other reconstruction methods such as DTI, GQI performs more accurately, and its advantages are quite obvious. As the fiber paths were clear, this is a positive sign that further studies should be made that increase the sample size and definitively show the advantages of GQI. If this can be achieved, the scope of GQI application will increase and GQI will likely become an auxiliary tool for neurosurgery in the future.


The associations of individual antiepileptic drugs (AEDs) with pregnancy duration and size at birth, and potential dose relations, are not well characterized.This cohort study used nationwide Swedish register data (1996–2013). Adjusting for smoking, epilepsy and other AED indications, we used linear and quantile regression to explore associations with pregnancy duration, and birth weight, length, and head circumference . We used logistic regression for preterm delivery, small for gestational age, and microcephaly. Lamotrigine was the reference drug.6,720 infants were exposed to AEDs in utero; AED exposure increased over the study period. Relative to lamotrigine-exposed infants, carbamazepine-exposed infants were born, on average, 1.3 days earlier ; were 0.1 standard deviations (SDs) lighter (-0.1 [-0.2 to 0.0]); and had a head circumference that was 0.2 SDs smaller (-0.2 [-0.3 to -0.1]). Pregabalin-exposed infants were born, on average, 1.1 days earlier (-1.1 [-3.0 to 0.8]); were 0.1 SDs lighter (-0.1 [-0.3 to 0.0]); and had the same head circumference as lamotrigine-exposed infants. Levetiracetam-exposed infants were born, on average, 0.5 days earlier (-0.5 [-2.6 to 1.6]); were 0.1 SDs lighter (-0.1 [-0.3 to 0.0]); and had a head circumference 0.1 SDs smaller (-0.1 [-0.3 to 0.1]). Valproic acid–exposed infants had, on average, the same duration of gestation and birth weight z-score as lamotrigine-exposed infants, but had a head circumference 0.2 SDs smaller (-0.2 [-0.2 to -0.1]). Associations between carbamazepine exposure and pregnancy duration and between valproic acid exposure and pregnancy duration and birth weight z-score were more negative at the left than at the right tails of the outcome distributions. Effect-measure modification and dose-response relations were noted for some of the associations.Relative to lamotrigine, valproic acid and carbamazepine were associated with smaller head circumference. Epilepsy and antiepileptic drugs (AEDs) have been associated with adverse pregnancy, fetal, and neonatal outcomes . AEDs diA meta-analysis has shown elevated point estimates for the association of AEDs, as a group, with shortened pregnancies and reduced birth size , but comFurthermore, previous research has assessed associations with dichotomized endpoints or associations using only the mean of the continuous distributions .The Swedish Medical Birth Register  collectsThe study population included all women with records for AEDs in pregnancy who delivered a live infant with gestational age of 24 to 42 completed weeks in 1996–2013 and their newborns. Infants born from women who immigrated less than 12 months before pregnancy and infants with chromosomal abnormalities were excluded . Infants with congenital malformations and no chromosomal abnormalities and infants from multiple pregnancies were included. All eligible infants per woman were included.We report on the five AEDs that were most commonly used in pregnancy in the last year of our study period: carbamazepine, valproic acid, pregabalin, levetiracetam, and lamotrigine. In Europe, carbamazepine is indicated for the treatment of epilepsy and pain of trigeminal neuralgia and for the prevention of manic-depressive psychosis in patients with bipolar disorder . ValproiWe defined three exposure windows for analysis: any time in pregnancy, first trimester (regardless of whether treatment was later discontinued), and first and second/third trimesters (“continuers”). To create the exposure variables, information on first-trimester exposure was obtained from prescriptions dispensed between the first day of the last menstrual period and gestational day 89 and from self-report in the first prenatal visit in women who started prenatal care by gestational week 15. Information on second-/third-trimester exposure was obtained from prescriptions dispensed between day 90 and the day before delivery, from self-reports in the first prenatal visit in women who started prenatal care after gestational week 15, and from self-reports in subsequent prenatal visits . Because of incomplete capture of self-reports after the first prenatal visit, exposure in continuers was defined only for the period for which dispensing data were available (deliveries in 2006–2013). Women and infants exposed to more than one AED were considered to be exposed to each of them.Dose was derived from dispensed prescriptions (deliveries in 2006–2013). For each prescription, dose was calculated by multiplying the number of packs dispensed by the number of DDDs per pack and by the number of milligrams in a DDD . The meaWe extracted medical and obstetric information from the national health registers, which derive their information from prenatal care records, hospitalization records, outpatient specialist care records, and dispensed prescriptions. Codes, source of data, timing of ascertainment, categorization, and other details for medical and other characteristics are presented in Study endpoints were duration of pregnancy, preterm delivery, birth weight, small for gestational age (SGA), length at birth, head circumference at birth, and microcephaly, all ascertained from the Medical Birth Register. Duration of pregnancy is predominantly based on ultrasound estimation  and is rIn the main analysis, continuous endpoints were analyzed using linear regression and quantile regression for the 10th, 50th, and 90th percentiles . We prodThe Regional Ethical Review Board in Stockholm, Sweden, approved the linkage of registers to perform this type of study (DNR 2013/862-31/5). This study was judged to be exempt from review by the RTI International institutional review board.As secondary and sensitivity analyses, to better understand the influence of the underlying maternal health problem being treated, we repeated the main analysis in mothers with a diagnosis of epilepsy or chronic pain. We also explored the influence of monotherapy versus polytherapy . To address potential exposure misclassification and biases related to missing data, we conducted analyses on women with definite exposure (women in whom AED use from self-reports and dispensed prescriptions were consistent) and a complete case analysis. Addressing whether associations might be driven by in-utero crowding or malformations, we repeated analyses in singletons with no major congenital malformations. We repeated the analyses in the first pregnancy or infant per woman to gain understanding on any statistical effect free from the correlation among siblings. We also explored associations separately in female and male infants. We explored effect-measure modification separately by smoking and use of selective serotonin reuptake inhibitors (SSRIs) in pregnancy in linear regression analyses by incorporating an appropriate interaction term into the regression models.In dose analyses, we compared the top tertile of mean daily dose with the bottom tertile (which served as the reference) for each individual AED, using linear regression. All models were adjusted as in the main analysis, and the weighted copy method was used for binary endpoints.We present results from a subset of analyses in the body of this paper; others, including analyses on birth weight, length, and head circumference as recorded , are included in The study population comprised 6,720 infants born to 5,112 women. Antiepileptic drug use in pregnancy increased from 181 exposed infants in 1996 to 607 in 2013 . In 2013Carbamazepine use decreased over the study period from 63% of AED-exposed infants in 1996 to 16% in 2013 ; mothersWe observed a pattern of slightly shorter pregnancies with linear regression models  and smaller infants after exposure to carbamazepine, relative to lamotrigine, with an asymmetrical effect in which the head circumference z-score was somewhat more affected (-0.2 [-0.3 to -0.1] SDs) than birth weight or birth length z-scores (both at -0.1 [-0.2 to 0] SDs) . AssociaDespite first appearing in 2006, pregabalin was the third most commonly used AED in this cohort in 2013 (16% of infants). Pregabalin users differed from users of other AEDs: pregabalin users were younger, had fewer years of education, lived less frequently with the infant’s father, and were more likely to be obese or smokers. Chronic pain was common among mothers of pregabalin-exposed infants , as were psychiatric conditions comprising psychoses, panic attacks, and other conditions , which was more notable in women with a diagnosis of epilepsy (-5.6 [-10.7 to -0.4] days on average) . Birth wFirst appearing in this cohort in 2002, levetiracetam use increased to be the fourth most commonly used AED in 2013 , birth weight was 0.1 SDs lighter (-0.1 [-0.3 to 0.0] SD), length was similar (0.0 [-0.1 to 0.1] SDs), and head circumference was 0.1 SD smaller (-0.1 [-0.3 to 0.1] SD) in pregnancies and infants exposed to levetiracetam than in those exposed to lamotrigine . In womeValproic acid exposure decreased from 18% of infants in 1996 to 8% in 2013 . CommonlOn average, valproic acid–exposed pregnancies had a duration similar to lamotrigine-exposed pregnancies (0 [-1.2 to 1.2] days), and infants were born with the same weight for gestational age (0 [-0.1 to 0] SDs) . HoweverLamotrigine use in pregnancy increased over the study period from 6% in 1996 to 47% in 2013 . MothersIn dose-response analyses, pregnancies exposed to high doses were, on average, 1.8 days shorter (-1.8 [-3.8 to 0.2]) than those exposed to low doses; the OR for preterm birth was 1.3 (0.7 to 2.2) . We did To put results on individual AEDs in perspective, we considered the size of the point estimates for other variables obtained from the main analysis. In all linear regression analyses for exposure at any time in pregnancy, the estimated effect of smoking was more negative than the estimated effect for all study AEDs on all study outcomes , which were generally milder than those observed for smoking or diabetes. Below, we contextualize our findings within what was previously known about the associations between the study AEDs and size at birth, congenital malformations and cognitive outcomes.On the basis of mean results from the main analysis for AED exposure at any time in pregnancy, carbamazepine-exposed infants were born 1 day earlier, were 0.1 SDs lighter and shorter, and had a head circumference that was 0.2 SDs smaller for their gestational age than infants exposed to lamotrigine; estimated effects were dose dependent. For carbamazepine versus lamotrigine in monotherapy, our literature search identified a relative risk for SGA of 1.3 (1.0 to 1.7)  and an OOn the basis of these reports, fetal head size measurements in pregnant women who use carbamazepine should be taken into consideration in planning future maternal and infant care. Lower doses appear to be preferable with regard to several offspring outcomes.We observed that pregabalin-exposed infants were born, on average, 1 day earlier; were 0.1 SDs lighter and shorter; and had similar head circumference for their gestational age than infants exposed to lamotrigine; no clear dose effects were seen. Because pregabalin is a relatively new AED, the literature on its safety in pregnancy is limited. Our literature search identified one study that reported elevated risk, with wide confidence intervals, for preterm delivery and SGA based on a small number of pregnancies exposed to pregabalin compared to unexposed pregnancies , 46. ItsIn our study, levetiracetam-exposed infants were born, on average, 0.5 days earlier; were 0.1 SDs lighter, with similar length; and were 0.1 SDs smaller in head circumference for their gestational age than those exposed to lamotrigine. One study identified in our literature search reported that the relative risk for the association between levetiracetam versus lamotrigine monotherapy and SGA was 1.3 (1.0 to 1.7) , which cIn our study, valproic acid–exposed infants had, on average, the same duration of gestation and birth weight for gestational age but were 0.2 SDs smaller in head circumference for gestational age than infants exposed to lamotrigine. Null mean associations masked opposite results in the two tails of the distributions of pregnancy duration and birth weight z-scores. Outcomes were worse in infants exposed to valproate in polytherapy in pregnancy, which has also been reported for congenital malformations . Our litRecommendations restricting the use of valproic acid in pregnancy are already in place , and ourThis study assessed the safety of lamotrigine, used as the reference for drug-to-drug comparisons, in dose analyses. We observed an association between high doses of lamotrigine and shorter pregnancies (1.8 days on average). In comparisons of women exposed to lamotrigine with those unexposed, published studies estimated null or adverse effects on pregnancy duration and birth weight , 20, 23,We treated all pregnancies as independent observations because statistical models incorporating within-woman correlation would not converge; results from a sensitivity analysis including only the first infant per woman  generallThis is an observational study that used existing data sources, with the strengths and limitations of this type of study. Limitations include that we cannot be certain that a woman used the medications that she was dispensed or certain of the timing of the use of the medication, both of which can result in misclassification of exposure. Diagnoses, including the outcomes, were not confirmed or validated for this study, which could result in misclassification of confounders and outcomes. A review of validation studies reported positive predictive values above 80% and often above 90% for a wide range of discharge diagnoses, including psychiatric and neurologic diagnoses . DespiteStrengths of the study design include the fact that data are collected prospectively as patients seek and receive health care, as well as our ability to incorporate exposure from both self-reports and dispensed prescriptions. Results from analyses that defined exposure based on concordant self-reports and dispensed prescriptions are consistent with the main analysis. We were able to adjust for multiple AED indications or uses and to explore associations in the tails of study outcomes using quantile regression, a method not often used in studies on drug safety. We thus identified that a zero association at the mean  can mask associations at the tails of the outcome distribution, as was seen in this study for valproic acid, and duration of pregnancy and birth weight z-score using quantile regression. Another strength of this study is our ability to define our endpoints as z-scores, which we preferred because z-scores enable assessing size independently of any effect on pregnancy duration. Because other researchers may be interested in results on birth weight, length, and head circumference without this transformation, we included those results in We observed different estimated effects on pregnancies with female and male fetuses for some associations, without a clear pattern. While these may reflect true effects of AEDs, they may also reflect differential fetal survival by sex perhaps in relation to sex-specific congenital malformations . Table 1The body of evidence on the associations between in-utero exposure to AEDs and maternal, pregnancy, fetal, and infant outcomes argue against combining all AEDs into a single group for safety pregnancy research. The relative prevalence of AED use in pregnancy has evolved over time, and drugs have different safety profiles, making results on the combined AEDs not comparable from one study to another and not reflective of the risk of any specific AED.We observed that commonly used AEDs have distinct safety profiles regarding duration of pregnancy and size at birth. In comparison with lamotrigine, valproic acid and carbamazepine had a more negative association with head circumference than other study AEDs, suggesting that fetal head size in exposed pregnancies should be monitored. To put our results in perspective, we note that the adverse effects of AEDs on the outcomes studied were generally smaller than those of smoking. Although no mean effect was observed, associations between valproic acid and the endpoints duration of pregnancy and birth weight for gestational age in the left tail of the distributions were toward shorter pregnancies and smaller infants.S1 File(DOCX)Click here for additional data file.S2 File(DOCX)Click here for additional data file.S3 File(DOCX)Click here for additional data file.