Research focusing on paternal mental health is limited, especially regarding the impact of the experience of poor mental health in the perinatal period. For example, little is known about the experiences of fathers who witness their partner’s traumatic birth and the subsequent impact on their mental health. Therefore, the aim of this study was to explore fathers’ experiences of witnessing a traumatic birth, how these experiences impacted their wellbeing, and what support they received during and following the traumatic birth.Sixty-one fathers were recruited via targeted social media to complete an anonymous online qualitative questionnaire regarding their birth trauma experience. Eligible participants were fathers aged eighteen or over, resided in the UK and had witnessed their partner’s traumatic birth (that did not result in loss of life). Thematic analysis was used to analyse the questionnaire data.Three main themes were identified: ‘fathers’ understanding of the experience’ ; ‘life after birth trauma’ ; and ‘the support fathers received vs what they wanted’ .Fathers reported that witnessing their partner’s traumatic birth had a significant impact on them. They felt this affected their mental health and relationships long into the postnatal period. However, there is no nationally recognised support in place for fathers to use as a result of their experiences. The participants attributed this to being perceived as less important than women in the postnatal period, and maternity services’ perceptions of the father more generally. Implications include ensuring support is available for both the mother and father following a traumatic birth, with additional staff training geared towards the father’s role. Concern for maternal mental health has risen in recent years, as shown by the expansion in research and public interest around the causes and impact of poor maternal mental health on the mother and her family. The mother’s mental health during pregnancy and up to a year postnatally is crucial not just to her wellbeing, but also the mental health of her partner . AdditioIn a meta-ethnographic study into mothers’ experiences of birth trauma, Elmir, Schmied, Wilkes and Jackson  identifiLimited research has addressed the impact of traumatic birth on fathers. Etheridge and Slade  in a quaIn a cross-sectional study of fathers who witnessed ‘normal’ births on maternity wards in Belgium, Eggermont, Beeckman, Van Hecke, Delbaere and Verhaeghe  found thThere is limited research around the experiences of fathers regarding pregnancy and childbirth, likely due to their historical nonattendance in the delivery room. King  noted thHowever, despite fathers attendance at births becoming more common, evidence suggests that men still do not feel welcomed by perinatal health professionals, In an analysis of 62 studies of perceptions about Swedish healthcare professionals from 2000 to 2015, Wells  found thWells  emphasisThe present study aimed to explore the following questions: what are the experiences of fathers who witnessed their partner’s traumatic birth; how do these experiences impact those fathers’ wellbeing; and what support did they receive during and following these experiences?A purposive sample of 61 participants was recruited. Inclusion criteria included being a UK-based father aged 18 or over and having witnessed their partner’s traumatic birth (single or multiple birth). The study was open to all fathers who perceived the experience as traumatic, rather than setting specific criteria regarding the intensity of that trauma. Exclusion criteria included: if the birth trauma experience was over ten years previously ; or if the participant’s partner and/or child had died as a result of the experience .Potential participants were invited via social media advertisements  targeting mental health support groups and national perinatal mental health charities. Those adverts included a link to online portal which described the study and invited participation. This recruitment method meant participants were able to access the necessary support they may have required during (and following) their completion of the study from those organisations. As a result, a wider audience could be reached. Participation was voluntary and anonymous.Nine participants were excluded because their experiences took place more than 10 years ago or because they were from outside of the UK. Flow of participants during the study is described in Fig. The study was a qualitative questionnaire study. This is a well-established method for gathering information about sensitive topics, as it maintains participant anonymity .An online (anonymous) qualitative questionnaire was created using Qualtrics™ to explore participants’ experiences and feelings of their partner’s traumatic birth. Given the nature of this subject, the questions posed were assessed for relevance and sensitivity by experts at Make Birth Better, a highly respected UK birth trauma network comprising perinatal health  professionals. These experts were also a source for signposting participants for support if required. The questionnaire consisted of 20 open-ended questions and took up to an hour to complete. It focused on pregnancy , the birth experience  and postnatal experiences , as well as the levels of support the participants received at each stage. The questionnaire is provided as supplementary online material.Make Birth Better (https://www.makebirthbetter.org/). Respondents were then invited to indicate whether they consented to participate. While consent is usually assumed when participants answer questions in anonymous surveys, this was specifically sought to ensure that participants fully understood the sensitivity of the study. Once consent was given, participants were presented with the study questions. Participants were also reminded that they could discontinue if they found the questionnaire distressing. After completing the questionnaire, participants were presented with debriefing information, through the online portal, further highlighting sources of support and providing more detail about the study. Traumatic birth was defined as “physical and emotional suffering during birth that resulted from either complications, physical injury or negative reactions during the birthing experience”.Access to an online portal for the study was distributed on social media through an anonymous link (as described earlier). The entire process of providing information about the study, giving consent, participation and debriefing was undertaken through this online portal. Initially, potential participants were presented with information, which explained the purpose of the study, what participation would entail and the inclusion criteria. Contact details of the study team were provided in case participants required further information. Details were provided regarding where to seek support if this was required. The main source of support was Thematic analysis was used in order to allow for the complexity of the data as individual and collective accounts. The six stages of thematic analysis were followed . The firA reflexive diary was completed through all stages of analysis to identify possible misconstructions of themes and create transparency in analysis .The study was approved by Bournemouth University (BU), Faculty of Science and Technology, Ethics Committee (BU Ethics ID 12939). The study focused on sensitive topics that included birth trauma and mental health, which many of the participants may not have spoken about before. Therefore, participants’ right to withdraw from the study was highlighted. Participants were told to write only what they were comfortable with sharing to reduce potential distress. Participants were also encouraged to access support they already receive or to seek further support for their experiences. The responses were kept anonymous to protect confidentiality and to give participants the chance to speak freely about their experiences.Participants came from all regions of the UK. Participant characteristics are reported in Table The data analysed emphasised the situations that contributed to or protected from the birth trauma experience. Three main themes were identified: ‘fathers’ understanding of the experience’; ‘life after birth trauma’; and ‘the support fathers received vs what they wanted’. The flow of themes is demonstrated in Fig. This first theme identifies the participants’ experiences during the birth of their child. This includes what participants believed contributed to their trauma experience as well as potential protective factors. This theme had several sub-themes: nothing can really prepare you for it; merely a passenger; not about me; and support from staff.Participants felt that they were not adequately prepared for the experience. They perceived preparation as information gained from antenatal classes and from healthcare professionals during the experience. Information was either not given or not provided to a standard of satisfaction. For example, one participant said “At no point was there any explanation to either my partner or myself to calm the situation.” (P16).Information given at antenatal classes also failed to prepare fathers for traumatic birth. Participants felt they focused more on standard deliveries and lacked detailed coverage of potential negative situations. For example, “They briefed us on the basic pain relief options for labour and the basics of a birth plan. These seem almost laughable in hindsight.” (P2), and “The antenatal classes are too positive and preparation for all eventualities was poor.” (P20).Participants explained that they were unable to understand what was going on around them due to lack of information or time to explain during the emergency. As a result, some reflected that the experience of traumatic birth may not be something you can prepare for: “To be honest, I don’t think anything could have prepared me for what happened.” (P3).The participants knew when something was wrong during the birth experience, but they were not involved in decision making or in relaying information. Often, they were also left alone which contributed to the trauma, as one participant described “When our son was taken away there was no one to ask what had happened to him for quite a while.” (P1).Overall, participants believed that they had not been properly made aware or given the opportunity to make themselves aware and prepared for the likelihood of a complicated birth, from antenatal classes and from staff during the experience. However, they recognised that it is not always possible to be prepared.A lack of control during the complicated birth experience was described as a major contributor to the trauma. Participants either felt they never had control, or control was taken away from them by the situation and/or staff. For example, one participant explained “I wasn’t involved. Merely a passenger.” (P60), and another said the lack of control made him feel as if: “I had lost all control of the situation, which scared me to death.” (P10).If any control was reported during the experience, it was from trying to help their partner, as one participant mentioned: “I did not feel in control at all, but I did feel very involved in looking after my partner’s welfare.” (P40).Fathers who reflected more positively believed they had some level of control , which could be considered a protective factor against later developing mental health problems. While they spoke about having little control and finding it traumatic, they also noted how they probably did not want any control in that situation: “I knew I had no control and I did not feel involved. I didn’t think it appropriate that I was involved to be honest.” (P4); “Felt I had no control at all as there was nothing I could do to fix the situation just had to wait for the doctors to sort things out.” (P52).In conclusion, this theme details how control featured in fathers’ experiences, how they attempted to create control by looking after the interests of their partner, while also exploring how having little control in this situation appeared to be most appropriate for fathers.This theme explores the roles fathers believed they had during the birth experience and their treatment as a result of being male. During the pregnancy and birth experience, participants suggested that being male may have impacted their treatment by professionals, family and friends, based on societal expectations around birth and the role men play in general. Participants mentioned not being listened to and their questions not being answered.Participant 7 described how he felt regarding his role during the birth: “I felt mostly like a spare wheel to be kept out of the way.” (P7) Participants often felt that their presence in the experience was not acknowledged: “No. I’m the male. My presence was often not acknowledged let alone my feelings.” “The midwives weren’t very helpful after the birth as my wife developed depression. They ignored my concerns.” (P9) and; “However, not being made to feel like the enemy, a useless caveman that has thoughtlessly impregnated this innocent girl, would be a start.” (P13).When fathers felt acknowledged, it was only as they were there to support their partners: “I remember feeling very emotional and almost breaking down when they wheeled her off, but quickly pulled myself together as I knew she still needed me to be strong and upbeat.” (P51).This treatment controlled the fathers’ views of themselves and sometimes prevented them from accessing and seeking help when needed, in some cases leading to further problems long after the birth. Participant 47 explained: “I never would of brought it up to anyone even my wife how could I possibly tell her how traumatised I was when she’s the person that had the ordeal of having a baby.” (P47).Overall, participants’ experiences of being male in this female dominated experience meant that they felt unimportant (like a spare wheel), with their role in supporting their partner. As a result, they felt they could not explore or discuss their thoughts and feelings during and after the experience.. This was also reflected by participant 51: “While, what seemed like muted panic or urgency was erupting around my wife, he [surgeon] calmly explained what was going on and what would happen. Not much of what he said went in, but his calmness was infectious.”. This behaviour from staff helped fathers to feel calmer about the situation and therefore more relaxed.When participants reported that staff were calm and communicated with the couple, this appeared to ease the father and act as a protective factor in their overall view of the experience and how they felt after the birth, as described by participant 26: “as the midwives and consultants were extremely calm, clear and communicated every stage with us.”Unfortunately, this level of support was not always possible, in some cases due to system issues:“Unfortunately, the shift changes right before things escalated, so we didn’t have much opportunity to build a rapport with the new midwife.” (P2).This theme explores the participants’ postnatal experiences, including expectations of and from fathers, their mental health and the way in which their birth experiences impacted their relationships. Sub-themes include perceptions of manhood after birth; inability to be happy; and impact on relationships.This sub-theme explores changes in the participants’ roles going into fatherhood and how this impacted their health. Some fathers found that as a result of the traumatic birth, they became the primary caregiver for their child and sometimes their partner, as this quote shows: “We didn’t expect the difficulties we would face with my wife’s recovery. She ended up with a few issues and I spent a bit of time off work looking after her.” (P12) Participant 13 also reflected on his experience of becoming the primary caregiver for his child and partner that eventually impacted his work role and friendships: “The trauma of my son’s birth put me immediately into what felt like sole-responsibility for my entire family 24/7, ultimately excluded me from colleagues and friends and I struggled to cope.” (P13).The trauma also impacted the participants’ expectations of fatherhood, where they felt that they did not meet the standards or expectations that society had given them. For example, they did not experience an instant bond with their child and in turn felt guilt and shame about themselves as fathers:“I expected to feel an instant bond with the baby and I didn’t. I came to have a very strong bond with my daughter and I think not getting it initially was a combination of an unrealistic expectation of a romanticised version of what it is to have a child and the situation I was in. Had my wife been fine I wouldn’t have felt so conflicted and it may have come easier at the start.” (P57).Participants also explored their role of being a ‘man’ and what their experiences meant in a female dominated experience. This also impacted how they coped with their experiences postnatally. They saw being a ‘man’ as being quiet and avoiding discussion of their experiences: “A man’s role in the birth is nothing to talk about really. Be quiet and man up, etc,” (P11). This was partly because they were aware of their partner’s trauma and believed it was greater than their own: “I chose not to think about it for some time; as a man, it does feel churlish to go on about your trauma when the female involved has this harrowing experience happening within her own body.” (P13).However, participants also acknowledged the stigma around discussing emotions with other men, and not wanting to burden their friends, preventing them from speaking up and seeking support. For example: “As a lad it’s not easy to talk to male mates. I’m sure they’d listen but I don’t want to be a burden or a downer.” (P31).In conclusion, this theme identifies how preconceived expectations of birth and the postnatal experience for men as men and fathers can contribute to feelings of unimportance around their own experiences. This in turn, leads to less support seeking and reinforces these expectations.Participants described how the postnatal period affected their daily lives and how the trauma still affected them in the present day. Traumatic births negatively affected their mental health during the postnatal period, leading to difficulties coping with everyday functioning: “Upset, distressed and unable to cope very well. It was a feeling about the fragility of life during the birth and the overwhelming nature of the birth and the subsequent days.” (P14) Some participants experienced the development of mental illness in some cases: “… develop [ed] OCD within weeks of the birth. That might have been about the life changes that becoming a father involved but it might be rooted in that birth experience too.” (P1)..” (P60).Most participants reported feelings and experiences during and after the birth trauma that can be linked to symptoms of PTSD. Participant 47 was diagnosed with PTSD and described flashbacks, triggers and avoidance: “I had flashbacks that seemed so real it was like I was there again, I deal with it better now but going back to the maternity wing of that hospital caused great anxiety, walking past the theatre doors etc the sound of a heart rate monitor sets me off even when it’s on the TV, I can’t watch things like Call the Midwife or One Born Every Minute or anything involving childbirth on the TV either.” (P47). Participant 60 also discussed flashbacks that were directly linked to the birth experience: “I regularly have flashbacks and see the number 61 on the heart rate monitor in my mindOverall, participants described a range of mental health problems in the days and weeks following the birth, with some incidences leading to mental health disorders, which continued to impact their lives up to the present day.This theme explores the impact the traumatic birth had on the fathers’ important relationships with their partner, children and friends. Most participants reported that the experiences brought them closer to their partner. Going through such a traumatic experience, including the fear that they could have lost their partners, created a stronger bond between couples: “Maybe there’s an extra layer to us as we survived such a difficult experience and we know that whatever happens in life we’re unlikely to encounter anything as testing.” (P3); “It’s made us closer because I know I could have lost her.” (P8).However, many fathers discussed struggling to form a bond with their child (and feeling guilty): “I wanted to be with my wife but I felt guilty that I didn’t want to be with the baby. When I was with the baby I didn’t feel the level of love that everyone says you do and I felt guilty about that. I was just really confused and frightened.” (P57) Participants also expressed having fears around more children. “Only in the way that I’m reluctant to have sex in case she accidentally gets pregnant.” (P51) These feelings also manifested as difficulty celebrating their children’s birthdays, and fears about emotional intimacy with their partners, which impacted their relationships long term: “We don’t talk about what went on that day, each birthday is very difficult and not a celebration.” (P16).In some cases, participants also felt this negatively impacted their relationships with friends, due to others lacking comprehension of the situation. As one participant explains: “I tried to talk to my friends, but most of them have no idea of children, or what it involves, so it’s hard for them to relate.” (P10).Overall, negative birth experiences made the relationship with partners stronger in some cases. However, it also had a negative impact on partner relationships through affecting bonds with their children and leading to avoidance of physical and emotional intimacy. Relationships with those outside of the family were also negatively impacted in some cases, as friends did not share the same experiences and could not understand.This theme consists of the levels of support fathers felt they received either personally, as a couple or for their partner, in relation to what support they believed would have been beneficial. It is split into three sub-themes that explore different time periods of the experience: prenatal support; birth support; postnatal support.During the pregnancy, participants reported receiving a good level of support, where all concerns raised were answered: “As much support as was needed. The pregnancy was pretty good to be honest so we didn’t require any additional support but whenever we had questions then we got the answers.” (P11) However, they did note that antenatal classes were very much tailored towards mothers. For example, when participant 51 was asked about the support he received prenatally, he said “Personally, none. But my wife was well looked after and supported. However, I never felt left out or unwelcome.” (P51).However, in retrospect, participants felt antenatal classes only discussed normal births, which they felt created an idealised experience. Participants reported wanting antenatal classes to expand on the breadth and depth of the childbirth experience, to cover departures from the norm: “… in retrospect, I see these as “idealised“ birth training classes. Breathing exercises, birth pool options, stages of normal labour etc,” (P29) and “More information on what a birth plan could involve, and learning about how variable each pregnancy is, as any change from the norm made us quite nervous.” (P10).Furthermore, participants felt that ideally antenatal classes would include more information around being included as a father. For example, one participant felt that: “I should have been more included from the beginning. A mother and father should both complete questionnaires regarding depression and a father should be asked how he is feeling or if there is anything that he wants to ask or doesn’t understand. These questions are solely aimed at the expectant mother whilst a father has to butt in and speak during a conversation he is only there to witness.” (P21) Participants also explained the importance of peer support for partners during the prenatal period: “Peer to peer support from other fathers, an antenatal session for partners on supporting birth & the early days and information tailored to males .” (P55).Overall, fathers felt they could have been provided with more information and involved more in sessions such as antenatal classes during the prenatal period.“In the 70ish hours before the actual birth support levels went up and down.” (P1).Participants described the levels of support varying throughout the birth as generally less positive than prenatal support. For example: However, the fathers often reported that this was understandable due to the emergency situation. They were aware that the lack of support for them meant that their partners were being saved: “Emotionally/mentally, I remember receiving very little support. Can’t fault them too much though - they were busy saving my partner and baby!” (P30).Nevertheless, participants would have liked to be informed and involved throughout the birth. They felt that being involved would have made them feel more useful: “I would have liked to have had someone to stay with me or at least pop in regularly to see if I was okay and to tell me what was happening with my wife.” (P8) and “To be made to feel like a useful part, to be involved and kept updated on what was going on and why” (P58).In some cases, they felt that the lack of support received contributed to them labelling the experience as traumatic: “More support in making decisions regarding this [implications of delivery] – this was a major contributor to the trauma of our delivery.” (P2).This theme explored how a lack of support was perceived by participants as a contributor to their traumatic experience. Participants wanted to be involved in making decisions and wanted someone to support them but were aware of the need to focus on the mother.Participants discussed support received in the months after the birth, plus what they felt would have been beneficial. Many fathers felt there was minimal support for themselves or their partners: “We had some follow up care for our daughter and 2 discussions with doctors regarding the delivery and what went wrong. These were minimally informative.” (P2). Some participants sought professional help as a result: “I paid for private therapy. My wife had no follow up from her mental health team except a 20 min meeting alone with them …” (P4).Participants felt a chance to discuss their experiences and receive explanations after the event would have helped them make sense of the situation. As participant 2 explains: “More information from doctors about what happened to us – and an interview, possibly with administration or some other body to help us understand what happened and to give feedback – this we would not get unless we took the initiative to pursue such an opportunity. I think this kind of debriefing should be standard when things go outside the parameters of a normal delivery.” (P2) Many participants reported wanting support from other dads, which could be provided via support groups, even mental health support/therapy themselves: “Maybe I could have joined a group of dads to discuss.” (P42); “Advice from other dads.” (P56).However, participants acknowledged that men do not always seek help: When asked how much support he received, one father replied “Very little, but I could have sought more help, so I put no blame there.” (P30) Participants suggested that help could be explicitly directed and made easier to find in an attempt to break down barriers that prevent men from seeking help: “Perhaps it would of been nice to be told about the support rather than having to seek it.” (P43).This final theme described the lack of or minimal amount of support for fathers in the postnatal period. Fathers felt that support could be given in the form of debriefs, ‘dad groups’ and support being made explicit to encourage fathers to seek support when they needed it.The current study explored narratives of 61 fathers who had witnessed their partner’s traumatic birth. The themes that emerged reflected fathers’ experiences of traumatic birth, how these experiences impacted their mental health, and fathers’ feelings regarding support they received.Participants felt that nothing could really prepare them for a traumatic birth, echoing the findings of Harvey and Pattison , who expThe fathers in the current study reported feeling a loss of control, which they linked to being left out of decision-making and having limited access to information during the birth and saw this lack of control as a major contributor to their perceived trauma. Fathers who reflected more positively on their experiences noted that they had some control during this experience. A sense of control has been identified as being important for men in Western societies . This reFathers’ experiences with staff greatly influenced their perceived trauma. For example, more positive experiences with staff appeared to act as a protective factor against low mood postnatally. On the other hand, participants associated negative experiences with staff (such as not being listened to) as contributing to the traumatic experience. Fathers in the current study felt that being a man in the birth experience affected how healthcare professionals treated them, reinforcing that they should not be involved as this was a woman’s domain, in line with previous evidence regarding fathers’ negative experiences with perinatal healthcare staff, such as being treated as less important than mothers However, the reasons for fathers not being given the support they need during childbirth may relate to attitudes within Western societies, where gender roles demand that men should be strong and in control, not needing help with their problems . Women tOur study found that perceptions of masculinity limited fathers from talking about their experiences and may have prevented them from seeking help. Vogel et al.  reportedThe impact of traumatic birth had serious implications for some of the participants in the current study, with mental health issues such as depression, anxiety, postnatal stress, obsessive-compulsive disorder (OCD) and PTSD symptoms being described. Similar mental health difficulties and relationship problems for fathers following their traumatic experiences have been reported elsewhere –9. FatheFathers in the current study reported that they were often neither offered nor sought support after witnessing their partner’s birth trauma, and were not aware of what support was available. This may have been due to men taking longer than expected to realise they had a problem, and consequently experiencing delays in detection of health issues (as was found by Wilhelm ). Many fHealthcare professionals need to be aware of factors that may prevent fathers from seeking help and professionals from providing support, and be ready to direct the fathers to where they can receive help and support. The fathers in the study stated that they felt ill-prepared for the possibility of birth trauma, and poorly informed about potential impact (for their partner and themselves) following that experience. This implies that adequate information during the experience and aftercare from birth trauma is key. Possible improvements to clinical practice could include offering parents the opportunity to understand what happened in the birthing process and be directed to opportunities for support if needed. This could be provided by the voluntary and charity sector, focusing on interventions such as peer specialist help, online support groups, or targeted interventions such as postnatal PTSD therapy.Fathers in this study indicated that they felt excluded by postnatal health professionals , claiming that those services were focused mostly on the mothers. This suggests it is essential that healthcare professionals recognise fathers as primary parents, in line with mothers, so that they can receive the necessary support.Many fathers discussed how the traumatic birth impacted the bond with their child. Services need to be provided to help fathers develop that relationship. If further or more complicated issues are identified during the debrief, parents could be referred to specialist NHS interventions. Follow-up screening and referral needs to be ongoing, as trauma symptoms can sometimes be delayed for several months .The current study generated rich and broad data based on the narratives of 61 fathers reflecting on their experience of witnessing their partner’s traumatic birth. By preserving participant anonymity through online questionnaires, this study elicited detail that might otherwise have been withheld. This is especially important as the data showed how difficult men find it to discuss birth trauma. However, questionnaires may limit the extent to which additional information can be generated. It could be useful for future studies to consider interview techniques that maintain anonymity, such as online interviews in real time. Such interviews might permit further probing of important perceptions.By advertising this study online, it was possible to raise awareness about birth trauma and men’s mental health. However, the fact that participants were recruited via social media linked to mental health support and national perinatal mental health charities, suggests the participants had engaged with mental health support at least to some degree, and fathers who had not engaged with mental health support services were likely underrepresented. This issue might be overcome by engaging men who are part of other fatherhood groups, perhaps not necessarily related to mental health support.Also, all participants reported that they were married, suggesting a lack of engagement of unmarried fathers. Future studies could explore whether there any differences for outcomes based on marital status. Further, 140 participants started the questionnaire but did not finish answering the questions. It is possible that the length of the questionnaire may have been a barrier to participation. Equally, some participants may have found the questions too distressing to answer. Future studies could pilot a range of questions to ensure that they gather the information needed without causing undue distress.A further limitation is that the questionnaire was subject to recall bias. Participants, particularly if the traumatic birth occurred a long time ago, may not remember it accurately, or their memories may have become distorted over time. The current study excluded participants if the birth trauma occurred more than 10 years previously. Future studies may consider whether that period is still too long.Future studies could explore how fathers’ perceptions differ according to the severity of the birth trauma encountered by their partner. In this study, we were careful to define birth trauma’ as any experience that might be considered to be traumatic. However, situations where there has been a more obvious threat to the welfare of mother and child may present different outcomes to other stressful birth events. Such an examination could potentially highlight how different types of traumatic experience might trigger poor mental health outcomes. Studies could also directly compare normal and traumatic births in a single study. Future research could also formally assess the impact of traumatic birth on fathers’ mental health using appropriate psychometric instruments.Other studies may also benefit from comparing the birth trauma experiences of men and women together, in order to identify similarities and differences in traumatic experiences. Following on from Iles et al. , who expResearch into effective interventions or preventative measures for fathers and their families may be crucial to fully address this area of research. This includes developing a deeper understanding of the barriers that prevent men from seeking help, as well as why practitioners may not offer support to fathers. By encompassing all perspectives from a traumatic birth, a better understanding can be achieved, resulting in preventative action, or, where this is not possible, effective aftercare.Our findings suggest that traumatic births can have a profound impact on some fathers, which can ultimately negatively impact their relationship with their family and their own mental health. Many fathers in this study reported feeling unable to access support during and following a traumatic birth, which were related to perceptions of the birth and treatment by perinatal staff. Many fathers in this study spoke about the impact that the traumatic birth had on how well they bonded with their new child. Several recommendations for clinical practice merit consideration: more education is needed for perinatal health professionals about the role of the father in the perinatal period; strategies are needed to encourage fathers to seek help; screening needs to be put in place to identify fathers who are most at risk of poor mental health; and services need to be developed to ensure fathers receive appropriate support for their own mental health and help nurture the father-infant relationship.Additional file 1. Questions for Birth Trauma Questionnaire.


There is growing concern about the developmental outcome of infants exposed to HIV in utero. HIV-infected women are at greater risk of premature delivery which poses a further developmental risk factor.To determine whether there is a difference between the development of premature infants born at 28–37 weeks gestational age that are HIV exposed but uninfected (HEU) compared with HIV-unexposed uninfected infants (HUU).A cross-sectional study was conducted in a Johannesburg state hospital. Thirty HEU and 30 HUU infants, aged between 16 days and six months, were assessed using the Bayley Scales of Infant and Toddler Development III.p = 0.003) and motor (p = 0.037) subscales. Expressive language was more affected in the HUU infants (p = 0.001), and fine (p = 0.001) and gross motor (p = 0.03) were affected as well. HUU infants with neonatal complications such as meningitis (p = 0.02) and neonatal jaundice (NNJ) (p = 0.01) are more likely to present with language and motor delay.The two groups were well matched for gestational age and birth weight; however, more HUU infants presented with neonatal complications. HUU infants had lower developmental scores than HEU infants in the language (Meningitis and NNJ have more impact on infant development than in-utero HIV and ARV exposure.It is important for all premature infants to be screened regularly in order to diagnose developmental delays early so as to ensure early intervention and improved quality of life. Human immunodeficiency virus-positive women who are not on antiretrovirals (ARVs) may transmit the infection to their babies during the An estimated 15 million babies are born prematurely every year WHO, . The incPremature infants are at an increased risk for growth failure, cerebral palsy, developmental delay and mental retardation , intrauterine growth retardation, foetal death, neonatal mortality and respiratory complications  in South Africa. This clinic provides follow-up services for at-risk infants and includes those discharged from neonatal intensive care and those born prematurely.A sample of convenience was used and the mothers of consecutive infants who met the inclusion criteria were invited to participate. Infants were included if they had a gestational age of 28–37 weeks and presented at the clinic between 16 days and 6 months of corrected age. HIV-exposed uninfected and HUU infants were eligible for inclusion. Infants were not eligible for inclusion if maternal HIV status was not known or if the infant presented with clinically obvious congenital conditions such as spina bifida.A total of 60 infants (30 HEU and 30 HUU infants) met the inclusion criteria and their caregivers agreed to participate in the study. The sample size was calculated using the Bayley scales of Infant Development (BSID) III, 27 infants per group allowed for a power of 90% and a confidence interval of ± 4.63.Infants were assessed using the BSID III in a quiet room. The BSID is considered to be the gold standard for infant developmental assessment globally. It has sound, well-established psychometric properties. The intra-rater reliability coefficients are excellent for the cognitive scale (Intraclass Correlation Coefficient (ICC) = 0.92–0.99) and good to excellent for the language (ICC = 0.88–0.98) and motor scale (ICC = 0.85–0.98). The inter-rater reliability coefficients are good to excellent for the cognitive (ICC = 0.87–0.97) and language scale (ICC = 0.76–0.95) and good for the motor scale (ICC = 0.77–0.89) . Caregivers completed a demographic information form which took approximately 10 min and clinical history was obtained from the infant’s hospital file.Descriptive statistics were conducted to condense the raw data with regard to information on the development of HUU and HEU infants. Tests used were means, standard deviation (SD) and confidence intervals (CIs). The level of significance was set at 0.05.t-test as the groups are unrelated.Inferential statistics were used to determine the differences between HUU and HEU infants. Test used was independent Ethical clearance was obtained from the Human Research Ethics Committee  University of the Witwatersrand (clearance number: M160438). Caregivers of the infants provided informed consent to participate before any assessments were done.p = 0.98). There were 43 (71.67%) infants in the late preterm category (32–27 weeks), 17 (28.33%) infants in the very preterm category (28–32 weeks) and no infants in the extremely preterm category (< 28 weeks). The mean corrected age in the HIV-exposed group at the time of assessment was 2.26 months and in the unexposed group it was 2.9 months (p = 0.09). The majority of infants were born with an LBW (67%) and there was no significant difference between the two groups for birth weight categories (p = 0.50)  was 33.13 weeks (2.43) for the HEU group and 33.20 (2.57) weeks for the HUU group (.50) see .p = 0.02) was seen in the number of infants who had a history of meningitis, with more HUU infants affected. Sixty-seven per cent of infants in the HUU group compared with 37% in the HEU group had a history of neonatal jaundice (NNJ) (p = 0.01).The clinical history of the two groups was similar for most factors assessed see . A signip = 0.97). Language (p = 0.00) and motor (p = 0.04) composite scores showed a significant difference between the groups, with the HUU having lower developmental scores. All mean composite scores fell within 1 SD of the norm (The composite scores of the BSID III were compared. There was no significant difference in the means of the cognitive composite scores between groups (the norm .p = 0.00) in the HUU infants. Scaled scores of both fine motor (p = 0.00) and gross motor (p = 0.03) were significantly lower in the HUU infants  and were at risk for delay in all subscales  when compared with the HEU group.p = 0.00) and motor (p = 0.05) aspects of development.Because of the discrepancy in history of NNJ and meningitis between the two groups, these two factors warranted further investigation. The number of children in each group with meningitis was too low to be able to undertake further statistical analysis; however, the children with NNJ could be compared. Infants with a history of NNJ had significantly lower composite scores in the language . Birth weight has been shown to have a negative impact on development  in Botswana, there is still no negative neurodevelopmental outcome when assessed with the BSID III. They assessed 313 HEU infants and concluded that there was no negative neurodevelopmental impact on children when they are exposed to the HIV virus In our study, the HUU infants had lower developmental scores in expressive language as well as fine and gross motor subscales of the BSID III. This group had more neonatal complications such as meningitis and NNJ, and this seems to have had more of an effect on the infant’s central nervous system (CNS) than HIV exposure.Human immunodeficiency virus-exposed uninfected infants are likely to be born prematurely because of the ARVs during pregnancy in order for Prevention of Mother to Child Transmission (PMTCT) (Nlend et al. Meningitis is a bacterial infection of the CNS and has the highest incidence in the neonatal period. The risk factors include prematurity, LBW, chorioamnionitis, prolonged rupture of membrane, premature rupture of membrane, low socio-economic status, need for resuscitation, prolonged hospitalisation and male infants (Heath & Okike High levels of circulating bilirubin in neonates can have severe and serious consequences as the bilirubin can cross the blood–brain barrier and attach to the developing brain tissue. The most vulnerable areas of the infant’s brain are those that control hearing and motor function Casey .Studies have shown that NNJ has an effect on the development of infants. Rosie et al.  found thIt would have been beneficial to follow up the infants at a later stage to determine whether their development would improve at a later age as the infants were very young. The small sample size and many possible confounding factors may have influenced the results of our study.in utero seem to have little effect on the development of an infant. Birth complications such as meningitis and NNJ have a much bigger negative impact on neonatal development. All premature infants, whether HEU or HUU, should have developmental follow-up post-discharge to ensure early intervention if the need arises.Our results suggest that HIV and ARV exposure in utero.Antiretrovirals in pregnancy are critical in preventing mother-to-child transmission of HIV and ensuring a healthier infant with less neurodevelopmental complications. Larger long-term follow-up studies are needed to monitor the developmental trajectories of infants exposed to HIV and ARVs


Neonatal mortality remains a serious public health concern in developing countries including Ethiopia. Ethiopia is one of the countries with the highest neonatal mortality in Africa. However, there is limited evidence on the incidence and predictors of neonatal mortality at the national level. Therefore, this study aimed to investigate the incidence of neonatal mortality and its predictors among live births in Ethiopia. Investigating the incidence and predictors of neonatal mortality is essential to design targeted public health interventions to reduce neonatal mortality.p-value of less than 0.2 were considered for the multivariable Gompertz gamma shared frailty model. In the multivariable Gompertez gamma shared frailty model, the Adjusted Hazard Ratio (AHR) with a 95% confidence interval (CI) was reported to identify significant predictors of neonatal mortality.A secondary data analysis was conducted based on the 2016 Ethiopian Demographic and Health Survey (EDHS) data. A total weighted sample of 11,022 live births was included in the analysis. The shared frailty model was applied since the EDHS data has hierarchical nature, and neonates are nested within-cluster, and this could violate the independent and equal variance assumption. For checking the proportional hazard assumption, Schoenfeld residual test was applied. Akakie Information Criteria (AIC), Cox-Snell residual test, and deviance were used for checking model adequacy and for model comparison. Gompertz gamma shared frailty model was the best-fitted model for this data since it had the lowest deviance, AIC value, and the Cox-Snell residual graph closet to the bisector. Variables with a Overall, the neonatal mortality rate in Ethiopia was 29.1  per 1000 live births. In the multivariable Gompertz gamma shared frailty model; male sex , twin birth , preceding birth interval less than 18 months , small size at birth , large size at birth  and did not have Antenatal Care (ANC) visit  were the significant predictors of neonatal mortality.Our study found that neonatal mortality remains a public health problem in Ethiopia. Shorter birth interval, small and large size at birth, ANC visits, male sex, and twin births were significant predictors of neonatal mortality. These results suggest that public health programs that increase antenatal care service utilization should be designed to reduce neonatal mortality and special attention should be given for twin births, large and low birth weight babies. Besides, providing family planning services for mothers to increase birth intervals and improving accessibility and utilization of maternal health care services such as ANC is crucial to improve neonatal survival. According to the World Health Organization (WHO), neonatal mortality is defined as the death of babies within 28 days of birth  and is cNeonatal mortality has decreased steadily over the past two decades, although this was the slowest in Sub-Saharan Africa (SSA), where 38% of global neonatal mortality occurred , 10. TheWhile Ethiopia has made large-scale investments and programs such as the implementation of the Health Extension Program (HEP), quality and accessibility of maternal healthcare services, and Millennium Development Goals, it is among the few countries with the highest NMR burden , 16. PreAccording to the EDHS reports, the neonatal mortality rate decreased from 49 per 1000 births in 2000  to 29 peA secondary data analysis was conducted based on the EDHS 2016 data. The 2016 EDHS survey was the fourth survey conducted in Ethiopia, situated in the Horn of Africa. Ethiopia has 9 regional states  and Tigray) and two Administrative Cities (Addis Ababa and Dire-Dawa). The EDHS used a stratified two-stage cluster sampling technique selected in two stages using the 2007 Population and Housing Census (PHC) as a sampling frame. Stratification was achieved by separating each region into urban and rural areas. In total, 21 sampling strata have been created. In the first stage, 645 Enumeration Areas (EAs) (202 in the urban area) were selected with probability selection proportional to the EA size and independent selection in each sampling stratum. In the second stage, on average, 28 households were systematically selected. A total weighted sample of 11,022 live births within 5 years preceding the survey were included. The detailed sampling procedure was presented in the full EDHS 2016 report .The outcome variable for this study was neonatal survival status categorized as being alive (coded as 0) or died (coded as 1). Neonatal mortality is defined as the death of live birth within 28 days of life. Age at death was recorded in days if the child died within 28 days of delivery. The independent variables considered for this study were categorized as socio-demographic and economic variables , child-related factors , and maternal healthcare services related factors .p-value> 0.05). For model selection, log-likelihood ratio test, deviance (−2LL), Akaike Information Criteria (AIC), and Cox-Snell residual plot were applied. Cox-Snell Residual test is the difference between an observed data point and a predicted or fitted value. A Cox-Snell residual considers the distribution and estimated parameters from the lifetime regression model. A model with the highest values of log-likelihood and the lowest value of AIC was the best-fitted model. Nested parametric models in generalized gamma  were compared based on deviance, and non-nested models (Gompertz and log-logistic) were compared using AIC. Deviance, AIC, and Cox-Snell residual graph showed that the Gompertz gamma shared frailty model had the lowest value and the closet graph to the bisector. Therefore, the Gompertz gamma shared frailty model was the best-fitted model for the data.The data were weighted using sampling weight, primary sampling unit, and strata before any statistical analysis to restore the representativeness of the survey and take into account the sampling design to get reliable statistical estimates. The sampling statisticians determine how many samples are needed in each stratum to get reliable estimates, in EDHS, some regions were oversampled, and some regions were under-sampled. So, to get statistics that are representative of Ethiopia, the distribution of neonate in the sample need to be weighted  such that it resembles the true distribution in Ethiopia by using sampling weight (v005), primary sampling unit (v021) and strata (v022). The descriptive and summary statistics were conducted using STATA version 14 software. The EDHS data has a hierarchical structure, and therefore neonates are nested within a cluster/EAs. This violates the traditional regression model assumption, which is the independence of observations and equal variance across clusters. We have checked whether there was clustering or not by running the frailty model . EA was used as a random effect (clustering variable). The theta parameter was used to assess whether there is significant clustering or not. The EDHS data were collected at two-level at individual and at the community level. Therefore, neonates in the same cluster are more of share similar characteristics than neonates in another cluster. The theta (frailty parameter) was significant at the null model . It showed that there was unobserved heterogeneity or shared frailty that needs to be taken into account to get a reliable estimate. Schoenfeld residual test was applied to check the Proportional Hazard (PH) assumptions, and the PH assumption was fulfilled  with 95% Confidence Interval (CI) was used to declare significant predictors of neonatal mortality.Variable with a http://www.dhsprogram.com. The data used for this study were publicly available with no personal identifier.Permission for data access was obtained from major demographic and health survey through an online request from A total of 11,022 live births were included in this study, of these, 5725 (51.9%) were males, and 292 (2.6%) were twin births. More than two-thirds (72.6%) of the births were delivered at home, and 89% were born to mothers lived in rural areas. About 5842 (53.0%) of the births were born to mothers aged 25–34 years, and 7284 (66.1%) were born to mothers who had no formal education. Three-fourth (75.1%) of the births were wanted, and 4836 (43.9%) were born to mothers who had 2–4 births  times higher than females. The hazard of neonatal death among twin births was 5.22  times higher than single births. Live births who were born within the preceding birth interval of fewer than 18 months was 2.07  times more at risk of death in the neonatal period compared to live births who had a preceding birth interval of 18–36 months. Children born to mothers who didn’t have ANC visits during pregnancy had 2.10  times higher risk of death during the neonatal period compared to children born to mother who had ANC visit. Those live births who were small size at birth and large size at birth was 1.64  and 1.53  times increased risk of death in the neonatal period compared to live births who were average size at birth  per 1000 live births with an Annual Rate of Reduction (ARR) of 2.6%. This was lower than a study reported in Nigeria , the posIn the Gompertz gamma shared frailty analysis; type of birth, preceding birth interval, birth size, sex of neonate, and ANC visit during pregnancy were significant predictors of neonatal mortality. In the current study, the hazard of neonatal mortality was higher among twin births than singletons. It was in line with a study reported in Ghana . This miThe hazard of neonatal mortality was higher among male births was than female births. This was consistent with study findings in Ethiopia , Sudan , and PakThe preceding birth interval was a significant predictor of neonatal mortality. Having the preceding birth interval of fewer than 18 months increases neonatal mortality risk than births with preceding birth interval of 18–36 months. This is supported by previous study findings in Indonesia , and NigLive births born to women who didn’t have ANC visits during pregnancy were at higher risk of death in the neonatal period than live births born to mothers who had ANC visits during pregnancy. This was consistent with study findings in Kenya  and BangMothers who perceived the size of their newborns were small and large size at birth had a higher risk of death in the first month of life compared to newborns who were average-sized at birth. It was consistent with a study in Bangladesh . This coThe strength of this study was, it was based on the weighted data to make it representativeness at national and regional levels. Therefore, it can be generalized to all live births during the study period in Ethiopia. Moreover, the use of shared frailty modeling that took into account the nested nature of the EDHS data and the variability within the community to get a reliable estimate and standard errors. This study had limitations. First, in EDHS, only surviving women were interviewed, and this could underestimate the neonatal mortality rate since maternal mortality is commonly associated with neonatal mortality. Furthermore, the EDHS survey did not incorporate clinically confirmed data; instead, it relied on mothers or caregivers report and might have the possibility of social desirability and recall bias, and variables like maternal obstetric complications such as Antepartum Hemorrhage (APH), preeclampsia, eclampsia, Premature Rupture of Membrane (PROM), infection, and congenital anomalies which may be considered as the most common cause of neonatal mortality were not addressed in this study because these variables were not available in EDHS data.The neonatal mortality rate in Ethiopia remains a major public health problem. Male sex, twin birth, shorter preceding birth interval, having no ANC visit, and small and large size at birth were significantly associated with increased risk of neonatal mortality. Therefore, to reduce neonatal mortality, integrated public health interventions are needed. Giving special medical care and follow up for twin births, small and large babies, and male births are mandatory to reduce the incidence of neonatal mortality. Providing family planning services for mothers to increase birth intervals and improving accessibility and utilization of maternal health care services such as ANC is crucial to improve neonatal survival.


A cavum septum pellucidum is a cerebrospinal fluid (CSF) filled cavity situated between the lateral ventricles and is considered as a normal anatomic variant sporadically seen on neuroimaging. While a cavum septum pellucidum is a relatively uncommon incidental neuroimaging finding, symptomatic cysts of the cavum septum pellucidum are very rare, with only a few cases reported in the literature so far. They are defined as fluid-filled structures with lateral bowing of the walls and membranes separated by at least 10 mm or more. We present the case of a 25-year-old male patient with a rapidly expanding cyst of the septum pellucidum with headaches refractory to conventional pharmacological therapy. A 3T magnetic resonance imaging (MRI) of the brain with contrast was performed, which confirmed the diagnosis. Due to the failure of non-interventional treatment, he was treated with therapeutic endoscopic fenestration of the cyst. Postoperatively, he reported a complete resolution of the presenting symptoms. Cavum septum pellucidum (CSP) cyst, cavum vergae, and cavum velum interpositum are various presentations of benign midline anterior intracranial cysts. They are pathological when symptomatic, which arise depending upon the size of the cysts. Cavum septum pellucidum cysts are rare lesions with an incidence of 0.04% . SymptomWe present the case of a 25-year-old right-handed male who presented with daily headaches for three weeks, which actually have been present and have been progressively increasing in intensity and frequency since he was 11. The pain was localized on the top of his head and the retro-orbital regions bilaterally and of a constant, dull, nagging nature. It was made worse with coughing, sneezing and straining, and relieved with lying down and sleep. Over the past five years, the headaches have been constant, present through the day, and have been worsened by looking up and upon standing up. He has also had difficulty concentrating. There was no history of visual changes, or changes in sleep, seizures, weakness, unsteadiness, fainting, or falls. He had been treated for tension headaches and migraines for over the same time at various clinics to no lasting effect. A cavum septum pellucidum cyst and cavum vergae were noted on a computed tomography (CT) scan during the evaluation of the headache at an outside clinic in 2015. On presentation to our clinic, the examination was unremarkable with stable vitals and no focal neurological deficits.A magnetic resonance imaging (MRI) of the brain with contrast was ordered, which revealed a cavum septum pellucidum cyst and cavum vergae. The 3 X 3 X 1.7 cm cavum septum pellucidum cyst was seen compressing the frontal horn mid bodies of lateral ventricles. The lateral ventricles were mildly enlarged bilaterally. Sections through the foramina of Monro revealed no definite communication from the cyst to the right lateral ventricle or the third ventricle. A minimal connection was appreciated to the left lateral ventricle. Partial luminal obstruction at the level of the left foramen of Monro was appreciated. There was no evidence of hydrocephalus or midline shift. An appreciable increase in size in cavum septum pellucidum from compared to a previous scan from 2015, from 1.3 X 0.9 cm to its current dimensions of 3 X 3 X 1.7 cm, was observed  is a thin, triangular, double membrane with the apex at the foramen of Monro and base towards the quadrigeminal cistern separating the frontal horns of the right and left ventricles. CSP is a potential cavity between the two leaves of septum pellucidum. A CSP cyst is defined as a fluid-containing structure between lateral ventricles at least 10 mm in width or with lateral bowing of the ventricular walls .It is more than just a neural tract that connects the corpus callosum and fornix in spite of the misconception that the septum pellucidum has no function (based on the poor understanding of its embryology and connections). It is a component of the limbic system that acts as a relay station to the main hippocampal and hypothalamic nuclei, as is evidenced by symptoms of mental retardation and learning disabilities seen with septum pellucidum lesions -4.The septum pellucidum is bounded superiorly by the inferior surface of the body of the corpus callosum; anteroinferior by the superior surface of the genu of the corpus callosum; posteroinferior by corpus and columns of the fornix; laterally by the medial wall of the frontal horns of the lateral ventricles and medially by the virtual space between the contralateral septum.The cavum septum pellucidum is a normal anatomic variant, is usually asymptomatic and discovered incidentally. Cavum vergae is the term assigned to the posterior extension of the CSP.In more than 85% of cases, the CSP fuses by three to six months of life. The prevalence of CSP sharply declines soon after delivery, such that it is 85% at one month, 45% at two months, and 15% at three to six months. It closes in a caudal to rostral fashion, resulting in obliteration of the caudal portion first (at 38 weeks of gestation). The anterior portion only obliterates by three to six months of age, which occurs due to the rapid growth of the corpus callosum and hippocampal alvei along with the concrescence of cerebral hemispheres leading to the fusion of the membranes of SP. Cavum vergae is present in around 30% of newborns and persists in only 1% of adults. Formerly, SP and CSP were known as fifth and sixth ventricles, respectively. However, since the cyst cavity is not continuous with the ventricular system and lacks the choroid plexus, this nomenclature is no longer used -6.Depending on its communication with the ventricles, CSP cysts are classified as communicating and non-communicating. Secondary communications may be formed by head trauma, surgery, or spontaneous rupture. CSP cysts may also be classified as asymptomatic  or symptomatic  as proposed by Shaw and Ellsworth ,8.Headache is the most common and consistent symptom associated with CSP cysts and is thought to be due to intermittent hydrocephalus provoked by positional changes and other maneuvers that cause a rise in the intracranial pressure . CSP cysts constitute a rare but extremely important cause of positional headaches that are potentially reversible. The differential diagnosis for anterior intracranial midline cysts includes asymmetric lateral ventricle cysts where the septum pellucidum is bowed but intact, the vein of Galen aneurysm, cavum septum arachnoid cyst, and an interhemispheric cyst related to agenesis of corpus callosum and cavum velum interpositum -11.Although rare, a cyst of cavum septum pellucidum should be included in the differential diagnosis when a patient presents with symptoms attributable to obstruction to cerebrospinal fluid (CSF) flow. The preferred neuroimaging modality is with a 3T MRI with contrast, which clearly shows a large intracranial midline interhemispheric cyst, along with delineating the extent and its communications with either lateral or the third ventricles. We present a rare case of enlarged symptomatic cyst of cavum septum pellucidum, presenting with episodic positional headaches not responding to pharmacological therapy. Complete resolution of the symptoms was seen after endoscopic fenestration of the cyst, establishing the correlation between headache and the cyst of cavum septum pellucidum.


Newborn screening for congenital adrenal hyperplasia (CAH) has one of the highest false positive rates of any of the diseases on the Wisconsin panel. This is largely due to the first-tier immune assay cross-reactivity and physiological changes in the concentration of 17-hydroxyprogesterone during the first few days of life. To improve screening for CAH, Wisconsin developed a second-tier assay to quantify four different steroids  by liquid chromatography–tandem mass spectrometry (LC–MSMS) in dried blood spots. From validation studies which included the testing of confirmed CAH patients, Wisconsin established its own reporting algorithm that incorporates steroid concentrations as well as two different ratios—the birth weight and the collection time—to identify babies at risk for CAH. Using the newly developed method and algorithm, the false positive rate for the CAH screening was reduced by 95%. Patients with both classical forms of CAH, salt-wasting and simple virilizing, were identified. This study replicates and expands upon previous work to develop a second-tier LC–MSMS steroid profiling screening assay for CAH. The validation and prospective study results provide evidence for an extensive reporting algorithm that incorporates multiple steroids, birth weight, and collection times. Congenital Adrenal Hyperplasia (CAH) is a group of autosomal recessive disorders caused by enzymatic defects within the biosynthetic pathways of mineralocorticoids, glucocorticoids, and sex hormones. The most common defect, accounting for greater than 90% of CAH cases, is due to 21-hydroxylase (21-OH) deficiency, and has an estimated prevalence in the United States of 1 in 16,000 to 1 in 20,000 . There aNewborn screening for 21-OH deficiency was first introduced in 1977 , with thIn recent years, newborn screening programs have implemented second-tier testing to reduce false positive rates. This second-tier test is typically performed on the original specimen, when the first-tier screening result—elevated 17-OHP—is abnormal. In 2004, Lacey et al. published the first report of a second-tier method for CAH . This meIn 2007, Janzen et al. published an original method validation and prospective study which incorporated analysis of 21-deoxycortisol in dried blood spots, along with the ratio of (17-OHP + 21)/F . The artThis study adds to the literature by outlining the method validation for four different steroids measured by LC–MSMS. Details on the development of an algorithm, which incorporates first-tier testing and second-tier analysis of multiple steroids and associated ratios, stratified by birth weight and the timing of specimen collection, are provided. Lastly, this study summarizes the year-long implementation of the second-tier test and its influence on positive predictive value and false positive screening rates for CAH within the Wisconsin population.n = 144), obtained through the Wisconsin NBS program, were also used for the validation. The true and false positive specimens were stored at −20 °C prior to analysis. For the prospective study, all dried blood spot specimens were collected between 0 and 168 h after birth and were stored at 4 °C after routine NBS was completed.A protocol (2019-0118) for the use of residual dried blood spot (DBS) newborn screening (NBS) specimens was approved by the Health Sciences Institutional Review Board (IRB) at the University of Wisconsin (3/28/2019). For the assay validation, DBS specimens from 18 patients with CAH were obtained from newborn screening laboratories and were de-identified according to the IRB-approved protocol. Residual, known false positives specimens . Plasma and washed RBC were combined in 50/50 v/v (to achieve a 50% hematocrit) to make whole blood.Standards for cortisol (F) and 17-hydroxyprogesterone (17-OHP) were purchased from Sigma . The standard for 21-deoxycortisol (21) was purchased from ChemCruz , and the standard for 4-androstene-3,17-dione (4-A) was obtained from Cambridge Isotopes . The isotopically labeled internal standards D-7, 4-androstene-3,17-dione , D-8, 21-deoxycortisol , D-8, 17-hydroxyprogesterone , and D-4, cortisol  were purchased from CDN isotopes . Acetonitrile and methanol HPLC–MS grade solvents were purchased from J.T. Baker through Fisher Scientific . Grade 903 filter paper for DBS preparation was purchased from Whatman GmbH . Sera Con II charcoal filtered de-lipidated plasma was acquired from SeraCare Life Sciences . Packed red blood cells (RBC) from Three different sets of quality control materials for the four steroids at varying concentrations were prepared. Whole blood was enriched with 15 ng/mL or 150 ng/mL of 17-OHP, 11, 21, and 4-A to prepare the low- and high-quality control materials respectively. The normal control was not inoculated with 17-OHP, 21, or 4-A. Cortisol was inversely spiked into the normal, low- and high-quality control materials at concentrations of 80, 15 and 5 ng/mL, respectively, to mimic patient profiles with high 17-OHP and low cortisol concentrations.Calibrators were prepared with equimolar enrichment of each steroid in the following levels: 0, 2.5, 5.0, 10, 50, 100 and 250 ng/mL. These calibrators were also used to assess the method’s linearity and limit of quantification.The unenriched and enriched whole blood pools used in creation of the quality control materials and calibrators were dispensed onto filter paper, dried overnight under ambient conditions, and stored at –20 °C in zip-closure plastic bags containing desiccant packets.As part of routine screening within Wisconsin, whole blood samples obtained from newborns between 0 and 168 h after birth were collected on Whatman GmbH grade 903 filter paper, dried, and sent to the Wisconsin NBS laboratory. 17-OHP was measured on all specimens using a time-resolved fluoroimmunoassay according to the manufacturer’s specifications . The results of this first-tier CAH screening were interpreted according to the birth weight of the newborn . Any speA 3.2 mm (⅛”) punch of the DBS specimen was placed into a 96-well, round-bottom polypropylene plate. The steroids  were extracted from the punch using 175 µL of an 80:20 acetonitrile/water solution containing 3 ng/mL of each internal standard, followed by shaking at 50 °C for 60 min. The extraction solution was transferred to a clean 96-well plate and dried under nitrogen gas for 35–40 min at a temperature of 40 °C. The dried well was reconstituted using 50 µL of 40:60 methanol/water solution with 0.3% formic acid and then shaken for 10 min at room temperature, prior to analysis.The steroids were separated by liquid chromatography using a Phenomenex Kinetex  5 µm C18 110A 50 × 2.1 mm column and analyzed using an AB Sciex API 4500 tandem mass spectrometer with a TurboV electrospray ionization source. The API 4500 was operated in positive-ionization mode with the ion spray voltage set to 1500 V, declustering potential 70 V, excitation potential of 10 V, and a collision cell exit potential of 13 V. Additional steroid dependent parameters are in Adequate baseline separation of the four steroids, the column wash and re-equilibration was achieved with a total run time of nine minutes. The injected sample volume was 20 µL. The steroids and associated internal standard were analyzed using the multiple reaction monitoring (MRM) pairs in The analytical method described above extracts, identifies, and quantifies four steroids. The described assay validation results below highlight these four steroids . To identify newborns with congenital adrenal hyperplasia due to 21-OH deficiency, the following three steroids  and two ratios [(17-OHP + 21)/F and (17-OHP + 4A)/F] were used for interpretation. p < 0.0001 and all tests are two-sided. For the population assessment, the four steroid values were log transformed to improve symmetry of the data and stabilize variance across the range of birth weight. Statistical analysis of the data was performed using non-parametric analysis of variance  and Mann–Whitney tests for follow-up pairwise comparisons. Significance was defined as R2) of >0.9970. The recovery of each steroid was within ±15% of expected concentration across the linear range.A complete clinical assay laboratory validation was performed for four steroids quantified within the second-tier assay . Assay precision was assessed using the two quality control specimens and the unenriched specimen analyzed in six replicates on seven different days. The intra- and inter-assay precision was less than 11% and 15% respectively for all four steroids at varying concentrations exceeding the limit of detection . The limit of quantification was assessed at 2.5 ng/mL for each steroid, with a CV of 26% or less. Linearity ranged from 0 to 500 ng/mL with slopes averaging between 0.83 and 1.15 and a coefficient of determination  after birth. The birth weights for these patient specimens ranged from 300 to 4810 g: 27% with a birth weight less than or equal to 1500 g; 28% with a birth weight between 1501 and 2500 g; and 45% with birth weight >2500 g. The 17-OHP values as measured by the first-tier immunoassay were within the normal range as determined by the birth weight adjusted cutoff  as assessed by the one-way ANOVA Kruskal–Wallis test. Androstenedione also declined in concentration with increasing birth weight and was statistically different between each of the three birth weight groups . Cortisol and 21-deoxycortisol were not statistically related to birth weight .For each steroid , the data was plotted and a linear regression of the log transformed value against a 5-knot restricted cubic spline for birth weight was fit, with the model stratified according to age at sample collection (before 24 h versus 24–168 h) . 17-hydrp-value <0.0001) as assessed by the Mann–Whitney test. Further stratification by timing of collection and birth weight, using the weight categories listed above, showed statistical differences between groupings for 17-OHP and 4-A . The Mann–Whitney tests performed on cortisol and 21-deoxycortisol were not consistently significant among the groups (stratified by birth weight and collection time).Steroid concentrations were also assessed by the timing of collection, either before 24 h, or at 24 h or greater; 61% of specimens were collected at 24 h or greater; and 39% of specimens were collected at less than 24 h. The 17-OHP, 4-A, F, and 21 concentrations in specimens collected before 24 h as compared to 24 h or greater were all statistically different . Within the 144 specimens, 9 (6.3%) were collected prior to 24 h and 135 (93.7%) were collected at 24 h or later. The birth weight in this population ranged from 403 to 4060 g; 19.4% had a birth weight ≤1500 g, 13.9% were between 1501 and 2500 g, and 66.7% were greater than 2500 g. None of the false positive specimens had all five markers (three steroids and two ratios) greater than 3stdev above the mean, nor were any of the individual markers greater than 10 standard deviations. However, 7 out of 144 specimens (~5%) had abnormal results, greater than 3stdev, for four of the five markers. The remaining 137 specimens had three or fewer markers above the 3stdev cutoff.An interpretation algorithm was proposed after analysis of the 18 specimens from confirmed cases, 144 false positive specimens, and 783 presumptively normal specimens. All newborns will continue to receive the routine first-tier immune assay to measure the 17-OHP concentration. If the 17-OHP value is determined to be abnormal, depending upon the birth weight adjusted cutoff, the specimen will be referred for second-tier testing. The second-tier test will measure four different steroid concentrations and two ratios. Specimens with 17-OHP, 4-A, 21, and the two ratios [(17-OHP + 4-A)/F and (17-OHP + 21)/F] above three standard deviations will be reported as abnormal (screened positive). Patients will be immediately referred for endocrine consultation and confirmatory testing. Likewise, any sample with any of the five markers (three steroids or two ratios) above 10 standard deviations will also be referred for immediate endocrine consultation and confirmatory testing. To allow for a conservative interpretation and to limit the possibility of false negative results, specimens with four of the five markers above the three standard deviation cutoffs would result in a request for repeat newborn screen See the algorithm in As per the Wisconsin protocol for babies in special care units, a routine repeat screen at 14 days of life will continue to be performed on all newborns with a birth weight <2200 g, regardless of the initial CAH result. These repeat specimens will be tested and evaluated using the same algorithm, with the exception of the first-tier 17-OHP cutoff. The repeat specimens will have a more stringent first-tier 17-OHP cutoff, dropping from initial birth weight cutoff to the next lower cutoff .A one-year prospective study incorporating second-tier testing for CAH was implemented into routine newborn screening using the algorithm in A calculation of the false positive rates within the prospective study  was determined to be 0.75% following first-tier testing, decreasing to 0.04% after second-tier testing and resulting in a greater than 95% reduction in false positive cases. The calculated positive predictive value [true positives/] before and after second-tier testing was also dramatically improved, from 1% to 17%.The introduction of newborn screening for CAH has profoundly impacted the well-being of affected individuals (approximately 3 to 6 newborns each year in Wisconsin) by reducing the morbidity and the risk of neonatal death due to salt-wasting crisis. However, the current first-tier screening protocol has a high false-positive rate (approximately 0.75% in Wisconsin), leading to unnecessary testing and clinical evaluations, along with parental anxiety and stress ,25. The The success of the second-tier test for CAH has been tempered recently with a concern for false-negative results. Previous reports of missed cases have largely been limited to the milder forms of CAH missed by first-tier analysis ,29,30. HThis study describes the Wisconsin experience with the validation and implementation of the second-tier LC–MSMS test, including the development of an algorithm for the interpretation of results. Wisconsin chose to analyze four different steroids . Assay performance metrics, including precision, accuracy, and linearity, were all consistent with previously reported studies. As part of the assay validation, a complete analysis of the steroid concentrations within the normal population was performed. Consistent with literature reports, steroid concentrations change over time and are also impacted by physiological differences between a premature, low-birth-weight baby compared to a full-term baby . TherefoFrom the assessment of the normal population, along with false positive and confirmed cases, an interpretation algorithm including multiple steroids  and two additional ratios, stratified by birth weight and specimen collection timing, was proposed. Sixteen of the confirmed cases of classical CAH (SV or SW) had all five markers elevated above 3 standard deviations from the mean. There was, however, a dramatic range in steroid concentration within the confirmed cases (17-OHP ranged from 6.14 to 395.00 ng/mL). The Wisconsin screening algorithm also incorporates provisions for when a single marker is elevated at a concentration greater than 10 standard deviations from the mean. One patient confirmed to have SV CAH was collected at 2 h of life. In this specimen, 3 markers were elevated, but both ratios were greater than 10 standard deviations from the mean. In addition, the Wisconsin modified algorithm, incorporating a 10 standard deviations cutoff from the mean, also detected a non-classical CAH patient. To address the potential for false negatives due to missed interpretations, the algorithm includes a “possible abnormal” reporting option to be used when four of the five markers are outside three standard deviations. The one-year prospective study achieved a 95% reduction in false positive rate to 0.04%, even with a conservative algorithm allowing for a “possible” abnormal interpretation. This tempered approach may be an appropriate alternative to minimize false negatives, but not substantially increase the false positive results. During the prospective study, 5 CAH patients were identified out of 63,725 analyzed . This is higher than the reported incidence of 1 in 20,000, and suggests that it is likely no cases of CAH were missed. The impact of the second-tier test on the entire newborn screening program is significant. Studies have demonstrated that the second-tier test for CAH reduces the burden of follow-up care and has improved clinical practice by minimizing the need for sub-specialty, endocrine evaluations . In addiThe risk of missed CAH cases, whether after first- or second-tier analysis, will always remain a concern for programs. The decrease in flux through the steroid synthesis pathways, largely due to cortisol inhibition or the lack of mature enzyme function, will continue to contribute to false negative rates. The incorporation of a more complete steroid panel, including measuring steroids within the mineralocorticoid pathway, may allow for a more thorough assessment of the pathway. Additionally, clinically relevant factors—such as birth weight or the timing of collection—should be incorporated into all screening algorithms, similar to what has been proposed by Rinaldo et al. . In the This study replicates and expands upon previous work to validate and implement a second-tier assay for classical CAH. Multiple steroids and ratios, along with appropriate adjustment for physiological factors, collection time and birth weight, enabled Wisconsin to suggest a more comprehensive screening algorithm that has not been previously delineated.


Annually, 14 million newborns require stimulation to initiate breathing at birth and 6 million require bag-mask-ventilation (BMV). Many countries have invested in facility-based neonatal resuscitation equipment and training. However, there is no consistent tracking for neonatal resuscitation coverage.The EN-BIRTH study, in five hospitals in Bangladesh, Nepal, and Tanzania (2017–2018), collected time-stamped data for care around birth, including neonatal resuscitation. Researchers surveyed women and extracted data from routine labour ward registers. To assess accuracy, we compared gold standard observed coverage to survey-reported and register-recorded coverage, using absolute difference, validity ratios, and individual-level validation metrics . We analysed two resuscitation numerators  and three denominators . We also examined timeliness of BMV. Qualitative data were collected from health workers and data collectors regarding barriers and enablers to routine recording of resuscitation.n = 3688) of babies were stimulated and 4.4% (n = 998) received BMV. Survey-report underestimated coverage of stimulation and BMV. Four of five labour ward registers captured resuscitation numerators. Stimulation had variable accuracy , BMV accuracy was higher , with small absolute differences between observed and recorded BMV. Accuracy did not vary by denominator option. < 1% of BMV was initiated within 1 min of birth. Enablers to register recording included training and data use while barriers included register design, documentation burden, and time pressure.Among 22,752 observed births, 5330 (23.4%) babies did not cry and 3860 (17.0%) did not breathe in the first minute after birth. 16.2% (Population-based surveys are unlikely to be useful for measuring resuscitation coverage given low validity of exit-survey report. Routine labour ward registers have potential to accurately capture BMV as the numerator. Measuring the true denominator for clinical need is complex; newborns may require BMV if breathing ineffectively or experiencing apnoea after initial drying/stimulation or subsequently at any time. Further denominator research is required to evaluate non-crying as a potential alternative in the context of respectful care. Measuring quality gaps, notably timely provision of resuscitation, is crucial for programme improvement and impact, but unlikely to be feasible in routine systems, requiring audits and special studies.The online version contains supplementary material available at 10.1186/s12884-020-03422-9. Annually, 7–14 million newborns 5–10%) are estimated to require stimulation to initiate breathing at birth and 6 million newborns require bag-mask-ventilation (BMV) . Intrapa–10% are numerator capturing the intervention (or a component) divided by a target denominator regarding clinical need. A good indicator may not include all of the clinical intervention but should “indicate” well and also not incentivise undesirable practices. Resuscitation coverage measurement has specific challenges. Clinical algorithms have multiple actions that could be used as numerators, notably: stimulation of the baby or the action of BMV. Suction is indicated for some babies, but inappropriate suctioning can be harmful, thus should be avoided for a measurement focus , most received BMV, ranging from 71.4% in Azimpur BD to 94.7% in Pokhara NP Fig.  but timeAmong newborns receiving any BMV on the labour ward, the proportion receiving the first ventilation breath within 1 min of birth ranged from 0.2% in Temeke TZ to 8.0% in Pokhara NP. Across the three denominators explored, time to initiation of BMV was similar Fig. .Fig. 9TLabour ward registers varied in design, between the five hospitals Fig. . BangladResuscitation practices were recorded in varying order into multiple documents   allowed the first validity assessment of measurement for neonatal resuscitation coverage in routine hospital registers and surveys, against a gold standard of clinical observation. We found that survey report poorly captured resuscitation indicators. Routine labour ward registers performed better, but variably, and have potential, especially with data quality improvement.Survey-reported coverage was challenging, which is not surprising. We found most women who reported their baby had trouble breathing after birth did not know if their baby had been stimulated or received BMV. We recommend resuscitation need or BMV questions should not be added to existing population-based surveys. Furthermore, the sample size required for this relatively low-incidence practice, would be challenging even in DHS surveys with large, nationally representative samples .The numerator for neonatal resuscitation is key. Stimulation by rubbing the baby’s back is easily conflated with the similar action of drying every newborn baby and was not recognized at all by mothers (< 3% in survey report). Suction is only necessary if the airway is blocked and a measurement focus on suction may unintentionally encourage this potentially harmful practice which can cause bradycardia. BMV is the most distinguishable option for a clear subset of non-breathing babies and had higher accuracy than stimulation. Though underestimated in surveys, accuracy of BMV was still performed better than stimulation by survey-report. Additionally, BMV is a more suitable intervention for which to assess quality and links to health facility assessments where standard questions include presence and recent use of neonatal bag and masks.Health facilities are where ~ 80% of women now deliver , providinumber of live births in a facility, with a footnote that this is pragmatic whilst ongoing work to test different denominators, including EN-BIRTH, is completed [Denominators are notably challenging for interventions such as resuscitation which are indicated based on clinical need for only a subset of babies . Currentompleted . Here weompleted . The redompleted –35 are lMeasuring the true denominator for clinical need for resuscitation is complex. Newborns require BMV if non-breathing/gasping after initial drying/stimulation or if they suffer subsequent apnoea at any time. Breathing well may be difficult to measure as the concept excludes gasping, fast breathing and grunting. It is critical to emphasise these breathing patterns during clinical training as BMV is indicated for some (e.g. gasping) but not all of these breathing patterns. EN-BIRTH observers collected breathing or not breathing as a binary variable because formative research suggested other breathing patterns were not feasible to capture. In our study, 2/5 registers captured non-breathing but as a composite non-crying and non-breathing indicator. Consequently, accuracy of this denominator in registers could not be assessed.Non-crying has potential utility as a denominator as it is simple for health workers to capture and is part of the process in assessing need for resuscitation. Additionally, crying at birth is a single event and thus more straightforward to record as opposed to breathing which is a process and might change over time, particularly for preterm babies. While not all non-crying babies will require further steps of resuscitation, almost all babies who do need BMV are non-crying. One study has shown babies breathing but not crying after birth have an increased risk of death . We founApgar scores are captured in all the routine hospital registers in our study, including in Pokhara NP, which captured no resuscitation interventions. Apgar scores do not capture interventions around the time of birth, rather describe a newborn’s physical condition and response to any interventions at 1 and 5 min after birth and are already known to have limitations, notably low inter-rater reliability. The one-minute Apgar score, which includes heart rate, does not fit well with current resuscitation algorithms which recommend checking the baby’s heart rate after a minute of ventilation (2 min after birth). As such, the Apgar score is not a useful denominator for neonatal resuscitation and as usually written in individual patient records, we suggest exploring replacing this column in routine labour ward registers with data elements that can be used for coverage measurement e.g. not crying after birth.Timely resuscitation is essential and even small delays in starting resuscitation can contribute to death or disability . Our assStrengths of this study include the multi-site and multi-country design and large sample size enabling the capture of multiple decision points on resuscitation algorithms. We evaluated how several possible numerators/denominators performed using clinical observation as a gold standard. We assessed possible bias in the observation data with double observation for a subset of cases. Overall, BMV had good inter-observer agreement. Whilst clinically trained observers provided gold standard data on coverage of interventions, subjectivity remains possible e.g. differentiating stimulation from immediate drying. To limit this, the tablet application was designed to capture stimulation in a specific neonatal resuscitation section separate from the immediate care practices, such as drying. The low coverage of stimulation amongst non-crying/breathing newborns (34–38%) may reflect poor quality of care or difficulty in measurement for stimulation by an observer.Some other limitations should be noted. Survey-reported coverage was assessed in exit survey, closer in time to the events in question than standard population-based surveys with 2–5-year reference periods. In survey, only women who answered ‘yes’ to a question asking whether their baby had difficulty breathing at birth were asked further questions about resuscitation, thus some who may have recognised newborn stimulation were not counted towards survey-reported coverage. Additionally, the EN-BIRTH study sample may be healthier than the average in these facilities . As the study sites were CEmONC hospitals, case mix, coverage, and measurement may differ at lower-level facilities.Importantly, the true denominator of babies in need of BMV will not be captured by facility measurement, especially the disadvantaged who are more likely to deliver at home in LMICs. However, home births are less likely to receive BMV in most LMICs, so facility measurement is likely to capture nearly all the numerator in terms of newborns receiving BMV. Hence approaches such as those used in immunisation when the denominator is missing may help to estimate the coverage of the whole population for contexts with many home births.Neonatal resuscitation is a high impact evidence-based intervention for a leading cause of under-five mortality, preventable stillbirth and disability. Yet the current lack of coverage measurement is impeding global tracking of scale-up in high-burden countries. We found bag-mask-ventilation was the most reliable numerator. Measuring the true denominator for clinical need is complex and further denominator research is required, including respectful care considerations, evaluating non-crying as a potential alternative. Based on these results, we do not recommend tracking this indicator through population-based survey. Register measurement of neonatal resuscitation has potential and if standardised and included in HMIS, could aid in tracking progress towards global targets across countries. An appropriate resuscitation denominator could potentially replace the Apgar score, which was recorded as a column in all five registers. Implementation research is needed regarding how to improve register data quality. Measuring and addressing quality of care gaps, notably for timely provision of resuscitation in the first minute, is crucial for programme improvement and impact, but unlikely to be feasible in routine systems, requiring audits and special studies. Improving data is possible and necessary, informing progress to meet global goals and meet every family’s aspiration that their baby will survive and thrive.Additional file 1. Data collection dates by site for the EN-BIRTH study.Additional file 2. EN-BIRTH metadata definitions of selected indicator options for validity testing.Additional file 3. STROBE statement—checklist of items that should be included in reports of observational studies.Additional file 4. EN-BIRTH data quality assurance for Gold standard – double observation and data entry.Additional file 5. Validity measures for stimulation  by hospital for EN-BIRTH study.Additional file 6. EN-BIRTH study – testing validity – stimulation coverage indicator 2 way tables.Additional file 7. Validity measures for BMV  by hospital and denominator option for EN-BIRTH study.Additional file 8. EN-BIRTH study – testing validity – BMV coverage indicator 2 way tables.Additional file 9. Validity measures for survey-reported crying at birth by hospital for EN-BIRTH study.Additional file 10. EN-BIRTH study – testing validity – cry at birth 2 way tables.Additional file 11. Recording order of neonatal resuscitation in hospital documents according to EN-BIRTH data collectors.Additional file 12. Barriers and enablers to routine recording of neonatal resuscitation.Additional file 13. Ethical approval of local institutional review boards, EN-BIRTH study.Additional file 14. Numerators and denominators for observed, survey-reported and register-recorded indicators.