What has not been reported is the effect that birth stories may have on primigravid women’s understandings of birth. Findings are presented from a qualitative study exploring how two generations of women came to understand birth in the milieu of other’s stories. The prior assumption was that birth stories must A Heideggerian hermeneutic phenomenological approach was used. Twenty UK participants were purposively selected and interviewed. Findings from the initial sample of 10 women who were pregnant in 2012 indicated that virtual media was a primary source of birth stories. This led to recruitment of a second sample of 10 women who gave birth in the 1970s-1980s, to determine whether they were more able to translate information into knowledge via stories told through personal contact and not through virtual technologies.Stories are difficult like that’, examines the birth story as problematic and considers how stories shape meaning. The second ‘It’s a generational thing’, considers how women from two generations came to understand what their experience might be. The third ‘Birth in the twilight of certainty,’ examines women’s experience of Being in a system of birth as constructed, portrayed and sustained in the stories being shared.Findings revealed the experience of ‘being-in-the-world’ of birth and of stories in that world. From a Heideggerian perspective, the birth story was constructed through ‘idle talk’ . Both oral stories and those told through technology were described as the ‘modern birth story’. The first theme ‘The women pregnant in 2012 framed their expectations in the language of choice, whilst the women who birthed in the 1970s-1980s framed their experience in the language of safety. For both, however, the world of birth was the same; saturated with, and only legitimised by the birth of a healthy baby. Rather than creating meaningful understanding, the ‘idle talk’ of birth made both cohorts fearful of leaving the relative comfort of the ‘system’, and of claiming an alternative birth. Thererience’ . Tellingerience’ . This maerience’ .; once the experience has structure there is potential for meaning to be determined and emotional responses considered [Articulating the birth experience into a story gives it structurensidered . Walsh snsidered . Savage nsidered , 8.learner’ may reconstruct knowledge amassed from the story [In the exchange that takes place when a story is told, the ‘he story . During he story . In posihe story .Contemporary literature relating to childbirth appears to be primarily concerned with issues of safety and risk , 12. A ssurely have a positive or negative influence on listeners and those stories must have the potential to steer women either towards or away from medical and/or midwifery-led models of care.This study was unique in that it considered how women from two different generations came to understand birth in the milieu of other women’s stories. The study started with the idea that birth stories must ‘simply a thing, any media object, which demonstrates…a clear (story arc) sequence’ and which has the capacity to engage its audience [An understanding of ‘storytelling’ where stories are personal to the storyteller, are spoken and heard in a classic model and are told on a one-to-one basis  was the audience . This noTo describe and consider how engaging with stories of birth influenced expectations and experiences of childbirth for two generations of women. For this purpose, birth stories encompassed personal oral stories as well as media and other representations of contemporary childbirth, all of which had the potential to elicit emotional responses and generate meaning in the interlocutor.contextualisation and amplification’ [An interpretative hermeneutic phenomenological approach underpinned the study design. Phenomenology studies the way things materialise in our experience as well as the ways we experience things in the world around us . In phenication’ .All attempts at understanding in hermeneutic phenomenology start with the researcher as an active participant and involve a moving back and forth between the self, the data and the literature. In phenomenological research the researcher takes with them a number of presumptions which govern the enquiry and potentially what can be discovered .To make sense of the meanings buried in the stories of the participants the primary researcher (LK) explored her presuppositions and understandings of the phenomenon. An interview was conducted with two members of the team and this highlighted a fundamental belief in the ability of most women to birth physiologically, a passion to foster positivity in relation to birth and a belief that birth experiences can permeate the whole of a woman’s life. This explication allowed the researcher to be open with the ‘other’ (the participants); this awareness, along with that gathered through the completion of a reflexive diary and via the sharing and discussion of transcripts with members of the team, contributed to the interpretation .A purposive sampling method  was used to recruit 20 women; 10 women who were expecting their first baby in 2013 and were registered on a ‘National Childbirth Trust’ (NCT) course and 10 women who had birthed in the 1970s-1980s and were members of the ‘National Federation of Women’s Institutes’ (NFWI) and the ‘Cambridge Businesswomen’s Network’ (CBN). The NCT, the UK’s largest childbirth charity, was targeted to try and ensure that the women had an interest in the significance of birth and provided a finite population from which to recruit. The NFWI and CBN were targeted to ensure (as far as possible) that the women would have a similar socioeconomic status as the women recruited from the NCT. There is a limited amount of data on NCT members but in a 2011 report, NCT members responding to a survey were described as 94% white, 50% early thirties and 86% with a higher degree .what does it mean to have experienced…?’ Questions such as ‘how do you understand your impending birth’? And ‘how did this story make you feel about your pregnancy?’ were used to encourage participants to share their experiences.Data was collected via face-to-face and telephone interviews. The interviews were audio-recorded, took between 45 to 90 min to complete and were transcribed verbatim. The interviews were non-structured and involved asking ‘hermeneutical questions’ as determined by Ironside . This me‘bring the unsaid into an open space’ by utilising a series of questions to stimulate thinking, writing and showing [The interpretation was informed by Smythe’s phenomenological approach; the approach allows the writer to  showing .crafted’ a story from each participant’s interview  and then interpreted from her perspective the meaning that lay behind the saying [Each of the transcripts was read by all members of the team; each considering their response, recognising the phrases that leapt out and seeing connections. The primary researcher ‘e saying . LK consRigour was ensured using the adapted framework devised by de Witt and Ploeg . Table 1Ethical approval was obtained from the Science, Technology, Engineering, Medicine and Health (STEMH) Ethics Committee in April 2012 (phase one), January 2014 (phase two) and an amendment was approved in November 2014 (project number: STEMH 005). Written consent was taken before the interviews were commenced, confidentiality of the data was guaranteed and anonymity of the participants ensured by the use of pseudonyms. Table This study suggests that birth stories are a significant part of the landscape of birth for childbearing women. An understanding of the way of being-in-the-world of birth, as illustrated by the participants’ stories and interpreted according to Heidegger’s philosophy, precedes a discussion of the themes putting these in context for the reader.being-in-the-world’ of birth; women experience aspects of this world in relation to other people in that world. Often these people are members of a woman’s family, her close friends and acquaintances. In their pregnancies women find themselves in a world that appears to operate in a certain way and where certain things have already shown up as important. Heidegger describes this as ‘thrownness’, explaining that Dasein (the human kind of being) is ‘thrown’ into its ‘there’ [Women’s pre-understandings about childbirth are rooted in their experience of ‘ ‘there’ . As ‘thr ‘there’ .‘Thrown’ into the world of birth, women are faced with an array of options and choose possibilities of action that are conditioned by their enculturation into the practices of their specific childbearing community. Thrown into this world women attune themselves, creating their existence in terms of what they see as possible. As ‘everyday being-with-one-another’ women are dependent on others and ‘they’ inconspicuously dominate the way to be [they’ alludes to the particular community into which we find ourselves thrown. It is a ‘primordial ‘publicness’ that serves as a shared basis for everyday understandings’ [one’ does according to the norms laid out by the ‘anyone’ of which we are a member.ay to be . Heideggandings’ . In our ‘thrown’ into a particular world of birth they also ‘fall’ into the dialogue and speech of that world (much of which may be ‘groundless’ and yet appear to be ‘authoritative’). This means that what is shared and heard about birth in everyday conversations and via the popular media makes a difference to what women understand about birth. Heidegger uses the term ‘Gerede’  to describe the way of speaking within our shared world [‘Idle talk’ is: ‘the form of intelligibility manifest in everyday linguistic communication - average intelligibility’ [vacuous high gossip’ suggesting that people use this way of communicating as a ‘pretence’; a means of appearing ‘busy’ and ‘well-informed’ in their everyday lives [Not only are women ed world . ‘Idle tibility’ . Steineray lives .horror stories’, ‘media portrayal’ and ‘too perfect and wonderful: being economical with the truth’ explore the social and cultural norms around the content and sharing of stories.This theme highlights the problematic nature of the stories being told and the difficulties of sharing stories. The sub-themes of ‘oh my god it’s so painful’, it’s just so painful’, kind of stories, elaborating with the comment, ‘You don’t get anyone who says, ‘it’s brilliant, calm, relaxed’. You just get these horror stories’. Most of the women seemed accepting of the negative stories; Isabel went as far as to say, ‘I have a morbid fascination with them’. For Stephanie it seemed another facet of modern life:‘What I found, it’s like you can go and buy something from Amazon, and you’ve got reviews. Some people will put up the good reviews but most of the people who are making the effort to put a review on is because it’s negative‘.The women who birthed in the 1970s-1980s similarly reported that negative stories were shared more readily and frequently than positive ones. Emma, for instance, said that she could not remember any specific stories but that ‘you always tend to get the horror stories don’t you?’ Carole, who suffered from ‘toxaemia’ whilst pregnant, said her mother ‘terrified’ her with stories about people she knew who had had the same problem and whose pregnancies had not been successful.The women birthing in the present day concentrated on the negative stories they had heard. Stephanie spoke about the, ‘‘being-in-the-world comes through story and through technology’; helping us to ‘solidify culture’ and share knowledge [so much understand the entities which are talked about’ but rather that we concentrate on what is claimed about the entity [complete groundlessness’ [What is shared and heard about birth in their everyday life makes a difference to what women understand about birth. Irwin describes how our nowledge . Heidegge entity . We acceessness’ .Obviously, I know they only pick certain stories to go on TV, they’ve got to make good TV so that’s why they do it’.‘Without exception the women birthing in the present day talked about media representations of birth and all mentioned watching (or not watching) a popular television programme. The women seemed clear that the stories shown were chosen for a reason, for instance Ruth said:‘In 99% of the cases there’s a woman who is lying on the bed in agony giving birth… a lot of them are forceps deliveries, and a lot don’t look particularly calm and enjoyable…but it makes good TV I guess’.For the women who gave birth in the 1970s-1980s media portrayals of birth were few and far between. The women described how they learnt about birth from conversations with other women, antenatal classes and books. Two of the women recalled seeing a video of a birth at an antenatal class but neither felt it had been very valuable. Meg was the exception saying that she had a ‘romantic idea’ of what it might be like to have a baby and that afterwards she felt:Quite bitter and twisted that people hadn’t been more honest about how difficult it could be, you know, to give birth’.‘When asked about contemporary television programmes Meg argued that ‘they probably are a more accurate representation than anything I was shown’ arguing that she would have found them useful.Isabel said:drama’ of birth as described by Ruth) is disseminated so widely women may find themselves ‘taken in a peculiar direction and….absorbed in the immediate, in fashions, in babble’ [what is said-in-the-talk’ but that what the talk is about is ‘understood only approximately and superficially’ [claims about birth as opposed to a genuine understanding of birth itself.In a world where the public way of understanding birth  is made ordinary through familiarity; the appearance of ‘horror’ in a story accommodated and then made invisible by that accommodation, with other interpretations effectively being ‘closed off’ [For many of the women positive birth stories were an anomaly and sed off’ .hearing positive stories, the women who birthed in the 1970s-1980s spoke about the fact that they were loath to tell positive stories for fear of making others feel bad. Penny for instance said that she was being careful about ‘pushing the whole breastfeeding thing’. For her the experience of breastfeeding was ‘magical’ and she wanted to promote it but she was conscious that people might have difficulties with feeding and might feel they had failed if they weren’t successful.Whilst the women giving birth in the present day were sceptical about it was all a bit shrouded in mystery: we let it take its course’, ‘this generation nothing’s private to them’ and ‘information seeking and saturation’ explore the information seeking behaviours of the women and consider what mattered to the two cohorts of women when anticipating birth.This theme explores how women from two different generations came to understand what their experience of birth might be. The sub-themes of ‘it will hurt, expect it to hurt’ she had no other knowledge but that instead ‘it was all a mystery until you actually gave birth’. The women talked about not really having a voice in their care and indicated that they looked to the health professional for guidance. For these women care was something provided by an ‘expert’ who made decisions for them. As passive recipients of care Pamela said that ‘we tended to just accept what we were told’ and ‘went through the procedures that were suggested’.The women who gave birth in the 1970s-1980s had little knowledge and understanding of birthing in their pregnancies. Sandra said that other than being told by the midwife that ‘‘terrified’ herself. Sophie said that there was ‘an element that I didn’t really want to know’ primarily it seemed because she did not want to know about the ‘things that could go wrong’.For many of the women ignorance was ‘bliss’; Carole explained that if she had had access to the internet when she was pregnant and had researched some of the complications she would have ‘Because she was born on New Year's Eve and I was thinking is this more about the time of year than actually about me, you know, about the baby. You know -- I did feel like that, but it was more of a process -- I'm not saying it was but that was how it felt at the time the process to get this baby born today rather than staff having to hang on’.Women in this era were birthing at a time where the norm was to birth in a hospital in a ‘system’ where birth was only considered normal in retrospect and where interventions were accepted as part of routine care; pregnant women were treated as hospital ‘patients’ under the care of an obstetrician and their care was typically focused on the needs of the institution as opposed to the needs of the individual . Paula’smedical professional’ had told her what was going to happen the assumption was ‘you need this and that’s it’.When asked why she went along with the suggestion Paula said that ‘you’ (women) did not question things then and as a ‘‘everydayness’ Dasein is ‘disburdened’ by the ‘they’; the ‘they’ make every choice and decision meaning that Dasein assumes a passive role and, in so doing, is disburdened of moral responsibility and autonomy [What emerged from the data overall was a strong sense of understanding as acceptance. Heidegger helps us to understand such passivity explaining how in its autonomy .it was just something somebody did when they got married’. Likewise Marie said ‘I don’t think I ever questioned what it was like….we were going to get a child at the end’.The majority of the women talked of birth as an overwhelmingly managed experience, as a consequence of pregnancy and a gateway to motherhood, with Meg saying that she did not really have any idea what being pregnant or giving birth was like but she figured that ‘alright’ and being able to take home a healthy baby. Paula explains, ‘I had two babies and everything was alright, so they were positive experiences for me’. Sophie was of a similar mind-set saying that, ‘you go into it thinking all I want really is a healthy baby’.Certainly for many of these women a positive experience was measured by things turning out ‘pretty private thing to talk about’ (Sandra). Likewise the women birthing in the present day said that they had not always felt comfortable speaking to their mothers or grandmothers about birth and that their mothers had not necessarily wanted to speak about birth with them. For some it was a cultural issue; Rebecca, for instance, was of Chinese origin and was born in Hong Kong. Her grandmother was educated in a very traditional manner and did not feel it was appropriate to discuss childbearing with her granddaughter. Similarly Lucy, also Chinese, expressed a similar view saying that ‘they can’t really talk about that in the past….it’s just a cultural influence. They just found that it is something very private, something quite embarrassing to talk about’.The women birthing in the 1970s-80s spoke at some length about the fact that birth was a ‘I think it was inappropriate to go into too much detail because, you know, genitals weren’t something you referred to in those days’. For others it was simply not something they talked about; Emma said that she had not really spoken with her mother about birth and did not feel she was in the position to ask her mother about birth saying ‘I’m sure it’s a generational thing. My mum wouldn’t have been as open about things as perhaps I would be with my daughter’.Meg said that she did not remember her mother saying very much about pregnancy and reasoned ‘we never discussed what it was like. It was different then to how it is now’. Sandra felt that it was a ‘pretty private thing to talk about’ and that young women ‘today’ talk about birth more than her own generation or the generation before that saying ‘in this generation nothings private to them - nothings off limits, they talk about everything’.Sandra commented that when she was pregnant she worked with women who had children but that ‘I feel like I have to be informed. Just because I’m like that with everything….. I would never just launch myself into something without reading up on it or researching it first’.‘The women appeared overloaded with information amassed from a variety of sources some of which they felt was conflicting (Rebecca) and some of which they weren’t sure was authoritative and therefore to be relied on (Mary). Stephanie, for instance, spoke about the fact that the more she read the more confused she got until she felt ‘I just really don’t know what I want to know because I just think well, I don’t know now‘. Many of the women reached a point where they were no longer open to information. Stephanie was very clear describing how she told her husband:‘I don’t want anything more because I’ve got to the point where I’ve reached saturation....I’m not buying any books. I’m not getting any in because I’ve just reached overload that I don’t actually know what is going on in my head’.Nearly all the women birthing in the present day relied heavily on the internet as a means of accessing birth stories and as a source of information. Mary talked about using it ‘where I need quick answers on things’ and Joanna suggested that it is a useful tool ‘if you’re having an ‘am I allowed to take Rennies or not’ moment’. For some the internet was not merely an information source but was also a place to access social support in the form of online communities. Charlotte explained:‘You can talk about anything on there, like if you're worried about birth or whatever and people have exactly the same sort of questions that I have‘.Despite the value many of the women placed on the virtual community some were quite sceptical about it. Mary got to the hub of the matter stating, ‘I mean you don’t know who they are. You don’t know whether it’s true. It might not be helpful. It might just scare you’. For Mary the internet could be a dangerous place as ‘everybody’s an expert’.The women birthing in the present day were searching for information on which to base their choices related to childbearing and as such they pursued many story mediums. There was a sense that they needed to ‘research’ birth much as you might research a new purchase. Charlotte explained:things reveal themselves to us ‘technologically’; that is they reveal themselves as resources for our ends. Heidegger explains that practices in this technological world come to be favoured in terms of their performance, according to some standard of efficiency, and that these standards provide the ultimate criterion for deciding on a course of action [In his account of technology Heidegger maintains that in the modern world f action .‘Oh because you can, it’s there. Yeah. I mean it’s an absurd world we live in; you can key in a question and get an answer to anything. You just don’t know whether it’s right’.In this study there was a sense that women appropriated the internet and integrated it into their experience of pregnancy and childbirth, using it to help them make choices and decisions. There was almost a sense of them having to use the resource because it was available; when Mary was asked why people accessed the internet for information  she said:Being in a system of birth as constructed, portrayed and sustained in the stories being shared. The sub-themes ‘on the conveyor belt of care’, ‘birth as a technological feat’ and ‘being a good patient and a good parent’ explore women’s experiences of this world and the responsibility and pressure they feel to behave appropriately; conforming to accepted conventions and, in so doing, further sustaining and ultimately propagating the ‘modern birth story’.This theme examines women’s experience of system’ of birth suggesting that they felt like one of the ‘processes’. Meg who gave birth in the 1970s-1980s, said that:I just felt like one of those processes…… your job was to produce this baby…it was about getting the baby out’.‘A number of the women discussed the notion of being part of a ‘I seemed to be just pushed from pillar to post on this kind of never ending conveyor belt’. For Meg being part of the system was a frightening experience as ‘nothing was explained’ and she did not feel that the people ‘caring’ for her were concerned about her welfare.Jean, who gave birth in the same era, said of her first birth. ‘process’ she had to go through to have her ‘dream baby’. Up until this point Ruth’s path to having a baby and becoming a mother had been keenly managed; any sense of uncertainty had been removed from the experience and Ruth felt ‘in control’ of what was happening. Being part of the ‘process’ of childbirth similarly reassured her and helped her maintain that feeling of control.For Ruth, however, who was pregnant in 2012 with a much wanted baby after fertility treatment, birth was merely another ‘system’ of birth saying that when ‘you’ (women) get pregnant there’s an assumption that you’ll do all the ‘routine things’ (like have ultrasound scans and screening) even though some of them are ‘supposedly optional’. Joanna remarked:‘It’s a bit like being on a conveyor belt and actually if you do nothing it’s just going to happen anyway. You turn up and you’re in the system and you just sort of potter along, going along to the next appointment when you have to’.For Joanna being in the ‘system’ might have felt a little impersonal but was ultimately reassuring because:t’s just so routine; you know what you’re meant to be doing and you know what you’re meant to be finding out and that they will check various things to make sure you’re still well’.‘IJoanna was reassured by the routine nature of the antenatal care; she was part of a system like every other woman and if there was anything to worry about she would need ‘special treatment’. As part of the ‘process’, Joanna was conforming to the social norms of care as shared in the stories she had seen and heard and, in doing so, disburdening herself of the need to make difficult choices and decisions.Joanna, pregnant in 2012, spoke at some length about her experience of the ‘have care and we take care. It is through care that we are able to understand ourselves and our existence. Care is the means by which facts, possibilities, people and events in the world matter to us. The world described by the majority of the participants in this study is one where caring involves ‘leaping in’ and ‘dominating’; health professionals taking up the burden of care and managing women’s births for them [Heidegger explains that the notion of ‘care’ is central to our being-in-the-world describing how the world can be defined as what we care for, and we can be defined as what cares for the world . As carefor them .natural thing to do’ explaining that she was a ‘no-fuss’ kind of person who did not anticipate complications. Speaking of her daughter’s experiences of birthing Jean said that she felt her experiences were made more complex by the volume of information available (circulated via the various storying mediums) and the technology relied on to ‘monitor’ maternal and fetal wellbeing.Jean, who gave birth in the 1970s-1980s, said that when she was pregnant she felt birthing was a ‘‘high tech’ saying she understood the need for technology from ‘the safety point of view’ and yet she felt uncomfortable with women being ‘attached to all these wires and goodness knows what else’. Jean’s language suggests that to ‘succeed’ in birth today women must yield to and exploit the technology surrounding it.Jean spoke of the world of birth now as ‘They had to break my waters to bring it on quicker because the waters weren’t breaking. I can remember having the waters broken. I could remember they put like a little clip on her head and I think that was so they could hear her heartbeat….. I could remember they put a belt around me which monitored the contractions’.Sandra’s own experiences of birthing were medically managed and for her this was clearly the norm; as a result the ‘modern’ landscape of birth portrayed by a myriad of assorted story mediums did not look very different. However for Paula birthing ‘technology’ such as ultrasound scans and electronic fetal monitors made the landscape of birth more complex but paradoxically had not necessarily improved women’s experience, saying of her daughter:‘She had a horrendous, horrendous time. And when she was actually delivering -- she had to go in for an epidural and she had -- because of all this pain she had with the pelvis and then she had a really bad reaction to the epidural. I mean I wasn't there – Paul her husband was with her and he actually thought she was going to die because she was out, you know, during that.’Conversely Sandra, who also gave birth in the 1970s-1980s, did not appear to think that birth was now more medicalised than when she birthed saying of her first birth:Paula was shocked that despite all the ‘preparation’ her daughter had done in the form of information gathering, and despite what she perceived to be ‘improvements’ in care (such as routine ultrasound scans) her daughter’s experience had been more negative than her own (when the information wasn’t as widely available and the technology not as well advanced).For a lot of the women birthing in the present day there was an expectation that birth would be medically managed; for some this was because they had health issues , for others, as discussed earlier, it was something they anticipated from the stories they had heard and the representations of birth they had seen (Stephanie and Isabel).facticity’ and ‘ruinance’ help us understand this; Heidegger’s view is that the human way of being is incomprehensible in isolation from a grasp of the world in which it ‘is’ [tempted, seduced, soothed or estranged’ by the world around it [’ by it.The experience of being-in-the-world of birth for these women was an experience of being in a world populated by doctors and technology; all in place to safely ‘manage’ their well-being and their births. Heidegger’s concepts of ‘ it ‘is’ . Dasein round it . The chiBeing ‘spoiled’ by the modern technological world is something which concerned Heidegger as he believed that technology held more danger than potential and had the capacity to obscure the meaningful presence of things; he spoke of the modern world as a world where things show up as having the potential to be ordered according to the norms of control and efficiency of that world . In thistechnological feat’ in which women are tasked with yielding to and exploiting technology is a disturbing one; in this interpretation women’s disembodied experience of birth is accepted as normal and mainstream. The problem with a meaning that supposedly increases the ‘orderability’ of birth and utilises calculative thought is that it sees women as standardised resources with reproductive capacities.The notion of birth as a ‘professionals will probably tell you - we want you like this’.Women birthing in the present day spoke about the responsibility to behave as a ‘good patient’ whilst pregnant and birthing, and perform as a ‘good parent’ both in relation to their developing foetus and newborn baby. Stephanie spoke about her previous experiences of attending hospital for operations and the ‘expected’ behaviour she would conform to; being told where to go, getting changed into a hospital gown and ‘allowing’ health professionals to do everything for her. Her expectation was that she would do the same in pregnancy saying that the ‘good patient’ involved ‘hopping up on the bed’, ‘lying still and being good’ and not ‘making a fuss’ or being a ‘nuisance to anyone’. Isabel said that she always wanted to please people and that when she went on to give birth she would be particularly anxious to please. Being a ‘good patient’ proved problematic however when Isabel attended the hospital for a glucose tolerance test; Isabel said she ‘wanted to do well’ but that it was the hardest 2 hours of her life as she felt so violently sick. Isabel did not want to ‘ruin the test’ which she felt was crucial to being a good patient but also significant in being a good parent as she ‘wanted to have the test to make sure that everything was fine’ with the baby.For Isabel being a ‘massive list of rules about your baby’. Isabel gave examples such as the need to keep doctor’s appointments whilst pregnant, the responsibility to get the baby vaccinated, and the necessity to ensure the baby sleeps in the ‘correct’ position and is covered by the right number of blankets. Isabel was undoubtedly anxious that she fit the requirements of a ‘good parent’ saying that she strove to be what she described as a ‘good vessel’ for her baby, by doing everything in her control to ‘help the baby’ and ‘protect it’; in this sense she was endeavouring to ‘tick all the boxes and get it all perfect’.Childbearing women in the modern world of birth are faced with an endless array of both expert and lay advice (much of it shared in the ‘modern’ birth story) about the ways in which they should protect their foetuses and babies from risk and promote their health and wellbeing. This ‘pressure’ to make the right choices and to fit the profile of the ‘perfect mother’ is encapsulated by what Isabel describes as the ‘Isabel’s desire to please everyone and her responsibility to protect her baby  suggested that she would seek out guidance and care which absolved her from responsibility and instead put others who had the necessary expertise in charge.right for her and her baby’. Doing what is right is a responsibility and Lucy talked to friends, watched the television and read books to try and get ready for the experience. Lucy believed that knowledge was power and that being informed would alleviate some of her fears about birth, helping her to have the experience that she wanted but ultimately helping her to make the right choices and decisions which would have the best possible outcome for her baby.Similarly at antenatal classes Lucy learned she could make decisions about what is ‘colonize consciousness’ and ‘come to constitute and sustain the lifeworld’ of birth [Birth stories are cultural ‘productions’ that convey various ideologies and belief systems shaping women’s expectations and experience of childbirth. Rather than merely reflecting existing ideas and values, the stories women tell embody the values and belief systems of our society and, in so doing, ‘of birth .This study showed that the information gleaned from birth stories did not create meaningful knowledge and understanding for women; thrown into the world of birth the women were similarly thrown into the dialogue of that world and the dialogue spoke of intervention, management and an increasing reliance on technology. The ‘idle talk’ shared shaped women’s expectations of birth and determined the way that they expected to ‘perform’ birth.For the women who gave birth in the 1970s-1980s a positive birth was characterised exclusively by the birth of a healthy baby; the journey towards which was a stepping stone to becoming a mother and an experience managed by the experts who were in place to help keep them safe. For the women who were pregnant in 2012 there were a myriad of different mediums available to help them prepare for birth and ensure they were able to make the ‘correct’ choices ensuring the health of their unborn baby and demonstrating their competency as mothers.safe passage’; with the ability to protect them from the ‘risks’ associated with birth and the knowledge to help them navigate choices to ensure a controlled, predictable outcome [Both groups of women understood care givers as holding the key to ‘ outcome , 38. Neirestricted by protocols, hierarchy and fear’ [In a context where choice in childbirth is increasingly considered paramount it is disturbing (but not surprising) that choice in this study was synonymous with safety. The study findings reinforce the notion that women’s agency and choice in birth is limited; ‘nd fear’  and thatnd fear’ .For both groups of women the stories shared persuaded them that birth was a ‘drama’ to be navigated and forgotten. Seeking sanctuary from the ‘drama’ of birth many of the women persuaded themselves they would be more secure within the system of birth where accountability rested with the experts. Both groups of women chose to accept the birth practices around them; experiencing themselves and their bodies as part of the wider machinery of birth rather than coping with uncertainty and taking responsibility for the consequences .A number of limitations are apparent in this study and may therefore affect the usability of its findings. The first is that the participants were all from England and the birth stories they heard and told were shared within the context of the prevailing maternity system. Whilst the phenomenological descriptions of birth stories outlined in this study may be shared by women in other high resource settings with similar models of maternity care and societal and cultural norms, they are unlikely to be replicated in contexts where the models of care and socio-cultural norms are fundamentally different.The women were recruited from a particular socio-economic demographic; most were white Caucasian and were from a largely from a middle class background. It was likely therefore that these women viewed the world through a lens skewed to their way of thinking and their way of being in the world.truthfulness’  is known to us by how it ‘resonates in felt, shared plausible meaning, and this resonance cannot be reified into proof’ [Finally LK’s ‘immersion’ in the study may be considered a limitation; however this research does not pretend to be objective. In hermeneutic phenomenology the researcher’s understandings are an intrinsic part of the interpretive process . As Crowo proof’ . A dynamOur findings suggest that women birthing today although able to access a huge array of information about childbirth, are not well prepared for birthing their babies. Rather they are overloaded with information sought in an attempt to prepare for the unexpected, address their anxiety and demonstrate their competency as mothers. Further these women are delimited by the ‘idle talk’ surrounding birth; which serves to emphasis the hype of birth as opposed to giving them any real understanding of birth and/or creating meaningful knowledge.Moving forward women need to be encouraged to seek out and share positive stories and be told how powerful these stories can be in reinforcing women’s capacity to birth. Women must be given the tools to appreciate the potential of birth to be something other than a drama in today’s childbearing world. The nature of the idle talk being shared around birth needs to change so that the default story is not impersonal, perilous and out of place.This study highlights a need for further research to qualify the relationship between what women see and hear about birth and their consequent expectations and experiences. Further it demonstrates that work is needed to ensure stories and media portrayals of birth support women’s confidence in their capacity to birth positively in a range of different circumstances.


Metformin reduces maternal and neonatal weight gain in gestational diabetes mellitus; however, this effect is poorly investigated in non-diabetic women. We performed this meta-analysis to investigate the effect of metformin intake during pregnancy on maternal and neonatal outcomes in obese non-diabetic women. We searched Medline, EMBASE, and Cochrane CENTRAL for eligible randomized controlled trials addressing the efficacy of metformin in pregnant obese non-diabetic women. Data were extracted and analyzed using RevMan software (Version 5.3). Neonatal birth weight was the key outcome. Secondary outcomes included maternal weight gain, the incidence of preeclampsia, and neonatal adverse effects .Pooled data from two RCTs (n=843) showed that metformin caused a significant reduction in maternal gestational weight gain , compared to placebo. The summary effect-estimate did not favor either of the two groups in terms of reduction of neonatal birth weight Z score . Metformin was associated with 41% reduction in the risk of preeclampsia; however, this reduction was not statistically significant ). None of the neonatal adverse events including stillbirth ) and congenital anomalies  differed significantly between the two groups.For obese pregnant women, metformin could decrease gestational weight gain with no significant reduction in neonatal birth weight. In light of the current evidence, metformin should not be used to prevent poor pregnancy outcomes in obese non-diabetic women. Maternal obesity during pregnancy is a major health problem that affects 25% of pregnant women . It is aFormer studies have shown that following dietary modifications and lifestyle interventions did not significantly reduce obesity-related complications during pregnancy -15. ReceOther studies examined the effect of metformin on pregnancy outcomes in women with polycystic ovarian syndrome , 22. RecIn light of these controversial findings, we performed a pooled analysis of both RCTs to evaluate the effect of metformin on maternal and fetal outcomes in obese non-diabetic women.We followed the PRISMA statement guidelines during the preparation of this meta-analysis. Moreover, all steps were performed in a strict accordance with the Cochrane handbook for systematic reviews of interventions (updated March 2011) .Literature search strategy We searched Medline (through PubMed), EMBASE, and the Cochrane Central Register of Controlled Trials to identify relevant studies published up to April 2016. The following search terms were used: ((Metformin) AND (Obese OR Overweight) AND (Pregnant OR Pregnancy OR Gestation*) AND (Non-diabetic OR Without diabetes)). Moreover, we scanned the reference lists of retrieved articles and checked the clinical trial registry  for additional studies.Criteria for considering studies for this reviewStudies were eligible if they were controlled clinical trials, which compared metformin to placebo in obese, pregnant, non-diabetic women. Only studies reporting the results of infant birth weight, maternal weight gain, or birth consequences were included. Excluded studies comprised pharmacokinetic analysis of metformin during pregnancy, reviews, secondary data analysis, and studies with unspecified data collection and analysis methods. Three authors  independently applied the selection criteria. The abstract screening was performed first, and then the full-text articles of eligible abstracts were retrieved and screened for eligibility to meta-analysis.Data extractionet al : a) Study characteristics, including first author's name, publication year, sample size, mean age, dosage, and duration of metformin intake; b) The primary outcome measure was the neonatal birth-weight Z score, which was defined as the difference between observed and expected birth weight with adjustment for gestational age, divided by the fitted standard deviation (SD); c) Maternal secondary outcome measures included gestational weight gain, defined as the difference in maternal weight between the day of randomization and the last antenatal visit; d) Maternal adverse events including preterm birth before 37 wk of gestation, gestational DM, preeclampsia, pregnancy-induced hypertension, delivery by CS, postpartum hemorrhage, defined as blood loss of 1 L or more, and e) Neonatal adverse events including death before 24 wk of gestation, stillbirth at 24 wk of gestation or later, congenital anomalies, and neonatal death. When the mean and SD were not provided, we calculated them from the median and inter-quartile range according to Wan et al . Risk of bias assessment in included studiesThe risk of bias in retrieved RCTs was assessed according to the Cochrane handbook of systematic reviews of interventions 5.1.0 (updated March 2011). We used the risk of bias assessment table provided in  of the same book . AccordiData synthesisWe used Review Manager (RevMan) software (version 5.3 for windows) during data synthesis. Changes in the primary and secondary outcomes were pooled as mean difference (MD) in a fixed effect meta-analysis model, using the inverse variance (IV) method. Adverse events were pooled as risk ratios (RR) in a fixed effect model using Mantel-Haenszel (M-H) method. The existence of heterogeneity was assessed by Chi-Square test and measured by I-square test. In the case of a significant heterogeneity (Chi-Square p<0.1), the random effects model was used.Literature search results2 and normal glucose tolerance. The summary of included studies and their main results are shown in Our search retrieved 150 unique articles. Following the abstract screening, only 11 references were eligible for full-text screening. Nine full-text articles were excluded as follows: Two single arm/irrelevant trials, three pharmacokinetic analyses, two literature reviews, and two case reports (29-37). Finally, two RCTs were found to be eligible for the final analysis  and blinding of outcome assessors . The summary of the risk of bias assessment domains is shown in Both included studies were of a low risk of bias in all domains, except for allocation concealment .In comparison with placebo, metformin did not show a significant reduction of neonatal birth weight Z score .The overall MD favored the metformin group over the placebo group in terms of maternal gestational weight gain .The total number of reported maternal adverse events did not differ significantly between the metformin and placebo groups . The pooled RRs for individual adverse events were as follows: Postpartum hemorrhage . The pooled RRs for individual adverse events were as follows: fetal death in terms of miscarriage and stillbirth . To account for between-study variability, we re-conducted the analysis of all fixed-effect outcomes under the random-effects model with no recorded difference in our results .The results of our analysis indicate that using metformin in obese, non-diabetic pregnant women significantly reduced maternal weight gain; however, it was not associated with a significant reduction in neonatal birth weight. The incidence of gestational DM, preeclampsia, as well as other maternal and fetal adverse events, did not differ significantly between the metformin and placebo groups. Our analysis supports the results of the MOP trial regarding the effect of metformin on maternal weight gain. This can be explained by the fact that the MOP trial was designed to address the limitations of the former EMPOWaR trial by increasing adherence to treatment and using a higher metformin dose of 3 grams per day instead of 2.5 gr/day in the EMPOWaR study. Observational studies have also shown that metformin can significantly reduce maternal weight gain in women with gestational DM or polycystic ovarian syndrome , 20, 38.On the other hand, our results are in agreement with the EMPOWaR trial regarding the lack of metformin efficacy in reducing the incidence of preeclampsia. Although metformin reduced the levels of interleukin-6 (IL-6) and C-reactive protein (CRP), which are commonly elevated in preeclampsia cases, the incidence of pre-eclampsia was similar in both arms of the EMPOWaR study . SimilarFormer pharmacological analyses have shown that metformin has a similar pharmacokinetic profile in both pregnant and non-pregnant women with the ability to cross the placenta, reaching similar concentrations in the fetal plasma to those in the maternal circulation . RegardiAlthough metformin conducted its pharmacodynamic effect (lowering blood glucose and insulin concentrations) in enrolled patients of both studies, it did not significantly affect the neonatal birth weight. As confirmed by the EMPOWaR trial, these results present a challenge to the 1952 Pederson theory that states that maternal hyperglycemia stimulates fetal hyperinsulinemia and therefore, increasing fetal weight . Other fDespite the lack of effect on neonatal birth weight, follow up of these siblings should be carried out to track the effect of metformin in their adult life. A former animal study showed that prenatal intake of metformin reduced the risk of obesity and glucose intolerance during adulthood (48). Moreover, a clinical trial on metformin in women with gestational DM showed that children, born to mothers who received metformin during pregnancy, had lower visceral fat at two years of age than children, born to mothers with insulin therapy during pregnancy . The mecStrength points: The large sample size of the included studies adds to the power of our analysis and increases its potential for generalizability. Moreover, including a widely heterogenous population in the MOP trial may allow for generalizing the results of this analysis beyond the studied population.LimitationLimitations for pooling data to summarize few studies include selective reporting, inadequate accounting for heterogeneity and publication bias. The fact that the MOP trial used a higher metformin dose on a more diverse population than the EMPOWaR trial may serve as another limitation. Further studies are warranted to verify the impact of metformin on both maternal and neonatal weights. Although not significant, few adverse events, such as preeclampsia, need for caesarian section, and neonatal death had a trend towards increasing in the metformin group; therefore, future studies are needed to further assess these outcomes. We are aware of another ongoing trial on the subject (ACTRN12612001277831).RecommendationsDespite the absence of major complications in the metformin groups, minor adverse events as gastrointestinal dysregulation, commonly seen with metformin, limit participation in these clinical trials. Finding ways to improve the pharmacokinetic profile of metformin can effectively ameliorate these side effects and increase patients' participation in future studies. As stated earlier, the safety and efficacy of metformin should be followed-up in both mothers and siblings to evaluate the long term results of metformin use in pregnancy.To recapitulate, metformin intake during pregnancy in obese, non-diabetic pregnant women reduces maternal weight gain without significant reduction of neonatal birth weight. In light of the current evidence, metformin should not be used to prevent poor pregnancy outcomes in obese non-diabetic women.The authors have no conflicts of interest to declare.


Several maternal and birth characteristics have been reported to be associated with an increased risk of many childhood cancers. Our goal was to evaluate the risk of childhood embryonal solid tumors in relation to pre- and perinatal characteristics.A case-cohort study was performed using two population-based datasets, which were linked through R software. Tumors were classified as central nervous system (CNS) or non-CNS-embryonal . Children aged <6 years were selected. Adjustments were made for potential confounders. Odds ratios (OR) with 95% confidence intervals (CI) were computed by unconditional logistic regression analysis using SPSS.Males, high maternal education level, and birth anomalies were independent risk factors. Among children diagnosed older than 24 months of age, cesarean section (CS) was a significant risk factor. Five-minute Apgar ≤8 was an independent risk factor for renal tumors. A decreasing risk with increasing birth order was observed for all tumor types except for retinoblastoma. Among children with neuroblastoma, the risk decreased with increasing birth order (OR = 0.82 (95% CI 0.67–1.01)). Children delivered by CS had a marginally significantly increased OR for all tumors except retinoblastoma. High maternal education level showed a significant increase in the odds for all tumors together, CNS tumors, and neuroblastoma.This evidence suggests that male gender, high maternal education level, and birth anomalies are risk factors for childhood tumors irrespective of the age at diagnosis. Cesarean section, birth order, and 5-minute Apgar score were risk factors for some tumor subtypes. Childhood embryonal solid tumors occur more frequently at younger ages suggesting that antenatal, perinatal, and early postnatal exposures may play a part in its pathogenesis , 2. ReprMost childhood cancers occur sporadically and etiological evidence for causes is poor. Hereditary or familial factors are evident in 10% of cases . SeveralA case-cohort study was performed by selecting cases and controls within the same total population at baseline which allows the advantages of both cohort and case-control designs . Data weOdds ratios (OR) and 95 percent confidence intervals (CIs) were computed by unconditional logistic regression analysis using SPSS version 21.0. The analysis of both all tumors and for each specific tumor group always included the total control group for comparison. Apgar score was categorized into three levels  and in two levels (≤8 versus >8) . To testAll data were kept strictly confidential, ensuring anonymity.The study was approved by the Research Ethical Committee of Instituto Nacional de Cancer (INCA) ref: 13596513.7.0000.5274.Maternal and perinatal characteristics of the controls and cases are presented in (. Materna.When we stratified according to age at diagnosis (≤24 months versus >24 months) higher maternal education level (≥12 years) and birth anomalies continued to be an independent risk factors among children aged ≤24 months.Among children diagnosed older than 24 months of age, delivery by cesarean section was a significant risk factor . Five-miChildhood embryonal tumors are frequently diagnosed before children reach the age of 5 years indicating that there are factors involved in utero or during early postnatal life. We selected children from two good quality Brazilian population-based datasets –19.The sample size among specific cancer types became small and our results were limited, which occurs with most studies assessing childhood solid tumors. Pediatric cancers comprise a heterogeneous group and it is unclear whether subgroups should be analyzed together. Causal associations with childhood cancer have begun to be documented . We founhttp://www.ibge.gov.br). We believe that our result is reliable because it was on the highest category. Maternal education is consider a indicator of social background which can be associated with a variety of health-related factors including risk factors associated with childhood cancer as occupational exposures, dietary patterns, exposure to infectious, immunization, breastfeeding [Maternal education has been used a proxy for socioeconomic status, though it is not perfect. It is a variable with good completeness in the SINASC dataset . In our tfeeding –28. And tfeeding , 27. A rtfeeding . Anothertfeeding . Severaltfeeding , 32. Unftfeeding .One of the strongest risk factors for childhood cancer is being born with a congenital anomaly. Carcinogenesis and congenital anomalies may have a common basis in some pediatric cancers , 33–35. The association between cesarean section and childhood cancer is inconsistent . CesareaBilateral and unilateral retinoblastoma were analyzed together. Bilateral retinoblastoma varies little worldwide, whereas unilateral retinoblastoma has a higher incidence in many developing countries suggesting environmental exposure contributing to its causation. , 46. UnfBirth order may be a marker of different hormonal exposures to the fetus, and higher birth order children may present with higher levels of microchimerism . MoreoveDifferent biologic pathways may be responsible for the association between Apgar score and childhood cancer. The 5-min Apgar score is a predictor of neonatal mortality and neurologic outcomes. A low Apgar score is a marker of suboptimal fetal environment and may be associated with compromised immune responses against tumors , 51. AmoBirth weight has been documented as a risk factor for several tumor types, including tumors occurring in adults . Our datChromosome-number abnormalities have been associated with altered recombination and increased maternal age. The most important factor linked to chromosomal aneuploidy in women is advancing maternal age. It is well established that chromosome-number abnormalities in offspring occur more frequently as maternal age advances . In our This study has the advantage of population-based birth and cancer registries from Brazil. No single cancer registry exits countrywide. People who moved from their city of birth to another city either those that were not born in there city which developed cancer would not have been identified in the study. This is one of our greatest limitations as has been described by others , 57. We The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.


Small for gestational age infants have an increased risk of immediate complications, short-term morbidity and mortality, and long-term neurologic and metabolic disorders in adulthood. Previous research has shown that reduced sleep duration is a risk factor for SGA birth. However, only a few studies have evaluated maternal sleep as a risk factor for SGA birth. In the present study, we investigated the relationship between the amount and quality of mothers’ sleep and infants’ birth weight.This cohort study (n = 8631) used data from the Japan Environment and Children’s Study, an ongoing cohort study that began in January 2011. Data on sleep status  and potential confounding factors were recorded. A log-binomial regression model was used to estimate the risk of small for gestational age birth, and the results were expressed as risk ratios and their respective 95% confidence interval. No significant results were observed for sleep duration or tiredness upon waking. Neither the amount nor the quality of mothers’ sleep was associated with the risk of small for gestational age birth. Small for gestational age (SGA) infants have an increased risk of immediate complications, short-term morbidity and mortality, and long-term neurologic and metabolic disorders in adulthood , 2 . SGAOne study showed that reduced sleep duration was a risk factor for SGA . HoweverData used in this study were obtained from the JECS, an ongoing cohort study that was started in January 2011. The JECS was designed to follow-up mothers using a survey until their newborns reached the age of 13 years. Its objective was to elucidate the effect of environmental factors on children’s health. The detailed methodology has been previously reported .In brief, pregnant women were recruited during the approximately 3-year recruitment period until March 2014. 15 study regions were selected throughout Japan. We met with as many pregnant women as possible who lived in the study area. One of the following recruitment protocols was carried out: (1) recruitment at the time of the first prenatal examination at participating health care institutions, and/or (2) recruitment at local government offices issuing the Mother–Child Health Handbook, which is a complimentary official booklet that all expecting mothers in Japan are given when they become pregnant. The JECS was conducted after obtaining written informed consent from all participants. However, we excluded those who had reasons that made it difficult for them to fill in the questionnaire in Japanese; for instance, if an individual was traveling to her hometown to deliver her baby, she could not participate in the survey , 8.As of the end of 2011, 9646 participants had delivered successfully. After excluding missing data and premature birth, we analyzed the data of the remaining 8631 women who had singleton, full-term  pregnancies . The prFollow-ups were done using self-administered questionnaires, which were filled out during the first and second trimesters of pregnancy and at 1 month after birth. We obtained the medical data by transcribing medical records which were updated during the first trimester, at the time of delivery, and 1 month after birth. The questionnaires collected data related to pregnancy history, general medical history, and confounding and modifying factors such as social and lifestyle factors. From the transcribed medical data, we collected the birth weights and other data related to pregnancy and childbirth, such as gestational age, parity, and labor complications.The sleep index was included in the questionnaire for the second trimester. As a quantitative index of sleep, we calculated “hours of sleep” as the time interval between when a pregnant woman went to bed and got out of bed. Duration of sleep was classified into five categories based on a previous study among pregnant Japanese women . As a quThe participants underwent ultrasonography during their first trimester, and for women with a difference of ≥7 days in their due date, as calculated from their last menstrual period, we used the due date derived from an ultrasound examination. Birth weights were transcribed from medical records. SGA was defined as birth weight <10th percentile of birth weight standards by gestational age for Japanese neonates .The covariates of maternal age, pre-pregnancy body mass index (BMI), parity, smoking, hypertension, and alcohol consumption were included in the questionnaire for the first trimester. Covariates of education and income were included in the questionnaire for the second trimester. The covariate of maternal weight gain during pregnancy was calculated based on information from medical records.We assessed the relationships among hours of sleep, tiredness upon waking and SGA birth in subjects who had single, full-term births. A log-binomial regression model was used to estimate crude risk, confounder-adjusted risk and 95% confidence interval (CI) for SGA birth. The following potential factors were assessed for confounder adjusted risk: maternal age, pre-pregnancy BMI, gestational age at birth, smoking, hypertension, alcohol consumption, and education. All statistical analyses were performed using SAS version 9.3 .The means of maternal age, gestational age at birth, and birth weight were 30.6 ± 4.98 years, 39.0 ± 1.14 weeks, and 3051 ± 369.85 g, respectively. Results of the univariate analysis for birth weight, which accounted for confounding background and social factors, are shown in a table in the previous article [2, who smoked, had hypertension, and had weight gain of <7 kg during pregnancy were 1.58 (95% CI 1.32–1.90), 1.48 (95% CI 1.11–1.97), 1.73 (95% CI 1.17–2.56), and 1.28 (95% CI 1.05–1.55), respectively, indicating that the risk of SGA birth was slightly elevated in these participants. When the pre-pregnancy BMI was ≥25 kg/m2 and weight gain during pregnancy was >12 kg, the SGA risk ratios were 0.60 (95% CI 0.43–0.85) and 0.52 (95% CI 0.41–0.66), respectively, indicating a slightly decreased risk for SGA birth.SGA risk ratios for participants with pre-pregnancy BMI < 18.5 kg/mCrude and adjusted risk ratios for the influence of sleep on birth weight are shown in Table In the present study, neither sleep duration nor tiredness upon waking was associated with risk of SGA birth. Similar to other biologic variables, daily sleep duration in any healthy adult population is normally distributed. The sleep duration of pregnant Japanese women is also normally distributed, and the most common sleep duration is 7–7.9 h . ConsistSleep disorders during pregnancy are known to influence the occurrence of hypertension in pregnant women , 13. ThuThis study showed that neither the amount nor the quality of mothers’ sleep was associated with the risk of SGA birth. Further studies will be needed to investigate the effect of various other factors such as sleep duration, working hours, and mental stress on the risk of SGA birth.Our study has a methodologic limitation in that the data on sleep duration were obtained by a self-administered questionnaire, and thus, may have been prone to misclassification. However, a previous study showed that self-assessed sleep duration yielded valid results in comparison with quantitative sleep assessment using actigraphy . Our stu


Alphaviruses are a group of enveloped viruses transmitted by mosquitoes. Many alphaviruses are neurotropic, being able to produce encephalitis in humans and animals. Among alphaviruses, both Semliki Forest (SFV) and Sindbis virus (SIN) have been extensively studied as models of viral pathogenicity. In mice, SFV and SIN can infect neurons in the central nervous system and virulent strains induce lethal encephalitis, while avirulent SFV strains induce demyelination . These vGiven the neurotropic nature of wtSFV, we investigated whether SFV iMVs could also infect the brain and induce disease in mice. Interestingly, iMVs were able to infect some organs, such as lungs and heart, when administered systemically. However, they did not reach the brain and did not induce any observable pathology, in contrast to wtSFV, which was detected in brain and killed 60% of mice a few days after infection .in vivo treatments that include vaccination or gene therapy. In this regard it will be interesting to test whether highly pathogenic alphaviruses, like Venezuelan equine encephalitis virus or Chikungunya virus, can also generate this kind of iMVs. If this is the case, iMVs derived from these viruses may potentially serve as “attenuated” vaccines for human use. In contrast to vaccines based on empty virus-like particles, iMVs, by replicating and expressing viral spike proteins in vivo, could in principle potentiate antiviral immune responses.These results suggested that iMVs could be potentially used for 4-fold lower than those obtained for wtSFV. This issue can be partially overcome through “packaging” the capsid-less SFV genome into conventional viral particles by providing the capsid gene in trans [in vitro. Notably, this propagative vector induced potent antitumor responses in a mouse model of colorectal cancer (unpublished data), suggesting that it could have potential use for tumor gene therapy.Moreover, we have shown that it is possible to insert foreign genes into the SFV genome devoid of capsid, leading to spreading of transgene expression in cell culture through the generation of “recombinant” iMVs. However, one potential drawback for the use of iMVs is that they are generated at very low titers, approximately 10in trans . Viral pin trans . When usRecently, the group of Ari Hinkkanen  has also revealed that a virulent strain of wtSFV (SFV4) can function as an efficient oncolytic agent against orthotopic gliomas in mice . In thisIn summary, while infectious iMVs challenge our view on the assembly of alphavirus they open a new scenario of potential applications in cancer biology, vaccinology and neuroscience.


Microcebus murinus) and measured two behavioral traits and two performance traits potentially involved in two functions: exploration behavior with pull strength and agitation score with bite force. We checked for the existence of behavioral consistency in behaviors and explored correlations between behavior, performance, morphology. We analyzed the effect of birth weight, growth, and litter size, while controlling for age, sex, and body weight. Behavior and performance were not correlated with one another, but were both influenced by age. Growth rate had a positive effect on adult morphology, and birth weight significantly affected emergence latency and bite force. Grip strength was not directly affected by early life traits, but bite performance and exploration behavior were impacted by birth weight. This study shows how early life parameters impact personality and performance.A whole suite of parameters is likely to influence the behavior and performance of individuals as adults, including correlations between phenotypic traits or an individual's developmental context. Here, we ask the question whether behavior and physical performance traits are correlated and how early life parameters such as birth weight, litter size, and growth can influence these traits as measured during adulthood. We studied 486 captive gray mouse lemurs ( These limitations are commonly referred to as “behavioral syndromes”  and marmots (Marmota flavivenris) . We investigated the effect of three early life parameters: body mass at birth, growth rate, and litter size on the previously described behavioral and performance traits.The aim of the present study was to combine the investigation of behavioral and physical performance limitations through the study of phenotypic correlations between traits in adults. We specifically tested the impact of early and current life parameters on adult phenotypes. To do so, we took advantage of a large colony of captive gray mouse lemurs, in which animals are monitored from birth to death. This small primate is an arboreal and nocturnal species that reproduces once a year, that is amenable for measurements of morphology and performance, and in which personality has already been described in captivity  in a captive colony of mouse lemurs. Individuals are housed in large cages in groups of three or four individuals. Ambient air temperature is maintained at 25°C and humidity is stable at around 30%. All individuals are fed ad libitum, weighed monthly, and maintained under artificial light conditions mimicking natural seasons.We collected data for 486 different gray mouse lemurs  connected to a charge amplifier (Kistler charge amplifier type 9865) as described in Thomas et al. . We condWe used a piezoelectric transducer  attached to a handheld charge amplifier  to record bite force. The transducer was placed between two plates that animals had to bite, as described in . We caught animals directly in their nest box between 1:00 to 5:00 pm, identified animals, and placed a single individual in the wooden box. Next, we placed the wooden box at the entrance of the home cage of the individual. We then waited at least 2 min so that the animal could habituate and calm down from the manipulation. The test consisted of opening the trap door and recording the latency for the animal to escape from the box and return to its home cage. The test lasted 5 min maximum. Individuals that never left the box within the allotted 5 min were given a score of 300 s. We conducted this test between 1 and 13 times per individual for a total of 1,238 tests. Some individuals were tested only once as they died before we could test them twice . Fifty‐eight individuals were tested over 2 years in summer in order to explore the long‐term repeatability. We waited at least 3 weeks before repeating the test with the same individual.We followed the same protocol as described in . Body weight at the time of each test was extracted from the colony database.2.2.4We extracted body weight at birth, body weight at 3 months, and body weight at testing, litter size, and mother identity from the colony data base. Growth rate was calculated as the weight gain in grams over during the first 3 months of life, which is the period during which most of the growth occurs in this species . We considered that an effect was statistically significant when its P‐value was below the threshold of α = 0.05.Physical performance and behavioral variables were log2.3.110‐transformed.We considered the first component of a PCA performed on the morphological traits as a marker of global body size. This axis explained 40% of the variance of the six morphological dimensions and was positively correlated with all dimensions (head and limbs). PCA scores were not log2.3.2We used rptR package to estimate repeatability of behavioral traits . For animals that were tested 1 year apart, average emergence latency was also repeatable between years .Emergence latency was repeatable on short timescales . When we added mother identity as a fixed effect, repeatability dropped  and lost significance, suggesting an important maternal effect on this behavior. Mother effect was then taken in consideration in following statistics as a random effect.The agitation score was repeatable , and growth rate  was not correlated with birth weight , bite force , and emergence latency , with individuals becoming larger and having higher bite force and a longer emergence latency in adulthood if they were heavier at birth , with higher growth rates leading to larger individuals. Growth rate also tended to influence pull strength positively  and emergence latency negatively , with individuals that grew less having longer emergence latencies than individuals that grew more. We found no detectable effect of litter size in these models  and higher agitation scores  than older individuals. Age also had a significant negative quadratic effect on both grip strength  and bite force , and a linear positive effect on morphology , with animals becoming larger with age  and bit less hard  than female ones. However, we did not find differences in overall size between the sexes. Body weight also had a positive impact on both grip strength  and bite force .Sex influenced bite force and the agitation score. Male ones were less agitated , suggesting that the effect or early life parameters had a higher impact on morphology than sexual dimorphism. Indeed, even if males were slightly heavier at birth , females grew more during their first 3 month of life  and had a higher growth rate .Sex differences may also be a source of limitation in behavior (Kappeler & Kraus, In conclusion, limitations in phenotypic variability can appear for various reasons in a population. Here we showed that early life parameters had both direct and indirect effects on the adult phenotype in a captive population of gray mouse lemurs. Birth weight had an impact on adult behavior and on bite force, which seems convergent with the hypothesis that early life impacts somatic state. Growth rate influenced adult performance through an effect on adult morphology. Taken together, these data show that limitations of behavioral variability and physical performances are the result of both early and current factors.None declared.Data were collected by the first author with the help of the fourth author, with the support of animal keepers from the colony. Long‐term data from the colony database were collected by animal keepers and the fifth author since the establishment of the colony and were recently assembled and monitored by the third author. Data analysis and writing were conducted by the first author with the help of the second, sixth, and last author. Click here for additional data file.


This is the first detailed study of the relation between cesarean birth and child cognitive development. We measure differences in child cognitive performance at 4 to 9 years of age between cesarean-born and vaginally-born children  participating in the Longitudinal Study of Australian Children (LSAC). LSAC is a nationally representative birth cohort surveyed biennially. Using multivariate regression, we control for a large range of confounders related to perinatal risk factors and the socio-economic advantage associated with cesarean-born children. Across several measures, we find that cesarean-born children perform significantly below vaginally-born children, by up to a tenth of a standard deviation in national numeracy test scores at age 8–9. Estimates from a low-risk sub-sample and lower-bound analysis suggest that the relation is not spuriously related to unobserved confounding. Lower rates of breastfeeding and adverse child and maternal health outcomes that are associated with cesarean birth are found to explain less than a third of the cognitive gap, which points to the importance of other mechanisms such as disturbed gut microbiota. The findings underline the need for a precautionary approach in responding to requests for a planned cesarean when there are no apparent elevated risks from vaginal birth. In the OECD, the rate of caesarean section has increased from 14.4% of deliveries in 1990 to 25.8% in 20092, growth that cannot be explained by increases in obstetric risk factors, including those associated with delayed and multiple infant pregnancy and maternal obesity6. Instead, this growth is believed to be related to increased maternal request and changes in clinical practice7. A concern is that many procedures are made without considering possible long-run implications, such as reduced fertility8. In this study, we concentrate on examining possible long-term implications for child cognitive development.Cesarean sections can save lives, but rates well above the World Health Organization’s recommended 15% ceiling in most developed countries suggest that many procedures are unnecessary11 and obesity12 that are also associated with impaired functioning and lower academic performance14. The surgical nature of cesarean procedures also poses postnatal maternal health risks15, with potential knock-on effects for the child’s development through altered mother-child interactions16 and lower rates of breastfeeding19.Cesarean birth may be directly and indirectly associated with negative child cognitive outcomes. The indirect association may occur through established links between cesarean birth and adverse child health outcomes, including asthma, type I diabetes, allergies24, with differences observed up until age seven24. Recently uncovered chemical signaling from the gut microbiota to the central nervous system, affecting memory, motivation, mood and stress reactivity, raises questions about the long-term cognitive effects of disturbed microbiota composition at a sensitive time in brain development26. Although causal impacts on child development are yet to be proven, altered signaling from disturbed gut microbiota is thought to be a possible driver of higher rates of cognitive disorders, especially autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), among cesarean-born children . In animal studies, there is mounting (and replicated) evidence of long-term cognitive impacts from early microbiota disturbance. These studies show that rodents lacking all gut bacteria from birth  have memory deficits28 and behavioral abnormalities30 when compared to animals with normal gut microbiota. Interestingly, these cognitive deficits in rodents can be corrected through the colonization of the intestine via a fecal transplant from the control group, but only if it occurs early in life. The implication is that there is a critical window to correct any disruption to the gut microbiota, after which cognitive impacts are permanent25.The direct association may occur through alterations to the infant’s gut microbiota. Unlike vaginally-born children whose gut is seeded by passing through the birth canal, the gut of cesarean-born children is seeded through contact with the mother’s skin and hospital surfaces. The result is long-term compositional differences in gut microbiota by mode of birthet al.31 has examined the relation between cesarean birth and cognitive outcomes. Using Australian hospital records linked to teacher-based assessments in the first year of school, they found a significant negative association across several developmental domains. We build on this study and that of previous health studies in several ways. First, we build on the work of Bentley et al.31 by using mediation analysis to test to what extent any relation is associated with lower rates of breastfeeding and adverse child and maternal health outcomes. This is important because it helps to identify the importance of direct effects, such as those related to disturbed gut microbiota and helps identify how widespread any effects may be within the population. Second, LSAC contains rich longitudinal cognitive test information that enables us to gain an insight into longer-term outcomes that are closely related to early academic achievement, an important predictor of lifelong earnings and health. These include academic test results that measure: school readiness at 4–5, vocabulary and comprehension at 4–5, 6–7 and 8–9 years, problem solving at 6–7 and 8–9 years and national achievement in numeracy and literacy at 8–9 years. Third, we more rigorously test the sensitivity of any relation to bias from confounding variables not observed in the data or ‘selection on unobserved covariates’. We do this using two methods — re-estimating on a sub-sample where selection on unobserved covariates is likely to be less of an issue  and by estimating lower-bound estimates under conservative assumptions about the magnitude of selection on unobserved covariates using the Oster32 technique. This helps to provide some guidance on whether estimated relation is plausibly causal.In this study, we estimate the relation between cesarean birth and child cognitive outcomes using data from the Longitudinal Study of Australian Children (LSAC), a nationally representative birth cohort surveyed biennially, and multivariate regression techniques. To the best of our knowledge, only Bentley 34. There are multiple cohorts of LSAC that are designed for examining specific development periods. In this study, we use the LSAC ‘B cohort’, which has an initial sample of around 5,100 infants born between March 2003 to February 2004, drawn randomly from all registered national births at the time. The initial survey, conducted between 6 months and a year after birth, contains rich perinatal information about the mother and study child along with detailed information on the parents’ background and current life circumstances. From the initial survey, children and their primary care giver are surveyed biennially. At the time of analysis, data were only available up until wave 5 (2014) of the survey when the children are 8–9.LSAC is an internationally recognized and widely-used longitudinal cohort survey of child health and developmentOf the initial 5,100 LSAC participants, we omit around 1,300 from the sample because of missing information by wave 5, due mainly to survey attrition. To examine the potential impact of attrition, for two measures that are observed in wave 3 (Peabody Picture Vocabulary and Who Am I?), we compare relations estimated using the full sample available at wave 3 and relations estimated at wave 3 on a restricted sample that remain in the survey until wave 5 . Using a two-sample t-test, we find no evidence that results estimated results at wave 3 are different for the full and restricted samples  and Brazil (54%) and higher than Finland, Norway and Sweden (around 17%)37.Whether participants in LSAC are cesarean born is identified in the initial survey by the primary care giver’s response to the question, “was…the type of birth/ delivery method a cesarean?” In our sample, approximately 30% of primary care givers report that their children were cesarean-born (between March 2003 and February 2004). To the extent that there is a stigma associated with elective procedures, a potential concern is that the rate of cesarean birth may be under-reported in LSAC . However, this is not borne out in national statistics from hospital records that show comparable rates of cesarean birth — 28% and 30% for 2003 and 2004 respectivelyNo data were specifically collected for this project. The data used was previously collected by the Australian Institute of Family Studies (AIFS) and was conducted in full accordance with all relevant guidelines and regulations as spelt out in the AIFS Ethics Committee approval. This includes obtaining consent for survey participation and use of anonymized information for research purposes, as approved by AIFS. AIFS provided anonymized data for this project under an individual license agreement. In the analysis and in preparing the manuscript, we have adhered to all requirements under the license agreement. Data can be made available upon request to the corresponding author, subject to approval from AIFS.There are two types of cognitive development measures in LSAC. The first are scores from three interviewer-administered tests conducted between ages 4 and 9 that are part of the LSAC survey and the second are scores from a national standardized test in numeracy and literacy at age 8–9 that are matched to LSAC participants. All cognitive measures are age-normalized and standardized with respect to the weighted sample mean and standard deviation 39 and the Matrix Reasoning test (MR)40. The PPVT is an age appropriate vocabulary test designed to measure a child’s knowledge of the meaning of spoken words and their comprehension and ability to respond. The test was carried out in survey when the children were aged 4–5, 6–7 and 8–9. WAI is an assessment of the child’s readiness for school and measures the child’s ability to perform a range of tasks, such as reading, writing, copying, and symbol recognition. WAI was only carried out when the children were 4–5. Finally, MR is a test of problem solving ability, based on the Wechsler Intelligence Scale for Children. The test is age appropriate and was conducted when the children were aged 6–7 and 8–9.The interviewer-administered cognitive tests from LSAC B are the Peabody Picture Vocabulary Test (PPVT)41. Imputing these values instead of omitting them makes little difference to our analysis . NAPLAN is conducted in all Australian schools to measure performance in numeracy and literacy at grades 3, 5, 7 and 9, corresponding to ages 8–9, 10–11, 12–13 and 14–15. In the case of literacy, performance is measured over the domains of reading, writing, grammar and spelling. Each student’s performance in NAPLAN, including their national ranking compared to similar-age students, is made available to schools and students to monitor performance. At the time of analysis, only NAPLAN data for grade 3 was available for the LSAC B cohort. For students who were not in grade 3 at the time of testing, usually because they commenced school at a later age than the rest of the cohort, we imputed their values. The imputation process involved two steps. The first step involved using the sample with observed grade 3 NAPLAN scores to estimate regression model relations between grade 3 NAPLAN scores and personal information (such as other interviewer-administered cognitive tests). In the second step, we use results from the first step to generate predicted NAPLAN values for those with missing scores, that is, we apply the estimated regression model relations to the personal characteristics of those with missing NAPLAN scores19. Adverse child health outcomes include measures of obesity and care giver reported diagnosis of asthma, ADD or ASD. While measures of asthma and obesity are available at the time of cognitive testing, measures for ADD and ASD are only available at ages 6–7 and 8–9 years. Because only around two-thirds of care givers answer questions related to ADD and ASD at age 6–7, we use information at age 8–9 years when the response rate is much higher. Obesity is measured by whether the child’s Body Mass Index (BMI) is above the upper-limit of normal range of 19.3 for those 4–7 years and 23 for 8–9 years. Breastfeeding and maternal health measures are from the initial sample (6–12 months after birth). Breastfeeding is a binary measure of whether the child was breastfed at three months or not. Two self-reported postnatal maternal health measures were used: whether any depressive symptoms were experienced in the last 4 weeks  and whether general health was reported as fair to poor .In this study we measure the extent to which any relation between cesarean birth and cognitive development is mediated by lower rates of breastfeeding and adverse child and maternal health outcomes. We selected these variables because they have been previously associated with cesarean birth and are available in the data42 and possibly the risk of cesarean birth, which means failure to control for it will lead to bias due to unobserved confounding. However, we stress that our results are not sensitive to the inclusion of this control, or other child and maternal health risks in the data . Excluding postnatal interventions and prenatal risk factors with high rates of missing observations makes little difference to the results  on a su32 method, which like approaches proposed by Rosenbaum44 and Altonji45, bounds the relation under assumptions about selection on unobserved covariates . Under the Oster method, we estimate the lower bound of the OLS relation between cesarean birth and measures of child cognitive development using the following:In the second approach, we use the Oster45 method that assigns 32 argues that assuming a value of 1 is unreasonable in the presence of measurement error. Under equation 49. For the former, the association is only significant for school readiness at 4–5 and for the latter; the association is only significant for school readiness at 4–5, vocabulary at 4–5 years and vocabulary at 6–7 years. In alternative models estimated on 37–40 week births with individual gestational week dummy variables, we find few significant differences in outcomes between 37, 38 and 39 weeks relative to the reference case of 40 weeks for any of the outcomes.The estimated OLS relations between cesarean birth and child cognitive outcomes (equation ) for all50.Turning to estimates in Table Results from the first stage of our mediating analysis suggest that cesarean birth is significantly associated with lower rates of breastfeeding and higher rates of obesity and ADD  are found to be unrelated to lower rates of breastfeeding and adverse child and maternal health, including the diagnosis of child cognitive disorders.We find a negative relation between cesarean birth and a range of cognitive outcomes measured from ages 4 to 9. These relations are established after controlling for the socio-economic advantage associated with cesarean birth in Australia and a rich set of perinatal risk factors that et al.31 study. First, our sensitivity analysis suggests that bias from unobserved confounding is unlikely to explain the results completely and that causal relations are plausible. This does not mean that we have established causal relations because bias from unobserved confounding is still possible. Potential perinatal risks not controlled for include inheritable genetic traits, such as a lack of maternal height, that may drive both cesarean birth )51 and child cognitive outcomes52. Second, our estimated relations persist long-term and are not confined to children with health problems. Bentley et al.31 used perinatal records linked to school starting-age measures of cognition and could not examine longer-term outcomes or quantify mediating effects. By showing that only a small part of the cognitive gap is explained by mediating factors, our results leave open the possibility that direct mechanisms, such as disturbed gut microbiota, may be important. However, we cannot rule-out the possibility that at least some of the residual effect is due to measurement error, for example, under-reporting of the presence of health conditions by the primary care giver, or that the mediating effects are biased by unobserved confounding.We make two important contributions to the Bentley Evidence presented in this study should motivate more research. Because experimentation is unsuitable, future studies may focus instead on instrumental variables estimation using large-scale linked hospital and child development administrative records. The instrumental variables approach exploits natural experiments, that is, random events that lead to variation in assignment to treatment without directly affecting outcomes. A limitation of this method is that the results only have a local treatment interpretation and cannot be generalized to those unaffected by the random event that led to assignment.With the above caveats in mind, the key message to medical practitioners is to take a precautionary approach when formulating birth plans, especially when there are no apparent elevated health risks from vaginal birth. Informing mothers of the risks and benefits of cesarean birth should be a priority, which may be formalized by incorporating education sessions into practitioner guidelines.Supporting Information


N = 753). We conducted multiple linear regression to examine if prenatal log specific gravity adjusted urinary phthalate exposure was related to birthweight in term and preterm (≤37 weeks) infants, stratified by sex. We observed a significant association between mono carboxy-isononyl phthalate (MCOP) exposure and increased birthweight in term males, 0.13 kg . In preterm infants, we observed a 0.49 kg  increase in birthweight in relation to a one log unit change in the sum of di-ethylhexyl phthalate (DEHP) metabolite concentrations in females (N = 33). In summary, we observed few associations between prenatal phthalate exposure and birthweight. Positive associations may be attributable to unresolved confounding in term infants and limited sample size in preterm infants.Phthalate exposure is widespread among pregnant women but whether it is related to fetal growth and birth weight remains to be determined. We examined whether first trimester prenatal phthalate exposure was associated with birth weight in a pregnancy cohort study. We recruited first trimester pregnant women from 2010–2012 from four centers and analyzed mother/infant dyads who had complete urinary phthalate and birth record data ( Low birth weight and intrauterine growth retardation are significant risk factors for future morbidity including obesity and poor cognitive function , yet ideSome rodent toxicologic studies indicate that gestational di-ethyl hexyl phthalate (DEHP) exposure leads to reduced birth weight in offspring ,7. In huOur aim was to assess prenatal first trimester phthalate exposure in relation to birth weight among term and preterm infants in a prospective multi-center pregnancy cohort study, The Infant Development and the Environment Study (TIDES). We hypothesized that first trimester DEHP exposures would be inversely associated with birth weight outcomes.We summarize recruitment of the TIDES cohort and its characteristics briefly; details are discussed elsewhere in Barrett et al. 2014 [First trimester urine was collected in sterile and phthalate-free polypropylene specimen cups during initial recruitment visits. Urine was transferred into 5 individual 2 mL cryovials, and stored in freezers at <−80 °C. We measured specific gravity using a handheld refractometer at the time of urine collection, which was calibrated with deionized water before each measurement. Specific gravity is used to correct for urinary dilution. Phthalate metabolite concentrations were analyzed at two different sites. Three hundred subject samples for mothers of female infants were analyzed at the Environmental Health Laboratory at the University of Washington (UW). Per a modified version of the CDC method 6306.03, glucuronidated phthalate monoesters underwent enzymatic deconjugation, followed by online-solid phase extraction (SPE) coupled with reversed high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) to quantify the simple monoesters in urine . An addiThe limit of detection (LOD) of metabolites was between 0.2 and 2.0 ng/mL for the UW samples and 0.2 and 0.6 ng/mL for the CDC samples. For concentrations below the LOD, a value equal to each sample’s specific LOD divided by the square root of 2 was used . All uriWe examined the distributions of demographic characteristics and specific gravity adjusted phthalate concentrations. All phthalate concentrations were log transformed for analysis because of skewedness. Gestational age at birth is an important factor to account for in birth weight analyses, and traditional methods of covariate adjustment in regression models may not be appropriate ,19,20. TThe majority of women were between 20–40 years old (93%), white (66%), and had a college degree (74%) . A smallIn male, term infants, MCOP was significantly associated with a 0.13 kg increase  in birth weight in relation to one log unit change of MCOP , and thiThe hypothesis that DEHP exposure would be inversely related to birthweight outcomes was not supported by our findings. In contrast, we observed positive associations in preterm infants. Possible explanations include differences in timing of exposure during pregnancy and exposure concentrations changing over time. Our study is one of two to examine first trimester exposures in relation to birth weight outcomes . Our finWe examined males and females separately based on differential growth patterns between the sexes. We observed a suggestion of sex-specific effects with DEHP being positively associated with birth weight in female, preterm infants, and MBP inversely associated with birth weight in male, preterm infants. Other birth cohort studies noted sex specific effects with respect to phthalate exposures, but findings differed with respect to phthalate and timing of exposure ,13. SeveOther birth cohort studies differed from ours based on timing of exposure as well as matrix of measurement. We examined first trimester exposures while cohorts in New York, China, and Europe measured concentrations in the second or third trimesters, and serum or cord blood samples were used for phthalate measurements in the European cohorts ,9,10,11.Primary predictors of birth weight included socio-economic factors and maternal infections . While tStrengths of our study include the prospective study design that examined women from four different locations and centers. Birth weight was recorded directly from the medical record, and all lab personnel performing phthalate analyses were blinded to fetal outcomes. We obtained one spot urine sample in the first trimester of pregnancy. Concentrations can be variable over pregnancy, but one major predictor of variability is time of day of urine collection because ingestion of meals is related to exposure concentrations . We examOur analysis found little evidence to support a relationship between first trimester prenatal phthalate exposure and birth weight; and while there is a suggestion of an effect in preterm infants in a sex-specific manner, the sample size is too small to draw conclusions. Future studies should examine first trimester exposures in relation to birth weight in larger sample sizes that can accurately assess impacts in premature infants.In summary, we observed few associations between prenatal phthalate exposure and birthweight. First trimester prenatal phthalate MCOP exposure was associated with increased birthweight in male infants only. We did observe a positive effect for DEHP in preterm, female infants but our findings should be interpreted with caution. Positive associations may be attributable to unresolved confounding in term infants or limited sample size in preterm infants.