Eubacterium saphenum, Fretibacterium sp. human oral taxon(HOT) 360, TM7 sp. HOT 356, and Rothia dentocariosa), and cultivable bacteria  in saliva samples. In addition, ELISA analyses were used to determine the IgG titres against periodontal pathogens in serum samples. Subjects were categorized into a Healthy group  and periodontitis/gingivitis group  according to their periodontal status. The brushing duration was significantly lower in the PG group compared to the H group. Twenty-two of 90 subjects delivered PLBW infants. There was no significant difference in periodontal parameters and serum IgG levels for periodontal pathogens between PLBW and healthy delivery (HD) groups. However, ordinal logistic regression analysis revealed that a higher abundance of Treponema denticola, Prevotella intermedia, Fretibacterium sp. HOT360 and lower levels of Rothia dentocariosa were significantly associated with the presence of periodontal disease during pregnancy. Moreover, the amount of Eubacterium saphenum in saliva and serum IgG against Aggregatibacter actinomycetemcomitans were negatively correlated with PLBW. Taken together, unculturable periodontitis-associated bacteria may play an important role both in the presence of periodontal inflammation during pregnancy and subsequent PLBW.Recent studies revealed culturable periodontal keystone pathogens are associated with preterm low birth weight (PLBW). However, the oral microbiome is also comprised of hundreds of ‘culture-difficult’ or ‘not-yet-culturable’ bacterial species. To explore the potential role of unculturable and culturable periodontitis-related bacteria in preterm low birth weight (PLBW) delivery, we recruited 90 pregnant women in this prospective study. Periodontal parameters, including pocket probing depth, bleeding on probing, and clinical attachment level were recorded during the second trimester and following interviews on oral hygiene and lifestyle habits. Saliva and serum samples were also collected. After delivery, birth results were recorded. Real-time PCR analyses were performed to quantify the levels of periodontitis-related unculturable bacteria ( Dysbiosis of the oral microbiome leads to oral diseases and is also associated with the progression of systemic diseases, such as cardiovascular disease2, diabetes mellitus3, and preterm low birth weight (PLBW)4.The oral microbiome plays an essential role both in the development of normal oral physiology and host defenseAggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), Porphyromonas gingivalis , Tannerella forsythia (T. forsythia), Treponema denticola (T. denticola), Fusobacterium nucleatum (F. nucleatum) and Prevotella intermedia(P. intermedia) are recognized as key periodontal pathogens6 and they have been used as diagnostic markers of periodontitis8. However, the oral microbiome is also comprised of hundreds of ‘difficult-to culture’ or ‘not-yet-cultivable’ bacterial species, and their functions remain unknown9.Recent molecular techniques have revealed that several culturable bacteria of the oral microbiome, such as Eubacterium saphenum (E. saphenum),Rothia dentocariosa (R. dentocariosa), Fretibacterium sp. HOT 360 and TM7 sp. HOT 356 have been commonly identified in the oral microbiome of periodontitis patients and these bacteria have been identified as opportunistic pathogens and are associated with periodontal disease and infections13.A growing body of literature has suggested that there is a link between periodontal disease and preterm low birth weight (PLBW). Most of these studies focused on the roles of culturable periodontal pathogens, and no study has specifically investigated the role of unculturable bacterial species in PLBW. Four unculturable or difficult-to-culture bacterial species Given the potential importance of unculturable periodontal-associated bacteria and limited knowledge about their role in periodontal disease and PLBW outcomes, we investigated this topic in the current study. We determined the levels of four unculturable or difficult-to-culture periodontitis-associated bacterial species and six culturable periodontal pathogens in saliva samples collected from Chinese pregnant women with or without periodontal disease. In addition, the association of PLBW with maternal periodontal conditions and serum IgG titers against periodontal pathogens were evaluated.The duration of tooth brushing in the Periodontitis/Gingivitis group was significantly shorter than that in the Healthy group Table . There wThere were no significant differences between the two groups in IgG antibodies against periodontal pathogens Fig. .Figure 1P. gingivalis, A. actinomycetemcomitans, T. forsythia, T. denticola, P. intermedia and Fretibacterium sp. HOT 360 in saliva in the PG group were significantly higher than those in the H group. In contrast, R. dentocariosa was significantly lower in the PG group.As showed in Fig. P. gingivalis and A. actinomycetemcomitans were positively correlated with BOP positive sites (%). Moreover, the bacterial load of P. intermedia, T. denticola and Fretibacterium sp. HOT 360 in saliva were positively correlated with mean PPD, mean CAL, and BOP positive sites (%). On the other hand, R. dentocariosa was negatively correlated with mean PPD, mean CAL, and BOP positive sites (%).Figure Seven of 90 pregnant women delivered PB infants and the other fifteen individuals delivered SGA infants. There was no significant difference in the gestational week at birth (birth week), birth weight, incidence (%) of PB, and SGA between the Healthy and Periodontitis/Gingivitis groups Table .Table E. saphenum was significantly lower in the PLBW group than that in the HD group (p < 0.01). There was no other significant difference in periodontal pathogens between the two groups.Aa showed in Fig. E. saphenum was positively correlated with the gestational week at birth . There was no other significant difference between bacteria and birth results.As showed in Fig. T. denticola, P. intermedia, Fretibacterium sp. HOT360 and low amount of R. dentocariosa in saliva were significantly associated with the presence of gingival inflammation during pregnancy  in alignment with the 1964 Helsinki declaration and its later amendments on comparable ethical standards. Written informed consent was obtained from all human subjects who participated in this investigation.34. The tail was set at one, the odds ratio at 2, Pr(Y = 1/X = 1)HO at 0.2, alpha error at 0.05, and power (1 – beta) at 0.8, R2 other X at 0, X distribution at normal, X parm μ at 0 and X parm σ at 1 for logistic regression, and the minimum sample size was estimated to be 88 participants.The present study was a longitudinal observational study. The optimal sample size was determined using the G*Power software35. Therefore, the PLBW group consisted of PB and/or SGA. The healthy delivery (HD) group was defined as pregnancy’s showing a gestational age ≥ 37 weeks and a birth weight of more than the 10th percentile for gestational age.Ninety Chinese pregnant women aged 21 to 39 who received a periodontal examination during their middle trimester of pregnancy were recruited in the Department of Periodontology, West China Dental Hospital, Sichuan University from May 2015 to May 2018. All subjects had a minimum of 20 teeth and did not receive any periodontal treatment or antibiotic treatment within three months of their participation in the study. Any subjects with systemic disease or multiple gestations were excluded. All patients were divided into a periodontitis/gingivitis group  and gingival health group  according to their periodontal status (described subsequently). After delivery, gestational age at birth, birth weight, infant gender, and delivery mode were recorded. Preterm birth (PB) was defined as a gestational age less than 37 weeks and small for gestational age (SGA) delivery was defined as a birth weight of less than the 10th percentile for gestational age based on Chinese normsAll pregnant women underwent a full-mouth periodontal examination at 26 to 28 weeks of gestation. Before the examination, information about confounding factors, such as oral hygiene behavior , smoking habits, socioeconomic characteristics , and an alcohol consumption habits was obtained by structured interviews.38.Periodontal examinations were performed by one periodontal specialist (C.Y.) with the use of a manual probe . The periodontal parameters, including pocket probing depth (PPD), clinical attachment level (CAL), and bleeding on probing (BOP), were recorded at all six sites for each tooth . Subsequently, subjects were divided into a periodontitis/gingivitis (PG) group (n = 70) and a Healthy (H) group (n = 20) according to periodontal status. Subjects showing BOP in > 25% of sites and/or ≥ 4 teeth with one or more sites of PPD ≥ 4 mm were placed in the PG group. Subjects who did not fit the above criteria were diagnosed as having clinical gingival health and were placed in the H groupg for 10 min at 4 °C. Subsequently, serum samples were collected and immediately stored at − 80 °C until further analysis.One mL of unstimulated saliva was obtained at the same time as the periodontal examination and then stored at − 80 °C. Participants were instructed to abstain from food intake and oral hygiene procedures for at least 2 h before saliva collection. Also, at 28 weeks of gestational age, peripheral blood samples were collected and centrifuged at 1500×E. saphenum, R. dentocariosa,Fretibacterium sp. HOT 360, TM7 sp. HOT 356, A. actinomycetemcomitans, P. gingivalis, T. forsythia, T. denticola, F. nucleatum, and P. intermedia41 . The amount of specific bacterial species in duplicate saliva samples were then quantified by real-time polymerase chain reaction (RT-PCR) using primers and TaqMan probes for The optimized thermal cycling conditions for amplification were carried out on a thermal cycler device  at 95 ºC for 30 s, 95 ºC for 5 s (40 cycles) and 60 ºC for 30 s. Standard curves were obtained by using tenfold serial dilutions of artificial synthetic genes, which contained the amplified region corresponding to 16S sequences of each bacteria .A. actinomycetemcomitans, P. gingivalis, T. forsythia, T. denticola, F. nucleatum and P. intermedia were determined using an enzyme-linked immunosorbent assay (ELISA) according to a previously described method42. The sonication-extracted antigens of P. gingivalis (ATCC 33277), A. actinomycetemcomitans (ATCC 43719), P. intermedia (ATCC 25611) and T. forsythia (ATCC 43037) were prepared by the method of Yano-Higuchi et al.43. Similarly, F. nucleatum (ATCC 25586) and T. denticola (ATCC 35405) antigens were prepared by previously described methods45.Serum antibody titers of IgG against the culturable periodontal pathogens including Serum levels of hs-CRP were measured using a commercial ELISA kit according to the protocol supplied by the manufacturer .Statistical analysis was performed using SPSS 20.0 software . Initially, the distribution pattern of the data was assessed using the Shapiro–Wilk test. Thereafter, an unpaired t-test was used to analyze the statistical differences in age, brushing frequency, brushing time, weeks at birth, and birth weight between the H and PG groups, or HD and PLBW groups, respectively. In addition, a Mann–Whitney U-test was used to analyze the mean PPD, mean CAL, sites with PPD ≥ 3 mm (%), sites with PPD ≥ 4 mm (%), sites with PPD ≥ 5 mm (%), BOP-positive sites (%), serum CRP concentration, the number of bacteria in saliva, and the serum IgG titer between the H and PG groups, or HD and PLBW groups. Also, a chi-squared test was used to analyze the primiparity rate, the utilization rate of dental floss or interproximal brushing, the utilization rate of mouth rinse, the amount showing more than 12-years of education, the amount with more than the local average income, the amount with dental insurance, Caesarean section rate, PB rate and SGA rate between the PG and H groups, or the PLBW and HD groups. Furthermore, Pearson's correlation coefficient test was used to analyze the correlation between periodontal parameters and bacterial load.P. gingivalis, A. actinomycetemcomitans, T. forsythia, T. denticola, P. intermedia, Fretibacterium sp. HOT 360, R. dentocariosa,E. saphenum in saliva and IgG against A. actinomycetemcomitans using ordinal regression analysis, respectively. Odds ratios and 95% confidence intervals were calculated. A P value less than 0.05 was considered statistically significant.To determine potential bacterial and periodontal risk factors for pregnant women, we evaluated correlations between the presence of periodontal disease or PLBW with PPD ≥ 5 mm (%), BOP, the duration of tooth brushing, the amount of Supplementary Information 1.


Home births in high risk pregnancies and unassisted childbirth seem to be increasing in the Netherlands. There is a lack of qualitative data on women’s partners’ involvement in these choices in the Dutch maternity care system, where integrated midwifery care and home birth are regular options in low risk pregnancies. The majority of available literature focuses on the women’s motivations, while the partner’s influence on these decisions is much less well understood. We aimed to examine partners’ involvement in the decision to birth outside the system, in order to provide medical professionals with insight and recommendations regarding their interactions with these partners in the outpatient clinic. An exploratory qualitative research design with a constructivist approach and a grounded theory method were used. In-depth interviews were performed with twenty-one partners on their involvement in the decision to go against medical advice in choosing a high risk childbirth setting. Open, axial and selective coding of the interview data was done in order to generate themes. Four main themes were found: 1) Talking it through, 2) A shared vision, 3) Defending our views, and 4) Doing it together. One overarching theme emerged that covered all other themes: ‘She convinced me’. These data show that the idea to choose a high risk birth setting almost invariably originated with the women, who did most of the research online, filtered the information and convinced the partners of the merit of their plans. Once the partners were convinced, they took a very active and supportive role in defending the plan to the outside world, as well as in preparing for the birth. Maternity care providers can use these findings in cases where there is a discrepancy between the wishes of the woman and the advice of the professional, so they can attempt to involve partners actively during consultations in pregnancy. That will ensure that partners also receive information on all options, risks and benefits of possible birth choices, and that they are truly in support of a final plan. Since approximately the 1960’s, men have been increasingly involved in the process of labor and birth, and are, in most western high income countries, generally expected to be present in the labor room–5. BecauTo date, there are limited data on partner involvement in decisions concerning place of birth and choice of birth attendant, neither when these choices conformed to the local maternity care system, nor when they were against medical advice.In most high income countries, hospital birth has become the norm, and home birth, even in low risk pregnancies, is considered by mainstream maternity care providers as against medical advice. HoweverIn the Netherlands, Hendrix et al. investigSeveral studies have been done in countries where all home births are against medical advice. Three Scandinavian studies–21 and aIn the Netherlands, 30% of all births are attended by community midwives, about half of which are home births. Almost This current study set out to examine the involvement of Dutch partners in the decision-making process concerning a home birth in a high risk pregnancy or UC in a country in which home birth for low risk women is integrated in regular maternity care. This information could help health care providers to involve partners in conversations concerning decision making surrounding choice of place of birth, whether within or outside the system. To that end, we interviewed the majority of the partners of the women who were the subject of our previous study.The COREQ criteria for reporting qualitative research were useThe majority of interviews (18) were conducted by the first and last authors (MH and LH), while the remaining five were conducted by three midwifery students under the supervision of the last author (LH). All interviewers are women, and both MH and LH are experienced in conducting interviews for qualitative studies. All interviewers have a background in midwifery/obstetrics, and LH also has a background in anthropology. EdM participated in designing the study, JvD, IdG, AS, FV and EdM gave constructive criticism on earlier drafts of this article, and approved the final version.None of the partners were known to the interviewers prior to the interviews. The partners were aware that the interviewers had a professional interest in birth outside guidelines, women’s rights and the Dutch maternity care system, and were known in the field as supporters of women’s rights and autonomy. All participants gave verbal informed consent for their quotes to be used.This exploratory qualitative research used a constructivist approach and a grounded theory method. This stInterviews were semi-structured by use of a topic list  but were™). After 10 interviews, the last author (LH) coded an interview as a peer review to see if any codes were missing, and one code was added. Coding was started from the bottom up, with each interview adding and building on the coding tree (All interviews were coded by the first author (MH). Data analysis was done using qualitative data analysis program MaxQDA , home Vaginal Births after Cesarean (VBAC)’s (6), home breech births (4) and twin home births (2). There were 25 live births and two intra partum deaths. The intra partum deaths involved one case of a quick and uncomplicated term breech birth, where the baby was born without vital signs, resuscitated and died several days later. The other case was a protracted and unmonitored term VBAC, where the baby died during labor, presumably due to asphyxia. There was no ruptured uterus. This was confirmed afterwards at cesarean section. The age of the partners ranged from 24 to 43 years, with almost half (43%) being older than 35. Most partners (86%) were employed, and two thirds (62%) were highly educated, of whom five (24%) had a university degree. Two partners were of Moroccan descent, all others were ethnic Dutch. For a minority of the partners (21%), the birth relevant for the interview was their wife/girlfriend’s first birth, while for most partners (67%), it was their wife/girlfriend’s second and/or third birth which was the subject of the interview. Almost half (43%) of the secondary care indications concerned a planned VBAC. Demographic data can be found in Home births are described as ‘attempted’ when the birth was not completed at home and transfer to the hospital was necessary, and, in one case, as ‘intended’, when an ante partum complication occurred, making it necessary for the couple to abandon their plans for a UC.After grounded theory analysis of the 23 interviews, four main themes emerged: “Talking it through”, “A shared vision”, “Defending our views”, and “Doing it together”. After careful consideration of the data, one overarching theme emerged, which was “She convinced me”.In all but one case (an attempted home VBAC), the idea to go against medical advice and choose a UC or a home birth in a high risk pregnancy was first suggested to the partners by their wives/girlfriends, whereas the partners themselves had no strong personal feelings or preferences about the birth setting. Deciding to go against medical advice in their birth choices was not a decision that was made overnight. All partners reported that this required a substantial amount of “talking things through” in order for them to agree to the proposed plan.Most of the partners in this study stated that the idea originated in a negative experience in regular maternity care. In either a previous or the current pregnancy, partners and their wives/girlfriends had experienced bad communication skills, paternalism, and a lack of flexibility, continuity, informed consent and shared decision making from maternity care providers. In many cases, there had been a conflict between the couple and providers, and in some cases even threats of legal action being taken by care providers against the couple:“So it was the same again: “Aren’t you afraid your child will die, your wife will die?’ Really putting pressure on us and then I got a bit angry like: This isn’t health care, this is not thinking things through together with people, this is only making things hard for them.” Partners reported that, because of these negative experiences, their wives/girlfriends decided to look for an alternative to regular care. They stated that the women suggested the idea of going against medical advice after doing extensive research, mostly on social media, which was then presented to the partners:“[She] really took all this in like a sponge, and spent night after night searching on Facebook groups about this subject, and the book ‘Free Birth’, […] and sometimes she would show me things.” “[Wife] spent a lot of time searching the internet for all kinds of articles. I didn’t have the opportunity to spend that much time on it, so…at one point I just assumed she knew more than I did.” During the interviews, it became clear that several partners had not done much research for themselves, rather they had been given limited information on the risks that the proposed birth plan entailed, and they appeared to be not quite aware of what risks they were taking. It appeared that the information at their disposal largely originated from their wives/girlfriends, in contrast to what they might have been told by medical professionals if they had been present for most or all consultations:“I wonder if this was a high risk pregnancy. Is this always considered high risk? […] OK, I did not experience this as high risk. […] Didn’t realize, either. I did think it was higher risk than a singleton pregnancy, but…didn’t really consciously think about it.” “What are the chances of an actual uterine rupture? They are no larger than that a firstborn comes out with a prolapsed umbilical cord. […] So we felt like: what is the big deal?” The information presented to them by the women convinced the partners that interventions could also cause pathology, and presence of care providers could interrupt the process of childbirth. They felt that hospital care was only focused on the biomedical model of childbirth, not taking into account that giving birth is a major life event. In addition, they stressed that evidence based medicine is limited, and not always applicable:“Giving birth is a natural thing. Basically, apart from a few complications, every woman can give birth normally. When you are in the hospital, it is a much smaller step […] to have an intervention. If you are not in the hospital, you will have to do more yourself. […] One intervention often leads to the next, with the whole cascade we had last time.” The partners had the impression that maternity care providers were afraid of legal consequences in case of a bad outcome, which would cause them to exaggerate risks communicated to the couple:“We mostly encountered people who were very afraid. Very afraid things would go wrong.” Midwives and obstetricians were accused of creating more and more conditions to be met, leaving the couples little choice but to either agree to all proposed measures or move outside the system and choose a home birth in a high risk pregnancy, or an unassisted childbirth:“And every time they made up another reason not to agree [to what we wanted].” Most couples had extensive conversations about the subject of a home birth in a high risk pregnancy, or an unassisted childbirth, in which they weighed the risks together:“I was often aware that it is actually just…actually a big risk…that you are at home. And you have to wait ten minutes for an ambulance….and you don’t have ten minutes.” Agreeing to support their wives/girlfriends in a decision to choose a home birth in a high risk pregnancy or a UC was not an easy choice to make for some partners, and required them to let go of their fears and embrace trust in a good outcome:“Well, that was a difficult process for me too. Actually, everything that you encounter, that I could encounter, that I am afraid of….is that real, is it justified or is there a solution to be found?” After much discussion and soul-searching, partners reported that they were convinced by the women’s arguments and agreed to their suggestions, which meant that they would also accept a bad outcome, if it came to that:“We talked through the implications together. What it could mean and what we would do with this [a bad outcome]. We clearly said to each other: we make this choice and we take responsibility for it ourselves.” “What does it mean that things could go wrong? Both with [wife] and with [baby]. And what does this do to me? And what do we need to go down this path together?” In summary, a (previous) negative experience in regular maternity care led the partner’s pregnant wives/girlfriends to suggest going against medical advice in their birth choices. This necessitated much discussion, during which the partners were convinced by the women’s arguments about negative aspects of maternity care and their research on social media into alternative birth options, and agreed to go down this path, support their wife/girlfriend and accept responsibility for this decision and the outcome together.During discussions, the partners became convinced by the women’s arguments, came to share their views on the best birth option for them, and agreed to the plan for a home birth in a high risk pregnancy, or an unassisted childbirth. This became a shared vision, in which not only the physical process of giving birth, but also the process of becoming a family played an important role:“I come from a family myself, where closeness is very important. That is a home situation. I want it to be like that for my children, I want to create that and contribute to it. I think that has only strengthened our choice for home.” Many partners believed that the way the birth went and how the baby came into the world would affect the dynamics of their family, their bond with the baby, and perhaps even the character of the child:“And the problem with [name child] actually was that we gave away too much [control] to those doctors, that our son did not actually have a connection with us. Not until much later. And that caused him a lot of stress. He slept badly. At home, he almost never slept. Awake a lot, crying a lot, those sort of things.” Partners stated that they felt that birth is a natural event, which has the best chance of proceeding without problems if left alone. They were convinced that in order to have a good birth, you need to do what feels right for you, and women have to be able to relax and have faith in themselves and those around them:“When a woman gets into the right mood, when she withdraws almost like an animal in the bushes and does her thing and closes off and when there is quiet and she makes her own [endorphins] or whatever is necessary, then birth will just take its course.” For some partners the ultimate form of trust is unassisted childbirth:“We are convinced that many things will sort themselves out if you just let things take their course and don’t disturb […], then usually it will go well.” Several men stated that they believed it was very important for the woman to feel good about the plans for the impending birth, since she was going to be the one who had to give birth:“What I can say about it, is that how [she] sees it and how [she] feels it, that that comes first. If [she] says now: ‘[next time] I want a C section up front’, then I would find that very difficult, but eventually I would support that.” “And then I felt like: if this is what you want, we’ll do it. Then there is only one thing I can do, and that is get behind her decision and support her in it.” Almost all partners reported that through conversation with their wives/girlfriends, they had become convinced by the women’s arguments and had developed a shared vision on the nature of childbirth, in which an intimate, undisturbed home environment played a large role in the chance of a successful normal birth.Having established a shared vision, most partners broached the subject of going against medical advice with their family and friends. The reactions they encountered ranged from supportive to outright hostile. The most frequent response they received was an aversion to risk taking in childbirth, which led family members and friends to counsel against the couple’s plans and in favor of a birth within protocol. Even though they had become convinced of the merit of the intended birth plan, partners found it difficult to explain their reasoning in their own social circle, which sometimes left them feeling insecure about the impending birth:“Their first reaction was very intense: ‘We do not approve of this! Do you even know what you are doing? You are insane!’ All sorts of phrases rained down on us. And yes, that made me insecure.” Some family members/friends considered midwives and obstetricians to be the experts and couples were warned that people could point fingers if things ended badly:“I think for every lay person, you know, who did not grow up with this, who grew up with the idea of: it happens in the hospital, so there will be a need for professionals… I think that can quickly give rise to the idea that having an unassisted home birth, with nobody there, not even a midwife, that is scary, that is dangerous, etcetera. That is, I think, the first reaction you have.” Some partners did not discuss their plans with anyone at all, whereas others were actually inspired by other couples of their acquaintance who had gone down the same route. A few couples encountered favorable responses from their social circle, and even attempted to convince others to make the same birth plans, after their birth had gone well:“And when you tell people how it went and [they] think: ‘Oh, I might want that too, or not, and [they] think: ok.’ Yes, it is quite the conversation starter, and I think that is fun and nice.” In addition to having to defend their plans in their own social circle, some partners also felt they had to defend the women against their care providers. In two cases, the partners even went to a hospital appointment alone, without the woman, to confront their obstetrician:“The last week before the due date the doctor wanted another meeting. [Wife] felt like: ‘I don’t want to talk unless he has something [new] to offer.’ […] She didn’t want to go, so I said: I will go and talk to him. […] It was a pretty stressful meeting. I was glad [wife] wasn’t there. She had gone through enough.” In conclusion, after having established a shared vision, most partners took it upon themselves to defend the couple’s plans in their own social circle, and some attempted to convince others, sometimes against negative responses. In addition, two partners even confronted a medical professional in order to defend their wife/girlfriend’s wishes.Having developed a shared vision and discussed their intentions for the birth in their own social circle, the couples started preparing together for the birth they had decided on. Most of the partners were very supportive. Some reported taking a preparatory class like hypnobirthing together with their wives/girlfriends, or going with the women to a designated clinic for couples who are considering birth choices against medical advice, in order to get all the information available. Several couples discussed their intentions with an obstetrician at their local hospital, so there would be a record of the situation and their intentions in case they needed help during the birth:“We went to the hospital just so we had seen them and to say: ‘Look, if things unexpectedly go differently, then we will come here, because we live five minutes away, so this is the hospital we will go to.’” Another way to prepare for an unassisted childbirth was getting some selected tests, so the couple would not be surprised during the birth by, for example, twins:“With the fifth [child] we eventually had an ultrasound done. But that was more because there was so much movement inside her abdomen that we thought: OK, it looks like there are too many limbs there.” Some couples made extensive and well thought out plans together for what to do in case they came across certain complications during the birth, whereas others decided doing so would only become a self-fulfilling prophecy:“Yes, I asked those questions, like what if she suddenly starts bleeding, you would have to call the ambulance. […] Or what if there is meconium in the water. Or what if the cord is around the head. […] [During the birth] I listened to [wife] very carefully for signs that she might need help.[…] If she would start acting funny then there would be a problem, but she didn’t.” “But actually we did the same thing as when you get into a car. You don’t think like: oh, if I get into an accident I will do such and such. We basically always assumed things would go well.” Most of the partners report writing an extensive birth plan together, often concerning intentions for a water birth. In a few cases, the unavailability of the option for a water birth in regular care was part of the process that led to the decision to choose home birth:“Well, the hospitals in this area didn’t offer that [a water birth]. That was confirmed during the conversation [in the clinic]. If during that conversation it had turned out that ‘Listen, that is possible here, with [midwife]’, […] you could do it in the bath, and…That didn’t happen, so […] we would have had to go elsewhere for that.” For some couples, the choice for having a home birth in a high risk pregnancy meant they had to find another midwife, since obstetricians do not attend home births, and their regular community midwives were unwilling to attend a high risk birth at home. Having to find a new provider, sometimes in the final stages of pregnancy, was a source of stress for the partners and their wives/girlfriends. The few midwives that were willing to attend such births were few and far between, meaning that travel distances could be further than couples would have liked:“That was quite a search. [wife] has telephoned a lot of people, and… look, because we were quite far along in the pregnancy, the time you have left is quite short. That may limit your options […].” When a midwife was found, it was also considered important by partners that there would be a ‘click’, a connection with the midwife in question and that the wishes of the couple would come first, not the guidelines:“When I shook her hand and looked into her eyes, I thought: this is the one.” “Someone to just be there, and attuned to our needs. Instead of us having to accommodate her, so to speak.” In cases of intended unassisted childbirth, partners reported that they chose this option because the couple did not see a great deal of use for a midwife, other than just to be there in case problems arose during the birth:“To my mind, the best scenario would be if you could deliver unassisted with a midwife present who just sits on the corner of the sofa with a cup of tea, and does nothing unless she is asked.” Finally, partners spoke of what they believed their own role during the birth should be. Several partners stated that they felt the role of the partner during both pregnancy and birth should be much larger than it currently is:“I think there is a world to gain in how you can help your wife to get in the right mood, that she almost detaches a little from the world, feels safe, calm, and…that the process gets going and the birth goes smoothly. […] Because right now, you are a bit like an appendage, you know…[…] You have your role, but you are not the one who will be doing it.” The partners wanted to be involved and felt that they should be both constant companion and defender of the woman, and help her get through the birth from start to finish, doing it together:“Listen, you [as a partner] have a role during the birth. You need to make sure your wife is heard […], and not overwhelmed by all the medical stuff.” “I can be there for you […]. I really want to be involved, and stay involved. And not that some protocol says I can’t be there or I can’t see certain things. I want to see them.” In summary, in addition to defending the couple’s ideas to others, partners also took an active role in making detailed plans for the birth and finding a new midwife. They felt that they should also have a larger role during the birth itself, helping and supporting their wife in giving birth in the way that she wanted.After careful consideration of all four major themes and their subthemes, a pattern can be discerned, at the core of which is the process of the women convincing the partners of their views .As stated previously, one partner brought up the idea of a home VBAC. In addition, two partners first suggested the idea of a water birth to the women, which may have been a factor in these couples’ ultimate decision to go against medical advice, since water births are not always available in hospitals, or not for every high risk pregnancy. In all other cases, the women first suggested the idea for a home birth in a high risk pregnancy or a UC to the partners, did most of the research, and discussed what they had found. These discussions were in-depth, during which much soul-searching on the side of the partners took place. Through these discussions, the partners became convinced not only of the merit of the women’s plans, but also of their objections to regular care and of their views on birth in general. This led to a shared vision for the desired care, and caused the partners to defend the birth plan to other parties, as well as actively participate in (preparations for) the actual event. Preparing for and going through the process of these births was, for most partners, an intense experience, which strengthened the bond in their relationship, and made them come through this stronger as a couple:“The fact that she provided information for all my questions, either scientific articles or just other stories, you know. I thought: ok, well, this has been researched so thoroughly by her, that I thought, I can support this. […] It sort of happened to me, you know. She started doing the research and I sort of got sucked into it.” “It was mostly my wife, I have to say. What she gave to me, I read, but she was the one who did all the research. […] There is so much information on the internet. You can’t just trust everything. […] But when she dives into something, she does it right, you know? […] But at first I was very critical. When I first heard of it [UC] I thought…I don’t know about this. It can’t hurt to have somebody there. But when we talked about it a lot, and [wife] had explained to me what the effect can be of just somebody being present….then I understood what she meant and how it works. And then I was convinced in the end that we can do without [a midwife]” Even in both cases where there was a bad outcome , the partners stated that, although things ended badly, they were still convinced the choice that was made was the right one, and they would make the same choice again if necessary. They reasoned that, when a decision is made on the right grounds, it is always the right decision, no matter how things end. However, one partner  differed from all other partners in respect that, in hindsight, he had some serious misgivings about the choices that were made prior to and during his wife’s birth. She persuaded him to go along with her plan for home birth by showing him research she found online, which left him not entirely convinced:“At some point you think: fine, you do the research then. On the other hand, it did occur to me: aren’t you using those articles that are the most convenient for you? […] I didn’t know that much about it, true. Then I would have to search for studies myself which would refute what [she] found. Then what would we actually be doing? That makes no sense at all.” His wife found a midwife on the other side of the country, which also struck him as strange:“I didn’t actually realize that [our choices] were that unusual until [wife] said: ‘I found a midwife from [across the country].’ I thought: wow, what? If you have to go that far afield, [twin home birth] must be a strange step to take. […] I did not actually talk to the midwife until the birth itself and…then I was not completely convinced and sure that this was the right decision.” At one point he was no longer fully on board with proceeding with a home birth, as he felt his family was threatened by social services being called in due to his wife’s refusal to go to the hospital:“Until that point it was [wife’s] birth, […] but at that moment something changed, because suddenly this was about my family too. […] I had reached the point where I thought: just give in and go to the hospital already, because….you may have some wishes concerning your birth, but how much are you willing to risk to make that happen?” Much later, the partner and his wife discussed the situation, but still did not agree:From what I saw of her here, I did not have a lot of confidence in [the midwife], I must say. […] It does not make conversations at home any easier. I have been told: ‘You are just like those doctors.’ Yes. It has been a pretty difficult time.” This qualitative study involved in depth interviews with 21 male partners of Dutch women who gave birth at home in a high risk pregnancy or had an unassisted childbirth, choices that are explicitly against medical advice.Unlike in the study by Bedwell et al., not allIn contrast with other studies,19,21,35In addition, in accordance with the findings by Longworth and DejoThis shared vision was evident through remarkable similarities in statements about the regular maternity care system between the partners in this study and their wives/girlfriends in our previous study. The intAs stated in the introduction, several previous studies have shown that, contrary to the findings of this study, men are quite often not very involved in the process of pregnancy and childbirth–5. EngagThe partners in the current study had a high level of engagement with the process of pregnancy and childbirth. Similar to studies by Jouhki et al. and ViisDejoy in her 2011 dissertation on the role of male partners in decision making around childbirth, found six main roles for partners in this process: bystandOnce they were convinced by their wife/girlfriend of the intended plan for the birth, they defended these views to their social circle. In accordance with the findings of Fenwick, SweeneyTwo partners went even further in their role as protector of the woman, and went to the hospital in her place to confront a maternity care provider. This phenomenon can also be found in the studies by Locock and DrapThis study shows, that in cases of birth wishes against recommendations, the women were the main and frequently the suspected only source of information for the men, and convinced the men of their ideas and plans. Therefore, when maternity care professionals are confronted with a pregnant woman who is planning on going against advice in her birth choices, it would be helpful to realize that she will most likely not make this decision alone. As Osamor and Grady state, “There is currently a lack of (internet) sources of information specifically designed for partners of pregnant women, with almost all sources focusing on the women themselves. We therefore recommend the construction of specific websites for and by prospective fathers and care providers, which not only provide information but also focus on decision making.Finally, a situation in which the chasm between professionals and pregnant women becomes so wide that it becomes necessary for the partner to advocate for the woman is an undesirable situation. Health care professionals should never allow themselves to end up on opposite sides from their patient, even if there is a disagreement on the best management plan. Instead, they should position themselves beside the woman, both physically and metaphorically. They should practice shared decision making, exploreThere are several strengths to this study. First, for a qualitative study, it is large, with 21 in-depth interviews with men with varying levels of education and different ages. Second, it is the first study on partner involvement in decisions regarding birth choices against medical advice in the Netherlands. This is important because it is likely that these occurrences are relatively rare here, since home birth for low risk women is integrated in the regular maternity care system, and therefore not against medical advice. Third, it is part of a larger project, for whiNaturally, there are also several limitations to this study. First, in approximately a third of cases the wife/girlfriend was present during the interview, which may have caused partners to give certain desirable answers. However, we did not discern any noticeable differences in answers between partners who were interviewed alone, and those who had their wife/girlfriend present. Second, we did not interview any partners whose wife/girlfriend wanted to go against medical advice in her birth choices, but where the partner convinced the woman to stay within regular maternity care. This is an important point, since it is likely that there may be many more of those cases, but they are impossible to trace, and therefore, no comparison on partner involvement in decision making can be made. Third, there was no member check in the form of either returning transcripts to the participants or organizing a feedback focus group. This was deemed impossible and/or impractical due to logistic and time restraints. However, we did not rely on field notes alone, rather, all interviews were transcribed verbatim. Therefore, there is little doubt concerning the actual words used by the participants. Fourth, since the partners were interviewed months to (in a few cases) several years after the events leading up to the relevant births, it is possible that, with the benefit of hindsight, they appear to have given the considerations concerning these births more thought and meaning than they actually did at the time. Finally, the interviews were performed by researchers from the field, with extensive background in Dutch maternity care, and a professional interest in birth choices against medical advice. It is possible that this fact influenced the tone and content of the interviews. Perhaps some participants were more, or less, negative about Dutch maternity care than they would otherwise have been. On the other hand, their professional expertise allowed the researchers to formulate pertinent questions, which helped in constructing a relevant topic list and likely added depth to the interviews.This qualitative interview study examines the involvement of partners in decision making concerning choices for a high risk birth setting against medical advice in the Netherlands. Four main themes were found: 1) Talking it through, 2) A shared vision, 3) Defending our views, and 4) Doing it together. From the data, one overarching theme emerged, and that was “She convinced me”. This study shows that the idea for having a home birth in a high risk pregnancy or an unassisted childbirth almost always originates with the women, who seem to be the main source of information for the partners. This information appears to be ‘filtered’ by the women, and convinces the partners of the merit of the women’s plans. They adopt and assimilate the women’s views on childbirth. They support these views, which are now shared, by defending the plan for a birth against medical advice in their social circle, as well as in contacts with maternity care providers. Once convinced, the partners are very involved in planning and preparing for the birth. Maternity care providers can use these data to attempt to involve partners more during consultations in pregnancy, especially in cases where there is a discrepancy between the wishes of the woman and the advice of the professional. That will ensure that partners also receive information on all options, risks and benefits of possible birth choices, and that they are truly in support of a final plan. More research is needed into partners’ satisfaction with births both inside and outside the system.S1 File(DOCX)Click here for additional data file. 18 Nov 2019PONE-D-19-18382‘She convinced me’- Partner involvement in choosing a high risk birth setting against medical advice in the Netherlands: a qualitative analysis.PLOS ONEDear Dr. Hollander,Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.Please note that Reviewer 3 recommended a "reject decision". We will thus consider absolutely necessary that you address in your revised manuscript all the methodological points raised by this reviewer, including the number of interviewed participants and the statistical analysis. 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Please see our Supporting Information guidelines for more information: http://blogs.PLOS.org/everyone/2011/05/10/how-to-check-your-manuscript-image-quality-in-editorial-manager/2. Please upload a new copy of Figure 1 as the detail is not clear. Please follow the link for more information: [Note: HTML markup is below. Please do not edit.]Reviewers' comments:Reviewer's Responses to QuestionsComments to the Author1. Is the manuscript technically sound, and do the data support the conclusions?The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: YesReviewer #2: YesReviewer #3: No**********2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: N/AReviewer #2: N/AReviewer #3: No**********3. Have the authors made all data underlying the findings in their manuscript fully available?PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.The Reviewer #1: NoReviewer #2: NoReviewer #3: Yes**********4. Is the manuscript presented in an intelligible fashion and written in standard English?PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #1: YesReviewer #2: YesReviewer #3: Yes**********5. Review Comments to the AuthorPlease use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. Reviewer #1: This qualitative study explores the involvement of 21 partners in the dmp regarding a home birth in a high risk pregnancy or unassisted childbirth.The study design is adapted. The researchers might specify whether the research paradigm is to aim for change in care practices or whether a specific objective for the organisation of care was targeted.It would be necessary to specify at the level of methodology the a priori of the researchers who are mentioned in an implicit way in the discussion.Ethical obligations have been met.Results are clear and well presented. Themes and sub themes are illustrated with verbatims.Regarding the motivations of the fathers, it seems that they mainly followed their wives. Were the researchers able to assess whether fear was a driving force among the partners, in terms of fear, whether it was to generate a couple conflict, or to upset their pregnant wife ?Finally, was the (future) child's well-being present in their speech ? If not, this could be mentioned.Some remarks regarding the discussionThe authors might avoid some repetitions in the discussion and conclusion.They could broaden the point of view on this dm issue by mentioning the role of emotions as the driving force behind decisions and the possible impact of cognitive biases, especially the "confirmation bias" that can be imagined in the way information transmitted to partners is described by some partners as "sorted" and accepted quite passively by them.Globally, the research paper is valuable:this work can concretely promote decisions involving partners. This work is original, and deals with a public health problem with significant health implications.This work can concretely promote decisions involving partners, who are also future fathers.Reviewer #2: I have read with great interest the paper of M. Hollander et al. and I think it is of scientific quality high enough and deserves publication in PLOS, providing the authors are willing to give some precisions.In summary, the authors conducted a qualitative research in order to understand better the role of women’ partners choosing high risk birth setting against medical advice. They interviewed 21 subjects and found 4 main themes: “Talking it through”, “A shared vision”, “Defending our views”, “Doing it together”. The overarching theme that covered all the others was “she convinced me”.First, I would like to congratulate the authors for their hard work putting through so many interviews and for the quality of their transcriptions.In general, the manuscript is well written and easy to read. However, it is a little bit long and the authors should go forward in their discussion and not only rephrase most of the results.A weakness of this study also lies in its retrospective nature and sometimes the long delay between pregnancy / delivery and the interview. This could have introduced a recognition bias. Furthermore, can the authors precise if the couples had subsequent pregnancies and their choices for delivery / issue of the pregnancy?The fact that the authors interviewed the partners of women previously interviewed in another study could also have introduced a bias as they might have read the results of the previous study. Obviously, this is also a strength of this study since it helped increasing the number of partners interviewed.Theses limits should appear clearly in their discussion.By any chance, did the authors observed if the partner answers were different when the woman was / was not here? Did they have a chance to transcript some of the physical language not otherwise expressed?When reading the study, I can’t help wonder whether the way these couple are dealing with the choice of delivery is unique or are they reproducing a pattern they are used to for different fields? Like buying a house, choosing where to live, work, etc etc….It would have been great to submit a general questionnaire to the couples to understand the way they usually process decisions and see whether their choice for birth place is different or not.Reviewer #3: This is a small study of fathers role in choosing home births in high risk patients.-21 subjects is a very small study and may not have statistical validityYou should ty to collect at least 50 subjects.You state that “This study is part of a larger project exploring out of the system birth, theWonderstudy27, in which we also interviewed women who went against medical advice intheir birth choices (home birth in a high risk pregnancy or UC), their partners and theirmidwives” therefore you should easily be able to recruit the required additional subjects.Line 146 you state “and two partners were interviewed twice.” Please explain whyYou state that “Most often the partner was interviewed alone, although in several cases, the woman was present in the room and occasionally joined in the conversation.” Please discuss how this may have biased your results.“Interviews were semi-structured by use of a topic list ” is this a validated question list. Please state yes or no. if no justify why it could be used.Did you consider doing any statistics on your findingOtherwise it has no support for any statement you use.Please list indications that the birth was transferred to the hospital, in those casesWhat special questions were prepared relative to the two intra-labor demises.I do not believe I can make any valid conclusion from the manner the data was collected and with the lack of statistical analysis. I will stop here.**********what does this mean?). If published, this will include your full peer review and any attached files.6. PLOS authors have the option to publish the peer review history of their article  digital diagnostic tool, Attachmentrenamed_4a2a2.docxSubmitted filename: Click here for additional data file. 23 Dec 2019http://journals.plos.org/plosone/s/supporting-information.1. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: We have included the captions at the end of the manuscript.http://blogs.PLOS.org/everyone/2011/05/10/how-to-check-your-manuscript-image-quality-in-editorial-manager/2. Please upload a new copy of Figure 1 as the detail is not clear. Please follow the link for more information: Unfortunately the video in this link does not play.We have reconverted our .docx file to .tiff. We think the detail is now clear.Reviewer #1: This qualitative study explores the involvement of 21 partners in the dmp regarding a home birth in a high risk pregnancy or unassisted childbirth.The study design is adapted. The researchers might specify whether the research paradigm is to aim for change in care practices or whether a specific objective for the organisation of care was targeted.We have added a statement to this effect at the end of the introduction.It would be necessary to specify at the level of methodology the a priori of the researchers who are mentioned in an implicit way in the discussion.We have expanded on the a priori position of the researchers in the method section of researchers and reflexivity.Ethical obligations have been met.Results are clear and well presented. Themes and sub themes are illustrated with verbatims.Thank you.Regarding the motivations of the fathers, it seems that they mainly followed their wives. Were the researchers able to assess whether fear was a driving force among the partners, in terms of fear, whether it was to generate a couple conflict, or to upset their pregnant wife ?Good question. No, that seemed not to be the case. The word fear was hardly ever mentioned by the fathers. The partners were mostly very protective and supportive of the women. We have added a few words in the discussion.Finally, was the (future) child's well-being present in their speech ? If not, this could be mentioned.Yes, it was, in quite a few cases. We also mention this in the results, in quotes from partner 6 and partner 18, and in the discussion.Some remarks regarding the discussionThe authors might avoid some repetitions in the discussion and conclusion.We have removed quite a few sentences from the discussion. We understand that the conclusion can also read as repetitive, however, we feel it must report all the main findings, for those readers who choose not to read the entire article. Therefore we have left this segment intact.They could broaden the point of view on this dm issue by mentioning the role of emotions as the driving force behind decisions and the possible impact of cognitive biases, especially the "confirmation bias" that can be imagined in the way information transmitted to partners is described by some partners as "sorted" and accepted quite passively by them.A comment on internet sources has been added.A table with proposals for integrating fathers is a useful but perhaps ambitious suggestion. There are already quite a few tables in this article, therefore we have elected not to create yet another. That could, however, be the focus of another (our next?) study on partner involvement.Globally, the research paper is valuable:this work can concretely promote decisions involving partners. This work is original, and deals with a public health problem with significant health implications.This work can concretely promote decisions involving partners, who are also future fathers.Thank you!Reviewer #2: I have read with great interest the paper of M. Hollander et al. and I think it is of scientific quality high enough and deserves publication in PLOS, providing the authors are willing to give some precisions.Thank you, and of course!In summary, the authors conducted a qualitative research in order to understand better the role of women’ partners choosing high risk birth setting against medical advice. They interviewed 21 subjects and found 4 main themes: “Talking it through”, “A shared vision”, “Defending our views”, “Doing it together”. The overarching theme that covered all the others was “she convinced me”.First, I would like to congratulate the authors for their hard work putting through so many interviews and for the quality of their transcriptions.Thank you again!In general, the manuscript is well written and easy to read. However, it is a little bit long and the authors should go forward in their discussion and not only rephrase most of the results.We have already done this in response to reviewer 1’s comments. The discussion is now less repetitive, and shorter than the one in our last PLoS One publication regarding the midwives involved in these cases :e0220489. doi: 10.1371/journal.pone.0220489).A weakness of this study also lies in its retrospective nature and sometimes the long delay between pregnancy / delivery and the interview. This could have introduced a recognition bias. Furthermore, can the authors precise if the couples had subsequent pregnancies and their choices for delivery / issue of the pregnancy?We have commented on the time lapse in the limitations section in response to reviewer 1.As for any subsequent pregnancies which may have occurred since we did the interviews in 2014-2016, we are aware of a few, through informal channels, although we have not formally spoken to the couples about this. With most couples there has been no further contact. Those subsequent births that we know of have all been against medical advice, once again.Since this is informal information on only a few cases we are not including this in the article.The fact that the authors interviewed the partners of women previously interviewed in another study could also have introduced a bias as they might have read the results of the previous study. Obviously, this is also a strength of this study since it helped increasing the number of partners interviewed.Theses limits should appear clearly in their discussion.Actually, the interviews with the partners took place around the same time (and often consecutively) as those with the women. The article on the women’s interviews was published approximately one year after we interviewed the last partner, so at the time of these interviews they were unaware of those results (as were we).By any chance, did the authors observed if the partner answers were different when the woman was / was not here? Did they have a chance to transcript some of the physical language not otherwise expressed?To the best of my recollection (and I did the vast majority of these interviews) there were no notable differences. We have added a statement to that effect. I also did not notice any body language conveying any pressure on the partner to give certain desirable answers. The couples appeared very much ‘in sync’.When reading the study, I can’t help wonder whether the way these couple are dealing with the choice of delivery is unique or are they reproducing a pattern they are used to for different fields? Like buying a house, choosing where to live, work, etc etc….It would have been great to submit a general questionnaire to the couples to understand the way they usually process decisions and see whether their choice for birth place is different or not.Indeed it would have. And I believe it might have shown the same pattern. But since we did not discuss their general decision making process, we do not know.Thank you both very much for your insightful suggestions.AttachmentResponse to reviewers.docxSubmitted filename: Click here for additional data file. 30 Jan 2020‘She convinced me’- Partner involvement in choosing a high risk birth setting against medical advice in the Netherlands: a qualitative analysis.PONE-D-19-18382R1Dear Dr. Hollander,We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.Please note that this decision has been made based on the current criteria that prevail for qualitative research, after careful consideration of the criticisms made by one reviewer, who recommended to reject the manuscript.  Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at onepress@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact With kind regards,Umberto SimeoniAcademic EditorPLOS ONEJournal requirements:In the Methods, please clarify whether the participants gave written or verbal informed consent for their quotes to be used in this article.Additional Editor Comments :Reviewers' comments:Reviewer's Responses to QuestionsComments to the Author1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.Reviewer #1: All comments have been addressedReviewer #2: All comments have been addressed**********2. Is the manuscript technically sound, and do the data support the conclusions?The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: YesReviewer #2: Yes**********3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: N/AReviewer #2: N/A**********4. Have the authors made all data underlying the findings in their manuscript fully available?PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.The Reviewer #1: YesReviewer #2: Yes**********5. Is the manuscript presented in an intelligible fashion and written in standard English?PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #1: YesReviewer #2: Yes**********6. Review Comments to the AuthorPlease use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. Reviewer #1: (No Response)Reviewer #2: Thank you for revising your manuscript. While it remains quite long to allow a quick reading, the main comments I had (which were mostly shared with reviewer number 1) were adressed in the revised version.Next time, think of giving couple a prior questionnary to understand the way they usually process life important decisions.**********what does this mean?). If published, this will include your full peer review and any attached files.7. PLOS authors have the option to publish the peer review history of their article (If you choose “no”, your identity will remain anonymous but your review may still be made public.Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.Reviewer #1: Yes: Laurence Caeymaex, MD, PhDReviewer #2: Yes: Yohann Dabi 5 Feb 2020PONE-D-19-18382R1 ‘She convinced me’- Partner involvement in choosing a high risk birth setting against medical advice in the Netherlands: a qualitative analysis. Dear Dr. Hollander:I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. onepress@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact plosone@plos.org. 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The soft tissue of the residual limb in transtibial prosthetic users encounters unique biomechanical challenges. Although not intended to tolerate high loads and deformation, it becomes a weight-bearing structure within the residuum-prosthesis-complex. Consequently, deep soft tissue layers may be damaged, resulting in Deep Tissue Injury (DTI). Whilst considerable effort has gone into DTI research on immobilised individuals, only little is known about the aetiology and population-specific risk factors in amputees. This scoping review maps out and critically appraises existing research on DTI in lower-limb prosthetic users according to (1) the population-specific aetiology, (2) risk factors, and (3) methodologies to investigate both.A systematic search within the databases Pubmed, Ovid Excerpta Medica, and Scopus identified 16 English-language studies. The results indicate that prosthetic users may be at risk for DTI during various loading scenarios. This is influenced by individual surgical, morphological, and physiological determinants, as well as the choice of prosthetic componentry. However, methodological limitations, high inter-patient variability, and small sample sizes complicate the interpretation of outcome measures. Additionally, fundamental research on cell and tissue reactions to dynamic loading and on prosthesis-induced alterations of the vascular and lymphatic supply is missing.We therefore recommend increased interdisciplinary research endeavours with a focus on prosthesis-related experimental design to widen our understanding of DTI. The results have the potential to initiate much-needed clinical advances in surgical and prosthetic practice and inform future pressure ulcer classifications and guidelines. Pressure injuries frequently affect individuals in hospitals, homes, and care settings. They are defined as “localised damage to the skin and underlying soft tissue”, and are caused by “intense and/or prolonged pressure or pressure in combination with shear” . The sevThis high number reflects the shortfalls in the prevention, diagnosis, and treatment of pressure injuries, which may be ascribed to ambiguities about their aetiology . An examDirect deformation can disrupt the integrity of skeletal muscle cells if the applied load is sufficiently high or prolonged.Ischemia is caused by a collapse of blood vessels, which obstructs the blood flow and therefore the cells’ oxygen and nutrient supply.Ischemia reperfusion describes the phase following load removal, where the reoxygenation of the tissue exacerbates ischemic damage, mainly due to oxidative stress.Impaired lymphatic drainage is induced by obstructed lymphatic vessels, which inhibits the removal of potentially damaging substances from the interstitial space and creates a toxic cell environment.The aetiology of DTI is affiliated with a variety of biomechanical, physiological, and biochemical processes on cell and tissue level , 12. In All these mechanisms contribute to the onset of inflammatory cascades and ultimately cell death. In healthy individuals the cellular damage is usually balanced out by regenerative processes. For certain populations, however, this equilibrium between stress-induced damage and recovery may be disturbed. Accordingly, researchers defined several internal and external determinants of DTI development for a number of risk groups like patients with spinal cord injury (SCI) and wheelchair users –19.Conversely, other populations such as transtibial amputees have gained less attention. During an amputation surgery, foot, ankle joint, and distal tibia and fibula are removed. To restore the capabilities of the amputee, a prosthesis is fitted to the residuum, which transfers forces between the ground and the body’s support structures during ambulation. The soft tissues that cover the stump become part of this load bearing system, even though they are not physiologically adapted to withstand high external forces. Consequently occurring skin problems, pain, and ulceration can lead to rejection of the prosthesis –23.Whilst the prevalence and incidence of superficial wounds is well documented , 22, onlWe therefore aim to map out and critically discuss research on DTI in transtibial amputees as a result of prosthetic use. Our focus is on (1) the population specific aetiology, (2) risk factors, and (3) methodologies to quantify and measure both. Because randomised controlled trials are sparse in rehabilitation science , we chosThe automated database search on the 14th of June 2019 resulted in 19 identified sources from Ovid Excerpta Medica, 12 from PubMed, and 68 from Scopus. Removal of duplicates left 72 articles for the screening process. After applying inclusion and exclusion criteria, 24 articles remained for full-text assessment, of which 11 met the eligibility criteria. An additional 5 articles were identified through references and forward-citation of these sources, amounting to 16 studies in total  discussed the aetiology of DTI, focussing mainly on residuum biomechanics. Between 2007 and 2011, Portnoy and colleagues conducted four experimental studies , 33, 34 Across all these scenarios, the researchers located peak loads at the distal end of the bones , 33, 34.Cellular deformation is only one of several aetiological factors of DTI. Mak et al. , 40 and A total of 68.75% (11) of the identified literature examined risk factors of DTI in transtibial prosthetic users. The population investigated in three experimental and two in silico studies amounts to 33, typically male (90.90%), transtibial amputees with traumatic amputation (84.84%), a mean age of 49 years, and an average weight of 81.1 kg. These studies, together with an additional in silico study and five review papers, were divided by non-prosthesis induced  and prosthesis-induced  risk factors.Non-prosthesis induced risk factors originate from intrinsic characteristics of the transtibial residuum. According to the literature body, those factors are tissue morphology, the mechanical properties of the soft tissue, and sensory impairments Table .Table 3Tissue morphology was the most frequently investigated determinant. Henrot et al.  and PortThe effect of sensory impairment was discussed by three papers. According to reviews , 40 the The mechanical properties of soft tissue were examined in two in silico studies. Both indicate a higher susceptibility of stiff muscle to loading damage compared to a flaccid one , 37. ThiThe prosthesis itself also influences the development of DTI in transtibial amputees. Relevant factors are socket design and prosthetic components Table . The mosTwo papers on prosthesis induced risk factors addressed components other than the prosthetic socket. Across two experimental studies, a total of 18 traumatic, mainly male (94%) and unilateral (94%) amputees with an average age of 49.8 years and weight of 85 kg participated. Researchers thereby investigated the influence of prosthetic foot design  as well All experimental and in silico studies (11) were included in an overview of methodologies in DTI research on transtibial prosthetic users. The studies were grouped by methodological approaches, namely finite element (FE) analysis, analytical modelling, acoustic signalling, and sensory analysis.FE analysis is based on computational models of the residuum with defined geometries, material properties, and boundary conditions. These models are numerically analysed to create visual stress and strain maps. With 54.54% (6), FE analysis constitutes the most common methodology in primary research , Ovid Excerpta Medica (Embase classic and Embase), and Scopus. It covered the first possible date for each database until June 2019, when we conducted the search. We utilised automatized categorisation of the MeSH term “pressure ulcer” or a database-specific equivalent. This inclusion of the generic pressure ulcer term ensured full coverage, as DTI was only recently accredited as separate pressure injury category . The fulWe scanned reference lists and forward-citation reports of eligible manuscripts for relevant articles that have not been identified in the automatic search. Additionally, we contacted an expert in the field of DTI for further literature suggestions.Primary and secondary sources were retrieved from the automatic search. We filtered out duplicate articles and duplicates published as conference proceedings with the aid of a citation software (Zotero 5.0.69).For further assessment, one reviewer (M.G.) screened the remaining articles. They had to be written in English, have an available full text, and have a title and abstract relevant to DTI as a result of prosthetic use. Studies on unrelated conditions and with amputations other than at transtibial level were excluded. Likewise, papers describing superficial, Stage 1, or Stage 2 pressure injuries were disregarded. To ensure a minimum qualitative standard, all papers had to be peer reviewed.In the following full-text examination, one reviewer (M.G.) evaluated the relevance, study group characteristics, and type of pressure injury. Additionally, transtibial prosthetics and DTI had to be the focus of the article. In case of uncertainty about eligibility of articles, a second reviewer (A.B.) was consulted and possible disagreements discussed until consensus was reached.By scanning through reference lists and forward-citations of eligible papers, we identified further resources. We validated their suitability with the previously described process, before including them in the final qualitative synthesis. We also retrieved recommendations on relevant literature from expert contact. All but one of the suggested sources were already included in the current synthesis, with the additional paper being irrelevant for this review.We extracted data from the combined search results according to suggestions by the JBI  and the Additional file 1. PRISMA-ScR Checklist. Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist.


Causal evidence links modifiable maternal exposures during the periconceptional period with offspring obesity. The interconception period may be an important time to intervene. We systematically identified studies examining change in modifiable maternal exposures between pregnancies and offspring adiposity. We searched for longitudinal studies published between 1990 and 2019, which included measurements taken on at least two occasions in the period from 1 year prior to the conception of the first birth to the time of the second birth, and which included a measure of adiposity in second, or higher order, siblings. Age, ethnicity and genetics were not considered modifiable; all other factors including length of the interpregnancy interval were. Eleven studies satisfied the inclusion criteria. Higher interpregnancy weight gain or loss, maternal smoking inception, mothers smoking in their first pregnancy and quitting, increasing the number of cigarettes smoked and longer interpregnancy intervals were positively associated with adiposity in second or higher order children. Vaginal birth after caesarean delivery was protective. Further research is needed to ascertain whether the risk of adiposity is fixed based on first pregnancy exposures or if interpregnancy change alters the risk for a subsequent child. This can inform the type and effectiveness of interventions for mothers prior to a subsequent pregnancy. The majority of research which has examined inter-pregnancy change, focuses on birth or neonatal outcomes such as large or small-for-gestational-age and premature birth.We aimed to systematically review the literature for longitudinal studies which characterized modifiable maternal exposures between successive live pregnancies and determine their associations with adiposity in second or higher order siblings.22.124 and this review is reported in line with the PRISMA guidelines.25 The following search strategy was piloted on EMBASE and adapted for the other platforms: [exp family planning/] OR .mp.)] AND[exp obesity/ OR exp body mass/OR exp overnutrition/OR ((obes* or overweight or overnutrition or adiposity or weight or body mass). mp.)] AND[exp progeny/OR exp child/or exp sibling/OR ((child* or offspring or infant or sibling* or progeny).mp.)]An electronic search was conducted using the bibliographic databases EMBASE (via Ovid), MEDLINE (via Ovid), CINAHL (via EBSCO), PsycINFO (via EBSCO) and Web of Science. A specialist librarian was consulted in advance, and the search was run on 30 March 2019. Studies were restricted to those based on human participants and published in English since 1990 to ensure that only the most up-to-date literature was reviewed. The protocol for this review was published on the international prospective register of international reviews, PROSPERO, reference CRD42019124344,2.2We only included longitudinal studies. Case control studies, cross-sectional studies and case reports were excluded.We did not consider age, ethnicity or genetics to be modifiable, but considered all other maternal behaviours and characteristics to be potentially modifiable exposures. Studies where measurements of the main exposure were taken on at least two occasions in the period from 1 year prior to the conception of the first pregnancy up to the time of the second birth were considered. At least one measurement should have been recorded in the period from 1 year prior to the conception of the first pregnancy and the first birth (Period 1) and at least one in the period from the time of the first birth to the time of the second birth (Period 2). 8The length of the interpregnancy interval was specifically included as a modifiable exposure as defined per individual study, even if the World Health Organization definition of the inter-pregnancy interval was not used (the period from the birth of one child to the conception of the subsequent pregnancy).z-scores, skinfold measurements and body adiposity. All time points were considered after the age of 1, without an upper age limit. The lower bound was given as 1 year to exclude studies focussing on neonatal outcomes, including foetal macrosomia.We considered studies where outcomes included a measure of adiposity in second or higher order siblings. Appropriate outcome measurements included categorical and continuous offspring BMI, weight for height 2.326 was used to screen titles for eligibility. A randomly selected sample of 10% of these titles was independently screened by two reviewers (EJT and SW). A 10% sample was chosen as a recent simulation study has shown that if the fraction being sampled for independent review is increased, there is no decrease in selection bias.27 At the title screening stage, the percentage agreement between the two reviewers was 98.9%, and discrepant titles were included for abstract screening. One author (EJT) reviewed the remaining titles. The same process was then followed for reviewing the abstracts of papers remaining after title screening. The agreement rate between the two reviewers (EJT and SW) was 100%, and accordingly, one author (EJT) reviewed the remaining abstracts.The screening management software RayyanFollowing abstract screening, the full texts of the remaining titles were accessed and reviewed by two reviewers (EJT and SW), with one exception where the discrepant title was only considered by one reviewer (EJT), due to copyright restrictions, and was excluded in any event.2.428 and this was undertaken by two reviewers (EJT and SW or EJT and NZ).A modified version of the Cochrane Collaboration data extraction form was used to conduct data extraction,p values were used.All eligible data were extracted, including for subgroup analysis and exposure multiple time points where these were reported. Where reported, confidence intervals which did not overlap the null were used to identify statistically significant associations. If these where not reported, 38 were formed using the National Heart Lung and Blood Institute assessment tool for observational cohort and cross-sectional studies.39 The remaining study is an individual patient data meta-analysis,40 and in this instance, we used the PRISMA-IPD checklist.41 The overall rating for addressing the risk of bias (good/fair/poor) is included in Quality assessment was also undertaken by two reviewers (EJT and SW). Key strengths and weaknesses of each of the cohort studiesa priori rather than a meta-analysis. Studies have been grouped based on the exposures being considered, and we summarize the effect sizes and precision for each included study.Since we expected significant variation in study exposures and design, a qualitative synthesis was planned 325  Birth Cohort Study.42 One study from America followed offspring from ages 9–14 years through ages 20–28 years, considering annual time points for 5 years and biennial time points thereafter.38 One study from Sweden used measurements taken at comprehensive health checks when the child was 4 years of age and used these to predict BMI on the child’s actual fourth birthday.37 Two studies utilized Swedish conscription data and only included outcome measurements for males.34Studies where the exposure was interpregnancy weight change,ed above . Most st37  inter-pregnancy intervals on offspring health. They found that, compared with a birth interval of 25 to 30 months, men born after an interval of at least 31 months had a higher probability of being affected by overweight/obesity in young adulthood. Between-family analysis showed an increasing trend as the interpregnancy interval increased, and within-family analysis showed a broadly similar pattern31  Birth Cohort Study,42 but both studies considered different outcome measurements and time points  but reported no increase in odds of offspring obesity for interpregnancy weight loss (>1 kg/m2), small gain (1 to <2 kg/m2) or moderate gain (2 to <4 kg/m2)29 (Adane et aI.kg/m2)29 .37 examined interpregnancy weight loss due to bariatric surgery between pregnancies. They found no association between the differences in BMI in week 10 of the pregnancy prior to, and the pregnancy after, surgery with differences in sibling’s BMI at age 4 years.Willmer et al.30 They found for a loss of ≥10% (compared with a change of ±3%) the odds of children being affected by overweight or obesity were increased by 30% and 90%, respectively, and that mean BMI z-score was also higher for a gain of ≥10% (compared with a change of ±3%)30 30 .30 and Willmer et al.37 utilized routinely collected population level data in Scotland and Sweden respectively, and included objectively measured outcomes, but in the former, maternal and child records were linked in only 44% of cases while in the latter, full details were only available for 71 child–woman triads. All the exposure and outcome measurements in the Adane et al.29 study were self-reported, and only 34% of women responded to the survey asking for their children’s details.The studies by Aucott et al.3.434 and fair40 in terms of their risk of bias  had higher mean BMI z-scores at age 5 than older siblings who were unexposed30 .30Aucott et al.xposed30 . BMI z-sz-score and the odds of overweight/obesity where mothers started smoking between pregnancies, always smoked or quit between pregnancies were higher30 38 38 . For wom4This systematic review included eleven studies that assessed maternal interpregnancy weight change, differences in maternal smoking status, changes in mode of birth and the length of the interpregnancy interval between successive pregnancies in relation to adiposity in second or higher order siblings from age one onwards. Higher interpregnancy weight gain or loss, starting smoking between pregnancies, smoking at the first pregnancy only, or an increase in the number of cigarettes smoked during successive pregnancies and longer interpregnancy intervals showed a positive association. Vaginal birth after caesarean had a protective effect. To our knowledge, this is the first time that evidence on this subject has been systematically reviewed.35 There was much variability in the confounders controlled for in the different analyses  at the screening stage of a random 10% sample of titles and abstracts was very high (98.9% and 100%), and two reviewers considered the full texts of studies remaining after abstract screening (EJT and SW). Data extraction and risk of bias assessments were undertaken by two authors (EJT and SW or EJT and NZ). We then followed a recent approach and listed strengths and weaknesses for each study using two commonly used checklists.14 maternal prepregnancy stress,16 supplement intake and lower maternal vitamin D status,56 and measures of social and economic status such as education and area of residence.18 Further research into changes in exposures and into combinations and interactions between exposures and the association with the magnitude of the risk of children being affected by overweight/obesity is recommended. We specifically recommend studies which examine differences in vitamin D, folic acid and other vitamin supplementation and those which consider different levels of gestational weight gain. We do not know whether a change in exposure between pregnancies modifies the risk of adiposity for a second or subsequent child or whether the risk is based on past exposures. The World Health Organization recommends a birth to conception interval of at least 24 months in order to avoid a range of poor maternal, perinatal, neonatal and birth outcomes which are particularly associated with intervals under 18 months.8 A number of included studies have found associations between the longest interpregnancy intervals and childhood adiposity, and research which combines the effect of the length of the preceding birth interval with other changes in maternal exposures is also recommended.There are a number of exposures, which are known to have an impact on offspring adiposity, which were not found in the literature searched for this review, for example, gestational weight gain,5Change in a number of exposures across successive pregnancies showed associations with greater adiposity in second or higher order siblings; substantial interpregnancy weight gain or loss, smoking in the first or second pregnancy only, or increasing the number of cigarettes smoked and longer interpregnancy intervals. Vaginal birth after a caesarean birth had a protective effect. There was considerable heterogeneity in the quality and methodology of the included studies.Further research into changes in modifiable maternal exposures and behaviours between successive pregnancies is recommended to see if the risk of adiposity for second or subsequent children is fixed based on earlier predictors or if this risk changes as exposures and behaviours change.