The nanosecond pulsed electric field (nsPEF) is investigated as an alternative plan for benign hepatic hydatid cyst. Altogether 72 C57B6 mice were included. Normal group (n = 12) had no parasite injection and the other 60 mice were used to induce hydatid cyst in liver by injecting protoscolices in portal vein. The liver hydatid cysts were exposed to nsPEF with different doses and then follow up. The standard surgery was performed as positive control. The hydatid cyst growth was monitored by ultrasound; the morphology was checked by gross anatomy and pathology was tested by H&E stain. In nsPEF-treated groups no hepatic failure nor bleeding were observed. As a comparison, in the surgery group, high post-treatment complications occurred (50%). Significant parasite growth inhibition was seen in high nsPEF dose group as compared with control group (P < 0.05). Pathological analysis confirmed destruction of hydatid cyst with sharp demarcation defined by the electrodes. Laboratory analysis showed nsPEF stimulated a time-dependent infection and recoverable liver function. The traumatic reactions defined by white blood count was significant lower than surgery groups (P < 0.05).Preliminary studies demonstrate nsPEF ablation can be applied on hepatic hydatid by inhibiting parasite growth, destructing the cyst and stimulating infections. In China, it affects 5% of the national population. About 100 million livestock animals are subjected to disease infection; among them more than 70% are sheep2. Cystic echinococcosis has been classified as one of the major parasitic diseases to be controlled urgently by 2020 by dog management, slaughterhouse hygiene control, health education and human patient treatment3.Human echinococcosis is a serious zoonotic disease worldwide distributed that jeopardizing human health and economic development. It is caused by the tapeworm of echinococcosis larvae in humans and sheep. It has been found in every continent except Antarctica and highly epidemic in the areas of animal husbandry development e.g. rural China, Russia, continental Europe and North America4. The WHO guideline suggest stage-specific treatment, e.g. uncomplicated cysts of the liver should be treated by non-surgical options such as percutaneous drainage accompanied with chemotherapy5.Currently the effective treatments against human cystic echinococcosis include chemotherapy and surgery. Due to the low absorption, the chemotherapy can only be used as an adjuvant to surgical treatment. Radical surgery is regarded as the most effective treatment but surgery causes severe complications such as biliary vessel infection, residual cyst abscess, interoperation planting and contamination6. Single cystic echinococcosis has big parasite cyst with high cyst fluid tension and active protoscolices, showing the highest risk of post-surgery recurrence. So in this study the single cystic echinococcosis was set up in the mouse liver as the experimental model to ablate the orthotopic cystic echinococcosis by nsPEF treatment in vivo  was introduced decades ago with fewer complications and less cost. Percutaneous techniques are particularly suitable for unilocular cysts, with or without detached endocystsivo Fig. .Figure 17. In this study, for the first time, the nanosecond pulse with different voltages  is a novel tumor ablation technology. By using the minimally invasive electrodes, high pulsed power is delivered with ultra-short electric pulses. The external electric field changes cell membrane potential, disrupting cell membrane structure and function, leading various anti-tumor effects. It has been proved effective in malignant tumors such as melanoma, skin tumor, and hepatocellular carcinomages Fig.  was applst, 4th and 8th week post nsPEF treatment was 5.02 ± 2.50 mm, 4.21 ± 2.82 mm and 4.68 ± 3.04 mm respectively. In the medium electric field strength group (14 kV/cm group), the average cyst diameter on the 1st, 4th and 8th week post nsPEF treatment was 3.93 ± 1.78 mm, 4.16 ± 1.86 mm and 4.28 ± 1.97 mm; In the low electric field strength group (7 kV/cm group), the average diameter on the 1st, 4th and 8th week post nsPEF treatment was 4.50 ± 1.34 mm, 5.56 ± 1.21 mm and 8.96 ± 1.56 mm, respectively; the control group on the 1st, 4th and 8th week was 3.18 ± 0.96 mm, 4.26 ± 1.08 mm, and 7.33 ± 2.81 mm, respectively , the average diameter on the 1st, 4th and 8th week after nsPEF treatment; The average diameter increase of medium dose of nsPEF treatment group (14 kV/cm) was−0.4 mm, 0.4 mm, −0.1 mm on the 1st, 4th and 8th week post nsPEF treatment respectively. The mean diameter increase of the of low dose of nsPEF treatment group (7 kV/cm) was 0.2 mm, 1.3 mm, 4.3 mm on the 1st, 4th and 8th week after nsPEF treatment, respectively. The mean diameter increase of the control group were 0.2 mm, 1.3 mm, 4.3 mm on the 1st, 4th and 8th week after nsPEF treatment, respectively.The average diameter increase of the high dose nsPEF group (21 kV/cm) increased −1.4 mm, −1.2 mm, −1.7 mm on the 1th week compared with the control group at the same time (P < 0.001). The diameter of echinococcus granulosus in the 7 kV/cm pulsed group showed no significant size difference vs control group  and nsPEF group vs baseline(P < 0.05). While over time, from 4 weeks to 8 weeks post nsPEF, WBC declined in nsPEF and control group but remained high in surgery group. cytokines were follow up to monitor possible post treatment cytokine storm Th1 and Th2 type cytokines were tested and showed no significant changes, indicating the current nsPEF dosage did not break immune tolerance formed in chronic parasite infection . But there was no difference between control group and nsPEF group, indicating that the liver function disorder came from as the comprehensive effect of parasite, electrode puncture and nsPEF ablation, indicating the damage of nsPEF caused to the liver is not as significant as surgery group. The non-thermal ablation did not cause massive necrosis and the residual liver lobes reacted with clean regeneration without cytokine storms. The pathological characters were in accord with laboratory exams. The trauma caused by surgery result in inflammatory situations. Marked by leukocyte surge Fig. .During nsPEF ablation, the electrodes were placed on the lateral wall of the hydatid cyst wall and achieved therapeutic effect. This placement can avoid puncture into the cyst and prevent cyst fluid spillage. One week after nsPEF, there was temporary WBC increase in nsPEF treated group but it was recoverable after 8 weeks. There is no anaphylactic reaction nor mortality during nsPEF and surgery. There was no bleeding or other post treatment complication found during follow up. Even the preventative scolicidal cheomotheray of albendazole had been routinely given and careful protection taken during surgery  has the significant inhabitation effect on the parasite cyst growth. There is also the limit for the parasite cyst size. Small cyst with diameter less than or equal to 1 cm was chosen to be treated by nsPEF, comparable to the human tumor size of ≤ 3 cm can be completely ablated by radiofrequency ablationThe study also proved the advantages of nsPEF ablation: it can maintain the integrity of hydatid cyst but destruct the inner layers, remain the normal surrounding liver tissue to the maximum extent; NsPEF can also be repeated and monitored by ultrasound.11. While our study use a cyst model other than cellular model to study the biological effect in an macro model with measurable and visible changes.Compared to conventional electrical pulses in micrometer scale, nanosecond pulsed electric field technology compress higher energy (kilovolt levels) in shorter pulses (nanoseconds). An ultra-short pulse duration, coupled with more rapid rising time, can lead to unique biological effect. E.g., 21 kV/cm for nanosecond pulses in this study compared to 1 kV/cm for conventional micrometer pulse electroporation. Previous studies assumed that nsPEF can affect the structure of cellular membrane to form tiny “nanopores”With the change of the electric field parameters, the mechanism of the biological effects produced by different pulse widths, different field strengths, different frequencies and different pulse numbers is different. In this experiment, some electric parameters were fixed . The field strength was changed from 0, 7, 14 to 21 kV/cm. NsPEF applied on hydatid cyst has triggered a variety of effects; the parasite cyst growth initiation was due to the direct destructive effects of the electric field on parasite structure. As a new physical ablation method, nsPEF has been proved safe and effective in mouse hepatic hydatid cyst. But the further big animal trials are still needed to get the comparable dose in human.in vivo on a murine hepatic hydatid cyst CE1 type. 2. NsPEF caused the direct destructive damage on the cyst wall. When the electric field strength is high enough (21 kV/cm), it can inhibit parasite growth significantly. It can also stimulate the host immune reaction by forming the inflammatory response zone and clean the debris. But the current dosage can not break the pre-existing immune tolerance formed in the chronic parasite infection. 3. The electrodes were placed on the lateral wall of the hydatid cyst wall and achieved therapeutic effect. This placement can avoid puncture into the cyst and prevent cyst fluid spillage. Although it has been used in tumor ablation and approve effective in tumor eradication and metastasis inhibition, it is still relatively new in hydatid cyst and requires much more experimental trials especially in big animals before being clinically used.Here we present a novel percutaneous treatment hydatid cyst with non-thermal puled electric field ablation, providing a possible alternative to open surgery with minimally invasive procedure of fewer post-surgery complications. 1. NsPEF showed inhibitory effect on liver cystic echinococcus Altogether 72 female 8-weeks old C57B/6 mice were purchased from Animal Center of Xinjiang Medical University and then maintained in the Animal Laboratory of the First Affiliated Hospital of Xinjiang Medical University (License number: SCXK 2010-0003). The animal experimental proposal was approved by the Institutional Animal Care and Use Committee of the First Affiliated Hospital of Xinjiang Medical University (IACUC-20141217003). All methods were performed in accordance with the relevant guidelines and regulations of The Declaration of Helsinki and National Institutes of Health Guide for Care and Use of Laboratory Animals.echinococcus granulosus injection. The other 60 mice were injected with echinococcus granulosus in mouse liver. After injection of 0.003 mg atropine in muscle, the C57B/6 mouse was put on mask for continuous inhalation anesthesia. Fixed on the operating table, 1.5 cm incision was made on the middle mouse abdomen. The intestine was removed to the left side of the abdominal cavity with sterile wet saline gauze to reveal the portal vein. The sterile syringe which was pre-filled with 200 echinococcus granulosus protoscolices in 100ul saline was injected in the portal vein. After 28 weeks, ultrasonography detected the cystic echinococcosis grew up in liver and the diameters were about 1 cm. IgG is a marker that reflects the host-parasite immune reaction. When a hydatid cyst develops in the liver, host IgG in the serum was significantly elevated, indicating an active parasite infection. So in this study hydatid activity has been confirmed by murine serum IgG. Then the mice with active cystic echinococcosis infection in liver were treated by nsPEF.Altogether 72 C57B/6 mice were included in this animal experiment. Among 60 mice, 12 were kept as normal without any In 2003 the World Health Organization Informal Working Group on Echinococcosis (WHO-IWGE) published standardized classification CE1-CE5 based on ultrasound images in order to promote the stage-specific management. In our current study, CE1 type, the single complete cystic echinococcosis cysts were induced and chosen for the nsPEF treatment. Because CE1 type is the most active among all types. It facilitates a more rational treatment approach evaluation and comparison.echinococcus granulosus were kept as normal for the immune baseline reference. The 60 mice with echinococcus granulosus liver were sent for nsPEF treatment. They were randomly divided into 5 groups with 12 mice in each group: control mice without nsPEF but received the same anesthesia and electrode placement; surgery group with standard open surgical procedure; nsPEF groups with three different dosages  was given to kill the residue parasite and prevent the secondary infection. When the abdomen was opened, the surrounding tissue was covered by the gauze soaked with 20% hypertonic saline to protect from parasite planting caused by accidental spillage of the cystic contents. After full exposure of liver and lesion. The hydatid cyst was evacuated by gentle suction. The daughter cyst and hydatid sand were completely removed. The cyst-biliary tract communication was identified and repaired. The cyst cavity was sterilized with 20% saline. Then the abdomen was rinsed and closed Fig. .2 inhalation. Blood and liver sample were collected for liver function test and pathological exams.After nsPEF treatment, the mice were recovered in the warm pad and then kept in the animal facility with free access to water and food supplies. Before treatment, the 1st, 4th, 8th week post nsPEF, the mice were routinely checked by ultrasound, tail vein blood collection and liver biopsy. At the 12nd week post nsPEF, the mice were euthanized by CODuring the 1st–8th post-nsPEF treatment follow-up period, the blood sample was taken from tail vein. Wwhite blood cell count was tested by an automated hematology count analyzer . Liver function and cytokine were tested by automatic biochemical analyzer . IgG was determined by nephelometric technique . The percentages of lymphocytes CD4/CD8 were detected by Flow-cytometry by IgG1-FITC, monoclonal fluorescent antibodies, CD4-FITC/CD8-FITC .On euthanasia, the mouse liver tissues were sectioned into 3 mm slices and then fixed in 4% formalin for 48 hours at 4 °C. Then the tissues were dehydrated through a series of graded ethanol baths to displace the water, and then infiltrated with wax. The wax blocks were sectioned into 5 μm slides and stained by H&E. The results were reviewed in the Pathological Department of the First Affiliated Hospital of Xinjiang Medical University.A portable ultrasound system  was used to monitor the hepatic hydatid cyst. The diameter of the hydatid cyst, the growth was measured over time. The images were reviewed based on the standardized classification of ultrasound images of hydatid cyst by the World Health Organization Informal Working Group on Echinococcosis (WHO-IWGE) published in 2003.The measurement results were present as the mean ± SEM and were analyzed by one-way ANOVA followed by the Tukey’s test and a t-test. The statistical analysis was compared between groups by a software . P values less than 0.05 were considered significant.


Small size at birth and rapid growth in early life are associated with increased risk of cardiovascular disease in later life. Short children born small for gestational age (SGA) are treated with growth hormone (GH), inducing catch-up in length. Leukocyte telomere length (LTL) is a marker of biological age and shorter LTL is associated with increased risk of cardiovascular disease.To investigate whether LTL is influenced by birth size, childhood growth and long-term GH treatment.We analyzed LTL in 545 young adults with differences in birth size and childhood growth patterns. Previously GH-treated young adults born SGA (SGA-GH) were compared to untreated short SGA (SGA-S), SGA with spontaneous catch-up to a normal body size (SGA-CU), and appropriate for gestational age with a normal body size (AGA-NS). LTL was measured using a quantitative PCR assay.We found a positive association between birth length and LTL (p = 0.04), and a trend towards a positive association between birth weight and LTL (p = 0.08), after adjustments for gender, age, gestational age and adult body size. Weight gain during infancy and childhood and fat mass percentage were not associated with LTL. Female gender and gestational age were positively associated with LTL, and smoking negatively. After adjustments for gender, age and gestational age, SGA-GH had a similar LTL as SGA-S (p = 0.11), SGA-CU (p = 0.80), and AGA-NS (p = 0.30).Larger size at birth is positively associated with LTL in young adulthood. Growth patterns during infancy and childhood are not associated with LTL. Previously GH-treated young adults born SGA have similar LTL as untreated short SGA, SGA with spontaneous catch-up and AGA born controls, indicating no adverse effects of GH-induced catch-up in height on LTL. Small size at birth and catch-up in weight for length in early life are associated with an increased risk for cardiovascular disease (CVD) in later life –3. The mTelomeres are noncoding repeating DNA sequences at the end of each chromosome. Their primary function is to maintain genomic stability ,12. TeloIn this study, we investigated whether size at birth, growth patterns during infancy and childhood, and GH treatment influence LTL of young adults. We hypothesized that small size at birth and accelerated weight gain during infancy lead to shorter LTL. We also hypothesized that the gradual catch-up in length caused by GH treatment does not lead to increased attrition of telomeres and thus does not influence LTL. To address the fact that those born SGA have an already increased risk for CVD, we compared the data of previously GH-treated young adults born SGA with untreated short young adults born SGA. To study whether GH-induced catch-up growth has a similar effect on LTL as spontaneous catch-up after SGA birth, we also compared the GH-treated group to a group of young adults born SGA with spontaneous catch-up (SGA-CU).2/day (0.035 mg/kg/d), sc at bedtime. Every three months, GH dose was adjusted to the calculated body surface area. The data of the GH group were compared to those of three subgroups based on their size at birth and their adult stature: untreated young adults born SGA (birth length <-2 SDS) with persistent short stature (adult height <-2 SDS) ; young adults born SGA (birth length <-2 SDS) with spontaneous catch-up growth resulting in a normal adult height (>-1 SDS) ; and young adults born appropriate for gestational age with a normal adult height (>-1 SDS) . In order to increase the statistical power for subgroup comparison, the cut-off values for small birth size and short adult height were set at <-2 SDS, and the cut-off-values for normal birth size and normal adult height were set at >-1 SDS.The total population consisted of 545 participants: 470 healthy participants from the PROGRAM and PREMS study cohorts ,16, and This study was conducted according to the Helsinki Declaration. The Medical Ethics Committee of Erasmus Medical Centre approved the study. Written informed consent was obtained from all participants and/or their parents.Birth data were obtained from hospital records, primary health care records and general practitioner records. Height was measured to the nearest 0.1 cm by a Harpenden stadiometer, weight to the nearest 0.1 kg by a scale . All anthropometric measurements were performed by a trained investigator, according to standardized methods. The measurements were performed twice, the mean value was used for analyses. Fat mass, fat mass percentage and lean body mass were measured on one Dual-energy X-ray Absorptiometry (DXA) machine  . QualityGenomic DNA was isolated from peripheral leukocytes using standard procedures. All LTL measurements were performed in the laboratory of the University of Leicester, using the quantitative PCR-based technique as previously described . Telomerhttp://www.growthanalyser.org). Fat mass percentage SDS was calculated according to age- and sex-matched Dutch reference values [Standard deviation scores (SDS) for birth length and birth weight were calculated in order to correct for gender and gestational age, and SDS for adult height and weight were calculated to correct for gender and age , all usie values . Becausee values .Means and SD were used to describe the distribution of continuous variables. Multiple linear regression analyses were performed to determine whether size at birth (i.e. birth length and birth weight) and childhood growth patterns (i.e. the degree of catch-up in length and weight from birth to adulthood) were significant predictors of LTL. Because of collinearity between birth weight and birth length, these variables were analyzed in separate models. Adjustments were made for age and gender, and additionally for gestational age, body composition, smoking and SES. Because the study group had been selected on birth length and adult height, the interaction term birth length SDS*adult height SDS was added to the analysis, in order to ensure that the effect of these variables was modeled correctly.Quartiles of weight gain during the first 12 months of life were determined in the total group, except for the GH-treated subjects and for men and women separately. ANCOVA was used to determine differences in LTL between the lowest and highest quartiles, corrected for age and gestational age. Lastly, we analyzed whether there were differences in LTL between the SGA-GH subgroup and the SGA-S, SGA-CU and AGA subgroups. In this analysis, we additionally adjusted for age, gender and gestational age. Results were considered statistically significant if the p-value was <0.05. Statistical package SPSS version 21.0  was used for all analyses.Clinical characteristics of the total study population (n = 470), and for men and women separately are shown in We analyzed the effects of size at birth and postnatal growth on LTL in a multiple regression analysis. First, birth length was analyzed . As expeThe same models were used to analyze the relation between birth weight and LTL . Insteadr = -0.08, p = 0.15). Subsequently, we stratified the population into quartiles based on weight gain in kg and Δweight (kg)/Δlength (cm) during the first 12 months of life. We analyzed the effect of weight gain and fat mass accumulation during the first 12 months of life on LTL. We found no significant correlation between weight gain in the first 12 months of life and LTL , in men (p = 0.91) and women (p = 0.97). The analyses for Δweight/Δlength during the first 12 months of life neither showed significant differences in LTL between the lowest and highest quartile in the total population (p = 0.31) and in men (p = 0.99), and there was a trend towards longer LTL in women with the highest Δweight/Δlength (p = 0.06), indicating no negative effect of fat mass accumulation during the first 12 months of life on LTL in early adulthood.The effect of long-term GH treatment on LTL was analyzed by comparing LTL between subjects born SGA and treated with GH (SGA-GH) versus age-matched untreated short subjects born SGA (SGA-S), subjects born SGA with spontaneous catch-up during childhood (SGA-CU), and AGA born controls with a normal adult stature (AGA-NS). Clinical characteristics of the subgroups are shown in We found a positive association between birth length and LTL, and a trend towards a positive association between birth weight and LTL. No associations were found between gain in weight for length during infancy and childhood and adult body size, and no influence of GH-induced catch-up growth on LTL.We performed a multiple regression analysis in the total group to analyze the effects of size at birth, adult body size and weight gain during childhood on LTL. Birth length was positively associated with LTL, and there was a trend towards a positive association between birth weight and LTL. These associations were adjusted for possible confounders, such as gender and gestational age, indicating an independent effect of size at birth on LTL. Since previous reports have shown that small size at birth is associated with risk for CVD in later life, it could be that LTL is one of the links between birth size and later life CVD-risk. Our results are in concordance with a recent study of de Zegher et al., showing that telomere lengths are shorter in SGA newborns than in AGA newborns . On the We found a positive association between gestational age and LTL. In a previous report we have shown that those born preterm have shorter LTL than those born at term , which cIn our study, extensive data on adult body composition were available: next to weight SDS and BMI, we also measured fat mass and lean body mass using DXA. We found no relation between fat mass percentage and LTL. This result is in contrast with previous studies, showing that obesity is associated with shorter LTL in both children and adults, probably due to the fact that obesity causes increased oxidative stress, which exacerbates telomere attrition ,29. The Gain in weight, gain in height and fat mass accumulation from birth to adulthood were not associated with LTL in our study. We previously showed that growth patterns during infancy have programming effects on health in later life ,30. We, To our knowledge, we are the first to evaluate whether GH treatment has an effect on LTL. Young adults born SGA who were treated with GH during childhood had similar LTL as age-matched untreated short subjects born SGA, subjects born SGA with spontaneous catch-up and controls born AGA with a normal stature. Thus, GH-induced catch-up in length does not lead to shorter LTL in young adults born SGA. It seems that a gradual catch-up in length, after the age of four years , does not lead to increased replicative stress. Since data on age-associated diseases, such as CVD, long after cessation of GH treatment are scarce, this result is reassuring . Our res2 was small in all analyses, indicating that there are other determinants of LTL, that were not included in our analyses.Although the multiple regression analyses resulted in significant associations between multiple variables and LTL, it should be noted that the RAs telomere length measured in different tissues of the same patient, are highly correlated ,37, LTL One of the main strengths of the present study is the large group of young adults that was included, with a great variation in size at birth and childhood growth patterns. Because we oversampled subjects with extreme variants of normal growth, such as subjects born SGA with and without catch-up growth, we created greater contrast in the study population, which contributed to more statistical power.In conclusion, we found that size at birth, gestational age and female gender are positively associated with LTL and smoking negatively, while adult fat mass and gain in weight and height from birth to adulthood and during infancy were not associated with LTL. Young SGA adults who received GH treatment during childhood have similar LTL as age-matched untreated short SGA, SGA with spontaneous catch-up and controls born AGA, indicating no adverse effects of GH treatment on LTL, which is reassuring.


Given the limited research into men’s experiences of being present at childbirth this study explored the experiences of fathers who found childbirth traumatic. The aim of the research was to investigate how men coped with these experiences; the impact on their lives; and their views on what may have helped to reduce distress.Participants were recruited via websites relating to birth trauma and parenthood. A consent and screening questionnaire was used to ensure that participants met the inclusion criteria of: being resident in the UK; being 16 years or older; having been present at the birth and answering yes to the question “At some point during the childbirth I experienced feelings of intense fear, helplessness or horror”. Semi-structured telephone interviews were completed with 11 fathers who reported finding childbirth traumatic. Participants also completed the Impact of Event Scale as a measure of trauma symptoms. Template Analysis was used to analyse the interview data.Childbirth was experienced as “a rollercoaster of emotion” because of the speed and unexpectedness of events. Men described fears of death, mirroring their partner’s distress; trying ‘to keep it together’ and helplessly watching a catastrophe unfold. Fathers felt themselves abandoned by staff with a lack of information. Men were subsequently distressed and preoccupied with the birth events but tended to feel that their responses were unjustified and tried to cope through avoidance. Men described the need for support but reluctance to receive it.Fathers may experience extreme distress as a result of childbirth which is exacerbated by aspects of current maternity care. Maternity services need to be aware of the potential impacts of fathers’ attendance at childbirth and attend to fathers’, as well as mothers’, emotional responses. Men are susceptible to a range of mental health problems following the birth of a child . PaternaUp to seven percent of women may experience symptoms of post-traumatic stress after childbirth, with prevalence of full Post-Traumatic Stress Disorder (PTSD) estimated at between 3 and 6% ; subjectQualitative research into women’s experiences has found that they may report trauma responses to births which are viewed by medical professionals as routine ; the subQualitative literature into men’s attendance at routine childbirth has identified that they experience uncertainty about their role in the labour setting, feelings of helplessness at the inability to support the partner in pain, but ultimately joy at the birth of a healthy child e.g., , 15); ho; ho15]);White  attempteThe limited literature in this area indicates that some men may experience symptoms of post-traumatic stress as a result of childbirth. There is very little research on the experiences of men who themselves found childbirth traumatic, regardless of whether they develop symptoms of post-traumatic stress. This study aimed to explore this phenomenon. The particular areas of investigation were: the factors that contributed to making the experience traumatic; the impact of the experience on the fathers in terms of their behaviour, relationships and how they tried to cope with the trauma; and what they believed could have supported them through the experience.www.dadsnet.net and www.mumsnet.com.The study took place in the UK. Participants were recruited via an advertisement displayed on the Birth Trauma Association website; in a newsletter of the Fatherhood Institute and on two internet forums: Inclusion criteria were that participants were: resident in the United Kingdom; aged 16 or older; had been present for the birth of the child; and described a trauma response to the birth of “fear, helplessness or horror” . ExclusiThe Impact of Event Scale (IES)  measuresEthical approval for the research was granted by the University of Liverpool Research Ethics Committee.Participants who responded to the study advertisement were sent a standard email response with the participant information sheet and a web link to access the online part of the study. Participants who accessed the website were presented with the participant information sheet for a second time before being asked to complete a consent form. They confirmed they met the inclusion criteria, including having experienced the birth as traumatic which was assessed with the question “At some point during the childbirth I experienced feelings of intense fear, helplessness or horror”. Participants who met the inclusion criteria and consented to take part then progressed to the IES . This waWhat was your experience of being at the birth of your child?What difficulties, if any, have you experienced following the birth?In what ways, if any, have these difficulties affected you and your partner?What things have you tried to help you manage how you’ve been feeling?How has your relationship with your partner been since the birth?How has your relationship with your child been since the birth?Is there anything that could have made your experience less difficult?Interviews took place between January and May 2014. Participants were asked to confirm they had understood the participant information; reminded of their right to withdraw and asked to confirm that they wished to continue with the study. They were also given an opportunity to ask any questions. Interviews then proceeded following the semi-structured schedule and were audio recorded. The questions were:What has it been like talking about your experiences?What motivated you to take part in the study?Two additional questions were added to the schedule after the first four interviews:Eight of the 11 interviews were transcribed by JE; the three remaining interviews by a professional transcriber. Interviews were analysed using Template Analysis, a form of thematic analysis, which can be adapted to suit the epistemological stand point of the researcher and incorporates elements of top-down and bottom-up analysis . This meTemplate analysis differs from other forms of thematic analysis in that it allows an outline template of key areas of interest, used to guide the analysis. The outline template is applied to the data and revised to incorporate new emergent themes, which are not already captured within the template. Subthemes are entirely populated by emergent data. Through this iterative process - which can involve the deletion or combination of information in the outline template - the final template, representing all the data, is developed.Template analysis is concerned with the relationships between codes and themes, which is represented in the hierarchical structure. Using these higher-order themes as a guide, the interview transcripts were analysed for emerging sub-themes. Each interview transcript was read several times to become familiar with the data. Transcripts were then annotated with emerging codes which were added to the template.An initial coding template following the structure of the interview guide was developed Fig. . Transcr, participated in the study. Figure Eleven men, aged between 27 and 45 years old The final template is illustrated in Fig. All participants described births in which complications had arisen . Another spoke of “the scream that came out of [his wife’s] throat” (F2); whilst another father recalled the contrast of holding his new born child in a room full of medical equipment with “blood dripping onto the floor” (F9).“y’know, the first at least 24, maybe even 36 h or whatever, was absolutely straightforward and happy and relaxed and y’know we were all feeling very well prepared for what was coming. And then, and then that last hour, it just descended from being very straightforward to very traumatic very quickly. Erm, in a way that I couldn’t have envisaged even half an hour before” (F6).Most fathers referred to rapid shifting of events and emotion during the birth. These created an impression of the birth as “a rollercoaster” (F10), comprising two main aspects: the suddenness and speed of situational changes and accumulation of stressful events. Several fathers described thinking that the labour would go well and without difficulty; others had anticipated that the birth may be more complicated but felt unprepared for the scale of difficulty. Lack of preparedness for a difficult birth meant that the suddenness with which events changed was key:“I just remember [the consultant’s] words……..’We’ve got to have it out now’ and it was all ‘Bang!’ and suddenly – I know it sounds daft but not being up close and personal with the NHS you’re limited kind of and I try and avoid those kind of soaps on TV - but it was like dramatic, everything happened. We suddenly then we were in a, in a, two minutes later we were in a delivery room and there’s a caesarean going on” (F10).The influx of additional medical staff with “more and more people turning up” (F3) to the labour room was recalled in many of the narratives as a sign that the situation had become urgent and often seemed overwhelming. The speed with which events took place contributed to a sense of disorientation and uncertainty:And it’s like this pull, push, pull, push, pull, push, in, out. Over, back of what’s happening; what’s not happening; what could happen; what might; what you thought would happen; what’s not (F1).Several fathers described continual fluctuations of experience, from thinking that “we were over the worst of it” (F3) and “on the home strait” (F10), when the baby was born or the labour seemed to be under control, to then experiencing further stressors with concern about the health of either the baby or their partner. This short-lived relief and the cumulative effect of stressful events and shifting experiences was illustrated by one father:This rollercoaster effect was a thread running throughout many of the narratives creating a level of uncertainty, anxiety and helplessness with which the fathers found it difficult to cope.All the kind of stuff that went on before that and all the stuff that went on after that might not have been that significant in themselves but when it’s all put in the mix together it just multiplies up (F3).Not all of the stressful events seemed traumatic in themselves but the multiplication of stressors led to distress for the men. Both situational and emotional aspects contributed to this. The partners of four men experienced medical mistakes such as pain relief being administered incorrectly, which added to the pain experienced and increased both the mothers’ and the fathers’ stress. Others recalled instances of lack of care from staff, or the experience of waiting for news and information.“You know, at one stage I was thinking, ‘sh**, I’m going to bring up a child on my own’” (F11).“I remember just sort of having a sense of my life, my whole life, sort of in some kind of pivot, I suppose. And just thinking, d’y’know, ‘Whatever happens here’ y’know, ‘is this the moment where, y’know, my, my partner dies and I, I have that and I have a son and I’m going to be a dad that brings this boy up by myself?’ (F9).Men described strong negative emotions during the birth which they tried to contain in an attempt to protect their partners from further distress. Ten of the 11 men described fears that their partner or baby would die:“from what was going on, y’know, the amount of people in the room and what she was looking like and what they were doing and all that kind of thing, I was thinking “oh god, this is 50/50” (F4).The strength of feeling was illustrated by the powerful language fathers used, referring to themselves as “terrified” (F9 and F10). These fears often arose from the men’s perception of what was happening:“the more that she was obviously in distress the more I became distressed on her behalf” (F6);“And the really traumatic part was just, the sort of, the scream that came out of her throat was absolutely horrible to…it just really hurt to see her in so much pain.” (F2).The pain of the woman and her suffering had a direct effect on the man as his distress mirrored hers:The experience for one father of hearing “for an hour my wife screaming in the room next to me and I wasn’t able to do anything about it” (F3) was the most traumatic aspect of the birth.Seven fathers referred to “trying to keep it together and be strong for [partner]” (F8), although this belied the emotion they were really feeling: “I wasn’t calm in my head but outwardly I was” (F7). This seemed to be motivated by the belief that, for the woman, seeing her partner upset was “not going to do her any good at all” (F9). Most of the men tried to hide their feelings but some were so overwhelmed by the experience that they could not maintain this façade and “broke down” (F11). Others were able to contain their emotion during the birth but became extremely distressed when on their own and “just broke down in tears” (F5).A “feeling of utter helplessness” (F7) was a key theme, with one father likening the experience to “watching a, yeah, a car go off a cliff and, you know, you’re just slightly too far away to actually do anything about it and you just sort of stand there and watch it all happen” (F4).“I felt helpless and I thought ‘I don’t know what’s going on’” (F10).“at that point I didn’t know what was going on. I didn’t know if she was in, y’know, was in physical danger, if my baby was, erm what was actually happening. I didn’t have a clue.” (F3)Perceiving themselves unable to do anything practical, alongside uncertainty from a lack of information and understanding of what was happening, also left the men feeling helpless:This was in contrast to their usual experiences of feeling in control: “I spend a lot of my life being in control of stuff and looking after stuff and managing stuff……I was in a situation where I was, er, I felt like I was…totally out of control” (F8).“There’s just nothing you can, you can do to sort of change what’s gonna happen and sort of thing. It, it’s up to somebody else to sort of sort out, or not as the case may be” (F4).Consequently, the men had to put their trust in the health professionals, which gave them a sense of unease:I’m sitting there. There’s no drugs in me, I’m not anaesthetised in anyway” (F1).“but at the same time I’m sitting there and Linked to the feeling of helplessness was the fact that the men were very conscious of the medical activity in front of them, the actions of staff and some of the visual images they were confronted with; in contrast sometimes to their partners:Suddenly, erm, I’m just handed the baby and, er, and [partner] and these ten or twelve people shoot out of the room……literally everybody left (F9);So I was just then left in that room on my own and I was in there for, I was in there for over an hour (F3);For several fathers, the experience of being present at the birth involved a period during which they felt abandoned or isolated. Men often found themselves alone either while their partner was being prepared for a surgical birth or when she was being attended to by medical staff after the birth. The men gave stark examples of how isolated they were at times:They took me and, er the babies back to a room whilst they said they were going to clean [wife] up a bit and what have you…It took about..it took her about half an hour then to reappear so …I thought “what the hell is going on here?” (F1).“So I was a little bit lost in, well, just this big empty room at the end of the day and I was just like ‘oh my god, what’s going on? What’s going on with [son]?’” (F5)This isolation increased anxiety and uncertainty about what was happening, intensifying the men’s fears that something was wrong:“When they sent me home at two in the morning and I remember just sitting in the kitchen for hours in bits” (F9).“’There you are. Go. And don’t come back in the morning til ten o’clock.’, I found that so difficult” (F7).For some, a sense of abandonment was felt keenly when they were told to leave the hospital after visiting hours and were left alone but very upset:This was sometimes compounded by the emphasis from staff that facilities were for the mother and child only, not for men. A notable exception was a man whose wife was very ill after childbirth and who was allowed to stay with her in hospital; being treated almost as another patient.A consequence of the nature of many of the births was that some of the first moments with their child, which the fathers had envisaged being shared, joyful events, were lost. They also found themselves in the position of having to negotiate dividing their time between their partner and baby.Five men made specific reference to the loss of anticipated positive experiences as a result of what happened during the birth. For some, the situational aspects and stress of what was happening left them with a sense of regret that they had missed out on the anticipated “magic moment” (F3) of birth. For others, the medical attention needed by their partner meant that some of the things that they had expected to do with them were done alone; “I just anticipated that we’d do it together” (F9). This was made more difficult when the men were aware that their partner would have wanted to do things such as change the first nappy and give the baby the first bottle. For some men their partner’s physical condition after the birth meant that they had to continue as the primary carer for the baby for some time after birth, which was a positive experience but one “tinged with guilt” (F10) that their partner would have wanted to do it.Fathers spoke of “flitting between” their partner and child (F10) and feeling that they were “torn between two posts” (F3). One father reported that he “couldn’t really comfort [partner] because I was holding the baby” (F5), whilst another did not want to leave his wife in theatre to go with his new-born daughter (F11). Although most of the fathers felt that the loss of shared experiences was a negative consequence of the birth, one man stated that although “there was no enjoyment of the moment” he did not think that this was a problem because “you can’t miss what you’ve never had” (F10). In addition, one man acknowledged that it was a “special thing…to be there for [baby]” (F9).“that became very mixed up with emotions of sort of anger, like ‘what on earth d’you think you’re doing?’ y’know? ‘Why…how could you possibly have been so negligent to do that?’” (F6).For some men, interactions with health professionals contributed to their distress during the birth. Five men described difficulties with staff due to feeling “dismissed” or through perceived lack of care: “I didn’t really feel like we were getting much help” and the midwife was “horrible” (F3), causing this to be central to finding the experience traumatic. One father expressed anger towards staff at their perceived negligence:Lack of sensitivity in the way staff spoke to either of the parents also caused distress for the men. One father described himself as “destroyed” (F7) by a comment from the midwife and another felt his partner’s difficulties were not acknowledged by staff, telling her “we have women who’ve had C-sections in here and they’re up and about” (F9).Nobody said anything. You know, that’s…even if the child was born and was dead I would’ve expected them to say something. Not just disappear around the corner. And, and because they didn’t, you kind of have to…where I was at the time I think “There must be a reason they’re not saying something. There must be a reason”.Some men were very angry about how they had been treated; others recognised the difficulty for staff of attending to them and giving information whilst they had a job to do in looking after the woman and child. However, they would have liked more communication. One father recalled vividly the sight of his daughter being “smuggled away” (F1) by staff as they tried to revive her, without acknowledging to him that she had been born:Other men expressed the difficulty of “waiting and waiting and waiting for something, for some information” (F8) and having “no explanation of anything” (F3) during the birth. Participant eight understood this as resulting from the fact that “this is very mundane for [staff] and they understand what’s happening and you don’t”.In the absence of communication from staff, some men tried to infer from body language or their surroundings what was going on; including “scanning for clues” (F8) in the operating theatre or trying to read the body language of the medical staff. Some gave positive descriptions of how staff had communicated with them through the birth, which gave them reassurance, but also reflected that there were times when they would have liked to have known more about what was happening.Several men reported changes in perception and a “heightened awareness” (F1) as the events of the birth took place. Most common was a sense of everything taking a long time; it “felt like forever” (F5); “it felt like about 3 days” (F3). This was usually in the periods when fathers were waiting for information and separated from their partners. Others reported the experience as “surreal” (F10) and that everything happened in “a blur” (F11) and “didn’t really register properly” (F4). Another described “the feeling of being removed slightly from the reality but still…you’re there; it’s very real. It’s so real that it’s unreal” (F1). Some of these effects continued to impact upon the men after the birth.Most fathers indicated that the birth experience had had some impact on them, to greater or lesser degrees. For some their distress continued to be acute, whilst for others the impact had lessened over time.For some of the fathers, the feeling of disconnection which had begun with the distortions of perception during the birth continued afterwards. The degree of disconnectedness ranged from being “completely shocked” (F7) and “stunned” (F1), to going onto “autopilot” (F10), to the man who “went off into some weird twilight zone kind of thing, I think…I sort of, not zoned out for 6 months but sort of…I had an odd reaction” (F4). This was in part related to how the men tried to cope with the enormity of the experience of birth.Preoccupation with the events of the birth continued in the weeks, months and even years afterwards; being “still fresh in my mind” (F11). Rumination was a feature for some men who found themselves “going over and over” (F3) what had occurred, with one father even trying to imagine what pain his partner must have been in. External stimuli, such as television programmes and stories of babies being born, triggered their memories of the birth and as a consequence they tried to avoid them. Some had flashbacks to the birth or relived it in their dreams. At the most severe end of this continuum, was a father who described such intrusive thoughts of the birth that, a year on, he never went to bed, instead watching television on the couch until he slept, “because even if I go to bed, even still the events of [the birth] go round and round and round in my head” (F1), preventing him from sleeping. Two fathers identified that the birth had had a delayed impact on them. They were both men with a previous history of depression, which after a period of around 12 months of coping, they felt was returning.For some men, the birth experience and its personal consequences adversely impacted up on their work. One father who described himself as previously very dedicated to work explained that he had had his “least productive twelve months” (F9) since first being employed; another had reduced his workload due to difficulties concentrating, and one man had taken a sabbatical from work “I kind of got to the point that I said, look I need to stop work for a bit and…take some time out” (F8). In contrast, participant four took refuge in his work; attempting to retain some normality through the belief that “I’ll just go back to [work] and everything will be fine”; another found work a helpful distraction.There’s no point going to work and saying “My head is all over the shop because of what happened back here” and, y’know, and it’s like you can’t say that to somebody who’s looking at the photo of your two beautiful new-borns. And they’re looking at you and “you should be pulling yourself together, forget about that now” (F1).Some men commented on their reluctance to discuss their experiences, particularly with their colleagues: “We’re like a lot of males, male-orientated and, sort of, like you don’t want to show your emotions and like it’s all a bit of a laugh. You make a joke of things all the time” (F5). The expectation that others may not understand or would dismiss their distress also affected how fathers shared their experiences of the birth.Men described feeling “much more emotional” (F5) and that this was unpredictable. Often they were unsure whether this was an effect of being at the birth or a normal response to becoming a parent but it was usually felt to be inappropriate. Participant ten recalled becoming emotional over a story he heard on the radio, explaining “that made me kind of go into tears. I thought, that’s not, that’s not right, I mean it’s a lovely story but…”.me” (F5); dismissing the experience of witnessing and being part of the birth because it was emotional, rather than physical:“I felt guilt…that I was feeling traumatised when, you know, obviously I hadn’t really gone through anything” (F11).Although for many of the men the experience of birth had a very significant impact on them, fathers indicated that they did not feel that they had a right to be affected because “nothing’s actually happened to “there’s no room, if you like, for me feeling sorry for myself, or, or having time to be a patient” (F1).Intertwined with this idea was the concept of masculinity and what the fathers expected of themselves. As one man explained, “someone had to be the strong one” (F8) andFathers felt that as they had not physically given birth it was their responsibility to “get on with it” (F1). These beliefs dictated the coping strategies that the men employed to deal with the effects of the birth.The men’s coping strategies seemed to be dictated by their beliefs about acceptable masculine roles such as stoicism, keeping emotions to themselves and being strong for others. Avoidance was the dominant theme and was evident at some level even for the men who spoke of their difficulties as resolved. Fathers referred to having “bottled it up” (F8) or “putting it in a box” (F1) and not “wanting to get into it too much” (F10). This occurred along a continuum from avoiding thinking or talking about the birth to the father mentioned previously who described himself as in a “twilight zone” (F4) for several months after the birth.“I kind of wonder if that’s because it had just been bottled up and held and like ‘come on, get on, get on, get on, get on, deal with it’” (F8).This also related to the idea of ‘getting on with it’ which included elements of avoidance such as hiding feelings from their partners because “I’m a big lad, I can look after myself” (F1) and not wanting their partner to “know how scared I was that night” (F5). Fathers tended to focus on the present and getting through each day, at the cost of addressing their emotions about the birth. However, most did acknowledge that, as a coping strategy, this had potential negative consequences. One father who described himself as “falling to pieces” as a delayed impact of the birth explainedThere were some exceptions to avoidance. One man had forced himself to think about the experiences as a way of dealing with them and felt that they were now resolved. Another tried to watch programmes about birth to help him deal with his feelings. Another described an almost desperate search for some context in which to understand his experience, “anything that could help me process what, you know, that, that day” (F11).Two fathers had sought help for their distress. Interestingly, these were both men who had a previous history of depression. Both described being aware of the signs that they were having difficulties with their mental health and both had also had some form of counselling or talking therapy on previous occasions. However, both had reached a significant level of distress before seeking help.The experience of the birth had various consequences, both positive and negative, on the men’s relationship with their partners and children.“I think her, her having such a kind of intense experience, it also brought home to me the fact that she was not just my wife any more, she was also the mother of my child” (F6).For some men the experience of the birth had a positive impact, including a deepening of feeling for their partner and the relationship taking on a new dimension:For others, the impact of the birth and how the men tried to cope with it acted as a barrier in the couple’s relationship. One man’s attempts to cope with his distress by withdrawing and hiding his emotions resulted in his partner perceiving that he was “blasé……that I didn’t care too much about what had happened” (F5). Other partners felt unsupported and, in some cases, the level of disconnection was such that the man felt there was little relationship left with his partner.The partner’s response to the birth also affected how the man felt. One explained that “it helped me to see her dealing with it” (F2), whilst for others the on-going emotional or physical effects of the birth on their partner prolonged their distress and it was “difficult to deal with her dealing with it” (F3). In some couples, the men and their partners had very different mechanisms for coping with the experience and some of the men commented on the very different perspectives that they had each had of the birth as “she didn’t see it from this angle” (F10).“It made me wary of the process of the delivery and where it might put me. And if I was to have that experience again, would it be worse? Could I cope?” (F7).For three men the experience had affected their feelings about future pregnancies. For one, “talk of another child means it’s all coming back” (F11); other fathers doubted their ability to cope:This had impacted on some of the relationships in that their partners had wanted to have more children sooner.All bar one of the men described that, despite the traumatic experience of the birth, their relationship with their child was, for the most part, positive. Some believed that the difficult experience of the birth and the effects on their partners had a positive consequence on increasing their bond with the baby, particularly if they had had to take on the role of primary carer for a period after birth; “I got very good at being hands on and doing it all right from the start” (F10).One exception was father 4, who felt that his relationship with his child was “uneasy”, which he attributed to the impact of her birth on him. He described himself as “zoned out” through the early months of her life and thought this was the cause of their lack of close relationship. The impact for him was long-lasting as his child was almost seven years old.A minority of the men felt that their difficulties with the birth were resolved; however for most there was a sense that something endured which was yet to be addressed. For some, the fact that things had still not “got back to normal” (F1) and that the effects of the birth were “still front and centre in our life” (F3) compounded their difficulties. Others felt that, although the impact on them had reduced, there was a lingering effect, “a cloud” (F10), and that the experiences still needed “straightening out in my head” (F9).Two main aspects could have reduced men’s distress: being prepared and the responses of staff and the health system. A third theme arose from the men’s comments: the need for support yet the difficulty of providing it to men, who are loath to be seen seeking help.Three men suggested that being aware that there could be difficulties would have reduced their distress during the events of the birth. Most had not anticipated anything other than a straightforward birth, suggesting that the knowledge that labour and birth is “not risk free” (F5) could have helped. An antenatal class demonstration of a surgical birth had helped one father feel reassured when he came to experience one. However, one man thought that “nothing can prepare you for it” (F8).Six men indicated that there were things that staff could do to help them through the process. They generally thought that better communication would have been helpful although they acknowledged the difficulty of doing this during the labour. However; most felt that after the birth “just having someone to talk to” (F7) and “anything that could maybe help me process what, you know, that, that day” (F11) would have been helpful. Following a difficult birth, fathers also desired acknowledgement from staff that it “wasn’t normal” (F1) and could be difficult for the man. Two fathers had had a follow-up meeting with members of the medical teams involved in the birth; another had decided with his partner to ask to view the medical notes in an attempt to help him process what had taken place during the birth. It seemed important to the men to be able to gain some context for their experience in order to be able to deal with it.There was a tension and contradiction in the men’s responses to the question of what would have helped them, which was that they expressed that there should be more support for fathers but also that men would be unlikely to access help.Most men seemed prepared for the attention during birth and immediately afterwards to be “all rightly on the mother” (F11); however, they also thought that men were “tertiary” (F10), often “overlooked” (F8) and “an afterthought” (F5) and that after the birth there was “nothing for the chap. Erm, and I felt I needed it far more than [wife] did” (F7).Despite believing that men should be supported, the fathers conveyed that men “don’t like to show weakness” (F11) or be seen to access help. One father explained that he would not have taken up any support offered at the time because “I’m a man” (F4), whilst another maintained that even when he was asked how he was feeling “you say you’re fine, because there are two people who are far more important” (F10). Some men commented that taking part in the study was useful because “talking about it helps” (F11), particularly “in a completely anonymous way” (F10). An opportunity to talk about their experience was often part of the motivation to participate. One father suggested that taking part had validated that his experience was difficult and upsetting as, “you’re allowed to be emotional about it because someone understands that it does affect the partner as well” (F5).This study provides new information concerning the nature of men’s experiences when they have found being present a childbirth traumatic; what factors contribute to the experience of childbirth as traumatic; and the consequences for them and their families. In summary, men who experienced childbirth as traumatic described this as a rollercoaster of emotions with events building on each other. They were fearful of the death of their partner and or baby, mirrored their partner’s distress but tried to present a controlled exterior whilst feeling they were helplessly watching a catastrophe unfold. They felt abandoned and isolated - often being excluded - and that staff did not inform them or treat them with sensitivity.They felt they lost the anticipated positive shared experiences with a newborn. In terms of their relationships with their partners, through respect for what she had endured, on occasions there were positive impacts and the relationship with the child was not generally adversely affected. However, postnatally the experience of birth continued to resonate, leading to disconnection, rumination and continued distress. Men tried to block and avoid these responses feeling that they were unjustified as ‘nothing had happened to them’. They recognised the need for help but were reluctant to seek this. All of the men met criterion A for PTSD . The IESThe men’s experience of the birth as “a rollercoaster” resonates with other findings on fathers’ experiences of non-traumatic childbirth . However, the fathers in the current study did not experience euphoria at the end of the process; for them, layers of stress accumulated throughout labour and birth and, for some, after birth. This is an important distinction, particularly when considered within a stress and coping framework . AccordMen have been found to favour problem-focused coping strategies for managing stress, which usually rely on taking control and action . Their fThe distortions of perception experienced by some fathers during the birth may indicate peritraumatic dissociation which, in women, has been shown to be an indicator of subsequent postnatal PTSD . It is nThe isolation and abandonment described by the men is also of interest. Men can often feel excluded to some degree during childbirth –30 but tThe birth experiences described had a significant impact on the fathers’ lives and functioning. Experiences of disconnection and preoccupation with the events are consistent with post-traumatic stress, as is avoidance, which was the primary coping strategy adopted by most of the men. Ideas about masculinity seemed to influence the men’s strategies for managing their distress. Pleck’s  gender-rme” and the view that being affected by the emotional aspects of the experience was in some way unjustified. This seems to have established how they would cope with the experience afterwards, leading to the avoidance strategies adopted. White’s study ).Men’s desire for preparation suggests that services need to acknowledge the different needs of fathers and mothers in pregnancy and birth. Men desired communication and information to help them contextualise their experiences. Antenatal care should include some information about what will happen during different types of births, including emergencies, in order to help provide this context. The study also highlights the importance of care for both parents, particularly during complicated births. Primarily, good care of the mother throughout the birthing process is likely to reduce distress for both parents; however, men and women have different experiences and perspectives through childbirth and there may be individual needs that should also be attended to, such as how fathers are supported during times that they cannot be present in surgical or emergency births. Fathers want to be near their families after distressing births  and repoThe effect of cumulative stressors on the men’s experience suggest that it may be difficult for health professionals to pick up on fathers’ distress, as what staff might view as minor incidents could be having a far greater impact on the men within the wider context of the birth experience. In addition, men’s reluctance to show what they perceive as weakness in the situation means that it is unlikely they will ask for support. Discussions within antenatal classes about possible responses to the birth experience could help to normalise these for men and thereby increase the likelihood of accepting support if it is needed. Acknowledgement of the needs of fathers during postnatal Health Visitor checks may also legitimise for men that their coping following childbirth, as well as the mother’s, is important and can be discussed. This may also be important in assessing post-natal support for the mother, given that traumatic birth experiences can impact negatively on the couple’s relationship.As mentioned, a father’s presence is now generally expected in modern western cultures; however, there is some emerging evidence to suggest that it can have a negative impact on the woman’s birth experience and some clinicians have argued against it as a practice . Given It was recognised prior to the research that telephone interviews may have limitations in terms of engaging participants and building rapport; however, several participants reported that the anonymity provided by a telephone conversation was preferable.Most fathers described some form of obstetric complication during the birth. This likely reflects the recruitment strategy of accessing men via trauma-related and fathers’ websites. It may mean that fathers who have found birth traumatic for reasons other than obstetric complications may have been less likely to find and take part in the study. Furthermore, the clear message that men are very reluctant to either acknowledge their difficulties or access support, and the dominant coping strategy of avoidance, indicate that there are likely to be men whose experiences would be important to the study but who would not come forward to participate.Longitudinal studies with fathers to investigate the risk factors for developing mental health difficulties such as PTSD following child birth, the prevalence and course of the difficulties are required. Almost all of the men in this study experienced objectively complicated births suggesting that further research into men’s experiences of non-routine childbirth would be useful and may help to clarify the factors that contribute to subjective distress. Future research could include intervention studies into how information is provided to fathers and how they are prepared for birth and supported afterwards. Additional research into the nature of couple’s experiences of a traumatic birth may also help to elucidate interactions between how the impact of a traumatic birth on each parent may affect how the other copes with their birth experiences.This study adds to current literature that suggests being present at childbirth can be an extremely distressing experience for men and one which may induce symptoms of post-traumatic stress, which can be severe and enduring. It suggests that it is essential for maternity services to routinely attend to the needs of fathers in their own right before, during and after childbirth. This may include: father-focused information about the birth process and their role; provision of continuous support for both parents through the birth process; and, following birth, the opportunity for families to remain together in hospital. Masculinity ideology may act as a barrier to men accessing help; therefore support structures, such as post-natal reviews or health visitor checks on the father’s coping, should be in place as a matter of course for all fathers.


Cigarette smoking has severe adverse health consequences in adults and in the offspring of mothers who smoke during pregnancy. One of the most widely reported effects of smoking during pregnancy is reduced birth weight which is in turn associated with chronic disease in adulthood. Epigenome-wide association studies have revealed that smokers show a characteristic “smoking methylation pattern”, and recent authors have proposed that DNA methylation mediates the impact of maternal smoking on birth weight. The aims of the present study were to replicate previous reports that methylation mediates the effect of maternal smoking on birth weight, and for the first time to investigate whether the observed mediation effects are sex-specific in order to account for known sex-specific differences in methylation levels.Methylation levels in the cord blood of 313 newborns were determined using the Illumina HumanMethylation450K Beadchip. A total of 5,527 CpG sites selected on the basis of evidence from the literature were tested. To determine whether the observed association between maternal smoking and birth weight was attributable to methylation, mediation analyses were performed for significant CpG sites. Separate analyses were then performed in males and females.AHRR, MYO1G, GFI1, CYP1A1, and CNTNAP2. The effect of maternal smoking on birth weight was partly mediated by the methylation of cg25325512 (PIM1); cg25949550 (CNTNAP2); and cg08699196 (ITGB7). Sex-specific analyses revealed a mediating effect for cg25949550 (CNTNAP2) in male newborns.Following quality control, 282 newborns eventually remained in the analysis. A total of 25 mothers had smoked consistently throughout the pregnancy. The birthweigt of newborns whose mothers had smoked throughout pregnancy was reduced by >200g. After correction for multiple testing, 30 CpGs showed differential methylation in the maternal smoking subgroup including top “smoking methylation pattern” genes The present data replicate previous findings that methylation can mediate the effect of maternal smoking on birth weight. The analysis of sex-dependent mediation effects suggests that the sex of the newborn may have an influence. Larger studies are warranted to investigate the role of both the identified differentially methylated loci and the sex of the newborn in mediating the association between maternal smoking during pregnancy and birth weight.The online version of this article (10.1186/s12864-018-4652-7) contains supplementary material, which is available to authorized users. Previous research has identified associations between maternal smoking during pregnancy and a range of health problems in the offspring [Cigarette smoking has severe adverse health consequences in adults and in the offspring of mothers who smoke during pregnancy . Despiteffspring , 3. One ffspring –6. Low bffspring , cognitiffspring , and chrffspring , 10, andffspring . Low birffspring , 13. On ffspring , 15.AHRR, GFI1, MYO1G, CYP1A1, and CNTNAP2.A plausible mechanism through which exposure to adverse intrauterine conditions may negatively impact longterm health is DNA methylation. Candidate CpG investigations and epigenome-wide association studies (EWAS) have found consistent associations between smoking and differential DNA methylation in adults –18. A nuPrevious authors have formulated the hypothesis that maternal smoking impacts birth weight via smoking-induced DNA methylation. According to this theory, differential methylation functions as a mediator, i.e., a variable that accounts for part of the relation between the predictor and the criterion , 36. IniThe aims of the present study were to replicate the previously reported mediating effects of methylation on the association between maternal smoking and birth weight, and for the first time to investigate whether the observed mediation effects are sex-specific. The analyses focused on high confidence smoking-related sites, and were restricted to CpG sites with: (i) significant association with smoking in a large recent meta-analysis ; or (ii)Analyses were also performed to determine whether the observed mediation effects were sex-specific, since: (i) methylation levels show substantial sex differences ; (ii) thData for the present study were derived from the POSEIDON study . A detailed description of the POSEIDON study is provided elsewhere . The stuA structured interview and a questionnaire battery were used to collect information concerning environmental-, sociodemographic-, medical-, and psychosocial risk factors for stress. A detailed description of these instruments is provided elsewhere . SociodeWhole cord blood was collected immediately after birth from n=313 newborn singletons. For n=299 newborns, automated genomic DNA extraction was performed using the chemagic Magnetic Separation Module I . For n=14 newborns, a low volume of umbilical cord blood (<2 mL) was obtained. For these 14 samples, DNA was isolated using the QIAamp DNA Blood Midi Kit . All genomic DNA samples were stored at -20 °C prior to analysis.DNA methylation was measured using the Illumina Infinium HumanMethylation450K Beadchip.Quality control (QC) and all statistical analyses were performed using the R version 3.2.5 statistical analysis software , and theP-value > 0.01) at more than 1% of positions) were excluded. Probes were excluded if any of the following criteria were met: beadcount <3; detection failure in more than 1% of samples; located within 10bp of a single nucleotide polymorphism (SNP); cross reactivity; X- or Y- linked status.Methylation intensity signals were extracted from raw intensity data using the preprocessENmix procedure . This inFor all downstream analyses, methylation intensity data were converted to M-Values . To deteTo avoid introducing additional heterogeneity with regard to birth weight, mothers whose pregnancy was complicated by premature delivery  or treatment for gestational diabetes were excluded prior to analysis. To minimize the risk of spurious associations due to small sample size and thus avoid false positives, the analysis was strictly limited to high confidence smoking-related CpG sites that had shown significant association with smoking in a large recent meta-analysis , and CpGTo exclude other significant loci in this sample, we also performed an EWAS on smoking (data not shown).Sites showing significant association with smoking (FDR<0.05) were then used to test whether methylation levels partly mediate the effects of maternal smoking on birth weight. This was performed using a quasi-Bayesian approach as proposed in Imai et al. ; for a m: Text, awww.egg-consortium.org [http://egg-consortium.org/birth-weight-2016.html) and MAGMA v1.06[http://www.internationalgenome.org/data). SNPs were assigned to a gene if the variant was located within 20kb flanking its transcript.Data on the trait “birth weight” were obtained from the EGG Consortium via the UK Biobank Resource. These data were downloaded from tium.org . Gene-baGMA v1.06. The appAfter technical QC, a total of 405,654 sites and 311 individuals were in principle available for analysis. A total of n=5,527 of these CpG sites had previously been reported associated with smoking (see above) and were therefore selected for association testing. After excluding prematurely delivered newborns and individuals receiving anti-diabetic treatment during pregnancy the final sample size was n=282 individuals . Of these, 13 males and 12 females were the offspring of mothers who had smoked throughout pregnancy. The general characteristics of the participants included in the present study are provided in Additional file The average difference in birth weight between the smoking and non-smoking groups was 209g. The newborns of smokers had a mean birth weight of 3,267g. The newborns of non-smokers had a mean weight of 3,476g (see Table n=144), the average birth weight was 189g lower in the smoking subgroup compared to the non-smoking subgroup, i.e., birth weight was 5.6% lower when mothers smoked. This difference however did not reach statistical significance. In male newborns (n=138), the average birth weight was significantly lower by 242g in the smoking subgroup compared to the non-smoking subgroup, i.e., birth weight was 6.7% lower when mothers smoked .Following correction for multiple testing, a total of 30 CpG sites showed significant differential methylation in the smoking subgroup .PIM1, p=0.005); cg25949550 ; and cg08699196 . Sex-specific analyses for these three CpG sites revealed that cg25949550  mediated the effect of maternal smoking on birth weight in male newborns . PIM1 and CNTNAP2 failed to achieve nominal significance (p>0.05). Single marker p-values of the SNPs at the ITGB7 locus are listed in Additional file In the gene-based-analysis, AHRR, GFI1, MYO1G, CYP1A1, and CNTNAP2. These represent the top five differentially methylated genes reported in adult smokers [The aims of the present study were to replicate the finding that the association between maternal smoking and birth weight is mediated by methylation, and to investigate whether the observed mediation effects are sex-specific. Differentially methylated CpG sites were detected in 13 genes, including  smokers , 60, 61, smokers , 32, 37.PIM1, CNTNAP2, and ITGB7 mediated the effect of maternal smoking on birth weight in the complete sample. The serine/threonine-protein kinase PIM1 has a marked anti-apoptotic effect, and its level is increased in lung tissue following exposure to cigarette smoke [PIM1 - corresponding to a decreased methylation level - protects against cell death induced by cigarette smoke and neutrophilic airway inflammation [ PIM1 is lower in smokers than in non-smokers. A lower methylation level can lead to an upregulation of gene expression. Thus, upregulation of PIM1 in smokers could be an adaptive process to protect against negative effects of cigarette smoking. In monkeys, research has shown that PIM1 is associated with body mass indeces after calorie restriction [CNTNAP2) encodes a member of the neurexin family, whose members function as cell adhesion molecules and receptors in the nervous system of vertebrates. Genetic variation in CNTNAP2 has been associated with the regulation of body weight [CNTNAP2 is lower in infants whose mothers smoked during pregnancy, presumably leading to higher gene expression. As loss of CNTNAP2 has been shown to lead to deficits in axonal excitability [ITGB7) encodes a protein that is a member of the integrin superfamily. Members of this family are adhesion receptors, which are involved in signaling from the extracellular matrix to the cell. High expression of ITGB7 has been found to be associated with poor survival of cancer cells [ITGB7 is increased, which may reduce its gene expression. A reduction in of ITGB7 expression might result in higher survival of cancer cells and, thus, oncogenesis.Mediation analysis of the 30 CpG sites revealed that CpG sites in the genes te smoke . Interesammation . In our triction . PIM1 betriction . The Cony weight . Interesy weight . CNTNAP2tability , lower mer cells . In the PIM1, CNTNAP2, and ITGB7 were not implicated in previous EWAS of birth weight [ITGB7 was strongly associated with birth weight . Furthermore, ITGB7 was found to be associated with the pathophysiology of childhood obesity in a Hispanic population [The genes h weight –71. Howeh weight , the prepulation .CNTNAP2 had a more pronounced effect in male newborns, and failed to reach significance in females. Further sex-specific mediation effects are possible. However, their detection will require larger samples.As methylation levels are known to be sex-specific already at birth, the present study involved sex-specific mediation analyses. Unsurprisingly, these suggest that the mediation effects can also be dependent on sex. The CpG site in PIM1 and CNTNAP2 , a description of the differentially methylated genes, Figure S1. , Figure S2. , Table S1. , Table S2. , and Table S3. ). (DOCX 76 kb)


The goal of integrated care is to offer a continuum of care that crosses the boundaries of public health, primary, secondary, and tertiary care. Integrated care is increasingly promoted for people with complex needs and has also recently been promoted in maternity care systems to improve the quality of care. Especially when located near an obstetric unit, birth centres are considered to be ideal settings for the realization of integrated care. At present, however, we know very little about the degree of integration in these centres and we do not know if increased levels of integration improve the quality of the care delivered. The Dutch Birth Centre Study is designed to evaluate birth centres and their contribution to the Dutch maternity care system. The aim of this particular sub-study is to classify birth centres in clusters with similar characteristics based on integration profiles, to support the evaluation of birth centre care.This study is based on the Rainbow Model of Integrated Care. We used a survey followed by qualitative interviews in 23 birth centres in the Netherlands to determine which integration profiles can be distinguished and to describe their discriminating characteristics. Cluster analysis was used to classify the birth centres.n = 10): which are mainly owned by primary care organizations and established as physical facilities to provide an alternative birthplace for low risk births; 2) “Multi-disciplinary-oriented birth centres” (n = 6): which are mainly multi-disciplinary oriented and can be regarded as facilities to give birth, with a focus on integrated birth care; 3) “Mixed Cluster of birth centres” (n = 7): which have a range of organizational forms that differentiate them from centres in the other clusters.Birth centres were classified into three clusters: 1)“Mono-disciplinary-oriented birth centres”  contains supplementary material, which is available to authorized users. The essence of integrated care is a continuum of care for service users, crossing the boundaries of public health, primary, secondary, and tertiary care –3. IntegIn the course of the last decade, several birth centres were established for various reasons , resulting in a substantial rise of births taking place in hospital maternity wards . FurtherThe Dutch Birth Centre Study was designed to evaluate the performance of birth centres and their possible added value to the quality of the Dutch maternity care . BecauseIn this study, we used a combination of surveys and qualitative interviews. The data generated by the interviews were used to validate the information from the questionnaires. The study was conducted from January 2014 until August 2015 as part of the Dutch Birth Centre Study .In this study, we used the concept of integrated care to construct a typology of birth centres. We based our work on a conceptual framework developed by Valentijn et al. . Their “Because a validated questionnaire to examine integrated care in birth centres was lacking, we constructed a questionnaire based on a survey that was used to examine integrated care in primary care organizations . For eacThe Dutch Birth Centre Study started with the identification of birth locations regarded as birth centres and the development of a definition for birth centres in the Netherlands , 21. SubThe aim of the interviews was to obtain an additional qualitative view of the degree and nature of integration in the birth centres, and to validate the collected data from the questionnaires. The first author (IB) visited the birth centres and interviewed all respondents.With participants’ informed consent, all interviews were audiotaped and transcribed verbatim. These transcriptions were collected per birth centre and coded deductively based on the determinants per dimension of integration . As a meThe analysis presented here is based on the quantitative data from the questionnaires. There are two stages in our analysis: (1) calculating the mean score on integration determinants and dimensions for each birth centre, (2) classifying the birth centres based on these mean scores.The questionnaire consists of six dimensions of integration, each divided into four determinants. First, we calculated the mean scores of all respondents per dimension for each birth centre (range 1–4). Then we calculated the mean scores of all respondents, including the first author (IB) for the birth centres on the six dimensions of integration (range 1–4). We also computed a total integration score per birth centre by calculating the mean score of the six dimensions combined (range 1–4).A four-step procedure was followed to classify the birth centres into different clusters . We condBetween January 2014 and April 2015, 23 birth centres were visited. During these visits, the first author interviewed 69  representatives and professionals working within or with a birth centre (range 2–5 per birth centre). Birth centre integration questionnaires were sent to 73 managers and professionals, 61 completed the questionnaire (response rate of 84%). One birth centre was unable to participate in the interviews, because of their workload. However, one professional completed the questionnaire. A researcher (MHi) who was familiar with this birth centre because of her involvement in another part of the Dutch Birth Centre Study also filled in the questionnaire based on her knowledge of this centre.Table p < .001) and with this analysis using the initial cluster centroids from the hierarchical method as seed points . Table p = .001), professional integration  = 15.0, p <.001), organizational integration  = 16.5, p < .001), functional integration  = 25.2, p < .001) and system integration  = 23.5, p < .001). No significant differences were found for the normative dimension  = 3.37, p = .55).Based on the hierarchical cluster analysis (using Ward’s method) the birth centres were classified into three clusters. This classification showed a good agreement with the non-hierarchical cluster analysis  and Multi-disciplinary-oriented birth centres (MUBC) n = 10) and is characterized by integration scores on the six dimensions of integration lower than the average score of all birth centres combined and lower than the birth centres in the other clusters. The results of the interviews indicated that birth centres in this cluster are mainly mono-disciplinary (primary care) oriented and are more focused on being a facility to give birth than on improving collaboration between care providers or realizing care integration. They were established as physical facilities to provide an alternative birthplace for low risk births. Some of these birth centres were established to reduce the pressure on hospital maternity wards, others to provide an alternative to home birth. Centres in this cluster are almost all owned by primary care organizations (community midwives or maternity care assistance organizations). They were not established with the intention to realize integrated care; their focus is more on practical issues. Protocols, guidelines and other agreements are not discussed in the birth centre itself, but at a different level, at local networks called “local maternity care consultation and cooperation groups” (MCCC-groups) [This cluster includes 43.5% of the birth centres (-groups) . These nn = 7) of the centres. Compared to all birth centres, these centres are characterized by lower scores than average on the professional, organizational and system integration dimensions and relatively higher than average scores on the clinical and functional integration dimensions. Their scores on normative integration were average. Birth centres in this cluster had higher scores on all integration dimensions compared to the cluster MOBC. Compared to cluster MUBC (described below) these centres had higher clinical integration scores and lower scores on the other dimensions. Both the results of the interviews and the questionnaire indicated that birth centres in this cluster differ more from each other in their organization than the centres in the other clusters. It is difficult to indicate an overall characteristic for the birth centres in this cluster except that they have the highest integration scores of all clusters on the clinical dimension ). In governance structure and ownership, they are more comparable to the birth centres in cluster MOBC, but on the functional dimension they are more comparable to the birth centres in cluster MUBC.Birth centres in this cluster make up 30.4% (n = 6) of the centres and are characterized by integration scores on the six dimensions of integration that are higher than the average scores of all the birth centres. The interviews taught us that birth centres in this cluster are mainly multi-disciplinary (both primary and secondary care) oriented. These birth centres can be regarded as facilities to give birth, with a focus on integrated (birth) care. They have governance structures consisting of both primary and secondary care organizations. The disciplines involved have formulated a joint vision on birth care and the birth centres themselves decide on agreements, protocols, and guidelines.Birth centres in this cluster comprise 26.1%  and in our interviews professionals working in or with these centres pointed out that collaboration in their region worked well. However, they have chosen to organize their birth centre apart from secondary care. In addition, they are focussed on achieving integration in the clinical dimension, which is probably closest to their own professional work.Our classification of birth centres is comparable with observations in other integrated care organizations. Shortell et al. developed a taxonomy of Accountable Care Organizations in the USA, based on eight attributes of these organizations such as size, scope of services offered, and the use of performance accountability mechanisms . They idThis study, part of the Dutch Birth Centre Study, is the first study to classify birth centres based on integration profiles. All birth centres in the Netherlands participated in this study, which gives a unique overview of the level of integration in birth centres. For our study, we used a self-constructed questionnaire because a validated was lacking. Using a non-validated questionnaire introduced some problems in the reliability of the results of our study. To minimize these problems, we developed a study design that used a standardised questionnaire combined with personal interviews. All interviews were conducted by the same researcher, who afterwards also completed the questionnaire. In this way, quantitative data derived from a non-validated questionnaire were complemented with qualitative data, increasing reliability. Another possible limitation of this study is the potential bias in the selection and number of respondents per birth centre. We asked managers of birth centres to select two or three care providers from different professions working within or with the birth centre to fill in the questionnaire and to be interviewed, which could result in selection bias. To counter this, the researcher also filled in the questionnaire complementing quantitative data with qualitative data.Our study shows that the birth centre integration questionnaire can differentiate between birth centres based on integration variables. Except on the normative dimension, we identified statistically significant differences between clusters of birth centres on all dimensions. However, the questionnaire needs validation. It is possible that respondents gave socially desirable answers to some integration determinants in the normative dimension (e.g. trust and reliable behaviour). In other dimensions the hierarchy of the answers to some of the questions is questionable. The results of this study and another study (assessing maternity care consultation and cooperation groups) will be used to validate the questionnaire, resulting in a validated instrument for future research in birth care. Based on this validation, the instrument can be used to assess integration aspects in other organizational forms in birth care, both national and international. With this assessment, recommendations for the organization of birth care in the future can be made. It will enable policy makers, health care financiers, professionals and users of maternity care to make an informed choice about the effectiveness of different ways of organizing care at birth.Based on the “birth centre integration questionnaire”, birth centres in the Netherlands can be classified in three clusters according to different integration profiles. Although based on a non-validated questionnaire, which has its limitations, results of this study will allow future assessments of the relationship between integration profile and quality, costs, experiences of clients and professionals, and perinatal and maternal outcomes of birth centre care. With this assessment, recommendations for the organization of birth care in the future can be made. Further research is needed to assess the validity of the birth centre integration questionnaire. Based on this validation, the instrument can be used to assess integration aspects in other organizational forms in birth care, both national and international.Additional file 1:Dutch Birth Centre Integration Questionnaire. A translation of the questionnaire (from Dutch to English) used in this study. (XLSX 18 kb)Additional file 2:Example of a topic list, used in the interviews. An example of a topic list used in the interviews. (DOCX 20 kb)