To describe clinical characteristics and preoperative management of a national cohort of infants with Hirschsprung's disease (HD).Population-based cohort study of all live-born infants with HD born in the UK and Ireland from October 2010 to September 2012.All 28 paediatric surgical centres in the UK and Ireland.305 infants presenting before 6 months of age with histologically proven HD.Incidence, clinical characteristics including gestational age, birth weight, gender, associated anomalies; age and clinical features at presentation; and use of rectal washouts or stoma.The incidence of HD in the UK and Ireland was 1.8 per 10 000 live births (95% CI 1.5 to 1.9). Male to female ratio was 3.3:1. An associated anomaly was identified in 23% (69), with 15% (47) having a recognisable syndrome. The proportion of infants who presented and were diagnosed in the neonatal period was 91.5% (279) and 83.9% (256), respectively. 23.9% (73) and 44.2% (135) passed meconium within 24 and 48 hours of birth. 81% (246) first presented to a hospital without tertiary paediatric surgical services, necessitating interhospital transfer. Initial colonic decompression was by rectal washouts in 86.2% (263) and by defunctioning stoma in 12.8% (39). Subsequently, 27.4% (72) of infants failed management with rectal washouts and required a delayed stoma, resulting in 36.4% (111) of infants having a stoma.In this population-based cohort, presentation outside the neonatal period was rare. Nearly half of the infants with HD passed meconium within 48 hours of birth and over one third were managed with a stoma. The estimated incidence of Hirschsprung's disease (HD) is approximately 1 in 5000 live births and more than 90% of cases present in the neonatal period.Most information on the epidemiology and early management of HD comes from retrospective case series, voluntary reporting surveys and surveys of intended practice.There is little published information on interactions between infants with HD and healthcare services prior to a diagnosis of HD being established.A quarter of infants with Hirschsprung's disease (HD) pass meconium within 24 hours of birth and nearly half within 48 hours of birth, limiting the validity of ‘timing of first meconium’ as a screening question for HD.One in three infants with HD is discharged home after birth, prior to diagnosis, placing a heavy burden on primary care to ensure timely referral.More than a third of infants with HD receive a stoma prior to definitive surgery—a higher rate than reported internationally and in contrast to surgeons reported intent.Hirschsprung's disease (HD) is characterised by the absence of intrinsic parasympathetic ganglia (aganglionosis) in the distal bowel, resulting in functional intestinal obstruction. Patients classically present during the neonatal period or early infancy.Worldwide, the estimated incidence of HD is approximately 1 in 5000 live births,Following confirmation of HD, initial management aims to maintain colonic decompression. Most paediatric surgeons advocate rectal washouts to achieve this, aiming to perform a primary pull-through,The aims of this study were to describe the incidence, clinical characteristics and management prior to definitive surgery in a national cohort of infants with HD in the UK and Ireland.All live-born infants, up to 6 months of age, diagnosed with HD , between the 1 October 2010 and 30 September 2012 were eligible for inclusion in the study. Cases were identified using the British Association of Paediatric Surgeons Congenital Anomalies Surveillance System.Duplicate reports were eliminated by comparing hospital of birth, gestation at birth and date of notification and follow-up with the reporting clinicians.Descriptive statistics were used to describe the basic demographics, associated anomalies and mode of presentation. We calculated the rate of HD with 95% CIs among live-born infants by using the denominator of total reported live births in England and Wales,Between 1 October 2010 and 30 September 2012, 305 infants with HD were identified in the UK and Ireland. Over the same period, there were 1 729 854 live births in the UK and Ireland.The basic demographics, associated anomalies and presenting features for the cohort are summarised in Overall, the HD cohort included 3.3 times more male than female infants  and 26 (9%) infants had a positive family history. An associated anomaly was identified in 69 infants (23%), with 47 (15%) of these having a recognisable syndromic association, including Down syndrome , Mowat-Wilson syndrome , congenital central hypoventilation syndrome  or Bardet-Biedl syndrome . An associated cardiac anomaly was identified in 29 infants (10%), which occurred in the context of an underlying predisposition syndrome in 22 out of 47 infants (47%) and in 7 out of 258 non-syndromic infants (3%). An associated urological anomaly was identified in 11 infants (4%), which occurred in the context of an underlying predisposition syndrome in 4 out of 47 infants (9%) and in 7 out of 258 non-syndromic infants (3%).Abdominal distension and bilious vomiting were the most common clinical features at presentation . In combThe initial method for colonic decompression , the final management prior to definitive surgery and the proportion of infants in each group undergoing definitive surgery within 1 year of diagnosis are summarised in Definitive surgery was carried out in 270 (89%) infants within 1 year of diagnosis, establishing the length of aganglionosis. The pathological TZ was rectosigmoid in 198 (73.3%), long segment  in 60 (22.2%), total colonic in 8 (3.0%) and unknown in 4 (1.5%).Nine infants (3%) died without undergoing definitive surgery. Seven of these infants had a stoma in situ at the time of death and seven had a syndromic association. The median age at death was 85 days (range 11–381). The cause of death was attributed to an underlying cardiac anomaly in five infants, sepsis in two infants, multiple comorbidities prompting withdrawal of treatment in one infant and was unclear in one infant.This study provides robust, population-level data for the UK and Ireland, with data collected directly from local surgeons, rather than ‘second hand’ from administrative databases. The population-based nature, together with high rates of case ascertainment and data accrual achieved, allow an accurate estimate of the incidence, clinical characteristics and current preoperative management of infants with HD in the UK and Ireland.To enable future comparative, age-matched analysis of long-term functional outcome, we limited our cohort to infants diagnosed before 6 months of age. Contemporary population-based studies confirm that around 90% of infants with HD are diagnosed within the neonatal periodFor a condition with a complex pattern of polygenic inheritance, characterised by variable sex-dependent penetrance of the most common known genetic mutations,In our cohort, 12% of infants with HD were born prematurely; nearly twice the overall rate of preterm birth for England and Wales (7.3%)In our cohort, more than one in five infants had an associated anomaly, with a syndromic association in 15% and an isolated additional anomaly in 7%. Overall, 1 in 11 infants had Down syndrome and this group accounted for 57.4% of infants with a predisposing syndrome. Infants with Down syndrome are estimated to have 40 times increased risk of HD.Between 94%Although paediatric surgeons are familiar with the management of HD, our findings indicate that the majority of these infants initially present to other primary or secondary healthcare services in the UK and Ireland. One third of infants in this cohort were discharged home after birth, prior to HD being suspected or diagnosed and over 80% first presented to a hospital without tertiary paediatric surgical services and required transfer to a paediatric surgical centre. As the majority of these infants presented initially to non-surgical specialities, these data highlight the importance of regional networking, including robust referral pathways to tertiary care services.intended practice of UK paediatric surgeons, only 15% would aim to perform a stoma prior to definitive surgery.actually performed in more than one third of infants, with 13% receiving a stoma without any attempts at rectal washouts, and a further 27% of infants initially managed with rectal washouts receiving a stoma, after the washouts failed to achieve adequate decompression. These findings provide robust information that can be used to counsel parents of infants with HD. Limited data exist to explain the higher than expected stoma rates observed in clinical practice compared with surveys of intended practice. In this cohort, the indications for stoma formation were mostly due to clinical concerns, rather than a consultant preference for this approach. Future work will be directed at identifying factors that increase the likelihood of stoma formation.Surveys of practice have demonstrated clear changes in surgeons' preference for the initial colonic decompression of infants with HD, with a move away from a staged approach and increased popularity of the primary pull-through.This study identified a national cohort of infants with HD in the UK and Ireland. The data provide a robust estimate of the incidence, clinical characteristics and associated anomalies of HD in the UK and Ireland. We report national outcome data for clinical markers such as time from presentation to diagnosis and stoma utilisation rates that can be used as a benchmark against which practice and outcomes in single centres can be compared and future changes in service provision measured. The data provide further evidence to challenge some of the previously held dogmas in HD, including the prevalence of preterm birth and the validity of timing of first meconium as a screening question for HD. There appears to be an increased use of home rectal irrigations and high stoma rates, both of which rely on adequate support services in the community. Furthermore, one in three infants with HD is discharged home after birth, prior to a diagnosis of HD, placing a heavy burden of responsibility on health visitors and general practitioners to ensure timely referral of these infants.


In a Gambian cohort with infants born between 1972 and 2011, we used multiple regression to test whether parental season of birth predicted offspring birth weight (n = 2097) or length (n = 1172), height-for-age z score (HAZ), weight-for-height z score (WHZ), and weight-for-age z score (WAZ) at 2 yr of age (n = 923). We found that maternal exposure to seasonal energy restriction in utero was associated with reduced offspring birth length . In contrast, paternal birth season predicted offspring HAZ at 24 mo  but had no discernible impact at birth. Our results indicate that periods of nutritional restriction in a parent’s fetal life can have intergenerational consequences in human populations. Fetal growth appears to be under matriline influence, and postnatal growth appears to be under patriline intergenerational influences.—Eriksen, K. G., Radford, E. J., Silver, M. J., Fulford, A. J. C., Wegmüller, R., Prentice, A. M. Influence of intergenerational in utero parental energy and nutrient restriction on offspring growth in rural Gambia.The prenatal environment can alter an individual’s developmental trajectory with long-lasting effects on health. Animal models demonstrate that the impact of the early life environment extends to subsequent generations, but there is a paucity of data from human populations on intergenerational transmission of environmentally induced phenotypes. Here we investigated the association of parental exposure to energy and nutrient restriction  Early life represents a critical window of phenotypic plasticity, and nutritional stressors during this period alter growth and development, resulting in permanent changes in metabolism and chronic disease susceptibility , 2. Subs7e.g., through altered maternal gestational metabolism) and epigenetic inheritance  of the West Kiang District in Gambia were included in this retrospective study. The data for this study were derived from birth records and recorded family data going back 43 yr. Birth weights and birth lengths were recorded within 72 h of birth by trained staff, regardless of whether the mother gave birth at the Medical Research Council facility or in her village. Birth weights from the 3 villages were recorded to the nearest 10 g with a Salter spring balance and tarred sling, which was calibrated regularly. Trained staff conducted regular anthropometric measurements of the offspring, from which the values at 24 ± 3 mo have been selected for this analysis.z score (HAZ), weight-for-age z score (WAZ), and weight-for-height z score (WHZ) at 2 yr of age. Z scores were calculated using the World Health Organization Anthro program (v.3.2) against the World Health Organization 2006 growth standard.Environmental conditions in Gambia are characterized by a long, hot, and dry season from November until May and a shorter wet season from June until October . Due to The potential confounding variables investigated were maternal age, parity, parental height, gestational age at birth, offspring sex, offspring season of birth, and season of offspring anthropometric measurements at 24 mo of age. Interactions of potential confounding variables, including offspring sex, were also investigated, but no interactions were found. Offspring month of birth and month of measurement were included in the multiple regressions using Fourier terms . The usez test and linear regression for hypothesis testing, was performed to examine the crude association between outcome variables (offspring growth) and exposure variables . Any crude associations between the outcome and exposure variables, identified with a value of P ≤0.05, were taken forward for multiple regression.Simple stratification, using Potential confounding variables were added to the multiple regressions one at a time. All statistical analyses were performed with STATA version 14.P = 0.05). In the multivariate analyses of birth length and maternal birth season, the excluded subjects did not have a different mean birth length compared with the included subjects. In the analysis of HAZ and paternal birth season, there was no difference in HAZ at 24 mo of age between included and excluded subjects.We identified 812 unique mothers and 447 unique fathers for whom season of birth was known. On average, fathers had 4 children  and mothers had 3 children , resulting in 2829 mother–offspring pairs and 1609 father–offspring pairs. There were considerable missing data for some variables, as shown in sd age of 26 ± 6.9 yr . The offspring mean ± sd WAZ (n = 1841), HAZ (n = 1839), and WHZ (n = 1839) values at 24 mo of age were –1.50 ± 0.97, –1.68 ± 1.21), and –0.87 ± 1.01, respectively. The prevalence of stunting (HAZ < 2) was 39%, indicative of chronic malnutrition over the study period of 43 yr. The proportions of wasting (WHZ < 2) and underweight (WAZ < 2) were 12 and 28% respectively.The fathers included in this cohort were born between 1946 and 1989, mothers between 1947 and 1995, and offspring between 1972 and 2011. Twenty-nine percent of the mothers were primiparous, with a mean ± ± 6.9 yr . Of a toP = 0.05] (P = 0.2) , −0.071 to −0.001;  = 0.05] . When adP = 0.2) . BecauseP = 0.2) .vs. hungry season) variable (data not shown).An additional sensitivity analysis with the exposure variable  expressed instead as a series of Fourier terms to reflect monthly variation was also conducted. This analysis produced results that were very similar for all outcome measurements to those obtained using the dichotomized (harvest P = 0.005) compared with harvest-season mothers (P = 0.02). There was no detectable association between length at birth and paternal birth season  (P = 0.004)  . Strong = 0.004) . Omittin= 0.004) .P = 0.1; birth length by sex interaction, P = 0.7; and HAZ by sex interaction, P = 0.9).None of the associations in via uterine constraint  give birth to babies that are slightly shorter than the babies of unexposed mothers. This impact is limited to fetal growth because there was no evidence of an association between maternal birth season and offspring postnatal growth measurements  at 24 mo of age. Although the observed crude difference in birth length was small (4.2 mm), the suggestion of a potential link between offspring birth length and maternal birth season is informative from a mechanistic point of view. It is known that birth size is strongly influenced by placental function , maternanstraint . Adjustmet al. . No evidence for an association between paternal season of birth and offspring birth size, WAZ, and WHZ at 24 mo of age was found. Our work is consistent with a previous study in this Gambian population that demonstrated no impact of paternal birth season on the next generation’s neonatal anthropometry .prima facie, our data suggest that when the infant is no longer subject to maternal in utero constraints, paternal influences on growth potential are more easily discerned, and hence paternal prenatal nutrition is associated with postnatal but not fetal growth.It is possible that an underlying association between paternal fetal environment and offspring fetal growth exists but is obscured by more dominant maternal placental and uterine influences on fetal growth and by the relatively smaller sample size available in this analysis. Indeed, several studies have found stronger maternal–offspring than paternal–offspring birth weight correlations , 42. Kuzin utero involving the erasure and, in male fetuses, the reapplication of epigenetic marks  a failure to recognize intergenerational limitors can lead to unrealistic expectations of interventions  and therefore to a loss of confidence and investment, and 2) attempts to override such limitations with higher and higher nutrient inputs can lead to metabolic disease in later life by imposing nutrient conditions that are not harmoniously tuned to the epigenetically entrained expectation of the nutrient  conditions to which an infant will be exposed throughout life.Although the effect sizes noted here based on parental season of birth are not large, they may be part of a wider constellation of prior-generation exposures that have important implications for interventions attempting to overcome growth and other developmental deficits in children in low-income settings. They might imply that children’s ability to benefit from additional nutrients, both in utero in a large population with comprehensive antenatal and child growth data collected over several decades. The data were of high quality with few inaccuracies, and field workers had received standardized training in data collection, increasing the validity and reliability of this study. This study had large sample sizes (minimum n > 650 for multivariable regression), which is unusual for studies of this type.An important strength of this study was the availability of high-quality data in an environment where seasonal nutritional restriction is experienced naturally in a repeating annual pattern. This provides a unique opportunity to explore the consequences of nutritional restriction Limitations of this study include confounders that were not explored because the data were not available, including maternal birth weight and socioeconomic status, which are known to be associated with fetal growth , 40, 43.Our data suggest that periods of nutritional restriction during both parents’ fetal life can have intergenerational consequences, affecting their offspring’s fetal and postnatal growth. We find that maternal birth in the hungry season is associated with reduced offspring birth length, whereas paternal birth in the hungry season is associated with reduced offspring HAZ at 24 mo of age. Further work is required to investigate the mechanisms through which the parental early life environment alters the developmental trajectory of their children. It is possible that early nutrition may influence maternal development and physiology, altering the maternal intrauterine environment, with consequences for offspring development. It is unclear whether parental nutritional restriction may alter behavioral or socioeconomic factors with consequences for offspring growth. Another intriguing possibility is that the epigenome of the developing parental germline, in flux in mid to late pregnancy, is altered by gestational nutritional status and contributes to altered offspring development. The developing germline has been shown to be vulnerable to nutritional compromise in lower mammals, but this hypothesis remains to be tested directly in a human population.


Changes in population birth outcomes, including increases in low birthweight or preterm births, have been documented after natural and manmade disasters. However, information is limited following the 2011 Fukushima Daiichi Nuclear Power Plant Disaster. In this study, we assessed whether there were long-term changes in birth outcomes post-disaster, compared to pre-disaster data, and whether residential area and food purchasing patterns, as proxy measurements of evacuation and radiation-related anxiety, were associated with post-disaster birth outcomes. Maternal and perinatal data were retrospectively collected for all live singleton births at a public hospital, located 23 km from the power plant, from 2008 to 2015. Proportions of low birthweight (<2500 g at birth) and preterm births (<37 weeks gestation at birth) were compared pre- and post-disaster, and regression models were conducted to assess for associations between these outcomes and evacuation and food avoidance. A total of 1101 live singleton births were included. There were no increased proportions of low birthweight or preterm births in any year after the disaster : 0.64–1.51; and preterm birth: 0.68, 95% CI: 0.38–1.21). No significant associations between birth outcomes and residential area or food purchasing patterns were identified, after adjustment for covariates. In conclusion, no changes in birth outcomes were found in this institution-based investigation after the Fukushima disaster. Further research is needed on the pathways that may exacerbate or reduce disaster effects on maternal and perinatal health. Perinatal health is a crucial aspect of public health. Birth outcomes, measureable as birthweight and gestational age at birth, have been found to predict both short- and long-term health trajectories of the neonate; a topic which has gained significant attention in the field of epidemiology ,2,3,4. ADisasters are one type of external stressor associated with changes in population birth outcomes. Increases in low birthweight births have been documented after natural disasters, chemical disasters and terrorism, with or without concurrent increases in preterm births ,18,19,20On 11 March 2011, Northeast Japan was struck by an earthquake and tsunami, triggering a nuclear disaster at Fukushima Daiichi Nuclear Power Plant. In contrast to the relatively immediate destruction of the earthquake and tsunami, the nuclear disaster has led to long-term societal changes such as prolonged evacuation , and chaIn this institution-based study we evaluated data from Minamisoma Municipal General Hospital (MMGH), located 23 km from the plant , to inveAll live singleton births at MMGH from April 2008 to 2015 were included in this study. On 12 March 2011, the 20 km radius of the power plant was classified as a restricted zone under mandatory evacuation orders by the central government of Japan . On 15 MData on maternal characteristics and birth outcomes were extracted from the hospital’s patient records. Maternal characteristics included age at time of the birth, number of previous deliveries (parity) and residential address. Birth data of birthweight, gestational age at birth, mode of delivery , date of delivery, and sex of the neonate were collected.The following two outcome measures were considered as primary birth outcomes of interest in this study: low birthweight (<2500 g at birth), and preterm birth (<37 weeks of gestation at birth).The difficulty of defining maternal exposure to a disaster has been previously noted . The preThis study additionally used data on maternal food purchasing patterns. Since March 2012, all pregnant women under the care of MMGH have been encouraged to undergo free Whole Body Counter (WBC) internal radiation contamination screenings at MMGH during their pregnancies. An exposure risk assessment questionnaire is given at the time of WBC screenings, which contains items on methods of acquiring the following six food products: rice, meat, fish, produce, mushrooms and milk. Each item has four choices: (a) purchasing food products at a supermarket based on origin (Fukushima vs. non-Fukushima); (b) purchasing food products at a supermarket without consideration of origin; (c) using local farms or consuming home grown foods with radiation inspection; or (d) without it.We extracted data on the food purchasing preferences of participants in the post-disaster period, with the hypothesis that avoidance of Fukushima products could be an indicator of radiation-related anxiety. If participants had undergone multiple WBC screenings during their pregnancy, questionnaire data were extracted from the screening closest to the date of delivery. In all WBC screenings of pregnant women from 2012 to 2015, there were no cases of detectable internal radiation contamination (detection limits with a 2-min scan: 210 Bq/body for Caesium-134 and 250 Bq/body for Caesium-137); therefore, internal radiation levels could not be considered as a variable for analysis in this study.We conducted two analyses. First, to evaluate any difference in the rates of post- versus pre-disaster birth outcomes, proportions of low birthweight and preterm birth were calculated for each period and compared, expressed as risk ratios (RRs).Second, to examine any associations of these two outcomes (low birthweight and preterm birth) with residential area at the time of the disaster or food purchasing patterns, adjusted for potential covariates, we performed multivariate logistic regression analyses with the post-disaster data. For model building, variables initially entered into the regression models were chosen based on univariate analyses. Additional model selection was performed using backward-stepwise method with p-to-remove of >0.05. Backward-stepwise regression starts with all the candidate variables in the model and removes the least significant variables until all the remaining variables are statistically significant. Basic variables, such as year, maternal age at time of birth, sex of neonate, and the number of previous deliveries, as well as those of main interest in this study  were incorporated into the final model regardless of their statistical significance as long as stable models were obtained. The partial F-test was used to verify the entry and removal of variables from the model. Since some participants had more than one delivery at MMGH during the study period, the regression model included a random effect at individual level to control for the fact that the same individual’s data were correlated.Ethics approval for this study was granted by the MMGH Institutional Review Board, reference number 27-21. Participant consent was not found to be necessary, as this was a retrospective analysis of hospital records. All data were anonymised prior to analysis.There were 1134 births recorded at MMGH from April 2008 through March 2015. Eleven sets of twins, three intentional abortions, four stillbirths and four miscarriages recorded as births were excluded, resulting in 1101 live singleton births (delivered from 1009 mothers) included in this study. By year, there were 236 births in 2008, 221 in 2009, 214 in 2010, 0 in 2011 , 90 in 2012, 162 in 2013, and 178 in 2014.p < 0.001). There were significant changes in maternal residential address patterns throughout years (p < 0.001) with post-disaster decreases in deliveries at MMGH by those who had been living outside Soso District or within the mandatory evacuation zone at the time of the disaster, alongside increases in those who had been living in areas under voluntary evacuation orders or areas of Soso District under no evacuation orders. Because there were few mothers aged <19 years old , we were unable to categorize this potentially high-risk group; maternal age at birth was instead categorized as <35 and >35 years, and a significant increase in mothers >35 years of age was observed after the disaster (p < 0.05). Other variables, such as sex of neonate, mode of delivery, and season of delivery were not significantly different by year.Maternal and neonatal characteristics by year are described in p < 0.05 and p < 0.01, respectively)  participated in the WBC screenings. Of the 29 study participants that did not undergo WBC screening, six had been living outside Soso District at the time of the disaster, and 19 delivered in the last year of the study period (2014–2015). Trends in food purchasing choices are outlined in the additional material, and indicate that avoidance of locally produced rice and produce significantly increased as years passed after the disaster (ctively) .p = 0.93; and RR of preterm birth: 0.68, 95% CI: 0.38–1.21, p = 0.19).The results of univariate analyses, showing no statistically significant associations between food purchasing patterns and low birthweight or preterm births, are displayed in This study retrospectively assessed all live singleton births from 2008 to 2014 in a hospital serving areas affected by the 2011 Fukushima Daiichi Nuclear Power Plant Accident, finding no significant long-term changes in the prevalence of low birthweight or preterm births after the disaster, compared to a pre-disaster period. There were additionally no associations between residential address at the time of the disaster or food purchasing patterns, and post-disaster birth outcomes. We did confirm a substantial decrease in the number of births occurring at MMGH after the disaster, with no births in 2011 due to departmental closure, followed by gradually increasing numbers in each post-disaster year.Previous studies on birth outcomes following the Fukushima disaster have produced mixed results, with some studies finding no significant changes in birth outcomes in areas affected by the nuclear disaster ,31,32, an = 401, 93.2%) had detectable levels of internal radiation contamination, and we therefore find it unlikely that radiation exposure would have had any effect on birth outcomes in this study. However, the Fukushima disaster has led to social disruption and public concern for radiation exposure [In terms of environmental exposures, nuclear disasters are rare and understudied events that present the danger of exposing populations to radioactive materials. However, impacts of nuclear disasters on population birth outcomes are not well studied, and likely to vary by the scale of each disaster. Studies after the Chernobyl nuclear disaster in 1986 indicate mixed evidence for a small increase in congenital anomalies, yet overall little effect on most pregnancies ,37. Radiexposure  which maexposure .Psychological stress is a frequently reported pathway from disaster occurrence to changes in population birth outcomes ,21,40. WThis is not the first time that contradictory results on birth outcomes after disasters have been observed. In addition to some inconsistency in findings between different disasters ,21, therp < 0.001), and in the proportions of mothers >35 years of age after the disaster (p < 0.05)  . This ch < 0.05) , it coulJapan is the most rapidly ageing country in the world, and had fertility rates below replacement levels since before the 2011 triple disaster . We coulThere are limitations to this study. First, we were unable to adjust analyses for maternal risk characteristics for low birthweight such as smoking and alcohol consumption, in addition to socioeconomic characteristics, because of limitations in data availability. Second, we did not have any data from April 2011 through March 2012, due to the closure of the Obstetrics and Gynecology Department in the study institution. Therefore, it was not possible to assess for any changes in birth outcomes in those who were pregnant at the time of the disaster (March 2011). Our lack of immediate post-disaster data may have contributed to the null results, and may not be directly comparable to studies that have assessed immediate post-disaster birth outcomes. The sample size was small for the analyses conducted, and although the data for this study comes from one institution, there are potential differences between our pre- and post-disaster samples that should be acknowledged as they could have caused sampling bias. As presented in the Discussion Section, post-disaster evacuation may have been patterned by socioeconomic factors, which could have influenced the population composition of those remaining in Soso District and thus participating in the post-disaster period of this study. It is further possible that disaster-related psychosocial stress may disproportionately affect women with low- or high-risk pregnancies, or those with lower or higher socioeconomic status, yet we were unable to assess for such characteristics due to limited data availability. For these reasons, we cannot rule out the possibility that sampling bias may have masked any real associations between the disaster and low birthweight or preterm birth.However, alongside these limitations, this study has unique strengths. Methodological investigation of evacuation and food purchasing patterns, in addition to a prolonged study period, are points that could be informative to future research. Although efficacy of food purchasing preferences as a measurement tool was limited in this study, we suggest that open discussion of the methodological process undertaken here may be of use to future research in disaster settings; in essence, this is not only a public health study but also an account of the exploratory methods undertaken in a data-constrained post-disaster context. We suggest that there is a great need for in-depth exploration of the pathways to adverse birth outcomes, and the potential for socioeconomic patterning, in future studies.The prevalence of low birthweight and preterm births did not significantly change in a hospital affected by the Fukushima Daiichi Nuclear Power Plant Accident, and there were no statistically significant associations between these birth outcomes and evacuation or food purchasing patterns in the post-disaster period. These results are inconsistent with previous findings on associations between disasters and adverse birth outcomes, and call for further research, particularly on the mechanisms by which disaster effects on maternal and perinatal health may be mediated.


Studies suggested the presence of foetal adrenal rhythms of cortisol, which are entrained in antiphase to maternal rhythms. In contrast, neonates are thought to have no adrenal rhythm until 2–3 months after birth. To test the hypothesis that a foetal-type adrenal rhythm is preserved after birth, saliva samples were collected from 65 preterm/term infants during hospital stay (30–40 weeks corrected age) at 10:00 and 19:00 h. Cortisol levels were assessed for their diurnal difference and dependence on antenatal/postnatal clinical variables. Cortisol levels were lower during periods 15–28 days and >28 days than ≤5 days of life. Lower cortisol was associated with pregnancy-induced hypertension (PIH), gestational age <28 weeks, and mechanical ventilation after birth. Higher cortisol was associated with vaginal delivery and non-invasive ventilation support at saliva collection. PIH and non-invasive mechanical ventilation at saliva collection were associated with cortisol levels even after adjustment for postnatal age. Cortisol levels were higher in the evening than in the morning, which was unassociated with gestational and postnatal age. Higher cortisol levels in the evening suggest the preservation of a foetal-type diurnal rhythm. Cortisol levels are associated with intrinsic and extrinsic variables, such as PIH, delivery mode, gestational age, and respiratory conditions. Non-invasive salivary markers have extensively been used in clinical and psychological studies to assess the circadian rhythm and stress response involving children and adults12345689101112In contrast to the lack of an adrenal circadian rhythm in newborn infants, Serón-Ferré and colleagues reported that cortisol levels of cord blood immediately obtained after elective caesarean birth had a clear diurnal rhythm with the acrophase in the afternoonApart from diurnal rhythms, plasma cortisol levels increase towards the end of pregnancy, and this is further accelerated during delivery1718We conducted a prospective study in a cohort of preterm and term infants to investigate whether a foetal-type adrenal rhythm is retained in newborn infants.A total of 130 samples were obtained from 65 cumulative newborn infants. Seven subjects were studied twice at an interval of 9.9 (2.0) days . Three sThe final cohort comprised 62 cumulative newborn infants  who were hospitalized because of low birth weight (n = 55), maternal hyper- or hypothyroidism (n = 2), or maternal gestational diabetes mellitus (n = 5) . Six newSalivary cortisol levels were higher in the evening compared with those in the morning (p = 0.018), the difference of which was not associated with gestational age at birth and postnatal/corrected age at the time of sample collection. .A persistent decline in cortisol levels with age was observed, with lower cortisol values between 15 and 28 days and at older than 28 days of life compared with those within 5 days of life  , and were available for serial saliva collection on the study day, were recruited. Based on our previous data in preterm and term infants, which observed biphasic diurnal increase in cortisol in the late afternoon and in correspondence with the birth timeSaliva samples were collected before and 1 h after regular feeding at 10:00 and 19:00 h. For sample collection, an absorbent swab  was gently inserted into the newborn infant’s mouth for approximately 5 min, allowing the swab end to absorb sufficient saliva. The sample was immediately centrifuged at 3000 rpm. Samples were initially kept at 4 °C, and were frozen at −80 °C after the last sample for the newborn infant was collected. Levels of salivary cortisol were determined by enzyme immunoassay . The limit of detection of this assay in our laboratory was 0.19 nmol/L, and the intra- and inter-assay coefficients of variation were 5.43% and 6.41%, respectively. Data collection was repeated up to twice for each patient with a minimum interval of 7 days.Clinical data were collected from an electronic patient record, including information (i) before delivery , (ii) after birth , and (iii) at the time of the study .Values are presented as mean (standard deviation) unless otherwise specified. For the current study, only cortisol values before feeding were analysed. Salivary cortisol values were normalized by transforming data into natural logarithms. Clinical variables were dichotomized using clinically relevant thresholds. Generalized estimating equations were used to simultaneously assess (i) the diurnal difference in cortisol values and its interaction with postnatal age, and (ii) the dependence of salivary cortisol values on 10 selected clinical variables by incorporating repeated observations in the morning and evening. P-values from multiple comparisons were presented without correction as clinical variables were chosen restrictively based on a priori hypothesis. Because of a known age-dependent decline in cortisol levels after birth1718How to cite this article: Kinoshita, M. et al. Paradoxical diurnal cortisol changes in neonates suggesting preservation of foetal adrenal rhythms. Sci. Rep.6, 35553; doi: 10.1038/srep35553 (2016).


Maternal adiposity in pregnancy is associated with offspring adiposity and metabolic dysfunction postnatally, including greater risk of nonalcoholic fatty liver disease (NAFLD). Recent genetic analyses suggest a causal effect of greater maternal body mass index on offspring birth weight and ponderal index, but the relative roles of the environment in utero or later in life remains unclear.We sought to determine whether markers of infant adiposity  were associated with markers of NAFLD in adolescence.This was a UK prospective birth cohort with 17 years of follow-up with liver function tests  (n = 1037 participants), and ultrasound scan assessed liver fat, volume, and sheer velocity at age 17 (n = 541 participants). Missing covariate data were imputed.Ultrasound and biochemical measures of NAFLD were measured.Birth weight, cord blood leptin, and adiponectin were not associated with a diagnosis of NAFLD. In adjusted analyses, 2 of 42 associations attained conventional 5% levels of significance. Birth weight was positively associated with liver volume . Cord high-density lipoprotein-cholesterol was positively associated with alanine aminotransferase ; however, this association was primarily mediated via offspring adiposity.In this extensive analysis, we found little evidence measurements of infant fat mass and birth size were related to adolescent markers of NAFLD. The association between birth weight and adolescent liver volume may indicate the contribution of greater organ size to birth weight and tracking of organ size. In a birth cohort of 1,037 children we found that there was no consistent evidence that birthweight, neonatal adiposity or umbilical cord lipids were associated with liver dysfunction in adolescence. Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease children in the developed world . The ideThese differences may reflect that assessments of the intrauterine contribution to the onset of metabolic disease in the offspring have primarily used birth weight, which reflects both fetal fat and lean mass. Umbilical cord blood leptin is now widely recognized as an accurate biomarker for neonatal fat mass, with higher levels associated with greater fat mass . Cord blhttp://www.bris.ac.uk/alspac/researchers/data-access/data-dictionary/). Ethical approval was obtained from the ALSPAC Law and Ethics Committee and from the National Health Service local ethics committee.The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective, population-based birth cohort study , 17. FulA total of 14 541 women were initially enrolled and cord blood samples were available for 5011 mother-offspring pairs. Details of all participants who attended the 17–18 follow-up clinic visits (n = 5081) provided blood-based indicators of liver function (n = 3188) and participated in the liver ultrasound substudy (USS) (n = 1887) have previously been reported in detail . A detaiCord blood samples were obtained at the time of delivery and spun in preparation for storage at −80°C since then. All cord samples were assayed at the University of Glasgow. Cord leptin and adiponectin were measured using commercially available ELISA kits . Cord lipids  were measured using a Roche Cobas C311 autoanalyzer using enzymatic reagents for lipid determination. Non-high-density lipoprotein (Non-HDL-c) was calculated as total cholesterol minus HDL-c. Analysis of the cord blood was completed within a maximum of three freeze-thaw cycles and remained at −80°C in between. The interassay coefficients of variability were 9.5% for leptin, 3.2% for adiponectin, 4.0% for HDL-c, 3.0% for cholesterol, and 2.7% for triglycerides.The protocol for USS assessment in ALSPAC has been published previously . BrieflyFasting blood samples (minimum of 6 h) were immediately spun and frozen at −80°C. Measurements were assayed shortly (3–9 mo) after samples were taken with no previous freeze-thaw cycles. All assays were completed in the same laboratory at the University of Glasgow. alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), and aspartate aminotransferase (AST) were measured by automated analyzer with enzymatic methods. All inter- and intraassay coefficients of variation for these blood-based assays were less than 5%.Potential confounders included in this analysis are as follows: maternal age; prepregnancy BMI; smoking status ; parity; occupational social class; complications during pregnancy (hypertensive or diabetic disorders); gestational age at birth; mode of delivery; and offspring's sex. Height, BMI, and fat mass at age 17.8 years were considered as potential mediators if any confounder adjusted associations were observed. Offspring weight and height at the 17-year clinic assessment were measured using standard procedures in light clothing, without shoes and used to calculate BMI. Weight was measured to the nearest 0.1 kg using Tanita scales. Height was measured to the nearest 0.1 cm using a Harpenden stadiometer. A narrow fan beam densitometer  was used to perform a whole-body duel-energy X-ray absorptiometry scan from which fat mass was measured.Offspring liver volume, fibrosis, and liver function tests were log transformed to produce an approximately normal distribution of residuals. Birth weight was adjusted for sex and gestational age using nonlinear regression fitting a Gompertz curve.Because human studies suggest that lower birth weight and animal studies suggest that higher birth weight is associated with a greater NAFLD risk, potential departure from linearity was explored by comparing a model in which the exposure was entered in thirds as two indicator variables and a model in which a linear relationship was assumed across the thirds, using a likelihood ratio test. The multivariable linear and logistic regression models were used to examine the associations between cord blood measures, birth weight and fatty liver, liver volume, fibrosis, and liver function tests at age 17 years. We tested for sex-exposure interactions, and because there was no evidence to support these, results are reported for male and female offspring combined.A series of multivariable regression models were constructed to adjust for potential confounders and mediators. The basic model (model 1) adjusted for offspring sex and age at outcome assessment. In model 2 we additionally adjusted for potential confounders: maternal age, smoking in pregnancy, parity, occupational social class, education, prepregnancy BMI, and alcohol consumption in pregnancy. Our plan was to then examine potential mediation by adjusting for each of offspring BMI, fat mass, height, and height squared at age 17 years in any confounder-adjusted associations that were not null.Supplemental Table 1). In the main paper, we present results from the imputed datasets and for comparison present results from those with complete data (n = 383–813) in the Supplemental Material .There were small amounts of missing data on some covariables included in the multivariable models. To deal with the missing data , 20 imputation data sets were generated by chained equations , with meAll analyses were performed using Stata MP version 12 (Stata Inc.).There was no strong evidence of associations between birth weight, cord leptin, and lipids with ultrasound-diagnosed fatty liver . Of 42 tTo examine the effects of potential mediators, we included offspring fat mass, height (and height squared), and BMI at age 17 years in the fully adjusted models. The association between birth weight and increased liver volume remained , whereas the association of cord HDL-c and ALT changed direction .Supplemental Tables 2 and 3).Associations were similar when restricted to a complete case, ie, including participants who had data on all off the exposures, confounders, and outcomes  or cord lipids are associated with later offspring markers of liver health when adjustment is made for maternal pregnancy characteristics that are likely to confound these associations.Birth weight has been associated both positively and negatively with liver transaminases , 24, 25 Adiponectin has consistently shown to be reduced in children and adults with confirmed NAFLD –30. Conv–Whereas previous studies of birth weight with later liver outcomes have been larger than this study, to our knowledge this is the largest study to examine cord blood measures in relation to subsequent liver outcomes, including measurements assessed by USS. The prospective design, long duration of follow-up, detailed anthropometric measures, and appropriate adjustment for maternal characteristics that could confound the associations are substantive strengths. We do, however, acknowledge several limitations. We used ultrasound to assess liver pathology because it has been shown to detect moderate to severe steatosis with similar accuracy as the gold standard liver biopsy while avoiding an unethical and invasive procedure . For lesIn animal models, insulin resistance, hyperketonemia, and hepatic steatosis were all features of male but not female offspring of obese mice , and the34–In the current study, there was no consistent evidence that birth weight, neonatal adiposity, or cord lipids were associated with liver dysfunction in adolescence. The association of maternal adiposity to later offspring NAFLD is likely to be a consequence of later environmental effects or in utero effects not mediated via in utero adiposity.


A negative experience in childbirth is associated with chronic maternal morbidities. The aim of this systematic review and meta-analysis was to identify currently available successful interventions to create a positive perception of childbirth experience which can prevent psychological birth trauma.Randomized controlled trials of interventions in pregnancy or labour which aimed to improve childbirth experience versus usual care were identified from 1994 to September 2016. Low risk pregnant or childbearing women were chosen as the study population. PEDRO scale and Cochrane risk of bias tool were used for quality assessment. Pooled effect estimates were calculated when more than two studies had similar intervention. If it was not possible to include a study in the meta-analysis, its data were summarized narratively.After screening of 7832 titles/abstracts, 20 trials including 22,800 participants from 12 countries were included. Successful strategies to create a positive perception of childbirth experience were supporting women during birth , intrapartum care with minimal intervention  and birth preparedness and readiness for complications . Most of the relaxation and pain relief strategies were not successful to create a positive birth experience .The most effective strategies to create a positive birth experience are supporting women during birth, intrapartum care with minimal intervention and birth preparedness. This study might be helpful in clinical approaches and designing future studies about prevention of the negative and traumatic birth experiences.The online version of this article (10.1186/s12978-018-0511-x) contains supplementary material, which is available to authorized users. The negative birth experience has been common event internationally; it may create a psychological birth trauma (PBT) for women which can lead to post- traumatic stress disorder (PTSD). This study’s aim is to collect effective prenatal and intrapartum care practices to prevent negative birth experiences. To achieve this goal, an outcome-based systematic review on RCTs was conducted.We aimed to find any intervention which can impact on the childbirth experience among low risk pregnant or childbearing women. Among 8685 search results published between 1994 and 2016, 20 unique RCTs were included.This review categorized strategies into four main group: supporting women during labour, relaxation and pain relief during birth, intrapartum care with minimal intervention, and birth preparedness. Successful strategies in prevention of negative birth experience were presence of a trained birth companion, relaxation through massage and music, early labour assessment to minimize obstetric interventions, and being prepared for childbirth through individual birth plan.This newly found list of successful strategies can shed light on clinical practice in order to create a positive perception of childbirth experience. We believe that emotional support programs for childbearing women should be implemented in countries’ maternal health plans. These programs can comprise a combination of successful strategies such as continuous labour support by a familiar person, reassuring physical contact using massage, and the continuity of midwifery care. Prevention of negative birth experience using these successful practices leads to the promotion of vaginal birth, high quality maternity care and the reduction of chronic psychological complications.Childbirth is one of the most challenging psychological events in a mother’s life, as 10–34% of all childbearing women are faced with traumatic birth experiences . A negatPrevention of psychological birth trauma (PBT) has been recommended as a new area of research in Oxford meeting. The meeting concluded that there are no published studies directly aimed at preventing psychological trauma in childbirth . HoweverOur current review of randomized controlled trials (RCTs) assesses all types of women-centered interventions designed to create a positive childbirth experience. Previous reviews did not aim to provide a comprehensive insight into the prevention strategies of negative childbirth experiences . TherefoEarly postpartum debriefing interventions as a prevention of psychological trauma were not found to be effective, therefore focusing on prenatal and intrapartum interventions was recommended . Such inConsidering the serious burden of PBT , 6, 8, 9The search process was conducted between July and September 2016. This research was ethically approved by Tehran University of Medical Sciences ethics committee (reference number IR.TUMS.VCR.REC.1395.374). Electronic databases included Embase, PubMed, Scopus, Web of Science and Cochrane Central Register for Clinical Trials; dissertations were searched in ProQuest theses database. Persian and Turkish databases, World Bank literature and Proceedings of relevant conferences were also searched. Expert researchers in this field were contacted by e-mail to inquire about unpublished or soon to-be-published RCT’s. An electronic search strategy was constructed using text words  recognized that childbirth could be a traumatic event that may cause PTSD [Using a definition from a literature review , we defiFull text of the included study needed to be in English, Persian or Turkish (the first author is fluent in these three languages). As childbirth experience might be affected by maternal socioeconomic status , 24, we Study inclusion, quality assessment and data extraction were conducted by two authors (M.T. and N.S) independently. A senior researcher (Z.T.) resolved disagreements by discussion. Quality assessment was based on the PEDro (Physiotherapy Evidence Database) scale and a modified Cochrane risk of bias tool for quality assessment of RCTs. The PEDro scale rated the trials’ methodological quality from 0 to 10 based on what they reported; the domains of scale are random allocation, allocation concealment, baseline similarity, blinding, measure of key outcomes from ≥85%, intention to treat analysis, between group comparison and point measures. RCTs with PEDro scores ≥6 were re-evaluated with the Cochrane tool . AdditioRCTs with low risk of bias were included in the review, without considering their results. The Cochrane Public Health data extraction template was modified to suit this review ; 6359 non-RCT articles were excluded at this stage. Then, they screened the abstracts of 1473 papers. The trials were removed if their abstracts did not meet the inclusion criteria. Based on the abstracts, it was apparent 41 papers had relevant interventions and outcomes. However, the information presented in 87 abstracts was insufficient for making decisions about the relevance of the trial so the full texts were evaluated. The references of these 128 papers were checked to discover additional related articles. As shown in Fig. The quality assessment of the included studies is shown in detail Fig. . MethodoAlmost 22,800 women took part in these trials. All 31 Turkish and 108 Persian articles were removed in the initial selection or quality assessment process; so, the final 20 trials were only in English. Four studies were carried out in the United Kingdom, three in Australia, three in the United States, two in Denmark, two in Canada and the reminder in seven other countries. Three trials did not state whether they were ethically approved by relevant institutional review boards. In this case, the authors were contacted by email and they confirmed that ethical approvals had been obtained prior to the implementation of interventions. From the 20 included trials, four were pregnancy interventions –40, 42, Other outcomes which were measured in the 20 studies included labour characteristics and birth outcomes, neonatal outcomes, labour pain, feelings of control during labour, ability to cope with fear, maternal self-esteem and self-worth, the rate of cesarean sections, the rate of epidural analgesia, satisfaction with care, post-partum depression and the success rate of breastfeeding. Neonatal outcomes were measured by various variables including birth weight , 38, 40,Interventions designed to improve the childbirth experience can be categorized into four main groups as follows:Seven studies compared continuous support versus usual care. Support was provided by a member of women’s social network (four studies) , 32, 35,P = 0.01)   Fig. .Fig. 3CoIn summary, meta-analysis of six studies indicates that supporting women during birth is an effective intervention for creating a more positive childbirth experience.P = 0.21). According to the reports, participants in the control groups of both studies received relatively similar intrapartum care, which was provided by the nurse or midwife.Seven randomized controlled trials tested relaxation and pain relief strategies to promote a positive maternal childbirth experience. Two trials compared water immersion during labour with routine care , 37, twoP = 0.06). No statistical difference was evident in other aspects of the maternal experience such as satisfaction with the birth experience (p = 0.45), ability to cope with birth and sense of control during labour [P = 0.01) [Hypnobirthing studies did not follow the same design of intervention and outcome measurements; therefore, their combination was impossible and a narrative synthesis of them is presented. One study assessed maternal perception of the birth experience by one dual-mode question; no difference was found between three groups  regarding the positive childbirth experience  . The resP = 0.03) [P < 0.001) [P < 0.40) [One study addressed the effect of massaging by the mother or her birth companion on self-reported birth experience; more positive perceptions of labour and sense of control were detected in the intervention group versus usual care  . The sat< 0.001) . In one  < 0.40) .In summary, three of seven studies indicate that relaxation during labour is effective for improving the childbirth experience.P < 0.001)  Fig. .Fig. 6CoP < 0.001) [P = 1.00) [The study that compared a caseload midwifery care approach  with standard care found that participants in the intervention arm were more likely to report positive childbirth experience  . In anot = 1.00) .In summary, three of four studies indicate that intrapartum care with minimal intervention is effective for creating a more positive birth experience.P < 0.001), however no difference was seen between the two groups at six weeks postpartum  [P = 0.01), feelings of control and fulfillment of expectations [Results of the “Ready for Child program” showed that women who had attended the antenatal birth classes reported a more favourable childbirth experience than the control group at evaluation five years after the birth  . Anotherctations .In summary, both studies indicate that birth preparedness is a successful strategy for improving the experience of birth.The study examined the effectiveness of women-based interventions on new mothers’ perception of the childbirth experience. The results of this systematic review identified four main categories of strategies applied in studies designed to improve the childbirth experience; some of these strategies have succeeded, while others have not.The meta-analysis of trials assessing labour support revealed the positive effect of trained companion’s presence on maternal birth experience. While training approaches varied across studies, the common point of these interventions is physical presence and emotional support from the companion. Results showed that labour support from a person in a close relationship with the childbearing woman rather than a hired companion was more effective in the promotion of a positive birth experience. All of these findings are in keeping with the review on continuous support during childbirth . In contEvidence from RCTs evaluating the effect of pain relief methods during labour on maternal experience are conflicting. Water relaxation was not found as a useful technique to minimize the risk of a negative birth experience, neither was epidural analgesia. A previous review in 2002 confirmed that pain relief is not considered to be an effective variable in satisfaction with the childbirth experience . ControvAccording to the current evidence, among all labour relaxation techniques, only massage and music can be recommended clinically for improving women’s childbirth experiences. Social support involved in the massage intervention, casts doubt on the association between the massage component of the intervention and a positive childbirth experience. This means that a more positive childbirth experience might be the consequence of receiving support during massage rather than the massage itself . The relTrials that aimed to prevent unnecessary obstetrical interventions through continuity of care from a primary midwife and empowering women with information to recognize the right time to go to hospital for the labour, were successful in promoting a positive maternal experience. Continuity of midwife care, improves the birth experience through various agents including maternal self-management of pain, ability to cope with the labour challenge, control over the birth process, support from trusted experts and reduction of stressful examinations and interventions , 48. IntIn an effort to prevent negative and traumatic birth experiences, previous studies made recommendations to reduce related risk factors including inadequate labor support, high obstetric intervention rates, the occurrence of emergency cesarean section or instrumental delivery, and feelings of loss of control , 49–51. Due to the nature of this review, studies were included based on their outcomes rather than their interventions. The childbirth experience was considered as a gold-standard outcome for relevant interventions but it should be noted that each included study measured various outcomes. Some studies were unsuccessful in reducing the negative birth experience however had a positive impact on some other outcomes  , 43, 44.The comparison of included interventions is a difficult task due to several factors including diversity in settings, socioeconomic disparities, variation in culture, and heterogeneity in outcome measurement tools. The socioeconomic variable was measured and controlled in 17 studies; they reported that socioeconomic status did not significantly differ between experiment and control groups. Other three studies did not assess participants’ socioeconomic status , 37, 43.The quality of evidence about childbirth experience (outcome) is inconsistent across the studies because different tools and timings of administration had been used in trials that met the inclusion criteria. Childbirth experience is a multidimensional variable, so unidimensionality of its measurement scale might damage the quality of findings , as was The authors of the current study attempted to include high-quality relevant trials as much as possible. The inclusion of studies from low, middle and high income countries with a considerable sample size is strength of this review. Participants in the control groups of all included studies received conventional care. The difference of the standard maternity care across cultural and geographic boundaries is an inherent limitation of this review. We carried out the necessary investigation about conventional care of studies that have been pooled in the meta-analyses. As mentioned in the results section, the routine care of homogenous trials was relatively similar. The conventional care in the labour support studies consisted relatively similar components including active management of labour, clinical assessment by obstetricians and midwives, and analgesia, as needed. The conventional care of water relaxation studies included midwife provided labour care, one-to-one support by nurse or midwife, and parenteral analgesia, as necessary. In early labour assessment studies, participants allocated to standard care did not received any instruction or advice related to the labour.The lack of blinding in the included trials is an unavoidable limitation in this review. To reduce response bias, some studies had used blinded interviewers and all studies had applied self-administrated method. Although self-evaluation measures might limit the accuracy of the findings, they are the most direct and valid approach currently available to determine the subjects’ perception of experience . To haveFuture researches aiming to improve the birth experience should evaluate psychological birth trauma as an outcome of their interventions. Interventions to help practitioners learn more about mother-friendly birth should be designed and assessed. In addition, it would be useful to assess the effectiveness of partner-based interventions on the maternal childbirth experience. One of the most important sub-groups requiring evidence to inform practice, is women with a fear of childbirth. Therefore, interventions designed for this special sub-group would deserve a separate review.This systematic review provides a summary of available strategies that had been designed to improve the maternal experience of childbirth. The aim of this study was to classify these strategies and identify those that were successful. Four main categories of strategies are supporting childbearing women, relaxation and pain relief during birth, minimizing obstetric interventions, and birth preparedness. Successful interventions were supporting women during labour, relaxation through massage and music, early labour assessment to minimize obstetric interventions, and birth preparedness. The main recommendation of this review is that emotional support programs for childbearing women should be implemented in countries’ maternal health plans. These programs can comprise a combination of successful strategies such as continuous labour support by a familiar person, reassuring physical contact using massage, and the continuity of midwifery care. There is a need for more clinical strategies that result in positive childbirth experiences. The results of this study might be helpful in planning clinical approaches and designing future studies regarding the prevention of negative and traumatic birth experiences.Additional file 1:Search strategy. (DOCX 17 kb)Additional file 2:Modified version of the Cochrane Public Health Group Data Extraction Template. (DOCX 58 kb)


Birth weight is a key factor for neonatal mortality and morbidity in most mammalian species. The great morphological variability in size, body weight and breed, as well as in skeletal and cranial conformation makes it challenging to define birth weight standards in dogs. A total of 3293 purebred pups were surveyed to study which maternal aspects can determine birth weight considering head and body shape, size, body weight and breed in bitches, as well as litter size and sex in pups. In our sample, multivariate analysis outcomes suggested that birth weight and litter size were directly proportional to maternal size. The maternal body shape influenced both birth weight and litter size, whereas the maternal head shape had impact only on birth weight. Sex differences in birth weight were found. Birth weight and litter size also varied among breeds. The results of the present study could have practical implications allowing one to identify pups in need of admission to intensive nursing care, as occurs in humans. A deeper knowledge of the factors that significantly influence birth weight could positively affect the canine breeding management helping to prevent and reduce neonatal mortality.p < 0.001) and litter size (p < 0.05) increased with maternal size and body weight. Birth weight was also influenced by the maternal head and body shape, with brachycephalic and brachymorph dogs showing the heaviest and the lightest pups, respectively (p < 0.001). Birth weight decreased with litter size (p < 0.001), and male pups were heavier than females (p < 0.001). These results suggest that canine morphotype, not only maternal size and body weight, can affect birth weight and litter size with possible practical implications in neonatal assistance. Despite increasing professionalism in dog breeding, the physiological range of birth weight in this species remains unclear. Low birth weight can predispose to neonatal mortality and growth deficiencies in humans. To date, the influence of the morphotype on birth weight has never been studied in dogs. For this purpose, an Italian census of birth weight was collected from 3293 purebred pups based on maternal morphotype, size, body weight and breed, as well as on litter size and sex of pups. Multivariate analysis outcomes showed that birth weight ( Birth weight has an important effect on fetal and neonatal health in humans. Due to their immature development and adaptive postnatal failure, underweight babies are prone to potential complications, especially impaired thermoregulation and hypoglycemia . TherefoCanis familiaris) recognized by the Fédération Cynologique Internationale (FCI). Bench standard defines the ideal characteristics for each breed including size (height at withers), body weight and morphometry of the adult dogs, while no specific information on the birth weight is provided. To date, despite a large number of studies on the puppy growth chart [Due to the wide phenotypic variability among breeds, dogs offer a unique opportunity to study correlations between morphology and birth weight. In fact, there are 337 breeds of domestic dogs , size (height at withers) and body weight (BW). An exploratory investigation of the influence of breed on birth weight was conducted in selected groups of dogs with the same morphotype.This study is based on data collected through an on-line questionnaire administered to Italian dog breeders from February 2014–September 2015 in the context of a national census promoted by the Università degli Studi di Milano in collaboration with the Ente Nazionale della Cinofilia Italiana (ENCI) to register the birth weight in the Italian purebred dog population. Participation in the questionnaire was freely decided by the breeders. In this case, the approval of the Ethics Committee does not apply.A large-scale prospective study to survey the birth weight (body weight of pups at birth (bBW)) of 3293 pups from a sample population of 588 purebred bitches of 99 breeds from a population of 154,195 dogs in Italy see  was perfThe Total Cephalic Index (TCI) is the ratio between the cranium width and the head length (tip of the nose-tip of the occiput). Based on their head shape, dogs were classified as brachycephalic (TCI > 50), mesocephalic (TCI = 50) and dolichocephalic (TCI < 50) . The CorThe distribution of birth weight and number of pups according to the maternal characteristics mentioned above was synthesized by the following indices: minimum, first quartile (1st Q), median, mean, third quartile (3rd Q) and maximum.k categories, one of the categories is considered as the “reference”, and k-1 dummy variables are generated to compare the mean of the response variable in each category with the mean of the response variable in the reference category. The number of pups per litter was included in the regression model in its original measurement scale. Residual analysis suggested the use of the logarithmic transformation of the birth weight. After logarithmic transformation, the regression coefficients can be related to the geometric mean of the response variable . For categorical variables, the exponent of the regression coefficient of each dummy variable was the estimate of the ratio between the geometric mean of birth weight of the category represented by the dummy variable and the geometric mean of the birth weight of the reference category. For litter size, the exponent of the regression coefficient was the estimate of the ratio between the geometric mean of the birth weight for each of two consecutive litter size values.The relationship between birth weight of the pups (response variable) and litter size, maternal characteristics and sex of pups (explicative variables) was evaluated by linear mixed regression model. Litter size, maternal characteristics and sex of pups were considered as fixed effects. The correlation among pups from the same litter was accounted for including in the model the mother’s identification code as a random effect. The categorical maternal characteristics and sex of pups were included in the regression model as dummy variables. For a categorical variable with t statistic. To perform adequate inference procedures, Satterthwaite’s approximation of the degree of freedom of the t statistic was applied. The relationship between the litter size (response variable) and the maternal characteristics (explicative variables) was evaluated by a generalized linear model with Poisson error. As the considered maternal characteristics are categorical, each characteristic dummy variable was generated as previously described. In this generalized linear model, the exponent of the regression coefficient of each dummy variable was the estimate of the ratio between the mean litter size of the category represented by the dummy variable and the mean litter size of the reference category. The null hypothesis of each regression coefficient equal to 0 was tested by the Wald statistic. For both Poisson and linear mixed regression models, the following results related to the explicative categorical variables are reported: model estimated mean of the response variable for each category; ratio between the estimated mean of the response variable in each category and the estimated mean of the response variable in the reference category; and the 95% confidence interval of the ratio. For the numerical explicative variable, the following results are reported: model estimated mean of the response variable for the lowest value of the explicative variable and the increase of the mean of the response variable for a one-unit increase of the explicative variable. For both the Poisson and linear mixed model, the effect of each explicative variable was evaluated firstly by univariate analysis, then a multivariable regression model was used to evaluate the joint role of all of the explicative variables. The authors consider the maternal body weight and size as correlated, so two alternative multivariable regression models were performed including weight and size, respectively. A parsimonious final model was obtained by the stepwise selection procedure.The null hypothesis of the regression coefficient equal to 0 for fixed effects was tested by the An exploratory analysis was performed to evaluate the association between breeds and birth weight and between breeds and litter size in dogs sharing the same morphotype. To obtain reliable results, only breeds represented by at least 15 litters were considered.p < 0.05.Statistical significance was accepted at The analysis was performed by the R Core Team 2016) software; R: A language and environment for statistical computing; R: Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0 ; package softwareThe distribution of pup number and birth weight according to combinations of maternal morphotype, size and body weight of dogs in the study is summarized in The birth weight ranged from 40–1250 g. The lightest pup was a German Spitz (Pomeranian-Zwergspitz) that died within 24 h after birth; its surviving littermate weighed 124 g. The heaviest pup was from a Mastino Napoletano dog that delivered eight healthy pups. For statistical purposes, 45 pups whose data were incomplete were excluded from our investigation, thus including a total of 3248 pups.In univariate analysis, maternal head shape significantly influenced the mean birth weight of brachycephalic dogs when compared to mesocephalic dogs . Similarp > 0.3).The mother’s size was directly related to the bBW. Similar results were obtained considering the mother’s body weight. Concerning the relationship between the logarithm of the bBW and the litter size, no evidence for a non-linear effect was found. The estimated bBW increased with the increase of the number of pups per litter. To clarify this result, the effect of litter size on birth weight was adjusted for mother’s size. In this case, the impact of litter size was not statistically significant and inversely proportional to birth weight  and was excluded from the final regression model by the stepwise procedure. Concerning the body shape, the mean bBW of brachymorph dogs was significantly lower than that of all other categories. As already mentioned, the average bBW increased with the decreasing of the litter size. Results of the final regression model are reported in When maternal head shape, body shape, body weight, number of pups per litter and the sex of pups were jointly considered, the mother’s head shape did not contribute significantly to the bBW  . German p < 0.05), while no significant differences were recorded among the other breeds. Few differences were found between mean bBW of German shepherd, golden retriever and Labrador retriever (reference): the estimated mean ratio was 0.9 and 1.03, respectively.The bBW was lower in WHWT than in Jack Russel terrier (p = 0.01). The ratio between mean litter size of German shepherd and golden retriever was 0.85 (p = 0.12). Only the comparison between Labrador and golden retriever was statistically significant. No significant differences in mean litter size between Jack Russel terrier and WHWT were recorded (mean ratio = 0.951).The ratio between mean litter size of Labrador retriever and golden retriever was 0.77 . These results were confirmed by multivariate analysis  and our inclusion of either live or stillborn pups. Severely underweight pups are not likely to survive. However, the relation between birth weight and neonatal mortality has not been investigated, beyond the aim of the present study. The body weight was reported to vary up to 40-times among adult dogs from different sizes and breeds, while it was only 10-times different at most among pups at birth . Our resData shown in this study are from a census, so they do not represent the registered database of ENCI during the same period see . Being tIn our canine population, the maternal head shape had a significant impact on birth weight of pups when morphotype, litter size and sex of pups were considered together with maternal size. Brachycephalic dogs had the heaviest pups. These data are consistent with studies reporting an association between low birth weight and small head circumference at birth in babies ,33. HoweThe maternal body shape influenced significantly both birth weight and litter size with brachymorph dogs delivering the lightest pups and a lower number of pups than anacholicomorph ones. Studies in humans highlighted the importance of maternal phenotype influence on birth weight, indicating that weight at birth is attributable to maternal anthropometry differences and not to maternal size variability alone . Maternal size and body weight were directly proportional to both birth weight and litter size in our sample. The same observation was reported in cats with birth weight increasing as maternal weight and height increased . SimilarA limit of the present study is the lack of data on the real maternal body weight, body condition score, gestational weight gain and caloric intake of the dogs included in the census. Therefore, we cannot exclude that the nutritional status of bitches may also affect the birth weight of pups as described in humans ,37. MoreAs expected on the basis of the literature, litter size was inversely proportional to birth weight, with weight reduction for each additional pup per litter ,35. A significant sex difference in birth weight was recorded, with male pups being the heaviest. Data reported in literature on this topic are conflicting. Some authors have found no difference on birth weight between male and female pups ,26. On tAs previously observed, ambiguous or malformed pups resulted in lighter birth weight than healthy ones . In humaHeritability for body weight at birth has been demonstrated in boxers . A signiThere is strong evidence that birth weight results from a complex interaction between genetic and environmental factors of parental, placental and fetal origin in humans . Due to


A 35-year-old woman, gravida 4 para 3 estimated at 9+1 weeks gestational age by uncertain last menstrual period, presented with vaginal bleeding. She endorsed unprotected intercourse eight weeks prior and took Plan B One-Step (“morning-after pill”) within 48 hours. Quantitative human chorionic gonadotropin (hcg) resulted at 30 mIU/ml. Bedside transabdominal ultrasound was concerning for ectopic pregnancy . Is thisRadiology performed a transvaginal ultrasound, which was negative for intrauterine or ectopic pregnancy. Obstetric consultants were uncertain if the structure seen at bedside represented an ectopic . RadioloThe daughter cyst sign indicates an uncomplicated ovarian cyst.are limited to case reports involving pediatric females with McCune –Albright Syndrome and precocious puberty, as well as fetuses with incidental cysts mimicking ectopic pregnancy.VideoPoint-of-care transabdominal ultrasound video clip demonstrating the uterus and daughter cyst in the axial plane.


To document the neonatal outcomes of preterm birth in twin pregnancies and to investigate whether perinatal and obstetric parameters are associated with clinical outcomes.0/7 to 366/7 gestational weeks) to twins were analyzed. Maternal/fetal descriptive and obstetric parameters, sonographic data, route of delivery, indication for cesarean section, birth weight, Apgar scores, head circumference, umbilical cord length and placental weight were noted.This retrospective trial was conducted on data gathered from 176 preterm twins delivered in the obstetrics and gynecology department of our tertiary care center. Data extracted from medical files of 88 pregnant women who gave preterm birth , gestational age (p=0.001), height (p=0.004) and head circumference (p=0.011). None of these variables exhibited a noteworthy effect on Apgar scores at 5th minute.The average age of the pregnant women was 28.8±6.4 years and ultrasonographic gestational age was 31.9±2.6 weeks. Apgar scores at 1Efforts must be made to achieve advancement of gestational age until delivery in the follow-up preterm of twins. A well-established algorithm with special emphasis to risk factors is necessary to standardize and popularize the appropriate management strategy. Popularization of the use of assisted reproductive technologies and the advancement in the average age at first childbirth have contributed to an increased incidence of twin pregnancies worldwide.2Twin delivery constitutes a challenge in daily obstetric practice which becomes even more difficult in cases with preterm birth.10In the current study, our purpose was to document the neonatal outcomes of preterm birth in twin pregnancies and to investigate whether perinatal and obstetric parameters are associated with clinical outcomes.This retrospective study was carried out in the obstetrics & gynecology department of our institution following the approval of local Institutional Review Board.0/7 to 366/7 weeks of gestation) to twins were analyzed. Exclusion criteria were ablatio placenta, placenta previa, twin-to-twin transfusion syndrome, fetal growth restriction , delayed birth of second twin  and any prenatal diagnosis of malformation of either twin.Data from medical files of 88 pregnant women who gave preterm birth (between 266/7 weeks in cases without findings of chorioamnionitis. Antibiotherapy (amoxicillin 2 g/day for a week) was given for premature rupture of membranes and pregnants with preterm labour routinely received corticosteroids to promote fetal pulmonary maturation. All vaginal and ceserean twin deliveries were accompanied by a senior attending obstetrician.Gestational age was determined with respect to the last menstrual date and ultrasonography during the first trimester. In case of discrepancy of more than 5 days between two diagnostic modes, ultrasonographic data was used. Tocolytics were administered up to 33st and 5th minutes after birth and length of umbilical cord were noted. Associations between Apgar scores and perinatal fetal measurements with descriptive and baseline obstetric features were sought. Apgar score served as a direct measure of perinatal morbidity, while head circumference, birth weight and length of umbilical cord were accepted as indirect indicators.Maternal and gestational ages, gender, route of delivery, indications for cesarean section, birth weight, head circumference, height, placental weight, Apgar scores at 1Analysis of data was made using IBM SPSS Statistics 20 program. Normal distribution of data was tested with Kolmogorov-Smirnov test. Two independent groups were compared by means of Independent-Samples T test and Mann-Whitney U tests. For qualitative variables, frequency and percentage (%) were utilized. Confidence interval was 95% and level of statistical significance was set at p<0.05.An overview of descriptive and obstetric characteristics in our series is shown in st and 5th minutes is shown in st minute were affected significantly by fetal birth weight (p=0.001). st minute significantly. Route of delivery (p=0.612) and gender (p=0.182) did not exhibit a remarkable effect on Apgar scores at 1st minute , nor length of the umbilical cord (p=0.367) had a noteworthy impact on Apgar scores of twins on 5th minute.Analysis of the impacts of gestational age according to menstrual period (p=0.233) or ultrasonography (p=0.102), height (p=0.220), head circumference (p=0.975), placental weight (p=0.401) and umbilical cord length (p=0.331) did not have a remarkable effect on Apgar scores on 1t minute . Similarst minute (p=0.118) and Apgar scores on 5th minute (p=0.426). Similarly, diagnosis of premature rupture of membranes did not have a remarkable effect on Apgar scores on 1st minute (p=0.135) and on 5th minute (p=0.211).We did not find any significant difference between the firstborn and secondborn twins with respect to Apgar scores on 1st minute (p=0.007) and on 5th minute (p=0.003) compared to firstborn twins delivered after <32 gestational weeks. In the same way, neonates born ≥32 gestational weeks had better Apgar scores on 1st minute (p=0.001) and on 5th minute (p<0.001) than the secondborn twins delivered <32 gestational weeks.For the firstborn twins, neonates born ≥32 gestational weeks displayed better Apgar scores on 1The objective of the present study was to outline the clinical outcomes in preterm births of twin pregnancies and to seek whether any perinatal, surgical and obstetric parameters are related with clinical outcomes. Our results yielded that advancement of gestational age is crucial to achieve acceptable fetal growth rates and better Apgar scores after birth. Particularly, Apgar scores at first minute are more prone to be influenced by perinatal variables.In 2006, 60% of the twins delivered in the United States were preterm and weighed less than 2500g.13Transvaginal cervical length or fetal fibronectin level can be used to distinguish pregnancies that are more likely to deliver prematurely.2One of the more common interventions that have been tried in the past was the use of prophylactic oral betamimetics to reduce the incidence of preterm birth in twin gestations.17The use of antenatal corticosteroids has been shown to decrease perinatal mortality, respiratory distress syndrome, necrotizing enterocolitis and systemic infections. However, in spite of the improvement provided by antenatal steroid treatment, it should not be administered repetitively.19The current retrospective study is noteworthy for several reasons: First, Apgar scores at first minute are affected more remarkably by perinatal factors in preterm twins and this circumstance must be considered during the interpretation of Apgar scores after birth. Determination of gestation age with respect to ultrasonography and menstrual date yielded consistent information and both of these measures can be used for obtaining reliable data. Efforts must be made to allow advancement of pregnancy in preterm twins and achievement of acceptable fetal growth can result in a better prognosis as reflected in Apgar scores at first minute. Our findings highlight that growth restriction and earlier occurence of delivery result in worse Apgar scores. Hence, they are risk factors for neonatal morbidity or mortality. Our results are in agreement to a recent study by Blickstein et al.Limitations of the study: It is retrospective study and unpreventable impacts of social, economical, personal and ethnic factors on our results. Also the small vaginal birth sample versus high cesarean delivery ratio is another limitation. Furthermore, this data reflects the experience of a single institution and randomization is usually impossible by means of delivery route in such trials due to ethical and legal issues. Therefore, extrapolations and interpretations of our results must be made with caution.In summary, we suggest that early recognition of risk factors and increased awareness on risks associated with preterm birth in twin pregnancies is important. Efforts must be made to provide advancement of gestational age until delivery to allow the fetal growth as much as possible. A well-established algorithm with special emphasis to these signs is necessary to standardize and popularize the appropriate management strategy.