Cystic echinococcosis (hydatidosis) in humans is an infectious disease caused by tapeworms of Echinococcus genus. Brain involvement is rare. The best treatment is surgery and intact cyst removal is mandatory to prevent recurrence and possible anaphylactic reaction.An 8-year-old girl presented with a 1-month history of malaise, headache and vomiting. On Physical examinations, she was disoriented with bilateral papilledema. Brain CT scan and MRI revealed a well-defined cystic mass in left temporo-parieto-occipital region with considerable midline shift without perilesional edema. The patient was diagnosed with brain hydatid cyst and underwent surgical excision of the cyst without rupture.Surgery is the most important part of intracranial hydatid cyst treatment, and surgeons should make every effort to remove them in toto without spillage. We hence decided to perform surgery and necessary precautions to prevent rupture and dissemination of hydatid were taken during the surgery.A neurosurgeon has to bear in mind brain hydatid cyst in the differential diagnosis of cystic cerebral lesions especially in children from rural areas. The hydrodissection technique is the gold standard for the surgical treatment of cerebral hydatid cyst disease. It can also be effectively applied to the treatment of giant cerebral hydatid cyst disease without rupturing the cyst. •Echinococcus genus.Hydatidosis in humans is an infectious disease caused by tapeworms of •Brain involvement is rare.•The best treatment is surgery.•Intact cyst removal is mandatory to prevent recurrence and possible anaphylactic reaction. Although CE may be located anywhere in the brain, it is most frequently found in both hemispheres, particularly in the middle cerebral artery territory with the parietal lobe being the most common site. Very rarely the cysts are located in the posterior cranial fossa or ventricles. In patients with cerebral hydatid disease, concurrent hepatic, pulmonary and other organ involvement has been reported. Brain involvement often presents as a well-defined isolated cystic lesion in the territory of the middle cerebral artery hydatid cyst in left parieto-occipital region who was treated in our hospital via left parieto-occipital craniotomy. The cyst was removed totally intact using Dowling's technique of hydrodissection. This case report has been reported in line with the SCARE Criteria 2hydatid cyst in the lungs and abdomen. Brain CT scan revealed a large, well-defined cystic lesion in the left temporo-parieto-occipital region with considerable mass effect  and produces Taeniid eggs that are released from the intestinal tract into the environment the metacestode, develops in internal organs, especially the liver and lungs Hydatid disease is an ancient disease and even was known to Hippocrates Hydatidosis has a worldwide distribution with annual incidence rate of 1–200 per 100,000. It is endemic in many sheep and cattle-raising geographic areas including Mediterranean countries, the Middle East, Eastern Europe and South America. In Iran, the hydatidosis is being actively transmitted and its annual incidence rate is estimated 0.61 per 100,000 Cerebral involvement is extremely rare, being seen in 2-3% of systemic disease and forming 2% of all space occupying lesions of the brain. This rarity, coupled with nonspecific symptoms, necessitates a high index of clinical suspicion and thus presents a diagnostic challenge It is observed more often in children and young adults and several case series reported a slight male prevalence Brain hydatid cysts are usually single and occurrence of multiple cysts is very rare The patients are usually asymptomatic or their symptoms are nonspecific since growth of the cysts is generally slow and therefore clinical manifestations tend to be nonspecific due to compression of involved tissues. The diagnosis depends on clinical suspicion, typically based on a history of living in, or having travelled to, an endemic area and is evaluated with imaging The signs and symptoms are nonspecific and the most common ones are reported to be headache, papilledema, and vomiting; however, any symptom due to increased intracranial pressure can be seen. Focal symptoms like hemiparesis, seizures, gait, or Vision Problems can be observed depending on the size and location of the cyst cerebral hydatid cyst both computerized tomography (CT) and MRI reveal a spherical cystic lesion with well-defined borders, a smooth thin wall with or without septation or calcification. The cyst wall is iso- or hyperdense with respect to the cerebral parenchyma on unenhanced CT and usually shows a rim of low intensity in both T1W and T2W images. Daughter cysts, if present, are considered pathognomonic but are rarely seen. Wall calcification is seen in less than 1 % of cases. Mass effect, with compression of midline structures and the ventricles, is a common finding, but surrounding edema and rim enhancement are generally not seen in uncomplicated cases. Thin rim of peripheral enhancement can be visualized due to fibrous capsule or secondary to superadded infection In hydatid cyst with mainly typical characteristics includes supratentorial cystic lesions like arachnoid cysts, cystic tumors, abscess, and porencephalic cysts. Arachnoid cysts are not spherical, porencephalic cysts are usually connected to the ventricular system and neither are entirely surrounded by brain tissue, cystic tumors usually have solid components that are enhanced after contrast injection, and abscesses typically demonstrate rim enhancement and oedema of surrounding white matter.The differential diagnosis of an intracerebral Hydatid cyst should be considered especially with supratentorial cystic lesions in young male patients with a history of living in an endemic area or having contact with farm dogs and cattle.As a conclusion, imaging is useful, but not always conclusive, in diagnosing brain hydatid cyst. CT detects calcification in the lesion better than MRI, whereas MRI is better for assessment the exact location and anatomic relationships of the lesion. Nevertheless, in some cases, despite use of advanced imaging techniques, the diagnosis is still problematic. The therapeutic options that can be used in cases of hydatid cysts include: surgical excision, PAIR , chemotherapy with anthelmintic agent (Albendazole), and conservative treatments, i.e., “watch and see”, which are useful in cases of inactive cysts. Small, heavily calcified cysts can be considered inactive or dead and can only be monitored periodically.hydatid cyst treatment, and surgeons should do their best to remove them in toto without spillage. The most common complication is a rupture of the cyst into the subarachnoid space which leads to widespread dissemination followed by severe inflammatory or anaphylactic response. Dowling's technique is the most accepted method nowadays. It requires a great osteoplastic flap, cautious handing during all the surgical steps, wide incision over the cyst, sloping the head of the table downward, and injecting saline between the cyst and the brain. In our case, we opted for surgical treatment, removed the cyst in toto and obtained a good outcome.Surgery is the mainstay of intracranial 4A neurosurgeon has to bear in mind brain hydatid cyst in the differential diagnosis of cystic cerebral lesions especially in children from rural areas. The hydrodissection technique is the gold standard for the surgical treatment of cerebral hydatid cyst disease. It can also be effectively applied to the treatment of giant cerebral hydatid cyst without rupturing the cyst.Written informed consent was obtained from the patient's parents/legal guardian for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.We obtained approval from the ethics committee of Urmia University of Medical Sciences, West Azerbaijan, Iran (Code: IR.UMSU.REC.1401.308).The authors have not received any funding for their paper.Design of the article the acquisition, analysis, or interpretation of data for the article .Data collection .Writing the paper (Amir Abbas Ghasemi).Amir Abbas Ghasemi.Not applicable.The authors had no conflicts of interest.


In general, a slightly higher number of boys are born than girls, and the sex ratio at birth  is reported to be 1.03–1.07 in many countries. However, pregnant women exposed to high levels of atmospheric particulate matter have a reduced sex ratio at birth. Exposure to air pollutants can also lead to premature birth, suggesting that inflammation within the body may affect pregnancy maintenance and fetal development. On the other hand, the effects of air pollutants carried from afar by monsoons on the sex ratio at birth in downstream areas have not been evaluated. We focused on the Goto Islands, where various air pollutants flow from the Eurasian continent. The objective of this study was to clarify the effects of the atmospheric level of each pollutant on the sex ratio at birth on the Goto Islands.We extracted observation data of particulate matter 2.5, sulfur dioxide, oxidants, nonmethane hydrocarbons, and methane from the National Institute for Environmental Studies database. In addition, the monthly sex ratio at birth was calculated using birth data from the National Statistics Center. To evaluate the effect of substance exposure just before fertilization on the sex ratio at birth, we analyzed the relationship between the observed pollutant level and the sex ratio at birth 9 months later. A stepwise generalized linear model was used to analyze the effects of air pollutant levels on the sex ratio at birth.p < 0.0001), sulfur dioxide (p = 0.0026), oxidant (p < 0.0001), nonmethane hydrocarbon (p < 0.0001), and methane (p < 0.0001) values. In the target population in the target period, the total number of births was 1835, and the sex ratio at birth was 0.967. Univariate analysis showed that the values of particulate matter 2.5 (p = 0.0157) and oxidants (p = 0.0047) correlated negatively with the sex ratio at birth. In addition, the results of multivariate analysis using the stepwise method in the model equation indicated that every 1 ppm increase in the observed OX value resulted in a 0.311 decrease in the sex ratio at birth (p = 0.0034).The observed values for all pollutants were significantly different between seasons, including the particulate matter 2.5 (We evaluated the relationship between seasonal variations in air pollutant levels and the sex ratio at birth 9 months later on the Goto Islands. We found that an increase in oxidant levels just before and after conception may be a risk factor for a lower sex ratio at birth. Due to the previously reported vulnerability of male fetuses, females who become pregnant when air pollutant concentrations are high may be more likely to have a female baby. It is necessary to evaluate the effects of oxidants on various aspects of pregnancy and childbirth.The online version contains supplementary material available at 10.1186/s12889-023-17418-5. In humans, the theoretical sex ratio at fertilization is 1:1, but the miscarriage rate for female fetuses is usually slightly higher than that for male fetuses .2 exposure due to environmental pollution [There are reports that the sex ratio at birth is reduced when mothers or fathers are exposed to chemicals. For example, children born to pregnant women exposed to tobacco , polychlollution . It has ollution . Furtherollution . Maternaollution . Furtherollution , 14, exp2 levels on Fukue Island actually change depending on the wind direction and speed. According to the Japan Meteorological Agency, westerly winds flow from southern China to Japan  throughout the year [Fukue Island is located in the Goto Islands of Nagasaki Prefecture, Japan Fig. . Aerosolthe year . During the year . In addi2) as sulfur oxide, oxidants (OXs) as oxidizing substances, nonmethane hydrocarbons (NMHCs), and methane (CH4) as other hydrocarbons, which were extracted from monthly Continuous Monitoring of Air Pollution reports [4 were conducted in the morning (6:00 a.m. to 9:00 a.m.), we used the monthly average value data.The Environmental Observatory of the National Institute for Environmental Studies monitors the concentrations of air pollutants in various parts of Japan and publishes the data. In this study, observational data for Fukue Island included data on PM2.5 as fine particulate matter, sulfur dioxide  was calculated.Observational data of air pollutants for 108 months (from April 2013 when observations of PM2.5 levels began in Fukue to March 2022) were used for analysis. In addition, to evaluate the effects of exposure to substances just before or after fertilization on the birth sex ratio, data on the number of births from January 2014 to December 2022 (9 months after the substance level observation period) were used.p value < 0.05 indicated significance.In accordance with the standards of the Japan Meteorological Agency, March to May is considered spring, June to August is considered summer, September to November is considered autumn, and December to February is considered winter. Air pollutant concentrations were plotted for each season, and comparisons between groups were performed using analysis of variance (ANOVA) or the Kruskal‒Wallis test. After these analyses, we used the Tukey‒Kramer test or the Steel-Dwass test as a multiple test to specifically analyze which seasons showed differences. A test method for comparison was selected based on the results of the Shapiro‒Wilk test. R studio (ver. 2022.07.2 + 576) was used for statistical analyses, and a Statistical analysis was conducted based on the correlation coefficient of the maximal information coefficient (MIC) , Spearma2 and CH4 levels tended to decrease from summer to autumn. Conversely, the observed values for NMHCs tended to be higher in summer. On the other hand, OXs had the highest correlation coefficients with the observation months (r = 0.6121) and tended to increase, with peaks in spring and autumn.Additional Fig. p < 0.0001), autumn (p < 0.0001), and winter (p = 0.009)). The observed value was lowest in autumn, and a significant difference was also observed between autumn and winter (p = 0.0389). SO2 levels were lowest in summer, and significant differences were observed in the other seasons (spring (p = 0.0079), autumn (p = 0.0129), and winter (p = 0.0192)). For OXs, the observed values tended to be highest in spring, and significant differences were observed in the other seasons (summer (p < 0.0001), autumn (p < 0.0001), and winter (p < 0.0001)). In addition, the observed values of OXs were the lowest in summer, and a significant difference was observed between autumn (p = 0.0003) and winter (p = 0.0299). The observed value of NMHCs tended to be lowest in winter, and there was a significant difference from the other seasons (spring (p = 0.0002), summer (p < 0.0001), and autumn (p = 0.0002)). Similar to the SO2 value, the observed value of CH4 was lowest in summer, and significant differences were observed in the other seasons (spring (p < 0.0001), autumn (p < 0.0001), and winter (p < 0.0001)).The observed values for each season are summarized in Table p = 0.0303) and between summer and winter (p = 0.0154); the sex ratio at birth tended to be lower in winter  and OXs  correlated negatively with the sex ratio at birth. The correlation coefficients between the observed level of SO2 (r = -0.1180), NMHCs (r = 0.0893) or CH4 (r = -0.1423) and the sex ratio at birth were low, and the fitted lines did not have a significant slope, even in the linear regression analysis .The relationship between the observed air pollutant level and the sex ratio at birth 9 months later was plotted, Spearman’s correlation coefficient was calculated, and linear regression analysis was performed Fig. . The obs2 (r = 0.5316) and between PM2.5 and OXs (r = 0.5092), and Fig. p = 0.0034), and the higher the observed OX value was, the lower the sex ratio at birth 9 months later (Table Additional Table 2 data observed at the summit of Mt. Fuji in Japan showed seasonality, with an increase from winter to spring. SO2 fluctuates with nitrogen oxide and 222Rn, but it is not clear whether this is truly continental [In the Japanese archipelago, including Fukue Island, air pollutants and the substances that cause them flow from the Eurasian continent due to seasonal winds. Data collected in China from June 2014 to February 2019 show that PM2.5 concentration tended to be higher in winter . On Fukutinental . TherefoIf different types of substances flow in the same air current at the same time, it is possible that the observed values of different substances on Fukue Island may correlate. However, since we wanted to observe the effects of each substance on the sex ratio at birth, we chose all these variables because it is possible that even if some correlation was observed, it would be necessary to incorporate all substances into the multivariate analysis. The results of this study showed that the sex ratio at birth tended to decrease in pregnant women who had exposure to high levels of oxidants in the air during the period of conception.It has been reported that exposure to ozone, the main oxidant, during early pregnancy can lead to shortened gestation and increased preterm birth rates , 32. To Recently, it has been reported that being pregnant with a male fetus may suppress the maternal immune response , 39. On It has been reported that pregnant women with high levels of cortisol, known as the stress hormone, have a higher risk of giving birth prematurely and giving birth to low-birth-weight babies, suggesting that the cortisol level may be a better measure than perceived stress for predicting birth outcomes , 42. EleIn this study, based on the hypothesis that maternal inflammation just before and after fertilization or implantation increases the probability of failure to maintain pregnancy with a male fetus, this study investigated the correlation between the level of air pollutants at the time of fertilization or implantation and the sex ratio at birth. The decrease in the sex ratio at birth due to oxidant exposure, which was also observed in this study, may have been due to the fragility of male fetuses, making it easier to conceive female fetuses and resulting in a decrease in the sex ratio at birth.Previous studies have reported that both paternal and maternal exposure to substances are factors that lower the birth sex ratio. Because this study only evaluated the relationship between atmospheric pollutant concentrations and the birth sex ratio, it was not possible to clarify whether this was due to paternal or maternal effects. In addition, various factors, such as maternal age, socioeconomic factors, medical history, and lifestyle habits during pregnancy, affect pregnancy and fetal development. Since this study used only data compiled and published within the jurisdiction of public health centers for analysis, it is necessary to clarify the influence of these individual maternal attributes and biomarkers, such as changes in female hormone and inflammatory cytokine levels, on the sex ratio at birth through more detailed research. Only monthly observation data were available for analysis. We could not calculate the individual timing of fertilization based on gestational age; thus, the relationship between daily air pollutant observational data and child sex could not be accurately evaluated. Further research is needed to clarify whether oxidant exposure has a strong effect on paternal gametes, ovaries, or the intrauterine environment.In this study, we considered the characteristics of seasonal variations in air pollutant levels on Fukue Island. We also evaluated the relationship between the observed concentrations of air pollutants and the sex ratio at birth and clarified that an increase in oxidant levels at conception was a risk factor for a lower sex ratio at birth. In this study, every 1 ppm increase in the observed OX value resulted in a 0.311 decrease in the sex ratio at birth in the model equation. Since it has been reported that events that decrease the sex ratio at birth are also risk factors for preterm birth, it is necessary to evaluate the effects of exposure to oxidants on pregnancy and childbirth from various aspects.Below is the link to the electronic supplementary material.Supplementary Material 1Supplementary Material 2Supplementary Material 3


The mortality rate in the first two months of life is high in canine species, estimated at about 10% of live-born puppies, and can certainly be improved. Early identification of neonates at higher risk of mortality is required. Using data collected from 8550 puppies shared on a voluntary basis by 127 French breeding kennels, we explored the early growth of puppies as well as its interconnections with birth weight and mortality within the first two months. Low-birth-weight puppies were found to grow less than others over the first days of life but more later (compensatory growth). Thresholds for growth rates allowing the identification of puppies at higher risk of mortality during their first two months of life were established and will be useful to identify puppies with insufficient early growth to improve their chances of survival.Puppy survival during their first weeks of life can be improved, and early detection of puppies with increased mortality risk is one of the keys to success. In the canine species, the few studies on this subject focused on birth weight, which reflects intrauterine growth. The present work aimed to explore the interconnections between birth weight, early growth and survival until two months of life in the canine species. In total, data from 8550 puppies born in 127 French breeding kennels were analysed. Five different growth rates were calculated to reflect the growth of puppies during their first week of life. Low-birth-weight puppies had lower growth than normal-birth-weight puppies over the first two days of life but higher growth rates thereafter. Growth-rate thresholds allowing the identification of puppies at higher risk of mortality during their first two months of life were lower for low-birth-weight puppies. These thresholds will help breeders and veterinarians to identify puppies at risk with particular needs for monitoring and nursing to improve their chances of survival. Canine newborns face a high mortality rate (approximately 10% of live-born puppies) during their first two months of life, i.e., during which they live with their mother at the breeder’s ,3,4. SucThe first objective of this study, based on data collected on a national scale, was to describe and compare early growth rates for low- and normal-birth-weight puppies. Then, this study explored the association between early growth (during the first week of life) and mortality rate over the first two months of life, considering the birth-weight category. Finally, specific growth-rate thresholds have been determined to allow breeders and veterinarians to assess the growth of puppies during their first days of life and identify those at higher risk of mortality over the first two months of life. ® messages, during canine exhibitions and via various dog breed associations  × 100. Prior to analysis, puppies with extreme values were removed, i.e., with values higher than the 75th centile plus 1.5 times the interquartile range (IQR) or lower than the 25th centile minus 1.5 times the IQR (Tukey’s method). Only puppies belonging to a breed represented by at least 100 individuals were included in the analysis.Puppies were categorized as low or normal birth weight (LBW or NBW) based on their status at 2 months , using thresholds defined by classification and regression tree (CART) analysis. To deal with the variability of birth weight depending on the breed ,23, threAfter a general description of the five growth-rate distributions, means were compared between NBW and LBW using univariate analyses of variance (ANOVA) after testing the assumptions. Then, CART analysis, following the same procedure as described above, was used to assess the ability of growth rate to discriminate between the survivors and the puppies that would die during the two first months of life. NBW and LBW were analysed separately, and cut-off values were determined for each growth rate .In the last part of the analysis, the CART procedure, using the same method as described above, allowed identifying weight-related variables with the highest discriminatory power to differentiate between puppies dying before two months of age and those still alive at the end of the period considered. The procedure was carried out three times: for puppies alive on Day 1, then those alive on Day 2 and finally those alive on Day 7. On Day 1, birth-weight category (LBW or NBW) and GR 0–1 were considered. On Day 2, birth-weight category, GR 0–1 and GR 1–2 were considered. Finally, on Day 7, birth-weight category, GR 0–1, GR 1–2 and GR 2–7 were considered. The relative discriminatory power of each variable included in the analysis was calculated in order to rank weight-related mortality risk factors on Day 1, 2 and 7. ggplot2 [dplyr [tidyr [rpart [caret [p < 0.05 was considered statistically significant, and statistical uncertainty was assessed by calculating 95% confidence intervals (95 CI).All the statistical analyses were performed using R software, version 4.2.1 , and theggplot2  for data2 [dplyr  and tidyr [tidyr  for datar [rpart  and caret [caret  to perfoData from a total of 8550 live-born puppies from 24 breeds, 1493 litters, and belonging to 127 French breeding kennels were included in this study . LittersAmong these 8550 puppies, based on their 0–2 months mortality and CART analysis, 1291 (15%) were classified as LBW and 7259 (85%) as NBW. Birth-weight-threshold values by breed are presented in A total of 8.9%  of live-born puppies died during the first two months of life, with most of the deaths  occurring during the neonatal period (between birth and Day 21).p < 0.001).CART analysis allowed the creation of two groups of puppies based on their status at 2 months . The overall mortality rate during the first two months of life was thus higher for LBW than for NBW puppies: 24.6% (95% CI: 22.3–27.1) vs. 6.1% (95% CI: 5.5–6.6), respectively. In addition, the time distribution of deaths was also different depending on the birth-weight category : LBW pupp < 0.01 for GR 0–1; F = 40.37, p < 0.001 for GR 1–2 and F = 15.86, p < 0.001 for GR 0–2). Conversely, later than Day 2, LBW presented higher growth rates than NBW; for GR 2–7  = 9.32, p < 0.01) and also for GR 0–7  = 5.21, p < 0.05). Overall growth rates, as well as values for LBW and NBW puppies, are described in For the five growth rates considered, CART analysis was able to determine thresholds discriminating two categories of puppies with different mortality risks, suggesting a link between early growth and mortality over the first two months after birth. Such a link was evidenced both for LBW and for NBW puppies, but growth-rate thresholds differ between the two categories . In the last part of the analysis, the relative importance of weight-related parameters over the first week after birth on mortality risk over the first two months was assessed using CART analyses. The method was applied three times by considering puppies alive on Day 1, then puppies alive on Day 2 and, finally, puppies alive on Day 7. Depending on the age at assessment, different growth rates were included in the CART analysis. Their relative importance, as well as that of birth weight, was assessed without regard to the timing of the measurements .The relative importance of the birth-weight category in distinguishing puppies alive or not at two months of age compared to one of the growth rates included in the CART analysis was high on Day 7, moderate on Day 2 and not significant on Day 1 . On Day In the scientific literature, different time windows have been used to describe postnatal mortality in the canine species , the need for investment is low, the practice is simple, requiring no specific skills, and the result is readily available. However, there is a lack of guidelines for assessing the adequacy of puppy growth. A threshold for a growth rate between birth and Day 2 based on the risk of neonatal mortality (Day 0–Day 21) was previously defined at −4% . In anotSince we evidenced the influence of birth weight together with growth rates over several periods on mortality rate, the final part of the analysis aimed at ranking the weight-related criteria according to their ability to discriminate puppies surviving from those dying before two months of age. The results revealed that growth rate could help to reduce but not totally reverse the deleterious impact of the birth-weight category. Interestingly, birth weight was important to discriminate surviving puppies not only for mortality during the first days of life but also after the first week. Indeed, the birth-weight category was the most discriminant criterion for puppies alive at Day 7 to assess their chances of survival until two months of age . This suThis study justifies and provides practical guidelines for the measurement of the daily growth rate of puppies during their first week of life. The cut-off values calculated in our study provide an easy tool for detecting and nursing puppies at increased risk of mortality. They could be relevant for breeders and veterinarians to objectively identify early puppies requiring particular attention. The next step towards improving canine health and welfare could be to define optimal growth by considering together the short- and long-term impacts of early growth. Indeed, optimal early growth probably does not mean maximum growth because of the potential risk of being overweight in adulthood. Cohort studies are needed to determine lower  and higher (risk of overweight) thresholds throughout early growth in the canine species.


A handheld optical device was developed to evaluate a newborn's skin maturity by assessing the photobiological properties of the tissue and processing it with other variables to predict early neonatal prognosis related to prematurity. This study assessed the device's ability to predict respiratory distress syndrome (RDS).To assess the device's utility we enrolled newborns at childbirth in six urban perinatal centers from two multicenter single-blinded clinical trials. All newborns had inpatient follow-up until 72 h of life. We trained supervised machine learning models with data from 780 newborns in a Brazilian trial and provided external validation with data from 305 low-birth-weight newborns from another trial that assessed Brazilian and Mozambican newborns. The index test measured skin optical reflection with an optical sensor and adjusted acquired values with clinical variables such as birth weight and prenatal corticoid exposition for lung maturity, maternal diabetes, and hypertensive disturbances. The performance of the models was evaluated using intrasample k-parts cross-validation and external validation in an independent sample.Models adjusting three predictors  or five predictors had a similar performance, including or not maternal diabetes and hypertensive diseases. The best global accuracy was 89.7  and specificity of 91.3% (95% CI: 88.7 to 93.5). The test correctly discriminated RDS newborns in external validation, with 82.3% (95% CI: 77.5 to 86.4) accuracy. Our findings demonstrate a new way to assess a newborn's lung maturity, providing potential opportunities for earlier and more effective care.http://www.ensaiosclinicos.gov.br/rg/RBR-3f5bm5/), and RBR-33mjf (online access: https://ensaiosclinicos.gov.br/rg/RBR-33rnjf/).RBR-3f5bm5 (online access:  Infant mortality is a critical human development indicator since it reflects the quality of assistance, and social, economic, and environmental factors . Most chTo achieve lower infant morbidity and mortality rates focused on the day of birth, early identification of lung maturity risk enhances chances of survival even based on referral safe transportation among facilities. Nevertheless, very often, especially late preterm infants are inappropriately classified as full-term newborns, delaying care for the former . This waLungs develop linearly before childbirth; however, the maturational competence for extrauterine breathing occurs later in pregnancy or under stressful influences such as maternal disease, placental dysfunction, and drug exposition . Under tWe analyzed two birth scenarios, one to provide predictive models and the other to apply them to a more realistic picture of the usage of the model. Accordingly, both studies were multicenter prospective, concurrent cohorts comprised of six urban referral perinatal centers. Five Brazilian urban referral centers for high-complexity perinatal care took part in the study: Clinical Hospital—Universidade Federal de Minas Gerais (as coordinator), Minas Gerais State; Sofia Feldman Hospital—Minas Gerais State; Hospital da Universidade Luterana do Brasil—Rio Grande do Sul State; Hospital Materno-infantil de Brasília—Federal District; and Hospital Universitário da Universidade Federal do Maranhão—Maranhão State. One referral center in Mozambique, the Maputo Central Hospital, the largest in the country, is headquartered in its capital.Both cohorts shared inclusion criteria for live newborns enrolled within the first day of life, with the available reference standard gestational age, and childbirth after 24 weeks of gestation. Combining the last menstrual period with obstetric ultrasound assessment, we assessed gestational age at birth following international consensus for the due date . Anhydran = 177, 58.0%).For transparency, the clinical trials register and details of enrollment remain public. From clinical trial 1, registered under the number RBR-3f5bm5 , we evalThe primary outcome was to predict the RDS. The reference standard for RDS diagnosis has a basis in clinical, laboratory, and radiological findings and respiratory outcomes . HoweverThe assessment of newborns' skin maturity with the optical device was possible with the development of the equipment. We already noticed a high agreement between gestational age calculated by this device with the best available gestational age as a reference, as well the accuracy for discrimination of preterm against term infants . The errIn this study, data temporality of predictors was the first day of life, a moment when the user did not receive the result of RDS prediction to provide test blinding. Alongside skin reflectance, automatically acquired with the device when it touches the sole of the newborn, clinical variables were added by the user, and machine learning algorithms delivered the RDS prediction and were stored in the processor . In the The testing steps were standardized and supported by the prior proof of concept publications. The sole was the site of the newborn's body with a higher correlation between the skin reflection and pregnancy dating than other body sites, with the advantage of fulfilling the patient security recommendation for minimum manipulation of newborns . The infAccording to recommendations for good clinical practices involving human research with medical devices, and according to the International Organization for Standardization (ISO 14155:2011), trained research assistants collected data on 65 demographic and clinical features and 25 skin variables. The framework of variables is available in a previous report  and median (IQR) to describe continuous variables for symmetric and asymmetric distributions, respectively. We used frequencies (%) for categorical variables. The Mean-T and Mann-Whitney U tests were used to compare the mean or median between two groups of interest as RDS yes or no, according to the variables’ parametric or non-parametric frequency distribution. For comparisons between frequencies, the Chi-square Test evaluated the independence hypothesis between categorical variables as preterm vs. RDS yes or no, and the Likelihood ratio chi-square statistic was the alternative when more than 20% of expected values were above five. ANOVA or Kruskall Wallis tests compared three groups analysis as RDS, TTN, and none according to the variables' parametric or non-parametric frequency distribution.P-values of <0.05 were considered suggestive of statistical significance. SPSS software  was used for statistical data analysis.The set of machine learning models provided outcomes for binary RDS (yes or no) and three classes . The choice of the best models occurred by means of reliability analysis. The accuracy of the prediction of best models was evaluated using sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio. n = 215) had RDS. In the validation scenario, we analyzed data from 263 pregnant women who gave birth to 308 newborns with birth weights under 2.5 kg (scenario 2). Three exclusions occurred due to incorrect enrollment. Among the 305 included newborns, 37.7% (n = 112) had RDS. An overview of participants, according to development and model validation steps with respective birth scenarios and test outcomes, for the best models of prediction, is shown in Newborns from two clinical trials summed up 1,085 tests with the medical device. From the baseline scenario dataset where we set the RDS predictive models, we analyzed data from 702 Brazilian pregnant women who gave birth to 781 newborns with gestational ages older than 24 weeks (scenario 1). One exclusion occurred due to uncertainty in either an TTN or RDS diagnosis. Among 780 included newborns, 325 (41.7%) were low-birth-weight (LBW), and 27.6% (p < 0.001) and hypertensive disease (p < 0.001) in birth scenario 1, but not in scenario 2 . An important baseline characteristic to highlight is the no-RDS subgroup profile with high maternal disease frequency, ventilatory support, and NICU admission. For instance, the no-RDS subgroup of LBW newborns in the validation scenario comprised 102 (53.1%) newborns with mothers affected by hypertensive diseases and 115 (59.6%) newborns admitted to NICU. In both scenarios, children with RDS had higher ACTMF exposition (p < 0.001), lower gestational age (p < 0.001), lower birth weight (p < 0.001), and lower first-minute Apgar score (p < 0.001) than those without RDS.The participants' baseline demographic and clinical characteristics are shown in p = 0.421), positive-pressure ventilation (p = 0.844), intubation at birth (p = 0.131) surfactant resuscitation steps, (p = 0.697), and mechanical ventilation (0.864) until 72 h of life. However, the LBW newborns in the birth scenario 2 had higher morbidity and mortality rates (p < 0.001) than newborns in the birth scenario 1.Comparing birth scenarios, the newborns had similar characteristics concerning rupture of membranes more than 18 h . The likelihood ratio for RDS increased approximately five times when the index test was positive . RegardiAnalyzing the confusion matrix for RDS prediction according to gestational age at birth , we founp = 0.002).In order to inspect similarities and differences between newborns with or without correct RDS prediction, we compared the clinical characteristics in the validation scenario . GestatiImproving healthcare equity is a primary goal of the United Nations — this aim makes the reduction of infant mortality a priority . DigitalThe same sort of study has been presented, integrating computational technology to identify predictors of neonatal mortality, such as the lecithin and sphingomyelin ratio by machine learning applied to mild-infrared spectra  or acousConsidering the very-LBW subgroup of analysis, our results with a three-variables predictive model achieved an accuracy of 84.9% . In comparison, using an extensive historical 14-year inpatient dataset and many predictive variables, Jaskari et al. classified bronchopulmonary dysplasia in a retrospective dataset of very-LBW, with an accuracy of around 0.899 AUROC . FurtherEarly detection of severe neonatal morbidities such as RDS is critical to halt disease progression and prevent further complications or death. Risk identification of the occurrence might provide means for opportune diagnosis and due care with surfactant access, enhancing chances of survival with minimal sequelae, even with the referral of newborns . In LMICWorldwide, hard decisions in scenarios with scarce resources are taken daily based on birth weight, with particular attention to late preterm births that account for most preterm births . Birth wThe role of the index test used to predict RDS might be a prompt risk indication immediately at birth, anticipating best practices of management in scenarios with limited resources or optimizing access to existing facilities. This study is a premarket approach using data from two clinical trials to validate the algorithm for real-time RDS prediction at birth. The skin reflection can be acquired from the device, and the user quickly introduces some clinical variables, as presented in Despite recent advances in the perinatal management of RDS, controversies still exist. Lower emphasis on radiographic diagnosis and classification of RDS, such as ground glass with air bronchograms, directs management toward a preventive surfactant treatment approach. Definitions based on blood gas analyses are also redundant, as management has moved towards a preventive surfactant treatment approach based on clinical assessment of the work of breathing and oxygen requirement to avoid worsening the syndrome. Current RDS management aims to maximize survival by minimizing complications such as air leaks and bronchopulmonary dysplasia .Despite the development of a new technology that allows skin maturity associated with birth data to be used as a marker of lung maturity, sources of potential bias can limit the generalizability of the outcomes. The development and validation scenarios had relevant differences regarding RDS frequency in newborns, morbidity, and mortality. Moreover, the accuracy of the machine learning models was sustained by a high specificity of 91.3% . In false-positive RDS prediction in LBW newborns, unnecessary interventions such as transferring to a referral center can occur in approximately 18% of newborns. Nonetheless, assuming the implementation of a screening test, a point-of-care prediction in conjunction with clinical protocols, this approach has the potential to enhance neonatal care. Future studies are necessary to measure the influence of disease incidence on generalizing the models, as in the primary care birth scenario or low complexity hospitals where the incidence of preterm birth and RDS is lower than ours. The performance of the prediction in the subgroups analysis considering ranges of gestational age and birth weight might still require further large samples.Regarding skin maturity importance in the model, the rationale which relies on a direct relationship between epidermal barrier competence and neonatal survival faces limitations after 35 weeks of gestation, when the epidermis is complete . TherefoThe objective measurement of skin maturity alongside machine learning models opens new opportunities to recognize complex patterns among variables in RDS outcome prediction. The models adjusted for skin reflection, birth weight, and ACTMF at birth as RDS predictors for 72 h of life achieved high accuracy in developing and validating modeling using clinical trial datasets. This study demonstrates a new way to assess neonatal lung immaturity, providing potential opportunities for more effective and early caring with an automated medical device tester.


The impact of different respiratory strategies at birth on the preterm lung is well understood; however, concerns have been raised that lung recruitment may impede cerebral haemodynamics. This study aims to examine the effect of three different ventilation strategies on carotid blood flow, carotid artery oxygen content and carotid oxygen delivery.2O , sustained inflation  or dynamic PEEP strategy  at birth, followed by 90 min of standardised ventilation. Haemodynamic data were continuously recorded, with intermittent arterial blood gas analysis.124–127-day gestation apnoeic intubated preterm lambs studied as part of a larger programme primarily assessing lung injury were randomised to positive pressure ventilation with positive end-expiratory pressure (PEEP) 8 cmHp < 0.0001, mixed effects model). Carotid oxygen content and oxygen delivery were similar between strategies. Maximum PEEP level did not alter cerebral haemodynamic measures.Overall carotid blood flow measures were comparable between strategies. Except for mean carotid blood flow that was significantly lower for the SI group compared to the No-RM and DynPEEP groups over the first 3 min (Although there were some short-term variations in cerebral haemodynamics between different PEEP strategies and SI, these were not sustained.Different pressure strategies to facilitate lung aeration at birth in preterm infants have been proposed. There is minimal information on the effect of lung recruitment on cerebral haemodynamics.This is the first study that compares the effect of sustained lung inflation and dynamic and static positive end-expiratory pressure on cerebral haemodynamics.We found that the different ventilation strategies did not alter carotid blood flow, carotid oxygen content or carotid oxygen delivery.This preclinical study provides some reassurance that respiratory strategies designed to focus on lung aeration at birth may not impact cerebral haemodynamics in preterm neonates. There has been considerable interest in the optimal methods of supporting lung aeration in preterm infants, including the use of adequate positive end-expiratory pressure (PEEP) or an initial sustained inflation (SI).6 Preclinical studies have repeatedly demonstrated that the use of adequate PEEP at birth, and preferably dynamic PEEP manoeuvres, optimises lung mechanics, aeration and reduces the risks of lung injury compared to SI.6 Recent clinical trials of fixed-duration SI in preterm infants have suggested potentially important adverse outcomes without lung protective benefits.7 Studies assessing ventilation strategies have primarily focused on respiratory outcomes. To date, there have been minimal reports detailing cerebrovascular responses to PEEP approaches at birth.Lung aeration is a fundamental component of the transition to air-breathing at birth.9 However, the behaviour of CeBF and oxygen delivery in preterm infants aerated by PEEP recruitment or SI at birth remains largely unknown. Whilst the use of PEEP is ubiquitous, PEEP strategies at birth have not been subjected to systematic evaluation in preterm infants, resulting in the use of variable PEEP levels.10 A SI at birth increased CeBF and carotid oxygen content compared to a low static PEEP with tidal inflations in preterm lambs.11 Beyond the respiratory transition at birth, excessive PEEP levels impacts haemodynamics in preterm lambs.13 The impact of higher PEEP levels at birth is less clear, with a recent pilot lamb study suggesting engorgement of micro-vessels and an increase in CeBF.14Cerebral blood flow (CeBF) decreases after birth in both healthy term lambs and infants as a proposed response to increasing oxygen saturation and cerebral oxygen delivery following spontaneous breathing.We hypothesised that measures of cerebral haemodynamics will be impacted by different PEEP levels or a SI at birth. We aimed to determine the effect of static and dynamic PEEP level strategies or a SI to facilitate lung aeration at birth on carotid blood flow (CBF), carotid arterial blood oxygen (CAO) content and carotid oxygen delivery in intubated preterm lambs.4All techniques and procedures were approved by the Animal Ethics Committee of the Murdoch Children’s Research Institute (MCRI), Melbourne, Australia in accordance with National Health and Medical Research Council (NHMRC) guidelines. This study was performed as part of a large inter-linked preterm lamb programme that aimed to determine the optimal methods of applying positive pressure ventilation (PPV) at birth. In the interest of animal reduction, and with the prior knowledge of our Animal Ethics Committee and funding body (NHMRC), some ventilation groups have been reported in different studies with distinctly separate aims.5 In summary, 124–127-day preterm lambs born via Caesarean section under general anaesthesia to betamethasone-treated (11.7 mg) ewes were instrumented before delivery. All ewes were from the same flock and studied over two breeding seasons of similar environmental factors. Instrumentation was performed on exteriorisation of the foetal chest and included endotracheal tube intubation (4.0 mm cuffed), passive drainage of foetal lung fluid, flow probe placement around a carotid artery  and occlusive cannulation of the contralateral carotid artery and external jugular vein. At delivery, the umbilical cord was cut and the lamb moved to a resuscitaire and weighed prior to commencing respiratory support (maximum delay between cord cut and first inflation 1 min). CBF, ventilation data, peripheral oxygen saturation (SpO2), heart rate and arterial blood pressure were recorded throughout . Arterial blood gas (ABG) analysis was performed at foetal , 5, 15 min and then 15 minutely after birth. Ketamine and midazolam infusions were titrated to minimum doses that suppressed breathing and maintained analgesia.The detailed methodology and complete set of outcome measures for the broader study has been reported previously.4 lambs were randomised to either (1) PPV at a PEEP 8 cmH2O with volume targeted ventilation (VTV) from birth for 90 min (No-RM), (2) an initial SI delivered at 35 cmH2O until aeration stability was achieved on real-time imaging of lung volume using electrical impedance tomography (mean (SD) 153.2 (24.3) s),6 or (3) a dynamic PEEP manoeuvre delivered over 3 min using PEEP steps of 2 cmH2O to a maximum of 14 cmH2O (20 s increments/PEEP step) or 20 cmH2O (10 s increments), depending on group allocation, followed by the same stepwise decreases to a final PEEP of 8 cmH2O (DynPEEP). After the initial intervention, the SI and DynPEEP groups were managed as per No-RM. Fraction of inspired oxygen and tidal volume (VT) were started at 0.3 and 7 ml/kg respectively, and both titrated using a standardised strategy to maintain pre-ductal SpO2 88–94% and arterial carbon dioxide 45–60 mmHg following the 5 min ABG, with surfactant therapy at 10 min.2As described in detail previously,2O; 140 s) rather than 1 and 2 min. In all groups, measures from 3 to 90 min were at PEEP 8 cmH2O. From the CBF data, the mean waveform amplitude, maximum, minimum, and overall mean were extracted. Carotid blood flow is non-linear with dependency on heart rate and systemic blood pressure, complicated by the possibility of the presence of a ductus arteriosus in a foetus. Multiple waveform measurements were, therefore, extracted to provide a comprehensive analysis of carotid blood flow. The maximum CBF corresponds to systolic blood pressure values, whilst the minimum corresponds to diastolic values. The amplitude measures the difference between the systolic and diastolic flow values (height of the waveform), while the mean incorporates all phases of the carotid blood flow. Values were then expressed by birth weight. In this study, the contralateral carotid artery was occluded for vascular access and, therefore, the absolute CBF refers to the flow measured in the remaining patent carotid artery. As occlusion of one carotid artery may influence the pattern of upper body flow distribution, we presented the data as both change from baseline for accuracy and in absolute values for ease of understanding. CAO content and carotid oxygen delivery were calculated from the ABG results using the following formulas:16A 2-min measurement of CBF and cardiorespiratory data were made immediately prior to cord clamping. CBF data were extracted at 10 s intervals during the foetal period, both intact cord (CI) and after cord clamping (CC) prior to commencing ventilation. CBF data were then extracted over 10 s at minutely intervals to 5 min after starting respiratory support, and over 20 s intervals at 10, 15, 30 and 90 min. In the DynPEEP groups, measures were made at maximum PEEP (80 s) and end of dynamic PEEP ; PaO2, arterial partial pressure of oxygen (mmHg).Hb, haemoglobin (g/dl); SaOCBF, carotid blood flow (ml/min).2 Previous preterm lamb studies reporting CBF and CAO content have shown important differences with 6/group.17 Our broader study was designed to investigate different ventilation strategies at birth, specifically SI and DynPEEP. In the interest of reduction, the No-RM group acted as a control across multiple studies. This resulted in an unbalanced number of lambs in each group. As reported in the original studies, there was no difference in adverse event rates between groups. Data were analysed using a mixed-effect model (Tukey post-tests) using ventilation strategy and time as principle variables. Within the DynPEEP group, subgroup analysis comparing the maximum delivered PEEP (14 vs. 20 cmH2O) was performed using a two-way analysis of variance. Analysis was performed in PRISM V9  and p < 0.05 considered significant.Sample size was determined by the primary studies that were powered to lung injury outcomes and required larger group sizes (approximately 20 lambs/group) than studies powered to cardiorespiratory measures.2 (No-RM lower) and minimum CBF and PaCO2 (both SI higher), with no significant differences in the absolute foetal CI mean and maximum CBF values.A total of 89 lambs from our data set were available for analysis. Twenty-one lambs were excluded because of unreliable CBF measures related to probe-vessel contact. No lambs were excluded based on clinical stability. Table p = 0.62-0.81 mixed effects models) while time did . In all groups, an overall increase in mean and minimum and a decrease in maximum and amplitude occurred following cord clamping. Mean, maximum and minimum waveform values were higher in the No-RM group compared with DynPEEP at the time of first inflations. All other timepoints and comparison of different ventilation strategies were comparable with no significant differences found in later timepoints. There was no difference in the CBF measures for the 14 and 20 cmH2O DynPEEP levels , with mean CBF increasing after cord clamping, before decreasing to pre-birth levels by 10 min. Strategy alone only impacted mean CBF (p = 0.049), while the combined impact of time and strategy was significant for mean (p < 0.0001), minimum (p = 0.0007) and maximum (p = 0.0012) CBF data, but not amplitude (p = 0.15). The change in mean and minimum CBF from foetal values was less during the first 3 min for the SI group. Thereafter, the different ventilation strategies were comparable with no difference in later timepoints. In all groups, clamping of the umbilical cord caused the largest change in CBF . Four lambs  had a CBF that persisted at zero or negative values throughout the study .There was high inter-subject variability in all groups, including the initial CI value. To account for this, Fig. p < 0.0001 for time). The combined impact of time and strategy was not statistically different (p = 0.19). High variability in CAO content occurred in all groups at 5 min, with DynPEEP being lower; however, this was not significant. Carotid oxygen delivery increased similarly after birth for all groups (p < 0.0001 for time and p = 0.50 combined time and strategy). No difference was found in the CAO content and carotid oxygen delivery measures for the 14 and 20 cmH2O maximum PEEP levels . The high intra-thoracic pressure and, therefore, higher pulmonary blood flow and left ventricular output created by SI ventilation may explain this difference compared to the other strategies which use tidal (cyclic) pressure changes. There is little agreement on the effects of SI on cerebral haemodynamics. A possible harmful effect of SI on cerebral oxygenation (measured with near-infrared spectroscopy) was found in a small study of preterm infants.25 Both an increase in CBF and carotid oxygen delivery (with increased risk of cerebrovascular injury),17 and a reduction in CBF compared to non-SI interventions have been reported in preterm lambs.11 These conflicting results may reflect the small sample sizes in each study (approximately 6/group). This is particularly relevant given the high level of inter-subject variability that we observed in our larger SI sample of 15, highlighting the importance of appropriately powered preclinical studies. We have also previously reported a high variability in the time and volume response needed to appropriately aerate the lung using a SI.27 There is no accepted definition of an ‘optimal’ SI approach, with pre-defined, and fixed, time being the most common.29 The use of a fixed duration SI is based on the false assumption that lung mechanics are the same in all recipients.27 We have previously shown that titrating the SI duration to the aeration response in real-time results in better respiratory outcomes than the 30 s SI most commonly used in lamb studies.6 In our earlier studies, a 30 s SI could be too short or unnecessarily excessive in terms of lung aeration.6 This may explain the mixed results in preclinical and clinical preterm SI studies, especially the unexplained higher early mortality in the SI group in the Sustained Aeration of Infant Lungs (SAIL) trial.30 While titrating the SI duration to response is not used clinically, in a preclinical study it is arguably preferable as it standardises the interventions' impact across all lambs irrespective of lung mechanics. Even with a titrated strategy to aeration, a SI provides no benefit in lung aeration and increases early injury markers compared to DynPEEP and No-RM.2 The clinical implications of the different CBF patterns found in this study are unknown and cannot be used to recommend one respiratory support strategy over another.CBF is a commonly reported measure of cerebral haemodynamic physiology.2 suggesting a possible foetal difference in the groups. The high variability indicates that the likely reason is a degree of transient hypoxia or asphyxia whilst moving to the resuscitaire following cord clamping, which is known to occur with as little as 45 s delay in ventilation.15 Importantly, the CAO content was similar in all groups by 10 min suggesting that any effect is transient. Irrespectively, these findings indicate that the higher PEEP at birth may impact cerebral oxygen delivery. Future well-powered studies with more arterial sampling intervals in the first 10 min are required. As we cannot conclude that there is not a potential impact on CAO content, clinical trials of DynPEEP, such as Positive End-Expiratory Pressure Levels during Resuscitation of Preterm Infants at Birth ,31 should include cerebral complications in their analysis.CAO content provides a measure to assess the availability of oxygen in the blood. CAO content increased from foetal values for all ventilation strategies, indicating that each group supported cerebral oxygenation similarly and successfully. Interestingly, the DynPEEP group did not show an initial increase in CAO content from the foetal baseline until 15 min, compared to 5 min in the SI and No-RM groups. The exact cause for this is unclear, and we can only speculate on the reasons. We have previously reported a lower dynamic respiratory system compliance prior to ventilation in this group of DynPEEP lambs at birth,32 Some preterm lamb studies have indicated a significant increase in oxygen delivery in the No-RM group compared to the SI groups, when ventilated with 100% oxygen.11 While this may indicate that the level of oxygenation influences cerebral haemodynamics, the lack of difference in our groups at 5 min (oxygenated in a standardised 30% inspired oxygen) supports our assertion that achieving lung aeration rather than the means of achieving it is the critical determinant of cerebral haemodynamics.2Carotid oxygen delivery, as a function of blood flow and oxygen content, is a thorough and accurate assessment of carotid haemodynamics. We found that the carotid oxygen delivery similarly increased from foetal levels in all groups, consistent with other comparisons between SI and No-RM in preterm lambs.4 this strategy may result in detrimental cardiovascular impacts. Impairment of pulmonary blood flow has been reported in a previous study of lambs managed with a DynPEEP approach between 4 and 10 cmH2O after respiratory transition.13 It should be noted that lung aeration was not measured in these studies, limiting any interpretation of the role of volume state (overdistension or recruitment). Our study has been the first to assess the use of DynPEEP on cerebral haemodynamics during the respiratory transition, and we have previously reported that overdistension was not a feature in our lambs.2 Thus, it is interesting that PEEP levels (between 8 and 20 cmH2O) did not significantly alter CBF or cerebral oxygen delivery. An important aspect of these PEEP strategies is the transient nature of high PEEP exposure while the lung is clearing foetal lung fluid. Current clinical approaches to DynPEEP also constrain PEEP increases to clinical need, based on oxygen and heart rate response,33 rather than pre-fixed PEEP values that should further limit any potential risk of inadvertent high intrathoracic pressure on haemodynamics.Despite the lung-protective benefits of DynPEEP at birth in preterm lambs,15 This cannot be confirmed as pulmonary or ductal blood flow was not measured in our study. As DynPEEP studies in infants are now being conducted, understanding the physiological impact of PEEP levels on pulmonary and ductal blood flow is needed.A redirection of CBF from the brain was noted in four lambs, most likely during diastole. It is possible that a redirection of blood flow to the ductal and pulmonary arteries caused this.26 but not representative of clinical practice. In our study, cerebral flow dynamics were assessed from a single carotid artery, with occlusion of the other. While this is common practice in lamb studies,34 it is not possible in humans. Ultrasound measures or near-infrared spectroscopy have been used in humans, including preterm infants, to assess CBF and cerebral oxygenation,37 and may have aided translatability. Extrapolating unilateral carotid blood flow measures to global cerebral haemodynamics requires caution, as unilateral occlusion may result in changes to the flow dynamics of the contralateral side.24 Further, our measures should not be assumed to represent the cerebral microvascular bed, with a recent preterm lamb pilot study suggesting that large and small cerebral vessel behaviour is not always uniform.14 Finally, we did not measure cerebral injury as an outcome.This study has limitations. Data were sourced from a large biobank of inter-linked preterm lamb studies primarily assessing lung injury resulting in unbalanced group sizes. Cerebral haemodynamics were not the primary outcome of these studies, leading to some lambs being excluded due to unreliable CBF data . In addition, we found little difference between the three ventilation strategies. Our study was not designed as a non-inferiority or equivalence trial and conclusions regarding cardiovascular and cerebrovascular safety should be made with caution. We studied anaesthetised apnoeic and intubated lambs, a common preclinical modelThere is a paucity of information on the cerebral haemodynamic effects of respiratory strategy at birth in preterm infants, despite the clear risk of injury in this population. Reassuringly, respiratory strategy did not impact cerebral haemodynamics, suggesting that clinicians can focus on strategies that optimise cardiorespiratory outcomes during the transition to air breathing.ARRIVE Author Checklist_Dahm_CBF_2022 copyDahm_CBF_Online supplementary data_R1_20Jul22


We found that PP-PTSD symptoms were higher among women who previously experienced physical  and sexual  assault and child abuse , with only associations with child abuse  remaining significant for subjective rates of traumatic birth experience. Perinatal loss and previous traumatic birth showed moderate but inconsistent effects. Support during labor did not have a buffering effect for participants with past traumatic experiences but showed a universally protective effect against PP-PTSD. Trauma-informed practices and allowing women to have a supportive birth team of choice during childbirth are promising avenues to minimize the incidence of PP-PTSD and improve the childbirth experience for all women.The aim of this study was to investigate the association of postpartum post-traumatic stress disorder (PP-PTSD) symptoms and subjective rates of traumatic birth experience with past traumatic life events . A sample of Russian women ( While childbirth can be a deeply meaningful and transformative experience for women, it is also associated with a significant risk of trauma. The prevalence of traumatic childbirth experiences varies widely, with studies showing that anywhere from 3% to 45.5% of women may perceive their childbirth as traumatic ,2,3. FurThus, addressing the risk factors for PP-PTSD for timely and accurate support and prevention is vital. Some of the strongest predictors of PP-PTSD and traumatic birth experience relate to the intrapartum risk factors, such as obstetric emergencies and infant complications , medicalSadly, these groups of factors usually occur unexpectedly, which limits the opportunities for prevention. However, there is an increasing number of studies indicating that there are pre-existing risk factors for developing PP-PTSD that could be addressed during pregnancy or even before conception. They include a history of psychiatric disorders ,22,28, dIndeed, PP-PTSD can be conceptualized both as the first-time onset related solely to childbirth in the absence of prior PTSD symptoms or any predisposing factors and as a pre-existing PTSD after previous traumatic events that are reactivated by childbirth ,5. The sFurthermore, it is estimated that up to 25% of pregnancies end with a perinatal loss, and perinatal grief is an important predictor of PTSD symptoms ,36. In aA prospective cohort study of 933 women from Australia showed that participants who developed PTSD after childbirth and those who did not differ in fourteen characteristics, of which seven were related to past traumatic events in their lives . Thus, tSupport during labor has been consistently associated with more positive birth experiences ,43 and aWhile the prevalence of clinically significant PP-PTSD is estimated at 15% in Russian women , to our Therefore, the main objective of this study was to investigate the association of PP-PTSD symptoms and subjective rates of traumatic birth experience with past traumatic life events, namely physical and sexual assault, child abuse, perinatal loss, and previous traumatic birth experience, as well as the cumulative traumatic experience in a Russian sample. Furthermore, we explored the association between PP-PTSD symptoms and subjective rates of traumatic birth experience and support during labor. Finally, the aim of this study was to examine whether support during labor buffered the effects of past traumatic life events so that it had a stronger protective effect among women with previous traumatic experiences in comparison to those without such experience. We expect to see that women who experienced any type of traumatic life events in the past have both higher symptoms of PP-PTSD and rate their childbirth experience as more traumatic. We further hypothesize that having a support person present will be associated with both lower symptoms of PP-PTSD and subjective rates of the traumatic birth experience. Support will also moderate the association between past traumatic experience and PP-PTSD so that there will be a significantly stronger effect of support for trauma survivors than for women without past traumas. Data for this cross-sectional study were collected from May to September 2022. Women received invitations to participate in the web-based survey via social media , antenatal classes, and classes for new parents as well as from the doctors and midwives in maternity hospitals and healthcare clinics. In total, 2954 women responded to the questions, and 2579 fulfilled the inclusion criteria .This present study was approved by the Ethical Committee of the Russian Psychological Society at Lomonosov Moscow State University (No: 345/2019). All participants signed the informed consent forms using the online tool Testograph prior to filling in the survey. The study design and procedures are compliant with the Declaration of Helsinki.The survey included questions about the participant’s age at the time of childbirth, highest achieved level of education (primary/secondary/tertiary), marital status (married/in relationship/single), and socioeconomic status (SES) in comparison to others in the current region of residence (low/middle/high).Respondents also answered questions regarding pregnancy and childbirth, such as parity, gestational age at childbirth, time since the childbirth, and mode of birth . Furthermore, women indicated whether they had a support person present at their childbirth and, if yes, who accompanied them (no support/partner/doula or private midwife/partner and doula or private midwife).Women were further asked to rate how traumatic they found their latest childbirth experience overall, on a scale from 0  to 10 (‘Extremely traumatic’).Next, there were questions asking to indicate whether the participants had ever experienced pregnancy loss, such as miscarriage or stillbirth, and, in case that they had given birth before, whether they considered their previous childbirth traumatic. Furthermore, women were presented with a list of other potentially very stressful and traumatic events . They were asked to tick the boxes next to the events they had experienced or witnessed at some point in their lives. For the purposes of this study, we focused on the traumatic experiences that were previously linked to perinatal mood and anxiety disorders, namely physical assault, sexual assault, and child abuse, as well as the cumulative traumatic experience that was calculated as the sum of traumatic events, potentially ranging between 0 = no trauma in the past and 8 = exposure to all types of traumatic events. The Russian version (Cronbach’s α = 0.87)  of the EWe used the City Birth Trauma Scale (CBiTS)  to assesIt is a self-report 31-item questionnaire, with 29 questions mapping onto DSM-5 diagnostic criteria and 2 questions relating to DSM-IV criteria . Scores All models were adjusted for the following maternal and birth-related characteristics previously associated with PPD and PP-PTSD as covariates: maternal age at the time of childbirth, level of education, marital status, socioeconomic status (SES), and previously diagnosed mental disorders as well as gestational age at birth, parity, time since the childbirth, and mode of birth ,24,57.Spearman’s correlation coefficient was used to estimate the relationship between PP-PTSD and PPD symptoms and the subjective rates of traumatic birth experiences.Multiple linear regression analysis examined the association between PP-PTSD symptoms as well as the subjective rates of traumatic birth experience and cumulative past traumatic experiences.We explored the association of the PP-PTSD symptoms and the subjective rates of traumatic birth experience with the categorical predictors  using generalized linear models.Logistic regression analysis was performed to assess the association between the clinically significant PP-PTSD (according to DSM-5) and the cumulative past traumatic experiences and support during labor. Finally, we tested whether support during labor moderated the association between past trauma and PP-PTSD symptoms and subjective rates of traumatic birth experience. In order to conduct that, we first stratified the sample by the presence of traumatic events in the past (any trauma (y/n), physical assault (y/n), sexual assault (y/n), child abuse (y/n), perinatal loss (y/n), and previous birth experience (none/not traumatic/traumatic) and performed multiple linear regression adjusted for covariates with support during labor (y/n) variable as the predictor. Next, we performed the interaction analyses using multiple linear and logistic binary regression, where the models were adjusted for the covariates and past traumatic experience and support variables’ main effects and the interaction component of these two variables as the predictor in order to explore whether the discovered differences were statistically significant. The level of significance was set to α = 0.05. All analyses were performed using SPSS 27 software .The demographic, childbirth, and trauma-related characteristics of participants are presented in p < 0.001). Both PPD  and PP-PTSD  also significantly correlated with the subjective rates of birth trauma, although to a lesser extent.n = 1388) indicated that they experienced or witnessed at least one traumatic event in the past. Furthermore, 23.1% of women experienced perinatal loss, and 20% said they had a traumatic childbirth experience previously. More than half of the participants , sexual assault , and child abuse . However, in relation to subjective rates of traumatic birth experiences, the association remained significant only for those who reported child abuse  in the past but not physical  or sexual assault . p < 0.001) but not physical  or sexual assault .Furthermore, there was a significantly higher risk of having PP-PTSD symptoms compatible with DSM-5 PTSD diagnosis if the participants had previously experienced child abuse  or subjective rates of traumatic birth experience . Similarly, we did not find statistically significant associations between previous traumatic birth experiences and the subjective rates of current traumatic birth experiences  (p < 0.001) ( = 0.10) . Contrar< 0.001) . p = 0.032) or previous traumatic birth  experience.However, the risk of having a clinical PP-PTSD diagnosis was significantly higher both in cases where the women had a perinatal loss  (p < 0.001).After adjustment for covariates, the highest PP-PTSD scores were among the participants who gave birth without support, slightly lower and almost equal scores were among women who gave birth in the presence of a partner or a doula/private midwife, and the lowest scores were among those who gave birth in the presence of both a partner and a doula/private midwife  . Figure p-values for all >0.066, data not shown). To estimate whether support during labor had a stronger effect among those who had traumatic experiences in the past in relation to PP-PTSD and subjectively rated traumatic birth experiences, we performed multiple regression analyses in the subsamples stratified by the presence of trauma in the past. p-values for all >0.50, data not shown). In the analysis with subjective rates of traumatic birth experience as the outcome, we found that support during labor was statistically significant in the subsamples with and without past trauma , and theTo our knowledge, this present work is the first to explore the association between traumatic birth experience and past traumatic life events that include physical assault, sexual assault, child abuse, perinatal loss, previous traumatic birth experience, and cumulative trauma in one study. Furthermore, we focused on the role of support during labor and its types, its association with PP-PTSD, and the potential buffering role for the participants with past traumatic experiences. We found that PP-PTSD symptoms were significantly higher among women with a history of physical and sexual assault, child abuse, and past traumatic birth experience, but not perinatal loss. Subjective rates of traumatic birth experience were significantly higher only among women with child abuse experience. In accordance with our hypotheses, we showed that support during labor was associated with lower PP-PTSD symptoms as well as subjective rates of traumatic birth experiences. However, contrary to our expectations, there was no buffering effect of the presence of a support person for women with past traumatic experiences.While PP-PTSD symptoms correlated significantly with subjective rates of traumatic birth experience in our study, this association was weaker than with PPD symptoms. It is in line with previous reports of the high comorbidity of PPD and PP-PTSD in Russia  and globWe further found that PP-PTSD symptoms were higher among women who experienced physical and sexual assault in the past, while there were no such associations with subjective rates of traumatic birth experiences. These results contribute to the line of studies that conceptualize PP-PTSD as pre-existing PTSD, which is reactivated by childbirth experience ,5, whereWe also show that past traumatic events act cumulatively such that the more traumas women reported, the higher were both PP-PTSD symptoms and subjective rates of traumatic birth experiences. Similarly, exposure to more traumatic events was associated with a higher risk of developing PTSD following childbirth in French , CanadiaInterestingly, we found no significant associations in both PP-PTSD symptoms and subjective rates of traumatic birth experience with perinatal loss experience. However, women were at 1.29 times higher risk of having PP-PTSD symptoms compatible with DSM-5 PTSD diagnosis if they experienced perinatal loss in the past. These results contribute to the contradictory evidence of the significance of perinatal loss on maternal mental health in subsequent pregnancies and the postpartum period ,40. PeriOur work is among the few studies that address the consequences of previous traumatic birth experiences for subsequent childbirth and postpartum mental health. We found that it was significantly associated with PP-PTSD but not the subjective rates of traumatic birth experience. Intriguingly, symptoms of post-traumatic stress following childbirth were almost as high in first-time mothers as in those whose previous birth was traumatic. It might indicate that it is not the previous traumatic birth that elevates the risk for a repeated traumatic birth, but, rather, a positive childbirth experience is a protective factor against PP-PTSD after following births. Indeed, higher birth satisfaction has been associated with lower rates of PP-PTSD in Turkey , CroatiaWe also show that support during labor has been a strong protective factor in our study: women who had at least one support person present at childbirth had a significantly lower risk of PP-PTSD, lower scores of PP-PTSD symptoms, and lower rates of subjective traumatic birth experiences. There are only two previous studies of PP-PTSD and support during labor in Russia, where, contrary to our current findings, there was no direct association between the presence of at least one birth companion and PP-PTSD ,24. HoweFurthermore, we show that both PP-PTSD symptoms and subjective rates of traumatic birth experience were lowest among women who had both their partner and a doula or private midwife present at birth, which is supported by a previous study where authors show similar results as our findings, with higher PP-PTSD symptoms among women with a single companion compared to those with two or more companions . Thus, aFinally, we hypothesized that support during labor had a stronger protective effect among women with previous traumatic experiences in comparison to those without such experience. Contrary to the study from the UK, where support during childbirth was buffering against traumatic birth events, with the strongest effects among women with previous histories of trauma or abuse , we did The strengths of our study include substantial sample size, the study design, use of validated questionnaires, and control for important covariates, such as mode of birth and history of mental disorders. However, several important limitations should be addressed when interpreting our results. First, our findings lack objective information on previous traumatic experiences and mental health conditions and rely solely on self-reports, which is a common limitation in perinatal studies, particularly in countries without extensive registry-based data. Second, in the question about past traumatic experiences, we did not ask about the timing of the traumatic events; thus, physical and sexual assault might overlap with childhood abuse experiences. Third, 37.5% of women in our sample had clinically significant depressive symptoms according to EPDS, which may bias their recollection of both past traumatic and childbirth experiences. Next, the data collection was completed online, which presents risks of the participants’ mistrust of the researchers and may affect the reliability of their responses. However, the online form of the study contributed to the wide geography of the regions from where the participants came, which is an important factor when collecting data in a country as big as Russia. Nevertheless, another limitation of the online form of the study is its restriction to the participants with access to a device with an Internet connection, which is not available in all regions of Russia. Furthermore, women in our study may also have been more active on social media platforms, which was our primary modality of recruitment. Our sample also consists of self-selected participants, thus presenting the risk of selection bias and lack of women from marginalized and high-risk groups. Finally, relative to the general population, where approximately 40% of adults aged 25–34 have higher education , our samA past traumatic experience is a significant risk factor for experiencing childbirth and labor as traumatic, with or without developing PP-PTSD. In particular, child abuse appears to be the strongest predictor of higher distress measured using both the CBiTS scale and subjective rates of traumatic birth experiences. Furthermore, there is a negative cumulative trauma effect, with each additional traumatic experience in the past putting women at increased risk for developing PP-PTSD. While our findings regarding perinatal loss and previous traumatic birth experience are less consistent, taken together, these findings point out the importance of collecting information about women’s past experiences during pregnancy. Therefore, trauma awareness training for midwives, obstetricians, and other caregivers working with women during the perinatal period is essential and trauma-informed practices during childbirth are warranted for the prevention of PP-PTSD. Finally, although we have not seen evidence of the buffering effects of non-medical support during labor for women with past traumatic experiences, the findings indicate its universal protective effect against traumatic birth experiences, particularly with more than one birth support person present at childbirth. Thus, providing continuous support during labor and allowing women to have a birth team of choice may be a simple and cost-effective approach for providing support in all birth settings, minimizing the incidence of PP-PTSD, and, overall, improving the quality of the childbirth experience.


The aim of this study was to describe the cumulative live birth rates (CLBRs) of young women with or without low prognosis according to the POSEIDON criteria after IVF/ICSI cycles and to investigate whether the diagnosis of low prognosis increases the risk of abnormal birth outcomes.Retrospective study.A single reproductive medicine center.From January 2016 to October 2020, there were 17,893 patients (<35 years) involved. After screening, 4,105 women were included in POSEIDON group 1, 1,375 women were included in POSEIDON group 3, and 11,876 women were defined as non-POSEIDON.Baseline serum AMH level was measured on the D2–D3 of menstrual cycle before IVF/ICSI treatment.Cumulative live birth rate (CLBR), birth outcomes.After four stimulation cycles, the CLBRs in POSEIDON group 1, POSEIDON group 3, and non-POSEIDON group reached 67.9% , 51.9% , and 79.6% , respectively. There was no difference in gestational age, preterm delivery, cesarean delivery, and low birth weight infants between the three groups, but macrosomia was significantly higher in non-POSEIDON group, after adjusting for maternal age and BMI.The POSEIDON group shows lower CLBRs than the non-POSEIDON group in young women, while the risk of abnormal birth outcomes in the POSEIDON group will not increase. UndeWith the introduction of the concept “cumulative live birth rate (CLBR)” , the conAs for infertile women who are at risk of low prognosis, the most concern is the opportunity to eventually take home a healthy baby. For this consideration, not only the chance of giving birth but also the health of newborns is also noteworthy. Furthermore, IVF treatment is connected to a higher risk of abnormal perinatal outcomes compared to natural pregnancy and intrauterine insemination . A studyOur center started the long-term delivery follow-up in the year 2016. Therefore, we retrospectively analyzed the clinical data of patients who had their first ovarian stimulation at the Reproductive Medicine Center of Tongji Hospital during the period from January 2016 to October 2020. The subsequent cycles of the studied populations were included until either the first live birth achieved or they dropped out of the cohort, whichever came first. The follow-up continued until 31 October 2021. We used AMH value to determine the ovarian reserve, and it was measured within 1 year before IVF/ICSI stimulation. Patients with any of the following characteristics were excluded (1): donor oocytes received, (2) oocytes cryopreservation, (3) without detailed information on ovarian stimulation, and (4) using “non-standard” ovarian stimulation protocol in the first cycle. For birth outcomes analysis, we excluded the vanishing twin syndrome and multiple live births. That is, patients with singleton pregnancies were only considered.Clinical pregnancy was determined by the ultrasonographic visualization of one or more gestational sacs. Live birth was defined as the birth of one or more live infant(s) after 28 weeks of gestation. This study was approved by the Institutional Review Board of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.We used POSEIDON criteria to categorize our studied subjects. Female age was recorded at the first stimulation cycle. We defined young patients as those with age <35 years. The study of Esteves et al.  found anDetails about ovarian stimulation, egg retrieval, IVF/ICSI, embryo culture, morphological grading, vitrification cryopreservation and warming procedures, and embryo transfer have been described in previous research , 15–17. Sociodemographic data, IVF/ICSI data, pregnancy outcomes, and birth outcomes of the patients who meet the criteria were abstracted from the electronic medical record system in our hospital. Whether women did or did not give birth at Tongji, information on pregnancy and delivery was collected through telephone interviews by trained nurses at certain points before and after childbirth. The content of the follow-up interviews was described elsewhere . Seven wpost-hoc test). Pregnancy outcomes were described in each entire treatment cycle, and CLBR was shown in a conservative manner. The conservative CLBR was calculated as the live births of all cycles (including the exact treatment cycle being described and previous cycles before it) divided by the number of people involved in the first cycle and was also reported as ratios and 95% confidence intervals (CIs). Birth outcomes were compared among patients who had singleton live birth, no matter which treatment cycle it occurred. Multiple logistic regression was performed on birth outcomes analysis to eliminate the confounding factors including maternal age and BMI. All these calculations were analyzed by SPSS 26.0 . p-values were two-sided, and p<.05 was considered statistically significant.Continuous variables are described as medians (first and third quartile) and were compared using Kruskal–Wallis or Mann–Whitney U test. Categorical variables were presented as frequency and were analyzed with Pearson chi-square or Fisher’s exact test  infant . HoweverThis study has some limitations. First of all, many patients in our study dropped out of the cohort without having a live birth. The reasons for not resuming treatment may be the financial burdens, psychological pressure, or medical advice from physicians to discontinue. Second, we only calculated the conservative CLBRs, but the condition may be superior because, according to the follow-up reviews, we were aware that some of the patients went to another center to continue their therapy. Third, due to the retrospective nature, we were unable to provide the situations of the pregnant mothers during the perinatal period. In addition, we were unable to provide the smoking status of the patients and the weight gain during pregnancy. Fourth, we only included the young POSEIDON groups in this research. Several previous studies did not set a control group, and among the research that took the non-POSEIDON group as the control group, a limited of them distinguish the patients according to age. Our study confirmed that the ovarian quantity may be the decisive factor in predicting success for young infertile women. We will further discuss the outcomes of elder POSEIDON patients in the near future.In conclusion, this long-term follow-up on pregnancy and delivery of young POSEIDON patients provides comprehensive information. It showed that after repeated ovarian stimulation, low responders can obtain more than 50% of live births. Diagnosing as a low responder did not increase the risk of abnormal birth outcomes, and normal responders may be associated with higher risk of delivering a macrosomia.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. The studies involving human participants were reviewed and approved by The Institutional Review Board of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.EY, YG, and LJ conceived of the study and participated in its design. EY and WL wrote the paper. WL and HJ analyzed the data. MZ, DC, XH, and YC collected the data. All co-workers have seen and agreed with the contents of the manuscript. All authors contributed to the article and approved the submitted version.