Anogenital distance (AGD) is a biomarker used for the evaluation of fetal androgen action. The disruption of fetal androgen action can affect the development of the reproductive system and adversely affect future reproductive functions. However, AGD may differ by race. Currently, there is a lack of data regarding the evaluation of AGD in large Han Chinese samples.AGD for neonates in Shanghai, China, was measured, and relevant factors that influenced AGD were analyzed.The AGD of full-term singleton neonates was measured within 3 days of birth, and the results were grouped according to gestational age and body weight at birth. In addition, relevant factors that influenced AGD were investigated.A total of 1,867 full-term singleton neonates were enrolled in this study. All the neonates were Han Chinese; among them, 986 were male, and 881 were female. Male AGD was 23.18 ± 3.17 mm, and female AGD was 11.65 ± 1.53 mm. Male AGD was 1.99 times longer than female AGD. With the increase in gestational age and body weight, AGD gradually increased. AGD was correlated with gestational age, body weight, and head circumference. The correlation between body weight at birth and AGD was highly significant.This study, for the first time, reported AGD measurement data for Chinese Han neonates. The results indicated that AGD was correlated with gestational age, body weight, and head circumference. The correlation between body weight at birth and AGD was highly significant. Anogenital distance (AGD) is the distance between the anus and the genitalia. It was originally used in rodents to distinguish between sexes. It exhibits sexual dimorphism, with male AGD being longer than female AGD . AGD is Chinese Han singleton neonates with a gestational age ≥37 weeks born in Shanghai, China, between January 2019 and December 2021 were enrolled. The exclusion criteria were as follows: mothers or neonates who had an incomplete medical history; neonates with combined severe malformations such as chromosomal diseases, critical congenital heart disease, or diaphragmatic hernia; neonates who were directly transferred to the neonatal intensive care unit for treatment due to other reasons; and neonates who presented genital malformations, hypospadias, or cryptorchidism. This study was approved by the Ethics Committee of Ruijin Hospital, Shanghai JiaoTong University School of Medicine. The guardians of all neonates were fully informed and signed an informed consent form.AGD was measured when neonates were asleep or in a calm state in a quiet and bright examination room with the room temperature maintained at ~25°C. Neonates were placed in a supine position with bilateral knee flexion to fully flex and abduct the hip and fully expose the perineum. An assistant secured the neonates in the above body position, and a professionally trained pediatrician performed the measurements and recorded the data. To minimize differences caused by measurements being taken by multiple personnel, all neonates were measured by the same pediatrician. Neonatal mobility was minimized during each measurement, and the pediatrician minimized skin contact at the measurement site as much as possible. A Vernier caliper was held in the right hand and slightly tilted toward the newborn's head. The measurement accuracy of the Vernier caliper used in this study was 0.05 mm. All measurements were completed within 72 h of birth.The measurement method was performed in accordance with a previous literature report . Male AGMaternal information included age, body weight, height, body mass index (BMI), gravidity, parity, smoking and drinking history, and education level. Neonatal data included gestational age, body weight, height, and head circumference. All data were acquired after the collection of a detailed medical history.s. Comparison between two groups was performed using the t-test. A two-way analysis of variance was used to compare the AGD between different genders, different gestational ages, and different birth weights. To study the relationship between maternal and neonatal factors and AGD, Pearson correlation analysis and multiple linear regression analysis were performed using AGD; maternal age, body weight, height, and BMI; and neonatal gestational age, body weight at birth, length, and head circumference. Maternal gravidity, parity, and education level were regarded as ordered data and were analyzed using the Spearman correlation analysis. P < 0.05 indicated statistical significance.Statistical analysis was performed using SPSS 26.0 statistical software. Measurement data are expressed as t = 98.211, P < 0.001). The male AGD was 1.99 times longer than the female AGD. AGD reference values for neonates with different gestational ages and for males and females are shown in F = 17.409, P < 0.001). A separate effect analysis of AGD between different gestational ages was then performed. There were differences in AGD among male neonates of different gestational ages, and the difference was statistically significant, F = 21.098, P < 0.001, partial η2 = 0.043. And there were differences in AGD among female neonates of different gestational ages, but the difference was not statistically significant, F=2.084, P = 0.080, partial η2 = 0.004. The AGD reference values for neonates with different body weights at birth and males and females are shown in F = 111.963, P < 0.001). A separate effect analysis of AGD between different body weights at birth was then performed. The comparison of AGD between male and female neonates with different body weights at birth indicated differences, and the differences were statistically significant . The penis length of male neonates was 18.90 ± 2.96 mm, and the penis width was 9.84 ± 1.18 mm. And with the increase of gestational age and body weight, the penis length and penis width also tend to increase gradually  were enrolled. The male AGD was 23.18 ± 3.17 mm, and the female AGD was 11.65 ± 1.53 mm; the male AGD was longer than the female AGD, and the difference was statistically significant   . The corNeonatal gestational age, weight at birth, body length at birth, and head circumference and maternal age, body weight, height, and BMI were used as independent variables, and AGD data were used as dependent variables for multiple linear regression analyses. The results of the analyses indicated that male and female neonatal gestational age, body weight at birth, and head circumference were correlated with neonatal AGD, of which the correlation between body weight at birth and AGD was highly significant .The development of the perineum and external genitalia is determined by dihydrotestosterone, resulting in a greater AGD in males than females . AGD is In women, a longer AGD is thought to be a masculinization effect and is caused by the excessively high level of androgen or ectopic activation of androgen receptors. It has been shown that a longer AGD in women is associated with elevated testosterone levels , 18. DauRegardless of neonate sex, an abnormally shortened or elongated AGD can be suggestive of some diseases or of abnormal development and can be suggestive of endocrine disruptor exposure during pregnancy. AGD measurements are relatively simple and non-invasive. Post-natal AGD measurement shows that the presence of an abnormal AGD in neonates has great significance for the early detection of diseases associated with abnormal sexual development and for guiding mothers to avoid excessive exposure to endocrine disruptors. However, there are few studies on the normal range for AGD. Some studies in western countries have reported AGD measurement values , 23, 24.Through the measurement and analysis of the AGD of neonates within three d after birth, this study confirmed that AGD is different between males and females. Male AGD was 1.99 times longer than female AGD; male AGD was 23.18 ± 3.17 mm, and female AGD was 11.65 ± 1.53 mm. One Turkish study with full-term neonates indicated that female AGD was 10.3 ± 0.2 mm and male AGD was 23 ± 0.6 mm . One stuThis study also grouped the neonates based on different gestational ages and body weights at birth. The results indicated that with the increase in gestational age or body weight at birth, male and female AGDs both showed gradual increasing trends. There were statistically significant differences in AGD between male neonates at different gestational ages, as well as between male and female neonates at different birth weights, while there were differences in AGD between female neonates at different gestational ages, but the difference was not statistically significant, which may be due to the small number of samples in some groups. The total sample size in this study was large; therefore, the results could provide normal AGD reference values for East Asian neonates with different gestational ages and body weights at birth. Furthermore, the results of the correlation analysis of neonatal AGD and neonatal factors indicated that the AGD of all neonates was significantly positively correlated with neonatal gestational age, body weight at birth, body length, and head circumference. The results of the correlation analysis of AGD and maternal factors indicated that male AGD was positively correlated with maternal body height. Female AGD was positively correlated with maternal body weight and BMI; however, the correlation was weak. Therefore, multivariate regression analyses were performed. The results showed that gestational age, body weight at birth and head circumference of both male and female neonates were correlated with neonatal AGD, of which the correlation between body weight at birth and AGD was highly significant. These findings are similar to those results reported in previous studies , 25, 26.In summary, this was a large-sample study that included Chinese Han full-term singleton neonates; the aim was to obtain AGD reference values for different sexes, gestational ages, and body weights at birth. The results indicated that neonatal gestational age, body weight at birth, and head circumference were correlated with neonatal AGD, of which the correlation between body weight at birth and AGD was highly significant. This study had certain limitations. The study center was in Shanghai, China, and the living environments of mothers enrolled in this study were similar; therefore, the influence of environmental factors on mothers was not included. Furthermore, long-term follow-up was not performed on these neonates; therefore, longitudinal data were not obtained. AGD reference data of children of different ages should be obtained through prospective cohort studies in the future to better investigate the clinical significance of AGD.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by the Ethics Committee of Ruijin Hospital, Shanghai JiaoTong University School of Medicine. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.WC, ZD, and HT contributed to conception and design of the study. WC drafted the manuscript and analyzed the data. XD and HT collected the patients information. ZD reviewed the manuscript and contributed to the literature overview. All authors contributed to manuscript revision, read, and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


We investigated the genomic and metabolic characteristics of the airway microbiome in mild, moderate, severe, and non-bronchopulmonary dysplasia (BPD) preterm infants and explored possible mechanisms underlying BPD.Twenty-eight preterm infants with gestational age ≤34 weeks and intubated within 24 h after birth were enrolled. According to the severity of BPD, the patients were divided into mild, moderate and severe BPD groups, and the non-BPD group was the control group. Tracheal aspirates (TA) were obtained at intubation and on day 7 after birth. The bacterium in the aspirates were sequenced by 16S rRNA, and the metabolomics of the aspirates were identified by high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-Q-TOF/MS). The correlation between the differential metabolite and differential bacteria was investigated using Pearson’s correlation coefficient corrected for gestational age and birth weight and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases.Stenotrophomonas increased, and the increased level of sn-glycerol 3-phosphoethanolamine was positively correlated with the severity of BPD. There was a significant positive correlation between the abundance of Stenotrophomonas and the level of sn-glycerol 3-phosphoethanolamine.There were significant differences in the diversity and composition of airway microbiome and metabolome between severe, moderate and mild BPD and non-BPD premature infants. At birth (day 1), the difference was more pronounced than at day 7. The diversity of airway microbial community decreased, the abundance of Stenotrophomonas, and increased level of sn-glycerol 3-phosphoethanolamine may have potential as biomarkers for BPD. The occurrence and severity of BPD are closely related to Stenotrophomonas, which may influence the composition of the lower airway microbiome through its metabolite sn-glycerol 3-phosphoethanolamine, and may be the triggering factor of the disease. The causal relationship needs further study.Decreased diversity of the airway microbiome, increased abundance of  Staphylococcus and Ureaplasma were the most the most common dominant organisms in the respiratory tract of infants. However, Lohmann et al. found that Acinetobacter was the predominant genus in the respiratory tract of infants at birth (Bronchopulmonary dysplasia (BPD) is a serious disease associated with premature that affects an estimated 50% of infants born at <28 weeks of gestation . Infantsat birth . In Wagnat birth . Lal’s iat birth  and Lohmat birth  complemeat birth –12. Baseat birth . Acevedoat birth . Bacteriat birth . TherefoIn this prospective observational cohort study, tracheal aspirates (TA) were collected during mechanical ventilation of infants to investigate: (1) airway microbiota at birth (Day 1) and on Day 7 after birth; (2) airway metabolomics characteristics at birth and on Day 7 after birth; and (3) the relationship between differential metabolites and specific bacteria in infants with severe BPD, moderate BPD, mild BPD, and non-BPD.This prospective observational cohort study was conducted at the Neonatal Intensive Care Unit of the Children’s Hospital of Chongqing Medical University between October 2017 and July 2018. The Institutional Review Board of Chongqing Medical University approved the protocol. Informed consent was received from the parents or guardians of all participants. The study was performed in accordance with approved guidelines.Infants born at <34 weeks gestation that underwent endotracheal intubation and mechanical ventilation in the first 24 h of life were included in this study. Exclusion criteria were: (1) clinical evidence of congenital heart disease ; (2) lethal congenital abnormality; (3) congenital sepsis; (4) evidence of pulmonary hypoplasia; or (5) futile cases  .Infants were divided into four groups stratified by the diagnosis and severity of BPD: severe BPD, moderate BPD, mild BPD, and non-BPD. BPD was diagnosed based on the need for supplemental oxygen at 28 days of age , 17. BPDClinical data were collected from a review of electronic medical records at study enrollment and during hospitalization. Information on maternal history, delivery, and clinical assessments was recorded.°C until further processing.Tracheal aspirates (TA) were collected during mechanical ventilation at birth (Day 1) and on Day 7 after birth according to a previously published protocol , 12, 17.http://www.ncbi.nlm.nih.gov/sra/PRJNA800242.Microbial genomic DNA from each sample was isolated and purified. The V4 region of the 16S rRNA gene from the microbial DNA was amplified using a polymerase chain reaction (PCR) with unique barcoded primers to create an “amplicon library” . The libP-value of < 0.05.Using the Quantitative Insights into Microbial Ecology (QIIME) 1.8.0 pipeline, the raw sequences were processed to concatenate reads into tags according to the overlapping relationship. Reads from each sample were separated with barcodes, and low-quality reads were removed. Processed tags were clustered at 97% similarity into operational taxonomic units (OTUs). The OTUs were assigned to taxa by matching to the Greengenes database (Release 13.8). Alpha diversity analyses (Shannon index) and beta diversity analyses [principal coordinate analysis (PCoA)] were performed. Comparison of microbiome composition among the four groups was performed using one-way ANOVA, and the differences of microbiome were considered statistically significant with a TA samples were analyzed using an ultra-high-performance liquid chromatography (UHPLC) system  coupled to a quadrupole time-of-flight mass spectrometer  at Shanghai Applied Protein Technology Co., Ltd.Samples were thawed at 4°C and 100 μL aliquots were mixed with 400 μL of cold methanol/acetonitrile  to remove the protein. After centrifuging for 15 min , the supernatant was dried in a vacuum centrifuge. For liquid chromatography-mass spectrometry (LC-MS), samples were dissolved in 100 μL acetonitrile/water . Pooled quality control (QC) samples were used to monitor the stability and repeatability of instrument analysis. The QC samples were inserted regularly and analyzed in every five samples.Raw LS electrospray ionization (ESI) MS data were converted into m/z format and analyzed for non-linear retention time (RT) alignment, peak detection, and filtration.P < 0.05 were considered statistically significant. Discriminatory metabolites within the data set were visualized as heat maps, which were generated using a hierarchical clustering algorithm. Molecules associated with significant changes were searched against the Kyoto Encyclopedia of Genes and Genomes (KEGG) database.1Processed data were normalized to total peak intensity, imported into SIMCA-P , and analyzed using Pareto-scaled principal component analysis (PCA). One-way ANOVA was used to determine the significance of each metabolite with a VIP value > 1. P < 0.05 was considered statistically significant.Statistical analysis was performed using SPSS version 22.0 for Windows . Normally distributed data are expressed as mean ± SD; non-normally distributed data are expressed as median and interquartile range (IQR). Between group differences were analyzed with Fisher’s Exact test for categorical variables and Kruskal-Wallis test for continuous variables after subsampling. Measurement data will also be compared by means of univariate analysis. We deal with the abnormal value by Pauta criterion . CorrelaIn this study, 28 premature infants were divided into 4 groups, including 8 severe BPD, 5 moderate BPD, 10 mild BPD, and 5 non-BPD. The demographic and clinical characteristics of the included infants are shown in P = 0.0019; P = 0.016; P = 0.001), the difference between moderate BPD group and non-BPD group was also found (P = 0.039), however, there was no difference between mild BPD group and control group (P = 0.196). For Day 7 after birth, the difference between severe BPD group and non-BPD group was found (P = 0.006), however the P-value for moderate BPD group vs. non-BPD group and mild BPD group vs. control group was 0.111 and 0.226, respectively. Principal coordinates analysis (PCoA) also showed a significant difference in the bacterial composition of the airway microbiome at birth (Day 1) between the four groups (The Shannon index was significantly lower at birth (Day 1)   (P = 0.064)   and on D (Day 1) , and the < 0.05) . But the= 0.064) . Then taTAs were subjected to LC/MS analysis in positive ion mode (ES+) and negative ion mode (ES-). Principle component analysis (PCA) was performed to reduce dimensionality in the dataset . ParametStenotrophomonas and sn-glycerol 3-phosphoethanolamine levels .Pearson’s correlation coefficient corrected by gestational age and birth weight was used to explore the functional correlation between the changes in the airway microbiome and differences in metabolites across the four groups at birth (Day 1) . There wStudies on the correlation between infant BPD and the airway microbiome are few and the results are not consistent –12, and Preterm birth is a strong predictor of BPD, with an inversely proportional incidence and severity , 23. In Prenatal steroid use was 40–75%, probably lower than in other studies , 27, wheOur results showed that multiple bacterial taxa can be identified in the respiratory secretions from intubated premature infants, even at birth and prior to surfactant administration. The diversity and composition of the airway microbiome at birth differs between infants with and without BPD, and the differences became less pronounced by Day 7 of life. Consistent with a previous report , our stuProteobacteria were the most abundant microbes in all infants. These data align with a previous report  were significantly different and 29 metabolites at day 7, indicating that the changes of metabolites were in parallel with the changes of airway microbiome. Among these metabolites, sn-glycerol 3-phosphoethanolamine content was positively correlated with the severity of BPD, which might be a potential metabolic biomarker for the early detection of BPD. The KEGG database showed that sn-glycerol 3-phosphoethanolamine has a role in glycerophospholipid metabolism. Glycerophospholipid has structural functions in bacteria, facilitates bacterial adaptation to environmental conditions, and is involved in bacteria–host interactions . Glycero disease . In thisStenotrophomonas, and increased level of sn-glycerol 3-phosphoethanolamine were positively associated with the severity of BPD, and might have potential as biomarkers for BPD. Thirdly, the abundance of Stenotrophomonas had a significant positive correlation with sn-glycerol 3-phosphoethanolamine level.Most study just compared the BPD group with non-BPD group , 42, 43,However, there were several limitations to this study. First, the sample size was small owing to very few preterm infants could obtain both 1- and 7-day specimens. But this study is still going on. More data will be reported at a later stage. Second, conclusions might not be extended to other populations, and only applies to infants with high incidence of BPD, such as low gestational age at birth, low birth weight, infectious diseases, etc. Third, the data provide no evidence that the airway microbiome directly causes BPD. This is just a prospective observational cohort study, in the near future validation experiments will be carried out. In addition to these, nearly all of the infants in the study were treated with antibiotics for more than 7 days. Only one infant was treated with antibiotics for 5 days. Therefore, the effect of antibiotics on the enrolled infants may be the same at the first week of life. While there was difference over the total number of days of antibiotic use, the effects of antibiotics were likely small during the study period.Stenotrophomonas, and increased level of sn-glycerol 3-phosphoethanolamine might have potential as biomarkers for BPD. The occurrence and severity of BPD are closely related to Stenotrophomonas, which might influence the composition of the lower airway microbiome through its metabolite sn-glycerol 3-phosphoethanolamine, and might be the triggering factor of the disease. The causal relationship needs further study.Decreased diversity of the airway microbiome, increased abundance of http://www.ncbi.nlm.nih.gov/sra/, PRJNA800242).Sequence data presented in the study are publicly available. This data can be found here: (The study involving human participants was reviewed and approved by the Institutional Review Board of Chongqing Medical University. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.QX and JY conceived and designed the study, collected the data, drafted the initial manuscript, and reviewed and revised the manuscript. DL designed the data collection instruments, collected data, carried out the initial analyses, and reviewed and revised the manuscript. QT and YH conceived and designed the study, coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


To understand the role of exposure to skin-to-skin contact and its minimum duration in determining exclusive breastfeeding at hospital discharge in infants weighing up to 1,800g at birth.A multicenter cohort study was carried out in five Brazilian neonatal units. Infants weighing ≤ 1,800g at birth were eligible. Skin-to-skin contact time was recorded by the health care team and parents on an individual chart. Maternal and infant data was obtained from maternal questionnaires and medical records. The Classification Tree, a machine learning method, was used for data analysis; the tree growth algorithm, using statistical tests, partitions the dataset into mutually exclusive subsets that best describe the response variable and calculates appropriate cut-off points for continuous variables, thus generating an efficient explanatory model for the outcome under study.versus 46%). In this group, those who received a severity score (SNAPPE-II) equal to zero increased their chances of breastfeeding (83% versus 63%).A total of 388 infants participated in the study, with a median of 31.6 (IQR = 29–31.8) weeks of gestation age and birth weight of 1,429g . The exclusive breastfeeding rate at discharge was 61.6%. For infant’s weighting between 1,125g and 1,655g, exposed to skin-to-skin contact was strongly associated with exclusive breastfeeding. Moreover, infants who made an average > 149.6 min/day of skin-to-skin contact had higher chances in this outcome (74% Skin-to-skin contact proved to be of great relevance in maintaining exclusive breastfeeding at hospital discharge for preterm infants weighing 1,125g–1,655g at birth, especially in those with lower severity scores. This separation can also harm interaction relationships that would be built in this sensitive and critical period after birth, when the first suckling at the breast should occur 3 .Premature birth can compromise the breastfeeding process due to the biological immaturity of the preterm infant and the mother-child separation due to the need for neonatal hospitalization 4 . Contact with the mother, her touch and speech promote breastfeeding 6 , stimulate lactation, and the progression of the sucking behavior in both full-term 6 and preterm infants 7 .Seeking to minimize the negative effects of mother-child separation, early skin-to-skin contact (SSC) is recommended during hospitalization in the neonatal unit, which consists of placing the infant in an upright position, wearing only diapers, on the mother’s chest 4 , since evidence shows that this practice promotes breastfeeding, reduces hypothermia, neonatal mortality, sepsis, and hospital stay length in preterm infants and/or newborns with low birth weight 12 . Furthermore, SSC is associated with greater emotional regulation, and better cognitive and motor development in the first year of life for these infants 13 .The World Health Organization recommends the use of SSC as a routine to care for infants 15 . Two meta-analysis studies investigated cut-off points for SSC time in neonatal outcomes and presented the failure to determine the minimum time needed to observe these associations as a limitation 12 .However, despite the association between SSC and exclusive breastfeeding (EBF) at hospital discharge being well established in the literature, how this kind of care fits into a broader explanatory framework, composed of other important elements in determining this outcome, is unclear. The literature also shows conflicting results regarding the length of SSC needed for the positive effects on breastfeeding Thus, our study aimed to understand the role of skin-to-skin contact in determining EBF at hospital discharge in infants weighing up to 1800 g at birth and investigated the minimum time required for this possible protective effect to appear. The answer to this question is extremely important to contribute to the health policies that support breastfeeding, providing a better quality of life for these infants, especially in low- and middle-income countries.This prospective cohort study is part of a multicenter research entitled “Effect of exposure time to SSC on clinical outcomes in low-birth-weight infants”. Five Brazilian neonatal units – considered references in Brazil for the Kangaroo Method – participated in this research, two from the Northeast, two from the Southeast, and one from the South of the country. The study was conducted from May 2018 to March 2020 after approval by ethics committee – Certificate of Presentation of Ethical Appreciation (CAAE Nº. 83803817.0.1001.5086). All parents who participated in the research signed the informed consent form.All live births in these institutions during the study period that met the following criteria were considered eligible: single delivery, birth weight up to 1,800g, and no malformations, severe perinatal asphyxia and/or genetic syndromes. The sample flowchart shows non-inclusion and exclusion criteria, as well as losses   .The definition of a cut-off point of ≤ 1,800g considered a pilot study that showed that infants with higher weights spent less time in the neonatal units, which could interfere with the observation of the effect of SSC on the outcome under study.For this research, the minimum sample size was set at 357 dyads. This was based on a pilot study that considered a 0.6 exposed/unexposed ratio and a 23% risk difference. A bilateral significance level of 95%, power of 99%, and type I error of 5% were considered.Maternal and infant variables were collected by using questionnaires applied to mothers, and completed with data from medical records, during the period of hospitalization of the neonate. The SSC was registered on cards attached to the bedside and filled out by the health team during the infant’s hospital stay. Parents were trained and encouraged to also register under the supervision of the health team. When the infant went to the SSC, the time the contact started, the time it ended, and who performed it (father or mother) were recorded. This procedure was performed at each new SSC during hospitalization.The SSC records were checked daily by previously trained research assistants, who encouraged parents and health professionals to continue the records and consolidated the total daily SSC time in a specific form.Variables related to maternal and infant characteristics and SSC time were collected to be included in the theoretical model, built from literature data, as follows:at hospital discharge .Main outcome: EBF time of exposure to SSC per day , calculated by dividing the total time of SSC practiced during hospitalization, in minutes, by the number of days on which this contact was made.Exposure variable: Explanatory variables relative to the mothers: Age ; Education level ; Marital status (with partner or without partner); Specific hypertensive gestation syndrome (SGHS); Use of alcohol during pregnancy (yes or no); Infection during pregnancy (yes or no); Type of delivery ; Use of corticosteroids before delivery (yes or no); Adequacy of prenatal care , considered adequate the prenatal care beginning until the 4th month of gestation and six or more consultations performed for a full-term pregnancy or a smaller number according to the gestational age at delivery .16 ; Score for Neonatal Acute Physiology – Perinatal Extension II (SNAPPE II), scored from 0 to 162 17 ; Early infection (within the first 48 hours of life of the infant); Late infection (> 48 hours of life of the infant); Time to perform the first SSC during hospitalization (in days).Explanatory variables relative to the infants: Birth weight in grams; Apgar score at the 5th minute of life; Gestational age (GA) at birth in weeks, calculated by the date of last menstrual period or first trimester ultrasound or the New Ballard score; Adequacy of weight for gestational age, categorized as adequate, small, or large for gestational age, according to Intergrowth 21 classification ® instrument and then exported to a Microsoft Office Excel ® , version 2016.The collected data was tabulated in a Google Form Quantitative data were represented by mean and standard deviation or medians and interquartile ranges, depending on distribution and normality criteria and categorical variables were presented as frequencies and percentages. To calculate the statistical difference between the variables GA and birthweight of the study sample and losses to follow-up, the Mann-Whitney test was used, which compares two independent means when impossible to assume the normal distribution of these variables.18 . The dependent variable used was “EBF at discharge”, considered the “root node”, and, from the set of predictor variables, the descendant nodes were selected and identified, by logical tests, until these nodes stopped dividing, ending this growth in “terminal nodes”. When analyzing continuous variables, the CT algorithm itself determined the most statistically appropriate cut-off points. Chi-Square Automatic Interaction Detection (CHAID) method was used to grow the tree 19 . The method maximized the significance of the chi-square statistic in each partition, which characterized CHAID as a structure of tests of significance. Due to the successive comparison tests applied in this technique, a correction factor for Bonferroni inequality was calculated by the CT algorithm, to obtain an adjusted level of significance. Thus, evaluating the entry of each variable in the model and verifying whether its contribution was significant or not among the predictor variables was possible. In summary, the CT, partitioned the dataset into mutually exclusive subsets that best described the response variable, exhaustively, using machine learning for this. The statistical package Stata ® 14.0 was used for the descriptive analysis and the IBM SPS Statistic ® for the CT.For the statistical analysis, the Classification Tree (CT) was used, a non-parametric method based on machine learning  capable of building data prediction models. The CT created an algorithm to identify the most important variables in the data set of the theoretical model and to develop an efficient explanatory model for the outcome under study We analyzed 388 infants   , with aversus 31.4 ± 2.6 weeks; p = 0.068) and birth weight .We lost follow-up of 181 of the infants (23.9%)   . HoweveThe variables and their most relevant cut-off points were birth weight , SSC time (> 149.6 min/day), and SNAPPE-II severity score (= 0). The first variable associated with EBF at the classification tree was birth weight. Infants over 1,665g at birth had an 85.7% chance of EBF at discharge. In those with a weight range between 1,125g and 1,655g who underwent SSC for more than 149.6 minutes/day, the chance of EBF at discharge increased from 61.1% to 74.4% compared with the group with shorter times of practice. The group that had longer SSC time and zero severity score at admission also obtained an 83.6% probability for EBF   .versus 63%).The SSC duration greater than 149.6 minutes/day (around 2 hours and 30 minutes) showed a strong association with EBF at hospital discharge in newborns with birth weight between 1,125g and 1,655g. Also, those who performed longer SSC/day and who scored zero SNAPPE-II at admission had a greater chance of this outcome  by constructing the CT, which considered the contribution of several maternal and neonatal variables used in the theoretical model of this study.Birth weight was the variable that best explained the outcome (EBF at discharge), being the most relevant to determine it. The CT algorithm subdivided the variable into three weight categories: < 1,125g (node 1), 1,125g – 1,665g (node 2), and > 1,665g (node 3). Nodes 1 and 3 are terminal, while node 2 was influenced by two other variables that increase the chances of EBF at discharge.Node 2 represents more than 60% of the studied sample, which comprises an intermediate birthweight category  and the chance of EBF at discharge among these infants was 61.1%. At this point, the CT creates a new subdivision introducing the SSC exposure time as a new explanatory and modifying factor for this probability. The algorithm establishes a cut-off point of 149.6 minutes , which created two new categories (nodes 4 and 5). Those who practiced more SSC/day showed a positive effect compared with those with less time. We observed the highest possibility of discharge with EBF (74%) in those who underwent SSC for more than 149.6 min/day (node 5), which represents an increase of 13.3 percentage points in the EBF rate for this intermediate weight range.23 .This denotes a clear influence of the time of SSC in the results of breastfeeding in this birth weight range. These results are even more relevant considering this weight range tends to be the most prevalent among preterm infants admitted to the NICU. This probability of EBF at discharge was also higher than the highest rate found (51.5%) in countries in various regions of Europe, in very preterm infants, where the practice of SSC varies greatly 24 . The SSC cut-off point of 149.6 min/day observed in our study was specifically associated with EBF (the gold standard of infant nutrition) 14 , which can directly contribute to their greater survival and better neurodevelopment after hospital discharge.The literature confirms the association between longer SSC times and greater chances of EBF at discharge. A similar study in Sweden found an association between preterm infants that had over 139 min/day of SSC with any form of breastfeeding (exclusive or supplemented with a formula) until the first month of corrected age 17 . Thus, we expected that infants with lower severity rates would be more likely to maintain breastfeeding. However, regardless of severity score, infants who performed longer SSC received a significant positive effect on EBF at discharge (increase to 74.4% compared to the previous node of 61.1%).In the explanatory graphic model of EBF determinants at discharge from the NICU, CT creates yet another subdivision among those infants with a longer SSC time (> 149.6 min), which is another factor that can influence this outcome: the SNAPPE-II score (infant severity index at admission). For the creation of these nodes (6 and 7), the cut-off point found by the CT algorithm was SNAPPE-II = 0. This means that the chances of breastfeeding increased from 74.4% in the previous node to 86.6% for those infants who received a score of zero. SNAPPE-II is a useful tool to assess the severity of infant’s illness and its correlation with neonatal mortality 16 . Each of these nodes also represents only 19.8% of the study sample. We observed the highest chance of discharge with EBF (85.7%) in the birth weight range greater than 1,655 g (node 3), which agrees with the literature. Late-preterm infants (34–36 weeks) are subject to less severe morbidities, such as mild breathing difficulties, hyperbilirubinemia, and hypoglycemia 10 , which increases the chances of positive results, such as maintaining EBF at discharge.Nodes 1 and 3 of CT represent weight ranges that comprise, in a greater proportion, extreme-preterm infants  and late-preterm infants , respectively 15 . Late-preterm infants are not subject to the same challenges as very preterm infants, such as longer hospital stays and greater difficulties in initiating and maintaining breast suction coordination 2 .A recent meta-analysis with a sample composed of late-preterm infants with an average weight of 2,312g (in the group using SSC) and 2,300g (in the control group) observed no statistically significant difference in breastfeeding rates at hospital discharge 16 , which can lead to additional complications such as intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, retinopathy of prematurity, among others, and can lead to the future development of neurobehavioral disorders 25 , thus reducing chances of maintaining EBF at discharge. However, the practice of SSC should be encouraged for this weight range since it can contribute to any form of breastfeeding at discharge for these extreme preterm infants, as a study of infants with less than 29 weeks of gestational age observed 9 .Node 1  is at the other end of these categories. Infants in this category had a chance of EBF at discharge of only 39%. This weight range is correlated with extreme prematurity In summary, the CT outlines a scenario in which the chances of EBF are maximized in two situations: infants weighing more than 1,655g at birth  and infants with birth weight between 1,125g and 1,655g  and who underwent more than 149.6 min/day of SSC. In the latter situation, the probability of EBF also increased for those with a null severity score at admission.26 . The scenario outlined in this study denotes that the use of SSC, especially if the daily average is greater than 149.6 minutes, is extremely relevant and can maximize the chances of EBF at discharge in most preterm infants admitted to the NICU.The EBF contributes to a better neuro-psychomotor development and better quality of life for these infants, especially if extended to the sixth month of corrected age or as long as possible As a limitation of the study, the absence of follow-up after hospital discharge stands out, at which time the maintenance of EBF becomes more challenging and tends to decrease over the months. Research in this regard is still needed. Another limitation was the loss of follow-up of 23.9% of the infants. However, this group of infants showed no statistical difference when compared with the sample group studied regarding the variables GA and birth weight.The participation of units from institutions in three different regions of the country is a positive point of the work. The prospective data collection and the choice of a method that allowed us to observe the cut-off point of the duration of this practice associated with the outcome in question are strengths of the study. We could create an explanatory model for the practice of EBF at the time of discharge from the neonatal unit, adjusted by several explanatory variables, and situate the practice of SSC in this context.This study reinforces SSC as a good neonatal care practice that contributes to increasing the chances of positive results in infants up to 1,800g at birth who need intensive care. We recommend a contact duration greater than 149.6 minutes/day to maximize the chances of a positive effect on EBF, especially among infants with birth weight of 1,125g to 1,655g admitted to the neonatal unit.


To define and analyze the concept of psychological birth trauma.The concept analysis method of Walker and Avant was used.Eight databases  were searched from inception to July 2022 for studies focused on psychological birth trauma.Of the 5,372 studies identified, 44 ultimately met the inclusion criteria. The attributes identified were (1) women’s subjective feelings, (2) intertwined painful emotional experiences, (3) originating in the birth process, and (4) lasting until postpartum. Antecedents were divided into two groups: pre-existing antecedents and birth-related antecedents. Consequences were identified as negative and positive.Psychological birth trauma is a more complex and comprehensive concept than previously thought, and should be regarded as a separate postpartum mental health problem. This study deepens the understanding of psychological birth trauma through a comprehensive concept analysis and also puts forward some suggestions for the prevention, identification, and intervention of psychological birth trauma, which provides a basis for assisting in the identification of psychological birth trauma and provides a reference for the development of rigorous assessment tools and the design of appropriate interventions in the future. Further research is needed to update and refine this concept. Childbirth, a major event in a woman’s life, is of a profound and complex nature . Not onlSome studies have focused on investigating the risk factors of psychological birth trauma, and multiple factors have been found, including some objective factors, such as preterm delivery , as wellRegrettably, not enough attention has been paid to the psychological birth trauma itself, and more attention seems to be focused on the diagnosable postpartum psychological problems, such as postpartum PTSD mentioned above. An international knowledge mapping exercise aimed at examining policies, services, and training provisions for women following traumatic birth showed that of the 18 European countries that participated, only the Netherlands has national policies on screening, treatment, and prevention of traumatic birth experiences . Adding A clear concept is the first key step to fully understanding this phenomenon and the basis for theoretical development . TherefoConcept analysis is a systematic process of developing, clarifying, and refining the phenomenon under analysis . This stA comprehensive search of PubMed, CINAHL Complete, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, VIP Information Chinese Journal Service Platform, and Chinese BioMedicine Literature Database was conducted from inception to July 2022. The following medical subject heading (MeSH) terms and text words were used: “traumatic childbirth,” “traumatic birth,” “traumatic labor,” “traumatic delivery,” “childbirth trauma,” “birth trauma,” “labor trauma,” “labor trauma,” “delivery trauma,” “psychological trauma” AND . The search was limited to studies published in English or Chinese. Specific details of the retrieval strategy are shown in Studies that explicitly investigated or discussed psychological trauma following birth from the perspective of postpartum women were included in this concept analysis. The following studies would be excluded: (1) investigating the intervention effects of certain measures on psychological birth trauma; (2) examining physical birth trauma only; (3) only exploring psychological trauma of bystanders during the birthing process, primarily women’s partners and healthcare professionals; (4) only testing the reliability and validity of the scale. Furthermore, to improve the precision of the concept of psychological birth trauma, we excluded studies that aimed to explore postpartum PTSD and its similar themes, including postpartum post-traumatic stress symptoms and post-traumatic stress. Studies on broader topics such as negative birth experiences were also excluded.n = 25) were the most, followed by quantitative studies (n = 9), and the remaining included systematic reviews (n = 5), mixed methods study (n = 1), scope review (n = 1), concept analysis (n = 1), discussion paper (n = 1), and middle range theory (n = 1).A total of 5,372 studies were identified, then 1,675 duplicated studies were excluded. After screening the titles and abstracts of the remaining studies, 3,558 studies were further excluded. After reading the full texts of 139 studies, 95 studies were excluded for a variety of reasons. Finally, a total of 44 studies were included in the concept analysis. The search process is presented in Defining attributes can be used to identify, understand, and differentiate a concept from other concepts . Analysi(1)Women’s subjective feelings;(2)Intertwined painful emotional experiences;(3)Originate in the birth process;(4)Last until postpartum.Women’s perception of psychological birth trauma is highly subjective . Each biFaced with an unfamiliar environment and care providers, as well as an unknown birth process, women don’t know if an event will occur that threatens their own or their baby’s safety, which makes them fearful and anxious .During birth, women have to bear severe labor pain and face all the actual or potential risks, they do not know what to do, and the cruel reality makes them feel helpless or even despairing .Women feel verbally and physically abused and discriminated against by care providers and their privacy is violated, which deprives them of their dignity .Women feel that they are not receiving adequate communication, explanation, emotional and practical support, and attention, they lose the power to express their thoughts and feelings as if they are a machine rather than a human, which makes them feel neglected and abandoned .Women feel deprived of decision-making and informed consent, their birth process is completely in the hands of care providers, and reality is not moving toward their expectations, which makes them feel out of control .Childbirth is a complex process involving medical acts and during which events that endanger the safety of the mother and baby may occur, which can be traumatic for women, especially when they believe that these events could have been avoided . In addiPersistence is a key attribute of psychological birth trauma . HoweverA model case is designed to demonstrate all defining attributes of the concept . The modMrs. M has been having regular uterine contractions for over 5 h. A midwife asked Mrs. M to take off the pants and she would do a vaginal examination to determine the extent of cervical dilation. At this time, several students suddenly entered the room. Mrs. M tried to cover her bottom with her gown, but a midwife took her hand away from the gown. The students also performed vaginal examinations without Mrs. M’s permission, and no explanation was given afterward. Mrs. M immediately recalled the scene of being sexually assaulted when she was a child. She felt that she had been raped again, which brought her overwhelming pain. Everything seemed to be normal during the whole birth process, and finally, Mrs. M gave birth to the baby successfully, which made the midwife satisfied. All the family members surrounded the baby, leaving Mrs. M in bed alone, no one asked how she was feeling. In the days that followed, Mrs. M still felt very distressed. She was reluctant to interact with her husband and baby, refused to breastfeed, and did not trust medical staff. When the child was 3 years old, Mrs. M became pregnant again. During the pregnancy, she was surrounded by fear that this birth would repeat the previous one, and she visited a psychotherapist several times.The authors constructed the borderline case to provide an example that embraces most of the attributes of psychological birth trauma. Mrs. N longed for a vaginal delivery and believed she could do it. Unfortunately, signs of fetal distress appeared at the beginning of the first stage of labor. Doctors told her that the prolonged labor process was dangerous to the fetus and that a cesarean section was needed as soon as possible. Mrs. N had never thought about a cesarean section, she was very scared. The doctor and midwife patiently explained to her again and gave her support and encouragement, which made Mrs. N relax. Subsequently, Mrs. N underwent an emergency cesarean section, and both mother and baby were safe. Although failed to achieve delivery vaginally as expected, Mrs. N was satisfied with the outcomes. When looking back on her birth experience, she feels supported by the healthcare providers and that she was doing the right thing.Antecedents are those events or incidents that must occur before or be in place prior to the occurrence of the concept . Hence, Birth-related antecedents are key contributors to the occurrence of psychological birth trauma. These include obstetric factors and factors related to healthcare professionals. Specifically, obstetric factors encompass severe pain or physical discomfort , long duConsequences are those events or incidents that appear as results of the concept . Thus, iSecondly, psychological birth trauma leads to changes in the mother’s roles. Several studies reported negative mother-infant interactions, with women expressing feelings of disengagement or feeble attachment to their children , and feeThirdly, psychological birth trauma affects the subsequent reproductive decisions, experiences, and coping behaviors. Women who have experienced psychological birth trauma are often fearful of future pregnancies , and somFourthly, psychological birth trauma leads to more health services utilization. Women with psychological birth trauma have longer postpartum hospital stays . In addiWhile most of the consequences of psychological birth trauma found in the literature are negative, it can also have positive outcomes. One study explored how women who have experienced psychological birth trauma rely on external and internal resources to move toward resilience . MoreoveAccording to The Traumatic Childbirth Perception Scale (STCP)  was deveThe Psychological Birth Trauma Questionnaire (QPBT)  was deveNotably, these two scales have not been used in studies in other countries, their English versions have not been identified yet.Based on an analysis of the literature, the concept of psychological birth trauma is clearly defined as follows:Psychological birth trauma refers to the woman’s subjective feeling caused by events directly or indirectly related to childbirth, which is manifested as intertwined painful emotional experiences that originate in the birth process and last until postpartum. It has a wide range of negative and, in some cases, positive effects on women. The conceptual model including the antecedents, attributes, and consequences of psychological birth trauma is shown in Based on a systematic search of the literature and the method of Antecedents in this concept analysis suggest that women in childbirth are vulnerable to a range of pre-existing factors that may contribute to psychological trauma. Identification of these factors, including demographic characteristics, personality traits, and medical and trauma experiences can help healthcare professionals to be more vigilant and thus aid in prevention. However, the prevention of birth-related antecedents appears to be more promising. The first is to emphasize professional management of labor, such as avoiding unnecessary medical intervention, adequately relieving labor pain, and improving medical clinical competence to reduce maternal and neonatal complications. In addition, obstetric management should aim to reduce psychological birth trauma, including creating a comfortable environment and allowing the woman’s partner to accompany her during birth, etc. Furthermore, it is imperative to improve the quality of women’s interactions with healthcare professionals during birth, which may be achieved by adequately communicating and explaining what happens, listening to women, and seeking to meet their expectations. Notably, further studies are needed to systematically assess these antecedents and to determine their magnitude and interrelationships.After examining the consequences of included studies, this concept analysis identified the profound negative effects of psychological birth trauma on women, including poor mental health, poor role of the mother, subsequent reproductive challenges, and increased health services utilization. Therefore, early identification and intervention of these women is crucial. In terms of identification, during the postpartum hospital stay, healthcare professionals are advised to be wary of symptoms that may indicate a woman has suffered psychological birth trauma, such as a dazed appearance, withdrawal, temporary amnesia, and detachment from the baby . If a moFurthermore, a limited number of studies have discussed interventions to reduce the negative effects of psychological birth trauma. A recent systematic review examined interventions to prevent women with recent traumatic birth from developing postpartum PTSD, including debriefing, encouraging skin-to-skin contact with healthy babies directly postpartum, structured psychological interventions, expressive writing, and seeing or holding the baby after stillbirth . The resReassuringly, this concept analysis found that while some women experienced some negative effects of psychological birth trauma, they gained some positive aspects that had not been mentioned in previous related concepts. Studies showed that some mothers who have experienced psychological birth trauma build resilience by using both external resources (such as faith and supportive relationships) and internal resources (such as recognizing the power of their own motherhood) . And, soSome limitations exist in this concept analysis. Firstly, studies were limited to English or Chinese, which restricts the scope of the review. Secondly, the studies included in this concept analysis were mostly qualitative, and quantitative studies were lacking due to the lack of widely validated tools for assessing psychological birth trauma. Thirdly, we excluded studies on postpartum PTSD, postpartum post-traumatic stress symptoms, postpartum post-traumatic stress, and negative birth experiences, which may contain content related to psychological birth trauma. Finally, we excluded studies that explored the feelings of bystanders  who may also experience psychological trauma as a result of witnessing the birth process. We, therefore, recognize that this definition may be subject to further development and adjustment.This concept analysis provides a comprehensive insight into psychological birth trauma, which is a more complex and comprehensive phenomenon than previously thought and should be considered as a separate postpartum mental health problem. Given the high incidence and far-reaching effects of psychological birth trauma, its prevention, identification and intervention are crucial, but relevant studies are insufficient and need to be further explored. This study provides a starting point for future theory and research, and provides researchers and healthcare professionals with information that can serve as the foundation for assisting in the identification of psychological birth trauma, and as the reference for developing rigorous assessment tools as well as designing appropriate interventions. In addition, further research is needed to expand the definition of psychological birth trauma from the perspective of bystanders during birth. We expect that this concept will continue to be updated and refined as knowledge on the subject develops.XS, XF, SC, RW, LS, HX, JH, ZZ, and AZ designed the study, critically revised the manuscript, and approved the final version. XS and XF conducted the literature retrieval, literature selection, data extraction, data analysis, and drafted the manuscript. All authors contributed to the article and approved the submitted version.


Placement of a levonorgestrel-releasing intrauterine system (LNG-IUS) is an effective treatment for adenomyosis, especially for patients who have severe dysmenorrhea symptoms but a strong desire to preserve fertility. Nonetheless, for patients with adenomyosis accompanied by an enlarged uterus, expulsion of the ring is a troublesome problem. In this study, we sewed and fixed the LNG-IUS in the uterus, which provides a good solution to this problem.In this prospective case series approved by the Ethics Committee of Hangzhou Women’s Hospital, 12 patients with adenomyosis were successfully enrolled after providing informed consent, and all patients underwent long-term postoperative follow-up.Twelve patients with adenomyosis underwent suture fixation with an LNG-IUS, and during the long-term postoperative follow-up, every patient experienced complete remission of their symptoms: a significant decrease in menstrual flow, relief of dysmenorrhea, and improvement in quality of life. Only one person reported expulsion a year later.In patients with adenomyosis suffering from dysmenorrhea or excessive menstrual blood loss, suture fixation of an LNG-IUS using the hysteroscopic cold knife surgery system is a minimally invasive and effective alternative treatment for adenomyosis and decreases the risk of LNG-IUS expulsion. Adenomyosis is a heterogeneous gynecologic condition with a range of clinical symptoms, the most common being heavy menstrual bleeding and dysmenorrhea. At present, total hysterectomy is considered the most effective treatment for uterine adenomyosis . HoweverTo address this problem, in our study, we proactively performed suture fixation of the LNG-IUS in the uterine cavity by using the hysteroscopic cold knife surgery system (HCSS).Inclusion criteria: (a) had menorrhagia or dysmenorrhea and met the diagnosis of "adenomyosis"; (b) had a strong desire to preserve the uterus; and c) had no fertility requirements in the short term.Preferred criteria: (a) enlarged uterus; (b) history of expulsion.Exclusion criteria: (a) contraindications to use of the LNG-IUS; (b) contraindications to hysteroscopic surgery; (c) other diseases of the reproductive tract ; (d) severe heart, lung, liver, and kidney insufficiency; (e) had received gonadotropin-releasing hormone a (GnRG-a) treatment within the previous 6 months; and (f) reluctance to participate in this study.The study was approved by the Ethics Committee of Hangzhou Women’s Hospital and started in January 2021. Twelve patients with adenomyosis have providing informed consent and been successfully enrolled thus far.The materials used in this study included the following: the levonorgestrel-releasing intrauterine system , hysteroscopic cold knife surgery system , endoscopic scissors, endoscopic needle holder, and the STRA TAFIXTM Spiral PGA-PCL .Under general anesthesia with the patient lying in the lithotomy position, hysteroscopy was performed using the HCSS . The HCSS is equipped with a diameter of 4 mm working channel, hysteroscopic surgical instruments such as scissors and grasping forceps can be inserted through it. We first assessed the uterine cavity morphology and endometrial condition. If polyps, endometrial thickening, intrauterine adhesions, etc., were found, corresponding treatments were performed first. If no abnormality was found, the appropriate amount of endometrial tissue was scraped off to create a good suture fixation environment that was clearly visible. We then fixed the intersection of the arms of the LNG-IUS in the circle at the tail of the STRA TAFIXTM Spiral PGA-PCL Fig.  and sutuPictorial Blood Loss Assessment Chart (PBAC)Blood loss was assessed according to the degree of blood staining on each sanitary napkin as follows: Mild: blood-stained area ≤ 1/3 of the entire sanitary napkin area; Moderate: blood-stained area occupies 1/3–3/5 of the entire sanitary napkin area; Severe: the blood-stained area is basically the entire sanitary napkin. The corresponding scores were 1, 5, and 20 points, respectively. In addition, blood clots smaller than a coin were given 1 point, while larger ones were given 5 points. The total score was calculated based on the score of each sanitary napkin and the numbers. A total score of 100 or more was considered to be menorrhagia.Visual Analog Scale (VAS)The degree of dysmenorrhea was assessed as follows: no pain (0 points), mild pain (1–3 points), moderate pain (4–6 points), and severe pain (7–10 points).Nottingham Health Profile (NHP)The NHP scale was used to evaluate the quality of life of patients and has good reliability. It provides a brief indication of a patient's perceived emotional, social, and physical health . It is fThe status of the LNG-IUS was evaluated by TVS. Menstrual flow was quantified with a pictorial blood assessment chart (PBAC), and the degree of dysmenorrhea was evaluated on a 100 mm visual analog scale (VAS). Both the PBAC scores and the VAS scores were recorded before and 1, 3, and 6 months after insertion of the LNG-IUS. Adverse reactions to the LNG-IUD were recorded in the medical records, including menstrual pattern changes, abdominal discomfort, abnormal vaginal discharge, and climacteric symptoms.In this study, twelve patients received LNG-IUS suture fixation, and all had symptoms of dysmenorrhea (4/12), excessive menstrual flow (3/12), or both (5/12). The depth of their uterine cavity was greater than 9 cm, with an average of 9.79 cm. Three patients had a history of expulsion, with an average time of expulsion of approximately one month after placement.After suture fixation of the levonorgestrel-releasing intrauterine system, when patients come for follow-up, we ask them about remission of symptoms and monitor the position of the LNG-IUS through ultrasound. The following three pictures vividly demonstrate the changes in menstrual flow, dysmenorrhea, and quality of life after surgery.As seen, the PBAC scores Fig.  and the Unfortunately, during follow-up, a patient experienced expulsion of the LNG-IUS after twelve months. Two other patients also exhibited a downward shift in the position of the LNG-IUS in the uterus on ultrasound; one occurred in the fourth month after the operation, and the other occurred in the sixteenth month. After identifying the problem, we thoroughly analyzed it and developed an improvement plan, which will be explained in detail in the follow-up discussion.Adenomyosis is a common gynecological disorder characterized by invasion of endometrial glands and stroma into the myometrium, which results clinically in abnormal uterine bleeding, pelvic pain, and infertility . Long-teHowever, high rates of LNG-IUS expulsion may be a deterrent to patients who have discontinued treatment of adenomyosis, especially those with a large uterus volume (> 150 mL) . A prospSome studies have confirmed that pretreatment with gonadotropin-releasing hormone analog (GnRHa) is beneficial to a certain extent in reducing the size of the uterus , 15, 16,To date, few studies have reported the role of LNG-IUS fixation. Currently on the market, there is Gynefix, which is specially designed to prevent the expulsion of IUDs, but Gynefix itself does not have a drug treatment effect comparable to that of Mirena and cannot replace Mirena at this point. It was asked whether the Mirena could be designed in the style of Gynefix to better address this problem. Practically, the idea is feasible, but due to the patent restrictions of the Mirena R&D company, the advancement of this design is nowhere in sight. Therefore, in our study, we proactively performed suture fixation of the LNG-IUS in the uterine cavity by using the hysteroscopic cold knife surgery system (HCSS), and satisfactory results were obtained. The symptom relief of patients with adenomyosis is similar to that in most prospective and retrospective studies. Notably, the incidence of expulsion of the LNG-IUS during our follow-up observation period was extremely low (1/12).We stitched the LNG-IUS on the posterior wall of the uterus and fixed it; theoretically, it was firmly fixed and could not be expelled. However, as stated in our results, one patient expelled the LNG-IUS after twelve months of follow-up, and two other patients showed a downward shift of the LNG-IUS in the uterus. The suture material used in this trial was polydioxone (PDO), which usually takes approximately 180–240 days to be absorbed . Given tTherefore, we made some adjustments involving replacement of the original absorbable thread with a nonabsorbable surgical suture  and improved the method of fixation. First, the nonabsorbable suture was tied to the arms and stem of the LNG-IUS. After the suture was fixed on the wall of the uterus, the suture was pulled to send the LNG-IUS into the uterus, and the knot was tied outside. Finally, the knot pushing device was used to push and fix the knot tightly Fig. . This imThe improved fixation of the LNG-IUS not only solves the previous problem of expulsion due to suture absorption but also achieves an ideal expulsion rate of zero. To date, we have completed more than 70 cases of suture fixation of the LNG-IUS with this improved approach. The patient group is being followed up, with the longest follow-up time being 10 months, and no expulsion has occurred. This improved approach simplifies the process of suturing and knotting in the uterus and involves a better method of knotting in vitro. On the one hand, the operation time is greatly shortened; on the other hand, the method involving knotting outside the body avoids repeatedly entering and leaving the uterus and reduces the risk of intrauterine infection. In addition, this improved approach greatly reduces the difficulty of the operation, and it is easy for clinicians to get started. Currently, our surgical team completes a case of suture fixation of the LNG-IUS in an average of 10 to 15 min, which is equivalent to completing a simple endometrial polypectomy. The operation cost is equivalent to that of an ordinary hysteroscopic surgery and placement of an IUD, and there is no additional operation cost. More generally, suture fixation of the LNG-IUS is the only surgical technique that truly achieves fixation thus far at home or abroad. With the improvements made by our team, the operation is simplified and easy to implement widely, and the cost is reasonable. Compared with patients who experience multiple expulsions and then require replacement of the Mirena multiple times, patients treated with our method benefit from a simple hysteroscopic operation for at least 5 years , which not only saves the economic cost of multiple purchases of Mirena devices but also alleviates patient worry about the incidence of expulsion, so that the vast number of patients with adenomyosis are no longer in deep pain.Our project is a case series about a new technique and has several limitations. First, this was a noncomparative prospective study. The number of cases included is relatively small, and the number of evaluation indicators could be further increased to include metrics such as changes in hemoglobin, CA125, uterine size, and so on. However, satisfactory results have been achieved in stages, and patients who have experienced expulsion have also received LNG-IUS fixation with the new suture fixation. We will continue to improve this innovative surgical method. A more perfect and rigorous RCT  is underway to evaluate the efficacy of LNG-IUS fixation, aiming to solve the problem of LNG-IUD expulsion.Suture fixation of the levonorgestrel-releasing intrauterine system better addresses the drawbacks of expulsion through a minimally invasive operation. At the same time, similar to normal placement of an LNG-IUS, it effectively relieves the dysmenorrhea and heavy bleeding symptoms of adenomyosis.


Preterm birth is associated with smaller body dimensions at birth. The impact on body size in later life, measured by body mass index (BMI) and height, remains unclear. A prospective register-based cohort study with 62,625 singletons from the Danish National Birth Cohort born 1996–2003 for whom information on gestational age (GA) at birth, length or weight at birth, and at least two growth measurements scheduled at the ages of 5 and 12 months, and 7, 11 and 18 years were available. Linear mixed effects with splines, stratified by sex, and adjusted for confounders were used to estimate standardised BMI and height. GA was positively associated with BMI in infancy, but differences between preterm and term children declined with age. By age 7, preterm children had slightly lower BMI than term children, whereas no difference was observed by adolescence (mean difference in BMI z-score − 0.28 to 0.15). GA was strongly associated with height in infancy, but mean differences between individuals born preterm and term declined during childhood. By adolescence, the most preterm individuals remained shorter than their term peers (mean difference in height z-score from − 1.00 to − 0.28). The lower BMI in preterm infants relative to term infants equalizes during childhood, such that by adolescence there is no clear difference. Height is strongly positively associated with GA in early childhood, whilst by end of adolescence individuals born preterm remain slightly shorter than term peers. Much literature has demonstrated that birth weight associates with postnatal body mass index (BMI) with positive linear J and U-shaped associations reported8. Birth weight is strongly related to gestational age at birth (GA)9, but the extent to which the association between birth weight and later BMI reflects differences in GA is unclear10.Exposures during fetal life may influence postnatal growth and cardio-metabolic health20 and reported positive associations in childhood21, while findings are mixed in adulthood22. However, wide variations in study design, mode of data collection, and use of covariates in the studies making it difficult to evaluate the evidence23. Some studies assessed gestational duration as a dichotomous variable reporting all preterm children in same exposure group24, while others compared growth of extremely preterm with term, which may hide important differences by degree of preterm3. We identified only two previous publications that reported associations with BMI and height for subgroups of preterm and term born children25.Some studies have investigated the associations between GA and BMI and, respectively, height26.In addition, majority of studies have examined the association without repeat measurements of BMI or height; hence, evidence on the longitudinal association between gestational age and BMI and height is limited. A life-course approach that enables tracking of BMI and height during infancy, childhood and in adolescence by where individuals have reached their maximum height and a stabilized BMI may add to the evidence27.The aim of this study was to examine longitudinal associations between length of gestation at birth and trajectories of BMI and height, respectively, from birth through adolescence. We explored sex-specific associations due to natural differences in growth28. Baseline information was planned to be collected at 12 and 30 weeks gestation, and follow-ups with information on height and weight were planned to be collected at 18 months and 7, 11 and 18 years. Information is linked with nation-wide registry data at Statistics Denmark32 as described below. Details of the DNBC are given elsewhere28.This is a longitudinal study using data from the Danish National Birth Cohort (DNBC), which includes information on 96,822 live-born children and their mothersn = 92,615)  during follow-up, and excluded individuals with less than two growth measurements after birth and without information on potential confounders: maternal education (n = 173), maternal pre-pregnancy BMI (n = 3894) and/or household income (n = 286). Before defining two specific populations for analysis, individuals with missing information on birth length (n = 374) or birth length < 30 cm or > 80 cm (n = 685), and with less than two measurements of height after birth  were excluded.Eligible for this study was any live-born singleton in the DNBC with a gestational age of 23–43 completed weeks at birth n = 92,65 , and individuals with less than two measurements of BMI (n = 594). Lastly, 39 individuals with BMI values ± 5 standard deviations from the mean was excluded, which left 61,969 individuals for analysis33.In the sample for BMI, we excluded an additional 620 individuals without information on birth weight or with implausible combined values of birth weight and GA , anamnestic information about LMP and cycle length and regularity, and the clinical judgement of the child. GA was converted to completed weeks and categorized into seven groups: extremely preterm (23–27 weeks), very preterm (28–31 weeks), moderately preterm (32–33 weeks), late preterm (34–36 weeks), early term (37–38 weeks), term (39–41 weeks), and post term (42–43 weeks).Information on GA in days was obtained from the Danish Medical Birth Register29. Mothers were interviewed when the child was around 18 months and asked to report the weight and height registered in the ‘Child’s book’ at the preventive child examinations in general practice at scheduled ages of 5 and 12 months (measured at 1–22 months). These were used in the analyses together with height and weight reported by mothers at questionnaire-based follow-ups, scheduled at ages of 7 (measured at 5–7 years) and 11 years (measured at 10–14 years)28. At the 18 year follow-up (in practice at 17–19 years), height and weight were self-reported by the adolescent.Information on birth weight and birth length was derived from the Danish Medical Birth RegisterFor each child, standardized scores (z-scores) of BMI and length at birth, and BMI and height after birth to age 19 years (228 months) were calculated separately for boys and girls. Standardization was done internally using 1-month categories.36. Information on maternal height (cm), maternal pre-pregnancy BMI (kg/m2), and maternal smoking during pregnancy (yes/no) was taken from questionnaires at 12 and 30 weeks of gestation. Information on maternal age at delivery (continuous in years); gestational diabetes, ICD-10: O24 (yes/no); gestational hypertension, ICD-10: O13 (yes/no); and pre-eclampsia, ICD-10: O14 (yes/no) was derived from Danish Medical Birth Registry. Maternal education was obtained from the Danish Population’s Education Register and operationalised as highest ongoing or completed education at child’s birth according to international classification standards37: low [ISCED-2011: 0–2], medium [ISCED-2011: 3–4], high [ISCED-2011: 5–8]). Household income was based on disposable household income extracted from the Income Statistics Register. The variable was divided by an equivalence factor according to household size (available at http://www.oecd.org) and recoded into internal quantiles per year. Birth weight was perceived as an intermediate variable on the causal pathway, hence not included in the models38.Confounders were selected a priori based on previous evidence39. Analyses were performed by sex due to natural differences in growth trajectories27.Linear-mixed effects models were used to estimate the association between GA in categories and BMI and height z-scores, respectively, from birth through age 19 years (228 months) while adjusting for confounders40. Therefore, to best approximate the relationship between GA and the standardized growth measurements, we included linear splines in our models with four internal knots  and two boundary knots (at birth and 228 months). The knots were chosen a priori based on amount of available data40.Linear splines are a commonly used type of regression spline for repeated measurements of non-linear growth trajectoriesThe linear mixed-effects model with linear splines (LME) accommodated for repeated measurements from the same child, without imposing any structure on the correlations among the time points using an unstructured covariance matrix. Also, in the LME models we accounted for clustering of children with same mothers. Age was set to 0 months at birth and included as a continuous variable, and the actual age in months at measurements of BMI and height was included in the models.41.Furthermore, nearly one-third of individuals was excluded from the eligible sample (32%)  Table, t2), mean maternal height (1.69 m), maternal education (high), household income (4th quartile), maternal smoking during pregnancy (no), gestational diabetes (no), gestational hypertension (no), and preeclampsia (no).The fitted LME models were used to predict sex-specific mean BMI and height z-scores by categories of GA with 95% confidence intervals (CIs) at six ages corresponding to the data collections: birth, 5 months, 1 year, 7 years, 11 years, and 18 years. For prediction, we used the following: mean maternal age at delivery (31.2 years), mean maternal pre-pregnancy BMI  and the study has furthermore been approved by the DNBC Steering Committee.2) was similar for preterm and term individuals after age 5 months, whilst height was consistently lower for preterm individuals throughout childhood and adolescence  in preterm infants between birth and 5 months Table , S1 Fig.By age 7 preterm children had a slightly lower BMI z-score than term children with largest mean differences for very preterm boys  and extremely preterm girls . During adolescence the mean BMI z-score was similar across categories of GA, with the largest mean differences relative to term children observed for extremely preterm girls at both 11 years  and 18 years . Results from the sensitivity analyses with sociodemographic variables were only slightly different with estimates away from the null, while sensitivity analyses without IPW and clustering, respectively, were consistent with the main findings  Tables.Extremely, very, moderately and late preterm children experienced catch-up in height (gain in z-score of > 0.67) within the first year of life Table , S2 Fig.The mean difference in height z-score between preterm and term attenuated between age 1 year and 7 years, yet extremely, very and moderately preterm remained relatively shorter than term. By age 11 and through age 18 years individuals born preterm remained slightly shorter than term with mean differences being greatest in extremely preterm girls . Results from the sensitivity analyses were overall similar to the main finding, though the analysis with adjustment for sociodemographic variables only scarcely changed the estimates away from the null  Tables.This study investigated trajectories of predicted BMI and height z-scores across categories of GA from birth through 18 years. In the first year of life, BMI and height were lower in preterm than in term infants. Mean difference in BMI and height between preterm and term attenuated during childhood, and continued to decrease towards zero for BMI by adolescence. At 18 years of age, individuals born preterm remained only slightly shorter than children born at term.n = 475) and Australia (n = 478) showing that a mean difference in BMI between extremely preterm and term is largest in infancy, whilst decreasing during childhood through adolescence45. The two studies reported lower mean difference in BMI at age 6 years  and 8 years , respectively, which corresponds the magnitude of association for our results in girls at age 7 years . Similar to our findings, the studies from UK and Australia found no difference in BMI for extremely preterm and term adolescents at age 18 and 19 years, respectively.This study agrees with two recent publications from United Kingdom (UK) (n = 3036) reporting lower mean BMI in both boys and girls (born ≤ 33 weeks) aged 6 years25. Also, we found that late preterm had similar mean BMI as term already following the first 5 months of life through adolescence, as reported previously in a Chinese study on 7 169 children aged 14 years, and at age 18 years in the study from Brazil46.Very and moderately preterm boys and girls remained lighter than term after birth through 7 years in our study. This is in line with findings from a recent cohort study from Brazil , respectively45. The study from UK reported a lower mean height z-score in 315 extremely preterm aged 6 years , 11 years , and 19 years , respectively, compared with term peers, which corresponds to the likes of the study from Australia.For extremely preterm children, our study suggests that the height remain shorter after birth through adolescence, although the mean differences attenuate with age. These findings agree with results from Australia and UK where extremely preterm was shorter than term peers through infancy, childhood and adolescence compared to term peers47.Our findings support that gestational duration affects height in early life, and that this pattern persists and includes the age where individuals reach their maximum height. This contrast previous genetically informed studies challenging that exposures during fetal life is associated with postnatal growthA strength of this study is the large sample size, and the ability to assess associations of seven categories of GA with BMI and height at birth and at scheduled ages 5 months, 1, 7, 11 and 18 years. Also, we were able to include maternal anthropometrics and measures of gestational hypertension and diabetes and preeclampsia.A key limitation of our study is missing data on one-third of participants due to loss-to-follow up or lack of reporting child height and weight, or maternal pre-pregnancy BMI. To account for potential biases due to missing data, in the main analyses we accounted for missing data using IPWs and found that results were broadly consistent with results obtained in sensitivity analyses without IPWs  Tables.Lack of growth measurements between age 2 to 5 and 13 to 16 years is also a limitation, which means we are not able to make any inference during two periods of dynamic change in size, namely adiposity rebound and puberty.48. Self-reporting of current BMI is a reasonably valid tool49, hence we neither considered this to bias the results. Our study uses data from a healthy population50 and there is a slightly overrepresentation of socially advantaged families in the study population .For preterm infants, the largest mean differences in BMI and height relative to term infants appear in the first years of life. However, despite magnitudes of potential clinical relevance in infancy (mean difference > 0.5 z-score)The lower BMI in preterm infants relative to term infants equalizes during childhood, such that by adolescence there is no clear difference. Height is strongly positively associated with GA in early childhood, whilst by end of adolescence preterm individuals remain only slightly shorter than term peers.Supplementary Information.