Low birth weight is a major contributory factor to infant mortality. Although low birth weight remains an important public health problem in Ethiopia, little emphasis is paid to its intervention as a means of reducing neonatal mortality. The aim of this study was to assess the magnitude of low birth weight and its associated maternal and neonatal factors in newborns delivered at the University of Gondar Comprehensive Specialized Hospital.p-value of <0.05 were used to identify factors associated with low birth weight.Hospital-based cross-sectional study was conducted, and 481 study participants were selected using systematic random sampling methods. Pre-tested interviewer-administered questionnaires were used to collect the data. Bivariable and multivariable binary logistic regression was implemented. Finally, the odds ratio with a 95% CI and a 2 , and grand multiparity  were factors positively associated with low birth weight. However, babies delivered from mothers with age > 35 years  had lower odds of low birth weight.The prevalence of low birth weight was 12.5% . Preterm birth , pregnancy-induced hypertension (PIH) , maternal body mass index (BMI) of < 18.5 kg/m2, and grand multiparity were independent factors that increase the low birth weight while maternal age > 35 years reduces the low birth weight. Therefore, healthcare professionals should emphasize the early identification and management of women with PIH, tackling prematurity, and preventing maternal malnutrition through nutritional counseling as much as possible.In this study, the prevalence of low birth weight was higher than in the previous studies. The study revealed preterm birth, PIH, BMI of < 18.5 kg/m It canal age) . It is anal age) . Globallnal age) , 3, 8, 9nal age) –13. In Enal age) –18. The nal age) . Low birnal age) . Factorsnal age) –23. In 2nal age) . The firnal age) , 25–30. nal age) , 31–37. This study was conducted at the University of Gondar Comprehensive Specialized Hospital, Gondar town, Northwest Ethiopia. It is one of the largest teaching hospitals in Ethiopia, located in the Central Gondar zone of Amhara Regional State. It is found 750 km away from Addis Ababa, the capital city of Ethiopia, and is serving more than 7.5 million people living in the Central Gondar Zone and the neighboring zone. It is composed of operating rooms, maternity units, intensive care units (ICUs), a fistula center, 13 different inpatients wards, and outpatient departments. The maternity units of the hospital provide different services such as antenatal, delivery, and postnatal services to women in the reproductive-aged group (15–49 years). According to the hospital directors’ annual reports, around 9,804 neonates were delivered at the University of Gondar Comprehensive Specialized Hospital in the year 2019/20. An institution-based prospective cross-sectional study was conducted from 1 March to 1 May 2020.All maternal-newborn pairs, who have attended delivery at the University of Gondar Comprehensive Specialized Hospital, were the source population, and those maternal-newborn pairs who have attended delivery during the data collection period were the study population.All neonates delivered at the University of Gondar Comprehensive Specialized Hospital during the study period were included. Twin newborns were excluded from the study.The sample size was calculated using a single population proportion formula with the assumption of 11.6% proportion taken from a similar study in Ethiopia , consideThe dependent variable for this study was low birth weight . The independent variables are socio-demographic variables , maternal anthropometric factors , obstetric- and medical-related factors , and newborn factors . Pregnancy-induced hypertension is defined as the presence of at least one of the following diseases: (A) previous hypertension, (B) gestational hypertension and pre-eclampsia, (C) previous hypertension and superimposed gestational hypertension with proteinuria .To collect the required data, pretested interviewer-administered questionnaires were used. The questionnaire was developed and modified from different literature. It was written in English, converted into Amharic, and translated back into English for suitability and acceptance in approaching respondents. In addition, medical records were reviewed to obtain additional data about maternal and newborn factors. The data were collected by four professional midwives working in the labor wards of the hospital. Anthropometric measurements were done for newborns and mothers using a standard anthropometric technique. The birth weight of a neonate was measured within 1 h of birth using a beam balance scale. The weight of the mothers was measured using a weight measuring scale and recorded accurately to 100 g. Maternal height was measured with calibrated height measuring steel connected to the beam balance and recorded with an accuracy of 0.5 cm. Women were instructed to remain standing up in erect position, with their barefoot close together, while a horizontal headpiece was lowered onto the mother’s heads. Then, maternal BMI was calculated accordingly. The last normal menstrual period was obtained from the mother’s chart since most of the mothers had regular ANC follow-ups. Moreover, if the last normal menstrual period was not documented in the chart, mothers were interviewed during labor. An early pregnancy ultrasound report (≤20 completed weeks of gestation) was also used. Finally, gestational age was determined using either the last normal menstrual period or a chart review of early ultrasound results.In total, 3 days of training were provided to data collectors on how to collect the data. Pre-testing of the questionnaire was conducted with 5% of mothers who were delivered in Debark hospital. Daily supervision of the data collectors was performed by the principal investigators. The collected data were checked for completeness and consistency before entry.p-value of < 0.2 were selected for multivariable binary logistic regression analysis. In the multivariable logistic regression analysis, adjusted odds ratios with corresponding 95% CIs were computed. Finally, variables with a p-value of < 0.05 were used to determine factors significantly associated with low birth weight. Model fitness was tested using the Hosmer–Lemeshow test (0.925). The multi-collinearity test between explanatory variables was assessed using variance influencing factor (VIF) and tolerance and the mean VIF was less than 5.The data were entered into Epidata version 4.6. Then, data were exported and analyzed using STATA version14 software. Descriptive statistics such as percentages, mean, and standard deviations (SD) were used to explain the characteristics of study participants. The findings were presented in the form of tables and text. A chi-square test was used to verify the assumptions. Variables that were passed at the chi-square test were selected for multiple logistic regression analyses. Bivariable and multivariable binary logistic regression analyses were carried out. In the bivariable analysis, variables with a A total of 481 respondents were involved in this study with a response rate of 100%. The mean age of the mothers was 28.2 (SD ± 5.4) years. About 85.3% of the study participants were between the age of 21 and 35 years old. Most (96.9%) of the participants were Amhara and 90.8% of them were orthodox religious followers. The majority (93.8%) of respondents were married, and around 47.6% were housewives. Regarding educational status, nearly 35% of the mothers were diploma holders and above. Concerning the income distribution, 10.6% of the mothers had a monthly income of ≤ 1,210 Ethiopian birr .In our study, majority (90.3%) of women had a height of >150 cm and nearly three-fourth (78.4%) of mothers had normal BMI .via spontaneous vaginal delivery  of the study participants had regular ANC follow-ups during pregnancy and 76.6% of them had at least four visits. Regarding the pregnancy status, the majority (72.6%) of pregnancies were wanted and planned. The majority of (88.2%) mothers had got dietary counseling by health professionals during their ANC follow-up period. Out of 481 mothers, 88.4% were term. One in ten mothers had a chronic medical illness during pregnancy (10%). Concerning the mode of delivery for current pregnancy, 54.1% of women were giving birth delivery .The mean birth weight of the newborns was 3,027 g (SD ± 584). The average gestational age of the neonates was 39 (SD ± 2) weeks. Out of the total number of poor Apgar score neonates (a score of < 7 at 5 min), 47.1% had low birth weight. Of the total number of birth defect neonates, 33.3% had low birth weight .The prevalence of low birth weight in this study was 12.5% . About 45% of the low birth weight neonates were preterm (<37 weeks of gestation).p-value in the bivariable analysis was > 0.2. In the multivariable logistic regression analysis: Maternal age of > 35 years, preterm birth, PIH, maternal BMI of < 18.5 kg/m2, and grand multiparity were statistically associated with low birth weight. In this study, mothers who deliver after the age of 35 years had 86% lower odds of low birth weight babies than those mothers between 21 and 35 years old . The odds of being low birth weight in babies born from mothers who gave preterm birth were 38 times greater than low birth weight in babies from those mothers who gave birth ≥ 37 weeks of gestation . Mothers with PIH had 2.6 times higher odds of giving low birth weight babies than their counterparts . The odds of being low birth weight in babies born from mothers whose BMI was less than 18.5 kg/m2 were 6.8 times higher than the odds of low weight in babies from mothers with a BMI of > 25 kg/m2 . The odds of being low birth weight in neonates born from grand multiparous women were four times higher than the odds of low birth weight in neonates from multiparous women   .In this study, the overall prevalence of low birth weight was 12.5%  which is in agreement with the study conducted in Dangla  and the In the current study, the prevalence of low birth weight infants was higher than in the studies conducted in Jimma , Ghana , Axum 2, and Yaz2 indicate the presence of under-nutrition that shows chronic malnutrition in adults. This might result in the impairment of fetal growth and development in the uterus. Therefore, low birth weight might easily occur. Malnutrition in pregnancy has also been related to decrease placental weight and surface area, which might restrict the transport of nutrients from the placenta to the fetus. Furthermore, poor maternal nutrition leads to a decrement in serum levels of hormones, such as leptin and estrogen, that results in fetal growth restriction , intrauterine growth retardation, small for gestational age, and weight gain during pregnancy.2 were the major associated factors of low birth weight. However, maternal age > 35 years was a protective factor. Therefore, early identification and management of women with PIH, tackling prematurity, and preventing maternal malnutrition through nutrition education during the ANC follow-up period are recommended to reduce the burden of low birth weight.The prevalence of low birth weight in this study was higher than in previous studies, implying that it continues to be a major public health concern. This study showed that preterm birth, PIH, grand multiparity, and BMI of < 18.5 kg/mThe 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 Ethical review board University of Gondar. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.DA and MW: conceptualization, formal analysis, methodology, resources, software, supervision, validation, visualization, and writing—original draft. DA: data curator and investigation. Both authors read and approved the final manuscript.


Apocrine carcinoma of the breast (APO) expresses HER2 in 30–50% of cases. This study explored the clinicopathological features and outcome of HER2+/APO and matched HER2+/NST cohort.We used the SEER database to explore the cohorts. Univariate and multivariate analyses were used to assess the survival. Based on ER and PR [steroid receptors/SR/] and HER2 status, we divided the cohorts to match the intrinsic molecular subtypes for comparisons.p < 0.001). HER2+/SR−/APO had a significantly lower histological grade than the HER2+/SR−/NST (p < 0.001). Breast cancer-related deaths were more prevalent in HER2+/NST . This was particularly evident between SR− subgroups  and was reaffirmed in breast cancer-specific survival in univariate analysis (p = 0.03). Other than race and SR status, HER2+/APO subgroups did not differ in clinicopathological parameters.We retrieved 259 cases of HER2+/APO. Most HER2+/APO were SR negative (65%). HER2+/APO were more prevalent in the 80+ age group (24.7% vs. 15.7%, Our study confirms the rarity of the APO and reveals that SR status in APO does not affect these patients' prognosis. HER2+/APO tumors tend to have a less aggressive phenotype and a more favorable outcome despite a markedly lower ER/PR positivity. Breast carcinoma with apocrine differentiation or apocrine carcinoma (APO) is a rare subtype of invasive breast cancer (~ 1%) that has a characteristic apocrine morphology along with the androgen receptor (AR) expression and the lack of estrogen receptor (ER) activity , 14, 21.The available clinical data on APO are contradictory due to the rarity of the disease and the use of different diagnostic criteria for APO , 19, 21.Despite the common HER2 expression, most of the available clinical studies have been focused on the triple-negative APO, while the clinical and survival data on HER2+/APO are sparse , 8. The We explored the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database to select our study cohort. The SEER database includes data on patients' demographics, tumor characteristics , the first course of treatment, treatment options , and follow-up for vital status. It encompasses data from eighteen population-based cancer registries covering approximately 1/3 of the US population.For our study cohort, we selected patients diagnosed with histologically confirmed invasive HER2-positive APO (HER2+/APO) between 2010 and 2016. In addition, we selected patients diagnosed with IBC NST with HER2 positivity (HER2+/NST) within the same period. The two groups (HER2+/APO and HER2+/NST) were further divided based on the SEER variable that codes ER and Progesterone Receptor (PR) [Steroid receptors/SR/] and HER2 status to form groups based on the intrinsic molecular subtypes, i.e., Apocrine Luminal B (HER2+/SR+/APO) and Apocrine HER2-Enriched (HER2+/SR−/APO) for HER2+/APO and HER2+/SR+/NST and HER2+/SR−/NST for HER2+/NST part of the cohort. SR status did not include androgen receptor. The study excluded in situ carcinomas (both apocrine and NST) and other special types of invasive breast carcinoma with HER2 positivity. We used the SEER*stat version 8.3.2 to generate a case-listing file.t test/Mann–Whitney U test.Patients’ demographical and clinicopathological characteristics, including age, hormone receptor status, stage, tumor grade, therapies , regional and distant metastases, as well as metastatic sites, were summarized by absolute and relative frequencies. Age was categorized as 18–49, 50–79, and ≥ 80 years. The difference in the distribution of clinicopathological characteristics was tested using Pearson Chi-square and/or Fisher's exact test, whichever was appropriate according to the expected cell counts. For continuous normally distributed variables, we give mean and standard deviation as measures of central tendency and variability; for those whose distribution is not normal, we give a median and interquartile range instead. We tested the equality of means/medians for normally/non-normally distributed variables using the p < 0.05 considered statistically significant.BCSS and OS were defined as a time in years between the cancer diagnosis and death from breast cancer, death due to any cause, respectively. Patients alive at the end of the follow-up were censored for both types of survival. We ran univariate Cox proportional hazards analysis to identify candidate prognostic factors for the multivariate analysis. For each of these, we produced Kaplan–Meier plots and performed log-rank tests after checking the appropriateness of proportional hazard assumption graphically using martingale and weighted Schoenfeld residuals. After identifying and deciding which prognostic factors will enter the multivariate analyses, we fitted a multivariate Cox regression model to estimate the effect of subtypes on survival while adjusting for other prognostic factors. In the multivariate analysis of BCSS and OS, aside from the HER2+/APO status, we included age , stage, tumor grade, surgery, and systemic therapies. To provide an additional check of the robustness of our findings w.r.t. modeling assumptions assumed for multivariate Cox regression, we applied propensity score caliper matching in the ratio of 3:1 in favor of the “control” group (HER2+/NST). The propensity score was estimated via a multivariate logistic regression model that included age , tumor grade, stage, size (in cm), lymph node status, the presence of distant metastasis, chemotherapy and radiation therapy. We applied the same model for propensity score and the same matching strategy for APO vs. NST comparisons  and the analysis for the effect of SR status among the APO subtype. All analyses were performed based on available cases using R Statistical Software  version 3.5.1. All tests were 2-sided, with The clinicopathological characteristics of the cohorts are summarized in Table p = 0.038, Table Among 446,806 breast malignancies diagnosed between 2010 and 2016, there were 259 with HER2+ APO subtype (HER2+/APO) (~ 0.06%). We also identified 52,860 HER2+ IBC NST (HER2+/NST) in the same period. The median follow-up for the pooled cohort was 31 months ; the median follow up for HER2+/APO was 27 months  and 31 months  for HER2+/NST cohort (p < 0.001). HER2+/APO were more prevalent in 80+ age group  compared with HER2+/NST cohort  (p < 0.001). HER2+/APO had a significantly lower SR (ER and PR) positivity than the HER2+/NST group (p < 0.001) (Table The average age of patients was 69.1 years in the HER2+/APO group and 65.3 years in the HER2+/NST group (p > 0.05), while radiotherapy was more commonly used in the HER2+/APO group compared with HER2+/NST (p = 0.05) . The treatment options (surgery and chemotherapy) were similar between HER2+/APO and HER2+/NST (5) Table .p = 0.264)  in the univariate Cox proportional hazards model. This difference was not statistically significant (p = 0.019). This difference was 1.5 times higher between ER-negative subgroups . It was reflected in the results of the univariate analysis of BCSS in those groups with unadjusted HR 2.22  and adjusted  HR 2.07 .Breast cancer as a cause of death was also more prevalent in HER2+/NST than in the HER2+/APO group  and significantly better BCSS  compared with HER2+/NST    (65%), while 91 patients 35%) were HER2+/SR+  APO. HER2+/SR+/APO subtype was more prevalent in the Black race, while HER2+/SR− APO were more frequent in other races (neither black nor white) (5% were Hp < 0.001); however, this age-related difference in survival curves completely dissipated when it came to BCSS (p = 0.423).The survival curves for two groups defined by SR status (ER and PR) were not significantly different by the log-rank test Fig. , althougp = 0.035).There were 91 HER2+/SR+/APO  cases and 36,556 HER2+/SR+ /NST  carcinomas. The mean age in HER2+/SR+/APO was 68.3 years, which was significantly higher than in the HER2+/SR+/NST group  and BCSS  .There were 167 cases of HER2+/SR−/APO and 16,186 HER2+/SR−/NST carcinomas. At diagnosis, the average age was 69.7 in the HER2+/SR−/APO group vs. 65.6 years in the HER2+/SR−/NST group. HER2+/SR−/APO was more prevalent in older populations than the HER2+/SR−/NST (p < 0.001). The chemotherapy frequency differed between the groups, with more chemotherapy applied in the HER2+/SR−/NST group (75.5%) compared with HER2-enriched APO (67.1%). The two cohorts did not differ regarding the tumor stage, lymph node, and distant metastases' patterns.HER2+/SR−/APO had a significantly lower histological grade than the HER2+/SR−/NST . Consequently, the apocrine morphology was associated with a better BCSS in univariate analysis (p = 0.030)  subtype of breast carcinoma whose diagnosis and clinical data, including outcome, remain challenging and controversial , 19. BasOur findings indicate that HER2-positive APO do substantially better compared with HER2-positive NST carcinomas. This is mainly reflected in BCSS and was independent of ER and PR status. Our results are in line with a recently published SEER cohort of triple-negative APO, which also revealed that these cancers had a better prognosis than TNBC NST . SeveralSome other findings from our study are consistent with the previous data, including a rarity of APO and a higher prevalence of APO among elderly patients , 21, 24.We observed some clinically relevant differences between the APO and NST groups. Thus, HER2+/SR−/APO had significantly lower histological grade than the NST carcinomas, which is in line with several previous studies and is probably due to the lower mitotic activity (and lower Ki-67 labeling) of apocrine cells , 19, 20.The current study has several limitations that reflect the nature of the SEER database. Firstly, the follow-up period was too short (~ 31 months), and long-term outcomes could not be assessed. This is particularly relevant for SR+ cases in both cohorts. Secondly, AR was not routinely provided, which could affect the classification of a proportion of HER2+/APO cases, particularly ER/PR-positive. In addition, the details (types and duration) on chemotherapy, endocrine, and anti-HER2 therapies were not provided in the SEER database, so their effects  and the overall impact on the outcomes could not be analyzed.We conclude that our cohort represents the largest HER2+/APO study reported to date. It confirmed the rarity of the HER2+/APO and revealed only marginal differences within the HER2+/APO regardless of ER/PR status. Compared with HER2+/NST, HER2+/APO tended to have a less aggressive phenotype and were associated with a more favorable clinical outcome (BCSS) despite a markedly lower/absent ER/PR expression. Further prospective studies should confirm the provided observations.


Serial developmental testing  and anthropometrics were obtained from n = 37 infants (29 AGA and 8 SGA) and analyzed via repeated measures analyses of variances. The percentage of body fat, percentage of lean mass, and weight gain were statistically significant between SGA and AGA groups at the first ADP assessment. There was no difference between the two groups in outpatient neurodevelopmental testing. Weight gain as “catch-up” body fat accrual occurs by 67 weeks of PMA. This catch-up growth is associated with normal SGA preterm neurodevelopment as compared to AGA preterm infants.To examine the growth and body composition of small for gestational age (SGA) and appropriate for gestational age (AGA) very low birth weight infants (VLBW) and their outpatient neurodevelopmental outcomes. From 2006–2012, VLBW infants ( Optimizing nutrition for preterm infants continues to be a challenge to curb postnatal growth faltering in the neonatal intensive care unit (NICU), especially in the small for gestational age (SGA) and very low birth weight (VLBW) population. Studies show growth of VLBW infants is associated with better neurodevelopmental outcomes ,2,3,4. PPrematurity has been linked to later metabolic disease given increased early adiposity ,9. Few sThe link between premature infant growth and neurodevelopment is observed in multiple studies ,3,4,5. EThe Capute Scales Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) is a standardized tool to assess pediatric development. This test has been established with acceptable sensitivity and specificity to detect a neurodevelopmental delay in the premature population and correlates well with the Bayley Scales of Infant Development-II ,15. The From 2006–2012, 366 infants admitted to MUSC’s level IV NICU underwent an air displacement plethysmography (ADP) using the PeaPod  as part of clinical care. After discharge, all VLBW infants were followed, outpatient. To clarify the association between neurodevelopmental outcomes and body composition, we chose to exclude several severe co-morbidities and sample a population of healthy preterm infants. A total of 92 VLBW SGA and VLBW AGA infants were selected for analysis after excluding necrotizing enterocolitis, retinopathy of prematurity stage 3, and grade III-IV intraventricular hemorrhage. A total of 57 infants had serial ADP assessments, while admitted to the MUSC NICU and as an outpatient. The average time of the first ADP assessment was 44 ± 8 weeks postmenstrual age (PMA) and the second ADP at 67 ± 6 weeks PMA. Infants receiving an ADP evaluation were not on mechanical or non-invasive ventilation and did not have intravenous fluids.n = 37, 29 AGA, and 8 SGA). ADP assessments were analyzed using independent samples t-test between VLBW SGA and VLBW AGA groups for anthropometric and body composition. Repeated measures analyses of variances were completed across four outpatient visits and for weight, length, head circumference, adjusted age CAT DQ, adjusted age CLAMS DQ, adjusted age gross motor DQ between VLBW SGA and VLBW AGA groups with Bonferroni adjusted pairwise comparisons, .After discharge, infants were then followed serially at outpatient at MUSC’s high risk NICU clinic where neurodevelopmental testing (CAT/CLAMS and Peabody Gross Motor) was performed along with anthropometric measurements including height, weight and head circumference at each outpatient visit. Chronological and adjusted age CAT, CLAMS, and Gross Motor DQs were obtained at each outpatient NICU clinic visit over four consecutive visits. Infants who had four consecutive outpatient visits were included to trend their neurodevelopment over time ) with fortification of 24 kcal/oz or 27 kcal/oz at clinician discretion based on in hospital growth patterns. This project was designated as exempted research by the MUSC Institutional Review Board and consent was not required to be obtained.Very low birth weight infants were started on either mother’s own milk or donor breast milk per feeding protocol on admission with parental nutrition supplement until they reach full enteral feeds (160 mL/kg/day). Enteral feeds were initiated within six hours of admission if the infant remained clinically stable. Infants were fortified to 24 kcal/oz on day of life 5–12 and reached full enteral feeds of 160 mL/kg/day by day 7–16 of life, corresponding to birth weight feeding protocol . InfantsThe demographics of all infants included in our study are shown in p < 0.05); however, there was no statistical difference in weight gain between the two groups between the first and second ADP. Linear growth and head circumference growth were not statistically significant between the SGA and AGA groups over time as shown in Anthropometric results from birth to ADP evaluations are shown in p < 0.05). However, at the second ADP assessment, there was no longer a statistical difference between the SGA and AGA body composition as the SGA cohort of VLBW infants increased fat from 14.3% to 19.2%. Fifty-seven VLBW infants had serial body composition assessments which are displayed in n = 37, n = 8 SGA, n = 29 AGA). The average adjusted age from visits 1, 2, 3, and 4 were 3.0 ± 1.5 months, 7.0 ± 2.7 months, 11.7 ± 3.4 months, and 17.3 ± 3.8 months, respectively. There was a statistically significant difference between the weight of SGA and AGA cohorts at the first outpatient visit as the SGA group was smaller; however, we did not see the difference between the two cohorts at visits 2–4. There was statistical significance between the head circumferences of the two groups across all outpatient visits; however, we did not see a difference between the cohort’s linear growth. We did not see a significant difference between the adjusted CAT, adjusted CLAMS, and adjusted gross motor DQs for each of the outpatient follow-up visits between the two groups. These data support previously reported findings, specifically, that a healthy cohort of SGA VLBW infants start with less body fat than AGA infants but after 50–60 weeks of PMA, the differences in fat are minimized between the two groups ,17,18.Premature infants accumulate body fat after birth, and at term equivalent age, they have higher fat mass and less fat-free mass than their term counterparts ,19,20,21SGA infants have lower body fat percent at birth and show recovery of adiposity over time compared to AGA counterparts ,21,24. ROur study adds to the literature on VLBW neurodevelopment with respect to growth. The infants followed had repeated neurodevelopmental testing, anthropometric assessments, and serial body composition assessments. These infants were specifically selected to represent an optimized sample of infants who did not have necrotizing enterocolitis, severe retinopathy of prematurity or grade III-IV intraventricular hemorrhage and represent a sample of healthy VLBW infants without significant co-morbidities.p = 0.003). Our data also demonstrated a significant difference in weight at the first outpatient visit where the mean age was 3.0 ± 1.5 months. This represents that the SGA cohort’s catch-up growth occurs between birth to around 3 months of adjusted age. As after the second ADP assessment (mean 67 weeks PMA) and between subsequent outpatient visits 2–4, there were no significant differences in growth (grams/day) and weight between SGA and AGA groups. Although the SGA cohort had significantly smaller head circumference than the AGA group, this did not impact their neurodevelopmental testing as we saw no difference across the Capute Scales CLAMS DQ, CAT DQ, and Gross Motor DQ for adjusted age. Linear growth between the SGA and AGA cohorts was also not significant from birth to outpatient follow-up.From birth to the first anthropometric assessment, there was a statically significant difference in weight gain (grams/day) between the SGA and AGA cohorts . Inconsistent follow-up was due to missed outpatient appointments or if infants did not need further interventional services from the clinic. We were unable to correct for maternal IQ or educational level, which was unknown in this cohort of infants. Given the structure of our NICU follow-up clinic, most infants at the time of outpatient follow-up were referred to South Carolina’s home therapy programs and most infants were involved in physical and occupational therapy services as a standard of care, which may have benefitted early neurologic testing scores. Lastly, our outpatient clinic utilizes the Capute Scales instead of Bayley for neurodevelopmental testing due to ease of administration with a shorter amount of training compared to the Bayley examinations. Additionally, our center promotes intensive post-discharge fortification of breastmilk and formula to 24 kcal/oz which is not a standard practice universally. More studies are needed on the association between discharge nutrition and neurodevelopmental outcomes. Moving forward with this research, observing a modern cohort of SGA VLBW and AGA VLBW infants utilizing the Bayley Infants Scales is warranted. Future studies should also be powered to detect a statistical difference between body fat and neurodevelopmental outcomes. Although modern nutritional changes for preterm infants have not substantially changed since this data collection, it would be prudent to study a modern cohort of infants prospectively.It is possible there was no difference between neurodevelopment across the two groups given the SGA cohort grew as well as the AGA cohort with early catch-up growth demonstrated by significant body fat accrual and weight gain of the SGA cohort before 60 weeks PMA. Furthermore, the increase in body fat and early weight gain in this SGA population may play a role in neuroprotection as alluded to in Okada et al.  as we saThe trajectory for catch-up growth of VLBW infants that reflects optimal neurodevelopment is still unknown. Our data reflects trends within a healthy preterm SGA cohort, whose increasing fat “catch-up” growth was not associated with the previously reported sub-optimal outcomes seen in this preterm SGA group and was comparable to the AGA group. Further studies should be completed to investigate the associations between body composition of preterm SGA infants, specifically adiposity within the NICU, neurodevelopment, and late-onset metabolic consequences.


Moderate and severe bronchopulmonary dysplasia (BPD) is a common pulmonary complication in premature infants, which seriously affects their survival rate and quality of life. This study aimed to describe the mechanical ventilation characteristics and evaluate their prediction performance for the risk of moderate and severe BPD in infants with gestational age <30 weeks and birth weight <1,500 g on postnatal Day 14.In this retrospective cohort study, 412 infants with gestational age <30 weeks and birth weight <1,500 g were included in the analysis, including 104 infants with moderate and severe BPD and 308 infants without moderate and severe BPD (as controls). LASSO regression was used to optimize variable selection, and Logistic regression was applied to build a predictive model. Nomograms were developed visually using the selected variables. To validate the model, receiver operating characteristic (ROC) curve, calibration plot, and clinical impact curve were used.2 (fraction of inspiration O2) were identified by LASSO regression analysis. The model constructed using these six predictors and a proven risk factor  displayed good prediction performance for moderate and severe BPD, with an area under the ROC of 0.917  in the training set and 0.931  in the validation set, and was well calibrated .From the original 28 variables studied, six predictors, namely birth weight, 5 min apgar score, neonatal respiratory distress syndrome (≥Class II), neonatal pneumonia, duration of invasive mechanical ventilation (IMV) and maximum of FiO2 had good prediction performance for predicting moderate and severe BPD in infants with gestational age <30 weeks and birth weight <1,500 g on postnatal Day 14.The model included gestational age, birth weight, 5 min apgar score, neonatal respiratory distress syndrome (≥Class II), neonatal pneumonia, duration of IMV and maximum of FiO The definition of BPD is oxygen support as needed for at least 28 days . Accordioderate 2%–30% or istance) . The quaistance) , 6. Moreistance) , 8. Ther2, and found that gestational age conveyed the most predictive information for BPD risk on Postnatal Days 1 and 3, and respiratory support on Days 7, 14, 21, and 28 . Infants with gestational age <30 weeks and birth weight <1,500 g were recruited at the Department of Pediatrics, Nanjing Maternity and Child Health Care Hospital from January 2018 to December 2021. This study was approved by the Ethics Committee of Nanjing Maternity and Child Health Care Hospital, and either a legal guardian or parent provided informed consent. Moderate and severe BPD is defined as oxygen requirement (FiO2 > 21%) for at least 28 days, and the need for any type of respiratory support at 36 weeks post-menstrual age , and maximum of FiO2 (%). IMV includes CMV and HFV, and NIMV includes CPAP, HFNC, BiPAP and NIPPV.The characteristics of mechanical ventilation and oxygen requirement included conventional mechanical ventilation (CMV), duration of CMV (days), high frequency ventilation (HFV), duration of HFV (days), continuous positive airway pressure (CPAP), duration of CPAP (days), high-flow nasal cannula (HFNC), duration of HFNC (days), Bi-level positive airway pressure (BiPAP), duration of BiPAP (days), nasal intermittent positive pressure ventilation (NIPPV), duration of NIPPV (days), invasive mechanical ventilation (IMV), duration of IMV (days), noninvasive mechanical ventilation (NIMV), duration of NIMV (days), duration of FiOt-test or Mann-Whitney test were used to compare the two study groups. For categorical variables, frequency (percentage) was displayed and compared using χ2 test or Fisher exact test.Statistical analyses were conducted by applying R (v4.1.3) software. Normally distributed continuous variables were displayed as mean (SD) and skewed distributed variables as median , and Student's P < 0.05), we sought to build predictive model for moderate and severe BPD in infants with gestational age <30 weeks and birth weight <1,500 g on postnatal Day 14. First, conforming to a ratio of 3 : 1, we randomly divided the 412 preterm infants into a training set with 309 infants and a validation set with 103 infants. To identify the best predictors of current risk factors, LASSO (least absolute shrinkage and selection operator) regression was performed in the training set using R glmnet package  provided good discrimination between true positives and false positives for the quality of the risk nomogram. Using the “best threshold” criteria of the ROC curve, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated to illustrate the model effects. To evaluate the calibration of the moderate and severe BPD risk nomogram, along with the Hosmer-Lemeshow test, the R rms package was used to draw the calibration curves. As well, clinical impact curves were drawn using the R rmda package to determine whether the nomogram is clinically practicable for predicting moderate and severe BPD. All statistical significance levels reported were two-sided, and P < 0.05 was considered to be significant.Additionally, the accuracy of the model was estimated using several validation methods using the data of training set and validation set, respectively , 18. RecIn total, 519 infants with gestational age <30 weeks and birth weight <1,500 g were recruited in Nanjing Maternity and Child Health Care Hospital from 2018 to 2021. We excluded 79 uncured infants hospitalized for less than 28 days and lost to follow-up after discharge; 3 infants with severe congenital malformation; 7 infants with pneumothorax or pleural effusion; 13 infants undergoing surgery; and 5 infants who died less than 28 days after birth. At last, 412 infants were included in the analysis , includiP < 0.001). Whereas the rates of neonatal asphyxia, neonatal respiratory distress syndrome (≥Class II), neonatal pneumonia, PDA, PDA treatment, IVH III/IV, sepsis, and NEC (≥Stage II) were significantly higher in infants with moderate and severe BPD , and the PDA size was also larger in infants with moderate and severe BPD (P = 0.002).The maternal characteristics, medication use, neonatal characteristics, mechanical ventilation and oxygen requirement up to postnatal Day 14 are shown in P < 0.01), whereas the rates of CPAP, HFNC and NIMV, and the duration of CPAP, HFNC and NIMV were significantly lower than that in control group (P < 0.001). For oxygen requirement, the maximum of FiO2 was significantly higher in infants with moderate and severe BPD (P < 0.001).We then focused on the characteristics of mechanical ventilation and oxygen requirement up to postnatal Day 14 between the two study groups. In infants with moderate and severe BPD, the rates of CMV, HFV, NIPPV and IMV, and the duration of CMV, HFV, NIPPV and IMV were significantly higher than those in control group . In order to evaluate the predictive model's discriminatory capacity, the ROC curve was used. The pooled AUC of the predictive model is 0.917  in the training set and 0.931  in the validation set, which indicates good performance . We also2, are important predictors for moderate and severe BPD in infants with gestational age <30 weeks and birth weight <1,500 g on postnatal Day 14. Using these 7 predictors, the constructed model displayed good prediction performance for moderate and severe BPD, with an AUC of 0.917 in the training set and 0.931 in the validation set, and was well calibrated. Further sensitivity analysis for severe BPD alone showed the pooled AUC of the model is 0.933 in the total data set. Previously identified risk factors for BPD include gestational age, birth weight, oxygen therapy, mechanical ventilation, and duration of assisted ventilation , neonatal pneumonia, duration of IMV and maximum of FiOtilation . These ftilation . These fIn this study, a novel statistical method (LASSO regression) was used to identify the predictors for moderate and severe BPD. LASSO regression analysis minimizes the prediction error of quantitative response variables by imposing constraints on model parameters and reducing the regression coefficients of some variables to zero , thus pr2 > 21%, and maximum of FiO2 in the infants with moderate and severe BPD were significantly higher than those in the control group, which was consistent with most studies , neonatal pneumonia, duration of IMV and maximum of FiO


To identify racial/ethnic disparities in postnatal growth by year and gestational age among very low birth weight infants.Total 37,122 infants, with birth weight 500–1500 g or gestational age 23–34 weeks in the California Perinatal Quality Care Collaborative in 2008–2016. Postnatal growth failure (PGF) was defined as change in weight Z-score from birth to discharge below −1.28. Multivariable regression analysis with birth hospital as random effect was used to estimate odds ratios (OR).Infants born to Hispanic mothers had highest risk of PGF at 30%, compared to white , Black , or Asian/Pacific Islander mothers . PGF incidence decreased from 2008 (27.4%) to 2016 (22.8%) with differences in trends by race. Each increasing gestational age week was associated with decreasing risk for PGF .Targeted interventions addressing PGF are needed to address disparities. Although the survival of preterm infants has improved markedly, postnatal growth remains a prominent concern for this population because of its link to brain growth and neurodevelopment. Postnatal growth among very low birth weight (VLBW) infants is influenced by a variety of factors, such as neonatal morbidities, nutrition-related factors, sex, and small for gestational age (SGA) . However, less is known about racial/ethnic disparities in postnatal growth in preterm infants.Measures of postnatal growth failure (PGF) for preterm infants have varied among studies –4. In thDisparities in fetal growth restriction, infant postnatal growth rates, and nutrition practice such as breast milk feeding exist by race and ethnicity –15. OffsOur objective was to investigate racial/ethnic differences in PGF among VLBW infants in California. We specifically focused on longitudinal trends in growth and factors associated with PGF.Data were extracted from the CPQCC database, which at the time of the study period included data collected across 132 NICUs that accounted for the care of more than 95% of VLBW infants born in California. Data from California’s Department of Health Care Access and Information were linked to CPQCC records to obtain detailed maternal information, including race, ethnicity, maternal education, and payer type.We included 37,122 infants who were born with a birth weight of 500–1500 g or with gestational age of 23–34 weeks from 2008 to 2016 and discharged alive before 50 weeks corrected gestational age. The limit of 50 weeks corrected gestational age was chosen to exclude those patients with special circumstances leading to longer hospitalization; the Fenton growth charts are available up to 50 weeks postmenstrual age (PMA). A subset of 20,019 infants born with a birth weight below 1000 g or gestational age of 23–28 weeks were selected for subgroup analysis. Infants with severe congenital anomalies were excluded, as were patients with missing data for birth weight, discharge weight, or sex. In addition, we excluded patients with a weight Z-score at birth or discharge more than five standard deviations above or below the expected mean as an error. The Institutional Review Board at Stanford University approved the study.https://www.ucalgary.ca/fenton/2013chart/. [Trained data abstractors prospectively gathered maternal, delivery, and neonatal data based on standardized definitions from the CPQCC manual of operations. Variable definitions align with those developed by the Vermont Oxford Network. Gestational age was determined by the best available estimate in weeks and days. Where sources disagreed, obstetric measures based on the last menstrual period or prenatal ultrasound took precedence over the neonatologist’s estimate based on physical examination. Weight was measured and recorded at birth and discharge. To control for variation in gestational age and postnatal age, body weight was converted into a Z-score using the provided calculator of the Fenton growth chart that can be downloaded at 3chart/. . SGA wasFeeding data were collected by choosing formula only or human milk only or human milk in combination with either fortifier or formula. Formula only indicated that the infant was discharged receiving formula milk as their only enteral feeding. Outborn was defined as the infant being born in another facility or at any location outside the enrolled center or home at any time after birth. Hypertension was defined according to the maternal or infant medical record stating the diagnosis of hypertension, chronic or pregnancy-induced, eclampsia, preeclampsia, seizures, toxemia, HELLP syndrome, with or without edema and proteinuria, or if a maternal blood pressure above 140 systolic or 90 diastolic was recorded before or during the current pregnancy. Chorioamnionitis was defined as the maternal medical record noting evidence of infection of the amniotic sac and fluid or infection of the uterine wall. CLD was defined as oxygen use at 36 weeks postmenstrual age; periventricular leukomalacia (PVL) as evidence of cystic PVL on cranial imaging at any time; necrotizing enterocolitis as clinical and radiographic findings stage 2 or 3; severe intraventricular hemorrhage (IVH) as grade 3 or 4 IVH by cranial imaging obtained before 28 days after delivery; severe retinopathy of prematurity as ≥ stage 3 disease or treatment with retinal ablation surgery or anti-vascular endothelial growth factor drug.2 tests to examine bivariate associations between characteristics and race/ethnicity. Linear regression models determined if the change in the incidence of PGF was significant over time and by gestational age, stratified by race/ethnicity. Multivariable logistic regression models with hospital accounted for as a random effect were used to examine risk factors associated with growth failure. Variables in the model included race/ethnicity, sex, gravidity, maternal education, maternal age, maternal insurance, SGA at birth, maternal hypertension, chorioamnionitis, CLD, gastrointestinal perforation, necrotizing enterocolitis, late-onset sepsis, with birth hospital applied as a random effect to adjust for clustering by site. Length of stay was highly correlated with included morbidities and was therefore not included as a covariate. All statistical analyses were performed using SAS version 9.4 . P-values < 0.05 were considered statistically significant.We used one-way ANOVA and χAmong 37,122 infants, the distribution of maternal race/ethnicity was 47% Hispanic, 26% white, 13% Black, 11% Asian/PI, and 3% other. For the 20,019 infants with birth weight below 1000 g or having gestational age of 23–28 weeks, the distribution of maternal race/ethnicity was 49% Hispanic, 25% white, 13% Black, 10% Asian/PI, and 3% other.Table P < 0.0001). Black infants were at lower risk of PGF compared to white infants . Asian/PI infants were not significantly different from white infants. The subgroup of infants born at <1000 g or at 23–28 weeks of gestation exhibited a similar pattern of SGA at birth and discharge and PGF as the larger cohort according to race/ethnicity; however, a lower incidence of SGA at birth and higher incidence of PGF was observed compared to the full cohort.Hispanic infants were at higher risk of PGF than white infants . Serial PGF trends over time differed significantly by race (P < 0.0001); infants born to Hispanic mothers were at higher risk of PGF than those born to white  or Black  or Asian/PI mothers   to 2016 (23%) (49) Fig. . For sub49) Fig. .Fig. 2InP < 0.0001). Each week of gestational age was associated with decreasing risk for PGF . For Hispanic infants, those between 25 and 33 weeks’ gestation showed the highest incidence of PGF. For Asian/PI infants, those between 23 and 24 weeks of gestation showed the highest incidence of PGF , and especially for infants born below 29 weeks’ gestation  . Maternal age, insurance type, maternal education, multiple pregnancy, maternal chorioamnionitis, early sepsis, and PVL did not significantly influence PGF rates. As for the subgroup below 1000 g or 28 weeks of gestation, race/ethnicity, sex, formula feeding only, and maternal hypertension were associated with PGF. Hispanic ethnicity was associated with increased risk of PGF, while Black race was associated with reduced risk (Table P < 0.0001). Maternal age, maternal education, SGA at birth, maternal chorioamnionitis, early onset sepsis, severe IVH, PVL, and CLD were not associated with PGF.In multivariable analysis, race/ethnicity in addition to the various morbidities, sex, formula feeding only, maternal hypertension, and SGA at birth were independently associated with PGF. Hispanic ethnicity was associated with higher risk of PGF, while Black race reduced the risk of PGF Table . Birth hIn this large population-based cohort of VLBW infants born in California, we demonstrated that race/ethnicity was associated with PGF. SGA at birth and discharge was highest among infants of Asian/PI mothers; however, the incidence of PGF was highest in Hispanic infants. Racial/ethnic disparities in postnatal growth among VLBW infants may have implications for careful monitoring and attention to nutrition.Being born SGA is a predictor of failure to grow and careful monitoring of nutrition and personalized strategies may be needed to improve outcomes. Racial/ethnic disparities in SGA at birth have been studied. Mexican American infants tended to have higher weight compared with non-Hispanic white infants between 30 and 37 weeks of gestation . Other sIf growth failure is determined based only on the percentage of body weight at discharge, SGA status at birth may have a disproportionate impact compared to other factors, and differences by gestational age and sex may be overlooked. In this study, among 6634 SGA infants, 96% remained SGA at discharge; however, only 29% noted SGA at discharge among 37,122 AGA infants. In this study, among infants between 23 to 28 weeks of gestation or <1000 g, SGA at birth was not significantly associated with PGF when considered in multivariable logistic regression with birth hospital accounted for as a random effect.The change in Z-score between birth and discharge has been used for evaluation of growth. We have similarly defined PGF as changes of weight z-score from birth to discharge below −1.28  and confirmed PGF was shown in 39% of the infant. We also found that Hispanic infants, while having a low incidence of SGA at birth, had the highest incidence of PGF in California NICUs. Hispanic ethnicity was an independent risk factor (OR 1.15) for PGF, adjusted for comorbidities and socioeconomic status.Although human milk is the preferred feeding choice for its known impact on prevention of necrotizing enterocolitis and its association with other short- and long-term clinical benefits, formula feeding at discharge has been associated with higher growth velocity , 27. A pPGF has been associated with various factors including nutrition, morbidities, sex, and SGA. In other studies, the comorbidities most associated with poorer postnatal growth included IVH, retinopathy of prematurity, necrotizing enterocolitis, isolated gastrointestinal perforation, and CLD , 30. OurP < 0.0001), highlighting variation across hospitals. Collaborative quality improvement initiatives supporting postnatal growth, such as the CPQCC Grow Baby Grow Collaborative, which was launched in 2018 to optimize the growth and nutrition of VLBW infants to reduce growth failure at discharge, may help mitigate hospital-level effects.Despite intensive treatment, chronic nutritional deprivation and growth failure in preterm infants continue to be challenging in the NICU. About a 10% (from 65 to 58%) decrease was noted during the early 2000s, with subsequent smaller incremental improvement from 55 to 50% between 2008 and 2013 . In the A strength of our study is the database including a large diverse population that covers over 95% of VLBW infants cared for in California. Given the varied population and care settings, our findings may hold lessons for other states. Our study has clinical relevance given the established association of PGF with adverse neurodevelopmental outcomes , 35. IntThis study had several limitations, including lack of quantitative nutritional data, monitoring of growth at only birth and discharge, and lack of assessment of other parameters of growth, including length and head circumference. Formula or human milk feeding data were collected only at discharge. Maternal smoking, maternal obesity, and maternal body mass index as potential covariates were not examined. Because infants who died before discharge or were discharged after 51 weeks postmenstrual age were excluded, the possibility of survivor bias and selection bias may exist. An association should not be interpreted as causal, given potential confounding from unobserved variables.We found racial and ethnic disparities among Hispanic, Black, Asian/PI, and white VLBW infants in early postnatal growth. Interventions implemented early in life to target this risk factor could help improve both short- and long-term outcome, particularly for Hispanic infants.


Results showed that the choice of diffusion protocol had the largest impact on the effect size. The effect size in fractional anisotropy (FA) across all WM tracts was 0.26 higher when derived by DTI than by DKI and 0.20 higher in 3T compared with 7T. The difference due to the diffusion protocol was larger than the difference due to magnetic field strength for the majority of diffusion parameters. In contrast, the difference between including or excluding different processing steps was near negligible, except for the correction of distortions from eddy currents and motion which had a clearly positive impact. For example, effect sizes increased on average by 0.07 by including motion and eddy correction for FA derived from 3T-DTI. Effect sizes were slightly reduced by the incorporation of denoising and Gibbs-ringing removal . Smoothing prior to diffusion model fitting generally reduced effect sizes. In summary, 3T-DTI in combination with eddy current and motion correction yielded the highest sensitivity to WM pathology in patients with SLE. However, our results also indicated that the 3T-DKI and 7T-DTI protocols used here may be adjusted to increase effect sizes.There are many ways to acquire and process diffusion MRI (dMRI) data for group studies, but it is unknown which maximizes the sensitivity to white matter (WM) pathology. Inspired by this question, we analyzed data acquired for diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) at 3T (3T-DTI and 3T-DKI) and DTI at 7T in patients with systemic lupus erythematosus (SLE) and healthy controls (HC). Parameter estimates in 72 WM tracts were obtained using TractSeg. The impact on the sensitivity to WM pathology was evaluated for the diffusion protocol, the magnetic field strength, and the processing pipeline. Sensitivity was quantified in terms of Cohen's  Diffusion MRI (dMRI) can be used to characterize the microstructure of white matter (WM) fiber tracts by parameters obtained with for example diffusion tensor imaging (DTI). Examples of such parameters include the mean, axial, and radial diffusivity  and the fractional anisotropy (FA). Changes in these parameters have been detected in numerous conditions, including aging , traumatb-values, in contrast to DTI where a single-shell acquisition is sufficient . This, in turn, necessitates diffusion encoding with longer gradient pulses, and therefore, DKI is performed with longer echo times than DTI, which reduces the baseline signal-to-noise-ratio (SNR). This is often compensated for by reducing the spatial resolution in DKI compared with DTI. DKI and DTI have been applied together before  in addition to the parameters obtained with DTI  . The kurfficient . Moreover before –38. Gener before , 30. Ther before  or due tr before , MS 31)b-values,r before , 36, 37,r before . Howeverr before . For exar before ] and othr before ]. Overalr before .How the magnetic field strength influences the sensitivity of dMRI to pathology has been less extensively investigated than the effect of the diffusion protocol, possibly because ultra-high-field (UHF) imaging  has only recently become relatively widely available for clinical research –45. For Apart from the diffusion protocol and the magnetic field strength, image processing can also affect sensitivity to pathology , 51–53. d was used as a measure of effect size, as it evaluates the difference in means between two populations normalized by their joint SD , the magnetic field strength (3T or 7T), and the inclusion of various processing steps . Data was acquired with three protocols: 3T-DTI, 3T-DKI, and 7T-DTI. The hypothesis was that 3T-DKI and 7T-DTI would show benefits compared with 3T-DTI, as these protocols are more resource-intensive in terms of either time (3T-DKI) or the use of a scarce but SNR-boosting resource (7T-DTI). We also hypothesized that a more extensive and, thus, computationally intensive processing pipeline that incorporates several state-of-the-art processing steps would be beneficial. To test these hypotheses, we performed a region-based effect-size analysis. Cohen's joint SD . The effjoint SD , 60.b-value scheme, and repetition and echo times (TR and TE) were adjusted for each protocol and system independently, and are reported in b-value data with lower SNR, the 3T-DKI was performed with a lower resolution than the 3T-DTI protocol in order to avoid noise-floor effects. A 7T-DKI protocol was not included due to limitations in total scan time per patient. The 7T-DTI protocol featured fewer encoding directions than the 3T-DTI protocol, also due to scan time prioritizations. The extent to which these protocol differences affected the results will be considered in the discussion.Imaging was performed on two different systems (3T Siemens Skyra and 7T Philips Achieva) with three different protocols, referred to as 3T-DTI, 3T-DKI, and 7T-DTI. The image resolutions, Table 3). Out of the 30 HC, 13 were scanned with all the three different protocols, 20 with at least 3T-DTI, 20 with at least 3T-DKI, and 21 with at least 7T-DTI. Out of the 76 patients with SLE, 59 were scanned with all the three acquisition protocols, 63 with at least 3T-DTI, 56 with at least 3T-DKI, and 54 patients with at least 7T-DTI.In total, 106 female subjects were scanned. Out of these, 76 were SLE patients and 30 HC. The Regional Ethical Review Board in Lund, Sweden approved the studies on 3T and 7T  and all participants gave written informed consent prior to the examinations. None of the controls had a history of neurologic, neurodegenerative, or psychiatric disorders. The 106 subjects were investigated with at least one of the acquisition protocols . We also evaluated the impact of Gaussian smoothing, by smoothing the diffusion-weighted imaging data using kernels with SDs ranging from 0 to 1 in units of 0.1 (refer to phase 4 in The seven pipelines that were examined in this study consisted of https://github.com/MIC-DKFZ/TractSeg).To obtain tract-specific parameter values, WM tract segmentation was performed using TractSeg , 60. ThiDiffusionKurtosisModel, again with weighted linear least squares. Examples of parameter maps are shown in We estimated the diffusion parameters using two approaches: DTI , which pd , which tends to be more heterogeneous and, thus, have higher SD than the controls group. This will, in turn, provide lower effect sizes than was would have been observed in a balanced setting. However, this does not affect the comparison of effect sizes, which is the main topic of the study.where uulations . Of noted in the absence of a true effect (a true d of zero) for group sizes of 56 and 20, as in 3T-DKI spans the range where the magnitude of d is below 0.54. Effect sizes larger than this can, thus, be considered significant on a 5% significance level  is less than 5% , that were weighted by each tract probability-mask. However, before the above multiplication, we first excluded the voxels that in the probability map had a probability value of less than 0.5.The results that are primarily reported have been derived from comparisons using all subjects, but complementary analyses were also performed using only subjects with data from all three protocols. These latter results are reported in the via MRI volumetry is approximately 0.07, 0.12, 0.08, and 0.07, respectively . In the end, we chose pipeline VII, which combines all three tested processing steps, since that pipeline was the closest among the four to the most preferable processing scheme in the literature , 52.Among all parameters from all protocols, the three that had the largest number of tracts with an effect size above 0.54 (significant before correction for multiple comparisons) were the mean and SD of FA and the mean RD, all derived by 3T-DTI. 3T-DTI yielded clearly higher effect sizes than 3T-DKI and 7T-DTI for the mean FA, with an average difference of 0.26 and 0.20, respectively. The FA was the parameter with the highest effect size overall. Among the DKI parameters, RK showed on average the largest effect sizes  yielded higher effect sizes than the 3T-DKI protocol for most parameters. In only three out of the eight parameter-wise comparisons, did DKI yield higher effect sizes: the mean AD and the SD of MD and RD refer to . OverallOur observation that DKI is less sensitive than DTI to WM pathology in SLE is not in accordance with findings in other pathologies. For example, DKI parameters revealed differences to a broader extent than DTI parameters across age groups , betweenb-values employed in DKI attenuate the signal considerably. This often necessitates a reduction in the spatial resolution to avoid the noise floor . Voxel size is known to affect group level results for DTI parameters . An incrse floor . In turnse floor .The field-strength analysis showed that 3T-DTI yielded smaller variation in tract volume and higher effect sizes than 7T-DTI. It could be argued that the latter was due to the shorter scan time of the 7T-DTI protocol, which featured fewer diffusion encoding directions than the 3T-DTI protocol . It, thus, had a slight disadvantage in terms of protocol performance. An additional analysis of a version of the 3T-DTI data subsampled to have only 30 directions did not substantially degrade its performance, however  rather than utilizing the higher baseline SNR for a higher resolution. Of note, De Santis et al. compared 3T-DTI and 7T-DTI at a higher image resolution than ours (1.5 mm isotropic) and found slightly higher effect sizes at 7T compared to 3T  was the most beneficial, whereas gross smoothing reduced effect sizes by up to 20%. Interestingly, smoothing has been applied in many studies involving DTI or DKI , 80–84.  did not . Note thWe identified four primary strengths of the current study. The first strength is the relatively large sample sizes (31 HC and 77 patients with SLE). Second, all processing steps were evaluated independently. Third, the segmentation of the tracts was performed by an automatic pre-trained method, which allowed us to not only investigate tracts over the whole brain but also eliminate bias from subjective tracking. Fourth, the statistical analysis of the tracts took place in the native space of each subject instead of a template space. Previous studies have predominantly used the Tract-Based Spatial Statistics (TBSS) pipeline to perform voxel-wise statistical between-group comparison of DTI/DKI metrics on MNI152 space . Howeverd is a metric of groupwise differences in the mean normalized by the joint SD. When computed per protocol, inter-protocol biases do not need to be considered. Third, the resolution of DKI was lower than that of DTI (2.3 mm isotropic vs. 2.0 mm isotropic). As mentioned above, the poorer resolution might explain the lower effect sizes with DKI, in particular, given that smoothing led to reduced effect sizes. Fourth, not all subjects were scanned with all three protocols, which might have induced some systematic sample-related differences in the results. However, the majority of subjects overlapped and the overall picture did not change when including only matching subjects . Even though patients with SLE manifest a variety of neuropsychiatric symptoms that resemble many other neurodegenerative diseases , 113, threfer to .In conclusion, effect sizes for detecting WM changes in patients with SLE were higher for DTI than DKI and higher for 3T than 7T. However, our results suggest that adjustments could be made to improve the protocols. For example, the sensitivity of 7T-DTI could potentially be enhanced by leveraging the higher baseline SNR of 7T for higher image resolution. Similarly, high-performance gradient coils could be utilized to reduce echo times and, thereby support a higher image resolution in DKI. Among the processing choices, eddy current and motion correction increase effect sizes, while no clear benefits seemed from denoising (MPPCA) and Gibbs-ringing removal. Smoothing was clearly detrimental for the effect sizes. However, the choice of diffusion protocol had a much greater impact than the choice of processing strategy.Data are available upon request to the authors. A formal data sharing agreement is required prior to sharing data. Raw imaging data cannot be shared due to legal concerns.The studies involving human participants were reviewed and approved by the Regional Ethical Review Board in Lund, Sweden. The patients/participants provided their written informed consent to participate in this study.EK contributed to the development of the pipelines, the conception and design of the analysis, the interpretation of the results, analysis of data and drafted the work. SW contributed to the design of the pipelines, the interpretation of data for the work and the revision of the work for important intellectual content. TR contributed to the acquisition of data for the work and the revision of the work for important intellectual content. AW contributed to the development of the pipelines. LK contributed to the revision of the work for important intellectual content. MC supervised the design of the pipelines and contributed to the interpretation of data for the work and the revision of the work for important intellectual content. PS contributed to the acquisition of data for the work, the interpretation of data for the work and the revision of the work for important intellectual content. MN contributed to the conception and design of the analysis, the interpretation of data for the work and the revision of the work for important intellectual content. All authors contributed to the article and approved the submitted version.The study was supported by Regional Research Funds (RegSkane-824651) (PS), SUS Foundation and Donations funds (PS), Alfred Österlund Foundation (PS), Swedish Rheumatism Association R-568371 (PS), and King Gustaf V's 80-year Foundation (FAI-2019-0559) (PS).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.


Preterm birth is defined as a syndrome that can be initiated via various mechanisms. During the past few decades, it has been an emerging health issue worldwide and thus, several actions to benefit public health have been undertaken to reduce its rate. Chorionic Villus Sampling (CVS) is one of the methods that are performed prognostically for prenatal diagnosis. However, several complications can occur after this invasive method is performed. The aim of this review is to identify whether CVS may result in preterm birth as a complication, compared to other invasive or non-invasive methods.A systematic literature review was conducted in PubMed and Scopus from inception until December 2021, to identify studies examining the above association. The research strategy included a combination of search and MESH terms related to CVS and preterm birth, Inclusion and exclusion criteria were set. The research was conducted by two researchers that thoroughly screened the articles and extracted the data.37 studies met the inclusion criteria. Comparisons were performed between CVS and amniocentesis or control group or between the different weeks that CVS was performed. No significant difference was observed in most of the studies when CVS was compared to amniocentesis, control groups, or between different weeks of gestation that was performed.The risk of preterm birth of women undergoing CVS was relatively lower or had no difference compared to the other methods or controls investigated. Therefore, CVS is considered as a safe prenatal diagnostic procedure with minimum rates of preterm birth as a complication.• The risk of preterm birth of women undergoing CVS was found to be relatively lower with no significant differences compared to the other methods or controls.• Future studies should be performed recruiting a large sample with women of different age and compare it with a control group that will not undergo any invasive method.


To evaluate the association between gestational diabetes mellitus (GDM) and infant outcomes in women of very advanced maternal age (vAMA) (≥45 years).This cohort study utilized data from the National Vital Statistics System (NVSS) database (2014–2019) in the United States. Preterm birth was the primary outcome, which was subdivided into extremely preterm, very preterm, and moderate or late preterm. The secondary outcomes were neonatal intensive care unit (NICU) admission, low birthweight and small for gestational age. Univariate and multivariate logistic regression analyses were used to explore the association between GDM and infant outcomes among vAMA women. Subgroup analyses were performed based on race and use of infertility treatment. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated.P < 0.001). Compared with women without GDM, those with GDM had a significantly increased risk of moderate or late preterm birth ; no significant association of GDM with extremely preterm birth and very preterm birth was observed. Women with GDM had a significantly greater risk of NICU admission than those without . GDM was associated with a significantly lower risk of low birthweight , and no significant association was found between GDM and small for gestational age  in vAMA women.A total of 52,544 vAMA pregnant women were included. All analysis made comparisons between women with vAMA and GDM and women with vAMA and no GDM. Women with GDM had a significantly higher risk of preterm birth than those without GDM (OR = 1.26, 95%CI = 1.18–1.36, vAMA women with GDM had an increased risk of preterm birth, especially moderate or late preterm birth. NICU admission and low birthweight were also associated with GDM among vAMA women.The online version contains supplementary material available at 10.1186/s12884-023-05449-0. Due to socio-economic development and advances in assisted reproductive technology (ART), the trend of more frequent births among older women, particularly those of very advanced maternal age ≥45 years) (vAMA), is likely to continue . A consi5 years (Preterm birth (< 37 weeks of gestation) is a common adverse infant outcome, resulting in approximately 1 million infant deaths each year . Even ifThis study aimed to evaluate the associations of GDM with preterm birth, NICU admission, low birthweight and small for gestational age in vAMA women using the National Vital Statistics System (NVSS) database (2014–2019) in the United States. Given that these associations may vary by race and use of infertility treatment, we further performed subgroup analyses.This was a cohort study. All data of pregnant women aged 45 or older who were tested for GDM and did not have pre-gestational diabetes were extracted from the NVSS 2014–2019. The NVSS database provides data on births and deaths as well as maternal characteristics in 50 states, New York City, District of Columbia, and 5 territories  of the United States . Partici2, underweight; BMI = 18.5–24.9 kg/m2, normal; BMI = 25.0–29.9 kg/m2, overweight; BMI = 30.0–34.9 kg/m2, obesity), delivery weight (lb), weight gain (lb), smoking before pregnancy (yes or no), smoking status 1st/2nd/3rd trimester , hypertension eclampsia (yes or no), gestational hypertension (yes or no), pre-pregnancy hypertension (yes or no), number of prenatal visits, the Special Supplemental Nutrition Program for Women, Infants, and Children , plurality, prior birth now living, prior birth now dead, prior other terminations, total birth order, gestational age (weeks), newborn sex , birth weight (g), infertility treatment used (yes or no), pregnancy method , method of delivery , preterm birth , NICU admission, low birthweight (yes or no), and small for gestational age (yes or no). WIC is a program intended to help low income pregnant women, infants, and children through age 5 receive proper nutrition by providing vouchers for food, nutrition counseling, health care screenings and referrals; it is administered by the U.S. Department of Agriculture . Infertility treatment referred to using fertility enhancing drugs, artificial insemination, intrauterine insemination, or using ART. ART included in vitro fertilization (IVF), gamete intrafallopian transfer (GIFT), and zygote intrafallopian transfer (ZIFT). Information on variables is available at https://www.cdc.gov/nchs/nvss/index.htm.Preterm birth was the primary outcome of this study, which was defined as births before 37 completed weeks of gestation. The World Health Organization (WHO) further subdivided preterm birth based on gestational age: extremely preterm (< 28 weeks), very preterm (28 to < 32 weeks), and moderate or late preterm (32 to < 37 weeks) . Seconda1, Q3)], and the Wilcoxon rank sum test was used for comparisons between groups. Categorical data of groups were compared with the Pearson’s χ2 test, and expressed as cases and the constituent ratio [n (%)]. Statistical power was calculated (power = 1). Missing data were imputed using multiple imputation , and the t-test was used for comparisons between groups. Non-normally distributed continuous variables were shown by median and quartile , anIn order to study the association between GDM and preterm birth among vAMA women, we established three models, and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. Model 1 was a univariate model. Model 2 was a multivariate model adjusting for maternal age at delivery, race, education, and newborn sex. Then all variables were included in a multivariable model for stepwise regression, and the following variables were adjusted for in Model 3: maternal age at delivery, race, education, newborn sex, pre-pregnancy weight, pre-pregnancy BMI, delivery weight, weight gain, smoking before pregnancy, hypertension eclampsia, gestational hypertension, pre-pregnancy hypertension, number of prenatal visits, plurality, total birth order, prior birth now living, prior other terminations, birth weight, pregnancy method, and method of delivery. Subgroup analyses were then performed based on race and use of infertility treatment to demonstrate if and how the association between GDM and preterm birth in vAMA women varied by race and use of infertility treatment. Further, preterm birth was subdivided into extremely preterm, very preterm, and moderate or late preterm birth. Logistic regression was used to investigate the association between GDM and different stages of preterm birth. Model 1 was a univariate model. Model 2 was a multivariate model correcting for maternal age at delivery, race, education, and newborn sex. Model 3 was a multivariate model correcting for maternal age at delivery, race, education, newborn sex, delivery weight, smoking status 2nd trimester, hypertension eclampsia, gestational hypertension, pre-pregnancy hypertension, number of prenatal visits, WIC, plurality, prior other terminations, total birth order, birth weight, pregnancy method, and method of delivery. As for the associations of GDM with NICU admission, low birthweight and small for gestational age in vAMA women, analytical methods were the same as those for the association between GDM and preterm birth, and subgroup analyses by race and use of infertility treatment were also conducted for these outcomes.P < 0.05 was considered to be statistically significant. All analyses were completed by SAS 9.4 software .All statistical analyses were two-sided, and n = 830), and women with missing information on gestational weeks (n = 41), newborn birth weight (n = 39), and NICU admission records (n = 30), 52,544 pregnant women were included in this study. The follow-up time was 37.62 ± 2.97 weeks. Figure There were a total of 53,484 pregnant women of vAMA in the NVSS database 2014–2019). After excluding women with infections presenting or treated during this pregnancy (4–2019. AP < 0.001), education (P < 0.001), pre-pregnancy weight (P < 0.001), pre-pregnancy BMI (P < 0.001), delivery weight (P < 0.001), weight gain (P < 0.001), number of prenatal visits (P < 0.001), prior other terminations (P < 0.001), total birth order (P < 0.001), WIC (P < 0.001), gestational age (P < 0.001), preterm birth (P < 0.001), prior birth now living (P < 0.001), prior birth now dead (P = 0.021), hypertension eclampsia (P = 0.020), gestational hypertension (P < 0.001), pre-pregnancy hypertension (P < 0.001), NICU admission (P < 0.001), method of delivery (P < 0.001), low birthweight (P = 0.030), infertility treatment used (P = 0.004), pregnancy method (P = 0.002) . Based on sensitivity analysis, the results were consistent before and after imputation. For different races, it was demonstrated that GDM was associated with a significantly increased risk of preterm birth in Asian  and White women . GDM was correlated to a significantly greater risk of preterm birth among women without  and with  infertility treatment ; no significant association was observed between GDM and extremely preterm birth and between GDM and very preterm birth . Based on sensitivity analysis, the results were consistent before and after imputation. According to subgroup analysis, GDM was associated with a significantly increased risk of NICU admission in Asian , Black , White , and other  races; a significant elevated risk of NICU admission was found in women with GDM, regardless of whether they received infertility treatment  or not  . Based on sensitivity analysis, the results were consistent before and after imputation. GDM was related to a significantly lower risk of low birthweight among Blacks . In women without infertility treatment, GDM was associated with a significantly reduced risk of low birthweight  . Based on sensitivity analysis, the results were consistent before and after imputation. As regards different races, White women with GDM had a significantly decreased risk of small for gestational age . There was no significant association between GDM and small for gestational age in women with non-infertility treatment and infertility treatment  in vAMA women applying data from the NVSS database. GDM was identified to be positively associated with the risk of preterm birth, especially moderate or late preterm birth; the risks of NICU admission and low birthweight were correlated with GDM in women of very advanced age. According to a prior meta-analysis, women ≥35 years old were more likely to have GDM and worse perinatal outcomes including preterm delivery, low birthweight infants and higher rates of NICU admission , which wAs for the possible causes of the association between GDM and preterm delivery in vAMA women, GDM has been associated with polyhydramnios , 32, andInterestingly, we found that the association between GDM and preterm birth varied by race in vAMA women. GDM was associated with a significantly higher risk of preterm delivery among Asians and Whites, while no association was identified among Blacks and other races. Some studies pointed out that in the United States, non-Hispanic Black race (compared with non-Hispanic White race) was a risk factor for preterm birth , 40, whin = 52,544) with adequate power (power = 1) was utilized to assess the associations between GDM and adverse infant outcomes  in pregnant women of very advanced age, making the results reliable. Different stages of preterm birth were also analyzed, and the aforementioned associations were further evaluated according to race and use of infertility treatment, which provides additional insights into these associations for different populations.Our study has several strengths. A large, nationally representative sample size , physical activity, psychological and social stress and depression during pregnancy, blood glucose, medication use , and socioeconomic factors (apart from education and WIC), which may influence our results. Third, this study focused on the U.S. population and has limited generalizability. Future studies are required to investigate the relationship between GDM and infant outcomes in vAMA women with consideration of the above covariates, so as to confirm our findings. This relationship can also be evaluated in populations from other countries. Notably, 76.92% of preterm births were caused by indicated delivery. Hypertension and the pregnancy method may be related to indicated preterm delivery in vAMA women. Future research can investigate the indications for indicated preterm delivery, and assess whether hypertension and the pregnancy method are associated with indicated preterm delivery.Based on our findings, vAMA women with GDM had higher risks of preterm birth and NICU admission than those without. Greater attention should be paid to vAMA women with GDM and early interventions should be taken to lower the risks. Improving GDM may be a viable approach. Since populations grouped by age and use of infertility treatment had different risks of adverse infant outcomes, individualized measures should be developed. vAMA women with pregnancy planning should be informed of increased risks of preterm birth and NICU admission when they had GDM and corresponding advice can be provided by clinicians or healthcare givers.GDM was associated with an increased risk of preterm birth, especially moderate or late preterm birth; the risks of NICU admission and low birthweight were correlated with GDM among vAMA women. More investigations are warranted to verify this conclusion.Additional file 1: Supplementary Table 1. Proportion of missing values.


N = 500) completed the PSAS alongside measures of subjective birth satisfaction and objective obstetric interventions/complications. Confirmatory factor analyses [CFA] tested eight models, theoretically derived from the preceding exploratory work. Structural equation modelling [SEM] tested associations between each PSAS factor and birth experience variables in the best-fitting model. An identical 51-item four-factor model fits the data well. SEM analyses revealed associations between lower perceptions of quality of intrapartum care and increased maternal competence and attachment anxieties, practical infant care anxieties, and infant safety and welfare anxieties. High subjective stress and negative emotional response to labour were associated with increased psychosocial adjustment to motherhood anxieties. Specific associations were found between neonatal care unit admission and practical infant care anxieties; and infant asphyxia and infant safety and welfare anxieties. Findings confirm construct and convergent validity of the four-factor PSAS and its use in measuring postpartum anxiety. Unique associations were also identified, indicating specific subjective and objective experiences occurring during birth may elicit a differential anxiety response, in that they are related to specific forms of postpartum anxiety which occur during the first postpartum year.The Postpartum Specific Anxiety Scale [PSAS] was developed and validated as a research tool with a four-factor structure; with predictive validity corroborated in studies examining infant-feeding and maternal bonding outcomes. The PSAS has not been examined in relation to birth experiences. We aimed to confirm the PSAS four-factor structure and examine these domains of anxiety in relation to subjective and objective birth experiences. Postpartum mothers (≤ 12-months;  The increasing recognition and prevalence of postpartum anxiety along with the persistent and far-reaching effects for mothers and infants poses a significant health and economic burden for healthcare systems and wider society  demonstrated the PSAS had good construct and convergent validity and excellent internal and test–retest reliability. The scale had a simple four-factor structure expressed as: (1) maternal competence and attachment anxieties, (2) infant safety and welfare anxieties, (3) practical infant care anxieties, and (4) psychosocial adjustment to motherhood.The Postpartum Specific Anxiety Scale .N = 500) with infants aged between birth and 12 months were recruited via advertisements posted on Facebook, Twitter, and other parenting sites and social media platforms which contained a link to an on-line survey about anxiety and birth experiences. Mothers had to be ≥ 18-years to participate. Maternal age ranged between 19 and 44 years  and infant age ranged between birth and 12 months . Women were predominately white (95%), from the UK (75%), married (58%), university educated (65%), and professionals (39%). Furthermore, 123 had a self-reported clinical diagnosis of anxiety (25%) and 90 had a self-reported clinical diagnosis of depression (18%). In relation to objective birth experience, 188 women had labour induced (38%), 123 women underwent a Caesarean section (25%), 65 women reported augmentation of labour (13%), 46 women experienced perineal laceration (9%), 43 women experienced breech birth (9%), 61 women experienced infant admission to neonatal care (12%), 52 women experienced a postpartum infection (7%), 49 women experienced postpartum haemorrhage (10%), 30 women experienced infant umbilical cord issues during birth (5%), 10 women’s infants experienced birth asphyxia (1.5%), and 10 women experienced placenta praevia (1.5%). Mean score for stress and emotional response to childbirth  were 4.23 (SD = 1.91), and that for quality of care experienced during childbirth  were 0.70 (SD = 1.26). Maternal and infant demographic and birth experience information can be found in Tables An opportunity sample of English-speaking mothers  being admitted to the main survey. Following this, an electronic information sheet and consent form were provided to confirm informed consent. The survey contained 82-items in total took 15-20 minutes to complete. Every item was compulsory (i.e. ‘forced response’). Upon completion, participants were provided with a full electronic debrief with signposting to relevant support information and were entered into a £25 prize draw. Responses were provided with a unique ID embedded within the survey software programme ensuring anonymity. Additionally, a ‘prevent ballot box stuffing’ option was embedded in the Qualtrics XM survey software preventing repeat responses.Maternal-related demographic questions were asked at the beginning of each survey including maternal age, country of residence, ethnicity, marital status, occupation, educational attainment, self-reported clinical diagnosis of anxiety, and self-reported clinical diagnosis of depression. Infant-related demographic questions were asked including, infant age, birth weight, multiple birth, birth order, and current feeding practices.The PSAS is a 51-item scale examining frequency of maternal and infant focused anxieties experienced by women during the first year following birth. The measure assesses four components of anxiety, specific to the postpartum period. Factor 1  contains 15-items addressing anxieties relating to maternal self-efficacy, parenting competence, and the mother–infant relationship. Factor 2 (Infant Safety and Welfare Anxieties) contains 11-items relating to fears about infant illnesses, accidents, and cot death. Factor 3  contains 7 items addressing anxieties relating to infant care such as feeding, sleeping, and general routine. Finally, Factor 4  contains 18 items addressing adjustment concerns following birth of the infant regarding management of personal appearance, relationships and support, work, finances, and sleep. Each answer is given a score on a Likert scale between 1 (‘Not At All’) and 4 (‘Almost Always’), with the maximum score being 204. Furthermore, scores of ≥112 may be indicative of clinically significant anxiety. The PSAS demonstrates excellent reliability .Objective birth experience questions were co-created with a midwife and addressed the presence of experiences including Caesarean section, induction, augmentation, infant admission to neonatal intensive care unit [NICU], forceps or ventouse assisted birth, postpartum haemorrhage, breech birth, postpartum maternal infection, infant asphyxia, placenta praevia, umbilical cord issues, and perineal laceration. These were presented as a list of different experiences and asked participants to tick which ones applied to their birth.The BSS-RI is a six-item questionnaire measuring women’s satisfaction with care and the experience of labour and birth. The scale assesses two domains of birth satisfaction, stress and emotional response experienced during childbearing and quality of care. Each item is scored on a Likert scale between 0 (‘Agree’) and 2 (‘Disagree’), with higher scores indicating a more positive appraisal of birth satisfaction. The BSS-RI demonstrates good reliability .A confirmatory factor analysis was performed using R version 4.0 using diagonally weighted least squares estimation Mîndrilã . Items wLinear regressions were then conducted using diagonally weighted least squares estimations to test associations between the subjective birth experience subscales  and the PSAS subscales. Binomial logistic regressions were then conducted using generalised linear model estimations to test associations between objective birth experiences and the PSAS subscales.p < .001). The four factors had good-to-excellent reliability . The overall scale demonstrated excellent reliability  . Modification indices indicated a covariance should be added between two pairs of residuals MI’s ≥ 10). As a result, the model fit improved . All items significantly loaded onto each factor (0. As a rp = .012). The model also found significant associations between low quality of care experienced during childbirth and high competence and attachment anxieties ; high infant safety and welfare anxieties ; and high practical infant care anxieties   and asphyxia and infant safety and welfare anxieties   maternal competence and attachment anxieties; (2) infant safety and welfare anxieties; (3) practical infant care anxieties; and (4) psychosocial adjustment to motherhood. The final model fits the data well and internal consistency was excellent, providing further supporting evidence for the reliability and construct validity of the PSAS. Importantly, this study also extends the utility of the PSAS for research across the first postpartum year.The confirmed structure also reflects more recent validations using the briefer derivatives of the PSAS: the 16-item Research Short Form (PSAS-RSF; Davies et al. The second aim of the study was to model associations between subjective and objective birth experiences and the individual PSAS subscales in the first postpartum year. The findings provide further evidence for the convergent validity of the PSAS, and also support our hypothesis, in that elements of both subjective and objective birth experience were associated with different domains of postpartum anxiety. In terms of subjective birth experience, poorer perceptions of quality of care experienced during birth were associated with higher levels of maternal competence and attachment anxieties, infant safety and welfare anxieties, and practical infant care anxieties. These findings reflect other work which has demonstrated the importance of quality of care during birth for maternal self-efficacy (Bryanton et al. Objective birth experience findings demonstrated infant NICU admission was associated with practical infant care anxieties across the first postpartum year. Infant admissions to NICU typically involve alteration to the immediate caregiving role, which has been noted in a recent review as the principal stressor for NICU parents (Govindaswamy et al. However, this differential anxiety response hypothesis is tentative as it was not supported in the other objective birth experience analyses. Both infant admission to NICU and infant asphyxia are serious and often unanticipated obstetric experiences with serious implications for infant health. Early stress research demonstrated the magnitude of a particular stressor determines the level and duration of the stress response (Horowitz et al. Should findings be replicated in other studies, healthcare professionals should be made aware that if mothers experience certain complications or interventions during birth, they may be more prone to experiencing certain forms of anxiety and therefore can be supported appropriately. For example, upon discharge from NICU, mothers may be offered further information on routine infant care tasks, which may alleviate these anxieties. Likewise, for mother of a baby who experienced infant asphyxia, additional reassurance from postnatal care providers should be offered to ameliorate infant safety and welfare anxieties upon discharge. Finally, if women present to primary care services or are noted in universal postnatal care provision, to have particular anxieties, healthcare providers should explore whether these anxieties are a result of an unresolved negative birth experience. Unlike the general anxiety measures currently used in clinical practice, using childbearing specific psychometric tools, such as the PSAS, may therefore facilitate conversations between healthcare providers and women who are presenting with postpartum anxiety symptoms. Future work to develop a modified clinical version of the PSAS is both necessary and imminent.Our sample size was adequate for the analyses performed, but a common problem in perinatal research conducted with online samples is homogeneity in demographic characteristics (Vignato et al. differential anxiety response hypothesis is therefore postulated. Further longitudinal studies are needed to examine the relationship between birth experiences and the PSAS subscales further and test this hypothesis.The current study confirmed the four-factor structure of the original 51-item English language PSAS and adds to a growing body of international evidence for the validity and reliability of the tool for assessing maternal and infant focused anxieties. We also provide the first evidence for the convergent validity of the PSAS in relation to subjective birth experiences. Notably, findings suggest specific objective and subjective experiences which occur during birth are related to specific forms of postpartum anxiety—a