To study the diffusion tensor-based fiber tracking feasibility to access the male urethral sphincter complex of patients with prostate cancer undergoing Retzius-sparing robot-assisted laparoscopic radical prostatectomy (RS-RARP).b value = 600 s/mm2. Acquisition parameters, together with patient motion and eddy currents corrections, were evaluated. The proximal and distal sphincters, and membranous urethra were reconstructed using the deterministic fiber assignment by continuous tracking (FACT) algorithm, optimizing fiber tracking parameters. Tract length and density, fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) were computed. Regional differences between structures were accessed by ANOVA, or nonparametric Kruskal–Wallis test, and post-hoc tests were employed, respectively, TukeyHSD or Dunn’s.Twenty-eight patients (median age of 64.5 years old) underwent 3 T multiparametric-MRI of the prostate, including an additional echo-planar diffusion tensor imaging (DTI) sequence, using 15 diffusion-encoding directions and a The structures of the male urethral sphincter complex were clearly depicted by fiber tractography using optimized acquisition and fiber tracking parameters. The use of eddy currents and subject motion corrections did not yield statistically significant differences on the reported DTI metrics. Regional differences were found between all structures studied among patients, suggesting a quantitative differentiation on the structures based on DTI metrics.The current study demonstrates the technical feasibility of the proposed methodology, to study in a preoperative setting the male urethral sphincter complex of prostate cancer patients candidates for surgical treatment. These findings may play a role on a more accurate prediction of the RS-RARP post-surgical urinary continence recovery rate. Urethral sphincter complex DTI is feasible at 3 T for prostate cancer patients.Subject motion and eddy currents corrections did not significantly influenced DTI metrics.DTI derived metrics differentiate the structures of the patients’ urethral sphincter complex.Study findings are a start point to predict post-surgical continence recovery rate.The male urethral sphincter complex is responsible for the maintenance of continence in rest and stress conditions and is comprised of two structural components, the proximal lissosphincter and the distal rhabdosphincter . WhereasDespite the latter, post-surgical urinary incontinence is still a common and incompletely understood long-term limiting side effect that severely impacts a patients’ quality of life . The knoThe aim of the present study was to visualize, map, and extract relevant DTI metrics in a larger dataset of male patients with prostate cancer that underwent RS-RARP, establishing a method for acquiring and processing this type of data. We intended to optimize acquisition parameters considering scan time and in-plane resolution, to select fiber tracking parameters for a deterministic tractography algorithm and to evaluate the need for eddy currents and patient motion correction. So, this study’s main purpose was to prove the technical feasibility of a 3 T MR-DTI sequence and to establish normative DTI metrics that could differentiate between the structures of the male urethral sphincter complex of prospective RS-RARP patients.3 were collected  were used for the processing and quantitative image analysis. Numeric variables age, body mass index (BMI), preoperative prostate-specific antigen (PSA) levels in ng/mL, and prostate volume (PV) in cmed Table . Additio3, field of view = 200 × 200 × 90 mm3, number of averages = 2, in-plane resolution = 0.31 × 0.31 mm2, slice thickness = 3 mm, slice number = 30, gap = 0.3 mm -, it was also implemented a DTI sequence for 3D visualization of the male urethral sphincter complex. This sequence was acquired in the Anterior–Posterior phase encoding direction by means of single-shot diffusion-weighted echo-planar imaging (DW-EPI) with parallel SENSE (sensitivity encoding) technique, using a reduction factor of 2. Acquisition parameters included 15 diffusion-encoding directions, b-value of 0 (b0) and 600 s/mm2, echo time = 68 ms, repetition time = 6600 ms, matrix size = 68 × 65 × 40 mm3, field of view = 200 × 200 × 120 mm3, number of averages = 1, in-plane resolution = 1.39 × 1.39 mm2, slice thickness = 3 mm, slice number = 40, gap = 0.3 mm, representing a sequence time of four minutes. Acquisition coverage, including the whole prostate gland and penile bulb, can be depicted in Fig. 2, for comparison purposes. For a subset of 17 patients, each image volume was co-registered to the baseline image (without diffusion weighting) to correct for patient motion. Additionally, for five of these patients, a DTI sequence was scanned with a b-value of 0 s/mm2 (b0) in the Posterior-Anterior (PA) phase-encoding direction to further correct for susceptibility induced distortions.Patients were scanned at a 3 T MRI scanner , equipped with a 32-channel phased-array abdominal coil, parallel imaging, and multi transmission radio-frequency capabilities. All participants were asked to fast for 4 h before the examination and to apply a microlax to minimize intestinal peristalsis that causes artifacts, although no empty bladder requirements were imposed. Apart from the standard clinical multiparametric-MRI protocol—including a T2-weighted sequence with the following parameters: echo time = 125 ms, repetition time = 4900 ms, matrix size = 288 × 230 × 30 mmeddy from FSL after calculating the susceptibility-induced off-resonance field using TOPUP that follows the method described in [To evaluate if the eddy currents induced-distortions were significant, the prostate contour was manually traced by the first author on the b0 image and overlaid on the DW image with a higher b-value and verified by a radiologist with more than 10 years of clinical experience in prostate imaging Fig. —A1 to C2ribed in  as impleribed in .Fig. 3OnTensor estimation and fiber tractography were performed using DSI Studio with the deterministic fiber assignment by continuous tracking (FACT) algorithm  for fibeTo determine optimal FA and angular thresholds, seeds were placed on the prostate and surrounding areas and a whole region fiber tractography was constructed while varying the thresholds manually Fig. . Based o3), fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) were extracted. FA is dimensionless, whereas AD, MD, and RD are in 10–3 mm2/s. Tract density was calculated by dividing the number of tracts by the volume occupied. Regional differences, meaning intra-subject DTI metrics differences between the proximal and distal sphincters and membranous urethra, were accessed by a one-way ANOVA . Additionally, the same statistical tests were used to compare DTI metrics using the two eddy currents correction methods and without correction. The comparison of DTI metrics with and without patient motion correction was done using a student’s t-test (or the nonparametric Mann–Whitney). Tukey or Dunn post-hoc tests followed ANOVA or Kruskal–Wallis, respectively. Statistical testing was conducted in Software R, v.3.5.0 [For each structure of every patient, seven DTI metrics were automatically calculated, the tract length (in mm) number and volume , green for anterior–posterior (y), and blue for superior-inferior (z). Furthermore, the fiber tractography results for the structures of interest, color-coded based on the DTI metric values, are represented on Fig. For one patient, the fiber orientation of the structures of interest can be observed Fig. —B1–B3 byMedian, interquartile range (IQR) and range (minimum and maximum) values on each DTI metric for the proximal, distal sphincters, and membranous urethra of the patients under study are represented on Table 2 and 15 diffusion-encoding directions allowed to get a good image resolution and to minimize sequence time up to four minutes. The choice of a lower b-value comparing to that used in brain studies was made on the basis of boosting the signal to noise ratio keeping a rather comfortable acquisition time. Also, the number of diffusion encoding directions was decreased which visually did not changed the overall shape of the structures, while enabling the increase in the number of acquired slices. Additionally, the refining of fiber tracking parameters for the fiber assignment by continuous tracking (FACT) algorithm on DSI Studio yielded a good fiber tracking representation of the sphincters and the membranous urethra. In fact, the selected values on FA threshold acknowledged that lower FA caused fibers to be tracked outside the structures of interest, whereas higher values restrained too much the tracked fibers. Subject motion and eddy currents corrections of prostate diffusion tensor images were not performed in most existing studies [The purpose of this study was to demonstrate the technical feasibility of a DTI sequence, that could potentially be implemented into the current imaging protocols to in vivo investigate the microstructure of the male urethral sphincter complex of prostate cancer patients undergoing RS-RARP. For this, various aspects on DTI of the male urethral sphincter complex were taken into account including the acquisition parameters, fiber tracking parameters and patient motion and eddy currents corrections, to optimize fiber tracking results. It was found that a single-shot DW-EPI sequence with parallel SENSE technique on a 3 T MRI scanner, using a b-value of 600 s/mm studies –24. In tNot only the proximal and distal sphincters (circular fibers), and membranous urethra  can be correctly depicted for twenty-eight patients, but also quantitative DTI metrics seem to be able to differentiate them. ANOVA comparisons, or the nonparametric test extension, on mean values of DTI metrics have identified statistically significant regional differences between structures, which proves the possibility of using DTI metrics to discriminate individual structures of the male urethral complex. For instance, FA in the proximal sphincter was statistically significantly increased compared with the other structures, concordantly with previous findings.The potential utility of DTI tractography of the structures of the urethral sphincter complex has been demonstrated by Zitja et al. that have investigated pelvic floor dysfunction in female subjects , and by In terms of study limitations, it is important to refer this study’s relatively small sample size (28 subjects), although larger than in previous studies on the sphincters , 25. In In this study, the visualization and quantification of the structure of the male urethral sphincter complex before RS-RARP was demonstrated to be feasible using the proposed optimized DTI methodology. This may guide surgeons prior to the procedure or aid in a treatment informed choice by presenting to patients his rate of post-surgical continence recovery based on individual sphincteric characteristics. Further studies are needed to investigate age-related differences of the male urethral sphincter complex, to correlate DTI findings with post-surgical questionnaire test scores that measure incontinence, and eventually, to test the reproducibility of DTI as a clinical tool.


Complications due to prematurity are a threat to child survival and full developmental potential particularly in low-income settings.The aim of the study was to determine the neurodevelopmental outcomes among preterm infants and identify any modifiable factors associated with neurodevelopmental disability (NDD)We recruited 454 babies  in a cohort study at birth from Iganga hospital between May and July 2018. We followed up the babies at an average age of 7 months (adjusted for prematurity) and assessed 211 preterm and 187 term infants for neurodevelopmental outcomes using the Malawi Developmental Assessment tool. Mothers were interviewed on care practices for the infants. Data were analyzed using STATA version 14.The study revealed a high incidence of NDD of 20.4% (43/211) among preterm infants compared to 7.5% (14/187) among the term babies, p < 0.001, of the same age. The most affected domain was fine motor (11.8%), followed by language (9.0%). At multivariate analysis, malnutrition and Kangaroo Mother Care (KMC) at home after discharge were the key factors that were significantly associated with NDD among preterm babies. The prevalence of malnutrition among preterm infants was 20% and this significantly increased the odds of developing NDD, OR = 2.92 (95% CI: 1.27–6.71). KMC practice at home reduced the odds of developing NDD, OR = 0.46, (95% CI: 0.21–1.00). Re-admission of preterm infants after discharge (a sign of severe illness) increased the odds of developing NDD but this was not statistically significant, OR = 2.33 (95% CI: 0.91–5.94).Our study has shown that preterm infants are at a high risk of developing NDD, especially those with malnutrition. Health system readiness should be improved to provide follow-up care with emphasis on improving nutrition and continuity of KMC at home. Complications due to prematurity and low birth weight are the leading cause of neonatal deaths worldwide, and in 2018 they contributed about 34% of the 2.5 million newborn deaths ,7. SurviInstitutional deliveries have increased over time in LICs, and in Uganda over 70% of mothers deliver from health facilities . EvidencThe few studies conducted in sub-Saharan Africa have focused on long-term outcomes of preterm babies, usually starting in the post-infancy period –18. A stThe aim of the current study was to determine the neurodevelopmental outcomes of preterm infants as compared to term normal birth weight babies, and identify any modifiable factors associated with NDD among preterm infants at 6–8 months of age in eastern Uganda in order to inform interventions that can appropriately address these challenges.The study utilized a prospective cohort design where preterm babies (exposed) and term/normal birth weight babies (unexposed) delivered in Iganga district hospital in Busoga region in eastern Uganda were followed up until 6 months (corrected age for the preterms) to establish their neurodevelopmental outcomes. Busoga region is the third largest region in Uganda with a population of about four million people, where over 80% reside in rural areas and depend on subsistence farming. The area is served by five general hospitals, including Iganga hospital and one regional referral hospital, with varying levels of capacity of neonatal care, with no access to neonatal intensive care or cerebral imaging.Iganga hospital is a 100-bed capacity hospital although by the time of the study it was admitting about 200 patients. The hospital served another five adjacent districts without hospitals. The annual deliveries in Iganga hospital were 7,113 in 2018, 10% of whom were preterm and low birth weight babies admitted to the neonatal care unit (NCU). The NCU was run by three midwives, student nurses, and a pediatrician who was based on the pediatric ward and visited the unit occasionally. The unit had incubators, oxygen cylinders and concentrators, a phototherapy machine, an improvised continuous positive airway pressure (CPAP) machine and other supplies essential for neonatal care. The hospital was one of the study sites for the Preterm Birth Initiative study (2016 to 2019) which provided some of the equipment and essential supplies at the start of the intervention ,24. HoweThe study population included babies born in Iganga hospital, who were preterm (with gestation age <37 weeks and Birth weight <2.5 kg) or term/normal birth weight babies, whose mothers were residents within a 20 km radius area of that hospital. The recruitment occurred at discharge for 3 months from May to July 2018. Neurodevelopmental assessment was carried out from November 2018 to May 2019 when the babies were 6–8 months of age (corrected for the preterm babies). We excluded all newborn babies who died before discharge and those with any congenital malformations such as spina bifida. Babies who died after recruitment were documented and reported but were excluded from the analysis for neurodevelopmental outcomes.A sample size of 454 participants (242 preterm-exposed and 212 term babies-non-exposed) achieving a power of 80% was computed using a sample size formula with the continuity correction (CC) factor by Fleiss , where wWe recruited preterm babies with gestation age (GA) <37 weeks and a birth weight of less than 2.5 kg consecutively until the sample size of 242 babies was attained. We assessed GA using the New Ballard score sheet  within 2Three midwives (one per duty shift) employed by the hospital were trained by the first author for 2 days to identify and register the eligible preterm and term infants in the same hospital. After obtaining informed consent, a questionnaire was administered to capture mothers’ socio-demographic characteristics, the antenatal care practices including use of anti-anemia medicines (Ferrous/Folate tablets), and any maternal morbidities like malaria in pregnancy, high blood pressure, diabetes, and history of admission during pregnancy. The physical location description to aid follow-up was also captured. Records were checked for perinatal factors surrounding the birth of the baby including duration of labor, labor complications , and the mode of delivery. The essential newborn care within the health facility was also documented. This included birth weight, head circumference measurement, APGAR score of the baby, and KMC for the preterm babies.Mothers were reached on phone at 3-months post discharge to ascertain whether the place of residence of the mother-baby pair had not changed. We employed five nurses/midwives as research assistants, supervised by the first author, for follow-up activities at 6 months of infants’ age (corrected age for preterm infants). We used the physical location description obtained from the mother either at the time of recruitment, or at 3 months (if location changed) and the telephone contacts given to locate the residence of the mother/baby pair. In some situations, babies could not be located at 6 months but at a later date due to challenges in identifying the physical location, or where mothers had travelled for various reasons, and gave appointments of home visit upon return. In other situations, the mother together with the infant had shifted from the original location to faraway places outside the catchment/study area. Such infants were considered as lost to follow-up. Similarly, those whose phone contacts were off on five attempts, and the physical locations given could not be traced, were registered as lost to follow-up.The research assistants were trained for 5 days to conduct physical and neurodevelopmental assessment of infants at 6 months (or more) after birth (corrected age for preterms). We used the Malawi Developmental Assessment Tool (MDAT) to assess the neurodevelopmental outcomes . The MDANeurodevelopmental assessment including Gross and Fine motor, Language and Social behavioral development were determined through use of the MDAT tool at 6–8 months’ chronological age for term infants, and corrected (adjusted) months of age for the preterm infants. Each child was scored either Pass or Fail for each domain per given age. The child was scored as fail in a given domain, if he/she failed more than two parameters of the expected at that age . Data frDescriptive statistics were used, stratified by term/preterm status of the infants, to determine the incidence of neurodevelopmental delay/disability. Chi-square tests were applied to categorical variables to assess any differences in maternal and infant characteristics as well as neurodevelopmental outcomes, between the preterm and term babies. In addition, odds ratios and confidence intervals were used to determine any factors associated with NDD among preterm babies.The Z-test was used to determine the infants’ physical development in terms of weight gain for age. Those whose Z-scores were less than −2 were considered to be under weight, while between −2 and −3 were said to be having moderate malnutrition, and those whose Z-scores were <-3 were categorized as severely malnourished. The physical development data were analyzed using the two – sample t-test to assess whether there is a difference in rate of physical development in terms of the mean weight, and mean head circumference between the term and preterm babies.A multivariable logistic regression was used to model the relationship between neurodevelopmental outcome among infants born preterm and the following independent factors: readmission of the infant after discharge following birth, the nutrition status , KMC at home, mother’s parity, and father’s occupation as a proxy for socioeconomic status. We examined the model goodness of fit using the Hosmer Lemeshows goodness of fit test, the model was considered a good fit if the p-value was less than 0.05. Non-significant factors or predictors were dropped except for those known predictors from literature. We used the log-likelihood ratio test to compare two models that is the full model and the reduced model and the AIC/BIC criteria to select a parsimonious model. We tested for presence of multicollinearity using variance inflation factor (VIF) analyses. Multicollinearity was present if VIF was >10 or tolerance (1/VIF) was <0.1 for any independent factors in the model. A parsimonious model was presented along with model fit statistics.Of the 454 infants recruited 398 (87.7%) were reached for neurodevelopmental assessment. Fifteen (15) infants (3.3%), all preterms, died between recruitment at discharge from the health facility and at 7 months of follow up .Figure 1The results show that there were significant variations in maternal characteristics among mothers with preterm babies compared to those with term babies . SpecifiThe study findings revealed no differences in gender between the preterm and term infants . The meaThe mean age at follow up was 7.2 months for term infants and 6.6 months corrected age for preterm babies. There were no differences in the percentage of preterm and term babies who developed complications after discharge, and those who sought care at the health facility. However, more preterm babies (22.4%) were admitted between discharge and the follow-up period compared to 12.7% term babies, p = 0.083 .The study results revealed significant differences in neurodevelopmental disabilities between term and preterm infants, with higher incidence of NDD among preterm babies (at 6.6 months of corrected age): 20.4% compared to 7.5% among term babies (p < 0.001). The disabilities among preterm infants were mostly in the Fine motor domain (11.8%), followed by Language development (9.0%), while among the term infants the disabilities were predominantly in the Social development domain (4.8%). There were no significant statistical differences in disabilities in the Social domain across the two groups of infants .Table 3.Similarly, there were significantly more infants with malnutrition as demonstrated by Z-score of less than −2 of weight for age among the preterm infants (18.6%) as compared to the term infants (2.1%), p = 0.001. Severe malnutrition was seen in 5.7% among preterm infants while there were no cases of severe malnutrition identified among the term babies.At bivariate analysis, malnutrition was found to be significantly associated with NDD, with 32.5% of cases with malnutrition having NDD , OR = 2.The results at multivariate analysis revealed a good fit for the model of the relationship of five independent factors and NDD among preterm infants, Hosmer-Lemeshow’s goodness of fit test, LR-chi of 15.71, p = 0.028 . MalnutrThis is one of the first studies in this setting to determine the neurodevelopmental outcomes and modifiable factors among preterm infants. The findings revealed a high incidence of NDD of 20.4%, and severe disability of 3.3% associated with malnutrition among preterm infants at 6.6 months of corrected age, as compared to 7.5%, and 0.5%, respectively (p = 0.001), among term normal birth weight babies. The most affected developmental domain among preterm infants was Fine motor, followed by the Language domain. There was no statistically significant difference in social behavioral development among preterms and term babies. This may be explained by the similarities in parental engagement and stimulation of these infants irrespective of GA at birth. These findings are important as they suggest that mortality, NDD and malnutrition are higher and occur early in preterm infants after hospital discharge in our setting.Our findings are interestingly similar in the domains affected to those of Do et al. (2019) in Vietnam  where prAlthough Gladstone et al. (2011) did not find any significant neurodevelopmental differences among term and preterm babies at 12 months, significant differences were reported at 18 months of corrected age . Others We found that malnutrition was the main factor associated with NDD among preterm babies. About 20% of preterm infants had malnutrition, of whom a third had NDD. Malnutrition due to poor feeding, infections, and/or poor gut development increases the vulnerability of preterm babies to developing NDD ,35. ChilAlthough almost all preterm infants had KMC at the health facility, only 77% continued KMC practice at home for 4.5 hours a day on average. KMC is effective in reducing morbidity, and improved growth and neurodevelopment –44. A CoPolicy and program implications of this work include: as we improve preterm survival, we should be aware of NDD with its social, health system, and economic implications. Systematic follow-up of these infants for nutrition, growth and neurodevelopment monitoring until at least catch-up growth is recommended , to acceThe study involved only one district-level hospital, hence limiting generalizability of the findings to the preterm babies in the whole country. However, this particular hospital is a typical district hospital in the country though may be considered to have had a higher-level quality of care compared to others in the country at that time as it had concerted capacity building efforts for newborn care under the Preterm Birth Initiative, meaning that findings elsewhere might be worse. In addition, we used the Ballard score for GA estimation due to lack of first trimester/early ultrasound scan (USS) during pregnancy for most of the mothers which may limit the accuracy of gestation age dating. In this setting, there were no mechanisms of diagnosing intraventricular hemorrhage, one of the commonest causes of disabilities among preterm babies, and no preventive treatment modalities for this complication. Despite these limitations, the findings are still useful since malnutrition can be prevented in this setting. Although the MDAT tool used has some areas of personal care, it is currently the only developmental assessment tool we know of which was developed and validated for rural African setting. In this study, we had an attrition rate of 12.3%. In estimating the sample size for our study, we took care of loss to follow-up by adjusting the sample size by more than 20% for the preterm babies. Therefore, the attrition rate of 12.3% would have very minimal or no effect on our results.Preterm infants in the study setting are at a high risk of developing neurodevelopmental disabilities. Under-nourished infants and those whose mothers did not consistently practice KMC at home were more likely to have NDD. Health system readiness should, therefore, be improved to provide systematic follow-up care, inclusive of growth and neurodevelopmental assessments, to prevent and address malnutrition. Increased nutrition support, and continuity with KMC at home after discharge from health facility can be helpful in curbing NDD among preterm infants in low resource settings.


Respiratory distress syndrome (RDS), a consequence of lung immaturity, is a serious complication of preterm birth and the primary cause of early neonatal mortality. Administration of antenatal steroids is a standard care method for mothers with anticipated preterm labor. However, the gestational age range at which antenatal corticosteroids (ACS) provide benefit has been subjected to debate. This study aimed to find the prevalence of ACS use in patients that developed/did not develop RDS.This cross-sectional study was conducted at Rafidia governmental surgical hospital. It is based on the data obtained from the files of mothers who gave birth to premature babies and from a face-to-face interview. One hundred and twenty-eight data collection forms were completed over a period of seven months.Approximately 64% of mothers, mothers who gave birth to premature babies, were given ACS, and about 33% of premature neonates developed RDS. Mothers who gave birth to newborns with RDS have lower odds of being administered ACS by 44% . However, the association became statistically not significant after adjusting gestational age, birth weight, gender, mother's age, intrauterine growth restriction (IUGR), mode of delivery and gestational hypertension . Higher risk of RDS was significantly associated with lower gestational age  and IUGR after adjustment . However, no significant association could be found between RDS and mode of delivery , maternal age  and gender of the baby .the overall prevalence of RDS in preterm infants was 33.3% and the identified risk factors were lower gestational age and IUGR. We showed that the administration of ACS wasn't significantly associated with the development of RDS after adjusting gestational age, birth weight, gender, mother's age, IUGR, mode of delivery and gestational hypertension, as the administration of ACS didn't fully meet the international guidelines. Pathophysiology; Epidemiology; Public health; Respiratory system; Women's health; Pediatrics; Intensive care medicine; Laboratory medicine; Respiratory distress syndrome; Antenatal corticosteroids; Prematurity; Lung immaturity; Surfactant; Preterm birth. The fThe administration of antenatal corticosteroids (ACS) to mothers at risk for premature birth is indicated to prevent RDS . LimitatPrenatal corticosteroids in mothers with expected premature delivery improve survival, reduce the risk of RDS, necrotizing enterocolitis and intraventricular hemorrhage, and a single course does not appear to associate with significant adverse effects of the mother or child . The optThis study aimed to determine the prevalence of ACS use in patients that developed/did not develop RDS.2We performed this cross-sectional study for all newborns under the age of 37 weeks of gestational, born between August 1, 2016 and March 7, 2017, at the Rafidia Governmental Surgical Hospital (RGSH), the central governmental hospital in the north West Bank of Palestine. The ethical approval was obtained from the Institutional Review Board (IRB) at An-Najah National University. Informed consent was obtained from all participating mothers and they have been affirmed that their contribution is voluntary.Participants in the study were the mothers who gave birth to premature babies. Mothers who received steroids for reasons other than pulmonary maturity of the fetus were excluded from the study. Dead newborns (stillbirths) have also been excluded, as death-finding investigations are not normally carried out in Palestine.The demographic, antenatal, obstetric, medical and medical history and information on the administration of corticosteroids, route of administration, approval and evaluation in NICU, treatment and mortality were analyzed in clinical charts and analyzed face-to-face. The data collection form was prepared after a literature review ,11,23,242 <50 mmHg or central cyanosis in the room air or additional oxygen demand to maintain PaO2> 50 mmHg or oxygen saturation> 85% within the first 24 h of life; and (2) chest radiography consistent with RDS (reticulogranular appearance for lung fields with or without low lung volume and air bronchograms) in the first 24 h of life [Gestational age is generally estimated as the difference between the first day of the last menstrual period and the date of delivery , and by  of life .2 >35 %), a subsequent dose of 3 ml/kg is administered within 12 h.The surfactant therapy Infasurf®  was administered to newborns based on the NICU protocol for RGSH: an initial dose of 3 ml/kg and, if necessary , remains >7 or FiOStatistical analysis was performed with SPSS® for Windows® version 22. Continuous variables were characterized by mean (±standard deviation) or median (minimum-maximum) if they had symmetric or asymmetric distribution respectively, and categorical variables by absolute and relative frequencies. For comparison of continuous variables, parametric tests (independent t-test) or nonparametric tests (Mann-Whitney U-test) were used if they had two or more than two categories, and chi-square or Fisher's exact test for comparison categorical variables, the latter for expected values below 5. A p-value below 0.05 was considered statistically significant.3One hundred and twenty eight mothers were included in our study. Mothers' characteristics are shown in In our cross-sectional study, 45.3% of mothers had a normal BMI, only 9 mothers had gestational hypertension and 2 mothers had gestational diabetes. The premature rupture of the membrane was present in 22.7% of the mothers. Thirty-seven mothers (40.2%) had previous premature birth, 70% of women had previous pregnancy, 23.9% of mothers had an inter-pregnancy interval of less than one year, 29 mothers (22.7%) were multiparous, 15% of mothers had a history of babies with RDS and 99 mothers (77.3%) were pregnant with singleton .Table 2RNewborn characteristics are summarized in ; about 5Forty-one (75.9%) newborns with RDS required surfactant administration with a median of almost one dose . InfantsFemale newborns developed RDS less frequently than males . HoweverThe gestational age at which prenatal corticosteroid was administered was lower in mothers whom newborns developed RDS than mothers whom newborns didn't develop RDS . However, there was no statistically significant time-difference between the last dose of a full steroid cycle and the delivery .Univariate analysis confirmed that mothers giving birth to newborns with RDS are less likely to get ACS . However, the association did not become statistically significant after adjusting gestational age, birth weight, gender, maternal age, IUGR, type of birth, and gestational hypertension  . AlthougThere was no statistically significant association between RDS and IUGR, maternal age or mode of delivery . The ass4The overall prevalence of RDS in preterm infants in our study was about 33.3%. The prevalence of RDS in preterm babies born at or before 34 weeks of gestation was higher than other studies . Also, tThe time between the last dose of a full cycle of prenatal corticosteroids and childbirth was not significantly associated with the development of RDS in preterm infants, which is incompatible with many studies suggesting that the optimal treatment interval is more than 24 h and less than 7 days after the start of steroid treatment, and the benefit is reduced beyond 14 days . This caThis is the first study to investigate the prevalence of RDS in Palestine and the rate of prenatal corticosteroids administration. In addition, this study focused on neonates who were delivered through all preterm gestational ages. The weakness of this study was its observational nature, the small sample size and a single hospital-based data collection. In addition, the information documented in the patient medical files was not properly completed and the coincidence that most cases were of late prematurity.5The overall prevalence of RDS in preterm infants was 33.3% and the identified risk factors were lower gestational age and IUGR. We have shown that the administration of a complete cycle of prenatal corticosteroids after adjustment is not significantly related to the development of RDS as the administration were not fully complied with ACOG guidelines. Further studies may be helpful to evaluate the factors hindering the implementation of ACS administrative guidelines.I. Ali, R. Batta and R. Yaseen: Conceived and designed the experiments; Performed the experiments; Analyzed and interpreted the data; Wrote the paper.J. Hasson: Conceived and designed the experiments; Performed the experiments.An-Najah National University, Nablus, Palestine.This work was supported by The authors declare no conflict of interest.No additional information is available for this paper.


Episiotomy was associated with breastfeeding at one month (0.112 **) (p < 0.01), and at six months (0.347 *) (p < 0.01). The prevalence of breastfeeding was lower in women who received epidural analgesia at three months (−0.140 **) (p < 0.01) and higher at six months (0.013 **) (p < 0.01). The percentages of breastfeeding at three months were significantly greater in women with no perineal tears (2.1) (p < 0.05). At six months, small rates of breastfeeding were found in women with greater parity (0.051 **) (p < 0.01). No significant association was detected, neither between the type of lactation and the mode of birth, nor between breastfeeding duration and the mode of birth. Conclusions: Epidural analgesia, episiotomy, perineal tears and parity influence the type of lactation and duration of breastfeeding during the six months after birth. The results suggest no association between the type of lactation and the mode of birth or between breastfeeding duration and the mode of birth.Background: Breastfeeding is a determinant of child and maternal health. However, evidence is limited on how mode of birth influences breastfeeding. Research aim: To examine the mode of birth and breastfeeding duration and the type of lactation at one, three and six months after birth in XXX, during 2017. Methods: Correlation study on breastfeeding duration and type of lactation during the six months after birth, and mode of birth, in a randomised sample. Women ≥18 years of age with term singleton infants, were included. Collected data through interviews and hospital records. Pearson’s and Spearman’s correlation analyses were conducted. SPSSv21 and α = 0.05 were used. Results: Breastfeeding duration was shorter in women with greater parity (−0.055 **) ( Breastfeeding is the essential physiological nutrition pattern for the attainment of an optimal and healthy growth and development, as stated by the International Pediatric Association (IPA), the American Pediatric Association (AAP), the Spanish Pediatric Association (AEPED), the World Health Organization (WHO), the Initiative for the Humanization of Birth and Lactation Assistance (IHAN), the United Nations International Children’s Emergency Fund (UNICEF) and the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) . The sciA descriptive, longitudinal and correlational study was carried out to examine the birth variables at the time of birth , the type of lactation at 1, 3 and 6 months and the average duration of breastfeeding. In addition, sequential observations of the variable type of lactation at 1, 3 and 6 months after birth, in a randomised sample, were conducted.The Research Ethics Committee of Jaén resolved and ruled in favour of this study on 29 September 2016, regulated by Andalusian Decree 439/2010 of December 14th, thus complying with article 12 of Law 14/2007 of July 3rd on Biomedical Research. The study was conducted in compliance with Law 14/2007 of July 3rd of Biomedical Research, following the precepts included in the Belmont Report and the Declaration of Helsinki (updated at the Brazil Summit 2013) for biomedical research. The authors also considered Law 41/2002 on patient autonomy. The personal data of the participants were treated in compliance with Organic Law 15/1999 of December 13th on the Protection of Personal Data, informing the participants about their ARCO rights . The anonymity of the participants was guaranteed, as well as the confidentiality of their data, which could not be accessed by people outside of the study, dissociating the personal data for their adequate protection during the data analysis.The study population was constituted by women giving birth to a full-term single healthy infant. The target population was set at 1172 women who gave birth in the year 2016 in the Hospital of Úbeda (Spain). The minimum number of mothers to interview was 100 for centres with over 300 infants under 2 years of age, according to the criteria established by the IHAN . ConsideSome of the variables collected were mother age, parity and breastfeeding education. Parity was referred to as the number of previous deliveries, classified as primiparous (no previous births) and multiparous (at least one previous birth)). The mothers were asked whether they attended educational sessions about breastfeeding during pregnancy.The independent variables related to the characteristics of birth were: mode of birth, epidural analgesia, episiotomy, perineal tears, sex of newborn and newborn weight.The mode of birth was classified as vaginal birth, Cesarean birth and obstetric birth. In this paper, obstetric birth is referred to as instrumental birth. The variables epidural analgesia and episiotomy were measured by two categories (“yes” and “no”). The type of perineal tear was classified as first-degree (Type I), second-degree (Type II) and third- and fourth-degree tears (Type III), according to the Royal College of Obstetricians and Gynaecologists . The sexThe dependent variables were the type of lactation and duration of breastfeeding.The type of lactation is defined by the criteria of the Spanish Health Survey . NaturalThe data were obtained through structured interviews via phone call with women who had given birth in the year 2017 in Úbeda (Spain). The birth records of the hospital provided data about the characteristics of the sample and birth variables. The women were asked about the type of lactation , describing each of them. Breastfeeding: only breast milk; mixed lactation: combination of breast milk and formula or artificial milk; and formula feeding: only formula or artificial milk . The women were not asked about the use of a bottle, since it can be used to administer any kind of milk. Repeated measurements of the study variables were recorded at three time points , with the aim of determining the prevalence of breastfeeding in the sample and its evolution over time. Likewise, they were asked whether they attended educational sessions about breastfeeding. The pertinent permits were requested to gain access to the database of birth records of the hospital of Úbeda . The principal investigator valued whether the participants met the inclusion criteria and did not meet any of the exclusion criteria. Data from the year 2017 were gathered during the first six months of the year 2018, and were subsequently loaded into an anonymised database. During the months of January, February and March 2018, the authors phoned the women who had given birth between 1 January 2017 and 30 June 2017. During the months of April, May and June 2018, the authors interviewed those women who had given birth in the second half of the year 2017. The women were informed about the purpose of the study, and their written consent was requested and collected. To ensure a sample size of 120 women, potential participants were discarded after four failed phone call attempts, subsequently selecting the next candidate in the list. All women included completed the three interviews.t-test did not show any significant results. To evaluate the differences between the type of lactation and the mode of birth, as well as between the type of lactation and the rest of the birth variables used in this study, the Chi-square test was applied, using contingency tables. Those values below 5% were considered significant. All analyses were performed using the SPSS v21 statistical software , Jaén, España.)A descriptive analysis was conducted for each of the variables of the database. The categorical variables are presented in a frequency table (number of cases and percentage), with the quantitative variables being expressed as mean, standard deviation, and minimum and maximum values. The description of the variable type of lactation with repeated measures on the same sample showed the evolution of such variables over time, in the first six months after birth . A correlation analysis was carried out to determine the possible relationships between the study variables, as well as the significance and direction of such relationships. With the aim of exploring the relationships between the categorized variables and the numerical indices, the Spearman’s correlation coefficient was used, and when there were correlations between quantitative variables, the Pearson product-moment correlation coefficient (PPMCC) was used. Regarding the comparison between the mean values, the Student’s Descriptive data of the sample and study variables are shown in The type of lactation at one, three and six months after birth is shown in p < 0.01) (p > 0.05) (p < 0.05) (The type of lactation at one month after birth was significantly related to episiotomy (0.112 **) ( < 0.01) , showing > 0.05) . Mixed l < 0.05)  to type p < 0.01), showing a lower value for breastfeeding. The percentages of breastfeeding at three months shown in p < 0.05), with a lower number of women of first-degree tears (−3.5) (p < 0.01), compared to the women who applied formula feeding. No relationship was found between the type of lactation at three months after birth and the mode of birth .The type of lactation at three months after birth was associated with the use of epidural analgesia (−0.140 **) (p < 0.05) and those who had been administered epidural analgesia (0.013 **) (p < 0.01). On the other hand, the prevalence of breastfeeding was lower in women with greater parity (0.051 **) (p < 0.01). Contingency p < 0.01). The mode of birth  was not associated with the type of lactation at six months after birth.The type of lactation at six months after birth was significantly related to some variables. The prevalence of women applying breastfeeding at six months after birth was higher in women who had been treated with episiotomy (0.347 *) (p < 0.01) (p < 0.01) (p < 0.01) (p < 0.05) (p < 0.05) . The duration of breastfeeding was associated with parity (−0.055 **) ( < 0.01) , thus, t < 0.01) . Althoug < 0.01) . The abs < 0.05) . The pra < 0.05) . The effp < 0.01) (p < 0.01) (p < 0.01) (p < 0.01), which could explain that epidural analgesia decreases breastfeeding duration. Thus, it is not possible to assert the existence of a relationship between these two variables. Moreover, no relationship was found between the mode of birth and the type of lactation at any time point, neither at one, three nor six months after birth.On the other hand, epidural analgesia was associated with a shorter total duration of breastfeeding (0.057 **) ( < 0.01) . The dur < 0.01)  and at t < 0.01) . In the p < 0.05), whereas being secundiparous is associated with a lower initiation (p < 0.01). However, other authors [p < 0.01) in our study.The average age of the study population was 32.16 years, which is in line with the average maternal age in Spain   and Anda authors ,24,29, s authors , state t authors . Our stu authors ,13,23,29 authors   is related neither to the type of lactation during the first six months after birth nor to the total duration of breastfeeding.In Spain, there is no official breastfeeding temporal monitoring system that follows the international guidelines to unify the indicators and methodology recommended to obtain comparable results, thus, further research on this topic is needed.


Background: While most studies on the association of preterm birth and cerebral palsy (CP) have focused on very preterm infants, lately, attention has been paid to moderately preterm [32 to <34 weeks gestational age (GA)] and late preterm infants (34 to <37 weeks GA).Methods: In order to report on the outcomes of a cohort of moderately and late preterm infants, derived from a population-based CP Registry, a comparative analysis of data on 95 moderately preterm infants and 96 late preterm infants out of 1,016 with CP, was performed.Results: Moderately preterm neonates with CP were more likely to have a history of N-ICU admission (p = 0.001) and require respiratory support (p < 0.001) than late preterm neonates. Birth weight was significantly related to early neonatal outcome with children with lower birth weight being more likely to have a history of N-ICU admission [moderately preterm infants (p = 0.006)/late preterm infants (p < 0.001)], to require ventilator support [moderately preterm infants (p = 0.025)/late preterm infants (p = 0.014)] and not to have neonatal seizures [moderately preterm infants (p = 0.044)/late preterm infants (p = 0.263)]. In both subgroups, the majority of children had bilateral spastic CP with moderately preterm infants being more likely to have bilateral spastic CP and less likely to have ataxic CP as compared to late preterm infants (p = 0.006). The prevailing imaging findings were white matter lesions in both subgroups, with statistically significant difference between moderately preterm infants who required ventilator support and mainly presented with this type of lesion vs. those who did not and presented with gray matter lesions, maldevelopments or miscellaneous findings. Gross motor function was also assessed in both subgroups without significant difference. Among late preterm infants, those who needed N-ICU admission and ventilator support as neonates achieved worse fine motor outcomes than those who did not.Conclusions: Low birth weight is associated with early neonatal problems in both moderately and late preterm infants with CP. The majority of children had bilateral spastic CP and white matter lesions in neuroimaging. GMFCS levels were comparable in both subgroups while BFMF was worse in late preterm infants with a history of N-ICU admission and ventilator support. Prematurity is highly associated with neonatal mortality and morbidity and also constitutes a well-recognized risk factor for cerebral palsy (CP) and other lifelong effects on neurodevelopmental functioning and childhood/adulthood morbidity. According to the WHO, preterm birth is defined as any birth before 37 completed weeks of gestation and this can be further subdivided on the basis of gestational age (GA): very preterm (28 to <32 weeks), moderately preterm (32 to <34 weeks) and late preterm (34 to <37 weeks) , 2. So fSeveral studies have shown that moderately and late preterm infants may suffer from respiratory distress syndrome (RDS) and other respiratory morbidities requiring respiratory support and neonatal intensive care unit (N-ICU) admission –9. AlthoAs far as long term sequelae is concerned, moderately and late preterm infants are reported to be at greater risk of CP and thus impaired motor function compared to term-born infants. The prevalence of CP rises with decreasing gestational age at birth and, additionally to motor manifestations, is frequently accompanied by cognitive and sensory impairment and epilepsy. The predominant abnormality among premature infants is spastic CP, mostly bilateral spastic . In termAbnormal neuroimaging findings are observed in the majority of children with CP. Based on the fact that CP is attributed to a non-progressive lesion or abnormality of the developing brain, the pathophysiology of CP depends on the time of occurrence of detrimental events during intra- and extra-uterine brain development. Disturbances during the first and second trimester of embryogenesis, when corticogenesis takes place, result in maldevelopments whereas disturbances during the third trimester when differentiation and “refining” events take place lead to predominant white matter injury mainly in the early third trimester and predominant gray matter injury in the late third semester when concerning cortical gray matter, basal ganglia and thalamus. However, given that CP is a clinical diagnosis, normal brain magnetic resonance imaging (MRI) does not exclude the diagnosis of CP –28. PrevPreterm birth has also been associated with an increased risk of epilepsy in childhood and intellectual disability with poorer neurodevelopmental outcomes of preterm infants at school age. The incidence of epilepsy has been shown to decrease with increasing gestational age but increases after 41 gestational weeks. In addition to intracranial hemorrhage and neonatal seizures, low Apgar score, N-ICU admission, respiratory support, antibiotic treatment during neonatal period and a major congenital anomaly have been associated with increased risk of epilepsy .Concerning developmental problems, it has been shown that preterm children are at significantly increased risk for adverse neurodevelopmental outcomes and intellectual disability compared to termborn peers. However, despite the fact that both early preterm and moderately-late preterm children have greater rates of developmental problems compared to full-term born children before school entry, after school entry persistent developmental problems are observed solely in the subgroup of early preterm children, indicating that moderately-late preterm children may develop better adaptation capacities –35. AparGiven that moderately and late preterm infants represent a multitudinous, insufficiently studied and vulnerable to health and developmental problems population among preterm infants, we conducted a comparative analysis on the short- and long-term outcomes of moderately (32 to <34 weeks GA) and late preterm infants (34 to <37 weeks GA) born in Greece based on population-based data of the Greek CP Registry.In this retrospective comparative study, the participants' sample was drawn from the CP Registry of Attica-Greece. Data on 95 children born at 32 to <34 weeks GA and 96 children born at 34 to <37 weeks GA out of 1016 with CP, born between 1999–2006, were analyzed in terms of their need for N-ICU admission, respiratory support with endotracheal intubation or continuous positive airway pressure (CPAP) ventilation, and the occurrence of neonatal seizures during the first 72 h after birth. Moreover, the clinical classification of Cerebral Palsy (CP) in spastic CP , dyskinetic CP  and ataxic CP  was assessed in children of both subgroups of moderately and late preterm infants . AdditioP-values of <0.05 were a priori considered statistically significant.The data were analyzed using the STATA 13 software package. Continuous variables  were tested for normality using the Kolmogorov Smirnov test. Since they were not normally distributed, they were expressed as median values (range). Comparisons of continuous variables across groups of patients were based on Mann Whitney U test. When compared in more than two groups  Kruskall Wallis test was performed. Categorical data were presented as frequencies and percentages and were compared with chi-square or Fisher's exact test, as appropriate and Because of the fact that our study is retrospective, missing values were observed in several variables, due to incomplete data recording. All participants, though, had complete data in variables representing type of CP, GMFCS, and BFMF levels, the primary outcomes for the registry, and gestational age. Since our aim was to simply describe and compare the subgroups of patients with different gestational ages (moderately preterm and late preterm infants), no method for missing data was utilized.Of the 95 infants in the moderately preterm population, sixty-one percent (61%) were boys, mean Birth Weight (BW) was 1,780 g  and mean Apgar score was 9 (3–10). Within the population of moderately preterm infants, of the 94/95 infants with available data concerning the need for N-ICU admission ninety six percent (96%) had a history of N-ICU admission, of the 86/95 infants with available data concerning the need for respiratory support eighty four percent (84%) underwent endotracheal intubation or CPAP ventilation and of the 72/95 infants with available data concerning the history of neonatal seizures eleven percent (11%) presented with seizures during the first 72 h after birth. The predominant CP type among moderately preterm infants was bilateral spastic CP in seventy six percent (76%), followed by unilateral spastic CP in fourteen percent (14%) and dyskinetic CP in five percent (5%) while none of the patients (0%) presented with ataxic CP and five percent (5%) of the subgroup of moderately preterm infants were non-categorized. Among the 59/95 of moderately preterm infants with available brain MRI, the prevailing neuro-imaging findings were predominant white matter lesions in seventy three percent (73%), followed by predominant gray matter lesions in fourteen percent (14%), miscellaneous changes in ten percent (10%), maldevelopments in two percent (2%) and normal imaging findings in two percent (2%) of the patients. The motor function status of moderately preterm infants was assessed concerning gross motor skills with fifty nine percent (59%) classified as GMFCS Level I-III and forty one percent (41%) classified as GMFCS Level IV-V and fine motor skills with sixty two percent (62%) classified as BFMF level I-III and thirty eight percent (38%) classified as BFMF level IV–V. Furthermore, among the 84/95 of moderately preterm infants with available data, forty three percent (43%) had a history of epilepsy and fifty seven percent (57%) did not. Among the 80/95 of moderately preterm infants with available IQ score sixty two point five percent (62.5%) were classified as intellectually disabled (IQ <70) and among the 82/95 of moderately preterm infants with available hearing acuity test hearing disability was confirmed in five percent (5%) .Sixty – four point six percent (64.6%) of all 96 late preterm infants were boys, mean BW was 2,310 g  and mean Apgar score was 9 (3–10). Within the population of late preterm infants, seventy nine percent (79%) were admitted in N-ICU during the neonatal period, of the 87/96 infants with available data concerning the need for respiratory support forty three percent (43%) of the patients required endotracheal intubation or CPAP ventilation and fifty seven percent (57%) did not and of the 81/96 infants with available data concerning the history of neonatal seizures twenty percent (20%) presented with seizures during the first 72 h after birth. The majority of late preterm infants had a diagnosis of spastic CP in eighty five percent (85%) classified as bilateral spastic CP in fifty seven percent (57%) and as unilateral spastic CP in twenty eight percent (28%) in the group of late preterm infants followed by ataxic CP in six percent (6%) and dyskinetic CP in two percent (2%) among late preterm infants while six percent (6%) of the patients were not categorized. Among the 72/96 of late preterm infants with available brain imaging with MRI, the prevailing finding was predominant white matter injury in fifty three percent (53%) of the patients, followed by predominant gray matter injury in twenty one percent (21%), miscellaneous changes in eighteen percent (18%), maldevelopments in six percent (6%) and normal imaging findings in two percent (2%) in the late preterm population. The motor function status of late preterm infants was assessed concerning gross motor skills with fifty eight percent (58%) classified as GMFCS Level I-III and forty two percent (42%) classified as GMFCS Level IV-V and fine motor skills with sixty two point five percent (62.5%) classified as BFMF level I-III and thirty seven point five percent (37.5%) classified as BFMF level IV-V, similarly to the subgroup of moderately preterm infants. In addition, among the 89/96 of late preterm infants with available data, forty nine percent (49%) had a history of epilepsy and fifty one percent (51%) did not. Among the 87/96 of late preterm infants with available IQ score sixty one percent (61%) were classified as intellectually disabled (IQ <70) and among the 91/96 of late preterm infants with available hearing acuity test hearing disability was confirmed in one percent (1%) .p = 0.006)/34 to <37 weeks GA (p < 0.001)] and to require respiratory support [32 to <34 weeks GA (p = 0.025)/34 to <37 weeks GA (p = 0.014)]. Additionally, moderately preterm neonates with higher birth weight were more likely to have seizures during the first 72 h after birth with statistically significant difference compared to moderately preterm neonates with lower birth weight, whereas there was not statistically significant difference in the late preterm population [32 to <34 weeks GA (p = 0.044)/34 to <37 weeks GA (p = 0.263)]. In the moderately preterm population, the mean BW of neonates who required N-ICU admission was 1,770 g  whereas the mean BW of neonates who did not was 2,235 g , the mean BW of neonates who required respiratory support was 1,750 g  whereas the mean BW of neonates who did not was 2,025 g , the mean BW of neonates who had seizures during the first 72 h after birth was 2,075 g  whereas the mean BW of neonates who did not was 1,980 g . In the late preterm population, the mean BW of neonates who required N-ICU admission was 2,200 g  whereas the mean BW of neonates who did not was 2,750 g , the mean BW of neonates who required respiratory support was 2,150 g  whereas the mean BW of neonates who did not was 2,515 g , the mean BW of neonates who had seizures during the first 72 h after birth was 2,450 g  whereas the mean BW of neonates who did not was 2,300 g   .p = 0.001) and require respiratory support (p < 0.001) compared to late preterm neonates indicating that gestational age serves a crucial role in the neonatal outcome of preterm infants (Moderately preterm neonates were more likely to have a history of N-ICU admission ( infants .p = 0.006). Moreover, in the moderately preterm population none of the neonates had ataxic CP indicating that moderately preterm infants have less frequently ataxic CP compared to late preterm infants , indicating that hearing disorder is not a major disability in infants of either subgroup.Among the 82/95 of moderately preterm infants and the 91/96 of late preterm infants with available data concerning auditory acuity, auditory disorder was observed in five percent  and one percent  respectively (p = 0.004) , with statistically significant difference between moderately preterm infants born at 32 to <34 weeks who required ventilator support and mainly presented with this type of lesion vs. those who did not and presented with gray matter lesions, maldevelopments or miscellaneous findings (= 0.004) .p = 0.019 and p = 0.017, respectively)  .Birth weight turned out to be significantly related to early neonatal outcomes of both moderately preterm (32 to <34 weeks GA) and late preterm infants (34 to <37 weeks GA) as neonates of both subgroups with smaller birth weight were more likely to have a history of N-ICU admission, require respiratory support and not to develop seizures during the first 72 h after birth. The higher incidence of N-ICU admissions and need for respiratory support in moderately and late preterm neonates with lower birth weight in our study provides an indication of the predictive nature of birth weight and is similar to results of previous studies associating low birth weight with an increased risk of any emergency respiratory admission to hospital during the neonatal period, infancy and even later childhood until adulthood , 42–44.In our cohort, moderately preterm infants were more likely to require respiratory support and have a history of N-ICU admission as neonates compared to their late preterm peers indicating that decreasing gestational age constitutes a negative prognostic factor for short term outcomes, in line with previous studies .In both subgroups of moderately and late preterm infants, the predominant CP type was spastic CP , as expected based on current literature , and braAdditionally, in the population of moderately and late preterm CP patients the classification of gross motor and fine motor function revealed comparable GMFCS and BFMF levels in both subgroups, with GMFCS and BFMF levels I-III in most patients. Several studies have been conducted so far concerning gross motor function in moderately and late preterm infants with CP indicating comparable results to ours, however, further studies are demanded in order to assess fine motor function in this population of infants as fine motor development of CP patients is poorly examined so far , 19–22.Epilepsy and intellectual impairment were documented in high percentages, similar in both subpopulations of moderately and late preterm infants with CP, in accordance with current literature –35, wherOur data support that moderately and late preterm infants constitute a population vulnerable for short-term complications and long-term unfavorable outcomes. Although, gestational age plays a crucial role for the short-term outcome and differentiates the clinical sequelae between moderately and late preterm infants during the neonatal period, the long-term outcomes of both subgroups of moderately and late preterm infants share common clinical features.It is important to carry out further studies in order to follow up moderately and late preterm infants during prenatal neonatal period and childhood and to define prenatal and perinatal risk factors in order to improve obstetric and neonatal treatment practices that could lead to better short- and long-term outcomes.Our study addresses the population of moderately and late preterm infants who represent the vast majority of infants born preterm and sheds light on short- and long-term outcomes of this subpopulation of CP patients providing data which appear to be consistent to current literature but also raise the necessity of further research.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.NS participated in the research design, the collection and statistical analysis of data and drafted the manuscript for intellectual content. MK, MG, HSt, FD, and GD participated in the collection of data. MP participated in the research design, the collection of data and revised the manuscript for intellectual content. EN participated in the research design, the collection and statistical analysis of data and revised the manuscript for intellectual content. HSk, HB, SM, ZD, AD, and MT participated in the diagnosis, treatment and follow up of patients, provided access to clinical data and revised the manuscript for intellectual content. AP conducted the research design, participated in the diagnosis, treatment and follow up of patients, provided access to clinical data, co-wrote the manuscript and revised the manuscript for intellectual content. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Introduction: Fetal inflammatory response syndrome (FIRS), defined as elevated umbilical cord blood interleukin-6 (IL-6) values > 11 pg/ml, is associated with an increased risk of neonatal morbidity and mortality. The primary aim of the present study was to evaluate a potential influence of FIRS on cerebral oxygen saturation (crSO2) and fractional tissue oxygen extraction (cFTOE) during immediate postnatal transition in preterm neonates. The secondary aim was to analyze the potential influence of FIRS on cerebral injury and mortality.Methods: Secondary outcome parameters of prospective observational studies were analyzed. Preterm neonates with measured IL-6 values from umbilical cord blood and cerebral near-infrared spectroscopy (NIRS) measurements during immediate transition after birth were included. Preterm neonates with FIRS (FIRS group) were matched 1:1 for gestational age (± 1 week) to preterm neonates without FIRS (non-FIRS group). crSO2, cFTOE, arterial oxygen saturation (SpO2), heart rate (HR), and fraction of inspired oxygen (FiO2) were compared between both groups. In addition, cerebral injury and mortality were compared between both groups.Results: A total of 46 preterm neonates were included. Twenty-three neonates in the FIRS group  were compared to 23 neonates in the non-FIRS group . cFTOE showed significantly lower values within the first 4 min and a trend toward lower values in minute 5 after birth in the FIRS group. There were no significant differences in crSO2 within the first 15 min after birth between the two groups. SpO2 was significantly lower in minutes 5 and 6 and HR was significantly lower in minutes 2 and 4 after birth in the FIRS group compared to the non-FIRS group. Survival without cerebral injury was similar in both groups.Conclusion: In preterm neonates with FIRS the crSO2 was similar despite significantly lower cFTOE values during the first minutes after birth. This observation may be a result of compromised oxygen consumption and delivery in the first minutes after birth in neonates with FIRS. Fetal inflammatory response syndrome (FIRS) is defined as elevated interleukin-6 (IL-6) values in umbilical cord blood IL-6 > 11 pg/ml)  enables non-invasive, continuous measurement of crSO2 and cerebral tissue fractional oxygen extraction (cFTOE) –15. RallThe primary aim of the present study was to evaluate whether there is an association between FIRS and crSO2/cFTOE in preterm neonates during the first 15 min after birth. We hypothesized that in preterm neonates with FIRS, crSO2 values are lower and cFTOE is higher due to compromised perfusion. In addition, our secondary aim was to analyze cerebral injury and mortality until term-equivalent age or before discharge in neonates with and without FIRS.In the present study secondary outcome parameters of prospective observational studies, conducted between May 2010 and November 2019 at the Division of Neonatology, Medical University of Graz, Austria, were analyzed. All studies were approved by the Regional Committee on Biomedical Research Ethics  and written parental consent was obtained before study inclusion.We included preterm neonates, in whom umbilical cord blood IL-6 values and crSO2 were measured during the first 15 min after birth. Exclusion criteria were major congenital anomalies. The preterm neonates were stratified into two groups according to their IL-6 values: neonates with IL-6 ≤ 11 pg/ml were assigned to the non-FIRS group, and those with IL-6 > 11 pg/ml to the FIRS group  with a neonatal transducer was used for crSO2 measurements. After birth the cord was clamped according routine after at least 30 s. Preterm neonates were placed on the resuscitation table under an overhead heater immediately after birth. The NIRS transducer was applied on the left fronto-parietal head in each neonate immediately after birth without disturbing routine medical care. The sensor was secured with a gauze bandage. crSO2 measurements were conducted during the first 15 min after birth. The sample rate (period) of NIRS measurements was 0.13 Hz (8 s).Arterial oxygen saturation (SpO2) and heart rate (HR) were measured with the IntelliVue MP30 monitor . The transducer was placed on the right hand/wrist.crSO2, SpO2 and HR were recorded continuously during the first 15 min after birth and stored every second in a multichannel system  for subsequent analyses. cFTOE was calculated for each minute: (SpO2-crSO2)/SpO2.Body temperature was measured in minute 15 after birth using a rectal probe. Blood pressure was measured by a pneumatic cuff applied to the right upper arm with the IntelliVue MP30 monitor  in minutes 5, 10, and 15 after birth. Afterwards, the mean of the three mean arterial blood pressure (MABP) values was calculated. Further, fraction of inspired oxygen (FiO2) was recorded and the need for respiratory support (continuous positive airway pressure (CPAP) or intubation) was documented.IL-6 was measured in umbilical cord blood plasma taken immediately after birth. The analysis of IL-6 was performed using the Endogen Interleukin-6 ELISA  according to the standard procedure. In addition, procalcitonin (PCT) levels were analyzed from the same umbilical cord blood sample. C-reactive protein (CRP) was determined twice after birth: within 24–48 h and 48–72 h after birth.Cerebral injuries were evaluated by routine cerebral ultrasound examinations carried out in all preterm neonates on the first, fourth, and eighth day after birth and at term age or before discharge, depending on what came first. We recorded any grade of IVH and PVL, and death.Preterm neonates in the non-FIRS group were matched for gestational age ± 1 week to those of the FIRS group. The matching ratio was 1:1.t-test or Mann-Whitney U test for continuous data and Chi-square test or Fishers's exact test for categorical data. A linear mixed model with fixed effect for time and first-order autoregressive covariance structure was used for calculation of overall effects and differences between groups at each minute. The course of parameters was analyzed starting with the second minute after birth until minute 15. The first minute of life was not analyzed due to the high number of missing values. For the visualization of the courses of analyzed parameter estimated values according to the linear mixed model with 95% confidence intervals (95%CI) are shown. Lower bound of the 95%CI for FiO2 were bounded to a minimum of 21%, since lower values are not physiological. A p-value of p < 0.05 was considered statistically significant. Statistical analyses were performed using SPSS 26.0 .Data are presented as mean and standard deviation or median and interquartile range (IQR) for continuous data and absolute and relative frequency for categorical data, respectively. Baseline differences between groups were analyzed using Two-hundred sixty-eight preterm neonates were included in the prospective observational studies. Ninety-nine preterm neonates, with IL-6 values available and crSO2 measurements within the first 15 min after birth, fulfilled the inclusion criteria. Sixty-one neonates showed IL-6 values ≤ 11 pg/ml (non-FIRS group) and 38 neonates had IL-6 values > 11 pg/ml (FIRS group). Twenty-three neonates in each group, matched for gestational age, were finally analyzed . Demogran = 4/non-FIRS group n = 5), preterm premature rupture of membranes (n = 6/n = 3), preeclampsia/HELLP syndrome/maternal hypertension (n = 4/n = 6), intrauterine growth restriction (n = 2/n = 3), and other reasons (n = 7/n = 6). Nineteen (83%) preterm neonates were delivered by cesarean section in the FIRS group and 23 (100%) neonates in the non-FIRS group.Indication for preterm birth were preterm labor (FIRS group Twenty (87%) preterm neonates in the FIRS group and 21 (91%) preterm neonates in the non-FIRS group needed respiratory support and/or supplemental oxygen (CPAP) within the first 15 min after birth. Four (17%) neonates in the FIRS group and one (4%) neonate in the non-FIRS group were intubated within the first 15 min after birth. None of the neonates needed cardiopulmonary resuscitation.The courses of crSO2 and cFTOE during the first 15 min after birth are demonstrated in SpO2, HR, and FiO2 during the first 15 min after birth are demonstrated in At term-equivalent age or before discharge no significant differences in cerebral injury or mortality were observed. Twenty (87%) preterm neonates in the FIRS group and 22 (96%) neonates in the non-FIRS group survived without cerebral injury. In the FIRS group one neonate had an IVH Grade I, one neonate an IVH Grade III and one neonate a PVL Grade I. The IL6 values of these neonates were 19.7, 686.2, and 959.9 pg/ml, respectively. In the non-FIRS group one neonate had a PVL Grade I . One (4%) preterm neonate of the FIRS group died .To our knowledge, this is the first study to evaluate the potential influence of FIRS on cerebral oxygenation measured with NIRS in preterm neonates during the first 15 min after birth. Preterm neonates with FIRS showed significantly lower cFTOE values in the first 4 min after birth compared to neonates in the non-FIRS group.One would also expect significantly higher crSO2 values when cFTOE is significantly lower. However, in the present study we did not observe significant differences in crSO2 despite significant differences in cFTOE between the groups. This suggests that in the FIRS group not only oxygen consumption but also oxygen delivery was lower, resulting in a similar crSO2 in both groups.Reduced oxygen consumption during inflammation and sepsis can be explained by mitochondrial dysfunction with impaired energy production . There aCerebral oxygen delivery is a function of Hb concentration, arterial oxygen content and cerebral blood flow depending on cardiac output and vascular resistance. SpO2 representing oxygen content was similar in both groups in the first 4 min. In neonates, cardiac output is strongly dependent on HR. Thus, HR determines strongly cerebral blood flow, depending on vascular resistance . HR was Rallis et al.  measuredIn the present study, there were no differences between the two groups in PCT, determined from umbilical cord blood, and in CRP values, taken on the first and on the second day after birth. Therefore, we assume that FIRS is not always linked with a neonatal infection. Ebenebe et al.  investigIn the present study, no significant differences in cerebral injury or mortality at term-equivalent age or before discharge were observed between the two groups, whereby the overall number of cerebral injury and death in both groups was low.Ozalkaya et al.  describeThe strength of the present study is the matching of the FIRS and non-FIRS group, rendering them comparable in terms of demographic parameters. However, due to matching the number of analyzed preterm neonates in both groups became rather small. Furthermore, the majority of IL-6 values in the FIRS group (median IL-6 19.7 pg/ml) was relatively low, although they fulfilled the evidence-based definition of FIRS (In preterm neonates with FIRS, crSO2 was similar despite significantly lower cFTOE values during the first minutes after birth compared to neonates without FIRS. This observation may be a result of compromised oxygen consumption and delivery in the first minutes after birth in neonates with FIRS.All datasets presented in this study are included in the article/The studies involving human participants were reviewed and approved by Committee on Biomedical Research Ethics, Medicial University of Graz, Auenbruggerplatz 2, 8036 Graz, Austria. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.CH, AA, and GP: substantially contributed to the conception and design of the work. CH, MB, NB-S, BS, LM, AA, BU, and GP: analysis and interpretation of data, drafting the work and revising it critically, final approval of the version to be published, and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.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.


Annually, 18 million babies are born to mothers 18 years or less. Two thirds of these births take place in South Asia and Sub-Saharan Africa. Due to social and biological factors, adolescent mothers have a higher risk of adverse birth outcomes. We conducted this study to assess the incidence, risk factors, maternal and neonatal health consequences among adolescent mothers.We conducted an observational study in 12 hospitals of Nepal for a period of 12 months. Patient medical record and semi-structured interviews were used to collect demographic information of mothers, intrapartum care and outcomes. The risks of adverse birth outcomes among adolescent compared to adult mothers were assessed using multivariate logistic regression.p-value< 0.001). One third of the adolescent mothers did not have formal education, while one in nine adult mothers did not have formal education . Compared to adult mothers, adolescent mothers had higher odds of experiencing prolonged labour , preterm birth  and of having a baby being small for gestational age . The odds of major malformation increased by more than two-fold in adolescent mothers compared to adult mothers .During the study period, among the total 60,742 deliveries, 7.8% were adolescent mothers. Two third of the adolescent mothers were from disadvantaged ethnic groups, compared to half of adult mothers (66.1% vs 47.8%, Women from disadvantaged ethnic group have higher risk of being pregnant during adolescent age. Adolescent mothers were more likely to have prolonged labour, a preterm birth, small for gestational age baby and major congenital malformation. Special attention to this high-risk group during pregnancy, labour and delivery is critical. In the Sustainable Development Goal era, the planet has witnessed the largest adolescent (10–19 years) cohort population in human history. There are approximately 1.2 billion adolescents worldwide, with more than 85% living in low- and middle-income countries . AdolescIn 2013, globally, 16 million girls between the ages of 15–19, and two million girls under age 15, became pregnant . There hAccording to the United Nations Population Fund (UNFPA), one third of all women between the ages 20 and 24 years report being married during adolescent period , 11. GloPregnancy during the adolescent period entails considerable risk for complications during labour such as placental tear, obstruction and long-term consequences of obstetric fistulae . AdolescIn Nepal in 2016, the median age at first marriage is 17.9 years among women. 52% of women are married by age 18, as compared to 19% of men . HoweverThe study has been reported as per the checklist for STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) .This is an observational study conducted for a period of 12 months in 12 public hospitals of Nepal between July 2017–June 2018 nested within a large-scale neonatal resuscitation program , 26. TheAll of these hospitals provided Comprehensive Emergency Obstetric and Neonatal Care Services . All theAll women admitted in the hospitals for delivery with gestational age 22 week or more were eligible to be enrolled in the study. Women consented to be enrolled in the main study at the time of admission for delivery. Written consent was taken from the women. Women who gave birth outside these hospitals but were admitted for postnatal complication care were excluded from the study.To collect maternal and newborn health data, a surveillance system was established in all the hospitals, with data collectors collecting clinical information of mothers and newborns using a data retrieval form : birth weight less than 10 centile as per the gestational age [onal age . The varMajor malformation: major congenital malformation-malformation of neural tube defect, cardiac and gastro-intestinal.Antepartum stillbirth: delivery of any fetus occurring after 22 weeks of gestation or with a birth weight more than 500 g that had with no FHS at admission and no signs of life at birth.Intrapartum stillbirth: delivery of a fetus occurring after 22 weeks’ gestation or with a birth weight 500 g or more, who had FHS at admission and no signs of life at birth.Pre-discharge neonatal mortality: neonatal death before discharge from the hospital.p < 0.20, was included in a multi-variate logistic regression analysis. During data analysis, missing values were treated as missing. All the statistical analyses were performed using SPSS version 25.Differences in the demographic, obstetric and neonatal characteristics between the adolescent and adult mother was assessed using the Pearson’s chi-squared test (χ2). Variables which had a difference of p-value < 0.001). More adolescent mothers lacked formal education compared to adult mothers . , the prevalence of babies born with small weight for gestational age was higher among the adolescent mothers compared to adult mothers , and the incidence of preterm birth was higher among adolescent mothers compared to adult mothers . The share of babies born with major malformation was higher from mother who were adolescent than adult . Adolescent mothers also had higher intrapartum stillbirth rate than adult mothers . Pre-discharge neonatal mortality was higher among adolescent mother compared to among adult mothers       Additional file 2. NePeriQIP registry formAdditional file 3. NePeriQIP Client Exit Interview form