The BetterBirth trial tested the effect of a peer coaching program around the WHO Safe Childbirth Checklist for birth attendants in primary-level facilities in Uttar Pradesh, India on a composite measure of perinatal and maternal mortality and maternal morbidity. This study aimed to examine the adherence to essential birth practices between two different cadres of birth attendants—nurses and auxiliary nurse midwives (ANMs)—during and after a peer coaching intervention for the WHO Safe Childbirth Checklist.This is a secondary analysis of birth attendant characteristics, coaching visits, and behavior uptake during the BetterBirth trial through birth attendant surveys, coach observations, and independent observations. Descriptive statistics were calculated overall, and by staffing cadre (staff nurses and ANMs) for demographic characteristics. Logistic regression using the Pearson overdispersion correction (to account for clustering by site) was used to assess differences between staff nurses and ANMs in the intervention group during regular coaching (2-month time point) and 4 months after the coaching program ended (12-month time point).p = 0.76). Practice adherence tapered to 49.2% among ANMs and 56.1% among staff nurses at 12 months, which was 4 months after coaching had ended (p = 0.68).Of the 570 birth attendants who responded to the survey in intervention and control arms, 474 were staff nurses (83.2%) and 96 were ANMs (16.8%). In the intervention arm, more staff nurses  received coaching at all pause points compared to ANMs . At baseline, adherence to practices was similar between ANMs and staff nurses (~ 30%). Overall percent adherence to essential birth practices among ANMs and nurses was highest at 2 months after intervention initiation, when frequent coaching visits occurred (68.1% and 64.1%, respectively, Overall, ANMs and nurses responded similarly to the coaching intervention with the greatest increase in percent adherence to essential birth practices after 2 months of coaching and subsequent decrease in adherence 4 months after coaching ended. While coaching is an effective strategy to support some aspects of birth attendant competency, the structure, content, and frequency of coaching may need to be customized according to the birth attendant training and competency.NCT2148952; Universal Trial Number: U1111–1131-5647.ClinicalTrials.gov:  Contributions to the literatureThis study provides specific details about a coaching program around the WHO Safe Childbirth Checklist and subsequent adherence to essential birth practices according to birth attendant cadre (staff nurses vs. auxiliary nurse midwives).This study describes implementation science methods for evaluating a birth attendant coaching program at scale in Uttar Pradesh, India.This study reports the occurrence of unqualified health facility personnel who deliver childbirth care at primary-level facilities in Uttar Pradesh, India.This study describes the demographic characteristics of birth attendants in primary-level facilities in Uttar Pradesh, India.In response to Millennium Development Goal 5 to reduce the maternal mortality ratio by 75% , there hTo address concerns about skilled birth attendants' competencies, multiple global agencies including the World Health Organization (WHO), United Nations Population Fund (UNFPA), United Nations Children’s Fund (UNICEF), International Confederation of Midwives (ICM), and International Federation of Gynecology and Obstetrics (FIGO) recently published a new definition for skilled birth attendants . The revCoaching is one method to improve clinical performance, including individualized feedback during real-time observation of specific behaviors to enhance performance . In the ClinicalTrials.gov: NCT2148952; Universal Trial Number: U1111–1131-5647). The trial took place in 120 public primary and community health centers throughout the state of Uttar Pradesh in northern India, described in detail elsewhere [This study is a secondary analysis of birth attendant characteristics, coaching visits, and behavior uptake during the BetterBirth trial. The BetterBirth trial was a matched-pair, cluster-randomized controlled trial studying the effect of a coaching-based implementation of the WHO's Safe Childbirth Checklist on a composite measure of perinatal mortality, maternal mortality, and severe maternal morbidity, all within 7 days after delivery  for these characteristics and presented them as frequencies and proportions or as a median with interquartile range, as appropriate.Coaches observed birth attendant adherence to essential birth practices only in the intervention arm. Birth attendants could be observed for 1 or more of 5 different observation points: 1) on admission, 2) just before pushing, 3) within 1 min of delivery, 4) within 1 h of delivery, and 5) before discharge . For analysis, we created four mutually exclusive categories to define who delivered the woman: doctor only, staff nurse and ANM, staff nurse only, or ANM only. Due to the small number of observations, we dropped deliveries attended by the doctor only or by the staff nurse and ANM jointly from further analyses. We stratified adherence to essential birth practices by observational time point and presented it by arm and staffing cadre. We also graphed adherence to four essential birth practices and the frequency of Checklist use by cadre, trial arm, and time point.Independent observers were nurses trained in childbirth care who received extensive training to record behavioral data with a standardized tool . ThroughUsing observations from independent data collectors, we created a flow chart of complication management for elevated blood pressure. At 12 months after coaching began, when independent data collectors observed birth attendants taking maternal blood pressure, they also recorded the corresponding values. We identified high blood pressure as diastolic blood pressure greater than or equal to 110 mmHg. Independent observers also recorded whether magnesium sulfate was appropriately administered to individuals with high blood pressure.The analyses of the birth attendant survey, coach observations, and data collector observations were descriptive with results presented in proportions and medians as described above. The main analysis describing relationships between birth attendant cadres and behaviors used data from the independent observer database. In particular, we calculated an overall percent of behavior adherence for ANM only and staff nurse only in both arms stratified by time point from initiation of coaching. We used logistic regression using the Pearson overdispersion correction (to account for clustering by site) to assess differences between staff nurses and ANMs in the intervention group at 2 and 12 months after coaching began. We did not conduct statistical testing for 0 and 6 months after coaching began due to the limited number of observations from only 5 sites.The BetterBirth trial protocol was approved by ethics review boards at Community Empowerment Lab, Jawaharlal Nehru Medical College, Harvard T.H. Chan School of Public Health, Population Services International, the WHO, and the Indian Council of Medical Research. The protocol was reviewed and reapproved on an annual basis. For coaching, each facility and birth attendant formally agreed to participate in the BetterBirth program as a quality improvement initiative at the beginning of the intervention. For independent observation, each facility and birth attendant consented to participate in the study. Prior to each observation, independent observers verbally confirmed that the birth attendant agreed to be observed. Women who presented for labor and delivery signed written consent to have independent observers present during their care.n = 474, 83.2%), and the remaining respondents were ANMs  responded, and 37 (5.7%) did not respond. Among the 610 respondents, 40 were Lady Medical Officers , who we excluded in the analysis of nurses and ANMs. Therefore, 570 birth attendants were included in our analysis, representing 88.1% of the total birth attendants surveyed. The majority of respondents were staff nurses  were attended by non-clinical facility staff (such as cleaners). Of the 328 births attended by non-clinical facility staff, 129 (39.3%) occurred in the control arm and 199 (60.7%) occurred in the intervention arm.In intervention facilities, all staff nurses and ANMs who responded to the survey received coaching at least once Table . Staff np = 0.76). At 12 months after coaching began (4 months after coaching ended), ANMs demonstrated 49.2% adherence to all essential birth practices, and nurses demonstrated 56.1% adherence (p = 0.69). However, they did not sustain the increased adherence to checking maternal blood pressure during admission, hand hygiene prior to delivery, and checking newborn temperature at 1 h after birth , just before pushing (49.7 vs. 15.1%), and within 1 h after birth  received magnesium sulfate as indicated Fig. .Fig. 4CBirth attendant competency has gained global attention as a critical foundation for high-quality childbirth care . The birNurses were coached more frequently across all 5 observation points than ANMs. This unequal amount of coaching may reflect the staffing ratios in primary-level facilities where there are more nurses than ANMs available for coaching in general and specifically during daytime hours when coaching visits took place. Coaches may have felt more comfortable with nurses due to similar demographic characteristics such as age. It is important for coaching programs to reach all birth attendants, regardless of staffing availability, so that all can receive the benefit of individual observation and feedback to improve performance. Inter-professional differences between ANMs and nurses—such as age, education, and experience—should be considered when designing coaching programs because they may influence the frequency and content of coaching interactions.At least 5% of deliveries were attended by non-clinical facility personnel, such as cleaners in the facility. While there is information regarding prevalence of unqualified personnel or traditional birth attendants who assist with deliveries in homes or communities , there iIn designing the BetterBirth coaching intervention, we assumed that all birth attendants met competency standards such as those set forth by the WHO based on abilities, skills, and knowledge rather than on educational or training qualifications alone. We did not measure birth attendant competency directly as a part of the BetterBirth trial. We designed the coaching intervention to help close the “know–do” gap by identifying and resolving opportunity, ability, motivation, and supply (OAMS) barriers—in short to facilitate skilled birth attendants practicing their competencies. The sharp increase in adherence to essential birth practices at 2 months after coaching began suggests that a coaching-based implementation of the Checklist can improve birth attendant behaviors, as measured by the ability to complete the steps of the Checklist, but such an improvement may require frequent, intensive coaching to sustain behavior change. Additionally, integration of new practices in health facilities often require extended efforts to sustain behavior change initially while more permanent integrating mechanisms take hold .It is important to note that we measured adherence to essential birth practices, but not necessarily the quality of those practices performed. Complication management remained problematic, as demonstrated by the example of abnormal blood pressure management. In India, pre-service training for nurses and midwives may not provide sufficient clinical experience to meet international competency standards . One croWith early frequent coaching, adherence to essential birth practices increased, but was not sustained over time for many practices. The Government of India has partnered with Jhpiego in implementing Dakshata, a quality improvement program that focuses on boosting birth attendant competency in multiple states . ProgramThese findings are subject to several limitations. As a secondary analysis of the BetterBirth trial, there may be measurement bias in identifying the specific cadre of birth attendant who was present during delivery. We assumed the birth attendant observed within 1 min of birth was also the birth attendant who attended the delivery. Additionally, it is possible that multiple birth attendants participated in the care of individual women over the course of their stay in the facility. These results relied upon independent observations, which may be vulnerable to the Hawthorne effect. However, we conducted observations repeatedly over several weeks, and long-term, repeated observations do not appear to affect behavior . FurtherHigh-quality care during childbirth depends on competent birth attendants who are equipped with the human resources and supplies needed to manage complications. In the BetterBirth trial, we used coaching to boost adherence to key essential birth practices on the WHO Safe Childbirth Checklist. Overall, ANMs and staff nurses responded similarly to the coaching intervention with the greatest increase in adherence to essential birth practices after 2 months of coaching, with subsequent decrease in adherence after the coaching intervention was completed. Coaching is an effective strategy to support some aspects of birth attendant competency; however, the structure, content, duration, and frequency of coaching may need to be customized according to the birth attendant cadre and competency.Additional file 1: Table S1. Baseline adherence to essential birth practices stratified by birth attendant cadre in 10 facilities in the BetterBirth trial.Additional file 2: Table S2. 2-month adherence to essential birth practices stratified by birth attendant cadre in 30 facilities in the BetterBirth trial.Additional file 3: Table S3. 6-month adherence to essential birth practices stratified by birth attendant cadre in 10 facilities in the BetterBirth trial.Additional file 4: Table S4. 12-month adherence to essential birth practices stratified by birth attendant cadre in 30 facilities in the BetterBirth trial.Additional file 5: Table S5. Average percent adherence to essential birth practices by time point and birth attendant cadre.


Prostatic utricle cyst is a rare congenital anomaly. Symptomatic cysts require treatment. Surgical excision is the treatment of choice, but is challenging due to close proximity to vas deferens, ejaculatory ducts, bladder, prostate, rectum and pelvic nerves. Complications include rectal injury, ureteral injury, impotence, infertility and faecal incontinence. We here report a rare complication in which bladder was accidentally removed during laparoscopic excision of prostatic utricle cyst. To best of our knowledge such a complication has never been reported previously. We also describe the possible cause of this accident and suggest ways to prevent this disastrous complication. Prostatic utricle cyst is a rare congenital anomaly. Cysts vary in size and presentations differ. Symptomatic cysts require treatment . SurgicaA 24 year old male presented to us with urinary diversion by bilateral percutaneous nephrostomies (PCN), performed six months ago. He had undergone laparoscopic surgery for removal of prostatic utricle cyst elsewhere. Postoperatively he developed anuria. A sonogram revealed bilateral hydro-ureteronephrosis. Bladder was not commented upon. This acute crisis was treated by bilateral PCN. Nephrostomogram revealed complete cut-off of both lower ureters .He had history of lower abdominal pain with burning micturition on and off since two years. Investigations had revealed a prostatic utricle cyst with infection. Following conservative management, he was asymptomatic for about 18 months. Recurrence of symptoms was associated with increase in cyst size . SurgicaSystemic examination was normal. Abdominal examination revealed port site scars, bilateral nephrostomies and coronal hypospadias. Investigations revealed normal hemogram and creatinine. Bilateral lower ureteric injury was the suspected diagnosis initially. Ascending and micturating cysto-urethrogram (MCU) showed smooth walled bladder with mildly reduced capacity and normal urethra .With evidence of bilateral ureteric cut-off and normal lower urinary tract, bilateral ureteric re-implantation was planned. Urethrocystoscopy showed normal anterior urethra. There was an opening on verumontanum, which accommodated 17 French cystoscope sheath easily. This lead to a smooth walled cavity containing about 200 mL of turbid fluid. The epithelium was not like normal urothelium. Ureteric orifices were not seen. Then we realized that this cavity was indeed the cyst which was falsely mistaken as bladder on MCU. The proximal urethra was completely cut off below the level of bladder neck, ending blindly. A situation of accidental urinary bladder cystectomy and not prostatic utricular cystectomy was realized. Further surgery was abandoned.Patient was explained about absence of urinary bladder. MRI pelvis confirmed the same . SurgicaPostoperative MCU showed good capacity neobladder and no extravasation . NephrosAt follow-up, he was voiding well with minimal residue and no incontinence. His outcomes in terms of ejaculation are yet not known.Prostatic utricles are remnants of Mullerian ducts. Normally Mullerian ducts regress under influence of mullerian regression factor and is represented by appendix testis  and utricle . Utricular anomalies result from incomplete regression of Mullerian ducts or incomplete androgen mediated closure of the urogenital sinus in form of prostatic utricular cyst .Mullerian duct remnants are uncommon. Incidence of enlarged prostatic utricle is 11-14% in association with hypospadias or intersex anomalies, more so with perineal hypospadias (>50%). About 10-25% show an association with renal agenesis / dysgenesis and 25% cases with hypospadias , perineal and anterior or posterior transrectal sagittal approaches. Complications include rectal injury, ureteral injury, impotence, infertility and faecal incontinence .In our patient there was accidental removal of urinary bladder. To best of our knowledge, such complication has never been reported. Possibly Foley catheter was lodged into utricular cyst, misleading the surgeon to excise urinary bladder.Preoperative cystourethroscopy could have shown that opening of utricle cyst was directly in line with urethra, bladder neck was high at an angle, and would have more clearly shown anatomical relationship of cyst with bladder.Preoperative cannulation of cyst has been described to facilitate laparoscopic identification and mobilization of cyst .Intraoperative flexible cystoscopy helps in identifying the bladder from cyst, by seeing light of cystoscope during laparoscopy. By chance, if bladder gets injured, it could be identified immediately.Preoperative cannulation of ureters with ureteral catheters helps in identifying them intraoperatively. By seeing the structure into which ureters enter, bladder could have been differentiated from cyst. Ureteral injury could be identified intraoperatively.Adopting above mentioned measures could potentially avoid such disastrous complication.


Moderately and late preterm children  have a greater risk of poorer growth. This seems to be associated with poorer neuropsychological functioning. Evidence is limited on whether this also holds for emotional and behavioral (EB) problems. Therefore, we assessed whether longitudinal growth from birth until age 7 was associated with EB problems at age 7 in MLPs.This study was part of the Longitudinal Preterm Outcome Project, a prospective cohort study. Data on growth  were obtained from assessments from birth until age 7. EB problems were assessed at age 7 with the Child Behavior Checklist. We assessed whether growth and EB problems were associated using logistic regression analyses, adjusting for multiple birth, parity, and socioeconomic status.We included 248 MLPs. Median gestational age was 34 weeks (interquartile range: 33–35 weeks). Mean birth weight was 2.2 kg (standard deviation: 0.5 kg). Postnatal growth measures were below the Dutch reference norm. EB problems were more prevalent in MLPs than in the general Dutch population. Generally, we found no associations between growth and EB problems; odds ratios ranged from 0.20 to 2.72.In MLPs, postnatal growth from birth until age 7 was not associated with EB problems at age 7. Poorer growth thus seems to relate to neuropsychological problems, but not to EB problems. This suggests that the etiologies of these problems differ at least partially. Worldwide, approximately 10% of all children are born preterm , impairePoorer neuropsychological functioning and EB problems may result from disruptions in brain development –20. SeveThis study was part of the Longitudinal Preterm Outcome Project , a prospective cohort study that was designed to investigate growth, development, and general health of preterm children, with emphasis on MLP birth. The study was approved by the Ethical Review Board of the University Medical Center of Groningen.Children were included during routine well-child care in preventive child health care organizations at the age of 4 years. These organizations assess more than 90% of the children in The Netherlands at regular intervals . ChildreFrom this community-based cohort, we invited parents of all 341 MLPs from the three northern provinces in the Netherlands to fill in questionnaires when their child had reached the age of 7 years. In total, 248 parents (73%) participated.Data on growth were obtained from records on well-child assessments from birth to the age of 4 years and from data collected additionally in a research setting at the age of 7 years. In The Netherlands, children have approximately 15 routine well-child assessments in preventive child health care organizations to monitor their mental and physical development, using structured interviews with parents, general physical examinations, and standardized screening procedures. Head circumference (HC) was assessed until the large fontanel was closed. Height and weight were measured using standardized measuring devices, i.e. an infantometer or stadiometer. Children were examined in the supine position until they reached the age of 24 months. From 24 months onwards the child was standing during measurements. We only present data on growth at birth and at the ages of 1, 4 and 7 years, because growth measures at these ages were available in most children.We converted all growth measures to z-scores based on the best available norm data. Height and HC at birth were converted according to Niklasson . Weight We measured EB problems at the age of 7 years using the validated Dutch version of the Child Behavior Checklist (CBCL) for 6–18 years ,38. The The Strengths and Difficulties Questionnaire (SDQ) is a brief behavioral screening questionnaire that is more widely used in clinical settings, because of its brevity and its ability to measure competences as well as problem behaviors ,41. MoreWe selected covariates based on previous studies on EB problems in preterm children –47. PeriFirst, we assessed background characteristics of the sample. Second, we assessed prevalence rates of clinical and subclinical EB problems. Third, we assessed whether growth  and clinical EB problems were associated using univariable and multivariable logistic regression analyses. The multivariable analyses were corrected for multiple birth, parity and SES. To assess the effect of gain in height, weight, and HC between two consecutive time points, we also corrected those analyses for height, weight, and HC of the first time point, respectively. We repeated the logistic regression analyses for the total difficulties score and the hyperactivity subscale of the SDQ.P-value of less than 0.01 to be statistically significant.We used IBM SPSS version 23.0  for statistical analyses. Correcting for multiple comparisons (Bonferroni), we considered a We included 248 MLPs, with a median GA of 34 weeks (interquartile rage: 33–35 weeks) and a mean birth weight of 2.2 kg (SD: 0.5 kg). Background characteristics are shown in In We found no associations between growth from birth until the age of 7 years and EB problems at the age of 7 years, with the exception of height gain . GreaterThis study showed that nearly all measures of longitudinal growth from birth until the age of 7 years were not associated with EB problems at the age of 7 years in MLPs. MLPs only had a greater risk of internalizing problems at the age of 7 years in case of greater height gain in the first year of life.These results do not support our hypothesis that poorer growth is associated with EB problems. This contrasts with findings of Pyhälä et al. who reported an association between poorer growth from birth to term age and higher levels of autism-spectrum traits in adolescence for children born with very low birth weight  . We wereOur results are consistent with those of previous studies that were unable to demonstrate an association between growth and EB problems –28. HoweIn our study, height gain in the first year of life was the only growth measure that was associated with EB problems. To our knowledge, we are the first to report a positive association between growth and EB problems. Since only a single association came out significantly and only in the multivariable analysis, we believe this may be a chance finding.An important strength of this study is its community-based sample. Furthermore, our analyses were comprehensively adjusted for effects that can be attributed to SES, as we used a composite score of the three most often used indicators of SES, i.e. education, income and occupation . Our stuOur findings imply that growth has hardly any effect on childhood EB problems. It seems that growth is associated with both neuropsychological functioning ,10] and  and 10]]In MLPs, longitudinal growth from birth until the age of 7 years was not associated with EB problems at the age of 7 years. These findings suggest that the etiologies of EB problems and of poorer neuropsychological functioning are at least partly different. These etiologies require further research.S1 Table# The multivariable analyses for gain in height, weight, and HC between two time points were also corrected for height, weight, and HC of the first time point, respectively. * P < 0.01.(DOCX)Click here for additional data file.


Very preterm birth, before the gestational age (GA) of 32 weeks, increases the risk of obstructed airflow in adulthood. We examined whether all preterm births (GA<37 weeks) are associated with poorer adult lung function and whether any associations are explained by maternal, early life/neonatal, or current life factors. Participants of the ESTER Preterm Birth Study, born between 1985 and 1989 (during the pre-surfactant era), at the age of 23 years participated in a clinical study in which they performed spirometry and provided detailed medical history. Of the participants, 139 were born early preterm (GA<34 weeks), 239 late preterm (GA: 34-<37 weeks), and 341 full-term (GA≥37 weeks). Preterm birth was associated with poorer lung function. Mean differences between individuals born early preterm versus full-term were -0.23 standard deviation (SD) : -0.40, -0.05)) for forced vital capacity z-score (zFVC), -0.44 SD  for forced expiratory volume z-score (zFEV1), and -0.29 SD  for zFEV1/FVC. For late preterm, mean differences with full-term controls were -0.02 SD , -0.12 SD  and -0.13 SD  for zFVC, zFEV1, and zFEV1/FVC, respectively. Examination of finer GA subgroups suggested an inverse non-linear association between lung function and GA, with the greatest impact on zFEV1 for those born extremely preterm. The subgroup means were GA<28 weeks: -0.98 SD; 28-<32 weeks: -0.29 SD; 32-<34 weeks: -0.44 SD; 34-<36 weeks: -0.10 SD; 36-<37weeks: -0.11 SD; term-born controls (≥37weeks): 0.02 SD. Corresponding means for zFEV1/FVC were -1.79, -0.44, -0.47, -0.48, -0.29, and -0.02. Adjustment for maternal pregnancy conditions and socioeconomic and lifestyle factors had no major impact on the relationship. Preterm birth is associated with airflow limitation in adult life. The association appears to be attributable predominantly to those born most immature, with only a modest decrease among those born preterm at later gestational ages. Preterm birth, or birth before 37 gestational weeks, accounts for approximately 11% of all births globally: annually ~15 million births worldwide , with a Children and adolescents born preterm have more airflow obstruction and manifest more airway disorders –8 than tOur aim was to assess lung function and pulmonary health in adults born preterm across the whole gestational age range. We hypothesized an inverse relationship between gestational age at birth and airflow impairment.We also explored whether potential associations with preterm birth may be attributed to neonatal conditions or to maternal pregnancy conditions underlying preterm birth.Participants come from the ESTER Preterm Birth Study, which comprises 1980 young adults. They were grouped by gestational age at birth into those born early preterm (GA<34 weeks), late preterm (GA 34-<37 weeks) and full-term (GA≥37 weeks) as the control group, which we refer to as ‘at term’ . ParticiFrom 2009 to 2011, 779 individuals with adequately verified lengths of gestation participated in a clinical study at a mean age of 23.3  years and underwent a thorough health examination, including spirometry; they reported on pulmonary health, physical activity, and smoking as well as family socio-demographics . Of the We obtained details on pregnancy, birth and postnatal period from medical records , calcula25-75%), forced expiratory flow at 75% of expired volume during FVC test (FEF75%), forced expiratory flow at 50% of expired volume during FVC test (FEF50%). Lung function data were converted into Global Lung Function Initiative z-scores using the Caucasian reference [Spirometry (n = 724) was performed  sitting upright following the standard spirometry technique described by the European Respiratory Society Guidelines . The sameference . Data weeference , based oeference .Bronchodilation test was performed , accordith percentile, by multiple logistic regression. We used two multi-variable regression models, adjusting for covariates related to intrauterine exposures , parental education, and participant health  were preformed using SPSS v.22 . Lung function, as the main outcome of interest, was compared between the preterm groups and the term-born controls as a continuous outcome by multiple linear regression. We also compared the proportion of participants with low zFVC, zFEV1 or zFEV1/FVC, defined as being below -1.645 SD, corresponding to 5In Model 1 or the basic model, we controlled for sex, age at the time of the clinical examination, and source cohort . In Model 2, we further adjusted for highest parental education and maternal smoking during pregnancy, which also served as an indicator of family socio-economic status , as well(GA), as well as its quadratic term (GA2).To further examine the relationship between gestational age and lung function, we present the linear regression analyses using finer gestational age groups  in We performed sensitivity analyses in order to test for the effect of gestational age on lung function without known fetal or neonatal causes of lower lung function. The following exclusions were applied in multiple linear regression analyses: (A) BPD, (B) small-for-gestational age (SGA): SD<-2 , (C) thoAdditionally, we explored the effect of obstructive airways disease on lung function within gestational age groups by comparing lung function among those with or without obstructive airways disease using the logistic regression method. As previously described , we form25%-75%, FEF75% were all lower among subjects born early preterm than among controls.Participants’ background details are provided in We ran multi-variable linear regression models to examine the impact of a range of covariates on the difference in adult lung function between early and late preterm groups compared with controls  as well Regression model 1 , (adjustth percentile). This is shown in We also assessed the proportion of participants whose FVC, FEV1 or FEV1/FVC z-score was below -1.645 SD , 28-<32 (n = 49), 32-<34 (n = 81), 34-<36 (n = 110), and 36-<37 (n = 129) versus term-born controls n = 341)), for the three key lung function outcomes: zFVC, zFEV1, and zFEV1/FVC. The mean differences from controls of these finer gestational age groups are provided in Independent univariate associations between lung function and individual covariates adjusted for in the regression models are provided in the supplementary material .Ninety-eight (98) infants (13.6%) had received respirator care ; the freWe assessed the effect of other prenatal and perinatal factors on adult lung function by applying the two regression models in the sensitivity analyses , where wOur aim was to study the effects of preterm birth on lung function and respiratory health in adulthood, incorporating the whole range of preterm gestational ages. Our results indicate an association between the degree of prematurity and airflow impairment in adult life. The strongest associated was detected among those born most immature. This association between gestational age and lung function was not attentuated by adjusting for underlying risk factors of preterm birth such as maternal pregnancy disorders, maternal smoking during pregnancy, altered fetal growth, or parental socio-economic status. However, maternal smoking during pregnancy on its own was a significant predictor of poorer adult lung function.Our study is in agreement with previous findings –4, 6–8 sWe performed sensitivity analyses excluding those who had received ventilator treatment. Our study shows that despite exclusions, poorer lung functions persisted and the effect was even stronger among those born early preterm. Previous studies have reported poorer long-term lung function among individuals who were born preterm but did not have BPD or any other severe condition that may impact lung function during the peri- or neonatal period: these individuals are often viewed as healthy in terms of pulmonary function . These ‘So far, only few studies have assessed lung function across the whole range of gestational ages. A longitudinal ALSPAC cohort study of 8-9-year olds reported reductions in zFEV1 of -0.49 among those born at 25–32 weeks of gestation, -0.49 among those born at 33–34 weeks, and 0.01 among those born at 35–36 weeks, compared with those born at term [Our findings do not indicate the mechanism of airflow impairment. The most significant contributor to airflow rate is resistance to airflow, which is primarily influenced by airway diameter . While aWhile our findings were largely independent of pregnancy conditions underlying preterm birth, maternal smoking during pregnancy was an independent predictor of airway obstruction. This is consistent with a recent Finnish study of adults born preterm at VLBW . AlthougOur findings indicate the risks for obstructive airways disease  was predicted both by preterm birth and intrauterine growth restriction, whereas hospital-treated asthma was predicted by preterm birth only—however, only among women . The HelOur participants are in their early twenties and at the age of maximum lung function. Even with normal natural decline in lung function, those with lower peak function are expected to reach symptomatic levels earlier. Moreover, this decline may be accelerated in those with observable airway obstruction in adulthood. The CARDIA cohort study performed spirometry among participants at 18–30 years of age and again at 35–50 years. Drops of over 5% in FEV1 and FVC were observed in those with airway obstruction at baseline, while less than 3% in those with normal baseline lung function . It is eper se. However, adults born preterm undertake less physical activity than those born at term [In terms of prevention, it is important to slow down the inevitable deterioration of lung function  and the  at term , which mWhile we have extensive prenatal and neonatal data, we lack data on childhood exposures, such as respiratory infections, that may predispose to chronic airways obstruction later on.Different diagnostic criteria for BPD were applied in our two source cohorts; among those recruited from the FMBR we were able to independently confirm the diagnosis by assessing the need of supplementary oxygen at 28 postnatal days from medical records, while in the NFBC the diagnosis was made by a clinician and we had no access to the individual criteria of diagnosis. It is therefore possible that we are missing a few NFBC individuals who would have had BPD according to the criteria we used for FMBR participants. Furthermore, treatment of preterm-born infants today differs from that of our participants who were born during the pre-surfactant era, when antenatal glucocorticoid treatment was only being introduced in Finland. Data on antenatal glucocorticoid treatment was only available for participants from the Finnish Medical Birth Registry born between1987 and 1989; 22.2% of those born early preterm had been exposed to the treatment. However, these limitations are relevant for individuals born very or extremely preterm and thus less pertinent for our study, which was designed to assess the whole spectrum of preterm birth and accordingly also had limited power to assess those born very or extremely preterm.Further, we have no data on parental respiratory health or atopy and cannot exclude confounding by these factors.Our study shows that adults born early preterm have airflow limitation. This association seems to be independent of underlying pregnancy disorders or risk factors, such as maternal gestational smoking or socio-economic position. Our study showed an inverse association between gestational age and obstructive airflow, much of which was due to those born most immature. In addition, adults born early preterm had slightly lower vital capacity, which may be partly explained by intrauterine growth restriction, which commonly affects this group. Most differences between those born late preterm and controls were not statistically significant. Our results are consistent with previous studies reporting an inverse relationship between the degree of prematurity and airflow obstruction.Obstructive airways disease may in part have its origins in preterm birth and prenatal life. We encourage healthcare professionals to be vigilant when dealing with individuals born at early gestational weeks even with no other significant health conditions impacting pulmonary development. These individuals represent a potential unacknowledged risk group for poor long-term lung health outcomes.S1 FigBlack line indicates zero difference from control.(TIF)Click here for additional data file.S1 TableThe ESTER birth cohort (births in Northern Finland during 1985–89); clinical examination during 2009–11.(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.S4 Table(DOCX)Click here for additional data file.


Antibiotics pose potential ecological risks in the water environment, necessitating their effective removal by reliable technologies. Adsorption is a conventional process to remove such chemicals from water without byproducts. However, finding cheap adsorbents with satisfactory performance is still a challenge. In this study, polystyrene microspheres (PSM) were enhanced to adsorb tetracycline by surface modification. Simple urea immersion was used to prepare urea-immersed PSM (UPSM), of which surface groups were characterized by instruments to confirm the effect of immersion. Tetracycline hydrochloride (TC) and doxycycline (DC) were used as typical adsorbates. The adsorptive isotherms were interpreted by Langmuir, Freundlich, and Tempkin models. After urea immersion, the maximum adsorption capacity of UPSM at 293 K and pH 6.8 increased about 30% and 60%, achieving 460 mg/g for TC and 430 mg/g for DC. The kinetic data were fitted by first-order and second-order kinetics and Weber–Morris models. The first-order rate constant for TC adsorption on UPSM was 0.41 /h, and for DC was 0.33 /h. The cyclic urea immersion enabled multilayer adsorption, which increased the adsorption capacities of TC on UPSM by two to three times. The adsorption mechanism was possibly determined by the molecular interaction including π–π forces, cation-π bonding, and hydrogen bonding. The simple surface modification was helpful in enhancing the removal of antibiotics from wastewater with similar structures. Antibiotics are a concern as contaminants in the water environment due to their potential ecological risks and ubiquitous distribution in the world . Among tMany effective techniques have been developed to remove or degrade residual antibiotics in wastewater, such as adsorption , advantaPolymer resin microspheres, with the merits of low cost, high porosity, large surface area, and adsorption capacity, have potential for commercial application ,20,21,222) on the adsorbent surface as a neutral anion receptor to link an ester group (–COO–R) in antibiotic molecules, in order to form chelated complexes with hydrogen bond acceptors like ditopic carboxylates. Another choice is to use a carbonyl group as an electron donor to enhance the π–π interaction and cation-π bonding. As a kind of simple and cheap commercial material, urea (CO(NH2)2) combined with two amino (–NH2) and one carbonyl (C=O) functional group, makes it a good agent to interact with tetracycline molecules.Tetracycline reagents have multiple functional groups , includiIn this paper, we modified the surface of polystyrene ethylenediaminetetraacetate (EDTA) microsphere (PSM) resin by simply immersing it in urea solution. Then, the urea modified PSM (UPSM) was characterized by Brunauer–Emmett–Teller (BET), x-ray photoelectron spectroscopy (XPS), and infrared (IR) to confirm the effects of impregnation. Later, we conducted adsorption experiments to evaluate their capacity to remove TC and DC from water. Finally, the interaction between antibiotic molecules and UPSM surface is discussed.Polystyrene EDTA microsphere (PSM) resins were synthesized according to a reported thermal-solvent method . The polThe urea-immersed PSM (UPSM) was acquired by immersing the PSM into 100 g/L of urea solution for 12 h. The urea solution was prepared by dissolving 5 g urea powder  in 50 mL of ultrapure water. Then 2 g of PSM was mixed with 50 mL of urea solution in a 100 mL 3-necked glass flask. The mixture was agitated in a thermostatic shaker at 150 rpm and 25 ± 1 °C for 12 h. After filtration, the UPSM were intensively washed by ultrapure water 10 times to remove the excessive urea. Then the UPSM were dried in an oven with desiccants at room temperature overnight.2 adsorption-desorption isotherm at liquid nitrogen temperature . The instrumental parameters were default as described in the manual and guidance. The surface area of UPSM was slightly higher than that of PSM, as shown in The surface morphologies of PSM and UPSM were characterized by using a scanning electron microscope . The SEM images were similar between PSM and UPSM, as shown in The surface functional groups of PSM and UPSM were identified by Fourier transform infrared (FT-IR) spectroscopy using the KBr tableting technique on an FT-IR spectrometer  in transmission mode. The elemental analysis was conducted by x-ray photoelectron spectroscopy (XPS) on an electron spectrometer  using 300 WAl-Ka radiation.The target antibiotic reagents, tetracycline hydrochloride (TC) and doxycycline hydrochloride (DC), were purchased from a commercial supplier . The molecular structures and other information of urea and tetracycline are shown in 2 > 0.999). Control experiments were conducted by mixing 40 mg/L tetracycline with 100 g/L urea with equal volume. After 12 h, the residual concentrations of TC and DC changed by less 1% of the initial values, indicating that tetracycline molecules are inert with urea in the solution.The concentrations of TC and DC in aqueous solution were determined on a UV-Vis spectrophotometer . The specific wavelength for TC was 360 nm and for DC was 325 nm according to the maximum absorption. The concentration was calibrated from linear standard curves (RHydrochloric acid (HCl) and sodium hydroxide (NaOH) were ordered from a local supplier  to prepare HCl solution in 0.1 mol/L (M) and NaOH in 0.1 M. The bulk pH of the solutions was adjusted before adsorption experiments by dosing drops of above acid and base manually. The instant pH value was read out by a laboratory pH meter 1 min after dosing.Preliminary adsorption experiments were conducted to determine the optimal bulk pH in the gradient range . Kinetic curves at the gradient pH were acquired by exposing 60 mg/L of TC or DC to 60 mg of UPSM. The results are shown in For isothermal experiments, tetracycline solutions at 16 levels of initial concentration (100–2000 mg/L) were prepared to expose to 60 mg of PSM or UPSM in a volume of 20 mL. The mixture was agitated in a thermostatic shaker at a speed of 150 rpm and temperature of 25 °C. The experiments lasted for 24 h to ensure that the adsorption reached the equilibrium state.For kinetic experiments, 60 mg of PSM or UPSM was dosed into tetracycline solutions at 5 levels of initial concentration (100–300 mg/L). The experiments lasted for 100 min and the concentrations of TC and DC were determined to obtain the kinetics.Recycling adsorption by UPSM was achieved by using urea immersion after the saturated adsorption of tetracycline. First, 40 mg/L of TC was adsorbed onto 60 mg of UPSM for 12 h. After that, the UPSM were rapidly washed by ultrapure water 10 times to remove urea. Second, the USPM were again immersed in 20 mL of urea solution at a concentration of 100 g/L for 12 h. Finally, the UPSM were cleaned and exposed to 40 mg/L of TC solution for an additional cycle of adsorption. In total there were 10 cycles of adsorption-immersion. The TC concentrations were analyzed for comparison with the control experiments using UPSM.USPM after 10 cycles were further examined for the desorption property under thermal, acidic, and alkaline treatment. Thermal desorption was conducted at 35 °C by soaking the UPSM in 20 mL of pure water in a water bath for 12 h. The acidic desorption was conducted by immersing the UPSM in 20 mL of 0.1 M HCl for 3 h. The alkaline desorption was achieved under similar conditions. Control experiments were conducted in parallel. The experimental duration was 7 h. The thermal stability of tetracycline was examined in a water bath at 95 °C for 1 h.qt) of tetracycline onto microsphere resin by the following equation, as described in the literature [qt is the surface loading of adsorbates on adsorbents (mg/g), M is the mass of adsorbent (g), V is the volume of the solution (L), and C0 and Ct are bulk tetracycline concentrations initially and at time t of the experiment, respectively (mg/L). In the case of isothermal experiments, subscript e was used instead of t to represent the equilibrium state, as qe and Ce.We evaluated the solid surface loading  was 13% higher than PSM’s. Consequently, the BET surface area of UPSM (112.42 m2/g) was about 60% higher than that of PSM (71.69 m2/g), according to Similar SEM images of PSM and UPSM  suggest 2/–NH) group in the range of 3300–3500 cm−1 [−1. Carbonyl groups in UPSM and PSM were slightly different, in the range of 2500–3400 cm−1. The broader band of UPSM at 1640–1650 cm−1 refers to the more singular hydrogen bonds between amino and carbonyl groups.The FT-IR spectra  suggest 500 cm−1 , UPSM haXPS analysis  was used2), the Langmuir and Freundlich models were not perfect to fit the data but better than the Tempkin model. The data-fitting results by the Langmuir model are shown in qm) of TC on UPSM was 460 mg/g at pH 6.8 and 25 °C. This capacity was about 60% higher than that on PSM (290 mg/g). The adsorption capacity of DC on UPSM (430 mg/g) was 30% higher than that on PSM (330 mg/g). The higher adsorption capacity of UPSM than PSM was accordant to the larger BET surface area than PSM.The parameters of isothermal models were close for TC and DC, as shown in The model parameters of the three kinetic models for tetracycline on UPSM are shown in t1/2 = ln2/K1, where K1 is the rate constant of first-order kinetics. According to K1 for TC and DC adsorption is 0.33 and 0.41 /h, respectively, indicating that 50% removal of initial concentration occurred in 1.7 and 2.1 h. This duration covers the practical hydraulic retention time in filters.Kinetics is useful to determine the optimal volume of reactors to ensure certain removal efficiency. The duration of half reduction can be calculated as The magnetic particles on graphene oxide nanosheets showed impressively high adsorption capacity for tetracycline at 714 mg/g . By compIt is better to estimate adsorption performance in similar concentrations of adsorbates in the actual matrix. Tetracycline in a surface water environment, e.g., rivers and lakes, is generally at trace levels of several μg/L . Its conn for both modes (n = 0.93 and n = 1.26) were close to 1, indicating linear isotherm in low concentrations. In single immersion mode, the bulk concentration was saturated at about 37 mg/L after 5 cycles, while it took 10 cycles to saturate at about 35 mg/L in cycle immersion mode. This result suggests that multilayer adsorption increased the capacity but such effect reduced gradually with the increasing number of layers. At Ce = 20 mg/L, the adsorption capacity was twice that in single immersion mode. The improvement was three times at Ce = 30 mg/L. The cycle urea immersion obviously increased the adsorption capacity of UPSM by two to three times.The isotherms of TC on UPSM by single and cycle urea immersion are compared in A desorption curve of TC from loaded UPSM by thermal treatment is shown in The insufficient desorption by HCl indicated chemical association during the adsorption, such as π–π electron donor–acceptor (EDA) interaction and hydrogen bonding. Hydrogen bonding can be formed between the amino groups of tetracycline and the carbonyl groups of EDTA. The ketone group in tetracycline molecules is a π-electron acceptor and the ester group (–COO–R) in EDTA is a strong electron donor. Adsorption might be enhanced by different couples of π–π EDA interactions, e.g., the interaction between the conjugated π-electron moiety, the cation-π bonding between the amino groups, and the π-electron rich structures on the solid surface.−1 appeared in the FT-IR spectra of loaded UPSM (−1 disappeared and the peak at 1650 cm−1 was blue shifted to about 1600 cm−1, which might be related to strong intermolecular hydrogen interactions between urea and tetracycline (After adsorption, specific peaks of pure tetracycline  in the rded UPSM a. The peacycline b.Urea immersion was used to modify microsphere resin to enhance its capacity of removing tetracycline reagents from water. The surface characteristics by XPS and FT-IR analysis confirmed successful urea immersion and tetracycline adsorption. The adsorption isotherms were explained by the Langmuir, Freundlich, and Tempkin models. The adsorption capacity of UPSM for TC was 460 mg/g and for DC was 430 mg/g, which were increased by 30% and 60%, respectively, by urea immersion. Adsorptive kinetic data were interpreted by first-order, second-order, and Weber–Morris models. The rate constant for TC adsorption on UPSM was 0.41/h and for DC was 0.33/h, indicating that the durations of 2.1 and 1.7 h were necessary for 50% removal of TC and DC, respectively.Desorption experiments revealed pure dissociation of TC from UPSM. The releasing rates were 0.4%, 3.7%, and 6.9% in 2 h by heating, NaOH, and HCl, respectively. Possible chemical bonding such as hydrogen bonding and π–π interaction may contribute to the adsorption enhancement. Using urea molecules as bridges, multilayer adsorption of tetracycline was possible, which was confirmed by repeated adsorption experiments on UPSM with cycle urea immersion. The adsorption capacity was two to three times higher than the UPSM with single urea immersion. In summary, urea immersion is satisfactory to modify the surface of microsphere resin to enhance the removal of tetracycline antibiotics from water.


Hospitalisation (2000–2015) and Immunisation Register datasets (1994–2015), showed that influenza hospitalisations (n = 53) and rates were 42.3 times higher in Aboriginal infants (AR 254 vs. 6); and that pertussis hospitalisations (n = 37) were 7.1 times higher in Aboriginal infants (AR 142.5 vs. 20.2) compared to non-Aboriginal infants. These baseline data are essential to assess the safety and effectiveness of influenza and pertussis vaccinations in pregnant women from the NT. Remote living Aboriginal women and infants stand to benefit the most from these vaccines.We conducted probabilistic data linkage of three population datasets for the Northern Territory (NT), Australia, to describe the incidence of preterm births, stillbirths, low birthweight and small for gestational age (SGA) per 1000 NT births; and influenza and pertussis hospitalisations per 1 00 000 NT births in infants <7 months of age, in a pre-maternal vaccination era. The Perinatal Trends dataset (1994–2014) formed the cohort of 78 382 births. Aboriginal mother–infant pairs (37%) had disproportionately higher average annual rates (AR) for all adverse birth outcomes compared to their non-Aboriginal counterparts; rate ratios: preterm births 2.2 (AR 142.4  Globally, pregnant women, particularly indigenous pregnant women and their infants, experience severe health consequences from influenza and pertussis infections compared to the general population , 2. Two pre-maternal vaccination uptake era. A World Health Organization (WHO) report has stressed that baseline information on the safety of immunisation during pregnancy is essential in order to distinguish between vaccine benefits and safety concerns in local populations [Despite these recommendations, systematic programs to monitor the uptake, safety and effectiveness of IIV and pertussis vaccines in pregnancy remain absent. To determine the safety and effectiveness of vaccination in pregnancy, it is critical to quantify the baseline rates of adverse birth outcomes and the disease burden from influenza and pertussis infections in early infancy in a ulations .2) yet has a relatively small population (~245 000) who are substantively younger and compared to the rest of Australia, have the highest population proportion who identify as Aboriginal [In Australia, pregnant women and Aboriginal and/or Torres Strait Islander  women and their infants are over-represented in notification and hospitalisation rates and intensive care unit (ICU) admissions for influenza and pertussis infections , 7. The original , 9. Smaloriginal  and littNote: *In the Northern Territory, ‘Aboriginal’ is the preferred official term for inclusively referring to both Aboriginal and Torres Strait Islander peoples. This respectfully acknowledges the relatively small percentage of the NT population who identify as Torres Strait Islanders and the greater proportion of these people who also identify as Aboriginal .In the NT between 2008 and 2012, laboratory-confirmed influenza infection notification rates were consistently highest in women of child-bearing age and Aboriginal children in the 0–<5 years age group  and has For infants to be considered protected against pertussis infection, the Australian National Immunisation Program (NIP) currently recommends a three-dose primary infant pertussis vaccination schedule; at 6–8 weeks, at 4 months and at 6 months of age . Despitepre-maternal vaccination uptake era.We aimed to describe the baseline incidence of adverse birth outcomes for the whole of the NT population by year of infant birth, remoteness and Indigenous status; we also aimed to describe the baseline incidence, severity and geographic variation of influenza and pertussis hospitalisations in infants from birth to 6 months of life by Indigenous status and region in a We used three de-identified, unit-record linked whole of NT population administrative datasets from the Developmental Outcomes of Children in the NT study,  to conduOur cohort encompassed all recorded NT births from 01 January 1994 to 31 December 2014 inclusive. This time period meant the birth cohort was expected to be vaccine naïve for either IIV or pertussis vaccines in pregnancy. The maternal pertussis vaccination program did not commence until April 2015 and there was a very small proportion of IIV uptake in pregnancy recorded during the 2009 H1N1 influenza pandemic until 2011 (<5%) . Uptake The NT Perinatal Trends dataset  encompassed a whole of NT population birth cohort from 01 January 1994 to 31 December 2014 inclusive. These data were used to establish the study cohort. Missing data were treated as such.The NT Hospital Inpatient Activity dataset  records all episodes of care for patients admitted to all NT hospitals. Our dataset captured all episodes of hospitalisations from 01 July 2000 to 31 December 2015 inclusive. We examined infant hospitalisations where a diagnosis of influenza and/or pertussis was recorded, based on the Australian modified International Statistical Classification of Diseases and Related Problems (ICD-10-AM) codes, for infants born in the NT whose mother had a record in the perinatal dataset .The NT Immunisation register (NTIR) captured all episodes of vaccinations administered in the NT from 01 January 1994 to 31 December 2015. Immunisation status was ascertained for recommended scheduled vaccines in hospitalised infants with an ICD-10-AM diagnosis of influenza and pertussis.A mix of deterministic and probabilistic linkage was used to match records from NT administrative datasets in health, education and welfare services for all children born between 01 January 1994 and 31 December 2014. This established the whole cohort for the Developmental Outcomes of Children in the NT study  and becaAustralian Bureau of Statistics (ABS) geographical classifications were used to compare demographic characteristics and birth outcomes by degrees of remoteness in the NT: Outer Regional, Remote and Very remote . The NT Infants in the hospitalisation and immunisation datasets who had no perinatal record were excluded from the cohort. Infants were excluded from being ‘at-risk’ of a hospitalisation if they had no record in the immunisation dataset indicating at least one vaccination episode in the first 12 months of life. Our reasoning was that evidence of health service activity in the 12 month period after birth constituted ongoing NT residency. Hospitalisation and immunisation records were excluded from the study cohort if infants were >12 months of age at the time of the encounter.The perinatal dataset was used to calculate proportions for maternal and infant demographic characteristics, maternal comorbidities and risk factors and birth outcomes and to calculate the incidence of adverse birth outcomes over the 20-year observation period. These factors were analysed by Indigenous status, region and remoteness. For continuous variables, means and medians were calculated depending on the distribution of the data.The birth outcomes of interest were: preterm births, stillbirths, low birthweight infants at term (LBWT) and small for gestational age (SGA). Infants born before 37 completed weeks' gestation were defined as preterm,  and stilFollowing data linkage, the infant outcomes of interest were the proportion and rate of hospitalisation for influenza and pertussis infections, calculated by year of infant birth, Indigenous status and remoteness for the first 6 completed months of life. Of specific interest was the number and rate of infant hospitalisations for influenza during the 2009 influenza A (H1N1) pandemic. The following ICD-10-AM codes were used when searching for diagnoses in all hospitalisation episodes: influenza, J09-J11; pertussis, A37- A37.9. Infant age in weeks at hospital admission, number of days hospitalised, ICU admissions and geographic distribution of hospitalisation were calculated.Average annual incidence rates (AR) for preterm births, stillbirths, LBWT and SGA were calculated per 1000 NT births, by year of infant birth, Indigenous status and remoteness. Rate ratios were calculated to compare rates between Aboriginal and non-Aboriginal (referent group) infants. Average annual incidence rates (AR) of infant influenza and pertussis hospitalisations were calculated per 1 00 000 NT population for infant age in weeks at time of hospitalisation, by year of infant birth, Indigenous status and by region. Rate ratios were calculated to compare rates between Aboriginal and non-Aboriginal (referent group) infants. As hospitalisations were only captured from 01 July 2000 onwards, infants born before 2000 were excluded from these analyses to prevent truncation bias. The total number of infant births from 01 July 2000 to 30 July 2014 was used as the denominator to calculate infant hospitalisation rates in weeks. Data were analysed using Stata v.14.1  and graphs and figures were constructed using Microsoft Excel and Stata v.14.1.This project was approved by the NT DoH/ Menzies School of Health Research (Menzies) Human Research Ethics Committee (HREC) reference number: 2017–2749, the DoH/Menzies Top End HREC, reference number: 2015–2333, the Central Australian HREC, reference number: 15–293, the Steering Committee of the Developmental Outcomes of Children in the NT study comprising key NT government agencies and the Aboriginal Medical Services Alliance of the NT (AMSANT). A stipulation of ethics approvals precluded the reporting of cell sizes <5.Based on the perinatal dataset, 47 220 individual women birthed 78 382 infants between 01 April 1994 and 31 December 2014 . Data onn = 76 489, 98%) with no difference between Aboriginal and non-Aboriginal mothers (98% vs. 97%). There were 1 878 sets of twins (2%) and 15 sets of triplets (<1%). We excluded 2 665 infants who did not have a record showing at least one vaccination episode in the first 12 months of life as per protocol because of lack of evidence of ongoing NT residency. There were 56 903 infant hospitalisations; 13 350 newborn admissions and 10 852 admissions for infants aged 7 months or older were not included as per protocol. Of the remaining 33 141 hospitalisations, Indigenous status was known for 32 701 infants (99%) and of these infants, 23 042 (70%) were Aboriginal.Most births were singleton (Most mother–infant pairs (63%) were from Outer regional areas; 37% were from Remote/Very remote areas. The mean maternal age of women at infant birth was 27 years (range 12–51 years) and 53% presented for antenatal care in the first trimester of pregnancy. Compared to Outer regional living women, women who lived in Remote/Very remote areas were younger, less likely to present for antenatal care in the first trimester and more likely to experience co-morbidities and have high-risk factors. Most women (74%), were Aboriginal compared to 16% non-Aboriginal (Tables S1 and S2).The median gestational age at birth of infants was 39 weeks and mean birthweight was 3253 grams. There was no clinically important variation in these birth outcomes by Indigenous status  however,Among 51 297 infants born in the 2000–2015 cohort, 15 346 (30%) were hospitalised at least once (33 141 episodes) before the age of 7 months. There were 57 infants hospitalised for influenza (0.2%) and 41 for pertussis (0.1%). There were nine deaths and 67% of these were Aboriginal infants from Remote/Very remote regions of the NT (data not shown elsewhere).n = 51, 96%), with a median age at admission of 17 weeks (range <1–30) and 91% (n = 48) lived in a Remote/Very remote setting. More infants were hospitalised with influenza in the Top End  than in Central Australia (CA)  and the majority of these infants were Aboriginal , (vs. 6), , . The AR (vs. 6), .Fig. 4.The NT recorded its first case of H1N1 pandemic influenza in May 2009 . Subsequn = 30/37, 81%); had not received any pertussis-containing vaccines prior to hospitalisation , were Remote/Very remote living  (vs. 20.2), particularly evident during the national epidemic years 2001, 2008 and 2011  had unknown Indigenous status and none had received a pertussis-containing vaccine as part of their infant schedule prior to hospitalisation. Of the remaining 37 infants with a known Indigenous status, most hospitalised for pertussis were Aboriginal 37, 68%) . Nearly 37, 68%) . The AR and 2011  and 8.F% . Nearlpre-maternal vaccination period were all disproportionately higher amongst Aboriginal infants than non-Aboriginal infants. These data are critical in order to monitor disease surveillance, assess vaccine effectiveness and evaluate the safety of the NT maternal influenza and pertussis vaccination programs. Given the size of our cohort, these data will provide a valuable future reference.This is the largest linked whole of population cohort of 78 382 mother–infant pairs from the NT of Australia to date, of which a substantial proportion (~37%) are Aboriginal. There are few whole of population studies with comparable long term data on Aboriginal and remote-living populations. Baseline observed incidence rates of adverse birth outcomes and infant influenza and pertussis hospitalisations in a Though there was a disparity in the incidence for all adverse birth outcomes between Aboriginal and non-Aboriginal women and infants, apart from preterm births, there was a reassuring downward trend over the observation period. The upward trend in preterm births experienced by Aboriginal women is concerning. It is unclear whether this upward trend is an artefact of improvements in survival rates of very preterm and extremely preterm infants who historically experienced higher mortality rates or a true increase due to persisting high levels of co-morbidities and risk factors among Aboriginal women. Remoteness of living is a known risk factor for adverse birth outcomes including preterm birth , and ourOur results confirm the heavy burden of illness from influenza infection in young Aboriginal infants, particularly during pandemic years. There is potential to reduce the number of infant hospitalisations, the length of stay in hospital and ICU admissions, particularly among Remote living Aboriginal infants under 6 months of age, by improving the uptake of IIV in pregnancy , 39. TheInfants <7 m hospitalised with pertussis infections in this study were either unvaccinated with a pertussis-containing vaccine during their infancy or were too young to have completed at least two doses of a pertussis-containing vaccine in order to confer adequate protection from infection. A review of pertussis hospitalisations is warranted post implementation of the maternal vaccination program, with the expectation that there should be a decrease in notifications and hospitalisations in these youngest infants, given the 91–95% vaccine effectiveness that has been demonstrated elsewhere , 25 and We acknowledge the potential biases that may arise from using routinely collected administrative data and the risk of their potential accuracy, as a limitation . The impNotification data for pertussis and influenza infections were not included in the datasets, however, given hospitalisation is an indication of disease severity, the results from our large study can be used to infer the burden of severe disease in the NT by age, remoteness, region and Indigeneity. Further, while the small number of actual infant influenza and pertussis hospitalisations is a limitation, clearly the burden was heaviest for remote living Aboriginal infants from the Top End. The inability to capture the infants who would have moved to the region is a limitation of any birth cohort but is unlikely to have significantly impacted the data.The NTIR did not record information for maternal vaccination status until 2010, given IIV in pregnancy was only recommended and not part of the funded scheduled immunisation program prior to this time. Unknown maternal vaccination status is, therefore, a limitation. There may be a small proportion of pregnant females aged 15–17 years from 2003 onwards (~<2%) who received a pertussis vaccination inadvertently as part of the school-aged dTpa booster vaccination program  althoughWe contribute whole of NT population baseline data for adverse birth outcomes and influenza and pertussis infections in early infancy in a pre-maternal vaccination era. Our study population comprises robust representativeness of Aboriginal and remote-living mother–infant pairs, demonstrating that Aboriginal women and infants potentially stand to benefit the most from maternal IIV and pertussis vaccination programs. In order to evaluate the impact of the maternal IIV and pertussis vaccination program of the NT, a subsequent review of the outcomes analysed in this paper, along with an assessment of vaccine uptake in pregnancy is required in the future.


We investigated whether the extent of fetal growth restriction (FGR) in terms of not only birth weight but length and head circumference at birth is correlated with an increased risk of bronchopulmonary dysplasia (BPD) in preterm infants.A total of 4,940 very low birth weight (VLBW) infants born between 23 and 31 weeks of gestation from 2013 to 2015 who were registered in the Korean Neonatal Network (KNN) database were enrolled. Infants with major congenital malformations and those with incomplete data were excluded. Z-scores for weight, length, and head circumference at birth were calculated from the Fenton 2013 growth curve. Multivariable logistic regression analysis was performed to determine whether the z-score for length at birth was associated with BPD or death before 36 postmenstrual weeks.A total of 4,662 VLBW infants were analyzed: 518 infants died before 36 postmenstrual weeks; 1,388 infants developed BPD. Decreased length at birth z-scores were significantly associated with an increased risk of BPD or death when adjusted for covariates (odds ratio (OR) 1.25 per 1-point decrease of length at birth z-score, 95% confidence interval (CI) 1.14–1.37). The association was particularly evident in infants born earlier than 29 weeks of gestation .Length at birth was inversely associated with an increased risk of BPD or death in VLBW infants born earlier than 32 weeks of gestation. Bronchopulmonary dysplasia (BPD) is a major complication in preterm infants. Although mortality rates among extremely premature infants have decreased dramatically, the number of infants with BPD has increased. Premature infants with BPD require a longer hospitalization than premature infants without BPD, and BPD remains a substantial lifelong burden.  Specificth percentile) had a significantly greater risk of developing BPD compared with the reference group (birth weight between the 25th and 75th percentiles). [In a previous study, SGA infants (birth weight <10ntiles).  Carl Bosntiles).  Most repIn the present study, we investigated whether the extent of FGR in terms of not only birth weight but also length and head circumference at birth was associated with increased risk of BPD or death before 36 weeks postmenstrual age (PMA) using a nationwide cohort of VLBW infants. We also assessed the relative impacts of the z-scores of these anthropometric measurements at birth on BPD or death before 36 weeks PMA in three different GA subgroups.+0 (week+day) and 31+6 gestational weeks from January 2013 to December 2015 and admitted to neonatal intensive care units participating in the Korean Neonatal Network (KNN). VLBW infants with major congenital malformations were excluded. The KNN is a nationwide VLBW infant registry that collects demographic and clinical data from 69 hospitals across South Korea using a standardized operating procedure. [This was a prospective cohort study of VLBW infants  born between 23ocedure.  ApproximThe KNN registry collects prenatal and neonatal data; the collected prenatal data include pregnancy-induced hypertension (PIH), oligohydramnios, clinical and histological chorioamnionitis, and administration of prenatal corticosteroids. The collected neonatal data include GA; weight, length and head circumference at birth; gender; and clinical information on respiratory distress syndrome (RDS), patent ductus arteriosus (PDA), culture-proven sepsis, and total duration of mechanical ventilation. The z-scores for weight, length, and head circumference at birth were calculated from the Fenton 2013 growth curve. Regarding the administration of prenatal corticosteroids, only cases in which prenatal corticosteroid therapy (betamethasone or dexamethasone) was completed within 7 days before delivery were counted. RDS was defined as a respiratory insufficiency that manifested at or shortly after birth, was accompanied by typical radiologic findings compatible with RDS, and required surfactant replacement therapy.The primary outcome was BPD or death before 36 weeks PMA. BPD was defined as the need for supplemental oxygen at 36 weeks PMA using the National Institute of Child Health and Human Development criteria. +0–25+6 weeks, 26+0–28+6 weeks and 29+0–31+6 weeks). The associations of anthropometric measurement values at birth and prenatal factors with BPD or death before 36 weeks PMA were evaluated in univariate analyses. Covariates were included in the multivariable logistic regression models if they were associated with the outcome at P<0.2 in univariate analyses. To reduce multicollinearity, which may be present between the anthropometric data at birth and their z-scores, we included only the z-scores of the anthropometric measurement values. To investigate whether the z-scores for weight, length and head circumference at birth are independently associated with BPD or death before 36 weeks PMA, multivariable logistic regression analyses with backward elimination were performed.Because GA has a substantial influence on the primary outcome, the study population was divided into three GA groups  and 95% confidence intervals (CIs). All statistical analyses were performed using SPSS ver. 22.0 software For comparisons of categorical variables, chi-squared and Fisher’s exact tests were performed. Continuous variables were compared using independent +0 and 31+6 weeks of gestation from January 2013 to December 2015 were enrolled in this study. After excluding 8 infants with an unknown BPD status at 36 weeks PMA and 270 infants without data on length or head circumference at birth, a total of 4,662 VLBW infants were finally included in the analysis. Their mean GA was 28+1±2+1 weeks, and their mean birth weight was 1,058±271 g. Of these VLBW infants, 518 (11.1%) died before 36 weeks PMA, and 1,388 (33.5% of surviving infants) infants developed BPD.A flow diagram of our study is presented in +0–25+6 weeks, 1,889 at 26+0–28+6 weeks, and 1,898 at 29+0–31+6 weeks. The number of SGA infants and the proportion of infants who had any degree of FGR (z-score below -1) were highest in the later GA group (29+0–31+6 weeks).The anthropometric measurement values at birth of the infants, and the maternal and neonatal characteristics in each GA group are displayed in +0–28+6 weeks GA group and the 29+0–31+6 weeks GA group. PIH was significantly associated with an increased risk of BPD or death only in the 26+0–28+6 weeks GA group. The administration of prenatal corticosteroids was not associated with BPD or death in any of the GA groups. The median z-scores for weight (A), length (B), and head circumference (C) at birth were significantly lower in the infants who developed BPD or died before 36 weeks PMA than in the infants who survived until 36 weeks PMA without BPD in all of the GA groups , and in the 26+0–28+6 weeks GA group , but not in the 29+0–31+6 weeks GA group. Decreased birth weight z-score was associated with an increased risk of BPD or death in the whole population , in the 26+0–28+6 weeks GA group , and in the 29+0–31+6 weeks GA group , but not in the 23+0–25+6 weeks GA group. Decreased head circumference z-score was not associated with increased risk of BPD or death in any of the GA groups. In the 23+0–25+6 weeks GA group, among the z-scores for the anthropometric measurement values at birth, only the length at birth z-score was significantly associated with BPD or death. +0–31+6 weeks GA group only.Other than the z-scores for the anthropometric measurement values at birth, low GA and male gender were consistently significantly associated with an increased risk of BPD or death in the whole population and in all three GA groups. RDS was significantly associated with an increased risk of BPD or death in the whole population as well as in the 29Gestational age, the z-scores for birth weight, length, and head circumference at birth, male gender, pregnancy induced hypertension, oligohydramnios, and RDS were included in the logistic regression model in the whole population and in each gestational age group. BPD, bronchopulmonary dysplasia; RDS, respiratory distress syndrome.+6 weeks), whereas the association of decreased birth weight z-score with BPD or death was observed in VLBW infants born at a middle to late GA (≥26+0 weeks). At middle GA (26+0–28+6 weeks), both decreased length at birth z-score and decreased birth weight z-score were associated with an increased risk of BPD or death. There have been several reports that FGR or SGA is associated with an increased risk of BPD. [th percentile of the population-based birth weight data obtained from infants born at the same GA. Most reports have demonstrated the association of FGR with BPD by using birth weight z-scores as a parameter of FGR. However, few studies have investigated the associations of other anthropometric indices of FGR, such as length and head circumference, with BPD. In this cohort of VLBW infants born earlier than 32 weeks of gestation, we investigated whether three different types of FGR, assessed as z-scores of birth weight, length and head circumference at birth, are associated with an increased risk of BPD or death. We found that only decreased length at birth z-score, among the z-scores of the three types of anthropometric measurement values, was significantly associated with BPD or death in the early GA group, in which the risk of BPD or death was substantial; however, the birth weight z-score was not associated with BPD or death in the early GA group. This finding may be due to the fact that on average, the birth weight z-score in the early GA group was higher than that in the other two more mature GA groups. In contrast, in the late GA group in which the risk of BPD or death is quite low, only decreased birth weight z-score was significantly associated with BPD or death. Decreased head circumference at birth z-score was not associated with BPD or death in the whole population and in any of the GA groups. These findings suggest that lengthwise FGR at an earlier GA when the lungs are in the late canalicular stage may be associated with the development of BPD or death. [In our nationwide cohort of VLBW infants born earlier than 32 weeks of gestation, decreased birth weight z-score, decreased length at birth z-score, low GA and male gender were significantly associated with an increased risk of BPD or death before 36 weeks PMA. Interestingly, the association of decreased length at birth z-score with BPD or death was observed in VLBW infants born at an early to middle GA ≤28+6 weeks, of BPD. ,16,17 Inr death. Gender and height are the most important predictors of lung function in both children and adults. It is well known that linear relationships exist between lung function and height. ,20 Heigh+0–28+6 weeks GA group). However, the statistical association between PIH and BPD or death disappeared after adjusting for other covariates.Among the maternal characteristics evaluated in this study, the administration of prenatal corticosteroids was not associated with BPD or death in any of the three GA groups. Oligohydramnios was not associated with BPD or death after adjusting for covariates. Several studies have demonstrated the relationship between intrauterine exposure to maternal preeclampsia and the risk of the infant developing BPD. Korhonen et al reported that preeclampsia is protective and reduces the incidence of BPD.  In contrAs mentioned in the Subject and methods section, we did not include the absolute anthropometric measurements at birth and their z-scores together in the same logistic regression models because of potential multicollinearity between them. Moreover, we aimed to assess the associations of z-scores of anthropometric measurements at birth, instead of the associations of absolute anthropometric measures at birth, with BPD or death because we focused on the extent to which FGR, reflected by z-scores, which were standardized by gender and gestational age, was associated with BPD or death.The limitation of the present study is that the infants’ lengths at birth were not adjusted for their parents’ heights. The KNN registry does not collect parental weight or height information. Because height is strongly influenced by genetics, fetal length might be related to parental height. A database with more detailed parental information will be needed to adjust for the genetic influence of parental height on fetal length. In addition, we did not have information regarding large airway problems such as tracheobronchomalacia, which can mimic BPD, and data on the nutritional status of the infants, which might have substantially affected the postnatal growth trajectory and neonatal outcomes including BPD. Information about the hospitals where the VLBW infants were admitted was not provided to individual researchers. The raw data were provided to the individual researchers after the hospital codes were deleted. Therefore, we were not able to include the hospital as a covariate in the analyses. Moreover, we did not include many postnatal factors, including PDA, sepsis, and the duration of mechanical ventilation in the analyses. These postnatal factors can contribute to the development of BPD.  InformatIn conclusion, we demonstrated that decreased fetal lengthwise growth was associated with an increased risk of BPD or death, especially in early GA infants, in a Korean nationwide cohort of VLBW infants born before 32 weeks of gestation. It can be speculated that fetal lengthwise growth is closely related with fetal lung growth and development, although the causal relationship between the two remains unrevealed. If lengthwise growth is also linked to lung growth and development during the postnatal period in preterm infants, a means of accelerating postnatal lengthwise growth could be a potential therapeutic approach for enhancing lung growth and development and thus alleviating BPD.S1 Table(DOCX)Click here for additional data file.


Hydatid disease present in certain parts of the world. Infection of the musculoskeletal system occur in less than 0.5%.A 24-year-old lady had a painful mass in the inner aspect of the right thigh. MRI of the thigh showed a mixed signal intensity lesion measured about 65*100 mm, the mass was related to the muscle and the superficial femoral artery and its cavity had multiple septations.During surgery an infected hydatid cyst of the muscle was found, evacuation was done with removal of the cyst. The patient was discharged next day and she received anthelminthic medications for 3 months.Hydatid cyst of the muscles present with gradually enlarging mass or complications such as nerve compression, infection or rupture.Treatment may be medical using anthelminthic medications. Complete surgical excision is the best surgical option; involvement of other organs should be excluded. Follow-up is recommended. •Hydatid cysts could affect various body parts causing wide range of clinical presentations.•Infection is one of the common complications of hydatid cysts.•Surgery is the main treatment option in most of the cases. The disease is mostly present in the developing countries, and transmitted by the fecal –oral route. The disease may be completely asymptomatic or may cause a variety of symptoms depending on the size and the presence or absence of complications. Infection in the musculoskeletal system is estimated to be less than 0.5%, this is because the cyst depends on high oxygen contents in the tissue for its growth and the muscle tissue has low oxygen contents and high lactic acid content which impedes the growth of the parasite .The disease may be discovered accidentally or the patient may present with mass at the affected site. Hydatid cyst is classified into five main stages depending on the radiological appearance, the viability of the cyst, and the contents. Stage one and two indicate an active disease in which the contents of the cyst are clear and there may be undulating membrane (water-lily sign), stage three indicates that the cyst is entering a transitional stage and the integrity of the cyst is decreased by the host defense mechanism or the medications, and stage four and five indicates that the cyst is entering an inactive stage when the walls of the cyst become thick and calcified .Serology may help in the diagnosis of hydatid disease but the final diagnosis is done by means of imaging. Ultrasound usually shows cyst lesion with single cavity or multiple cavities inside, ultrasound can also help in excluding hydatid cyst in other intra-abdominal organs, the best imaging information for muscle hydatid cysts are gained from the MRI which shows the location of the cyst, and its relations to the muscles and other structures, it also helps in excluding the presence of hydatid cyst in other parts of the body ,2.The work in this case report has been reported in line with the SCARE 2018 criteria .2Clinical findings: A 24-year-old lady presented with gradually enlarging painful mass in the inner aspect of the upper thigh for the last 3 months, the patient noticed the mass accidentally during bathing. The mas was painless at the beginning but became painful with attacks of low grade fever mainly at the night. The patient had non-relevant past medical and past surgical histories.During examination, the patient has normal general examination and examination of the mass showed a tender mass about 8*10 cm in the medial aspect of the right upper thigh with multiple enlarged ipsilateral inguinal lymph nodes.The family history was negative for chronic illnesses. There was no history of chronic drug administration and the psychosocial history was negative.Diagnostic assessment: The white blood cells were elevated with raised inflammatory markers. MRI of the thigh showed a mixed signal intensity lesion located in the medial aspect of the right upper thigh and measured about 65*100 mm, the mass was related to the muscle compartment and appeared to be associated with the superficial femoral artery, there was no any associated bone abnormality and the lesion had multiple internal septations giving the possibility of either necrotic mass, cold abscess, or tumor. Therapeutic Intervention: During exploration the lesion appeared to be an infected hydatid cyst of the muscle compartments of the medial aspect of the thigh, evacuation of the cavity was done with removal of the hydatid cyst, the cavity of the cyst was washed with chlorhexidine, low pressure suction drain was put in the cavity which was removed after 3 days. The operation was done by 3 specialist surgeons who were specialized in the field of the vascular and general surgery.2.1The patient then was reevaluated to exclude hydatid cysts in other parts of the body by chest X-ray and abdominal ultrasound which showed no evidence of cysts in the chest and the abdomen.The patient was discharged on the next day and she received anthelminthic medications for 3 months.3Although hydatid cyst may occur mostly affects the liver and the lungs and infection in other organs may be secondary to infection of these sites but primary hydatid cyst of the muscles or some other rare anatomical places is well reported in literatures ,6.Many cases of muscle involvement are reported and the most common site of muscular involvement is the neck region followed by muscles of the trunk and then the root of the limbs, this is explained by the rich vascular supply in the above mentioned regions as hexacanth embryos are passed to various parts of the body through the blood stream .Hydatid cyst of the muscles usually presents with a gradually enlarging mass which may be painful, some cysts may cause complications such as nerve compression causing pain, infection or rupture after trauma which may lead to allergic reaction .Hydatid disease should be one of the differential diagnoses of any soft tissue mass in any part of the body particularly in patients from endemic areas .Intramuscular hydatid cysts may cause diagnostic difficulties especially when the radiological appearance is atypical like in our case because the patient in this case presentation presented with infected cyst and the radiological appearance was confusing, so the patient was sent for tru cut biopsy to exclude soft tissue tumors .The treatment of hydatid cyst depends on many factors such as the location of the cyst, the symptoms produced by the cyst, and the presence or absence of complications. The recommended treatment of hydatid cyst of the muscle is complete surgical resection of the entire cyst without opening the cavity to avoid spillage of the contents to decrease the recurrence rate. It is mandatary to exclude hydatid cyst in other parts of the body particularly the lungs when the surgery is done under general anesthesia ,9.Medical therapy with anthelminthic medications may be used with variable responses, calcified cysts usually doesn't respond to medical treatment, medical therapy may be also used preoperatively and postoperatively to decreases the recurrence rate .I thought that I had a tumor in my thigh and I was worried too much about that, after surgeries my worries had gone but I am worried now about the recurrence of the development of cysts elsewhere in my body.An informed written consent was taken from the patient for reporting this case and the accompanying images.The authors are the source of the funding.Not commissioned, externally peer reviewed.No ethical committee approval was needed; consent have been taken from the family to report their findings.No source of funding other than the authors.The surgeon who performed the procedure: Dr Ahamd Mohammad Sharif Tahir, Dr Alaa S. Bahjat and Dr Ayad Ahmad Mohammed.Study design, writing, and the final approval of the manuscript: Dr Ayad Ahmad Mohammed.N/A.Dr Ayad Ahmad Mohammed.No conflicts of interest present.