Low birth weight is highly prevalent in rural India. As a chronic undernutrition problem, poor birth outcomes are closely related to various nutritional factors more prominently the poor maternal anthropometry at conception. The purpose of the study was to identify how compromised maternal nutritional status in early pregnancy affects the birth size of rural Indian mothers.n = 204) from 14 villages in Mulshi Taluka of Pune District, Maharashtra, India. Maternal weight (Wt), height (Ht), body fat percent (BF%), head circumference (HC), and sitting height (SHT) were measured at early pregnancy (< 13 weeks of gestation) and infants’ weight and length were measured within 24 h of birth. Groups means were tested using a ‘t’ test while the trend in means was tested using ANOVA.It was a prospective observational study on singleton pregnant women (2). Mean birth weight was low (2655 ± 507 g) and prevalence of LBW and stunting at birth was highest among mothers in the lower tertile of each of the anthropometric indicators. In particular, stunting was significantly higher for mothers in lower tertile compared to higher tertile of Wt (44.6 Vs 64.6%) and was also true for HC (43.7 Vs 60.6%). Risk for LBW and stunting at birth was almost similar and was significant (p < 0.01) for mothers in the lower tertile of Wt, Ht, BMI, SHT, HC, and BF% as compared to those in the higher tertile of these measurements.Mothers were young (21.46 ± 2.09 yrs), thin (46.46 ± 6.1 kg), short (153.39 ± 5.79 cm), and poorly nourished (19.74 ± 2.41 kg/mAll the anthropometric indicators of current undernutrition at first trimester as well as that in utero reflected by smaller HC, impose risk for LBW and stunting at birth especially among young rural mothers. Low birth weight (LBW) is a major concern worldwide especially in a developing country like India with a prevalence of 30–35% . Though 2) has shown a significant influence on the risk of LBW [In particular, among various maternal anthropometric indicators maternal weight has been mostly explored in previous studies. For example, rural women from India , Sri Lank of LBW , 15, 16.k of LBW , menarchk of LBW , and park of LBW  also havUnlike low birth weight, short birth length or stunting at birth has not been studied widely. Most anthropometric indicators studied are reflective of the mother’s current nutritional status rather than her past nutritional status and it is necessary to take into consideration the role of her past undernutrition too. For example, height and its components especially leg length/sitting height is known to be an indicator of past malnutrition but is never studied with risk of LBW or stunting at birth. The same is the case with maternal HC which is known as a surrogate measure of maternal undernourishment in-utero . We, theThe prospective cohort study was conducted across three primary health centers (PHC) in rural areas of Mulshi Taluka, Pune, Maharashtra. These primary health centers covered 14 villages and approximately 5000 beneficiaries. The villages had a well-established network of community workers such as Anganwadi workers and ASHA  workers who were involved in door-to-door registration and tracking of newly married young women and their subsequent pregnancies. These women were referred to the nearest PHC by community health workers and hence tracking them within the first 3 months of gestation for the study in a well-established setup was possible. The sample size was determined considering the prevalence of LBW of 30%, an allowable error of 7%, a level of significance of 5%, and considering loss to follow up of 15%. Though the exact estimate was 196 we enrolled 208. Multiple pregnancies [. The head circumference was measured using a Seca non-stretchable tape to the nearest 0.1 cm. The tape was placed on the widest part of the forehead and around the widest part of the back of the head while measuring. The body fat % was measured using an analyzer HBF 210 Omron Corporation validated and used in other Indian studies [Maternal anthropometry was measured in duplicates by the researcher using standard tools and calibrated instruments. Weight was measured using a digital weighing balance (HBF 210 Omron Corporation) to the nearest 100 g while the woman stood barefoot and with minimal clothing. Standing height was measured using a Seca stadiometer to the nearest 0.1 cm while the woman stood barefoot. The pregnant woman was asked to sit on a table with feet off the floor comfortably placed on a stool, using a Seca non-stretchable tape sitting height was measured as the distance between the vertex and the base to the nearest 0.1 cm while being seated studies  as well.Since all the deliveries took place at the PHC the birth weight (g) and birth length (cm) of the neonate was measured after delivery within the first 24 h after birth by the health care staff. A SAT B30 weighing balance was used for these measurements. The WHO definition of low birth weight (LBW) babies i.e. birth weight less than 2500 g and that of stunting, low length (< 45 cm) , 24 for The socio-economic and demographic information was collected through a structured questionnaire redeveloped after the focus group discussions conducted by the researchers among pregnant women, community stakeholders, and family members. The questionnaire consisted of various questions to identify their socio-economic status, demographics, and obstetric history. It was field-tested and amended after a pilot study. The questionnaire was then filled by the researcher through one-to-one interviews with the pregnant women on registration at the PHC.The study was as per the Declaration of Helsinki and was approved by the Institutional Ethics Committee of Symbiosis International Deemed University. Written informed consent was obtained from participants voluntarily. Formal permissions from medical officers of PHC were also obtained before the initiation of the study in Mulshi Taluka.p-value of < 0.05 was considered to be significant.The measured variables were checked for normality and expressed in terms of mean ± standard deviation or percentages. Maternal anthropometric variables were divided into tertiles to assess the extent of change in lower and upper tertiles in association with birth weight and birth length. Means of groups were compared using a t-test and the linear trend was tested using one-way ANOVA. Logistic regression was used to estimate the risk (Odds Ratio) for LBW and stunting. The risks were also adjusted for maternal age but not for other socioeconomic variables as they were not found to be related. Analysis was performed using the statistical package for Social Sciences (SPSS) . A Most of the mothers (77.5%) were young (21.46 ± 2.09 years) at conception. 77.4% had low levels (<10th standard) of school education and 42.2% were occupied as farming/laborer in addition to their household work. 42.2% of the husbands were also educated up to 10th grade and 79.9% were engaged in unskilled jobs such as driver, or owned a small shop, or worked as a clerk. A large proportion (66.5%) of mothers were married before 20 years of age and 59.3% had delayed menarche (< 14 years). Monthly income was low  in the majority (69.1%) of the families (Table 2). The cut-off for maternal weight for risk of LBW is given as 38 Kg and 5% of mothers in our study belonged to this category. Similarly, 4.4% of the mothers were shorter than risk cut-off for height (145 cm) and almost 33.8% of mothers were below BMI cut-off of 18.5 Kg/m2 indicating chronic energy deficiency. Though such risk cut-offs are not available for other anthropometric measures the Normal values have been suggested by few studies for BF% (< 30%) [Mothers were thin (mean weight 46.46 ± 6.1 Kg), short (mean height 153.39 ± 5.79 cm) and undernourished (mean BMI 19.74 ± 2.41 Kg/m (< 30%)  and HC ( (< 30%)  and mean (< 30%)  for Indip < 0.05) from lower tertile to higher tertile for all maternal nutritional status indicators. The difference in the mean birth weights and lengths between lowest and highest tertile of maternal weight was highest . The prevalence of LBW and that of stunting at birth were highest for mothers in the lower tertile and decreased significantly  from lower to higher tertile for most indicators. It was interesting to note that the prevalence of stunting at birth was higher than that for LBW in the case of each indicator. In particular, the prevalence of stunting was significantly higher than that for LBW, for lower tertile of maternal weight  and smaller head circumference  highlighting the importance of both current and past maternal undernutrition. Additionally, it is worthwhile to note that the prevalence of stunting at birth is over 30% even in higher tertile of maternal height as well as sitting height as both are reflective of the mother’s past undernutrition  for lower maternal weight followed by lower BMI , smaller HC , and lower BF% .These findings remained unchanged even after adjusting both the risks for maternal age suggesting an independent influence of maternal nutritional status on neonatal anthropometry. Thus, our observations report for the first time the effect of compromised maternal nutritional status on the risk of stunting at birth in addition to the risk of LBW. Additionally, our findings highlight the importance of the mother’s past undernutrition as reflected by smaller HC and short height and sitting height in addition to current undernutrition Table .Table 4Maternal nutritional status has been considered to be the most important factor influencing birth outcomes. LBW due to poor pre-pregnancy weight , 29, poo2). These observations are similar to those reported by Raje et al., 2015 [The mothers in our study were overtly undernourished with poor maternal anthropometry. 33.5% of mothers were chronically undernourished . The prevalence of LBW was 27.5% which was similar to that reported for South Asia  and was closer (24.7%) to the region-specific western rural populations of India . The preSeveral studies have reported a positive correlation between maternal anthropometry and mean birth weights in different populations –36. IndiThe highest prevalence of stunting at birth was observed in the lower tertile of maternal weight, the indicator of current undernutrition, as well as among mothers in the lowest tertile of HC, the indicator of maternal undernutrition in utero. These observations highlight the enormous intergenerational impact of compromised maternal nutritional status more on stunting at birth than that of LBW and hence deserves further attention.Although, the factors associated with the birth outcome are well studied those associated with risk of LBW or stunting at birth are not , 41. IdeAlthough maternal nutritional status indicators such as shorter sitting height, smaller head circumference have shown to be associated with LBW  , their aWe would like to mention some of the limitations. Firstly, the study does not address other factors such as physical activity and diet which are also known to affect the birth outcome. Because all women came from farming families with similar socio-economic backgrounds it is unlikely to affect the associations of maternal anthropometry with birth outcome observed in this study. Maternal diet being a major avenue will be dealt with in another communication and cannot be accommodated in the same paper. Other factors such as substance abuse are not culturally acceptable and hence have not been considered.The observation in this study that smaller SHT, like smaller maternal HC, seems to be a surrogate measure of maternal undernutrition in utero and deserves attention considering the Barker hypothesis for risk of metabolic diseases in later life , 46. The


The terminal ventricle (TV) of Krause is a rare cystic dilation of the conus’ central canal. Due to limited understanding surrounding its pathophysiology, optimal management remains controversial. We report a 25-year-old female presenting with acute paraparesis. Magnetic resonance imaging spine revealed a cystic conus medullaris lesion in keeping with an incidental TV cyst. However, the patient experienced a rapid resolution of symptoms. We hypothesize that the TV cyst spontaneously ruptured and auto-decompressed. To our knowledge, this is the first reported case of an enlarging symptomatic TV cyst with spontaneous rupture and resolution of symptoms, highlighting the variable natural history of this condition. The terminal ventricle (TV) is a dilation of the conus’ central canal, lined by ependymal cells containing CSF. It was first reported by Stilling in 1859, termed the fifth ventricle by Krause in 1875 and is formed during embryogenesis at the caudal aspect of the central canal and is thought to regress in early childhood . KernohaIt is clinically important to differentiate between a TV and TV cyst: TV is a persistent, typically asymptomatic anatomical variant of little clinical significance. TV/conus medullaris cyst is an abnormal cystic dilation, which may progress leading to neurological symptoms.The natural history of TV cysts is poorly understood with some reports suggesting a benign non-progressive course and others describing a more hazardous natural history with cyst enlargement and consequent conus medullaris syndrome , 7–9.The authors present a case of acute neurological decline secondary to progressive dilatation of a TV cyst with spontaneous rupture and resolution of symptoms captured with magnetic resonance imaging (MRI). The pathogenesis of enlarging symptomatic TV cysts is hypothesized and presented.A 25-year-old female presented with a three week history of lower back pain, headache, photophobia and sudden onset paraparesis. On examination, she had 3/5 power in all myotomes of the lower limb with subjective paraesthesia below the knees (L3 dermatome) bilaterally. There was no acute sphincteric, bladder, bowel or perineal sensory dysfunction. She had presented 10 years previously with similar symptoms with spontaneous resolution.Neurological consultation was sought, and lumbar puncture was performed which revealed a normal cerebrospinal fluid (CSF) profile. On Day 4 of admission she was re-reviewed by the neurologists where she was found to have no movement in her lower limbs (0/5 power). Her lower limb reflexes were present bilaterally with downgoing plantar responses. A whole spine MRI was performed which revealed a TV cyst . On Day We can only hypothesize rather than prove that the cyst was the cause of this patient’s neurological deficit. The transient neurological signs correlate with the transient results on imaging, whereby the cyst ruptured and later re-expanded again, as discussed below. Neurologist advice was sought, and no other abnormalities in the neuro-axis were found. Hoover’s sign was also negative.She underwent a short period of inpatient physiotherapy and was discharged home. The patient did not attend further outpatient follow-up. Seven months later she attended her local emergency department with symptoms of bilateral non-dermatomal leg paraesthesia. Lumbo-sacral MRI demonstrated modest enlargement of the TV cyst in keeping with recollection. In the absence of a progressive motor or localizing neurological deficit, surgery was not felt to be indicated and she remains under outpatient surveillance.This is the first report of symptomatic enlargement of a TV cyst with spontaneous rupture and subsequent recollection. The case offers an insight into the condition’s pathogenesis and natural history.The TV cyst’s natural history remains poorly understood and it is unknown why a small number undergoes progressive and symptomatic cystic dilation. Symptomatic cases in the literature have been managed surgically and the follow-up of conservatively managed asymptomatic patients is limited. The longest reported follow-up is 10 years during which there was an increase in cyst volume from 1.5 to 3.2mls . Serial We propose, based on our case, there is a loss of communication of the TV cyst with the central canal at some stage in early adult life. Persistent TV implies obstruction of physiological CSF flow which could be due to ependymal cell growth/death, cellular debris thus proteinaceous build-up increasing relative oncotic pressure. This compressive effect on the conus medullaris leads to neurological symptoms. However, once the intracystic pressure exceeds the transmural pressure of the cyst wall within a closed intraspinal compartment surrounded by ligamentous and bony structures, the cyst ruptures. Therefore, there is an acute relief of compression on the conus and symptom resolution. Although spontaneous rupture may decompress the cyst, this may be a transient phenomenon supported by our serial imaging findings. This supports surgical marsupialization for persistently symptomatic cases with excision of the cyst wall to prevent recurrence.Interestingly, the patient reported associated meningism prior to rupture as evidenced by the first MRI scan. We hypothesize that sudden cyst expansion/dissection of neural tissue may have potentially caused inflammation and/or vascular injury leading to meningism. Lumbar puncture samples were not specifically examined for CSF bilirubin. Previous cases where intraoperative samples have been taken for fluid analysis revealed CSF with no detectable external constituents.et al. [et al. [In view of the spectrum of clinical presentation, in an attempt to guide management, de Moura Batista et al.  offered et al. , revised [et al. . This deThis is the first reported case of a symptomatic enlarging TV cyst with spontaneous rupture and clinical improvement. This report offers new insight into the pathogenesis and natural history of TV cysts. We believe initial surveillance in the absence of neurology is safe and marsupialization is mandated in those with progressive neurology and should be considered in recurrent episodes associated with significant neurological decline.The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest , or non-financial interest  in the subject matter or materials discussed in this manuscript.No funding was received for this research.All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (name of institute/committee) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.The patient has consented to the submission of the case report for submission to the journal.


To explore the status of parental nutrition practice of hospitalized late preterm infants and the factors influencing the clinical prescription.A multi-center, prospective cohort study was conducted during October 2015 to October 2017. Infants born after 34 weeks and before 37 weeks were enrolled from twenty-five hospitals in the Beijing area of China. Data of enteral and parenteral nutrition were collected.A total of 1,463 late preterm infants were enrolled in this study, 53.9% of infants were supported by parenteral nutrition. Over 60% of 34 weeks’ infants were on parenteral nutrition during the 2nd to the 4th day. Logistic regression analysis showed that gestational age(GA) , birth weight , hypoglycemia , small for gestational age (SGA) , feeding intolerance , neonatal respiratory distress syndrome (NRDS) , neonatal infection(OR = 1.56 95%CI 1.16–2.10), and slow enteral nutrition advancement rate  were factors influencing the administration of parenteral nutrition.Over half of hospitalized late preterm infants were prescribed with parenteral nutrition. Infants with lower GA, lower birth weight, diagnosed with hypoglycemia, SGA, feeding intolerance, NRDS, neonatal infection, or a slower rate of enteral nutrition advancement had a higher likelihood of receiving parenteral nutrition. Nutritional practices in early life may impact short-term complications of preterm infants as well as their later neurologic and metabolic health; therefore, nutritional support is an important part of comprehensive management for preterm infants –3. NutriWe conducted a multi-center clinical study to explore the status of nutritional practices of hospitalized late preterm infants in the Beijing area of China. For enteral nutrition, previous data showed that exclusive human milk feeding rate was as low as 4.5% and about half of late preterm infants did not regain birth weight at discharge . Parente+0 through 36+6 weeks gestational age (GA) between October 2015 to October 2017 and admitted to the neonatal intensive care units (NICUs) or neonatal nurseries of 25 hospitals within the first 3 days of life were included.Preterm infants born at 34Exclusion criteria included infants with major congenital anomalies and/or gastrointestinal diseases, infants who transferred to other medical institutions before discharge or died within the first 72 h of life.www.clinicaltrials.gov as NCT02605577 on November 16, 2015.This is a multi-center study conducted based on data from 25 member hospitals affiliated to Beijing Cooperative Multi-Center Preterm Infants Network. The 25 member hospitals include 20 level III hospitals and 5 level II hospitals. Written informed consent was obtained by parents at time of infants’ admission. This trial was registered at The data collection form was designed as a software program installed in tablet computers and provided to all the participating hospitals. The length and head circumference measurement were standardized, and the weighing scales were calibrated. Standardized operation manuals were handout to participating hospitals containing instructions and the definitions. Complications are defined from “Practice of Neonatology (4th edition)” . ExclusiBaseline data were obtained soon after admission, and outcome data were sent to database through everyday submission or at the time the infants were discharged. Neonatologists in charge of the enrolled infants completed the medical charts after completing daily medical visit. Basic data included GA , gender, Apgar score, birth weight (BW), length, head circumference, whether diagnosed as small for gestational age (SGA), asphyxia, hypothermia, neonatal respiratory distress syndrome (NRDS), apnea, transient tachypnea of newborn, hyperbilirubinemia, hypoalbuminemia, anemia, neonatal infection, early and late-onset sepsis, meningitis, hypoglycemia, hyperglycemia, feeding intolerance, necrotizing enterocolitis (NEC) and intra-ventricular hemorrhage (IVH) during hospital stay. These complications were diagnoses or emerged before the application of parenteral nutrition.The time regaining birth weight, weight at discharge, length at discharge, head circumference at discharge, and weight growth velocity (GV) were recorded and calculated, as well as the average enteral nutrition advancement rate.x = the day with the lowest body weight, y = length of stay /.RRID: SCR_019096) was used for statistical analysis. The Kolmogorov–Smirnov test was used to determine whether the variables were normally distributed. Data were presented as mean ± standard deviation for normally distributed variables, and percentages  for variables that were not normally distributed. Comparisons of categorical variable between two or more groups were performed by the χ2 test or fisher exact test. Comparisons of continuous variables that was not normally distributed between two groups were performed by Mann–Whitney test. Comparisons of continuous variables that among three groups were performed by ANOVA for normal distribution data or Kruskal–Wallis test for abnormal distribution data. Binary logistic regression was also used to determine the influencing factors of parenteral nutrition. The level of significance was set at p < 0.05.The Statistical Package for the Social Sciences (SPSS) for Windows, version 24.0  weeks. Basic characteristics are shown in About 53.9% (788/1463) of infants were supported by parenteral nutrition containing amino acids and lipid emulsion for more than one day. The proportion of infants on parenteral nutrition changed over time and was inversely related to GA. Over 60% of 34 weeks’ infants were on parenteral nutrition during the 2nd to the 4th day, At the end of the 1st week, infants on parenteral nutrition decreased to 10–40% . InfantsUnivariate-analysis showed that GA, birth weight, birth length, birth circumference, incidence of SGA, feeding intolerance, hypoglycemia, NRDS, neonatal infection, apnea, anemia, growth velocity, volume of enteral nutrition at discharge and enteral nutrition advancing rate had significant difference between the parenteral nutrition (PN) and non-parenteral nutrition (non-PN) group . Late prp < 0.0001] and higher possibility to regain birth weight at discharge than infants without PN .Late preterm infants with PN had higher growth rate [11.2  g/kg/d vs. 8.5  g/kg/d, Binary logistic regression analysis showed that infants with lower GA or lower birth weight, infants diagnosed with hypoglycemia, SGA, feeding intolerance, NRDS, neonatal infection, and infants with lower enteral nutrition advancement rate had higher possibility to start parenteral nutrition .Enteral nutrition, especially breast milk, is the first option for late preterm infants, but sometimes, it may not be established as expected. Except for the separation of mother and sick late preterm infant and the insufficient attention on benefit of exclusive human milk feeding, the coordinated sucking ability that allows for the provision of sufficient intake by sucking feeds is not well developed until 34 weeks . And thaFor extremely preterm infants, the parenteral nutrition is initiated as soon as possible after delivery to prevent nutrition deficit , 17, whiMany factors influenced the clinical decision to initiate and sustain parenteral nutrition. Logistic regression analysis revealed that GA, birth weight, hypoglycemia, SGA, feeding intolerance, NRDS, neonatal infection, and low enteral nutrition advancement rate were independently associated with the application of parenteral nutrition.Late preterm infants with lower GA and birth weight had higher possibility of immature gastrointestinal tract and medical deliberated slower enteral nutrition progress due to the worry of feeding intolerance. Parenteral nutrition became ineluctable sometimes, but lasted shorter duration than extremely premature infants. The starting volume of amino acid and lipid emulsion were also found to be related to GA; infants with smaller GA tend to have higher volume of amino acid and lipid emulsion infusion as shown in our study.The occurrence of medical problems in infants born with a GA of 34–36 weeks was significantly higher than in infants born at term. Accordingly, another indication of parenteral nutrition were clinical comorbidities such as hypoglycemia, SGA, feeding intolerance, NRDS, and neonatal infection like that revealed in our study. These findings were in agreement with previous data reported in literature from Italy, which showed that birth weight ≤2000 g, GA of 34 weeks and being born SGA, infants having developed a respiratory distress syndrome and having required a surgical intervention resulted to be independently associated with a higher risk of receiving a nutritional support. In some institution, protocols were set as infants with a birth weight <1500 g and infants presenting with any clinical condition that could hinder the beginning of enteral nutrition or that could interfere with the ability to feed exclusively by mouth .p < 0.0001) and higher possibility to regain birth weight at discharge . However, the causes of initiating parenteral nutrition did not negatively affect the growth of these late preterm infants. When enteral nutrition advancement is not as good as expected, parenteral nutrition should be initiated to ensure the total energy intake and optimal growth  g/kg/d vs. 8.5 g/kg/d, l growth –23. But This multi-center prospective cohort study lacks long term follow-up data of these late preterm infants, especially in terms of neurodevelopmental and metabolic prognosis. Optimal nutritional strategy for late preterm infants to achieve better neurodevelopment and body composition should be investigated in well-designed randomized controlled trials.Over half of hospitalized late preterm infants were supported by parenteral nutrition. The application of parenteral nutrition concentrated on the second to the fourth day. Infants with lower GA or lower birth weight, and infants diagnosed with hypoglycemia, SGA, feeding intolerance, NRDS, neonatal infection, slower enteral nutrition advancing rate had higher possibility to start parental nutrition. Late preterm infants with enteral nutrition plus parenteral nutrition had higher growth rate than infants with exclusively enteral feeding support.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethical Committee of Peking Union Medical College Hospital. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.MQ collected the data, performed the analysis, and drafted the initial version of the manuscript. ZL had primary responsibility for the study design, data analysis, and interpretation, and reviewed and revised the manuscript. DW and KS supervised the data collection and were involved in data interpretation. LY, JL, XQ, XZ, TH, and YL was involved in software and data collection. 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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Azospirillum ‘Er-20’ (nitrogen fixing) and Agrobacterium ‘Ca-18’ (phosphorous solubilizing) were used for inoculation, while control treatment had no PGPR inoculation. Six N doses, i.e., 100, 80, 75, 70, 60 and 50% of the N required by chili were included in the study. Data relating to growth traits, biochemical attributes and yield related traits were recorded. Interaction among N doses and PGPR inoculation significantly altered all growth traits, biochemical attributes and yield related traits. The highest values of the recorded traits were observed for 100% N with and without PGPR inoculation and 75% N with PGPR inoculation. The lowest values of the recorded traits were noted for 50% N without PGPR inoculation. The PGPR inoculation improved the measured traits compared to the traits recorded noted in same N dose without PGPR inoculation. Results revealed that PGPR had the potential to lower 25% N requirement for chili. Therefore, it is recommended that PGPR must be used in chili cultivation to lower N requirements.Nitrogen (N) is a macronutrient desired by crop plants in large quantities. However, hiking fertilizer prices need alternative N sources for reducing its requirements through appropriate management practices. Plant growth promoting rhizobacteria (PGPR) are well-known for their role in lowering N requirements of crop plants. This study assessed the impact of PGPR inoculation on growth, allometry and biochemical traits of chili under different N doses. Two PGPR, i.e.,  Nitrogen (N), phosphorous (P) and potassium (K) are the important mineral nutrients for the optimum growth and production of plants in commercial agricultural systems . NitrogeTherefore, it is necessary to overcome the negative impacts of fertilizers  by incre2PO4) and diabasic (HPO4-2) ions [After N, P is one of the most important elements playing key roles in energy transfer, signal transduction, biosynthesis of macromolecules, respiration and photosynthesis . The P i-2) ions . The PGP-2) ions .Potassium is major macronutrient after P required for normal growth of crop plants. Deficiency of K is becoming a major constraint in crop production resulting in poor growth, small seeds and lower yields. Parmar and Sindhu  reportedCapsicum frutescens L.) belongs to Solanaceae family and genus Capsicum. Solanaceae family contains 3000 species and 90 genera [Chili (0 genera –30. It i0 genera . Chili i0 genera . Low N aAzospirillum Er-20) and P-solubilizing (Agrobacterium Ca-18) PGPRs for improving chili production under low N availability. Similarly, different N doses were used to assess the yield losses caused by decreasing N availability. It was hypothesized that different N doses will differ in growth and productivity of chili. It was further hypothesized that PGPRs’ inoculation will improve growth and yield of chili under reducing N doses.Therefore, this study assessed the role of synergistic inoculation of N-fixing (-1), medium available N (300 kg/ha), medium available P (21.2 kg/ha), high available potassium (701 kg/ha) and 1.2% organic matter.This study was conducted in polythene tunnels at Department of Horticulture, Bahauddin Zakariya University Multan, Pakistan . Soil was sandy clay loam  with slightly alkaline pH (7.8), good electrical conductivity (0.72 ds mAzospirillum Er-20 (N-fixing) and Agrobacterium Ca-18 (P-solubilizing) were obtained from National Institute for Biotechnology and Genetic Engineering, Faisalabad, Pakistan . The bacterial strains were grown in 1 L LB broth medium at 28°C for 48 hours to get the optimum growth (CFU ≥109 mL-1). Bacterial cells were then harvested by centrifugation at 4000 × g for 20 min at 4°C and suspended in 1 L of saline solution (w/v 0.89% NaCl).Chili seedlings were procured from Jafar group, Multan, Pakistan . Two PGPR strains, i.e., The PGPR mixture was prepared by adding 5 g PGPR and 100 ml water. Before transplanting, the roots of seedlings were dipped in PGPR mixture for half hour. Transplanting was completed in the morning and irrigation was applied soon after transplanting.nd irrigation was applied after 2 weeks of transplanting. Further irrigation was applied according to the field and weather condition. All other cultural practices were followed as recommended for growing chili crop under field conditions. Insects, pests were controlled by the foliar application of insecticide Actara (0.63 g/l).The seedlings were either dipped (PGPR inoculation) or not dipped (no PGPR inoculation) in PGPR mixture. The P and K were applied at their recommended doses, whereas N doses were 100, 80, 75, 60, 60 and 50% of the recommended N for chili. Seedlings were transplanted on 60 cm apart ridges 60 cm by keeping plant to plant distance of 30 cm. Seedlings were transplanted on Dec 22, 2015. Irrigation was applied just after transplanting the seedlings and 2Data relating to plant height at flowering and harvesting stage, shoot fresh and dry weight, root fresh and dry weight, root length and stem diameter were recorded. For dry weight, plant samples were dried in an electric kiln at 60°C for 72 hours and weighed. Three samples were collected from each treatment. Data relating to total number of fruits per plant, fresh and dry weight of fruit, fruit length and fruit width were also recorded at harvest. Ten plants were randomly selected from each experimental unit. All fruits on the plants were harvested during each picking and weighed. From the fresh weight, yield/ha was calculated. Leaf samples were collected for determining antioxidant capacity and total phenolic following Singleton and Rossi . SamplesHere, Ao = reading of control, A1 = value of absorbance.Chlorophyll content in the fruits was measured by following the method of Arnon . Fresh 1Here, ABS 663 = absorbance at 663 nanometers, ABS 645 = absorbance at 645 nanometer, V = volume of acetone used, W = weight of sample.The carotenoid content of fruit was estimated by the method of Kichtenthaler and Wellburn . One graThe total phenolic content was analyzed by following Singleton and Rossi . Folin-CData collected were analyzed statistically by using Fisher Analysis of variance (ANOVA) technique . Least sIndividual and interactive effects of PGPR inoculation and N doses significantly altered different growth traits, including plant height at flowering and maturity, stem diameter, root length, and fresh and dry weights of roots and shoot with some exceptions for individual effects of PGPR inoculation for stem diameter, root length and shoot fresh weight .Different growth traits, including plant height at flowering and maturity, stem diameter, root length, and fresh and dry weights of roots and shoot were significantly affected by interactive effect of PGRP inoculation and N doses . OverallIndividual and interactive effects of PGPR inoculation and N doses significantly altered different reproductive and yield-related traits, including yield, chlorophyll contents, total number of fruits, fruit fresh and dry weight and length and width .Different reproductive and yield-related traits, including yield, chlorophyll contents, total number of fruits, fruit fresh and dry weight and length and width were significantly affected by interactive effect of PGRP inoculation and N doses . OverallIndividual and interactive effects of PGPR inoculation and N doses significantly altered different biochemical traits, including antioxidant activity and capacity, total phenolic contents, carotenoids, leaf chlorophyll content and fruit chlorophyll a and b contents with some exceptions . HoweverDifferent biochemical traits, including antioxidant activity and capacity, total phenolic contents, carotenoids, leaf chlorophyll content and fruit chlorophyll a and b contents were significantly affected by interactive effect of PGRP inoculation and N doses . OverallDifferent growth, yield, and biochemical attributes of chili significantly differed among different N doses and confirmed our first hypothesis. Likewise, PGPR inoculation significantly increased growth, yield, and biochemical attributes of chili compared to no PGPR inoculation confirming our second hypothesis. Overall, PGPR used in the current study have potential to reduce N requirement of chili by 25% without any yield losses. Similar results for PGPR inoculation have been reported for different crops like cucumber, tomato and legumes , 38–40. B. stratosphericus-NFB3, B. cereus MNB1 and P. simie-NTB2 increased plant of chili over the untreated plants [It has been reported three PGPR isolates, i.e., d plants . Bi et ad plants  reportedd plants .A significant increase in the fresh weight of root with PGPR inoculation in cabbage seeds was reported by Turan et al. . Hence, Bacillus mycoides T8 and Bacillus subtilis OSU-142 alone or in combinations significantly increased the fruit length in quince [Foliar and floral applications of different PGPR strains, i.e., n quince . Hence, n quince , 12.The current study indicated that decreasing N availability suppressed growth, yield, and biochemical attributes of chili. However, PGPR inoculation significantly improved these traits even under low N availability. Overall, the PGPR inoculation with 75% N availability produced similar traits as of 100% N availability. Thus, it is concluded that PGPR has the potential to lower N requirement of chills crop; thus, these can be used to improve chili productivity with low N availability.


Adverse birth outcome (ABO) can lead to higher rates of poor health and infection for newborns, as well as long-term neurological and health problems. Hence, the aim is to identify determinants of ABOs among mothers who gave birth in hospitals in West Shewa zone, Ethiopia.A hospital-based, unmatched, case-control study was conducted from March 5 to July 29, 2020, among 591 mothers (171 cases and 420 controls) who had given birth in hospitals found in West Shewa zone. The questionnaire was collected using census and survey processing system (CS-Pro) version 7.1. The data were entered into Epi-data version 3.1 and analyzed by SPSS software version 23. Descriptive statistics, bivariate analysis, and multivariate logistic regression analysis were performed. Finally, P-value <0.05 was used to declare and include variables with statistically significant in predicting the outcome variable.On multivariate analysis, urban residence , lack of family support during child bearing , pregnancy type , short interpregnancy interval , less than four antenatal care (ANC) visits , and having current obstetric complication  were significantly associated with adverse birth outcomes.Residence, lack of family support during childbearing, pregnancy type, short inter-pregnancy interval, having current obstetric complications, and number of ANC visits were identified as determinants of adverse birth outcome. Therefore, improving family support, increasing inter-pregnancy interval through family planning counselling and provision, and having the recommended ANC follow-up were recommended. Preterm is defined as a baby born alive before 37 weeks of pregnancy are completed [An adverse birth outcome (ABO), which includes preterm births (PTB) and low birth weight (LBW), are major drivers of morbidity and mortality in neonates and infants , 2, 3. Aompleted . Low birompleted .The majoompleted ,10. Globompleted . Regionaompleted . ABOs arompleted , 13, 14.ompleted , 16, 17.In Ethiopia, different studies have shown that the prevalence of ABOs is within the range of 13.9% to 37.6% , 23, 24.The study was conducted in hospitals found in West Shewa, Oromia, region, Ethiopia, from March 5 to July 29, 2020. Ambo town is the capital city of the West Shewa zone, which is located 114 kilometres to the west of Addis Ababa. West Shewa zone has 8 public hospitals, 96 government health centres, 526 health posts, and 77 private clinics. The total population in the zone is 2,058,676, of whom 1,030,175 were females.A hospital-based, unmatched, case-control study was conducted. All mothers who gave birth in hospitals in the zone were our source population. Cases were mothers with adverse birth outcome, including preterm birth, low birth weight, or stillbirth; controls were mothers with live births whose infants had birth weights greater than 2,500 grams at birth and were born at term.The sample size was calculated by Epi info stat calc software. The proportion of mothers having complications during childbirth among controls was used to determine the sample size from the study conducted in Jimma . The assA structured interview questionnaire in English was prepared and translated into the local language, Afan Oromo, by the translator; it was then translated back into English by a third person to check for consistency. The questionnaire gathers information on sociodemographic characteristics, past obstetric and gynaecologic experiences, the current obstetric experience, and the characteristics of the newborn at birth; it was adapted from the EDHS  and other reviewed literature and modified according to the local context , 25,30. The data were collected using CS-Entry for the android version and exported to SPSS version 23 for analysis. Binary logistic regression analysis was done to evaluate the association of ABOs with each independent variable separately. Variables with a p-value <0.2 were entered into the multivariable logistic regression models. Model fitness was tested with Hosmer-Lemeshow goodness of fit test. Furthermore, multicollinearity was checked between the independent variables and (VIF), and tolerance to test multicollinearity and VIF (variance inflation factors) was less than 10 and tolerance >0. Finally, the strength of association was measured by both crude and adjusted odds ratios, with a 95% CI for exposure variables and ABOs. The statistical significance level was declared at p-value < 0.05.A total of 591 mothers (171 cases and 420 controls) were included, with a response rate of 100%. Concerning the educational status of mothers, 56 (32.7%) of the cases are unable to read and write, and 88 (21.0%) of the controls have college or above educations. Of the controls, 118 (28.1%) were farmers 60 (35.1%) of the cases stated their occupations as housewife or mother. The majority of the cases (62.6%) and the controls (58.7%) were Protestant by religion. Ninety (52.6%) of the cases and 164 (28.8%) of the controls were lived in rural areas. The result of this study shows that 12.3% of cases and 6.0% of the control had a record of pre-existing medical illness, with 35 (20.5) cases experiencing anaemia. Forty-nine (11.7%) of the control and 23 (13.5%) of the cases had histories of abortion in their past pregnancies. Concerning family planning, 117 (68.4%) of cases and 275 (65.5%) of controls cases use family planning for birth spacing Fifty-nine (34.5%) cases had history of one-time pregnancy, and 113 (26.9%) of controls had four or more pregnancies. In terms of planning, 138 (80.7%) cases and 351 (83.6%) of the controls had planned the current pregnancy. A higher proportion of cases and controls didn’t develop complications during the current pregnancy. Fifty-one (29.8%) of the cases and 186 (44.3%) of the controls attended four or more ANC visits. The neonatal assessment results indicated that 57.9% of the cases and 65.7% of the controls were male. The first minute APGAR score showed that 25.1% of neonates among the cases and 23.6% among the controls were severely asphyxiated. While 115 (67.3%) of the cases cried at birth, 56 (32.7%) didn’t cry. The percentage of cases receiving skin-to-skin was 82.5%; the percentage of controls receiving such care was 77.9 %. Bivariate logistic regression analysis was performed using odds ratios (OR) and 95% CI. The predictor variables with p-value less than 0.2 in the bivariate logistic regression analysis were entered into the multivariable logistic regression analysis model to control the influence of potential confounding variables. The correlation between the independent variables was checked.After controlling for confounders using multivariable analysis residence, lack of family support during childbearing, pregnancy type, short inter-pregnancy interval, current obstetric complications, and number of ANC visits were identified as determinants of ABOs. =1.43,95% CI=1.23-4.48). Furthermore, mothers who have no family support during childbearing had a five times greater chance to develop ABOs as compared with mothers who had family support . The number of antenatal care visits was found to be associated with the incidence of ABOs, with mothers who had fewer than four antenatal care visits being twice as likely to experience adverse birth outcomes as compared to their counterparts with four or more such visits . Mothers who gave birth to twins had a four times greater chance of an ABO than mothers who gave birth to a singleton . Mothers having current obstetric complications were twice as likely to experience adverse birth outcomes as compared to mothers with no current obstetric complications .Mothers who live in urban areas are 1.5 times less likely to develop ABOsas compared with women living in rural areas . The odds of having adverse birth outcomes increases twofold for mothers whose birth intervals are less than two years, as compared to their respective referent group  and in China , 24, 25.The number of antenatal care (ANC) visits is significantly associated with ABOs: mothers who had fewer than four ANC visits were twice as likely to have ABOs as those who had four or more such visits. This finding is supported by studies conducted in Cameroon, India, Malawi, Addis Ababa, and in Ethiopia, in Tigrai region, Amhara region,and North Shewa zone , 36, 37.Having a history of current obstetric complications was also found to be significantly associated with ABOs. The chance of developing an abnormal birth outcome among mothers with current histories of child-related abnormal birth outcome was twice as high as the chances of mothers without such complications. A study conducted in Gambia and Nigeria showed that mothers with a current history of child-related abnormal birth outcomes are at greater risk of giving birth to a baby with abnormal outcomes ,39. SimiMothers who have no support during childbearing had a five times greater chance of developing adverse birth outcomes as compared to mothers who have partner support. This study was in line with a study done in the United States that found that women with a supportive partner were 63% less likely to have low birth weight infants and nearly two times less likely to have a pregnancy loss, as compared to those with no partner support . Those wShort inter-pregnancy interval is also found to be a determinant of ABOs. The odds of having an ABO were 1.43 times greater among mothers with short birth intervals, as compared to mothers having optimal birth spacing. This result is in line with studies in Tanzania; California, Ohio, and elsewhere across the United States; and Bangladesh , 43, 44,In this study, mothers having current obstetric complications were three times more likely to develop adverse birth outcomes as compared to mothers with no history of current complications. This result is supported by studies conducted in Gondar, Ethiopia; Hosanna, Ethiopia; and a university and hospital in Nashik, India. ,23,32.The result of this study revealed that residence, lack of family support during childbearing, pregnancy type, short inter-pregnancy interval, current obstetric complications, and a number of ANC visits were determinants of adverse birth outcome. Therefore, improving family support, inter-pregnancy intervals through family planning counselling and provision, having the recommended ANC visits, were recommended.


As the Guest Editor of this Special Issue, I would like to express my gratitude to all the authors who have contributed. I am thankful that we were able to accept a number of interesting articles of high quality among those received for publication.An estimated 15 million infants worldwide are born before completing 37 gestational weeks, with resulting complications. Despite all efforts, preterm birth is still the predominant reason for an estimated one million neonatal deaths annually and a significant contributor to childhood morbidities. Modern perinatal and neonatal care has led to a substantial reduction in infant deaths and disability rates, yet preterm birth remains an ongoing challenge. It is a multifactorial event with a broad variety of causal factors, potentially involving multiple disciplines during antenatal and postnatal care.Vaginal dysbiosis and infection are among the most frequent causes of preterm births. Early diagnosis is essential as it is well known that delayed treatment initiation increases the risk of preterm birth. In clinical practice, conventional diagnostic procedures are time consuming and require medical staff and equipment. As part of this Special Issue, Foessleitner et al.  reportedMoreover, the importance of thorough antenatal care was confirmed in the article by Ferrillo et al. , who repIn cases where infection has finally resulted in preterm rupture of membranes and subsequent preterm birth, culture-proven sepsis is currently considered the gold standard for the diagnosis of early-onset neonatal sepsis. As part of this Special Issue, Grill et al.  have evaThe cited articles confirm the multidisciplinary approach that is needed to adequately address preterm birth, offering healthcare professionals an insight into its complexity, thereby providing an understanding and promotion of various strategies. This approach is pursued in this Special Issue’s excellent review by Schachinger et al. , who sumFinally, in our issue, Gorczyca et al.  have addTaken together, the articles in this Special Issue have added to the increasing knowledge of preterm birth and its pathogenic role, and have provided a better understanding of established or newly developed approaches for this multifactorial event. I would, herein, like to thank all the authors and reviewers for their significant and highly appreciated contribution to our Special Issue, and for making it a valuable collection of studies that are very interesting to read and learn from.Contributing to the understanding of preterm birth, which compromises the health of our future generations, is without a doubt a challenge worth investing.


The effect of the total PCB levels and the effects of PCB congener mixtures were analyzed using a linear regression model and a generalized weighted quantile sum regression model (gWQS). The birth weight of newborns was significantly associated with maternal exposure to PCB mixtures in the gWQS model. The results suggest that exposure to PCB mixtures results in low newborn birth weight. However, specific impacts of individual PCB congeners could not be related to newborn birth weight.Maternal exposure to polychlorinated biphenyls (PCBs) during pregnancy is associated with a low birth weight; however, the congener-specific effects of PCB congeners are not well defined. In this study, we used maternal serum samples from the Chiba Study of Mother and Child Health (C-MACH) cohort, collected at 32 weeks of gestational age, to analyze the effects of PCB congener exposure on birth weight by examining the relationship between newborn birth weight and individual PCB congener levels in maternal serum (n = 291). The median total PCB level in the serum of mothers of male and female newborns at approximately 32 weeks of gestation was 39 and 37 ng g Low newborn birth weight is associated with the development of various diseases, such as hypertension in later life ,2,3,4. TPolychlorinated biphenyls (PCBs) have not been manufactured since the 1970s because of their toxicity to human health. However, they remain in the environment and are still detected in human tissues owing to their persistent nature . StudiesThe Chiba Study of Mother and Child Health (C-MACH)—a birth cohort study in Japan that focused on the effects of environmental health on fetuses—has been conducted since 2014  through selected ion monitoring (SIM) analysis using the NICI-MS detector. Our analytical protocols were accredited by the Japan Accreditation Board and compliant with ISO/IEC 17025:2005 standards. During the entire analytical sequence, blank determinations were carried out at intervals of 20 samples to identify contamination. The detection limits for individual PCBs in this study ranged from 0.2 to 0.8 ng g−1 fat wt, and PCB congener surrogate recovery rates ranged from 70.7 to 140%. For quality control and assurance of the PCB analysis, our laboratory participated in an inter-calibration exercise based on the Standard Reference Material 1957; PCB values determined in this study were typically within the certified range [Serum concentrations of 17 PCB congeners  were analyzed using gas chromatography (GC) with negative ion chemical ionization qMS (NICI-qMS), as described by Eguchi et al. , becauseed range .corrplot . PCB concentrations below the limit of detection (LOD) were assigned according to LOD/√2 for Spearman’s rank correlation analysis.Data processing and analysis were performed using R ver. 4.0.5. Correlations between exposures and outcomes were determined using Spearman’s rank correlation coefficient with the R package tableone . A linear regression model was implemented using the base R function. Linear WQS with multiple imputations was used to calculate samples with PCB concentrations below the LOD and investigate the effects of PCB mixtures using the gWQS package [Differences based on newborn sex, the hospital of birth, in exposure, covariates, and outcomes were determined using the Kruskal–Wallis test with the R package  package . WQS reg package . In this package  package. package  package.−1 lipid wt, respectively. The detected PCB congeners were correlated with one another (rs: 0.49–0.99, s: 0.49–0.71. s: 0.53–0.78. Details of the individual participants, including serum PCB levels, are listed in p = 0.046, p = 0.26, female newborns: β = −45.9, p = 0.17, The results of the linear regression model are presented in There are two possible reasons for the different results obtained using the WQS and linear regression models. First, multicollinearity was avoided with correlation observed among the congeners in the mixture of PCBs in WQS, which is the unidirectionality of the index and the ensemble step; second, the WQS model can evaluate the mixture effects of PCB congeners . AlthougDue to the specific effects of individual PCB congeners not being well determined in our previous study , we explHowever, the importance of weights of individual PCB congeners of gWQS were not consistent, indicating that the effects of PCB exposure on birth weight may not be congener-specific . Since iMaternal serum samples from the C-MACH cohort, collected at a gestational age of 32 weeks, were used to examine the relationship between newborn birth weight and individual PCB congener levels. Linear regression and gWQS models were used in this study, and results from the gWQS model suggested that PCB mixture exposure was associated with low newborn birth weight. It was, however, observed that the impact on birth weight from antiestrogenic PCB congeners detected in the serum was relatively low. Unlike PCB mixtures, a significant correlation was not observed between individual congeners and birth weight, indicating that the effects of PCB exposure on birth weight may not be congener-specific.While these data provide insight into the potential association of PCB exposure and low birth weight, we acknowledge that our study has several limitations. For instance, unmonitored contaminants, including unmonitored PCB congeners in this study may have contributed to low birth weights in addition to the PCBs measured in this study. Other important limiting factors include the lack of information on PCB exposure before pregnancy, and a small sample size, which may have affected the study results.Further research on a larger scale is required, including detailed studies on the individual effects of each congener.


The results reveal that women who participate in the SREP are more likely to pursue a major in a STEM field and continue on to a STEM occupation compared to non-SREP students, national female averages, and national subsets. Participants attribute their outcomes to an increase in confidence, establishment of technical and professional skills, and other traits strengthened through the SREP experience. These data suggest that implementing similar experiential programs for women in science and engineering at the high school stage could be a promising way to combat the remaining gender gap in STEM fields.There remains a large gender imbalance in the science, technology, engineering and mathematics (STEM) workforce deriving from a leaky pipeline where women start losing interest and confidence in science and engineering as early as primary school. To address this disparity, the Science Research & Engineering Program (SREP) at Hathaway Brown School was established in 1998 to engage and expose their all-female high school students to STEM fields through an internship-like multi-year research experience at partnering institutions. We compare data from existing Hathaway Brown School SREP alumnae records from 1998–2018 ( In the last 20 years, substantial gains have been made in the effort to increase the number of women in STEM  fields , 2. WhilStarting in 1998, a multi-year STEM research experience has been ongoing at Hathaway Brown School (HB), an all-female private school in Shaker Heights, OH. The program was established to encourage the pursuit of STEM majors for women and increase confidence and empowerment by giving this all-female population of high school students the opportunity of an internship-like research experience in a STEM field by partnering students with researchers at local universities and institutions. Based on outcomes from the Science Research & Engineering Program (SREP) alumnae from 1999–2018, we demonstrate that the SREP, and similar experiential programs for high school girls, may be one step to increasing women in STEM fields and bridging the confidence gap that drives women away from STEM and leadership roles.The STEM pipeline is a metaphor for the pathway students enter in early education until college graduation that intends for a finalized destination in a STEM occupation. From 1998–2016, women earned 50.2% of STEM bachelor’s degrees , 12. DesAfter college, women earn half or more of advanced degrees at every level overall; however, in STEM fields this varies largely by discipline. In 2017, women earned 43.6% and 45.2% of STEM Master’s and doctoral degrees, respectively. Women are still separated by a wide margin from men for degrees in engineering, mathematics, computer sciences and the physical sciences  . FinallyAt all stages of the STEM pipeline, a consistent obstacle for women is confidence, whether it be their attitudes and expectations about mathematics and science careers as early as kindergarten , 19, theAs early as middle school and into high school, female students show less interest and confidence than male students in mathematics, even though they display similar levels of performance . Male hiIn the context of women, the STEM pipeline has been under intense scrutiny in order to determine at what stages girls and, later women, gain their interest in STEM or leave the track to pursue a Non-STEM occupation , 29. HowA large number of explanations for this decrease have been identified at the level of secondary school. Most prominent concerns include stereotype bias , 35, lacThe HB SREP experience gives an all-female high school student population the chance to work in the laboratory of an engineer, research scientist, or clinical investigator for 2–3 years. Students generally read and study the literature in the field and learn the relevant techniques while assisting others in the lab before taking on an original research project of their own. This is usually a small piece of the overarching research goals of the lab. The multi-year commitment allows the student time to develop and establish confidence in herself and her abilities, bridging the confidence gap that is often cited as one facet of why women leave the STEM pipeline.At the time the SREP was established, internships were largely reserved for undergraduates or non-college track students in secondary schools with a focus on vocational training . This maHere, we take a retrospective view of 20 years of SREP alumnae (1998–2018) to determine if participation in the SREP increased retention in the STEM pipeline and whether outcomes were attributed to the bridging of the confidence gap through SREP during the critical high school years. Pipeline indicators were measured by declaration of STEM college majors, completion of those majors, and occupational outcomes. HB SREP participants were compared with HB students who did not participate in SREP in the same timeframe (HB Non-SREP), students nationally, and White and Asian female subsets of the national data as these particular race/ethnic groups are a better match to demographics of SREP participants. We also examined the completion of professional and graduate degrees by SREP alumnae in relation to the same groups to reflect on qualifications for leadership. Finally, the perceived traits and skills, particularly confidence and competence, acquired during the SREP experience and reported by SREP alumnae are explored as we believe that addressing the confidence gap through this model positively affects pipeline outcomes and could warrant the implementation of programs like the SREP elsewhere to bolster women in STEM fields.Given the 20 years of alumnae data on a program housed in an all-female high school environment coupled with a multi-year experience that cultivates the relationship of the student in a professional science setting, we found ourselves in the unique position to evaluate the impact of these factors. We present evidence that women who have participated in the SREP are more likely to pursue a STEM major and occupation compared to both national norms and specific subgroups and alumnae credit their SREP experience with strengthening their confidence and empowerment, technical and professional skill set, and giving them the voice to be heard as women in their post high school careers.The aim of this retrospective study was to gain an understanding of whether an internship-like experience in high school in a STEM field can influence retention of women in the STEM pipeline and whether this is attributed in part to participation in the SREP.This study was deemed exempt by the Hathaway Brown School Institutional Review Board as the research was conducted in a commonly accepted educational setting involving normal educational practices on existing data. All sources were de-identified after merging.The SREP is a program at Hathaway Brown School, an all-female private school for K-12 in Shaker Heights, OH that partners with academic, industrial, and private institutions to promote research experiences for students in grades 9–12. Students interested in the experience can learn about the program in grade 9 or 10 through a one semester Introduction to Research Seminar class that meets once per week. Students range from those interested in science and engineering to those unsure what a career in one of these fields might entail and are simply enrolling for exploration. In class, students learn about research areas through discussions with the Director of Research, listen to presentations from older SREP students on their projects, and read research spotlights in scientific journals in addition to learning how to write cover letters, resumes, and communicate effectively. Through these processes, students can decide if they wish to pursue a placement and if so, can focus in on particular areas and eventually begin identifying faculty at local institutions with whom they might like to work by reading institutional webpages. Students interested in pursuing a placement with a research group follow the Introductory class with a Research Seminar class that meets once per week every semester until graduation. Curriculum within the Research Seminar class includes learning how to locate and read literature to bolster scientific literacy, practice sharing work through poster and oral presentations to hone presentation skills, and culminates in the writing of a formal paper written in the format of a scientific research article.To obtain a placement with a research group arranged by the Director of Research students must have As and Bs in their classes, receive recommendations from their teachers, meet standardized test score requirements , and commit to volunteering 2–3 summers in the lab for seven weeks of full days and once per week after school during the academic year. Students apply by submitting a cover letter, resume, and list of scientists who interest them to the Director of Research, who then reaches out on their behalf to inquire about a placement. The Director of Research individually matches students with a laboratory aligned with the student’s personal interests by contacting the principal investigator, research lead, or manager directly and explaining the program, particular student, and goals of the SREP. Students who cannot fulfill the academic or time requirements or simply wish to have more flexibility may endeavor to find a placement through family connections and are still supported by the Director of Research and Research Seminar class.The Director of Research initiates a meeting and interview with the student and principal investigator or lead and their group after mutual interest is determined and then the student is encouraged to navigate her placement independently with the Director of Research available for support and coaching. Students develop communication and organizational skills while they form a relationship with the research group. The student is typically paired with a direct supervisor like a postdoctoral scholar, graduate student, or technician in the lab for mentoring on a day-to-day basis and learns the techniques and specialized information relevant in order to eventually earn the privilege to work on an original research project of her own that aligns with the lab’s overarching goals and will contribute to the research of the group. The necessity of planning schedules and working through conflicts in addition to the nature of research and inherent setbacks develops confidence, courage, empowerment, reliability, and responsibility. It is likely that these soft skills, in addition to the science and engineering core, provide the structure to succeed further down the pipeline.n = 495) completed 619 projects that were categorized into project areas according to standard science and engineering disciplines. Some students participated in more than one project in the same lab and a trivial number completed projects in different labs. Every project was classified categorically by discipline. During the first 20 years of the SREP, biological and life science projects were the most prevalent (39%). The second highest percentage of students participated in engineering projects (30%) including materials science, macromolecular, chemical, biomedical, robotics, and mechanical and aerospace engineering. The remaining project disciplines are substantially lower, with clinical and bioinformatics at 14%, physical sciences  at 8%, and the rest at 5% or below  were obtained providing data on race/ethnicity demographics, awarded college majors, graduate and professional degrees, and occupations for both SREP (n = 495) and Non-SREP alumnae . The database is not comprehensive for every data point due to the nature of self-reporting and thus sample size varies for each research question. In some cases, subsets of the 20-year group were analyzed if certain graduation years had not had time to reach the milestones analyzed . HB does not collect information on household income, guardian educational background, or family structure, but attracts predominantly middle-to upper-class families that are likely more highly educated than most American families.The HB Advancement Office maintains a database on all HB alumnae. For the purposes of this research, data on all HB alumnae from 1998–2018 (n = 1246), HB had an overrepresentation of White students  and Asian , Reviewers' comments:Reviewer's Responses to QuestionsComments to the Author1. Is the manuscript technically sound, and do the data support the conclusions?The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: PartlyReviewer #2: No**********2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: N/AReviewer #2: No**********3. Have the authors made all data underlying the findings in their manuscript fully available?PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.The Reviewer #1: NoReviewer #2: Yes**********4. Is the manuscript presented in an intelligible fashion and written in standard English?PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #1: YesReviewer #2: Yes**********5. Review Comments to the AuthorPlease use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. Reviewer #1: It is impressive result the SREP graduates are awarded more S&E degree than the national female average. The result looks clear and teachers’ long-term efforts is wonderful, but there are several lack of description and analysis.1.First, more data of SREP at the school is needed. There are 619 SREP projects, at least, the author should classify and add projects’ field % like Table 2. The SREP graduates ration in the “Biological/agricultural sciences” and “Engineering” are awarded more than the average, it should be discussed the relation between the project fields.2.Not only the projects’ field, but also the more detail about the SREP program should be discussed. The actual situation cannot be seen, such as how the teachers prepared the project, negotiated, and how much they were involved in the operation.3. The discussion is needed how the options in Fig 5 were selected. These items should be discussed in combination with the SREP design concept.4.Overall results and discussions are not clearly separated. Especially since it is a treatise and not an article, it is not suitable to write a conclusion in the subsection title.Reviewer #2: Lines 44-45: should say: while men and women students… equal numbers…Line 56: is it a private school or charter school? I am not sure what an “independent school” is?Line 80-81: If they have comparable aspirations, why would girls reference careers requiring college and boys would not? This is not clear.Line 82: This also seems contradictory: if scores are equal, how could they favor boys? There is obviously a lot of nuance in this literature and I think the precision of the writing needs to be improved in this section of the paper.Lines 190-200: SREP sounds amazing. I think we need more details about how the program fit within their high school coursework  In the summer, were they paid or just volunteers?More importantly (in terms of a selection bias issue): How were students selected for it?What are the sociodemographics of the student body at this school and in SREP? .I think the authors should pose research questions at the end of the introduction. Without doing that, it is hard to see how the different data sources and variables are going to be used (on pages 9-11). For example, I don’t know how supplemental survey which 25% of the cases responded too will be used.In the data section, the authors also do not introduce how they will determine the control group or control population. Line 263 mentions some sources, but not specifically what they are and how they are used.Line 261: The statistics section does not discuss any actual statistical approaches. What tests are used?Line 268: The authors report that their alumni are not nationally representative, but they need to actually show the reader how they diverge from national stats so that we can use that information to evaluate the comparisons. So compare actual percentages between groups.Line 271: says that the purpose is to assess SREP as a model. It seems very late in the paper to be stating that as the goal. Also, is that what the analyses really achieve? In lines 278-9: another goal is stated. The paper should have one goal  and it should be introduced early in the paper and then the analyses should support that goal).Section at Line 282: This does not seem to be results, it seems like background on the program, I would move it back to the section on SREP, unless you create new research questions that include this as one of the questions.Line 305: This heading seems to be one of the key research questions. Pose it earlier.!Line 316: Is there a way to get these national stats for white and Asian women alone? Since we know that minority students are less likely to go into STEM careers, the national averages are lower than they would be for the group of students from this school. There might be better comparison stats than national averages when your students are not nationally representative.Line 361: What does being “more firmly committed” mean? I would recommend just using language about switching majors in the headings for clarity.Line 377-378: I am not convinced that that gap could not be explained by the SES and race/ethnicity differences between the students in your sample and the national averages.I would recommend posing a series of research questions (at the end of the intro) that lead the reader through the results.Line 568: The issues of selection bias in this paper are HUGE and since those who do STREP are not representative in any way, I am just convinced that the national stats are the right comparison group. I think they could be utilized in the paper, but I don’t think they should be the featured story since the HB alumnae are not even close to representative .One better comparison group would be HB students who did not do STREP. I don’t see why (line 582) this group could not have been made available. That does not make sense to me, given that the study is already using alumni records. The paper has a really cool set of data and I like it in many ways, but it is fundamentally flawed. Research looking at this question about the impact of program participation on STEM trajectories would use propensity score matching to match each SREP student with controls, conduct multivariate stats, and then that would isolate the effect of SREP on their trajectory and you could really say that it helped and by how much it helped.In the absence of that, it seems like making multiple comparisons is probably best. Comparing local stats for the community/city in which HB is located, comparing by race/ethnicity nationally, comparing to national averages, etc.Comparing to national statistics only is not very meaningful, given that it appears this group is quite a bit more affluent and advantaged than the average American woman. One possibility is to look at all the stats by race, so find national stats for white woman and Asian women and compare to them. However, since those stats for the HB alumni were not reported, I cannot provide definitive advice here on how to move forward. The current approach is problematic.The tables and figures are missing captions and notes. The reader needs to know the N of the groups and the source of the data in all of them. I also think basic tables are missing, such as descriptive stats on the HB alumni group .**********what does this mean?). If published, this will include your full peer review and any attached files.6. PLOS authors have the option to publish the peer review history of their article  digital diagnostic tool,  9 Jun 2021REVIEWER 1 1. First, more data of SREP at the school is needed. There are 619 SREP projects, at least, the author should classify and add projects’ field % like table 2. The SREP graduates ration in the “biological/agricultural sciences” and “engineering” are awarded more than the average, it should be discussed the relation between the project fields. Figure 1 has been converted to Table 1  and moved to the Methods under the “Program description” subsection to classify the project field in a similar way to the majors in Table 2.2. Not only the projects’ field, but also the more detail about the SREP program should be discussed. The actual situation cannot be seen, such as how the teachers prepared the project, negotiated, and how much they were involved in the operation. The authors agree that information was lacking and have expanded on the “Program description” subsection (Lines 222-279) to include the details of how this program works and expand on the information about participants, how placements were established and the role of the Research Director, students, and curriculum.3. The discussion is needed how the options in fig 5 were selected. These items should be discussed in combination with the SREP design concept. The authors have added a “Purpose of the study” subsection to the Introduction to address how the perceived character qualities that students feel they have gained through their participation in the SREP have potentially impacted the outcome (Line 263-268). In addition, these particular skills sets are called out in the “Program description” (Line 229-232 & 237-240) to explain how they are incorporated as learning objectives.4. Overall results and discussions are not clearly separated. Especially since it is a treatise and not an article, it is not suitable to write a conclusion in the subsection title. The authors appreciate this observation and have relocated or removed the sections of text in the results that were more suited for the discussion . The Conclusions section is also no longer a subsection, but a main section (Line 750).REVIEWER 2 Lines 44-45: should say: while men and women students… equal numbers… Corrected. (Line 46-47)Line 56: is it a private school or charter school? I am not sure what an “independent school” is? Revised. An independent school is a subcategory of private school, but private is familiar and will suffice here. (Line 59)Line 80-81: if they have comparable aspirations, why would girls reference careers requiring college and boys would not? This is not clear. The authors agree that this statement and entire paragraph is problematic. After consideration, the paragraph has been removed (Lines 142-147) as it attempted to briefly address elementary and middle school stages of the STEM pipeline, but, as the reviewer rightly observes, there is nuance in the literature that cannot be adequately summarized in a short paragraph. This entire section has been rearranged to focus on the high school experience as it impacts the STEM pipeline and excludes discussion of earlier timepoints. (Lines 128-157).Line 82: this also seems contradictory: if scores are equal, how could they favor boys? There is obviously a lot of nuance in this literature and i think the precision of the writing needs to be improved in this section of the paper. See above Lines 190-200: SREP sounds amazing. I think we need more details about how the program fit within their high school coursework  In the summer, were they paid or just volunteers? The authors agree that information was lacking and have expanded on the “Program description” subsection under the Methods to include further details including relation to coursework, logistics of time, and compensation (Lines 222-268). More importantly (in terms of a selection bias issue): how were students selected for it? A selection system does introduce additional selection bias. The requirements of the program have been detailed as well as alternative options (Lines 242-254).What are the sociodemographics of the student body at this school and in SREP? . The authors have added available percentage data under Methods and the “Sources” subsection  to include the details on the race/ethnicity of the HB student body and those who participated in SREP. As noted (Line 298-300) HB does not collect information on household income, guardian educational background, or family structure so these demographics were unavailable.I think the authors should pose research questions at the end of the introduction. Without doing that, it is hard to see how the different data sources and variables are going to be used (on pages 9-11). For example, i don’t know how supplemental survey which 25% of the cases responded too will be used. A “Purpose of the study” subsection has been added to the Introduction to pose research questions and goals of the study (Line 187-214).In the data section, the authors also do not introduce how they will determine the control group or control population. Line 263 mentions some sources, but not specifically what they are and how they are used. The “Sources” subsection of the Methods has been expanded and now includes information on HB Non-SREP students as controls and lists the publicly accessible databases and tables that were used for comparison groups for each analysis . Line 268: the authors report that their alumni are not nationally representative, but they need to actually show the reader how they diverge from national stats so that we can use that information to evaluate the comparisons. So compare actual percentages between groups. The authors have acquired all demographic data available for HB SREP and Non-SREP students and have added available percentage data under Methods and the “Sources” subsection (Line 302-330) to include the details on the race/ethnicity. As noted in (Line 298-300) HB does not collect information on household income, guardian educational background, or family structure so these demographics were unavailable.Line 271: says that the purpose is to assess SREP as a model. It seems very late in the paper to be stating that as the goal. Also, is that what the analyses really achieve? In lines 278-9: another goal is stated. The paper should have one goal  and it should be introduced early in the paper and then the analyses should support that goal). Authors agree that the goals stated throughout the paper appeared disparate and unrelated and need fine-tuned. Lines 403-408 (previously 278-9) have been removed and reworded in a “Purpose of the study” subsection in the Introduction that ties the educational and occupational outcomes assessed to the skill sets learned through the SREP to link bridging the confidence gap to a reduction in leakage in the STEM pipeline (Line 187-214). Section at line 282: this does not seem to be results, it seems like background on the program, i would move it back to the section on srep, unless you create new research questions that include this as one of the questions. Discipline dispersal in the SREP has been converted from Figure 1 to Table 1 (Line 270-279) and moved to the Methods under the “Program description” subsection to help characterize the SREP.Line 305: this heading seems to be one of the key research questions. Pose it earlier.! Key research questions have been streamlined and related to achieve one overall goal. The research question is now posed earlier within the “Purpose of the study” subsection in the Introduction (Line 187-214). Line 316: is there a way to get these national stats for white and asian women alone? Since we know that minority students are less likely to go into stem careers, the national averages are lower than they would be for the group of students from this school. There might be better comparison stats than national averages when your students are not nationally representative. The authors appreciate the reviewer’s ideas and expertise on how to address the lack of ideal controls in this study. The authors have reviewed the publicly available databases and have added White female and Asian female subgroups as a better comparison than the national averages as suggested in all analyses possible (Lines 326-300). National averages were retained for wholistic comparisons.Line 361: what does being “more firmly committed” mean? I would recommend just using language about switching majors in the headings for clarity. The language here is was unnecessarily confusing and the authors appreciate your recommendation for clarification. The wording has been changed to include switching majors (Line 479-482).Line 377-378: i am not convinced that that gap could not be explained by the ses and race/ethnicity differences between the students in your sample and the national averages. The authors agree that this is a limitation of the study and have addressed the race/ethnicity differences by including demographic data on HB students (Table 2) and comparing to subgroups of White women and Asian women as a closer comparison. Unfortunately, HB does not keep records on SES (Line 297-300) and therefore this variable cannot be specifically controlled.I would recommend posing a series of research questions (at the end of the intro) that lead the reader through the results. Key research questions have been streamlined and related to achieve one overall goal. The research questions are now posed earlier within the “Purpose of the study” subsection at the end of the Introduction (Line 187-214).Line 568: the issues of selection bias in this paper are huge and since those who do srep are not representative in any way, i am just convinced that the national stats are the right comparison group. I think they could be utilized in the paper, but i don’t think they should be the featured story since the hb alumnae are not even close to representative . The authors recognize the selection bias and have tried to be transparent about the issues in the Limitations section (Lines 733-748). We have also now included comparisons to HB Non-SREP students in all cases where there was data available  to do so.One better comparison group would be hb students who did not do srep. I don’t see why (line 582) this group could not have been made available. That does not make sense to me, given that the study is already using alumni records.  We have included comparisons to HB Non-SREP students in all cases where there was data available including demographics (Table 2), college majors awarded (Table 4)., advanced degrees , and occupations  and have explained why data is not available for other comparisons (Line 297-300).The paper has a really cool set of data and i like it in many ways, but it is fundamentally flawed. Research looking at this question about the impact of program participation on stem trajectories would use propensity score matching to match each srep student with controls, conduct multivariate stats, and then that would isolate the effect of srep on their trajectory and you could really say that it helped and by how much it helped.In the absence of that, it seems like making multiple comparisons is probably best. Comparing local stats for the community/city in which hb is located, comparing by race/ethnicity nationally, comparing to national averages, etc. The authors fully agree and would have preferred to use propensity score matching; however, as the data necessary for this type of statistical analysis is not available and cannot be collected retrospectively, the use of proportion test was the best fit (Line 392-394).We appreciate your recommendation on alternative options given the circumstance. While we have kept the comparisons to national averages, we have used HB demographics to identify that our SREP group has a higher representation of Whites and Asians  and are therefore now including comparisons to national averages for White women and Asian women for as many analyses as possible . Community/city averages were not available. Comparing to national statistics only is not very meaningful, given that it appears this group is quite a bit more affluent and advantaged than the average american woman. One possibility is to look at all the stats by race, so find national stats for white woman and asian women and compare to them. However, since those stats for the hb alumni were not reported, i cannot provide definitive advice here on how to move forward. The current approach is problematic. All HB demographics that were available were pulled to identify representation in HB and within the HB SREP (Table 2). As there is a higher representation of Whites and Asians compared to the national population, we have included comparisons to national averages for White women and Asian women for as many analyses as possible (Line 328-330). The tables and figures are missing captions and notes. The reader needs to know the n of the groups and the source of the data in all of them. I also think basic tables are missing, such as descriptive stats on the hb alumni group . Apologies for the missing captions and notes. Notes for tables and captions for figures were included within the document and figures were separate as instructed for submission. However, additional notes and sample size values have been added where they were missing previously. Table 2 was also added which includes the race/ethnicity demographics of the HB SREP and Non-SREP populations compared to the national population. Table 3 was added to summarize where all national stats originate and where they are used.AttachmentResponse to Reviewers.docxSubmitted filename: Click here for additional data file. 5 Oct 2021A multi-year science research or engineering experience in high school gives women confidence to continue in the STEM pipeline or seek advancement in other fields: A 20-year longitudinal studyPONE-D-20-34867R1Dear Dr. Miller,We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. 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