The final ablation zone created with irreversible electroporation (IRE) depends on the size, shape and strength of the electric field that is influenced by several parameters. A profound understanding of the effect of IRE parameter alterations on the electric field are a prerequisite for a safe and effective treatment. Here, we demonstrate a semolina in castor oil model that enables visualization of the static electric field developed by a high-voltage generator between two needle-electrodes. We intuitively visualize the variation in electric field line pattern for selected IRE parameters; active needle length, inter-needle distance, applied voltage and presence of a nearby metal stent, by cameras in three dimensions. The observations were compared to and supported by two-dimensional numerical simulations of the electric field. Our semolina model visualizes the disturbance of the electric field by a metal stent, potentially leading to an incomplete tumour ablation between the needles. The reduction in electric field strength and the area at risk for incomplete tumour ablation are confirmed by the numerical simulations. The semolina model provides insight in the fundamental physics of the electric field, the effect of alterations in IRE parameter combinations and presence of a metal stent within the ablation zone. IRE uses a high-voltage external electric field and electric pulses of microsecond duration to change the transmembrane potential of tumour cells, resulting in permanent permeabilization of the cell membrane6. Membrane permeabilization disturbs the cell’s mechanisms to maintain homeostasis, finally leading to cell death via a necrotic pathway presumably or apoptosis9. Tumour cells are ablated while the extracellular matrix, collagen and elastic fibres, such as blood vessels and bile ducts remain intact10.Irreversible electroporation (IRE) is theoretically a non-thermal ablation technique, which makes it especially suitable for ablation of tumours near vital structures, such as locally advanced pancreatic tumours12. It is currently unknown whether IRE can be safely and effectively applied in patients with a metal stent in situ close to the ablation site. Detrimental effects of a metal object on IRE outcomes have been suggested in literature. In a case report, severe complications have been described after IRE treatment in the proximity of a metal stent, potentially caused by unintended thermal effects13. A retrospective clinical study demonstrated that IRE near small metal surgical clips (< 1 cm to tumour margin or needle electrodes) resulted in distortion of the electric field and inadequate coverage of the tumour, a less effective cell death and reduced treatment efficacy14. The presence of a metal clip was also significantly related to local tumour progression. In vivo experiments in swine and pig liver showed a redistributed and unpredictable ablation zone and thermal damage due to the proximity of a metal clip or stent16. Contradictory results with regard to temperature effects, electric field disturbance, and safe performance of IRE without complications in proximity of metal implants or stent were shown in ex vivo, in vivo and simulation studies20. The oncologic outcome of IRE is potentially influenced by a metal stent. But when and to what extent a metal stent affects the electric field distribution and associated thermal effects, both in terms of efficacy and safety, remains unclear20. Thermal effects without the presence of a metal stent have been observed in clinical practice as well, especially directly around the needle-electrodes23. An inhomogeneous electric field distribution and corresponding locally high current density gives rise to these thermal effects23. Thermal effects are difficult to predict, with potential consequences for local control of IRE procedures and damage to adjacent critical structures.Biliary drainage is frequently required in patients with pancreatic tumours. The use of a metal stent is usually preferred because of fewer stent-related complications (e.g. cholangitis) and less stent dislocations compared to plastic stents27. Visual insight in the electric field line pattern may offer a more profound understanding of the influence of IRE parameter settings, locations of potential thermal effects, and presence of a nearby metal stent on the ablation zone. This could enable the determination of parameter settings to provide a precise and controlled tissue ablation. The aim of this study was to visualize the variation in electric field line pattern for selected IRE ablation parameters and the presence of a metal stent in proximity of the needles.The size and shape of the ablation zone depends on several IRE parameters, such as the pulse timing, applied voltage, electrode configuration and active needle length as well as tissue propertiesTo evaluate the electric field line pattern, we designed a semolina in castor oil model consisting of a fixed experimental setup, containing a high-voltage generator and two needle-electrodes placed in a transparent tube filled with castor oil and semolina Fig. . Semolin30. In order to determine how our semolina in castor oil model relates to these computer simulations, two-dimensional numerical models were used to predict the electric field distribution, field line pattern and electric field strength in V/cm in the centre between the needles and compared to the fundamental results provided by the semolina model. These results were supported by two-dimensional numerical simulations.A common method for analysis of the electric field distribution are computer simulationsThe semolina model provides fundamental insight in the electric field by a novel and intuitive visualization of electric field lines in an IRE simulation setting. The results provided by this semolina model could be used to validate and calibrate numerical simulations, which are frequently used in clinic for IRE simulation. With exception of pulse application and specific tissue properties, the effect of specific IRE parameters settings can be investigated in the semolina in castor oil model. Therefore, the model forms a comparison with IRE.The semolina model requires relatively high voltages (up to 9.0 kV) in comparison to clinical IRE and does not provide the ability for pulse delivery since a constant static electric field is essential in visualization of electric field lines. During all experiments, the high-voltage generator measured a current of 0.00 mA, corresponding to a current at least smaller than 5 µA, which compared to a static electric field.The electric field line pattern was clearly visualized in the reference experiment by alignment of semolina according to the direction of the electric field Fig. . ParalleThe area in which electric field lines were observed increased with a larger active needle length Fig. . Two pheThe electric field line pattern after alteration of the inter-needle distance to 1.5 cm is visualized in Fig. The applied voltages of 5.4 kV, 6.4 kV and 7.4 kV in combination with an inter-needle distance of 2.5 cm corresponded to an electric field strength of 2.2 kV/cm, 2.6 kV/cm and 3.0 kV/cm respectively. Figure The presence of a metal stent in between the needles, with a distance between the needles and stent shorter than the inter-needle distance, caused a redistribution of the electric field towards the stent Fig. . RedistrTwo-dimensional numerical simulations were performed to predict the electric field distribution and electric field line patterns for an inter-needle distance of 2.5 cm in presence and in absence of a metal stent Fig. . Castor The effect of selected IRE parameters and presence of a metal stent on the electric field line pattern were successfully visualized by the semolina model in three dimensions, supported by two-dimensional numerical simulations of the electric field distribution and field line pattern. The distribution of electric field lines around and between the needles as well as the density of electric field lines were clearly influenced by alteration of the inter-needle distance, active needle length and applied voltage. Electric field lines were not visualized in a trapezoidal shaped area adjacent to the metal stent due to disturbance of the electric field. Numerical simulations demonstrated a substantial reduction in electric field strength in the trapezoidal shaped area, in this specific needle-stent configuration a factor of two reduction. Building upon this information, areas of potential incomplete IRE ablation near a metal stent and locations where thermal effects may occur could be determined.31. While the required electric field strength was achieved in absence of a stent. The trapezoidal shaped area, outlined by a redistribution of the aggregated semolina between the needles and stent, confirms the occurrence of such areas. This fits with the observation of vital liver tissue directly adjacent to the stent observed after IRE in in vivo porcine liver19. Prior animal studies and experimental research revealed that proximity of a metal stent resulted in an unpredictable asymmetrical ablation zone and potential ineffective tumour ablation, theoretically explained by attraction of the electric field20. How and to what extent the electric field is disturbed by a metal stent was not clear. This hampered the ability to predict the deformation of the ablation zone and to effectively adjust for this during IRE treatment in presence of a metal stent. Our semolina model provides insight in the occurrence of electric field disturbances. The aggregation of semolina according to the electric field can be used to visualize the areas of (in)effective ablation and identify possible locations where undesired thermal effects may occur in the presence of a metal stent. Our study visualized the redistribution of the electric field towards the metal due to its lower electrical resistance in comparison to castor oil or tissue. Redistribution led to a locally high density of electric field lines between the needles and stent and corresponded to the areas of highest electric field strength along the path between the needles and stent as observed by numerical simulations. These observations could explain the increase in current in presence of a metal stent as observed in previous studies and occurrence of thermal effects directly around the needles and along the path between the needles and stent19. It is important to realize that the distance between the metal stent and ablation zone or IRE electrodes in combination with the size of the metal object determines whether the electric field is significantly disturbed17. Clinicians should be aware of the reduction in electric field strength as a consequence of a metal stent near the IRE electrodes. An increase in pulse number could potentially at least partially counteract the occurrence of an ineffective tumour ablation near a metal stent14. However, it is a delicate balance between an effective ablation and thermal effects or damage.A metal stent leads to a substantial reduction in electric field strength in the area halfway between the needles and gives rise to areas with potentially insufficient electric field strength to induce irreversible electroporation. Numerical simulations of the 3.0 kV potential difference confirmed that the electric field strength was below the IRE threshold of 680 V/cm for an effective tumour ablation in the centre between the needles in the presence of a metal stent34. Severe complications during IRE of a pancreas tumour were presumed to be related to heating of the metal stent in a case report13. Mean maximum temperatures of 65.3 °C and incomplete ablation were observed for IRE in the presence of a metal clip or stent within the ablation zone in porcine liver versus 47.3 °C for absence of metal (p = 0.007)16. Multiple studies that performed temperature measurements during IRE without proximity of a metal stent near the needle-electrodes, showed divergent results, varying from a maximum temperature rise of 1.15 °C and successful ablations without thermal damage to measured peak temperatures of 79 °C with certain thermal damage34. The occurrence of thermal effects and thermal damage depend on the IRE protocol and heat transfer to surrounding tissue during ablation34. Based on the observed semolina aggregation and numerical simulations in absence of a metal stent, the area most at risk of thermal effects and damage is the area directly adjacent to the needles. All electric field lines leave and enter the needle in that small area. Our finding of a locally high density of electric field lines near the needles corresponds to a high current density and coincides well with experimental observations of temperature increase near the needles35. Potential thermal effects near the needles and incomplete tumour ablation in presence of a metal stent should be predicted and considered during IRE treatment planning to ensure an effective and safe IRE procedure.The occurrence of thermal injury during a regular IRE treatment and the impact of a metal stent on the local temperature distribution and thermal injury remains controversial35. A relatively low electric field strength halfway between the needles makes it harder to reach the required IRE threshold of 680 V/cm and potentially limiting an adequate tumour ablation in this area31. The observed interruption in electric field strength in Fig. 35. The electric field strength should be > 1665 V/cm to visualize an uninterrupted electric field line pattern  in combination with semolina experiments and numerical simulations are desirable to obtain a more profound insight in clinical IRE and personalized treatment.In conclusion, we demonstrated a semolina in castor oil model to intuitively visualize the electric field line pattern, allowing insight into the effect of combinations of selected clinical IRE ablation parameters. The results provided by the semolina model were supported by two-dimensional numerical simulations. A disturbance and redistribution of the electric field was shown in combination with a substantial reduction in electric field strength in both the semolina model as well as by numerical simulations when a metal stent was placed near the needle-electrodes. Caution should be taken when performing IRE in vicinity of a metal stent, which could give rise to unpredictable heating and incomplete tumour ablation.39. A visualization of the experimental setup is presented in Fig. The electric field line pattern was visualized in a static electric field by semolina (dipole) in castor oil  (electric insulator)The effect of variation in inter-needle distance, active needle length and applied voltage (kV) on the electric field line pattern were assessed Fig. . As refeElectric field lines were visualized by aggregation of semolina where the electric field strength in combination with the force exerted by the viscous castor oil exceeded the gravitational force on semolina. Three camera body —lens combinations (Pentax 12 mm f/1.4 c-mount H1214-M) were used to visualize the development of electric field lines in the frontal, longitudinal and transverse plane of the needles  with two stainless steel needles  and a nitinol metal stent  inside was built to perform numerical simulations in castor oil Fig. . COMSOL Numerical simulations were used to predict the electric field distribution (V/cm) and electric field line pattern for an inter-needle distance of 2.5 cm and applied voltage of 3.0 kV and 9.0 kV in presence as well as in absence of a nitinol metal stent. The electric field strength was also evaluated halfway between the needles in point  for applied potential differences of 3.0, 5.4, 6.4, 7.4 and 9.0 kV in absence of a metal stent and for both 3.0 kV and 9.0 kV in presence of a metal stent. Table The raw images were cropped uniformly to the same area in the centre of the image, the image ratio was unchanged. The obtained semolina pattern images were visually analyzed and characterized descriptively. Results provided by the two-dimensional numerical models were compared qualitatively to the results provided by the semolina in castor oil model.


In the present systematic review, we argue that maternal experiences of interpersonal discrimination at least partially account for the disproportionate rates of adverse birth outcomes in minority populations. Since the 1990s, research in this area has slowly, but steadily increased, shedding more light on the insidious nature of interpersonal discrimination and its toxic health effects. With the aim of bringing this topic to the fore in academic as well as clinical settings, this paper provides a state-of-the-art review of the empirical knowledge on the relationship between maternal experiences of discrimination and birth outcomes. Of 5901 articles retained in the literature search, 28 met the predefined inclusion criteria. Accounting for a range of health and behavioral factors, the vast majority of these studies support the notion that maternal experiences of interpersonal discrimination predict a range of adverse birth outcomes, including preterm birth, low birth weight, and various physiological markers of stress  in both mother and child pre- and postpartum. Several moderators and mediators of this relationship were also identified. These related primarily to the type (first-hand and vicarious), timing , frequency, and pervasiveness of discrimination experienced, as well as to maternal mental health and coping. More research into these factors, however, is required to definitively determine their significance. We discuss these findings as they relate to the general health repercussions of interpersonal discrimination, as well as in terms of applied prenatal care and interventions. Ultimately, we argue that assessing maternal experiences of interpersonal discrimination in prenatal care may represent a considerable asset for mitigating existing majority-minority disparities in adverse birth outcomes. Adverse birth outcomes represent a significant public health issue. In developed countries, over 10% 1.25 million) of all births are preterm 5 million,4,5,6,7,By way of explanation, the literature points to the increased burden of everyday psychosocial stress borne by minority populations. Past research particularly emphasizes the stress associated with the persistent interpersonal discrimination that minorities are uniquely subjected to on a regular basis throughout their lives . This evWithin this context, two separate lines of research have extensively documented the positive associations between both discrimination and AL and between AL and adverse pregnancy and birth outcomes. For example, in a comprehensive meta-analysis, Pascoe and Richman  extracteIntegrating this evidence, emerging scientific studies have directly examined the extent to which maternal experiences of interpersonal discrimination predict adverse birth outcomes in minority populations ,24,25,26N = 12) than Giurgescu et al. (N = 10), and three more than Alhusen et al. (N = 9). For the present review, however, we have retained a total of 28 empirical studies on the topic of interest. Given the apparent growth in research in this area in the past four years, previous reviews currently appear to be considerably outdated.We identified three systematic reviews of the evidence on the link between maternal experiences of interpersonal discrimination and adverse birth outcomes. In 2011 Giurgescu et al.  appraiseTo facilitate, through our review of the evidence, a greater understanding and awareness of the extent to which discrimination “gets under the skin” of minority women and their offspring, eroding their physical health and wellbeing.To push this topic to the fore not only in research endeavors, but also importantly in applied health care settings. Specifically, we argue that maternal experiences of discrimination may be operationalized as a risk factor in prenatal and postpartum care and underscores the need for care approaches designed to mitigate the health repercussions associated with discrimination.In light of the confines of previous assessments of the evidence, we argue that the knowledge in this area can be significantly expanded by updating past review efforts and critically integrating new and emerging empirical findings. In particular, we will identify any relevant themes and variations in the evidence base that might have been unclear in past reviews, or that have emerged in subsequent research. In order to build a more complete, empirical model of the relationship between maternal experiences of interpersonal discrimination and adverse birth outcomes, we also aim to determine any potential pathways that might explain this relationship and highlight any gaps in knowledge that require further study. Additionally, in contrast to past efforts, we will explicitly evaluate the quality of the evidence base, using validated research quality assessment tools. Ultimately, with the present review, we hope to make two key scientific contributions:www.prisma-guidelines.org.This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines see . Full prWe searched a diverse range of scientific journals for literature on the association between maternal experiences of interpersonal discrimination and pregnancy outcomes in minority populations. Specifically, we executed an extensive and rigorous search of the following databases: Academic Search Premier; AMED; Global Health; SocINDEX with Full Text; CINAHL Plus with Full Text; E-Journals; MEDLINE; Psychology and Behavioral Sciences Collection; SCOPUS; Science Direct, Women’s Studies International. We also searched Web of Knowledge and Google Scholar for any references that might have been missed in the database search. Finally, we manually combed through reference lists of relevant papers and reviews for any additional articles that were not picked up in the previous two search strategies.The predefined Boolean/phrase search terms that we employed related directly to the variables of interest: Interpersonal discrimination and pregnancy outcomes. We defined interpersonal discrimination broadly as any form of discriminating interpersonal behavior. As such, this term covered any explicit, implicit, and covert  person-to-person discriminatory behavior towards individuals from any minority group, including those defined by race, ethnicity, gender, sexuality, religion, nationality, and physical disability. We chose not to include studies on systemic discrimination as this type of discrimination impacts on people via pathways and processes  that differ considerably from interpersonal discrimination. In terms of pregnancy outcomes, we focused on pregnancy and birth complications, including gestational age at delivery, PTB, birth weight, birth initiation (spontaneous vs. induced), and stillbirth. Other outcomes of interest included postpartum child development and health.The paper reported empirical studies on the relationship between the maternal experience of interpersonal discrimination and pregnancy- and/or birth-related outcomes.The paper reported quantitative results.The paper was in English.The full text was available.The paper had undergone scientific peer review.The exact literature search syntax was as follows: “Discrimination” and/or “prejudice” and/or “stereotype” and/or “bias” and/or “stigma” and/or “racism” and/or “sexism” and/or “ageism” AND “birth” and/or “birth outcomes” and/or “delivery outcomes” and/or “vaginal birth” and/or “labor induction” and/or “preterm birth” and/or “gestation” and/or “birth weight” and/or “stillbirth” and/or “birth complications” and/or “pregnancy complications”. Search limiters were specified to exclude non-peer-reviewed studies, newspaper articles, and non-English language text. We did not limit search results by publication date. Once the search had been executed, articles were scrutinized and retained based on the following inclusion criteria:Each database hit was evaluated by the authors in three rounds against the inclusion criteria. First, papers that clearly did not relate to the topic of interest were rejected . Second, abstracts of papers retained in the first round were reviewed. Any articles that failed to meet the inclusion criteria were discarded. Finally, the search results that remained after the first two rounds of evaluation were downloaded and examined in full-text detail for relevance see . Only paIn the final round of results evaluation, we systematically appraised the methodological quality of the retained papers. To this end, we used the Quality Assessment Tool for Quantitative Studies (QATQS) . The QATn = 80); the paper reported on mental health issues  rather than physical pregnancy- or birth-related health complications for mother or baby (n = 13); the paper did not cite empirical research  (n = 6); the paper reported exclusively on qualitative results (n = 14); the paper provided insufficient statistical or methodological detail for assessment (n = 5); or a combination of some or all of these issues. Ultimately, a total of 28 papers were retained for the review. In the following sections, we will present the main findings from these studies.The database search turned up a total of 5901 hits . Of thesn = 1) and New Zealand (n = 2). In terms of study populations, all of the articles centered on racial/ethnic minorities in White-majority societies. Most focused purely on Black women in the US (n = 21); however, papers also reported on Turkish immigrants in Germany (n = 1), ethnic minorities in New Zealand (n = 2), or Latina, Asian, Dominican, and/or Puerto Rican women in the US (n = 4). The average sample size across studies was N = 1602 . Various research designs were employed in the retained papers, including prospective cohort (n = 10), cross-sectional (n = 7), case-control (n = 5), hybrid retrospective/prospective cohort (n = 2), retrospective cohort (n = 1), descriptive correlational (n = 1), and longitudinal designs (n = 2).Of the 28 papers included in the present review, a single study was published in the 1990s, nine studies were published in the 2000s, 17 articles were published in the 2010s, and one paper was published in 2020. As such, the evidence included in this review spans four decades, though all but two studies were published between 2000 and 2019. Further, 25 articles reported on US-based studies. The remaining three papers were from Germany (n = 2) [n = 1) [n = 23), including Krieger et al.’s [n = 13) [n = 5) [n = 3) [n = 2) [n = 1) [n = 13) [n = 7) [n = 7) [n = 5) [n = 4) [n = 14), birth weight (n = 14), gestational age at birth (n = 7), or a combination of these. PTB was defined as less than 37 weeks of gestation in all relevant studies. Studies also focused on maternal and child physiological outcomes, however, including hypertension, maternal and child cortisol secretion and stress reactivity, inflammation, and diastolic blood pressure (n = 4).The main predictor and outcome measures varied somewhat across studies see . In all n = 2) ,31 and/oet al.’s  Experien[n = 13) ,39,40,41[n = 13)  Everyday [n = 5) ,44,45,46 [n = 3) ,47,48, t [n = 2) ,49, and  [n = 1) . Six stu [n = 1) ,53,54,55[n = 13) ,52,54,55 [n = 7) ,39,40,41 [n = 7) ,38,44,53 [n = 5) ,44,48, w [n = 4) ,47,50,52The inter-rater research quality evaluations were conducted by the first author and a research assistant. Overall, independent assessments were well-aligned see  QATQS. Sn = 15), before moving on to studies that look at infant birth weight (n = 14). Finally, we review evidence on pregnancy-related physiological outcomes (n = 4). While we categorize results by the outcome definitions provided in each article, we consider it pertinent to acknowledge the potential interrelationships between these outcomes. For example, low birth weight is often comprised of potentially overlapping outcomes of preterm birth and/or fetal growth restriction . Thus, in spite of our categorical presentation of the evidence in terms of outcome, we implore the reader to consider these effects as potentially interconnected.In the following paragraphs, a brief description will be given of the main findings of each of the papers retained for this review see . Given tN = 11,582). The study sample included people from 11 US states and New York City. The authors focused on the extent to which participants had been upset by experiences of racism in the 12 months prior to giving birth. They also tested whether prenatal care moderated any such relationship. Taking into account a range of socioeconomic and health-related variables, results indicated that compared to mothers who did not report feeling upset by experienced racism, mothers who had been upset by such racism (n = 1645) had 29% higher odds of giving birth preterm . While this relationship appeared to vary by level of prenatal care, the interaction term was statistically non-significant.In a population-based cross-sectional study, using data from the 2004–2012 Pregnancy Risk Assessment Monitoring System, Bower et al.  assessedN = 173) to examine the association between preterm labor and direct and vicarious racial discrimination among Black women. The study specifically concerned frequency of racism experienced in childhood, adolescence, and/or adulthood. The authors found that for each one-unit increase in reported direct racial discrimination during adolescence  the odds of PTB increased by 48% . Likewise, each one-unit increase in reported vicarious racial discrimination  experienced in childhood was associated with a 45% increase in odds of preterm labor . There was no relationship between adult direct or vicarious racial discrimination and PTB.A similar cross-sectional study by Daniels et al.  drew datIn a prospective cohort study of 1962 pregnant women in Central North Carolina between 1996 and 2000, Dole et al.  investign = 152) and White (n = 200) pregnant women in Birmingham, AL, Oakland, CA, Chicago, IL, and Minneapolis, MN [n = 16) had experienced racial discrimination in at least three situations. By contrast, only 5% (n = 1) of White women who had given birth preterm had experienced any discrimination. Further analyses revealed that the odds for PTB among women who had experienced three or more instances of racial discrimination were 205% higher  than for women who had not experienced any such discrimination.Another prospective cohort study focused on the link between birth outcomes and frequency of lifetime experiences of racial discrimination. This research included a sample of 352 Black  or reported that people had acted afraid of them at least once a week (n = 50), had 30%  and 40%  higher odds of giving birth preterm, respectively, than those who did not report such treatment. For women with less than 12 years of education (n = 46), racial discrimination in housing, as a customer, and in terms of being feared by others, similarly increased the odds of PTB by 140% , 240% , and 100% , respectively.Another case-control study examined the link between PTB and different types of everyday racial discrimination . The sample included 422 Black mothers of preterm babies compared to 4544 Black mothers of full-term babies. Controlling for a wide range of health, demographic, and SES factors, Rosenberg et al.  found thN = 1410). For the purposes of the study, the sample was divided into quartiles designating extent and stressfulness of experienced discrimination . Women in the 2nd to 4th discrimination quartiles  had greater odds of PTB than women the first quartile. However, only differences between the 1st and 2nd quartiles were statistically significant, with women in the second quartile having 67% greater odds of PTB than women in the first quartile . The authors also discovered a non-linear moderating effect of depression where women with mild-to-moderate depressive symptoms (as opposed to severe symptoms) in the second discrimination quartile had a predictive probability of PTB twice as high as their first-quartile counterparts. In other words, racial discrimination predicted PTB only in women with lower-grade depression as opposed to severe depression.In a similar retrospective cohort study on the impact of racial microaggressions on birth outcomes, Slaughter-Acey et al.  found thSlaughter-Acey et al.’s results resonate with those of Misra et al. . They inn = 2308) and Turkish immigrant women in Germany (n = 217). Results indicated that Turkish women who had experienced ethnic discrimination in the 12 months prior to giving birth had 319% increased odds of giving birth preterm than women who had not experienced discrimination  = 8.18, p < 0.01, OR = 4.19). Similarly, in a longitudinal cohort study from New Zealand, Thayer et al. [β = −1.06 week, 95% CI, −1.8 week, −0.3 week) or unfair treatment in the workplace , the criminal justice system , or in banking .Finally, two studies from outside the US provide further support for the link between maternal experience of discrimination and PTB. Scholaske et al.  conducteny n = 21. Resultsn = 32), those who experienced medium levels of discrimination exhibited higher cortisol levels (a known risk factor for PTB) during pregnancy than those who experienced low levels of discrimination . Overall, however, greater cortisol levels predicted earlier birth only for mothers who reported low levels of discrimination. Further, results also indicated a protective effect of discrimination on leukocyte glucocorticoid sensitivity (another risk factor for PTB).In addition to the 11 articles described above that all indicate a negative impact of maternal experiences of interpersonal discrimination on PTB and/or gestational age at birth, another four studies report null effects. Specifically, Gillespie and Anderson  conducteβ = 0.52, p < 0.01), but not PTB (p > 0.05). Similar to the study by Gillespie and Anderson, however, these results were based on an exceedingly small sample (N = 72) who reported generally low levels of discrimination.Comparable results were generated in a study by Giurgescu et al.  on the lN = 9470) and Mendez et al. [In another two studies that collected data from much larger samples, Grobman et al.   vs. Black mothers of normal-weight children, (n = 208). The authors found that the experience of lifetime discrimination in at least one of five life domains  (n = 58) increased the odds of giving birth to VLBW children by 90% . Being the target of discrimination in at least two domains, increased the odds to 110% , and having these experiences in three or more life domains, increased the odds further to 220% . This pattern suggests a dose-response relationship between pervasiveness of lifetime racial discrimination and risk of infant VLBW.In Collins et al.’s second study , the samn = 104 vs. mothers of normal-weight infants ≥2500 g n = 208) in Chicago, IL, the authors found that experiencing racial discrimination in one or more life domains increased the odds of VLBW by 90% . For women who had experienced racial discrimination in three or more life domains, odds of VLBW increased by 170% .Complementing the findings of Collins et al., Lespinasse et al.  also looβ = −0.25, 95% CI, −0.45 to −0.04), at six months of age , and at three years of age . The offspring of mothers who reported racial discrimination in 1–2 life domains were (though non-significantly) in between the two other cohorts (discrimination in 0 vs. >3 life domains) in terms of weight, suggesting a dose-response relationship.Dixon et al.  conducten = 407) and White (n = 222) mothers in Saginaw County, MI, Carty et al. [Next, in a cross-sectional study of Black  in Los Angeles, CA. Accounting for a wide range of SES, demographic, and health factors, the authors found that for each one-unit increase in overall maternal experience of lifetime racial discrimination infant birth weight decreased by 39.59 g. Breaking this association down, the authors found that racial discrimination experienced vicariously in childhood was the main driver of this effect. Indeed, for each one-unit increase in maternal vicarious childhood experiences of discrimination, infant birth weight decreased by 167.85 g , suggesting a dose-response relationship.Further, while the studies by Collins et al., Lespinasse et al., and Dixon et al. examined frequency and/or pervasiveness of racial discrimination in various life domains, Dominguez et al.  focused β = −0.27, p < 0.10), while direct racial discrimination experienced in adulthood accounted for a significant amount of variance in birth weight . Further, maternal vicarious and direct childhood experiences of racial discrimination interacted with change in prenatal diastolic blood pressure (DBP) to impact negatively on birth weight . Specifically, for women who had vicariously experienced racial discrimination in approximately two childhood domains, infant birth weight decreased by 19.98 g for every 1 mmHg increase in maternal DBP . This association was not evident in women who had experienced no such discrimination.Similar to Carty et al. and Dominguez et al., Hilmert et al.  also invn = 257), each one-unit increase in overall racism was associated with 45% greater odds of low infant birth weight . Disentangling this effect, the authors found that the odds for low infant birth weight increased 184% for each one-unit increase in vicariously experienced racism in women over 25 years old . A similar, but non-significant trend in direction was evident for the link between infant birth weight and direct racism in women over 25 years old. These associations did not emerge in the results for women under 25 years old.Extending the line of research into the impact of direct and vicarious maternal discrimination, Slaughter-Acey et al.  conducten = 158) and Latina (n = 262) women in New York City, NY. Consistent with the previously cited research, results indicated an inverse association between frequency of maternal everyday discrimination and infant birth weight . Interestingly, the authors also found that this association was mediated by increased depressive symptoms during pregnancy . In raw numbers, this translates into an infant birth weight decrease of 49 g for every one-point increase in maternal everyday discrimination. While maternal prenatal stress also correlated with maternal experiences of discrimination , this variable did not predict or mediate birth outcome.Next, Earnshaw et al.  conducteIn a similar prospective cohort study that also took into account antenatal depression, Mustillo et al.  looked aβ = −243 g, 95% CI, −425 g, −60.2 g; . Somewhat counter-intuitively, Asian women who had experienced discrimination in housing (vs. Asian women who had not experienced such discrimination) were more likely to have children of higher birth weight .The only article that reported on maternal discrimination and infant birth weight and was conducted outside of the US, was the aforementioned longitudinal cohort study by Thayer et al. . Complemt = 2.39, p = 0.02), though given the exceedingly small cell size (only n = 10 women reported religious discrimination), this outcome may at best be suggestive rather than actually statistically meaningful. Similarly, while Grobman et al. [Finally, of the articles that included infant birth weight as an outcome variable, three reported only marginal or no effect of experienced discrimination. Specifically, in a prospective cohort study of 108 Black women in Northern CA, Daiely  found non et al.  found thn et al.  failed tn = 38, White n = 18) in Ohio, US, and measured lifetime pervasiveness of experienced maternal discrimination. Results showed that Black women exhibited substantially higher levels of IgG antibody titers than White women during each trimester and postpartum. Further, women who reported high discrimination showed higher EBV VCA IgG antibody titers than women who reported low discrimination in the first (p = 0.03) and second trimesters (p = 0.04) as well as postpartum (p = 0.06). The authors note that the small cell sizes represent a limitation, however, and the results should be interpreted cautiously.While other articles retained for this review tested physiological variables as mediators of the relationship between maternal experience of discrimination and birth outcomes , two studies focused explicitly on pregnancy- and/or birth-related physiological outcome variables. Christian et al.  examinedn = 22) exhibited higher levels of evening cortisol levels (m = 1.25 ng/mL) than women who had experienced low levels of discrimination  or none at all . Further, the infants of women who had experienced discrimination (n = 19) vs. those of women who had not experienced discrimination (n = 41), exhibited greater cortisol responses to vaccination .In a similar study, Thayer et al.  assessedTo sum up our review of the evidence, we have created a preliminary process model for the relationship between interpersonal discrimination and adverse birth outcomes . While tThe results reported in the reviewed papers overwhelmingly support the conclusion that maternal experiences of interpersonal discrimination are positively associated with increased risk of adverse pregnancy outcomes. Controlling for an extensive range of covariates, 24 out of 28 articles presented empirical evidence that indicate strong links between interpersonal discrimination and infant birth weight, PTB, gestational age at birth, and both maternal and infant physiological stress reactivity. Of the remaining four studies, three reported inverse, albeit statistically non-significant connections between the variables of interest ,38,52, aWhile the overall association between maternal experiences of discrimination and adverse birth outcomes is rather clear, there are nonetheless a number of notable themes and variations that emerge from the reviewed studies. These include principally the type of discrimination , and the recurring moderating or mediating roles of stress and depression.n = 16) measured lifetime experiences of discrimination, while others focused on past-year discrimination (n = 10) or everyday discrimination (n = 3). These different conceptualizations of discrimination fluctuated markedly in predictive reliability. Specifically, of the 16 studies that included measures of lifetime discrimination, all but two [In virtually all of the studies, the frequency and/or pervasiveness of interpersonal discrimination in individuals’ lives comprised the main gauge of discrimination. However, across studies, the time spans tapped for discriminatory experiences varied. Most studies . This resonates well with the findings noted above that it is lifetime exposure to discrimination, as opposed to more recent shorter-term exposures, which appear to impact on birth outcomes. These conclusions also dovetail nicely with the broader literature on the weathering effect of discrimination. Here, it is, namely, the cumulative build-up of discrimination-related stress and allostatic load that over time wears and tears on the body, slowly causing it to break down [The remaining eight studies that included measures of depression and/or stress found no significant explanatory power associated with any of these variables ,43,52,55eak down ,62.N = 12) as the present review (N = 28). Further, all of the studies published since these previous reviews were conducted have been of moderate or high quality  associated with discrimination-related stress. In conjunction with past evidence on these types of physical outcomes , this research thus helps solidify more objective insight into the harmful biological consequences of being subjected to interpersonal discriminatory behavior.There are also a few limitations to the evidence base that need to be noted. First and foremost, with the exception of two studies from New Zealand and one from Germany, all of the research retained for this review is from the US. Further, the vast majority of these articles focus on discrimination against Black Americans, with only a handful including other ethnicities as well. Based on the current evidence then, conclusions about the present subject matter extends nearly exclusively to Black women in the US. In other words, given the unique history of subjugation and discrimination against Black Americans, the evidence base may not generalize in the exact same way to other minority populations. Of additional relevance in this context is the fact that the for-profit model of the US health care system poses significant challenges in terms of equal access compared to other, government-funded models such as those implemented in Germany and New Zealand. Further, determining whether other bases for discrimination—be it gender, age, mental health, disability, sexuality, etc.—have comparable effects on birth outcomes is somewhat tricky, and ultimately requires further research.Another shortcoming relates to the measure of discriminatory experiences employed in the reviewed studies. While we listed the multidimensional operationalization of discrimination as a strength above, this is mostly by comparison to existing research. That is, beyond the effects of frequency and pervasiveness, other elements of discrimination appeared largely untapped in the research or lacked in detail. For example, more knowledge is required on the extent to which vicarious experiences of discrimination are moderated by social proximity of the target. That is, are the harmful effects of vicarious experiences of discrimination dependent on the extent to which the perceiver is personally connected to the target ? This may be a pertinent avenue for future research—particularly given the increasing number of cases of racial and gender-based discrimination that make it into the public eye in the US, the EU, and elsewhere.n = 13). While this scale has high validity and reliability scores [Further, the most common discrimination measure across studies was the Krieger Everyday Discrimination Scale  of the effectiveness of prenatal care approaches in the US that take a more patient-centered approach than most hospital protocols. These programs are based on providing extensive social, emotional, and instrumental support during pregnancy as a protective buffer against psychosocial stressors such as discrimination. Some of these have produced impressive preliminary results. Of particular note, a comprehensive evaluation of the outcomes . The res disease .Discrimination is an omnipresent, persistent, and insidious societal issue. This review contributes to the growing body of literature on the link between discrimination and health. Specifically, it emphasizes the fact that maternal experiences of interpersonal discrimination have grave physical implications that may extend beyond women’s individual health to negatively affect their pregnancy and offspring. As illustrated in


Obstructive Sleep Apnea (OSA) is a highly prevalent condition that is associated with several comorbidities including cardiovascular disease (CVD). Recent studies have revealed mixed results as to whether standard OSA therapy reverses CVD in adult patients. Thus, many advocate for earlier recognition of OSA induced CVD, as early as childhood, to prompt treatment antecedent to the onset of irreversible CVD. Here we investigated if the serum level of miR-92a, a known biomarker for CVD, can be used to identify patients with OSA in both children and adults.Consecutive snoring patients undergoing polysomnography were recruited for determination of circulating miR-92a, in addition to inflammatory and metabolic profiles. We assessed whether circulating miR-92a was associated with OSA severity.Using two separate cohorts of adults (n=57) and children (n=13), we report a significant increase in the serum level of miR-92a in patients with severe OSA (p=0.021) and further demonstrate a significant correlation  with serum miR-92a levels and the apnea hypopnea index (AHI), a primary measure of OSA severity. Stepwise regression analysis revealed that serum miR-92a levels were independently associated with AHI , age  and LDL cholesterol levels .Our study is the first to establish that miR-92a is a useful biomarker for OSA severity in both children and adults. Given the canonical role of miR-92a on endothelial dysfunction, miR-92a may be useful to identify early onset CVD in OSA patients or stratify patient CVD risk to identify those that may benefit from earlier OSA treatment. Obstructive Sleep Apnea (OSA) is highly prevalent in both children and adults and defined by recurrent episodes of soft tissue impingement into the oral pharynx leading to an intermittent cessation of normal ventilation during sleep. As a consequence, patients with OSA experience episodic oxyhemoglobin desaturation, hypercapnia, frequent arousals during sleep, and subsequent sleep fragmentation. Epidemiological studies suggest that at least 10% of adults and 2–3% of the children have OSA with clinical consequences –7. MoreoWhile some have suggested that adult and pediatric OSA are different diseases, the impact of obesity on the phenotype of pediatric OSA has made these two conditions more similar than different . FurtherOf note, OSA is associated with cardiovascular disease (CVD) in both children and adults. Longitudinal studies of adult patients with severe OSA have shown a three-fold increase in the risk of all-cause mortality, and a higher cardiovascular mortality at 18-year follow-up, respectively ,17. OSA In children, recent studies have shown that OSA is also associated with CVD . Recent The vascular endothelium, which lines the luminal arterial wall, is an important tissue type that governs vascular health or diseases such as atherosclerosis ,34. As tThe study of extracellular microRNA (miRs) have gained considerable traction for the identification of ED. Extracellular miRs are 21–23 nucleotide non-coding nucleic acids found in serum, plasma or other body fluids –38. In sOur laboratory has shown an increased expression of miR-92a within serum samples isolated from patients with coronary artery disease or chronic kidney disease ,41. We hGiven the association of OSA with both CVD and dyslipidemia –47, we tResearch was approved by the institutional ethics committee of Xi’an Number One hospital (IRB# xadyyy2018028). Adult patients were recruited and written consent was obtained prior to enrollment. Patients diagnosed with OSA met the published guidelines for the diagnosis and treatment of obstructive sleep apnea syndrome . PatientStudy procedures were approved by the Institutional Review Board at University of California, San Diego (IRB# 170408). From February 2017-August 2019, consecutive children were approached for recruitment for participation in this study. Children with craniofacial syndromes, Down syndrome or other defined genetic abnormalities, neuromuscular or other congenital disorders or other systemic diseases were excluded. Children with identified central sleep apnea  were also excluded from this study. Finally, children with hypertension, uncontrolled diabetes, or history of smoking including vaping  were excluded.Caenorhabditis elegans miR-39 (cel-miR-39) was added to the serum prior to the addition of three volumes of Trizol LS reagent. Following isolation, miRs were reverse transcribed with TaqMan™ MicroRNA Reverse Transcription Kit (Applied Biosystems. Cat# 4366597) according to the manufacturer’s instructions. Following traverse transcription, the levels of miR-92a were determined via qPCR using the Applied Biosystems™, TaqMan™ Universal Master Mix II, no UNG (Cat# 4440040). Expression levels were determined using the Δ−Δct method using cel-miR-39 spike in as a reference. Fold change values were then determined by dividing the expression level with the average of the expression level of the primary snoring for each site.miR isolation was performed using Trizol LS reagent according to the manufacturer’s instructions. 500 uL of patient serum was used for the isolation and analysis of miR levels and 2 nM reference 2) was assessed by pulse oximetry, with simultaneous recording of the pulse waveform. The bilateral electrooculogram, 8 channels of electroencephalogram , chin and anterior tibial electromyograms, and analog output from a body position sensor were also monitored. PSG was scored by board registered technologists (RPSGT) and interpreted by board certified sleep physicians according to the 2017 American Academy of Sleep Medicine Manual for the Scoring of Sleep and Related Events [Sleep studies were performed in adults were performed at Xi’an Number One hospital using the somnolab 2 system and in children at Rady Children’s Hospital using Nihon Koden  PSG equipment and software. The following parameters were measured: chest and abdominal wall movement by inductance plethysmography, heart rate by electrocardiography, air flow using nasal pressure and oronasal thermistor. In children, additional monitoring using a side-stream end-tidal capnograph (Nihon Koden) to provide breath-by-breath assessment of end-tidal carbon dioxide levels. Arterial pulse oxygen saturation  ; the oxygen desaturation index (ODI) was defined as the number of desaturation events ≥ 3% per hour of TST; the lowest SaOResults are presented as means ± SD, unless stated otherwise. All numerical data were subjected to statistical analysis using paired t tests or analysis of variance followed by post hoc tests (Tukey) as appropriate. Chisquare analysis was performed on categorical data concerning demographic characteristics of the various groups. Finally, univariate correlation analyses (Spearman rank) and multivariate linear regression modelling were performed to explore the relationships between sets of variables. Statistical analyses were performed using SPSS version 26.0 . For all comparisons, a two-tailed P value less than 0.05 was considered to define statistical significance.2 for adults, or based on BMI>95th percentile for children . Successful identification of miR-92a from serum occurred in 70 patients . In fourteen patients  levels of miR-92a was not quantifiable due to extraction error. A comparison of demographic, polysomnographic, inflammatory and metabolic markers of included versus excluded children did not reveal any statistically significant differences apart from total cholesterol levels (p=0.048) . The avechildren .From polysomnography data, the average ± SD apnea hypopnea index was 20.4 ± 22.1 events/hr . In adul2 miR-92a expression (p=0.021 from primary snoring patients) (Summary of serum data for metabolic and hepatic biomarkers can be found in atients) .2 miR-92a revealed that AHI , and ODI  had statistically significant associations  and C-reactive protein (CRP)  concentrations were significantly associated with delta log2 miR-92a.Evaluating univariate correlation of all serum biomarkers and polysomnography parameters with delta logciations . Of infl2 miR-92a using a stepwise reverse linear regression model, in which, in addition to AHI, LDL cholesterol, CRP , and other relevant biological covariates such as age, BMI, and sex . In this model, age  and LDL Cholesterol  also emerged as significantly associated with delta log2 miR-92a, while sex, BMI and CRP were unassociated.Despite findings from the univariate analysis, we assessed the association of AHI and delta log and sex  were conTo our knowledge, our study is the first addressing OSA consequences using both pediatric and adult cohorts. Our study found that independent of age, BMI, and sex, the presence of OSA was associated with an increase in miR-92a expression, and in a severity dependent fashion. We believe that miR-92a may represent an important biomarker for OSA as it provides both mechanistic insights and a potential therapeutic target for subsequent studies.Our selection to investigate miRNAs and specifically miR-92a expression was deliberate. Elevation of miR-92a has been found to prevent angiogenesis  impairinED represents a very early manifestation of CVD  such thain vivo studies have demonstrated that LDL cholesterol promotes miR-92a upregulation [Here we present that miR-92a may be an ideal biomarker for OSA and possibly OSA induced CVD. OSA has been shown to induce ED in both children –32 and igulation . NotwithHowever, it is important to acknowledge the limitations of our study. First, the study is limited by a small sample size, particularly in females and in children. Nonetheless, the inclusion of children further strengthened the statistical relationship, and also confirmed that utility of this biomarker across a broad age group. Future studies will aim to assess miR-92a in larger cohorts of both adults and children with an aim to increase the number of females in our cohort. A larger sample size could better delineate other factors that are associated with miR-92a beyond the AHI. Second, due to the logistics of our study, we were unable to assess for endothelial function specifically in patients using techniques such as flow mediated dilation; these studies could further evaluate the relationship between OSA, ED and miR-92a. However, using two diverse cohorts across separate geographical locations certainly adds to the external validity of this biomarker. Finally, we did not assess the effect of OSA treatment on miR-92a expression. While studies assessing treatment of OSA using continuous positive airway pressure (CPAP) are complex, this approach would better delineate the bidirectional relationship between OSA and miR-92a levels. However, we strongly believe that pilot data such as those which we report here are necessary before the risk and expense of a clinical trial can be justified or even properly designed.The identification of a miR-92a as a valid biomarker in identifying OSA may also help to classify patients at risk for CVD. Knowing that increased miR-92a implies poor vascular health, this finding could help identify OSA patients that are susceptible to CVD. Recent focus has occurred regarding phenotypic clustering in OSA patients with only subsets being at major cardiovascular risk. Such studies have not included pediatric patients systematically to date. We would be supportive of use of biomarkers (such as miR-92a) to classify patients for research studies e.g. to enroll high risk patients into clinical trials with appropriately focused endpoints. Clinically, assaying for miR-92a in OSA patients could help clinicians identify at risk patients that could lead to strategies such as earlier aggressive treatment or determining which patients require closer monitoring and follow up.Sup file


Uganda has one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes between adolescents (age 12–19 years) and mothers (age 20–34 years) in four urban hospitals.Maternal demographics, HIV status, and birth outcomes of all live births, stillbirths, and spontaneous abortions delivered from August 2015 to December 2018 were extracted from a hospital-based birth defects surveillance database. Differences in the distributions of maternal and infant characteristics by maternal age groups were tested with Pearson’s chi-square. Adjusted odds ratios (aORs) and 95% confidence intervals (CI) were calculated using logistic regression to compare the prevalence of adverse birth outcomes among adolescents to mothers 20–34 years.A total of 100,189 births were analyzed, with 11.1% among adolescent mothers and 89.0% among older mothers. Adolescent mothers had an increased risk of preterm delivery , low birth weight , and early neonatal deaths . Newborns of adolescent mothers had an increased risk of major external birth defects , specifically, gastroschisis  compared to mothers 20–34 years. The difference between the prevalence of gastroschisis among adolescent mothers  was statistically significant when compared to mothers 20–34 years .This study found that adolescent mothers had an increased risk for several adverse birth outcomes compared to mothers 20–34 years, similar to findings in the region and globally. Interventions are needed to improve birth outcomes in this vulnerable population. Adolescent pregnancies are a global problem occurring in high-, middle-, and low-income countries with Uganda having one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes, including major external birth defects, between adolescents, (age 12–19 years) and mothers (age 20–34 years) in four urban hospitals.All informative births, including live births, stillbirths, and spontaneous abortions; regardless of gestational age, delivered at four selected hospitals in Kampala from August 2015 to December 2018 were examined. Demographic data were obtained by midwives through maternal interviews and review of hospital patient notes.Of the 100,189 births, 11.0% were among adolescent mothers and 89.0% among mothers (20–34 years). Adolescent mothers were more likely than mothers (20–34 years) to have an infant with preterm delivery, low birth weight, early neonatal death, and major external birth defects. Adolescent pregnancies were also associated with an increased risk of gastroschisis when compared to mothers (20–34 years).In conclusion, this study found that adolescent mothers had an increased risk for several adverse birth outcomes compared to mothers 20–34 years. Research on the potential underlying causes or mechanisms for these adverse outcomes among adolescent births is necessary to identify possible interventions. Pregnancies among 15–19 year-old females account for 16 million (11%) births worldwide yet they contribute to 23% of the maternal disease burden attributed to pregnancy and childbirth [Uganda has one of the youngest populations in sub-Saharan Africa, with children and adolescents 12–19 years constituting more than half 55%) of the population in 2014 5% of the, potentiAlthough several studies have found a higher risk of adverse birth outcomes such as preterm birth, low birth weight (LBW), and early neonatal deaths (ENND), with adolescent births, , 7–13, sMost studies , 14, 19 Therefore, using a large dataset obtained from an ongoing hospital-based birth defect surveillance study, we compared the occurrence of adverse birth outcomes , including the rates and prevalence of specific major external birth defects among adolescent mothers (12–19 years) and mothers (20–34 years) in Uganda, a low-middle income setting. The findings from this study would therefore be used as a benchmark for researchers and policymakers to understand the current estimate of the burden of adverse birth outcomes among adolescent births in a low-income Sub-Saharan African country.We extracted and analyzed verified data collected between August 2015 and December 2018 from an ongoing birth defects surveillance system implemented at four major hospitals in Kampala, Uganda . These hWe defined adolescent births for this analysis as those occurring in women 12–19 years of age at delivery and the comparative group as births among women 20–34 years of age at delivery. There were no births to women younger than 12 years of age, and births of mothers ≥ 35 years of age were excluded because the risk for adverse obstetrical and perinatal outcomes has been shown to increase over age 34 , 25.We defined gestational age as the interval between the date of delivery and the last menstrual period (LMP) in completed weeks; if the LMP was unknown or missing, a clinical estimate of gestational age was used, such as estimates from fundal height or abdominal ultrasound. We defined preterm delivery as live births occurring at gestations of less than 37 weeks. Low birth weight (LBW) was defined as an infant weighing less than 2,500 g measured within 24 h after birth using digital scales among term (≥ 37 weeks) live births. Early neonatal death (ENND) was defined as death among live neonates born at term during the first 48 h or before the mother was discharged from the hospital. Stillbirth was defined as a baby born with no signs of life at or after 28 weeks’ gestation, while a spontaneous abortion was defined as fetal death at less than 28 weeks' gestation. Birth defects were confirmed through bedside examination by a physician and review of photographs, narrative descriptions, and or drawings by a birth defects expert who verified or reassigned the diagnosis code. Details of the birth defect ascertainment and classification have been described previously . The defData were analyzed using STATA version 15 statistical software . Descriptive statistics of maternal and infant characteristics by maternal age group were calculated as frequencies and percentages, and the differences between proportions were tested with Pearson’s chi-square test.We used multivariable logistic regression analysis to estimate crude and adjusted odds ratios  along with their 95% confidence intervals (CIs) for the associations between adolescent births, and adverse birth outcomes with the 20–34 years age group as the reference. Separate multivariable logistic regression models were generated for preterm birth, LBW, ENND, each major birth defect category , and each of the 16 specific birth defects. The analysis of preterm birth was limited to live births; while that of LBW and ENND was limited to term live births. The following covariates were considered for adjustment: parity, mode of delivery, singleton/multiple delivery, number of antenatal visits, and initiation time of prenatal care. The specific covariates used in each model were selected based on previous studies , 26–28, Birth prevalence per 10,000 births for seven categories of major external birth defects and 16 specific birth defects  was calcThose defects that were considered genetic, for example, anencephaly with Spina Bifida or OEIS complex  which comprises a combination of defects including omphalocele, exstrophy of the cloaca, imperforate anus, and spinal defects, were included in prevalence estimates, but not be included in etiologic or risk factor analysis since the etiology of the defects are known or suspected , 31.A total of 96,938 pregnancies with 100,189 births among mothers 12 to 34 years of age were captured. Of these, 11,028 (11.0%) births were among adolescent mothers and 89,161 (89.0%) births were among mothers (20–34 years). The age distribution of the study population of all mothers aged 12 to 34 years is shown in Fig. Table Adolescent mothers were significantly more likely than mothers (20–34 years) to have preterm (< 37 weeks) live births   compared to mothers (20–34 years) . The odds of major external birth defects were higher among adolescents in comparison to mothers (20–34 years) . Talipes equinovarus was the most prevalent major external birth defect among adolescent mothers   remained significantly associated with adolescent pregnancy (Table In this study, we observed that adolescent mothers were more likely to have an infant with the adverse birth outcome of preterm delivery, LBW, ENND, or a major external birth defect such as gastroschisis as compared to mothers 20–34 years. Previous studies have also found an increased risk for preterm delivery in adolescent births , 14, 19,Comparable to findings from a study exploring the impact of early motherhood on neonatal mortality in 45 low and middle-income countries , our stuIn this study, adolescent mothers were more likely to deliver a newborn with a birth defect when compared with mothers 20–34 years. These findings are consistent with findings from studies in North America and Europe , 39. OurAlthough the number for some birth defects were small in our study, our findings suggest that gastroschisis was significantly higher among adolescent mothers when compared to mothers 20–34 years. The strong association between adolescents births with gastroschisis has also been reported by other studies , 39, 41.Our study also found that adolescent mothers were associated with increased odds of musculoskeletal defects as well as malformations of eyes and ears combined. In one retrospective cohort study in the United States of America,  Chen et We also found that a significantly higher proportion of HIV-infected adolescents were not on ART at conception or delivery compared to women 20–34 years, which is consistent with findings from the Uganda Population-Based HIV Impact Household-based National Survey . MaternaThis study’s strengths include a large sample size, which made it possible to assess the association between adolescent births and possible risk factors of adverse birth outcomes. In addition, our study used an active birth defects case ascertainment and collection of data to ensure accuracy and improved birth defect detection and reporting versus extraction of data from medical records. Also, the physical examination of newborns by trained staff and several levels of external birth defect review ensured consistent birth defect classification and coding.Unlike other studies that only include live births , 40, thiStudy limitations include surveillance activities being conducted at four major urban hospitals located in the capital city and is not representative of adolescent births nationally . HoweverIn addition, this study did not control for several risk factors known to influence reproductive health outcomes such as social-economic status, level of education, tobacco smoking, alcohol drinking, maternal nutrition, and the use of folic acid since this information was not captured in the surveillance , 46.Finally, it has been demonstrated that adolescents are not a homogeneous group, and therefore differ in their emotional or cognitive development , and thaOur study is one of the few studies reporting adverse birth outcomes among adolescents in Uganda Our results corroborate previous findings in both developed and developing countries on birth outcomes and demonstrate that adolescent births are at risk for several neonatal adverse birth outcomes. With the growing population and high rates of adolescent births in Africa, the number of adverse birth outcomes is likely to increase and thereby remains a key public health concern .Further research on individual, socio-cultural, environmental, economic, and health service-related factors are required to identify practicable and scalable measures to decrease adolescent pregnancy and to identify and reduce obstacles that discourage the use of qualified antenatal services, that would prevent or reduce adverse reproductive outcomes such as neonatal deaths, low birth weight, birth defects, and mother to child transmission of HIV. The establishment of dedicated adolescent-friendly antenatal care programs would help improve neonatal and adolescent health , and, beAdditional file 1. Definition of Birth defects


Assessment of the repeatability of diffusion parameter estimations in the upper leg muscles of healthy adults over the time course of 2 weeks, from a simultaneous bilateral upper leg DTI measurement.λ1, λ2, and λ3), mean diffusivity (MD), and fractional anisotropy (FA). DTI parameters per muscle were calculated with and without intravoxel incoherent motion (IVIM) correction together with SNR levels per muscle. Bland-Altman plots and within-subject coefficient of variation (wsCV) were calculated. Left-right differences between muscles were assessed.SE-EPI DTI datasets were acquired at 3 T in the upper legs of 15 active adults at a time interval of 2 weeks. ROIs were manually drawn for four quadriceps and three hamstring muscles of both legs. The following DTI parameters were analyzed: 1st, 2nd, and 3rd eigenvalue , λ1 , and λ3 . wsCV values of FA were 15.2% for the IVIM-corrected data and 13.9% for the standard analysis. The SNR  and wsCV values were similar for the left and right leg and no left-right bias was detected.The Bland-Altman analysis showed good repeatability of all DTI parameters except FA for both the IVIM-corrected and standard data. wsCV values show that MD has the highest repeatability , followed by Repeatability was good for standard DTI data and slightly better for IVIM-corrected DTI data. Our protocol is suitable for DTI of the upper legs with overall good SNR.• The presented DTI protocol is repeatable and therefore suitable for bilateral DT imaging of the upper legs.• Additional B1+calibrations improve SNR and repeatability.• Correcting for perfusion effects improves repeatability.The online version of this article (10.1007/s00330-019-06403-5) contains supplementary material, which is available to authorized users. Muscle injuries are the most prevalent injuries in elite and recreational sports . AlthougOver the past decades, diffusion tensor imaging (DTI) MRI emerged as a promising technique to evaluate muscle tissue repair . PreviouDespite its promise for diagnosis and follow-up of sports-related muscle injury, repeatability of the muscle DTI method needs to be established and a couple of experimental hurdles need to be overcome. First, most DTI studies with 3-T MRI systems targeting the upper legs have been performed in a single left or right leg, because imaging of both legs resulted in varying image quality stemming from B1 inhomogeneities . However+ calibrations. We hypothesized that additional prescans prior to DTI could improve B1+ homogeneity [The combined main aims of this study were therefore to assess the repeatability of diffusion parameter estimations in the upper leg muscles of healthy active from a simultaneous bilateral upper leg DTI measurement, with and without IVIM correction. Furthermore, we also considered the benefits of additional B1ogeneity .This study was waived by the local IRB as no patients participated. We obtained written informed consent from all volunteers prior to the study.Eighteen healthy subjects, 16 males and 2 females, mean age 28.4 ± 5.2 years (range 22–40 years) with no recorded upper leg injury in the half-year prior to this study were recruited. Inclusion criteria were the following: healthy, at least 18 years old, and active in sports. Subjects engaged in sports activities on average 2.9 times per week and were instructed to continue with their sport/exercise regimen. Exclusion criteria were the following: MRI contra-indications, injury of one of the leg muscles seen on MRI, or unable to fully complete both scanning sessions. The protocol was performed twice with a 2-week interval . One subject was excluded based on a muscle injury detected at the first scanning session and two subjects had incomplete datasets due to scheduling conflicts. Thus, 15 subjects  were finally included.+ field. The geometrical planning for the second session was carefully matched to one of the first session using anatomical landmarks and saved images of the slice planning.MRI was acquired with a 3-T Philips Ingenia MRI scanner  using a 16-channel receive array coil placed on top of the legs in combination with 12 receive coils in the patient table. Subjects were placed supine and feet first in the scanner. Dielectric pads were placed on top of the left upper leg and under the right upper leg . These pb values for the purpose of IVIM correction [Axial DTI sequence with multiple rrection ;Axial T2-weighted sequence for anatomical reference;Axial PD-weighted DIXON sequence for the purpose of segmentation;Coronal T2-weighted sequence to assess potential muscle injury (exclusion criterion).The MRI examination consisted of four sequences:b values (no. gradient orientations) = 0 (1×), 1 (8×), 5 (3×), 10 (3×), 20 (3×), 50 (3×), 100 (3×), 200 (10×), 400 (10×), 600 (12×) s/mm2 , scan duration 11 m 8 s, receiver bandwidth 27.9 Hz/pixel, echo times of the axial PD-weighted DIXON sequence: 1.35 ms, 2.45 ms, 3.55 ms, 4.65 ms, 5.75 ms, and 6.85 ms.Total scanning time was 25 min. Table b value using NLS model . The isotropic perfusion component of the signal is calculated and subtracted from the signal of all diffusion directions and b values. The perfusion-corrected signal of all b values and directions was then used for tensor estimation using an iterative weighted linear least squares (iWLLS) algorithm [For the IVIM-corrected data, first, the full IVIM model was fitted to the average signal per lgorithm .+ calibration scan, a SENSE reference scan, and a coil survey scan. The prescans are proprietary Philips technology and are currently performed automatically on Philips Ingenia Systems (since release R5.3.0) at the beginning of the protocol and any time when a substantial change in the field of view or movement of the scanner table occurs. We performed additional prescans prior to the DTI sequence for 5 subjects.The 30-s prescans included a B1https://github.com/mfroeling/DTITools) for Wolfram Mathematica 11.3. First, the diffusion-weighted images were pre-processed using a principle component analysis (PCA) noise suppression algorithm [λ1, λ2, and λ3 from which mean diffusivity (MD) and fractional anisotropy (FA) were calculated. Diffusion attenuation was either modeled using a single exponential decay model—this will be referred to as “standard”—or by IVIM modeling to correct the diffusion parameters for the effects of pseudo-diffusion (perfusion) [σ) of the noise was mapped through the PCA denoising process [σ map was used for the SNR estimations [σ. In case of SNR < 20, this muscle was excluded from further analysis [DTI data were processed using the custom-built software DTITools (lgorithm . Subsequlgorithm  to correlgorithm  was usedrfusion) . The lat process . This σ imations . SNR wasanalysis .www.itksnap.org) in the out-of-phase PD-weighted DIXON  images. The segmentation was performed slice by slice, carefully excluding subcutaneous fat  and left (L) legs: rectus femoris (RF), vastus medialis (VM), vastus intermedius (VI), vastus lateralis (VL), semitendinosus (ST), biceps femoris long head (BF), and semimembranosus (SM). Manual segmentation of the muscles was performed in ITK-snap  , which was calculated as the ratio of the standard deviation of the paired differences to the mean.t tests were done to compare the wsCV values per DTI parameter for the IVIM-corrected data with standard data. The same approach was used to compare wsCV values per DTI parameter between the subgroups of 5 and 10 subjects for the IVIM-corrected data. Significance was set at p < 0.05. The minimal detectable difference, defined as 1.96 × standard deviation of the paired differences, was calculated per muscle per DTI parameter.The statistical analysis was performed for the standard and IVIM-corrected data, and separately for the right and left legs. Paired samples SNR calculations for 420 muscles (15 participants × 7 muscles per leg × 2 legs × 2 time points) resulted in the exclusion of 50 (11.9%) muscles due to insufficient SNR (< 20) leaving 185 muscle pairs (370) for further analysis. Mean SNR for all included muscles was 44.5 ± 8.9.Mean SNR of all muscles was 41.8 ± 16.0 for the right and 41.7 ± 17.1 for the left leg. An overview of the numbers of included and excluded muscles per subject, as well as mean SNR values, is given in Supplemental Tables + shimming, chemical shift artifacts and shading artifacts (B1+-field inhomogeneities) were present in a majority of the images , λ1 , and λ3 . FA had the lowest repeatability of all DTI parameters, 15.2% for the IVIM-corrected data and 13.9% for the standard analysis. For an overview of the wsCV and its standard deviation (SD) per DTI parameter, calculated as the mean of all muscles per DTI parameter, see Table λ1 (p = 0.003) and MD (p = 0.02) were significantly lower for the IVIM-corrected data. The wsCV values of λ2 (p = 0.14), λ3 (p = 0.96), and FA (p = 0.05) for the IVIM-corrected data were also lower but not significantly. The mean wsCV (IVIM-corrected data) was comparable for the left and right legs , followed by The IVIM-corrected DTI data showed slightly lower values for the minimal detectable difference compared with the standard analysis. This was the case for all DTI parameters except FA , λ3 (p = 0.03), and MD (p = 0.04), but not for λ1 (p = 0.06) and FA (p = 0.1).For this group, 2 muscles out of 140 muscles (5 subjects × 7 muscles × 2 legs × 2 time points) were excluded from the analysis due to insufficient SNR (< 20). Mean SNR  was 50.0 ± 12.2 for the 5 subjects with additional calibration vs. 37.6 ± 16.9 for the 10 standard subjects. The mean wsCV values per DTI parameter for the IVIM-corrected data were lower for these 5 subjects compared with those for the 10 subjects with the regular protocol  and 2 quadriceps (VM and VI) muscles of the left and right legs Fig.  in order+ calibration improved SNR and repeatability of the DTI parameter estimations. Lastly, we found that the data quality (SNR) and repeatability (wsCV) of the DTI parameters were similar for the left and right legs.Our research showed good repeatability of the DTI parameters in the upper leg muscles using a clinically applicable protocol suited for imaging of both legs simultaneously. The repeatability became even slightly better after IVIM correction for perfusion. Furthermore, performing an additional B1+ field inhomogeneities were regionally observed. The direction of the fat shift was chosen from anterior to posterior ensuring that residual fat signal would not shift into the commonly injured hamstring muscles. However, this resulted in some fat artifacts in the quadriceps muscles. The residual fat signal is caused by suboptimal fat suppression due to B0-field inhomogeneities. A research pre-pulse (saturation pulse) did improve suppression of the lipid olefinic resonance, but at the cost of decreased overall data quality caused by direct saturation of water, as this lipid resonance is very close to the water peak.The overall quality of the images was visually judged good. However, chemical shift artifacts by residual unsuppressed fat and shading due to B1+ inhomogeneities due to constructive and destructive interference of the transmit field are a common problem at ultrahigh fields (≥ 7 T). However, B1+ inhomogeneities can also lead to regional loss of signal (shading artifacts) at 3 T in particular in the thighs, hips, and pelvis region. In this work, we employed dielectric pads to locally augment the transmit field and reduce the shading artifacts. Although in many cases the shading was still slightly visible, the pads were capable of recovering most of the signal as evidenced from similar high SNR levels for both the right (41.8 ± 16.0) and left (41.7 ± 17.1) legs.B1+ calibration prior to the DTI sequence for five subjects. This further improved signal homogeneity, reduced the fat and chemical shift artifacts, and increased SNR with fewer muscles excluded, i.e., 2 out of 140 muscles versus 48 out of 280 muscles. Importantly, the wsCV values per DTI parameter were lower, suggesting higher repeatability. This is also in line with the simulation work of Damon [To investigate whether we could further optimize the transmit field homogeneity, we performed additional manual B1of Damon . Additioof Damon . This coThe muscle DTI parameter values were comparable with those reported in previous studies , 29. IVIλ2, and λ3  [We found that the wsCV values for the three eigenvalues and MD were on average lower after IVIM modeling. In contrast, wsCV values for FA were on average higher after IVIM correction. A similar pattern was observed when comparing our IVIM-corrected diffusion parameters to previous work in forearm muscles . Furtherusivity) , 30, 31.Some limitations of the study should be acknowledged. Firstly, we included 13 males and only 2 females. This was done to reflect the demographics of our hamstring injury patients, which are predominantly male soccer players. Men have a higher incidence rate of hamstring injuries compared with women, even when practicing the same sport . Secondl+ calibration was only performed for 5 subjects. We believe that repeatability would have been even higher if this additional B1+ calibration had been performed for all subjects.Additionally, SNR values were estimated from the PCA denoising and not from a separate noise map acquisition. This may have resulted in a systemic underestimation of the SNR and exclusion of some datasets based on the strict SNR threshold of 20. Better SNR estimates would improve the repeatability of the DTI parameters due to the known correlation between SNR and repeatability . Further+ calibration further improved the repeatability. On average, wsCV values were slightly lower than the values reported in previous studies. We plan to use this protocol in future studies on subjects with leg muscle injury.DTI parameters , except FA, were repeatable. IVIM correction and additional B1ESM 1(DOCX 3675 kb)


Primary cesarean birth rates were high among women who were either nulliparous (Group 2) or multiparous (Group 4) with a single, cephalic, term fetus who were induced, augmented, or underwent cesarean birth before labor in our study cohort.  The objective of this analysis was to determine what risk factors were associated with cesarean birth among Robson Groups 2 and 4.  This study was a prospective hospital-based cross-sectional analysis of a convenience sample of 1,000 women who delivered at Mizan-Tepi University Teaching Hospital in the summer and fall of 2019. n = 113) of the total population (n = 993). The cesarean birth rate in Robson Group 2 (n = 56) was 37.5% and in Robson Group 4 (n = 57) was 24.6%. In Robson Group 2, of all prelabor cesareans (n = 5), one birth was elective cesarean by maternal request; the intrapartum cesarean births (n = 16) mostly had a maternal or fetal indication (93.8%), with one birth (6.2%) indicated by “failed induction or augmentation,” which was a combined indication. In Robson Group 4, all 4 women delivered by prelabor cesarean had a maternal indication (one was missing data), and 3 of the intrapartum cesareans were indicated by “failed induction or augmentation.” In multivariable modeling of Robson Group 2, having a labor duration of “not applicable” increased the risk of cesarean delivery ). The odds of requiring maternal antibiotics was the only notable outcome with increased risk ). In multivariable modeling of Robson Group 4, having a labor longer than 24 hours trended towards a significant association with cesarean ), and women had a more dilated cervix on admission trended toward having a lower odds of cesarean ).  Women in Robson Groups 2 and 4 comprised 11.4% ( Though rates of primary cesarean birth among women who have a term, single, cephalic fetus and are induced, augmented, or undergone prelabor cesarean birth are high, those that occur intrapartum seem to be associated with appropriate risk factors and indications, though we cannot say this definitely as we did not perform an audit. More research is needed on the prelabor subgroup as a separate entity. The World Health Organization recommends applying the Robson classification for cesarean birth to birth cohorts to better understand which of ten mutually exclusive subgroups are contributing to cesarean birth rates , 2. AnalWe conducted a hospital-based, prospective, cross-sectional study at Mizan-Tepi University Teaching Hospital (MTUTH), located in Mizan Aman in the Southern Nations, Nationalities, and People's Region (SNNPR). We observed the sample of all women who presented to the facility and gave birth on labor and delivery at MTUTH between May 6 and October 21, 2019, which was the point at which we observed 1,000 births. Women were required to deliver at or after 28 completed weeks of pregnancy to be included in the overall cohort. Women included in Robson Groups 2 and 4 were included in this analysis. Highly trained physicians collected deidentified data through a combination of chart review and structured interview at admission, delivery, and discharge. After data were collected on paper forms and reviewed for completeness, it was entered into REDCap for storage on a password protected server at the University of Colorado, Aurora, Colorado, USA [p < 0.05 were included in a multivariable Poisson model with robust error variance  to determine which covariates were independently associated with cesarean birth. Subsequently, individual logistic regressions  of maternal and perinatal outcomes (significant in the bivariate comparisons) were run with the outcomes as the dependent variable and cesarean birth as the independent variable, adjusted for all covariates significant in the multivariable Poisson model, to describe the association between cesarean birth and adverse pregnancy outcomes.STATA software version 15.2  was used for analysis. Bivariate comparisons of sociodemographic, obstetric, birth, and pregnancy outcomes of women experiencing vaginal versus cesarean birth were performed, utilizing Fisher's exact, chi-squared, and Kruskal–Wallis tests depending on the variables. All covariates significant to Despite the quality improvement nature of the work and the fact that only deidentified data were collected, oral consent was obtained from each woman before any of her data were recorded. This quality improvement survey was given an exempt from human subjects' research approval (COMIRB # 18–2738) by the University of Colorado, and approval was given by Mizan-Tepi University Teaching Hospital.Our study cohort is defined in n = 5) underwent prelabor cesarean and the remainder  were delivered during the course of labor. In one of five women delivered prelabor, the indication was clearly identified as cesarean birth by maternal request, with the remaining women delivered for reportedly maternal or fetal indications. Intrapartum cesareans were reportedly performed for the following indications: maternal (37.5%), fetal (56.3%), and failed induction or augmentation of labor (6.2%). Comparatively, among Robson Group 4, all prelabor cesareans (n = 4) had a maternal indication (n = 1 was missing), while three of the total intrapartum cohort (n = 10) underwent cesarean birth for failed induction or augmentation of labor. The remaining intrapartum cesareans in this cohort had a maternal (n = 2), fetal (n = 4), or combined maternal/fetal indication (n = 1).p=0.007), and there was a trend towards significance of more infants < 2500 g being delivered by cesarean . Maternal postpartum antibiotic administration  was more common after cesarean birth, as was a lower five-minute Apgar score . Multivariable modeling, which included labor duration and birthweight as covariates, found that only a labor duration of “not applicable” was associated with an increased risk of cesarean when compared to labor less than 12 hours . In subsequent individual logistic regressions adjusted for labor duration, cesarean birth in Robson Group 2 women was associated with an increased odds of maternal postpartum antibiotic use  but not with Apgar score.p=0.04) and were more likely to have a labor longer than 24 hours , and there was a trend toward a significant difference in their admission cervical dilation . Maternal postpartum antibiotic use  and lower five-minute Apgar score  were more common after cesarean birth, but macerated stillbirth was less common . In multivariable modeling of the association of these risk factors  with cesarean birth in this subgroup, labor duration of longer than 24 hours  and likelihood of cesarean birth with each increasing centimeter of cervical dilation on admission  had borderline significance. Logistic regressions of the association of cesarean birth with pregnancy outcomes did not converge.Of 113 women at MTUTH who had term, singleton, cephalic fetuses and underwent induced or augmented labor or prelabor cesarean birth, the overall (and primary) cesarean birth rate was 31.0% (data not shown). For nulliparous women in this cohort, the rate was higher at 37.5% and for multiparous women lower at 24.6%. All intrapartum cesarean births in this population reportedly had maternal or fetal indications for cesarean delivery, while at least one of the prelabor surgeries was qualified as cesarean birth by maternal request (though no audit was performed). Across the whole cohort, prolonged duration of labor was associated with cesarean birth. In Group 2, lower birthweight had a trend toward significance, Apgar scores were lower, and maternal antibiotic usage was higher after cesarean delivery. In Group 4, urban living was associated with cesarean birth, and less cervical dilation on admission trended toward significance. Similar to Group 2, Apgar score and maternal antibiotic usage were higher after cesarean birth in bivariate comparisons but unable to be assessed by multivariable modeling given the small sample size.Prolonged duration of labor stands out as an important predictor of cesarean birth in Robson Groups 2 and 4. Traditional obstetric teaching suggests that nulliparous women should deliver within 20 hours of the onset of labor and multiparous women with 14 hours . More reThe partogram is currently in use at MTUTH but has variable levels of completion, which would be an area for quality improvement at the facility. While prior Cochrane reviews have questioned the association of partogram use with improved pregnancy outcomes, more recent literature has suggested that use of the tool as intended is associated with the decision to proceed to cesarean birth and reduced stillbirth . An audiRegarding intrapartum decision-making support tools, there are applications designed for smartphones that assist providers with interpreting fetal heart rate monitoring and the partogram , 15. If Despite the recognition that obstructed labor, of which duration of labor is a proxy measure, is an appropriate indication for cesarean birth, as stated previously, time alone may not be a rich enough variable to support the decision to move to cesarean. Fortunately, organizations in other countries have introduced guidelines for prevention of primary cesarean birth that focus on additional specific measures of labor and delivery progress . AdherenRobson Groups 2 and 4 have a higher primary cesarean birth rate 31.0%) than that of Robson Groups 1 and 3 , the latter of which are known to contribute most significantly to primary cesarean birth rates, globally 1.0% than. This isThe limitations of our study are the small sample size of the subgroups of interest and the lack of audit to confirm indication for cesarean birth. Additionally, we were unable to calculate a logistic regression for Group 4 due to the small sample. Strengths of our study include the collection of a comprehensive set of covariates and outcome measures to allow for good hypothesis generation.In conclusion, we have not determined with this analysis what accounts for the higher cesarean birth rate among Robson Groups 2 and 4, except for the fact that some cesareans are performed before the onset of labor. There is not enough information regarding the circumstances of women undergoing prelabor cesarean birth at MTUTH in this cohort beyond very general indications, which would be a great area for further evaluation. We do know that one woman was granted cesarean birth by maternal request, and it will be important to watch the trend in this practice over time to determine if it is becoming more common, which the World Health Organization does not recommend –22. We w