Prematurity and low birth weight predispose preterm infants to cardiovascular disease in later life. Is the metabolic profile of these children impacted by the relation between birth weight and gestational age (GA)? This study aimed to evaluate whether the relationship between birth weight and GA of preterm infants has a positive correlation with the metabolic profile from birth to the sixth month of corrected age. This is a longitudinal, prospective study with a cohort of 70 preterm and 54 term infants, who were enrolled in the study and shared into two groups: Appropriate for GA (AGA) and Small for GA (SGA), both classified at birth by Fenton and Kim curves. Longitudinal evaluation of anthropometry measures and blood samples of total cholesterol, glucose, triglycerides, and insulin were collected at birth, NICU discharge, and the sixth month of corrected age. Data were analyzed using descriptive and inferential statistical analysis . The effect size was 0.15, power was 0.92, and confidence interval 95%. No significant statistical differences were observed in relation to biochemical tests between AGA and SGA groups. However, a significant increase in triglyceride results above the reference values for age in the SGA group was observed throughout the follow-up. Changes observed in the preterm infant metabolic profile show no correlation with adequacy of birth weight. Preterm lipid profile requires continuous evaluation at follow-up, due to the increased cardiovascular risk in later life. Low birth weight (LBW) has been associated with childhood morbidity and mortality, which presents direct influence in later life with the development of diseases such as hypertension, dyslipidemia, and type 2 diabetes. The combination of these diseases with alterations in body size, metabolic parameters, and blood pressure characterize metabolic syndrome (MeS) . EvidencIn addition to overweight and obesity, prematurity and LBW have been related to MeS components such as insulin resistance, increased blood glucose, cholesterol, triglycerides, and blood pressure changes. Therefore, a child born under this situation is predisposed to chronic health conditions in adult life .Moreover, nutritional impairments in fetal and neonatal life have consequences related to newborn infants’ growth and development processes, exposing them to a higher probability of metabolic diseases in other stages of life. Furthermore, premature infants are likely to develop changes in their long-term health . This unIn this context, a suboptimal intrauterine environment in the early stages of life causes repercussions on a preterm infant’s growth, predisposing him or her to long-term health problems such as diabetes and MeS. In the 1980s, Barker and Osmond’s study  developeThe LBW and preterm infants had postnatal growth restriction in common; therefore, neither group could maintain the fetal growth pattern. Thus, they presented a high risk of metabolic alterations. Although the literature provides evidence, studies that analyze preterm and LBW infants before the first year of life are not enough to elucidate the lack of research about MeS’s components in these groups. Then the question is whether the metabolic profile of preterm infants is impacted by the relation between birth weight and GA.In this way, the study aimed to evaluate if the relationship between birth weight and GA of preterm infants has a positive correlation with the metabolic profile from birth to the sixth month of corrected age, in comparison to term infants.A longitudinal, prospective study was conducted on a preterm infant cohort hospitalized in the Neonatal Intensive Care Unit (NICU) at a teaching hospital in Paraná State, Brazil, from May 2015 to December 2016. This preterm infant cohort was compared to a term cohort that was born at the same teaching hospital during the same period. The study was approved by the research ethics committee under process No. 1,134,712. The informed consent form was read and signed by parents or guardians prior to the study.The preterm infants eligible for the study were born at the hospital, admitted at the NICU, and under treatment for 7 or more days at the unit, and their blood samples were collected upon admission and discharge from the NICU. In addition, participants who attended all appointments at the outpatient follow-up were included. Exclusion criteria were the presence of congenital malformation, inborn metabolism errors or chromosomal anomalies, and death during hospitalization or after hospital discharge.Thus, 115 preterm infants and their mothers were selected for the study. From this sample, 70 completed the follow-up and attended the four visits at the follow-up clinic, as follows: first week after hospital discharge; first and third months after discharge; and at the sixth month of corrected age (CA).The study’s term cohort was composed of newborns without any comorbidities and who were born between 37 weeks and 41 weeks and 6 days of GA. Children of adolescent mothers or those who had a disease were excluded from the sample. Consequently, 162 term infants and their mothers were enrolled in the sample. Among them, 54 completed the follow-up evaluation at the sixth month of life.At the NICU, preterm infants’ data were collected at admission, covering information related to the delivery, birth, and anthropometric measures. The outpatient appointment was scheduled for the first week after the preterm and term infants were discharged. However, the preterm infants were followed until the sixth month of CA and term infants until sixth month of life. All data were collected by the responsible researcher at the NICU and maternity unit and were tabulated in Excel for Windows and double checked.The glucose, triglyceride, cholesterol, and insulin blood samples were collected at two points for the preterm and term infant cohorts: 1) from 24 to 72 hours after birth and 2) at the sixth month of CA for the preterm infants and sixth month of life for the term infants. The medical care team required the blood samples as part of the assistance during the NICU or maternity hospitalization and in the follow-up program. However, the blood samples for use in this research were obtained from the material discharged right after the NICU medical team’s required screening. The exams were collected by venipuncture using a butterfly with an evacuated tube and an adaptor, all processed by the institutional laboratory. The exams were realized by dry chemistry method with 10 mg/dL of test sensibility for the triglyceride, 20 mg/dL for glucose, and 50 mg/dL for cholesterol. The insulin exam was analyzed by electrochemiluminescence method with 0.03 nIU/mL of test sensibility.®) with a sensitivity of 5 g. Length measurements (presented in centimeters) were obtained using an anthropometric aluminum ruler with the infant in dorsal decubitus. Until 40 weeks of CA, to calculate the Z score of weight and length and to establish the relation between birth weight and GA by Fenton and Kim’s  on a digital scale , Small for GA (SGA), and Adequate for GA (AGA). This classification is able to efficiently display fetal growth, considering LGA when the newborn is above the 90th percentile; SGA when the infant is below the 10th percentile, and AGA between 10th and 90th percentiles.Descriptive statistics were analyzed to assess whether prematurity and its consequences have an influence on or correlation with the preterm infants’ metabolic changes after hospital discharge .The biochemical variables  were evaluated at two points: admission and at the sixth month of CA/sixth month of life. From the birth weight to classification, the preterm and term infants were divided into two groups: AGA and SGA. All variables were evaluated between each group (AGA and SGA) according to the GA (term and preterm infants) by repeated measures ANOVA test. Each variable was analyzed for the two mentioned times, followed by the LSD-Fisher test.The variables were previously evaluated regarding the distribution of the data through the Shapiro-Wilk test, as well as the homogeneity of the variances using the Cochran test. All statistical analyses were performed using the Statistica 7.0 program. The tests presented a 0.92 power with a mean effect size of 0.15 and a type I error of 0.05 (Gpower 3.1).The sample initially constituted 115 preterm infants, 70 of whom concluded the follow-up. The LGA sample was lost in the follow-up. Among this group, the gender distribution frequency was similar  in initial and final samples. Sixty percent of preterm infants were born within 32-36 weeks, and 40% weighed between 1,000 and 1,499 g. Eighty-nine percent of preterm infants were classified as AGA, whereas 11% were classified as SGA. Forty-four percent of the sample were hospitalized at the NICU for more than 21 days.The term infant sample was initially constituted of 162 participants; however, 54 completed the sixth month follow-up. The gender distribution frequency was equivalent . Of this group, 85.18% were considered AGA, 7.41% were considered SGA, and 7.41% were LGA. During the follow-up, among the 54 who completed the process, 50 were AGA and four were SGA.The comparison of anthropometric characteristics  between During the follow-up, no significant difference in the glucose values  was identified in the evaluation of the term and preterm infants, classified as AGA and SGA . HoweverRegarding the triglyceride variable, the interaction of GA, birth weight classification, and follow-up were verified , neverthThe cholesterol variable  did not Finally, the insulin variable neither presented statistical differences in the interaction of those factors  nor were differences observed in any of the isolated factors.Metabolic plasmatic parameters showed different profiles during growth. Thus, while the plasma lipid levels (triglycerides and cholesterol) increased during growth, the plasma glucose and insulin levels decreased, suggesting preterm infants altered their metabolism along their growth .No statistically significant difference was observed in the metabolic profile variables between preterm and term infants, considering the AGA and SGA birth weight classifications. In both groups, the glycemic profile showed stabilization of the serum levels throughout the evaluations. Therefore, insulin presented a decrease until the sixth month of CA for preterm and at the sixth month of life for term infants. Regarding the lipid profile, a gradual increase was noted in serum values from birth to the sixth month for both groups.The glycaemia at birth for the preterm infant group was higher than the term group. Nevertheless, the preterm infants considerably reduced the glycaemia value at the sixth month of CA. At birth, both groups presented glycemic rates of 54 mg/dL, which is above normal levels for neonatal glycaemia . The SGAThe insulin results highlight an inverse graph, where higher values are found at birth and reduced levels are identified for both groups along the follow-up. The SGA group presented higher serum insulin values at birth, which decreased until the sixth month. Higher plasmatic concentration of catecholamines  are preserved in preterm infants with acuter answers for epinephrine when compared to term infants. This situation promotes the insulin decrease and, consequently, an increase in the glucagon concentration .Preterm infants with very low birth weight  have higher levels of plasmatic insulin, suggesting a peripheral insulin resistance . In chilA Spanish study  also assThe triglyceride results also do not present a significant statistical difference between the AGA and SGA groups (p = 0.4660). Even so, it is important to highlight that at birth the AGA and SGA preterm infant groups showed lower serum triglyceride values than the term infants. In addition, these values presented gradual increases along the follow-up evaluation, with much higher rates than the Brazilian and European Atherosclerosis Society and the European Federation of Clinical Chemistry and Laboratory Medicine consensus, which were established as adequate for age ,21. ThisAlterations in fetal and neonatal cholesterol metabolism are important to understand not only during infancy, but for an individual’s long-term health because coronary heart disease has been proposed to be linked to abnormal cholesterol metabolism in the fetus and newborn. Our data showed no significant difference between the term and preterm groups (p = 0.495); both of them presented gradually increasing total cholesterol from birth to sixth months regardless of whether they were AGA or SGA. De Jong and cols.  found siA recent systematic review  presenteEvidence from the literature converges ,25 when Moreover, a study  has estaAnnual biochemical testing is an important routine in preterm infant follow-up. This analysis could contribute to establishing preterm infants’ metabolic profiles, since prematurity and SGA are considered predictive factors for metabolic changes.The short period of preterm follow-up observation can be considered a limitation of the study. However, despite the brief follow-up (only until the sixth month of CA), the study may identify the need for attention to the metabolic effects of preterm birth and SGA. Although the SGA sample for both term and preterm infants in our study was reduced and therefore points to another limitation of our research, the findings suggest SGA preterm infants should be considered require special consideration in follow-up interventions. So, when planning a specific care program for this group during hospitalization and after NICU discharge, these elements should be taken into account. According to the literature review, preterm birth and very low birth weight are associated risk factors to cardiovascular diseases. Besides this fact, literature has indicated a higher atherogenic lipid profile among adults who were born preterm . Our stuWhen comparing preterm infants with a control group of term infants of the same age and from the same population, the present study’s results are more reliable. However, it should be noted that the results were stratified into subgroups of adequate or small for gestational age. In spite of the proportions within each group represented, the SGA group was closest to the Brazilian rates, which vary from 5.6 to 10.6% of all live births . In our In conclusion, the metabolic profile from birth to the sixth month of CA was not influenced by the birth weight and GA of the preterm infant. However, the triglyceride exam could be considered an earlier serum biomarker for MeS among preterm infants. Based on our findings, the importance of following the preterm infant metabolic profile may be evidenced, since triglyceride levels might be a possible predictor of higher cardiovascular disease risk during their lives.Prematurity and the questions involved in the follow-up of preterm infants require further studies, mainly related to metabolic alterations and early catch up and how these aspects influence a child’s health during late childhood, adolescence, and adulthood. Interdisciplinary long-term longitudinal studies on metabolic markers in preterm infants are challenging when evaluating the risk of developing future alterations, such as MeS, which demand complex and diverse knowledge.


To perform an economic cost analysis of the implementation of a short cervix screening program to reduce preterm birth in singleton pregnancies in a short-term time horizon.We performed a cost-benefit economic analysis using the P5 trial database, a randomized multicenter clinical trial for prevention of preterm birth. Data collection was conducted from July 2015 to March 2019 in 17 different Brazilian hospitals. We conducted a cost analysis for universal cervical screening in singleton pregnancies between 18 weeks and 22 weeks plus 6 days. In subjects with a cervical length ≤ 25 mm, the analysis incorporated the costs of administering 200 mg/day of vaginal progesterone prophylactically until 36 weeks gestation. These findings were subsequently compared with the economic implications of forgoing cervical screening. The time horizon comprised from birth to 10 weeks postpartum. The outcome was measured monetarily in Brazilian real (R$) from the perspective of the Unified Health System.Among 7,844 women, 6.67% (523) had a cervix ≤ 25 mm. The cost of screening with transvaginal ultrasound and vaginal progesterone for prevention of births with < 34 weeks was estimated at R$ 383,711.36, while non-screening generated an estimated additional cost of R$ 446,501.69 (related to the 29 non-screened preterm deliveries). Thus, screening and prophylaxis would generate a final cost reduction of R$ 62,790.33, constituting a possible cost-benefit strategy.Universal short cervix screening for preterm birth has lower costs compared to non-screening within a short-term time horizon, which suggests an interesting benefit-cost ratio. Future studies should consider the cost-effectiveness of prophylactic treatment using sensitivity analyses in different scenarios within the Brazilian health system, as well as analyses that consider the long-term costs associated with preterm births, to robustly justify the implementation of a short cervix screening program. Spontaneous preterm birth (SPB) can be predicted by identifying a short cervix, preferably evidenced by transvaginal ultrasound (TVUS) in the second trimester of pregnancy 2 . Some authors advocate universal screening of pregnant women between 18 and 24 weeks in order to identify women at increased risk of preterm birth and implement therapies to prevent preterm delivery 4 .Preterm birth affects one in ten births worldwide, and the pursuit of a reduction in this incidence remains one of the major challenges of medicine 5 . An individual patient data (IPD) meta-analysis of 2018 found that the use of vaginal progesterone reduced SPB with < 34 weeks by 28%  among women with short cervix (≤ 25mm) and estimated a number needed for treatment of 18 6 . The most recent IPD meta-analysis on the use of progesterone (EPPPIC study) also found benefit with prophylactic use of vaginal progesterone and identified a reduction of preterm delivery with < 34 weeks by 22% 7 .Among the interventions to prevent preterm birth, progesterone is a widely used treatment to reduce preterm delivery, with few side effects and good adherence 8 . Several analyses show that universal screening has a good benefit-cost ratio when compared to not performing TVUS or offering it only when patients have a previous history of preterm delivery. However, there is still controversy as to whether or not to perform universal screening for short cervix 11 . Since these economic results vary depending on the prevalence of preterm birth in each population and on the transfers made by the health care provider, the results of the economic analyses of implementing or not a screening program depend on the country where the analysis is carried out; thus requiring decisions to be individualized.After the EPPPIC study, the Society of Maternal-Fetal Medicine and the American College of Obstetricians and Gynecologists reaffirmed the prophylactic use of progesterone in singleton pregnancy women with a cervix length ≤ 25 mm diagnosed between 18 0/7 and 22 6/7 weeks of gestation 1 . According to the World Health Organization, there are 279,300 preterm births/year in Brazil 14 . In 2014, the Brazilian EMIP study involving 5,296 Brazilian pregnant women found an incidence of 12.3% premature births, with 2/3 of this total being SPBs 15 . The average cost of care required per preterm birth is estimated to be USD 1,427 for Brazil 16 . Given this high incidence of preterm births, it is necessary to project the costs of universal screening in the Brazilian population. Currently, Brazil does not have a screening program that is universal or geared toward patients with a history of preterm birth, and progesterone, still the best therapeutic option for the prevention of preterm birth, is not included in the group of standardized drugs provided by the Unified Health System (SUS).In the world ranking of preterm birth, Brazil is in ninth position in absolute numbers and with 11.2% of preterm births, being directly responsible for 2.2% of all preterm births in the world In this sense, the objective of this study is to evaluate whether there is an economic benefit in the implementation of a cervical length screening program during pregnancy, followed by prophylactic treatment with vaginal progesterone of women then identified with a higher risk, compared to the costs associated with premature births, if not screened.versus no screening. By using a model where patients have 100% coverage and adherence to the proposed treatments, we estimate the costs of a universal screening program for preterm birth with the implementation of a well-established preventive treatment for all identified women at increased risk of preterm delivery (cervix ≤ 25mm) versus the cost linked to preterm deliveries that were not avoided due to the option of not screening. The outcome was measured monetarily using the Brazilian real (R$) as the reference currency and considering the values of the year 2021, from the perspective that the health care provider is SUS.This is a cost-benefit ratio economic analysis, in which we compare the two scenarios of economic consequences: the implementation of a universal screening program for preterm birth 17 . P5 is a randomized clinical trial with Brazilian pregnant women with cervical length ≤ 30 mm, identified through TVUS between 18–22 weeks of gestation. Coordinated by the Universidade Estadual de Campinas (UNICAMP) and involving 17 reference maternity hospitals in Brazil in three regions, P5 evaluated the effectiveness of isolated vaginal progesterone in relation to vaginal progesterone associated with cervical pessaries in the prevention of preterm delivery in pregnant women with short cervix. Data collection of the first phase of this study ( screening with TVUS) took place between July 2015 and March 2019. Cervix measurement was performed by an experienced professional sonographer following the protocol of the Fetal Medicine Foundation and with strict control of images and technical corrections when necessary, using a standardized device. All data were included in the P5 trial online database. In the second phase of the study , pregnant women with a cervix ≤ 30 mm were randomized into two groups: one group received vaginal progesterone 200 mg/day + cervical pessary and the other group received only vaginal progesterone 200 mg/day. The pregnant women in the clinical trial were followed up to 10 weeks after the probable date of delivery. The P5 study was evaluated and approved by the Unicamp Reasearch Ethics Commission (Opinion 1.082.011) and also by the Comissão Nacional de Ética em Pesquisa  (Opinion 1.055.555), and registered in the Brazilian registry of clinical trials .This study is a secondary analysis of the P5 Study on Pessary and Progesterone in Preterm Birth Prevention 18 .To estimate the number of women who would be identified and treated, we targeted pregnant women with a singleton pregnancy. Those with a uterine cervix ≤ 25 mm, identified through TVUS during the second trimester , are at an increased risk of preterm delivery before 34 weeks. Consequently, they should receive 200 mg/day of vaginal progesterone as a preventive treatment for preterm birth. Based on a recent meta-analysis on the subject, we consider as a reference that the number needed for treatment in this group is 18, that is, for every 18 pregnant women with a cervix ≤ 25 mm who receive progesterone among those identified with a cervix ≤ 25 mm up to 36 weeks of gestation, one SPB < 34 weeks is avoided The P5 database contains the screening records of 7,892 women with singleton pregnancies, with 48 of whom lacked information regarding cervical measurement. Among the 7,844 women with complete screening data, the incidence of cervix ≤ 25 mm was 6.67%, a total of 523 patients. Following the literature information that for every 18 patients treated with vaginal progesterone we could reduce one SPB < 34 weeks, we can assume that universal screening followed by progesterone prophylaxis could reduce in our sample a total of 29 preterm deliveries < 34 weeks. To estimate the costs associated with treatment, we assumed in this model that treatment with vaginal progesterone 200 mg/day will be accepted and followed optimally by the patients identified from the 20th week to the 36th week of pregnancy.Agência Nacional de Vigilância Sanitária  market regulation table—Drug Price Lists 19 . To estimate the value of daily treatment with vaginal progesterone, considering that it is not available in SUS among standardized drugs, we carried out a price survey including five large drugstore chains operating in Brazil and used the average value of one 200 mg progesterone capsule for vaginal use.Due to the limitation of data in the literature that could help us identify the average cost of a SPB < 34 weeks in Brazil, we used our P5 trial database to calculate how much a preterm birth would cost based on the average value found in our sample of preterms births with < 34 weeks among the women with a cervix ≤ 25 mm. In constructing this value, we considered the costs of inputs and procedures from birth to the first 10 weeks after the probable date of delivery, including possible neonatal readmissions, according to the follow-up period of the research subjects defined by the P5 trial protocol to identify persistent neonatal pathological conditions   . We didIn the calculation to estimate the average cost of SPB < 34 weeks, of the 41 pregnant women in the clinical trial with a cervix length of ≤ 25 mm, all experienced spontaneous preterm delivery (SPB) before 34 weeksSPB. Of these, 10 pregnancies had an adverse outcome with fetal or neonatal death. A total of five pregnancies evolved to fetal death and two newborns evolved to neonatal death with less than 24 hours of life; therefore, these seven births did not enter the cost assessment because there was no record of the costs associated with these early deaths. Thus, a total of 34 newborns were analyzed to calculate the average cost of preterm birth. Of these, 28 were considered with adverse outcome (82.35%), having presented some type of neonatal morbidity and three of them evolved to neonatal death during the follow-up period of the study. The average cost of SPB up to 10 weeks after the probable date of delivery was estimated at R$ 15,396.61 per newborn, which would give a total of R$ 446,501.69 associated with non-screening, that is, the cost of 29 SPBs < 34 weeks that were not avoided   . In theAmong the analyzed costs related to preterm birth, the main responsible for the final cost was the newborn’s length of stay in the ICU, with an average cost of R$ 13,882.61 per birth. Of the 34 newborns analyzed, 47% required pulmonary surfactant. Additionally, 41.2% received magnesium sulfate for neuroprotection. Meanwhile, 55.9% underwent a transfontanelle ultrasound. Lastly, 11.2% experienced seizure episodes that necessitated the use of an anticonvulsant.The analysis estimated that implementing a screening program with TVUS in the second trimester of pregnancy to identify pregnant women with a cervix measure ≤ 25 mm, followed by prophylactic treatment with vaginal progesterone up to 36 weeks of gestation, costs less than the average of a SPB below 34 weeks. Considering the effectiveness of progesterone previously reported in the literature, its ideal use and the existence of an existing infrastructure for screening, the universal screening strategy for the prevention of preterm birth represents a saving of R$ 2,165.18 for each preterm birth avoided in a short-term projection, in which only the first 10 weeks after the probable date of delivery were considered.21 . An American article considering a prevalence of 8% of cervixes ≤ 25 mm and prophylaxis with vaginal progesterone estimated that universal screening would have prevented 30,545 preterm deliveries < 34 weeks in 2013 22 . However, it is important to note that preterm birth of < 34 weeks is associated with long-term cost-generating consequences, such as cognitive, respiratory, cardiovascular, auditory and visual sequelae, which were not measured in this study 23 , but may further influence on the economic impact and cost reduction to the health care provider if considered 25 . Moreover, the reduction of preterm birth-related fetal and neonatal mortality, gain in quality of life for children and families, and reduced loss of productivity for parents or guardians were also not part of this study 26 . International studies that included these factors in their analysis indicated that universal screening is cost-effective in preventing preterm birth below 34 weeks 28 .Previous studies have advocated universal screening considering the positive economic repercussions Our study used the prevalence of cervix ≤ 25 mm of a large sample of Brazilian pregnant women from different regions of the country. Preterm births used as a reference for the average cost of preterm birth were followed during the valuation period, providing complete data regarding the costs involved in the analyzed time horizon. However, as a limitation, this study did not consider in the analysis the costs prior to performing the ultrasound examination, such as the costs related to the ultrasound device, clinic, and physical infrastructure.29 .In this regard, we consider that it would be possible to use the same device reserved for routine obstetric ultrasound and the same probe used during the obstetric ultrasound of the first trimester, not significantly burdening the costs related to equipment and infrastructure in centers that already perform routine prenatal ultrasound exams. The examination can and should be performed at the same time when the pregnant woman seeks the health care unit for obstetric or morphological GUS in the second trimester and by the same professional, considering an increase of 5–10 minutes in the examination time. Information from the National Health Survey (PNS) carried out in Brazil in 2013 with women from all over the national territory showed that 99.7% of the women interviewed had undergone some ultrasound during pregnancy, which makes it clear that this prenatal examination is already incorporated into the health care culture of the Brazilian population and that it has easy access 30 .However, implementation of the screening program would require trained professionals to perform cervical measurement. This control in the quality of the exam provided is feasible, since the technique for measuring the cervix is simple, with a learning curve that requires little time. The training for this technique is available for free and online on the Fetal Medicine Foundation platform, with evaluation and audit of images at the end of the course; therefore, it is accessible to professionals without significant cost increase Notably, in order to estimate the cost of preterm delivery, we considered the costs related to the first 10 weeks after the probable date of delivery; additionally, the costs related to the five fetal deaths and two neonatal deaths of our sample were not added. We consider this a limitation of our study. A long-term analysis could provide even more impactful results as to the cost-benefit ratio of implementing the screening program.31 .Our study also presents the limitation of not considering the costs associated with the follow-up of women identified as at risk of preterm birth. It is true that, after a short cervix is identified, each patient will form their perception of risk and this can lead to more anxiety, stress, prenatal consultations, and work-related losses. At the same time, building a good doctor-patient relationship—which should be the premise of all medical care and which does not add to the final cost—can provide the necessary clarifications and guidance to reduce this state of vulnerability and facilitate adherence to the proposed treatment Thus, we can consider this analysis as a preliminary cost study, a first step towards a more attentive look into the possibility of implementing TVUS for uterine cervix measurement in the second trimester as a screening program for preterm birth in Brazil. We understand that the decision to use the costs of preterm birth treatment according to the SUS table  and the values of short cervix treatment according to CMED/ANVISA , ultimately overestimate the costs of prevention and underestimate the costs of treatment and, therefore, underestimate the reduction and costs with screening. Even with this consideration, we found a cost reduction favorable to screening.However, the development of more robust results will require cost-effectiveness analysis with the modeling of several other factors that directly influence the incremental cost result, such as the acceptability to undergoing the screening, the real adherence to the treatment offered, and the work-related losses of women at higher risk of preterm delivery, enabling the estimation of values more consistent with reality through sensitivity analyses.Considering the above, we conclude that universal screening of short cervix for prevention of preterm birth with TVUS in the second trimester of pregnancy, associated with prophylaxis with vaginal progesterone for pregnant women identified with a cervix ≤ 25 mm, presents lower costs in relation to non-screening within a short-term time horizon, which suggests an interesting benefit-cost ratio in the implementation of universal screening of short cervix for prevention of preterm birth in Brazil. New studies that also consider the cost-effectiveness of prophylactic treatment using sensitivity analyses in different scenarios within the Brazilian health care system are necessary to robustly justify the screening of preterm birth. 1 . A predição do parto pré-termo espontâneo (PPE) pode ser feita pela identificação do colo uterino curto, evidenciado preferencialmente através da ultrassonografia transvaginal (USTV) no segundo trimestre de gestação 2 . Alguns autores defendem a realização de um rastreio universal das gestantes entre 18 e 24 semanas a fim de identificar as mulheres sob risco aumentado de prematuridade e implementar terapias para prevenir o parto pré-termo 4 .O parto pré-termo afeta um a cada dez nascimentos em todo mundo, e a busca pela redução dessa incidência continua sendo um dos grandes desafios da medicina 5 . Uma individual patient data (IPD) metanálise de 2018 identificou que o uso da progesterona vaginal reduziu o PPE < 34 semanas em 28%  entre mulheres com colo uterino curto (≤ 25 mm) e estimou um número necessário para tratamento de 18 6 . A mais recente IPD metanálise sobre o uso da progesterona (EPPPIC study ) também encontrou benefício com o uso profilático da progesterona vaginal e identificou uma redução de parto pré-termo < 34 semanas em 22% 7 .Entre as intervenções para prevenir a prematuridade, a progesterona é um tratamento bastante utilizado para redução do parto pré-termo, com poucos efeitos colaterais e boa adesão study , a Sociedade de Medicina Materno-Fetal e o American College of Obstetricians and Gynecologists reafirmaram o uso profilático da progesterona em mulheres com gestação única e colo uterino com comprimento ≤ 25mm diagnosticado entre 18 0/7 e 22 6/7 semanas de gestação 8 . Muitas análises mostram que o rastreio universal tem uma boa relação custo-benefício quando comparado à conduta de não realizar a USTV ou oferecer apenas quando as pacientes apresentam história prévia de parto pré-termo. Entretanto, ainda existe controvérsia quanto a realizar ou não o rastreio universal para colo curto 11 . Como esses resultados econômicos variam a depender da prevalência do parto pré-termo em cada população e dos repasses feitos pelo provedor de saúde, os resultados das análises econômicas de implementar ou não um programa de rastreio variam a depender do país onde a análise é realizada e, portanto, as decisões precisam ser individualizadas.Após o EPPPIC 1 . Segundo a Organização Mundial da Saúde, nascem 279.300 prematuros/ano em nosso país 14 . Em 2014, o estudo brasileiro EMIP envolvendo 5.296 gestantes brasileiras encontrou uma incidência de 12,3% de partos prematuros, com 2/3 desse total sendo PPE 15 . Estima-se que o custo médio dos cuidados necessários por nascimento prematuro seja de $ 1.427 dólares para o Brasil 16 . Diante dessa alta incidência de partos prematuros, é necessário projetar os custos do rastreamento universal na população brasileira. Atualmente o Brasil não possui um programa de rastreio universal nem direcionado para pacientes com histórico de prematuridade, e a progesterona, ainda hoje a melhor opção terapêutica para prevenção de prematuridade, não faz parte do grupo de medicamentos padronizados oferecidos pelo Sistema Único de Saúde (SUS).No ranking mundial de prematuridade, o Brasil encontra-se na nona posição em números absolutos e com 11,2% de nascimentos prematuros, sendo responsável direto por 2,2% de todos os nascimentos prematuros no mundo Nesse sentido, o objetivo deste estudo é avaliar se existe benefício econômico na implementação de um programa de rastreamento do comprimento cervical durante a gestação, seguido pelo tratamento profilático com progesterona vaginal das mulheres então identificadas com maior risco, em comparação aos custos atrelados aos nascimentos prematuros, se optado pelo não rastreamento.versus o não rastreamento. Utilizando-nos de um modelo em que as pacientes apresentam 100% de cobertura e adesão aos tratamentos propostos, valoramos os custos de um programa de rastreio universal para prematuridade com implementação de um tratamento preventivo bem estabelecido para todas as mulheres identificadas com risco aumentado de parto pré-termo (colo ≤ 25 mm) versus o custo atrelado aos partos prematuros não evitados pela opção do não rastreamento. O desfecho foi medido monetariamente usando como moeda de referência o real brasileiro (R$) e considerando os valores do ano 2021, na perspectiva de que o provedor é o SUS.Esta é uma análise econômica do tipo custo-benefício na qual comparamos os dois cenários de consequências econômicas: a implementação de um programa de rastreio universal para prematuridade 17 . O P5 é um ensaio clínico randomizado com gestantes brasileiras com o comprimento cervical ≤ 30 mm, identificadas a partir de USTV entre 18–22 semanas de gestação. Coordenado pela Universidade Estadual de Campinas (Unicamp) e envolvendo 17 maternidades de referência do Brasil em três regiões, o P5 avaliou a efetividade da progesterona vaginal isolada em relação à progesterona vaginal associada ao pessário cervical na prevenção do parto pré-termo em gestantes com colo curto. A coleta de dados da primeira fase desse estudo ( screening com USTV) ocorreu entre julho de 2015 e março de 2019. A medida do colo foi realizada por profissional ultrassonografista experiente seguindo o protocolo da Fetal Medicine Foundation e com rigoroso controle de imagens e correções técnicas quando necessário, utilizando um aparelho padronizado. Todos os dados foram incluídos no banco de dados on-line do P5 trial. Na segunda fase do estudo (ensaio clínico) gestantes com colo ≤ 30 mm foram randomizadas em dois grupos: um grupo recebeu progesterona 200 mg/dia por via vaginal + pessário cervical e o outro grupo recebeu apenas a progesterona vaginal 200 mg/dia. As gestantes do ensaio clínico foram seguidas até 10 semanas após a data provável do parto. O estudo P5 foi avaliado e aprovado pelo CEP da Unicamp (Parecer 1.082.011) e também pela Comissão Nacional de Ética em Pesquisa (Conep) (Parecer 1.055.555), e cadastrado no registro brasileiro de ensaios clínicos .Este estudo é uma análise secundária do Estudo P5 – Pessário e Progesterona na Prevenção do Parto Pré-termo 18 .Para estimar o número de mulheres a serem identificadas e tratadas, partimos do pressuposto de que gestantes com gravidez única , com colo uterino ≤ 25 mm identificado através de USTV no segundo trimestre de gestação  têm risco aumentado de parto pré-termo < 34 semanas e, portanto, devem receber progesterona vaginal 200mg/dia como tratamento preventivo para prematuridade. A partir de recente metanálise sobre o tema, consideramos como referência que o número necessário para tratamento neste grupo é 18, ou seja, a cada 18 gestantes com colo ≤ 25mm que recebem progesterona entre as identificadas com colo uterino ≤ 25mm até 36 semanas de gestação, um PPE < 34 semanas é evitado O banco de dados do P5 contém o registro de rastreamento de 7.892 mulheres com gestação única, com 48 pacientes apresentando perda de informação com relação à medida do colo. Entre as 7.844 mulheres com dados completos do rastreamento, a incidência de colo ≤ 25mm foi de 6,67%, um total de 523 pacientes. Seguindo a informação da literatura de que a cada 18 pacientes tratadas com progesterona vaginal poderíamos reduzir um PPE < 34 semanas, podemos supor que o rastreamento universal seguido de profilaxia com progesterona poderia reduzir em nossa amostra um total de 29 partos prematuros < 34 semanas. Para estimar os custos associados ao tratamento, assumimos nesse modelo que o tratamento com progesterona vaginal 200 mg/dia será aceito e seguido de forma ideal pelas pacientes identificadas da 20ª semana até a 36ª semana de gestação.19 . Para estimar o valor do tratamento diário com a progesterona vaginal, tendo em vista que ela não é disponibilizada pelo SUS entre os medicamentos padronizados, realizamos um levantamento de preço incluindo cinco grandes redes de farmácias atuantes no Brasil e utilizamos o valor médio de uma cápsula de 200mg de progesterona para uso vaginal.Devido à limitação de dados na literatura que pudessem nos ajudar a identificar o custo médio de um PPE < 34 semanas nascido no Brasil, utilizamos nosso banco de dados do P5 trial para calcular quanto custaria um nascimento prematuro a partir do valor médio identificado em nossa amostra de prematuros < 34 semanas nascidos entre as mulheres com colo ≤ 25mm. Na construção desse valor, foram considerados os custos de insumos e procedimentos desde o nascimento até as 10 primeiras semanas após a data provável do parto, incluindo possíveis readmissões neonatais, conforme o período de seguimento dos sujeitos de pesquisa definido pelo protocolo do P5 trial de maneira a identificar condições patológicas neonatais persistentes   . Não coNo cálculo para estimar o custo médio do PPE < 34, 41 gestantes participantes do ensaio clínico com colo ≤ 25mm tiveram um PPE < 34 semanas. Destas, 10 gestações tiveram desfecho adverso com óbito fetal ou neonatal. Um total de cinco gestações evoluíram com óbito fetal e dois recém-nascidos evoluíram para óbito neonatal com menos de 24h de vida, portanto esses sete nascimentos não entraram na avaliação de custo por não haver registro dos custos associados a esses óbitos precoces. Dessa forma, um total de 34 recém-nascidos foram analisados para o cálculo do custo médio da prematuridade. Destes, 28 foram considerados como não saudáveis , tendo apresentado algum tipo de morbidade neonatal e três deles evoluíram para óbito neonatal durante o período de seguimento do estudo. O custo médio do PPE até 10 semanas após a data provável do parto foi estimado em R$ 15.396,61 por recém-nascido, o que daria um total de R$ 446.501,69 associados ao não rastreamento, ou seja, o custo de 29 PPE < 34 semanas que não foram evitados   .Na amostra de rastreio do Estudo P5 com dados de 7.844 mulheres, a média de colo uterino foi 36,9mm e a incidência de colo ≤ 25mm foi 6,67% (523 gestantes). Estimamos um custo total para o rastreio universal de toda a amostra de R$ 189.824,80 e um custo total de tratamento profilático com progesterona de 523 gestantes com colo curto de R$ 193.886,56; perfazendo um total de R$ 383.711,36 para evitar 29 partos prematuros. Esse resultado identificou que o rastreio universal associado ao tratamento profilático com progesterona vaginal apresentou boa relação custo-benefício em curto prazo, com redução de custos totais estimada em R$ 62.790,33    .Entre os custos analisados relacionados ao nascimento prematuro, o maior responsável pelo custo final foi o tempo de internação do recém-nascido em UTI, com um custo médio de R$ 13.882,61 por nascimento. Entre os 34 recém-nascidos analisados, 47% necessitaram de surfactante pulmonar, 41,2% receberam sulfato de magnésio para neuroproteção, 55,9% realizaram ultrassonografia transfontanela e 11,2% apresentaram episódios convulsivos sendo necessário o uso de anticonvulsivante.A análise estimou que implementar um programa de rastreio com USTV no segundo trimestre de gravidez para identificação de gestantes com medida de colo ≤ 25 mm, seguido de tratamento profilático com progesterona vaginal até as 36 semanas de gestação, tem um custo inferior ao custo médio de um PPE abaixo de 34 semanas. Considerando a efetividade da progesterona relatada previamente em literatura, seu uso ideal e a existência de uma infraestrutura já existente para a realização do rastreamento, a estratégia de rastreio universal para prevenção da prematuridade representa uma economia de R$ 2.165,18 para cada parto pré-termo evitado numa projeção de curto prazo, na qual foram consideradas apenas as 10 primeiras semanas após a data provável do parto.21 . Um artigo americano considerando uma prevalência de 8% de colos ≤ 25mm e a profilaxia com progesterona vaginal estimou que o rastreio universal teria prevenido 30.545 partos pré-termo < 34 semanas no ano de 2013 22 . Entretanto, é importante lembrar que a prematuridade < 34 semanas está associada a consequências de longo prazo geradoras de custos, como sequelas cognitivas, respiratórias, cardiovasculares, auditivas e visuais, que não foram mensurados nesse estudo 23 , mas que poderiam trazer ainda mais impacto econômico e redução de gastos ao provedor de saúde se consideradas 25 . Mais ainda, também não fizeram parte deste estudo a redução da mortalidade fetal e neonatal associada à prematuridade, o ganho de qualidade de vida da criança e sua família, assim como a redução da perda de produtividade dos pais ou responsáveis pela criança 26 . Estudos internacionais que incluíram esses fatores em sua análise indicaram que o screening universal tem custo-benefício efetivo para prevenir prematuridade abaixo de 34 semanas 28 .Estudos anteriores têm defendido o rastreio universal considerando as repercussões econômicas positivas Nosso estudo utilizou a prevalência de colo ≤ 25mm de uma grande amostra de gestantes brasileiras de distintas regiões do país. Os nascimentos prematuros utilizados como referência para o custo-médio da prematuridade foram seguidos durante o período de valoração, permitindo dados completos quanto aos custos envolvidos no horizonte temporal analisado. Entretanto, como limitação, o presente estudo não considerou na análise os custos prévios à realização do exame de ultrassonografia, como os custos relacionados ao aparelho de ultrassonografia, clínica e infraestrutura física.29 .Sobre isso, consideramos que seria possível utilizar o mesmo aparelho reservado para ultrassonografia obstétrica de rotina e a mesma sonda utilizada durante a ultrassonografia obstétrica do primeiro trimestre, não onerando expressivamente os custos relacionados a aparelhagem e infraestrutura nos centros que já realizam exames ultrassonográficos de rotina de pré-natal. O exame pode e deve ser feito no mesmo momento em que a gestante procura a unidade de saúde para realização de USG obstétrica ou morfológica do segundo trimestre e pelo mesmo profissional, sendo considerado um acréscimo de 5–10 minutos no tempo de exame. Informação proveniente da Pesquisa Nacional em Saúde (PNS) realizada no Brasil em 2013 com mulheres de todo o território nacional mostrou que 99,7% das mulheres entrevistadas tinham realizado alguma ultrassonografia durante a gestação, o que deixa claro que esse exame do pré-natal já está incorporado na cultura de saúde da população brasileira e que apresenta facilidade de acesso 30 .A implementação do programa de rastreio, todavia, necessitaria de profissionais treinados para realização da medida do colo uterino. Esse controle na qualidade do exame oferecido é factível, visto que a técnica para medida do colo é simples e com curva de aprendizado que demanda pouco tempo, sendo possível realizar treinamento on-line e gratuito na plataforma da Fetal Medicine Foundation sem custo, com avaliação e auditoria de imagens ao término do treinamento; portanto, disponível e acessível para capacitação dos profissionais sem expressivo acréscimo de custo Vale ressaltar que para estimar o custo do parto pré-termo, em nossa análise foram considerados os custos relativos às primeiras 10 semanas após a data provável do parto e também não foram somados os custos relacionados aos cinco óbitos fetais e dois óbitos neonatais da nossa amostra. Nós consideramos esta uma limitação de nosso estudo. Uma análise de longo prazo poderia trazer resultados ainda mais impactantes quanto ao custo-benefício da implementação do programa de rastreio.31 .Nosso estudo também apresenta a limitação de não valorar os custos atrelados ao seguimento das mulheres identificadas sob risco de prematuridade. É verdade que, após ser identificado colo uterino curto, cada paciente formará sua percepção de risco e isso pode gerar mais ansiedade, estresse, consultas de pré-natal e perda laboral. Ao mesmo tempo, a construção de uma boa relação médico-paciente, que deve ser premissa de todo atendimento médico e que não agrega custo final, pode trazer os esclarecimentos e orientações necessários para reduzir esse estado de vulnerabilidade e facilitar a adesão ao tratamento proposto Podemos assim considerar esta análise como um estudo de custo preliminar, um primeiro passo para um olhar mais atencioso à possibilidade de implementar a USTV para medida do colo uterino no segundo trimestre como um programa de rastreio para a prematuridade no Brasil. Entendemos que a decisão de utilizar os custos do tratamento da prematuridade conforme a tabela SUS  e os valores do tratamento para o colo curto conforme CMED/Anvisa , em última análise, superestimam os custos de prevenção e subestimam os custos de tratamento e, por conseguinte, subestimam a redução e custos com o rastreamento. Mesmo com essa consideração, encontramos uma redução de custos favorável ao rastreamento.Entretanto, para o desenvolvimento de resultados mais robustos, será necessária uma análise de custo-efetividade com a modelagem de diversos outros fatores que influenciam diretamente no resultado do custo incremental, como por exemplo, a aceitabilidade à realização do rastreamento, a real adesão ao tratamento oferecido e a perda laboral das mulheres sob maior risco de parto pré-termo, permitindo estimar valores mais condizentes com a realidade através das análises de sensibilidade.Diante do exposto, concluímos que o rastreamento universal do colo curto para a prevenção da prematuridade com USTV no segundo trimestre de gestação, associado à profilaxia com progesterona vaginal para as gestantes identificadas com colo ≤ 25 mm, apresenta menores custos em relação ao não rastreamento dentro de um horizonte temporal de curto prazo, o que sugere uma interessante relação custo-benefício na implementação do rastreio universal do colo curto para a prevenção do parto pré-termo no Brasil. Novos estudos que também considerem a custo-efetividade do tratamento profilático utilizando-se de análises de sensibilidade em diferentes cenários dentro do sistema de saúde brasileiro são necessários para justificar com robustez o rastreamento da prematuridade.


To evaluate the relationship between maternal vascular malperfusion and acute intrauterine infection/inflammation with neonatal outcomes.This was a retrospective study of women with singleton pregnancies who completed placenta pathological examination. The aim was to study the distribution of acute intrauterine infection/inflammation and maternal placental vascular malperfusion among groups with preterm birth and/or rupture of membranes. The relationship between two subtypes of placental pathology and neonatal gestational age, birth weight Z-score, neonatal respiratory distress syndrome, and intraventricular hemorrhage was further explored.P < 0.001) and , respectively. The incidence of maternal vascular malperfusion and acute intrauterine infection/inflammation were  and , respectively. Acute intrauterine infection/inflammation was associated with shorter gestational age  and decreased weight  than those with no lesions in preterm birth. When two subtype placenta lesions co-occurrence, shorter gestational age  and decreased weight  were observed in preterm. Consistent findings were observed in preterm births with or without premature rupture of membranes. In addition, acute infection/inflammation and maternal placenta malperfusion alone or in combination were associated with an increased risk of neonatal respiratory distress syndrome (adjusted odds ratio (aOR) 0.8, 1.5, 1.8), but the difference was not statistically significant.990 pregnant women were divided into four groups, including 651 term, 339 preterm, 113 women with premature rupture of membranes, and 79 with preterm premature rupture of membranes. The incidence of respiratory distress syndrome and intraventricular hemorrhage in four groups were (0.7%, 0.0%, 31.9%, 31.6%, Maternal vascular malperfusion and acute intrauterine infection/inflammation alone or co-occurrence are associated with adverse neonatal outcomes, which may provide new ideas for clinical diagnosis and treatment. Preterm birth is a common cause of neonatal morbidity and mortality, accounting for about 12 percent of all newborns . A fullyElisabeth B et al. found that AI was associated with necrotizing enterocolitis (NEC) in extremely preterm infants (< 28 weeks) , and MVM was associated with decreased fetal birth weight . Other sTherefore, this study aims to retrospectively explore data from our hospital and discuss the relationship between the single or co-occurrence of MVM and AI with outcomes such as gestational age (GA), birth weight, neonatal respiratory distress syndrome (RDS), and intraventricular hemorrhage (IVH) in literature , 19, 20.A single-center, retrospective study was performed at Zhongda Hospital of Southeast University in Nanjing, Jiangsu Province, China. We searched the records of 5,074 pregnant women who were admitted between 01. January. 2021 and 31. December. 2022. 4084 pregnant women who did not meet the requirements were excluded: (1) Repeated hospitalizations for other diseases prior to delivery, (2) No placental pathology, (3) twins, (4) foreigners, (5) Malignant tumor, (6) pregnant female <20 weeks or >42 weeks of gestation, and (7) women with incomplete information. Finally, the cohort included 990 singletons with a gestational age of 20 + 0 to 41 + 6 weeks . The stuThe following maternal clinical data were collected from the Electronic medical record system: Pre-pregnancy BMI, Education, Age, Delivery mode, Diabetes, and Hypertension. The neonatal data that was recorded from the Electronic medical record system included: GA, birth weight, Neonatal intensive care unit (NICU), 1-minute Apgar score and 5-minute Apgar score, Small for gestational age (SGA), large for gestational age (LGA), gender, RDS and IVH. In addition, We calculated birth weight Z-scores for different sexes using L, M, and S values from WHO reference data .The diagnosis of MVM, according to the results presented by Amsterdam and Redline, mainly includes , MVM is used as a whole, not graded , 22—AI iAccording to MVM and AI, the two placental lesions were divided into four groups: None of the MVM nor AI (MVM-/AI-), AI alone (MVM-/AI+), MVM alone (MVM+/AI-), co-occurrence of MVM and AI (MVM+/AI+).P values were corrected for multiple testing using the Bonferroni procedure. Categorical variables are expressed as quantities and percentages. The continuous variables were expressed as mean ± standard deviation if normally distributed and as median  if not normally distributed. Linear regression was used to simulate the GA and birth weight Z-score  and expressed as β, P. We conducted logistic regression analyses to determine the associations between placental findings and neonatal RDS and IVH. Results were expressed as Odds Ratio (OR) 95% confidence intervals (CI). The covariates selected a priori mainly included age, college education, and pre-pregnancy BMI. During the discussion of RDS and IVH, the GA covariate will be added as an adjustment. R (Version 4.2.2) software was used for the above statistical analysis, and P < 0.05 was considered statistically significant.Maternal and infant information was grouped according to preterm birth and rupture of membranes. Categorical variables were analyzed with chi-square tests. After Continuous variables were tested for normal distribution and homogeneity of variance, using ANOVA or Kruskal-Wallis test, as appropriate. From 01. January. 2021 to 31. December. 2022, clinical information on 990 pregnant women and newborns was assessed. Pregnant women were divided into four groups based on preterm birth and premature rupture of membranes. There were 651 term pregnant women, including 538 with intact membranes and 113 with PROM. There were 339 preterm pregnant women, including 260 with intact membranes and 79 with PPROM .P < 0.001). Preterm pregnancy with intact membranes was more likely to develop hypertension . Newborns in preterm pregnancy with intact membranes were more likely to have a 1-minute Apgar score < 7 , 5-minute Apgar score < 7 . Newborns in preterm pregnancy with intact membranes were more likely to have RDS  and BPD  and the IVH  adverse outcomes. Among the four groups, Placental lesions are more likely to occur in preterm infants with intact membranes, including decidual arteriopathy  and placental infarction . However, FIRS  and severe HCA  were higher in pregnant women with PPROM. Advanced Syncytial knots , Perivillous fibrin deposition  and Intervillous fibrin deposition  were not statistically significant among the four groups . MVM-/AI+ and MVM+/AI+ were associated with shorter gestational weeks of newborns . MVM-/AI + and MVM+/AI+ with intact membrane  PPROM  may result in a shorter gestational age in preterm birth. In reference to MVM-/AI-, MVM+/AI+ was associated with lower birth weight for preterm birth . In preterm infants, MVM-/AI+ and MVM+/AI+ with intact membrane  versus PPROM  were associated with lower birth weight ; however, this association was not observed after further adjustment for gestational age at birth as a covariate . No assoProper placental function is essential for exchanging and transporting nutrients and waste between mothers and newborns. This study investigated the relationship between MVM, AI alone, or with co-occurrence of adverse outcomes in pregnant women in China and further investigated the relationship between placental disease and preterm birth with or without PPROM.The following key information was obtained through this retrospective study. First, although no effect of MVM was observed on either outcome, pathological features of MVM and AI were dominant in preterm birth with intact membranes and PPROM. It is suggested that MVM and AI are two important subtypes of placental lesions. This partly explains the differences between the different types of preterm birth. Second, the presence of MVM or AI alone and co-occurrence was associated with shorter GA and lower birth weight in newborns. The coexistence of MVM and AI may be a unique pathological form that needs attention, providing a unique perspective and thought for explaining the pathological mechanism of neonatal diseases. Finally, the presence of MVM or AI alone and co-occurrence in RDS reflects an increasing trend of disease risk, suggesting that different degrees of placental lesions may be closely related to the risk of disease occurrence. Predicting the severity of diseases from the perspective of placental lesions may be possible and may provide theoretical support for implementing disease intervention and reducing the risk of short—and long-term poor prognosis of diseases.In this study, AI alone, MVM alone, MVM, and AI co-occurrence were associated with lower birth weight and shorter GA in preterm birth. Karen Mestan’s study confirmed that placental infection/inflammation is related to postpartum fetal growth and may be an effective indicator for predicting postpartum fetal growth failure . The infThe diagnosis of MVM does not depend on any single placental finding but rather on a series of findings involving primary changes in the maternal decidual vasculature of the mother and/or secondary changes in the villous parenchymal . MVM is As a result, pathologists will likely encounter lesions of AI and MVM in daily practice and provide useful information about the underlying causes of preterm birth . In respThis study’s limitations are as follows: first, the present study is a single-center retrospective study, and evidence from a large-sample multi-center prospective study is required to determine whether the findings apply to the women in China. Second, there is still a gap in the interpretation of placenta pathology in our hospital compared with other countries. Although we also supplemented the data by integrating indicators from other literature, standardized diagnostic templates are still needed to identify placental lesions in subsequent clinical diagnosis and treatment to enhance the general value of clinical reports and identify potential therapies.The strengths of this study are as follows. First, data in this study is from the Chinese population, which is of particular reference value for comparing different races to those previously documented. Second, the present study provides evidence on the relationship between the appearance of placental pathology alone or co-occurrence and guides subsequent researchers to design and further explore the research direction. Thirdly, through this study, we also realized the non-standardization and application limitations of the existing placental pathology interpretation and made timely improvements. The subsequent standardized diagnosis of placenta pathology promotes the universality of placental pathological interpretation reports. In clinical application, it can guide the diagnosis and treatment of diseases more scientifically.MVM and AI are two important subtype placental lesions associated with adverse outcomes in preterm infants. AI or MVM alone and a combination of both lesions may be associated with an increased risk of certain diseases. Therefore, it is of great significance to improve the standard of placental pathology interpretation to standardize its general application, guide disease diagnosis, and make the diagnosis and treatment plan scientifically.


Large racial and ethnic disparities in adverse birth outcomes persist. Increasing evidence points to the potential role of racism in creating and perpetuating these disparities. Valid measures of area-level racial attitudes and bias remain elusive, but capture an important and underexplored form of racism that may help explain these disparities. Cultural values and attitudes expressed through social media reflect and shape public norms and subsequent behaviors. Few studies have quantified attitudes toward different racial groups using social media with the aim of examining associations with birth outcomes.We used Twitter data to measure state-level racial sentiments and investigate associations with preterm birth (PTB) and low birth weight (LBW) in a multiracial or ethnic sample of mothers in the United States.A random 1% sample of publicly available tweets from January 1, 2011, to December 31, 2021, was collected using Twitter’s Academic Application Programming Interface . Analyses were on English-language tweets from the United States that used one or more race-related keywords. We assessed the sentiment of each tweet using support vector machine, a supervised machine learning model. We used 5-fold cross-validation to assess model performance and achieved high accuracy for negative sentiment classification (91%) and a high F1 score (84%). For each year, the state-level racial sentiment was merged with birth data during that year (~3 million births per year). We estimated incidence ratios for LBW and PTB using log binomial regression models, among all mothers, Black mothers, racially minoritized mothers , and White mothers. Models were controlled for individual-level maternal characteristics and state-level demographics.Mothers living in states in the highest tertile of negative racial sentiment for tweets referencing racial and ethnic minoritized groups had an 8% higher (95% CI 3%-13%) incidence of LBW and 5% higher (95% CI 0%-11%) incidence of PTB compared to mothers living in the lowest tertile. Negative racial sentiment referencing racially minoritized groups was associated with adverse birth outcomes in the total population, among minoritized mothers, and White mothers. Black mothers living in states in the highest tertile of negative Black sentiment had 6% (95% CI 1%-11%) and 7% (95% CI 2%-13%) higher incidence of LBW and PTB, respectively, compared to mothers living in the lowest tertile. Negative Latinx sentiment was associated with a 6% (95% CI 1%-11%) and 3% (95% CI 0%-6%) higher incidence of LBW and PTB among Latina mothers, respectively.Twitter-derived negative state-level racial sentiment toward racially minoritized groups was associated with a higher risk of adverse birth outcomes among the total population and racially minoritized groups. Policies and supports establishing an inclusive environment accepting of all races and cultures may decrease the overall risk of adverse birth outcomes and reduce racial birth outcome disparities. Low birth weight (LBW) and preterm birth (PTB) are widely used indicators of reproductive health ,2 and arRacism is a well-established social determinant of health that operates at and across multiple levels. This includes the internalized, personally mediated , institutional, structural, and cultural dimensions of racism . InternaExposure to racism is also a psychosocial stressor that, when experienced chronically, has demonstrated negative health effects that contribute to birth outcome disparities ,19. MateAn emerging body of research has revealed the foundational role of cultural racism in perpetuating race-based disparities. Cultural racism is the infusion of the ideology of racial hierarchy into the values, language, imagery, symbols, and unstated assumptions of the larger society . It is dand county-level to see how they related to birth outcomes within and across racial or ethnic groups.Twitter represents a rapid mode of communication, with millions of tweets sent daily by users across the globe, 80%-90% of whom have publicly accessible Twitter profile . CulturaA random sample comprising 1% of publicly available tweets from January 1, 2011 to December 31, 2021 was collected using Twitter’s Academic Application Programming Interface. We restricted our analyses to tweets that were in English, from the United States, and used one or more race-related keywords (We assessed the sentiment of each tweet using a support vector machine (SVM), a supervised machine learning model. A full description of our model has been previously described by Nguyen and colleagues . Our traTo assess historical trends in sentiment, average negative sentiment scores for each racial and ethnic group along with the sentiment scores referencing racially minoritized groups were plotted as a function of time. The line chart was plotted using the “Matplotlib” library in Python . We visuIndividual birth outcomes data through 2011-2021 were obtained from restricted US natality files that included geographic identifiers. The latest year the natality files are currently available is 2021. We chose 2011 to examine trends in the last decade. In addition, Twitter introduced Twitter “Places” for geotagging tweets in June 2010 . The natWe adjusted for potential confounders at the individual- and area-level when assessing the association between racial sentiment and birth outcomes. Individual-level covariates in our models included birth year, maternal age , race , Hispanic ethnicity, marital status (married or unmarried), education , and first birth (yes or no), and prenatal care initiation during the first trimester (yes or no). We also adjusted for state-level characteristics, including proportions of non-Hispanic Black and Latinx individuals, population density (per square mile), and economic disadvantage (standardized factor score) ,45 summaP<.05. Our primary models examined the association between state-level sentiment toward all racially minoritized groups on birth outcomes among the full sample, racially minoritized mothers, and White mothers. Follow-up analyses examined associations between state-level sentiment toward individual racial groups  and birth outcomes for those groups specifically. Sensitivity analyses were conducted to examine the association between county-level racial sentiment and birth outcomes. Although all tweets collected had place information that permitted the identification of the state, only 60%  of tweets collected had place information to identify the county. Thus, we consider the county-level analyses to be supplementary. Sensitivity analyses also excluded tweets from users who tweeted more than 1000 times per year, which represented less than 1% (n=1066) of all tweets. Stata MP 16 [For each year, the state-level racial sentiment was merged with birth data during that year. The racial sentiment was coded in tertiles for analysis assessing associations with birth outcomes. We estimated incidence ratios for LBW and PTB (separately) using log binomial regression models with state-level racial sentiment as our independent variable of interest, and controlled for individual-level maternal characteristics and state-level demographic characteristics. We evaluated statistical significance at ta MP 16  was usedThis study was determined exempt by the University of Maryland College Park Institutional Review Board (1797788-1).Among the terms assessed, the top 20 terms by year were present in 86%  of all tweets concerning a racial or ethnic minority group . Black pApproximately 55% of births were to White mothers; 22% of the samples were Latinx. Black and Asian mothers made up 15%  and 6%  of the sample, respectively. The majority of women were US born , and 31%  completed college or beyond.The state-level negative racial sentiment was consistently associated with adverse birth outcomes controlling for individual maternal characteristics and state-level sociodemographic characteristics  and 2. FWhen examining race- and ethnic-specific sentiment and birth outcomes, the strongest and most consistent associations were found for negative sentiment in tweets referencing Black people and birth outcomes among Black mothers. Black mothers living in states in the third tertile of negative Black sentiment had a 6% higher incidence of LBW and a 7% higher incidence of PTB compared to mothers living in the lowest tertile states. Negative sentiment in tweets referencing Latinx individuals was associated with a 6% and 3% higher incidence of LBW and PTB, respectively, comparing Latinx mothers living in the highest compared to the lowest tertile states. Negative sentiments referencing White individuals was not associated with birth outcomes among White mothers .Sensitivity analyses excluded tweets from users who tweeted more than 1000 per year. The estimates changed slightly, but all main conclusions remain the same  and sentiment  to birth outcomes. For instance, Medicaid is known to mitigate racial health disparities , but staPolicies that support racial literacy and cultural competency training as well as policies and supports that promote racial equity more broadly  and establish an inclusive social environment accepting of all races and cultures may improve population health, decreasing the overall risk of adverse birth outcomes and reducing racial-birth outcome disparities. Additionally, our results suggest that policies and practices that ostracize, stigmatize, or otherwise isolate certain racial or ethnic groups and increase hostility directed toward them may exacerbate adverse birth outcomes, which would perpetuate the impact of racism or discrimination on future generations.This study represents advancement in our ability to assess racial sentiment at a more fine-grained level as a means to provide more detailed explanations for racial disparities in birth outcomes. Social media provide a unique opportunity to examine racial sentiment across time, geographic location, and for different racial groups. By examining the relationship between sentiment and birth outcomes across racial groups, we are better able to assess the specificity and generalizability of cultural racism in the outcomes for different groups. Future work can build on our findings, and use this work to inform policy aimed at reducing racial disparities in health.


Using the Lambda Mu Sigma (LMS) method, the Generalized Additive Models for Location Scale, and Shape (GAMLSS) package, smoothed percentile charts (3–97) covering GA from 23 to 42 weeks were constructed. Results. The mean birth weight of boys was 3453 ± 540 g, and this was higher compared with that of girls (3317 ± 509 g). At each gestational age, boys exhibited higher birth weights than girls. The weight range between the 10th and 90th percentiles was 1061 g for boys and 1016 g for girls. Notably, the birth weight of Polish newborns was higher compared to previously published international growth standards. Conclusion. The reference values for birth weight percentiles established in this study for Polish newborns differ from the global standards and are therefore useful for evaluating the growth of newborns within the national population. These findings hold clinical importance in identifying neonates requiring postbirth monitoring.Introduction. Percentiles of birth weight by gestational age (GA) are an essential tool for clinical assessment and initiating interventions to reduce health risks. Unfortunately, Poland lacks a reference chart for assessing newborn growth based on the national population. This study aimed to establish a national reference range for birth weight percentiles among newborns from singleton deliveries in Poland. Additionally, we sought to compare these percentile charts with the currently used international standards, INTERGROWTH-21 and WHO. Materials and Methods. All singleton live births ( Percentiles of birth weight are an essential tool for assessing neonatal health in both epidemiological research and clinical practice ,2. TheseCurrently, the global birth weight standards INTERGROWTH-21 (IG-21) and the World Health Organization’s Fetal Growth Charts  are recommended for assessing birth weight ,16,17. TDistinguishing between normal and abnormal neonatal weight gain remains a significant challenge in obstetrics and pediatrics, not only in Poland but in many countries worldwide. The existing reference charts, such as IG-21 and WHO Fetal, do not include data from Poland, which is the largest country in Central−Eastern Europe, with an annual number of live births of approximately 350,000 ,17,22. CThis study aimed to establish a national reference range for birth weight percentiles among newborns from singleton deliveries in Poland. Additionally, we sought to compare these percentile charts with the currently used international standards IG-21 and WHO.In this study, we conducted a retrospective analysis of live births based on data from 3,849,388 individual birth records reported to the Central Statistical Office in Poland between 2010 and 2019. We used an anonymized data set to construct birth weight curves for singletons at GA between 23 and 42 weeks. These curves were then compared to the global birth weight standards of the IG-21 and the WHO ,26. Our Gestational age in our study was determined by the experienced obstetric staff and was based on the interval, measured in full weeks, between the first day of the last menstrual period (LMP) and the actual day of delivery. Additionally, birth weight was routinely measured immediately after birth using an electronic scale.To establish a normal range of birth weight, we applied certain exclusion criteria, which involved removing records of multiple births, GA below 23 weeks, and above 42 weeks, and cases of newborns without registered GA, birth weight, and sex of newborns, amounting to a total of 104,035 records. Additionally, using the Tukey method, we excluded 114 records containing outliers in birth weight . After tIn this study, we presented birth weight curves at 1-week intervals of gestation, focusing on single births. Live births between 23 and 42 weeks of gestation were classified into birth percentiles to establish a normal range of birth weight for GA. We created curves and tables for newborns, stratified by sex, using smoothed estimated curves, and for the mean and standard deviation (SD) calculated from the distribution of birth weights. Standards for calculating centiles SGA were defined as <3rd, <5th, and <10th percentiles, and LGA as >90th, >95th, >97th percentiles of birth weight for GA.t-tests, while Pearson’s chi-square tests were used for qualitative variables. All calculations were performed using the R program. To fit the growth percentile curves, we employed the Generalized Additive Models for Location, Scale, and Shape (GAMLSS) package [p-value lower than 0.05 was considered statistically significant.To achieve this, we utilized the Lambda−Mu−Sigma (LMS) method  to trans package , and forThe sex-specific distribution of birth weight at GA in the Polish population between 2010 and 2019 was analyzed using the 3rd, 5th, 10th, 50th, 90th, 95th, and 97th percentiles. These percentiles were then compared to the global standards of IG-21 and the WHO ,26.During the period from 2010 to 2019, the study included 1,928,659 boys and 1,816,580 girls from single pregnancies, resulting in a gender ratio of 1.06. After assessing birth weight, it was found that boys and girls with low birth weights (<2500 g) accounted for 3.97% and 4.77%, respectively. When considering GA, preterm births (<37 weeks) for boys and girls were 6.01% and 5.18%, respectively, while term births (37–41 weeks) were 92.63% and 93.40%.p < 0.001). Notably, the difference in birth weight between boys and girls increased with GA, ranging from 22 g at 23 gestational weeks to 162 g at 41 and 42 gestational weeks, with statistical significance observed (p < 0.001) across the entire GA range  for singleton births, boys consistently exhibited higher birth weights than girls at each GA. For instance, at the 50th percentile, boys had a mean birth weight of 3634 g, which was, on average, 158 g higher than that of girls (3476 g). The difference in birth weight between the sexes increased as the pregnancy progressed, with the smallest difference observed in the 3rd percentile . At the 97th percentile, the differences were most pronounced, with an 88 g gap at 23 weeks of gestation and a 190 g gap at 42 weeks of gestation .For babies born at 40 weeks of gestation in the Polish population, the birth weight values at the 3rd, 5th, 10th, 50th, 90th, 95th, and 97th percentiles were higher compared to both the IG-21 and the WHO standards. Between 2010 and 2015, which coincides with the IG-21 and WHO studies, boys born at 40 weeks of gestation in Poland had a birth weight of 3.60 kg at the 50th percentile, which was 0.22 kg higher than the IG-21 standard and 0.08 kg higher than the WHO standard. In girls, the birth weight at the 50th percentile was 3.44 kg, which was 0.18 kg higher than the IG-21 standard and 0.11 kg higher than the WHO standard .97th in boys. The most significant weight gain occurred in the SGA3rd–10th percentiles, with the lowest increase seen in the SGA3rd percentiles for both boys (81 g) and girls (85 g) compared to SGA5th  and SGA10th . The weight gain for the 50th percentile was about half that of SGA3rd (39 g for boys and 45 g for girls). In the LGA90th–97th percentiles, the growth was slower compared to the other percentiles . The range between the 10th and 90th percentiles was 1061 g for boys and 1016 g for girls. Over the analyzed decade, the values of birth weight from SGA3rd and SGA10th by 190 g, and for girls by 150 g and 160 g, respectively, and for boys in LGA90th and LGA97th by 230 g and 240 g, and for girls by 180 g and 190 g, respectively. Similarly, when compared to the WHO standard, the birth weight for Polish newborns at 40 weeks was higher for both sexes in SGA5th by 40 g, and in LGA95th by 90 g. These discrepancies lead us to believe that the global standards may not be adequately adapted to the Polish context, and other authors have also raised doubts regarding the discrepancies in birth weight values [Our results indicate that, compared to the global IG-21 standard, the birth weight of Polish newborns born at 40 weeks of gestation (in period 2010–2015) was higher for boys in SGAt values ,32,33. HThe percentile birth weight of Polish newborns was consistently higher when compared to the IG-21 and the WHO standards for low-risk populations, although our population was not entirely ideal. We included less strict criteria to reduce high-risk pregnancies, but this approach did not eliminate the maternal and fetal health burden. One possible explanation for these differences is the existence of geographical and regional variations in genetic characteristics, maternal phenotype, and physiology that can influence the course of pregnancy and fetal growth . FurtherIt is essential to emphasize that the Polish population is ethnically homogeneous, and this factor could have played an important role in the observed differences in birth weight when compared to Poland and the multiethnic populations used in the IG-21 and the WHO standards. Additionally, our analysis covered the stable period of 2010–2019, which is suitable for assessing weight percentiles due to stable health conditions. During this time, there was no significant mass influx of refugees from neighboring countries, which could introduce variations in health characteristics among pregnant women.We also believe that the higher weight percentile values of Polish newborns may be attributed to specific factors such as socio-economic status, environment, and medical care, which can influence the health conditions of women of reproductive age and pregnant women. These conditions are generally related to the level of economic development in different countries. This is evident in the visible differences in newborn birth weights among high-income countries, such as Sweden (3623 g), the Netherlands (3542 g), Ireland (3514 g), and the USA (3502 g), compared to low-income countries, such as Bhutan (3210 g) and India (3055 g) .Moreover, there is evidence that geographical settings may play a role in the similarity of birth weights among neighboring countries. For example, a study in Germany  reportedAn analysis of the 10-year changes in percentile birth weight in Poland showed an increase in median birth weight in 2019 compared to 2010. For boys, the median birth weight increased by 39 g, from 3634 to 3595 g, and for girls, it increased by 45 g, from 3476 to 3431 g. These results are consistent with other studies conducted in high-income countries, which also reported similar upward trends in birth weight since the end of the last century ,41. The This is the first study to present birth weight percentiles according to GA for single births based on the entire Polish population. The use of a national registry of all live births, encompassing 3.7 million births, is a significant strength of this study, as it allowed for the analysis of birth weight for GA among preterm infants, which might be underrepresented in other studies . FurtherHowever, it is important to consider certain limitations when interpreting the study’s findings. The retrospective nature of the data used for the analysis limited the ability to examine factors related to adverse birth weight outcomes. For example, maternal chronic diseases like hypertension and gestational diabetes mellitus, which can affect fetal growth and the duration of pregnancy, were not included in the analysis . It is pOur study may have certain limitations related to the methodology used for collecting information on GA. It is important to note that the GA data relied on available information from official records in obstetric care, and the assessment of GA was conducted using either the LMP method or ultrasound. Therefore, the results should be interpreted with caution. It is worth mentioning that similar challenges in GA assessment have been encountered in other research studies ,54. To aAn additional difficulty in interpreting our findings is the variations in the SGA and LGA cut-off values among different studies. The IG-21 study describes the 3rd, 10th, 50th, 90th, and 97th percentiles, while the WHO study employs the 5th, 50th, 90th, and 95th percentiles.Despite these acknowledged limitations, we firmly believe that our current study, based on a large sample size, serves as a valuable Polish reference that can enhance the assessment of newborns and be beneficial to clinicians in their practice.In this article, we have established a comprehensive reference of percentiles and curves for birth weight, utilizing a large population-based dataset of newborns from singleton deliveries in Poland over the period 2010–2019. Our research demonstrates that the birth weight of Polish neonates surpasses the global standards set by the IG-21 and the WHO, especially when compared to populations from countries with differing levels of economic development to Poland.The findings of this study hold clinical significance as they can aid in the identification of newborns who require close monitoring during the immediate postnatal period. Additionally, they offer an opportunity to proactively prevent short-term and long-term adverse health outcomes. The reference values described by us can be used as a basis for testing in various SGA or LGA risk groups.