Reduced fetal cerebral blood flow predicts perinatal mortality in a mouse model of prenatal alcohol and cannabinoid exposure.

BACKGROUND: Children exposed prenatally to alcohol or cannabinoids individually can exhibit growth deficits and increased risk for adverse birth outcomes. However, these drugs are often co-consumed and their combined effects on early brain development are virtually unknown. The blood vessels of the fetal brain emerge and mature during the neurogenic period to support nutritional needs of the rapidly growing brain, and teratogenic exposure during this gestational window may therefore impair fetal cerebrovascular development. STUDY DESIGN: To determine whether prenatal polysubstance exposure confers additional risk for impaired fetal-directed blood flow, we performed high resolution in vivo ultrasound imaging in C57Bl/6J pregnant mice. After pregnancy confirmation, dams were randomly assigned to one of four groups: drug-free control, alcohol-exposed, cannabinoid-exposed or alcohol-and-cannabinoid-exposed. Drug exposure occurred daily between Gestational Days 12-15, equivalent to the transition between the first and second trimesters in humans. Dams first received an intraperitoneal injection of either cannabinoid agonist CP-55,940 (750 µg/kg) or volume-equivalent vehicle. Then, dams were placed in vapor chambers for 30 min of inhalation of either ethanol or room air. Dams underwent ultrasound imaging on three days of pregnancy: Gestational Day 11 (pre-exposure), Gestational Day 13.5 (peri-exposure) and Gestational Day 16 (post-exposure). RESULTS: All drug exposures decreased fetal cranial blood flow 24-hours after the final exposure episode, though combined alcohol and cannabinoid co-exposure reduced internal carotid artery blood flow relative to all other exposures. Umbilical artery metrics were not affected by drug exposure, indicating a specific vulnerability of fetal cranial circulation. Cannabinoid exposure significantly reduced cerebroplacental ratios, mirroring prior findings in cannabis-exposed human fetuses. Post-exposure cerebroplacental ratios significantly predicted subsequent perinatal mortality (p = 0.019, area under the curve, 0.772; sensitivity, 81%; specificity, 85.70%) and retroactively diagnosed prior drug exposure (p = 0.005; AUC, 0.861; sensitivity, 86.40%; specificity, 66.7%). CONCLUSIONS: Fetal cerebrovasculature is significantly impaired by exposure to alcohol or cannabinoids, and co-exposure confers additional risk for adverse birth outcomes. Considering the rising potency and global availability of cannabis products, there is an imperative for research to explore translational models of prenatal drug exposure, including polysubstance models, to inform appropriate strategies for treatment and care in pregnancies affected by drug exposure.

The Implications of Socioeconomic Status by ZIP Code on Maternal-Fetal Morbidity and Mortality in San Antonio, Texas.

Introduction Over the past 20 years, the number of pregnancy-related fatalities in the United States has been on the rise. Increases in maternal and fetal mortality have been attributed to low socioeconomic status (SES). This raises the question of whether all geographical locations are proportionally affected by this upward trend in pregnancy-related fatalities. San Antonio is one of the largest cities in the United States and is known for its economic segregation. This study aims to compare the maternal and fetal health outcomes of mothers from diverse socioeconomic backgrounds in San Antonio, Texas. Methods To analyze the relationship between pregnancy-related mortality rates and SES in San Antonio, Texas, the International Classification of Diseases (ICD)-10 codes for maternal and fetal demise and their associated risk factors were identified. The ICD-10 codes were used to compare the health outcomes of pregnant women from the highest SES ZIP Code (78255, median income $124,397) to women from the lowest SES ZIP Code (78207, median income $25,415) using the Texas Inpatient Public Use Data File for 2016, which contains information on 93-97% of all hospital discharges in San Antonio, Texas. Results Notably, pregnant women from the high SES ZIP Code were admitted to the hospital from clinics or a physician's office (68.8%), while pregnant women from the low SES ZIP Code were admitted to the hospital from non-healthcare facilities like home or workplace (62.5%). In addition, a greater percentage of patients from the low SES ZIP Code were Black (4.3% vs 1.3%) or Hispanic (88.5% vs 35.1%). Compared to women from the high SES ZIP Code, women from the low SES ZIP Code experienced more fetal deaths and a higher prevalence of maternal and fetal risk factors such as obesity (47.6% vs 32.5%), asthma (1.7% vs 1.3%), hypertension (0.8% vs 0%), substance abuse (0.5% vs 0%), diabetes mellitus (9.8% vs 7.8%), preeclampsia (7.7% vs 2.6%), and multiple C-sections (35.5% vs 28.6%). Finally, fetal mortality rates were higher in the low SES ZIP Code (1.1% vs 0%). Although there were no statistically significant maternal or fetal mortality differences between the ZIP Codes, the trend suggests that women's health outcomes in San Antonio are not equitable. Discussion Analysis reveals disproportionate health outcomes for women in south San Antonio. Further investigation is warranted to better understand the role social and medical factors play in these results. Investigating the relationship between SES and pregnancy-related mortality can help to better inform healthcare providers and identify ways to improve women's health outcomes in San Antonio, Texas.

Adverse pregnancy, fetal and neonatal outcomes in women with sickle cell disease in a Middle Eastern country.

BACKGROUND: Sickle cell disease in pregnancy is associated with high maternal and fetal mortality. However, studies reporting pregnancy, fetal, and neonatal outcomes in women with sickle cell disease are extremely limited. OBJECTIVES: The objectives of the study are to determine whether women with sickle cell disease have a greater risk of adverse pregnancy, fetal, and neonatal outcomes than women without sickle cell disease and identify the predictors of adverse pregnancy, fetal, and neonatal outcomes in women with sickle cell disease. DESIGN: A retrospective pair-matched case-control study was conducted to compare 171 pregnant women with sickle cell disease to 171 pregnant women without sickle cell disease in Muscat, Sultanate of Oman. METHODS: All pregnant Omani women with sickle cell disease who delivered between January 2015 and August 2021 at Sultan Qaboos University Hospital and Royal Hospital, who were either primipara or multipara and who had a gestational age of 24-42 weeks, were included as patients, whereas women who had no sickle cell disease or any comorbidity during pregnancy, who delivered within the same timeframe and at the same hospitals, were recruited as controls. The data were retrieved from electronic medical records and delivery registry books between January 2015 and August 2021. RESULTS: Women with sickle cell disease who had severe anemia had increased odds of (χ2 = 58.56, p < 0.001) having adverse pregnancy outcomes. Women with sickle cell disease had 21.97% higher odds of delivering a baby with intrauterine growth retardation (χ2 = 17.80, unadjusted odds ratio = 2.91-166.13, p < 0.001). Newborns born to women with sickle cell disease had 3.93% greater odds of being admitted to the neonatal intensive care unit (χ2 = 16.80, unadjusted odds ratio = 1.97-7.84, p < 0.001). In addition, the children born to women with sickle cell disease had 10.90% higher odds of being born with low birth weight (χ2 = 56.92, unadjusted odds ratio = 5.36-22.16, p < 0.001). Hemoglobin level (odds ratio = 0.17, p < 0.001, 95% confidence interval = 0.10-3.0), past medical history (odds ratio = 7.95, p < 0.001, 95% confidence interval = 2.39-26.43), past surgical history (odds ratio = 17.69, p < 0.001, 95% confidence interval = 3.41-91.76), and preterm delivery (odds ratio = 9.48, p = 0.005, 95% confidence interval = 1.95-46.23) were identified as predictors of adverse pregnancy, fetal, and neonatal outcomes in women with sickle cell disease. CONCLUSION: As pregnant women with sickle cell disease are at increased risk for pregnancy, fetal, and neonatal adverse outcomes; improved antenatal surveillance and management may improve the outcomes.

Outcomes of liver diseases in pregnant females: A study from a tertiary care medical center in Pakistan.

Objective: To determine the etiologies and outcomes of liver disease in pregnancy in a developing country. Method: A total of 336 consecutive pregnant women with liver disease were included in this prospective cohort study conducted at the Department of Gastroenterology, Jinnah Postgraduate Medical Center, Karachi from August 2019 to August 2021. Patients' baseline demographic, clinical, and laboratory data and outcomes were collected on a pre-designed questionnaire. Results: Among all the pregnant females, the most common liver disease was acute hepatitis E virus (HEV) infection (37.2%), followed by preeclampsia (PEC)/eclampsia (EC), hemolysis, elevated liver enzymes & low platelets (HELLP) syndrome, and hyperemesis gravidarum (HG). The most common maternal complications were fulminant hepatic failure (FHF) in 14.9% and placental abruption in 11.0%. Fetal complications included intrauterine death (IUD) in 20.8% and preterm birth in 8.6%. The maternal and neonatal mortality rates were 11.6% and 39.6%, respectively. Among the predictors, low maternal weight, low body mass index (BMI), and low hemoglobin (Hb) were associated with increased maternal mortality. Low fetal weight, height, maternal systolic blood pressure (SBP), and low maternal Hb were independent predictors of fetal mortality. Conclusion: In our cohort of pregnant females in a tertiary care medical center, acute HEV was the most common liver disease, followed by PEC/EC, HELLP, and HG. Maternal and fetal deaths were alarming in this group of patients and demanded careful management.

Neurological disorders in pregnant women in low- and middle-income countries-Management gaps, impacts, and future prospects: A review perspective.

Neurological disorders during pregnancy are a substantial threat to women's health, particularly in low- and middle-income countries. Furthermore, a critical shortage of mental health workers and neurologists exacerbates the already pressing issue, where a lack of coordination of respective healthcare among multidisciplinary teams involved in managing these conditions perpetuates the current state of affairs. Financial restrictions and societal stigmas associated with neurological disorders in pregnancy amplify the situation. Addressing these difficulties would necessitate a multifaceted approach comprising investments in healthcare infrastructure, healthcare professional education and training, increased government support for research, and the implementation of innovative care models. Improving access to specialized treatment and coordinated management of antenatal neurological diseases will precipitate improved health outcomes for women and their families in low- and middle-income countries.

Maternal diaphragmatic hernia in pregnancy: A systematic review with a treatment algorithm.

BACKGROUND: Diaphragmatic hernia (DH) is extremely rarely described during pregnancy. Due to the rarity, there is no diagnostic or treatment algorithm for DH in pregnancy. AIM: To summarize and define the most appropriate diagnostic methods and therapeutic options for DH in pregnancy based on scarce literature. METHODS: Literature search of English-, German-, Spanish-, and Italian-language articles were performed using PubMed (1946-2021), PubMed Central (1900-2021), and Google Scholar. The PRISMA protocol was followed. The search terms included: Maternal diaphragmatic hernia, congenital hernia, pregnancy, cardiovascular collapse, mediastinal shift, abdominal pain in pregnancy, hyperemesis, diaphragmatic rupture during labor, puerperium, hernie diaphragmatique maternelle, hernia diafragmática congenital. Additional studies were identified by reviewing reference lists of retrieved studies. Demographic, imaging, surgical, and obstetric data were obtained. RESULTS: One hundred and fifty-eight cases were collected. The average maternal age increased across observed periods. The proportion of congenital hernias increased, while the other types appeared stationary. Most DHs were left-sided (83.8%). The median number of herniated organs declined across observed periods. A working diagnosis was correct in 50%. DH type did not correlate to maternal or neonatal outcomes. Laparoscopic access increased while thoracotomy varied across periods. Presentation of less than 3 days carried a significant risk of strangulation in pregnancy. CONCLUSION: The clinical presentation of DH is easily confused with common chest conditions, delaying the diagnosis, and increasing maternal and fetal mortality. Symptomatic DH should be included in the differential diagnosis of pregnant women with abdominal pain associated with dyspnea and chest pain, especially when followed by collapse. Early diagnosis and immediate intervention lead to excellent maternal and fetal outcomes. A proposed algorithm helps manage pregnant women with maternal DH. Strangulated DH requires an emergent operation, while delivery should be based on obstetric indications.

Umbilical Cord Diseases Affecting Obstetric and Perinatal Outcomes.

BACKGROUND: (1) The aim of this article is to describe the physiopathology underlying umbilical cord diseases and their relationship with obstetric and perinatal outcomes. (2) Methods: Multicenter case series of umbilical cord diseases with illustrations from contributing institutions are presented. (3) Results: Clinical presentations of prenatal ultrasound findings, clinical prenatal features and postnatal outcomes are described. (4) Conclusions: Analysis of our series presents and discusses how umbilical cord diseases are associated with a wide variety of obstetric complications leading to a higher risk of poor perinatal outcomes in pregnancies. Knowing the physiopathology, prenatal clinical presentations and outcomes related to umbilical diseases allow for better prenatal counseling and management to potentially avoid severe obstetric and perinatal complications.

Prevalence and risk of stillbirth according to biologic vulnerability phenotypes in the municipality of São Paulo, Brazil: A population-based cohort study.

OBJECTIVE: To estimate the prevalence and risk of stillbirths by biologic vulnerability phenotypes in a cohort of pregnant women in the municipality of São Paulo, Brazil, 2017-2019. METHODS: Retrospective population-based cohort study. Fetuses were assessed as small for gestational age (SGA), large for gestational age (LGA), adequate for gestational age (AGA), preterm (PT) as less than 37 weeks of gestation, non-PT (NPT) as 37 weeks of gestation or more, low birth weight (LBW) as less than 2500 g, and non-LBW (NLBW) as 2500 g or more. Relative risks (RR) with robust variance were estimated using Poisson regression. RESULTS: In all 442 782 pregnancies, including 2321 (0.5%) stillbirths, were included. About 85% (n = 1983) of stillbirths had at least one characteristic of vulnerability, compared with 21% (n = 92524) of live births. Fetuses with all three markers of vulnerability had the highest adjusted RR of stillbirth-SGA + LBW + PT (RR 155.00; 95% confidence interval [CI] 136.29-176.30) and LGA + LBW + PT (RR 262.04; 95% CI 206.10-333.16) when compared with AGA + NLBW + NPT. CONCLUSION: Our findings show that the simultaneous presence of prematurity, low birth weight, and abnormal intrauterine growth presented a higher risk of stillbirths. To accelerate progress towards reducing preventable stillbirths, one must identify the circumstances of greatest biologic vulnerability.

DeepCTG® 1.0: an interpretable model to detect fetal hypoxia from cardiotocography data during labor and delivery.

Introduction: Cardiotocography, which consists in monitoring the fetal heart rate as well as uterine activity, is widely used in clinical practice to assess fetal wellbeing during labor and delivery in order to detect fetal hypoxia and intervene before permanent damage to the fetus. We present DeepCTG® 1.0, a model able to predict fetal acidosis from the cardiotocography signals. Materials and methods: DeepCTG® 1.0 is based on a logistic regression model fed with four features extracted from the last available 30 min segment of cardiotocography signals: the minimum and maximum values of the fetal heart rate baseline, and the area covered by accelerations and decelerations. Those four features have been selected among a larger set of 25 features. The model has been trained and evaluated on three datasets: the open CTU-UHB dataset, the SPaM dataset and a dataset built in hospital Beaujon (Clichy, France). Its performance has been compared with other published models and with nine obstetricians who have annotated the CTU-UHB cases. We have also evaluated the impact of two key factors on the performance of the model: the inclusion of cesareans in the datasets and the length of the cardiotocography segment used to compute the features fed to the model. Results: The AUC of the model is 0.74 on the CTU-UHB and Beaujon datasets, and between 0.77 and 0.87 on the SPaM dataset. It achieves a much lower false positive rate (12% vs. 25%) than the most frequent annotation among the nine obstetricians for the same sensitivity (45%). The performance of the model is slightly lower on the cesarean cases only (AUC = 0.74 vs. 0.76) and feeding the model with shorter CTG segments leads to a significant decrease in its performance (AUC = 0.68 with 10 min segments). Discussion: Although being relatively simple, DeepCTG® 1.0 reaches a good performance: it compares very favorably to clinical practice and performs slightly better than other published models based on similar approaches. It has the important characteristic of being interpretable, as the four features it is based on are known and understood by practitioners. The model could be improved further by integrating maternofetal clinical factors, using more advanced machine learning or deep learning approaches and having a more robust evaluation of the model based on a larger dataset with more pathological cases and covering more maternity centers.

Defined, low threshold for caesarean section and multidisciplinary team management improves fetal outcome from acute pancreatitis in pregnancy.

BACKGROUND: Acute pancreatitis in pregnancy (APIP) is associated with increased maternal and fetal mortality. OBJECTIVES: We sought to determine whether a low threshold for cesarean section (C-section) in severe acute pancreatitis (SAP) or Predict SAP improves maternal and fetal outcomes in patients with APIP. METHODS: We identified patients with APIP at a single institution from a prospective database and studied fetal and maternal health in APIP before (2005-2014) and after (2015-2019) introduction of multidisciplinary team management with a defined, lowered threshold for C-section. The primary end point was fetal mortality comprising abortion and perinatal death. Risk factors associated with fetal mortality were analyzed by univariable and multivariable logistic regression analysis. RESULTS: A total of 165 patients with APIP were eligible for analysis. There was a highly significant increase in patients undergoing C-section from 37 (30.8%) of 120 during 2005-2014 to 27 (60%) of 45 in 2015-2019 (P = 0.001), with a highly significant fall in fetal mortality from 37 (30.8%) of 120 to 3 (6.7%) of 45 between the same periods (P = 0.001), when maternal mortality fell from 6 to zero (P = 0.19). Maternal early systemic inflammatory response syndrome (SIRS) (odds ratio [OR] 6.98, 95% confidence interval [CI] 1.53, 30.80, P = 0.01) and SAP (OR 3.64, 95%CI 1.25, 10.60, P = 0.02) were two independent risk factors associated with fetal mortality. CONCLUSIONS: Multidisciplinary collaboration and a defined, low threshold for C-section improve fetal outcomes in patients with APIP.

Padrões espaciais da mortalidade fetal e carência social no estado de Pernambuco, Brasil / Spatial patterns of fetal mortality and social deprivation in the state of Pernambuco, Brazil / Estándares espaciales de mortalidad fetal y privación social en el estado de Pernambuco, Brasil

A mortalidade fetal é um indicador da assistência obstétrica e de condições de vida capaz de refletir o estado de saúde da mulher e a qualidade e a acessibilidade dos cuidados no pré-natal e na assistência intraparto. Com o objetivo de analisar os padrões espaciais da mortalidade fetal, a evitabilidade dos óbitos e a carência social no estado de Pernambuco, foi realizado um estudo ecológico considerando municípios, regiões de saúde e mesorregiões como unidades de análise. Incluíram-se os óbitos fetais registrados no Sistema de Informação sobre Mortalidade no período de 2010 a 2017. Classificou-se a evitabilidade dos óbitos pela Lista Brasileira de Causas de Mortes Evitáveis por Intervenções do Sistema Único de Saúde. Aplicou-se a estatística descritiva e o teste qui-quadrado para comparação de proporções das causas de morte. Na elaboração do índice de carência social, utilizou-se a técnica de análise fatorial por componentes principais com o teste de esfericidade de Bartlett para identificar a matriz de correlação. Com o índice calculado, os municípios foram agrupados em estratos de carência social pela técnica de k-means. Foram aplicadas a análise bayesiana e a estatística espacial de Moran para identificação de áreas prioritárias de mortalidade fetal e do índice de carência social. Registraram-se 12.337 óbitos fetais, sendo 8.927 (72,3%) por causas evitáveis. As variáveis idade da mãe, número de filhos mortos, tipo de gravidez, tipo de parto e peso ao nascer estiveram relacionadas à evitabilidade do óbito. Na construção do índice de carência social, o teste de esfericidade de Bartlett (χ² de 144,463; p < 0,01) e o coeficiente KMO (0,8) mostraram que as correlações entre os itens eram adequadas para a análise fatorial, assim como as correlações entre os indicadores. O índice de carência social indicou dois fatores que, juntos, explicaram 77,63% da variância total. A taxa de mortalidade fetal evitável apresentou aumento entre estratos de carência social, com taxas de 7,99 por mil nascimentos (baixa carência), 8,06 por mil (média carência), 8,83 por mil (alta carência) e 10,7 por mil (muito alta carência). O índice global de Moran verificou autocorrelação espacial significativa para a taxa de mortalidade fetal bayesiana (I = 0,10; p = 0,05), para a taxa de mortalidade fetal evitável bayesiana (I = 0,13; p = 0,03) e para o índice de carência social (I = 0,53; p = 0,01). Alguns municípios das mesorregiões do São Francisco e do Sertão Pernambucano tiveram simultaneamente elevada mortalidade fetal e mortalidade fetal evitável, além de índice de carência social muito alto. A análise espacial identificou áreas com maior risco para a mortalidade fetal. O índice de carência social relacionou alguns determinantes das mortes fetais em áreas com piores condições de vida. Detectaram-se áreas prioritárias para a intervenção de políticas públicas de redução da mortalidade fetal e seus determinantes.

Fetal mortality is an indicator of obstetric care and living conditions, capable of reflecting the state of women's health and the quality and accessibility of prenatal care and intrapartum care. To analyze the spatial patterns of fetal mortality, preventability of deaths, and social deprivation in the state of Pernambuco, an ecological study was carried out considering municipalities, health regions, and mesoregions as units of analysis. Fetal deaths registered in the Mortality Information System in the period from 2010 to 2017 were included. The deaths are classified as preventable by the Brazilian List of Causes of Preventable Deaths by Interventions of the Unified Health System. Descriptive statistics and the Qui-square test were applied for comparisons of proportions of causes of death. In the elaboration of the social deprivation index, the factorial analysis technique by principal components with the Bartlett's sphericity test was used to identify the correlation matrix. With the calculated index, the municipalities were grouped in social deprivation strata by the k-means technique. Bayesian analysis and Moran's spatial statistics were applied to identify priority areas of fetal mortality and the index of social deprivation. There were 12,337 fetal deaths registered, of which 8,927 (72.3%) were due to preventable causes. The variables of mother's age, number of dead children, type of pregnancy, type of birth, and weight at birth were related to preventability of death. In the construction of the social deprivation index, Bartlett's sphericity test (χ² of 144.463; p < 0.01) and the KMO coefficient (0.8) showed that the correlations between the items were adequate for factor analysis, as well as the correlations between the indicators. The social deprivation index pointed to two factors that, together, explained 77.63% of the total variance. The rate of preventable fetal mortality showed an increase among social deprivation strata, with rates of 7.99 per thousand births (low deprivation), 8.06 per thousand (medium deprivation), 8.83 per thousand (high deprivation), and 10.7 per thousand (very high social deprivation). The global Moran index verified significant spatial autocorrelation for the Bayesian fetal mortality rate (I = 0.10; p = 0.05), for the Bayesian preventable fetal mortality rate (I = 0.13; p = 0.03) e for the o social deprivation index (I = 0.53; p = 0.01). Some municipalities of the mesoregions of São Francisco and of Sertão of Pernambuco have simultaneously high fetal mortality and preventable fetal mortality, in addition to a very high rate of social deprivation. The spatial analysis identified areas with the highest risk for fetal mortality. The index of social deprivation relates to some determinants of fetal deaths in areas with the worst living conditions. We detected priority areas for the intervention of public policies to reduce fetal mortality and its determinants.

La mortalidad fetal es un indicador de la asistencia obstétrica y de las condiciones de vida capaz de reflejar el estado de salud de la mujer y la cualidad y accesibilidad de los cuidados en el prenatal y la asistencia intraparto. Con el objetivo de analizar los estándares espaciales de la mortalidad fetal, la evitabilidad de los fallecimientos y la privación social del estado de Pernambuco (Brasil), se realizó un estudio ecológico con los municipios, las regiones de salud y las mesorregiones como unidades de análisis. Se incluyeron los fallecimientos fetales registrados en el Sistema de Información sobre Mortalidad en el período de 2010 a 2017. Se clasificó la evitabilidad de los fallecimientos desde la Lista Brasileña de Causas de Muertes Evitables por Intervenciones en el Sistema Único de Salud. Se aplicaron la estadística descriptiva y la prueba de chi-cuadrado para comparar las proporciones de las causas de muerte. En la elaboración del índice de privación social, se utilizó la técnica de análisis factorial por componentes principales con la prueba de esfericidad de Bartlett para identificar la matriz de correlación. Con el índice calculado, los municipios se agruparon en estados de privación desde la herramienta de k-means. Se aplicaron el análisis bayesiano y la estadística espacial de Moran para identificar las áreas prioritarias de la mortalidad fetal y el índice de privación social. Se registraron 12.337 fallecimientos fetales, de los cuales 8.927 (72,3%) fueron por causas evitables. Las variables edad de la madre, número de hijos muertos, tipo de embarazo, tipo de parto y peso al nacer estuvieron relacionadas con la evitabilidad del fallecimiento. En la construcción del índice de privación social, la prueba de esfericidad de Bartlett (χ² de 144,463; p < 0,01) y el coeficiente de KMO (0,8) mostraron que las correlaciones entre los ítems estaban adecuadas para el análisis factorial, así como las correlaciones entre los indicadores. El índice de privación social señaló a dos factores que juntos explican el 77,63% de la variancia total. La tasa de mortalidad fetal evitable tuvo un aumento entre los estados de privación social, con tasas de 7,99 por mil nacimientos (baja privación), 8,06 por mil (mediana privación), 8,83 por mil (alta privación) y 10,7 por mil (muy alta privación). El índice global de Moran evaluó la autocorrelación espacial significativa para la tasa de mortalidad fetal bayesiana (I = 0,10; p = 0,05), para la tasa de mortalidad fetal evitable bayesiana (I = 0,13; p = 0,03) y para el índice de privación social (I = 0,53; p = 0,01). Algunos municipios de las mesorregiones de São Francisco y de Sertão Pernambucano tuvieron alta mortalidad fetal, además del índice de privación social muy alto. Un análisis espacial identificó áreas con mayor riesgo de mortalidad fetal. El índice de privación social relacionó algunas de las causas de las muertes fetales en áreas con peores condiciones de vida. Se detectaron las áreas prioritarias a la intervención de las políticas públicas para reducir la mortalidad fetal y sus determinantes.

Temporal Trends in Stillbirth in Greece: A Longitudinal Population-Based Study.

INTRODUCTION: Stillbirths are a major public health issue and a key population health indicator. The aim of this study was to comprehensively investigate and present time trends in stillbirth in Greece. METHODS: Data on all live births and stillbirths were derived from the Hellenic Statistical Authority, covering a 65-year period from 1957 to 2021 and the annual stillbirth rate (SBR) was calculated, defined as the number of stillbirths per 1,000 live births and stillbirths (total births). Trends in the SBR were assessed using joinpoint regression analysis with calculation of the annual percent change (APC) with a 95% confidence interval (95% CI) and level of statistical significance p<0.05. RESULTS: The SBR in Greece, after an initial increasing trend (1957-1965: APC=2.6, 95% CI: 0.5 to 4.7, p=0.016), and an all-time high of 15.8 per 1,000 births in 1966, recorded a four decades period of continuous improvement (1965-2003: APC=3.0, 95% CI: -3.2 to -2.8, p<0.001) and reached a historic low in 2008 (3.3 per 1,000 births) (a decrease by 79%). However, the SBR stagnated at an elevated level during the decade 2006-2016 and showed a steeply upward trend during the most recent period 2016-2021 (APC=7.4, 95% CI: 3.0 to 12.1, p=0.001). In 2021, the SBR was 5.3 per 1,000 births, 60% up from 2008. It was estimated that the SBR improvement for the 1967-2021 period resulted in 50,914 stillbirths averted (7.9 per 1,000 births), but the recent increase in the SBR has led to 1,200 additional fetal deaths (1.0 per 1,000 births) during 2009-2021. CONCLUSION: After an impressive decline for almost four decades the SBR gradually deteriorated during the economic crisis and finally showed an alarming rising trend after 2015, resulting in an increasing burden of fetal deaths in Greece. Further public health interventions are needed to address preventable risk factors and ensure access to optimized antenatal monitoring.

Prevalence and Mode of Birth in Late Fetal Mortality in Spain, 2016-2019.

(1) Background: The rate of cesarean sections in late fetal mortality remains high. We aimed to determine the prevalence of late fetal mortality in Spain and risk factors for cesarean birth in women with stillbirth ≥ 28 weeks gestation between 2016-2019. (2) Methods: A retrospective observational study with national data between 2016-2019. A total of 3504 births with fetal dead were included. Sociodemographic, obstetrical and neonatal variables were analyzed using univariate and multivariate logistic regression (MLR), with cesarean birth with a stillborn ≥ 28 weeks gestation as the dependent variable. (3) Results: The late fetal mortality rate was 2.8 × 1000; 22.7% of births were by cesarean section. Factors associated with cesarean were having a multiple birth (aOR 6.78); stillbirth weight (aOR 2.41); birth taking place in towns with over 50,000 inhabitants (aOR 1.34); and mother's age ≥ 35 (aOR 1.23). (4) Conclusions: The late fetal mortality rate increased during the period. The performance of cesarean sections was associated with the mother's age, obstetric factors and place of birth. Our findings encourage reflection on how to best put into practice national clinical and socio-educational prevention strategies, as well as the approved protocols on how childbirth should be correctly conducted.

Mortalidade fetal em gestantes com COVID-19 e outros desfechos materno-fetais: uma revisão integrativa da literatura / Fetal mortality in pregnant women with COVID-19 and other maternal-fetal outcomes: an integrative literature review

Objetivo: Analisar os resultados apresentados sobre a relação entre COVID-19 e gravidez, com foco no desfecho fetal. Fontes dos dados: Foi realizada a busca de artigos publicados entre 1 de janeiro de 2020 e 1 de junho de 2021 nas bases de dados PubMed, Embase e Cochrane, utilizando os seguintes descritores: "coronavirus infections", "coronavirus disease 2019", "COVID-19", "fetal mortality" e "fetus mortality". Seleção dos estudos: Foram encontrados 99 artigos, sendo selecionados 28 artigos para leitura completa por meio dos critérios de inclusão e exclusão. Ao final, 14 artigos foram escolhidos para serem incluídos na presente revisão. Coleta de dados: Para a extração dos dados dos artigos selecionados, utilizou-se o instrumento validado por Ursi (2005), modificado para se adequar à demanda do tema em questão. Síntese dos dados: Encontrou-se que a infecção por COVID-19 aumentou a morbimortalidade das gestantes, principalmente aquelas que já possuíam algum fator de risco para a doença grave. Além disso, a maioria dos estudos mostrou uma taxa aumentada de nascimentos prematuros entre os filhos de mães infectadas. Não foram demonstrados resultados consistentes de aumento nas taxas de aborto, mortalidade fetal ou transmissão vertical. Conclusão: Ações de saúde devem priorizar o cuidado materno-fetal com o objetivo de prevenir a doença nas gestantes e acompanhar de forma mais cuidadosa aquelas infectadas pelo vírus, de forma a prevenir a morbimortalidade materna e a prematuridade, que são importantes marcadores de saúde pública.(AU)

Objective: To analyze the results presented on the relationship between COVID-19 and pregnancy, focusing on fetal outcome. Data sources: We searched for articles published between January 1, 2020 and June 1, 2021 in PubMed, Embase and Cochrane databases, using the following descriptors: "coronavirus infections", "coronavirus disease 2019", "COVID-19", "fetal mortality" and "fetus mortality". Selection of studies: 99 articles were found, and 28 articles were selected for full reading through inclusion and exclusion criteria. In the end, 14 articles were chosen to be included in this review. Data collection: To extract data from selected articles, the instrument validated by Ursi (2005) was used, modified to suit the demand of the topic in question. Data synthesis: It was found that COVID-19 infection increased the morbidity and mortality of pregnant women, especially those who already had some risk factor for severe disease. In addition, most studies have shown an increased rate of preterm births among children of infected mothers. No consistent results of increased rates of miscarriage, fetal mortality or mother-to-child transmission have been demonstrated. Conclusion: Health actions should prioritize maternal- fetal care in order to prevent the disease in pregnant women and more carefully monitor those infected with the virus, in order to prevent maternal morbidity and mortality and prematurity, which are important public health markers.(AU)

Investigation of stillbirths in Brazil: A systematic scoping review of the causes and related reporting processes in the past decade.

BACKGROUND: Recognizing the causes of stillbirths and their associated conditions is essential to reduce its occurrence. OBJECTIVE: To describe information on stillbirths in Brazil during the past decade. SEARCH STRATEGY: A literature search was performed from January 2010 to December 2020. SELECTION CRITERIA: Original observational studies and clinical trials. DATA COLLECTION AND ANALYSIS: Data were manually extracted to a spreadsheet and descriptive analysis was performed. RESULTS: A total of 55 studies were included; 40 studies (72.2%) used the official data stored by national public health systems. Most articles aimed to estimate the rate and trends of stillbirth (60%) or their causes (55.4%). Among the 16 articles addressing the causes of death, 10 (62.5%) used the International Classification of Diseases; most of the articles only specified the main cause of death. Intrauterine hypoxia was the main cause reported (ranging from 14.3% to 54.9%). CONCLUSION: Having a national system based on compulsory notification of stillbirths may not be sufficient to provide quality information on occurrence and, especially, causes of death. Further improvements of the attribution and registration of causes of deaths and the implementation of educational actions for improving reporting systems are advisable. Finally, expanding the investigation of contributing factors associated with stillbirths would create an opportunity for further development of prevention strategies in low- and middle-income countries such as Brazil.

Relationship between historical developments in the percentages of low birthweight and fetal mortality in Spain.

OBJECTIVE: To document the differences in low birthweight in different population subgroups and to analyze its possible relationship with fetal mortality rates in Spain. METHOD: We used the microdata on live births and stillbirths since 1975 to 2020 from the Spanish National Statistics Institute to examine differentials in delivering a low birthweight controlling for different sociodemographic variables and to determine the relationship between low birthweight and fetal mortality. No statistical analysis was necessary beyond the calculation of percentages and rates. RESULTS: The data at our disposal for Spain confirm the historical increase in the incidence of low birthweight and allow us to link trends in low birthweight with a decrease in the fetal mortality rate. When fetal mortality is high, the incidence of low birthweight is low, given that a natural selection effect takes place. CONCLUSIONS: The surprising historical increase in the incidence of low birthweight in Spain can be explained by the improvement in mortality rates. As more fetuses of lower gestational age are born alive, cases of low birthweight also increase.

Spatial dynamics of fetal mortality and the relationship with social vulnerability.

OBJECTIVES: To analyze the spatial-temporal patterns of fetal mortality according to its relationship with social vulnerability, identifying priority areas for intervention. METHODS: Ecological study conducted in the state of Pernambuco, Northeast region of Brazil, from 2011 to 2018. The mean fetal mortality rate per city was calculated for the studied period. A cluster analysis was performed to select cities with homogeneous characteristics regarding fetal mortality and social vulnerability, then the Attribute Weighting Algorithm and Pearson correlation techniques were employed. In the spatial analysis it was used the local empirical Bayesian modeling and global and local Moran statistics. RESULTS: Twelve thousand nine hundred and twelve thousand fetal deaths were registered. The fetal mortality rate for the period was 11.44 fetal deaths per 1,000 births. The number of groups formed was 7, in which correlation was identified between fetal mortality and dimensions, highlighting the correlations between fetal mortality rate and the Index of Social Vulnerability urban infrastructure for the municipalities in group 1 and 5, the values of the correlations found were 0.478 and 0.674 respectively. The spatial analysis identified areas of higher risk for fetal mortality distributed in regions of medium, high and very high social vulnerability. CONCLUSIONS: The study allowed observing the existing correlations between fetal mortality and social vulnerability and identifying priority areas for intervention, with a view to reducing fetal mortality in the state.

Embarazo abdominal a término con recién nacido vivo sin malformaciones. Reporte de caso: revisión de la bibliografía / Abdominal term pregnancy with a live newborn without malformations. Case report: literature review

Resumen ANTECEDENTES: El embarazo abdominal representa el 1% de los embarazos ectópicos, con una mortalidad materna que puede alcanzar, incluso, hasta el 20% y una mortalidad fetal hasta del 90%. CASO CLÍNICO: Paciente de 31 años, en curso de las 39 semanas del segundo embarazo. El primero se atendió, sin complicaciones, en el domicilio cuando tenía 25 años; enseguida se le indicó, como método anticonceptivo, acetato de medroxiprogesterona inyectable trimestral. Acudió al Hospital Regional Docente de Cajamarca debido a un dolor abdominal luego de siete controles prenatales. Se ingresó al servicio de Obstetricia al tercer día con pródromos de labor de parto, feto en transverso y placenta previa. En la cesárea de urgencia el útero se encontró de 18 cm, la placenta adherida al epiplón, intestino, colon sigmoide, recto y pared izquierda del útero. Se obtuvo una recién nacida con Apgar 8-9, sin malformaciones. Se practicaron: extracción de la placenta, histerectomía abdominal subtotal y salpingooforectomía izquierda. El sangrado intraoperatorio fue de 1800 mL por lo que ameritó la transfusión de dos paquetes globulares. La madre y su hija evolucionaron favorablemente por lo que se dieron de alta del hospital, sin complicaciones. CONCLUSIÓN: El embarazo abdominal es un evento raro, sobre todo si llega a término y con un recién nacido vivo saludable. A pesar de los estudios ultrasonográficos, el embarazo abdominal no es de diagnóstico fácil; por eso casi todos se diagnostican durante la cirugía. Si la placenta no afecta estructuras vasculares extensas, ni órganos abdominopélvicos, podrá retirse, con cuidados extremos, para no originar males mayores.

Abstract BACKGROUND: Abdominal pregnancy represents 1% of ectopic pregnancies, with a maternal mortality that can reach up to 20% and a fetal mortality of up to 90%. CLINICAL CASE: 31-year-old female patient, in the course of 39 weeks of her second pregnancy. The first pregnancy was attended, without complications, at home when she was 25 years old; she was immediately prescribed quarterly injectable medroxyprogesterone acetate as a contraceptive method. She went to the Regional Teaching Hospital of Cajamarca due to abdominal pain after seven prenatal check-ups. She was admitted to the obstetrics service on the third day with prodromes of labor, transverse fetus and placenta previa. In the emergency cesarean section the uterus was found to be 18 cm, the placenta adhered to the omentum, intestine, sigmoid colon, rectum and left wall of the uterus. A newborn was obtained with Apgar 8-9, without malformations. Placental extraction, subtotal abdominal hysterectomy and left salpingo-oophorectomy were performed. Intraoperative bleeding was 1800 mL, which required the transfusion of two packs of red blood cells. The mother and daughter evolved favorably and were discharged from the hospital without complications. CONCLUSION: Abdominal pregnancy is a rare event, especially if it is carried to term with a healthy live newborn. Despite ultrasonographic studies, abdominal pregnancy is not easily diagnosed; therefore almost all are diagnosed during surgery. If the placenta does not affect extensive vascular structures or abdominopelvic organs, it can be removed, with extreme care, so as not to cause greater harm.

Análise espacial da mortalidade fetal por sífilis congênita no Município do Recife-PE-Brasil entre 2007 e 2016 / Análisis espacial de la mortalidad fetal por sífilis congénita en el municipio de Recife-PE-Brasil entre 2007 y 2016 / Spatial analysis of fetal mortality from congenital syphilis in the municipality of Recife-PE-Brazil between 2007 and 2016

Resumo Objetivo analisar a distribuição espacial da mortalidade fetal por sífilis congênita entre os bairros do Município do Recife-PE. Método estudo ecológico, realizado a partir do indicador epidemiológico taxa de mortalidade fetal por sífilis congênita, agregado ao nível dos bairros, em dois quinquênios: 2007 a 2011 e 2012 a 2016. O padrão de autocorrelação espacial foi determinado pelos Índices de Moran Global e Local, com significância estatística inferior a 5% e representado em mapas BoxMap e MoranMap que apontaram as áreas com taxas altas, baixas e em transição epidemiológica e os clusters de maior interesse epidemiológico. Resultados foram notificados 208 óbitos fetais. O Índice Global de Moran evidenciou autocorrelação espacial positiva em grau razoável, no primeiro quinquênio (I = 0,351 e p-valor = 0,01) e, em grau fraco, no segundo quinquênio (I = 0,189 e p-valor = 0,02). Os Distritos Sanitários I e VII obtiveram os maiores percentuais de bairros que formaram o cluster de altas taxas do indicador com 63,3% e 38,4% no primeiro e segundo quinquênios, respectivamente. Conclusões e implicações para a Prática a análise espacial apontou as áreas críticas para ocorrência do indicador, podendo contribuir para o investimento nas áreas prioritárias de prevenção da transmissão vertical da sífilis.

Resumen Objetivo Analizar la distribución espacial de la mortalidad fetal por sífilis congénita entre los barrios de Recife-PE. Método Estudio ecológico, basado en el indicador epidemiológico tasa de mortalidad fetal por sífilis congénita, agregada a nivel de barrio, en dos quinquenios: 2007 a 2011 y 2012 a 2016. El patrón de autocorrelación espacial fue determinado por los Índices Moran Global y Local, con significancia estadística menor al 5% y representados en mapas de BoxMap y MoranMap, que indicaron áreas con tasas de transición alta, baja y epidemiológica y conglomerados de mayor interés epidemiológico. Resultados Notificadas 208 muertes fetales. El Índice Global de Moran mostró un grado razonable de autocorrelación espacial positiva en el primer quinquenio (I = 0,351 y p-valor=0,01) y un grado débil en el segundo quinquenio (I = 0,189 y p-valor=0,02). Los Distritos Sanitarios I y VII presentaron los mayores porcentajes de barrios que formaron el cluster de tasas altas del indicador con 63,3% y 38,4% en el primer y segundo quinquenio, respectivamente. Conclusión e Implicación para la Práctica El análisis espacial señaló las áreas críticas para la ocurrencia del indicador, que podrían contribuir a la inversión en áreas prioritarias para la prevención de la transmisión vertical de sífilis.

Abstract Objective To analyze the spatial distribution of fetal mortality due to congenital syphilis among the neighborhoods of the city of Recife-PE. Method Ecological study, based on the epidemiological indicator fetal mortality rate due to congenital syphilis, aggregated at the neighborhood level, in two five-year periods: 2007 to 2011 and 2012 to 2016. The pattern of spatial autocorrelation was determined by the Moran Global and Local Indexes, with statistical significance lower than 5% and represented in BoxMap and MoranMap maps that indicated areas with high, low and epidemiological transition rates and clusters of greater epidemiological interest. Results It was reported 208 fetal deaths. The Moran Global Index showed a reasonable degree of positive spatial autocorrelation in the first five-year period (I = 0.351 and p-value = 0.01) and a weak degree in the second five-year period (I = 0.189 and p-value = 0.02). Sanitary Districts I and VII had the highest percentages of neighborhoods that formed the cluster of high rates of the indicator with 63.3% and 38.4% in the first and second five-year periods, respectively. Conclusions and Implications for Practice The spatial analysis pointed out the critical areas for the occurrence of the indicator, which could contribute to investment in priority areas for the prevention of vertical transmission of syphilis.

Corrigendum: Risk Factors for Maternal and Fetal Mortality in Acute Fatty Liver of Pregnancy and New Predictive Models.

[This corrects the article DOI: 10.3389/fmed.2021.719906.].