Performance of the First-Trimester Cervical Consistency Index to Predict Preterm Birth.

Background/Objectives: Preterm birth (PTB) remains a significant global health challenge. Previous attempts to predict preterm birth in the first trimester using cervical length have been contradictory. The cervical consistency index (CCI) was introduced to quantify early cervical changes and has shown promise across various clinical scenarios in the mid-trimester, though testing in the first trimester is lacking. This study aims to assess the cervical consistency index performance in predicting preterm birth during the first trimester of pregnancy. Methods: In this prospective cohort study, focused exclusively on research, women with singleton pregnancies, both with and without a history of spontaneous preterm birth (sPTB), were included. The primary outcome was sPTB before 37 weeks, with a secondary outcome of sPTB before 34 weeks. CCI measurements were taken between 11+0 to 13+6 weeks of gestation. Receiver operating characteristic (ROC) curves were generated, and sensitivity and specificity were calculated for the optimal cut-off and for the 5th, 10th, and 15th percentile. Intraobserver and interobserver agreements were assessed using the intraclass correlation coefficient (ICC). Results: Among the 667 patients analyzed, the rates of sPTB before 37 and 34 weeks were 9.2% (61/667) and 1.8% (12/667), respectively. The detection rates (DRs) for CCI predicting PTB before 37 and 34 weeks were 19.7% (12/61) and 33.3% (4/12). Negative predictive values were 91.8% (546/595) and 98.7% (588/596), while the areas under the curve (AUC) for sPTB before 37 and 34 weeks were 0.62 (95% CI: 0.54-0.69) and 0.80 (95% CI: 0.71-0.89), respectively. Of the 61 patients with preterm birth, 13 (21.3%) had a preterm birth history; in this group, the CCI percentile 10th identified 39% (5/13). Intraobserver ICC was 0.862 (95% CI: 0.769-0.920), and interobserver ICC was 0.833 (95% CI: 0.722-0.902). Conclusions: This study suggests that utilizing CCI in the first trimester of pregnancy could serve as a valuable tool for predicting preterm birth before 34 weeks of gestation, demonstrating robust intraobserver and interobserver reliability.

Earlier detection of gestational diabetes impacts on medication requirements, neonatal and maternal outcomes.

AIM: Gestational diabetes (GD) is a global health concern with significant implications for maternal and neonatal outcomes. This study investigates the association between early GD (eGD) diagnosis (<24 weeks), pharmacotherapy requirements and adverse neonatal outcomes. MATERIALS AND METHODS: A cohort of 369 pregnant women underwent a 75-g oral glucose tolerance test. Maternal variables, pharmacotherapy prescriptions and neonatal outcomes were analysed employing t-tests, χ2 tests, and logistic regression. A p < .05 was considered significant. RESULTS: Early GD increased the odds of neonatal hypoglycaemia [odds ratio (OR): 18.57, p = .013] and respiratory distress syndrome (OR: 4.75, p = .034). Nutritional therapy prescription by an accredited nutritionist was the most common treatment in women diagnosed after 24 weeks, but those with eGD required more frequently specialized nutritional consulting + metformin to achieve glycaemic control (p = .027). eGD was associated with a higher requirement of nutritional therapy prescription + metformin (OR: 2.26, 95% confidence interval: 1.25-4.09, p = .007) and with maternal hyperglycaemia during the post-partum period at 2 h of the oral glucose tolerance test (OR: 1.03, 95% confidence interval: 1.02-1.13, p = .024). CONCLUSION: Timely diagnosis and personalized treatment of GD are desirable because an earlier presentation is related to a higher risk of adverse neonatal and maternal outcomes.

Routine third-trimester ultrasound assessment for intrauterine growth restriction.

Intrauterine growth restriction significantly impacts perinatal outcomes. Undetected IUGR escalates the risk of adverse outcomes. Serial symphysis-fundal height measurement, a recommended strategy, is insufficient in detecting abnormal fetal growth. Routine third-trimester ultrasounds significantly improve detection rates compared with this approach, but direct high-quality evidence supporting enhanced perinatal outcomes from routine scanning is lacking. In assessing fetal growth, abdominal circumference alone performs comparably to estimated fetal weight. Hadlock formulas demonstrate accurate fetal weight estimation across diverse gestational ages and settings. When choosing growth charts, prescriptive standards (encompassing healthy pregnancies) should be prioritized over descriptive ones. Customized fetal standards may enhance antenatal IUGR detection, but conclusive high-quality evidence is elusive. Emerging observational data suggest that longitudinal fetal growth assessment could predict adverse outcomes better. However, direct randomized trial evidence supporting this remains insufficient.

Performance of machine-learning approach for prediction of pre-eclampsia in a middle-income country.

OBJECTIVE: Pre-eclampsia (PE) is a serious complication of pregnancy associated with maternal and fetal morbidity and mortality. As current prediction models have limitations and may not be applicable in resource-limited settings, we aimed to develop a machine-learning (ML) algorithm that offers a potential solution for developing accurate and efficient first-trimester prediction of PE. METHODS: We conducted a prospective cohort study in Mexico City, Mexico to develop a first-trimester prediction model for preterm PE (pPE) using ML. Maternal characteristics and locally derived multiples of the median (MoM) values for mean arterial pressure, uterine artery pulsatility index and serum placental growth factor were used for variable selection. The dataset was split into training, validation and test sets. An elastic-net method was employed for predictor selection, and model performance was evaluated using area under the receiver-operating-characteristics curve (AUC) and detection rates (DR) at 10% false-positive rates (FPR). RESULTS: The final analysis included 3050 pregnant women, of whom 124 (4.07%) developed PE. The ML model showed good performance, with AUCs of 0.897, 0.963 and 0.778 for pPE, early-onset PE (ePE) and any type of PE (all-PE), respectively. The DRs at 10% FPR were 76.5%, 88.2% and 50.1% for pPE, ePE and all-PE, respectively. CONCLUSIONS: Our ML model demonstrated high accuracy in predicting pPE and ePE using first-trimester maternal characteristics and locally derived MoM. The model may provide an efficient and accessible tool for early prediction of PE, facilitating timely intervention and improved maternal and fetal outcome. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Eficiencia de un enfoque de aprendizaje automático para la predicción de la preeclampsia en un país de ingresos medios OBJETIVO: La preeclampsia (PE) es una complicación grave del embarazo asociada a morbilidad y mortalidad materna y del feto. Dado que los modelos de predicción actuales tienen limitaciones y pueden no ser aplicables en situaciones con recursos limitados, se propuso desarrollar un algoritmo de aprendizaje automático (AA) que ofrezca una solución con potencial para desarrollar una predicción precisa y eficiente de la PE en el primer trimestre. MÉTODOS: Se realizó un estudio de cohorte prospectivo en Ciudad de México para desarrollar un modelo de predicción de la PE pretérmino (PEp) en el primer trimestre utilizando AA. Para la selección de variables se utilizaron las características maternas y los múltiplos de la mediana (MdM) obtenidos localmente para la presión arterial media, el índice de pulsatilidad de la arteria uterina y el factor de crecimiento placentario sérico. El conjunto de datos se dividió en subconjuntos de datos de entrenamiento, de validación y de test estadístico. Se empleó un método de red elástica para la selección de predictores, y el rendimiento del modelo se evaluó mediante el área bajo la curva de características operativas del receptor (ABC) y las tasas de detección (TD) con tasas de falsos positivos (TFP) del 10%. RESULTADOS: El análisis final incluyó a 3050 mujeres embarazadas, de las cuales 124 (4,07%) desarrollaron PE. El modelo de AA mostró una buena eficiencia, con un ABC de 0,897, 0,963 y 0,778 para la PEp, la PE de aparición temprana (PEat) y cualquier tipo de PE (todas las PE), respectivamente. Las TD con TFP del 10% fueron del 76,5%, 88,2% y 50,1% para la PEp, PEat y todas las PE, respectivamente. CONCLUSIONES: Nuestro modelo de AA demostró una alta precisión en la predicción de la PEp y la PEat utilizando características maternas del primer trimestre y MdM calculados localmente. El modelo puede proporcionar una herramienta eficiente y accesible para la predicción temprana de la PE, facilitando la intervención oportuna y la mejora de los resultados maternos y del feto.

Influential Serum Kinases (Non-sFlt-1) and Phosphatases in Preeclampsia-Systemic Review and Metanalysis.

The early identification of women with an increased risk of preeclampsia (PE) is desirable, but apart from soluble fms-like tyrosine kinase-1 (sFlt-1), few biomarkers have previously been identified as relevant for predicting preeclampsia. Since kinases and phosphatases regulate critical biological processes and previous evidence suggests a potential role of these molecules in preeclampsia, we performed this systematic review and metanalysis. The objective was to determine if there are kinases and phosphatases whose serum levels are different between women with and without PE, being relevant biomarkers of PE. We followed the recommendations of Cochrane and the Preferred Reported Items for Systematic Reviews and Metanalysis (PRISMA) to perform this study. The MESH terms preeclampsia, kinases, phosphatases, angiopoietins, soluble tyrosine protein kinase receptor (sTIE2), and cellular-mesenchymal-epithelial transition factor (c-MET) were combined to find relevant articles in the PubMed, PROSPERO, and Cochrane databases. Then, a qualitative and quantitative analysis was performed in R Studio software. From 580 abstracts identified, 37 were included in the final analysis, which comprised 24,211 pregnant women (2879 with PE and 21,332 women without PE [HP]. The pooled analysis showed that serum creatine kinase (CK) (SMD: 2.43, CI 95% 0.25-4.62) was significantly higher in PE, whereas sTIE2 and anti-angiogenic factor soluble c-Met (sMet)were significantly lower in PE than in HP (SMD: -0.23, CI95% -0.37 to -0.09; and SMD:0.24, CI95% 0.01-0.47, respectively). Adenosine monophosphate-activated protein kinase (AMPK), angiopoietin-1 (ANG-1), angiopoietin-2 (ANG-2), the ratio angiopoietin-1/angiopoietin-2, acid phosphatase, and alkaline phosphatase were not different between women with PE and HP. In summary CK, sTIE2, and c-MET are relevant biomarkers of PE. It is desirable to incorporate them into current models for PE prediction to evaluate their utility as biomarkers.

Total Antioxidant Capacity in Obese and Non-Obese Subjects and Its Association with Anthropo-Metabolic Markers: Systematic Review and Meta-Analysis.

The total antioxidant capacity (TAC) has been related to the development of and complications associated with chronic diseases, but its importance during obesity is not entirely clear. We conducted a systematic review and meta-analysis to clarify whether there are differences or similarities in the TAC between subjects with obesity (SO) and subjects with normal weight (NW). Following the recommendations of PRISMA and Cochrane, we performed a systematic search in the PubMed, Scopus, Web of Science, Cochrane, and PROSPERO databases, identifying 1607 studies. Among these, 22 studies were included in the final analysis, comprising 3937 subjects (1665 SO and 2272 NW) in whom serum TAC was measured, and from these 19,201 subjects, the correlation of serum TAC with anthropo-metabolic parameters was also estimated. The Newcastle-Ottawa method was used for the evaluation of the risk of bias. Using a random-effect model (REM), TAC was reduced in SO independently of age (SMD, -0.86; 95% CI -1.38 to -0.34; p = 0.0012), whereas malondialdehyde (SMD, 1.50; 95% CI 0.60 to 2.41), oxidative stress index (SMD, 1.0; 95% CI 0.16 to 1.84), and total oxidant status (SMD, 0.80; 0.22 to 1.37) were increased. There were seven significant pooled correlations of TAC with anthropometric and metabolic parameters: weight (r = -0.17), hip circumference (r= -0.11), visceral adipose index (r = 0.29), triglycerides (r = 0.25), aspartate aminotransferase (r = 0.41), alanine aminotransferase (r = 0.38), and uric acid (r = 0.53). Our results confirm a decrease in TAC and an increase in markers of oxidative stress in SO and underpin the importance of these serum biomarkers in obesity.

Diagnostic yield of exome sequencing in isolated fetal growth restriction: Systematic review and meta-analysis.

The aim of this study was to determine the diagnostic yield of exome sequencing (ES) above that of chromosomal microarray analysis (CMA) or karyotyping in fetuses with isolated fetal growth restriction (FGR). This was a systematic review conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Selected studies included those with (a) only fetuses with FGR in the absence of fetal structural anomalies and (b) negative CMA or karyotyping results. Only positive variants classified as likely pathogenic or pathogenic determined as causative of the fetal phenotype were considered. A negative CMA or karyotype result was treated as the reference standard. Eight studies with data on ES diagnostic yield, including 146 fetuses with isolated FGR, were identified. Overall, a pathogenic variant determined as potentially causative of the fetal phenotype was found in 17 cases, resulting in a 12% (95% CI: 7%-18%) incremental performance pool of ES. The vast majority were studied before 32 weeks'gestation. In conclusion, a monogenic disorder was prenatally found in association with apparently isolated FGR in 12% of these fetuses.

Características poblacionales y placentarias asociadas a óbito en infección asintomática por SARS-CoV-2 / Population characteristics and placental findings associated with stillbirth in asymptomatic SARS-CoV-2 infection

Resumen Objetivo: Comparar características poblacionales y hallazgos placentarios asociados a óbito, en mujeres con infección asintomática por coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2) al momento de la resolución del embarazo. Material y métodos: Estudio transversal analítico, mujeres con diagnóstico de óbito e infección asintomática por SARS-CoV-2. Se excluyeron pacientes con patología ginecológica y aquellas con más de una prueba RT-PCR. Resultados: No hay diferencia estadísticamente significativa entre las pacientes con infección asintomática por SARS-CoV-2 comparadas con pacientes sin infección para las características poblacionales como edad materna, antecedentes obstétricos, edad gestacional, escolaridad, estado civil, hábito tabáquico y enfermedades crónico-degenerativas. Tampoco hubo diferencia en los hallazgos placentarios de corioamnionitis, vasculitis, deciduitis, trombosis, aterosis aguda y necrosis fibrinoide. Conclusiones: No hay diferencia estadísticamente significativa en las características poblacionales y placentarias en embarazadas con diagnóstico de óbito, con y sin infección asintomática por SARS-CoV-2. Tenemos datos insuficientes para afirmar alguna característica asociada a óbito en pacientes con infección por SARS-CoV-2 asintomática.

Abstract Objective: To compare population characteristics and placental findings associated with stillbirth, in women with asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at the time of delivery. Materials and methods: Analytical cross-sectional study women with a diagnosis of stillbirth and with asymptomatic SARS-CoV-2 infection. Patients with gynecological pathology and those with more than one RT-PCR test were excluded. Results: There is no statistically significant difference between patients with asymptomatic SARS-CoV-2 infection compared to patients without infection for population characteristics such as maternal age, obstetric history, gestational age, education, marital status, smoking habit, chronic-degenerative diseases. There was no difference in placental findings of chorioamnionitis, vasculitis, deciduitis, thrombosis, acute atherosis, and fibrinoid necrosis. Conclusions: There is no statistically significant difference in the population and placental characteristics, in pregnant women diagnosed with stillbirth with and without confirmed asymptomatic SARS-CoV-2 infection. For the moment, we have insufficient data to affirm any population characteristic associated with stillbirth in patients with asymptomatic SARS-CoV-2 infection.

Effects of maternal characteristics and medical history on first trimester biomarkers for preeclampsia.

Objective: To identify and quantify the effects of maternal characteristics and medical history on the distribution of Placental Growth Factor (PlGF), mean arterial pressure (MAP), and Uterine Artery Mean Pulsatility Index (UtA-PI); and to standardize the expected values for these biomarkers in the first trimester to create unique multiples of the median (MoMs) for Latin-American population. Methods: This is a prospective cohort built exclusively for research purposes of consecutive pregnant women attending their first-trimester screening ultrasound at a primary care center for the general population in Mexico City between April 2019 and October 2021. We excluded fetuses with chromosomal abnormalities, major fetal malformations, and women delivering in another care center. Linear regression was used on log-transformed biomarkers to assess the influence of maternal characteristics on non-preeclamptic women to create MoM. Results: Of a total of 2,820 pregnant women included in the final analysis, 118 (4.18%) developed PE, of which 22 (0.78%) delivered before 34 weeks of gestation, 74 (2.62%) before 37 weeks, and 44 (1.56%) from 37 weeks gestation. Characteristics that significantly influenced PLGF were fetal crown rump length (CRL), maternal age, nulliparity, body mass index (BMI), chronic hypertension, Lupus, spontaneous pregnancy, polycystic ovary syndrome (PCOS), hypothyroidism, preeclampsia (PE) in a previous pregnancy, and mother with PE. MAP had significant influence from CRL, maternal age, PE in a previous pregnancy, induction of ovulation, a mother with PE, chronic hypertension, BMI, and hypothyroidism. UtA-PI was influenced by CRL, maternal age, a mother with PE, chronic hypertension, and gestational diabetes mellitus (GDM) in a previous pregnancy. Conclusion: Population-specific multiples of the median (MoMs) for PlGF, MAP, and UtA-PI in the first trimester adequately discriminate among women developing preeclampsia later in pregnancy.

Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis.

INTRODUCTION: Despite a growing body of research on the risks of SARS-CoV-2 infection during pregnancy, there is continued controversy given heterogeneity in the quality and design of published studies. METHODS: We screened ongoing studies in our sequential, prospective meta-analysis. We pooled individual participant data to estimate the absolute and relative risk (RR) of adverse outcomes among pregnant women with SARS-CoV-2 infection, compared with confirmed negative pregnancies. We evaluated the risk of bias using a modified Newcastle-Ottawa Scale. RESULTS: We screened 137 studies and included 12 studies in 12 countries involving 13 136 pregnant women.Pregnant women with SARS-CoV-2 infection-as compared with uninfected pregnant women-were at significantly increased risk of maternal mortality (10 studies; n=1490; RR 7.68, 95% CI 1.70 to 34.61); admission to intensive care unit (8 studies; n=6660; RR 3.81, 95% CI 2.03 to 7.17); receiving mechanical ventilation (7 studies; n=4887; RR 15.23, 95% CI 4.32 to 53.71); receiving any critical care (7 studies; n=4735; RR 5.48, 95% CI 2.57 to 11.72); and being diagnosed with pneumonia (6 studies; n=4573; RR 23.46, 95% CI 3.03 to 181.39) and thromboembolic disease (8 studies; n=5146; RR 5.50, 95% CI 1.12 to 27.12).Neonates born to women with SARS-CoV-2 infection were more likely to be admitted to a neonatal care unit after birth (7 studies; n=7637; RR 1.86, 95% CI 1.12 to 3.08); be born preterm (7 studies; n=6233; RR 1.71, 95% CI 1.28 to 2.29) or moderately preterm (7 studies; n=6071; RR 2.92, 95% CI 1.88 to 4.54); and to be born low birth weight (12 studies; n=11 930; RR 1.19, 95% CI 1.02 to 1.40). Infection was not linked to stillbirth. Studies were generally at low or moderate risk of bias. CONCLUSIONS: This analysis indicates that SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction. As more data become available, we will update these findings per the published protocol.

Risk factors for anxiety and depression among pregnant women during the COVID-19 pandemic: Results of a web-based multinational cross-sectional study.

OBJECTIVE: To assess risk factors for anxiety and depression among pregnant women during the COVID-19 pandemic using Mind-COVID, a prospective cross-sectional study that compares outcomes in middle-income economies and high-income economies. METHODS: A total of 7102 pregnant women from 12 high-income economies and nine middle-income economies were included. The web-based survey used two standardized instruments, General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9). RESULT: Pregnant women in high-income economies reported higher PHQ-9 (0.18 standard deviation [SD], P < 0.001) and GAD-7 (0.08 SD, P = 0.005) scores than those living in middle-income economies. Multivariate regression analysis showed that increasing PHQ-9 and GAD-7 scales were associated with mental health problems during pregnancy and the need for psychiatric treatment before pregnancy. PHQ-9 was associated with a feeling of burden related to restrictions in social distancing, and access to leisure activities. GAD-7 scores were associated with a pregnancy-related complication, fear of adverse outcomes in children related to COVID-19, and feeling of burden related to finances. CONCLUSIONS: According to this study, the imposed public health measures and hospital restrictions have left pregnant women more vulnerable during these difficult times. Adequate partner and family support during pregnancy and childbirth can be one of the most important protective factors against anxiety and depression, regardless of national economic status.

Clinical risk factors of adverse outcomes among women with COVID-19 in the pregnancy and postpartum period: a sequential, prospective meta-analysis.

OBJECTIVE: This sequential, prospective meta-analysis sought to identify risk factors among pregnant and postpartum women with COVID-19 for adverse outcomes related to disease severity, maternal morbidities, neonatal mortality and morbidity, and adverse birth outcomes. DATA SOURCES: We prospectively invited study investigators to join the sequential, prospective meta-analysis via professional research networks beginning in March 2020. STUDY ELIGIBILITY CRITERIA: Eligible studies included those recruiting at least 25 consecutive cases of COVID-19 in pregnancy within a defined catchment area. METHODS: We included individual patient data from 21 participating studies. Data quality was assessed, and harmonized variables for risk factors and outcomes were constructed. Duplicate cases were removed. Pooled estimates for the absolute and relative risk of adverse outcomes comparing those with and without each risk factor were generated using a 2-stage meta-analysis. RESULTS: We collected data from 33 countries and territories, including 21,977 cases of SARS-CoV-2 infection in pregnancy or postpartum. We found that women with comorbidities (preexisting diabetes mellitus, hypertension, cardiovascular disease) vs those without were at higher risk for COVID-19 severity and adverse pregnancy outcomes (fetal death, preterm birth, low birthweight). Participants with COVID-19 and HIV were 1.74 times (95% confidence interval, 1.12-2.71) more likely to be admitted to the intensive care unit. Pregnant women who were underweight before pregnancy were at higher risk of intensive care unit admission (relative risk, 5.53; 95% confidence interval, 2.27-13.44), ventilation (relative risk, 9.36; 95% confidence interval, 3.87-22.63), and pregnancy-related death (relative risk, 14.10; 95% confidence interval, 2.83-70.36). Prepregnancy obesity was also a risk factor for severe COVID-19 outcomes including intensive care unit admission (relative risk, 1.81; 95% confidence interval, 1.26-2.60), ventilation (relative risk, 2.05; 95% confidence interval, 1.20-3.51), any critical care (relative risk, 1.89; 95% confidence interval, 1.28-2.77), and pneumonia (relative risk, 1.66; 95% confidence interval, 1.18-2.33). Anemic pregnant women with COVID-19 also had increased risk of intensive care unit admission (relative risk, 1.63; 95% confidence interval, 1.25-2.11) and death (relative risk, 2.36; 95% confidence interval, 1.15-4.81). CONCLUSION: We found that pregnant women with comorbidities including diabetes mellitus, hypertension, and cardiovascular disease were at increased risk for severe COVID-19-related outcomes, maternal morbidities, and adverse birth outcomes. We also identified several less commonly known risk factors, including HIV infection, prepregnancy underweight, and anemia. Although pregnant women are already considered a high-risk population, special priority for prevention and treatment should be given to pregnant women with these additional risk factors.

Impact of Protease Inhibitor-Based Highly Active Antiretroviral Therapy on Fetal Subcutaneous Fat Tissue in HIV-Pregnant Women in a Middle-Income Country.

BACKGROUND: HIV infection continues to be a global public health challenge, affecting approximately 1.7 million reproductive-aged women. Protease inhibitor-based highly active antiretroviral therapy (PI-HAART) has significantly reduced the risk of vertical transmission of HIV from mother to child. Nevertheless, concerns linger regarding the long-term effects, particularly on body composition, notably subcutaneous fat tissue (SFT). Although HIV-associated lipodystrophy syndrome (LS) has been well documented in adults and older children, its impact on fetuses exposed to PI-HAART remains underexplored. This study aims to evaluate SFT in the fetuses of HIV-pregnant women exposed to PI-HAART, assessing the potential clinical implications. METHODS: We conducted a comparative study between HIV-pregnant women receiving PI-HAART and an HIV-negative control group. Fetometry measurements were obtained via 3D ultrasound. SFT in the fetal arm and thigh segments was assessed. Data were analyzed using lineal multivariate regression and receiver-operating characteristics (ROC)-curve analysis. RESULTS: Fetuses exposed to PI-HAART exhibited a significant reduction in subcutaneous fat, particularly in the proximal third-middle union of the femur (coefficient: -2.588, p = 0.042). This reduction was correlated with lower newborn serum glucose levels (65.7 vs. 56.1, p = 0.007; coefficient: -1.277, p = 0.045). CONCLUSIONS: Our study sheds light on the connection between PI-HAART, fetal subcutaneous fat, and neonatal health. These findings might reveal the long-lasting effects of PI-HAART on newborns and children's well-being. Our results emphasize the need for a more balanced approach to managing pregnant women with HIV in developing countries and open new venues for research on the impact of intrauterine PI-HAART exposure on energy metabolism and fetal programming.

Association between 25-OH Vitamin D Deficiency and COVID-19 Severity in Pregnant Women.

Evidence from studies in the general population suggests an association between vitamin D insufficiency/deficiency and COVID-19 susceptibility and disease severity. The present study was performed on 165 third-trimester pregnant women at the time of delivery. Seventy-nine women tested negative for SARS-CoV-2. From 86 women testing positive, 32 were asymptomatic, 44 presented a mild form of the disease, and 10 experienced severe symptoms. Serum 25-OH vitamin D levels were measured on blood samples collected on admission. Low vitamin D levels were detected in symptomatic but not asymptomatic COVID-19 patients compared to healthy women (p = 0.0227). In addition, 20 (45.4%) pregnant women in the mild COVID-19 group and 6 (60%) in the severe group were vitamin D deficient (p = 0.030). On the other hand, lasso regression analysis showed that 25-OH vitamin D deficiency is an independent predictor of severe COVID-19 with an odds ratio (OR) of 5.81 (95% CI: 1.108-30.541; p = 0.037). These results show the relationship between vitamin D deficiency in pregnant women and the severity of COVID-19 infection and support the recommendation to supplement with vitamin D to avoid worse COVID-19 outcomes during pregnancy.

Intrauterine transfusion of a hydropic fetus with anemia due to a giant chorioangioma: A case report.

Giant chorioangiomas are a potentially life-threatening condition that may require intrauterine therapy. We describe a case of a large chorioangioma (>4cm) diagnosed at 30 weeks of gestation causing severe fetal anemia and hydrops. An intrauterine blood transfusion was performed at 31 weeks with reversal of the anemia and hydrops. The neonate was born at 37 weeks showing respiratory distress syndrome that required neonatal intensive care unit admission but was discharged at 30 days of life. Further evaluation at two months of age showed no signs of abnormal neurodevelopment. When timely indicated, intrauterine transfusion of a hydropic fetus with anemia due to a giant chorioangioma is a potentially life-saving therapy that shows good neurodevelopment of the surviving fetus.

Prediction of Neonatal Respiratory Morbidity Assessed by Quantitative Ultrasound Lung Texture Analysis in Twin Pregnancies.

The objective of this study was to evaluate the performance of quantitative ultrasound of fetal lung texture analysis in predicting neonatal respiratory morbidity (NRM) in twin pregnancies. This was an ambispective study involving consecutive cases. Eligible cases included twin pregnancies between 27.0 and 38.6 weeks of gestation, for which an ultrasound image of the fetal thorax was obtained within 48 h of delivery. Images were analyzed using quantusFLM® version 3.0. The primary outcome of this study was neonatal respiratory morbidity, defined as the occurrence of either transient tachypnea of the newborn or respiratory distress syndrome. The performance of quantusFLM® in predicting NRM was analyzed by matching quantitative ultrasound analysis and clinical outcomes. This study included 166 images. Neonatal respiratory morbidity occurred in 12.7% of cases, and it was predicted by quantusFLM® analysis with an overall sensitivity of 42.9%, specificity of 95.9%, positive predictive value of 60%, and negative predictive value of 92.1%. The accuracy was 89.2%, with a positive likelihood ratio of 10.4, and a negative likelihood ratio of 0.6. The results of this study demonstrate the good prediction capability of NRM in twin pregnancies using a non-invasive lung texture analysis software. The test showed an overall good performance with high specificity, negative predictive value, and accuracy.

Inflammatory-Metal Profile as a Hallmark for COVID-19 Severity During Pregnancy.

Pregnancy makes women more susceptible to infectious agents; however, available data on the effect of SARS-CoV-2 on pregnant women are limited. To date, inflammatory responses and changes in serum metal concentration have been reported in COVID-19 patients, but few associations between metal ions and cytokines have been described. The aim of this study was to evaluate correlations between inflammatory markers and serum metal ions in third-trimester pregnant women with varying COVID-19 disease severity. Patients with severe symptoms had increased concentrations of serum magnesium, copper, and calcium ions and decreased concentrations of iron, zinc, and sodium ions. Potassium ions were unaffected. Pro-inflammatory cytokines IL-6, TNF-α, IL-8, IL-1α, anti-inflammatory cytokine IL-4, and the IP-10 chemokine were induced in the severe presentation of COVID-19 during pregnancy. Robust negative correlations between iron/magnesium and zinc/IL-6, and a positive correlation between copper/IP-10 were observed in pregnant women with the severe form of the disease. Thus, coordinated alterations of serum metal ions and inflammatory markers - suggestive of underlying pathophysiological interactions-occur during SARS-CoV-2 infection in pregnancy.

Fetal Liver Volume Assessment Using Magnetic Resonance Imaging in Fetuses With Cytomegalovirus Infection†.

Objective: To assess fetal liver volume (FLV) by magnetic resonance imaging (MRI) in cytomegalovirus (CMV)-infected fetuses compared to a group of healthy fetuses. Method: Most infected cases were diagnosed by the evidence of ultrasound abnormalities during routine scans and in some after maternal CMV screening. CMV-infected fetuses were considered severely or mildly affected according to prenatal brain lesions identified by ultrasound (US)/MRI. We assessed FLV, the FLV to abdominal circumference (AC) ratio (FLV/AC-ratio), and the FLV to fetal body volume (FBV) ratio (FLV/FBV-ratio). As controls, we included 33 healthy fetuses. Hepatomegaly was evaluated post-mortem in 11 cases of congenital CMV infection. Parametric trend and intraclass correlation analyses were performed. Results: There were no significant differences in FLV between infected (n = 32) and healthy fetuses. On correcting the FLV for AC and FBV, we observed a significantly higher FLV in CMV-infected fetuses. There were no significant differences in the FLV, or the FLV/AC or FLV/FBV-ratios according to the severity of brain abnormalities. There was excellent concordance between the fetal liver weight estimated by MRI and liver weight obtained post-mortem. Hepatomegaly was not detected in any CMV-infected fetus. Conclusion: In CMV-infected fetuses, FLV corrected for AC and FBV was higher compared to healthy controls, indicating relative hepatomegaly. These parameters could potentially be used as surrogate markers of liver enlargement.

Protocol for a sequential, prospective meta-analysis to describe coronavirus disease 2019 (COVID-19) in the pregnancy and postpartum periods.

We urgently need answers to basic epidemiological questions regarding SARS-CoV-2 infection in pregnant and postpartum women and its effect on their newborns. While many national registries, health facilities, and research groups are collecting relevant data, we need a collaborative and methodologically rigorous approach to better combine these data and address knowledge gaps, especially those related to rare outcomes. We propose that using a sequential, prospective meta-analysis (PMA) is the best approach to generate data for policy- and practice-oriented guidelines. As the pandemic evolves, additional studies identified retrospectively by the steering committee or through living systematic reviews will be invited to participate in this PMA. Investigators can contribute to the PMA by either submitting individual patient data or running standardized code to generate aggregate data estimates. For the primary analysis, we will pool data using two-stage meta-analysis methods. The meta-analyses will be updated as additional data accrue in each contributing study and as additional studies meet study-specific time or data accrual thresholds for sharing. At the time of publication, investigators of 25 studies, including more than 76,000 pregnancies, in 41 countries had agreed to share data for this analysis. Among the included studies, 12 have a contemporaneous comparison group of pregnancies without COVID-19, and four studies include a comparison group of non-pregnant women of reproductive age with COVID-19. Protocols and updates will be maintained publicly. Results will be shared with key stakeholders, including the World Health Organization (WHO) Maternal, Newborn, Child, and Adolescent Health (MNCAH) Research Working Group. Data contributors will share results with local stakeholders. Scientific publications will be published in open-access journals on an ongoing basis.

Severe smallness as predictor of adverse perinatal outcome in suspected late small-for-gestational-age fetuses: systematic review and meta-analysis.

OBJECTIVE: To investigate the performance of severe smallness in the prediction of adverse perinatal outcome among fetuses with suspected late-onset small-for-gestational age (SGA). METHODS: A systematic search was performed to identify relevant studies in PubMed, Web of Science and Scopus. Late-onset SGA was defined as estimated fetal weight (EFW) or abdominal circumference (AC) < 10th percentile diagnosed at or after 32 weeks' gestation, while severe SGA was defined as EFW or AC < 3rd percentile or < 2 SD. Random-effects modeling was used to generate hierarchical summary receiver-operating-characteristics (HSROC) curves. The performance of severe SGA (as a presumptive diagnosis) in predicting adverse perinatal outcome among singleton pregnancies with suspected late-onset SGA was expressed as area under the HSROC curve (AUC), sensitivity, specificity and positive/negative likelihood ratios. The association between suspected severe SGA and adverse perinatal outcome was also assessed by random-effects modeling using the Mantel-Haenszel method and presented as odds ratio (OR). The non-exposed group was defined as non-severe SGA (EFW ≥ 3rd centile). RESULTS: Twelve cohort studies were included in this systematic review and meta-analysis. The studies included a total of 3639 fetuses with suspected late-onset SGA, of which 1246 had suspected severe SGA. Significant associations were found between suspected severe SGA and composite adverse perinatal outcome (OR, 1.97 (95% CI, 1.33-2.92)), neonatal intensive care unit admission (OR, 2.87 (95% CI, 1.84-4.47)) and perinatal death (OR, 4.26 (95% CI, 1.07-16.93)). However, summary ROC curves showed limited performance of suspected severe SGA in predicting perinatal outcomes, with AUCs of 60.9%, 66.9%, 53.6%, 57.2%, 54.6% and 64.9% for composite adverse perinatal outcome, neonatal intensive care unit admission, neonatal acidosis, Cesarean section for intrapartum fetal compromise, low Apgar score and perinatal death, respectively. CONCLUSION: Although suspected severe SGA was associated with a higher risk of perinatal complications, it performed poorly as a standalone parameter in predicting adverse perinatal outcome. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.