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.

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.

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.

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.

Factors associated with cancer treatment delay: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Treatment delays are significantly associated with increased mortality risk among adult cancer patients; however, factors associated with these delays have not been robustly evaluated. This review and meta-analysis will evaluate factors associated with treatment delays among patients with five common cancers. METHODS AND ANALYSIS: Scientific databases including Ovid MEDLINE, Elsevier Embase, EBSCOhost CINAHL Plus Full Text, Elsevier Scopus and ProQuest Dissertations and Theses Global will be searched to identify relevant articles published between January 2000 and October 2021. Research articles published in the USA evaluating factors associated with treatment delay among breast, lung, prostate, cervical or colorectal adult cancer patients will be included. The primary outcome of the meta-analysis will be the pooled adjusted and unadjusted odds of treatment delay for patient, disease, provider and system-level factors defined according to specified time intervals. The secondary outcomes will be mean or median treatment delay for each cancer site according to first treatment and the influence of factors on the pooled mean treatment delay for each cancer site (via meta-regression analyses). Results from qualitative and mixed-methods studies will be narratively synthesised. Three reviewers will independently screen records generated from the search and two reviewers will independently extract data following a consensus agreement. Statistical heterogeneity will be assessed with a standard I2 test and funnel plots will be conducted to evaluate publication bias. Risk of bias will be assessed independently by two authors using validated tools according to the article's study design. ETHICS AND DISSEMINATION: Formal ethical approval is not required because the work is being carried out on publicly accessible studies. The findings of this review will be disseminated through a peer-reviewed scientific journal, academic conferences, social media, and key stakeholders. PROSPERO REGISTRATION NUMBER: CRD42021293131.

The heart after surviving twin-to-twin transfusion syndrome.

BACKGROUND: The persistent changes in cardiac structure and function in children who survived twin-to-twin transfusion syndrome remain a matter of concern and controversy. Current fetal echocardiographic parameters and their postnatal evolution can help improve our understanding of the subject. OBJECTIVE: To describe the echocardiographic changes of monochorionic fetuses affected by twin-to-twin transfusion syndrome, the recipient and the donor, before and after laser photocoagulation and to determine their evolution in the third trimester and during their first year of life. STUDY DESIGN: An observational study was conducted including 55 uncomplicated monochorionic diamniotic twins and 78 pairs with twin-to-twin transfusion syndrome, 44 stage I-II and 34 stage III-IV, prospectively enrolled from 2015 until 2018. Comprehensive echocardiography was performed at 4 time periods: before laser photocoagulation, at 24 to 72 hours after surgery, at 28 to 30 weeks of gestation, and at 6 to 12 months after birth. Echocardiographic parameters were transformed to z-scores or indexed for heart area, estimated fetal weight, or body mass surface. RESULTS: At diagnosis, recipients in all stages presented larger hearts (cardiothoracic ratio z-score: 2.77 [0.8] vs controls: -0.03 [0.5]; P<.001) and signs of ventricular hypertrophy (left end-diastolic ventricle wall thickness: 2.68 [0.7] vs controls -0.03 [0.7]; P<.001), along with systolic (cardiac index recipients: 317 [114] mL/min/kg vs controls: 400 [120] mL/min/kg, P<.001) and diastolic impairment (isovolumetric relaxation time z-score: 2.76 [0.6] vs controls: 0.05 [0.6]; P<.001). Donors presented smaller ventricular areas and diameters when compared with controls (left end-diastolic ventricle area z-score: -1.48 [1] vs 0.03 [0.9]; P<.001), along with decreased longitudinal motion (tricuspid annular plane systolic excursion z-score: -0.9 [1] vs controls -0.04 [1]; P<.001) and shorter ejection time z-score (-1.5 [0.7] vs controls: 0.0 [0.7]; P<.001). After surgery, an improvement in functional parameters was observed in both fetuses, whereas most morphometric changes prevailed in donors and recipients in the prenatal period. Postnatally, cardiac remodeling persisted in recipients (left relative wall thickness: 0.34 [0.02] vs controls: 0.30 [0.02]; P<.001), whereas donors mainly presented a decreased longitudinal motion in infancy (tricuspid annular plane systolic excursion z-score: -0.72 [0.7] vs controls: 0.23 [0.9]; P<.05). CONCLUSION: Cardiac remodeling is present in both fetuses at the twin-to-twin transfusion syndrome diagnosis, whereas diastolic dysfunction is only significant in the recipient. Fetal therapy improves most echocardiographic parameters, although postnatally, the echocardiographic changes persist in both fetuses.

Effect of multiple pregnancy and laterality on infant neurodevelopment.

OBJECTIVE: The objective of this study is to investigate the effect of type of pregnancy (singleton, dizygotic, and monozygotic) on infant neurodevelopment and to explore how laterality operates in this relationship. METHODS: We constructed a prospective cohort of low-risk women with singleton, monozygotic, and dizygotic pregnancies. Laterality was evaluated using the Edinburgh's scale of laterality, while neurodevelopment was assessed using the Ages & Stages Questionnaire (ASQ). The confounding, modifying, and mediating effect of laterality on the relationship between multiple pregnancy and neurodevelopment was explored by linear regression. RESULTS: We included 207 singletons, 77 dizygotic, and 75 monozygotic pregnancies. The mean age (SD) at assessment of neurodevelopment was 48.5 (7.5) months. There was a significant trend to poorer neurodevelopment across singleton, dizygotic and monozygotic pregnancies in communication (52.2, 47.6 and 42.3; p < .001) and fine movements (49.6, 44.5 and 35.2; p < .001) even after adjusting for confounders. As compared to singletons, both dizygotic (39.6% vs. 22.7%; p < .001) and monozygotic (39.3% vs. 22.7%; p < .001) pregnancies had a higher frequency of non-right laterality. Laterality was not associated with neurodevelopment, nor confounded, mediated or modified the effect of multiple pregnancy on neurodevelopment. CONCLUSION: The association of multiple pregnancy to poorer neurodevelopment was independent of children laterality.

Prescriptive standards of echocardiographic morphometric and functional parameters in uncomplicated monochorionic diamniotic fetuses.

OBJECTIVE: To create prescriptive standards of cardiac morphometric and functional parameters in a cohort of uncomplicated monochorionic diamniotic (MCDA) twins. METHOD: Fetal echocardiography was performed in a cohort of uncomplicated monochorionic twin fetuses scanned longitudinally, including comprehensive morphometric and functional parameters, using 2-D imaging, M-mode and conventional Doppler. A multilevel polynomial hierarchical model adjusted by gestational age and estimated fetal weight was used to fit each cardiac parameter. RESULTS: The global heart dimensions including the atrial and ventricular areas, the ventricles dimensions and myocardial wall thicknesses and most of the functional parameters, such as the longitudinal myocardial motion and the biventricular cardiac output showed a positive quadratic increment throughout pregnancy. On the other hand, the left ejection fraction, shortening fraction and right fractional area change decreased with gestational age. Scatterplots for the main structural and functional parameters and ratios by gestational age, with mean, 5th, 10th, 90th, and 95th percentiles are provided. Regression equations by estimated fetal weight are also created. CONCLUSION: We provide specific comprehensive echocardiographic prescriptive standards for uncomplicated MCDA twin fetuses following current standardized methodology. The implementation of these charts will potentially help to better identify abnormal cardiovascular parameters associated to monochorionic complications.

Performance of Indocyanine-Green Imaging for Sentinel Lymph Node Mapping and Lymph Node Metastasis in Esophageal Cancer: Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Lymphatic mapping with indocyanine-green (ICG) and near-infrared light fluorescent imaging is widely used for sentinel lymph node staging in different types of cancer but is not fully accepted for all procedures because studies have reported heterogeneous results. This study aimed to assess the detection rate (DR) of ICG imaging for sentinel lymph node mapping (SLNM) and lymph node metastases (LNMs) in esophageal cancer. METHODS: A systematic search was performed to identify relevant studies examining the use of ICG imaging for SLNM in patients with esophageal cancer. Extracted results were pooled in a single-proportion meta-analysis, with a random-effects model, presented as forest plots. RESULTS: Six studies were included in the analysis. The ICG DR for SLNM was 89% [95% confidence interval (CI) 71%-96%]. The pooled sensitivity and specificity values for the detection of LNMs were 84% (95% CI 64%-94%) and 15% (95% CI 3%-45%), respectively. A trend towards a lower DR was found with increasing mean latency time between ICG injection and SLNM. CONCLUSIONS: ICG imaging is a technique that potentially could improve lymph node yield excision and, as a consequence, improve the detection of lymph node metastases.

Uncomplicated Monochorionic Twins: Two Normal Hearts Sharing One Placenta.

Cardiovascular dysfunction has been reported in complicated monochorionic diamniotic (MCDA) pregnancies; however, little is known whether hemodynamic changes occur in uncomplicated MCDA twins. A prospective observational study was conducted including 100 uncomplicated MCDA twins matched by gestational age to 200 low-risk singletons. Echocardiography was performed at 26-30 weeks gestation and cord blood B-type natriuretic peptide (BNP) was measured at delivery. In both groups, z-scores for echocardiographic parameters were within normal ranges; however the monochorionic group had larger atrial areas (mean (standard deviation) right atria-to-heart ratio: 17.0 (2) vs. 15.9 (1); p = 0.018; left atria-to-heart ratio: 17.0 (3) vs. 15.8 (2); p < 0.001) and signs of concentric hypertrophy (right relative wall thickness: 0.66 (0.12) vs. 0.56 (0.11); p < 0.001; left relative wall thickness: 0.69 (0.14) vs. 0.58 (0.12); p < 0.001). Longitudinal function was increased in twins, leading to higher tricuspid annular plane systolic excursion (6.9 mm (0.9) vs. 5.9 mm (0.7); p < 0.001) and mitral annular plane systolic excursion (4.9 mm (0.8) vs. 4.4 mm (1.1); p < 0.001. BNP levels at birth were also higher in MCDA twins (median [interquartile range]: 20.81 pg/mL [16.69-34.01] vs. 13.14 pg/mL [9.17-19.84]; p < 0.001). Thus, uncomplicated MCDA fetuses have normal cardiac shape and function, but signs of cardiac adaptation were identified by echocardiographic and biochemical parameters, when compared with singletons.

Coronavirus Disease 2019 in Pregnancy: A Clinical Management Protocol and Considerations for Practice.

The coronavirus disease 2019 (COVID-19) pandemic has represented a major impact to health systems and societies worldwide. The generation of knowledge about the disease has occurred almost as fast as its global expansion. The mother and fetus do not seem to be at particularly high risk. Nevertheless, obstetrics and maternal-fetal medicine practice have suffered profound changes to adapt to the pandemic. In addition, there are aspects specific to COVID-19 and gestation that should be known by specialists in order to correctly diagnose the disease, classify the severity, distinguish specific signs of COVID-19 from those of obstetric complications, and take the most appropriate management decisions. In this review we present in a highly concise manner an evidence-based protocol for the management of COVID-19 in pregnancy. We briefly contemplate all relevant aspects that we believe a specialist in obstetrics and maternal medicine should know, ranging from basic concepts about the disease and protection measures in the obstetric setting to more specific aspects related to maternal-fetal management and childbirth.

Development and validation of a multivariable prediction model of spontaneous preterm delivery and microbial invasion of the amniotic cavity in women with preterm labor.

BACKGROUND: Early spontaneous preterm delivery is often associated with microbial invasion of the amniotic cavity and/or intraamniotic inflammation. OBJECTIVE: The objective of the study was to develop and validate clinically feasible multivariable prediction models of spontaneous delivery within 7 days and microbial invasion of the amniotic cavity in women admitted with diagnose of preterm labor and intact membranes below 34 weeks. STUDY DESIGN: We used data from a cohort of women admitted from 2012 to 2018 with diagnosis of preterm labor below 34 weeks who had undergone amniocentesis to rule out microbial invasion of the amniotic cavity. The main outcome was spontaneous delivery within 7 days from admission. The secondary outcome was microbial invasion of the amniotic cavity, defined by a positive culture and/or 16S ribosomal RNA gene in the amniotic fluid. The sample (n = 358) was divided into derivation (2012-2016) and validation cohorts (2017-2018). Logistic regression models using a stepwise selection of variables were developed for the outcomes evaluated. We explored as predictive variables ultrasound cervical length measurement at admission, maternal C-reactive protein, gestational age, amniotic fluid glucose, and interleukin-6 (expressed as log units). Models were developed in the derivation cohort and applied to the validation cohort and diagnostic performance was calculated. RESULTS: The derivation cohort included 263 women and the validation cohort 95 women. One hundred five of the women (39%, 105 of 268) spontaneously delivered in the following 7 days and 68 (19%, 68 of 358) had microbial invasion of the amniotic cavity. For spontaneous delivery within 7 days after admission, 4 predictors were identified: cervical length at admission, gestational age, amniotic fluid glucose, and interleukin-6. The diagnostic performance of the model was assessed in the validation cohort using the receiver operating characteristic curve and showed an area under curve of 0.86 (95% confidence interval, 0.77-0.95) with a detection rate of spontaneous delivery within 7 days of 87%, a false-positive rate of 33%, a negative predictive value of 80%, and a negative likelihood ratio of 0.1908. For microbial invasion of the amniotic cavity, 2 independent predictors of the amniotic cavity were identified: amniotic fluid glucose and maternal C-reactive protein. The receiver operating characteristic curve and an area under curve in the validation cohort was 0.83 (95% confidence interval, 0.70-0.96) with a detection rate of 76%, a false-positive rate of 8%, a negative predictive value of 93%, and a negative likelihood ratio of 0.2591. CONCLUSION: In women with preterm labor, we propose 2 clinically feasible prediction models to classify as low vs high risk of spontaneous delivery within 7 days and of microbial invasion of the amniotic cavity. The models showed a high diagnostic performance and could be of value to optimize clinical management.

Blood parameters in fetuses infected with cytomegalovirus according to the severity of brain damage and trimester of pregnancy at cordocentesis.

BACKGROUND AND OBJECTIVE: Cytomegalovirus (CMV) remains a major cause of congenital infection and disease. During pregnancy, symptomatic cases can be detected through ultrasound (US) features, nevertheless, prognostic assessment is difficult. The aim of this study was to assess the predictive value of specific blood parameters in CMV infected fetuses. STUDY DESIGN: Twenty-eight CMV-infected fetuses in which a cordocentesis had been performed were included. Fetuses were considered severely or mildly affected according to prenatal US/MRI brain damage. Fetal blood parameters were assessed for the prediction of severe brain abnormalities, and compared according to the trimester of pregnancy. Logistic regression and receiver operating curve analysis were performed. RESULTS: Thrombocytopenia (≤100,000/mm3; p:0.03) and high levels of gamma-glutamyl transpeptidase (GGT) (≥151 IU/L; p:0.02) signaled severity. For the prediction of brain damage, GGT levels ≥ 183 UI/l achieved 71% sensitivity, 83% specificity (AUC: 0.78), and OR of 2.05 (95% CI: 1.22-3.43) per 100 IU/l increase, adjusted for gestational age. However, thrombocytopenia (91% vs 50%; p: 0.04), ß2 microglobulin >10.4 mg/l (60% vs 0% p: 0.03), CMV-DNA >50,000 copies/ml (80% vs 25%; p: 0.02), and positive IgM (70% vs 17%; p: 0.04) were observed significantly more often in severely damaged fetuses sampled ≤28 weeks than thereafter. CONCLUSION: In CMV infected fetuses, thrombocytopenia and high levels of GGT are associated with severe US/MRI brain abnormalities. Nevertheless, among severely affected fetuses, blood parameters, with exception of GGT, change according to gestational age. Fetal blood could be less predictive of brain damage in the third trimester.

A systematic review and meta-analysis of randomized controlled trials comparing 17-alpha-hydroxyprogesterone caproate versus placebo for the prevention of recurrent preterm birth.

BACKGROUND: Preterm birth causes an increased risk for perinatal morbidity and mortality. OBJECTIVE: To determine whether mid-trimester 17-alpha-hydroxyprogesterone caproate (17-OHPC) reduces the risk of recurrent preterm birth and adverse perinatal outcomes. SEARCH STRATEGY: Systematic search to identify relevant studies published in different languages, registered after 2000, using appropriate MeSH terms. SELECTION CRITERIA: Inclusion criteria were women between 16 and 26+6  weeks of pregnancy with history of preterm delivery in any pregnancy randomized to either 17-OHPC or placebo/no treatment. DATA COLLECTION AND ANALYSIS: The number of preterm births and adverse outcomes in the 17-OHPC and placebo arms over the total number of patients in each randomized group were used to calculate the risk ratio (RR) by random-effects models using the Mantel-Haenszel method. Between-study heterogeneity was assessed using tau2 , χ2 (Cochrane Q), and I2 statistics. MAIN RESULTS: Four studies were included. There was a 29% (RR 0.71; 95% CI, 0.53-0.96; P=0.001), 26% (RR 0.74; 95% CI, 0.58-0.96; P=0.021), and 40% (RR 0.60; 95% CI, 0.42-0.85; P=0.004) reduction in recurrent preterm birth at <37, <35, and <32 weeks, respectively, in the 17-OHPC group compared with placebo. The reduction in neonatal death was 68% (RR 0.32; 95% CI, 0.15-0.66; P=0.002). CONCLUSIONS: 17-OHPC could reduce the risk of recurrent preterm birth at <37, <35, and <28 weeks and neonatal death. PROSPERO: CDR42017082190.

Diagnostic performance of third-trimester ultrasound for the prediction of late-onset fetal growth restriction: a systematic review and meta-analysis.

OBJECTIVE: The objective of the study was to establish the diagnostic performance of ultrasound screening for predicting late smallness for gestational age and/or fetal growth restriction. DATA SOURCES: A systematic search was performed to identify relevant studies published since 2007 in English, Spanish, French, Italian, or German, using the databases PubMed, ISI Web of Science, and SCOPUS. STUDY ELIGIBILITY CRITERIA: We used rrospective and retrospective cohort studies in low-risk or nonselected singleton pregnancies with screening ultrasound performed at ≥32 weeks of gestation. STUDY APPRAISAL AND SYNTHESIS METHODS: The estimated fetal weight and fetal abdominal circumference were assessed as index tests for the prediction of birthweight <10th (i.e. smallness for gestational age), less than the fifth, and less than the third centile and fetal growth restriction (estimated fetal weight less than the third or estimated fetal weight <10th plus Doppler signs). Quality of the included studies was independently assessed by 2 reviewers, using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. For the meta-analysis, hierarchical summary receiver-operating characteristic curves were constructed, and quantitative data synthesis was performed using random-effects models. The sensitivity of the abdominal circumference <10th centile and estimated fetal weight <10th centile for a fixed 10% false-positive rate was derived from the corresponding hierarchical summary receiver-operating characteristic curves. Heterogeneity between studies was visually assessed using Galbraith plots, and publication bias was assessed by funnel plots and quantified by Deeks' method. RESULTS: A total of 21 studies were included. Observed pooled sensitivities of abdominal circumference and estimated fetal weight <10th centile for birthweight <10th centile were 35% (95% confidence interval, 20-52%) and 38% (95% confidence interval, 31-46%), respectively. Observed pooled specificities were 97% (95% confidence interval, 95-98%) and 95% (95% confidence interval, 93-97%), respectively. Modeled sensitivities of abdominal circumference and estimated fetal weight <10th centile for 10% false-positive rate were 78% (95% confidence interval, 61-95%) and 54% (95% confidence interval, 46-52%), respectively. The sensitivity of estimated fetal weight <10th centile was better when aimed to fetal growth restriction than to smallness for gestational age. Meta-regression analysis showed a significant increase in sensitivity when ultrasound evaluation was performed later in pregnancy (P = .001). CONCLUSION: Third-trimester abdominal circumference and estimated fetal weight perform similar in predicting smallness for gestational age. However, for a fixed 10% false-positive rate extrapolated sensitivity is higher for abdominal circumference. There is evidence of better performance when the scan is performed near term and when fetal growth restriction is the targeted condition.

Osteocalcin Serum Levels in Gestational Diabetes Mellitus and Their Intrinsic and Extrinsic Determinants: Systematic Review and Meta-Analysis.

BACKGROUND: Undercarboxylated osteocalcin (ucOC) increases insulin release and insulin resistance in mice. In humans, evidence is scarce but a correlation of ucOC and total osteocalcin (tOC) with glycemic status markers has been demonstrated. The relationship of ucOC and tOC with gestational diabetes mellitus (GDM) has been even less characterized. OBJECTIVE: To assess the mean difference of tOC and ucOC serum concentrations among nondiabetic pregnant women and women diagnosed as GDM in the second trimester of pregnancy and to determine the possible intrinsic and extrinsic contributors to this difference. METHODS: A systematic search was performed to identify relevant studies published in English and Spanish using PubMed, SCOPUS, ISI Web of Knowledge, and PROSPERO database for meta-analysis. Observational studies measuring mean serum levels of osteocalcin among GDM, with at least 10 subjects analyzed in each group were selected. Mean difference (MD) by random effects model was used. Heterogeneity between studies was assessed using Cochran's Q, H, and I 2 statistics. RESULTS: From 38 selected studies, 5 were retained for analysis for a total of 1119 pregnant women. Serum concentrations of tOC were not significantly different among women with GDM and nondiabetic pregnant controls (MD: 1.56; 95% CI: -0.70 to 3.82; p = 0.175). Meanwhile, ucOC serum levels were significantly higher among women with GDM (MD: 1.17; 95% CI: 0.24 to 2.11; p = 0.013). The only factor influencing tOC was the UV index, showing a reduction in mean difference between GDM and controls when exposed to higher concentrations of UV rays. CONCLUSIONS: This meta-analysis provides evidence to support the use of ucOC as a potential marker for GDM rather than tOC, yielding very little variability among studies and no difference among methods or brands used for its analysis.