Assessment of fetal cardiac function in early fetal life: feasibility, reproducibility, and early fetal nomograms.

BACKGROUND: Fetal cardiology has shown a rapid development in the past decades. Fetal echocardiography is not only used for the detection of structural anomalies but also to assess fetal cardiac function. Assessment of the fetal cardiac function is performed mostly in the second and third trimesters. The study of fetal cardiac function at the end of first trimester has not been investigated properly, and there is a lack of reference values at early gestational weeks. OBJECTIVE: This study aimed to assess if the measurement of time-related parameters of cardiac function in the left ventricle of the fetal heart is feasible and reproducible at the end of the first trimester. If possible, we provide nomograms of these parameters from 11 to 13+6 gestational weeks. STUDY DESIGN: We conducted a prospective observational study from March to September 2022. The study was carried out in 2 hospitals (Hospital Universitari Dexeus, Barcelona, and Hospital VITAHS 9 Octubre, Valencia, Spain). The scans were performed by 3 specialists in fetal medicine. The exclusion criteria were fetal cardiac rhythm abnormalities, abnormal nuchal translucency, abnormal ductus venosus, fetal malformations, stillbirth, estimated fetal weight <10 percentile, diabetes, and gestational hypertensive disorders. The cardiac function parameters studied in the left ventricle were isovolumetric contraction time, isovolumetric relaxation time, ejection time, filling time, cycle time, myocardial performance index, ejection time fraction, and filling time fraction. We study the feasibility and intra- and interobserver reproducibility of these parameters using the interclass correlation coefficient. Nomograms were created and the percentiles of the values of the different parameters were calculated. RESULTS: A total of 409 cases were recruited but only 296 could be included in the statistical analysis once the exclusion criteria were applied. The intraobserver reproducibility study was excellent (interclass correlation coefficient >0.900), and the interobserver reproducibility study was good (interclass correlation coefficient >0.700). The data regression analysis showed that cycle time, filling time, isovolumetric contraction time, and filling time fraction increased with gestational age, whereas ejection time fraction decreased with gestational age and myocardial performance index (mean, 0.43±0.08), isovolumetric relaxation time (mean, 0.04±0.01), and ejection time (mean, 0.16±0.01) remained constant from 11 to 13 weeks. CONCLUSION: The study of fetal cardiac function is feasible and reproducible at 11 to 13+6 gestational weeks. Nomograms of the studied parameters are provided.

Prevalence of corpus callosum pathology in an unselected population. Should assessment of the corpus callosum be included in the routine 20 weeks scan?

OBJECTIVES: To determine the prevalence of abnormalities of the corpus callosum (AbnCC) in a non-selected population, to propose a systematic screening protocol for AbnCC in all populations through direct assessment, and to describe the follow-up and prognosis of all AbnCC cases diagnosed in our clinical setting. METHODS: This was a retrospective review of the prevalence of AbnCC over 11 years. We included a sagittal assessment of the corpus callosum (CC) in the second-trimester scan. AbnCC was classified into complete agenesis of CC (ACC) and dysgenesis of CC (DCC; including small, partial agenesis, thick and with lipoma). RESULTS: Of the 38,586 second-trimester scans performed during our screening, 43 cases of AbnCC were detected (prevalence of 0.8/1000). Of the AbnCC cases, 10 cases were identified as ACC (29.40%) and 24 as DCC (70.59%). Follow-up investigations showed that in the 43 cases with AbnCC, 76.5% had other associated ultrasound abnormalities, 26.5% had genetic abnormalities, 11.8% had other MRI abnormalities, and 25% of the children had neurodevelopmental delays (8.8% of the total), which were severe in only one case. CONCLUSIONS: AbnCC is found in approximately 0.8/1000 of cases in an unselected population. The findings suggest that systematic and direct assessment of the CC as part of screening ultrasound in the second trimester of gestation should be recommended as a routine practice.

Fetal Megacystis: Associated Structural Abnormalities and Obstetric Outcomes.

Purpose: We evaluated the obstetrical outcomes, ultrasonographic characteristics, and final diagnosis in pregnancies with fetal megacystis (FM). Methods: We evaluated the obstetrical outcomes and associated structural abnormalities of fetuses with FM detected between FM between 2000 and 2021. Results: 17 FM were diagnosed, 16 had follow up. 16 were early megacystis. 14/16 (87.5%) of pregnancies were terminated, 1/16 (6.25%) resulted in intrauterine death, and 1/16 (6.25%) survived. FM was associated with 13 other abnormal sonographic findings in 12/16 (75%) pregnancies. The most common associated ultrasound abnormality was umbilical cord cyst in 3/16 (18.75%). Recognized etiologies included posterior urethral valves (2), trisomy 18 (2), trisomy 13 (1), Prune Belly syndrome (1), and Megacystis-Microcolon-Hypoperistalsis syndrome (1). Conclusion: Most FM are detected in the 2nd trimester, most are electively terminated, are associated with other ultrasonic abnormalities in 75%, most commonly umbilical cord cyst, and have an identifiable cause in 44%.

Prenatal screening after preimplantation genetic testing for aneuploidy: time to evaluate old strategies.

RESEARCH QUESTION: How does first-trimester aneuploidy screening perform in pregnancies achieved through IVF with preimplantation genetic testing for aneuploidy (PGT-A) in a medical setting? DESIGN: This retrospective cohort study was undertaken in a single tertiary care centre between January 2013 and June 2022. In total, 20,237 women had prenatal follow-up at the study centre and were included in the study. The women were divided into three groups: singleton pregnancies conceived through the transfer of a PGT-A-screened euploid embryo (n = 510); singleton pregnancies conceived through IVF without PGT-A (n = 3291); and singleton pregnancies conceived naturally (n = 16,436). RESULTS: The conventional combined screening test for pregnancies conceived through IVF with PGT-A had specificity of 91%; sensitivity could not be calculated as there were no cases of fetal aneuploidy in this group. In 89.1% of pregnancies conceived through IVF with PGT-A with high risk for trisomy 21, 18 or 13, the result was related to advanced maternal age (>35 years at time of screening). CONCLUSIONS: The current screening strategy for trisomies 21, 18 and 13 can generate unnecessary tests in pregnancies achieved through IVF with PGT-A. A new protocol is needed for these patients, with greater weight given to ultrasound markers.

"Screening for small-for-gestational age neonates at early third trimester in a high-risk population for preeclampsia".

BACKGROUND: Strategies to improve prenatal detection of small-for-gestational age (SGA) neonates are necessary because its association with poorer perinatal outcome. This study evaluated, in pregnancies with first trimester high risk of early preeclampsia, the performance of a third trimester screening for SGA combining biophysical and biochemical markers. METHODS: This is a prospective longitudinal study on 378 singleton pregnancies identified at high risk of early preeclampsia according to a first trimester multiparametric algorithm with the cutoff corresponding to 15% false positive rate. This cohort included 50 cases that delivered SGA neonates with birthweight < 10th centile (13.2%) and 328 cases with normal birthweight (86.8%). At 27-30 weeks' gestation, maternal weight, blood pressure, estimated fetal weight, mean uterine artery pulsatility index and maternal biochemical markers (placental growth factor and soluble FMS-Like Tyrosine Kinase-1) were assessed. Different predictive models were created to evaluate their performance to predict SGA neonates. RESULTS: For a 15% FPR, a model that combines maternal characteristics, estimated fetal weight, mean uterine artery pulsatility index and placental growth factor achieved a detection rate (DR) of 56% with a negative predictive value of 92.2%. The area under receiver operating characteristic curve (AUC) was 0.79 (95% confidence interval (CI), 0.72-0.86). The DR of a model including maternal characteristics, estimated fetal weight and mean uterine artery pulsatility index was 54% (AUC, 0.77 (95% CI, 0.70-0.84)). The DR of a model that includes maternal characteristics and placental growth factor achieved a similar performance (DR 56%, AUC 0.75, 95% CI (0.67-0.83)). CONCLUSIONS: The performance of screening for SGA neonates at early third trimester combining biophysical and biochemical markers in a high-risk population is poor. However, a high negative predictive value could help in reducing maternal anxiety, avoid iatrogenic interventions and propose a specific plan for higher risk patients.

Strategies for the prediction of late preeclampsia.

Objectives: To evaluate different strategies for the prediction of late preeclampsia. Methods: A retrospective study was undertaken. A predictive model including maternal parameters (maternal age, maternal BMI, maternal history of preeclampsia or intrauterine growth restriction (PE/IUGR) or maternal chronic disease, and maternal arterial pressure) and mean pulsatility index (PI) of uterine Doppler was created. It was evaluated as an independent model in each trimester, considering 11-13.6 weeks, 20-22.6 weeks and 32-33.6 weeks consequently, and as an integrated model. Results: In the group of late preeclampsia, patients were more obese and had higher incidence of chronic hypertension. Uterine artery pulsatility index (UtA PI) and mean blood pressure were increased in all three trimesters. When evaluating all three models independently, third trimester model performed better than the other two with a sensitivity of 79% and specificity of 82%. The area under the receiver-operating characteristic (ROC) curve (AUC) was 0.86. The integration of all three determinations did not improve third trimester's model. Conclusion: Prediction of late preeclampsia at third trimester seems to be possible if maternal characteristics, blood pressure and UtA Doppler are included.

Serum activin A and follistatin levels in gestational diabetes and the association of the Activin A-Follistatin system with anthropometric parameters in offspring.

CONTEXT: The Activin A-Follistatin system has emerged as an important regulator of lipid and glucose metabolism with possible repercussions on fetal growth. OBJECTIVE: To analyze circulating activin A, follistatin and follistatin-like-3 (FSTL3) levels and their relationship with glucose metabolism in pregnant women and their influence on fetal growth and neonatal adiposity. DESIGN AND METHODS: A prospective cohort was studied comprising 207 pregnant women, 129 with normal glucose tolerance (NGT) and 78 with gestational diabetes mellitus (GDM) and their offspring. Activin A, follistatin and FSTL3 levels were measured in maternal serum collected in the early third trimester of pregnancy. Serial fetal ultrasounds were performed during the third trimester to evaluate fetal growth. Neonatal anthropometry was measured to assess neonatal adiposity. RESULTS: Serum follistatin levels were significantly lower in GDM than in NGT pregnant women (8.21±2.32 ng/mL vs 9.22±3.41, P = 0.012) whereas serum FSTL3 and activin A levels were comparable between the two groups. Serum follistatin concentrations were negatively correlated with HOMA-IR and positively with ultrasound growth parameters such as fractional thigh volume estimation in the middle of the third trimester and percent fat mass at birth. Also, in the stepwise multiple linear regression analysis serum follistatin levels were negatively associated with HOMA-IR (ß = -0.199, P = 0.008) and the diagnosis of gestational diabetes (ß = -0.138, P = 0.049). Likewise, fractional thigh volume estimation in the middle of third trimester and percent fat mass at birth were positively determined by serum follistatin levels (ß = 0.214, P = 0.005 and ß = 0.231, P = 0.002, respectively). CONCLUSIONS: Circulating follistatin levels are reduced in GDM compared with NGT pregnant women and they are positively associated with fetal growth and neonatal adiposity. These data suggest a role of the Activin-Follistatin system in maternal and fetal metabolism during pregnancy.

Maternal and cord blood adiponectin multimeric forms in gestational diabetes mellitus: a prospective analysis.

OBJECTIVE: To analyze the relationship between maternal adiponectin (mAdiponectin) and cord blood adiponectin (cbAdiponectin) multimeric forms (high molecular weight [HMW], medium molecular weight [MMW], and low molecular weight [LMW]) in a cohort of gestational diabetes mellitus (GDM) and normal glucose-tolerant (NGT) pregnant women. RESEARCH DESIGN AND METHODS: A total of 212 women with a singleton pregnancy, 132 with NGT and 80 with GDM, and their offspring were studied. Maternal blood was obtained in the early third trimester and cord blood was obtained at delivery. Total adiponectin and the multimeric forms of adiponectin were determined in cord blood and maternal serum. Spearman rank correlation and stepwise linear correlation analysis were used to assess the relationship between cbAdiponectin levels and clinical and analytical parameters. RESULTS: No differences in cbAdiponectin concentration or its multimeric forms were observed in the offspring of diabetic mothers compared with NGT mothers. The HMW-to-total adiponectin ratio was higher in cord blood than in maternal serum, whereas the MMW- and LMW-to-total adiponectin ratio was lower. Cord blood total and HMW adiponectin levels were positively correlated with birth weight and the ponderal index (PI), whereas cord blood MMW adiponectin was negatively correlated with the PI. In addition, cbAdiponectin and its multimeric forms were correlated with mAdiponectin concentrations. In the multivariate analysis, maternal multimeric forms of adiponectin emerged as independent predictors of cbAdiponectin, its multimers, and their distribution. CONCLUSIONS: cbAdiponectin concentrations are independently related to mAdiponectin levels and unrelated to the diagnosis of GDM. Maternal multimeric forms of adiponectin are independent predictors of the concentrations of cbAdiponectin and its multimeric forms at delivery.