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Introduction: This study aimed to determine the effect and clinical impact of physiological characteristics on the 95th/5th centile of the umbilical artery (UA) Doppler and the cerebroplacental ratio (CPR), at 36+ weeks., Methods: From the multicenter randomized trial "Ratio37," we selected 4,505 low-risk pregnant women between June 2016 and January 2020. We registered physiological characteristics and the pulsatility indexes (PI) of the UA and middle cerebral artery (36-39 weeks). The 95th/5th centile of the UA PI and CPR was modeled by quantile regression. To evaluate the clinical impact of adjusting Doppler, we retrospectively applied gestational age (GA) and fully adjusted standards to 682 small for gestational age (SGA)-suspected fetuses (37 weeks) from a cohort of consecutive patients obtained between January 2010 and January 2020., Results: Several physiological characteristics significantly influenced the 95th/5th centile of the UA and CPR PI. The fully adjusted 95th centile of the UA was higher, and the 5th centile of the CPR was lower than GA-only-adjusted standards. Of the 682 SGA fetuses, 150 (22%) were classified as late fetal growth restricted only by GA and 112 (16.4%) when we adjusted Doppler. These 38 fetuses had similar perinatal outcome than the SGA group., Discussion: The 95th/5th centile of the UA and CPR PI is significantly influenced by physiological characteristics. Adjusting Doppler standards could differentiate better between FGR and SGA., (© 2021 S. Karger AG, Basel.)

Objective: To construct valid reference standards reflecting optimal cerebroplacental ratio and to explore its physiological determinants., Methods: A cohort of 391 low-risk pregnancies of singleton pregnancies of nonmalformed fetuses without maternal medical conditions and with normal perinatal outcomes was created. Doppler measurements of the middle cerebral artery and umbilical artery were performed at 24-42 weeks. Reference standards were produced, and the influence of physiological determinants was explored by nonparametric quantile regression. The derived standards were validated in a cohort of 200 low-risk pregnancies., Results: Maternal body mass index was significantly associated with the 5th centile of the cerebroplacental ratio. For each additional unit of body mass index, the 5th centile was on average 0.014 lower. The derived 5th, 10th, and 50th centiles selected in the validation cohort were 5, 9.5, and 51% of the measurements., Conclusions: This study provides methodologically sound prescriptive standards and suggests that maternal body mass index is a determinant of a cutoff commonly used for decision-making., (© 2020 S. Karger AG, Basel.)

Objective: The aim of this article is to assess the use of the anterior cervical angle (ACA) as a predictor of spontaneous preterm delivery (sPTD) at 20+0-24+6 weeks of gestation in an unselected population., Methods: We conducted a nested case-control study that included 93 women who later delivered spontaneously <34 weeks of gestation and 225 controls. The ACA was assessed retrospectively on all selected images using ImageJ® software. The concordance correlation coefficient was determined for the assessment of interobserver variability. Continuous variables were adjusted by maternal characteristics and expressed as the z-score or multiples of the expected normal median (MoM) of the unaffected group. Logistic regression analysis was used to evaluate whether any maternal characteristics and ultrasound variables were significantly associated with sPTD <34 weeks., Results: ACA z-score values were significantly greater in women who later delivered <34 weeks compared to controls (ACA z-score = 1.32 ± 0.57 vs. -0.09 ± 0.35; p = 0.035). The best prediction of sPTD <34 weeks was provided by a model that combined cervical length (CL) MoM, ACA z-score and maternal characteristics. For a fixed false-positive rate of 10%, the detection rate for this model was 37.6%., Conclusion: A model combining maternal history, CL and ACA at 20+0-24+6 weeks of gestation can predict approximately 40% of the severe preterm births., (© 2016 S. Karger AG, Basel.)

Objective: The aim of this study was to determine the role of nerve growth factor (NGF) in the first-trimester screening for preeclampsia (PE)., Methods: Uterine artery Doppler (UtAD) was determined transvaginally. Maternal concentrations of NGF were assessed in 42 patients who subsequently developed PE and in 95 controls. Quantile and multivariate regression analyses were performed for the NGF and UtAD adjustment and expressed as the multiple of the median (MoM) of the unaffected group. Logistic regression analysis was conducted to identify the best model for the prediction of PE., Results: The maternal plasma concentration of NGF exhibited a trend towards lower values in patients who subsequently developed early-onset PE (e-PE) compared to controls (10.7 vs. 38.2 pg/ml, respectively; p = not significant). The median MoM NGF in the all-PE, e-PE and control groups was 0.97 (95% CI 0.13-3.36), 0.62 (95% CI 0.16-2.19) and 1.00 (95% CI 0.20-2.94), respectively (p = not significant). The best predictors of PE were previous PE, chronic hypertension and UtAD. With a false-positive rate of 10%, the detection rates (DRs) of all-PE and e-PE were 38 and 50%, respectively. The addition of MoM NGF did not improve the DR of PE., Conclusion: First-trimester NGF tends to be lower in patients who subsequently develop e-PE., (© 2016 S. Karger AG, Basel.)

Objective: To evaluate in normally growing fetuses at routine 32-36 weeks scan the performance of maternal angiogenic factors, Doppler and ultrasound indices in predicting smallness for gestational age (SGA) at birth., Methods: A cohort of 1,000 singleton pregnancies with normal estimated fetal weight (EFW, ≥10th centile) at 32-36 weeks scan was included. At inclusion, Doppler indices (mean uterine artery pulsatility index [mUtA-PI], cerebroplacental ratio and normalized umbilical vein blood flow by EFW (ml/min/kg) were evaluated, and blood samples were collected and frozen. Nested in this cohort, maternal circulating placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were assayed by enzyme-linked immunosorbent assay in all cases with a birth weight <10th centile by customized standards and in an equivalent number of controls (birth weight ≥10th centile)., Results: 160 cases were included (80 SGA and 80 controls). EFW (2,128 vs. 2,279 g, p < 0.001), mUtA-PI z-values (-0.25 vs. -0.65, p = 0.034) and sFlt-1/PlGF ratio (11.10 vs. 6.74, p < 0.005) were lower in SGA. The combination of sFlt-1/PlGF ratio and EFW resulted in a 66.3% detection rate for subsequent SGA, with 20% of false-positives. Fetal Doppler indices were not predictive of SGA., Conclusions: In normally growing fetuses, maternal angiogenic factors add to ultrasound parameters in predicting subsequent SGA at birth. This supports further research to investigate composite scores in order to improve the definition and identification of fetal growth restriction., (© 2015 S. Karger AG, Basel.)

Objective: To describe perinatal outcomes achieved with cord occlusion (CO) in monochorionic twins with severe selective intrauterine growth restriction (sIUGR) and abnormal umbilical artery Doppler in the IUGR twin (types II and III)., Methods: We studied a consecutive series of 90 cases of sIUGR with abnormal Doppler treated with CO of the IUGR fetus. Abnormal Doppler was defined as continuous (type II, n = 41) or intermittent (type III, n = 49) absent/reversed end-diastolic flow. All cases presented at least one of the following severity criteria: gestational age (GA) <22 weeks, inter-twin estimated weight discordance >35%, reversed end-diastolic umbilical artery flow or ductus venosus pulsatility index >95th centile. We prospectively recorded pregnancy course and perinatal outcome., Results: Median GA at surgery was 20.6 weeks and mean duration 22.4 min. Miscarriage (<24 weeks) occurred in 3.3% (3/90) and preterm delivery <32 weeks in 7.1% (6/84) of continuing pregnancies. GA at delivery was 36.4 weeks and neonatal survival of the larger twin was achieved in 93.3%., Conclusion: In a consecutive series studied by an experienced team, CO in monochorionic twins with severe sIUGR type II or III was associated with delivery >32 weeks in 92.9% and neonatal survival of the normal twin in 93.3% of pregnancies., (© 2015 S. Karger AG, Basel.)

Objective: To evaluate the fetal mechanical PR interval in fetuses from pregnancies with intrahepatic cholestasis of pregnancy (ICP)., Methods: A case-control study was conducted in the Maternal-Fetal Medicine Unit at Hospital Carlos Van Buren between 2011 and 2013. Fetal echocardiography was performed in patients with ICP and normal pregnancies. Demographic and clinical characteristics were compared using the Mann-Whitney U test for continuous variables. A p value <0.05 was considered significant., Results: 51 patients with ICP were compared with 51 unaffected pregnancies. There were no significant differences in neither demographic nor clinical characteristics between the two groups. The fetal PR interval was significantly longer in the ICP group when compared to the control group (134.6 ± 12 vs. 121.4 ± 10 ms, p < 0.001). Moreover, four fetuses from the ICP group had a mechanical PR interval >150 ms, which is compatible with a first-degree atrioventricular block. Two fetuses were identified in the neonatal period and were transferred to pediatric cardiology for follow-up, with a normal mechanical PR after the first month of life., Conclusions: We demonstrated that the fetal cardiac conduction system is altered in fetuses of patients with ICP. Further research is necessary to determine whether this alteration is related to stillbirths seen in ICP., (© 2016 S. Karger AG, Basel.)

Objective: To characterize patients with atypical preeclampsia (PE), in relation to socio-demographic characteristics, clinical presentation, maternal complications and perinatal outcome., Materials and Methods: Between July 1, 2011 and November 30, 2013, a cohort was created of women attended at a Obstetric High-dependency Unit who met criteria for atypical PE: gestational hypertension with severe hypertension or symptoms or laboratory signs suggestive of microangiopathy/hemolysis; normotensive proteinuria with the presence of symptoms or laboratory signs suggestive of microangiopathy/hemolysis; presence of PE or eclampsia or HELLP syndrome appearing after 48 h postpartum, and, PE or eclampsia appearing before 20 weeks of pregnancy., Results: A total of 200 women fulfilling criteria for atypical PE, were included: 61.5% corresponded to non-proteinuric gestational hypertension, 35.5% to normotensive proteinuria and 3% to PE/eclampsia in late postpartum. Criteria for severe maternal morbidity were present in 12% of the cases and there were no maternal deaths. There were 6 perinatal deaths., Conclusion: Atypical preeclampsia is a type of preeclampsia not fully recognized that is associated with maternal and neonatal morbidity, mainly related to smallness-for-gestational-age and low birth weight. Vasospasm symptoms are a key element to detect this condition.

Aim: To establish normal ranges of maternal placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and sFlt-1/PlGF ratio at 32-41 weeks' gestation and to evaluate the influence of maternal characteristics, and of fetoplacental Doppler., Material and Methods: Serum levels of PlGF, sFlt-1 and sFlt-1/PlGF ratio were measured in 300 noncomplicated pregnancies (30 at each gestational week between 32 and 41). Quantile regression analysis was used to derive gestational age (GA)-adjusted normal ranges, and to account for characteristics that might influence serum levels. The relationship with Doppler indices was tested, including umbilical artery pulsatility index and middle cerebral artery pulsatility index., Results: PlGF decreased with GA from 32 weeks, while sFlt-1 and sFlt-1/PlGF ratio increased steadily. None of the factors evaluated showed any significant influence on the levels of angiogenic factors. PlGF multiple of the median significantly correlated with mean uterine artery Doppler (R -0.17; p = 0.029)., Conclusions: In normal pregnancies during the third trimester, serum PlGF decreases, sFlt-1 increases and sFlt-1/PlGF ratio increases with GA. Angiogenic factor levels needed no adjustment for factors such as smoking, body mass index, blood pressure or parity.

Maternal listeriosis is often associated with mild symptoms for the patient, but fetal infection can lead to severe adverse perinatal outcome. The most described antenatal symptoms are reduced fetal movements and an abnormal fetal heart rate trace. We present a case of fetal listeriosis suspected by ultrasound findings of fetal gastrointestinal compromise, neonatal diagnosis and outcome., (Copyright © 2013 S. Karger AG, Basel.)

Objective: To explore the association between fetal cerebroplacental ratio (CPR) and frontal brain perfusion at third trimester with neonatal neurobehavioral performance in normally grown fetuses., Methods: CPR and frontal brain perfusion measured by fractional moving blood volume (FMBV) were assessed in 258 consecutive healthy fetuses at routine third trimester scan (32-35.6 weeks). Neonates were evaluated with the Neonatal Behavioral Assessment Scale. The association between Doppler parameters and neurobehavior was analyzed by MANCOVA (multiple analysis of covariance) and logistic regression, with adjustment for smoking, socioeconomic class, mode of delivery, gestational age at birth, postnatal days at examination and gender., Results: Fetuses with increased FMBV (in the upper quartile) had lower neurobehavioral scores in all areas, reaching significance in motor (5.6 vs. 5.8; p = 0.049), social (6 vs. 6.4; p = 0.006) and attention (5.3 vs. 5.9; p = 0.032). Fetuses with increased FMBV had higher risk of abnormal (<10th centile) motor (OR 3.3; 95% CI 1.36-8.1), social (OR 2.9; 95 CI% 1.33-6.5) and attention (OR 2.5; 95% CI 1.1-5.8) scores. Fetuses with lower CPR (in the lower quartile) did not differ in their neurobehavioral scores from those with normal values., Conclusions: Normally grown fetuses with increased frontal brain perfusion have poorer neurobehavioral competences, suggesting a disrupted neurological maturation. The results support the existence of forms of placental insufficiency not detected by current definitions of growth restriction., (Copyright © 2013 S. Karger AG, Basel.)

Objective: To assess the value of gestational age and cardiovascular Doppler indices in predicting perinatal mortality in a multicenter cohort of early-onset intrauterine growth-restricted (IUGR) fetuses., Methods: A multicenter prospective cohort study including 157 early-onset (<34 weeks) IUGR cases with abnormal umbilical artery (UA) Doppler was conducted. Cardiovascular assessment included the ductus venosus (DV), the aortic isthmus flow index (IFI), and the myocardial performance index (MPI). Isolated and combined values to predict the risk of perinatal death were evaluated by logistic regression and by decision tree analysis, where the gestational age at delivery, UA, and middle cerebral artery (MCA) were also included as covariates., Results: Perinatal mortality was 17% (27/157). All parameters were significantly associated with perinatal death, with individual odds ratios (OR) of 25.2 for gestational age below 28 weeks, 12.1 for absent/reversed DV atrial flow, 5.3 for MCA pulsatility index <5th centile, 4.6 for UA absent/reversed diastolic end-flow, 1.8 for IFI <5th centile, and 1.6 for MPI >95th centile. Decision tree analysis identified gestational age at birth as the best predictor of death (<26 weeks, 93% mortality; 26-28 weeks, 29% mortality, and >28 weeks, 3% mortality). Between 26 and 28 weeks, DV atrial flow allowed further stratification between high (60%) and low risk (18%) of mortality., Conclusions: Gestational age largely determines the risk of perinatal mortality in early-onset IUGR before 26 weeks and later than 28 weeks of gestation. The DV may improve clinical management by stratifying the probability of death between 26 and 28 weeks of gestation., (Copyright © 2012 S. Karger AG, Basel.)