External validation of Fetal Medicine Foundation competing-risks model for midgestation prediction of small-for-gestational-age neonates in Spanish population.

OBJECTIVE: To examine the external validity of the new Fetal Medicine Foundation (FMF) competing-risks model for prediction in midgestation of small-for-gestational-age (SGA) neonates. METHODS: This was a single-center prospective cohort study of 25 484 women with a singleton pregnancy undergoing routine ultrasound examination at 19 + 0 to 23 + 6 weeks' gestation. The FMF competing-risks model for the prediction of SGA combining maternal factors and midgestation estimated fetal weight by ultrasound scan (EFW) and uterine artery pulsatility index (UtA-PI) was used to calculate risks for different cut-offs of birth-weight percentile and gestational age at delivery. The predictive performance was evaluated in terms of discrimination and calibration. RESULTS: The validation cohort was significantly different in composition compared with the FMF cohort in which the model was developed. In the validation cohort, at a 10% false-positive rate (FPR), maternal factors, EFW and UtA-PI yielded detection rates of 69.6%, 38.7% and 31.7% for SGA < 10th percentile with delivery at < 32, < 37 and ≥ 37 weeks' gestation, respectively. The respective values for SGA < 3rd percentile were 75.7%, 48.2% and 38.1%. Detection rates in the validation cohort were similar to those reported in the FMF study for SGA with delivery at < 32 weeks but lower for SGA with delivery at < 37 and ≥ 37 weeks. Predictive performance in the validation cohort was similar to that reported in a subgroup of the FMF cohort consisting of nulliparous and Caucasian women. Detection rates in the validation cohort at a 15% FPR were 77.4%, 50.0% and 41.5% for SGA < 10th percentile with delivery at < 32, < 37 and ≥ 37 weeks, respectively, which were similar to the respective values reported in the FMF study at a 10% FPR. The model had satisfactory calibration. CONCLUSION: The new competing-risks model for midgestation prediction of SGA developed by the FMF performs well in a large independent Spanish population. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Comparison of color Doppler uterine artery indices in a population at high risk for adverse outcome at 24 weeks' gestation.

OBJECTIVE: To compare uterine artery Doppler velocity and impedance indices in the presence and absence of uterine artery waveform notches, in the prediction of adverse pregnancy outcome in high-risk women. METHODS: One hundred and fifty-seven women identified at Doppler screening as being at 'high risk' underwent a further uterine artery Doppler assessment at 24 weeks' gestation. Pulsatility and resistance indices and minimum, time averaged and time averaged maximum velocities were measured, and the presence of bilateral notches noted. Adverse outcomes were pre-eclampsia, birth weight less than the tenth centile, placental abruption and intrauterine death. The best cut-off for each parameter was assessed by univariate logistic regression, and the comparative performance of the screening parameters was assessed using kappa values. RESULTS: The best performing index in the presence of bilateral notches was mean resistance index, for a cut-off of 0.67, giving a kappa value of 0.65. Mean pulsatility index and lowest pulsatility index performed similarly well, both with kappa values of 0.58. All velocity indices apart from lowest minimum velocity had kappa values of < 0.4. When indices were analyzed, irrespective of notch status, mean resistance and mean pulsatility indices performed similarly, with kappa values of 0.49 and 0.46, respectively; mean minimum velocity had a kappa value of 0.4. CONCLUSIONS: In a high-risk population, uterine artery Doppler mean resistance indices perform better than do velocity indices in the prediction of adverse pregnancy outcome, irrespective of notch status.

Platelet changes and subsequent development of pre-eclampsia and fetal growth restriction in women with abnormal uterine artery Doppler screening.

OBJECTIVES: To investigate whether, in women with abnormal uterine artery Doppler, platelet volume and function will identify a subgroup of women at increased risk of pre-eclampsia and intrauterine growth restriction and whether in-vitro platelet aggregation precedes the onset of clinical disease. DESIGN: Platelet number, volume and aggregation induced by collagen or adenosine 5'-diphosphate were evaluated in 16 non-pregnant controls, 29 pregnant women with normal uterine artery Doppler and 31 pregnant women with abnormal Doppler, hence at risk of pre-eclampsia and intrauterine growth restriction at 23 weeks. Outcome of pregnancy was recorded in each case. RESULTS: Twelve women in the group with abnormal uterine artery Doppler subsequently developed pre-eclampsia and/or intrauterine growth restriction. All women with normal uterine artery Doppler had a normal pregnancy outcome. No differences in platelet count or in vitro platelet aggregation induced by collagen were observed between the groups. Mean platelet volume was greater in those with abnormal Doppler who had intrauterine growth restriction or normal pregnancy outcome compared with normal Doppler (10.3 and 10.3 vs. 9.4 fL, P = 0.004 and P = 0.01, respectively). Aggregation induced by adenosine diphosphate was higher in women with abnormal Doppler who developed pre-eclampsia or intrauterine growth restriction compared with those with normal outcomes (66.5 and 66.5 vs. 21%, P = 0.02, P = 0.03, respectively). CONCLUSIONS: Women with abnormal uterine artery Doppler at 23 weeks show alterations in mean platelet volume and platelet function that relate to subsequent adverse outcome.

Síndrome de transfusión feto-fetal / Twin-twin transfusion syndrome

El síndrome de transfusión feto-fetal (STFF) es una complicación que se presenta en un 10-15 per cent de las gestaciones gemelares monocoriales biamnióticas. Es una afección exclusiva de este tipo de gemelaridad y se caracteriza por la presencia de anastomosis arteriovenosas cuyo flujo unidireccional no está equilibrado por otras conexiones vasculares y, por consiguiente, se produce la secuencia oligoamnios-hidramnios. La afección fetal es debida a una hipovolemia del gemelo donante y a una hipervolemia del gemelo receptor. Presentamos nuestra experiencia en este tipo de enfermedad. En los casos presentados, diagnosticados al final del segundo trimestre, se llevaron a cabo como medida terapéutica amniodrenajes seriados, los cuales permitieron prolongar la gestación para la maduración pulmonar fetal, aunque no solucionaron el STFF. Realizamos, asimismo, una revisión en cuanto a las diferentes opciones de tratamiento actual que van desde la conducta expectante, con una mortalidad cercana al 100 per cent, hasta los tratamientos etiológicos basados en la ablación selectiva con láser de los vasos comunicantes con una supervivencia de al menos un gemelo del 70 per cent, con una tasa de handicap neurológico menor al 5 per cent. (AU)

One-stage screening for pregnancy complications by color Doppler assessment of the uterine arteries at 23 weeks' gestation.

OBJECTIVE: To estimate the value of screening for preeclampsia and fetal growth restriction by performing color Doppler assessment of uterine arteries at 23 weeks' gestation in predicting adverse pregnancy outcome. METHODS: Women with singleton pregnancies who attended routine ultrasonography at 23 weeks had color Doppler uterine artery imaging. Bilateral uterine artery notches were noted and left and right uterine artery pulsatility indices (PI) were measured. A mean PI of more than 1.45 was considered increased. Screening characteristics for predicting preeclampsia and delivery of small-for-gestational-age infants were calculated. RESULTS: Of 1757 pregnancies, increased PI was present in 89 (5.1%) and bilateral notches were noted in 77 (4.4%). Twenty-three of 65 women (35.3%; 95% confidence interval [CI] 23.9, 48.2) had increased PI and later developed preeclampsia, and 8 of 10 (80%; 95% CI 44.4, 97. 5) with preeclampsia required delivery before 34 weeks. The respective values for women with bilateral notches were 21 of 65 (32. 3%; 95% CI 21.2, 45.1) and 8 of 10 (80%; 95% CI 44.4, 97.5). The sensitivity of increased PI was 30 of 143 (21%; 95% CI 14.6, 28.6) for delivery of an infant with birth weight below the tenth percentile and 7 of 10 (70% 95% CI 34.8,93.3) for birth weight below the tenth percentile delivered before 34 weeks. The respective values for bilateral notches were 19 of 143 (13.3%; 95% CI 8.2, 20) and 5 of 10 (50%; 95% CI 18.7, 81.3). CONCLUSION: A one-stage color Doppler screening program at 23 weeks identified most women who subsequently developed serious complications of impaired placentation associated with delivery before 34 weeks. The screening results were similar when the high-risk group was defined as women with increased PI or bilateral notches.

Increased fetal erythroblasts in women who subsequently develop pre-eclampsia.

In pregnancies complicated by pre-eclampsia (PET) and/or intrauterine growth restriction (IUGR) there is an increased number of fetal cells in the maternal circulation. The aim of this study was to investigate whether this increase in fetal cells precedes the onset of these pregnancy complications. Doppler ultrasound studies at 24 weeks gestation have shown that increased impedance to flow in the uterine arteries identifies pregnancies with impaired placental perfusion that subsequently develop PET and/or IUGR. We obtained maternal blood from 18 pregnancies with abnormal Doppler results at 22-24 weeks gestation and from 10 normal controls. Fetal erythroblasts were enriched from maternal blood by triple density gradient centrifugation and magnetic cell sorting with CD71 antibody, and the percentage of these erythroblasts was determined. The median proportion of fetal erythroblasts in the group with abnormal Doppler results was 4.5% (range 1-12%), which was significantly higher than in the control group [median 1% (range 0-3%; P < 0.001)]. Furthermore, within the group with abnormal Doppler the median proportion of fetal erythroblasts was higher in the 10 cases which subsequently developed PET and/or IUGR [median 5.5% (range 3-12%)], than in those with normal pregnancy outcome [median 2% (range 1-5%; P < 0.01)]. These findings suggest that impaired placental perfusion is associated with an increase in feto-maternal cell traffic, which precedes the onset of PET and/or IUGR by several weeks.

Fetal cells in maternal blood of pregnancies with severe fetal growth restriction.

The aim of this study was to examine whether, in pregnancies with severe early onset fetal growth restriction, the number of fetal erythroblasts in maternal blood is increased. The percentage of fetal erythroblasts in maternal blood, enriched by triple density gradient centrifugation and anti-CD71 magnetic cell sorting, was determined in 10 singleton pregnancies with severe intrauterine growth restriction in which there was Doppler ultrasound evidence of impaired placental perfusion. The values were compared to those of 10 normal pregnancies at the same gestational range of 22-26 weeks. In the growth restricted pregnancies the median number of fetal erythroblasts per 100 nucleated cells in maternal blood enriched for fetal cells was significantly higher than the median value in the control pregnancies (8.5% compared with 1%; P < 0.001). These data suggest that impaired uteroplacental perfusion and severe fetal growth restriction may be associated with placental damage leading to increased feto-maternal cell traffic. Alternatively the rate of transfer of fetal cells into the maternal circulation is not altered but in growth restriction the proportion of fetal erythroblasts in fetal blood is increased.

Assessment of umbilical arterial and venous flow using color Doppler.

OBJECTIVE: To estimate the umbilical artery and vein blood volume flow using B-mode and Doppler ultrasound in the second and third trimesters of pregnancy. DESIGN: This was a cross-sectional study of 129 singleton, healthy pregnancies at 23-33 weeks' gestation. The umbilical artery and vein cross-sectional area, time-averaged velocity and pulsatility index were measured in a free loop of cord, and the fetal weight was estimated. Ranges for each parameter were obtained; from these the blood flow for the vein and artery was calculated, and the average flow corrected for fetal weight was derived. RESULTS: The median time for examination was 6 min. The mean cross-sectional area and time-averaged velocity for both the vein and artery increased linearly with gestation. The umbilical artery flow correlated closely with the average vein flow (r = 0.9, p < 0.001). There was a significant, though poor, inverse correlation between the umbilical artery pulsatility index and the average umbilical flow (r = -0.25, p < 0.05). The average umbilical flow (calculated from the mean of arterial and venous flow), corrected for estimated fetal weight, decreased from 189.2 ml/kg per min at 23 weeks to 176.2 ml/kg per min at 33 weeks' gestation. CONCLUSION: The estimates of fetal umbilical flow obtained by this Doppler method are consistent with previously published data. Averaging the arterial and venous flow is theoretically advantageous in reducing the inherent errors in estimating either the arterial or the venous flow. This method of measuring umbilical flow may have clinical potential in assessing fetal health and disease processes.

The role of insulin-like growth factor binding protein-1 phosphoisoforms in pregnancies with impaired placental function identified by doppler ultrasound.

This study was performed to investigate the hypothesis that insulin-like growth factor binding protein-1 (IGFBP-1) is involved in the pathogenesis of trophoblast invasion and impaired placentation in human pregnancy. The role of total and non-phosphorylated IGFBP-1 in women with fetal growth restriction and in high risk pregnancies identified by uterine artery Doppler ultrasound screening was examined. This was a prospective study of women booked for antenatal care having second trimester anomaly scans and Doppler screening between 22-26 weeks gestation. Women were divided into three groups and compared: normal uterine artery Doppler and normal fetal growth (control group, n = 10); abnormal Doppler and normal fetal growth [bilateral uterine artery notches (BN; n = 16); abnormal Doppler and intrauterine growth restriction (IUGR; n = 8)]. Maternal serum was collected, stored and assayed simultaneously for total and non-phosphorylated IGFBP-1. There was elevated total and non-phosphorylated IGFBP-1 (mean 44.99 +/- 12.19 and 29.61 +/- 10.38 microg/l respectively) in the IUGR group compared with controls (mean 17.96 +/- 3.24 and 12.18 +/- 1.55 microg/l, P < 0.05). This finding suggests that the various IGFBP-1 isoforms, the degree of phosphorylation and the ratios of these different forms locally may be important during trophoblast invasion and may be implicated in clinical manifestations of impaired placentation later in the second trimester.