OBJECTIVE: To evaluate the performance of an artificial intelligence (AI) and machine learning (ML) model for first-trimester screening for pre-eclampsia in a large Asian population.
METHODS: This was a secondary analysis of a multicenter prospective cohort study in 10 935 participants with singleton pregnancies attending for routine pregnancy care at 11-13+6 weeks of gestation in seven regions in Asia between December 2016 and June 2018. We applied the AI+ML model for the first-trimester prediction of preterm pre-eclampsia (<37 weeks), term pre-eclampsia (≥37 weeks), and any pre-eclampsia, which was derived and tested in a cohort of pregnant participants in the UK (Model 1). This model comprises maternal factors with measurements of mean arterial pressure, uterine artery pulsatility index, and serum placental growth factor (PlGF). The model was further retrained with adjustments for analyzers used for biochemical testing (Model 2). Discrimination was assessed by area under the receiver operating characteristic curve (AUC). The Delong test was used to compare the AUC of Model 1, Model 2, and the Fetal Medicine Foundation (FMF) competing risk model.
RESULTS: The predictive performance of Model 1 was significantly lower than that of the FMF competing risk model in the prediction of preterm pre-eclampsia (0.82, 95% confidence interval [CI] 0.77-0.87 vs. 0.86, 95% CI 0.811-0.91, P = 0.019), term pre-eclampsia (0.75, 95% CI 0.71-0.80 vs. 0.79, 95% CI 0.75-0.83, P = 0.006), and any pre-eclampsia (0.78, 95% CI 0.74-0.81 vs. 0.82, 95% CI 0.79-0.84, P < 0.001). Following the retraining of the data with adjustments for the PlGF analyzers, the performance of Model 2 for predicting preterm pre-eclampsia, term pre-eclampsia, and any pre-eclampsia was improved with the AUC values increased to 0.84 (95% CI 0.80-0.89), 0.77 (95% CI 0.73-0.81), and 0.80 (95% CI 0.76-0.83), respectively. There were no differences in AUCs between Model 2 and the FMF competing risk model in the prediction of preterm pre-eclampsia (P = 0.135) and term pre-eclampsia (P = 0.084). However, Model 2 was inferior to the FMF competing risk model in predicting any pre-eclampsia (P = 0.024).
CONCLUSIONS: This study has demonstrated that following adjustment for the biochemical marker analyzers, the predictive performance of the AI+ML prediction model for pre-eclampsia in the first trimester was comparable to that of the FMF competing risk model in an Asian population.

To longitudinally and cross-sectionally study the differences in the uterine artery pulsatility index (UTPI), umbilical artery pulsatility index (UAPI) and placental vascularization indices (PVIs, derived from 3-dimensional power Doppler) between normal and placental insufficiency pregnancies throughout gestation.
UTPI, UAPI and PVI were measured 6 times at 4- to 5- week intervals from 11 to 13+6 weeks-36 weeks. Preeclampsia (PE) and fetal growth restriction (FGR) were defined as placental insufficiency. Comparisons of UTPI, UAPI and PVI between normal and insufficiency groups were performed by one-way repeated measures analysis of variance.
A total of 125 women were included: monitored regularly from the first trimester to 36 weeks of gestation: 109 with normal pregnancies and 16 with placental insufficiency. Longitudinal study of the normal pregnancy group showed that UTPI and UAPI decreased significantly every 4 weeks, while PVIs increased significantly every 8 weeks until term. In the placental insufficiency group however, this decrease occurred slower at 8 weeks intervals and UTPI stabilized after 24 weeks. No significant difference was noted in PVIs throughout pregnancy. Cross-sectional study from different stages of gestation showed that UTPI was higher in the insufficiency group from 15 weeks onward and PVIs were lower after 32 weeks.
Compared to high-risk pregnancies with normal outcome, UTPI and UAPI needed a longer time to reach a significant change in those with clinical confirmation of placental insufficiency pregnancies and no significant change was found in PVI throughout gestation. UTPI was the earliest factor in detecting adverse outcome pregnancies.

UNASSIGNED: To study the predictive accuracy of maternal characteristics, mean arterial pressure, uterine artery doppler and maternal ophthalmic artery doppler in second trimester for subsequent development of pre-eclampsia.
UNASSIGNED: A prospective cohort study of 440 women at 19-24 weeks\' gestation. It included recording of maternal demographic characteristics and calculation of HDP Gestosis Score, measurement of MAP and ultrasound evaluation for fetal anatomy, Uterine artery doppler and maternal ophthalmic artery doppler. The mean Peak Systolic Velocity ratio was obtained by taking two sets of reading from both eyes. The statistical analysis was done using independent t-test for quantitative variables and chi-square test, Fisher\'s exact test for qualitative variables and Area Under Curve was obtained at 10% False Positive Rate.
UNASSIGNED: Among 440 pregnant women, 43(10.8%) developed Hypertensive Disorder of Pregnancy (8 early onset PE, 16 late onset PE and 19 GHTN) and 42 were lost to follow up, with an incidence rate of 10.8%. Combination of Gestosis Score + OAD PSV Ratio had highest AUC of 0.73. Whereas combination of Gestosis Score + MAP + UtAPI + OAD-PSV Ratio had highest sensitivity of 97.67%. The OAD PSV ratio improved detection rate of Gestosis Score (from 90 to 100%) for prediction of development of PE, especially Preterm PE at 10% FPR.
UNASSIGNED: Maternal Ophthalmic artery doppler study significantly improved prediction of development of PE at 19-24 weeks\' gestation, both independently as well as in combination with HDP-Gestosis Score, MAP and uterine artery doppler.

To examine the external validity of the Fetal Medicine Foundation (FMF) competing-risks model for the prediction of small-for-gestational age (SGA) at 11-14 weeks\' gestation in an Asian population.
This was a secondary analysis of a multicenter prospective cohort study in 10 120 women with a singleton pregnancy undergoing routine assessment at 11-14 weeks\' gestation. We applied the FMF competing-risks model for the first-trimester prediction of SGA, combining maternal characteristics and medical history with measurements of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF) concentration. We calculated risks for different cut-offs of birth-weight percentile (< 10th , < 5th or < 3rd percentile) and gestational age at delivery (< 37 weeks (preterm SGA) or SGA at any gestational age). Predictive performance was examined in terms of discrimination and calibration.
The predictive performance of the competing-risks model for SGA was similar to that reported in the original FMF study. Specifically, the combination of maternal factors with MAP, UtA-PI and PlGF yielded the best performance for the prediction of preterm SGA with birth weight < 10th percentile (SGA < 10th ) and preterm SGA with birth weight < 5th percentile (SGA < 5th ), with areas under the receiver-operating-characteristics curve (AUCs) of 0.765 (95% CI, 0.720-0.809) and 0.789 (95% CI, 0.736-0.841), respectively. Combining maternal factors with MAP and PlGF yielded the best model for predicting preterm SGA with birth weight < 3rd percentile (SGA < 3rd ) (AUC, 0.797 (95% CI, 0.744-0.850)). After excluding cases with pre-eclampsia, the combination of maternal factors with MAP, UtA-PI and PlGF yielded the best performance for the prediction of preterm SGA < 10th and preterm SGA < 5th , with AUCs of 0.743 (95% CI, 0.691-0.795) and 0.762 (95% CI, 0.700-0.824), respectively. However, the best model for predicting preterm SGA < 3rd without pre-eclampsia was the combination of maternal factors and PlGF (AUC, 0.786 (95% CI, 0.723-0.849)). The FMF competing-risks model including maternal factors, MAP, UtA-PI and PlGF achieved detection rates of 42.2%, 47.3% and 48.1%, at a fixed false-positive rate of 10%, for the prediction of preterm SGA < 10th , preterm SGA < 5th and preterm SGA < 3rd , respectively. The calibration of the model was satisfactory.
The screening performance of the FMF first-trimester competing-risks model for SGA in a large, independent cohort of Asian women is comparable with that reported in the original FMF study in a mixed European population. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Small-for-gestational-age (SGA) neonates are at increased risk of perinatal mortality and morbidity. We aimed to investigate the performance of uterine artery pulsatility index (UtA-PI) at 19-24 weeks\' gestation to predict the delivery of a SGA neonate in a Chinese population.
This was a retrospective cohort study using data obtained between January 2010 and June 2018. Doppler ultrasonography was performed at 19-24 weeks\' gestation. SGA was defined as birth weight below the 10th centile according to the INTERGROWTH-21st fetal growth standards. The performance of UtA-PI to predict the delivery of a SGA neonate was assessed using receiver-operating-characteristics (ROC)-curve analysis.
We included 6964 singleton pregnancies, of which 748 (11%) delivered a SGA neonate, including 115 (15%) women with preterm delivery. Increased UtA-PI was associated with an elevated risk of SGA, both in neonates delivered at or after 37 weeks\' gestation (term SGA) and those delivered before 37 weeks (preterm SGA). The areas under the ROC curve (AUCs) for UtA-PI were 64.4% (95% CI, 61.5-67.3%) and 75.8% (95% CI, 69.3-82.3%) for term and preterm SGA, respectively. The performance of combined screening by maternal demographic/clinical characteristics and estimated fetal weight in the detection of term and preterm SGA was improved significantly by the addition of UtA-PI, although the increase in AUC was modest (2.4% for term SGA and 4.9% for preterm SGA).
This is the first Chinese study to evaluate the role of UtA-PI at 19-24 weeks\' gestation in the prediction of the delivery of a neonate with SGA. The addition of UtA-PI to traditional risk factors improved the screening performance for SGA, and this improvement was greater in predicting preterm SGA compared with term SGA. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

BACKGROUND: Early pregnancy loss (EPL) or spontaneous loss of an intrauterine pregnancy within the first trimester occurs commonly worldwide. It is useful to predict the possibility of fetal chromosomal abnormalities using other cheap and easily available markers.
OBJECTIVE: This study aimed to evaluate whether the uterine artery pulsatility index (UtA-PI) can predict fetal chromosomal abnormality in early pregnancy loss (EPL).
METHODS: This was a retrospective cohort study including 148 women who underwent dilation and curettage for missed abortion. The UtA-PI was measured and evaluated by transvaginal ultrasound. Abnormal UtA-PI was identified through the mean of left and right UA-PI ≥ 90th percentiles of the relevant values for the corresponding gestational age. Copy number variation sequencing (CNV-seq) was performed on EPL cases without maternal cell contamination.
RESULTS: 107 (72.3%) cases were classified with normal UtA-PI, while 41 (27.7%) cases were classified with abnormal UtA-PI. The fetal chromosomal abnormality rate was significantly higher in cases with normal UtA-PI than in those with abnormal UtA-PI (67.3% vs 22.0%, P = 7.1 × 10-7). Compared to cases with abnormal UtA-PI, the risk of fetal chromosomal abnormalities in cases with normal UtA-PI increased with an odds ratio of 7.3 (95% confidence interval [CI]: 3.2‒17.0, P = 4 × 10-7). The predictive value of normal UtA-PI alone for fetal chromosomal abnormalities was shown to have an area under the curve of 0.67‒0.71 in our population.
CONCLUSIONS: The UtA-PI seems to be lower and less likely to be elevated in EPL with fetal chromosomal abnormalities compared to those without aneuploidies. We suggest that UtA-PI should be examined in all EPL patients.

Miscarriage is a major concern in early pregnancy among women having conceived with assisted reproductive treatments. This study aimed to examine potential miscarriage-related biophysical and biochemical markers at 6 weeks\' gestation among women with confirmed clinical pregnancy following in vitro fertilization (IVF)/embryo transfer (ET) and evaluate the performance of a model combining maternal factors, biophysical and biochemical markers at 6 weeks\' gestation in the prediction of first trimester miscarriage among singleton pregnancies following IVF/ET.
A prospective cohort study was conducted in a teaching hospital between December 2017 and January 2020 including women who conceived through IVF/ET. Maternal mean arterial pressure, ultrasound markers including mean gestational sac diameter, fetal heart activity, crown rump length and mean uterine artery pulsatility index (mUTPI) and biochemical biomarkers including maternal serum soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), kisspeptin and glycodelin-A were measured at 6 weeks\' gestation. Logistic regression analysis was carried out to determine significant predictors of miscarriage prior to 13 weeks\' gestation and performance of screening was estimated by receiver-operating characteristics curve analysis.
Among 169 included pregnancies, 145 (85.8%) pregnancies progressed to beyond 13 weeks\' gestation and had live births whereas 24 (14.2%) pregnancies resulted in a miscarriage during the first trimester. In the miscarriage group, compared to the live birth group, maternal age, body mass index, and mean arterial pressure were significantly increased; mean gestational sac diameter, crown rump length, mUTPI, serum sFlt-1, glycodelin-A, and the rate of positive fetal heart activity were significantly decreased, while no significant differences were detected in PlGF and kisspeptin. Significant prediction for miscarriage before 13 weeks\' gestation was provided by maternal age, fetal heart activity, mUTPI, and serum glycodelin-A. The combination of maternal age, ultrasound (fetal heart activity and mUTPI), and biochemical (glycodelin-A) markers achieved the highest area under the curve (AUC: 0.918, 95% CI 0.866-0.955), with estimated detection rates of 54.2% and 70.8% for miscarriage before 13 weeks\' gestation, at fixed false positive rates of 5% and 10%, respectively.
A combination of maternal age, fetal heart activity, mUTPI, and serum glycodelin-A at 6 weeks\' gestation could effectively identify IVF/ET pregnancies at risk of first trimester miscarriage.

Background and Objectives: In this study, we aimed to describe the clinical and ultrasound (US) features and the outcome in a group of patients suspected of or diagnosed with early onset intrauterine growth restriction (IUGR) requiring iatrogenic delivery before 32 weeks, having no structural or genetic fetal anomalies, managed in our unit. A secondary aim was to report the incidence of the condition in the population cared for in our hospital, data on immediate postnatal follow-up in these cases and to highlight the differences required in prenatal and postnatal care. Materials and Methods: We used as single criteria for defining the suspicion of early IUGR the sonographic estimation of fetal weight < p10 using the Hadlock 4 technique at any scan performed before 32 weeks’ gestation (WG). We used a cohort of patients having a normal evolution in pregnancy and uneventful vaginal births as controls. Data on pregnancy ultrasound, characteristics and neonatal outcomes were collected and analyzed. We hypothesized that the gestational age (GA) at delivery is related to the severity of the condition. Therefore, we performed a subanalysis in two subgroups, which were divided based on the GA at iatrogenic delivery (between 27+0 WG and 29+6 WG and 30+0−32+0 WG, respectively). Results: The prospective cohort study included 36 pregnancies. We had three cases of intrauterine fetal death (8.3%). The incidence was 1.98% in our population. We confirmed that severe cases (very early diagnosed and delivered) were associated with a higher number of prenatal visits and higher uterine arteries (UtA) pulsatility index (PI) centile in the third trimester—TT (compared with the early diagnosed and delivered). In the very early suspected IUGR subgroup, the newborns required significantly more NICU days and total hospitalization days. Conclusions: Patients with isolated very early and early IUGR—defined as ultrasound (US) estimation of fetal weight < p10 using the Hadlock 4 technique requiring iatrogenic delivery before 32 weeks’ gestation—require closer care prenatally and postnatally. These patients represent an economical burden for the health system, needing significantly longer hospitalization intervals, GA at birth and UtA PI centiles being related to it.

BACKGROUND: Placental hypoxia and resultant oxidative stress have been associated with the development of preeclampsia. Oxidative stress promotes the formation of advanced glycation end products.
OBJECTIVE: This study aimed to assess whether serum levels of advanced glycation end products during the early stage of pregnancy are a predictive biomarker of early-onset and late-onset preeclampsia.
METHODS: This was a nested case-control study that included 6 women with early-onset preeclampsia, 21 women with late-onset preeclampsia, and 50 age- and body mass index-matched healthy female control subjects. All women enrolled in the study had a complete medical history, including mean arterial pressure and uterine artery pulsatility index measurements. Furthermore, the women underwent blood chemistry analysis, including circulating levels of advanced glycation end products, soluble fms-like tyrosine kinase-1, and placental growth factor. Clinical measurements and biochemistry were evaluated at 11 to 13 and 19 to 24 weeks of gestation.
RESULTS: The median serum concentrations of advanced glycation end products at 11 to 13 weeks of gestation were significantly higher in patients with early-onset preeclampsia than in those with late-onset preeclampsia and control subjects (6.62 vs 4.10 vs 3.77; P<.05), but no significant difference was found in advanced glycation end products at 19 to 24 weeks of gestation among the 3 groups. The advanced glycation end product-to-placental growth factor ratio in the first trimester of pregnancy was significantly higher in patients with early-onset preeclampsia than in those with late-onset preeclampsia or control subjects (0.78 vs 0.10 vs 0.10; P<.05). The area under the receiver operating characteristic curve values for patients with early-onset preeclampsia were 0.782 (95% confidence interval, 0.522-0.922), 0.855 (95% confidence interval, 0.433-0.978), and 0.925 (95% confidence interval, 0.724-0.983) for the advanced glycation end product and placental growth factor levels and advanced glycation end product-to-placental growth factor ratios, respectively. This population achieved a 100% detection rate for predicting early-onset preeclampsia at a screen-positive rate of 10% by combining the advanced glycation end product-to-placental growth factor ratio and the mean arterial pressure.
CONCLUSIONS: The study results suggested that an elevated advanced glycation end product-to-placental growth factor ratio and mean arterial pressure at 11 to 13 weeks of gestation could be a potential biomarker for predicting the future development of early-onset preeclampsia.

Data on the effects of selenium (Se) supplementation on clinical outcomes, metabolic profiles, and pulsatility index (PI) in high-risk mothers in terms of preeclampsia (PE) screening with quadruple tests are scarce. This study evaluated the effects of Se supplementation on clinical outcomes, metabolic profiles, and uterine artery PI on Doppler ultrasound in high-risk mothers in terms of PE screening with quad marker. The current randomized, double-blind, placebo-controlled trial was conducted among 60 high-risk pregnant women screening for PE with quad tests. Participants were randomly allocated into two groups (30 participants each group), received either 200 µg/day Se supplements (as Se amino acid chelate) or placebo from 16 to 18 weeks of pregnancy for 12 weeks. Clinical outcomes, metabolic profiles, and uterine artery PI were assessed at baseline and at the end of trial. Se supplementation resulted in a significant elevation in serum Se levels (β 22.25 µg/dl; 95% CI, 18.3, 26.1; P < 0.001) compared with the placebo. Also, Se supplementation resulted in a significant elevation in total antioxidant capacity (β 82.88 mmol/L; 95% CI, 3.03, 162.73; P = 0.04), and total glutathione (β 71.35 µmol/L; 95% CI, 5.76, 136.94; P = 0.03), and a significant reduction in high-sensitivity C-reactive protein levels (β - 1.52; 95% CI, - 2.91, - 0.14; P = 0.03) compared with the placebo. Additionally, Se supplementation significantly decreased PI of the uterine artery in Doppler ultrasound (β - 0.09; 95% CI, - 0.14, - 0.04; P = 0.04), and a significant improvement in depression (β - 5.63; 95% CI, - 6.97, - 4.28; P < 0.001), anxiety (β - 1.99; 95% CI, - 2.56, - 1.42; P < 0.001), and sleep quality (β - 1.97; 95% CI, - 2.47, - 1.46; P < 0.001). Se supplementation for 12 weeks in high-risk pregnant women in terms of PE screening with quad marker had beneficial effects on serum Se level, some metabolic profiles, uterine artery PI, and mental health. IRCT Registration: htpp:// www.irct.ir ; identifier IRCT20200608047701N1.