Ophthalmic artery Doppler at 36 weeks' gestation in prediction of pre-eclampsia: validation and update of previous model.

OBJECTIVE: To validate and extend a model incorporating maternal ophthalmic artery Doppler at 35-37 weeks' gestation in the prediction of subsequent development of pre-eclampsia (PE). METHODS: This was a prospective validation study of screening for PE (defined according to the 2019 American College of Obstetricians and Gynecologists criteria) by maternal ophthalmic artery peak systolic velocity (PSV) ratio in 6746 singleton pregnancies undergoing routine care at 35 + 0 to 36 + 6 weeks' gestation (validation dataset). Additionally, the data from the validation dataset were combined with those of 2287 pregnancies that were previously used for development of the model (training dataset), and the combined data were used to update the original model parameters. The competing-risks model was used to estimate the individual patient-specific risk of delivery with PE at any time and within 3 weeks from assessment by a combination of maternal demographic characteristics and medical history with PSV ratio alone and in combination with the established PE biomarkers of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1). We evaluated the predictive performance of the model by examining, first, the ability to discriminate between the PE and non-PE groups using the area under the receiver-operating-characteristics curve and the detection rate (DR) at fixed screen-positive (SPR) and false-positive rates of 10% and, second, calibration by measuring the calibration slope and calibration-in-the-large. McNemar's test was used to compare the performance of screening by a biophysical test (maternal factors, MAP, UtA-PI and PSV ratio) vs a biochemical test (maternal factors, PlGF and sFlt-1), low PlGF concentration (< 10th percentile) or high sFlt-1/PlGF concentration ratio (> 90th percentile). RESULTS: In the validation dataset, the performance of screening by maternal factors and PSV ratio for delivery with PE within 3 weeks and at any time after assessment was consistent with that in the training dataset, and there was good agreement between the predicted and observed incidence of PE. In the combined data from the training and validation datasets, good prediction for PE was achieved in screening by a combination of maternal factors, MAP, UtA-PI, PlGF, sFlt-1 and PSV ratio, with a DR, at a 10% SPR, of 85.0% (95% CI, 76.5-91.4%) for delivery with PE within 3 weeks and 65.7% (95% CI, 59.2-71.7%) for delivery with PE at any time after assessment. The performance of a biophysical test was superior to that of screening by low PlGF concentration or high sFlt-1/PlGF concentration ratio but not significantly different from the performance of a biochemical test combining maternal factors with PlGF and sFlt-1 for both PE within 3 weeks and PE at any time after assessment. CONCLUSION: Maternal ophthalmic artery PSV ratio at 35-37 weeks' gestation in combination with other biomarkers provides effective prediction of subsequent development of PE. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Ophthalmic artery Doppler and biomarkers of impaired placentation at 36 weeks' gestation in pregnancies with small fetuses.

OBJECTIVES: First, to compare ophthalmic artery peak systolic velocity (PSV) ratio and biomarkers of impaired placentation at 36 weeks' gestation in women who delivered a small-for-gestational-age (SGA) or growth-restricted (FGR) neonate, in the absence of hypertensive disorder, with those of women who developed pre-eclampsia (PE) or gestational hypertension (GH) and of women unaffected by SGA, FGR, PE or GH. Second, to examine the associations of PSV ratio, uterine artery pulsatility index (UtA-PI), placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) with birth-weight Z-score or percentile. METHODS: This was a prospective observational study of women with a singleton pregnancy attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, ultrasound examination of fetal anatomy and growth, and measurement of maternal ophthalmic artery PSV ratio, UtA-PI, PlGF and sFlt-1. Values of PSV ratio, UtA-PI, PlGF and sFlt-1 were converted to multiples of the median (MoM) or delta values. Median MoM or deltas of these biomarkers in the SGA, FGR, PE and GH groups were compared with those in the unaffected group. Regression analysis was used to examine the relationship of PSV ratio delta, UtA-PI MoM, PlGF MoM and sFlt-1 MoM with birth-weight Z-score, after exclusion of PE and GH cases. RESULTS: The study population of 9033 pregnancies included 7696 (85.2%) that were not affected by FGR, SGA, PE or GH, 182 (2.0%) complicated by FGR in the absence of PE or GH, 698 (7.7%) with SGA in the absence of FGR, PE or GH, 236 (2.6%) with PE and 221 (2.4%) with GH. Compared with unaffected pregnancies, in the FGR and SGA groups, the PSV ratio delta and sFlt-1 MoM were increased and PlGF MoM was decreased; UtA-PI MoM was increased in the FGR group but not the SGA group. The magnitude of the changes in biomarker values relative to the unaffected group was smaller in the FGR and SGA groups than that in the PE and GH groups. In non-hypertensive pregnancies, there were significant inverse associations of PSV ratio delta and UtA-PI MoM with birth-weight Z-score, such that the values were increased in small babies and decreased in large babies. There was a quadratic relationship between PlGF MoM and birth-weight Z-score, with low PlGF levels in small babies and high PlGF levels in large babies. There was no significant association between sFlt-1 MoM and birth-weight Z-score. CONCLUSIONS: Ophthalmic artery PSV ratio, reflective of peripheral vascular resistance, and UtA-PI, PlGF and sFlt-1, biomarkers of impaired placentation, are altered in pregnancies complicated by hypertensive disorder and, to a lesser extent, in non-hypertensive pregnancies delivering a SGA or FGR neonate. The associations between the biomarkers and birth-weight Z-score suggest the presence of a continuous physiological relationship between fetal size and peripheral vascular resistance and placentation, rather than a dichotomous relationship of high peripheral resistance and impaired placentation in small compared to non-small fetuses. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Incidence of stillbirth: effect of deprivation.

OBJECTIVES: To examine the relationship between the English index of multiple deprivation (IMD) and the incidence of stillbirth and assess whether IMD contributes to the prediction of stillbirth provided by the combination of maternal demographic characteristics and elements of medical history. METHODS: This was a prospective, observational study of 159 125 women with a singleton pregnancy who attended their first routine hospital visit at 11 + 0 to 13 + 6 weeks' gestation in two maternity hospitals in the UK. The inclusion criterion was delivery at ≥ 24 weeks' gestation of a fetus without major abnormality. Participants completed a questionnaire on demographic characteristics and obstetric and medical history. IMD was used as a measure of socioeconomic status, which takes into account income, employment, education, skills and training, health and disability, crime, barriers to housing and services, and living environment. Each neighborhood is ranked according to its level of deprivation relative to that of other areas into one of five equal groups, with Quintile 1 containing the 20% most deprived areas and Quintile 5 containing the 20% least deprived areas. Logistic regression analysis was used to determine whether IMD provided a significant independent contribution to stillbirth after adjustment for known maternal risk factors. RESULTS: The overall incidence of stillbirth was 0.35% (551/159 125), and this was significantly higher in the most deprived compared with the least deprived group (Quintile 1 vs Quintile 5). The odds ratio (OR) in Quintile 1 was 1.57 (95% CI, 1.16-2.14) for any stillbirth, 1.64 (95% CI, 1.20-2.28) for antenatal stillbirth and 1.89 (95% CI, 1.23-2.98) for placental dysfunction-related stillbirth. In Quintile 1 (vs Quintile 5), there was a higher incidence of factors that contribute to stillbirth, including black race, increased body mass index, smoking, chronic hypertension and previous stillbirth. The OR of black (vs white) race was 2.58 (95% CI, 2.14-3.10) for any stillbirth, 2.62 (95% CI, 2.16-3.17) for antenatal stillbirth and 3.34 (95% CI, 2.59-4.28) for placental dysfunction-related stillbirth. Multivariate analysis showed that IMD did not have a significant contribution to the prediction of stillbirth provided by maternal race and other maternal risk factors. In contrast, in black (vs white) women, the risk of any and antenatal stillbirth was 2.4-fold higher and the risk of placental dysfunction-related stillbirth was 2.9-fold higher after adjustment for other maternal risk factors. CONCLUSIONS: The incidence of stillbirth, particularly placental dysfunction-related stillbirth, is higher in women living in the most deprived areas in South East England. However, in screening for stillbirth, inclusion of IMD does not improve the prediction provided by race, other maternal characteristics and elements of medical history. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.