Preeclampsia

• Effect of race on the measurement of angiogenic factors for prediction and diagnosis of pre-eclampsia
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  Wright A, von Dadelszen P, Magee LA, Syngelaki A, Akolekar R, Wright D, Nicolaides KH
  BJOG 2023;130:78-87
  The study examined 29,035 women with singleton pregnancies at 35+0 to 36+6 weeks' gestation, including 654 (2.3%) who subsequently developed preeclampsia (PE). In the PE group PlGF is reduced and sFlt-1/PlGF ratio is increased. However, in black, compared with white women, mean PlGF was higher and sFlt-1/PlGF ratio was lower. Consequently, screening for PE with fixed cut-offs in PlGF or sFlt-1/PlGF diagnostically disadvantages black women. It is essential that measured levels of PlGF be adjusted for race as well as other maternal characteristics.
• Preterm and term pre-eclampsia: relative burdens of maternal and perinatal complications
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  von Dadelszen P, Syngelaki A, Akolekar R, Magee LA, Nicolaides KH
  BJOG 2023;130:524-530
  The study examined the relative burdens of maternal and perinatal complications for preterm and term preeclampsia. In an unselected population of 40,241 women with singleton pregnancies, 298 (0.7%) and 1194 (3.0%) developed preterm and term PE, respectively. Women with preterm (versus term) PE more commonly experienced adverse maternal or perinatal events (severe hypertension, maternal mortality/major morbidity, perinatal mortality/major neonatal morbidity, neonatal unit admission for ≥48 hours, birthweight <3rd percentile). However, since the incidence of term PE is higher than that of preterm PE, in absolute terms, most maternal complications occurred in women with term PE, as did a large proportion of perinatal complications. Consequently, increased efforts should be made to decrease the incidence of term pre-eclampsia.
• Screening for pre-eclampsia by maternal serum glycosylated fibronectin at 11-13 weeks' gestation
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  Sokratous N, Bednorz M, Sarli P, Morillo Montes OE, Syngelaki A, Wright A, Nicolaides KH.
  Ultrasound Obstet Gynecol 2023:62:504-511.
  The case-control study examined the performance of screening for preterm and term preeclampsia (PE) at 11-13 weeks' gestation by maternal factors and combinations of maternal serum glycosylated fibronectin (GlyFn), mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF). We examined 100 cases of preterm-PE, 100 of term-PE and 1000 normotensive controls. The detection rate, at 10% fixed false-positive rate, of delivery with PE at <37 weeks (preterm PE) in screening by maternal risk factors with MAP, UtA-PI and PlGF (triple test) was 80%. The detection rate of the triple test was similar to that of screening by a combination of maternal factors, MAP, UtA-PI and GlyFn (79%) and that of screening by a combination of maternal factors, MAP, PlGF and GlyFn (81%). The performance of screening for term PE by all combinations of biomarkers was poor. GlyFn is a potentially useful biomarker in first-trimester screening for preterm PE, but the findings of this case-control study need to be validated by prospective screening studies.
• Prediction of hypertensive disorders after screening at 35-36 weeks' gestation: comparison of angiogenic markers with competing-risks model.
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  Schiattarella A, Magee LA, Wright A, Syngelaki A, Akolekar R, Von Dadelszen P, Nicolaides KH.
  Ultrasound Obstet Gynecol 2023;62:345-352
  The study examined 34,782 women with singleton pregnancies at 35+0 to 36+6 weeks' gestation, including 831 (2.4%) who subsequently developed preeclampsia (PE). The performance of screening for PE by the competing-risks model triple test (maternal risk factors plus multiple of the median values of MAP, PlGF and sFlt-1) was superior to that of PlGF concentration alone or the sFlt-1/PlGF concentration ratio for the development of PE within 1 week, within 2 weeks and at any time from screening.
• ASPRE trial: effects of aspirin on mean arterial blood pressure and uterine artery pulsatility index trajectories in pregnancy.
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  Rolnik DL, Syngelaki A, O'Gorman N, Wright D, Poon LC, Nicolaides KH.
  Ultrasound Obstet Gynecol 2023;61:691-697.
  The mechanism by which aspirin prevents preeclampsia (PE) is poorly understood, and its effects on biomarkers throughout pregnancy are unknown. This longitudinal secondary analysis of the ASPRE trial investigated the effects of aspirin on mean arterial pressure (MAP) and mean uterine artery pulsatility index (UtA-PI). Trajectories of raw and MoM values of UtA-PI showed a significantly steeper decline in the aspirin group than in the placebo group, with the difference mainly driven by a more pronounced reduction before 20 weeks of gestation. In contrast, aspirin had no effect on MAP.
• Preeclampsia prevention by timed birth at term
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  Magee LA, Wright D, Syngelaki A, von Dadelszen P, Akolekar R, Wright A, Nicolaides KH.
  Hypertension 2023;80:969-978.
  Most preeclampsia (PE) occurs at term and presently, there are no effective preventative strategies. The study aimed to identify the optimal PE screening and timing of birth strategy for prevention of term PE. The study showed that the best approach would be screening at 35-36 weeks’ gestation by the FMF competing risks model (maternal risk factors plus multiple of the median values of MAP, PlGF and sFlt-1) and subsequent timing of birth (37, 38, 39, 40 weeks) depended on PE risk. Such risk-stratified timing of birth at term may more than halve the risk of term PE.
• Incidence of pre-eclampsia: effect of deprivation
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  Arechvo A, Wright A, Syngelaki A, von Dadelszen P, Magee LA, Akolekar R, Wright D, Nicolaides KH
  Ultrasound Obstet Gynecol 2023;61:26-32
  The objective of the study was to examine the relationship between the English index of multiple deprivation (IMD) and the incidence of preeclampsia (PE), evaluate the distribution of IMD in a cohort of ethnically diverse pregnant women in South East England and assess whether IMD improves the prediction of PE compared with that provided by the 'history-only' competing-risks model (based on maternal characteristics and medical history). The study examined 159,125 women with a singleton pregnancy who attended a routine hospital visit at 11 + 0 to 13 + 6 weeks' gestation. The incidence of PE was higher in women living in the most deprived areas in South East England and in black women (vs those of other racial groups), who also live in areas of higher deprivation. However, in screening for PE, inclusion of IMD does not improve the prediction of PE provided by race and other maternal characteristics and elements of medical history.

Small for gestational age

• Personalized stratification of pregnancy care for small for gestational age neonates from biophysical markers at midgestation
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  Papastefanou I, Wright D, Syngelaki A, Akolekar R, Nicolaides KH
  Am J Obstet Gynecol 2023;229:57.e1-57.e14
  Antenatal identification of pregnancies at high risk of delivering small for gestational age (SGA) neonates may improve the management of the condition and reduce the associated adverse perinatal outcomes. In a series of publications, we have developed a new competing-risks model for prediction of SGA, and we demonstrated that the new approach has a superior performance to that of the traditional methods. The next step in shaping the appropriate management of SGA is the timely assessment of these high-risk pregnancies according to an antenatal stratification plan. The study examined 96,678 singleton pregnancies undergoing routine ultrasound examination at 19-24 weeks of gestation. It demonstrated the stratification of pregnancy care based on individual patient risk derived from the application of the competing-risks model for SGA that combines maternal risk factors with sonographic estimated fetal weight and uterine artery pulsatility index.

Gestational diabetes

• Fetal cardiac function at midgestation in women who subsequently develop gestational diabetes
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  Huluta I, Wright A, Cosma LM, Hamed K, Nicolaides KH, Charakida M.
  JAMA Pediatr 2023;177:718-725.
  Fetuses in women with gestational diabetes (GD) compared with those without GD show evidence of subclinical cardiac functional and morphological changes. However, it is uncertain whether glycemia or the adverse maternal underlying risk factor profile is the main driver for fetal cardiac remodeling. This was a prospective nonintervention screening study of 5620 women with singleton pregnancies at 19 to 23 weeks' gestation, including 470 who developed GD. The study showed that in fetuses of the GD group compared with the non-GD group, there was mild increase in interventricular millimeter thickness and left atrial area, without changes in cardiac function. This suggests that the adverse maternal risk factor profile and not only the glycemia might contribute to cardiac remodeling noted in fetuses of women with GD.

Preterm birth

• Vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in twin gestations: a systematic review and meta-analysis.
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  Conde-Agudelo A, Romero R, Rehal A, Brizot ML, Serra V, Da Fonseca E, Cetingoz E, Syngelaki A, Perales A, Hassan SS, Nicolaides KH.
  Am J Obstet Gynecol 2023:S0002-9378(23)00317-4.
  This systematic review evaluated the efficacy of vaginal progesterone in randomized controlled trials for the prevention of preterm birth <34 weeks’ gestation and adverse perinatal outcomes in twin gestations. It concluded that vaginal progesterone does not prevent preterm birth, nor does it improve perinatal outcomes in unselected twin gestations, but it appears to reduce the risk of preterm birth occurring at early gestational ages and of neonatal morbidity and mortality in twin gestations with a sonographic short cervix. However, more evidence is needed before recommending this intervention to this subset of patients.