First-trimester screening with specific algorithms for early- and late-onset fetal growth restriction

Crovetto, F.; Triunfo, Stefania; Crispi, F.; Rodrı́guez-Sureda, Vı́ctor; Roma, Elionor; Domı́nguez, Carmen; Gratacós, Eduard; Figueras, F.

doi:10.1002/uog.15879

Cited by 78 publications

(73 citation statements)

References 33 publications

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“…The performance of each of our models, though comparable with reports by others,[37] was insufficient to warrant introduction into clinical practice. Additional information in later gestation may be necessary to improve prediction of risk for SGA.…”

Section: Discussionsupporting

confidence: 45%

Prediction of Small for Gestational Age Infants in Healthy Nulliparous Women Using Clinical and Ultrasound Risk Factors Combined with Early Pregnancy Biomarkers

et al. 2017

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ObjectiveMost small for gestational age pregnancies are unrecognised before birth, resulting in substantial avoidable perinatal mortality and morbidity. Our objective was to develop multivariable prediction models for small for gestational age combining clinical risk factors and biomarkers at 15±1 weeks’ with ultrasound parameters at 20±1 weeks’ gestation.MethodsData from 5606 participants in the Screening for Pregnancy Endpoints (SCOPE) cohort study were divided into Training (n = 3735) and Validation datasets (n = 1871). The primary outcomes were All-SGA (small for gestational age with birthweight <10th customised centile), Normotensive-SGA (small for gestational age with a normotensive mother) and Hypertensive-SGA (small for gestational age with an hypertensive mother). The comparison group comprised women without the respective small for gestational age phenotype. Multivariable analysis was performed using stepwise logistic regression beginning with clinical variables, and subsequent additions of biomarker and then ultrasound (biometry and Doppler) variables. Model performance was assessed in Training and Validation datasets by calculating area under the curve.Results633 (11.2%) infants were All-SGA, 465(8.2%) Normotensive-SGA and 168 (3%) Hypertensive-SGA. Area under the curve (95% Confidence Intervals) for All-SGA using 15±1 weeks’ clinical variables, 15±1 weeks’ clinical+ biomarker variables and clinical + biomarkers + biometry /Doppler at 20±1 weeks’ were: 0.63 (0.59–0.67), 0.64 (0.60–0.68) and 0.69 (0.66–0.73) respectively in the Validation dataset; Normotensive-SGA results were similar: 0.61 (0.57–0.66), 0.61 (0.56–0.66) and 0.68 (0.64–0.73) with small increases in performance in the Training datasets. Area under the curve (95% Confidence Intervals) for Hypertensive-SGA were: 0.76 (0.70–0.82), 0.80 (0.75–0.86) and 0.84 (0.78–0.89) with minimal change in the Training datasets.ConclusionModels for prediction of small for gestational age, which combine biomarkers, clinical and ultrasound data from a cohort of low-risk nulliparous women achieved modest performance. Incorporation of biomarkers into the models resulted in no improvement in performance of prediction of All-SGA and Normotensive-SGA but a small improvement in prediction of Hypertensive-SGA. Our models currently have insufficient reliability for application in clinical practice however, they have potential utility in two-staged screening tests which include third trimester biomarkers and or fetal biometry.

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Section: Discussionsupporting

confidence: 45%

Prediction of Small for Gestational Age Infants in Healthy Nulliparous Women Using Clinical and Ultrasound Risk Factors Combined with Early Pregnancy Biomarkers

et al. 2017

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“…Previous studies have investigated the relationships between sFlt-1 and/or PlGF and late-onset FGR, but most have utilized methods not readily translated into clinical practice for a general antenatal population. These methods include placental rather than plasma protein analysis [24]; multi-modality integrated models [25, 26]; prior ultrasound diagnosis of SGA [27–33]; and investigation confined to cases of preterm infants [32]. Our large cohort specifically enabled us to compare the utility of sFlt-1, PlGF, and their ratio, in all cases of a SGA infant as well as in a ‘SGA only’ cohort, actively removing the impact of participants with concurrent preeclampsia.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have measured the analytes at a variety of gestations, including first [26, 37] and second trimesters [38], in a longitudinal fashion [12], and at delivery [31, 39]. However, early measurement of the angiogenic factors is not predictive of late-onset disease [38], except if included in a complex model incorporating several maternal, ultrasonographic and blood-based risk factor assessments [26] – difficult to incorporate into clinical practice.…”

Section: Discussionmentioning

confidence: 99%

“…However, early measurement of the angiogenic factors is not predictive of late-onset disease [38], except if included in a complex model incorporating several maternal, ultrasonographic and blood-based risk factor assessments [26] – difficult to incorporate into clinical practice. In preeclampsia, the predictive performance of the analytes is improved when measured closer to the onset of disease [15].…”

Section: Discussionmentioning

confidence: 99%

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Assessing the sensitivity of placental growth factor and soluble fms-like tyrosine kinase 1 at 36 weeks’ gestation to predict small-for-gestational-age infants or late-onset preeclampsia: a prospective nested case-control study

MacDonald

Tran

Kaitu’u-Lino

et al. 2018

BMC Pregnancy Childbirth

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BackgroundFetal growth restriction is a disorder of placental dysfunction with three to four-fold increased risk of stillbirth. Fetal growth restriction has pathophysiological features in common with preeclampsia. We hypothesised that angiogenesis-related factors in maternal plasma, known to predict preeclampsia, may also detect fetal growth restriction at 36 weeks’ gestation. We therefore set out to determine the diagnostic performance of soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), and the sFlt-1:PlGF ratio, measured at 36 weeks’ gestation, in identifying women who subsequently give birth to small-for-gestational-age (SGA; birthweight <10th centile) infants. We also aimed to validate the predictive performance of the analytes for late-onset preeclampsia in a large independent, prospective cohort.MethodsA nested 1:2 case-control study was performed including 102 cases of SGA infants and a matched group of 207 controls; and 39 cases of preeclampsia. We determined the diagnostic performance of each angiogenesis-related factor, and of their ratio, to detect SGA infants or preeclampsia, for a predetermined 10% false positive rate.ResultsMedian plasma levels of PlGF at 36 weeks’ gestation were significantly lower in women who subsequently had SGA newborns (178.5 pg/ml) compared to normal birthweight controls (326.7 pg/ml, p < 0.0001). sFlt-1 was also higher among SGA cases, but this was not significant after women with concurrent preeclampsia were excluded. The sensitivity of PlGF to predict SGA infants was 28.8% for a 10% false positive rate. The sFlt-1:PlGF ratio demonstrated better sensitivity for preeclampsia than either analyte alone, detecting 69.2% of cases for a 10% false positive rate.ConclusionsPlasma PlGF at 36 weeks’ gestation is significantly lower in women who subsequently deliver a SGA infant. While the sensitivity and specificity of PlGF currently limit clinical translation, our findings support a blood-based biomarker approach to detect late-onset fetal growth restriction. Thirty-six week sFlt-1:PlGF ratio predicts 69.2% of preeclampsia cases, and could be a useful screening test to triage antenatal surveillance.Electronic supplementary materialThe online version of this article (10.1186/s12884-018-1992-x) contains supplementary material, which is available to authorized users.

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“…We have also determined whether this association is modified by an abnormal fetal size (EFW<10th) at 20–24 weeks of gestation. All fetuses were followed until delivery and the clinical outcomes were defined as follows: 1) early SGA as an EFW <10 th percentile at <34 weeks of gestation; 32 2) late SGA as an EFW <10th percentile at ≥34 weeks of gestation 33,34 ; and 3) SGA at birth as birthweight <10 th percentile 35 . The information provided by Doppler parameters at 20–24 weeks of gestation was not used for clinical management.…”

Section: Methodsmentioning

confidence: 99%

A Low Cerebroplacental Ratio at 20-24 Weeks of Gestation Can Predict Reduced Fetal Size Later in Pregnancy or at Birth

et al. 2017

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Aim: To determine whether Doppler evaluation at 20-24 weeks of gestation can predict reduced fetal size later in pregnancy or at birth. Methods: Fetal biometry and Doppler velocimetry were performed in 2,986 women with a singleton pregnancy at 20-24 weeks of gestation. Predictive performances of the umbilical artery pulsatility index (UA-PI) or the mean uterine artery pulsatility index (UtA-PI) >95th percentile, middle cerebral artery pulsatility index, or cerebroplacental ratio (CPR) <5th percentile for early small for gestational age (SGA; <34 weeks of gestation), late SGA (≥34 weeks of gestation), or SGA at birth (birthweight <10th percentile) were analyzed. Results: The prevalence of early SGA, late SGA, and SGA at birth was 1.1, 9.6, and 14.7%, respectively. A CPR <5th percentile had a positive likelihood ratio (LR+) of 8.2 (95% confidence interval [CI] 5.7-12.0) for early SGA, a LR+ of 1.6 (95% CI 1.1-1.2) for late SGA, and a LR+ of 1.9 (95% CI 1.4-2.6) for SGA at birth. A UtA-PI >95th percentile was associated with late SGA and SGA at birth, while an UA-PI >95th percentile was associated with early SGA. Associations were higher in fetuses with an estimated fetal weight <10th percentile. Conclusion: Fetal biometry and Doppler evaluation at 20-24 weeks of gestation can predict early and late SGA as well as SGA at birth.

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First-trimester screening with specific algorithms for early- and late-onset fetal growth restriction

Abstract: Objective To develop optimal first-trimester algorithms for the prediction of early and late fetal growth restriction (FGR). Methods (AUC: 0.76 (95% CI,

Cited by 78 publications

References 33 publications

Prediction of Small for Gestational Age Infants in Healthy Nulliparous Women Using Clinical and Ultrasound Risk Factors Combined with Early Pregnancy Biomarkers

Prediction of Small for Gestational Age Infants in Healthy Nulliparous Women Using Clinical and Ultrasound Risk Factors Combined with Early Pregnancy Biomarkers

Assessing the sensitivity of placental growth factor and soluble fms-like tyrosine kinase 1 at 36 weeks’ gestation to predict small-for-gestational-age infants or late-onset preeclampsia: a prospective nested case-control study

A Low Cerebroplacental Ratio at 20-24 Weeks of Gestation Can Predict Reduced Fetal Size Later in Pregnancy or at Birth

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