title: Prediction of Small for Gestational Age Infants in Healthy Nulliparous Women Using Clinical and Ultrasound Risk Factors Combined with Early Pregnancy Biomarkers.
abstract: OBJECTIVE
  Most 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.
  
  
  METHODS
  Data 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.
  
  
  RESULTS
  633 (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.
  
  
  CONCLUSIONS
  Models 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.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand.|South Auckland Clinical School, Middlemore Hospital, Department of Paediatrics: Child and Youth Health, University of Auckland, Auckland, New Zealand.|National Women's, Auckland District Health Board, Auckland, New Zealand.
authors.forename: Lesley M E
authors.initials: LM
authors.lastname: McCowan
authors.affiliation: Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand.|Department of Paediatrics, University of Auckland, Auckland, New Zealand.
authors.forename: John M D
authors.initials: JM
authors.lastname: Thompson
authors.affiliation: Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand.
authors.forename: Rennae S
authors.initials: RS
authors.lastname: Taylor
authors.affiliation: Liggins Institute, University of Auckland, Auckland, New Zealand.
authors.forename: Philip N
authors.initials: PN
authors.lastname: Baker
authors.affiliation: Division of Women's Health, Women's Health Academic Centre, King's College London and King's Health Partners, London, United Kingdom.
authors.forename: Robyn A
authors.initials: RA
authors.lastname: North
authors.affiliation: Division of Women's Health, Women's Health Academic Centre, King's College London and King's Health Partners, London, United Kingdom.
authors.forename: Lucilla
authors.initials: L
authors.lastname: Poston
authors.affiliation: Robinson Research Institute and School of Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Claire T
authors.initials: CT
authors.lastname: Roberts
authors.affiliation: Section of Obstetrics and Gynaecology, Leeds Institute of Biomedical & Clinical Sciences, University of Leeds, Leeds, United Kingdom.
authors.forename: Nigel A B
authors.initials: NA
authors.lastname: Simpson
authors.affiliation: Section of Obstetrics and Gynaecology, Leeds Institute of Biomedical & Clinical Sciences, University of Leeds, Leeds, United Kingdom.
authors.forename: James J
authors.initials: JJ
authors.lastname: Walker
authors.affiliation: Maternal and Fetal Heath Research Centre, University of Manchester, Manchester, United Kingdom.
authors.forename: Jenny
authors.initials: J
authors.lastname: Myers
authors.affiliation: INFANT (The Irish Centre for Fetal and Neonatal Translational Research) Department of Obstetrics and Gynaecology, University College, Cork, Ireland.|The Department of Obstetrics and Gynaecology, University College Cork, Ireland.
authors.forename: Louise C
authors.initials: LC
authors.lastname: Kenny
mesh_terms: D015415:Biomarkers; D005260:Female; D005865:Gestational Age; D006801:Humans; D007236:Infant, Small for Gestational Age / Q000378:metabolism*; D010298:Parity; D011247:Pregnancy; D011256:Pregnancy Outcome; D011263:Pregnancy Trimester, Third; D011379:Prognosis; D012307:Risk Factors; D016216:Ultrasonography, Prenatal
chemical_list: D015415:Biomarkers