Dataset Information

Clinical, ultrasound and molecular biomarkers for early prediction of large for gestational age infants in nulliparous women: An international prospective cohort study.

ABSTRACT:

Objective

To develop a prediction model for term infants born large for gestational age (LGA) by customised birthweight centiles.

Methods

International prospective cohort of nulliparous women with singleton pregnancy recruited to the Screening for Pregnancy Endpoints (SCOPE) study. LGA was defined as birthweight above the 90th customised centile, including adjustment for parity, ethnicity, maternal height and weight, fetal gender and gestational age. Clinical risk factors, ultrasound parameters and biomarkers at 14-16 or 19-21 weeks were combined into a prediction model for LGA infants at term using stepwise logistic regression in a training dataset. Prediction performance was assessed in a validation dataset using area under the Receiver Operating Characteristics curve (AUC) and detection rate at fixed false positive rates.

Results

The prevalence of LGA at term was 8.8% (n = 491/5628). Clinical and ultrasound factors selected in the prediction model for LGA infants were maternal birthweight, gestational weight gain between 14-16 and 19-21 weeks, and fetal abdominal circumference, head circumference and uterine artery Doppler resistance index at 19-21 weeks (AUC 0.67; 95%CI 0.63-0.71). Sensitivity of this model was 24% and 49% for a fixed false positive rate of 10% and 25%, respectively. The addition of biomarkers resulted in selection of random glucose, LDL-cholesterol, vascular endothelial growth factor receptor-1 (VEGFR1) and neutrophil gelatinase-associated lipocalin (NGAL), but with minimal improvement in model performance (AUC 0.69; 95%CI 0.65-0.73). Sensitivity of the full model was 26% and 50% for a fixed false positive rate of 10% and 25%, respectively.

Conclusion

Prediction of LGA infants at term has limited diagnostic performance before 22 weeks but may have a role in contingency screening in later pregnancy.

SUBMITTER: Vieira MC

PROVIDER: S-EPMC5453528 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Clinical, ultrasound and molecular biomarkers for early prediction of large for gestational age infants in nulliparous women: An international prospective cohort study.

Vieira Matias C MC McCowan Lesley M E LME Gillett Alexandra A Poston Lucilla L Fyfe Elaine E Dekker Gustaaf A GA Baker Philip N PN Walker James J JJ Kenny Louise C LC Pasupathy Dharmintra D

PloS one 20170601 6

<h4>Objective</h4>To develop a prediction model for term infants born large for gestational age (LGA) by customised birthweight centiles.<h4>Methods</h4>International prospective cohort of nulliparous women with singleton pregnancy recruited to the Screening for Pregnancy Endpoints (SCOPE) study. LGA was defined as birthweight above the 90th customised centile, including adjustment for parity, ethnicity, maternal height and weight, fetal gender and gestational age. Clinical risk factors, ultraso ...[more]

PMID: 28570613

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Project description: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.

Project description:Small for gestational age (SGA) infants comprise up to 50% of all stillbirths and a minority are detected before birth. We aimed to develop and validate early pregnancy predictive models for SGA infants.5628 participants from SCOPE, a prospective study of nulliparous pregnant women, were interviewed at 15 ± 1 weeks' gestation. Fetal anthropometry, uterine and umbilical Doppler studies were performed at 20 ± 1 weeks'. The cohort was divided into training (n = 3735) and validation datasets (n = 1871). All-SGA (birthweight <10th customised centile), Normotensive-SGA (SGA with normotensive mother) and Hypertensive-SGA (SGA with mother who developed hypertension) were the primary outcomes. Multivariable analysis was performed using stepwise logistic regression firstly using clinical variables and then with clinical and ultrasound variables. Receiver operator curves were constructed and areas under the curve (AUC) calculated.633 infants (11.3%) in the whole cohort were SGA; 465 (8.3%) Normotensive-SGA and 165 (3.0%) Hypertensive-SGA. In the training dataset risk factors for All-SGA at 15 ± 1 weeks' included: family history of coronary heart disease, maternal birthweight <3000 g and 3000 g to 3499 g compared with ? 3500 g, >12 months to conceive, university student, cigarette smoking, proteinuria, daily vigorous exercise and diastolic blood pressure ? 80. Recreational walking ? 4 times weekly, rhesus negative blood group and increasing random glucose were protective. AUC for clinical risk factors was 0.63. Fetal abdominal or head circumference z scores <10(th) centile and increasing uterine artery Doppler resistance at 20 ± 1 weeks' were associated with increased risk. Addition of these parameters increased the AUC to 0.69. Clinical predictors of Normotensive and Hypertensive-SGA were sub-groups of All-SGA predictors and were quite different. The combined clinical and ultrasound AUC for Normotensive and Hypertensive-SGA were 0.69 and 0.82 respectively.Predictors for SGA of relevance to clinical practice were identified. The identity and predictive potential differed in normotensive women and those who developed hypertension.

Project description:ObjectivesTo develop a predictive model for pre-eclampsia based on clinical risk factors for nulliparous women and to identify a subgroup at increased risk, in whom specialist referral might be indicated.DesignProspective multicentre cohort.SettingFive centres in Auckland, New Zealand; Adelaide, Australia; Manchester and London, United Kingdom; and Cork, Republic of Ireland.Participants3572 "healthy" nulliparous women with a singleton pregnancy from a large international study; data on pregnancy outcome were available for 3529 (99%).Main outcome measurePre-eclampsia defined as ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg, or both, on at least two occasions four hours apart after 20 weeks' gestation but before the onset of labour, or postpartum, with either proteinuria or any multisystem complication. Preterm pre-eclampsia was defined as women with pre-eclampsia delivered before 37(+0) weeks' gestation. In the stepwise logistic regression the comparison group was women without pre-eclampsia.ResultsOf the 3529 women, 186 (5.3%) developed pre-eclampsia, including 47 (1.3%) with preterm pre-eclampsia. Clinical risk factors at 14-16 weeks' gestation were age, mean arterial blood pressure, body mass index (BMI), family history of pre-eclampsia, family history of coronary heart disease, maternal birth weight, and vaginal bleeding for at least five days. Factors associated with reduced risk were a previous single miscarriage with the same partner, taking at least 12 months to conceive, high intake of fruit, cigarette smoking, and alcohol use in the first trimester. The area under the receiver operating characteristics curve (AUC), under internal validation, was 0.71. Addition of uterine artery Doppler indices did not improve performance (internal validation AUC 0.71). A framework for specialist referral was developed based on a probability of pre-eclampsia generated by the model of at least 15% or an abnormal uterine artery Doppler waveform in a subset of women with single risk factors. Nine per cent of nulliparous women would be referred for a specialist opinion, of whom 21% would develop pre-eclampsia. The relative risk for developing pre-eclampsia and preterm pre-eclampsia in women referred to a specialist compared with standard care was 5.5 and 12.2, respectively.ConclusionsThe ability to predict pre-eclampsia in healthy nulliparous women using clinical phenotype is modest and requires external validation in other populations. If validated, it could provide a personalised clinical risk profile for nulliparous women to which biomarkers could be added. Trial registration ACTRN12607000551493.

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Project description:ObjectivesThe objectives of this study are to determine whether abnormalities on neonatal cranial ultrasound (CUS) are associated with minor motor abnormalities at 2 years' corrected age (CA) and to assess functional outcomes and resource utilization among children with minor motor abnormalities.MethodsInfants born at <27 weeks in the National Institute of Child Health and Human Development Neonatal Research Network between January 1, 2010, and December 31, 2014, who underwent neuroimaging with CUS at both <28 days and ≥28 days and were evaluated at 18 to 26 months' CA, were included. Follow-up included Bayley-3, neuromotor examination, Gross Motor Function Classification System (GMFCS) level, and parent questionnaires about special services and resource needs. Children were classified by the most severe motor abnormality at 18 to 26 months' CA as follows: none, minor, or major motor function abnormality. Minor motor abnormalities were defined as any of the following: (1) Bayley-3 motor composite, fine motor score, or gross motor score 1 to 2 SDs below the test normative means; (2) mild abnormalities of axial or extremity motor skills on standardized neuromotor examination; or (3) GMFCS level 1.ResultsA total of 809 (35%) of 2306 children had minor motor function abnormalities alone. This did not increase substantially with CUS findings (no intraventricular hemorrhage [IVH]: 37%, grade I IVH: 32%, grade II IVH: 38%, grade III/IV IVH: 30%, isolated ventriculomegaly: 33%, and cystic periventricular leukomalacia: 24%). The adjusted odds of minor axial and upper extremity function abnormalities and GMFCS level 1 were significantly higher in children with more severe CUS findings. Children with minor motor abnormalities had increased resource utilization and evidence of functional impairment compared with those without motor function abnormalities.ConclusionMinor motor abnormalities at 2 years' CA are common and cannot be predicted by neonatal CUS abnormalities alone. Minor motor abnormalities are associated with higher resource utilization and evidence of functional impairment. These findings have important implications for early counseling and follow-up planning for extremely preterm infants.

Project description:BackgroundBoth obesity and gestational diabetes (GDM) are associated with adverse outcomes. Diet during pregnancy impacts weight gain and fetal growth. Therefore, we aimed to explore non-pharmacological treatment success depending on pre-pregnancy body weight and its association with large for gestational age (LGA) infants in women with GDM.MethodsIn our observational study we investigated 57 singleton pregnant women with GDM. All women received standard treatment, including healthy diet education and regular medical checkups. Data were collected through blood analysis, medical records and questionnaires assessing diet before conception and during pregnancy. Differences in dietary patterns were compared in normal weight and overweight/obese group using Mann-Whitney U, Wilcoxon Signed Rank Test or Kruskal-Wallis test, as appropriate. Logistic regression was used for prediction of LGA. p-value less than 0.05 was used for statistical significance.ResultsPreconceptionally, the Mann-Whitney U test showed that the normal-weight group (n = 41) more frequently consumed fruits (U = 116.5, p < 0.001), eggs (U = 189.5, p = 0.02), cheese (U = 148.0, p = 0.003) compared to the overweight/obese group (n = 16), that consumed more beef (U = 407.0, p = 0.03) and low-calorie beverages (U = 397.0, p = 0.05). During pregnancy both groups improved their diet, with no differences detected. Personality types differed only preconceptionally with regard to healthy diet. Excessive gestational weight gain did not significantly differ between body-weight groups (16.6% vs. 23.1%), neither did the incidence of LGA infants (46.2% vs. 43.8%). Significant predictors of LGA were paternal height (OR = 1.12, 95% CI 1.01-1.23), 3rd trimester HbA1c (OR = 0.50, 95% CI 0.26-0.97), unemployment (OR = 4.80, 95% CI 1.12-20.61) and diet improvement during pregnancy (OR = 1.19, 95% CI 1.02-1.39). After adjustment improvement in diet was no longer a significant predictor for LGA.ConclusionEven though dietary patterns of the participants significantly improved during pregnancy, LGA infants were born independently of pre-pregnancy weight or diet and despite good glycemic control. Further research is needed to explore social determinants of health and whether solutions outside the health sector could provide efficient means in preventing adverse pregnancy outcomes as well as improving metabolic health.

Dataset Information

Clinical, ultrasound and molecular biomarkers for early prediction of large for gestational age infants in nulliparous women: An international prospective cohort study.

Objective

Methods

Results

Conclusion

Publications

Clinical, ultrasound and molecular biomarkers for early prediction of large for gestational age infants in nulliparous women: An international prospective cohort study.

Similar Datasets

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