Customized Charts Research Articles

Customized vs population-based growth charts to identify neonates at risk of adverse outcome: systematic review and Bayesian meta-analysis of observational studies.

To compare the effectiveness of customized vs population-based growth charts for the prediction of adverse pregnancy outcomes. MEDLINE, ClinicalTrials.gov and The Cochrane Library were searched up to 31 May 2016 to identify interventional and observational studies comparing adverse outcomes among large- (LGA) and small- (SGA) for-gestational-age neonates, when classified according to customized vs population-based growth charts. Perinatal mortality and admission to the neonatal intensive care unit (NICU) of both SGA and LGA neonates, intrauterine fetal demise (IUFD) and neonatal mortality of SGA neonates, and neonatal shoulder dystocia and hypoglycemia as well as maternal third- and fourth-degree perineal lacerations in LGA pregnancies were evaluated. The electronic search identified 237 records that were examined based on title and abstract, of which 27 full-text articles were examined for eligibility. After excluding seven articles, 20 observational studies were included in a Bayesian meta-analysis. Neonates classified as SGA according to customized growth charts had higher risks of IUFD (odds ratio (OR), 7.8 (95% CI, 4.2-12.3)), neonatal death (OR, 3.5 (95% CI, 1.1-8.0)), perinatal death (OR, 5.8 (95% CI, 3.8-7.8)) and NICU admission (OR, 3.6 (95% CI, 2.0-5.5)) than did non-SGA cases. Neonates classified as SGA according to population-based growth charts also had increased risk for adverse outcomes, albeit the point estimates of the pooled ORs were smaller: IUFD (OR, 3.3 (95% CI, 1.9-5.0)), neonatal death (OR, 2.9 (95% CI, 1.2-4.5)), perinatal death (OR, 4.0 (95% CI, 2.8-5.1)) and NICU admission (OR, 2.4 (95% CI, 1.7-3.2)). For LGA vs non-LGA, there were no differences in pooled ORs for perinatal death, NICU admission, hypoglycemia and maternal third- and fourth-degree perineal lacerations when classified according to either the customized or the population-based approach. In contrast, both approaches indicated that LGA neonates are at increased risk for shoulder dystocia than are non-LGA ones (OR, 7.4 (95% CI, 4.9-9.8) using customized charts; OR, 8.0 (95% CI, 5.3-10.1) using population-based charts). Both customized and population-based growth charts can identify SGA neonates at risk for adverse outcomes. Although the point estimates of the pooled ORs may differ for some outcomes, the overlapping CIs and lack of direct comparisons prevent conclusions from being drawn on the superiority of one method. Future clinical trials should compare directly the two approaches in the management of fetuses of abnormal size. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Improving customized fetal biometry by longitudinal modelling

Objective: To develop customized biometric charts to better define abnormal fetal growth.Methods: A total of 1056 singleton fetuses from the Raine Study underwent serial ultrasound biometry (abdominal circumference [AC], head circumference, and femur length) at 18, 24, 28, 34, and 38 weeks’ gestation. Customized biometry trajectories were developed adjusting for epidemiological influences upon fetal biometry using covariates available at 18 weeks gestation. Prediction accuracy (areas under the receiver operating characteristic curve [AUC] and 95% confidence interval [95%CI]) was evaluated by repeated random sub-sampling cross-validation methodology.Results: The model for derived estimated fetal weight (EFW) performed well for EFW less than 10th predicted percentile (AUC = 0.695, 95%CI, 0.692–0.699) and EFW greater than 90th predicted percentile (AUC = 0.705, 95%CI, 0.702–0.708). Fetal AC was also well predicted for growth restriction (AUC = 0.789, 95%CI, 0.784–0.794) and macrosomia (AUC = 0.796, 95%CI, 0.793–0.799). Population-derived, sex-specific charts misclassified 7.9% of small fetuses and 10.7% of large fetuses as normal. Conversely, 9.2% of those classified as abnormally grown by population-derived charts were considered normal by customized charts, potentially leading to complications of unnecessary intervention.Conclusions: Customized fetal biometric charts may offer improved ability for clinicians to detect deviations from optimal fetal growth and influence pregnancy management.

An assessment of gene-by-gene interactions as a tool to unfold missing heritability in dyslexia

Even if substantial heritability has been reported and candidate genes have been identified extensively, all known marker associations explain only a small proportion of the phenotypic variance of developmental dyslexia (DD) and related quantitative phenotypes. Gene-by-gene interaction (also known as "epistasis"--G × G) triggers a non-additive effect of genes at different loci and should be taken into account in explaining part of the missing heritability of this complex trait. We assessed potential G × G interactions among five DD candidate genes, i.e., DYX1C1, DCDC2, KIAA0319, ROBO1, and GRIN2B, upon DD-related neuropsychological phenotypes in 493 nuclear families with DD, by implementing two complementary regression-based approaches: (1) a general linear model equation whereby the trait is predicted by the main effect of the number of rare alleles of the two genes and by the effect of the interaction between them, and (2) a family-based association test to detect G × G interactions between two unlinked markers by splitting up the association effect into a between- and a within-family genetic orthogonal components. After applying 500,000 permutations and correcting for multiple testing, both methods show that G × G effects between markers within the DYX1C1, KIAA0319/TTRAP, and GRIN2B genes lower the memory letters composite z-score of on average 0.55 standard deviation. We provided initial evidence that the effects of familial transmission of synergistic interactions between genetic risk variants can be exploited in the study of the etiology of DD, explain part of its missing heritability, and assist in designing customized charts of individualized neurocognitive impairments in complex disorders, such as DD.

Twin Pregnancy and Antenatal Examination: An Overview

Total twinning rate has increased dramatically during the past 20 years, especially in Europe and the United States. This increase is mainly attributed to the widespread implementation of assisted reproductive techniques (ART). Twin gestation presents hazards at all ranges of gestational period, including risk for fetal wastage, fetal growth restriction, preterm labor, congenital abnormalities, twin-to-twin transfusion syndrome (TTTS) regarding monochorionic twins, and increased mortality rates. This review presents a summary of the appropriate antenatal examination strategy in twin pregnancies and, in parallel, emphasizes the main clinical problems that still pose controversies. Detection of chorionicity, measurement of nuchal translucency, fetal growth assessment based on twin-adjusted customized charts, structural anomaly scan, invasive procedures, non-stress test, biophysic profile, and MRI performance are the main issues analyzed. Finally, because twin gestations represent a challenging reality of modern obstetrics, this review also elucidates on the domains characterized by lack of evidence-based consensus, therefore raising the need for further research.

Customized growth charts for twin gestations to optimize identification of small-for-gestational age fetuses at risk of intrauterine fetal death

Customized growth charts developed for singleton pregnancies have been shown to be more effective than population-based ones at identifying small-for-gestational age (SGA) fetuses at risk for intrauterine fetal death (IUFD). We sought to compare the association between SGA and IUFD in twins using customized growth charts designed for twin gestations compared to those designed for singletons. This was a retrospective cohort study using a database including singleton and twin pregnancies undergoing ultrasound examination between 16 and 20 weeks' gestation. After excluding preterm births < 34 weeks, congenital anomalies and stillbirths, we identified 51, 150 singleton births. Coefficients for significant physiological and pathological variables affecting birth weight for singletons were derived using backward stepwise multiple regression. The same process was repeated for twin births (1608 pairs), also adjusting for chorionicity. Customized growth charts for each pregnancy were derived using these two regression models for optimal birth weight at term and a proportionality equation. The association between SGA < 10(th) percentile, defined using the twin and singleton-customized charts, and IUFD were compared. Statistical analysis, including calculation of adjusted odds ratios (OR) for IUFD and screening accuracy using each chart, was performed. The derived coefficients for optimal birth weight for twins were different from those for singletons, with lower constants and root mean square error (3422 and 288.9, respectively, in twins vs 3543 and 416 in singletons). Among 3786 twin infants, IUFD was seen in 123 (3.2%). The numbers of fetuses identified as SGA were 575 (15.2%) and 504 (13.3%) by the singleton and twin charts, respectively. Fetuses classified as SGA by the twin-specific customized charts were at a significantly increased risk for IUFD (adjusted OR, 2.3 (95% CI, 1.4-3.5)), whereas those classified as SGA by the singleton-customized charts were not (adjusted OR, 1.2 (95% CI, 0.7-2.0)). Customized charts designed specifically for twins are more effective at identifying twin pregnancies at risk for IUFD than are those derived using singleton birth data.

OC23.03: Customized growth chart for twin gestations to optimize identification of small for gestational age (SGA) fetuses at risk for intra‐uterine fetal death (IUFD)

We sought to compare the association between SGA and IUFD in twins using customized growth charts designed for twin gestations versus using one designed for singletons. This is a retrospective cohort study using a database including singleton and twin pregnancies seen for ultrasound between 16 and 20 weeks gestation. After excluding preterm births, congenital anomalies, and stillbirths (excluded only from derivation data), we identified 73,875 singleton births. Coefficients for significant physiological and pathological variables affecting fetal growth were derived using backward stepwise multiple regression for singletons (Cust_Singlechart). The same process was repeated including only twin births (1893 pairs) in the regression models and adjusting for chorionicity (cust_Twinchart). The association between SGA < 10th percentile defined using the twin versus singleton customized charts and IUFD were compared. Statistical analyses including OR, 95% confidence interval (CI), and screening accuracy using each chart was performed. The derived coefficients for fetal growth for cust_Twinchart are different from those for cust_Singlechart; with lower constants and R2 (2744 and 279 in twins; versus 3244 and 416 in singletons, respectively). Among 3786 twin infants, IUFD was seen in 123 (3.2%). The numbers of pregnancies identified as SGA were: 972 (25.7%), and 371 (9.8%) by the cust_Singlechart and cust_Twinchart, respectively. The association between SGA and IUFD and screening efficiency using both customized charts are shown in the table. OC23.03: Table 1. Customized growth chart for twins versus singletons and fetal death Customized charts designed specifically for twins are more efficient at identifying twin pregnancies at risk for IUFD compared with those derived using singleton birth data.

OC23.04: A risk model for pre‐eclampsia based on maternal characteristics and uterine artery Doppler during the first trimester of pregnancy

for significant physiological and pathological variables affecting fetal growth were derived using backward stepwise multiple regression for singletons (Cust Singlechart). The same process was repeated including only twin births (1893 pairs) in the regression models and adjusting for chorionicity (cust Twinchart). The association between SGA <10th percentile defined using the twin versus singleton customized charts and IUFD were compared. Statistical analyses including OR, 95% confidence interval (CI), and screening accuracy using each chart was performed. Results: The derived coefficients for fetal growth for cust Twinchart are different from those for cust Singlechart; with lower constants and R2 (2744 and 279 in twins; versus 3244 and 416 in singletons, respectively). Among 3786 twin infants, IUFD was seen in 123 (3.2%). The numbers of pregnancies identified as SGA were: 972 (25.7%), and 371 (9.8%) by the cust Singlechart and cust Twinchart, respectively. The association between SGA and IUFD and screening efficiency using both customized charts are shown in the table. Conclusions: Customized charts designed specifically for twins are more efficient at identifying twin pregnancies at risk for IUFD compared with those derived using singleton birth data.

OP31.02: Single nucleotide polymorphism in pre‐eclampsia prediction

prenatal clinic setting. Maternal levels of PAPP-A were measured at the time of the first prenatal visit (9 to 13+6 weeks) as part of the combined ultrasound and biochemical screening study. Low PAPP-A was defined as the lowest 5% of values for gestational age ( 1.9 MoM). Intrauterine growth restriction was defined as birth-weight ≤3th centile according to our local customized charts. The risk of IUGR in women with a low PAPP-A and normal AFP was compared with a control group with low PAPPA and high AFP. No results were reported to either the obstetrician or patient. Results: A total of 5617 pregnant women were attended for prenatal care in our institution between January 2010 and December 2011. Of the 301 patients with a PAPP-A < 0.4 MoM, 141 had a determination of AFP done between 15 and 18 weeks and perinatal outcome is known for 96 of these patients. Women with a low PAPP-A were not more likely to have elevated levels of AFP. Only 4 patients (4.2%) had a low PAPP-A and high AFP. We had 6 cases of IUGR (6%): 3 cases (3.2%) in the group of low PAPP-A and normal AFP and 3 cases (75%) in the group of low PAPP-A and high AFP. The odds ratio for delivering a baby with IUGR for women with low PAPP-A and high AFP was 89 (95% confidence interval [CI] 7–1127). Conclusions: Although the small numbers of the study, this preliminary data suggest that low maternal levels of PAPP-A between 8 and 13+6 weeks and high levels of AFP between 15 and 18 weeks are highly associated with IUGR.