Appendix 2.
Predictive Characteristics* of Biomarkers for Fetal Alcohol Spectrum Disorders and Associated Symptoms
| Author | Sample Description | PAE/FASD | Control Sample | Biomarker | Source of Biomarker | Outcome | Sensitivity | Specificity | PPV | NPV | Accuracy | AUC from ROC |
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| Andreu et al., 201927 | 55 native Spanish children (ages 8–12) from the Meconium Project and 98 children adopted from Eastern European communities | 55 native Spanish children with FASD; 33 FAEE > 2 nmol/g; of 98 children from Eastern Europe: 31 with FASD, 42 partial FAS, 6 ARBD, and 5 ARND | 31 FAEE < 2 nmol/g | Serum IGF-II (below 5th percentile) | Infant blood | FASD diagnosis | 12.7 | 100 | 100 | 14.8 | 24.2 | |
| Serum IGF-II (below 5th percentile) | Infant blood | FASD diagnosis | 39.0 | 96.8 | 98.8 | 19.4 | 46.6 | |||||
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| Balaraman et al., 201657 | Ukrainian pregnant mothers at prenatal care visits | 22 Heavy alcohol-affected | 23 No PAE | Selected mRNAs mid to late pregnancy | Maternal blood | Defined by self-report and child outcome | 81.8 | 91.3 | 90.0 | 84.0 | 86.7 | |
| Change in mRNAs | 77.3 | 73.9 | 73.9 | 77.3 | 75.6 | |||||||
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| Lee et al., 201832 | Meconium samples from infants born in hospitals— Uijeongbu St. Mary’s Hospital, Catholic University of Korea | 5 with HC and length ≤ 10th percentile | FAEE < 0.5 nmol/g | FAEE 0.5 nmol/g | Meconium | Growth delay—HC, length < 10th percentile | 40.0 | 92.8 | 68.0 | |||
| FAEE < 2 nmol/g | FAEE 2 nmol/g | Meconium | 20.0 | 98.0 | 68.0 | |||||||
| FAEE < 0.5 nmol/g | FAEE 0.5 nmol/g | Meconium | 50.0 | 92.8 | 79.0 | |||||||
| FAEE < 2 nmol/g | FAEE 2 nmol/g | Meconium | 25.0 | 98.0 | 79.0 | |||||||
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| Niemelä et al., 201643 | All live births in Finland from 1987 to 2005 were matched to a prenatal serum specimen biobank and compared to FAS in Finnish Register of Congenital Malformations | 385 Mothers of children with FAS + 95 PAE but no FAS | 745 Controls (mothers no PAE and no child effects) | CDT ≥ 1.79% | Maternal blood | Self-report/ FAS diagnosis | 39.5/4.2 | 96.4 | 3.6 | .78/.53 | ||
| GGT ≥ 40 U/L | 41.0/13.7 | 95 | 5 | .82/.72 | ||||||||
| Combo CDT–GGT ≥ 3.35 | 54.0/14.7 | 95.3 | 4.7 | .87/.73 | ||||||||
| EtG ≥ 0.1 mg/L | 16.9/6.1 | 100 | 0 | .58/.56 | ||||||||
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| Niemelä et al., 201644 | All live births in Finland from 1987 to 2005 were matched to a prenatal serum specimen biobank and compared to FAS in Finnish Register of Congenital Malformations | 385 Mothers of children with FAS | 745 Controls (mothers no PAE and no child effects) | CDT ≥ 1.79% | Maternal blood | FAS diagnosis | 12.5 | 99.3 | 90.6 | 68.7 | 69.7 | |
| GGT ≥ 40 U/L | 33.0 | 96.4 | 82.5 | 73.6 | 74.8 | |||||||
| Combo CDT–GGT ≥ 3.35 | 33.5 | 98.0 | 89.6 | 74.0 | 76.0 | |||||||
| EtG ≥ 0.1 mg/L | 16.9 | 100 | 100 | 70.0 | 71.7 | |||||||
Prediction characteristics evaluated in each study included sensitivity, specificity, NPV, PPV, accuracy, and AUC derived from ROC curves. Sensitivity refers to the probability that the test is positive when the condition is present. Specificity refers to the probability that the test is negative when the condition is not present. PPV refers to the probability that the condition is present when the test is positive. NPV refers to the probability that the condition is not present when the test is negative. Accuracy refers to the overall probability that the case is correctly classified from the test. Finally, AUC is derived from creating receiver operating curves by plotting the true positive rate (sensitivity) relative to the false positive rate (1-specificity). The area under the curve references the area on the graph created by the regression line relative to the chance rate of prediction. Values of 1 would indicate perfect condition and values of 0.50 would indicate chance prediction using a yes/no model. Predictive validity values are presented as percentages with the exception of AUC values, which are reported in proportions of accurate diagnostic classification with values of 0 to 1.00.
Note: ADHD, attention-deficit/hyperactivity disorder; ARBD, alcohol-related birth defects; ARND, alcohol-related neurodevelopmental disorder; AUC, under the curve; CDT, carbohydrate-deficient transferrin; EtG, ethyl glucuronide; FAEE, fatty acid ethyl esters; FAS, fetal alcohol syndrome; FASD, fetal alcohol syndrome disorders; GGT, gamma-glutamyltransferase; HC, head circumference; IGF-II, insulin-like growth factor-II; mg/l, milligrams per liter; mRNAs, messenger RNAs; nmol/g, nanomoles per gram; NPV, negative predictive value; PAE, prenatal alcohol exposure; PPV, positive predictive value; ROC, receiver operating characteristic; U/L, units per liter.