Quad test for fetal aneuploidy screening as a predictor of small-for-gestational age fetuses: a population-based study

Abstract

Background To identify the relationship between quadruple test for aneuploidy screening (alpha-fetoprotein: AFP; free beta-human chorionic gonadotropin: b-hCG; unconjugated estriol: uE3 and inhibin-A: IHA) and fetal growth restriction and to construct predictive models for small-for-gestational-age (SGA) fetuses. Methods Women who underwent quadruple test for aneuploidy were followed-up for final outcomes. The multiples of the median (MoMs) of the four biochemical markers for the SGA group and those of normal fetuses were compared. The models for predicting SGA by the individual biomarkers and their combination were constructed using binary logistic regression analysis, and their diagnostic performances in predicting SGA were determined. Results Of 10,155 eligible pregnant women, 578 (5.7%) and 9577 (94.3%) had SGA and normal growth, respectively. High levels of AFP, b-hCG and IHA but low levels of uE3 significantly increased the risk of SGA. The constructed predictive equations had predictive performance for SGA, with areas under the receiver-operated characteristic curve of 0.724, 0.655, 0.597, 0.664 and 0.754 for AFP, b-hCG, uE3, IHA, and the combination, respectively. Conclusion The quad test for aneuploidy screening could also be used as a predictor of SGA, without extra-effort and extra-cost.

Mitochondrial dysfunction-induced high hCG associated with development of fetal growth restriction and pre-eclampsia with fetal growth restriction

“…In previous reports, high hCG in maternal blood has been observed from early pregnancy in patients with FGR and PE 9 – 11 . Therefore, we first investigated whether hCG was also elevated in the postnatal placentas of these patients.…”

“…hCG is produced by syncytiotrophoblasts (STB) and peaks between the 7th and 10th weeks of pregnancy, with a nadir at 18th weeks 8 . Several studies have demonstrated that patients with FGR and PE exhibit higher blood levels of hCG from early pregnancy until before delivery 9 – 11 , and placental dysfunction may reflect the increased hCG levels 12 – 15 . Therefore, we speculated that high hCG is a risk factor for the development of FGR and PE.…”

Prediction of Pregnancy Complications With Maternal Biochemical Markers Used in Down Syndrome Screening

“…AFP is then transported to maternal serum through the placenta or by diffusion across fetal membranes [15,16]. Elevated msAFP values are found to be associated with the fetalmaternal-placental barrier disruption, placental vascular damage or bleeding, or feto-placental ischemia and can compromise the development of a structurally normal fetus [16,17]. The relationship between the AFP increase in the second trimester and pregnancy complications (such as gestational hypertension, preeclampsia, fetal loss, preterm delivery, IUGR, placental abruption, and bleeding) has also been established [14][15][16][17].…”

“…Elevated msAFP values are found to be associated with the fetal-maternal-placental barrier disruption, placental vascular damage or bleeding, or feto-placental ischemia and can compromise the development of a structurally normal fetus [ 16 , 17 ]. The relationship between the AFP increase in the second trimester and pregnancy complications (such as gestational hypertension, preeclampsia, fetal loss, preterm delivery, IUGR, placental abruption, and bleeding) has also been established [ 14 - 17 ]. Therefore, the link between AFP increase and IUGR yielded by our analyses is supported by empirical evidence [ 17 ].…”

The Effect of Selenium Supplementation on Clinical Outcomes, Metabolic Profiles, and Pulsatility Index of the Uterine Artery in High-Risk Mothers in Terms of Preeclampsia Screening with Quadruple Test: a Randomized, Double-Blind, Placebo-Controlled Clinical Trial

“…Combination of the clinical, biochemical, and biophysical markers is likely to increase the predictive power of screening examinations [ 36 ]. Currently, the implementation of serum biomarker screening quad test (AFP, alpha-fetoprotein; BHCG, beta-human gonadotropin; uE3, unconjugated estriol; and IHA, inhibin-A) for fetal aneuploidy has commenced worldwide, and many studies have shown that additional information derived from such screenings, other than aneuploidy risk estimation, can also be used to identify the risk of adverse obstetric outcomes, such as fetal growth restriction, PE, and preterm birth [ 37 , 38 ].…”