DiGeorge syndrome chromosome region deletion and duplication: Prenatal genotype-phenotype variability in fetal ultrasound and MRI.

OBJECTIVE: The aim of the study was to assess genotype-phenotype correlation of prenatally diagnosed fetal DGS and dup22q11 syndrome by fetal molecular genetic analysis, fetal ultrasound, and/or MRI. METHODS: In this retrospective consecutive case series, pregnant women were screened for fetal anomalies during a period of 10 years. Fetal genotype was assessed in 72 cases upon the occurrence of five prenatal fetal phenotypic features: cardiac anomalies, hypo/aplastic thymus, craniofacial malformations, urinary abnormalities, or IUGR; genotype-phenotype correlation was tested to potentially improve prenatal diagnosis of fetal DGS and dup22q11 syndrome. RESULTS: Fetal genotypes of deletions or duplications in proximal clusters of LCR22s (A-B) were associated with fetal cardiac anomalies in combination with hypo/aplastic thymus and craniofacial malformations, suggesting a correlation with deleted HIRA. TOF associated with aplastic thymus in combination with renal defects indicated a relevant correlation with TBX1 deletion. Deletions in central LCR22s (B-D) with the loss of CRKL supposed a trend of genotype-phenotype correlation with fetal urinary abnormalities. CONCLUSION: Genotype-phenotype correlation might improve prenatal diagnosis of fetal DGS and dup22q11 syndrome. Hence, prenatal screening and counseling is highly enhanced by a combination of fetal molecular genetic analysis, fetal ultrasound, and/or MRI. The implications of these findings remain to be explored.

Combination of first trimester serum afamin levels and three-dimensional placental bed vascularization as a possible screening method to detect women at-risk for adverse pregnancy complications like pre-eclampsia and gestational diabetes mellitus in low-risk pregnancies.

OBJECTIVE: Aim of the study was to assess the correlation of first trimester serum afamin levels with three-dimensional placental bed vascularization in pregnant women and its prognostic value for predicting pre-eclampsia and future fetal and maternal complications during pregnancy. METHODS: In this nested case-control study all pregnant women registered for delivery during a period of 3 years were routinely screened in the first trimester. Serum afamin levels were assessed in 764 women and correlated to 5 pregnancy outcome groups: gestational hypertension (n = 76), pre-eclampsia (n = 33), intrauterine growth restriction (n = 91), pre-term birth (n = 39), gestational diabetes mellitus (n = 170); In addition, measurements of first trimester myometrial vascularization index were performed and, in combination with afamin tested as a possible screening method to detect women at-risk for the development of adverse complications in low-risk pregnancies at the time of the first trimester. RESULTS: The results showed significantly higher serum afamin levels in women with pre-eclampsia (P<.05) and gestational diabetes mellitus (P<.05) compared to healthy pregnant women. There was no significant difference in serum afamin levels between all other pregnancy outcome groups and healthy controls. In women developing pre-eclampsia during pregnancy, afamin (OR = 1.0197, P < .05) and myometrial vascular index (OR = 0.9235, P < .001) were verified to have a significant prognostic value. Detection of pre-eclampsia in first trimester screening by a combination of afamin and myometrial vascular index performed best (AUC = 0.818). DISCUSSION: Hence, first trimester screening for pre-eclampsia could be provided by a combination of afamin and placental bed vascularization. Moreover, the combination of first trimester serum afamin levels with BMI could provide a possible screening for gestational diabetes mellitus.

First trimester serum afamin concentrations are associated with the development of pre-eclampsia and gestational diabetes mellitus in pregnant women.

OBJECTIVE: Aim of this study was to assess the prognostic capability of afamin to predict pregnancy complications. METHOD: First-trimester screening was consecutively performed in 4948 pregnant women, of whom 474 women developed pregnancy complications [gestational hypertension (n=84), pre-eclampsia (n=30), intrauterine growth restriction (n=107), preterm birth (n=44), and gestational diabetes mellitus (n=209)]. To each woman with pregnancy complications an uncomplicated pregnancy was matched for body mass index. Afamin serum concentrations were measured in 948 pregnant women at the first-trimester screening. RESULTS: Median afamin concentrations were significantly higher in women developing pre-eclampsia or gestational diabetes mellitus when compared to women with uncomplicated pregnancies (76mg/L vs. 65mg/L, p=0.001 and 80mg/L vs. 69mg/L, p<0.001). There was no difference in median afamin values between all other pregnancy complications and their matched controls. Increased afamin (i.e. >65mg/L) was a strong and independent predictor for the development of pre-eclampsia (risk ratio, 24.58; 95%CI, 2.82-214.12; p=0.004) as well as gestational diabetes mellitus (risk ratio, 2.07; 95%CI, 1.33-3.22; p=0.001). CONCLUSION: In this large nested case-control study increased afamin concentrations were a strong and independent predictor for pre-eclampsia and gestational diabetes mellitus, suggesting a potential role of afamin as predictive marker for pregnancy-related metabolic disorders.