Very low alpha‐fetoprotein in Down syndrome maternal serum screening

Müller, Françoise; Dreux, Sophie; Sault, Corinne; Galland, Armelle; Puissant, Hugues; Couplet, G.; Lemay, Catherine; Larcher, Marie-Estelle; Renom, Gilles

doi:10.1002/pd.646

Cited by 14 publications

(3 citation statements)

References 18 publications

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“…Its frequency was estimated to be 1/ 105 000. 2 In such situations, the difficulty is to distinguish real low AFP values in patients at high risk of maternal or fetal abnormalities 7 from congenital absence of AFP. 3 Indeed, molecular defect in the AFP gene expression could conceal 1 of the 18 clinical manifestations observed in case of low levels of serum AFP.…”

Section: Discussionmentioning

confidence: 99%

A new mutation in the AFP gene responsible for a total absence of alpha feto-protein on second trimester maternal serum screening for Down syndrome

et al. 2008

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Alpha feto-protein (AFP) is a major plasma protein produced by the yolk sac and the liver during the fetal period. During the second trimester of pregnancy, APF and bhCG serum concentrations are commonly used for screening Down syndrome. AFP deficiency is rare (estimated to be 1/105 000 newborns) and only one sequence alteration has previously been reported in the AFP gene. We report a new mutation in exon 5 of the AFP gene, leading to a total absence of AFP on 2nd-trimester maternal serum screening for Down syndrome, confirmed on the amniotic fluid. Despite this, fetal development and birth were normal. After PCR-amplification, the whole AFP gene was sequenced. The new mutation was a guanine to adenine transition in position 543 creating a premature stop codon in position 181. In order to search for eventual modifications of the amniotic fluid profile, proteins were separated by electrophoresis and compared with 10 normal amniotic fluids sampled at the same developmental age (18 weeks). In the amniotic fluid of our patient albumin rate was reduced whereas alpha1 and beta protein fractions were increased, suggesting that AFP deficiency may modify the distribution of protein fractions. This observation emphasizes the complex molecular mechanisms of compensation of serum protein deficiency. Studies on other families with AFP deficiency are necessary to confirm this observation.

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Section: Discussionmentioning

confidence: 99%

A new mutation in the AFP gene responsible for a total absence of alpha feto-protein on second trimester maternal serum screening for Down syndrome

et al. 2008

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“…Again, the fetal malformation and adverse conditions can be classified according to the calculated multiple of a population AFP median compared with the patient's AFP median value. Low-AFP disorders categorized by various investigators have included low birth weight, multiple pregnancies, fetal wastage, perinatal death, spontaneous abortions, stillbirths, and neonatal deaths (109)(110)(111). An association was also found between second-trimester low HAFP levels and subsequent Sudden Infant Death Syndrome (SIDS).…”

Section: Adverse Pregnancy Complications/outcomes Related To Hafp Levelsmentioning

confidence: 99%

Physiology of Alpha-Fetoprotein as a Biomarker for Perinatal Distress: Relevance to Adverse Pregnancy Outcome

Mizejewski

2007

Exp Biol Med (Maywood)

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The many physiologic roles of human alpha-fetoprotein (HAFP) and its correlation with perinatal distress/pregnancy outcome are rarely addressed together in the biomedical literature, even though HAFP has long been used as a biomarker for fetal birth defects. Although the well being of the fetus can be monitored by the measurement of gestational age-dependent HAFP in biologic fluid levels (serum, amniotic fluid, urine, and vaginal fluids) throughout pregnancy, the majority of clinical reports reflect largely second trimester and (less likely) first trimester testing due to regulatory clinical restrictions. However, reports of third-trimester and pregnancy term measurement of HAFP levels performed in clinical research and/or investigational settings have gradually increased over the years and have expanded our base knowledge of AFP-associated pregnancy disorders during these stages. The different structural forms of HAFP (isoforms, epitopes, molecular variants, etc.) detected in the various biologic fluid compartments have been limited by antibody recognition of specific epitopic sites developed by the kit manufacturers based on antibody specificity, sensitivity, and precision. Concomitantly, the advances in elucidating the various biologic actions of AFP are opening new vistas toward understanding the physiologic roles of AFP during pregnancy. The present review surveys HAFP as a biomarker for fetal distress during the perinatal period in view of its structural and functional properties. An attempt is then made to relate the AFP fluid levels to adverse pregnancy complications and outcomes. Hence, the present review was divided into two major sections: (I) AFP structure and function considerations and (II) the relationship of AFP levels to the distressed fetus during the third trimester and at term.

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“…Elevated MSAFP levels with a screen positive rate of 5% or less can detect 75%-90% of NTDs and ≥95% of anencephaly [11], which is the most severe type of NTD that is incompatible with life [1]. Abnormally low AFP values [15] (most often a median value of <0.5) are associated with Down syndrome and other chromosomal abnormalities. MSAFP levels may also detect 85% of the ventral wall defects [11].…”

Section: Introductionmentioning

confidence: 99%

Point-of-Care Quantification of Serum Alpha-Fetoprotein for Screening Birth Defects in Resource-Limited Settings: Proof-of-Concept Study (Preprint)

Srinivasan¹,

Finkelstein²,

Erickson³

et al. 2020

Preprint

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BACKGROUND Maternal serum alpha-fetoprotein (MSAFP) concentration typically increases during pregnancy and is routinely measured during the second trimester as a part of screening for fetal neural tube defects and Down syndrome. However, most pregnancy screening tests are not available in the settings they are needed the most. A mobile device–enabled technology based on MSAFP for screening birth defects could enable the rapid screening and triage of high-risk pregnancies, especially where maternal serum screening and fetal ultrasound scan facilities are not easily accessible. Shifting the approach from clinic- and laboratory-dependent care to a mobile platform based on our point-of-care approach will enable translation to resource-limited settings and the global health care market. OBJECTIVE The objective of this study is to develop and perform proof-of-concept testing of a lateral flow immunoassay on a mobile platform for rapid, point-of-care quantification of serum alpha-fetoprotein (AFP) levels, from a drop of human serum, within a few minutes. METHODS The development of the immunoassay involved the selection of commercially available antibodies and optimization of their concentrations by an iterative method to achieve the required detection limits. We compared the performance of our method with that of commercially obtained human serum samples, with known AFP concentrations quantified by the Abbott ARCHITECT chemiluminescent magnetic microparticle immunoassay (CMIA). RESULTS We tested commercially obtained serum samples (N=20) with concentrations ranging from 2.2 to 446 ng/mL to compare the results of our point-of-care assay with results from the Abbott ARCHITECT CMIA. A correlation of 0.98 (<i>P</i><.001) was observed on preliminary testing and comparison with the CMIA. The detection range of our point-of-care assay covers the range of maternal serum AFP levels observed during pregnancy. CONCLUSIONS The preliminary test results from the AFP test on the mobile platform performed in this study represent a proof of concept that will pave the way for our future work focused on developing a mobile device–enabled quad-screen point-of-care testing with the potential to enable the screening of high-risk pregnancies in various settings. The AFP test on the mobile platform can be applied to enable screening for high-risk pregnancies, within a few minutes, at the point of care even in remote areas where maternal serum tests and fetal ultrasound scans are not easily accessible; assessment of whether clinical follow-up and diagnostic testing may be needed after a positive initial screening evaluation; and development of surveillance tools for birth defects.

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Very low alpha‐fetoprotein in Down syndrome maternal serum screening

Cited by 14 publications

References 18 publications

A new mutation in the AFP gene responsible for a total absence of alpha feto-protein on second trimester maternal serum screening for Down syndrome

A new mutation in the AFP gene responsible for a total absence of alpha feto-protein on second trimester maternal serum screening for Down syndrome

Physiology of Alpha-Fetoprotein as a Biomarker for Perinatal Distress: Relevance to Adverse Pregnancy Outcome

Point-of-Care Quantification of Serum Alpha-Fetoprotein for Screening Birth Defects in Resource-Limited Settings: Proof-of-Concept Study (Preprint)

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