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4370
REVIEW
ABSTRACT
Second trimester biomarkers were initially introduced with the intent of screening for neural tube defects and then
subsequently for Down syndrome. It was soon realized that these markers can be indirect evidence of abnormal
placentation and, therefore, can be used for screening for adverse pregnancy outcomes. Several new biomarkers have
subsequently been described with conicting ndings regarding their efciency for screening for adverse pregnancy
outcomes. Although a biologically feasible mechanism has been proposed for the role of these biomarkers, they still
fall short of an ideal screening test to be clinically useful. 2014 John Wiley & Sons, Ltd.
INTRODUCTION
Second trimester maternal serum biomarker screening was rst
introduced into the eld of obstetrics in the 1970s with the
discovery of elevated levels of alpha-fetoprotein (AFP) in the
maternal serum of pregnancies affected by fetal open neural
tube defects (NTDs). Approximately one decade later, low
maternal serum levels of AFP were identied in pregnancies with
fetal trisomy 21. Since that time, AFP has been combined with
other maternal serum biomarkers, including human chorionic
gonadotrophin (hCG), unconjugated estriol, and inhibin A, in
order to improve the detection rate of fetal aneuploidy in the
second trimester of pregnancy.
These biomarkers are secreted by the placenta and enter the
maternal bloodstream in small amounts throughout gestation.
The detection of abnormal biomarker levels in fetal trisomies
suggest that aneuploid fetuses demonstrate a degree of fetal
placental immaturity that results in both unregulated
hypersecretion and undersecretion of both fetal and placental
products.1 This suggests that abnormal levels of this biomarker
may be representative of abnormal placentation and, thus,
associated with adverse pregnancy outcomes such as
preeclampsia, fetal growth restriction (FGR), preterm delivery,
and fetal loss. Abnormal maternal serum markers obtained during
the rst trimester of pregnancy are also risk factors for subsequent
adverse pregnancy outcomes; however, these rst trimester
markers will not be addressed in this review. The objective of this
review is to critically evaluate the current literature regarding
abnormal levels of maternal serum biomarker in the second
trimester of pregnancy and their association with and screening
efciency for adverse pregnancy outcomes.
K. R. Goetzinger et al.
636
637
K. R. Goetzinger et al.
638
Angiogenic factors
Circulating angiogenic factors include vascular endothelial
growth factor and placental growth factor. They are thought
to contribute to normal trophoblastic proliferation and
implantation.73 Soluble fms-like tyrosine kinase-1 (sFlt-1) is
able to block the effects of vascular endothelial growth factor
and PIGF by inhibiting interaction with their receptors.
Ischemic trophoblasts have been shown to synthesize
antiangiogenic factors, notably sFlt-1.74 This deprives the
maternal vascular endothelium of these essential angiogenic
2014 John Wiley & Sons, Ltd.
CONCLUSION
In recent years, much interest has been shown in identifying
biomarkers of placental dysfunction in the rst and second
639
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