Elevated Maternal Serum Alpha-fetoprotein Research Articles

Correlation between elevated maternal serum alpha-fetoprotein and ischemic placental disease: a retrospective cohort study

ABSTRACT Background To evaluate the correlation between elevated maternal serum alpha-fetoprotein (AFP) in the second trimester and ischemic placental disease (IPD). Methods A retrospective cohort study was conducted to analyze the data of 22,574 pregnant women who delivered in the Department of Obstetrics at Hangzhou Women’s Hospital from 2018 to 2020, and were screened for maternal serum AFP and free beta-human chorionic gonadotropin (free β-hCG) in the second trimester. The pregnant women were divided into two groups: elevated maternal serum AFP group (n = 334, 1.48%); and normal group (n = 22,240, 98.52%). Mann-Whitney U-test or Chi-square test was used for continuous or categorical data. Modified Poisson regression analysis was used to calculate the relative risk (RR) and 95% confidence interval (CI) of the two groups. Results The AFP MoM and free β-hCG MoM in the elevated maternal serum AFP group were higher than the normal group (2.25 vs. 0.98, 1.38 vs. 1.04) and the differences were all statistically significant (all P < .001). Placenta previa, hepatitis B virus carrying status of pregnant women, premature rupture of membranes (PROM), advanced maternal age (≥35 years), increased free β-hCG MoM, female infants, and low birth weight (RR: 2.722, 2.247, 1.769, 1.766, 1.272, 0.624, 2.554 respectively) were the risk factors for adverse maternal pregnancy outcomes in the elevated maternal serum AFP group. Conclusions Maternal serum AFP levels during the second trimester can monitor IPD, such as IUGR, PROM, and placenta previa. Maternal women with high serum AFP levels are more likely to deliver male fetuses and low birth weight infants. Finally, the maternal age (≥35 years) and hepatitis B carriers also increased maternal serum AFP significantly.

Timing of maternal serum alpha fetoprotein testing in pregnancy and association with adverse perinatal outcomes

Elevated maternal serum alpha-fetoprotein (MS-AFP ≥2.5MoM) is associated with adverse pregnancy outcomes (APO); however, there is limited data on the association of gestational age [GA] timing of the MS-AFP assay and APO. We sought to determine if there was an optimal GA for the MS-AFP assay in the second trimester that best predicts APO.

Recurrence Rate for Isolated Elevated Maternal Serum Alpha-Fetoprotein Levels and Pregnancy Outcomes.

Objective: To examine the rate of recurrence for elevated isolated maternal serum alpha-fetoprotein (MSAFP) and its associated adverse outcomes during a subsequent pregnancy. Materials and Methods: A retrospective cohort study of pregnant multiparous women who had elevated MSAFP levels during an initial and a subsequent pregnancy between 1994 and 2020. Results: Twenty-seven out of 344 (7.8%) women with elevated MSAFP had recurrent elevated MSAFP in a subsequent pregnancy. Four women were excluded due to missing data. Of the 23 women included, 5 (22%) had fetal growth restriction (FGR), 2 (9%) had pre-eclampsia, 9 (35%) had preterm births, and 2 (9%) had fetal death/miscarriage in their subsequent pregnancy. Looking at individual outcomes, 60% of women had recurrence of preterm labor, 33% had recurrence of fetal death, and 25% had recurrence of FGR. Conclusion: Women with elevated MSAFP levels during an initial pregnancy should be informed during preconception counseling about their risk of recurring elevated MSAFP and its associated adverse outcomes risks.

How Common are Uterine Doppler Abnormalities for Pregnant Patients with Elevated Maternal Serum Alpha-Fetoprotein (MS-AFP)?

How Common are Uterine Doppler Abnormalities for Pregnant Patients with Elevated Maternal Serum Alpha-Fetoprotein (MS-AFP)?

Pregnancy outcomes of women with elevated second-trimester maternal serum alpha-fetoprotein

ObjectiveThe aim of this study was to investigate the overall distribution of pregnancy outcomes in women with elevated second-trimester maternal serum alpha-fetoprotein (MS-AFP), and to determine the risk of adverse pregnancy outcomes (APOs) by MS-AFP level. Materials and methodsWe retrospectively analyzed the clinical data of 429 women with elevated MS-AFP (≥2.5 multiple of the median (MOM)) and 1555 women with normal MS-AFP (0.5–2.49MOM) from a total of 46,741 prenatally screened singleton pregnant women. The overall distribution of APOs of the two groups, the risk of APOs by MS-AFP level, and the predictive value of elevated MS-AFP to APOs were analyzed. ResultsThe incidence rate of APOs in elevated MS-AFP group was significantly higher than that in normal MS-AFP group (42.89 vs. 8.23%). In elevated MS-AFP group, the top three APOs, in term of incidence rate, were structural fetal abnormalities (7.93%), spontaneous abortion (7.46%) and preterm birth (7.23%); regarding to the risk, the top three APOs were stillbirth, spontaneous abortion and early-onset preeclampsia (odds ratio 35.98, 20.81 and 8.58 respectively). For structural fetal abnormalities, MS-AFP had predictive values for fetal open neural tube defects (ONTDs), gastroschisis and multiple malformations. ConclusionElevated MS-AFP is associated with increased risks of APOs. ONTDs complicate merely a small proportion of pregnancies with elevated MS-AFP, and the rest of them have high risks of obstetric complications. MS-AFP can help to identify these women at high risk of APOs in earlier second-trimester.

The predictive value of maternal serum screening tests for adverse pregnancy outcomes

Aim: Free beta-human chorionic gonadotropin (Fβ-hCG), pregnancy-associated plasma protein-A (PAPP-A), alpha-fetoprotein (AFP), unconjugated estriol (uE3), and inhibin-A have been shown to be useful not only in identifying chromosomal abnormalities in the first and second trimesters, but also in predicting adverse pregnancy outcomes (APOs). In this study, we aimed to investigate the predictive value of maternal serum screening tests for various APOs including preeclampsia, intrauterine growth retardation (IUGR), preterm labor, and gestational diabetes mellitus (GDM).Material and Methods: The study was carried out at our clinics and included a total of 220 pregnant women who respectively underwent the double and quadruple marker testsduring the 11th to 14th and 15th to 22nd gestational weeksbetween January 2017 and December 2018. Patient data (maternal age, parity/gravidity, gestational age, history of infertility, use of in vitro fertilization, maternal/fetal complications, preterm labor, mode of delivery, birth weight, and length of stay in the neonatal intensive care unit) were reviewed retrospectively.Results: The AFP levels were statistically significantly higher in patients with IUGR (p=0.022),GDM (p=0.036), and preterm labor (p=0.021), compared to the control group with no APO. No significant correlation was found between preeclampsia and the serum markers.Conclusion: Our results show that elevated maternal serum AFP levels might be associated with various APOs,requiring closer patient follow-up for early diagnosis and treatment.

First-trimester maternal serum alpha fetoprotein is associated with ischemic placental disease

While elevated second-trimester maternal serum alpha fetoprotein has been associated with adverse pregnancy outcomes, the utility of first-trimester maternal serum alpha fetoprotein in predicting these outcomes is limited. Some laboratories have been including maternal serum alpha fetoprotein as part of the first-trimester analyte screening for aneuploidy and preeclampsia, offering its potential utility in predicting pregnancy outcomes. Our primary objective was to determine the association between elevated first-trimester maternal serum alpha fetoprotein and preeclampsia as well as ischemic placental disease (a composite of preeclampsia, fetal growth restriction, and/or placental abruption). Secondary outcomes included early-onset preeclampsia requiring delivery at <34 weeks gestation, fetal growth restriction, placental abruption, preterm delivery, fetal demise, and spontaneous abortion. An institutional review board-approved multisite retrospective cohort study was performed including all patients with first-trimester maternal serum alpha fetoprotein as part of routine first-trimester aneuploidy screening from April 2015 through January 2017. Pregnancies with multiple gestations, known structural or chromosomal abnormalities, known malignancy, and incomplete delivery records were excluded. Delivery records were reviewed for baseline characteristics and adverse pregnancy outcomes. The optimal cutoff point for first-trimester maternal serum alpha fetoprotein to predict these outcomes was assessed, and an elevated maternal serum alpha fetoprotein was considered >2.0 multiple of the median. A Fisher exact test and odds ratios were used to determine the association between elevated first-trimester maternal serum alpha fetoprotein and adverse pregnancy outcomes. Spearman correlation coefficient assessed the relationship between first- and second-trimester maternal serum alpha fetoprotein. Of 1478 patients with first-trimester maternal serum alpha fetoprotein, 1280 had complete records available for review (86.6%). There was no association demonstrated between elevated first-trimester maternal serum alpha fetoprotein (>2.0 multiple of the median) and the primary outcome, overall preeclampsia (5.8% vs 4.6%, odds ratio, 1.29, 95% confidence interval, 0.58-2.91). However, there was an increased incidence of ischemic placental disease, 15.8% vs 7.7% (odds ratio, 2.26, 95% confidence interval, 1.33-3.87) in those with an elevated alpha fetoprotein. Also, elevated first-trimester maternal serum alpha fetoprotein was associated with a higher incidence of fetal growth restriction (7.5% vs 2.3%, odds ratio, 3.40, 95% confidence interval, 1.56-7.42) and preterm birth (18.3% vs 10.3%, odds ratio, 1.95, 95% confidence interval, 1.18-3.21). Also, a positive correlation between first- and second-trimester maternal serum alpha fetoprotein was demonstrated (rho= 0.46, P < .0001). Elevated first-trimester maternal serum alpha fetoprotein is associated with ischemic placental disease, fetal growth restriction, and preterm birth. This suggests that elevated maternal serum alpha fetoprotein may help to identify high risk pregnancies as early as the first trimester of pregnancy. Future studies are necessary to determine whether the addition of first-trimester maternal serum alpha fetoprotein to existing algorithms can improve the early detection of ischemic placental disease.

A rat model of placental inflammation explains the unexplained elevated maternal serum alpha‐fetoprotein associated with adverse pregnancy outcomes

It has been reported in numerous studies that elevated maternal serum alpha-fetoprotein (MS-AFP) is associated with adverse pregnancy outcomes (APO), such as pre-eclampsia, stillbirth, preterm birth and fetal growth restriction. However, the mechanism linking elevated MS-AFP and APO is obscure. In this study, we tried to explore the mechanism by using pregnant rats. Lipopolysaccharide (LPS) was used to induce placental inflammation in pregnant rats. Maternal serum and placental inflammatory cytokines and placental morphology were used to assess the level of placental inflammation. The incidences of APO and the levels of MS-AFP were evaluated. The expressions of alpha-fetoprotein (AFP) in the related organs and fetal serum AFP levels were detected. Compared to saline-treated pregnant rats, LPS led to elevated maternal serum and placental inflammatory cytokines and a higher rate of placental inflammation. Lipopolysaccharide resulted in the features of APO and at the same time elevated MS-AFP. Maternal serum alpha-fetoprotein levels were significantly correlated to the evaluation parameters of APO. Lipopolysaccharide did not increase the expressions of AFP in fetal liver, maternal liver and placenta, but reduced the fetal serum AFP levels. The phenomenon that elevated MS-AFP is associated with APO, which has been reported in human pregnancies, is observed in our rat model. Placental inflammation can be the potential cause linking the two manifestations together. Although the source of elevated MS-AFP is not identified, fetal blood circulation is suspected. Our study may provide an animal model for the future studies on this subject.

Impact of Elevated Second Trimester Maternal Serum Alpha-Fetoprotein on Pregnancy Outcome-A Prospective Observational Study

Introduction: The major goal behind prenatal screening is to identify and intervene in high risk pregnancy. Measurement of second trimester maternal serum alpha-fetoprotein (MSAFP) has been shown to be useful in screening both for Aneuploidies and neural tube defects7-9. Additionally in Pregnancies with normal fetus, high levels of MSAFP is associated with increased risk of adverse pregnancy and fetal outcome. Aim: To determine the association between the second trimester MSAFP and adverse pregnancy outcome. Method: This Prospective observational study was conducted in 200 antenatal women of gestational age between 14-24 weeks, with singleton pregnancy. Determination of maternal serum AFP levels was carried out and were followed till delivery. Fetal outcome was reported in terms of live birth, still birth, neonatal death. Results: The mean age of study subjects with MSAFP?2MoM was slightly higher compared to those with MSAFP>2 MoM and the difference was not statistically significant (P>0.05).The frequency of pregnancy outcomes were as following; 10(5%) Pre-eclampsia, 20(10%)Preterm labour, 7(3.5%)PROM ,18(9%) Oligohydraminos, 2(1%)Still birth.There were significant correlation between Preterm labour, Pre-eclampsia, Oligohydramnios and higher MSAFP levels and was statistically significant. But corelation between PROM, Still birth and MSAFP levels were not significant. Conclusion: Unexplained elevated second trimester MSAFP is associated with adverse pregnancy outcomes such as preeclampsia, oligohydramnios and preterm labour. So it would be worthwhile for screening pregnant women in second trimester for MSAFP, as it would help to identify high risk pregnancies

Gastroschisis and Omphalocele: A Case report

Fetal gastroschisis and omphalocele are congenital defects of abdominal wall that are often diagnosed by prenatal ultrasound done for routine screening or for obstetric indications such as evaluating an elevated maternal serum alpha fetoprotein (AFP).Regular antenatal checkup and Prenatal ultrasound could potentially identify the overwhelming majority of abdominal wall defects and accurately distinguish omphalocele from gastroschisis. But in a developing country like Bangladesh neglected patients fail to seek antenatal visit and prenatal diagnosis. Here we report a case of gastroschisis and omphalocele diagnosed incidentally during last trimester.TAJ 2015; 28(2): 64-65

Gastroschisis and Omphalocele: A Case report

Fetal gastroschisis and omphalocele are congenital defects of abdominal wall that are often diagnosed by prenatal ultrasound done for routine screening or for obstetric indications such as evaluating an elevated maternal serum alpha fetoprotein (AFP).Regular antenatal checkup and Prenatal ultrasound could potentially identify the overwhelming majority of abdominal wall defects and accurately distinguish omphalocele from gastroschisis. But in a developing country like Bangladesh neglected patients fail to seek antenatal visit and prenatal diagnosis. Here we report a case of gastroschisis and omphalocele diagnosed incidentally during last trimester.TAJ 2014; 27(2): 58-62

Is unexplained elevated maternal serum alpha-fetoprotein still important predictor for adverse pregnancy outcome?

The purpose of this study was to determined the predictive value of maternal serum alpha-fetoprotein (MSAFP) as a marker for adverse pregnancy outcomes. This study was carried out at Dr. Zekai Tahir Burak Women's Health Education and Research Hospital between 2009 and 2010. This study included a total of 1,177 pregnant women, including 170 in the study group and 1,007 in the control group. Pregnancy outcomes and characteristics were analyzed with regard to the MSAFP value. Gestational week, birth weight and APGAR scores were significantly lower in the elevated MSAFP group (p < 0.001). Adverse pregnancy outcomes, such as preterm delivery, preterm premature rupture of membranes (PPROM), oligohydramnios and intrauterine growth restriction (IUGR) rates were increased in the elevated MSAFP group. Although ultrasound outweighs as a screening method for neural tube defects and non-invasive prenatal testing outweighs for aneuploidy screening MSAFP level in the second trimester is still an important predictor for poor maternal/fetal outcomes.

230: Do elevated first-trimester maternal serum alpha-fetoprotein (MSAFP) levels predict elevated second trimester levels?

230: Do elevated first-trimester maternal serum alpha-fetoprotein (MSAFP) levels predict elevated second trimester levels?

Analysis of first and second trimester maternal serum analytes for the prediction of morbidly adherent placenta requiring hysterectomy

Morbidly adherent placenta (MAP) is a growing concern currently and is still a diagnostic challenge for obstetricians. As emergency hysterectomy due to unscheduled delivery in MAP carries significant risks, we aimed to evaluate whether first and second trimester serum analytes may be used in the prediction of MAP requiring hysterectomy. A retrospective chart review of all identified cases of placenta previa totalis with and without MAP was performed. A total of 316 pregnant women diagnosed as placenta previa totalis were identified and included in the analysis. Cases were examined in three groups (Group 1: 204 nonadherent placenta previa patients; Group 2: 61 MAP patients managed with endouterine hemostatic square sutures and/or Bakri balloon tamponade; and Group 3: 51 patients with MAP requiring hysterectomy). Among all first and second trimester screening analytes only maternal serum alphafetoprotein (MS-AFP) levels were significantly higher in patients with MAP requiring hysterectomy (p < 0.001). According to the Receiver Operating Characteristic (ROC) analysis performed for the predictive value of MS-AFP levels, the area under the curve (AUC) was 0.742 [95% confidence interval (CI): 0.505–0.979]. The best MS-AFP cut-off value was 1.25 multiple of the median (MoM) with 85.94% sensitivity and 71.43% specificity (p = 0.036). The best predictors which affect the increased risk of hysterectomy, was further evaluated by multivariate logistic regression analyses. Only elevated maternal serum alphafetoprotein (MS-AFP) was found to be an independent predictor of MAP requiring hysterectomy [odds ratio (OR) = 25.329, 95% confidence interval (CI):1.487–43.143, p = 0.025]. In conclusion, increased second trimester MS-AFP levels independently predict morbidly adherent placenta requiring hysterectomy among women with placenta previa totalis.

Elevated maternal serum alpha fetoprotein (MSAFP) level in second trimester as a screening test for predicting adverse pregnancy outcome

Elevated maternal serum alpha fetoprotein (MSAFP) level in second trimester as a screening test for predicting adverse pregnancy outcome

Does Elevated Alpha-fetoprotein During Pregnancy Protect Against Breast Cancer Later in Life? A Commentary

Elevated maternal serum alpha-fetoprotein (sAFP) has been associated with a future breast cancer risk reduction in previously pregnant women. Past reports have indicated that the presence of high sAFP concentrations in the second and third pregnancy trimester could convey a protective effect against breast cancer later in life. During pregnancy, elevations of sAFP can be attributed to: a) twins and multiple pregnancies; b) fetal defects such as spina bifida and anencephaly; c) gestational hypertension; d) pre-eclampsia; and e) ethnicity. AFP is also elevated in adults with DNA repair diseases such as ataxia telangiectasia and Fanconi anemia. Normally, AFP is a growth enhancing agent; however, a conformationally-altered form of AFP (known as transformed AFP) as well as AFPderived peptides have been shown to be growth-inhibitory agents. It has further been demonstrated that various third domain AFP short amino acid sequence stretches can bind and interact with mutated and/or misfolded proteins of the cell cycle DNA repair process that erroneously allow replication of cells with damaged DNA. Thus, there appears to be at least three possible mechanisms working singly or in concert that might explain the observed breast cancer risk reduction in later the life of previously pregnant women.

Maternal serum markers, characteristics and morbidly adherent placenta in women with previa.

To examine associations with morbidly adherent placenta (MAP) among women with placenta previa. Women with MAP (cases) and previa alone (controls) were identified from a cohort of 236,714 singleton pregnancies with both first and second trimester prenatal screening, and live birth and hospital discharge records; pregnancies with aneuploidies and neural tube or abdominal wall defects were excluded. Logistic binomial regression was used to compare cases with controls. In all, 37 cases with MAP and 699 controls with previa alone were included. Risk for MAP was increased among multiparous women with pregnancy-associated plasma protein-A (PAPP-A) ⩾95th percentile (⩾2.63 multiple of the median (MoM); adjusted OR (aOR) 8.7, 95% confidence interval (CI) 2.8 to 27.4), maternal-serum alpha fetoprotein (MS-AFP) ⩾95th percentile (⩾1.79 MoM; aOR 2.8, 95% CI 1.0 to 8.0), and 1 and ⩾2 prior cesarean deliveries (CDs; aORs 4.4, 95% CI 1.5 to 13.6 and 18.4, 95% CI 5.9 to 57.5, respectively). Elevated PAPP-A, elevated MS-AFP and prior CDs are associated with MAP among women with previa.

CRB2 Mutations Produce a Phenotype Resembling Congenital Nephrosis, Finnish Type, with Cerebral Ventriculomegaly and Raised Alpha-Fetoprotein

We report five fetuses and a child from three families who shared a phenotype comprising cerebral ventriculomegaly and echogenic kidneys with histopathological findings of congenital nephrosis. The presenting features were greatly elevated maternal serum alpha-fetoprotein (MSAFP) or amniotic fluid alpha-fetoprotein (AFAFP) levels or abnormalities visualized on ultrasound scan during the second trimester of pregnancy. Exome sequencing revealed deleterious sequence variants in Crumbs, Drosophila, Homolog of, 2 (CRB2) consistent with autosomal-recessive inheritance. Two fetuses with cerebral ventriculomegaly and renal microcysts were compound heterozygotes for p.Asn800Lys and p.Trp759Ter, one fetus with renal microcysts was a compound heterozygote for p.Glu643Ala and p.Asn800Lys, and one child with cerebral ventriculomegaly, periventricular heterotopias, echogenic kidneys, and renal failure was homozygous for p.Arg633Trp in CRB2. Examination of the kidneys in one fetus showed tubular cysts at the corticomedullary junction and diffuse effacement of the epithelial foot processes and microvillous transformation of the renal podocytes, findings that were similar to those reported in congenital nephrotic syndrome, Finnish type, that is caused by mutations in nephrin (NPHS1). Loss of function for crb2b and nphs1 in Danio rerio were previously shown to result in loss of the slit diaphragms of the podocytes, leading to the hypothesis that nephrosis develops from an inability to develop a functional glomerular barrier. We conclude that the phenotype associated with CRB2 mutations is pleiotropic and that the condition is an important consideration in the evaluation of high MSAFP/AFAFP where a renal cause is suspected.

Gastroschisis and Omphalocele: A Case report

Fetal gastroschisis and omphalocele are congenital defects of abdominal wall that are often diagnosed by prenatal ultrasound done for routine screening or for obstetric indications such as evaluating an elevated maternal serum alpha fetoprotein (AFP). Prenatal ultrasound could potentially identify the overwhelming majority of abdominal wall defects and accurately distinguish omphalocele from gastroschisis. Here we report two cases of gastroschisis and omphalocele diagnosed at routine prenatal ultrasound. NJR I VOL 2 I ISSUE 1 42-45 Jan-June, 2012 DOI: http://dx.doi.org/10.3126/njr.v2i1.6980

Lack of Association between Unexplained Elevated Maternal Serum Alpha Fetoprotein and/or Human Chorionic Gonadotropin and the Occurrence of Placental Thrombotic Lesions

Objective To investigate the significance of unexplained elevated maternal serum alpha fetoprotein (MSAFP) and/or human chorionic gonadotropin (HCG) on the occurrence of placental thrombotic changes. Study design Between January 2007 to April 2009, placentas of all women who delivered and had unexplained elevated MSAFP and/or HCG (above 2 MOM) were sent to histological examination. Women were divided into 2 groups. Group A included women who had uneventful pregnancies and delivered at term. Group B included women with antepartum complications attributed to thrombosis. Women in both groups (A and B) had elevated MSAFP and/or HCG. Group C was a frequency matched group of women who had normal MSAFP and HCG levels with uneventful pregnancies and delivered at term. Main outcome measure Incidence of placental thrombotic lesions in each group. Results Of 9695 women who delivered during the study period there were 76 women with elevated MSAFP and or HCG, 48 in group A and 28 in Group B. Group C, included 30 women. The number of placentas in which any thrombotic lesion was identified was 22 (45.8%), 19 (67.9%) and 10 (33%) respectively. Changes differed significantly only between group B and C ( p = 0.03). Although the rate of changes in group A was higher than in group C it did not reach statistical significance even when considering only women with two abnormal results (MSAFP and HCG) or when a cutoff of 2.5 MOM or more was set. Conclusion Placental histopathological changes are associated with pregnancy complications and can only marginally be attributed to unexplained elevated MSAFP and/or HCG.