Maternal Serum Alpha-fetoprotein Levels Research Articles

Adjustment of maternal serum alpha‐fetoprotein levels in women with pregestational diabetes

Decreased second trimester levels of maternal serum alpha-fetoprotein (MSAFP) have been reported in women with pregestational diabetes leading some laboratories to use a correction factor. The aim of this study is to determine if MSAFP levels in pregnant women with diabetes managed on oral antidiabetic agents is lower than non-diabetic controls and require adjustment similar to those on insulin. We performed a nested case/control study of an existing dataset using women with pregestational diabetes who had routine MSAFP values available. Before adjusting the MSAFP value for weight, both the diabetic patients who used insulin (n = 68) and those who used oral antidiabetic agents (n = 37) showed a non-significant trend toward a lower multiples of the median (MoM) as compared with controls (n = 244). After converting the raw MSAFP values to race-adjusted MoM and adjusting for weight, the median MSAFP MoM for women taking insulin (1.01) versus those on oral antidiabetic agents (1.00) were essentially the same. Furthermore, both of the diabetic groups were virtually identical to non-diabetic controls. In our study, women with pregestational diabetes managed on either insulin or oral antidiabetic agents had weight-adjusted MSAFP MoM levels equivalent to those in control pregnancies and did not require a correction factor.

Fetomaternal transfusion after amniocentesis and cordocentesis

To compare the extent of fetomaternal transfusion after amniocentesis and cordocentesis. Three-hundred and forty-five amniocentesis and 268 cordocentesis were performed for genetic indications. The extent of fetomaternal transfusion was calculated on the basis of the maternal serum alpha-fetoprotein level changes. The mean fetomaternal transfusion was 6.3 and 62 μL in the amniocentesis and cordocentesis groups, respectively. Transplacental needle passage and longer procedural time were risk factors for fetomaternal transfusion. The frequency of transplacental passage was higher and the procedural time was longer in the cordocentesis group. The fetal loss rate was 1.17% after amniocentesis and 1.2% after cordocentesis, respectively. Cordocentesis causes more injury to the extrafetal compartment, which results in a higher level of fetomaternal transfusion. However, though a nearly ten times higher fetomaternal transfusion was observed after cordocentesis, there was no essential difference in pregnancy outcome between the two groups.

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.

Second Trimester Detection of Arthrogryposis Multiplex Congenita with Two-Dimensional Ultrasound

Arthrogryposis multiplex congenita (arthrogryposis) is a rare condition that describes multiple severe bony deformities and contractures in the newborn. Arthrogryposis has a prevalence of 1 in 3000, however, at least 1 in 200 neonates are born with some degree of joint contractures, the most common being talipes equinovarus (1 in 500) and congenital hip dislocation (1 in 200–500). In 2007 a case of arthrogryposis was diagnosed at a district general hospital at 17 weeks following a detailed scan due to a marginally raised maternal serum alphafetoprotein level. The pregnancy was terminated and a postmortem examination identified further underlying anomalies that may have been the cause of the arthrogryposis. This report assesses the value of prenatal ultrasound in the identification of arthrogryposis.

726: The effect of oral hypoglycemic agents on maternal serum alpha-fetoprotein levels in diabetic pregnancies

Past studies have shown decreased levels of MSAFP in women with preconceptional diabetes, leading many laboratories to use a correction factor. Type II diabetes has become more prevalent secondary to rising obesity rates and oral hypoglycemics (OHA) have become a popular alternative to insulin in these patients. It is not clear whether the routine adjustment of MSAFP will be applicable to women on OHA, or whether this historical adjustment is still warranted.

Prenatal Genetic Testing

CME Educational Objectives 1. Describe the currently available prenatal screening and diagnostic tests for Down syndrome. 2. Recognize the autosomal recessive conditions for which carrier testing is available and determine how these should be offered to women during the preconception and prenatal period. 3. Identify the appropriate use of genetic services during the preconception and prenatal period.

Mid‐trimester amniotic fluid C‐reactive protein, ferritin and lactate dehydrogenase concentrations and subsequent risk of spontaneous preterm labour

Preterm delivery is a serious problem in obstetrics. A pre-existing inflammation in the first half of gestation has been proposed as a possible condition that leads to preterm delivery. Our aim was to compare C-reactive protein (CRP), ferritin and lactate dehydrogenase (LDH) concentrations in mid-trimester amniotic fluid of patients with preterm and term deliveries and to found out their predictive values for preterm delivery. The study was conducted on 90 pregnant women who underwent genetic amniocentesis between the 15th and the 20th weeks of gestation. The samples were carried immediately to the laboratory for cytogenetic and biochemical examination. Non-parametric tests and receiver-operating characteristic curve analysis were used for statistical purpose. This study showed women with preterm delivery at < 37 weeks (n = 17) had a higher median of amniotic fluid LDH concentration than those women who delivered at term (n = 73) (P = 0.003). Amniotic fluid LDH concentration of > 120 IU/L had a sensitivity of 59% and a specificity of 81% in the prediction of spontaneous preterm delivery at < 37 weeks. Maternal serum alpha-fetoprotein levels were higher in patients delivered preterm compared with term deliveries (P = 0.036). Mid-trimester LDH is found to be quite effective in the prediction of preterm delivery. Pre-existing intrauterine inflammatory process early in gestation may be an important risk factor for preterm delivery.

The Ability of the Quadruple Test to Predict Adverse Perinatal Outcomes in a High-risk Obstetric Population

To determine the ability of the quadruple Down's syndrome screening test (quad screen) to predict other adverse perinatal outcomes (APO) in a high-risk obstetric population. A tertiary medical centre in West Virginia. We retrospectively reviewed 342 obstetric patients with quad screen data from a single clinic. The quad screen included maternal serum levels of alphafetoprotein (AFP), human chorionic gonadotrophin (hCG), uncongjugated oestriol (uE(3)), and inhibin A. The risk of APO was compared between patients with at least one abnormal marker versus no abnormal markers and >or=2 abnormal markers versus <2 abnormal markers. Abnormal markers were determined by cut-off values produced by Receiver Operator Characteristic (ROC) curves and the FASTER trial. Unadjusted and adjusted effects were estimated using logistic regression analysis. The risk of having an APO increased significantly for patients with abnormal markers by about three-fold using ROC and two-fold using FASTER trial thresholds. The quad screen shows value in predicting risk of APO in high-risk patients.

Maternal and fetal serum transformed alpha‐fetoprotein levels in normal pregnancy

To evaluate transformed alpha-fetoprotein (t-AFP) (a new molecular conformation of alpha-fetoprotein) levels in maternal serum and fetal serum in normal pregnancy. Prospective longitudinal study. Fifty pregnant women were studied in two groups: 25 were evaluated in each trimester of pregnancy and near term (12, 20, 32 and 36 weeks) and the other 25 were evaluated at the time of planned cesarean section at term. In the first group, maternal serum t-AFP was measured and in the second group, maternal and fetal serum t-AFP were analyzed. Maternal serum t-AFP levels (medians) were 14.73 ng/mL in the first trimester, 28.29 ng/mL in the second trimester, 30.45 ng/mL in the early third trimester and 8.06 ng/mL in late pregnancy. t-AFP levels were significantly higher in maternal than in fetal serum (P < 0.001). There were no significant correlations between AFP and t-AFP levels in maternal versus fetal serum. t-AFP increases during pregnancy until the early third trimester and then falls before delivery. t-AFP levels are higher in maternal than in fetal serum which suggests that native AFP is transformed to t-AFP either in the mother or in the placenta.

RETIRED: Obstetrical Complications Associated With Abnormal Maternal Serum Markers Analytes

RETIRED: Obstetrical Complications Associated With Abnormal Maternal Serum Markers Analytes

Maternal Biochemical Serum Screening for Down Syndrome in Pregnancy With Human Immunodeficiency Virus Infection

To estimate the influence of human immunodeficiency virus (HIV) infection and antiretroviral therapy on maternal serum markers levels and the false-positive rate with biochemical maternal serum screening for Down syndrome. We performed a 1:1 matched case-control study comparing 132 HIV-infected women with single pregnancy to controls selected among non-HIV-infected women matched on geographical origin and fetal sex. Of HIV-infected women, 47.7% were receiving antiretroviral therapy. Groups did not differ in multiples of the median (MoM) levels of total human chorionic gonadotrophin. The MoM alpha fetoprotein level did not differ between total HIV-infected women and control women but was significantly lower for untreated HIV-positive women compared with control women (0.91 compared with 1.03 MoM, P<.01) and compared with treated HIV-positive women (0.91 compared with 1.18 MoM, P<.01). The false-positive rate of biochemical screening did not differ between groups. Untreated HIV infection is associated with lower maternal serum alpha fetoprotein levels. Nevertheless, the false-positive rate of double-marker second-trimester Down syndrome serum screening did not appear to be affected in our sample of HIV-infected women, whether women were receiving antiretroviral therapy at the time of the test or not.

Effect of anti-epileptic drugs in pregnancy and teratogenesis.

Epilepsy raises special concern in women during pregnancy. Antiepileptic drugs are known to induce major and minor malformations in the foetus. Aim of the study was to find an association between maternal serum alpha fetoprotein levels, foetal abnormalities and antiepileptic drugs mediated teratogenicity. Maternal serum alpha feto protein levels, kidney and liver function tests in age matched normal pregnant women and seizure free epileptic pregnant women during 12-14 weeks of gestation were estimated. Cases were subjected to ultrasonography at 11(th)-14(th) week of pregnancy and again at 20(th) week of pregnancy. maternal serum alfa feto protein was assayed by a specific Electro Chemiluminescence Immuno Assay test. There was no significant difference in kidney and liver function tests in cases as compared to controls. There were elevated levels of alpha feto protein in cases as compared to controls but this was not statistically significant. No anomalies were detected in ultrasound reports. Most women had normal full term delivery with healthy children but of low birth weight. No correlation was seen between maternal serum alfa feto protein levels and antiepileptic drug leading to teratogenesis.

Maternal serum alpha-fetoprotein values in type 1 and type 2 diabetic patients

Maternal serum alpha-fetoprotein (MSAFP) values are reported to be lower in type 1 diabetic patients, and a correction factor is often applied. We sought to determine whether type 2 diabetic patients require the same MSAFP adjustments as type 1 diabetic patients. We performed a retrospective review of MSAFP levels from a university laboratory in type 1 and type 2 diabetic patients between July 2000 and August 2006, matched 1:2 with controls. Groups were compared using analysis of variance and Student t testing. Seventy-seven type 1 and 75 type 2 diabetic patients were compared with 304 controls. Type 1 and type 2 diabetic patients differed significantly from each other and controls before corrections. Diabetic patients were similar to each other, but significantly lower than controls, after weight corrections. These differences were eliminated by a 10% correction factor. Type 1 and type 2 diabetic patients require both weight and diabetes corrections to adjust MSAFP values to nondiabetic levels.

Antenatal Depression: Navigating the Treatment Dilemmas

“Ms. A” was a 35-year-old married Caucasian health care professional with a history of recurrent major depressive disorder that responded well to treatment with a selective serotonin reuptake inhibitor (SSRI). She discontinued her antidepressant prior to conception for a planned pregnancy because she did not want to expose her baby to medication. She soon relapsed, and by the first trimester of her pregnancy, she was in a major depressive episode. Her symptoms included anhedonia, tearfulness, irritability, insomnia, and diminished appetite. She presented for participation in an open-label pilot trial of omega-3 fatty acids for antenatal major depressive disorder (1). At intake, after hearing the risks and benefits of available treatment options, Ms. A declined antidepressant medication and a referral for psychotherapy and consented to participate in the study of omega-3 fatty acids, which she started at 16 weeks’ gestation. She was assessed every 2 weeks throughout pregnancy. At 8 weeks she had not responded to omega-3 fatty acids and was again presented with other treatment options, including medication and psychotherapy. She again declined these treatments and continued to do so throughout the remainder of her pregnancy. She was concerned about the safety of medications in pregnancy and believed that taking medication would make her a bad mother. She also declined referral for psychotherapy, stating that she was “too busy.”

Levels and correlates of alpha-fetoprotein in normal pregnancies among Caucasian and Chinese women

Alpha-fetoprotein has been suggested to have anti breast cancer properties both in adult life and in utero. We studied correlates of maternal serum alpha-fetoprotein levels in normal singleton pregnancies. This was a prospective study relying on women attending maternal units in major teaching hospitals in Boston, USA and Shanghai, China. Specifically, 212 Caucasian women in Boston, and 196 Asian women in Shanghai provided blood samples at the 16th and 27th gestational week. Maternal serum alpha-fetoprotein levels were measured and correlated with maternal and newborn parameters through multiple regression procedures, controlling for a set of potential confounders, including maternal levels of measured hormones. Alpha-fetoprotein was strongly inversely associated with maternal prepregnancy body mass index (-4.73 ng/l at the 27th week per 1 kg/m of body mass index, with 95% confidence intervals -7.09 to -2.36), whereas it was not related to parity, gender of offspring or birth weight. Duration of gestation was inversely associated with maternal alpha-fetoprotein levels, particularly among Caucasian women (-0.22 weeks per 60 ng/l of alpha-fetoprotein at the 27th week, with 95% confidence intervals -0.39 to -0.05). In normal pregnancies, maternal alpha-fetoprotein is inversely related to prepregnancy body mass index and appears to have a physiologic role on duration of gestation rather than on birth weight.

Maternal and biochemical predictors of antepartum stillbirth among nulliparous women in relation to gestational age of fetal death

To determine whether maternal serum levels of alphafetoprotein (alpha-FP) and human chorionic gonadotrophin (hCG) at 15-21 weeks provided clinically useful prediction of stillbirth in first pregnancies. Retrospective study of record linkage of a regional serum screening laboratory to national registries of pregnancy outcome and perinatal death. West of Scotland, 1992-2001. A total of 84,769 eligible primigravid women delivering an infant at or beyond 24 weeks of gestation. The risk of stillbirth between 24 and 43 weeks was assessed using the Cox proportional hazards model. Logistic regression models within gestational windows were then used to estimate predicted probability. Screening performance was assessed as area under the receiver operating characteristic (ROC) curve. Antepartum stillbirth unrelated to congenital abnormality. The odds ratio (95% CI) for stillbirth at 24-28 weeks for women in the top 1% were 11.97 (5.34-26.83) for alpha-FP and 5.80 (2.19-15.40) for hCG. The corresponding odds ratios for stillbirth at or after 37 weeks were 2.44 (0.74-8.10) and 0.79 (0.11-5.86), respectively. Adding biochemical to maternal data increased the area under the ROC curve from 0.66 to 0.75 for stillbirth between 24 and 28 weeks but only increased it from 0.64 to 0.65 for stillbirth at term and post-term. Women in the top 5% of predicted risk had a positive likelihood ratio of 7.8 at 24-28 weeks, 3.7 at 29-32 weeks, 5.1 at 33-36 weeks and 3.4 at 37-43 weeks, and the corresponding positive predictive values were 0.97, 0.33, 0.47 and 0.63%, respectively. Maternal serum levels of alpha-FP and hCG were statistically associated with stillbirth risk. However, the predictive ability was generally poor except for losses at extreme preterm gestations, where prevention may be difficult and interventions have the potential to cause significant harm.

Prenatal sonographic findings of Klippel‐Trénaunay‐Weber syndrome

We describe the prenatal sonographic findings in a case of Klippel-Trénaunay-Weber syndrome including fetal ascites and subcutaneous cystic lesions associated with a relatively low level of maternal serum alpha-fetoprotein and a relatively high level of maternal serum beta-human chorionic gonadotrophin. Klippel-Trénaunay-Weber syndrome may present prenatally with fetal ascites and an abnormal maternal serum screening result in addition to fetal limb hypertrophy and subcutaneous cystic lesions.

Elevated maternal second‐trimester serum alpha‐fetoprotein as a risk factor for placental abruption

To analyze the association of second-trimester maternal serum alpha-fetoprotein (MSAFP) and free beta human chorionic gonadotrophin (MSbeta-hCG) levels to placental abruption. Fifty-seven women with placental abruption and 108 control women without placental abruption were tested for second-trimester MSAFP and MSbeta-hCG levels as a part of a trisomy 21 screening program. Discriminatory cutoff levels for MSAFP were sought to predict placental abruption. The median of the MSAFP multiples of median (MoM) (1.21) was significantly higher in the abruption group than in the control group (1.07) (p = 0.004). In multivariate analysis, elevated MSAFP remained an independent risk factor for placental abruption when adjusting for other risk factors (parity >/= 3, smoking, previous placental abruption, preeclampsia, bleeding in II or III trimester, and placenta previa). MSAFP >/= 1.5 MoM had a sensitivity of 29% and a false-positive rate of 10%. The levels of the MSbeta-hCG MoM did not differ between the cases and the controls. Although second-trimester MSAFP levels are higher in women with subsequent placental abruption, the clinical usefulness of this test is limited due to low sensitivity and high false-positive rate.

Risk prediction for Down’s syndrome in young pregnant women using maternal serum biomarkers: determination of cut‐off risk from receiver operating characteristic curve analysis

The aim of this study was to establish a predictive model for Down's syndrome using maternal age as well as maternal serum levels of alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG), and to identify an optimal cut-off risk in women under the age of 35 years to improve sensitivity. Logistic regression models were utilized to predict fetal Down's syndrome as a function of maternal age and logarithm of levels of AFP as well as hCG using training data of 20 pregnancies with fetal Down's syndrome and 9730 unaffected pregnancies. Validation was performed using data of another nine affected pregnancies and 3496 unaffected pregnancies. Receiver operating characteristic (ROC) curves were plotted. Based on the newly established logistic regression equations, the optimal cut-off risk from the ROC curve analysis was at 1:499, with a 17.8% false-positive rate and a 90.0% sensitivity. A suboptimal cut-off risk was estimated at 1:332, with a 12.0% false-positive rate and an 80% sensitivity. A predictive model for Down's syndrome was developed using logistic regression. By ROC curve analysis and clinical consideration, the cut-off risk for young pregnant women could be determined.

Maternal and biochemical predictors of spontaneous preterm birth among nulliparous women: a systematic analysis in relation to the degree of prematurity

Nulliparous women are at increased risk of spontaneous preterm birth. Other maternal and biochemical risk factors have also been described. However, it is unclear whether these associations are strong enough to offer clinically useful prediction. It is also unclear whether the predictive power of these factors varies in relation to the degree of prematurity. The risk of spontaneous preterm birth associated with maternal characteristics and second trimester serum screening data was analysed in a dataset of 84 391 first births in Scotland between 1992 and 2001 using Cox and logistic regression. Variation in the relative risk of preterm birth over the period 24-36 weeks was assessed using a test of the proportional hazards assumption. The risk of spontaneous preterm birth was positively associated with maternal serum levels of alpha-fetoprotein, socioeconomic deprivation, number of previous therapeutic abortions, smoking, and being unmarried and was negatively associated with height and body mass index. The risk of preterm birth at 24-28 weeks, but not later gestations, was increased in association with maternal levels of human chorionic gonadotrophin >95th percentile, maternal age <20, and two or more previous miscarriages. The area under the receiver operating characterise curve (95% CI) for models based on these factors was 0.67 (0.63-0.71) for 24-28 weeks, 0.65 (0.62-0.68) for 29-32 weeks, and 0.62 (0.61-0.63) for 33-36 weeks. Time to event analytic methods can identify factors that are differentially associated with spontaneous preterm birth according to the degree of prematurity. However, models based on maternal and biochemical data perform poorly as a screening test for any degree of spontaneous preterm birth.