Elevated Maternal Serum Research Articles

First‐trimester biochemical screening for fetal chromosome abnormalities and neural tube defects

Alpha-fetoprotein (AFP), unconjugated oestriol (UE3), intact human chorionic gonadotrophin (intHCG), and the free beta subunit of chorionic gonadotrophin (F beta HCG) were investigated in a series of 21 chromosomally abnormal and 14 open neural tube defect pregnancies ascertained from a series of 14,000 prospectively collected maternal serum samples at 6-14 weeks' gestation. In 16 cases of Down's syndrome, significant reductions were found for AFP (0.65 multiples of the normal median) and UE3 (0.67 MOM). IntHCG levels were unaltered (0.97 MOM) but a significant increase was found for F beta HCG (1.96 MOM). Significant correlations were found for AFP and UE3 in the controls and for intHCG and F beta HCG in both the control and the Down's syndrome pregnancies. In a group of five trisomy 18 pregnancies, median MOMs were for AFP 0.71, for UE3 0.34, for intHCG 0.27, and for F beta HCG 0.15. None of 13 pregnancies with open neural tube defects at 8-13 weeks gestation had elevated maternal serum AFP levels, whereas matched second-trimester samples from the same pregnancies at 16-18 weeks gestation all had significantly elevated AFP levels. Thus, biochemical screening for chromosome abnormalities may be practicable in the first trimester using free beta human chorionic gonadotrophin in combination with AFP and maternal age. However, a separate screening protocol using AFP at 15-18 weeks gestation would still be required for effective detection of neural tube defects.

Transfer of maternally administered magnesium sulfate into the fetal compartment of the rat: Assessment of amniotic fluid, blood, and brain concentrations

Our purpose was to determine whether parenteral magnesium sulfate crosses the rat placenta and enters the fetal brain. Twenty-eight pregnant female Long-Evans rats were divided into four groups, seven animals in each group. These groups included the following: single saline solution injection group evaluated after 20 minutes (control), single magnesium sulfate injection (270 mg/kg) evaluated after 20 minutes, and prolonged (2 and 4 hours) serum magnesium elevation (270 mg/kg loading and then 27 mg/kg every 20 minutes for maintenance). Each animal was killed, and maternal and fetal sera, amniotic fluid, and specific brain areas were analyzed for levels of magnesium. Statistical analysis included analysis of variance, multiple comparison procedure, and linear regression analysis. All three regimens of maternal subcutaneous magnesium sulfate resulted in significantly elevated maternal serum magnesium concentrations (p < 0.01). Fetal blood magnesium concentration rose from 3.9 +/- 0.3 to 4.9 +/- 0.1 mg/dl after 2 hours of continuous injections (p < 0.05), and to 5.3 +/- 0.0 mg/dl after 4 hours (p < 0.01). Amniotic fluid magnesium concentrations rose from 4.2 +/- 0.2 to 5.1 +/- 0.1 mg/dl after 4 hours (p < 0.05). Maternal blood magnesium concentrations were significantly correlated with amniotic fluid concentrations (r = 0.59, p < 0.01). Four hours of maternal magnesium sulfate treatment resulted in a 25% increase in magnesium concentrations in the fetal forebrain (38.3 +/- 2.3 to 47.9 +/- 3.5 mg/dl/gm, p < 0.05). No significant changes in magnesium concentrations were detected in hindbrain. Magnesium sulfate injected subcutaneously into rats crosses the placenta within 2 hours of sustained magnesium levels, enter the fetal blood-brain barrier, and concentrates in the forebrain.

Maternal serum biochemical markers in pregnancies with fetal parvovirus B19 infection

Hydrops fetalis and fetal death caused by fetal parvovirus B19 infection have been reported to be associated with elevated maternal serum alpha-fetoprotein (AFP), based on a total of six cases. It has been suggested that the absence of AFP elevation may be reassuring. Maternal serum levels of the Down syndrome screening markers unconjugated oestriol and human chorionic gonadotropin in cases of fetal parvovirus infection have not been previously reported. We report four cases of hydrops fetalis and fetal death caused by fetal parvovirus infection, each with unremarkable second-trimester levels of AFP, unconjugated oestriol, and human chorionic gonadotropin.

Prenatal sonographic diagnosis of placental infarction in association with elevated maternal serum alpha-fetoprotein

Prenatal sonographic diagnosis of placental infarction in association with elevated maternal serum alpha-fetoprotein

Elevated maternal serum AFP and normal ultrasound: What next?

Given the discovery of intracranial changes observed in fetuses with open spina bifida, the wisdom of routinely performing amniocentesis on persons with unexplained maternal serum alpha-fetoprotein elevations is now being questioned. The detection rate for spina bifida with a targeted ultrasound examination is greater than 95%. Yet one must also consider the sensitivity of ultrasound in detecting other anomalies, such as ventral wall defects and fetal karyotype anomalies. Although the sensitivity of ultrasound for neural tube defects has improved dramatically in recent years, it cannot detect all chromosome or structural anomalies that may be detected by amniocentesis. Therefore, patients should be made aware of their specific risks following a targeted ultrasound and offered the option of amniocentesis.

Chorionic villus sampling followed by amniocentesis in the same pregnancy.

In our consecutive series of 2,574 chorionic villus sampling (CVS) patients, 146 women (5.7%) underwent a subsequent amniocentesis in the same pregnancy for the indications of absent or insufficient villi (3.3%), elevated maternal serum alpha-fetoprotein (0.93%), CVS mosaicism (0.89%), culture failure (0.23%), specimen contamination (0.15%), and CVS aneuploidy (0.12%). Patients presenting for a CVS should be informed of the possible need for a subsequent amniocentesis in the same pregnancy. There is a need for individual prenatal diagnosis programs to analyze their own data and provide genetic counseling information which pertains specifically to their institution.

142 Unexplained Elevated Second Trimester Maternal Serum Hch Is Not Associated with Adverse Pregnancy Outcome

142 Unexplained Elevated Second Trimester Maternal Serum Hch Is Not Associated with Adverse Pregnancy Outcome

345 Unexplained Elevated Maternal Serum Alpbafetoprotein and Placental Abnormalities

345 Unexplained Elevated Maternal Serum Alpbafetoprotein and Placental Abnormalities

337 Elevated Maternal Serum Inhibin in Preeclamptic Pregnancies with Intrauterine Growth Retardation

337 Elevated Maternal Serum Inhibin in Preeclamptic Pregnancies with Intrauterine Growth Retardation

7 Elevated Maternal Serum α-Fetoprotein (MSAFP) and Subsequent Fetal Loss

7 Elevated Maternal Serum α-Fetoprotein (MSAFP) and Subsequent Fetal Loss

Is elevated maternal serum α-fetoprotein a prognostic indicator in pregnancy associated with systemic lupus erythematosus?

SummaryMaternal serum α-fetoprotein is more commonly elevated (> 2 multiples of the median) in pregnancy associated with systemic lupus erythematosus (35 per cent compared with 5 per cent for a general obstetric population, P < 001). An elevated α-fetoprotein level is, in this series, a predictor of fetal loss, pregnancy induced hypertension and premature delivery (before 34 weeks) in the lupus patient.

183 Amniocentesis An Targeted Ultrasonography Im the Evaluation of Elevated Maternal Serum AFP (MSAFP)

183 Amniocentesis An Targeted Ultrasonography Im the Evaluation of Elevated Maternal Serum AFP (MSAFP)

Congenital nephrosis: Detection of index cases through maternal serum α-fetoprotein screening

Congenital nephrosis is an autosomal recessive disorder with an incidence of 1 in 8000 in Finland, but it is quite rare in non-Finnish populations. In families known to be at risk, prenatal detection is possible by means of maternal serum and/or amniotic fluid a-fetoprotein levels. We report the antenatal diagnosis of four cases of congenital nephrosis, three of which were index cases, through maternal serum a-fetoprotein screening. The diagnosis was confirmed at birth in two infants. Two patients elected to terminate their pregnancies, and the diagnoses were confirmed pathologically (obliteration of foot processes on electron microscopy of fetal glomeruli) in both. In cases of elevated maternal serum α-fetoprotein, with unexplained and marked elevations of amniotic fluid a-fetoprotein and normal acetylcholinesterase levels, the diagnosis of congenital nephrosis must be considered regardless of ethnic origin.

Elevated maternal serum human chorionic gonadotropin associated with a chromosomal deletion

Elevated maternal serum human chorionic gonadotropin associated with a chromosomal deletion

Elevated maternal serum α-fetoprotein levels and midtrimester placental abnormalities in relation to subsequent adverse pregnancy outcomes

OBJECTIVE: Unexplained elevations of maternal serum α-fetoprotein levels in the second trimester ofpregnancy are associated with adverse pregnancy outcomes, including intrauterine growth retardation, preterm delivery, preeclampsia, and abruptio placentae. In addition, elevations of maternal serum α-fetoprotein have been associated with placental lesions detected during second-trimester ultrasonographic evaluations. We examined the relationship between adverse pregnancy outcomes and unexplained elevations of maternal serum α-fetoprotein and placental abnormalities in the second trimester of pregnancy. STUDY DESIGN: During the period from January 1989 to March 1991 we conducted a cohort study of201 women with an elevated maternal serum α-fetoprotein (≥2.0 multiples of the median) and a second-trimester ultrasonographic evaluation at Swedish Hospital Medical Center and 211 women with normal maternal serum α-fetoprotein levels who had also undergone ultrasonographic evaluation at the same institution. All women in this investigation had singleton pregnancies without fetal anomalies. RESULTS: Elevated maternal serum α-fetoprotein was associated with the following adverse pregnancyoutcomes: low birth weight (adjusted risk ratio 3.7), preterm delivery (adjusted risk ratio 3.6), intrauterine growth retardation (adjusted risk ratio 4.0), preeclampsia (adjusted risk ratio 3.8) and abruptio placentae (adjusted risk ratio 4.8). Placental abnormalities detected during second-trimester ultrasonographic evaluations were also associated with adverse pregnancy outcomes: low birth weight (adjusted risk ratio 2.0), preterm delivery (adjusted risk ratio 2.3), intrauterine growth retardation (adjusted risk ratio 1.4), and abruptio placentae (adjusted risk ratio 9.0). A joint positive history of second-trimester elevations of maternal serum α-fetoprotein and placental abnormalities was more strongly associated with the following adverse infant outcomes: low birth weight (adjusted risk ratio 6.9), preterm delivery (adjusted risk ratio 5.6), and intrauterine growth retardation (adjusted risk ratio 5.3). CONCLUSIONS: Unexplained elevated levels of maternal serum α-fetoprotein and placental abnormalitiesdetected in the second trimester of pregnancy are associated with particularly poor pregnancy outcome. Careful examination for placental abnormalities should be part of the evaluation of elevated maternal serum α-fetoprotein. ( Am J Obstet Gynecol 1992;167:1032–7.)

Diffuse mesangial sclerosis in a fetus

An 18-week fetus was born following termination of pregnancy by prostaglandin induction. Pregnancy was terminated because of elevated maternal serum alpha-fetoprotein and ultrasonographic evidence of severe oligohydramnios, intrauterine growth retardation, non-visualization of the bladder, dolichocephaly and possible mild hydrocephalus. Pathologic examination disclosed diffuse mesangial sclerosis and histologic evidence of the nephrotic syndrome. To our knowledge this is the first reported example of ante-natal diffuse mesangial sclerosis; of fetal congenital nephrosis other than Finnish type; and of fetal congenital nephrosis with prominent glomerular lesions.

Unexplained elevated maternal serum α-fetoprotein is not predictive of adverse perinatal outcome in an indigent urban population

The null hypothesis of this study is that in an urban, indigent obstetric population at high risk for adverse perinatal outcome, unexplained elevations of maternal serum alpha-fetoprotein are not an additional predictor of adverse perinatal outcome. Perinatal outcomes of 72 patients from a clinic for indigent patients with unexplained elevated maternal serum alpha-fetoprotein levels were compared with those of matched controls from the same population with normal maternal serum alpha-fetoprotein levels. Subjects and controls were matched for age, race, parity, and presence or absence of Hollister risk factors. The frequency of adverse perinatal outcome in the two groups was subjected to matched-pair chi 2 analysis. Adverse perinatal outcome occurred in 38.9% (28 of 72) of subjects with unexplained elevated maternal serum alpha-fetoprotein levels greater than or equal to 2.5 multiples of the median, compared with 31.9% (23 of 72) of controls with normal maternal serum alpha-fetoprotein levels (p = 0.5). No statistically significant difference in adverse perinatal outcomes was found. Elevated maternal serum alpha-fetoprotein levels offer little if any additional predictive value for adverse perinatal outcome in populations already at high risk for such outcomes on the basis of obstetric or socioeconomic criteria.

Ultrasound Detection of Neural Tube Defects in Patients with Elevated Maternal Serum Alpha-Fetoprotein

We conducted this study to determine the accuracy of ultrasound in the prenatal diagnosis of neural tube defects in women with elevated maternal serum alpha-fetoprotein (MSAFP). Among 905 pregnancies, 49 neural tube defects were correctly diagnosed by ultrasound alone; one was not. Ultrasound scanning had 98% sensitivity and 100% specificity for the detection of neural tube defects. The predictive value of a positive ultrasound diagnosis was 100% and of a negative ultrasound 99.9% for neural tube defects. Forty-three other structural abnormalities were also detected in patients with elevated MSAFP, including 19 abdominal wall defects, seven chromosomal abnormalities, five urinary tract abnormalities, one cardiac abnormality, and 11 others. Two chromosomal abnormalities were not detected. We suggest that ultrasound can be used reliably to detect neural tube defects, thereby avoiding the risks of amniocentesis.

Does unexplained second-trimester (15 to 20 weeks' gestation) maternal serum α-fetoprotein elevation presage adverse perinatal outcome? Pitfalls and preliminary studies with late second- and third-trimester maternal serum α-fetoprotein

Several reports have suggested that persons with an unexplained maternal serum α-fetoprotein elevation at 15 to 20 weeks' gestation are at an increased risk for a variety of other pregnancy complications (e.g., preeclampsia) and adverse perinatal outcomes (e.g., fetal death, low-birth-weight infants). However, ascertainment biases could explain some of these reported findings, and predictive value of unexplained elevated maternal serum α-fetoprotein levels in the prediction of pregnancy complications seems limited. If elevated second-trimester levels were truly predictive of pregnancy complications, we reason that third-trimester levels could prove even more useful. We thus studied late second-trimester and early third-trimester (24 to 36 weeks' gestation) maternal serum α-fetoprotein levels with the same enzyme immunoassay we use to evaluate routine second-trimester (15 to 20 weeks' gestation) levels. Values rose up to 32 weeks and fell slightly thereafter. Variance was greater than at 15 to 20 weeks but not so great as to preclude clinical usefulness in the third trimester. Of 279 women with a normal (0.4 to 2.49 multiples of the median) maternal serum α-fetoprotein value at 15 to 20 weeks' gestation, 270 (96.8%) showed levels in the same range later in gestation; however, none of six singleton pregnancies with unexplained maternal serum α-fetoprotein levels > 2.50 multiples of the median at 15 to 20 weeks' gestation showed maternal serum α-fetoprotein levels in this range at 24 to 36 weeks' gestation. The relationship between second- and third-trimester maternal serum α-fetoprotein levels in abnormal pregnancies remains to be elucidated in a large sample. Thus we are conducting not only cohort but also cross-sectional studies. Preliminary findings suggest that women with preterm premature rupture of membranes or with premature labor show elevated late second-trimester and early third-trimester maternal serum α-fetoprotein levels; however, larger sample sizes are necessary.

Is an elevated maternal serum CA125 in early pregnancy an indicator of abnormal fetal karyotype? A retrospective analysis

SummaryIt has been suggested that early first trimester maternal serum CA125 levels may be raised in pregnancies complicated by fetal chromosome anomalies. A retrospective study of maternal serum CA125 levels at 6–8 weeks in 8 pregnancies with a variety of fetal karyotypic abnormalities failed to confirm this finding.