MSAFP Screening Research Articles

1107 The role of MSAFP screening in prenatal diagnosis of omphalocele

1107 The role of MSAFP screening in prenatal diagnosis of omphalocele

Is MSAFP Still a Useful Test for Detecting Open Neural Tube Defects and Ventral Wall Defects in the Era of First-Trimester and Early Second-Trimester Fetal Anatomical Ultrasounds?

Introduction: To evaluate whether maternal serum α-fetoprotein (MSAFP) improves the detection rate for open neural tube defects (ONTDs) and ventral wall defects (VWD) in patients undergoing first-trimester and early second-trimester fetal anatomical survey. Material and Methods: A cohort of women undergoing screening between 2005 and 2012 was identified. All patients were offered an ultrasound at between 11 weeks and 13 weeks and 6 days of gestational age for nuchal translucency/fetal anatomy followed by an early second-trimester ultrasound at between 15 weeks and 17 weeks and 6 days of gestational age for fetal anatomy and MSAFP screening. All cases of ONTD and VWD were identified via query of billing and reporting software. Sensitivity and specificity for detection of ONTD/VWD were calculated, and groups were compared using the Fisher exact test, with p < 0.05 as significance. Results: A total of 23,790 women met the criteria for inclusion. Overall, 15 cases of ONTD and 17 cases of VWD were identified; 100% of cases were diagnosed by ultrasound prior to 18 weeks' gestation; none were diagnosed via MSAFP screening (p < 0.001). First-trimester and early second-trimester ultrasound had 100% sensitivity and 100% specificity for diagnosing ONTD/VWD. Discussion: Ultrasound for fetal anatomy during the first and early second trimester detected 100% of ONTD/VWD in our population. MSAFP is not useful as a screening tool for ONTD and VWD in the setting of this ultrasound screening protocol.

360: Does first-trimester ultrasound predict obstetrical and neonatal outcomes in monochorionic diamniotic twin pregnancies?

lucency ultrasound with evaluation of the fetal anatomy at 11-14 weeks AND an early second trimester fetal anatomical survey between 15 and 17 weeks. All cases of ONTD diagnosed in our unit were identified using ICD-9 codes, and all MSAFP results over the same time frame were queried. Groups were compared using Fisher Exact test with p 0.05 as significance. RESULTS: Our unit performed 17,656 nuchal translucency ultraounds and 21,436 early anatomical surveys, and sent 11,809 speciens for MSAFP during the study period. 11 ONTD were diagnosed y our unit during this time frame (incidence of 0.56 to 0.67 per 1000). 1/11 ONTD (100%) were diagnosed by ultrasound; 0/11 (0%) were etected after MSAFP screening (p 0.0001). 7/11 cases (64%) were iagnosed during the first trimester; 4/11 (36%) were diagnosed at the arly second trimester anatomy scan. No cases of ONTD were diagosed after 18 weeks’ gestation, and no cases of ONTD were missed by ur unit (sensitivity 100%). CONCLUSION: Ultrasound for fetal anatomical survey during the first and early second trimester detected 100% of ONTD in our population with the majority identified in the first trimester. MSAFP was not useful as a screening tool for neural tube defects in the setting of this ultrasound screening protocol.

Genetic sonography: the historical and clinical role of fetal echocardiography

The association of congenital heart defects with trisomy 21 was reported over 50 years ago and heart defects remain one of the most common and lethal abnormalities present postnatally in individuals affected by Down syndrome1–4. The purpose of this Editorial is to review the use of second-trimester fetal echocardiography as an adjunct to the genetic sonogram from a clinical perspective, based on my experience over the past 20 years5–13. The following topics are discussed as they relate to trisomy 21: (1) the incorporation of ultrasound evaluation of the fetal heart as part of the genetic sonogram and comparison of it with other screening modalities from a historical perspective; (2) the postnatal incidence of congenital heart defects; (3) the prenatal incidence of structural and functional heart abnormalities; (4) the relative risk for various cardiac findings; and (5) the suggested use of fetal echocardiography as part of the genetic sonogram given current screening technologies.

Antenatal Ultrasound and Magnetic Resonance Imaging in Localizing the Level of Lesion in Spina Bifida and Correlation With Postnatal Outcome

The level of the lesion is the single most accurate predictor of the functional neurologic outcome in infants having spina bifida. The investigators retrospectively compared the results of the prenatal ultrasound examination and magnetic resonance imaging (MRI) with the postnatal surgical and MRI findings in a series of 12 antenatally and 5 postnatally diagnosed cases of spina bifida referred for surgical treatment in the years 2000 to 2002. Both the level of the lesions and the cranial head signs were compared with neurologic status after a mean follow up of 12 months. For the 12 parentally diagnosed cases, the median gestational age at the time of diagnostic ultrasound was 20 weeks and delivery was at 38 weeks. The 5 postnatally diagnosed cases also had an ultrasound examination at 20 weeks, but the spine lesions were not identified. Eight of the 12 women who had prenatal diagnosis and 2 of the 5 with postnatal diagnosis took folic acid periconceptionally. The MSAFP screening test was offered to 16 of the 17 study patients, but 8 of the 12 prenatally diagnosed women and all 5 with postnatal diagnosis declined. Three women with prenatal diagnosis accepted MSAFP testing and 2 were positive; the third had a fetus with a closed lumbar lesion. Four of the 12 (33%) prenatal cases and 3 of the 5 (60%) postnatal cases had high lesions with the lowermost part of the defect at or above L3, and 8 of the 12 prenatal (67%) and 2 of the 5 (40%) postnatal cases had low lesions with the uppermost part of the defect at or below L4. The antenatal findings correlated with the postnatal findings in 8 (67%) of the 12 antenatal cases; in 2 cases, ultrasound predicted a defect 2 vertebral bodies higher than it actually was, and in 2 cases, the defect was predicted to be 2 vertebral bodies lower. One or more head signs were seen sonographically in 10 of 12 antenatally diagnosed cases (83%). Seven infants had ventriculomegaly and Arnold-Chiari malformations confirmed in all cases by postnatal MRI. In contrast, although 8 of the 12 sonographically diagnosed cases also had antenatal MRI, the findings correlated with postnatal findings in only 4 cases and were inaccurate in 4 cases. There was a discrepancy between the antenatal ultrasound and MRI findings in 4 of 8 cases evaluated with both modalities; MRI was more accurate in 2 cases and ultrasound was more accurate in 2 cases. More than 90% of infants had motor deficits of varying severity. Neither the level of the spinal lesion nor the presence of ventriculomegaly correlated significantly with developmental milestones or with morbidity or motor function at follow up; 82% of all infants appeared to be developing normally regardless of the level of the defect. Low spinal lesions were associated with increased bladder morbidity compared with highly placed lesions (odds ratio, 10.0; 95% confidence interval, 1.05-95.01), but overall, the numbers of high and low lesions were too small to draw meaningful conclusions. In this study, antenatal ultrasonography was fairly accurate in diagnosing and characterizing open spine defects, and antenatal MRI did not add to the diagnostic success. The ultrasound findings, in fact, correlated better than did MRI with the surgical or postnatal MRI findings with respect to both the level of the lesion and head signs.

Do women who have first trimester down syndrome screening require serum MSAFP screening?

Do women who have first trimester down syndrome screening require serum MSAFP screening?

Maternal serum alpha-fetoprotein in fetal anal atresia and other gastro-intestinal obstructions.

The fetal gastro-intestinal (GI) tract contributes to alpha-fetoprotein (AFP) levels in amniotic fluid and hence to those in maternal serum (MS). This study retrospectively analysed results of second trimester MSAFP screening in cases of fetal GI tract obstruction. 18 cases of fetal GI obstruction were diagnosed amongst 17,036 women who underwent MSAFP screening between 1979 and 1997: seven had oesophageal atresia, four had duodenal atresia, six had anal atresia, and one had both anal and oesophageal atresia. MSAFP in pregnancies of a fetus with anal atresia was significantly lower than the population median. MSAFP in cases of fetal oesophageal or duodenal atresia was low but these differences did not reach significance.

Maternal serum alpha-fetoprotein in fetal anal atresia and other gastro-intestinal obstructions

The fetal gastro-intestinal (GI) tract contributes to alpha-fetoprotein (AFP) levels in amniotic fluid and hence to those in maternal serum (MS). This study retrospectively analysed results of second trimester MSAFP screening in cases of fetal GI tract obstruction. 18 cases of fetal GI obstruction were diagnosed amongst 17 036 women who underwent MSAFP screening between 1979 and 1997: seven had oesophageal atresia, four had duodenal atresia, six had anal atresia, and one had both anal and oesophageal atresia. MSAFP in pregnancies of a fetus with anal atresia was significantly lower than the population median. MSAFP in cases of fetal oesophageal or duodenal atresia was low but these differences did not reach significance. © 1998 John Wiley & Sons, Ltd.

Influence of provider characteristics and insurance status on maternal serum alpha-fetoprotein screening.

The maternal serum alpha-fetoprotein test (MSAFP) was developed to screen for neural tube defects. Little is known about the adoption of the MSAFP test. This study examines the effect of provider specialty and geographic location and patient insurance status on MSAFP test use in Washington State. We conducted a retrospective cohort study of MSAFP use in low-risk obstetric patients of five provider groups. MSAFP use was examined for Medicaid and privately insured patients, as well as for the patients of the five provider types. Patients of urban and rural obstetrician-gynecologists were most likely to have MSAFP testing (80.4 percent and 77.0 percent, respectively); patients of urban certified nurse midwives and rural family physicians were least likely to have MSAFP testing (64.2 percent and 62.2 percent, respectively). Patients of certified nurse midwives were more likely to decline MSAFP testing when offered (26.1 percent). Medicaid-insured women were significantly less likely to have MSAFP testing than privately insured women (60.5 percent versus 79.1 percent, P < or = 0.05). Providers and patients did not uniformly use MSAFP screening. Efforts should be made to ensure that all patients are adequately informed of screening tests for neural tube defects.

Endometrial and fetoplacental markers in pregnancies with fetal congenital nephrosis.

Congenital nephrotic syndrome of the Finnish type [CNF] is an autosomal recessive disorder leading to death in early childhood, if treated conservatively without early renal transplantation. Prenatal screening at midtrimester is feasible by measuring maternal serum alpha-fetoprotein [MSAFP], elevated amniotic fluid [AF] AFP being the only diagnostic test in population screening. We studied whether concentrations of other pregnancy-related markers offer any ancillary procedure for screening. In a prospective case-control study, the concentrations of maternal serum human chorionic gonadotropin [hCG], unconjugated estriol [uE3], human placental lactogen [hPL] and placental protein 14 [pp14] were measured in samples from six singleton pregnancies associated with fetal CNF and from 18 matched controls at 15 weeks of gestation. In the CNF group, mean hCG and pp 14 concentrations were slightly elevated, whereas uE3 and hPL concentrations were within the lower normal range. None of these differences were statistically significant and the distribution of these values was too wide to use them for screening. Low unconjugated E3 and elevated hCG concentrations were expected, since newborns with CNF are growth-retarded and have large placentas. The extent of these alterations was not sufficient to identify high risk pregnancies. Substantial differences in the maternal serum concentrations of hPL and pp 14 were not observed. Hence, MSAFP screening at midtrimester is the strategy of choice for prenatal detection of CNF.

Prognostic significance of unexplained elevated amniotic fluid alpha-fetoprotein

To compare the prognostic values of unexplained elevated amniotic fluid alpha-fetoprotein (AF AFP > or = 2.0 multiples of the median [MoM]) and unexplained elevated maternal serum alpha-fetoprotein (MSAFP > or = 2.5 MoM). We accessed a data base containing the results of MSAFP screening tests, genetic amniocenteses, and pregnancy outcome data on all women undergoing second-trimester genetic amniocentesis from October 1988 through August 1994. After excluding all patients whose elevated AFP levels had any identifiable cause (positive AF acetylcholinesterase, AF blood contamination, fetal malformation or aneuploidy, multiple gestation, etc), 5743 cases were analyzed. Relative risks (RR) for selected pregnancy complications were determined. Elevated MSAFP, with any AF AFP, was associated with fetal growth restriction (RR 2.5, 95% confidence interval [CI] 1.4-4.4), stillbirth (RR 3.5, 95% CI 1.4-8.3), preeclampsia (RR 2.8, 95% CI 1.1-7.0), and preterm delivery (RR 2.8, 95% CI 2.3-3.4). Elevated AF AFP, with any MSAFP, was associated with preeclampsia (RR 4.4, 95% CI 2.0-10.0) and preterm delivery (RR 1.7, 95% CI 1.3-2.4). Elevation of both AF AFP and MSAFP was associated with preterm delivery (RR 4.0, 95% CI 2.8-5.7). When elevated AF AFP was found in association with a normal MSAFP, the RR to develop preeclampsia was 4.6 (95% CI 1.9-11.2). Maternal serum alpha-fetoprotein is a better predictor of late pregnancy complications than AF AFP. However, unexplained elevated AF AFP appears to be especially predictive of preeclampsia.

Antenatal Diagnosis of Pediatric Surgical Anomalies: Counseling the Family

Improvements in screening and diagnostic techniques now mean that hundreds of congenital anomalies can be antenatally diagnosed. It is, however, impossible and inappropriate to submit all pregnant women to a barrage of investigations. Screening is necessary before specific invasive investigations are initiated. These include history, physical examination, MS-AFP screening, estriol and hCG screening, and a Level II ultrasonography scan. Once at-risk pregnancies have been identified, a multidisciplinary team approach is commenced and further studies including Level II ultrasonography, amniocentesis, chorionic villus sampling, or cordocentesis can be performed so that an accurate diagnosis is available. Counseling of the parents throughout is essential so that appropriate decisions regarding this and further pregnancies can be made.

47 One Year Experience with a State-Wide Expanded MSAFP Screening Program

47 One Year Experience with a State-Wide Expanded MSAFP Screening Program

Trisomy 18 Detected by MSAFP Screening

Trisomy 18 Detected by MSAFP Screening

Ultrasound and Maternal Serum α-fetoprotein Screening

Ultrasound provides important complementary information at two levels in the case of both elevated and depressed maternal serum α-fetoprotein (MSAFP) test results. Office scanning is capable of explaining about 30% of apparent elevations of MSAFP, and about 50% of low values by correcting gestational age and detecting multiple gestation or fetal death. Targetted or high detail referral ultrasound is capable of diagnosing over 90% of the structural malformations associated with elevated MSAFP. including neural tube, ventral wall, and urinary tract defects. This diagnostic capability allows for specific counseling in the event of a positive diagnosis and for relative risk adjustment in the case of a normal examination. The patient may then consider further invasive testing in light of an adjusted risk for malformation. It has been demonstrated that many patients will decline invasive testing. Careful review suggests that the low sensitivity and poor predictive value of ultrasound in the detection of aneuploidy do not support ultrasound as a primary screening tool but do support its adjunctive use with MSAFP screening.

Effect of normal msafp screening on maternal age for genetic amniocentesis*

Routine maternal serum a-fetoprotein (MSAFP) screening for neural tube defects is considered by many to be standard obstetrical care, and recently many have encouraged this test to screen for Trisomy-21 (Down's syndrome). We questioned whether, after a normal MSAFP screen, the risk of Trisomy-21 decreases enough to warrant modifying the recommended age for genetic amniocentesis for Down's syndrome. A logistic regression was developed which, using reported values for sensitivity and specificity for MSAFP detection of Trisomy-21 and assuming a constant threshold risk in opting for amniocentesis, indicates that genetic amniocentesis for Trisomy-21 may be deferred in some women who have a normal MSAFP screening. Sensitivity analysis of varying thresholds for a normal MSAFP demonstrates that a 37 year old woman with a median MSAFP level has the same risk for Trisomy-21 as an unscreened women who is 4.5 years younger. An abnormal MSAFP is useful in screening for neural tube defects and possibly for Trisomy-21. A normal MSAFP may allow for delaying the potentially risky amniocentesis in otherwise low-risk pregnancies.

Laboratory Components of a Maternal Serum α-Fetoprotein Screening Program

The growing acceptance of maternal serum α-fetoprotein (MSAFP) screening as a vital part of obstetrical care coupled with the marketing of commercial AFP kits has encouraged clinical laboratories to begin the business of MS AFP testing. The tendency among laboratories has been to approach prenatal MS AFP screening as a diagnostic process. Understandably, the diagnostic manner is familiar to all laboratories, yet there is a distinction between diagnosis and screening. Screening results in the identification of an increased-risk patient subgroup that contains most, if not all, affected cases. To achieve an optimal program of MS AFP screening requires coordination of several components centered around the laboratory. Through preliminary assay set-up and continuous monitoring of performance, to effective communication to educate about screening and inform of ret risk and recommend tests for diagnosis, and finally to evaluate pregnancy outcome as a measurement of efficient detection, the laboratory must function within the screening protocol. We will focus on the laboratory role throughout the MS AFP screening protocol with emphasis on the adjustments needed for a screening approach. The laboratory that operates outside a screening protocol not only undermines the reliability of the test but also contributes to ambivalence about MSAFP screening for fetal defects.

Maternal Serum α-Fetoprotein Screening

Maternal serum alpha-fetoprotein screening should be offered to all patients as a routine component of prenatal care. The benefits of MSAFP screening have far exceeded early expectations. This technology not only provides an efficient and cost-effective method of screening for neural tube defects that is applicable to all pregnancies but also provides the physician with important information relevant to a number of other birth defects and complications of pregnancy. Our knowledge of variables affecting MSAFP levels measured during pregnancy is rapidly evolving, and further refinements in the application of MSAFP screening will almost certainly occur. Such refinements can serve only to extend the benefits of this new and very valuable technology in improving the health and well being of mothers and infants.

α-Fetoprotein Screening

The Committee on Genetics of the American Academy of Pediatrics endorses the following guidelines for maternal α-fetoprotein screening, developed by the American Society of Human Genetics.1 Before maternal serum α-fetoprotein (MSAFP) screening is started, the following minimal criteria should be met. 1. Adequate physician/health professional education: The objective of this education is to assure that physicians and other health care professionals understand the nature and range of severity of each of the detectable conditions and anomalies, the objectives of screening and testing, the importance of timing and reporting the low predictive value of test results, and the follow-up procedures and counseling. 2. Access to a qualified MSAFP and amniotic fluid α-fetoprotein laboratory: Criteria for quality control in these laboratories are detailed in the full statement. 3. Adequate facilities and personnel for follow-up of abnormally high or low MSAFP values: Counseling, level I and level II sonography, amniocentesis, and qualitative amniotic fluid acetylcholin-esterase assay should be available. 4. Adequate patient education: Information should be provided on the nature of the defects detectable by MSAFP screening, on confirmatory procedures, and on the options available should an abnormal result be confirmed. The optimal time for MSAFP screening is between 16 and 18 weeks of gestation. The common MSAFP screening protocol would include: first serum specimen evaluation, second serum specimen evaluation (if indicated), counseling, ultrasonography, amniocentesis, amniotic fluid α-fetoprotein testing (acetylcholinesterase and fetal blood evaluation), karotyping. Once the program is underway, physician's offices, laboratories, and referral centers should have staff available who can answer questions concerning procedures related to MSAFP screening.

FIRST TRIMESTER MATERNAL SERUM ALPHA-FETOPROTEIN (MSAFP) SCREENING FOR CHROMOSOME DEFECTS

Second trimester MSAFP screening for low values is proving valuable in the detection of fetal chromosome defects in women < 35 yrs. of age. Detection prior to 16 wks. would be desirable. To determine whether low MSAFP values also occur in the first trimester in association with a fetal chromosomal abnormality, we used a “simultaneous-sandwich” radioimmunoassay with polystyrene beads coated with anti-AFP monoclonal antibodies, using solid phase support. The coefficient of variation was<5% for this assay which is about 10 x more sensitive than conventional RIAs. Blood was sampled in 359 cases just before CVS (chorionic villus sampling) in Milan. Fetal age was usually assessed by 2 ultrasound studies± 1 wk. apart, and chromosomes of the villi analysed. Sera were sent blind & only after AFP assay results were sent to Milan were karyotypes released. MSAFP≤0.6 MOM occurred in 5/17 (45.5%) significant fetal chromosome defects (trisomy 21, 18 [2], 13 & unbal. 13/14 translocation) while 2 (18.2%) were<0.5 MOM. 11/17 (64.7%) affected fetuses had MSAFP<median. 1/5 trisomy 21 fetuses had MSAFP< 0.5 MOM. About 75% of trisomy 21 offspring are delivered by women< 35 yrs. of age. These results suggest that first trimester MSAFP screening could identify a significant number of these pregnancies early enough for CVS. Further study is necessary to determine the optimum week for efficient screening.