Normal Maternal Serum Alpha-fetoprotein Research Articles

Systems Thinking Approach on Foetal Abnormalities Due to Alpha-Fetoprotein Level

Foetal complications due to abnormal Alpha-Fetoprotein (AFP) levels are becoming a serious matter. The risk of adverse pregnancy outcomes (APOs) is substantially greater in the raised maternal serum-alpha fetoprotein (MS-AFP) group than in the normal MS-AFP groups. The top three APOs in terms of occurrence rate in the increased MS-AFP group were structural foetal abnormalities, spontaneous abortion, and premature delivery. Low levels of AFP in the maternal may indicate a risk of Down syndrome. This is a critical matter that needs to be investigated and dealt with seriously, based on the systems thinking approach. This research aims to investigate screening methods on AFP foetal based on system thinking approach. The main purpose of the study is to provide an analytical and integrated approach to deal with foetal complications due to AFP level. This integrated approach comprises various analytical aspects, including conceptual framework, data analysis, evaluation of the screening methods. How systems thinking can contribute to improve all these aspects of foetal complications will be investigated. The methodology will enable to conduct a detailed explanation to the major problems of AFP in the form of a causal loop diagram based on the holistic view of the systems thinking approach. It is expected that the application of a systems approach could provide an effective method of analysis for understanding and managing the foetal abnormalities by considering all aspects in a holistic manner and clearer methods of intervention to reduce the cases.

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.

Associations between pregnancy outcomes and unexplained high and low maternal serum alpha-fetoprotein levels.

To determine the relationship between adverse pregnancy outcomes and maternal serum alpha-fetoprotein (MSAFP) levels. A retrospective cohort study was conducted on consecutive singleton pregnancies, screened for fetal Down syndrome, in the northern part of Thailand. The prospective database of our fetal Down screening program was assessed to recruit all consecutive records. Pregnancies with medical complication and fetal abnormality were excluded. The recruited women were categorized into three groups: normal (≥0.76 to ≤2.0 MoM), low (<0.76 MoM) and high (>2.0 MoM) MSAFP levels. Of 7,110 screened women, 5,486 met inclusion criteria, including 240; 5,016 and 230 in the group of high, normal and low MSAFP levels, respectively. The rates of preterm birth, pregnancy-induced hypertension (PIH), fetal growth restriction (FGR), fetal death, low birth weight (LBW) and low APGAR scores were significantly higher in women with high MSAFP levels (11.7 vs. 6.6 %, 7.5 vs. 3.3 %, 7.5 vs. 3.3 %, 2.1 vs. 0.3 %, 15.8 vs. 6.7 %, and 2.9 vs. 0.5 % respectively), with relative risk of 1.76, 2.28, 2.27, 7.46, 2.35 and 6.09, respectively. The rates of preterm birth, FGR and LBW were significantly lower in low MSAFP levels with relative risk of 0.39, 0.26 and 0.26, respectively, whereas the rates of PIH and fetal death and low Apgar scores were not significantly different. Pregnant women with high MSAFP levels had an increased risk of poor pregnancy outcomes, while those with low MSAFP levels had a significantly lower risk of such outcomes.

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.

Implications of atypical biochemical data in a case of presumed anencephaly

Anomaly scan on a 21 year old primigravida at 22 weeks showed absence of the superior portion of the calvarium with poorly defined cerebral tissue floating in the amniotic fluid. Maternal serum alphafetoprotein (MSAFP) at 18 weeks was 1.4 MOM. The patient was counseled for anencephaly and amniocentesis was performed. Biochemical data consisting of amniotic fluid alphafetoprotein (AFAFP) of 1.94 MOM with weak positive acetylcholinesterase (ACHE) was atypical of classic anencephaly; karyotype was 46, XX. Following termination, fetopsy showed a gaping cranial defect with protruding brain tissue, partially covered by attenuated translucent skin; meninges were torn and congested. Amniotic bands were identified explaining the cranial findings. Radial aplasia and imperforate anus further suggested VATER. While normal MSAFP can be seen with anencephaly, a normal AFAFP and weak positive ACHE are atypical. In the context of the post-mortem findings, it is presumed that without pregnancy termination, expansion of the cranial anomaly would have eventually lead to unequivocally abnormal biochemical results. This case suggests that alternative etiologies, in particular amniotic bands, be considered when atypical biochemical data is seen at midtrimester in the presence of apparent anencephaly.

Abnormal maternal serum alpha fetoprotein and pregnancy outcome

The objective was to assess the occurrence of miscarriages, low birth weight, and karyotype abnormalities found with low and elevated maternal serum alpha-fetoprotein (MSAFP) among women who had genetic amniocentesis performed. A retrospective study of 2,159 women who had MSAFP analysis prior to amniocentesis was conducted. Pregnancy outcomes were obtained from record review and physicians follow-up. Limits of MSAFP used in analysis were <0.5 adjusted multiples of the median (MOM) (lower levels) and >2.0 MOM (upper levels). Autosomal trisomy was found in 1.6% with low, 0.9% normal, and 0.6% with elevated MSAFP values. Sex chromosome abnormalities were present only in patients with normal MSAFP, [45X (n = 6), 47XXY (n = 2), 69XXX (2)]. Of five open neural tube defects, four had elevated MSAFP and one had a normal value. Omphalocele was identified in four patients, two with normal and two with elevated MSAFP. Gastroschisis was found in one low and one elevated MSAFP. Amniotic fluid alpha-fetoprotein (AFAFP) values did not correlate with MSAFP values. Patients with low MSAFP levels had a greater prevalence of abnormal karyotype (19 of 249, prevalence = 0.076) than patients with an elevated MSAFP level (2 or 166, prevalence = 0.012 OR (odds ratio) = 0.20 (Pvalue = 0.024) when unadjusted for maternal age, and OR = 0.09 (Pvalue = 0.001) when adjusted for maternal age. Spontaneous abortion occurred more often in patients with elevated (4 of 166, or 4%) than normal or low (20 of 1948, or 1%) values of MSAFP (odds ratio 4.32, P = 0.020 when adjusted for maternal age). Birth weight below 2,500 g was present less frequently with low or normal MSAFP (136 of 1,760, or 7.7%) than in elevated MSAFP (21 of 144 or 14.6%) (odds ratio 2.04, P = 0.005, unadjusted; and odds ratio = 2.32, P = 0.003, adjusted for maternal age). Female fetuses were present more often with low MSAFP (136 of 249, or 55%) than elevated levels 43% (71 of 164, or 43%; P = 0.024). We conclude that patients undergoing genetic amniocentesis with MSAFP <.5 MOM are less likely to miscarry, deliver a low birth weight newborn, or have a male infant than patients with MSAFP levels >2.0 MOM. J. Matern.–Fetal Med. 7:304–307, 1998. © 1998 Wiley-Liss, Inc.

Abnormal maternal serum alpha fetoprotein and pregnancy outcome.

The objective was to assess the occurrence of miscarriages, low birth weight, and karyotype abnormalities found with low and elevated maternal serum alpha-fetoprotein (MSAFP) among women who had genetic amniocentesis performed. A retrospective study of 2,159 women who had MSAFP analysis prior to amniocentesis was conducted. Pregnancy outcomes were obtained from record review and physicians follow-up. Limits of MSAFP used in analysis were <0.5 adjusted multiples of the median (MOM) (lower levels) and >2.0 MOM (upper levels). Autosomal trisomy was found in 1.6% with low, 0.9% normal, and 0.6% with elevated MSAFP values. Sex chromosome abnormalities were present only in patients with normal MSAFP, [45X (n = 6), 47XXY (n = 2), 69XXX]. Of five open neural tube defects, four had elevated MSAFP and one had a normal value. Omphalocele was identified in four patients, two with normal and two with elevated MSAFP. Gastroschisis was found in one low and one elevated MSAFP. Amniotic fluid alpha-fetoprotein (AFAFP) values did not correlate with MSAFP values. Patients with low MSAFP levels had a greater prevalence of abnormal karyotype (19 of 249, prevalence = 0.076) than patients with an elevated MSAFP level (2 or 166, prevalence = 0.012 OR (odds ratio) = 0.20 (P value = 0.024) when unadjusted for maternal age, and OR = 0.09 (P value = 0.001) when adjusted for maternal age. Spontaneous abortion occurred more often in patients with elevated (4 of 166, or 4%) than normal or low (20 of 1948, or 1%) values of MSAFP (odds ratio 4.32, P = 0.020 when adjusted for maternal age). Birth weight below 2,500 g was present less frequently with low or normal MSAFP (136 of 1,760, or 7.7%) than in elevated MSAFP (21 of 144 or 14.6%) (odds ratio 2.04, P = 0.005, unadjusted; and odds ratio = 2.32, P = 0.003, adjusted for maternal age). Female fetuses were present more often with low MSAFP (136 of 249, or 55%) than elevated levels 43% (71 of 164, or 43%; P = 0.024). We conclude that patients undergoing genetic amniocentesis with MSAFP <.5 MOM are less likely to miscarry, deliver a low birth weight newborn, or have a male infant than patients with MSAFP levels >2.0 MOM.

Altered newborn gender distribution in patients with low mid-trimester maternal serum human chorionic gonadotropin (MShCG).

to determine if the sex ratio (male/female) is altered in infants born to patients with low mid-trimester maternal serum human chorionic gonadotropin (MShCG). Between 2/1/90 and 1/3/91, 3,116 patients underwent prenatal screening using second-trimester maternal serum alpha-fetoprotein (MSAFP), MShCG, and maternal serum unconjugated estriol (MSuE3). Among these, there were 132 patients with low second-trimester MShCG (< 0.4 MoM), normal MSAFP and MSuE3. The gender distribution of these term, normal newborns was compared to that of 237 controls, matched for race, maternal age, and referral source and delivered at term to mothers with normal mid-trimester MSAFP, MSuE3, and MShCG. The gender distribution of these two groups of newborns was also compared to that of 78 term newborns from the same obstetrical population delivered to mothers with second-trimester MShCG > 2.5 MoM and normal MSAFP and MSuE3. All patients had a complete obstetrical history. Forty-nine percent of the controls were male vs. 62% of the group with slow second-trimester MShCG (P < .01). Within the group with low MShCG, 59% of infants were male when the MShCG was between 0.19 and 0.4 MoM (A) and 80% when the MShCG was < 0.2 MoM (B) (control vs. A vs. B P < .005). The sex ratio in the high-MShCG group was similar to control. The data suggest that gender distribution is different from normal in patients with low mid-trimester MShCG.

Disturbed zinc metabolism and reduced birthweight related to raised maternal serum alpha-fetoprotein in normal human pregnancies.

The hypothesis was examined that altered maternal zinc metabolism is involved in the low birthweight associated with raised maternal serum alpha-fetoprotein (MSAFP). Mothers with clinically normal pregnancy and normally formed infant but with raised MSAFP (> 90th percentile) had lower than normal plasma zinc concentration, raised leucocyte zinc and disturbed zinc-albumin relationship. They delivered offspring with lower birthweights than did women with normal MSAFP concentration, due both to shorter pregnancy and slower intrauterine growth. These results and others identify a subgroup of mothers associated with low infant birthweight, those with raised MSAFP, who have altered zinc distribution.

Clinical significance of low levels of second-trimester maternal serum human chorionic gonadotropin.

To determine if unexplained low second-trimester maternal serum human chorionic gonadotropin (MShCG) is a useful predictor of complications of pregnancy. Between 2/1/90 and 1/3/91, 3,116 patients underwent prenatal screening using second-trimester maternal serum alpha-fetoprotein (MSAFP), MShCG and maternal serum unconjugated estriol (MSuE3). Among these, there were 160 patients with complete obstetrical history who had second-trimester MShCG < 0.4 multiples of the median (MoM). These were compared to 261 controls with complete obstetrical history and a normal second-trimester MSAFP, MSuE3 and MShCG. No differences were found in gestational age at delivery, neonatal weight, premature rupture of membranes or pregnancy loss. The relative risk of pregnancy-induced hypertension in the study group was 0.29 (p < 0.01) and that of gestational diabetes was 0.3 (p < 0.05). Only when low MShCG was associated with a high or low MSAFP or low MSuE3 was there a significantly increased loss of pregnancy (relative risk 11.7; p < 0.0001). The data suggest that second-trimester MShCG < 0.4 MoM by itself has no influence on the outcome of pregnancy.

Twin pregnancies in the second trimester in women in an alpha-fetoprotein screening program: sonographic evaluation and outcome.

We correlated sonographic findings with fetal outcomes in women with unsuspected twin pregnancies who had sonography in the second trimester as part of a screening program for maternal serum alpha-fetoprotein (MSAFP) level and history of neural tube defect. The study group consisted of 97 women with twin pregnancies who participated in a screening program for MSAFP level and history of neural tube defect. Seventy-three had normal MSAFP levels, 21 had elevated MSAFP levels, and two had low MSAFP levels. One patient had a family history of anencephaly. All 97 patients had sonography during their second trimester of pregnancy. Sonographic findings were reviewed retrospectively for information on gestational age, fetal anomalies, sex of the fetus, location of the placenta, presence and thickness of a dividing membrane, and interpretation of amnionicity and chorionicity. Information on fetal outcome included gestational age at delivery, survival, birth weight, sex, congenital anomalies, obstetric complications, amnionicity, chorionicity, and placental abnormalities. Amnionicity and chorionicity were correctly detected on sonograms in 44 (90%) of 49 diamniotic-dichorionic gestations, 23 (72%) of 32 diamniotic-monochorionic gestations, and two (50%) of four monoamniotic-monochorionic gestations. Fetal anomalies were present at delivery in five neonates and had been correctly detected at sonography in one (hemivertebra); one fetus with duodenal atresia had abnormal sonographic findings in the third trimester. Missed anomalies included absent forearm, cleft lip and palate, and imperforate anus. Sex of the fetuses was correctly predicted on the basis of sonographic findings in 40 of 43 pairs. Nine twin pairs had possible twin-twin transfusion syndrome suspected sonographically on the basis of abnormal fluid volumes, discrepant growth measurements, and abnormal findings on Doppler studies. Outcomes included two confirmed cases of the syndrome (two survivors, two deaths) and three probable cases (six deaths); four pregnancies resulted in eight survivors who were delivered after 34.4 weeks' gestation and had birth weights in the 25th percentile or higher. Survival rates for diamniotic-dichorionic, diamniotic-monochorionic, and monoamniotic-monochorionic gestations were 90%, 91%, and 50%, respectively. Fetuses in women with MSAFP levels greater than 4.5 multiples of the median and with monochorionic placentation had lower survival rates than fetuses in women with normal MSAFP levels and monochorionic placentation (67% vs 96%). Half the fetuses delivered after 20 weeks' gestation had birth-weight discordance of less than 10%. Premature deliveries occurred in 56% of pregnancies. The results suggest that (1) sonography is useful in predicting placentation, (2) placentation may be helpful in predicting fetal outcome, (3) increased MSAFP levels correlate with increased perinatal mortality in diamniotic-monochorionic pregnancies, and (4) caution should be taken in diagnosing and determining prognosis for suspected twin-twin transfusion syndrome in the second trimester.

Circulating intercellular adhesion molecule-1 in amniotic fluid, maternal serum α-fetoprotein levels, and intrauterine growth retardation

Our purpose was to determine if circulating intercellular adhesion molecule-1, a marker of chronic inflammation, is present in amniotic fluid in midtrimester, is increased in patients with elevated maternal serum alpha-fetoprotein level, and is associated with intrauterine growth retardation. Amniotic fluid circulating intercellular adhesion molecule-1 levels were assayed by enzyme-linked immunoassay in 273 samples obtained by midtrimester amniocentesis in gestations involving a single, structurally normal fetus. The control group consisted of 108 patients with normal maternal serum alpha-fetoprotein levels and 165 patients with elevated levels. Intrauterine growth retardation was diagnosed if birth weight was < 10th percentile for the clinically estimated gestational age. Circulating intercellular adhesion molecule-1 was detectable in amniotic fluid in 105 of 273 samples (38%). In the control group it was detectable in amniotic fluid in seven of 108 (6%). In patients with elevated maternal serum alpha-fetoprotein 97 of 164 (59%) had detectable levels (p < 0.001). Of the 273 cases 38 (14%) had intrauterine growth retardation. Of these 23 (59%) had detectable circulating intercellular adhesion molecule-1 levels (p < 0.001). Of the seven cases of intrauterine growth retardation with normal maternal serum alpha-fetoprotein levels, one (14%) had detectable circulating intercellular adhesion molecule-1. Of the 31 cases of intrauterine growth retardation with elevated maternal serum alpha-fetoprotein 22 (71%) had detectable circulating intercellular adhesion molecule-1. When circulating intercellular adhesion molecule-1 was detectable in amniotic fluid, increasing levels was significantly related to decreasing gestational age at delivery (p < 0.005). Midtrimester amniotic fluid from normal pregnancies does not generally contain detectable circulating intercellular adhesion molecule-1. Detectable amniotic fluid levels are significantly related to a birth weight < 10th percentile at delivery and to elevated midtrimester maternal serum alpha-fetoprotein levels. Increasing circulating intercellular adhesion molecule-1 levels are related to shortened length of gestation. This test may contribute to risk assessment for intrauterine growth retardation and prematurity. Circulating intercellular adhesion molecule-1 is a known marker of inflammatory processes; its further study may also improve understanding of the pathophysiologic mechanisms of certain cases of intrauterine growth retardation and prematurity.

Maternal serum alpha‐fetoprotein levels and fetal outcome in early second‐trimester oligohydramnios

Early second-trimester oligohydramnios was associated with normal maternal serum alpha-fetoprotein (MSAFP) levels in nine out of 26 cases (35 per cent). Congenital malformations of the fetal urinary tract resulting in fetal anuria were present in nine cases; in seven of them, normal MSAFP levels were measured. In contrast, normal MSAFP levels were established in only 2 out of the 17 cases without fetal malformations. These data suggest that fetal urine is the major source of elevated AFP in the maternal compartment in early second-trimester oligohydramnios. This is further supported by the lack of any relationship between concentrations of MSAFP non-reactive with Concanavalin A, originating mainly from the yolk sac-derived amniotic fluid AFP pool, and the presence of fetal diuresis. Three out of 26 women had experienced early second-trimester oligohydramnios in a previous pregnancy, suggesting the existence of a recurrence risk for this condition.

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.

Relationship Between Second Trimester Maternal Serum Alpha-Fetoprotein and Umbilical Artery Doppler Velocimetry and Their Association with Preterm Delivery

One explanation for an abnormal maternal serum alpha-fetoprotein (MSAFP) may be an abnormal placenta. A specimen for MSAFP and a series of umbilical artery waveforms were obtained prior to amniocentesis from 144 consecutive women referred for either maternal age (n = 85), a persistently elevated MSAFP unassociated with a structural abnormality (n = 42), or a low MSAFP (n = 17). Almost 50% of deliveries before 37 weeks and 60% of neonatal birthweights below the tenth percentile occurred in the high MSAFP group. We observed that the systolic-diastolic ratio (S/D), pulsatility index, and resistance index tended to be higher in women referred for an elevated MSAFP. Confining analyses to the elevated MSAFP group, the MSAFP in multiples of the median correlated with birthweight independent of the gestational age at delivery (p less than 0.001). In addition, the S/D related directly to MSAFP (p less than 0.03) and indirectly to the gestational age at delivery (p less than 0.04). None of these relationships was observed in the groups of women referred for either maternal age (who had a normal MSAFP) or a low MSAFP. Employing a stepwise multiple linear regression, we found that the gestational age at delivery could be predicted during the midsecond trimester using a combination of the umbilical artery S/D and MSAFP. When the analyses and predictions were limited to subjects whose MSAFP still exceeded 2 multiples of the median at the time of amniocentesis, the positive predictive value for preterm delivery was 100% and the negative predictive value was 93%.(ABSTRACT TRUNCATED AT 250 WORDS)

Prenatal Diagnosis and Perinatal Management of Frontoethmoidal Meningoencephalocele

Frontoethmoidal meningoencephaloceles (FEM) are exceedingly rare in the western hemisphere, Australia, and Europe with an estimated frequency of 1 in 40,000 live births. Among the inhabitants of Thailand, Burma, Malaysia, Indonesia, and parts of the Soviet Union, however, the frequency is as high as 1 in 5000, accounting for 15% of all neural tube defects (NTD). Normal maternal serum alpha-fetoprotein (MSAFP) values usually will be found in these cases since most encephaloceles are closed, skin covered defects. Correct interpretation of the sonographic findings is crucial in establishing a diagnosis as well as giving prognostic and recurrence risk information. To our knowledge, this is the first reported case of prenatally diagnosed FEM. Perinatal management, differential diagnosis for disorders associated with this malformation, and epidemiologic information regarding this rare condition are discussed. It is anticipated that the prenatal sonographic findings may be applied to establish this diagnosis in similarly affected fetuses.

Implications of 'low maternal serum alpha‐fetoprotein levels: Are maternal age risk criteria obsolete?

An association has been reported between 'low' maternal serum alpha-fetoprotein (MSAFP) and fetal chromosome abnormalities, notably Down syndrome. We suggest the predictive value be used for genetic counselling when a 'low' MSAFP is found, and present an illustrative risk table. It can also be seen that normal MSAFP in a woman may lower her age-related risks below that previously defined as 'high risk'. However, until good estimates of sensitivity and specificity are available from prospective, population based studies, patients should be told that any risk estimates are rough approximations. When good estimates are available, use of age risks alone may become obsolete.

The impact of maternal serum alpha fetoprotein screening on open neural tube defect births in North‐East Scotland

Over the three years period 1980-1982, 18 256 pregnancies in the Grampian Region of N-E Scotland including the islands of Orkney and Shetland were screened for raised levels of maternal serum alpha fetoprotein (MSAFP) in the second trimester. Thirty six cases of fetal open neural tube defect in singletons were detected (18 anencephaly and 18 spina bifida). Four additional cases of open spina bifida were associated with normal MSAFP levels although two of these were detected by amniotic fluid AFP measurement when amniocentesis was carried out because of previous NTD history. A further three cases of open spina bifida and two of anencephaly occurred in unscreened pregnancies. The MSAFP screening programme alone was thus instrumental in reducing the birth incidence of open neural tube defects by 36 out of 45 cases (80 per cent) in singletons.

Results and Benefits of a Maternal Serum α-Fetoprotein Screening Program

Maternal serum alpha-fetoprotein (MSAFP) screening was offered in a private suburban practice to 21,000 nondiabetic and 442 diabetic women with apparently normal pregnancies. Using 2.5 or greater multiples of the median as the normal upper limit, 249 (1.2%) had a raised MSAFP level. There were 25 neural tube defects (NTDs) (1.2/1,000 births); 18 were detected by screening and two by ultrasound scanning. Three had closed spina bifida lesions. Two had anencephaly with normal MSAFP levels, but were studied at more than 24 weeks' gestation. An additional 13 with raised MSAFP levels had other congenital defects. One in 400 women screened had a recommended amniocentesis; 26.4% of them had a fetus with an NTD or major malformation. Our detection efficiency before 24 weeks' gestation for anencephaly was 85.7% (12/14), 62.5% (5/8) for open and closed spina bifida, and 1/1 for encephalocele. A raised MSAFP level occurred in ten (2.3%) of the 442 diabetic women, four (0.9%) of whom had a fetus with an open NTS. A screening program should be established only where there is linked excellent interdisciplinary support among obstetrician, laboratory, clinical geneticist, ultrasonographer, and an identified program coordinator.