Amniotic Fluid Alpha-fetoprotein Levels Research Articles

The correlation with abnormal fetal outcome and a high level of amniotic fluid alpha-fetoprotein in mid-trimester

ObjectiveTo evaluate the correlation of high levels [>2.0 multiples of median (MoM)] of amniotic fluid alpha-fetoprotein (AFAFP) in midtrimester with abnormal fetal outcome. Materials and methodsWe retrospectively studied 6245 pregnant women with singleton pregnancy who had undergone amniocentesis between 15 and 27 weeks’ gestation at Mackay Memorial Hospital between January 2014 and June 2020. Fifty-five cases had high AFAFP levels (>2.0 MoM). We investigated the abnormal fetal outcomes. ResultsAmong the fifty-five cases with high AFAFP levels (>2.0 MoM), thirty (54.5%) had fetal chromosomal abnormalities, major structural abnormalities, and/or adverse obstetric events. Eight cases (14.5%) had chromosomal abnormalities including trisomy 21 (3 cases), trisomy 18 (3 cases), mosaic trisomy 18 (1 cases), and mosaic ring 13 (1 case). Seventeen cases (30.9%) had major structural abnormalities including abdominal wall defect (6 cases) and central nervous system (5 cases), gastrointestinal tract (3 cases), cardiovascular (2 cases), and genitourinary tract (2 cases) abnormalities. Fifteen cases (27%) had adverse obstetric events, including preterm delivery (5 cases), intrauterine fetal demise (4 cases), small for gestational age (4 cases), preeclampsia (4 cases), gestational diabetes mellitus (2 cases), gestational hypertension (1 case), preterm prelabor rupture of membrane (1 case), prolonged labor (1 case), and preterm uterine contraction (1 case). ConclusionA high AFAFP level (>2.0 MoM) in midtrimester can be associated with abnormal fetal outcome, including chromosomal abnormalities, major structural abnormalities, and adverse obstetric events. Women with a prenatal diagnosis of high AFAFP levels (>2.0 MoM) should be alerted of the possibility of abnormal fetal outcomes, and further detailed genetic studies and serial sonographic examinations are recommended.

Alpha-fetoprotein as a tool to distinguish amniotic fluid from urine, vaginal discharge, and semen.

To estimate whether alpha-fetoprotein (AFP) can be used to distinguish amniotic fluid absorbed in sanitary pads from other similarly absorbed substances (semen, urine, and normal vaginal discharge). A prospective cohort study. Urine and amniotic fluid specimens were collected from 52 pregnant women admitted for labor. Semen specimens were collected from 17 men undergoing infertility evaluation. Alpha-fetoprotein concentrations were measured directly from urine, amniotic fluid, and semen and from pads instilled with samples from these specimens. Alpha-fetoprotein concentrations were also measured from pads absorbed with normal vaginal discharge collected from 27 pregnant women. Alpha-fetoprotein levels in amniotic fluid (245.38 ± 21.03 ng/mL, n = 52) were significantly higher than those measured in maternal urine (0.84 ± 0.17 ng/mL, n = 52, P < .001), or semen (1.52 ± 0.35 ng/mL, n = 17, P < .001). The same trend was seen when AFP was extracted from pads: amniotic fluid levels (19.44 ± 1.98 ng/mL, n=52) were significantly higher than those of urine (undetectable, n=52), semen (undetectable, n = 17), or normal vaginal discharge (0.53 ± 0.16 ng/mL, n = 27, P < .001). Receiver operator characteristic curve analysis demonstrated 96.2% sensitivity and 100% specificity for distinguishing the presence of amniotic fluid from normal vaginal discharge on sanitary pads (cutoff 3.88 ng/mL, area under the curve 0.99). When the diagnosis of rupture of membranes is in doubt, AFP levels can assist in differentiating amniotic fluid from other bodily fluids. A method that utilizes sanitary pads and an assay for AFP quantification may be an accurate and convenient way to confirm the diagnosis of rupture of membranes.

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

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

18p deletion syndrome: foetal phenotype and cytogenetic characterization

Monosomy for the short arm of chromosome 18 is one of the most common autosomal deletion syndromes, with an estimated incidence of about 1:50000 live-born. The phenotype of this chromosome imbalance is greatly variable, often not evident at birth. In this communication we describe a case prenatally diagnosed of de novo 18p deletion.Amniocentesis was performed at 17 weeks of gestational age on a 39-year-old gravid. The family history was unremarkable and the pregnancy was uncomplicated. At the time of the amniocentesis the amniotic fluid alphafetoprotein level was slightly lower than normal. The pregnancy was terminated at 18 weeks, after the cytogenetic response. At the time the ultrasonographic examination showed reduced biparietal diameter and head circumference, normal limbs, normal thoracic, abdominal and pelvic organs. The external examination of the aborted foetus showed: weight 380 gr; ipsicephaly and nuchal oedema, no facial dysmorphic signs, normal ears, limbs of normal length, overlapping toes in the right foot. External genitalia were normal. At the autopsic examination the right lung showed four lobes; all the other organs of thorax, abdomen and pelvis were normal.Cytogenetic analysis of cultured amniocytes showed a de novo 18p deletion. FISH studies allowed us to define the foetal karyotype as: 46,XX, del(18)(p10pter).ish del(18)(tel18p-, dim D18Z1). The phenotypic spectrum of 18p- syndrome may include: round face, ptosis, flat and broad nasal bridge, wide mouth with short upper lip, small mandibles, irregular teeth and dental caries, large, protruding ears, often low and posteriorly rotated, short neck, pectus excavatum, kyphoscoliosis, hands and feet anomalies. The main malformations are holoprosencephaly (HPE), cardiac defects and genital anomalies. Growth retardation, psychomotor delay and mental insufficiency, often mild, are constant symptoms of the syndrome. The foetal phenotype is inconsistent, but the increased nuchal translucency (INT) seems to be a sonographic sign suggestive of this chromosomal abnormality. This further stress the importance of accurate morphological ultrasonographies, mainly in the second trimester, in order to prevent rare and oligosymptomatic chromosomal syndromes.

18p deletion syndrome : foetal phenotype and cytogenetic characterization

Monosomy for the short arm of chromosome 18 is one of the most common autosomal deletion syndromes, with an estimated incidence of about 1:50000 live-born. The phenotype of this chromosome imbalance is greatly variable, often not evident at birth. In this communication we describe a case prenatally diagnosed of de novo 18p deletion.Amniocentesis was performed at 17 weeks of gestational age on a 39-year-old gravid. The family history was unremarkable and the pregnancy was uncomplicated. At the time of the amniocentesis the amniotic fluid alphafetoprotein level was slightly lower than normal. The pregnancy was terminated at 18 weeks, after the cytogenetic response. At the time the ultrasonographic examination showed reduced biparietal diameter and head circumference, normal limbs, normal thoracic, abdominal and pelvic organs. The external examination of the aborted foetus showed: weight 380 gr; ipsicephaly and nuchal oedema, no facial dysmorphic signs, normal ears, limbs of normal length, overlapping toes in the right foot. External genitalia were normal. At the autopsic examination the right lung showed four lobes; all the other organs of thorax, abdomen and pelvis were normal.Cytogenetic analysis of cultured amniocytes showed a de novo 18p deletion. FISH studies allowed us to define the foetal karyotype as: 46,XX, del(18)(p10pter).ish del(18)(tel18p-, dim D18Z1). The phenotypic spectrum of 18p- syndrome may include: round face, ptosis, flat and broad nasal bridge, wide mouth with short upper lip, small mandibles, irregular teeth and dental caries, large, protruding ears, often low and posteriorly rotated, short neck, pectus excavatum, kyphoscoliosis, hands and feet anomalies. The main malformations are holoprosencephaly (HPE), cardiac defects and genital anomalies. Growth retardation, psychomotor delay and mental insufficiency, often mild, are constant symptoms of the syndrome. The foetal phenotype is inconsistent, but the increased nuchal translucency (INT) seems to be a sonographic sign suggestive of this chromosomal abnormality. This further stress the importance of accurate morphological ultrasonographies, mainly in the second trimester, in order to prevent rare and oligosymptomatic chromosomal syndromes.

Predictive value of mid-trimester amniotic fluid high-sensitive C-reactive protein, ferritin, and lactate dehydrogenase for fetal growth restriction

Fetal growth restriction (FGR) is surprisingly common with placental dysfunction occurring in about 3% of pregnancies and despite advances in obstetric care, FGR remains a major problem in developed countries. The purpose of this study is to find out the predictive value of amniotic fluid high sensitive C-reactive protein (hs-CRP), ferritin, and lactate dehydrogenase (LDH) for FGR. This prospective strategy of this study has been conducted on pregnant women who underwent genetic amniocentesis between 15th and 20th weeks of gestation. All patients were followed up on until delivery. Patients with abnormal karyotype and iatrogenic preterm delivery for fetal and maternal indications were excluded. The samples were immediately sent to laboratory for cytogenetic and biochemical examination. Non-parametric tests and receiver-operator characteristic curve analysis were used for statistical purpose. A significant correlation between incremental amniotic fluid alpha fetoprotein (alphaFPr) and LDH levels and FGR at gestational weeks 15th-20th was found out. We also found an optimum cut-off value> 140 IU/L for the amniotic fluid LDH concentration with a sensitivity of 87.5% and a specificity of 82.4% for the prediction of FGR. Once the LDH value is confirmed, it could serve as a prediction factor for FGR at the time of genetic amniocentesis at gestational weeks 15-20.

Prenatal diagnosis of open and closed spina bifida

To identify criteria useful for differentiating closed from open spina bifida antenatally. A retrospective study of cases of spina bifida diagnosed in a referral center between 1997 and 2004. Of 66 cases of fetal spina bifida diagnosed at a median gestational age of 21 (range, 16-34) weeks, detailed follow-up was available for 57. Of these, open defects were found in 53 (93.0%) and closed defects in four (7.0%). Closed spina bifida was associated in two cases with a posterior cystic mass with thick walls and a complex appearance, while in two cases the spinal lesion could not be clearly differentiated from an open defect, particularly at mid-gestation. Open spina bifida was always associated with typical alterations of cranial anatomy, including the so-called 'banana' and 'lemon' signs, while in closed spina bifida the cranium was unremarkable. When the data were available, levels of amniotic fluid alpha-fetoprotein were always abnormally elevated with open spina bifida and within normal limits with closed forms. In this study 7% of cases of spina bifida diagnosed in utero were closed. The differentiation between open and closed forms is best shown by the sonographic demonstration of abnormal or normal cranial anatomy.

Historical Perspectives

This month’s Historical Perspectives is in a slightly different format, but should be of considerable interest to readers of NeoReviews. Professor Nicholas Wald is an epidemiologist who has evaluated and written about a variety of topics, but he is best known for his work on screening methods, particularly in the area of maternal serum alpha-fetoprotein (AFP) and fetal abnormalities. Because of his continuing heavy commitments and to minimize the disruption of his schedule, I posed a number of questions to him, to which he responded with detailed answers. Before moving to his responses, some background information seems in order. Shortly before publication of the article highlighted this month, evaluation of amniotic fluid in cases of open spina bifida and other neural tube defects had shown increased levels of AFP. (1) Somewhat later, it was shown that abdominal wall defects, as well as neural tube defects, could contribute to increased levels of amniotic fluid AFP. (2) In his responses, Professor Wald documents the sequence of events that followed, noting that Professor David Brock in Edinburgh described the association of increased levels of maternal serum alpha-fetoprotein (MSAFP) with fetal anencephaly, which triggered the idea that this also might be true of open spina bifida. Thus, MSAFP was used as a screening tool for the detection of neural tube and abdominal wall defects. Elevated MSAFP levels were noted in other “at-risk” pregnancies (3) and twin pregnancies. (4) To provide better standardization, Professor Wald introduced the concept of “multiples of the median” (MoM) at different gestational ages. Approximately a decade passed before the association was made between low MoMs for AFP and chromosomal defects, particularly Down syndrome. Soon thereafter, several other serum markers for Down syndrome were described, and by linking them to maternal age, screening became increasingly valuable. In the early 1980s, Dr …

Are Amniotic Fluid Alpha-Fetoprotein Levels Influenced by the Gender in Twin Pairs?

Objectives: To examine the assumption that amniotic fluid alpha-fetoprotein (AFAFP) levels are different in female and male twin fetuses. Design: Amniotic fluid levels of AFP in pregnancies with female and male fetuses in gender-concordant and gender-discordant twins were compared. A t test of p < 0.05 was considered significant. Material and Methods: Between 1995 and 1999, 332 genetic amniocenteses on twin pregnancies were performed at Meir Hospital, Kfar Saba, and Rambam Hospital, Haifa, Israel. One hundred and sixty-six were concordant for gender (84 females and 82 males) while 166 pairs differed in their gender. The amniotic fluid AFP levels of each sac were measured using fluorescent immunoassay methods by an AutoDELFIA machine. Results: The mean levels of AFAFP were lower in female twins compared to their male counterparts in same-gender twins (p = 0.07), although the difference was quite small. Nevertheless, there was no such difference between AFAFP of male versus female fetuses in gender-discordant twins. Conclusions: The levels of AFAFP were higher in the male twins of gender-concordant twins in comparison to female twins. No such difference was found between female versus male fetuses in gender-disconcordant twins.

Congenital nephrotic syndrome.

Congenital nephrotic syndrome (CNS) is a rare disorder that presents within 3 months of birth. It is characterized by massive proteinuria, edema,hypoalbuminemia, hyperlipidemia,hypogammaglobulinemia, and hypercoaguability. Without meticulous medical care and eventual renal transplantation, affected infants generally die by 6 months of age.CNS can have primary and secondary etiologies. The most common is CNS of the Finnish type. As a primary etiology, its cause remains unknown. Less common primary etiologies include diffuse mesangial sclerosis, minimal change nephrotic syndrome, and focal segmental glomerulosclerosis. Secondary CNS consists of known etiologies for which specific therapy is aimed at the underlying disease. These include infections, such as syphilis,toxoplasmosis, cytomegalovirus, hepatitis, and human immunodeficiency virus. Other secondary causes are mercury intoxication, genetic malformation syndromes such as XY gonadal dysgenesis, and systemic illnesses such as systemic lupus erythematosus and amyloidosis.Congenital nephrotic syndrome in Finland (CNF) constitutes the majority of CNS cases in the world. Infants who have idiopathic CNS in other parts of the world follow a similar course as infants who have CNF. Those who have CNF are born preterm, are small for gestational age, and have large placentas that comprise more than 25% of the birthweight. Affected infants develop proteinuria prenatally, and most exhibit edema within the first week of life. Distinctive physical features include wide cranial sutures, large open fontanelles, small nose, wide-set eyes,low-set ears, and umbilical hernia. In general, they feed and grow poorly because of substantial loss of proteins, effects of edema, and increased incidence of pyloric stenosis and reflux. They require early diagnosis and aggressive medical and surgical intervention.Diagnosis can be initiated prenatally. Elevated maternal serum and amniotic fluid alpha-fetoprotein (AFP)levels during the 15th to 20th weeks of gestation may identify those at risk,particularly in families that have a prior history. Because an elevated AFP level is nonspecific and can indicate many other obstetric complications,ultrasonography is helpful. Genetic analysis provides a definitive diagnosis. CNF has been linked to a defect in chromosome 19q13.1 and more specifically, to the“nephrin” gene. The product of this gene is a protein associated with the function of the glomerular filtration barrier. Mutations cause CNF and may be implicated in other diseases that involve proteinuria. Genetic analysis also differentiates patients who are carriers from those who ultimately develop CNF.Treatment for infants who have CNF focuses on reaching an ideal weight and nutritional status for renal transplantation, the only cure for the condition. Medical management includes providing a high-calorie and high-protein diet, vitamin supplementation,albumin administration, and diuretic therapy. Attention is directed at preventing and treating infections and thromboembolic events for which these infants are at high risk. Patients eventually need bilateral nephrectomy combined with peritoneal dialysis for ultimate renal transplantation. CNF does not recur following renal transplantation, and catch-up growth and normalization of development can be achieved.Infants in whom CNS is not treated have a complex and bleak clinical course. In vitro genetic analysis offers new hope for recognition and early intervention. Further, improvements in medical care and solid organ transplantation extend the hope for cure and normalization of growth and development. For some patients, CNS is no longer a fatal disease.Inheritance of this rare disorder usually is autosomal recessive,but sporadic cases have been found. Localization of the nephrin gene and association of CNF with mutations have allowed for improved prenatal diagnosis and medical intervention.

Amniotic fluid alpha-fetoprotein is not a useful biological marker of pregnancy outcome.

The aim of our study was to determine if the amniotic fluid alpha-fetoprotein (AFP) level could be a useful predictive biochemical marker of pregnancy outcome. Amniotic fluid AFP measurement was prospectively carried out over a three-year period. After excluding factors susceptible to modifying AFP measurements, 587 subjects with gestational age between 14 and 20 weeks were selected to compare the amniotic fluid AFP mean levels depending on the occurrence of an adverse outcome. No significant associations between amniotic fluid AFP level and poor pregnancy outcome, i.e. pre-eclampsia, preterm delivery, premature rupture of fetal membranes, fetal growth retardation and placental abnormalities were observed. The routine measurement of amniotic fluid alpha-fetoprotein during an amniocentesis procedure was not considered useful in predicting pregnancy complications.

Amniotic fluid alpha-fetoprotein testing in native Japanese women.

Owing to differences in maternal serum alpha-fetoprotein, human chorionic gonadotrophin and oestriol levels between native Japanese and Caucasian women screened in this laboratory, a study was conducted to measure amniotic fluid alpha-fetoprotein (AFAFP) levels in native Japanese pregnancies. When the native Japanese AFAFP levels were compared with a United States (non-Black) population, the Japanese medians did not decrease as rapidly over the 14 to 22 weeks of gestation period investigated. At 14 weeks, the difference was negligible, graduating to a difference of 20 per cent by 22 weeks' gestation. Native Japanese pregnancy AFAFP levels should be interpreted based upon population data from that group alone. From these findings, prenatal screening laboratories should be encouraged to collect preliminary data for comparison before screening is initiated for a defined ethnic group.

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.

Prenatal characteristics of congenital nephrosis: results of a survey.

The purpose of this study was to evaluate the prenatal characteristics of congenital nephrosis of the Finnish type (CNF). Patients presenting with elevated maternal serum and/or amniotic fluid alpha-fetoprotein levels, normal ultrasound examinations and normal fetal karyotypes were included. A retrospective cohort study was conducted using questionnaires sent to all board certified clinical geneticists. Perinatal outcome, including histologic verification of CNF, was obtained. Forty index cases met the above criteria. Ten cases ultimately did not have the diagnosis of CNF, with a median MSAFP level of 7.59 MoM (range 2.7-27.64 MoM) and a median AFAFP level of 10.99 MoM (range 1.47-128.6 MoM). In the affected cohort of index pregnancies, the initial median MSAFP level was 14.49 MoM (range 3.1-38.0 MoM); the median AFAFP level was 40.0 MoM (range 2.4-80.9). MSAFP and AFAFP levels may be lower than previously recognized in patients carrying fetuses with CNF. There is significant overlap between the affected and unaffected patients.

Amniotic fluid alpha-fetoprotein determination at the time of genetic amniocentesis: has it outlived its usefulness?

The purpose of this retrospective study was to evaluate the utility of routine measurement of amniotic fluid alpha-fetoprotein levels at the time of second trimester genetic amniocentesis (mean gestational age, 17.3 weeks +/- 2.5 weeks standard deviation; median, 16.8 weeks; range, 15 to 22 weeks). During the study period 7174 patients underwent second trimester genetic amniocentesis. Outcome data were available in all cases. In 79 (1.1%) cases the amniotic fluid alpha-fetoprotein level was > or = 2.0 multiples of the median. Thirty-three of the 79 (42%) patients had normal ultrasonograms, and in 31 of 33 (94%) the amniotic fluid alpha-fetoprotein level was between 2.0 and 3.0 multiples of the median. Forty-six of the 79 (58%) patients had abnormal ultrasonographic findings, and of these, 82% were neural tube defects, abdominal wall defects, or cystic hygromas. Acetylcholinesterase was positive in 37 cases, all of which had abnormal ultrasonographic findings. None of the fetuses with negative findings on sonographic screening had detectable abnormalities at birth. In this study, with over 7000 patients, amniotic fluid alpha-fetoprotein and acetylcholinesterase levels did not increase the detection of fetal abnormalities. On the basis of these results, routine measurement of amniotic fluid alpha-fetoprotein level at the time of routine genetic amniocentesis (15 to 22 weeks) does not appear justified.

PRENATAL SCREENING FOR CONGENITAL NEPHROSIS IN EAST FINLAND: RESULTS AND IMPACT ON THE BIRTH PREVALENCE OF THE DISEASE

Congenital nephrosis of the Finnish type (CNF) is inherited as an autosomal recessive trait which maps to the long arm of chromosome 19. The disease causes massive proteinuria, and renal transplantation in early neonatal life is the only effective treatment. Prenatal diagnosis, usually in high-risk families, depends on the analysis of alpha-fetoprotein (AFP) levels in maternal serum (MS) or amniotic fluid (AF). We studied the effectiveness of MSAFP measurement as a method of screening all pregnant women for congenital nephrosis. Between 1 January 1979 and 31 December 1992, all pregnant women (N = 110,858) attending maternity care units in East Finland were offered serum AFP measurement as part of a screening programme. All patients whose MSAFP value was > or = 2.5 multiples of the median (MOM) at 15-18 weeks' gestation were given an ultrasound examination and if no morphological abnormality was found, they were then offered amniocentesis. Altogether, 105,880 pregnant women (96 per cent) in East Finland participated in the screening for CNF. A total of 47 cases of CNF were diagnosed during the study period. Elevated AFP concentrations in maternal serum and amniotic fluid (> or = 2.5 MOM) were found in all screened (44/105,880) affected pregnancies except one. The most typical feature of a CNF pregnancy was a very high AFP concentration in the amniotic fluid. As a result of the screening, the prevalence at birth of CNF decreased from 1:2600 to 1:11,086. The possibility of CNF has to be taken into account in pregnancies with a ¿false-positive' elevated AFP result (normal ultrasound and no detectable acetyl cholinesterase).

Amniotic Fluid Alpha-fetoprotein Levels in Midtrimester Pregnancies

Objective The purpose of this study is to establish the normal levels of α-fetoprotein in amniotic fluid between 15 and 22 weeks of gestation. Method Amniotic fluid Alpha-fetoprotein(AFAFP)levels were measured by enzyme-immunoassy in pregnant women between 15 and 22 weeks of gestation for variety of indication of amniocentesis from October, 1994 to July, 1996 at Mokdong Hospital Ewha Womans University. The study group was selected from normal karyotype at prenatal genetic diagnosis and no congenital anomaly of fetus. Results The normal level of AFAFP was the highest at 16weeks and then it declined gradually as gestational weeks increased. The mean±SD levels of AFAFP from 15 to 22weeks were 16.9±5.7, 20.4±9.8, 13.8±6.8, 10.9±3.0, 8.1±2.3, 6.9±3.9, 5.6±1.6, 4.7±0.6µg/ml respectively, the median levels of AFAFP from 15 to 22weeks were 14.7, 16.2, 12.3, 11.0, 7.8, 5.5, 5.3, 4.8µg/ml, respectively. Conclusion We consider that this preliminary data normal AFAFP levels by each gestation weeks can be used as reference value for screening of anomalies or genetic disorder.

Are routine alpha-fetoprotein and acetylcholinesterase determinations still necessary at second-trimester amniocentesis? Impact of high-resolution ultrasonography

To audit routine measurement of alpha-fetoprotein (AFP) and acetylcholinesterase in amniotic fluid (AF) samples obtained at second-trimester amniocentesis. We reviewed retrospectively 1737 consecutive AF specimens obtained for cytogenetic evaluation over a 4-year period and routinely assayed for AFP and acetylcholinesterase. In all instances, high-resolution ultrasonography was performed before amniocentesis. Details of pregnancy outcome of all cases with AF AFP levels greater than 2.0 multiples of the median and a positive or faint acetylcholinesterase band were obtained. There were 31 abnormal results (1.8%, 1 of 56). Of these, 25 cases had elevated AF AFP and/or positive acetylcholinesterase. Ultrasonography correctly identified all 18 fetuses with anomalies associated with abnormal levels of these biochemical markers, including open neural tube defects and/or anterior abdominal wall defects (17 cases) and fetal hydrops (one). In the remaining seven, no fetal anomalies were detected, and all neonates were structurally normal after birth. In addition, six pregnancies with faint acetylcholinesterase and normal AF AFP showed no fetal abnormalities at ultrasonographic examination and post-delivery. High-resolution ultrasonography was more accurate than AF biochemistry in the detection of congenital anomalies associated with elevated AFP levels and acetylcholinesterase in the AF. Routine measurement of these biochemical markers in AF samples obtained for cytogenetic analysis appears to have a very low yield and would therefore not be cost-effective in practices where high-resolution ultrasonography is performed before amniocentesis.

Elevated levels of amniotic fluid alpha-fetoprotein: sonographic evaluation.

From 1978 to 1990, 263 fetuses with an elevated level of amniotic fluid alpha-fetoprotein (AF-AFP) (> 2.0 multiples of the median) were examined with targeted fetal sonography. All cases of AF-AFP elevation among 22,355 genetic amniocenteses were represented. Sonography correctly showed 32 open neural-tube defects, including 20 myelomeningoceles, and depicted 94% (63 of 67) of the anomalous fetuses. Two of five anomalous fetuses with normal sonograms, however, had extremely high AF-AFP levels leading to prospectively correct diagnoses of congenital nephrosis. Therefore, programmatically, 97% (65 of 67) of the anomalous fetuses were recognized. The three programmatic misdiagnoses were all detected in the neonatal period and surgically corrected; subsequent development was normal. The combination of an elevated AF-AFP level and a detailed sonogram allowed distinction between a normal and an anomalous fetus in 99% of cases. When elevated levels are noted, AF-AFP analysis followed by detailed sonography is highly successful for the detection and characterization of anomalous fetuses and the recognition of normal fetuses with physiologic increases of this protein in the amniotic fluid.