Amniotic Fluid Alpha-fetoprotein Research Articles

Correlation Between Amniotic Fluid Alpha-Fetoprotein and Adverse Pregnancy Outcomes

Correlation Between Amniotic Fluid Alpha-Fetoprotein and Adverse Pregnancy Outcomes

Fetal and Placental Causes of Elevated Serum Alpha-Fetoprotein Levels in Pregnant Women.

The most common association related to alpha-fetoprotein (AFP) is fetal neural tube defect (NTD), and indeed, this is where the international career of this protein began. In times when ultrasonography was not yet technically advanced, the detection of high levels of AFP in maternal serum (MS-AFP) and amniotic fluid was the basis for suspecting neural tube defects. In cases where there was no confirmation of NTD, other causes were sought. It has been established that high titers of MS-AFP could originate in other defects or diseases, such as (1) increased proteinuria in severe fetal kidney diseases; (2) pathological overproduction in liver diseases; (3) penetration through the membranes of gastrointestinal organs exposed to amniotic fluid; (4) passage through the walls of skin vessels; and as a side effect of (5) hepatic hematopoiesis and increased transfer through the edematous placenta in fetal anemia. This article provides a review of the current literature on congenital defects and genetic diseases in the fetus where an elevated level of MS-AFP may serve as the initial diagnostic clue for their detection.

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.

High-Risk Pregnancy Is Associated With Increased Alpha-Fetoprotein Concentrations in the Amniotic Fluid and Foal Plasma

This study aimed to determine alpha-fetoprotein (AFP) concentrations in amniotic fluid, plasma of mares and respective foals: carrying normal pregnancies and delivering healthy foals (n = 20; Group 1); carrying apparently normal pregnancies and delivering sick foals (n = 15; Group 2); carrying high-risk pregnancies and delivering sick foals (n = 14; Group 3). High-risk pregnancy was defined by a history of premature udder development/lactation or increased of the combined thickness of the uterus and placenta, or vulvar discharge and/or mares' systemic illness. Sick foals were affected by neonatal encephalopathy, sepsis, prematurity/dysmaturity, or hypoxic-ischemic encephalopathy. Based on histological examination of the chorioallantois, AFP trend was analyzed in pregnancies with pathologic (PFM) and normal fetal membranes (NFM). Concentrations of AFP were measured using a commercially available immunoassay previously validated for horses. Mares' plasma AFP did not change during the last 15–20 days of pregnancy in the three groups, and there was no difference among them. Amniotic fluid AFP was higher in Group 3 (P = .014). Foals’ plasma AFP concentration was higher from birth to 72hours in foals of Group 2 and 3 than in healthy ones, and foals of Group 3 had the highest value. The strong association (r = 0.84; P < .0001) between AFP in amniotic fluid and foals' plasma at birth is likely due to the presence of AFP in fetal urine. AFP was higher in pregnancy with PFM than with NFM in mare's plasma at admission (P = .031), amniotic fluid (P = .004), foal's plasma at birth (P = .002), at 24 (P = .005) and at 72 hours of life (P = .004). AFP is higher in pregnancy with histopathological lesions of the chorioallantois providing the evidence of the differences between pregnancy with a normal placental barrier and the more compromised ones. The increased AFP concentration in the amniotic fluid and plasma of high-risk foals suggests upregulation.

Diagnostic value of alpha-fetoprotein in the implementation of non-immune fetal hydrops due to parvovirus b19 infection during pregnancy

Background. Intrauterine infection remains the main problem of perinatology. Early diagnosis of such infection causes enough difficulties and requires improvement. This study is devoted to the problem of predicting non-immune fetal hydrops if a woman is infected with parvovirus B19 in the II trimester of pregnancy.Objectives: to improve the diagnosis of non-immune fetal hydrops on the basis of changes in the α-fetoprotein (AFP) value in maternal blood during parvovirus B19 infection .Materials and methods. Serial AFP determination in blood serum of pregnant women infected with parvovirus B19 (n = 16) at 18–20–22 weeks of pregnancy was carried out. Biochemical analysis of AFP in amniotic fluid was performed after prenatal invasive examination in fetuses with non-immune hydrops. The obtained data were compared with similar indicators of pregnant women from the control group (n = 16) with a normal course of pregnancy in the II trimester. Transabdominal amniocentesis was performed under ultrasound control at 16–20 weeks of gestation for fetuses with non-immune hydrops. Determination of the AFP value in the blood serum of pregnant women in the II trimester was performed with a chemiluminescence immunoassay analyzer.Results. It was established that the AFP level in maternal blood reaches and exceeds threshold values (2.6 ± 0.05 MoM) on average 2.5 ± 0.5 weeks before the manifestation of severe fetal anemia in infected fetus with non-immune hydrops (r = 0.768, p &lt; 0.001). That is, a sharp AFP increase in the blood of a pregnant woman infected with parvovirus B19 is a predictor of the development of non-immune fetal hydrops due to parvovirus B19 infection.Conclusions. The described method has proven to be highly effective, it is allows reducing the frequency of ultrasound examinations for infected women, because the fetus is not always infected from an infected mother. This technique can be used as a predictor of intrauterine parvovirus B19 infection in the II trimester, which will allow the development of new approaches to the early diagnosis of non-immune fetal hydrops, as well as contribute to timely intrauterine hemotransfusion.

Laboratory screening and diagnosis of open neural tube defects, 2019 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG)

Open neural tube defects (ONTDs) include open spina bifida (OSB) and anencephaly. These defects are caused by incomplete closure of the neural tube at about 4 weeks of pregnancy. Levels of early second-trimester maternal serum (ms) alpha-fetoprotein (AFP) are sufficiently elevated in affected pregnancies to be used as a population-based screening test. The basic screening methodology was described in the late 1970s and screening programs were active a few years later. By identifying pregnancies with the highest msAFP levels, about 80% of OSB and 95% of anencephaly can be identified as early as 16 weeks gestation. The interpretation of msAFP levels is complicated by the need to consider multiple factors such as gestational age, maternal weight, maternal race, multiple gestations, and more. Testing for AFP and acetylcholinesterase in amniotic fluid and/or identification of the lesion by targeted ultrasound is considered diagnostic of ONTD. When a diagnosis is made, options include termination, surgery after delivery, or in utero surgery, depending on factors such as location and size of the defect, and the presence of any additional anomalies. Screening for ONTD should be performed as part of a comprehensive program linking primary obstetrical care providers, laboratorians, and high-risk clinicians.

Study of concentration of amniotic fluid alpha-fetal protein in thalassemia fetus.

To test the hypothesis that concentration of amniotic fluid alpha-fetal protein (AFAFP) is increased in thalassemia fetus. A total of 135 cases of amniocentesis admitted from July 2013 to December 2014 were included in this study. Among them 98 cases of normal fetuses were assigned into control group and 37 cases of thalassemia fetus were included as thalassemia fetus group. Alpha-fetoprotein levels detected by enzyme linked immunosorbent assay and the alpha-fetoprotein concentration were compared between the two groups. There is no significant difference in gestational age between the two groups. 1. AFP concentration in thalassemia fetus group was significantly higher than that of normal control group [(1541.65±734.78)μg/mL vs. (2728.84±1539.97)μg/mL], and amniotic fluid AFP concentration was related to fetal thalassemia. 2. AFAFP concentration in pure α-thalassemia fetus was higher than that of β-thalassemia fetus or mixed α- and β-thalassemia fetus, but the difference was not significant. Concentration of amniotic fluid alpha-fetal protein is increased in thalassemia fetus. AFP concentration in α-thalassemia fetus was higher than that of β-thalassemia or mixed α- and β-thalassemia fetus but difference was not significance. Further studies are needed to explore the possible correlation between Down syndrome and biochemical markers of thalassemia.

Proteins of neural tube defects

Neural tube defects(NTD)are a common congenital malformations in humans leading to infant mortality or severe disability.The etiology of NTD is complicated, with both environmentaland genetic contributions.It has been found that the protein markers associated with NTD are mainly maternal serum alpha fetoprotein, amniotic fluid alpha fetoprotein and amniotic fluid glial fibrillary acidic protein.This article reviews the protein biomarks related with NTD. Key words: Neural tube defects; Maternal serum alpha fetoprotein; Amniotic fluid alpha fetoprotein; Amniotic fluid glial fibrillary acidic protein; S100 protein

Is the ratio of maternal serum to amniotic fluid AFP superior to serum levels as a predictor of pregnancy complications?

The use of maternal serum alpha fetoprotein (MSAFP) levels as a predictor of pregnancy complications (PC) is well established. We hypothesized that the ratio between the MSAFP/AFAFP levels (RATIO) will more accurately predict PC than MSAFP levels alone. Women who had a MSAFP test followed by amniocentesis were divided into two groups: those who had PC comprised the study group and those who had an uneventful pregnancy served as the control group. Data regarding pregnancy and delivery course were collected. The RATIO between the study and the control groups was compared. 166 women were included in the study, of which 24 had PC. A significant correlation was found between the RATIO and intrauterine growth restriction (IUGR) and week of delivery. Six pregnancies had elevated MSAFP levels; two with RATIO below 2 had uneventful pregnancies. Among the other four pregnancies with RATIO above two, one had IUGR and the other, placental abruption. Our data suggest that the RATIO might serve as a predictor of IUGR and week of delivery. Although the number of patients in the current study was relatively small, the novelty of the proposed simple marker implies that a larger scale study is warranted. Such studies may confirm this finding and a possible advantage of using this RATIO instead of or in addition to MSAFP values for better prediction of pregnancies at risk for PC.

Elevated second-trimester maternal serum β-human chorionic gonadotropin and amniotic fluid alpha-fetoprotein as indicators of adverse obstetric outcomes in fetal Turner syndrome.

The objective of this study was to determine the ability of biochemical analytes to identify adverse outcomes in pregnancies with Turner syndrome. Maternal serum and amniotic fluid (AF) marker concentrations were measured in 73 singleton pregnancies with Turner syndrome (10-22 weeks of gestation). Fetal Turner syndrome was definitively established by cytogenetic analysis. Two subgroups, fetuses with hydrops fetalis versus fetuses with cystic hygroma, were compared. Receiver operating characteristic curves and relative risk were established for a cut-off multiples of the median ≥3.5 for β-subunit of human chorionic gonadotropin (hCG) or AF alpha-fetoprotein (AFP). Forty-nine (67%) of 73 pregnant women had an abnormal maternal serum. While levels of pregnancy-associated plasma protein-A and free β-subunit (fβ)-hCG were not different to those of the control group, AFP, unconjugated estriol and β-hCG concentrations were significantly different in the study group (P < 0.05), when compared to those of unaffected pregnancies. Levels of β-hCG in pregnancies with hydrops fetalis were significantly higher than in those with cystic hygroma (P <0.0001), as were AF-AFP concentrations (P <0.0015). In addition, abnormalities in both maternal serum β-hCG and AF-AFP predicted fetal death. The relative risk of adverse obstetric outcome was 10.667 (P = 0.0004; 95% confidence interval [CI]: 1.554-73.203) for β-hCG and 2.19 (P = 0.0256; 95% CI: 1.001 to 4.779), for AF-AFP. Maternal serum β-hCG and AF-AFP levels may preferentially identify those Turner syndrome pregnancies with the highest risk of fetal death.

孕中期羊水AFP水平与不良妊娠结局分析

目的：了解孕中期羊水AFP水平及其与不良妊娠的关系。方法：对孕中期妊娠25,038例羊水采用酶联免疫吸附法进行AFP检测，随访妊娠结局，建立羊水AFP参考值及2.5 MoM。结果：孕16~23 w羊水参考值上限为15,665.6~28,766.9 ng/ml，2.5 MoM为18,712.3~38,694.3 ng/ml，且其值随孕周增加而降低，开放神经管缺陷、颈部淋巴管瘤、死胎和腹部畸形妊娠羊水AFP异常比例较高，其他不良妊娠结局则较低，但其AFP值明显增加。结论：羊水AFP异常升高与神经管缺陷、颈部淋巴管瘤、死胎和腹部畸形等不良妊娠相关，但仍有一定漏诊和误诊，应结合动态超声监测以确诊和排除相关畸形。 Objective: To investigate the level of second trimester amniotic fluid alpha-fetoprotein (AFP) and the relationship between the level of AFP and adverse pregnancy outcomes. Methods: The concen-tration of AFP in amniotic fluid sample from 25,038 second trimester pregnancy women was de-tected by using enzyme linked immunosorbent assay. The outcomes were recorded. Results: The upper limit of reference range and 2.5 MoM of the AFP in different gestational weeks are from 15,665.6 to 28,766.9 ng/ml and from 18,712.3 to 38,694.3 ng/ml, and the level of AFP was high with increasing gestational age. The proportion of abnormal AFP were higher in Neural tube defects (NTDs), cystic hygroma, fetal demise and ventral wall defects (VWDs), and that were low in others, but all of them had abnormal increased AFP value significantly. Conclusion: Levels of AFP correlate with the likelihood of NTDs, cystic hygroma, fetal demise and VWDs. But some pregnancies were misdiagnosed or missed. In order to identify and eliminate related deformities, ultrasound should be needed for further diagnosis.

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.

Routine measurement of amniotic fluid alpha-fetoprotein and acetylcholinesterase: the need for a reevaluation

The objective of the study was to evaluate whether the current screening regimen of measuring amniotic fluid alpha-fetoprotein (AF-AFP) at the time of amniocentesis and reflex acetylcholinesterase testing vs ultrasound alone to detect neural tube and ventral wall defects offers improved diagnostic accuracy and cost benefit. A retrospective chart review on all patients who had amniocentesis performed at 1 center over the past 11 years was performed. Those with an elevated AF-AFP were compared with those whose AF-AFP was within normal limits. Ultrasound findings and outcomes were reviewed in all cases to assess whether neural tube defects (NTDs) or ventral wall defects (VWDs) were missed by AF-AFP or ultrasound screening. A cost-benefit analysis was then performed. Of 6232 women who underwent amniocentesis between January 2002 and December 2012, 81 had an elevated AF-AFP with or without a positive acetylcholinesterase (AChE). Of these 81 women, 13 had NTDs and 5 had VWDs. The sensitivity of the detailed ultrasound was 100% in detecting NTDs and VWDs, whereas that of the AF-AFP ranged from 22% to 77%, with the inclusion of AChE. The total expenditure for AF-AFP in our sample set (n = 6232 amniocentesis at $76.00 per AF-AFP) was $473,632, and all NTDs and VWDs were detected by ultrasound. Translated to a national laboratory (>42,447 samples/year), the cost savings in 2011 alone would be $3,225,972. Given the accuracy of high-resolution ultrasound in the detection of both NTDs and VWDs, measuring AF-AFP and AChE as a reflex-screening test is not a cost-effective approach.

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.

A meningomyelocele with normal intracranial signs on ultrasound and false-negative amniotic fluid alpha-fetoprotein and acetylcholinesterase

Neural tube defects are the major targets of prenatal diagnoses, along with Down syndrome. Prenatal diagnosis of spina bifida is possible at second trimester of gestation through α-fetoprotein and acetylcholinesterase biochemistry assays and ultrasound. In particular, the discovery of characteristic intracranial signs on ultrasound leads to a very high diagnosis rate. However, it is rare for spina bifida to present without intracranial signs while also showing normal values of maternal serum α-fetoprotein, amniotic fluid α-fetoprotein, and acetylcholinesterase. In our hospital, a fetus with spina bifida was delivered at 37+5 weeks' gestation by cesarean section, and was continually followed up over 2 years to date.

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.

Potential Function of Amniotic Fluid in Fetal Development—Novel Insights by Comparing the Composition of Human Amniotic Fluid with Umbilical Cord and Maternal Serum at Mid and Late Gestation

Amniotic fluid (AF) is a dynamic and complex mixture. Up to now, little is known about the physiological functions of AF in the process of fetal development. We suppose that AF carries components such as proteins or peptides, which contribute to the regulation of fetal development. Compositions including biochemical components and tumor markers were determined in human AF, umbilical cord serum (UCS) and maternal serum (MS) from the same subject in the range of 15-42 weeks of gestation. (1) The levels of primary electrolytes such as sodium, chloride, anion gap and osmotic pressure in AF was almost the same as in UCS and MS. (2) The levels of organic substances, including total protein, glucose, triglycerides, cholesterol and various enzymes, were markedly lower in AF than in UCS and MS, especially for total protein, which was 8- and 12.5-fold lower in AF than in UCS and MS, respectively. (3) The levels of tumor markers, including carcinoembryonic antigen, ferritin, cancer antigen 125 and 199, and alpha-fetoprotein in AF displayed different dynamic changes compared to UCS and MS as gestation advanced. This study demonstrated that AF is not a result of simple filtration from the blood but an independent fluid. We speculate that proteins or peptides in the amniotic fluid modulate the process of fetus development since they possess potent bioactivity on cellular growth and proliferation. AF provides a pathway to transport these "regulators" to the fetus and thus plays a pivotal role in fetal development.

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.

Routine assessment of amniotic fluid alpha‐Fetoprotein in early second‐trimester amniocentesis is no longer justified

Open fetal neural tube defects are often followed by an increase in alpha-Fetoprotein concentration in amniotic fluid. For over 25 years there has been a routine to measure amniotic fluid alpha-Fetoprotein in conjunction with early genetic amniocentesis. The efficacy of such a screening test in a low-risk population has been questioned but never evaluated in a Swedish population. Data were reviewed retrospectively from all consecutive early second-trimester genetic amniocenteses from two hospitals during the years 1993-2003. Indications for the genetic amniocenteses were maternal age > or = 35 years, maternal anxiety or a history of fetal aneuploidy. A questionnaire was sent to all obstetric clinics in Sweden regarding current common policy and experience of routine amniotic fluid alpha-Fetoprotein measurements, in the detection of open fetal neural tube defects. A total of 1,813 samples were included. In eight cases (0.4%) the amniotic fluid alpha-Fetoprotein concentrations were > or = 3 multiples of median, but five of them were false positive (63%). Out of the three true positive cases, one had clinical relevance. In the other two cases the detection of open fetal neural tube defects was of subordinate importance. In Sweden, during 2004, 91% of the obstetric clinics performed routine assessment of amniotic fluid alpha-Fetoprotein at second-trimester genetic amniocentesis, but only 9% regarded the analysis useful in clinical practice. According to our results, routine measurement of amniotic fluid alpha-Fetoprotein in early second-trimester genetic amniocentesis, to rule out a risk of open fetal neural tube defects, does not seem justified. The clinical usefulness seems to be limited.

Amniocentesis for Twin Pregnancies: Is Alpha-Fetoprotein Useful in Confirming that the Two Sacs Were Sampled?

Objective: To assess if amniotic fluid alpha-fetoprotein (AFAFP) could be useful to determine if both sacs are sampled during an amniocentesis for twin pregnancies. Method: We reviewed all amniocenteses performed on twin pregnancies over a 5-year period. Inclusion criteria were restricted to pregnancies where both karyotypes and AFAFP were available on each fetus. Pregnancies complicated by fetal anomalies were excluded. The following information was obtained: maternal age, gestational age at the procedure, karyotypes, AFAFP values, pregnancy and neonatal outcome. Placental pathology reports were used to confirm chorionicity. Analysis was performed to evaluate the impact of the fetal gender and chorionicity on the AFAFP values. Results: 260 pregnancies were reviewed. Mean maternal age was 36.9 years (33.6, 40.1). Gestational age at the time of the procedure was 16.2 weeks (14.5, 17.9). Complications included 1.8% of misdiagnosis (discrepancy between karyotype and gender). The difference of AFAFP values between the two fetuses was statistically larger in dichorionic pregnancies than in monochorionic gestations. Fetal gender had no influence on the AFAFP. Conclusion: Amniocentesis in twin pregnancies is associated with a 1.8% risk of misdiagnosis. AFAFP can help to assess the chorionicity of a twin pregnancy. When the difference between the two values is <0.2 MoM and the chorionicity was thought to be dichorionic and the two karyotypes are similar, then failure to sample both sacs should be suspected.