Elevated Maternal Serum Α-fetoprotein Research Articles

Prenatal Genetic Diagnosis of Congenital Nephrotic Syndrome

Congenital nephrotic syndrome (CNS) of the Finnish type is an autosomal recessive disorder caused by mutations in the gene encoding nephrin (NPHS1). A 31-year-old primigravida woman from the Philippines was referred to Seoul St. Mary’s Hospital with an abnormally elevated maternal serum α-fetoprotein (MSAFP) level of 8.5 multiples of the median (MoM) at 16+1 weeks gestation. The MSAFP level was 11.25 MoM when measured at Seoul St. Mary’s Hospital. The amniotic fluid tested negative for acetylcholine esterase and had an α-fetoprotein level of 41.09 MoM. The karyotype was normal. Analysis of the NPHS1 gene in amniotic fluid by massively parallel sequencing revealed mutations associated with CNS. Cesarean delivery was performed at 37+4 weeks gestation due to transverse presentation. The neonate was not severely affected; there was no evidence of proteinuria or renal failure. However, because symptoms usually appear within 2 weeks to 1 month of age, close monitoring that includes regular blood and urine testing should be conducted.

Diagnosis and Management of Placental Mesenchymal Disease. A Review of the Literature.

To review what is currently known about placental mesenchymal dysplasia (PMD) including imaging techniques for diagnosis and differentiation from a molar pregnancy, genetics, maternal/fetal effects, and management. A literature search by research librarians at 2 universities was undertaken using the search engines PubMed and Web of Science. The search terms used were "etiology" OR "cause" OR "risk" OR "risks" OR "epidemiology" OR "diagnosis" OR "therapy" OR "prognosis" OR "management" AND "placental mesenchymal dysplasia" OR "placenta" AND "mesenchymal dysplasia." No limit was put on the number of years searched. The etiology of PMD remains uncertain, although there are a number of theories on causation. An elevated maternal serum α-fetoprotein level, slightly elevated human chorionic gonadotropin level, normal karyotype, multicystic lesions on ultrasound, and varying degrees of flow within cysts using color Doppler (stained-glass appearance) are helpful in making the diagnosis. On pathologic examination of the placenta, PMD is differentiated from molar pregnancy by the absence of trophoblastic hyperplasia. Fetal complications of PMD include hematologic disorders, Beckwith-Wiedemann syndrome, liver tumors, fetal growth restriction, preterm delivery, and intrauterine fetal demise. Maternal complications include gestational hypertension, preeclampsia, HELLP (hemolysis, elevated liver function tests, low platelets) syndrome, and eclampsia. Accurate diagnosis of PMD is imperative for appropriate management and surveillance to minimize adverse maternal and fetal outcomes. The importance of a correct diagnosis of PMD is important because it can be misdiagnosed as a partial molar pregnancy or a complete mole with coexisting normal fetus, and this can result in inappropriate management.

Elevated maternal serum α-fetoprotein after minor trauma during pregnancy may predict adverse fetal outcomes.

We evaluated the relationship between minor trauma during pregnancy and elevated maternal serum α-fetoprotein level. This is a retrospective review of pregnant patients admitted to Fukui Prefectural Hospital with trauma during a 10-year period. Charts were reviewed for maternal age, gestational age, injury characteristics, Injury Severity Score, the presence of abdominal pain, systolic pressure and heart rate on arrival, fetal hemoglobin level, and maternal serum α-fetoprotein (MSAFP) concentration on arrival. Fifty-one pregnant patients with any trauma were treated at Fukui Prefectural Hospital. All patients were hemodynamically stable and had minor trauma. An adverse pregnancy outcome occurred in three patients (5%). One patient's fetus had a left kidney injury. Intrauterine fetal death occurred in two patients. The time from injury to fatal death was 180 minutes in one patient and 18 hours in the other patient. The mean ± SD fetal hemoglobin was 0.57% ± 0.88%. The mean ± SD MSAFP was 511 ng/mL ± 1,263 ng/mL. Three patients with adverse pregnancy outcome had a high MSAFP of greater than 1,000 ng/mL. High level of MSAFP may be a predictor of poor fetal outcome following trauma during pregnancy regardless of the severity of the trauma or the mother's hemodynamic status. Epidemiologic study, level V.

Elevated midtrimester α-fetoprotein and delivery markers of inflammation in a preterm population

Objective: Determine whether elevated second trimester maternal serum α-fetoprotein (AFP) is associated with clinical and histopathologic markers of inflammation at preterm delivery. Methods: 105 women <32 weeks’ gestation were included. AFP levels were dichotomized at 2.0 multiples of the median (MoM). Rates of neonatal morbidities, clinical chorioamnionitis, cord blood IL-6 level, and placental inflammatory findings were compared. Results: Thirteen (12.4%) had elevated AFP. Fewer women with AFP ≥2 MoM had histologic placental or membrane rupture site inflammation, funisitis, or placental culture positive for Mycoplasma and Ureaplasma species, compared to those with normal AFP. Neonatal death was increased in the elevated AFP group (23.1% vs. 2.27%, RR 10.6). Elevated AFP was associated with a nonsignificant increase in indicated birth (54% vs. 35%; p = 0.225). Virtually all inflammatory findings were confined to the spontaneous delivery group. Conclusion: Elevated midtrimester AFP conveyed significant risk of neonatal death, but was negatively associated with clinical or histopathologic inflammation in preterm infants.

Unexplained elevated maternal serum α-fetoprotein and/or human chorionic gonadotropin and the risk of adverse outcomes

Objective The study was undertaken to determine the risks of adverse obstetric outcomes in pregnant women with unexplained elevations of maternal serum α-fetoprotein (MSAFP) and/or human chorionic gonadotropin (hCG) and to determine whether these risks vary by prepregnancy risk status. Study design All women who underwent double-marker screening (MSAFP + hCG) between 1994 and 2000 and were delivered of an infant in Nova Scotia, Canada, during this period were identified from a hospital serum screening database and a provincial perinatal database. Patients with inaccurate dating, major structural anomalies, or chromosomal abnormalities were excluded. The primary outcomes studied were preeclampsia, abruptio placentae, fetal growth restriction, fetal death, and preterm birth. Women with medical or previous obstetric complications were designated high risk. Logistic regression, controlling for confounding factors, was used to estimate the relative risks (RRs) and 95% CI for elevated levels of MSAFP and/or hCG and each of the outcomes. Results Among the 14,374 women who met the study criteria, 5,789 were designated high risk. Except for abruptio placentae, unexplained elevated MSAFP or elevated hCG levels were independently associated with all the outcomes in both high- and low-risk women. Elevated screening values were associated with increased risk of abruptio placentae among low-risk women only. Particularly large RRs were seen for fetal death in both high- and low-risk women (RR = 4.9, 95% CI 2.7-8.7 for elevated MSAFP or hCG in high- and low-risk women combined). Conclusion Unexplained elevated levels of MSAFP and/or hCG are associated with an increased risk of most pregnancy complications. Increased antenatal surveillance of these patients is important regardless of prepregnancy risk status.

Prevalence of viral DNA in amniotic fluid of low-risk pregnancies in the second trimester

Aim: The association between fetal viral infection and adverse pregnancy outcome is well documented. However, the prevalence of common viral pathogens in the amniotic fluid of normal pregnancies is not established. The purpose of this study was to determine this prevalence in asymptomatic patients. Methods: This was a prospective observational study of patients at low risk for viral infection who were referred for second-trimester genetic amniocentesis. In patients with normal fetal anatomy on ultrasound and a normal fetal karyotype, a 2-ml aliquot of amniotic fluid obtained at amniocentesis was analyzed by multiplex polymerase chain reaction for cytomegalovirus (CMV), parvovirus B19, adenovirus, enterovirus, herpes simplex virus (HSV), respiratory syncytial virus (RSV) and Epstein-Barr virus (EBV). Results: Among 686 patients, advanced maternal age was the most common indication for genetic testing (n = 469, 68.4%), followed by elevated aneuploidy risk on triple screen (n = 164, 23.9%), elevated maternal serum α-fetoprotein (n = 20, 2.9%), previous aneuploidy (n = 16, 2.3%) and family history of inheritable disease (n = 14, 2.1%). Forty-four (6.4%) amniotic fluid samples were positive for viral genome. A single genome was amplified in 41 samples (93%). In three samples, two viral genomes were identified. Adenovirus was most frequently identified (37/44), followed by CMV (5/44), EBV (2/44), enterovirus (2/44) and RSV (1/44). Parvovirus and HSV were not identified. There was a bimodal seasonal variation in prevalence, with the highest prevalence during the summer and late winter. Conclusion: Viral genome is commonly found in amniotic fluid with a sonographically normal fetus, and the prevalence follows a seasonal pattern. The mechanism, significance and effects of this asymptomatic viral presence require further study.

Prevalence of viral DNA in amniotic fluid of low-risk pregnancies in the second trimester

Aim: The association between fetal viral infection and adverse pregnancy outcome is well documented. However, the prevalence of common viral pathogens in the amniotic fluid of normal pregnanciesis not established. The purpose of this study was to determine this prevalence in asymptomatic patients.Methods: This was a prospective observational study of patients at low risk for viralinfection who were referred for second-trimester genetic amniocentesis. In patients with normal fetal anatomy on ultrasound and a normal fetal karyotype, a 2-ml aliquot of amniotic fluid obtained at amniocentesiswas analyzed by multiplex polymerase chain reaction for cytomegalovirus (CMV), parvovirus B19, adenovirus, enterovirus, herpes simplex virus (HSV), respiratory syncytial virus (RSV) and Epstein-Barrvirus (EBV).Results: Among 686 patients, advanced maternal age was the most common indication for genetic testing (n = 469, 68.4%), followed by elevated aneuploidy risk on triple screen(n = 164, 23.9%), elevated maternal serum α-fetoprotein (n = 20, 2.9%), previous aneuploidy (n = 16, 2.3%) and family history of inheritable disease (n = 14, 2.1%). Forty-four(6.4%) amniotic fluid samples were positive for viral genome. A single genome was amplified in 41 samples (93%). In three samples, two viral genomes were identified. Adenovirus was most frequently identified(37/44), followed by CMV (5/44), EBV (2/44), enterovirus (2/44) and RSV (1/44). Parvovirus and HSV were not identified. There was a bimodal seasonal variation in prevalence, with the highest prevalenceduring the summer and late winter.Conclusion: Viral genome is commonly found in amniotic fluid with a sonographically normal fetus, and the prevalence follows a seasonal pattern. The mechanism,significance and effects of this asymptomatic viral presence require further study.

The association of abnormal α-fetoprotein and adverse pregnancy outcome: Does increased fetal surveillance affect pregnancy outcome?

Objective: Our purpose was to investigate whether adverse outcomes associated with elevated maternal serum α-fetoprotein levels may be prevented by intensive antenatal monitoring. Study Design: Records of patients with elevated maternal serum α-fetoprotein values of ≥2.0 multiples of the median between 1995 and 1999 were reviewed. Pregnancy histories were analyzed to determine whether intensive antenatal monitoring (twice-weekly nonstress tests and determinations of the amniotic fluid index) would have detected the adverse outcomes when routine obstetric care would have missed them. Women with elevations explained by multiple gestations, structural abnormalities, or a fetal death were excluded. Results: The study enrolled 136 patients. Twenty-three patients were excluded because of multiple gestations, structural or chromosomal abnormalities, or fetal death or for lack of available follow-up. Seventy-eight patients had no perinatal complications, but 12 of these patients underwent heightened surveillance. One of these patients was subjected to an induction of labor. Thirty-five pregnancies had complications (21 with preterm labor, 7 with pregnancy-induced hypertension, 6 with growth restriction or oligohydramnios, 1 with abruptio placentae, and 1 with vasa previa). Of these 35 pregnancies, 22 were followed up with routine obstetric care and 13 with heightened surveillance. Heightened surveillance did not achieve earlier or improved detection in this group. These results suggest that routine pregnancy management is an adequate strategy for providing care to pregnant patients with unexplained elevated maternal serum α-fetoprotein levels. Adverse outcomes were detected with routine pregnancy management or were undetectable even with intensive management. Conclusion: Increased risks of pregnancy-induced hypertension, preterm delivery, intrauterine growth restriction, intrauterine fetal death, oligohydramnios, and abruptio placentae are associated with elevated maternal serum α-fetoprotein levels. However, in our study, routine pregnancy management was an acceptable method of detecting these adverse outcomes when they were detectable. (Am J Obstet Gynecol 2001;184:1549-55.)

Prenatal Diagnosis and Elective Termination of Neural Tube Defects in Hawaii, 1986–1997

Objective: To determine the influence of various factors on the prenatal diagnosis and elective termination of neural tube defects (NTDs) in Hawaii in 1986–1997. Methods: Data from a birth defects registry were analyzed and included 245 cases. Results: 74% of the cases were prenatally diagnosed and 48% were terminated. Anencephaly was more likely to be prenatally diagnosed and electively terminated than spina bifida or encephalocele. Other factors such as maternal age, race/ethnicity, place of residence, and elevated maternal serum α-fetoprotein influenced the prenatal diagnosis and/or elective termination of NTD-affected pregnancies. However, a given factor may influence prenatal diagnosis and elective termination in different ways. Conclusions: Various diagnostic and demographic factors can influence the prenatal diagnosis and the subsequent termination of NTD-affected pregnancies.

Cost-benefit analysis of targeted ultrasonography for prenatal detection of spina bifida in patients with an elevated concentration of second-trimester maternal serum α-fetoprotein

Objective: The objectives of this study were to examine (1) the diagnostic accuracy requirements (from the cost-benefit point of view) of targeted ultrasonography versus genetic amniocentesis for prenatal detection of spina bifida in women with an elevated level of maternal serum α-fetoprotein, (2) the ultrasonographic accuracy of previously published studies from the cost-benefit point of view, and (3) the possible economic impact for the United States of offering targeted ultrasonography instead of routine amniocentesis to this group of patients. Study Design: Our cost-benefit formula was based on the hypothesis that the cost of universal genetic amniocentesis in patients with an elevated concentration of maternal serum α-fetoprotein in the second trimester should be at least equal to the cost of universal targeted ultrasonography, with amniocentesis used only for those with abnormalities on a sonogram. The main components of the formula included the diagnostic accuracy of targeted ultrasonography (sensitivity and specificity for detecting spina bifida), the cost of the amniocentesis package, the cost of targeted ultrasonography, and the lifetime cost of spina bifida not detected by targeted ultrasonography. After appropriate manipulation of the formula, a graph was constructed to represent the balance between the sensitivity and false-positive rate of targeted ultrasonography and was used to examine the accuracy of previously published ultrasonographic studies from the cost-benefit point of view. Sensitivity analyses included a range of prevalences of spina bifida in women with elevated maternal serum α-fetoprotein from 1:50 to 1:200 and false-positive rates of targeted ultrasonography from 1% to 10%. Results: Assuming overall prevalences of spina bifida of 1:50, 1:100, or 1:200 among women with elevated maternal serum α-fetoprotein, we found targeted ultrasonography to be beneficial only if the overall sensitivities for detecting fetal spina bifida were >88%, >76%, and >51%, respectively. All 17 studies published after the mid-1980s, which used the “cranial signs” for detecting spina bifida, had accuracies compatible with economic benefits (sensitivities, 92% to 100%; false-positive rates, 0% to 3%). Conclusion: The benefit of second-trimester targeted ultrasonography for fetal spina bifida depends on diagnostic accuracy (ie, sensitivity and false-positive rate). Currently achieved ultrasonographic accuracies are compatible with net benefits. Targeted ultrasonography in patients with an elevated level of second-trimester maternal serum α-fetoprotein in the United States has the potential for annual savings of approximately $36 million to $49 million and for avoiding 268 fetal deaths. (Am J Obstet Gynecol 1999;180:1227-33.)

Unexplained elevated maternal serum alpha-fetoprotein: what is the appropriate follow-up?

Unexplained elevations of maternal serum alpha-fetoprotein exist in approximately 1% of the obstetric population. A consensus has been reached that these women face an increased risk of adverse pregnancy outcome. Whether their overall risk can be altered by the currently available surveillance modalities, however, remains controversial. Current research has focused on identifying those pregnancies with the highest risks of either fetal growth restriction, pre-eclampsia, preterm delivery or intrauterine fetal demise. Markedly increased maternal serum alpha-fetoprotein (over 4.0 multiples of the median), elevations of other serum markers such as human chorionic gonadotropin and abnormal umbilical Doppler flow are associated with the greatest risk of poor pregnancy outcome. When initiating surveillance of the pregnancy with unexplained elevated maternal serum alpha-fetoprotein consideration of these factors is receiving increased attention.

Elevated maternal serum midtrimester α-fetoprotein levels are associated with fetoplacental ischemia

Objective: Elevation of maternal serum α-fetoprotein in the second trimester is associated with poor pregnancy outcome, including fetal death, preterm delivery, and fetal growth restriction. We hypothesized that placental ischemia may be the common underlying pathogenesis of these outcomes. Thus we tested angiogenin, a potent inducer of neovascularization, in midtrimester amniotic fluid of patients with elevated maternal serum α-fetoprotein values to determine whether α-fetoprotein elevation is due to ischemia with subsequent stimulation of angiogenesis. Study Design: In this case-control study, patients with elevated maternal serum α-fetoprotein levels (≥2.0 multiples of the median, n = 9) at triple screen were matched with two controls ( n = 18) on the basis of year of amniocentesis and maternal age, race, and parity. The median elevation of maternal serum α-fetoprotein in the study population was 4.01 multiples of the median (range 2.65 to 7.24 multiples of the median). Inclusion criteria were (1) singleton gestation, (2) no evidence of fetal structural or chromosomal anomalies, and (3) genetic amniocentesis. Amniotic fluid was immunoassayed for angiogenin (Quantikine, R&D Systems; sensitivity 0.026 ng/ml, interassay and intraassay coefficients of variation 4.6% and 2.9%, respectively). Statistical analysis included one-way analysis of variance and regression with p < 0.05 significant. Angiogenin and maternal serum α-fetoprotein values were normalized with use of natural log transformation for statistical analysis. Results: Angiogenin values were significantly elevated in patients with high maternal serum α-fetoprotein levels (median 31.1 [range 9.2 to 54.6] vs 17.1 [range 9.0 to 29.2] ng/ml, p = 0.02). Mean gestational age at sampling, maternal age, and year of amniocentesis were not significantly different between the study and control groups (each p > 0.05). As anticipated, there was a significant increase in preterm deliveries and small-for-gestational-age neonates in the patients with elevated maternal serum α-fetoprotein levels (each p < 0.01). Conclusions: Midtrimester amniotic fluid angiogenin levels are significantly elevated in patients with elevated midtrimester maternal serum α-fetoprotein levels. Because angiogenin is a known marker of tissue ischemia, resulting in neovascularization, we hypothesize that elevation of maternal serum α-fetoprotein levels at triple screen is due to placental ischemia.

Prenatal Characteristics of Congenital Nephrosis

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 α-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 una...

Term delivery after hepatocellular carcinoma resection in previous pregnancy

Screening of the maternal serum α-fetoprotein at the second trimester of pregnancy is a standard obstetric practice for detection of fetal malformation. However, an elevated maternal serum α-fetoprotein level may not always be of fetal origin, some maternal diseases could present with an elevated maternal serum α-fetoprotein. High serum concentration (>500 ng/mL) of α-fetoprotein is noted in 70% of patients with hepatocellular carcinoma in the United States and in 85% of those in Africa, Japan and Taiwan (1). Although hepatocellular carcinoma occurs predominantly in male, sporadic cases of hepatocellular carcinoma have been reported in pregnant women (2-5). These patients invariably died within one year after diagnosis. Herein, we report a pregnant women who was found to have a high maternal serum α-fetoprotein during routine screening. A diagnosis of hepatocellular carcinoma was made and she underwent surgical resection of the tumor. A subsequent pregnancy with successful childbirth was achieved.

Uterine artery Doppler velocimetry in the detection of adverse obstetric outcomes in women with unexplained elevated maternal serum α-fetoprotein levels

OBJECTIVE: We hypothesized that in pregnancies complicated by unexplained elevations of maternal serum α-fetoprotein, second-trimester uterine artery Doppler findings would detect adverse obstetric outcomes. STUDY DESIGN: One hundred three subjects with unexplained elevations of maternal serum α-fetoprotein had uterine artery Doppler velocimetry studies performed at the time of targeted ultrasonographic examination (17 to 22 weeks). A resistance index >95th percentile or the presence of a uterine notch was considered abnormal. Adverse outcomes included preeclampsia, preterm birth, low birth weight, intrauterine growth restriction, abruptio placentae, and fetal death. Statistical analysis was performed by Student t test, χ 2 analysis, and stepwise logistic regression analysis. RESULTS: An elevated uterine resistance index was associated with an increased relative risk for both preeclampsia (relative risk 41.82, 95% confidence interval 5.36 to 326.13) and low birth weight (relative risk 4.65, 95% confidence interval 1.90 to 11.39). A uterine artery notch was associated with an increased risk of preeclampsia (relative risk 52.22, 95% confidence interval 6.82 to 399.70), preterm birth (relative risk 3.21, 95% confidence interval 1.32 to 7.81), and a low birth weight (relative risk 4.18, 95% confidence interval 1.64 to 10.66). when the presence of a uterine notch, vaginal bleeding, and level of maternal serum AFP were analyzed, by stepwise logistic regression, the presence of a notch was found to be the only significant factor (odds ratio 6.95, 95% confidence interval 1.24 to 39.10) for the development of an adverse outcome. CONCLUSIONS: Abnormal uterine artery Doppler findings are associated with an increased frequency of adverse obstetric outcomes in women with unexplained elevated maternal serum AFP levels. Abnormal Doppler findings demonstrated high sensitivity for the development of preeclampsia but were less sensitive in predicting other outcomes. the presence of a uterine artery notch is a better independent predictor of adverse outcome than are early vaginal bleeding or maternal serum AFP level.

Elevated maternal serum α-fetoprotein levels: What is the risk of fetal ancuploidy?

Objective: Our purpose was to present the findings of a project to determine the efficacy of including routine fetal karyotyping in the investigation of an elevated maternal serum α-fetoprotein concentration.Study design: Targeted ultrasonographic examinations were performed in 658 patients with elevated maternal serum α-fetoprotein levels. The scans were normal normal in 557 women, of whom 427 consented to amniocentesis; 435 fetuses were karyotyped. In the 101 patients with abnormal ultrasonographic examinations 75 had fetal karyotyping.Results: In the 435 fetuses with normal scans, two had karyotypic anomalies, a 47,XYY and an inherited balanced transiocation. Three fetuses with normal karyotypes and high amniotic fluid α-fetoprotein levels had congenital nephrosis. In the 101 patients with abnormal scans, 75 features were karyotyped. There were four aneuploidies. Among the 26 patients with abnormal scans who declined amniocentesis one fetus with multiple anomalies was karyotyped after delivery and triploidy was discovered.Conclusions: These results provide little justification for including fetal karyotyping in the investigation of elevated maternal serum α-fetoprotein when the targeted ultrasonographic examination is normal. When it is abnormal, selective rather than routine karyotyping is more appropriate.

Aplasia cutis congenita: A rare cause of elevated α-fetoprotein levels

We present a catastropic case of aplasia cutis congenita from a pregnancy complicated by elevated maternal serum and amniotic fluid α-fetoprotein levels and a positive acetylcholinesterase. Delivery occurred at 27 weeks 1 day after premature rupture of membranes with chorioamnionitis. The neonate lacked >90% of its skin and died.

Procedure-related fetal losses in transplacental versus nontransplacental genetic amniocentesis

OBJECTIVE: We hypothesize that loss rates after amniocentesis do not differ in transplacentaland nontransplacental taps performed by experienced operators. STUDY DESIGN: Subjects were 1000 women undergoing second-trimester amniocentesis: 745 were referred for maternal age; 132 for positive maternal serum α-fetoprotein screens, 41 indicating a risk for fetal neural tube defect, 91 indicating a risk for fetal chromosome abnormality; and 123 were referred for other reasons. All procedures were videotaped. The placenta was anterior in 518 cases; in 306 of these the needle went through the placenta. All pregnancies were prospectively evaluated through delivery. RESULTS: There were 13 losses among the 1000 procedures (1.3%). The transplacental losses occurred from 4 to 71 days after procedure, median 26.5 days; the nontransplacental losses from 12 days after procedure to term, median 25 days. The loss rate was essentially similar in the two categories: six transplacental (1.96%) and seven nontransplacental 91%) (relative risk 1.52 [95% confidence limits 0.84 to 2.75], p = 0.23). If the three patients with elevated maternal serum α-fetoprotein values were excluded from data analysis, the loss rates in the two groups were virtually identical (relative risk 0.98 [95% confidence limits 0.38 to 2.54], p = 1.0000). CONCLUSION: Transplacental amniocentesis does not appear to increase the fetal loss rate in the hands of experienced surgeons. Moreover, in view of the time span between amniocentesis and loss in both groups, a procedural cause seems questionable.

Risk of anomalies as a function of level of elevated maternal serum α-fetoprotein

Objective: Most neural tube defects risks, are not actual but mathematic extrapolations. We sought to evaluate this risk and to compare actual performance.Study Design: This was a retrospective study of a referral population with elevated maternal serum α-fetoprotein results between 1987 and 1992. Ultrasonography results, delivery records, and autopsy results were compared with entry levels of maternal serum α-fetoprotein, and the percentage of fetal anomalies detected in this study was evaluated.Results: A total of 773 patients with elevated maternal serum α-fetoprotein levels were evaluated. There was a progressive increase in the incidence of anomalies as a direct function of the level of the maternal serum AFP, varying from 3.4% at a level of 2.5 to 40.3% at a level>7.0.Conclusion: Data from this study support the correlation of maternal serum AFP levels with the risk of neural tube defect and ventral wall defects.

Elevated second-trimester human chorionic gonadotropin levels in association with poor pregnancy outcome

Objective: Our purpose was to determine whether abnormal pregnancy outcome is associated with elevated maternal serum human chorionic gonad otropin levels.Study Design: Maternal serum a-fetoprotein and human chorionic gonadotropin levels were measured in stored second-trimester serum obtained before scheduled genetic amniocentesis from 126 women with poor pregnancy outcomes, excluding aneuploidy and structural abnormalities (complications group), and 126 matched women with normal outcomes (control group).Results: More women with complications had elevated human chorionic gonadotropin levels (≥2.0 multiples of the median) (14%) than did control women (3%) (p = 0.01). Both elevated human chorionic gonadotropin and maternal serum α-fetoprotein levels were significantly associated with preterm delivery and fetal death. Elevated maternal serum α-fetoprotein was significantly associated with early postamniocentesis complications and fetal growth restriction, whereas elevated human chorionic gonadotropin was associated with preeclampsia.Conclusion: Elevated human chorionic gonadotropin, similar to unexplained elevated maternal serum α-fetoprotein, is significantly associated with abnormal pregnancy outcomes.