Second-trimester Maternal Serum Alpha-fetoprotein Research Articles

Outcomes of pregnancies diagnosed with circumvallate placenta, and use of uterine artery pulsatility index and maternal serum alpha-fetoprotein for prediction of adverse outcomes

ObjectivesTo evaluate the outcomes, and predictive value of uterine artery pulsatility index (UtA-PI) and second-trimester maternal serum alpha-fetoprotein (MSAFP) for adverse obstetric outcomes in cases with morphologically confirmed circumvallate placenta by comparison with normal pregnancies. Study designThis prospective study was conducted in a tertiary referral hospital between January 2017 and December 2019. During the study period, 77 patients with a circumvallate placenta and 77 patients without any placental or feto-maternal diseases or abnormalities were evaluated. The final diagnosis was made based on macroscopic examination of the placenta soon after birth. Demographic characteristics, MSAFP, obstetric complications, haemoglobin after delivery, gestational week of birth, fetal sex, 1- and 5-min Apgar scores, postnatal complications and type of delivery were retrieved from hospital records. Bilateral mean transabdominal UtA-PI and MSAFP were evaluated for the prediction of adverse outcomes. SPSS Version 21.0 for Windows was used for statistical analysis, and receiver operating characteristic (ROC) curves were used for the prediction model of adverse outcomes. ResultsSmoking rate, MSAFP, preterm birth and intrauterine growth restriction (IUGR) were higher in the patients with a circumvallate placenta (p = 0.005, 0.00, 0.025 and 0.027, respectively). The cut-off value of MSAFP was 1.41 (0.60–3.32) and the cut-off value of UtA-PI was 1.2 using the ROC curves, and had sensitivity of 73.7 % and specificity of 71.9 %, and sensitivity of 73.7 % and specificity of 76.3 %, respectively (p < 0.05). ConclusionsCircumvallate placenta was associated with a higher rate of IUGR, preterm birth and bleeding at the time of delivery. In patients with a circumvallate placenta, UtA-PI and MSAFP may be valuable as predictors of IUGR.

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.

First-trimester maternal serum alpha-fetoprotein is not a good predictor for adverse pregnancy outcomes: a retrospective study of 3325 cases

BackgroundIt is well known that second-trimester maternal serum alpha-fetoprotein (MS-AFP) is a predictor for adverse pregnancy outcomes (APOs), such as preterm birth, stillbirth, preeclampsia and small for gestational age (SGA). However, it is unknown whether first-trimester MS-AFP is also predictive of APOs.MethodsWe retrospectively reviewed the data on the first-trimester MS-AFP levels and pregnancy outcomes of 3325 singleton pregnant women. The cutoff value of 2.5 multiple of the median (MoM) was used to evaluate the risks of APOs regarding MS-AFP. The receiver operating characteristic (ROC) curves were used to evaluate the predictive efficiencies of MS-AFP to these disorders.ResultsA total of 181 pregnancies resulted in preterm birth, 32 in stillbirth, 81 in preeclampsia, and 362 in SGA. Compared to women with MS-AFP < 2.5MoM, those with MS-AFP ≥ 2.5MoM had increased risks (odds ratio, 95% confidence interval) of preterm birth (2.53, 1.65~3.88), preeclampsia (3.05, 1.71~5.43) and SGA (1.90, 1.34~2.69), and had an earlier distribution of gestational weeks at delivery (P = 0.004) and a lower distribution of neonatal birth weights (P = 0.000), but the actual between-group differences were minuscule. The areas under ROC curves were 0.572 (P = 0.001), 0.579 (P = 0.015) and 0.565 (P = 0.000) for preterm birth, preeclampsia and SGA, respectively. Subdivisions for the disorders did not obviously improve the performances of MS-AFP.ConclusionsElevated first-trimester MS-AFP is associated with increased risk of preterm birth, preeclampsia and SGA. However, the predictive efficiencies were low and it is not a good predictor for these APOs.

Pregnancy outcomes of women with elevated second-trimester maternal serum alpha-fetoprotein

ObjectiveThe aim of this study was to investigate the overall distribution of pregnancy outcomes in women with elevated second-trimester maternal serum alpha-fetoprotein (MS-AFP), and to determine the risk of adverse pregnancy outcomes (APOs) by MS-AFP level. Materials and methodsWe retrospectively analyzed the clinical data of 429 women with elevated MS-AFP (≥2.5 multiple of the median (MOM)) and 1555 women with normal MS-AFP (0.5–2.49MOM) from a total of 46,741 prenatally screened singleton pregnant women. The overall distribution of APOs of the two groups, the risk of APOs by MS-AFP level, and the predictive value of elevated MS-AFP to APOs were analyzed. ResultsThe incidence rate of APOs in elevated MS-AFP group was significantly higher than that in normal MS-AFP group (42.89 vs. 8.23%). In elevated MS-AFP group, the top three APOs, in term of incidence rate, were structural fetal abnormalities (7.93%), spontaneous abortion (7.46%) and preterm birth (7.23%); regarding to the risk, the top three APOs were stillbirth, spontaneous abortion and early-onset preeclampsia (odds ratio 35.98, 20.81 and 8.58 respectively). For structural fetal abnormalities, MS-AFP had predictive values for fetal open neural tube defects (ONTDs), gastroschisis and multiple malformations. ConclusionElevated MS-AFP is associated with increased risks of APOs. ONTDs complicate merely a small proportion of pregnancies with elevated MS-AFP, and the rest of them have high risks of obstetric complications. MS-AFP can help to identify these women at high risk of APOs in earlier second-trimester.

First-trimester maternal serum alpha fetoprotein is associated with ischemic placental disease

While elevated second-trimester maternal serum alpha fetoprotein has been associated with adverse pregnancy outcomes, the utility of first-trimester maternal serum alpha fetoprotein in predicting these outcomes is limited. Some laboratories have been including maternal serum alpha fetoprotein as part of the first-trimester analyte screening for aneuploidy and preeclampsia, offering its potential utility in predicting pregnancy outcomes. Our primary objective was to determine the association between elevated first-trimester maternal serum alpha fetoprotein and preeclampsia as well as ischemic placental disease (a composite of preeclampsia, fetal growth restriction, and/or placental abruption). Secondary outcomes included early-onset preeclampsia requiring delivery at <34 weeks gestation, fetal growth restriction, placental abruption, preterm delivery, fetal demise, and spontaneous abortion. An institutional review board-approved multisite retrospective cohort study was performed including all patients with first-trimester maternal serum alpha fetoprotein as part of routine first-trimester aneuploidy screening from April 2015 through January 2017. Pregnancies with multiple gestations, known structural or chromosomal abnormalities, known malignancy, and incomplete delivery records were excluded. Delivery records were reviewed for baseline characteristics and adverse pregnancy outcomes. The optimal cutoff point for first-trimester maternal serum alpha fetoprotein to predict these outcomes was assessed, and an elevated maternal serum alpha fetoprotein was considered >2.0 multiple of the median. A Fisher exact test and odds ratios were used to determine the association between elevated first-trimester maternal serum alpha fetoprotein and adverse pregnancy outcomes. Spearman correlation coefficient assessed the relationship between first- and second-trimester maternal serum alpha fetoprotein. Of 1478 patients with first-trimester maternal serum alpha fetoprotein, 1280 had complete records available for review (86.6%). There was no association demonstrated between elevated first-trimester maternal serum alpha fetoprotein (>2.0 multiple of the median) and the primary outcome, overall preeclampsia (5.8% vs 4.6%, odds ratio, 1.29, 95% confidence interval, 0.58-2.91). However, there was an increased incidence of ischemic placental disease, 15.8% vs 7.7% (odds ratio, 2.26, 95% confidence interval, 1.33-3.87) in those with an elevated alpha fetoprotein. Also, elevated first-trimester maternal serum alpha fetoprotein was associated with a higher incidence of fetal growth restriction (7.5% vs 2.3%, odds ratio, 3.40, 95% confidence interval, 1.56-7.42) and preterm birth (18.3% vs 10.3%, odds ratio, 1.95, 95% confidence interval, 1.18-3.21). Also, a positive correlation between first- and second-trimester maternal serum alpha fetoprotein was demonstrated (rho= 0.46, P < .0001). Elevated first-trimester maternal serum alpha fetoprotein is associated with ischemic placental disease, fetal growth restriction, and preterm birth. This suggests that elevated maternal serum alpha fetoprotein may help to identify high risk pregnancies as early as the first trimester of pregnancy. Future studies are necessary to determine whether the addition of first-trimester maternal serum alpha fetoprotein to existing algorithms can improve the early detection of ischemic placental disease.

Acetabulum of the hip bone: A morphometric study in south coastal region

To evaluate the outcomes, and predictive value of uterine artery pulsatility index (UtA-PI) and second-trimester maternal serum alpha-fetoprotein (MSAFP) for adverse obstetric outcomes in cases with morphologically confirmed circumvallate placenta by comparison with normal pregnancies.This prospective study was conducted in a tertiary referral hospital between January 2017 and December 2019. During the study period, 77 patients with a circumvallate placenta and 77 patients without any placental or feto-maternal diseases or abnormalities were evaluated. The final diagnosis was made based on macroscopic examination of the placenta soon after birth. Demographic characteristics, MSAFP, obstetric complications, haemoglobin after delivery, gestational week of birth, fetal sex, 1- and 5-min Apgar scores, postnatal complications and type of delivery were retrieved from hospital records. Bilateral mean transabdominal UtA-PI and MSAFP were evaluated for the prediction of adverse outcomes. SPSS Version 21.0 for Windows was used for statistical analysis, and receiver operating characteristic (ROC) curves were used for the prediction model of adverse outcomes.Smoking rate, MSAFP, preterm birth and intrauterine growth restriction (IUGR) were higher in the patients with a circumvallate placenta (p = 0.005, 0.00, 0.025 and 0.027, respectively). The cut-off value of MSAFP was 1.41 (0.60–3.32) and the cut-off value of UtA-PI was 1.2 using the ROC curves, and had sensitivity of 73.7 % and specificity of 71.9 %, and sensitivity of 73.7 % and specificity of 76.3 %, respectively (p < 0.05).Circumvallate placenta was associated with a higher rate of IUGR, preterm birth and bleeding at the time of delivery. In patients with a circumvallate placenta, UtA-PI and MSAFP may be valuable as predictors of IUGR.

Management strategy in pregnancies with elevated second-trimester maternal serum alpha-fetoprotein based on a second assay

To assess maternal-fetal outcomes in pregnancies associated with persistently elevated second-trimester maternal serum alpha-fetoprotein. A retrospective cohort study in 658 patients with maternal serum alpha-fetoprotein ≥2.5 multiple of median, performed at routine Down syndrome screening. Maternal serum alpha-fetoprotein was assayed a second time in 341 of them. Outcomes were recorded in all cases. The group with unexplained maternal serum alpha-fetoprotein persistently ≥2.5 multiple of median was associated with more pregnancy complications 37 of 92 (40.2%) as fetal death, preeclampsia, intrauterine growth restriction, and congenital nephrotic syndrome, compared with the group with maternal serum alpha-fetoprotein that returned to a normal level 37 of 226 (16.4%) (P < .001). When maternal serum alpha-fetoprotein returns to a normal level on a second assay, the risk of adverse outcome significantly decreases, but these pregnancies are still at risk of complications and therefore need close surveillance. Repeat maternal serum alpha-fetoprotein assay allows identification of patients who should be offered amniocentesis to evaluate the risk of nephrotic syndrome and epidermolysis bullosa. Alpha-fetoprotein should be monitored in pregnancies associated with unexplained high maternal serum alpha-fetoprotein. A management strategy based on ultrasound examination, second maternal serum alpha-fetoprotein assay and amniocentesis is proposed to improve prenatal counseling and management of such pregnancies. However, a prospective study remains necessary to evaluate it.

Maternal serum hCG, PAPP‐A and AFP as predictors of hemoglobin Bart disease at mid‐pregnancy

To evaluate the ability of maternal serum-free β-human chorionic gonadotrophin (β-hCG), pregnancy-associated plasma protein-A (PAPP-A), and alpha fetoprotein (AFP) levels in the screening of fetuses with hemoglobin (Hb) Bart's disease among pregnancies at risk. Pregnancies at risk for fetal Hb Bart's disease scheduled for cordocentesis at 18 to 22 weeks were recruited into the study. Maternal serum-free β-hCG, PAPP-A, and AFP concentrations were measured before cordocentesis, and the final fetal diagnosis of Hb Bart disease was based on fetal Hb typing using high-performance liquid chromatography. Of 57 recruited pregnancies, 11 had fetal Hb Bart's disease and 46 were unaffected. Maternal serum alpha-fetoprotein (MSAFP) concentrations were significantly higher in women with fetal Hb Bart's disease than those with unaffected fetuses (median 99.53 vs 50.83, P < 0.001), whereas the concentrations of free β-hCG and PAPP-A were not significantly different between the two groups (P = 0.543 and 0.777, respectively). Second-trimester MSAFP may be clinically a useful screening test for fetal Hb Bart's disease among pregnancies at risk.

The impact of crown–rump length measurement error on combined Down syndrome screening: a simulation study

To evaluate the impact of a 5-mm error in the measurement of crown-rump length (CRL) in a woman undergoing ultrasound and biochemistry sequential combined screening for Down syndrome. Based on existing risk calculation algorithms, we simulated the case of a 35-year-old-woman undergoing combined screening based on nuchal translucency (NT) measurement and early second-trimester maternal serum markers (human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP) expressed as multiples of the median (MoM)). Two measurement errors were considered (+ or - 5 mm), for four different CRLs (50, 60, 70 and 80 mm), with five different NT measurements (1, 1.5, 2, 2.5 and 3 mm) in a patient undergoing biochemistry testing at 14 + 4, 15, 16, 17 or 18 weeks' gestation. Four different values for each maternal serum marker were tested (1, 1.5, 2 and 2.5 MoM for hCG, and 0.5, 0.8, 1 and 1.5 MoM for AFP), leading to a total of 3200 simulations of the impact of measurement error. In all cases the ratio between the risk as assessed with or without the measurement error was calculated (measurement error-related risk ratio (MERR)). Over 3200 simulated cases, MERR ranged from 0.53 to 2.14. In 586 simulations (18.3%), it was < 0.66 or > 1.33. Based on a risk cut-off of 1/300, women would have been misclassified in 112 simulations (3.5%). This would go up to 33 (27.5%) out of the 120 simulations in women with 'borderline' risk, with 1.5 MoM for hCG and 0.5 MoM for AFP, and NT measurement of 1 or 2mm. Down syndrome screening may be highly sensitive to measurement errors in CRL. Quality control of CRL measurement should be performed together with quality control of NT measurement in order to provide the highest standard of care.

Elevated maternal second‐trimester serum alpha‐fetoprotein as a risk factor for placental abruption

To analyze the association of second-trimester maternal serum alpha-fetoprotein (MSAFP) and free beta human chorionic gonadotrophin (MSbeta-hCG) levels to placental abruption. Fifty-seven women with placental abruption and 108 control women without placental abruption were tested for second-trimester MSAFP and MSbeta-hCG levels as a part of a trisomy 21 screening program. Discriminatory cutoff levels for MSAFP were sought to predict placental abruption. The median of the MSAFP multiples of median (MoM) (1.21) was significantly higher in the abruption group than in the control group (1.07) (p = 0.004). In multivariate analysis, elevated MSAFP remained an independent risk factor for placental abruption when adjusting for other risk factors (parity >/= 3, smoking, previous placental abruption, preeclampsia, bleeding in II or III trimester, and placenta previa). MSAFP >/= 1.5 MoM had a sensitivity of 29% and a false-positive rate of 10%. The levels of the MSbeta-hCG MoM did not differ between the cases and the controls. Although second-trimester MSAFP levels are higher in women with subsequent placental abruption, the clinical usefulness of this test is limited due to low sensitivity and high false-positive rate.

Three‐stage contingent screening for Down syndrome

To demonstrate the potential value of three-stage sequential screening for Down syndrome. Protocols were considered in which maternal serum pregnancy associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (hCG) measurements were taken on all women in the first trimester. Those women with very low Down syndrome risks were screened negative at that stage and nuchal translucency (NT) was measured on the remainder and the risk reassessed. Those with very low risk were then screened negative and those with very high risk were offered early diagnostic testing. Those with intermediate risks received second-trimester maternal serum alpha-fetoprotein, free beta-hCG, unconjugated estriol and inhibin-A. Risk was then reassessed and those with high risk were offered diagnosis. Detection rates and false-positive rates were estimated by multivariate Gaussian modelling using Monte-Carlo simulation. The modelling suggests that, with full adherence to a three-stage policy, overall detection rates of nearly 90% and false-positive rates below 2.0% can be achieved. Approximately two-thirds of pregnancies are screened on the basis of first-trimester biochemistry alone, five out of six women complete their screening in the first trimester, and the first-trimester detection rate is over 60%. Three-stage contingent sequential screening is potentially highly effective for Down syndrome screening. The acceptability of this protocol and its performance in practice, should be tested in prospective studies.

Predicting the result of additional second-trimester markers from a woman's first-trimester marker profile: a new concept in Down syndrome screening

To describe a method for deciding whether an individual's first-trimester Down syndrome screening test result justifies further testing in the second trimester. Statistical modelling was used to estimate the distribution of second-trimester marker profiles for a given first-trimester profile and hence the probability of a final positive result, using a 1 in 250 term cut-off. A multi-variate log Gaussian model was used with published parameters. Markers were maternal serum pregnancy-associated plasma protein-A and free beta-human chorionic gonadotrophin (hCG) at 10 weeks, nuchal translucency at 11 weeks, and second-trimester maternal serum alpha-fetoprotein, total hCG, unconjugated estriol and inhibin-A. To illustrate the method, the model was applied to a published series of 24 Down syndrome and 367 unaffected pregnancies. Modelling predicts that for 63% Down syndrome and 0.4% unaffected pregnancies having first-trimester tests, there is a 50% or more probability of a final positive result. A step-wise sequential screening policy based on immediate prenatal diagnosis for those with high probability and second-trimester testing for the remainder would have a 90% detection rate and 1.7% false-positive rate. Modelling also predicts 8.0% Down syndrome and 89% unaffected pregnancies with probabilities below 3%. A contingent screening policy restricting second-trimester testing to those with 3-49% probabilities would have an 88% detection rate and 1.4% false-positive rate. Predicting the probability of a positive final result from the first-trimester marker profile has potential utility, either as a decision aide for individual women or as a formal part of screening policy in selecting a subset of women for second-trimester testing.

Second-trimester maternal serum levels of alpha-fetoprotein and the subsequent risk of sudden infant death syndrome.

Unexplained stillbirth and the sudden infant death syndrome (SIDS) share some features. A raised maternal serum level of alpha-fetoprotein during the second trimester of pregnancy is a marker of placental dysfunction and a strong predictor of the risk of unexplained stillbirth. It is unknown whether alpha-fetoprotein levels also predict the risk of SIDS. We linked a prenatal-screening database for women in western Scotland with databases of maternity, perinatal death, and birth and death certifications to assess the association between second-trimester levels of maternal serum alpha-fetoprotein and the subsequent risk of SIDS. Among 214,532 women with singleton births, there were 114 cases of SIDS (incidence, 2.7 per 10,000 births among women with alpha-fetoprotein levels in the lowest quintile and 7.5 per 10,000 births among those with levels in the highest quintile). When the lowest quintile was used as a referent, the unadjusted odds ratios for SIDS for the second through fifth quintiles were 1.7 (95 percent confidence interval, 0.8 to 3.5), 1.8 (95 percent confidence interval, 0.9 to 3.7), 2.5 (95 percent confidence interval, 1.3 to 4.8), and 2.8 (95 percent confidence interval, 1.4 to 5.4), respectively (P for trend = 0.001). The risk of SIDS varied inversely with the birth-weight percentile and the gestational age at delivery; after adjustment for these factors, the odds ratios for SIDS were 1.7 (95 percent confidence interval, 0.8 to 3.5), 1.7 (95 percent confidence interval, 0.8 to 3.5), 2.2 (95 percent confidence interval, 1.1 to 4.4), and 2.2 (95 percent confidence interval, 1.1 to 4.3), respectively (P for trend = 0.01). There is a direct association between second-trimester maternal serum alpha-fetoprotein levels and the risk of SIDS, which may be mediated in part through impaired fetal growth and preterm birth.

Second-trimester maternal serum alpha-fetoprotein (MSAFP) is elevated in women with adverse pregnancy outcome associated with inherited thrombophilias.

Obstetric complications, such as severe pre-eclampsia, fetal growth restriction, abruptio placentae, or stillbirth are associated with abnormally elevated second-trimester maternal serum alpha-fetoprotein (MSAFP) and beta subunit of human chorionic gonadotrophin (betahCG). This has been attributed to placental abnormalities. Women with thrombophilias have been shown to have abnormalities of the placenta resulting in adverse pregnancy outcome in these patients. The purpose of the present study was to evaluate whether women with pregnancy complications and inherited thrombophilias have abnormally elevated second-trimester MSAFP or betahCG. Sixty-two women with pregnancy complications were tested for inherited thrombophilias several months after delivery. The thrombophilia group included 29 women with pregnancy complications and an inherited thrombophilia and the control group included 33 other patients without thrombophilia. Patients in the thrombophilia group had a higher median MoM MSAFP compared to the controls (1.337 vs. 1.086, p=0.0516). The incidence of abnormally elevated MSAFP (>2.5 MoM) was also significantly higher in the thrombophilia group compared to controls (21% vs. 3%, p=0.04). Neither the median MoM betahCG nor the incidence of abnormally elevated betahCG were significantly different between the groups. We conclude that second trimester MSAFP, but not betahCG, is abnormally elevated in patients with thrombophilia and obstetric complications.

Second-trimester maternal serum alpha-fetoprotein and risk of adverse pregnancy outcome

Objective: To determine the risk of adverse pregnancy outcome by maternal serum alpha-fetoprotein (MSAFP) level. Methods: We followed 77,149 pregnant women and their infants from MSAFP screening in the 15th to 20th week of gestation until 1 year after birth. Information on pregnancy outcome was obtained from national registries. The relative risks (RRs) and 95% confidence intervals (CIs) for adverse pregnancy outcome were estimated according to the level of MSAFP, with adjustment for confounders. Results: A total of 638 pregnancies resulted in spontaneous abortion, 289 in stillbirth, and 437 in infant death. Compared with women with MSAFP levels at 0.75–1.24 multiples of the median (MoM), those with MSAFP levels greater than or equal to 2.5 MoM had an increased risk of spontaneous abortion (RR 12.5; 95% CI 9.7, 16.1), preterm birth (RR 4.8; 95% CI 4.1, 5.5), small for gestational age (RR 2.8; 95% CI 2.4, 3.2), low birth weight (RR 5.8; 95% CI 5.0, 6.6), and infant death (RR 1.9; 95% CI 1.2, 2.8). Women with MSAFP levels below 0.25 MoM had an increased risk of spontaneous abortion (RR 15.1; 95% CI 9.3, 24.8), preterm birth (RR 2.2; 95% CI 1.3, 3.8), and stillbirth (RR 4.0; 95% CI 1.0, 16.0); those with levels less than 0.5 MoM had an increased risk of infant death (RR 1.9; 95% CI 1.2, 3.0). The increased risk of infant death remained after the subtraction of recognized conditions associated with extreme MSAFP values. Conclusion: Pregnant women with extreme MSAFP values in the second trimester have an increased risk of fetal and infant deaths. Obstet Gynecol 2001;97:277–82.

Second-Trimester Maternal Serum Alpha-Fetoprotein and Risk of Adverse Pregnancy Outcome

In Brief Objective To determine the risk of adverse pregnancy outcome by maternal serum alpha-fetoprotein (MSAFP) level. Methods We followed 77,149 pregnant women and their infants from MSAFP screening in the 15th to 20th week of gestation until 1 year after birth. Information on pregnancy outcome was obtained from national registries. The relative risks (RRs) and 95% confidence intervals (CIs) for adverse pregnancy outcome were estimated according to the level of MSAFP, with adjustment for confounders. Results A total of 638 pregnancies resulted in spontaneous abortion, 289 in stillbirth, and 437 in infant death. Compared with women with MSAFP levels at 0.75–1.24 multiples of the median (MoM), those with MSAFP levels greater than or equal to 2.5 MoM had an increased risk of spontaneous abortion (RR 12.5; 95% CI 9.7, 16.1), preterm birth (RR 4.8; 95% CI 4.1, 5.5), small for gestational age (RR 2.8; 95% CI 2.4, 3.2), low birth weight (RR 5.8; 95% CI 5.0, 6.6), and infant death (RR 1.9; 95% CI 1.2, 2.8). Women with MSAFP levels below 0.25 MoM had an increased risk of spontaneous abortion (RR 15.1; 95% CI 9.3, 24.8), preterm birth (RR 2.2; 95% CI 1.3, 3.8), and stillbirth (RR 4.0; 95% CI 1.0, 16.0); those with levels less than 0.5 MoM had an increased risk of infant death (RR 1.9; 95% CI 1.2, 3.0). The increased risk of infant death remained after the subtraction of recognized conditions associated with extreme MSAFP values. Conclusion Pregnant women with extreme MSAFP values in the second trimester have an increased risk of fetal and infant deaths. Pregnant women with extreme serum alpha-fetoprotein values in the second trimester have an increased risk of fetal and infant deaths.

Second-trimester maternal serum alpha-fetoprotein and human chorionic gonadotrophin screening for Down's syndrome in Hong Kong

Second-trimester maternal serum screening for fetal Down's syndrome is well established in many Western countries. Its usefulness and acceptability is unknown in the Asian countries. Between June 1994 and December 1996, we offered second-trimester serum AFP and hCG screening to pregnant women in Hong Kong who were less than 35 years old and without other risk factors for chromosome abnormalities. Each woman was assigned a risk of having a Down's syndrome term pregnancy by using a computer software program that took into account her age. weight, AFP and hCG MOMs. All those with a risk of one in 250 or greater were designated screen-positive, subject to the revision of gestation by ultrasound examination. 9,177 women with singleton pregnancies (93 per cent were Chinese) were screened. The uptake of screening was 75 per cent. 281 women (three per cent) were initially classified to be screen-positive. After revision of the gestation by ultrasound examination, 183 women (two per cent) were 'true' screen-positive and 164 (90 per cent) accepted the offer of amniocentesis. Eight of these pregnancies were affected by Down's syndrome and all the women elected pregnancy termination. The odds of being affected, given a positive screening result, were one in 23. Six Down's syndrome pregnancies were missed by screening programme. The detection rate was 57 per cent. The study showed that second-trimester serum screening for fetal Down's syndrome was feasible and accepted in the Hong Kong population.

Association of low unconjugated estriol in the second trimester and adverse pregnancy outcome

Objective: To investigate the association between a low unconjugated estriol (uE3) in the second trimester and adverse pregnancy outcomes. Methods: Three hundred nine women who underwent second-trimester maternal serum alpha-fetoprotein (AFP)-hCG-uE3 screening were divided into two groups: those with uE3 at most 0.75 multiples of the median (MoM) ( n = 81) and those with uE3 exceeding 0.75 MoM ( n = 228). Entry criteria included: hCG below 2 MoM, AFP below 2 MoM, age less than 35 years at delivery, complete prenatal records, and completed delivery. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for a variety of adverse pregnancy outcomes. Results: After adjusting for smoking and hCG, women with uE3 at or below 0.75 MoM were found to have significantly higher odds of developing fetal growth restriction, low amniotic fluid index (AFI), and small for gestational age (SGA) with ORs (and 95% CIs) of 6.73 (2.55,17.74), 3.85 (1.53, 9.68), and 2.89 (1.27, 6.57), respectively, for each of the outcomes. Conclusion: Low uE3 in the second trimester appears to be associated with fetal growth restriction, low AN, and SGA, and the risk seems to be independent of risk for adverse infant outcome associated with elevated AFP or hCG.

The association between hypertensive disorders of pregnancy and abnormal second-trimester maternal serum levels of hcg and alpha-fetoprotein

To examine the association between hypertensive disorders of pregnancy and second-trimester maternal serum alpha-fetoprotein (MSAFP) and hCG levels. The proportions of abnormal second-trimester MSAFP and hCG levels in the serum samples from 65 women with true pregnancy-induced hypertension or preeclampsia (cases) were compared to the proportions of abnormal levels in all 1943 women without this disorder in the same cohort in a hospital setting. Maternal serum alpha-fetoprotein and hCG levels of the 65 cases also were compared to those of 325 completely uncomplicated matched control pregnancies, selected from the same cohort. Fisher exact test and Student t test were used for statistical analysis and P < .05 was considered statistically significant. An MSAFP level at least 2.5 multiples of the median (MoM) was found in two of 65 cases (3.1%) and in 27 of 1943 women (1.4%) in the rest of the cohort, a nonsignificant difference (relative risk [RR] = 2.2; P = .24). The statistical power to identify a significant difference for this RR was .27. An hCG level of at least 2.5 MoM was found in six cases (9.2%) and in 89 (4.6%) of women in the rest of the cohort, also a nonsignificant difference (RR = 2.0; P = .12). The statistical power to identify a significant difference for this RR was .38. The mean (+/-standard deviation) logarithms of the MSAFP and hCG MoMs in the 65 cases (0.039 +/- 0.191 and 0.048 +/- 0.265, respectively) were not significantly different from those in the 325 matched controls (0.006 +/- 0.148 and -0.010 +/- 0.244, respectively; P = .12 and .08, respectively). Although a weak association cannot be excluded, this study found no clinically important increase in risk of developing subsequent hypertensive disorders of pregnancy among women with abnormal second-trimester levels of MSAFP or hCG.

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

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