Second-trimester maternal serum alpha-fetoprotein and risk of adverse pregnancy outcome(1)

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 placental changes associated with elevated maternal serum alpha-fetoprotein

Measuring maternal serum alpha-fetoprotein (AFP) levels in the second trimester is an effective screening test for identifying pregnancies at increased risk for neural tube defects. In the absence of a neural tube defect there are many nonpathologic and pathologic causes for elevated AFP including underestimated gestational age, twin gestation, impending fetal death, and rare fetal malformations. In this series, intraplacental sonolucent spaces were detected in a significant percentage of second trimester pregnancies with elevated serum AFP in the absence of any other cause for the elevation. It is postulated that these cystic spaces are a conduit for the transfer of fetal blood into the maternal circulation, thus accounting for the nonpathologic AFP elevation in the maternal serum.     

Correlation of abnormal second trimester maternal serum alpha-fetoprotein (MSAFP) levels and adverse pregnancy outcome.

This study investigated the relationship between abnormal second trimester MSAFP levels and adverse pregnancy outcome. The findings revealed an association between low birth weight, prematurity and antepartum haemorrhage with abnormal unexplained high levels of second trimester MSAFP levels. However, macrosomia and increased gestational age at delivery were reported in relation to unexplained low levels of MSAFP in the second trimester. The positive predictive values for this test were poor (9-12%), that would question the use of this test to formulate a treatment plan. As the negative predictive values were high (96%), this test might be used to reassure women about their pregnancy.     

Effect of aspirin in prevention of adverse pregnancy outcome in women with elevated alpha-fetoprotein

Abstract

Background: To evaluate the effect of low-dose aspirin in prevention of adverse pregnancy outcomes (APO) in women with second trimester alpha-fetoprotein (AFP) >2.5 multiple of median (MOM) and to compare aspirin effect on women with normal and abnormal uterine artery (UtA) Doppler. The primary outcome was the adverse pregnancy outcome.

Methods: This randomized controlled trial was conducted in singleton pregnant women, who had unexplained AFP >2.5 MOM and gestational age between 15 and 18 weeks of gestation. They were assigned randomly to receive either aspirin (N?=?65) or control (N?=?68). UtA Doppler velocimetry studies were performed at the time of targeted ultrasonographic exam.

Results: Two groups were comparable regarding the maternal characteristics. The frequency of APO in aspirin and control groups were 26.1% versus 44.1% (p?=?0.045), the frequency of preterm delivery before 34 weeks were 3.2% versus 22.0% in aspirin and control group, p?=?0.001. Other outcomes were similar in both groups. The frequency of adverse outcomes in women with abnormal UtA Doppler was 39.1% in aspirin and 60.0% in control group, p?=?0.556.

Conclusion: Low-dose aspirin reduces APO and delivery before 34 weeks of gestation in pregnant women with unexplained elevated AFP.     

Elevated maternal serum alpha-fetoprotein (MSAFP): interpretation and follow-up

Maternal serum alpha-fetoprotein screening should be offered to all patients as a routine component of prenatal care. The benefits of MSAFP screening have far exceeded early expectations. This technology not only provides an efficient and cost-effective method of screening for neural tube defects that is applicable to all pregnancies but also provides the physician with important information relevant to other complications of pregnancy. Our knowledge of variables affecting MSAFP levels measured during pregnancy is rapidly evolving and further refinements in the application of MSAFP screening will almost certainly occur. Such refinements can only serve to extend the benefits of this new and very valuable technology in improving the health and well-being of mothers and infants.     

Unexplained elevated maternal serum beta-HCG concentration and adverse pregnancy outcome

OBJECTIVE: To investigate the association between unexplained elevated maternal serum beta-Human chorionic gonadotrophin (HCG) in the second trimester of pregnancy and adverse pregnancy outcome. METHODS: In a case-controlled study of 3463 women who opted for second-trimester serum screening for Down syndrome, 142 were found to have a serum beta-HCG of > or =3.5 multiples of the median (MoM), 56 of whom had a serum beta-HCG of > or =5.0 MoM. These women were compared with a control group of women with serum beta-HCG within the 95% confidence interval around the median. RESULTS: In the elevated beta-HCG group (> or =5 MoM) significantly more babies required admission to the special care baby unit (p = 0.02) and were small for gestational age (SGA) (p = 0.03). The mean birth weight was also significantly lower in the group with elevated beta-HCG. Women with a serum beta-HCG of > or =5, > or =6, > or =7 or > or =8 MoM were associated with SGA babies in 40, 44, 64 and 86% respectively. All babies born to the six women with beta-HCG of 8.75-24.1 MoM were SGA. CONCLUSION: Increased surveillance is necessary in pregnancies where the maternal serum beta-HCG in the second trimester is inexplicably elevated to > or =5 MoM.     

Tuboovarian pregnancy associated with elevated maternal serum alpha-fetoprotein. A case report.

Tuboovarian implantation is a rare form of pregnancy that is difficult to diagnose in early gestation. A patient with a tuboovarian pregnancy presented with abnormally elevated initial screening maternal serum alpha-fetoprotein (MSAFP). The elevated MSAFP and a pelvic mass of uncertain etiology on ultrasonography delayed the diagnosis until laparotomy was performed. Elevated MSAFP accompanied by oligohydramnios and a pelvic mass is a particularly suspect finding for a tuboovarian or other type of extrauterine implantation.     

Screening and management of inherited thrombophilias in the setting of adverse pregnancy outcome

Inherited thrombophilic conditions are associated with adverse pregnancy outcomes, including severe pre-eclampsia, fetal loss, abruptio placentae, and intauterine growth restriction. Although the prevalence of these complications is approximately 8% in the general population, their presence is associated with a significantly increased recurrence risk. Thrombophilic conditions most strongly associated with adverse pregnancy outcome include factor V Leiden, prothrombin gene mutation, and deficiencies of protein S, protein C, and antithrombin. Other thrombophilic conditions, such as protein Z deficiency, also appear to be associated with an increased risk of pregnancy complications. Antenatal administration of heparin to prevent pregnancy complications has shown promise in small studies, but a randomized, placebo-controlled trial is necessary to determine whether heparin administration is beneficial in preventing adverse pregnancy outcome.     

Unexplained elevated maternal serum alpha-fetoprotein is not predictive of adverse perinatal outcome in an indigent urban population.

OBJECTIVE: The null hypothesis of this study is that in an urban, indigent obstetric population at high risk for adverse perinatal outcome, unexplained elevations of maternal serum alpha-fetoprotein are not an additional predictor of adverse perinatal outcome. STUDY DESIGN: Perinatal outcomes of 72 patients from a clinic for indigent patients with unexplained elevated maternal serum alpha-fetoprotein levels were compared with those of matched controls from the same population with normal maternal serum alpha-fetoprotein levels. Subjects and controls were matched for age, race, parity, and presence or absence of Hollister risk factors. The frequency of adverse perinatal outcome in the two groups was subjected to matched-pair chi 2 analysis. RESULTS: Adverse perinatal outcome occurred in 38.9% (28 of 72) of subjects with unexplained elevated maternal serum alpha-fetoprotein levels greater than or equal to 2.5 multiples of the median, compared with 31.9% (23 of 72) of controls with normal maternal serum alpha-fetoprotein levels (p = 0.5). No statistically significant difference in adverse perinatal outcomes was found. CONCLUSIONS: Elevated maternal serum alpha-fetoprotein levels offer little if any additional predictive value for adverse perinatal outcome in populations already at high risk for such outcomes on the basis of obstetric or socioeconomic criteria.     

Isolated low second-trimester maternal serum beta-human chorionic gonadotropin is not associated with adverse pregnancy outcome

OBJECTIVE: We investigated whether low human chorionic gonadotropin from maternal serum screening is associated with adverse pregnancy outcome. STUDY DESIGN: Women between 15 and 20 completed weeks of gestation who had a maternal serum screen performed from June 1999 to November 2001 were studied. Cases included women with human chorionic gonadotropin values of 0.5 and <2.0 multiples of the median, and estriol values of >0.6 and <2.0 multiples of the median. Control subjects were selected randomly from the population of women with normal values for all three analytes. RESULTS: There were 146 case subjects and 292 control subjects. There was no increased risk in the study group compared with the control subjects for preterm delivery, intrauterine fetal death, low birth weight, abruptio placentae, preeclampsia, or preterm premature rupture of membranes. CONCLUSION: An isolated low human chorionic gonadotropin level from second-trimester maternal serum screening is not associated with adverse pregnancy outcome.     

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.     

Placental sonolucency and pregnancy outcome in women with elevated second trimester serum alpha-fetoprotein levels.

BACKGROUND AND PURPOSE: Women with unexplained elevation of serum alpha-fetoprotein (AFP) are at increased risk for adverse pregnancy outcomes, including small for gestational age neonate, preterm labor, abruptio placentae, preeclampsia, intrauterine fetal death, and congenital malformations. This study investigated the association between placental sonolucency, elevation of maternal serum AFP, and pregnancy outcomes. METHODS: Singleton pregnancies (n = 168) with second trimester serum AFP level >/= 2.0 weight-adjusted multiples of the median (MoM) were recruited as the study group. Women with second trimester serum AFP level between 0.4 and 2.0 weight-adjusted MoM (n = 150) served as controls. A maternal Kleihauer-Betke stain was obtained for all participants. All participants were prospectively evaluated and the pregnancy complications were assessed by chart analysis after delivery. RESULTS: Compared with control subjects, women with placental sonolucent areas were not at increased risk for pregnancy complications, while women without sonolucent areas had higher risk of pregnancy complications. Singleton pregnancies with elevated serum AFP level had increased incidence of feto-maternal hemorrhage when placental sonolucency was observed. CONCLUSIONS: Our data suggest that feto-maternal hemorrhage may be the major factor contributing to elevated maternal serum AFP levels in pregnancies carrying placental sonolucencies. Screening for pregnancies with both elevated serum AFP and placental sonolucencies would help to identify the low-risk cases and facilitate cost-effective obstetric management.     

Risks associated with an elevated maternal serum alpha-fetoprotein level.

Among 58,187 women tested, 1002 had a maternal serum alpha-fetoprotein measuring greater than or equal to 2.5 multiples of the median after correction for race, weight, and insulin-dependent diabetes. They were stratified into three groups: group 1, 2.5 to 2.9; group 2, 3.0 to 5.0; group 3, greater than or equal to 5.0 multiples of the median. The initial risk of a serious abnormality detected by ultrasonography or amniocentesis was 17% (5%, 12% and 65% in groups 1, 2, and 3, respectively). After correction for twins and dates, this risk became 23% (7%, 18%, and 71% in groups, 1, 2, and 3, respectively). Among the women with high maternal serum alpha-fetoprotein levels, 556 (77%) had normal ultrasonographic and amniocentesis studies, and the risk of adverse pregnancy outcome ws 27% (19%, 29%, and 70% in groups 1, 2, and 3, respectively). There was a statistically significant increase in late fetal and perinatal death, prematurity and growth retardation, oligohydramnios, abruptio placentae, preeclampsia, and congenital abnormalities. The overall risk for abnormality or adverse outcome was 24% in group 1, 41% in group 2, and 91% in group 3.     

Maternal serum alpha-fetoprotein (MSAFP) and fetal growth

Early mid-trimester screening of maternal serum alpha-fetoprotein (MSAFP) for the detection of neural tube defects is becoming a routine part of obstetrical care. In singleton pregnancies in the absence of fetal chromosomal abnormalities and anatomical anomalies high levels of AFP have been variably related to increased risk for low birthweight infant outcome. The overall relationship, if any, of maternal serum AFP to infant birthweight has, however, not been previously characterized. Between 15 and 20 weeks gestation, MSAFP values were determined for 110 women carrying single, anatomically and karyotypically normal fetuses. Statistical analysis utilizing polynomial and multilinear regression was used to determine the relationship of early mid-trimester MSAFP first to neonatal birthweight and then to gestational age and birthweight adjusted for gestational age. For every increase of one multiple of the median in MSAFP, neonatal birthweight fell 322 grams. This was accounted for almost entirely by decreased fetal growth; early mid-trimester MSAFP was linearly related to birthweight adjusted for gestational age ten times more strongly than to gestational age alone. The explanation for this relationship remains speculative, but the utility of routine AFP screening for the antenatal detection of intrauterine growth retardation certainly deserves further study.     

Association between first trimester maternal serum pregnancy associated plasma protein-A and adverse pregnancy outcome

AIMS: To investigate whether low pregnancy associated plasma protein-A (PAPP-A) levels in the first trimester of pregnancy are associated with subsequent intrauterine fetal growth restriction, stillbirth and preterm delivery. METHODS: A retrospective review of pregnancy outcomes was undertaken in women who had PAPP-A carried out in the first trimester of pregnancy at the time of nuchal translucency scan. Pregnancy outcomes were assessed by the review of medical records, and postal questionnaires. Delivery details were collected, including livebirth, neonatal birthweight and gestational age at delivery. The chi2 test was used to investigate the association between low first trimester serum PAPP-A levels and adverse fetal outcomes. Unpaired t-test was used for continuous variables. Sensitivities and specificities were then calculated. RESULTS: A total of 894 women who had blood collected for PAPP-A were identified, and data was obtained for 827 deliveries. Each had a normal karyotype. There were six intrauterine deaths, 13 babies with birthweights below the 3rd centile, 55 babies weighing below the 10th centile, and 96 women who delivered prematurely. Four of six intrauterine deaths had low PAPP-A levels (<0.5 multiples of the median), with a relative risk of 13.75. Low PAPP-A levels were associated with fetal weight below the 10th centile (P = 0.01) but not the 3rd centile. There was no statistically significant association between low maternal serum PAPP-A levels and preterm delivery. CONCLUSION: At 11-13 weeks' gestation, low maternal serum PAPP-A levels are associated with fetal death in utero and birthweight below the 10th centile. First trimester PAPP-A may be a useful tool for identifying pregnancies at risk of adverse fetal outcomes.