The association between unexplained second-trimester maternal serum hCG elevation and pregnancy complications.

OBJECTIVE: We conducted this cohort analytic study to determine whether women with unexplained elevations of maternal serum hCG at 16-20 weeks' gestation are at increased risk for pregnancy complications and adverse perinatal outcomes. METHODS: The inclusion criteria were a singleton gestation, a confirmed gestational age, and an hCG level greater than 2.5 multiples of the median (MOM). The exclusion criteria were fetal anomalies, an abnormal karyotype, and a maternal serum alpha-fetoprotein (MSAFP) level greater than 2.5 MOM. A group of randomly selected women with normal hCG and MSAFP levels served as controls. RESULTS: Of the 6011 women screened, 284 (4.7%) had an unexplained elevated hCG level. Patients with elevated levels of hCG had a significantly higher risk for hypertension (odds ratio 4.4; 95% confidence interval [CI] 1.9-10) and fetal growth restriction (odds ratio 2.8; 95% CI 1-7). Women with hCG levels greater than 4 MOM also had an increased risk of preterm delivery (odds ratio 3.3; 95% CI 1.3-8.2). CONCLUSION: Pregnancies with unexplained elevated hCG levels should be regarded as high-risk pregnancies and managed accordingly.     

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.     

The association of abnormal alpha-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 alpha-fetoprotein levels may be prevented by intensive antenatal monitoring. STUDY DESIGN: Records of patients with elevated maternal serum alpha-fetoprotein values of > or =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 alpha-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 alpha-fetoprotein levels. However, in our study, routine pregnancy management was an acceptable method of detecting these adverse outcomes when they were detectable.     

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.     

Adverse obstetric outcome in low- and high- risk pregnancies: predictive value of maternal serum screening

OBJECTIVE: To determine whether the relationship between adverse pregnancy outcome and elevated maternal serum alpha-fetoprotein (MSAFP) and/or maternal serum hCG levels in women whose fetuses have no chromosomal abnormalities or neural tube defects is restricted to pregnancies with a priori elevated risk for pathology or also present in low-risk pregnancies. METHODS: The outcomes of pregnancy in two groups of patients with elevated MSAFP and/or maternal serum hCG values were compared with the outcomes of a reference group with normal serum values. The first study group consisted of 83 women without pre-existing risk for poor outcome as defined by the guidelines of the Dutch Society of Obstetrics and Gynecology. The second study group consisted of 62 women with a priori elevated risk according to these guidelines. RESULTS: Fetal or neonatal death, pregnancy-induced hypertension, placental abruption, placenta previa, preterm delivery, delivery of infants with birth weights in the 2.3rd percentile, and complications during the third stage of labor occurred significantly more often in patients with elevated values and low a priori risk than in women with normal values and without pre-existing risk factors. There was no significant increase in adverse pregnancy outcome in women with elevated values and high a priori risk compared with women with normal values and elevated a priori risk. CONCLUSION: In women at low risk, elevated MSAFP and/or maternal serum hCG values are predictive of adverse pregnancy outcome. In women with a priori elevated risk, abnormal serum values do not increase this risk.     

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.)     

Unexplained elevated midtrimester maternal serum levels of alpha fetoprotein, human chorionic gonadotropin, or low unconjugated estriol: recurrence risk and association with adverse perinatal outcome

OBJECTIVE: To determine if women experiencing an unexplained elevated maternal serum alpha fetoprotein (MSAFP; > or =2.0 MoM) or human chorionic gonadotropin (hCG; > or =2.0 MoM), or low unconjugated estriol (E3; < or =0.5 MoM) in one pregnancy are at increased risk for similar results in a subsequent pregnancy, and to determine if recurrence of these analyte extremes is associated with adverse perinatal outcome. METHODS: We identified all women delivering two consecutive singleton pregnancies at one hospital between 1992-1997 for whom second trimester trisomy 21 serum screen was performed in each pregnancy. All screens were performed in a single laboratory. Each pregnancy delivered after 20 weeks and had gestational age confirmed by ultrasound prior to 24 weeks. Subjects were excluded if a fetal anomaly or aneuploidy was present. Adverse outcomes included abruption, oligohydramnios, preeclampsia, preterm membrane rupture, preterm delivery, stillbirth, birthweight <10th centile, and admission to neonatal intensive care unit (NICU). RESULTS: A total of 538 women had 1,076 pregnancies meeting inclusion criteria; 12/515 (2.3%) of women with a normal MSAFP, 28/470 (6.0%) with a normal hCG, and 11/504 (2.2%) with a normal E3 in the first pregnancy had an anomalous result for the respective analyte in the second pregnancy. In contrast, only 4/23 (17.4%) patients with an elevated MSAFP (P = 0.003), 14/44 (31.8%) with an elevated hCG (P < 0.001), and 2/10 (20.0%) with a low E3 (P < 0.025) in the first pregnancy had the same analyte anomaly recur in the second pregnancy. The odds ratios for recurrent elevated MSAFP, hCG, and low E3 were 7.5, 5.3, and 9.2, respectively. Adverse perinatal outcomes occurred with similar frequency, regardless of MSAFP, hCG, or E3 results in consecutive pregnancies, using women with normal MSAFP, hCG, and E3 results in one or both pregnancies as controls. CONCLUSIONS: Women experiencing an anomalous serum analyte in one pregnancy are at significant risk to experience the same analyte result in a subsequent pregnancy.     

Utilidad de la alfafetoproteína sérica materna como parámetro de riesgo del embarazo

ObjectiveTo show that pregnant women with an unexplained maternal serum alphafetoprotein (MSAFP) elevation are at increased risk for adverse perinatal outcomesPatients and methods43.424 pregnant women were studied prospectively from the early second trimester until delivery. A risk factor for preterm delivery, fetal death, before and after 28 weeks of gestation, and low birth weight infants was calculated from the clinical history and MSAFP concentrationsResultsIn all the groups increasing levels of MSAFP are significatively associated with adverse perinatal outcomes, showing a significative difference with regard to the control group of pregnancies (MSAFP < 2,5 multiples of the median [MDM]). The highest relative risk was observed from pregnancies with fetal death before 28 weeks of gestationConclusionsPregnant women with unexplained elevations of MSAFP are at increased risk for adverse perinatal outcomes. However, the MSAFP, because of its low sensitivity, can not be considered as a screening tool to select this kind of pregnancies     

Hyperhomocysteinemia, pregnancy complications, and the timing of investigation

OBJECTIVE: To assess associations between vitamin-dependent homocysteine metabolism and vascular-related pregnancy complications by considering interval between delivery and postpartum investigation and maternal age. METHODS: Case-control study performed at the University Medical Center Nijmegen in the Netherlands. Patients had experienced pregnancy-induced hypertension (n = 37), preeclampsia (n = 144), hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome (n = 104), recurrent early pregnancy loss (n = 544), abruptio placentae (n = 135), intrauterine growth restriction (n = 144), or intrauterine fetal death (n = 104). Controls comprised 176 women with uncomplicated obstetric histories. Oral methionine loading tests and fasting vitamin profiles were performed more than 6 weeks after delivery. Odds ratios and 95% confidence intervals were calculated after logistic regression analysis. RESULTS: Hyperhomocysteinemia was associated with an approximately 2-fold to 3-fold increased risk for pregnancy-induced hypertension, abruptio placentae, and intrauterine growth restriction. Cobalamin deficiency was associated with HELLP syndrome, abruptio placentae, intrauterine growth restriction, and intrauterine fetal death. Pyridoxal 5-phosphate deficiency increased the risk for pregnancy-induced hypertension 4-fold. These associations lost their significance after adjustment for time interval and maternal age. High red cell folate was associated with a decreased risk for abruptio placentae and intrauterine growth restriction. An increased creatinine concentration was associated with pregnancy-induced hypertension, preeclampsia, HELLP syndrome, and abruptio placentae. CONCLUSION: Hyperhomocysteinemia and vitamin deficiencies are largely determined by the interval between delivery and postpartum investigation and by maternal age. Time interval and maternal age should be considered in the risk estimation for vascular-related pregnancy complications.     

The changing pattern of fetal death, 1961-1988.

The aim of this study was to assess any changes in cause-specific fetal death rates in the nonreferred population of a tertiary care unit. The fetal death rate (per 1000 births) among 88,651 births diminished from 11.5 in the 1960s to 5.1 in the 1980s. Fetal death due to intrapartum asphyxia and Rh isoimmunization has almost disappeared. Toxemia and diabetes continue to make similar and small contributions to fetal death rates. There has been a significant decline in unexplained antepartum fetal deaths and in those caused by fetal growth retardation, but no significant change in the death rate due to intrauterine infection or abruptio placentae. During the 1960s, the risk of fetal death was increased in women with hypertension, diabetes, or a history of stillbirth; during the 1980s, only women with a history of insulin-dependent diabetes were at risk. Improved application of current knowledge may help decrease the fetal death rate caused by fetal growth retardation. Reduction in deaths due to abruptio placentae, intrauterine infections, or lethal malformations, as well as unexplained antepartum deaths, appears to depend on better understanding of the etiology of these disorders.     

Very low second-trimester maternal serum alpha-fetoprotein: Association with high birth weight

OBJECTIVE:To investigate the relationship between very low maternal serum alpha-fetoprotein levels (MSAFP), neonatal size, and possible associations with obstetric complications. METHODS: This is a retrospective case-control study in a population managed prospectively by a standardized protocol. Perinatal outcomes were compared between patients with unexplained very low MSAFP (less than or equal to 0.25 multiples of the median) and control pregnancies with normal MSAFP, matched by precise gestational age, parity, maternal age within 1 year, and gender of the newborn. RESULTS:Of the 84,909 women screened, 464 (0.55%) met the definition of very low MSAFP. On tertiary evaluation, 226 had dates reassigned by ultrasound. After exclusion of overt diabetics, patients who were not pregnant, invalidated MSAFP, and 17 patients lost to follow-up, 178 women (0.21% of the total) had true very low MSAFP. True very low MSAFP was associated with subsequent miscarriage in 67 women and with fetal aneuploidy and/or serious abnormalities in 12 patients, leaving a population of 97 women (1.14 per 1000 women screened) with unexplained very low MSAFP. Without obvious demographic or obstetric factors, these women had heavier babies, more babies above the 90th percentile, more delivery complications caused by large birth weight (41 versus 16, chi(2), P <.001) compared with gestational-age matched controls from the same screened population who had normal MSAFP. CONCLUSION:Very low MSAFP predicts an unusually high rate of large birth weight infants, with increased fetal, intrapartum, and neonatal consequences. Maternal medical conditions or obvious demographic factors do not explain these consequences. These findings suggest a role for close fetal surveillance in the third trimester and extended efforts to assess maternal and neonatal glucose status.     

Elevated maternal serum alpha-fetoprotein: association with placental sonolucencies, fetomaternal hemorrhage, vaginal bleeding, and pregnancy outcome in the absence of fetal anomalies.

Elevated maternal serum alpha-fetoprotein (MSAFP) levels have been associated with an increased incidence of both placental sonolucencies and pregnancy complications. We designed a prospective study to test the hypothesis that the presence of these sonolucencies or a positive maternal Kleihauer-Betke stain would be associated with an elevated risk of obstetric complications. We enrolled 95 women with singleton pregnancies, elevated MSAFP, and no evidence of fetal anomalies on second-trimester ultrasound evaluation. Placental sonolucencies were documented at the time of ultrasound examination, and a maternal Kleihauer-Betke stain for fetal cells was obtained on the same day. Complications of pregnancy included fetal growth retardation, preterm delivery, late vaginal bleeding (at or after the 20th week of gestation), and fetal death. Women with elevated MSAFP had an increased incidence of placental sonolucencies, positive maternal Kleihauer-Betke stains, first-trimester vaginal bleeding, late vaginal bleeding, preterm delivery, fetal growth retardation, and fetal death compared with controls. Thirty-nine of 95 women with elevated MSAFP (41.1%) had at least one complication. In women with elevated levels, neither the presence of placental sonolucencies nor a positive Kleihauer-Betke stain correlated with first-trimester vaginal bleeding, the MSAFP level, or an increased risk of pregnancy complications. First-trimester vaginal bleeding was associated with an increased risk of preterm delivery in subjects with elevated MSAFP.     

Elevated maternal serum alpha-fetoprotein values. How low is high?

Most maternal serum alpha-fetoprotein (MSAFP) screening programs are set up with the goal of prenatal detection of fetal neural tube defects. It is also commonly accepted that MSAFP testing yields many false-positive results. Screening programs commonly utilize schemata that identify abnormal levels of MSAFP as greater than 2.5 multiples of the median (MOM) and also recommend two abnormal values before initiating ultrasound evaluation. Our pilot program evaluating obstetric outcomes found that 21 of the 29 women with elevated MSAFP values (greater than 2.0 MOM) eventually developed significant pregnancy management changes or complications of pregnancy. Thus, we believe that the use of MSAFP screening solely for the purpose of detecting fetal neural tube defects is inconsequential relative to its usefulness in detecting other pregnancy abnormalities. We also believe that ultrasound evaluation should be accomplished after the first abnormal value and that the cutoff of 2.5 MOM should be lowered to at least 2.0.     

Elevated maternal serum alpha-fetoprotein with low unconjugated estriol and the risk for lethal perinatal outcome

OBJECTIVE: To determine whether a combination of elevated maternal serum alpha-fetoprotein (MSAFP) and low unconjugated estriol (E3) concentration identifies pregnancies at particularly high risk for fetal abnormality or poor outcome. METHODS: Pregnancy outcomes were reviewed for women with elevated MSAFP (> or =2.0 MoM) from our database of 50,315 women who had received triple marker testing from 1993-1998. Outcomes for those with low E3 (< or =0.7 MoM) were compared with those with normal E3 (>0.7 MoM). The incidences of fetal death, neural tube defects, chromosome abnormalities, congenital abnormalities, preterm birth, small-for-gestational age (SGA), twins, and inaccurate dates were compared in the two groups using Fisher's exact test with P < 0.05 considered significant. RESULTS: Of the 50,315 women screened, 1,435 (2.85%) had an elevated MSAFP. Pregnancy outcomes were obtained in 94% of those with elevated MSAFP and 70% of all patients screened. Neural tube defects were present in 57 fetuses/infants (21 anencephalic, 29 spina bifida, 7 encephalocele) of which 46 (81%) had an elevated MSAFP. Of the 1,435 women with an elevated MSAFP, 199 (14%) had a low E3. Compared to those women with elevated MSAFP but normal E3, women with elevated MSAFP and low E3 were at significantly increased risk for fetal death (20.6% vs. 2.8%, relative risk (RR) 8.9), anencephaly (9.0% vs. 0.1%, RR 122.8) and chromosome abnormality (2.5% vs. 0.6%, RR 4.0). CONCLUSIONS: Pregnancies complicated by elevated second trimester MSAFP and low E3 are at a particularly high risk (32%) for lethal perinatal outcomes. Twins, while a common cause of elevated MSAFP, are rarely found when an elevated MSAFP is associated with low E3.     

Mathematic modeling to predict abruptio placentae

OBJECTIVE: This study was undertaken to identify correlates of abruptio placentae and to develop a mathematic model for the prediction of abruptio placentae. STUDY DESIGN: A total of 170,258 singleton birth records from 1991 to 1996 contained in the Schleswig-Holstein perinatal database were analyzed. Fifty-two recognized obstetric risk factors were subjected to univariate analysis. Correlates of abruptio placentae then underwent stepwise forward binary logistic regression. A constant value B(0), coefficients B(1) through B(p), an odds ratio, and a 95% confidence interval were calculated for individual correlates. RESULTS: Abruptio placentae occurred in 874 of 170,258 singleton gestations (0.5%). Of the 52 risk factors 31 proved to be correlates of abruptio placentae, with 16 among primiparous women and 25 among multiparous women. Ten correlates for primiparous, women and 13 for multiparous women emerged from the linear regression, with 7 correlates being shared by both primiparous and multiparous women. CONCLUSION: The probability that abruptio placentae will occur (p) can be calculated according to the following expression: p = e (z)/(1 + e (z)), where z = B(0) + B(1), em leaderB(p). For example, for a primiparous woman who smokes with bleeding at >28 weeks' gestation and a male fetus in the breech position, the following calculation would yield the chance of abruptio placentae:z = -2.25 + 2.51 + 0.41 + 0.24 + 0.60 = 1.51; p = e (1.51)/ (1 + e (1.51)) = 4. 53/5.53 = 0.82, or 82%.     

Maternal serum human chorionic gonadotropin as a marker for the delivery of Low-Birth-Weight Infants in women with unexplained elevations in maternal serum α-Fetoprotein

We wished to ascertain whether the measurement of maternal serum human chorionic gonadotropin (MShCG) in the serum of pregnant women with unexplained elevations of maternal serum α-fetoprotein (MSAFP) would more precisely define those women at risk of adverse pregnancy outcomes.

MShCG was measured in samples of serum obtained from women in the second trimester of pregnancy who had elevated MSAFP, normal Level II ultrasounds, and normal fetal karyotypes. Based on the characteristics of a receiver-operator curve for MShCG and birth weight, patients were divided into two groups and pregnancy outcomes were compared.

Pregnant women with an unexplained elevation in MSAFP, who also had an abnormal MShCG (≤0.5 MoM ≥2.5) were at significantly greater risk of delivering a low-birth-weight infant compared to women with a normal MShCG (43% and 15%, respectively; P = 0.013). They were also more likely to deliver a preterm infant (48% and 11.9%), respectively; P = 0.001). In the prediction of low birth weight, an abnormal MShCG had a sensitivity of 50%, a specificity of 81%, and a positive predictive value of 43%; in the detection of preterm delivery the values were 59%, 88%, and 48%, respectively.

These findings suggest that in pregnant women with a second trimester unexplained elevation in MSAFP, abnormal MShCG levels may identify a group of women at high risk of preterm delivery or delivery of a low-birth-weight infant.     

Extremely high maternal serum alpha-fetoprotein levels at second-trimester screening.

Maternal serum alpha-fetoprotein (MSAFP) screening is widely used for the detection of open neural tube defects (NTDs) and a variety of other anomalies and complications. We examined the outcomes of 44 pregnancies with MSAFP elevations of 8 or more multiples of the median (MoM) from among 40,676 screened pregnancies. At the initial evaluation by ultrasound, 82% of the patients had at least one finding that may have accounted for the elevation. Approximately 45% of the fetuses had a major fetal anomaly, 25% died, 16% had an identifiable placental abnormality, and 5% had an underestimation of gestational age; 18% of the elevations remained unexplained after ultrasound. In follow-up of the pregnancies, all of those with an unexplained elevation after initial ultrasound had at least one obstetric complication or placental abnormality. The overall positive predictive value of an MSAFP value of 8 or more MoM for NTDs was 22.7%. The proportion of infants born alive in the overall group was low, with only 16 live births among 46 fetuses. The majority of the nonviable outcomes were associated with a fetus with a major anomaly that was terminated or died before 20 weeks. Of the live-born infants, 31% had a major anomaly, 19% had intrauterine growth retardation (IUGR) and an anomaly, 12.5% had IUGR without an anomaly, and 25% were preterm. Eighty-eight percent of those pregnancies with a live-born infant had at least one obstetric complication. Among pregnancies with MSAFP of 8 or more MoM, the majority are associated with large structural fetal anomalies or fetal death before 20 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic hypertension in pregnancy

Chronic hypertension in pregnancy is associated with increased rates of adverse maternal and fetal outcomes both acute and long term. These adverse outcomes are particularly seen in women with uncontrolled severe hypertension, in those with target organ damage, and in those who are noncompliant with prenatal visits. In addition, adverse outcomes are substantially increased in women who develop superimposed preeclampsia or abruptio placentae. Women with chronic hypertension should be evaluated either before conception or at time of first prenatal visit. Depending on this evaluation, they can be divided into categories of either "high risk" or "low risk" chronic hypertension. High-risk women should receive aggressive antihypertensive therapy and frequent evaluations of maternal and fetal well-being, and doctors should recommend lifestyle changes. In addition, these women are at increased risk for postpartum complications such as pulmonary edema, renal failure, and hypertensive encephalopathy for which they should receive aggressive control of blood pressure as well as close monitoring. In women with low-risk (essential uncomplicated) chronic hypertension, there is uncertainty regarding the benefits or risks of antihypertensive therapy. In my experience, the majority of these women will have good pregnancy outcomes without the use of antihypertensive medications. Antihypertensive agents are recommended and are widely used in these women despite absent evidence of either benefits or harm from this therapy. These recommendations are based on dogma and consensus rather than on scientific evidence. There is an urgent need to conduct randomized trials in women with mild chronic hypertension in pregnancy.     

Sensitivity and specificity of screening for Down syndrome with alpha-fetoprotein, hCG, unconjugated estriol, and maternal age.

The sensitivity and specificity of maternal serum screening for Down syndrome with different biochemical markers were evaluated. Detection rates with different combinations of maternal serum alpha-fetoprotein (MSAFP), hCG, and unconjugated estriol (uE3) were established by retrieving and analyzing 54 serum specimens from women with confirmed Down syndrome pregnancies, compared with 657 specimens from women with normal outcomes. With a risk cutoff of 1:270 at the second trimester, the detection rate with MSAFP, hCG, and uE3 was two to three times higher than with MSAFP alone. With all three markers, the detection rate for Down syndrome increased from 50 to 77% as maternal age increased, and was 60% in a representative screened population. If uE3 was omitted, the detection rate decreased from 60 to 48%. One thousand women were screened prospectively, either with MSAFP or with all three markers prospectively, either with MSAFP or with all three markers and 4.1% with MSAFP. With the three markers, the positive predictive value for Down syndrome was 2.2% overall and as high as 5.9% in older women. Therefore, the addition of hCG and uE3 to the maternal serum screen increases the positive predictive value by 50-300%, depending on maternal age. These results confirm the efficacy of screening for Down syndrome using maternal age and three serum markers.     

Detection of trisomy 18 by double screening in a low-risk pregnant population

OBJECTIVE: A combination of low concentrations of maternal serum alpha fetoprotein (MSAFP) and human chorionic gonadotropin (hCG) was used to screen for trisomy 18 in early 2nd-trimester pregnancies in a low-risk child-bearing population. METHODS: Women less than 37 years of age were offered screening between 15 and 20 weeks of gestation. Those pregnancies showing low concentrations of MSAFP (<0. 75 multiples of the median) and hCG (<0.5 multiples of the mean) were considered positive. If gestational age was confirmed, genetic counselling and invasive prenatal diagnosis were offered. RESULTS: Between January 1995 and December 1996, 19,491 women were screened, of whom 252 were found to be positive (1.25%). 145 invasive procedures were carried out, and 3 cases were detected. The odds of a fetus being affected after a positive screen result were 1 in 36. CONCLUSIONS: Measurement of low concentrations of MSAFP and hCG in pregnant women less than 37 years of age is an effective screening test for Edward's syndrome, but with regard to the natural history of this genetic condition, it can result in overuse of invasive tests which in turn can harm chromosomally normal pregnancies. This stresses the need to evaluate these pregnancies further with detailed ultrasonographic assessment and selective fetal karyotyping only.