First Trimester Sex Hormone-Binding Globulin and Subsequent Development of Preeclampsia or Other Adverse Pregnancy Outcomes

Objective. To investigate whether first trimester maternal serum sex hormone-binding globulin (SHBG) concentrations are altered in women who subsequently develop preeclampsia or other pregnancy complications. Population. Women undergoing first trimester combined ultrasound and biochemical screening for chromosomal anomalies. We searched the database and identified 32 pregnancies resulting in miscarriage, 64 pregnancies with preexisting or gestational diabetes mellitus, 107 with fetal growth restriction, 103 with preeclampsia, 64 with pregnancy-induced hypertension, and 26 with spontaneous preterm delivery. We also selected 400 controls from among the population of pregnancies that had a delivery of a normal baby with no pregnancy complications. Methods. Maternal serum SHBG concentrations were measured retrospectively using a competitive chemiluminescent immunoassay. The levels between those with normal outcome and those resulting in adverse outcome were compared. Results. The median maternal serum SHBG concentration was not significantly different from controls, in those that subsequently developed preeclampsia (median MoM 1.05), nonproteinuric hypertension (median MoM 0.94) or preterm delivery (median MoM 1.15). The levels were significantly lower in those with diabetes (median MoM, 0.81 p = 0.0005) and those pregnancies resulting in miscarriage (median MoM 0.80, p = 0.008). Conclusion. First trimester maternal serum SHBG concentrations are no different from controls in women who subsequently develop preeclampsia, pregnancy-induced hypertension, fetal growth restriction, or preterm delivery. Levels are reduced in those who subsequently miscarry or in those presenting with diabetes.     

First trimester maternal serum free beta human chorionic gonadotrophin and pregnancy associated plasma protein A as predictors of pregnancy complications

Objective To examine the value of first trimester maternal serum free β human chorionic gonadotrophin (β hCG) and pregnancy associated plasma protein A (PAPP-A) as predictors of pregnancy complications.
Design Screening study.
Setting Antenatal clinics.
Population Singleton pregnancies at 10–14 weeks of gestation.
Methods Maternal serum free β hCG and PAPP-A were measured at 10–14 weeks of gestation in 5584 singleton pregnancies. In the 5297 (94.9%) pregnancies with complete follow up free β hCG and PAPP-A were compared between those with normal outcome and those resulting in miscarriage, spontaneous preterm delivery, pregnancy induced hypertension or fetal growth restriction and in those with pre-existing or gestational diabetes.
Results Maternal serum PAPP-A increased and β hCG decreased with gestation. The multiple of median maternal serum PAPP-A was significantly lower in those pregnancies resulting in miscarriage, pregnancy induced hypertension, growth restriction and in those with pre-existing or gestational diabetes mellitus, but not in those complicated by spontaneous preterm delivery. The level was < 10th centile of the reference range in about 20% of the pregnancies that subsequently resulted in miscarriage or developed pregnancy induced hypertension or growth restriction, and in 27% of those that developed gestational diabetes. Maternal serum free β hCG was < 10th centile of the reference range in about 15% of the pregnancies that subsequently resulted in miscarriage or developed pregnancy induced hypertension or growth restriction, and in 20% of those that developed gestational diabetes.
Conclusion Low maternal serum PAPP-A or β hCG at 10–14 weeks of gestation are associated with subsequent development of pregnancy complications.     

First-trimester maternal serum activin A in pre-eclampsia and fetal growth restriction.

OBJECTIVE: To investigate whether the reported increase in maternal serum activin A concentration in pre-eclampsia is evident from the first trimester. DESIGN: This was a case-control study carried out in antenatal clinics among singleton pregnancies at 10-14 weeks of gestation. METHODS: Activin A concentration was measured in stored maternal serum samples obtained at 11-14 weeks of gestation from 131 women who subsequently developed pre-eclampsia, 77 who developed non-proteinuric pregnancy-induced hypertension, 141 with fetal growth restriction in the absence of hypertensive complications and from 494 normotensive controls. RESULTS: Compared to the median activin A level in the control group (1.00 MoM), the median MoM in the patients who subsequently developed pre-eclampsia and pregnancy-induced hypertension (1.49 MoM and 1.32 MoM, respectively) was significantly increased (p < 0.001), and in patients with fetal growth restriction (1.02 MoM) it was not significantly different (p = 0.57). In the pre-eclampsia group (n = 131) the disease was considered to be sufficiently severe to necessitate iatrogenic delivery before 35 weeks in 25 patients, and in this group the median MoM was 1.92. CONCLUSION: Maternal serum activin A concentration at 12 weeks of gestation in pregnancies which subsequently develop hypertensive disease is increased, whereas in those complicated by fetal growth restriction it is normal.     

Second-trimester maternal serum marker screening: maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, estriol, and their various combinations as predictors of pregnancy outcome.

OBJECTIVE: We evaluated the value of all 3 common biochemical serum markers, maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, and unconjugated estriol, and combinations thereof as predictors of pregnancy outcome. STUDY DESIGN: A total of 60,040 patients underwent maternal serum screening. All patients had maternal serum alpha-fetoprotein measurements; beta-human chorionic gonadotropin was measured in 45,565 patients, and 24,504 patients had determination of all 3 markers, including unconjugated estriol. The incidences of various pregnancy outcomes were evaluated according to the serum marker levels by using clinically applied cutoff points. RESULTS: In confirmation of previous observations, increased maternal serum alpha-fetoprotein levels (>2.5 multiples of the median) were found to be significantly associated with pregnancy-induced hypertension, miscarriage, preterm delivery, intrauterine growth restriction, intrauterine fetal death, oligohydramnios, and abruptio placentae. Increased beta-human chorionic gonadotropin levels (>2.5 multiples of the median [MoM]) were significantly associated with pregnancy-induced hypertension, miscarriage, preterm delivery, and intrauterine fetal death. Finally, decreased unconjugated estriol levels (<0.5 MoM) were found to be significantly associated with pregnancy-induced hypertension, miscarriage, intrauterine growth restriction, and intrauterine fetal death. As with increased second-trimester maternal serum alpha-fetoprotein levels, increased serum beta-human chorionic gonadotropin and low unconjugated estriol levels are significantly associated with adverse pregnancy outcomes. These are most likely attributed to placental dysfunction. CONCLUSION: Multiple-marker screening can be used not only for the detection of fetal anomalies and aneu-ploidy but also for detection of high-risk pregnancies.     

Association between second-trimester isolated high maternal serum maternal serum human chorionic gonadotropin levels and obstetric complications in singleton and twin pregnancies

OBJECTIVE: The purpose of this study was to examine the clinical significance of high maternal serum human chorionic gonadotropin levels in the second trimester in singleton and twin pregnancies within the Ontario maternal serum screening program. STUDY DESIGN: The study group comprised 564 women with singleton pregnancies with total maternal serum human chorionic gonadotropin levels of > or =4.0 multiples of the median (MoM) and serum marker alpha-fetoprotein levels of <2.0 MoM. The cases were matched with 1692 control subjects who had both serum marker alpha-fetoprotein levels and maternal serum human chorionic gonadotropin levels of <2.0 MoM. The second part of the study comprised 93 twin pregnancies with maternal serum human chorionic gonadotropin levels of > or =5.0 MoM and serum marker alpha-fetoprotein levels of <4.0 MoM; the control group (n = 1496) had serum marker alpha-fetoprotein levels of <4.0 MoM and maternal serum human chorionic gonadotropin levels of <5.0 MoM. The final part of the study included 25 women with extremely high maternal serum human chorionic gonadotropin levels (> or = 14;10 MoM). RESULTS: Of the singleton pregnancies with maternal serum human chorionic gonadotropin levels of > or = 14;4.0 MoM, 22.5% had severe adverse obstetric outcomes, compared with only 10.9% of the matched control population (P =.001). Women with markedly elevated maternal serum human chorionic gonadotropin levels had significantly increased risks of having spontaneous miscarriage, small-for-gestational-age infants, pregnancy-associated hypertensive disorder, and preterm delivery. Of the women with twin pregnancies with high maternal serum human chorionic gonadotropin levels (> or =5.0 MoM), 71% had at least one complication (such as miscarriage and preterm delivery) compared with 55.3% in the control group. Finally, 23 of 25 women with extremely high maternal serum human chorionic gonadotropin levels (> or = 14;10 MoM) had serious adverse outcomes (such as fetal abnormalities, pregnancy-associated hypertensive disorder, premature separation of placenta, intrauterine growth restriction, neonatal respiratory distress syndrome, and neonatal jaundice). CONCLUSION: Pregnancies with an elevated maternal serum human chorionic gonadotropin level are associated with adverse obstetric outcomes. Increased maternal and fetal surveillance is warranted in these pregnancies.     

Decreased maternal serum placenta growth factor in early second trimester and preeclampsia

OBJECTIVE: To compare early second-trimester maternal serum placenta growth factor concentrations in patients with subsequent development of preeclampsia and those with normal pregnancies. METHODS: We conducted a case-control analysis of stored maternal serum of 27 women who subsequently developed preeclampsia and 227 randomly selected normal controls during the gestational period of 14-19 weeks. Using such a sample size, there was a greater than 95% power to test a difference in the primary study interest. A quantitative sandwich enzyme immunoassay was used to measure the maternal serum placenta growth factor concentration. For statistical analysis, Mann-Whitney U tests, multiple linear regression analysis, multivariable logistic regression model, and receiver-operating characteristic (ROC) curve were used. P <.05 was considered statistically significant. RESULTS: Maternal serum placenta growth factor concentration was associated with the occurrence of subsequent preeclampsia (P <.001) and gestational age (P <.001). The median (interquartile range) of multiples (MoM) of the gestational age stratified median for placenta growth factor in preeclampsia was 0.55 (0.33, 0.85). The ROC curve revealed that the specificity was 70% when the diagnostic sensitivity was 70%, and the optimal cutoff value of placenta growth factor MoM was 0.76. The risk of developing preeclampsia subsequently was increased 2.5-fold for maternal serum placenta growth factor concentration decrements of 0.1 MoM. CONCLUSION: A decreased maternal serum placenta growth factor concentration in the early second trimester is highly associated with the subsequent development of preeclampsia, but a large prospective study is needed to explore its use as an early predictor for the condition.     

Maternal serum level of placental growth factor in diabetic pregnancies

OBJECTIVE: To determine if maternal serum placental growth factor (PlGF) concentration at 11-14 weeks in pregnancies complicated by diabetes, including those with preexisting diabetes and those that developed gestational diabetes subsequently, differed from that in normal, uncomplicated pregnancies. STUDY DESIGN: PlGF concentration was measured in stored maternal serum samples obtained at 11-14 weeks of gestation from 82 women with diabetic pregnancies, including 32 with preexisting diabetes and 50 with gestational diabetes, and 400 normal controls. Gestational diabetes mellitus was diagnosed with the 75-g oral glucose tolerance test and by applying World Health Organization criteria. RESULTS: When expressed as the multiple of the median and adjusted for gestation, the log transformed values of PlGF were significantly higher (P < .05) in the diabetic group (mean multiple of the median, [MoM] 1.14; SD 0.11) as compared to the controls (mean MoM, 1.00; SD, 0.11). On further comparison between the diabetic groups with the controls, significant differences were found in the groups with gestational diabetes (mean MoM, 1.15; SD, 0.12) and non-insulin dependent diabetes (mean MoM, 1.16; SD, 0.09) but not in those complicated by insulin-dependent diabetes (mean MoM, 1.09; SD, 0.10). CONCLUSION: These findings suggest that in the first trimester of pregnancy the level of maternal PIGF was already significantly increased not only in pregnancies complicated by noninsulin dependent diabetes but also in those with gestational diabetes. The implications of these findings remain to be explored.     

Maternal Serum Human Placental Growth Hormone (hPGH) at 11 to 13 Weeks of Gestation in Preeclampsia

Objective. Human placental growth hormone (hPGH) is produced by human placenta and plays a central role in the maternal metabolic adjustments to pregnancy. The objective of this study was to investigate the maternal serum concentration of hPGH at 11–13 weeks of gestation in pregnancies that subsequently developed preeclampsia (PE), and to examine the possible association with uterine artery pulsatility index (PI) and maternal serum pregnancy-associated plasma protein-A (PAPP-A). Methods. The maternal serum concentration of hPGH at 11–13 weeks was measured in a case–control study from 60 cases that developed PE and 120 unaffected controls. The measured hPGH concentration was converted into a multiple of the expected median (MoM) in unaffected pregnancies. Regression analysis was used to determine the significance of association between hPGH MoM with uterine artery PI MoM and PAPP-A MoM. Results. In the pregnancies that subsequently developed PE the median serum hPGH concentration was not significantly different from that in the unaffected group (0.92 versus 1.00 MoM), whereas uterine artery PI was increased (1.31 versus 1.01 MoM) and serum PAPP-A was decreased (0.76 versus 1.01 MoM). In the group that developed PE there was no significant association between serum hPGH MoM and gestational age at delivery, uterine artery PI MoM, or serum PAPP-A MoM. Conclusion. The finding that in the PE group serum hPGH level during the first trimester is normal suggests that it is unlikely that this hormone plays a role in the pathogenesis of PE.     

Prediction of pregnancy complications by first-trimester maternal serum PAPP-A and free beta-hCG and with second-trimester uterine artery Doppler

BACKGROUND: Previous studies have shown an association between low first trimester maternal serum free beta-hCG and PAPP-A and subsequent development of pregnancy complications. Similarly, uterine artery Doppler in the late second trimester has shown that high impedance to flow is associated with increased risk for preeclampsia and fetal growth restriction. The objective of this study is to determine whether there is an association between the maternal serum concentration of PAPP-A and free beta-hCG at 11-13(+6) weeks with the uterine artery pulsatility index (PI) at 22-24 weeks, and secondly, to compare the screening characteristics of the two methods in the prediction of adverse pregnancy outcome. METHODS: Maternal serum PAPP-A and free beta-hCG at 11-13(+6) weeks and uterine artery PI at 22-24 weeks were measured in 4390 women with singleton pregnancies. Pregnancies with chromosomal defects or fetal anomalies were excluded. The biochemical and Doppler measurements were compared between those with normal outcome and those resulting in spontaneous preterm delivery, pre-eclampsia and fetal growth restriction (FGR). Detection rates using a combination of the biochemical and Doppler measurements were investigated. RESULTS: In the pregnancies resulting in pre-eclampsia (n = 64) and FGR (n = 172), the median PAPP-A was lower (0.844 and 0.813 MoM), the median uterine artery mean PI was higher (1.56 and 1.18) but the median free betahCG was not significantly different (0.923 and 0.933 MoM) than in the normal outcome group. In the preterm delivery group (n = 159), the median free beta-hCG (0.944 MoM) and uterine artery mean PI (1.06) were not significantly different from normal but the median PAPP-A (0.928 MoM) was significantly lower than normal. In screening for pre-eclampsia, the detection rate, for a 5% false-positive rate, was 14.1% for PAPP-A, 54.7% for uterine artery mean PI and 62.1% for a combination of PAPP-A and uterine artery mean PI. CONCLUSION: Maternal serum PAPP-A at 11-13(+6) of gestation is significantly lower in adverse pregnancy outcomes. The combination of first trimester serum PAPP-A and uterine artery mean PI at 22-24 weeks improves the screening efficacy for the prediction of pre-eclampsia.     

Decreased first trimester PAPP-A is a predictor of adverse pregnancy outcome

OBJECTIVE: Low levels of maternal serum pregnancy associated plasma protein-A (PAPP-A) have been linked to chromosome anomalies such as trisomy 21, 13 and 18, triploidy and sex chromosome aneuploidy. Low levels of PAPP-A have also been implicated in spontaneous miscarriage. The purpose of this study was to evaluate whether low levels of first trimester PAPP-A are predictive of other adverse pregnancy outcomes. STUDY DESIGN: The study included patients with singleton pregnancies who underwent combined first trimester screening using nuchal translucency (NT) and maternal serum free beta-human chorionic gonadotrophin (free beta-hCG) and PAPP-A at 10-13 weeks' gestation. Patients with chromosome aberrations or fetal anomalies were excluded. Serum marker levels were expressed as gestational age-specific multiples of the median (MoMs). The incidences of various adverse pregnancy outcomes (spontaneous preterm labor, fetal growth restriction (FGR), proteinuric and non-proteinuric pregnancy induced hypertension (PIH), intrauterine fetal demise, oligohydramnios, spontaneous miscarriage and placental abruption) were evaluated, according to maternal PAPP-A MoM levels. RESULTS: Of the 1622 patients in the study, pregnancy complications were observed in 184 (11.3%). Patients with PAPP-A < or =0.25 MoM had significantly higher rates of FGR (RR = 3.12), proteinuric PIH (RR = 6.09), spontaneous miscarriage (RR = 8.76). No statistically significant differences were noted for other adverse outcomes evaluated Women with PAPP-A < or =0.50 MoM also had significantly higher rates of FGR (RR = 3.30) and spontaneous miscarriage (RR = 3.78). CONCLUSIONS: We conclude that decreased levels of first trimester maternal serum PAPP-A are predictive not only of chromosome anomalies but also of adverse pregnancy outcome.     

C-reactive protein at 11–13 weeks’ gestation in spontaneous early preterm delivery

Objective: To examine the potential value of maternal serum level of C-reactive protein (CRP) in the first trimester of pregnancy in the prediction of spontaneous early preterm delivery. Methods: Maternal serum concentration of high-sensitivity CRP at 11–13 weeks’ gestation was measured in a case–control study of singleton pregnancies delivering phenotypically normal neonates, including 30 cases with spontaneous delivery before 34 weeks, with 15 cases presenting with contractions and 15 cases presenting with preterm premature rupture of membranes, and 90 matched controls delivering after 37 weeks. The median multiple of the median (MoM) serum CRP in the two outcome groups was compared. Results: The median serum CRP MoM was not significantly different in the spontaneous early preterm delivery group compared to the term delivery group (1.101, IQR = 0.572–1.985 vs. 0.975, IQR = 0.577–1.923; p = 0.813). The prevalence of CRP MoM above the 75th percentile was not significantly different between the early preterm delivery group compared to the term delivery group (26.7 vs. 24.4%; p = 0.811). In the preterm delivery group, the median serum CRP MoM in those presenting with contractions was not significantly different from those presenting with PPROM (1.175, IQR = 0.403–2.122 vs. 1.027, IQR = 0.659–1.940; p = 0.713). High-sensitivity CRP did not significantly improve prediction for preterm delivery over regular CRP. Conclusions: Measurement of maternal serum CRP at 11–13 weeks is unlikely to be useful in screening for spontaneous early preterm delivery.     

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.     

Maternal Plasma P-selectin at 11 to 13 Weeks of Gestation in Hypertensive Disorders of Pregnancy

Objective. To determine if development of preeclampsia is preceded by altered maternal plasma P-selectin and if the levels are related with uterine artery pulsatility index. Methods. Plasma P-selectin and uterine artery pulsatility index were measured at 11–13 weeks in 121 cases that subsequently developed preeclampsia, 87 cases that developed gestational hypertension and 208 unaffected controls. Results. In the preeclampsia group the median multiple of the median in controls (MoM) P-selectin and uterine artery PI were significantly increased (1.2 MoM and 1.3 MoM). There was no significant association between P-selectin and uterine artery pulsatility index in either the preeclampsia or control group. Conclusion. In pregnancies that develop preeclampsia there is evidence of platelet activation from the first trimester. However, there is no direct link between the degree of impaired placentation and platelet activation.     

First trimester maternal serum free human chorionic gonadotropin as a predictor of adverse pregnancy outcome

OBJECTIVE: The purpose of this study was to evaluate whether abnormal levels of first trimester maternal serum free human chorionic gonadotropin (beta-hCG) are predictive of adverse pregnancy outcomes. METHODS: The study included 1,622 consecutive patients with singleton pregnancies who underwent first trimester Down syndrome screening using nuchal translucency, and maternal serum free beta-hCG and pregnancy-associated plasma protein-A. Patients with fetal anomalies or chromosome aberrations were excluded from the study. The incidences of various adverse pregnancy outcomes were evaluated according to maternal serum free beta-hCG levels. Outcome variables included spontaneous miscarriage, proteinuric and non-proteinuric pregnancy-induced hypertension, fetal growth restriction, intrauterine fetal demise, spontaneous preterm delivery, oligohydramnios and placental abruption. RESULTS: No significant differences were noted between groups for any of the demographic variables. The only statistically significant result was an increase in the relative risk for spontaneous miscarriage (RR = 6.33) at free beta-hCG <0.2 multiples of the medians. No other statistically significant result was noted for the other adverse outcomes or for the overall complication rate. CONCLUSION: Low free beta-hCG is associated with a higher incidence of spontaneous miscarriage but is a poor predictor of other pregnancy complications.     

Maternal serum ferritin at 11- to 13-week gestation in spontaneous early preterm delivery

Objective: To examine the potential value of maternal serum level of ferritin in the first trimester of pregnancy in the prediction of spontaneous early preterm delivery. Methods: Maternal serum concentration of ferritin at 11–13-week gestation was measured in a case-control study of singleton pregnancies delivering phenotypically normal neonates, including 30 cases with spontaneous delivery before 34 weeks and 90 matched controls delivering after 37 weeks. The median multiple of the median (MoM) serum ferritin in the two outcome groups was compared. Results: The median serum ferritin MoM was not significantly different in the spontaneous early preterm delivery group compared with the term delivery group (1.143, interquartile range [IQR] 0.578–2.383 vs. 1.059, IQR 0.641–1.644, p = 0.725). Conclusions: Measurement of maternal serum ferritin at 11–13 weeks is unlikely to be useful in screening for spontaneous early preterm delivery.     

Mid-trimester placentation assessment in high-risk pregnancies using maternal serum screening and uterine artery Doppler.

OBJECTIVE: To determine the value of uterine artery velocimetry and mid-trimester maternal serum AFP/hCG measurements in predicting pregnancy complications in a high-risk group of pregnant patients. METHODS: Eighty-eight patients with chronic hypertension, previous preeclampsia, and thrombophilia were included. Maternal serum AFP/hCG was examined between 15-16 weeks gestation. Levels > 3 multiple of median (MoM) for hCG and > 2 MoM for AFP were considered abnormal. Color Doppler ultrasound was performed at 23-24 weeks gestation. Diastolic notching and pulsatility index (PI) above the 95th percentile were considered abnormal. RESULTS: Thirty-three patients had abnormal uterine artery waveform: 8 patients had abnormal maternal serum hCG and 5 had abnormal maternal serum AFP. Bilateral abnormal uterine artery waveform was associated with pregnancies complicated by lower gestational age at delivery (p=0.05) and birth weight (p<0.01), higher rates of preeclampsia (p=0.006), SGA (p=0.0001), preterm delivery (p=0.0001), and cesarean section rate (p<0.0001) in comparison to patients with normal uterine artery Doppler. Pregnant women with elevated hCG had higher rates of preeclampsia (p=0.006); preterm delivery (p=0.005) and SGA (P=0.03) and, lower birth weight (p=0.001). No significant differences were noted for clinical outcomes according to AFP data. Conclusions. Abnormal uterine artery waveform is superior to maternal serum hCG for identification of placental pathology leading to preterm delivery, low birth weight, and preeclampsia in high-risk pregnant patients.     

Maternal serum laeverin (aminopeptidase Q) measured in the first trimester of pregnancy does not predict preeclampsia

Objective: The aim of this study was to compare the laeverin level in maternal serum from first trimester (11–14 weeks) of pregnancy between normal pregnancies and pregnancies that later developed preeclampsia (PE).

Material and methods: This was a case-cohort study. The laeverin concentration was measured in cases with preterm PE (n?=?55), term PE (n?=?95), and a reference group of randomly selected women with normal pregnancy outcome (n?=?200) in stored serum samples collected from the double-test as part of the combined first trimester trisomy 21 screening program. The samples were thawed and analyzed for laeverin. The median gestational age at blood sampling was 77 days (range 57–96 days). Multiple regression analysis was performed to establish a normal median. Concentrations were converted to multiples of the median (MoM) and groups were compared using the Mann–Whitney U-test.

Results: In the reference group, laeverin was significantly correlated with gestational age (r?=?0.18, p?=?.01) and its concentration ranged from 41–393 µg/L. No significant differences in the median laeverin MoM were found between the reference group (1.01 MoM) and cases with preterm PE (0.98 MoM) or term PE (0.96 MoM).

Conclusions: First trimester maternal serum laeverin level cannot be used to predict preeclampsia.     

Total activin A in maternal blood as a marker of preterm delivery in low-risk asymptomatic patients

OBJECTIVES: To retrospectively evaluate whether increased serum levels of total activin A (t-activin A) are found in women who subsequently experience preterm delivery (PTD). METHODS: Data on maternal serum t-activin A concentrations were available from a total of 84 singleton pregnant women and included 14 PTD pregnancies, each matched for gestational age and length of freezer storage, with 5 control pregnancies having term delivery (TD). Analyte values were expressed as multiple(s) of the control median. RESULTS: The median t-activin A for controls and cases was 1.00 +/- 0.45 and 1.27 +/- 0.53 MoM, respectively. Univariate analysis of the MoM values was performed using the Kaplan-Meier algorithm. Differences in the rate of delivery using a t-activin A MoM cut-off of > or = 1 SD (equivalent to 1.26 MoM) were analysed using the log rank test. The cumulative rate of PTD (< 37 weeks) was significantly higher for women with t-activin A concentrations > or = 1.26 MoM than those with t-activin A concentrations below this cut-off (40% vs.. 10%, p-value = 0.0218 log rank test). CONCLUSIONS: T-activin A concentration is higher in women who will develop PTD in a low-risk population. T-activin A values are inversely proportional to the time elapsed from blood test to delivery. Prospective studies would determine the precise discriminability of this marker for PTD and the best week for performing the blood test, allowing for a proper calculation of the detection rate and a positive predictive value.     

The value of early third-trimester maternal serum alpha-fetoprotein determination.

The value of determination of maternal serum of alpha-fetoprotein (MSAFP) concentration in the second trimester is well established. In addition to open neural tube defects, pregnancies associated with elevated second-trimester MSAFP have been shown to be at increased risk for a variety of problems, including low birth weight, preterm delivery, and pregnancy-induced hypertension (PIH). We evaluated the potential usefulness of MSAFP in the early third trimester. MSAFP concentration was determined in over 200 women at the time of glucose screening. Results were analysed with regard to gestational age at sampling, maternal weight, race, diabetes, and presence of twins. MSAFP was twice as high in twin gestation, but not affected by race or the presence of diabetes. In contrast to levels in early gestation, third-trimester MSAFP does not appear to be predictive of preterm delivery, low birth weight, or PIH.     

Correlation between spontaneous preterm birth and mid-trimester maternal serum estriol

Abstract

Objective: Elevated third trimester salivary estriol levels have been associated with preterm birth. We evaluated whether maternal estriol concentrations from second trimester serum correlated with preterm delivery.

Methods: A retrospective cohort study of 7767 patients evaluated with second trimester aneuploidy screening. Unconjugated serum estriol was measured by immunoassay, expressed as multiples of the median (MoM) for gestational age and evaluated for association with preterm (<37 week) birth.

Results: Elevated maternal serum estriol was significantly associated with preterm birth (1.15 MoM versus 1.03 MoM for delivery at term, OR 1.69 CI 1.41 to 2.02). 9.95% of spontaneously laboring patients <34 weeks had estriol MoM?>?2, as opposed to 6.23% of >34 week deliveries (p?=?0.031). There was a direct correlation between level of estriol concentrations and gestational age at time of delivery.

Conclusions: Elevated second trimester maternal serum unconjugated estriol is independently associated with a higher rate of spontaneous preterm birth.