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.     

Predicting complications of pregnancy with first-trimester maternal serum free-betahCG, PAPP-A and inhibin-A

OBJECTIVE: To find whether fbetahCG, PAPP-A and inhibin-A levels in maternal serum or fetal nuchal translucency (NT) thickness at the first-trimester screening for trisomy 21 (T21) might detect women at high risk for adverse pregnancy outcomes. METHODS: A retrospective analysis of 1136 women with singleton pregnancy between 10 and 14 weeks. Women with pregnancy complications were allotted to five subgroups: small for gestational age (SGA), large for gestational age (LGA), gestational diabetes (GDM), hypertensive disorders, preterm delivery; women with normal pregnancy represented the control group. NT, maternal serum fbetahCG, PAPP-A and inhibin-A were measured. Mann-Whitney test was used for the comparison of fbetahCG, PAPP-A, inhibin-A and NT between a subgroup of a certain pregnancy complication and the control group. Multivariate logistic regression models were built to explore the relationship among different variables and the occurrence of pregnancy complications. RESULTS: PAPP-A values were significantly lower in women who delivered SGA babies (n=51, 0.76 MoM; p=0.002) and significantly higher in women who delivered LGA babies (n=120, 1.12 MoM; p=0.036). In women with GDM (n=27), fbetahCG, PAPP-A and inhibin-A were insignificantly lower than in controls, whereas in women with hypertensive disorders (n=56) no significant differences between the groups were found. In women with a preterm delivery (<34 weeks) (n=17), inhibin-A levels were significantly higher (1.25 MoM; p=0.015). CONCLUSION: Low PAPP-A level is associated with the delivery of an SGA baby and high PAPP-A with the delivery of an LGA baby. High inhibin-A is associated with preterm delivery before 34 weeks. Feto-placental products in the first trimester do not prove to be useful as a screening tool for predicting pregnancy complications.     

Use of the combined first-trimester screen result and low PAPP-A to predict risk of adverse fetal outcomes

OBJECTIVES: To investigate associations between combined first-trimester screen result, pregnancy associated plasma protein-A (PAPP-A) level and adverse fetal outcomes in women. METHODS: Pregnancy outcomes for 10,273 women participating in a community based first-trimester screening (FTS) programme in Western Australia were ascertained by record linkage to birth and birth defect databases. A first-trimester risk cut-off of > or = 1 in 300 defined screen positive women. RESULTS: Screen positive pregnancies were more likely to have Down syndrome and birth defects (chromosomal or nonchromosomal) than screen negative pregnancies. When birth defects were excluded, screen positive pregnancies were at increased risk of pregnancy loss, low birth weight and preterm birth. Pregnancies with low PAPP-A (< or =0.3 multiples of the median (MoM)) had higher risk of chromosomal abnormality, birth defect, preterm birth, low birth weight, or pregnancy loss, compared to those with PAPP-A > 0.3 MoM. In pregnancies without birth defects, low PAPP-A was a stronger predictor of preterm birth, low birth weight or pregnancy loss than a screen positive result. CONCLUSIONS: Women with positive screen or low PAPP-A were at increased risk for some adverse fetal outcomes. The sensitivity of these parameters was insufficient to support primary screening, but increased surveillance during pregnancy may be appropriate.     

The impact of assisted reproductive technology on the association between first-trimester pregnancy-associated plasma protein a and human chorionic gonadotropin and adverse pregnancy outcomes

We evaluated the impact of assisted reproductive technology (ART) on the association between first-trimester pregnancy-associated plasma protein A (PAPP-A) and human chorionic gonadotropin (β-hCG) and adverse pregnancy outcomes. PAPP-A and β-hCG levels were obtained between 11 and 13 (6)/ (7) weeks' gestation and converted to multiples of the median (MoM). MoM < 5th percentile was defined as low PAPP-A or β-hCG and those > 90th percentile as high. Adverse outcomes included small-for-gestational-age (SGA) infants, preeclampsia, pregnancy loss, and preterm delivery (PTD). Univariate and multivariate analyses were used to estimate the association. Of 4000 women meeting the inclusion criteria, 265 (7.6%) pregnancies were conceived by ART. ART pregnancies with low PAPP-A had a higher risk of having an SGA infant (odds ratio [OR] = 4.1, 95% confidence interval [CI] 1.2, 14.0) or PTD < 32 weeks (OR = 5.3, 95% CI 1.5, 18.6) compared with non-ART pregnancies with low PAPP-A (OR = 2.8, 95% CI 1.7, 4.7; OR = 3.9, 95% CI 2.1, 7.0, respectively). High PAPP-A was associated with pregnancy loss (OR = 6.1, 95% CI 1.1, 33.7) in ART pregnancies. Low β-hCG was associated with increased risk for PTD only in ART pregnancies (OR = 8.3, 95% CI 1.9, 35.9) for PTD < 37 weeks (OR 6.1, 95% CI 1.6, 23.0) for PTD < 35 weeks and (OR = 10.8, 95% CI 2.7, 43.7) for PTD < 32 weeks. High β-hCG was associated with increased risk for SGA (OR = 1.6, 95% CI 1.0, 2.5) and PTD < 37 weeks (OR = 1.4, 95% CI 1.0, 1.9) in non-ART pregnancies. The association between PAPP-A and β-hCG with adverse pregnancy outcomes is influenced by the mode of conception.     

Pregnancy-Associated Plasma Protein A Levels in Late First Trimester Pregnancies with Small-for-Gestational Age Neonates: A Prospective Case–Control Study

Objective

We aimed to investigate the association of pregnancy associated plasma protein A (PAPP-A) levels in late first trimester with small for gestational age (SGA) neonates and adverse pregnancy outcomes in a low-income setting.

Methods

The inclusion criteria were late first trimester (11–13 + 6 weeks) women with singleton and non-anomalous pregnancy. Enrolled participants were sampled for PAPP-A and prospectively followed up for delivery outcome and antenatal complications. A multiple of median (MoM) was calculated and statistically compared between groups.

Results

Out of total 284 subjects, 14.54% delivered SGA babies and formed cases (Group A), 66.5% delivered appropriate for gestational age (AGA) neonates with uneventful antenatal period (controls, Group B), and 19.3% were AGA group with adverse pregnancy complications (Group C). The late first trimester median PAPP-A MoM was significantly lower (0.61) in Group A compared to Group B (1.47). Using receiver operating characteristic (ROC) curve for PAPP-A MoM, optimal cutoff value was found at 0.45 MoM, with positive predictive value of 56.2%, specificity of 92.6% and sensitivity of 45%. The median interquartile range (IQR) of PAPP-A MoM value in Group C in comparison with Group B was significantly lower except for abruption. At PAPP-A MoM cutoff value <1, <0.8, <0.6 and <0.4, the odds ratio for adverse pregnancy outcome was 8.30, 7.29, 10.97 and 10.60, respectively, indicating an inverse relationship.

Conclusion

With 0.45 MoM cutoff of PAPP-A, the detection rate, specificity and positive predictive value for SGA were 45, 92.6 and 56.2%, respectively. As PAPP-A MoM values decreased, the odds ratio of having adverse pregnancy outcomes increased.

     

Pregnancy-associated plasma protein A and alpha-fetoprotein and prediction of adverse perinatal outcome

OBJECTIVE: To describe the association between pregnancy associated plasma protein A (PAPP-A), alpha-fetoprotein (AFP) and adverse perinatal outcome. METHODS: We conducted a multicenter prospective cohort study of 8,483 women attending for prenatal care in southern Scotland between 1998 and 2000. The risk of delivering a small for gestational age infant, delivering preterm, and stillbirth were related to maternal serum levels of PAPP-A and AFP. RESULTS: Women with a low PAPP-A were not more likely to have elevated levels of AFP. Compared with women with a normal PAPP-A and a normal AFP, the odds ratio for delivering a small for gestational age infant for women with a high AFP was 0.9 (95% confidence interval [CI] 0.5-1.6), for women with a low PAPP-A was 2.8 (95% CI 2.0-4.0), and for women with both a high AFP and a low PAPP-A was 8.5 (95% CI 3.6-20.0). The odds ratio for delivering preterm for women with a high AFP was 1.8 (95% CI 1.3-2.7), for women with a low PAPP-A was 1.9 (95% CI 1.3-2.7), and for women with both a low PAPP-A and a high AFP was 9.9 (95% CI 4.4-22.0). These interactions were statistically significant for both outcomes (P = .03 and .04, respectively). There was a nonsignificant trend toward a similar interaction in relation to stillbirth risk. Of the women with the combination of a low PAPP-A and high AFP, 32.1% (95% CI 15.9-52.4) delivered a low birth weight infant. CONCLUSION: Low maternal serum levels of PAPP-A between 10 and 14 weeks and high levels of AFP between 15 and 21 weeks gestation are synergistically associated with adverse perinatal outcome. LEVEL OF EVIDENCE: II-2.     

First-trimester combined screening for Down syndrome: prediction of low birth weight, small for gestational age and pre-term delivery in a cohort of non-selected women

OBJECTIVE: To establish the relationship between the first-trimester screening markers [pregnancy-associated plasma protein A (PAPP-A), free human chorionic gonadotrophin-beta (beta-hCG), nuchal translucency (NT)], the Down syndrome (DS) risk estimate, and the adverse outcomes such as low birth weight, small for gestational age (SGA) and pre-term delivery. METHODS: A retrospective cohort study including 1,734 non-selected singleton pregnancies consecutively enrolled into the programme of first-trimester combined screening for DS in a 12-month period at a single centre. Data from the Prenatal Patient Registry in ASTRAIA were combined with the Danish National Newborn Screening Registry and Danish Birth Registry. RESULTS: There was a significant relation between low PAPP-A MoM, low beta-hCG MoM, increased risk estimate for DS and low birth weight and SGA. Low PAPP-A MoM and increased NT showed a significant relation to pre-term and spontaneous pre-term delivery. Low PAPP-A MoM showed a significant relation to early pre-term delivery. CONCLUSION: First-trimester screening markers exhibited a significant relation to low birth weight, SGA and to some extent, to pre-term and early pre-term delivery. The screening performance of individual markers was poor.     

First trimester screening for Down syndrome in rhesus negative women

OBJECTIVES: To explore the effect of maternal rhesus status on first-trimester screening markers for Down syndrome. METHODS: We accessed a database of singleton pregnancies undergoing first-trimester genetic screen with maternal Rh status documented and pregnancy outcome information available. Excluded were cases of fetal chromosomal or structural abnormalities, or maternal systemic disease. Results of maternal serum pregnancy-associated plasma protein A (PAPP-A) and beta-human chorionic gonadotrophin (beta-hCG) adjusted for gestational age were compared between Rh-negative and Rh-positive women with p < 0.05 considered significant. RESULTS: Two thousand two hundred and two pregnancies fulfilled the study criteria, and 160 of them (7%) were Rh negative. Only free beta-hCG corrected multiples of the median (MoM) values were statistically increased in Rh-negative women (p < 0.009). Using a cut-off of 1:300, screen-positive rates of maternal serum biochemistry were not significantly different between Rh-negative and Rh-positive women (12.5 vs 10.4%, p = 0.41). CONCLUSION: The present study focused on measurements of beta-hCG and PAPP-A in the sera of women with Rh-negative blood group. Women with Rh-negative blood type have similar first-trimester serum PAPP-A MoM values as Rh-positive women, but significantly higher beta-hCG MoM values. However, there was no significant difference in the screen-positive rate for Down syndrome between the two groups.     

Pregnancy outcome in the setting of extremely low first trimester PAPP-A levels

Background: Serum pregnancy-associated plasma protein-A (PAPP-A) is part of first trimester Down syndrome screening. Low levels have been associated with adverse outcome as well as chromosomal abnormality.
Aims: To assess the incidence of adverse outcome when PAPP-A levels are at or below 0.2 multiples of the median (MoM).
Methods: Data on consecutive patients attending a first trimester screening program were collected. Those with PAPP-A levels ≤ 0.2 MoM were divided into three groups: ≤ 0.1 MoM; 0.11–0.15 MoM; and 0.16–0.2 MoM.
Results: Screening 44 535 patients resulted in 197 with PAPP-A levels ≤ 0.2 MoM. The incidence of karyotypic abnormality increased with decreasing PAPP-A levels. In the absence of chromosome abnormality, pregnancy outcomes were defined as 'normal' in at least 30% and 'good' in at least 60%, with both percentages increasing as the PAPP-A level rose. The PAPP-A levels were significantly lower in the group with a poor outcome. The incidence of prematurity was similar in the three groups, but higher than the statewide average, while the incidence of extreme prematurity appeared to be related to reducing PAPP-A levels. The incidence of growth restriction in the three groups was similar, but was still double the incidence in the normal population.
Conclusion: If the PAPP-A level is ≤ 0.2 MoM and the karyotype is normal, there is an increased risk of adverse outcome. Even with PAPP-A below 0.1 MoM, a good outcome can be expected in 60% of cases. Careful morphological assessment is suggested and later monitoring of fetal growth and well-being.     

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.     

The recurrence risk of adverse outcome in the second pregnancy in women with rheumatic disease1

OBJECTIVE: To study recurrence risks of adverse pregnancy outcome in the second pregnancy in women with rheumatic disease. METHODS: In a national population-based cohort study, women with rheumatic disease recorded from 1967 to 1995 in the Medical Birth Registry of Norway were compared with mothers without such diagnoses with regard to recurrence risks of adverse pregnancy outcomes in the second pregnancy. The odds ratios (ORs) of all outcomes were adjusted for maternal age, those of cesarean delivery for time period, and those of preeclampsia for interpregnancy interval. RESULTS: Women with rheumatic disease an dadverse pregnancy outcome in the first pregnancy had a statistically significant higher recurrence risk of the same event in the second pregnancy than women without rheumatic disease (preeclampsia: OR 2.22; 95% confidence interval [CI] 1.18, 4.19) (cesarean delivery: OR 1.52; 95% CI 1.05, 2.21) (preterm birth: OR 1.86; 95% CI 1.12, 3.11). In women with rheumatic disease diagnosed between the first and second births, a significantly increased recurrence risk of low birth weight occurred. Women with rheumatic disease also had a higher occurrence of markers for placental dysfunction (preeclampsia, preterm birth, or small for gestational age) in the second birth after any of these outcomes in the first birth (OR 1.35; 95% CI 1.02, 1.78) (35.1% versus 29.2%). CONCLUSION: The recurrence risk of an adverse outcome in the second pregnancy is increased in any woman, but was even higher in women with a rheumatic disease. These patients should be counseled accordingly, be closely monitored during pregnancy, and have access to appropriate subspecialists.     

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.     

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.     

Impact of high maternal hemoglobin at first antenatal visit on pregnancy outcomes: a cohort study

AIM: To determine whether high maternal hemoglobin (Hb) at first antenatal visit is associated with adverse pregnancy outcomes. METHODS: A retrospective cohort study was conducted in 920 singleton pregnancies who started their antenatal booking in the first trimester (125 g/L) were matched 1:1 with those who had normal Hb values (110-124 g/L) according to age group and parity. Adverse pregnancy outcomes including preeclampsia, gestational diabetes mellitus (GDM), preterm delivery, low birth weight (LBW), and small for gestational age (SGA) infants between both groups were compared. RESULTS: Complete obstetric records of 426 and 448 women who had high and normal Hb levels, respectively, were studied. By uni- and multivariable analyses, women with high Hb levels had significantly higher rates of preeclampsia and GDM than those with normal Hb levels; their adjusted relative risks were 3.8 (95% confidence interval [CI]; 2.0, 7.1) and 3.3 (95% CI; 1.8, 6.0), respectively. Rates of preterm delivery, low birth weight, and small for gestational age infants between the two groups were not significantly different. CONCLUSION: Our findings suggest that high Hb in the first trimester is associated with subsequent preeclampsia and GDM.     

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.     

Niveles séricos de PAPP-A y β-hCG en el primer trimestre del embarazo como predictores de resultados obstétricos desfavorables en el Hospital Universitario Nuestra Señora de Candelaria

Many studies have documented the association between low PAPP-A and β-hCG values in maternal serum during the first trimester and adverse maternal-foetal effects.To assess this relationship a retrospective analysis of cases and controls was carried out, based on a cohort of patients with a single pregnancy who underwent first-trimester screening between 2017 and 2018. For the group of cases, patients with MoM levels PAPP-A and/or β-hCG equal to or below the 5 th percentile were selected. The control group was obtained by making a randomized selection of all patients with MoM PAPP-A levels and/or β-hCG above that percentile.The analysis of our results showed that in groups with low levels of MoM PAPP-A and MoM β- hCG, we observed a higher risk of developing restricted intrauterine growth than in the control group (OR: 2.7 and 3.17, respectively). In the MoM PAPP-A ≤ p5 group we also obtained a 3.8-foldhigher risk of global hypertensive states of pregnancy (CI: 1.94-7.83) and 7.9-fold higher risk of antepartum foetal death (CI: 1.09- 217.4). These two variables were not statistically significant in the MoM β-hCG ≤ p5 group.Our findings confirmed that low levels of PAPP-A and β-hCG in the serum of pregnant women are associated with a high risk of developing obstetric complications, so they could be used for their early detection and the prevention of poor obstetric results.     

First trimester maternal serum pregnancy-associated plasma protein-A is a predictive factor for early preterm delivery in normotensive pregnancies

Abstract

In this study, we investigated whether the concentrations of pregnancy-associated plasma protein-A (PAPP-A) or free β-hCG (fβhCG) in the first trimester can identify women at increased risk of subsequent preterm delivery in the absence of hypertensive disorders. Preterm and early preterm deliveries are defined as those deliveries before completing 37 and 34 weeks, respectively. A total of 868 women were enrolled into this study. According to the level of the markers, the patients were evaluated in three groups: 1 – maternal serum level ≤5th percentile, 2 – between 5th and 95th percentiles, 3 – ≥95th percentile. In the group of patients with a PAPP-A level ≤5th percentile [≤0.35 multiples of the median (MoM)], mean gestational age (GA) at delivery, mean birth weight and the number of the cases with early preterm delivery were significantly lower than the others. Mean level of PAPP-A was significantly lower in cases with early preterm than term deliveries (0.58?±?0.32 versus1.09?±?0.69; p?=?0.01). Maternal serum level of fβhCG did not show significant difference between these groups (0.84?±?0.45 versus 1.17?±?0.77; p?=?0.15). Low levels of maternal serum PAPP-A (≤0.35 MoM) (Odds ratio?=?7; 95% confidence interval 1.8–27.7; p?=?0.0048) significantly predicted early preterm delivery in normotensive pregnancies. Women with low levels of PAPP-A at first trimester have a higher risk of early preterm delivery even in the absence of hypertensive disorders.     

The efficacy of first-trimester PAPP-A and free beta hCG levels for predicting adverse pregnancy outcome

OBJECTIVE: To determine whether first-trimester measurements of maternal serum PAPP-A and free beta hCG levels were associated with adverse pregnancy outcomes. STUDY DESIGN: First trimester maternal serum free beta hCG and PAPP-A were measured in 490 singleton pregnancies. Pregnancies were followed by the fetal-maternal unit, and predictive efficacy of these markers for small for gestational age (SGA) babies, gestational diabetes mellitus and hypertensive disorders were analyzed by cut-off values determined by using a ROC analysis, and also, by using the fifth percentile as the cut-off value. RESULTS: The sensitivities for PAPP-A in predicting pregnancies with a SGA baby and those complicated by a hypertensive disorder were 49% and 73%, respectively, when optimal cut-off values were used. Specificities were 76% and 65%, respectively. Serum free beta hCG had no predictive value for individual pregnancy outcomes. CONCLUSION: Efficacy of first trimester maternal serum markers in predicting adverse pregnancy outcome is low. Even after optimization of cut-off values, these markers do not appear to be clinically acceptable as an effective tool for screening for adverse pregnancy outcomes.     

Maternal serum free-beta-chorionic gonadotrophin, pregnancy-associated plasma protein-A and fetal nuchal translucency thickness at 10-13(+6) weeks in relation to co-variables in pregnant Saudi women

OBJECTIVE: To establish normative values and distribution parameters of first-trimester screening markers, namely, fetal nuchal translucency (NT), maternal serum free beta-human chorionic gonadotrophin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A), at 10 to 13(+6) weeks of gestation in Saudi women and to evaluate the effect of co-variables including maternal body weight, gravidity, parity, fetal gender, twin pregnancy, smoking and ethnicity on these markers. METHODS: A cohort of Saudi women (first cohort n = 1616) with singleton pregnancies prospectively participated in the present study, and fetal NT together with maternal serum free beta-hCG and PAPP-A were determined at 10 to 13(+6) weeks of gestation. The distribution of gestational age-independent multiples of the median (MoM) of the parameters was defined and normative values were established, and correction for maternal body weight was made accordingly. The influence of various co-variables was examined using the data collected from the first and the second (n = 1849) cohorts of women and 62 twin pregnancies, and compared with other studies. RESULTS: All markers exhibited log-normally distributed MoMs. Gestational age-independent normative values were established. Maternal body weight was corrected, particularly for maternal free beta-hCG and PAPP-A using standard methods. Fetal NT showed a negative relationship with increasing gravidity (r = -0.296) or parity (r = -0.311), whereas both free beta-hCG and PAPP-A exhibited a significant positive relationship. There was a significant increase in the MoM of free beta-hCG in female fetuses. Smoking decreased MoM values of free beta-hCG (by 14.6%; P < 0.01) and PAPP-A (by 18.8%; P < 0.001). Twin pregnancy showed significant increases in MoM values of free beta-hCG (by 1.87-fold) and PAPP-A (by 2.24-fold), with no significant changes in fetal NT MoM values. Fetal NT MoM values were lower in Africans and Asians but higher in Orientals, as compared to Saudi women (P < 0.05; in each case). MoM values (body weight-corrected) of free beta-hCG were 25.2% higher in Africans and 19.4% higher in Orientals but 6.8% lower in other Arabian and Asian (by 5.8%) women as compared to Saudi women (P < 0.05; in each case). CONCLUSIONS: The normative values and distribution parameters for fetal NT, maternal serum free beta-hCG and PAPP-A were established in Saudi singleton pregnancies, the maternal body weight together with smoking, twin pregnancy and ethnicity being important first-trimester screening co-variables. Gravidity, parity and fetal gender are also considered to influence one or more of the first-trimester markers examined.     

Low levels of maternal serum PAPP-A in the first trimester and the risk of pre-eclampsia

BACKGROUND: Low levels of pregnancy associated plasma protein-A (PAPP-A) have been previously shown to be associated with pregnancies that subsequently develop pre-eclampsia. The objective of this study was to establish the relative risk for pre-eclampsia at various PAPP-A levels as an aid to counselling and follow up of pregnancies. METHODS: Maternal serum PAPP-A and free ss-human chorionic gonadotropin (ss-hCG) levels at 11 to 13 weeks of gestation from 224 singleton pregnancies that subsequently developed pre-eclampsia were compared to those from 47,770 normal singleton pregnancies resulting in live births after 37 weeks with birth weight greater than or equal to the 10th centile of normal for gestation. In all cases, the measured PAPP-A and free ss-hCG levels were expressed as multiple of the median (MoM). The association between metabolite levels and the incidence of pre-eclampsia was assessed by comparing the relative incidence at a number of MoM cut-offs and at various centiles. At various marker levels, the likelihood ratio for pre-eclampsia was also calculated. RESULTS: In the pre-eclampsia group the median PAPP-A MoM was significantly reduced (0.772 MoM, p < 0.0001) whilst the median free beta-hCG MoM was not different from controls (0.981 MoM, p = 0.26). With decreasing levels of PAPP-A, the likelihood ratio for pre-eclampsia increased. At the 5th centile of normal (PAPP-A MoM 0.415) the odds ratio was increased 4-fold and at this cut-off 15% of cases of pre-eclampsia would be identified. CONCLUSIONS: The graphical presentation of a likelihood ratio curve for pre-eclampsia at any PAPP-A MoM level is likely to be useful in counselling women with low levels of PAPP-A and a normal karyotype. Use of low levels of PAPP-A for selecting women for further follow-up with uterine artery Doppler may further improve the clinical discrimination.