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.     

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.     

First-trimester ADAM12 and PAPP-A as markers for intrauterine fetal growth restriction through their roles in the insulin-like growth factor system

BACKGROUND: PAPP-A is a marker used as part of the most effective method of screening for chromosomal anomalies in the first trimester. ADAM12 is a recently discovered pregnancy associated member of the ADAM (a multidomain glycoprotein metalloprotease) family. Recently, ADAM12 has been shown as a potential marker for early screening for chromosomal anomalies. Both PAPP-A and ADAM12 have been identified as proteases to insulin-like growth factor binding proteins. In this role, they may have a regulatory function in controlling the amount of free bioactive insulin-like growth factor (IGF). We therefore wish to examine if the levels of either of these proteases are related to various growth related adverse pregnancy outcomes. MATERIALS AND METHODS: PAPP-A and ADAM12 were measured in a subset of samples collected at 11 to 14 weeks as part of an OSCAR clinic screening for chromosomal anomalies. Follow-up of pregnancies screened between September 1999 and August 2003 identified 1705 pregnancies with an outcome of intrauterine fetal demise on or after 24 weeks, preterm delivery at 24-34 weeks or 35-36 weeks, very low birthweight (<1.5 kg), low birthweight (<2.5 kg), large birthweight (>4.5 kg), and birth weight below the 3rd or 5th or 10th centile for gestation. A series of 414 normal outcome pregnancies constituted the control group.Marker levels were adjusted for gestation and maternal weight and the log MoM of the markers were compared using t-test of unequal variance between the control group and the various adverse outcome groups. RESULTS: ADAM12 and PAPP-A concentrations were reduced in low for gestational age birth weights and in all births with weights below 2.5 kg. There was a linear relationship between the severity of the IUGR and the decrease in PAPP-A and ADAM12. In the larger babies, only ADAM12 was found to be significantly increased in babies above the 90th centile of weight for gestation. CONCLUSIONS: The results of our study are compatible with the proposed role of ADAM12 and PAPP-A in promoting growth and development by breaking down IGF binding proteins and causing the release of free IGF for uptake into cells to promote growth. In those cases that eventually result in poor fetal growth, levels of PAPP-A and ADAM12 at 11-14 weeks are significantly lower than normal-in this instance, lowered PAPP-A and ADAM12 would result in less free IGF being available for cell uptake and growth stimulation. Further studies may elucidate if screening using such modalities can lead to new potential treatments for poorly growing fetuses.     

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.     

Use of insulin glargine during pregnancy: a case-control pilot study

OBJECTIVE: To determine whether the use of insulin glargine during pregnancy is associated with an increase in the incidence of fetal macrosomia or adverse neonatal outcome. DESIGN: A matched case-control study. SETTING: Women's Centre, John Radcliffe Hospital, Oxford, UK. SAMPLE: Sixty-four pregnant women treated with insulin during their pregnancies, 20 with type I diabetes and 44 with gestational diabetes. METHODS: Two groups of women were compared in matched pairs. A study group of 32 pregnant women with diabetes treated with insulin glargine during their pregnancy and a control group of 32 pregnant women treated with an intermediate-acting human insulin (isophane or insulin zinc suspension) and matched for weight at booking, height, gestation at delivery, parity, fetal sex, duration of insulin use in pregnancy and glycaemic control during the third trimester of pregnancy (glycosylated haemoglobin [HbA(1c)] concentration and mean blood glucose concentration). MAIN OUTCOME MEASURES: Birthweight, centile birthweight, the incidence of fetal macrosomia (birthweight > 90th percentile) and neonatal morbidity in the two study groups. RESULTS: There was no significant difference between the birthweight or centile birthweight of babies born to the women treated with insulin glargine during pregnancy and that of the babies born to those in the control group treated with intermediate-acting human insulin. The overall incidence of fetal macrosomia was 12/32 (37.5%) in the insulin glargine group and 13/32 (40.6%) in the control group. There was no significant difference in neonatal morbidity between the groups. CONCLUSIONS: The results of this pilot study indicate that insulin glargine treatment during pregnancy does not appear to be associated with increased fetal macrosomia or neonatal morbidity.     

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.     

Efficacy of intrauterine volume, fetal abdominal area and biparietal diameter measurements with ultrasound in screening for small-for-dates babies

Summary. The efficacy of total intrauterine, intra-amniotic and placental volume measurements with ultrasound in screening for low birthweight (10th and 3rd centile) was compared prospectively with fetal biparietal diameter and abdominal area measurements at 32 and 36 weeks gestation in an unselected population of 362 women. In all of them the gestation was dated by ultrasound in the first half of pregnancy. Reference values were from a separate normal population studied previously. Total intrauterine volume showed the highest sensitivity in predicting babies weighing 10th centile (58% at 32 weeks and 62% at 36 weeks) and those weighing 3rd centile (78% at 32 weeks and 83% at 36 weeks). A higher number of false-positive tests resulted in a lower predictive value of a positive test (mean 34% for babies weighing 10th centile) than that found for abdominal area (mean 54%). Abdominal measurements selected a smaller'at risk'group. Biparietal diameter, intra-amniotic and placental volume measurements had inferior predictive capability than total intrauterine volume and abdominal area. For screening purposes abdominal area measurements are presently more suitable than intrauterine volume. The higher sensitivity of intrauterine volume, particularly in early third trimester, is an advantage that requires further investigation with reference to intrauterine growth retardation.     

Zinc deficiency is not a cause for abortion, congenital abnormality and small-for-gestational age infant in Chinese women

Zinc concentration in serum and hair was measured in a cross-sectional study of 437 Chinese women of whom 310 were normal controls studied at various stages of pregnancy and up to 12 months after delivery. The rest had spontaneous abortions, fetuses with a birthweight below the 10th centile for gestation or congenital abnormalities. Zinc concentration fell throughout normal pregnancy, the fall being greater in serum than in hair. There was no correlation between serum and hair levels. The infant birthweight had a positive correlation with serum level but a negative correlation with hair level. Abortion, low birthweight and congenital abnormality were not associated with low concentrations of zinc in plasma or hair.     

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.     

Zinc deficiency is not a cause for abortion, congenital abnormality and small-for-gestational age infant in Chinese women

Summary. Zinc concentration in serum and hair was measured in a cross-sectional study of 437 Chinese women of whom 310 were normal controls studied at various stages of pregnancy and up to 12 months after delivery. The rest had spontaneous abortions, fetuses with a birthweight below the 10th centile for gestation or congenital abnormalities. Zinc concentration fell throughout normal pregnancy, the fall being greater in serum than in hair. There was no correlation between serum and hair levels. The infant birthweight had a positive correlation with serum level but a negative correlation with hair level. Abortion, low birthweight and congenital abnormality were not associated with low concentrations of zinc in plasma or hair.     

First-trimester maternal placental protein 13 levels in pregnancies resulting in adverse outcomes

BACKGROUND: In a previous study, reduced levels of maternal serum placental protein 13 (PP13) in the first trimester have been correlated with adverse pregnancy outcomes. The objective of this study was to compare first-trimester PP13 levels in control pregnancies with pregnancies resulting in one or more of the following adverse outcomes: intrauterine growth restriction (IUGR), small and very small (3rd, 5th, 10th centile) for gestational age (SGA), low (<1.5 and < 2.5 kg) birth weight (LBW), macrosomia (the > 90th centile), large birth weight (>4.5 kg), preterm (35-36 weeks) and very early (<34 weeks) delivery (PTD), and intrauterine fetal demise (IUFD). METHODS: Maternal serum samples from 1940, 11 to 14 weeks singleton pregnancies, were assayed for PP13 and the concentrations were corrected for gestational age, maternal weight, smoking status, and ethnic origin. A comparison of the levels of PP13 in 364 controls and 1576 adverse outcome categories was made. PP13 levels were expressed in terms of both concentration and multiple of medians (MoMs). RESULTS: Comparison of PP13 MoMs from SGA, PTD, and low birth weight samples with control pregnancy samples showed no statistically significant difference. In macrosomic pregnancies (>90th centile), levels of PP13 were significantly higher than controls (p = 0.0263) although the number of cases in this study was small. CONCLUSION: Decreased levels of PP13 were not significantly correlated with the studied adverse pregnancy outcomes of IUGR, PTD low birth weight, and IUFD. Further studies are required to evaluate if measurement of PP13 has any value in the early assessment of pregnancies.     

Maternal opiate use: pregnancy outcome in patients managed by a multidisciplinary approach.

The outcome of 39 pregnancies in 35 pregnant opiate users is reported. These women were managed by a multidisciplinary team resulting in 36 live births, one stillbirth. one spontaneous miscarriage and one induced abortion. The majority of patients were stabilised on methadone before the third trimester. The women were characterised by a high prevalence of previous obstetric and medical problems, 43.6% of the women were single and 87.2% unemployed The mean (SD) gestational age was 38.2 +/- 2.3 weeks, mean (SD) birth weight was 2980 +/- 543 g. There were eight cases of preterm deliveries, all occurred beyond 32 weeks' gestation. One preterm and two term babies had a birth weight below the 10th centile. Thirty-two (86.5%) women had a normal vaginal delivery, seven (10.8%) had caesarean section and one (2.7%) had forceps delivery. Comprehensive antenatal care in conjunction with methadone maintenance appears to result in a pregnancy outcome comparable with a general obstetric population.     

Is obstetric and neonatal outcome worse in fetuses who fail to reach their own growth potential?

OBJECTIVES: To determine the perinatal outcome of fetuses who had birthweights less than that expected from early third trimester ultrasound scanning. DESIGN: Retrospective estimation of centile fetal weight at early third trimester ultrasound scanning compared with actual centile birthweight corrected for gestational age, parity and sex. SETTING: Teaching Hospital Obstetric Unit, London. SUBJECTS: 197 unselected women with singleton cephalic pregnancies who were delivered at term in our unit between October 1989 and May 1990. MAIN OUTCOME MEASURES: CTG abnormality, need for fetal blood sampling in labour, meconium-staining of the amniotic fluid, mode of delivery, Apgar scores at 1 and 5 min, need for transfer of baby to neonatal unit, and need for neonatal intubation of the neonate at delivery. RESULTS: An actual birthweight greater than 5% less than the birthweight estimated from ultrasound scanning identified 44 babies (22%) with an increased risk of CTG abnormalities (chi 2 = 8.38, P less than 0.0025; Odds ratio (OR) = 2.54; 95% CI 1.36 to 4.78) and need for operative delivery (chi 2 = 5.81, P less than 0.0125; OR = 1.94; 95% CI 1.15 to 3.27), when compared with the remainder of the sample. Overall 14 (32%) of this group had birthweights above the 50th centile. A group of 44 babies selected as being the smallest for gestational age, without reference to growth pattern, had a similar excess morbidity. (All this group had birthweights below the 39th centile). CONCLUSIONS: This study supports the hypothesis that in-utero fetal growth pattern is as important for perinatal outcome as being small for gestational age per se.     

Pregnancy-associated plasma protein A, free beta-hCG, nuchal translucency, and risk of pregnancy loss

OBJECTIVE: To estimate the likelihood of clinical early and late pregnancy loss as a function of first-trimester maternal serum analytes and fetal nuchal translucency measurements. METHODS: Study subjects were recruited for a National Institute of Child Health and Human Development-sponsored multicenter cohort study initially designed to study the detection of Down syndrome during the first trimester of pregnancy. The cohort consisted of women who had a live fetus between 10 and 14 weeks of gestation and had no significant vaginal bleeding. Women with prior fetal trisomy (T21/18) and those with structural or chromosomal abnormalities in the index pregnancy were excluded. First-trimester screening consisted of pregnancy-associated plasma protein A (PAPP-A), free beta-hCG, and nuchal translucency. Pregnancy loss rates in women with various levels of PAPP-A, free beta-hCG, or nuchal translucency (less than 1st, less than 5th, more than 95th, and more than 99th percentile) were compared with losses in women with normal values (5th to 95th percentile). RESULTS: The mean gestational age at screening of 7,932 women meeting study criteria was 12.1 weeks. Loss rates were only 0.36% at less than 20 weeks after normal free beta-hCG, PAPP-A, and nuchal translucency. Conversely, low levels of PAPP-A and free beta-hCG as well as increased nuchal translucency were individually associated with increased early loss. These associations persisted after controlling for maternal age and race using logistic regression analysis. CONCLUSION: Normal values of PAPP-A, free beta-hCG, and nuchal translucency are associated with a very low risk of pregnancy loss at less than 20 weeks.     

Association of maternal serum progesterone in early pregnancy with low birth weight and other adverse pregnancy outcomes

Objective: To investigate the association of serum progesterone in first trimester with low birth weight (LBW, birth weight <2500?g) and other adverse pregnancy outcomes including hypertensive disorders of pregnancy, preterm delivery, premature rupture of membranes at term, and preterm premature rupture of membranes in a general population.

Methods: We conducted a cohort study of 263 women with low-risk singleton intrauterine pregnancies who had a spot serum progesterone measurement in the first trimester in a Singapore tertiary maternity hospital. Study outcomes were retrieved from clinical records. Follow-up data were available for 131 women. Univariate and multivariate logistic regression analyses were performed to assess the association of low serum progesterone (<35?nmol/L) with LBW and other adverse pregnancy outcomes.

Results: Low serum progesterone was associated with a significantly increased risk of LBW (adjusted odds ratio: 5.28 [1.02, 27.3]; p=0.047). Low serum progesterone was associated with a significantly increased risk of hypertensive disorders of pregnancy in univariate analysis (unadjusted odds ratio: 8.43 [1.31, 54.2]; p=0.025).

Conclusion: Low serum progesterone in the first trimester is a significant risk factor for LBW and possibly other placental dysfunction disorders such as hypertensive disorders of pregnancy. Further studies with larger sample sizes are needed to confirm the associations.     

Maternal serum hyperglycosylated human chorionic gonadotrophin (HhCG) in the first trimester of pregnancies affected by Down syndrome,using a sialic acid-specific lectin immunoassay

In a series of 54 cases of pregnancies complicated by Down syndrome and 224 unaffected pregnancies we examined maternal serum levels of hyperglycosylated human chorionic gonadotrophin (HhCG) in samples collected in the first trimester (11-13 weeks) using a sialic acid-specific lectin immunoassay. We compared these levels with those of other potential first trimester serum markers [free beta-hCG, pregnancy-associated plasma protein A (PAPP-A) and total hCG (ThCG)] and modeled detection rates and false-positive rates of various biochemical markers in conjunction with fetal nuchal translucency (NT) and maternal age using an maternal age standardized population. Maternal serum HhCG in cases of Down syndrome were significantly elevated (median MoM 1.97) with 24/54 (44%) of cases above the 95th centile for unaffected pregnancies. Free beta-hCG was also elevated (median MoM 2.09) with 33% of cases above the 95th centile. PAPP-A levels were reduced (median MoM 0.47) with 38% below the 5th centile. ThCG levels, whilst elevated (median MoM 1.34), had only 20% of cases above the 95th centile. Maternal serum HhCG levels were not correlated with fetal NT but showed significant correlation with ThCG and free beta-hCG and with PAPP-A in the Down syndrome group (r=0.536). Maternal serum HhCG levels in cases with Down syndrome had a significant correlation with gestational age, increasing as the gestation increased. When HhCG was combined together with fetal NT, PAPP-A and maternal age, at a 5% false-positive rate the modeled detection rate was 83%, some 6% lower than when free beta-hCG was used and some 4% better than when ThCG was used. Maternal serum HhCG is unlikely to be of additional value when screening for Down syndrome in the first trimester.     

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.     

Low PAPP-A levels between 11 and 13(+6) weeks of gestation and the risk of preeclampsia

PAPP-A is one of the 2 biochemical markers of the first trimester Down syndrome serum screening. In Bulgaria this screening was first performed in 2006. The threshold values for evaluation of the risk of development of preeclampsia used by the researchers vary in a wide range. Nevertheless in the last several years the most used value is 0.4 MoM. The aim of represented study is evaluate the low PAPP-A levels as a marker for development of preeclampsia alone, or in combination with some risk factors. The data of 194 singleton pregnancies that underwent a first trimester Down syndrome screening between January 2008 and June 2009 had been analyzed. Twenty three patients (11.6%) developed preeclampsia, of which 8 required delivery before 34th gw. The control group includes 134 women who had term deliveries of healthy babies. Nine out of 23 (39%) patients with preeclampsia, 5 out of 8 (62.5%) patients with early onset preeclampsia and 42 out of 134 (30.4%) controls had PAPP-A levels below 0.4 MoM. These levels are associated with relative risk for development of preeclampsia of 1.5 times. Low PAPP-A levels in the first trimester were associated with a low prognostic value for development of preeclampsia and early preeclampsia before 34th gw. When low PAPP-A levels are added to the maternal age and especially results of Doppler evaluation of the uterine arteries significant prognostic value improvement was observed.     

Growth retardation in preterm infants

This paper combines earlier results on the relation between birthweight and gestational age, and the relation between fetal weight and ultrasound measurements of the fetal biparietal diameter (BPD) and mean abdominal diameter (AD) to investigate whether preterm infants (viewed as a group) are smaller than unborn fetuses of the same gestational age. The birthweight distribution for each sex at 223 and 258 days gestation was derived from the birthweight-for-gestational age charts based on 3888 newborn infants. The sex-specific intrauterine weight distribution was estimated from ultrasound measurement of the fetal BPD and AD performed on randomly selected fetuses of gestational age 223 and 258 days. The birthweights were lower than the intrauterine weights, especially early in pregnancy and for female infants. Thus, the 10th birthweight centile for girls at day 223 corresponds to the 4th centile of the 'true' intrauterine weight, and the 'true' intrauterine 10th centile corresponds to the 25th centile birthweight at day 223.     

Growth retardation in preterm infants

Summary. This paper combines earlier results on the relation between birthweight and gestational age, and the relation between fetal weight and ultrasound measurements of the fetal biparietal diameter (BPD) and mean abdominal diameter (AD) to investigate whether preterm infants (viewed as a group) are smaller than unborn fetuses of the same gestational age. The birthweight distribution for each sex at 223 and 258 days gestation was derived from the birthweight-for-gestational age charts based on 3888 newborn infants. The sex-specific intrauterine weight distribution was estimated from ultrasound measurement of the fetal BPD and AD performed on randomly selected fetuses of gestational age 223 and 258 days. The birthweights were lower than the intrauterine weights, especially early in pregnancy and for female infants. Thus, the 10th birthweight centile for girls at day 223 corresponds to the 4th centile of the'true' intrauterine weight, and the'true' intrauterine 10th centile corresponds to the 25th centile birthweight at day 223.