Maternal serum activin A levels in association with intrauterine fetal growth restriction

Objective To assess maternal serum activin A as a potential marker of fetal growth restriction.
Design A cohort study.
Setting A maternal–fetal medicine unit, university teaching hospital.
Population Fifty-seven women with a small fetus (less than 10th centile for gestation) referred for assessment of fetal size by ultrasound biometry.
Methods At the time of presentation for fetal biometry, maternal blood was collected for activin A measurement. The case records of each woman were independently reviewed after delivery and the pregnancy grouped into one of three groups: constitutionally small fetus, intrauterine growth restricted (IUGR) fetus or IUGR fetus and maternal pre-eclampsia (IUGR–pre-eclampsia). Activin A levels in the three groups were compared.
Main outcome measures Maternal serum activin A levels.
Results Sixteen of the 57 pregnancies were classified as constitutionally small, 17 as IUGR and 24 as IUGR–pre-eclampsia. Expressed as multiples of a normal median (MoMs), the median (95% CI) activin A level in the constitutionally small pregnancies was 1.12 (0.72–1.39) MoMs significantly lower than the level in both the IUGR pregnancies, 3.00 (1.84–4.11) MoMs, and the IUGR–pre-eclampsia pregnancies, 7.96 (5.73–10.62) MoMs (   P = 0.002 and 0.0001 for IUGR vs constitutionally small and IUGR–pre-eclampsia vs constitutionally small, respectively  ).
Conclusions Maternal serum activin A may be useful in the assessment of the small for gestational age fetus.     

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

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

Relationship among placenta previa, fetal growth restriction, and preterm delivery: a population-based study

OBJECTIVE: To examine the independent contributions of prematurity and fetal growth restriction to low birth weight among women with placenta previa. METHODS: A population-based, retrospective cohort study of singleton live births in New Jersey (1989-93) was performed. Mother-infant pairs (n = 544,734) were identified from linked birth certificate and maternal and infant hospital discharge summary data. Women diagnosed with previa were included only if they were delivered by cesarean. Fetal growth, defined as gestational age-specific observed-to-expected mean birth weight, and preterm delivery (before 37 completed weeks) were examined in relation to previa. Severe and moderate categories of fetal smallness and large for gestational age were defined as observed-to-expected birth weight ratios below 0.75, 0.75-0.85, and over 1.15, respectively, all of which were compared with appropriately grown infants (observed-to-expected birth weight ratio 0.86-1.15). RESULTS: Placenta previa was recorded in 5.0 per 1000 pregnancies (n = 2744). After controlling for maternal age, education, parity, smoking, alcohol and illicit drug use, adequacy of prenatal care, maternal race, as well as obstetric complications, previa was associated with severe (odds ratio [OR] 1.37, 95% confidence interval [CI] 1.25, 1.50) and moderate fetal smallness (OR 1.24, 95% CI 1.17, 1.32) births. Preterm delivery was also more common among women with previa. Adjusted OR of delivery between 20-23 weeks was 1.81 (95% CI 1.24, 2.63), and 2.90 (95% CI 2.46, 3.42) for delivery between 24-27 weeks. OR for delivery by each week between 28 and 36 weeks ranged between 2.7 and 4.0. Approximately 12% of preterm delivery and 3.7% of growth restriction were attributable to placenta previa. CONCLUSION: The association between low birth weight and placenta previa is chiefly due to preterm delivery and to a lesser extent with fetal growth restriction. The risk of fetal smallness is increased slightly among women with previa, but this association may be of little clinical significance.     

Socio-economic, demographic and obstetric risk factors for late fetal death of unknown etiology in Lithuania: a case--referent study

BACKGROUND: The purpose of this study was to evaluate the association between third trimester unexplained prelabor fetal deaths and various socio-economic, demographic and obstetric factors in Lithuania. METHODS: A case-referent study on 58 women with third trimester fetal death and 116 women with live fetus at term was carried out. Inclusion criteria for women in the first group (cases) were: prelabor fetal death of unknown etiology, singleton pregnancy >26 weeks of gestation and intact fetal membranes. For each case two referent women were recruited, admitted during the same period in active phase of labor at term (>37 weeks of gestation) with intact fetal membranes and fetus alive. Data were obtained by interview, anthropometry and by reviewing the medical records. Several potential socio-economic, demographic and obstetrical risk factors for unexplained fetal death were investigated. RESULTS: Univariate analyses determined several factors that were associated with fetal death of unknown etiology: low educational level, single marital status, low income, etc. After secondary logistic regression analysis only three independent variables remained significantly associated with otherwise unexplained stillbirth: small for gestational age fetus (OR 29.6; 95% CI 6.2-141.6), low income (OR 7.4; 95% CI 3.1-17.6), and maternal white blood cell count more than 16,000/mm3 (OR 5.4; 95% CI 1.4-21.6). Body mass index, smoking, occupation of women and other evaluated parameters were not confirmed to be significant risk factors. CONCLUSION: Small for gestational age fetus, low income and elevated maternal white blood cell count are factors significantly associated with late prelabor fetal death in Lithuania.     

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.     

Fetal activin A: associations with labour, umbilical artery pH and neonatal outcome

OBJECTIVE: To define the ontogeny of umbilical artery activin A at term and to evaluate activin A as a potential marker of perinatal hypoxia. DESIGN: A cohort study. SETTING: A university teaching hospital delivery suite. POPULATION: A convenience sample of 141 term pregnancies. METHODS: At delivery, umbilical artery and vein bloods were collected for blood gas measurements and subsequent measurement of activin A. Activin A levels were correlated with blood gas measurements and with labour and neonatal outcomes. MAIN OUTCOME MEASURES: Umbilical arterial activin A and pH. RESULTS: The median (95% CI) umbilical arterial activin A level at delivery was 1.38 (1.34-1.70) ng/mL. Levels varied significantly across gestation (P= 0.03), increasing from 36 to 38 weeks, thereafter decreasing to a nadir at 41 weeks. In 60 matched samples, the median (95% CI) venous and arterial activin A levels were 0.89 (0.81-1.06) ng/mL and 1.38 (1.21-1.61) ng/mL, respectively (P < 0.0001). Mean umbilical arterial pH was 7.20 (7.06-7.38; 5-95th centiles) and was not significantly correlated with log10 activin A (r=- 0.01; P= 0.68). Compared with healthy controls, there was no difference in arterial activin A in neonates identified as having suffered significant intrapartum asphyxia (P= 0.96). Fetal activin A levels were significantly lower in cases delivered by emergency caesarean section for complications during the first stage of labour compared with cases delivered vaginally (P= 0.003). CONCLUSIONS: Umbilical artery activin A does not appear to be a sensitive marker of fetal oxygenation or of risk of hypoxic-ischaemic encephalopathy.     

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.     

Prenatal alcohol exposure, CYP17 gene polymorphisms and fetal growth restriction

OBJECTIVE: To determine the association of maternal CYP17 gene polymorphisms and prenatal alcohol consumption with intrauterine growth restriction (IUGR). STUDY DESIGN: A case-control study in singleton livebirths was conducted at the Liverpool Women's Hospital between 2004 and 2005. Cases (n=90) were mothers with an IUGR baby and controls (n=180) those with a normal birthweight infant. Maternal genomic DNA was extracted from buccal smears and PCR (RFLP) was used for genotyping. RESULTS: Amongst cases, the prevalence of the maternal CYP17 homozygous wild type "A1A1", heterozygous "A1A2" and homozygous "A2A2" variants was 36.7%, 47.7% and 15.6%, which did not differ significantly from their prevalence amongst controls (p=0.6). The proportion with prenatal alcohol exposure was significantly higher in cases than controls (45.6% versus 30.6%, p=0.01). Mean birthweight was significantly lower in mothers with the CYP17 A1A1 genotype compared to those with variant genotypes (A1A2/A2A2) in both the alcohol-exposed (p=0.03) and non-exposed groups (p=0.01). In all women regardless of genotype, IUGR risk increased in mothers exposed to alcohol during pregnancy (OR, 2.9, 95% CI; 1.8-4.2, p=0.01). There was a significant interaction between the CYP17 A1A1 genotype and prenatal alcohol consumption for fetal growth restriction (adjusted OR, 1.4, 95% CI; 1.1-1.9, p=0.04). CONCLUSION: The association between prenatal alcohol exposure and intrauterine fetal growth restriction was modulated by the maternal CYP17 A1A1 genotype.     

Association of smoking during pregnancy and fetal growth restriction: subgroups of higher susceptibility

OBJECTIVE: To analyze the association between maternal smoking and fetal growth restriction, defined as a failure to achieve the growth potential, and to define subgroups of higher susceptibility for this association. STUDY DESIGN: A definition of growth restriction by customized birthweight standards applied to 13,661 non-malformed singleton deliveries. Customization was performed by maternal ethnic origin, height, booking weight, parity, gestational age at delivery and fetal gender. The adjusted risk of smoking for customized smallness-for-gestational age and the identification of subgroups with higher susceptibility were assessed by logistic regression. RESULTS: Overall, the adjusted odds ratio of smoking (all levels of exposure grouped) for the occurrence of growth restriction was 1.9 (95% confidence interval: 1.69-2.13). Smoking was etiologically responsible for 13.9% (95% confidence interval: 11.2-16.5) of the cases of growth restriction occurring in the population. Smoking resulted in an increasingly greater risk of growth restriction with progressive levels of cigarette consumption. The risk of smoking for fetal growth restriction was significantly greater in older women and those with a previous history of spontaneous preterm delivery. CONCLUSIONS: Smoking is associated with a higher risk for growth restriction. In addition, older pregnant women and those with a previous history of preterm delivery have an increased susceptibility.     

激活素A和卵泡休止素与先兆子痫的相关性研究

目的　探讨先兆子痫患者血清中激活素A和卵泡休止素水平及其mRNA在胎盘组织中的表达 ,及其与先兆子痫发病的关系。方法　 2 0例足月妊娠先兆子痫孕妇作为先兆子痫组 ,2 0例足月妊娠血压正常孕妇作为对照组。应用酶联免疫吸附试验 (ELISA)检测两组孕妇血清中激活素A和卵泡休止素水平。应用半定量逆转录 聚合酶链反应 (RT PCR)技术检测两组孕妇分娩后胎盘组织中激活素AmRNA和卵泡休止素mRNA的相对表达强度。将两组孕妇的胎盘组织激活素AmRNA的表达强度与血清激活素A水平进行直线相关分析。结果　 (1)先兆子痫组孕妇血清中激活素A水平为 (33 7± 6 6 ) μg/L ,明显高于对照组的 (9 9± 2 1) μg/L(P <0 0 1)。先兆子痫组孕妇血清中卵泡休止素水平为 (5 1± 0 6 ) μg/L ,与对照组的 (4 7± 0 3) μg/L比较 ,差异无显著性 (P >0 0 5 )。 (2 )先兆子痫组胎盘组织中激活素AmRNA为 1 11± 0 2 1,明显高于对照组的 0 6 1± 0 17(P <0 0 1)。先兆子痫组胎盘组织中卵泡休止素mRNA为 0 5 7± 0 31,与对照组的 0 5 4± 0 2 7比较 ,差异无显著性 (P >0 0 5 )。(3)在先兆子痫组和对照组孕妇中 ,血清中激活素A水平与胎盘组织激活素AmRNA相对表达强度呈正相关 [相关系数 (r) =0 89,P <0 0 1]。结论     

Folate, vitamin B12, and homocysteine levels in South Asian women with growth-retarded fetuses

OBJECTIVE. To investigate whether intrauterine growth retardation (IUGR) and preterm delivery in a poor population of South Asia was associated with altered maternal and fetal levels of folate, vitamin B12, and homocysteine. SUBJECTS AND METHODS. Hundred and twenty-eight pregnant women from a low socio-economic strata in the city of Lahore, Pakistan were followed with ultrasound of fetal growth from the 12th week of pregnancy. Blood samples were drawn from the woman and the cord at delivery. Serum was analyzed by a chemiluminescent immunoassay for folate and vitamin B12 and by fluorescence polarization immunoassay for total homocysteine (tHcy). RESULTS. Fourty-six infants showed IUGR. In term, but not preterm, deliveries with IUGR, maternal and cord blood folate levels were half of those in deliveries of normal birth weight infants (P=0.004 and P=0.005). The risk of IUGR was reduced among women with folate levels in the highest quartile (OR 0.31, 95% CI 0.10--0.84). There was no association between vitamin B12 and IUGR. Total homocysteine levels were higher in women delivering IUGR infants (P=0.02). There was an inverse correlation between cord blood folate and tHcy levels (r=-0.26, P=0.006). We also found increased risks for hypertensive illness (OR 3.5, 95% CI 1.4--8.6) and premature delivery (OR 2.5, 95% CI 1.1--6.2) in women in the highest quartile of tHcy. CONCLUSIONS. The occurrence of IUGR increased with low maternal and cord concentrations of folate and high maternal levels of tHcy. Further studies on the effects of vitamin B supplementation through pregnancy are warranted.     

Can ultrasound fetal biometry predict fetal hyperinsulinaemia at delivery in pregnancy complicated by maternal diabetes?

OBJECTIVE: The aim of this study was to determine whether there is an association between ultrasound fetal biometry and amniotic fluid insulin levels at delivery in women with pre-existing diabetes or impaired glucose tolerance in pregnancy. STUDY DESIGN: This retrospective cohort study identified 93 women who had amniotic fluid insulin levels measured at time of delivery. Standardised estimated fetal weight and fetal growth velocity were calculated from serial third trimester fetal ultrasound measurements. RESULTS: Women with pre-existing diabetes had significantly greater mean growth velocity [1.39 (95% CI: 0.43-2.23) versus 0.39 (95% CI: -01.7-0.95); p=0.04], significantly greater mean estimated fetal weight (EFW) Z score prior to delivery [2.36 (95% CI: 1.82-2.9) versus 1.38 (95% CI: 1.02-1.74); p=0.002] and greater mean birthweight centile [82 (95% CI: 0.74-0.89) versus 67 (95% CI: 58-76); p=0.02] than those with GDM/IGT. Amniotic fluid insulin levels demonstrated a similar significant difference between the pre-existing and GDM/IGT groups [20.5 (95% CI: 12.9-28.1) versus 8.5 (95% CI: 5.4-11.7); p=0.001]. An association between fetal growth and size and amniotic fluid insulin was observed in women with pre-existing diabetes. Positive likelihood ratios were 1.67 and 2.08, respectively, for the prediction of liquor insulin greater than the 95th centile in women with pre-existing diabetes. CONCLUSION: Ultrasound measures of fetal size and growth used in this study are not sufficiently accurate to predict those infants likely to be at risk from the adverse effects of fetal hyperinsulinaemia.     

Accuracy of serum uric acid in predicting complications of pre-eclampsia: a systematic review

BACKGROUND: Pre-eclampsia is one of the largest causes of maternal and fetal mortality and morbidity. Hyperuricemia is often associated with pre-eclampsia. OBJECTIVE: To determine the accuracy with which serum uric acid predicts maternal and fetal complications in women with pre-eclampsia. STUDY DESIGN: Systematic quantitative review of test accuracy studies. SEARCH STRATEGY: We conducted electronic searches in MEDLINE (1951-2004), EMBASE (1980-2004), the Cochrane Library (2004:4) and the MEDION database to identify relevant articles. A hand-search of selected specialist journals and reference lists of articles obtained was then carried out. There were no language restrictions for any of these searches. SELECTION CRITERIA: Two reviewers independently selected the articles in which the accuracy of serum uric acid was evaluated to predict maternal and fetal complications of pre-eclampsia. DATA COLLECTION AND ANALYSIS: Data were extracted on study characteristics, quality and accuracy to construct 2 x 2 tables with maternal and fetal complications as reference standard. Summary likelihood ratios for positive (LR+) and negative LR(-) test results are generated for various threshold levels of uric acid. MAIN RESULTS: There were 18 primary articles that met the selection criteria, including a total of 3913 women and forty-one 2 x 2 tables. In women with pre-eclampsia, a positive test result of uric acid greater than or equal to a 350-micromol/l threshold predicted eclampsia with a pooled likelihood ratio (LR) of 2.1 (95% CI 1.4-3.5), while a negative test result had a pooled LR of 0.38 (95% CI 0.18-0.81). For severe hypertension as the outcome measure, the LRs were 1.7 (95% CI 1.3-2.2) and 0.49 (95% CI 0.38-0.64) for positive and negative test results, respectively, and for caesarean section the LRs were 2.4 (95% CI 1.3-4.7) and 0.39 (95% CI 0.20-0.76). For stillbirths and neonatal deaths the respective LRs were 1.5 (95% CI 0.91-2.6) and 0.51 (95% CI 0.20-1.3). For the prediction of small-for-gestational-age fetus, the pooled LRs were 1.3 (95% CI 1.1-1.7) and 0.60 (95% CI 0.43-0.83) for positive and negative results, respectively. AUTHOR'S CONCLUSION: Serum uric acid is a poor predictor of maternal and fetal complications in women with pre-eclampsia.     

Factors associated with fetal demise in fetal echogenic bowel.

OBJECTIVE: The purpose of this study was to determine risk factors associated with intrauterine fetal demise in fetuses with unexplained echogenic bowel that is diagnosed in the second trimester. STUDY DESIGN: A retrospective case-control study compared fetuses with echogenic bowel and fetal demise with fetuses with echogenic bowel who were live born. Fetuses affected with cystic fibrosis, aneuploidy, or congenital infection and fetuses diagnosed with major anomalies were excluded. Variables examined in the determination of risk factors for intrauterine fetal demise included intrauterine growth restriction, oligohydramnios, elevated maternal serum alpha-fetoprotein levels, and elevated maternal serum beta-hCG levels. Statistical analysis was performed with the Fisher exact test, Student t test, and logistic regression analysis. RESULTS: One hundred fifty-six fetuses met the inclusion criteria. There were 9 cases of intrauterine fetal demise and 147 live born control fetuses. The median gestational age of intrauterine fetal demise was 22.0 weeks (range, 17-39 weeks). Intrauterine growth restriction occurred more frequently in cases of intrauterine fetal demise than in live born infants (22.2% vs 0.7%; P =.009), as did oligohydramnios (44.4% vs 2.0%; P <.001) and elevated maternal serum alpha-fetoprotein levels (80.0% vs 7.7%; P: =.001). With the use of logistic regression analysis, elevated maternal serum alpha-fetoprotein was the strongest independent risk factor that was associated with intrauterine fetal demise (odds ratio, 39.48; 95% CI, 11.04%-141.25%). CONCLUSION: In our series, there was a 5.8% incidence of intrauterine fetal demise in fetuses with unexplained echogenic bowel. Elevated maternal serum alpha-fetoprotein is the strongest predictor of fetal demise in fetal echogenic bowel.     

High levels of fetal cell-free DNA in maternal serum: a risk factor for spontaneous preterm delivery

OBJECTIVE: This study was conducted to determine whether there is a relationship between the concentration of fetal cell-free DNA in maternal serum and the duration of pregnancy in women who are at high risk for preterm delivery because of either preterm labor or preterm premature rupture of the membranes. STUDY DESIGN: Sera were collected and frozen from 71 women with a male fetus. Maternal serum fetal cell-free DNA concentration was measured with the use of real-time polymerase chain reaction amplification of DYS1. Fetal cell-free DNA concentrations were converted to multiples of the median. The following groups were studied: group 1: women with preterm labor and intact membranes who were delivered at > or = 36 weeks of gestation (n = 21); group 2: women with preterm labor who were delivered at <36 weeks of gestation (n = 29); and group 3: women with preterm premature rupture of the membranes in labor (n = 20) or not in labor (n = 1) who were delivered prematurely (<36 weeks of gestation). Kaplan-Meier and Cox regression analyses were used to analyze the relationship between fetal cell-free DNA concentrations and the likelihood of preterm delivery. RESULTS: A cut-off value for fetal cell-free DNA of 1.82 multiples of the median was chosen for analysis. The cumulative rate of early preterm delivery (<30 weeks of gestation) was significantly higher for women with fetal cell-free DNA concentrations of > or = 1.82 multiples of the median than those with fetal cell-free DNA concentrations below this cut-off (45% [95% CI, 36%-74%] vs 18% [95% CI, 11%-25%]; P = .008]. The cumulative rate of preterm delivery (<36 weeks of gestation) was also significantly higher at > or = 1.82 multiples of the median (73% [95% CI, 52%-93%] vs 66% [95% CI, 54%-79%]; P = .02). After adjustment for covariates, Cox analysis showed that fetal cell-free DNA at > or = 1.82 multiples of the mechanisms of disease that are associated with a mean hazard rate of delivery of 1.57 (P = .005). CONCLUSION: High concentrations of fetal cell-free DNA in maternal serum are associated with an increased risk of spontaneous preterm delivery. This observation may have implications for the understanding of the mechanisms of disease that is associated with preterm labor.     

Maternal serum activin A, inhibin A, and follistatin in pregnancies with appropriately grown and small-for-gestational-age fetuses classified by umbilical artery Doppler ultrasound

OBJECTIVE: The purpose of this study was to examine the relationship of maternal serum activin A, inhibin A, and follistatin with fetal growth and placental function. STUDY DESIGN: Inhibin A, activin A, and follistatin were measured in maternal serum that was stored from normally grown (control subjects, n = 50) and small-for-gestational-age pregnancies (n = 49), prospectively classified as normal small-for-gestational-age pregnancy or fetal growth-restricted pregnancy with the use of umbilical artery Doppler ultrasound. RESULTS: Activin A and inhibin A were significantly increased in fetal growth-restricted pregnancies compared with control subjects (activin A: regression coefficient, 0.54, P <.001; inhibin A: regression coefficient, 0.47, P =.003). The activin:follistatin ratio was significantly higher in fetal growth-restricted pregnancies compared with control subjects (P <.001). There were no significant differences between analyte levels of normal small-for-gestational-age pregnancies and control subjects. CONCLUSION: Maternal serum activin A, inhibin A, and activin:follistatin ratio are raised in fetal growth-restricted pregnancies but not in normal small-for-gestational age pregnancies. This provides further evidence of the difference between subgroups within small-for-gestational-age pregnancies and emphasizes the need to stratify for this in research.     

Serum activin A and inhibin A elevated in pre-eclampsia: no relation to insulin sensitivity

OBJECTIVE: To assess the possible role of serum levels of activin A, inhibin A and pro-alpha inhibin (pro-alphaC) in insulin sensitivity in pre-eclampsia. DESIGN: A prospective study. SETTING: Helsinki University Central Hospital. PARTICIPANTS: Twenty-two nulliparous women with proteinuric pre-eclampsia and 16 healthy nulliparous controls in the third trimester of pregnancy. METHODS: Serum samples were collected before and after intravenous injection of glucose (0.3 g/kg) and insulin (0.03 IU/kg) (the minimal model for testing insulin sensitivity), and were assayed for activin A, inhibin A and pro-alphaC. MAIN OUTCOME MEASURES: Comparison of the levels of activin A, inhibin A and pro-alphaC between pre-eclamptic and healthy pregnant women, and the association of these proteins with insulin sensitivity. RESULTS: In pre-eclampsia elevated levels of activin A (139%, P = 0.0001), inhibin A (39%, P = 0.003), and pro-alphaC (92%, P = 0.0008) were observed. The amount of proteinuria (0.3-10.5 g/day) correlated positively with serum concentrations of activin A (P = 0.01) and inhibin A (P = 0.02). These glycoproteins were not associated with insulin sensitivity either in women with pre-eclampsia or controls. A 2.9-fold rise in blood glucose and a 52.5-fold rise in insulin during testing using the minimal model were not accompanied by any significant changes in activin A, inhibin A, and pro-alphaC. CONCLUSION: Activin A, inhibin A, and pro-alphaC are elevated in pre-eclampsia but do not appear to relate to the insulin sensitivity in pre-eclamptic or normal pregnancies.     

Maternal serum and umbilical cord blood leptin concentrations with fetal growth restriction

OBJECTIVE: To ascertain whether fetal growth restriction is associated with alterations of leptin concentrations in umbilical cord blood and maternal serum. METHODS: Maternal serum and umbilical cord blood leptin concentrations were determined by immunoradiometric assay at term in 43 women with uncomplicated singleton pregnancies (group A) and in 27 women with singleton pregnancies complicated by fetal growth restriction (group B), all with normal pregravid body mass index (BMI). RESULTS: Maternal serum leptin concentrations were significantly higher in group B compared with group A (45.0 ng/mL [range 34.2-54.9] versus 29.0 ng/mL [range 24.7-33.3]; P<.01). Umbilical cord blood leptin levels were significantly lower in group B compared with group A (8.4 ng/mL [range 3.6-13.2] versus 13.1 ng/mL [9.7-16.5]; P<.01). Maternal serum leptin levels were not significantly correlated with maternal BMI or with neonatal birth weight in either group. Umbilical cord blood leptin concentrations were significantly correlated with neonatal birth weight in both groups. CONCLUSION: Growth restricted fetuses at term show umbilical cord blood leptin concentrations significantly lower than those in normal fetuses, suggesting that fetal adipose tissue is a major source of leptin. Maternal serum leptin concentrations are higher in the presence of a growth restricted fetus. This increase might be due to an intrinsic placental mechanism, by which small placentas produce more leptin as a compensatory mechanism, or to early hypoxia.