Maternal midtrimester serum AFP and free beta-hCG levels in in vitro fertilization twin pregnancies

We aimed to compare the levels of alpha-fetoprotein (AFP) and free beta-human chorionic gonadotrophin (beta-hCG) levels as multiples of the median (MoM) values between spontaneous and in vitro fertilized (IVF) twin pregnancies. The control group of spontaneous singleton pregnancies was used for calculating the gestational age specific median levels of the values. Within a cohort of 19 310 pregnancies, 145 twin pregnancies were identified. The data were collected from Down syndrome (DS) screening programmes in four University catchment areas in Finland between 1994-98. Maternal midtrimester serum marker levels were measured across gestational weeks 14-18. There were no fetal chromosome anomalies in either of the twin groups or the singleton group. Serum AFP of 145 and beta-hCG values of 39 spontaneous twin pregnancies were compared to the values of 6548 singleton pregnancies. In IVF twins 30 AFP and 29 beta-hCG values were compared to the levels of the control group. Both AFP and beta-hCG values were twice as high in the spontaneous twin pregnancies (medians 2.18 and 1.83 MoM respectively) as in the singleton group (medians 1.00 and 1.00 MoM respectively). In IVF twin pregnancies beta-hCG levels were higher (median 2.20 MoM) than in spontaneous twins (p=0.08), whereas no significant difference was found in AFP levels (2.30 MoM). In conclusion, the higher levels of beta-hCG levels in IVF twin pregnancies should be considered in DS screening to avoid high false positive rates.     

Maternal serum inhibin-A in pregnancies complicated by insulin dependent diabetes mellitus

We have examined whether insulin dependant diabetes mellitus (IDDM) affects maternal serum levels of inhibin-A, a recently described prenatal marker of Down's syndrome, by comparing levels in 169 women with IDDM with levels in 432 nondiabetic pregnant women between 15 and 20 weeks of gestation. There was a small but significant increase in the inhibin-A level in the diabetic women only when levels were corrected for maternal weight: median MoM 1.17 ( P < 0.01 vs controls, Student's t test). The underlying mechanism for this elevation in pregnancies complicated by IDDM currently remains obscure.     

Calcium sensing receptor in pregnancies complicated by gestational diabetes mellitus

Introduction

Infants born from mothers with Gestational diabetes mellitus (GDM) experience several complications, including a higher rate of postnatal hypocalcemia. In this study, we investigated the association between calcium sensing receptor (CaSR) and neonatal hypocalcemia observed in GDM pregnancies.

Methods

Our study consisted of 58 pregnant women with GDM and 40 healthy women and their neonates. CaSR placental expression was evaluated with immunohistochemistry and Western Blot. Three CaSR single nucleotide polymorphisms, A986S, R990G, Q1011E, were evaluated in neonate's genomic DNA. Serum Ca, P, Mg, 25(OH)D and PTH were measured in cord blood and at 2nd day of life.

Results

GDM neonates had lower mean cord blood Ca levels than controls (2.47 ± 0.21 mmol/l vs 2.59 ± 0.13 mmol/l, p = 0.001) while 15.5% developed postnatal hypocalcemia. CaSR expression was lower in GDM than in healthy placentas (p < 0.001). In the GDM group, reduced CaSR immunostaining in the syncytiotrophoblast (p = 0.042) and extravillous cytotrophoblasts (p = 0.002) was associated with lower Ca cord blood levels. Moreover, the absence of the S allele of the A986S polymorphism was associated with lower serum Ca levels both at birth (AA:2.41 ± 0.23 mmol/l, AS + SS: 2.57 ± 0.12 mmol/l, p = 0.002) and at 2nd day of life (AA:2.05 ± 0.22 mmol/l, AS + SS: 2.20 ± 0.18 mmol/l, p = 0.019).

Conclusions

Our results showed that CaSR is under-expressed in GDM compared with healthy placentas and this alteration may be associated with the lower Ca levels measured in cord blood of GDM infants. Placental CaSR seems to exert a local effect in fetal Ca homeostasis, which is dissociated from its contribution to the regulation of Ca homeostasis in postnatal life.     

Antenatal fetal testing in pregnancies complicated by gestational diabetes mellitus

Most obstetricians adapt some form of strategy for antenatal fetal testing in pregnancies complicated by gestational diabetes mellitus (GDM). There are, however, wide differences of opinion among providers as to the preferred protocol for such testing. The optimal method of fetal surveillance, the gestational age at which to start testing, the frequency of testing, and even whether all patients with GDM require antenatal testing are all controversial, unresolved issues. Indeed, in the absence of prospective, randomized clinical trials, it is impossible to determine whether antenatal fetal testing is beneficial in uncomplicated GDM. Moreover, it appears that even with the use of well-defined antenatal testing protocols, it is unavoidable that some women with GDM will experience an unexplained third trimester stillbirth. Pending the availability of solid data based on prospective trials, it is prudent to incorporate antenatal fetal testing in the management scheme of women with gestational diabetes.     

Maternal serum cytokine levels in pregnancies complicated by PROM

OBJECTIVE: The aim of the study was to evaluate the maternal serum cytokines levels in pregnancies complicated by premature rupture of membranes (PROM). MATERIALS AND METHODS: Maternal serum of IL-1 beta, IL-4, IL-6, IL-8 and TNF-alfa levels were assessed in patients with PROM between 24-34 weeks of pregnancy (n = 45). Control group consisted of healthy pregnant women (n = 41) at 24-34 weeks of gestation. Serum cytokines concentrations were measured by commercial available enzyme-linked immunosorbent assays. C-reactive protein level and WBC were estimated in both groups. RESULTS: Compared to healthy pregnant, the group of patients with PROM had significantly higher serum levels of IL-1 beta (0.76 pg/ml vs 0.41 pg/ml, p = 0.022), TNF-alfa (1332.46 pg/ml vs 58.01 pg/ml, p < 0.00001) and IL-8 (15.79 pg/ml vs 0 pg/ml, p < 0.00001). CRP concentration and WBC were also significantly higher in serum of pregnant women with PROM then in healthy ones (CRP: 10 mg/l vs 0 mg/l, p = 0.043; WBC: 13,188 +/- 3625/mm3 vs 9132 +/- 1913/mm3, p < 0.00001). No significant differences in IL-6 and IL-4 levels were found between groups. CONCLUSION: Differences in serum maternal levels of cytokines between patients with premature ruptures of membranes and healthy pregnant women suggest that reasons and/or consequences of PROM results in changes in immunological system.     

Maternal serum alpha-fetoprotein levels in low birth weight singleton pregnancies

Maternal serum alpha fetoprotein (MSAFP) measurement between 16 and 21 weeks gestation is used to define a group of women with an increased risk of fetal abnormality, particularly open neural tube defect. The test is strongly gestation dependent and women with high MSAFP levels require sonar scan examination to define gestation, exclude twins and examine the fetus for obvious malformation or death. It has been reported that women with no primary cause for raised MSAFP have an increased incidence of low birth weight babies. Conflicting reports have separately ascribed these to premature delivery and to intra-uterine growth retardation. We have studied the relationship between MSAFP and low birth weight infants with respect to both prematurity and retarded fetal growth. MSAFP values were expressed as multiples of the appropriate weekly median (MOM) values relating to normal pregnancies with normal outcomes at term. For our normal population an MSAFP value of 2 MOM is the 95% centile, i.e. 5% of normal outcome pregnancies of sure gestation will have MSAFP values in the second trimester which are at or above 2 MOM. Information was available on 389 women whose infants were liveborn singletons weighing 2.5 kg or less. 33 (8.5%) of these women had MSAFP greater than 2 MOM (p less than 0.005) and of the 145 women whose babies weighed less than 2 kg, 17 (11.7%) had MSAFP at this level (p less than 0.001) Tab. I).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of exercise on placental blood flow in pregnancies complicated by hypertension, diabetes or intrahepatic cholestasis

The effects of a standardized exercise test on intervillous placental blood flow were studied in 13 hypertensive, 10 diabetic and 8 cholestatic pregnant women in late pregnancy, and the results were compared with those of a normal control group. Analysis of variance for repeated measures revealed that in all the pathologic groups, placental blood flow was lower than in the controls. In all groups placental blood flow rose slightly 1 min after the cessation of exercise. The diabetics showed a decreased placental blood flow 30 min after the cessation of the exercise test (p less than 0.02). In diabetics, a fall was found in stroke volume, from 63 +/- 12 ml (mean +/- SD) before the exercise to 53 +/- 11 ml 30 min after the cessation of exercise (p less than 0.05), and a rise in peripheral vascular resistance, from 1540 +/- 200 (mean +/- SD) dynes/cm5 before exercise to 1750 +/- 390 dynes/cm5 30 min after the cessation of exercise (p less than 0.05). Pre-eclamptic patients had a higher peripheral vascular resistance than had normal controls. Pre-eclamptic, diabetic and cholestatic patients had lower cardiac index values than the normal subjects. The difference was significant in the pre-eclamptic and diabetic patients at 30 min after the cessation of exercise. Maternal heart rate, and systolic, diastolic and mean arterial blood pressures rose significantly from values at rest to values at the end of exercise in all groups. One of the pre-eclamptic patients showed a 74% decline in placental blood flow 1 min after the cessation of exercise coincident with fetal bradycardia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Amniotic fluid and cord plasma erythropoietin levels in pregnancies complicated by preeclampsia, pregnancy-induced hypertension and chronic hypertension

AIMS: The purpose of the present study was to compare fetal and neonatal outcomes with amniotic fluid erythropoietin (EPO) levels obtained in the antepartum period in pregnancies complicated by preeclampsia, pregnancy-induced hypertension or chronic hypertension. METHODS: Erythropoietin concentrations were measured in amniotic fluid within 2 days before delivery and in cord blood at birth in 75 hypertensive women and in 23 healthy controls delivered by cesarean section before labor contractions. Erythropoietin levels did not influence clinical decisions. RESULTS: Amniotic fluid erythropoietin levels correlated highly significantly with cord plasma EPO levels and were significantly higher in pregnancies complicated by hypertension than in control pregnancies. Umbilical arterial pH, acid-base and blood gas values at birth were not different from controls. Both cord plasma and amniotic fluid erythropoietin levels correlated with cord blood pH, acid-base and blood gas values at birth in the study group. Newborn infants admitted to the newborn intensive care unit had significantly higher fetal erythropoietin levels and were more acidotic, hypoxemic and hypoglycemic than infants admitted to the normal care nursery. CONCLUSIONS: Our findings suggest that elevated amniotic fluid erythropoietin levels are markers of chronic or subchronic fetal hypoxia and are associated with neonatal morbidity in pregnancies complicated by hypertension.     

Maternal and umbilical resistin levels do not correlate with infant birth weight either in normal pregnancies and or in pregnancies complicated with gestational diabetes

Objective.?To evaluate the role of resistin in the pathophysiology of insulin resistance during pregnancy and on the birth weight of infants born from women with gestational diabetes (GDM).

Material and methods.?Thirty women diagnosed with GDM were compared to 30 normal pregnant controls. Maternal serum resistin and insulin levels were measured at the time of the oral glucose tolerance test screening. In addition, umbilical levels of resistin and insulin were measured at the time of delivery.

Results.?There was no difference in maternal serum resistin levels in women with GDM as compared to normal controls at 24–26 weeks. There was no difference in umbilical resistin levels between the infants born in the two groups. There was no correlation between infant weight and either maternal resistin at 24–26 week or umbilical resistin levels.

Conclusion.?There were no significant differences in umbilical resistin levels between infants born of women with GDM as compared to normal pregnant women. In addition, there was no correlation between resistin levels during pregnancy, as well as between umbilical resistin levels and neonatal birth weight. In conclusion, resistin seems to play a rather minor role in the pathophysiology of GDM and the energy metabolism during fetal life.     

Maternal and neonatal outcomes in pregnancies complicated by gestational diabetes. a nation-wide study

Objective: To estimate the association between gestational diabetes mellitus (GDM) and adverse pregnancy and neonatal outcomes in Denmark.

Methods: A population-based cohort study including all singleton pregnancies in Denmark from 2004 to 2010 (n?=?403?092). Maternal complications during pregnancy and delivery and fetal complications were classified according to the International Classification of Diseases 10th Revision.

Results: The final study population consisted of 398?623 women. Of these, 9014 (2.3%) had GDM. Data were adjusted for maternal age, parity, smoking, gestational age, birth weight, BMI, gender of the fetus and calendar year. The risk of preeclampsia, caesarean section (both planned and emergency) and shoulder dystocia was increased in women with GDM. In the unadjusted analysis, the risk of thrombosis was increased by a factor 2 in the GDM patients, but in the adjusted analysis this association disappeared. Post-partum hemorrhage was similar in the two groups. The GDM women had an increased risk of giving birth to a macrosomic neonate although the unadjusted analysis did not show any difference between the two groups. Low Apgar score was increased in the GDM, but this association disappeared in the adjusted analysis. Stillbirth was comparable in the two groups.

Conclusions: Women with GDM still have increased incidence of obstetric and neonatal complications, which could imply that treatment of women with GDM should be tightened.     

Increased incidence of spontaneous abortion in pregnancies complicated by maternal diabetes mellitus

A retrospective sample of 164 pregnancies in the years 1956 to 1975 of 78 insulin-dependent diabetic women was examined to assess the extent of the risk of clinically recognizable spontaneous abortion relative to the expected risk in a comparable population. This study was done before the implementation of the policy to establish good control of maternal diabetes before conception was attempted. After control of data for pregnancy number, maternal age, and epoch, the risk of spontaneous abortion among the diabetic women was almost double the estimate of the expected risk (p less than 0.001).     

胎膜早破时母血、羊水、脐血中细胞因子IL-6、IL-8、VCAM-1含量监测及其临床价值

目的探讨母血、羊水、脐血中三种细胞因子白细胞介素-6、8（interleukin-6、8）、血管细胞黏附分子-1（vascular cell adhesion molecule，VCAM—1）对胎膜早破、绒毛膜羊膜炎和新生儿预后判断的I临床意义。方法采用双抗体夹心酶联免疫吸附法检测58例胎膜早破及38例正常妊娠孕妇（对照组）母血、羊水、脐血中IL-6、IL-8、VCAM—1水平的动态变化，同时进行胎膜的病理检查。结果胎膜早破组母血、羊水、脐血中IL-6、IL-8、VCAM-1的含量均高于对照组，母血、羊水、脐血中IL-6、IL-8、VCAM—1的含量随破膜时间的延长而增高，尤其破膜时间超过24h增高更为明显。绒毛膜羊膜炎患者母血、羊水、脐血中IL-6、IL-8、VCAM—1水平明显高于非绒毛膜羊膜炎患者，差异具有显著性（P〈0．05，P〈0．01），胎膜早破组产妇所生新生儿Apgar评分≤7分者，其母血、羊水、脐血中IL-6、IL-8、VCAM—1的含量显著高于Apgar≥8分的新生儿（P〈0．05，P〈0．01）。结论IL-6、IL-8、VCAM—1三种细胞因子联合检测可用于胎膜早破并绒毛膜羊膜炎的早期诊断，对新生儿预后判断也具有一定的临床价值。     

Obstetric and perinatal outcomes of singleton pregnancies conceived via assisted reproductive technology complicated by gestational diabetes mellitus: a prospective cohort study

Background

Growing evidence indicates that the risk of obstetric and perinatal outcomes is higher in women with assisted reproductive technology (ART). However, there is little known about pregnancy related complications and co-morbidity in gestational diabetes mellitus (GDM) following singleton pregnancies achieved by ART in comparison with spontaneous conception (SC).

Methods

Two hundred sixty singleton pregnant women conceived by ART and 314 pregnant women conceived by spontaneous conception (SC) were participated in this prospective cohort study. All participants were enrolled after GDM screening through one-step oral glucose tolerance test (OGTT) and then grouped into GDM and non-GDM groups. Women were followed for pregnancy outcomes including pregnancy-induced hypertension (PIH), preeclampsia, antepartum hemorrhage (APH), cesarean section (CS), preterm birth (PTB), intrauterine growth restriction (IUGR), being small or large for gestational age (SGA or LGA), macrosomia, low birth weight (LBW), respiratory distress, neonatal hypoglycemia, NICU admission and perinatal mortality from antenatal visits to delivery. Confounding factors were adjusted in logistic regression model in order to estimate adjusted odds ratios (aORs).

Results

Among 260 ART and 314 SC, 135 and 152 women were GDM women, respectively. Higher maternal age and pre-gravid BMI, shorter duration of gestation and lower gestational weight gain were observed in GDM groups (ART-GDM and SC-GDM) compared to those of the SC group. ART-GDM group had a higher risk (95% confidence interval) of obstetric complications including PIH [aOR:7.04 (2.24–22.15)], preeclampsia [aOR:7.78 (1.62–37.47)], APH [aOR:3.46 (1.28–9.33)], emergency CS [aOR:2.64 (1.43–4.88)], and perinatal outcomes such as PTB [aOR:3.89 (1.51–10.10)], LBW [aOR:3.11 (1.04–9.30)] and NICU admission [aOR:4.36 (1.82–10.45)], as well as neonatal hypoglycemia [aOR: 4.91 (1.50–16.07)], compared to SC group. SC-GDM group showed a higher risk of PIH [aOR: 4.12 (1.31–12.89)], emergency CS [aOR: 2.01 (1.09–3.73] and LGA [aOR: 5.20 (1.07–25.20)], compared to SC group. Additionally, ART group had a higher risk of PIH [aOR: 3.46(1.02–11.68), preeclampsia 5.29 (1.03–27.09), and NICU admission [aOR: 2.53 (1.05–6.09)] compared to SC. Insulin requirement (41.8% vs. 25.7%) was significantly higher in ART-GDM group compared to SC-GDM group.

Conclusion

The findings of this study suggest that GDM occurring after ART conception increases the risk of adverse obstetric and perinatal outcomes.

     

Cardiovascular risk markers in pregnancies complicated by diabetes mellitus or preeclampsia

ObjectiveTo explore biomarkers indicating cardiovascular disease in pregnant women with diabetes or preeclampsia, since these women are at increased risk for future cardiovascular disease.Study designEDTA-plasma from 262 women in gestational week 24–42 (healthy pregnancies n = 71, preeclampsia n = 105, type 2 diabetes n = 17, gestational diabetes n = 61, diabetes with preeclampsia n = 8) was analyzed by immunoassay for neopterin, midregional pro-adrenomedullin (MR-proADM) and C-terminal pro-arginine vasopressin (CT-proAVP). The diabetes groups were also analyzed for midregional pro-atrial natriuretic peptide (MR-proANP), and compared to previously reported MR-proANP concentrations for healthy, normotensive and preeclamptic patients.ResultsIn contrast to preeclampsia, median plasma MR-proANP was not increased in pregnancies complicated by diabetes, but in fact lower, compared to healthy pregnancies. Neopterin was increased in diabetic pregnancies and in late onset preeclampsia, compared to healthy pregnancies. Median plasma MR-proADM was increased in pregnancies complicated by gestational diabetes or preeclampsia, compared to healthy pregnancies. Median plasma MR-proANP was increased in diabetic pregnancies complicated by preeclampsia compared to pregnant women with diabetes only.ConclusionWomen with pregnancies complicated by diabetes mellitus or preeclampsia are at risk for future cardiovascular disease, but differ in circulating cardiovascular biomarker profile. A cardiovascular biomarker profiling during pregnancy might prove helpful in identifying women at risk for future cardiovascular disease, thus enabling targeted prophylactic interventions and follow-up.     

Maternal serum vitamin D levels in pregnancies complicated by neural tube defects

Objective: The association between vitamin D deficiency and abnormal neural development has been proposed previously. We aimed to evaluate maternal serum vitamin D levels in pregnancies complicated by neural tube defects (NTDs) and compared them with healthy pregnant women.

Methods: A total of 60 pregnant women were included in this controlled cross-sectional study. Thirty of the patients whose pregnancies were complicated by meningocele, meningomyelocele, encephalocele, anencephaly and fetal acrania constituted the study group, whereas 30 normal pregnant women constituted the control group. The main parameters recorded for each woman were as follows: age, body mass index (BMI), gestational week (GW), gravidity, abortion, co-morbidities, dressing style, consumption of milk and dairy products and serum levels of 25(OH)VitD₃, calcium, albumin and total protein.

Results: The mean maternal serum 25(OH)VitD₃ level was 6.2?±?5.0?ng/ml in the study group and 9.1?±?7.3?ng/ml in the control group (p: 0.071). The mean maternal serum calcium level was statistically significantly higher in the control group, and calcium-rich dietary intake was also more common in this group (p?<?0.05). There was no statistically significant difference between groups in terms of age, BMI, GW, dressing style and serum levels of albumin and total protein.

Conclusions: Vitamin D deficiency is common among pregnant women, and maternal serum calcium levels were lower in pregnancies complicated by NTD than healthy pregnant women. Larger further studies are required to evaluate the effects of calcium-rich dietary sources or vitamin D and calcium in the development of NTDs.     

Maternal and fetal amino acid concentrations in normal pregnancies and in pregnancies with gestational diabetes mellitus

OBJECTIVE: This study was undertaken to compare amino acid concentrations in normal pregnancies and pregnancies with gestational diabetes (GDM), a condition associated with altered fetal growth. STUDY DESIGN: Maternal and fetal amino acids were evaluated by high-performance liquid chromatograph at the time of delivery in 16 normal and 17 GDM pregnancies. Fetal weights were not different, but placental weights were significantly higher and fetal/placental weight ratios were significantly lower in GDM compared with normal. RESULTS: Ornithine was significantly increased in GDM mothers. In umbilical vein and artery of GDM significant increases were observed for valine, methionine, phenylalanine, isoleucine, leucine, ornithine, glutamate, proline, and alanine, whereas glutamine was significantly decreased. CONCLUSION: Placental amino acid exchange is altered in GDM pregnancies. Moreover, the changes observed for glutamine and glutamate in the umbilical samples suggest that in GDM the fetal hepatic production of glutamate is increased, likely as a consequence of the endocrine changes in the fetal compartment.     

Second trimester amniotic fluid myo-inositol concentrations in women later developing gestational diabetes mellitus or pregnancy-induced hypertension

Objective: To evaluate myo-inositol concentrations in amniotic fluid in women later developing gestational diabetes and hypertension.

Methods: A retrospective study was carried out with three groups of amniotic fluid samples (15–18 gestational weeks): 30 gestational hypertension pregnancies, 30 gestational diabetes pregnancies, and 30 normal pregnancy.

Results: A significant difference was observed in myo-inositol concentrations between the median gestational diabetes values (124.0?µmol/L, IQR 90.0–162.5) and the control group values (79.0?µmol/L, IQR 62.0–107.5), but also with gestational hypertension median values (79.0?µmol/L, IQR 67.75–92.0) (p?<?0.001).

Conclusions: This study has shown that myo-inositol concentrations in amniotic fluid increased significantly in women later developing gestational diabetes compared to the control group.