Changes in LDL and HDL subclasses in normal pregnancy and associations with birth weight, birth length and head circumference.

Pregnancy is associated with alterations in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses, but the exact pattern of these variations remains controversial. This study investigates longitudinal changes of plasma LDL and HDL particles distributions during the course of normal pregnancy, as well as associations of maternal LDL and HDL subclasses distributions before delivery with parameters of newborn size. Blood samples were collected from 41 healthy pregnant women throughout entire pregnancy, before delivery and 7 weeks postpartum. LDL and HDL subclasses were determined by gradient gel electrophoresis, while other biochemical parameters were measured by standard laboratory methods. During gestation LDL size significantly decreased (P < 0.001), due to reduction in relative proportion of LDL I (P < 0.01) and increase of LDL II (P < 0.001) and IIIA (P < 0.05) subclasses. In the same time, HDL size and proportions of HDL 2a particles significantly decreased (P < 0.001), with concomitant increase of HDL 3b and 3c subclasses (P < 0.05). Observed alterations were associated with changes in serum triglyceride levels. Rearrangement in LDL subclasses distribution during gestation was transient, while postpartum HDL subclasses distribution remained shifted toward smaller particles. Higher proportion of LDL IVB in maternal plasma before delivery was an independent predictor of smaller birth weights and lengths, while higher proportions of LDL IVB and HDL 2a subclasses were independent determinants of newborns' smaller head circumferences. Routine gestational and prenatal care in otherwise normal pregnancy could be complemented with evaluation of LDL and HDL particles distribution in order to ensure an adequate size of the newborn.

Association of the atherogenic index of plasma and oxidative stress status with weight gain during non-complicated pregnancy.

BACKGROUND: Pregnancy is a stressful condition linked with altered lipid profile, increased oxidative stress and increased inflammation processes. The purpose of the present study was to determine the associations between those alterations with increased weight gain during pregnancy. METHODS: The atherogenic index of plasma (AIP) and oxidative stress status parameters were determinated in 50 healthy and 172 pregnant women with non-complicated pregnancy. Pregnant women were divided in four groups according to body mass index (BMI) values (BMI quartiles). RESULTS: Oxidative stress parameters were significantly lower in the control group compared with all the pregnant women quartiles. Unexpectedly, differences in oxidative stress parameters between BMI quartiles groups were not significant. The antioxidant defence parameters remained quite similar in the different BMI quartiles. Weight gain and paraoxonase-1 (PON1) activities were independently associated with increased AIP while weight gain and triglyceride concentration were found to be significant predictors of PON1 activities. CONCLUSIONS: The results of our current study indicate the association of maternal weight gain during pregnancy and altered lipid profile, elevated oxidative stress and changed antioxidative capacity of PON1. Taken together all these facts indicate possible increased risk of cardiovascular disease (CVD) development in later life if the weight gain during pregnancy is excessive.

The influence of maternal smoking habits before pregnancy and antioxidative supplementation during pregnancy on oxidative stress status in a non-complicated pregnancy.

BACKGROUND: As a physiological condition closely linked with increased susceptibility to oxidative stress, pregnancy can be further compromised by cigarette smoking. Inadequate nutrition and reduced intake of antioxidants can also disrupt the prooxidant/antioxidant relationship and contribute to oxidative stress. Increased oxidative stress during pregnancy may be involved in several complications of pregnancy, such as preterm labor, fetal growth restriction, preeclampsia and miscarriage. OBJECTIVES: The aim of this study was to investigate the influence of maternal smoking habits before pregnancy on the parameters of oxidative stress and the antioxidative defense system, lipid profile parameters and paraoxonase-1 (PON1) activity during the third trimester of uncomplicated pregnancies. MATERIAL AND METHODS: Healthy pregnant women (n = 86) were divided into non-smoking and smoking groups, and into groups taking vitamin supplements and not taking them. Oxidative damage was measured through the levels of thiobarbituric acid-reacting substances (TBARS) and plasma antioxidant status was evaluated by measuring total antioxidant capacity (TAC). RESULTS: TBARS concetration was significantly higher (p < 0.05) and PON1 activity was significantly lower (p < 0.05) in the smokers' group. No significant differences were found in the investigated parameters in relation to vitamin supplement intake. CONCLUSIONS: Habitual smoking before pregnancy is associated with increased oxidative stress. Vitamin supplementation has no effect on the oxidative stress status of healthy pregnant women.

Longitudinal changes in PON1 activities, PON1 phenotype distribution and oxidative status throughout normal pregnancy.

The purpose of the present study was to determine changes in plasma paraoxonase-1 activity (an indicator of paraoxonase phenotype) throughout normal pregnancy and its relationship with maternal oxidative stress status. The frequencies of the paraoxonase-1 phenotype in the studied population were determined using a two-substrate (paraoxon/diazoxon) activity method. As a parameter of oxidative stress status we measured the redox balance. Paraoxonase-1 activity significantly decreased at gestational week 32. In addition, the lipid profile was more atherogenic. Redox balance was significantly increased across gestational weeks. There were independent direct associations between maternal smoking habits before pregnancy, glucose concentrations and redox balance with PON1 activity in the third trimester. This study shows that pregnancy is followed by a decrease in PON1 activity and increased risk for development of cardiovascular diseases. We conclude that changes in paraoxonase-1 status during pregnancy are associated with maternal oxidative stress status and smoking habits.

Screening for aneuploidies by maternal age, fetal nuchal translucency and maternal serum biochemistry at 11-13+6 gestational weeks.

INTRODUCTION: Aneuploidies are the major cause of perinatal death and early psychophysical disorders. OBJECTIVES: In this study, we analyzed detection and false-positive rates of screening for aneuploidies in the first trimester by the combination of maternal age, fetal nuchal translucency (NT) thickness and maternal serum free beta-human chorionic gonadotrophin (beta-hCG), and pregnancy-associated plasma protein-A (PAPP-A) at 11-13+6 weeks of gestation, using the appropriate software developed by the Fetal Medicine Foundation. METHODS: Our screening study for aneuploidies analyzed 4172 singleton pregnancies from January 2006 to December 2010. The sensitivities and false-positive rates using the combined aneuploidies determination for the risk cut-off of 1:275 were evaluated. RESULTS: In the trisomy 21 pregnancies, the fetal NT was higher than 95th centile, in 72.8%, serum free b-hCG concentration it was above the 95th centile in 55% and serum PAPP-A was below the 5th centile in 47% of the cases. In the trisomy 18 and 13, the fetal NT was above 95th centile in 66.6% and 44.4% of the cases, respectively.The serum free b-hCG concentration was above the 95th centile in 0 and 10%, but serum PAPP-A was below 5th centile in 80.9% and 88.8% of pregnancies. In the trisomy 21 pregnancies the median free beta-hCG was 2.3 MoM and the median PAPP-A was 0.45 MoM. Chromosomal abnormalities were detected in 169 fetuses: trisomy 21 (97), Turner syndrome (19), trisomy 18 (28), trisomy 13 (11) and others (14). Detection rate of combined screening for aneuploides were 86.0% with false positive rate of 5.3% (mean age 33 +/- 4.9 years, > 35 years in 35% of pregnancies). CONCLUSION: Our study suggests that the strategy of first-trimester combined screening of biochemical values and ultrasonographic parameters at 12 gestational weeks identifies higher percentage of aneuploidies with a lower false-positive rate than a single parameter strategy.

Changes in Doppler blood flow velocity in middle cerebral artery in response to airborne sound in low- and high-risk human fetuses.

OBJECTIVE: To examine fetal auditory perception in low- and high-risk pregnancies in period from 27 to 31 weeks gestational age with the aim to establish diagnostic parameters in prenatal detection of the degree of hearing development in a fetus. METHODS: Method of prenatal hearing screening was applied on 80 women divided in two groups: Control group (C=22), consisted of pregnant women with low-risk pregnancies, and Experimental group (E=58), consisted of pregnant women with high-risk pregnancies (pregnancies with diagnosis of: preterm delivery, hypertension and/or intrauterine growth restriction (IUGR), diabetes). PHS was applied in period from 27 to 31 weeks gestational age. Brain circulation changes in fetal middle cerebral artery (MCA) caused by defined sound stimulus, as the indicator of fetal auditory reactions, were registered on Doppler ultrasound apparatus. After visualization of MCA, a sound stimulus was delivered. The stimulus consisted of one defined sound which is a digitally produced sound with the intensity of 90 dB, frequency range of 1500-4500 Hz, and duration of 0.2s (click) and it was presented only once. Measurements in observed artery were taken before (baseline) and after defined sound stimulation. RESULTS: Results showed that the absolute and relative difference in Pulsatility index (baseline and after sound stimulation) were greater for the high-risk group compared to the low-risk group (absolute difference: mean=0.36 vs mean=0.36) (relative difference: mean = ∼ 18% vs mean = ∼ 12%). When the low-risk group and the three high-risk group mean pairs were compared using multiple t-test, the diabetic group differed from the low-risk and two other high-risk groups; the low-risk and the two other high-risk groups did not differ from each other. Fetuses from pregnancies with diagnosis of diabetes demonstrated the most expressive reactibility and significantly higher absolute and relative changes of Pi values (absolute difference: mean=0.54, relative difference: mean=25.49%). CONCLUSION: The values of Pulsatility index (Pi) registered by PHS in low- and high-risk pregnancies may be used as differential and diagnostic parameters in fetal auditory perception examination. Fetuses from pregnancies with diagnosis of diabetes demonstrated significantly higher absolute and relative changes of Pi values compared to other groups of examined fetuses.

Antioxidative defense enzymes in placenta protect placenta and fetus in inherited thrombophilia from hydrogen peroxide.

Our aim was to investigate the activities of antioxidative defense enzymes in the placenta, fetal blood and amnion fluid in inherited thrombophilia. Thrombophilia was associated with nearly threefold increase of activity (p < 0.001) of the placental catalase (81.1 +/- 20.6 U/mg of proteins in controls and 270.0 +/- 69.9 U/mg in thrombophilic subjects), glutathione (GSH) peroxidase (C: 20.2 +/- 10.1 U/mg; T: 60.0 +/- 15.5 U/mg), and GSH reductase (C: 28.9 +/- 5.6 U/mg; T: 72.7 +/- 23.0 U/mg). The placental activities of superoxide dismutating enzymes--MnSOD and CuZnSOD, did not differ in controls and thrombophilia. Likewise, the activities of catalase and SOD in the fetal blood, and the level of ascorbyl radical which represents a marker of oxidative status of amniotic fluid, were similar in controls and thrombophilic subjects. From this we concluded that in thrombophilia, placental tissue is exposed to H(2)O(2)-mediated oxidative stress, which could be initiated by pro-thrombic conditions in maternal blood. Increased activity of placental H(2)O(2)-removing enzymes protects fetus and mother during pregnancy, but may increase the risk of postpartum thrombosis.

[Longitudinal analysis of arterial Doppler parameters in growth retarded fetuses]. / Longitudinalna analiza arterijskih dopler parametara kod zastoja u rastu ploda.

Doppler parameters enable noninvasive and direct detection of placental insufficiency and brain sparing effect, which occurs as an adaptive mechanism to chronic hypoxemia. It is of great interest if further changes of Doppler parameters, which occur after the detection of the first pathologic value, can anticipate a moment of fetal distress. We investigated growth-restricted fetuses with the brain sparing effect in the time interval between the detection of blood flow redistribution until the distress. The aim of our study was to evaluate longitudinally Doppler parameters in umbilical (Aum), medial cerebral (MCA), renal (AR) and femoral (AF) artery, and find: 1) if there are significant changes in their value; 2) the character and time interval of these changes; and 3) if they differ from changes in biophysical profile (BFP). Prospective clinical study evaluated 35 pregnancies with fetal growth restriction. Fetuses were selected for the study if: 1) there were pathologic cerebral/umbilical (C/U) ratio, 2) at least four Doppler examinations in 3-4 days interval were performed and 3) prepartal fetal distress, defined as silent fetal heart rate pattern with spontaneous and late decelerations, was present. In 28 neonates after delivery umbilical artery gas and acid-base status was determined. Blood flow velocity waveforms were evaluated in Aum, MCA, AR, and AF. Arterial blood flow was estimated by pulsatility index (Pi), while in Aum we also used: present end-diastolic velocity (PEDV), absent end-diastolic velocity (AEDV) and reverse end-diastolic velocity (REDV). All of the fetuses were monitored by cardiotocogram (CTG) once to twice a day and by BFP twice a week. Elective Cesarean section was done in the presence of distress, except if severe immaturity or extreme malnutrition occurred. Etiological factors of placental insufficiency were: 1) hypertensive syndrome (n = 26), 2) chronic renal disease (n = 3), 3) primary antiphospholipid syndrome (n = 2), 4) diabetes mellitus (n = 1), 5) cardiac disease (n = 1) and 6) unknown (n = 2). Initial Doppler examination, with the detection of pathological C/U, was done in time interval between 26. to 32. weeks of gestation (wg) (29.4 +/- 2.5); delivery was between 29. to 34. wg (32.2 +/- 1.9); and average body weight was 1327 +/- 245 g. Pathological BFP was registered in 91.4% of fetuses. Cesarian section has not been done, in spite of distress, in two fetuses (5.7%) due to their extreme immaturity and/or malnutrition, so they died "in utero". Hypoxemia was registered in 96.4% (27/28) neonates, while acidosis in 71.4% (20/28). Neonatal morbidity was 93.9% (31/33), neonatal mortality 8.6%, while perinatal mortality was 14.3%. We found high significant difference (P < 0.001) in Pi Aum, Pi ACM and Pi AR in the time interval between the detection of pathological C/U ratio and fetal distress, while the difference was insignificant for the values of Pi AF (table). The value changes are characterized by: continuing increase of Pi Aum, with a maximum in the last week before the distress; biphasic character of PI MCA--tendency to decrease in the first two and significant increase in the last week; and significant increase of Pi AR one and a half week before the distress (table, graphic). Three weeks before the distress in 7 (53.8%) cases we registered PEDV, in 6 (46.2%) AEDV, while we didn't register REDV in any case. In the last week there were 3 (8.6%) PEDV, 23 (65.7%) AEDV and 9 (25.7%) REDV. Significant changes in Doppler parameters suggest that even after the blood redistribution in growth restricted hypoxemic fetuses further haemodynamic changes occur. Preterminal increase in Pi Aum can be due to: 1) release of leucotrien, tromboxan and free oxygen radicals and consecutive vasoconstriction in villous arteries; 2) increase of diastolic arterial pressure as a result of hypoxic-ischemic central nervous system (CNS) insult; 3) decreased combined heart minute volume in preterminal phase of hypoxemia. The increase of Pi MCA values is a result of hypoxic-ischemic CNS insult. As a consequence of hypoxia ischemia occurs by two mechanisms: local vasodilatatory agents production decrease, or due to the brain edema. The increase of Pi AR values can be explained by severe hypoxemia with the failure of local autoregulation of renal blood flow. The greatest changes in BFP values were registered in the first half, while in Doppler parameters in the second half of the studied interval suggesting that Doppler parameters more accurately announce fetal distress. We can conclude the following: 1) fetal distress appears after the presence hypoxic-ischemic CNS insult, and therefore late when sequels are concerned; 2) if the fetus is mature, elective delivery should be planed after the appearance of pathological C/U ratio, or with the pathological BFP at the latest, in order to avoid post-hypoxic sequels; 3) if the fetus is immature, pregnancy can be prolonged safely, in spite of pathological C/U ratio and BFP, with intensive monitoring of Doppler parameters until the detection of their increased values.