Maternal second trimester serum tumor necrosis factor-alpha-soluble receptor p55 (sTNFp55) and subsequent risk of preeclampsia.
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Preeclampsia is characterized by diffuse vascular endothelial dysfunction. Tumor necrosis factor-alpha (TNF-alpha), which plays a key role in the cytokine network responsible for immunoregulation, is also known to contribute to endothelial dysfunction and other metabolic disturbances noted in preeclampsia. Results from cross-sectional studies and one longitudinal study indicate that TNF-alpha (or its soluble receptor, sTNFp55) is increased in the peripheral circulation and amniotic fluid of women with preeclampsia as compared with normotensive women. Between December 1993 and August 1994, prediagnostic sTNFp55 concentrations (a marker of excessive TNF-alpha release) were measured in 35 women with preeclampsia and 222 normotensive women to determine whether elevations precede the clinical manifestation of the disorder. Logistic regression procedures were used to calculate maximum likelihood estimates of odds ratios and 95% confidence intervals. Mean second trimester (15-22 weeks' gestation) serum sTNFp55 concentrations, measured by enzyme-linked immunosorbent assay, were 14.4% higher in preeclamptic women than in normotensive controls (716.6 pg/ml (standard deviation 193.6) vs. 626.4 pg/ml (standard deviation 158.0); p = 0.003). The relative risk of preeclampsia increased across successively higher quintiles of sTNFp55 (odds ratios were 1.0, 1.3, 2.1, and 3.7, with the lowest quintile used as the referent; p for trend = 0.007). After adjustment for maternal age, adiposity, and parity, the relative risk between extreme quintiles was 3.3 (95% confidence interval 0.8-13.4). These findings indicate that the level of TNF-alpha in maternal circulation is increased prior to the clinical manifestation of the disorder, and they are consistent with the hypothesized role of cytokines in mediating endothelial dysfunction and the pathogenesis of preeclampsia. Further work is needed to identify modifiable risk factors for the excessive synthesis and release of TNF-alpha in pregnancy, and to assess whether lowering of TNF-alpha concentrations in pregnancy alters the incidence and severity of preeclampsia. (+info)
Normal pregnancy is associated with enhanced endothelium-dependent flow-mediated vasodilation.
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Normal pregnancy is characterized by reduced systemic vascular resistance, which may be mediated by nitric oxide (NO). We compared endothelial vasomotor function in 71 normal pregnant women (13 in first, 29 in middle, and 29 in last trimester) to 37 healthy age-matched controls. With external ultrasound, brachial artery diameter was measured at rest, during reactive hyperemia [with increased flow causing endothelium-dependent dilation (FMD)], and after sublingual nitroglycerin (causing endothelium-independent dilation). Compared with controls, resting flow and brachial artery diameter were significantly higher during the middle and last trimesters. Reactive hyperemia was reduced in all pregnant groups. FMD increased from the first trimester (by 26%), reaching the highest value in the last trimester (to 47% above nonpregnant values). FMD was significantly correlated to pregnancy status (nonpregnant or pregnant) and to vessel size. Nitroglycerin-induced dilation was similar in pregnant and nonpregnant women. A longitudinal study of eight women evaluated in the first, middle, and last trimesters confirmed an increase in FMD throughout pregnancy. The study supports the idea that basal and stimulated NO activity is enhanced in normal pregnancy and may contribute to the decrease in peripheral resistance. (+info)
Is normal pregnancy atherogenic?
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Serum cholesterol, triacylglycerols and low-density lipoprotein (LDL) subfractions were determined in 120 primagravid women during normal gestation (40 in each trimester) and in 20 non-pregnant age-matched controls. LDL subfractions were determined by PAGE, and an LDL score was calculated. The higher the score, the smaller the subfractions. The objective of the study was to determine the effects of the hyperlipidaemia, high oestrogen concentrations and insulin resistance known to exist in normal pregnancy on LDL subfraction formation. Pregnant women had an increased mean serum cholesterol concentration [5.78 (S.D. 1.09) mmol/l] in the first trimester compared with the non-pregnant controls [5.11 (0.77) mmol/l; P<0.01]. The serum cholesterol concentration increased progressively throughout gestation to a mean of 8.14 (1.39) mmol/l in the third trimester (P<0.001 compared with the second trimester). Triacylglycerol concentrations in the first trimester were similar to those of controls, and there was a non-significant increase by the second trimester to 1.32 (0.44) mmol/l. However, by the third trimester the mean triacylglycerol concentration had doubled [2.58 (0.98) mmol/l; P<0.001 compared with the first and second trimester]. During gestation the LDL score increased dramatically, from 1.17 (0.39) during the first trimester to 2.01 (0.37) in the second trimester (P<0.001) to 2.73 (0.48) in the third trimester (P<0.001 compared with the second trimester). Thus an atherogenic lipid profile develops during normal gestation. The significance of these changes remains unclear, but thay may have important implications for mother and foetus. (+info)
The effects on fetal development of high alpha-fetoprotein and maternal smoking.
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OBJECTIVES: This study determined the risk of impaired fetal growth resulting from the interaction between maternal smoking during pregnancy and unexplained elevated concentrations of maternal serum alpha-fetoprotein (MSAFP). METHODS: This observational study involved 123 pregnant smokers with unexplained second-trimester elevated concentrations of MSAFP, 827 smokers with normal levels, and 471 nonsmokers with raised levels. RESULTS: By logistic regression, coincident smoking and elevated MSAFP levels were found to be associated with increases in the low basic risks of prematurity, small-for-gestational-age births, low birthweight, and need for neonatal care. CONCLUSIONS: Maternal smoking has an adverse effect on fetal development in pregnancies with unexplained elevated MSAFP concentrations. Such pregnancies merit close surveillance. (+info)
The 'Mickey Mouse' sign and the diagnosis of anencephaly in early pregnancy.
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OBJECTIVES: To assess the sonographic screening for anencephaly in the first trimester in a low-risk obstetric population. METHODS: Since 1994, 5388 women attended our clinic for a first-trimester scan (11-14 weeks of gestation) and screening for structural and chromosomal abnormalities. The patients underwent transabdominal scanning, and transvaginal scanning if necessary. RESULTS: The ultrasonographic appearances of anencephaly in the first trimester are different from the familiar second-trimester signs. The cerebral hemispheres are present and exposed to the surrounding amniotic fluid. The ultrasound appearances in the coronal section of the head are best described as 'Mickey Mouse face'. There were six cases of anencephaly (incidence 1.1:1000). All cases were diagnosed in the first trimester and five demonstrated this sign. There were no false-positive diagnoses. The crown-rump length was significantly reduced in all affected fetuses. CONCLUSION: First-trimester ultrasonographic diagnosis of anencephaly is accurate, but sonographers should be familiar with the ultrasound appearances that are different from those in the second trimester. (+info)
Dystrophic calcification of the fetal myocardium.
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Intramural cardiac masses were detected antenatally in three fetuses by echocardiography. The masses were initially thought to be rhabdomyomas. All three pregnancies were terminated and histology showed dystrophic calcification in all, with no evidence of tumour. Therefore, dystrophic calcification of the fetal myocardium may have a similar appearance to single or multiple rhabdomyomas. This should be considered when counselling parents after detection of masses in the fetal heart, particularly when considering the risk of associated tuberous sclerosis. (+info)
Low maternal weight gain in the second or third trimester increases the risk for intrauterine growth retardation.
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Low maternal weight gain during pregnancy has been suggested as a cause of intrauterine growth retardation (IUGR). However, pregnancy weight gain and fetal growth vary greatly throughout pregnancy. We examined the relationship between maternal weight gain in individual trimesters to the risk of IUGR in 10,696 women enrolled in the National Collaborative Perinatal Project (NCPP) and the Child Health and Development Study (CHDS). Low weight gain was defined as <-0.1 kg/wk for the first trimester and <0.3 kg/wk for the second and third trimester. IUGR was defined as a birth weight <2500 g in full-term infants. Low weight gain in the first trimester was not associated with an increased risk of IUGR. After controlling for confounding factors (maternal height, body mass index, parity, race, toxemia, diabetes), low weight gain in the second trimester was associated with a relative risk of IUGR of 1.8 (1.3-2.6) in the NCPP cohort and 2.6 (1.6-4.1) in the CHDS cohort. Similarly, low weight gain in the third trimester was associated with a relative risk of IUGR of 1.7 (1.3-2.3) in the NCPP cohort and 2.5 (1.7-3.8) in the CHDS cohort. After correcting for weight gain in other trimesters, this increased risk remained. Increased risk of IUGR was observed with low second and third trimester weight gain across the spectrum of maternal body mass index. The risk of low weight gain in the second or third trimester was significantly lower in teenagers and significantly greater in overweight women and women aged 35 y or older. Low weight gain in either the second or third trimester was associated with a significantly greater risk of intrauterine growth retardation in two distinct cohorts. We conclude that increased awareness of maternal weight gain in mid and late pregnancy is critical to identifying infants at risk for IUGR. (+info)
IgM heavy chain complementarity-determining region 3 diversity is constrained by genetic and somatic mechanisms until two months after birth.
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Due to the greater range of lengths available to the third complementarity determining region of the heavy chain (HCDR3), the Ab repertoire of normal adults includes larger Ag binding site structures than those seen in first and second trimester fetal tissues. Transition to a steady state range of HCDR3 lengths is not complete until the infant reaches 2 mo of age. Fetal constraints on length begin with a genetic predilection for use of short DH (D7-27 or DQ52) gene segments and against use of long DH (e.g., D3 or DXP) and JH (JH6) gene segments in both fetal liver and fetal bone marrow. Further control of length is achieved through DH-specific limitations in N addition, with D7-27 DJ joins including extensive N addition and D3-containing DJ joins showing a paucity of N addition. DH-specific constraints on N addition are no longer apparent in adult bone marrow. Superimposed upon these genetic mechanisms to control length is a process of somatic selection that appears to ensure expression of a restricted range of HCDR3 lengths in both fetus and adult. B cells that express Abs of an "inappropriate" length appear to be eliminated when they first display IgM on their cell surface. Control of N addition appears aberrant in X-linked agammaglobulinemia, which may exacerbate the block in B cell development seen in this disease. Restriction of the fetal repertoire appears to be an active process, forcing limits on the diversity, and hence range of Ab specificities, available to the young. (+info)