Early pregnancy azathioprine use and pregnancy outcomes

BACKGROUND: Azathioprine (AZA) is used during pregnancy by women with inflammatory bowel disease (IBD), other autoimmune disorders, malignancy, and organ transplantation. Previous studies have demonstrated potential risks. METHODS: The Swedish Medical Birth Register was used to identify 476 women who reported the use of AZA in early pregnancy. The effect of AZA exposure on pregnancy outcomes was studied after adjustment for maternal characteristics that could act as confounders. RESULTS: The most common indication for AZA use was IBD. The rate of congenital malformations was 6.2% in the AZA group and 4.7% among all infants born (adjusted OR: 1.41, 95% CI: 0.98–2.04). An association between early pregnancy AZA exposure and ventricular/atrial septal defects was found (adjusted OR: 3.18, 95% CI: 1.45–6.04). Exposed infants were also more likely to be preterm, to weigh <2500 gm, and to be small for gestational age compared to all infants born. This effect remained for preterm birth and low birth weight when infants of women with IBD but without AZA exposure were used as a comparison group. A trend toward an increased risk of congenital malformations was found among infants of women with IBD using AZA compared to women with IBD not using AZA (adjusted OR: 1.42, 95% CI: 0.93–2.18). CONCLUSIONS: Infants exposed to AZA in early pregnancy may be at a moderately increased risk of congenital malformations, specifically ventricular/atrial septal defects. There is also an increased risk of growth restriction and preterm delivery. These associations may be confounded by the severity of maternal illness. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.     

Oxidative stress early in pregnancy and pregnancy outcome

The objectives of this study were to determine whether oxidative stress early in pregnancy influenced pregnancy outcome. A combination of assays were used for exogenous and endogenous anti-oxidants together with two well accepted biomarkers for oxidative stress, the urinary excretion of 8-iso-PGF_2α (a biomarker marker for lipid oxidation, n=508) and 8-oxo-7,8 dihydro-2 deoxyguanosine (8-OHdG, a biomarker for DNA oxidation, n=487). The two biomarkers tracked different pregnancy outcomes. Isoprostanes were associated with an increased risk of pre-eclampsia and a decreased proportion of female births. In contrast, 8-OHdG tracked lower infant birthweight and shortened gestation duration. Birth defects were associated with low levels of 8-OHdG.     

Oxidative stress early in pregnancy and pregnancy outcome

The objectives of this study were to determine whether oxidative stress early in pregnancy influenced pregnancy outcome. A combination of assays were used for exogenous and endogenous anti-oxidants together with two well accepted biomarkers for oxidative stress, the urinary excretion of 8-iso-PGF(2alpha) (a biomarker marker for lipid oxidation, n=508) and 8-oxo-7,8 dihydro-2 deoxyguanosine (8-OHdG, a biomarker for DNA oxidation, n=487). The two biomarkers tracked different pregnancy outcomes. Isoprostanes were associated with an increased risk of pre-eclampsia and a decreased proportion of female births. In contrast, 8-OHdG tracked lower infant birthweight and shortened gestation duration. Birth defects were associated with low levels of 8-OHdG.     

Limitations of the nonhuman pregnancy kit for pregnancy diagnosis in baboons

The Nonhuman Primate Pregnancy Test (NHPPT) kit was evaluated for diagnosis of pregnancy in baboons. Unreadable controls rendered 33% of all tests inconclusive. Refrigeration and dilution did little to improve the number of inconclusive tests. Positive-and false-negative results from readable tests on days 20 to 27 of confirmed pregnancy were 75% and 25%, respectively. The NHPPT did not always provide an accurate diagnosis of pregnancy and often proved unreadable.     

Purification and characterization of early pregnancy factor from human pregnancy sera

Early pregnancy factor (EPF) is a pregnancy-associated protein detected in the maternal serum by using the rosette inhibition assay and by evaluating the suppression of adoptive transfer of contact sensitivity. Because of its inhibitory effect on the functional reactivity of immunocompetent cells, EPF is thought to be involved in immunoregulation of the maternal immune system during early pregnancy. EPF was purified six million-fold from the serum of pregnant women between 5 and 12 weeks of gestation. The specific activity of purified EPF was approximately 8 x 10(8) units/mg. The purification scheme involved sequential DEAE-cellulose chromatography, S-Sepharose chromatography, concanavalin A-Sepharose chromatography, heparin-Sepharose chromatography, Mono S fast protein liquid chromatography, and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The purified protein has an apparent molecular weight of 21,500 as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 28,000 by gel permeation high pressure liquid chromatography. The isoelectric point of purified EPF moiety is 6.5. The biological activity was susceptible to the proteolytic enzyme trypsin, acidic pH conditions, organic solvents, and sodium dodecyl sulfate, but stable to heat treatment at 56 degrees C for 30 min and the reducing agent dithiothreitol. The biological and physicochemical properties of EPF appear to be distinct from other pregnancy-associated and immunoregulatory proteins.     

Effects of aspirin consumption during pregnancy on pregnancy outcomes: meta-analysis

BACKGROUND: We assessed the effects and safety of aspirin treatment during pregnancy on fetal and neonatal outcomes. METHODS: We searched MEDLINE (1966–2001), EMBASE (1980–2000), TOXLINE (1994–2000), EBM Cochrane Database of Systematic Reviews (1991–2000), Reproductive Toxicology (2001), teratology texts, and bibliographies of all the included studies. We looked for published randomized controlled studies reporting aspirin treatment to improve outcomes of moderate‐ and high‐risk pregnancies. The key words used to search for articles about exposure to aspirin were salicylic acid, pregnancy, and pregnancy complications; key words used to search for outcome were neonatal diseases and abnormalities. Based on our search strategy, 1904 citations were identified; their titles and abstracts were reviewed by one reviewer. Of these citations, 182 papers were selected for detailed review. Two reviewers independently determined whether a study should be included in the final analysis. In cases of disagreement, the decision was based on the assessment of a third reviewer. RESULTS: Data were extracted independently by each reviewer. We calculated the pooled relative risk (RR) or weighted mean difference and 95% confidence intervals (CI), assuming a random‐effect model. Thirty‐eight studies met the inclusion criteria. The risk for miscarriage did not differ between women treated with aspirin and placebo (seven studies; RR, 0.92; 95% CI, 0.71–119). Women who took aspirin had a significantly lower risk of preterm delivery than did those treated with placebo (22 studies; RR, 0.92; 95% CI, 0.86–0.98). There was no significant difference in perinatal mortality (20 studies; RR, 0.92; 95% CI, 0.81–1.05) and in the rate of small‐for‐gestational‐age infants (12 studies; RR, 0.96; 95% CI, 0.87–1.07) among offspring of mothers treated with aspirin and those of mothers treated with a placebo. CONCLUSION: For women with moderate‐ and high‐risk pregnancies, aspirin treatment seemed to have a small but significant effect on reducing the rate of preterm deliveries, but did not reduce the rate of perinatal death. Birth Defects Research (Part B) 68:70–84, 2003. © 2003 Wiley‐Liss, Inc.     

Hemorrhage of late pregnancy

Rupture of the uterus, cesarean section and uterine atony were the major causes of maternal death associated with hemorrhage of late pregnancy for the five years 1945 to 1949 in New York County. Shock occurred earliest in rupture of the uterus and cesarean section, while in uterine atony there was some delay before shock was evident. Placenta previa was preceded by an initial small hemorrhage, and the time interval before shock was relatively long. It appeared that in cases of retained placenta, manual removal of the organ and hysterectomy were unduly delayed. Ten per cent of the maternal deaths reviewed were associated with severe transfusion reactions. Early recognition of a serious situation, rapid blood replacement and hysterectomy might have salvaged most of the patients.