The determinants of maternal homocysteine in pregnancy: findings from the Ottawa and Kingston Birth Cohort.

OBJECTIVE: Observational studies have linked elevated homocysteine to vascular conditions. Folate intake has been associated with lower homocysteine concentration, although randomised controlled trials of folic acid supplementation to decrease the incidence of vascular conditions have been inconclusive. We investigated determinants of maternal homocysteine during pregnancy, particularly in a folic acid-fortified population. DESIGN: Data were from the Ottawa and Kingston Birth Cohort of 8085 participants. We used multivariable regression analyses to identify factors associated with maternal homocysteine, adjusted for gestational age at bloodwork. Continuous factors were modelled using restricted cubic splines. A subgroup analysis examined the modifying effect of MTHFR 677C>T genotype on folate, in determining homocysteine concentration. SETTING: Participants were recruited in Ottawa and Kingston, Canada, from 2002 to 2009. PARTICIPANTS: Women were recruited when presenting for prenatal care in the early second trimester. RESULTS: In 7587 participants, factors significantly associated with higher homocysteine concentration were nulliparous, smoking and chronic hypertension, while factors significantly associated with lower homocysteine concentration were non-Caucasian race, history of a placenta-mediated complication and folic acid supplementation. Maternal age and BMI demonstrated U-shaped associations. Folic acid supplementation of >1 mg/d during pregnancy did not substantially increase folate concentration. In the subgroup analysis, MTHFR 677C>T modified the effect of folate status on homocysteine concentration. CONCLUSIONS: We identified determinants of maternal homocysteine relevant to the lowering of homocysteine in the post-folic acid fortification era, characterised by folate-replete populations. A focus on periconceptional folic acid supplementation and improving health status may form an effective approach to lower homocysteine.

Development of a guinea pig model of chorioamnionitis and fetal brain injury.

OBJECTIVE: The purpose of this study was to develop a guinea pig model of chorioamnionitis to study the mechanisms that lead to fetal brain injury. Study design Pregnant guinea pigs at 70% gestation were inoculated intracervically with 1000 to 2500 colony-forming units of Escherichia coli. Guinea pigs were killed 2 to 3 days after bacterial inoculation. Maternal blood and fetal amniotic fluid samples were analyzed for proinflammatory cytokine tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 levels with the use of enzyme-linked immunosorbent assay kits. Fetal brains were stained for evidence of cell death with NeuroTacs stain. RESULTS: Of 34 maternal guinea pigs that were given an intracervical inoculation of E coli, 8 guinea pigs showed microbiologic evidence of chorioamnionitis in the amniotic fluid. Tumor necrosis factor-alpha and interleukin-6 were significantly higher (P<.05) in amniotic fluid samples that were obtained from sows that were subjected to intracervical inoculation with bacteria as compared with control animals (n=6 control maternal animals). These results were observed even if no bacteria were found subsequently on culture of the amniotic fluid from inoculated animals, which indicated that indirect exposure to infectious agents was sufficient to cause an elevated inflammatory response in the fetus. Levels of white matter injury were greater in fetuses that were exposed to bacterial infection in utero, as compared with control animals (P<.05). This result was found in the staining of periventricular and cortical white matter for the immunolabeling of activated caspase 3 and NeuroTacs staining for cells that exhibited evidence of apoptotic cell death (positive stain with evidence of karyorrhexis). CONCLUSION: Intracervical inoculation with E coli results in chorioamnionitis in guinea pigs that is associated with fetal brain injury.

What women believe about oral contraceptives and the effect of counseling.

OBJECTIVES: To evaluate Canadian women' s knowledge of the risks, benefits and side effects of oral contraceptives (OCs) and the effect of counseling. STUDY DESIGN: Six-hundred and forty-nine Canadian women filling an OC prescription at Shopper's Drug Mart stores completed the survey. Respondents recorded whether or not they had discussed 12 separate issues about OC use with their healthcare provider. Optimal responses to multiple-choice questions were compared between those reporting counseling to those reporting no counseling, using Fisher's Exact Tests. Women were also questioned on what they were told about associated cancer risks. RESULTS: Eighty percent or more of the women selected the optimal response for the questions relating to dysmenorrhea, leg pain and co-medication. Less than half of survey respondents identified the optimal response for nausea, breakthrough bleeding, breast tenderness, acne, headaches and weight change. Counseling made a significant impact on selection of the optimal response for 7 of the 12 questions (p < 0.004, adjusted significance level). Fifty-two percent indicated that they did not know what they were told about the risk of uterine and ovarian cancer when on the pill. A significant proportion of women said they would phone their physician for relatively minor problems such as breakthrough bleeding (65%), breast tenderness (55%) and acne (54%). CONCLUSIONS: The knowledge level of Canadian women on the pill regarding risks, benefits and side effects of the pill remains deficient in several key areas. Adequate counseling by healthcare providers can help women recognize the pill's positive health benefits, and may result in fewer unnecessary physician contacts and unwanted pregnancies.