Women's perspectives of the fetal fibronectin testing process: a qualitative descriptive study.

BACKGROUND: In 2009 the Ontario Ministry of Health and Long Term Care funded the implementation of province-wide fetal fibronectin testing in Ontario hospitals. This paper reports results from the provincial evaluation that sought to describe the experience of fetal fibronectin testing from the perspective of women with symptoms of preterm labour. METHODS: A descriptive qualitative design was used, employing semi-structured telephone and face-to-face interviews with women who had fetal fibronectin testing. RESULTS: Five hospitals participated in recruiting women for the study and 17 women were interviewed. Women described their experiences of fetal fibronectin testing as an emotional process that moves from expecting, to feeling, to hoping for reassurance; and then to re-defining what is required to feel reassured. Women described feeling anxious while waiting for fetal fibronectin results. When test results were negative, women described feeling a sense of relief that their symptoms would not likely lead to an imminent preterm birth. Women with positive results expressed feeling reassured by the care decisions and quick action taken by the health care team. CONCLUSION: Fetal fibronectin testing was acceptable and beneficial to these women with symptoms of preterm labour. Implications for practice and future research are suggested.

Relationships among biomarkers of one-carbon metabolism.

One-carbon metabolism is a network of metabolic pathways, disruption of which has been associated with cancer and other pathological conditions. Biomarkers of these pathways include homocysteine (HCY), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH). A better understanding of the relationships between these biomarkers is needed for their utilization in research. This study investigated the relationships between fasting concentrations of plasma HCY, SAM, SAH and the ratio of SAM:SAH, and serum folate, vitamin B(12) and creatinine in a healthy adult population. A cross-sectional study recruited 678 volunteers; only subjects with complete data (n = 581) were included in this analysis. Correlations were used to examine bivariate relationships among the biomarkers and multivariate linear regression determined independent relationships with HCY, SAM and SAH treated as dependent variables in separate models. Multivariate logistic regression examined determinants of a low SAM:SAH ratio (defined as having a SAM:SAH ratio in the bottom quartile and SAH value in the top quartile). HCY correlated inversely with folate and vitamin B(12) and weakly correlated with SAH and creatinine. Both SAM and SAH correlated with creatinine but were independent of serum folate and vitamin B(12). In multivariate analyses, folate, vitamin B(12), creatinine, sex and age were associated with HCY; age and creatinine were determinants of SAM, and sex and creatinine determinants of SAH. Finally, male sex and increasing creatinine levels were associated with having a low SAM:SAH ratio. Findings suggest that HCY, SAM and SAH are relatively independent parameters and reflect distinct aspects of one-carbon metabolism.

Folic acid supplementation in early second trimester and the risk of preeclampsia.

OBJECTIVE: The objective of the study was to evaluate the association between folic acid supplementation in early second trimester and the risk of developing preeclampsia. STUDY DESIGN: We carried out a prospective cohort study between October 2002-December 2005. We recruited women who had their prenatal care visit (12-20 weeks' gestation) at the Ottawa Hospital and Kingston General Hospital. All charts for participants with a diagnosis of preeclampsia were audited and blindly adjudicated by 4 study investigators to validate the diagnosis. RESULTS: A total of 2951 pregnant women were included in the final analysis. Supplementation of multivitamins containing folic acid was associated with increased serum folate (on average 10.51 micromol/L), decreased plasma homocysteine (on average 0.39 micromol/L), and reduced risk of preeclampsia (adjusted odds ratio, 0.37; 95% confidence interval, 0.18-0.75). CONCLUSION: Supplementation of multivitamins containing folic acid in the second trimester is associated with reduced risk of preeclampsia.

The effect of tobacco exposure on maternal and fetal thyroid function.

OBJECTIVE: To determine the effect of smoking on maternal and fetal thyroid function. STUDY DESIGN: This prospective cohort study involved healthy women undergoing elective cesarean section for term singleton infants. Maternal and fetal thyroid indices were compared between smokers (n=21) and non-smokers (n=83). RESULTS: Maternal thyrotropin (TSH) concentrations were significantly lower in smokers than non-smokers (1.75 mIU/L versus 2.15 mIU/L, respectively, p=0.007), with similar free thyroxine (FT4) concentrations (9.59 pmol/L versus 9.56 pmol/L, p=0.755). For women who smoked, the correlation between the average number of cigarettes smoked per day and maternal TSH concentrations was -0.427, p=0.054. Infants of smokers and non-smokers had similar umbilical TSH (5.43 mIU/L versus 5.82 mIU/L, p=0.124) and FT4 concentrations (13.06 pmol/L versus 13.57 pmol/L, p=0.049). CONCLUSION: We demonstrated for the first time that women who smoke during pregnancy have significantly lower TSH concentrations than non-smokers.

Folic Acid Supplementation in Pregnancy and the Risk of Pre-Eclampsia-A Cohort Study.

This prospective cohort study designed to assess the effect of folic acid supplementation in pregnancy on the risk of preeclampsia (PE) took place in Ottawa, ON and Kingston, ON, Canada, from September 1, 2002 to August 31, 2008. Pregnant women, less than 20 weeks gestational age were recruited and delivered in the Ottawa region and the Kingston General Hospital. Demographic characteristics of the study participants and the patterns of supplementation of folic acid were described and occurrence of PE between women with folic acid supplementation during pregnancy and women without were compared. Multiple logistic regression was used in the estimation of the independent effect of supplementation of folic acid. Additional analyses assessing the effect of low RBC and serum folate and dose-response relationship were performed. Analyses were performed in all study participants, and then in high risk and low risk sub-groups, respectively. A total of 7,669 participants were included in the final analysis. Ninety five percent of the study participants were taking folic acid supplementation in early second trimester. The rate of PE was lower in the supplementation group than in the no supplementation group, and the difference was statistically significant in high risk women. Similar patterns of associations were observed in analysis by RBC and serum folate levels and in dose-response analysis. Folic acid supplementation in pregnancy may reduce PE risk in pregnant women, especially in those women with increased risk of developing PE.

Biomarker measurements in a coastal fish-eating population environmentally exposed to organochlorines.

The Lower North Shore region of the St. Lawrence River is home to a fish-eating population that displays an unusually high body burden of several organochlorines, including polychlorinated biphenyls (PCBs) and dioxin-like compounds (DLCs). We measured biomarkers indicative of liver enzyme induction and investigated the relationship with organochlorine body burden in adult volunteers from this population. We determined plasma concentrations of PCBs and chlorinated pesticides by high-resolution gas chromatography (HRGC) with electron capture detection. DLC concentrations were measured by the dioxin-receptor chemically activated luciferase expression (DR-CALUX) assay and in a subset of participants, by HRGC/high-resolution mass spectrometry. We measured cotinine, d-glucaric acid, and porphyrins in morning urine samples and determined liver CYP1A2 activity in vivo using the caffeine breath test. Neither DLC concentrations as measured by the DR-CALUX nor PCB-153 concentrations, the latter representing total PCB exposure, were correlated with biomarkers of effects. Smoking (morning urinary cotinine concentration) was positively related to CYP1A2 activity as measured by the caffeine breath test (p < 0.01). Liver CYP1A2 activity was in turn negatively correlated with PCB-105:PCB-153 and PCB-118:PCB-153 congener ratios (p < 0.05). Hence, despite the relatively high body burden of PCBs and DLCs in this population, only smoking had a significant correlation with biomarkers of hepatic enzyme induction. Our data are consistent with smoking-induced liver CYP1A2 activity altering heme metabolism and increasing the biotransformation of mono-ortho PCB congeners.

Correlation between self-reported smoking status and serum cotinine during pregnancy.

Maternal smoking is associated with adverse perinatal outcomes. Because of concerns of underreporting, investigators routinely perform biochemical testing to confirm smoking status, such as serum cotinine, a major metabolite of nicotine, adding an increased cost to examine compliance. The objectives of this study were to determine the sensitivity and specificity of self-reported smoking with serum cotinine as the gold standard and to determine the correlation between self-reported smoking in cigarettes per day and serum cotinine levels. In this cross-sectional study, we surveyed women during the first trimester of pregnancy on their tobacco exposure. A total of 40 women reported that they were smokers, and 40 were nonsmokers, 1 of whom had quit 5 days prior. The mean (+/-S.D.) serum cotinine value among smokers was 155 (+/-122) ng/l, vs. 1 (+/-6) ng/l in nonsmokers, p<0.001. The sensitivity of self-reported smoking status was 97.6%, and the specificity was 100%. Comparing the reported number of cigarettes smoked and the serum cotinine level, the Spearman correlation coefficient was 0.92 (p=0.015) overall and 0.67 (p=0.088) for the subgroup of smokers. This study demonstrates that self-reported smoking exposure during pregnancy is highly accurate. The high correlation coefficient suggests that this is a robust surrogate for cotinine levels.

Free thyroxine and thyroid-stimulating hormone reference intervals in very low birth weight infants at 3-6 weeks of life with the Beckman Coulter Unicel DxI 800.

OBJECTIVES: To establish reference intervals for thyroid stimulating hormone (TSH) and free thyroxine (FT4) at 3-6 weeks of age in very low birth weight (VLBW) infants with the Beckman Coulter Unicel DxI 800 by gender, birth weight (BW) and gestational age (GA) subgroups. DESIGN AND METHODS: A 4 year retrospective cohort of 308 VLBW infants (GA=27.9 weeks, BW=992.3g) was studied. All blood samples for TSH and FT4 were analyzed using the modified fTSH2 (TSH) and two-step competitive enzyme immunoassay (FT4). Reference intervals were evaluated according to the most recent Clinical and Laboratory Standards Institute (CLSI) guidelines. RESULTS: The study provides non-parametric 95% reference intervals with associated 90% confidence intervals for FT4 and TSH derived from 308 infants screened at a median of 31 days. The reference intervals for this population are TSH=1.14-11.04 mIU/L and FT4=10.9-21.4 pmol/L. TSH statistically differed according to birth weight (<1000 g vs 1000-1499 g) while FT4 differed according to gender and gestational age at time of testing (<32 weeks vs ≥ 32 weeks); however, these differences were not clinically significant and a single reference interval for each analyte is reported. CONCLUSION: The results of this study highlight the importance and complexity of establishing appropriate reference intervals for thyroid function testing for the preterm population.

A comparison of glucose concentration in paired specimens collected in serum separator and fluoride/potassium oxalate blood collection tubes under survey 'field' conditions.

OBJECTIVES: There are no direct comparisons of blood glucose values in samples collected with barrier serum tubes (SST) and NaF/potassium oxalate (NaF/KOx) plasma tubes. Collection of samples in SST tubes can offer considerable savings and specimen processing advantages for national level surveys. DESIGN AND METHODS: Serum and plasma samples were collected under 'field conditions' from a single draw of 3692 individuals participating in the Canadian Health Measures Survey. The samples were analyzed retrospectively using the VITROS GLU Slide method (glucose oxidase-based). RESULTS: There was a high rate of hemolysis in the NaF/KOx tubes (86.2%) while hemolysis was infrequently observed with the SST tubes (2%). Comparing only blood draws where no hemolysis was observed in both tubes (n=495; paired t-test) showed no effect of tube type on serum/plasma glucose concentrations. This was also observed when data was restricted to cases when only SST samples were not hemolyzed (n=3546; paired t-test). CONCLUSIONS: These data show that both collection tubes can be used under survey collection and processing conditions to measure glucose with our assay system with no difference in reported results.

Thrombophilia and the risk for hemodialysis vascular access thrombosis.

Vascular access thrombosis is the most common and costly complication in hemodialysis patients. The role of thrombophilia in access thrombosis is not established. A case-control study was conducted of 419 hemodialysis patients to determine whether thrombophilia was associated with arteriovenous fistula or graft thrombosis. Participants were enrolled from three in-center and five satellite dialysis units associated with a Canadian academic health science center that provides dialysis services in a catchment area of one million. Patients were tested for factor V Leiden, prothrombin gene mutation, factor XIII genotype, methylenetetrahydrofolate reductase genotype, lupus anticoagulant, anticardiolipin antibody, factor VIII, homocysteine, and lipoprotein (a) concentrations. Overall, 59 (55%) patients with access thrombosis had at least one thrombophilia compared with 122 (39%) patients without access thrombosis (unadjusted odds ratio [OR], 1.91; 95% confidence interval [CI], 1.23 to 2.98). After controlling for important risk factors, the association between any thrombophilia and access thrombosis remained (adjusted OR, 2.42; 95% CI, 1.47 to 3.99). For each additional thrombophilic disorder, the odds of access thrombosis increased significantly (adjusted OR, 1.87; 95% CI, 1.34 to 2.61). This study suggests that thrombophilia is associated with access thrombosis in dialysis patients. Large, multicenter, prospective cohort studies are needed to confirm the observations from this case-control study.

Folate levels in pregnant women who smoke: an important gene/environment interaction.

OBJECTIVE: The objective of this study was to determine whether serum and red blood cell folate levels were decreased in pregnant women who smoke and whether total plasma homocysteine levels were elevated. STUDY DESIGN: In this cross-sectional study, serum folate, red blood cell folate, and homocysteine were measured in pregnant first- and early second-trimester pregnant women who smoked (case subjects) and pregnant women who did not smoke (control subjects). In addition, vitamin B(12), albumin, creatinine, cotinine, and hematocrit levels and methylenetetrahydrofolate reductase status were determined and compared between groups. RESULTS: Pregnant women who smoked had significantly lower concentrations of serum folate (22.7 vs 29.4 nmol/L; P =.001) and lower concentrations of red blood cell folate (766 vs 900 nmol/L; P =.038 [not significant]) than pregnant women who did not smoke. Dietary folate intake was not significantly different between pregnant women who smoked and pregnant women who did not smoke. Homocysteine levels were also not significantly different between the groups. For each genotype of methylenetetrahydrofolate reductase, lower levels of serum folate were observed in pregnant women who smoked, with the lowest folate levels seen in homozygous mutant methylenetetrahydrofolate reductase 677TT (18.6 nmol/L in pregnant women who smoked vs 24.2 nmol/L in pregnant women who did not smoke). CONCLUSION: Both serum folate and red blood cell folate are lower in pregnant women who smoked than in pregnant women who did not smoke, although homocysteine levels are not significantly different. There is an important gene environment interaction between methylenetetrahydrofolate reductase gene activity and tobacco exposure on serum folate levels. Lower levels of serum folate may account for the higher rate of miscarriage, stillbirth, abruptio placentae, and fetal anomalies that are observed in pregnant women who smoke. Pregnant women who smoke may benefit from higher doses of folic acid periconceptionally.