Associations of Maternal Vitamin B12 Concentration in Pregnancy With the Risks of Preterm Birth and Low Birth Weight: A Systematic Review and Meta-Analysis of Individual Participant Data.

Vitamin B12 (hereafter referred to as B12) deficiency in pregnancy is prevalent and has been associated with both lower birth weight (birth weight <2,500 g) and preterm birth (length of gestation <37 weeks). Nevertheless, current evidence is contradictory. We performed a systematic review and a meta-analysis of individual participant data to evaluate the associations of maternal serum or plasma B12 concentrations in pregnancy with offspring birth weight and length of gestation. Twenty-two eligible studies were identified (11,993 observations). Eighteen studies were included in the meta-analysis (11,216 observations). No linear association was observed between maternal B12 levels in pregnancy and birth weight, but B12 deficiency (<148 pmol/L) was associated with a higher risk of low birth weight in newborns (adjusted risk ratio = 1.15, 95% confidence interval (CI): 1.01, 1.31). There was a linear association between maternal levels of B12 and preterm birth (per each 1-standard-deviation increase in B12, adjusted risk ratio = 0.89, 95% CI: 0.82, 0.97). Accordingly, B12 deficiency was associated with a higher risk of preterm birth (adjusted risk ratio = 1.21, 95% CI: 0.99, 1.49). This finding supports the need for randomized controlled trials of vitamin B12 supplementation in pregnancy.

Folic acid supplementation in early pregnancy and the risk of preeclampsia, small for gestational age offspring and preterm delivery.

OBJECTIVE: To assess whether folic acid intake during the first trimester of pregnancy is related to pregnancy outcomes preeclampsia, low birth weight or preterm birth. STUDY DESIGN: Prospective cohort study of 3647 women who were followed from the first trimester of pregnancy. Detailed information on quantity of folic acid intake before and during the first three months of pregnancy was recorded. Pregnancy outcome data were abstracted from obstetric records. RESULTS: Lean mothers who used folic acid supplementation the month before pregnancy had a 40% reduced risk of developing preeclampsia. The adjusted odds ratio (OR) with 95% confidence intervals (95%CI) for preeclampsia in lean mothers (BMI<25) who used folic acid supplements the month before pregnancy was 0.6 (95% CI 0.4-1.0). Obese mothers who used folic acid supplementation in the first trimester had an increased, but not statistically significant risk for preterm birth (adjusted OR 1.9 with 95% CI 0.9-4.0). There were no significant associations between folic acid supplementation and low birth weight. CONCLUSION: Our study supports a possible protective effect of folate intake in early pregnancy on preeclampsia in lean mothers. There was no support for any beneficial effect of folic acid use on preterm birth or low birth weight, and we found no evidence of any harmful effects of folate use for the outcomes included in our study.

Steroids for acute spinal cord injury.

BACKGROUND: Acute spinal cord injury is a devastating condition typically affecting young people, mostly males. Steroid treatment in the early hours after the injury is aimed at reducing the extent of permanent paralysis during the rest of the patient's life. OBJECTIVES: To review randomized trials of steroids for human acute spinal cord injury. SEARCH METHODS: We searched the Cochrane Injuries Group Specialised Register (searched 02 Aug 2011), The Cochrane Central Register of Controlled Trials 2011, issue 3 (The Cochrane Library), MEDLINE (Ovid) 1948 to July Week 3 2011, EMBASE (Ovid) 1974 to 2011 week 17, ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) 1970 to Aug 2011, ISI Web of Science: Conference Proceedings Citation Index- Science (CPCI-S) 1990 to Aug 2011 and PubMed [www.ncbi.nlm.nih.gov/sites/entrez/] (searched 04 Aug 2011) for records added to PubMed in the last 90 days). Files of the National Acute Spinal Cord Injury Study (NASCIS) were reviewed (NASCIS was founded in 1977 and has tracked trials in this area since that date). We also searched the reference lists of relevant studies and previously published reviews. SELECTION CRITERIA: All randomized controlled trials of steroid treatment for acute spinal cord injury in any language. DATA COLLECTION AND ANALYSIS: One review author extracted data from trial reports. Japanese and French studies were found through NASCIS and additional data (e.g. SDs) were obtained from the original study authors. MAIN RESULTS: Eight trials are included in this review, seven used methylprednisolone. Methylprednisolone sodium succinate has been shown to improve neurologic outcome up to one year post-injury if administered within eight hours of injury and in a dose regimen of: bolus 30mg/kg over 15 minutes, with maintenance infusion of 5.4 mg/kg per hour infused for 23 hours. The initial North American trial results were replicated in a Japanese trial but not in the one from France. Data was obtained from the latter studies to permit appropriate meta-analysis of all three trials. This indicated significant recovery in motor function after methylprednisolone therapy, when administration commenced within eight hours of injury. A more recent trial indicates that, if methylprednisolone therapy is given for an additional 24 hours (a total of 48 hours), additional improvement in motor neurologic function and functional status are observed. This is particularly observed if treatment cannot be started until between three to eight hours after injury. The same methylprednisolone therapy has been found effective in whiplash injuries. A modified regimen was found to improve recovery after surgery for lumbar disc disease. The risk of bias was low in the largest methyprednisolne trials. Overall, there was no evidence of significantly increased complications or mortality from the 23 or 48 hour therapy. AUTHORS' CONCLUSIONS: High-dose methylprednisolone steroid therapy is the only pharmacologic therapy shown to have efficacy in a phase three randomized trial when administered within eight hours of injury. One trial indicates additional benefit by extending the maintenance dose from 24 to 48 hours, if start of treatment must be delayed to between three and eight hours after injury. There is an urgent need for more randomized trials of pharmacologic therapy for acute spinal cord injury.

Folic acid supplementation in early pregnancy and asthma in children aged 6 years.

OBJECTIVE: The objective of the study was to assess whether folic acid intake during the first trimester of pregnancy is related to asthma in the offspring by the age of 6 years. STUDY DESIGN: This was a prospective cohort study of 1499 women who were followed up from the first trimester of pregnancy. Their children were followed up until they were 6 years old. RESULTS: Fifty-one percent of the women used folic acid in the month before conception and 88% in the third month of pregnancy. The adjusted odds ratio for asthma per 100 µm increase in the average daily intake of folic acid was 0.98 (95% confidence interval, 0.93-1.04). For categories of daily folate intake, there was no evidence of associations with childhood asthma or evidence of any dose response relation for any time period (all P(trend) > .05). CONCLUSION: Our results do not support any association of folic acid supplementation in pregnancy and asthma risk in offspring by age 6 years.

Interpretation of 2002 Centers for Disease Control guidelines for group B streptococcus and evolving provider practice patterns.

We investigated if clinicians were altering their care of group B streptococcus (GBS)-positive women in labor to achieve 4 hours of intrapartum antibiotic prophylaxis based on their interpretation of the 2002 Centers for Disease Control (CDC) guidelines on prevention of perinatal GBS disease. We surveyed all clinicians with privileges on the labor floor at our institution about their interpretation and clinical application of the 2002 CDC guidelines. Seventy of 96 eligible clinicians (72.9%) completed our survey. In our survey, only 22.9% of clinicians reported not altering their management of labor in GBS-positive pregnancies that achieved less than 4 hours of prophylaxis. These alterations included "laboring down" or delaying pushing; turning off or decrease an oxytocin infusion; or delaying or avoiding artificial rupture of membranes. Clinicians are altering their management of labor to attempt to achieve 4 hours of intrapartum prophylaxis. The 2002 CDC guidelines do not specifically recommend prolonging labor and are being interpreted differently in the clinical setting than the authors may have intended. The effects and consequences of this interpretation are unknown.

The evidence base for complementary and alternative medicine: methods of Evidence Mapping with application to CAM.

BACKGROUND: There is widespread concern regarding the adequacy of evidence for specific practices under the rubric of "complementary and alternative medicine" (CAM). OBJECTIVE: To map the evidence pertaining to many commonly used CAM practices. DESIGN: In 2000, the Yale Prevention Research Center was funded by the Centers for Disease Control and Prevention to conduct a "systematic review" of the evidence underlying CAM. The investigative team, working in collaboration with CAM practitioners, developed a systematic and replicable 9-step process termed evidence mapping. The process stipulates means for specifying the boundaries of the subject to be mapped in MeSH terms, and the characteristics used to situate retrieved articles in the overall map of evidence. SETTING: Yale Prevention Research Center, Derby, CT. RESULTS: Steps completed thus far have led to the identification of over 4,000 papers distributed across 207 condition-treatment pairs. Of these pairs, 58% (n = 121) have been studied with one or more RCTs (1,070 total RCTs), and 23% (n = 47) have been the subject of one or more meta-analyses (86 total meta-analyses). Thirty-seven condition/treatment pairs (18%) had no identifiable supporting studies. CONCLUSIONS: The novel methods of evidence mapping reported are useful and practical in characterizing the extent, distribution, and methodologic quality of research pertaining to a broad topic in medicine. Applied to CAM, they suggest that summary judgments about the quantity or quality of underlying evidence are overly simplistic.

Heterogeneity in assessing self-reports of caffeine exposure: implications for studies of health effects.

BACKGROUND: Coffee and its metabolite caffeine are widely studied for their health effects but with inconclusive results. Caffeine is particularly difficult to assess, and therefore we explore heterogeneity of caffeine exposure. METHODS: We categorized caffeine exposure among 2,478 pregnant women in southern New England during 1996-2000 by the traditional laboratory-based methods of M. Bunker and M. McWilliams. A subsample was examined to ascertain caffeine levels of brewed or purchased beverages actually consumed. RESULTS: More than half (56.6%) of women drank coffee since becoming pregnant. Serving sizes ranged from 2 to 32 oz and are considerably larger than laboratory standards, which are typically 8-10 oz, as compared with the standard of 5 to 6 oz. Conversely, caffeine content per serving of coffee was one-third the laboratory standard, eg, 100 mg caffeine compared with 300 mg for a 10-oz cup. Tea brewed more than 3 minutes contained 42 mg caffeine as compared with the standard of 94 mg. When the amount of caffeine actually consumed was measured, one-quarter (24.8%) of subjects traditionally classified as consuming 300+ gm caffeine daily were reclassified as consuming 150-299 mg. CONCLUSION: Misclassification of caffeine consumption increases difficulty in identifying health effects from caffeine. Some combination of more precise consumption data and a biomarker such as paraxanthine may more precisely estimate exposure.