Joel Evans, MD discusses various recent medical studies.

by Joel M. Evans, MD 

Continued Exposure to Maternal Distress in Early Life is Associated with an Increased Risk of Childhood Asthma.

Am J Respir Crit Care Med. 2008;177:142-147 

Kozyrskyj AL, Mai XM, McGrath P, Hayglass KT, Becker AB, Macneil B.

Rationale: Evidence is emerging that exposure to maternal distress in early life plays a causal role in the development of childhood asthma.

Objectives: Because much of the data are from high-risk cohorts, we undertook a birth cohort study in a complete population of children to test this association.

Methods: Using Manitoba, Canada’s, health care and prescription databases, this longitudinal study assessed the association between maternal distress during the first year of life and onward, and asthma at age 7 in a 1995 birth cohort of 13,907 children.

Measurements and Main Results: Maternal distress was defined on the basis of health care or prescription medication use for depression or anxiety. Asthma status was derived from health care and prescription records for asthma, using a definition validated by comparison to pediatric allergist diagnosis. Multiple logistic regression was used to determine the likelihood of asthma (odds ratio [OR], 95% confidence interval [95% CI]). Independent of well-known asthma risk factors, our population-based study of a non-high-risk cohort demonstrated an increased risk of childhood asthma (OR, 1.25; 95% CI, 1.01-1.55) among children exposed to continued maternal distress from birth until age 7. Exposure to maternal depression and anxiety limited to the first year of life did not have a demonstrable association with subsequent asthma. Of interest, we observed that the risk of asthma associated with continued maternal distress was increased in children living in high- versus low-income households (OR, 1.44; 95% CI, 1.12-1.85).

Conclusions: Maternal distress in early life plays a role in the development of childhood asthma, especially if it continues beyond the postpartum period.

Comment: This article is important because it addresses a topic that is not studied much in the obstetric literature: the effect of maternal emotions on the health, both physical and emotional, of the child. The purpose of the study was to determine whether maternal distress in early life was associated with the development of childhood asthma in a complete population of children (13,907), including children who were or were not predisposed to asthma. This is a crucial question from a holistic perspective because the definition of a holistic health practitioner as is germane to this paper is one who investigates all causes of illness, including emotional, environmental and genetic. Thus, the possibility that there is a link between the emotional state of a new mother and the physical health of the child is vitally important.

Maternal distress was defined as a healthcare visit or prescription medication use for depression or anxiety from birth to age 7. There was no attempt to study maternal stress/distress during pregnancy or the effect of breastfeeding. Asthma status was determined from medical and prescription records for asthma, using a definition validated by comparison with diagnosis by a pediatric allergist.

The authors found that the risk for childhood asthma was increased among children exposed to continued maternal distress from birth until age 7 years (OR 1.25), which importantly was independent of well-recognized asthma risk factors. However, if the exposure to maternal depression and anxiety occurred only during the first year of life, it was not associated with development of asthma. Interestingly, children living in high-income vs low-income households had an even greater increased risk for asthma associated with continued maternal distress (OR 1.44).

These important findings, that stress/anxiety/depression in the mother during the first 7 years of life is associated with increased risk of asthma in children, speak to the many different ways that the stress response in mothers can affect children. The next step is to try to elucidate the causative pathways. Until that is done, all of us caring for new mothers should emphasize the importance of preventing and treating stress, anxiety and depression before, during and after pregnancy with: relaxation techniques, meditation, conflict resolution, adequate sleep, physical exercise, good nutrition, EPA:DHA supplementation, and adequate folate intake.

Consumption of Brussels Sprouts Protects Peripheral Human Lymphocytes Against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and oxidative DNA-damage: Results of a Controlled Human Intervention Trial.

Mol Nutr Food Res, 2008; 52(3): 330-341

Hoelzl C, Glatt H, Meinl W, Sontag G, Haidinger G, Kundi M, Simic T, Chakraborty A, Bichler J, Ferk F, Angelis K, Nersesyan AKnasmüller S. 

To find out if the cancer protective effects of Brussels sprouts seen in epidemiological studies are due to protection against DNA-damage, an intervention trial was conducted in which the impact of vegetable consumption on DNA-stability was monitored in lymphocytes with the comet assay. After consumption of the sprouts (300 g/p/d, n = 8), a reduction of DNA-migration (97%) induced by the heterocyclic aromatic amine 2-amino-1-methyl-6-phenyl-imidazo-[4,5-b]pyridine (PhIP) was observed whereas no effect was seen with 3-amino-1-methyl-5H-pyrido[4,3-b]-indole (Trp-P-2). This effect protection may be due to inhibition of sulfotransferase 1A1, which plays a key role in the activation of PhIP. In addition, a decrease of the endogenous formation of oxidized bases was observed and DNA-damage caused by hydrogen peroxide was significantly (39%) lower after the intervention. These effects could not be explained by induction of antioxidant enzymes glutathione peroxidase and superoxide dismutase, but in vitro experiments indicate that sprouts contain compounds, which act as direct scavengers of reactive oxygen species. Serum vitamin C levels were increased by 37% after sprout consumption but no correlations were seen between prevention of DNA-damage and individual alterations of the vitamin levels. Our study shows for the first time that sprout consumption leads to inhibition of sulfotransferases in humans and to protection against PhIP and oxidative DNA-damage.

Comment: Most integrative practitioners are aware of the health benefits of the cruciferous vegetables (broccoli, cabbage, cauliflower, kale, brussel sprouts) concerning detoxification, estrogen metabolism and breast cancer prevention. This article is important because it demonstrates that brussel sprouts possess direct anti-oxidant properties and protect DNA from oxidative damage. This data means that brussel sprout consumption has the possibility to have a protective effect against a wide range of cancers, not just breast cancer, in addition to ameliorating the effects of oxidative stress in many other disorders.

Total Joint Replacement After Glucosamine Sulphate Treatment in Knee Osteoarthritis: Results of a Mean 8-year Observation of Patients from Two Previous 3-year, Randomised, Placebo-controlled Trials.

Osteoarthritis Cartilage, 2008; 16(2): 254-60

Bruyere O, Pavelka K, Rovati LC, Gatterová J, Giacovelli G, Olejarová M, Deroisy R, Reginster JY

Objective: To assess the incidence of Total Joint Replacement (TJR) during the long-term follow-up of patients with knee osteoarthritis (OA) formerly receiving treatment with glucosamine sulphate or placebo.

Methods: Knee OA patients participating in two previous randomised, placebo-controlled, double-blind, 3-year trials of glucosamine sulphate and receiving treatment for at least 12 months, were systematically contacted to participate in a long-term follow-up retrospective assessment of the incidence of total knee replacement.

Results: Out of 340 patients with at least 12 months of treatment, 275 (i.e., 81%) could be retrieved and interviewed for the present evaluation: 131 formerly on placebo and 144 on glucosamine sulphate. There were no differences in baseline disease characteristics between groups or with the patients lost to follow-up. The mean duration of follow-up was approximately 5 years after trial termination and treatment discontinuation, making up a total of 2178 patient-years of observation (including treatment and follow-up). Total knee replacement had occurred in over twice as many patients from the placebo group, 19/131 (14.5%), than in those formerly receiving glucosamine sulphate, 9/144 (6.3%) (P=0.024, chi-square test), with a Relative Risk that was therefore 0.43 (95% confidence interval (CI): 0.20-0.92), i.e., a 57% decrease compared with placebo. The Kaplan Meier/Log-Rank test survival analysis confirmed a significantly decreased (P=0.026) cumulative incidence of total knee replacements in patients who had received glucosamine sulphate. A pharmacoeconomic analysis in a subgroup of subjects suggested that patients formerly on glucosamine sulphate had recurred to less symptomatic medications and use of other health resources than those from the placebo group during the last year of follow-up.

Conclusions: Treatment of knee OA with glucosamine sulphate for at least 12 months and up to 3 years may prevent TJR in an average follow-up of 5 years after drug discontinuation.

Comment: This is an important study because it addresses an area that is rarely researched in CAM: assessing the effects of CAM interventions after the termination of a study.  Here the authors found that patients in the treatment (glucosamine sulphate) arm of a knee osteoarthritis study were 57% less likely to require a knee replacement and were more likely to need less significant medical intervention than the placebo group in the years (mean 5 years) of follow up. This finding lends support to the theory that glucosamine sulphate causes long term changes in joint structure and/or function. Since the research findings on glucosamine sulfate have been mixed, this most recent positive study supports the clinical findings of many integrative practitioners that glucosamine sulfate is a useful part of their treatment plan for osteoarthritis.

Vitamin D Deficiency and Risk of Cardiovascular Disease

Circulation, 2008; 117(4): 503-11

Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, Benjamin EJ, D’Agostino RB, Wolf M, Vasan RS.

Background: Vitamin D receptors have a broad tissue distribution that includes vascular smooth muscle, endothelium, and cardiomyocytes. A growing body of evidence suggests that vitamin D deficiency may adversely affect the cardiovascular system, but data from longitudinal studies are lacking.

Methods and Results: We studied 1739 Framingham Offspring Study participants (mean age 59 years; 55% women; all white) without prior cardiovascular disease. Vitamin D status was assessed by measuring 25-dihydroxyvitamin D (25-OH D) levels. Prespecified thresholds were used to characterize varying degrees of 25-OH D deficiency (< 15 ng/mL, < 10 ng/mL). Multivariable Cox regression models were adjusted for conventional risk factors. Overall, 28% of individuals had levels < 15 ng/mL, and 9% had levels < 10 ng/mL. During a mean follow-up of 5.4 years, 120 individuals developed a first cardiovascular event. Individuals with 25-OH D < 15 ng/mL had a multivariable-adjusted hazard ratio of 1.62 (95% confidence interval 1.11 to 2.36, P=0.01) for incident cardiovascular events compared with those with 25-OH D > or = 15 ng/mL. This effect was evident in participants with hypertension (hazard ratio 2.13, 95% confidence interval 1.30 to 3.48) but not in those without hypertension (hazard ratio 1.04, 95% confidence interval 0.55 to 1.96). There was a graded increase in cardiovascular risk across categories of 25-OH D, with multivariable-adjusted hazard ratios of 1.53 (95% confidence interval 1.00 to 2.36) for levels 10 to < 15 ng/mL and 1.80 (95% confidence interval 1.05 to 3.08) for levels < 10 ng/mL (P for linear trend=0.01). Further adjustment for C-reactive protein, physical activity, or vitamin use did not affect the findings.

Conclusions: Vitamin D deficiency is associated with incident cardiovascular disease. Further clinical and experimental studies may be warranted to determine whether correction of vitamin D deficiency could contribute to the prevention of cardiovascular disease.

Comment: It seems like a new Vitamin D study is published almost every week. This is one of the latest Vitamin D studies showing a health promoting effect, but what makes this study different is that instead of looking at cancer or bone health, heart disease is the subject of the study. The famed Framingham Study Group looked at Vitamin D status and heart disease in a longitudinal fashion over a mean follow up interval of 5.4 years. Because of the well known positive effect of Vitamin D on cardiac muscle and endothelial function it should come as no surprise that those with lower levels had an increased risk of cardiovascular events. Although the authors say further studies are warranted, I feel this study is another solid piece of science supporting the practice of documenting and titrating Vitamin D dosing to achieve optimal levels in all of our patients, regardless of diagnosis, in order to achieve health and wellness.

Joel M. Evans, M.D. is an Assistant Clinical Professor of Obstetrics, Gynecology and Women’s Health at Albert Einstein College of Medicine. He is also the author of The Whole Pregnancy Handbook (Gotham 2005).