In-Depth Look: Peanut Butter Consumed During Pregnancy May Increase Asthma Risk for Child

A recent study on the topic was already featured here and this post provides a detailed analysis of the original article and related concepts.

If nut products (defined as peanut butter) are eaten regularly during pregnancy, the risk of asthma in the child increases significantly, according to a study published in the American Journal of Respiratory and Critical Care Medicine.

Maternal diet during pregnancy has the potential to affect airway development and to promote T-helper-2–cell responses during fetal life. The authors investigated the influence of maternal food consumption during pregnancy on childhood asthma outcomes from 1 to 8 years of age.

A birth cohort study consisting of a baseline of around 4,000 pregnant women (atopic and nonatopic) were asked about their frequency of consumption of fruit, vegetables, fish, egg, milk, milk products, nuts, and nut products during the last month. Their children were followed until 8 years of age.


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There were no associations between maternal vegetable, fish, egg, milk or milk products, and nut consumption and longitudinal childhood outcomes.

Daily consumption of nut products (peanut butter) increased the risk of childhood wheeze daily versus rare consumption, dyspnea, steroid use, and asthma symptoms.

The authors concluded that daily consumption of nut products increased the risk of asthma outcomes during the first 8 years of life.

The strange thing is that daily consumption of nuts was not significantly associated with a higher prevalence of asthma.

Best advice? "It's probably a good idea not to eat peanut products all the time during pregnancy." It is highly unusual to find someone who eats nuts or nut products every single day during their pregnancy but that was the only group of women who had an increased risk of their children developing asthma during the study.

Bottom line:

Nuts
No effect on child's asthma symptoms

Products of nuts
Peanut butter
Pervasive and persistent (daily) consumption
Probable association with asthma symptoms

On the other hand, Prenatal Exposure to n-3 Polyunsaturated Fatty Acids May Protect Against Asthma. Intake of n-3 polyunsaturated fatty acids (n-3 PUFAs) in pregnancy may have prophylactic effects against asthma in children, according to a study reported in the July issue of the American Journal of Clinical Nutrition.

Where do you find PUFAs? Study participants received four 1-g gelatin capsules per day containing fish oil providing 2.7 g n-3 PUFAs.

In-Depth Look: Peanut Butter Consumed During Pregnancy May Increase Asthma Risk for Child

PP-ICONS SHORTCUT

The most important information to look for when reviewing an article can be summarized by the acronym "PP-ICONS," which stands for the following:

Problem
Patient or population
Intervention
Comparison
Outcome
Number of subjects
Statistics

Problem: Possible connection between diet of pregnant mothers and children asthma

Population: 4,146 pregnant women and their children followed between years 1-8.

Intervention: Observation of the cohort of children until 8 years of age for development of asthma.

Comparison: Comparison between different groups of pregnant women and their children according to diet consumption.

Outcomes: Wheeze, dyspnea, steroid use.

There were no associations between maternal vegetable, fish, egg, milk or milk products, and nut consumption and longitudinal childhood outcomes. Daily consumption of nut products (peanut butter) increased the risk of childhood wheeze (odds ratio [OR] daily versus rare consumption, 1.42; dyspnea (OR, 1.58), steroid use (OR, 1.62), and asthma symptoms (OR, 1.47).

Number of subjects: Complete data were obtained for 2,832 children.

Statistics: Complicated statistics. No relative risk or absolute risk were calculated. Impossible to calculate number needed to harm (NNH): an epidemiological measure that indicates how many patients need to be exposed to a risk factor to cause harm in one patient that would not otherwise have been harmed (defined as the inverse of the attributable risk).

Bottom line:

Nuts
No effect on child's asthma symptoms

Products of nuts
Peanut butter
Pervasive and persistent (daily) consumption
Probable association with asthma symptoms

IN DETAIL

Study: Maternal Food Consumption during Pregnancy and the Longitudinal Development of Childhood Asthma.

Investigators: Saskia M. Willers and colleagues. All based in the Netherlands: Division Environmental Epidemiology, Utrecht University; National Institute for Public Health and the Environment; Department of Epidemiology, University Medical Centre Groningen; Erasmus Medical Centre/Sophia Children's Hospital, Rotterdam.

Utrecht University is one of the oldest universities in the Netherlands and one of the largest in Europe. It is rated as the seventh best university in Europe with an annual budget of €653 million. Erasmus University Rotterdam is the largest and one of the foremost academic medical centers in the Netherlands.

Source: American Journal of Respiratory and Critical Care Medicine Vol 178. pp. 124-131, July, (2008).

Funding: Supported by the Netherlands Organization for Health Research and Development; the Netherlands Organization for Scientific Research; the Netherlands Asthma Fund; the Netherlands Ministry of Spatial Planning, Housing, and the Environment; and the Netherlands Ministry of Health, Welfare and Sport.

Conflict of Interest: None.

Rationale: Maternal diet during pregnancy has the potential to affect airway development and to promote T-helper-2–cell responses during fetal life. This might increase the risk of developing childhood asthma or allergy.

What is fetal programming theory or Barker hypothesis?
Adverse events during pregnancy can result in impaired growth in the fetus and long-term physiologic or metabolic changes. In 1997, David Barker claimed a connection between intrauterine growth and disease in later life.

Several studies have provided evidence on associations between maternal diet during pregnancy and asthma and allergy in childhood. However, most studies have used cross-sectional statistical analyses to investigate this relationship.

This study provides evidence on the relationship between maternal diet during pregnancy and longitudinal development of childhood asthma.

What is the difference between cross-sectional analysis and longitudinal analysis?
Both are observational studies. Cross-sectional study is a "snapshot" which "freezes" a specific moment in time of characteristics of a disease in a population. The fundamental difference between cross-sectional and longitudinal studies is that cross-sectional studies take place at a single point in time and that a longitudinal study involves a series of measurements taken over a period of time, often many decades.

In a sense, a cross-sectional study is like taking a single snapshot and a longitudinal study is like making a video from multiple photos for many years.

Objective: Authors investigated the influence of maternal food consumption during pregnancy on childhood asthma outcomes from 1 to 8 years of age.

Study Design/Methods:
A birth cohort study consisting of a baseline of 4,146 pregnant women (1,327 atopic and 2,819 nonatopic). These women were asked about their frequency of consumption of fruit, vegetables, fish, egg, milk, milk products, nuts, and nut products during the last month. Their children were followed until 8 years of age. Longitudinal analyses were conducted to assess associations between maternal diet during pregnancy and childhood asthma outcomes over 8 years.

How was the birth cohort selected?
The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study, set up in 1996, consisted of a natural history part and an intervention part: 10,232 pregnant women completed a validated screening questionnaire at their prenatal health care clinic, 7,862 women were invited to participate, 4,146 women agreed.

Follow-up of the children was at 3 months of age and yearly from 1 to 8 years of age.

What was the intervention in Prevention and Incidence of Asthma and Mite Allergy (PIAMA) study?
Children born to allergic mothers were enrolled in a double-blind placebo-controlled trial for evaluating the use of mite-impermeable mattress and pillow covers. Children born to allergic and non-allergic mothers were enrolled in a 'natural history' study to assess the role of environmental and dietary risk factors for the development of allergic disease in childhood.

Assessment of Maternal Diet during Pregnancy
Expectant mothers were asked "How often did you consume vegetables, fresh fruit, fish, egg, milk, milk products, nuts, and nut products such as peanut butter during the last month?" Answer options were (1) never, (2) one to three times a month, (3) once a week, (4) two to four times a week, (5) more than four times a week, (6) once a day, or (7) several times per day. These frequency values were combined into three categories: rarely (value 1 and 2), regularly (value 3, 4, and 5), and daily (value 6 and 7).

In the Dutch population, tree nuts, peanuts, almonds, Brazil nuts, cashews, macadamia nuts, pistachios, are regarded as nuts.

For nut products, daily and regular consumption were compared with rare consumption as a reference category.

Assessment of the Child's Diet at 2 Years of Age for Confounding
The child's dietary data on fruit, vegetables, fish, egg, full cream milk, butter, and peanut butter consumption at 2 years of age were used to check for potential confounding by the child's diet.

Child's Health Outcomes
The yearly follow-up questionnaires contained the International Study of Asthma and Allergies in Childhood (ISAAC) questions on asthma, rhinitis, and eczema.

What is ISAAC?
ISAAC was formed in 1991 to facilitate research of asthma, allergic rhinitis and eczema by promoting a standardized methodology able to be used in diverse locations around the world. It consisted of 3 phases.

The main outcomes were wheeze, dyspnea, prescription of inhaled corticosteroids for respiratory problems, and the composite variable "asthma symptoms" in the last 12 months.

Data on wheeze were available from 1 to 8 years of age, data on dyspnea, and steroid use from 3 to 8 years of age.

How did they define "asthma"?
The composite variable "asthma symptoms" from 3 to 8 years of age was based on the wheeze, dyspnea, and steroid use outcomes (in the last 12 months).

Statistical Analyses
Generalized estimating equations (GEEs) were used to assess the associations between maternal diet and childhood asthma during the first 8 years of life.

What is generalized estimating equations?
Generalized estimating equations (GEEs) are used fit the parameters of a generalized linear model where unknown correlation is present. Generalized linear model was developed as a way of unifying various other statistical models, including linear regression, logistic regression and Poisson regression, under one framework.

What are the potential confounders?
Sex, education, parental allergy, maternal smoking, smoking in the home, breast feeding, older siblings, birth weight, maternal overweight, supplement use during pregnancy.

The associations between maternal intake of different food groups and different wheezing phenotypes were calculated by polytomous logistic regression analyses.

What is polytomous logistic regression analysis?
Logistic regression is one of the generalized linear models. It predicts the probability of occurrence of an event by fitting data to a logistic curve. Logistic curve is the most common sigmoid (S-shaped) curve: the initial stage of growth is approximately exponential; then, as saturation begins, the growth slows, and at maturity, growth stops. Logistic regression uses several predictor variables, for example, the probability that a person has a heart attack within a specified time period might be predicted from knowledge of the person's age, sex and body mass index.

Logistic sigmoid function with S-shaped curve: the initial stage of growth is approximately exponential; then, as saturation begins, the growth slows, and at maturity, growth stops.

The linear regression curve is different:
A linear regression equation with one independent variable represents a straight line.
Polytomous regression is an extension of logistic regression which copes with multi-category dependent variables.

The final models were adjusted for the same confounders used for the GEE analyses.

Multivariate logistic regression analyses were used to investigate the associations between maternal diet and sensitization to food allergens at 8 years of age.

What is multivariate logistic regression analysis?
Multivariate analysis describes observation of more than one statistical variable at a time. There are many different models. Regression analysis attempts to determine a linear formula that can describe how some variables respond to changes in others.

Results:
The initial population consisted of 4,146 pregnant women, 4,112 filled in the pregnancy questionnaire, 80% of them were at 30-36th week of gestation.

Was the dietary consumption statistically different outside of the timeframe 30-36 weeks?
No.

Only 243 mothers (6.2%) ate nut products (peanut butter) daily. Even smaller number (55, 1.4%) ate nuts daily. Only one woman ate fish daily (not an easy feat) and only six ate eggs daily.

Asthma symptoms are shown in Table 3. Prevalence of wheeze and dyspnea strongly decreased with time.

The composite variable "asthma symptoms" (based on 3: wheeze, dyspnea, setroid use) decreased from 23% at 3 years of age to 13% at 8 years.

Associations between Maternal Food Consumption and Childhood Asthma

There were no associations between maternal vegetable, fish, egg, milk or milk products, and nut consumption and longitudinal childhood outcomes!

Nuts
No effect on child's asthma symptoms

Products of nuts
Peanut butter
Pervasive and persistent (daily) consumption
Probable association with asthma symptoms

Regular consumption of nut products (once a week to more than 4 times a week) did not increase the risk significantly but the daily consumption (once a day to several times per day) did (p less than 0.05).

What is the difference between odds ratio, realtive risk and attributable risk? How can we calculate the number needed to harm (NNH)?

Odds ratio is defined as the odds of disease in exposed persons divided by the odds of disease in unexposed persons. An odds ratio of 1 indicates that the condition under study is equally likely in both groups. An odds ratio greater than 1 indicates that the condition is more likely in the first group (experimental group). And an odds ratio less than 1 indicates that the condition is less likely in the first group (experimental group). In most circumstances, the odds ratio is a close approximation to relative risk.

Attributable risk is the disease rate in exposed persons minus that in unexposed persons. It is the measure of association that is most relevant when making decisions for individuals.

Relative risk is the ratio of the disease rate in exposed persons to that in people who are unexposed. It is related to attributable risk by the formula: Attributable risk= rate of disease in unexposed persons x (relative risk- 1).

Relative risk is less relevant to making decisions in risk management than is attributable risk. For example, given a choice between a doubling in their risk of death from bronchial carcinoma and a doubling in their risk of death from oral cancer, most informed people would opt for the latter. The relative risk is the same (two), but the corresponding attributable risk is lower because oral cancer is a rarer disease.

The number needed to harm (NNH) indicates how many patients need to be exposed to a risk factor to cause harm in one patient. It is defined as the inverse of the attributable risk.

Was maternal nut product consumption associated with sensitization to food allergens or a high total IgE level?
No.

Was there an effect from the child's diet?
No. Maternal diet during pregnancy and the child's diet at 2 years were strongly associated. However, including the child's consumption of fruit, vegetables, fish, egg, and peanut butter in the models did not change the results.

Any bias due to allergic mothers avoiding certain foods?
Maternal food allergy could be a reason to avoid consumption of certain foods. However, dietary intake of atopic and nonatopic mothers were no significantly different.

Exclusion of mothers who never ate fish, egg, or nuts and nut products did not change the results.

Did food supplements affect the results?
Supplements were used by 83% of the pregnant women. All multivariate analyses were adjusted for maternal supplement use and did not alter the results.

Discussion:
There was no association between the maternal intake of the investigated food groups and childhood asthma symptoms until 8 years of age, except for daily nut products (peanut butter).

Nuts
No effect on child's asthma symptoms

Products of nuts
Peanut butter
Pervasive and persistent (daily) consumption
Probable association with asthma symptoms

What are the study limitations?
Limited information on food groups
Complicated statistics
No relative risk or attributable risk to calculate number needed to harm (NNH)

There was only information on the frequency of intake of larger food groups. The questionnaire did not contain questions on intake of more specific foods or portion sizes.

For example, in a UK study by Willers et al., there was a beneficial effects of maternal apple consumption on wheeze and asthma in children but not of maternal total fruit consumption.

There may be effects of fruit-specific (or nut product-specific) nutrients that cannot be found when only analyzing the effect of total fruit consumption.

This study showed an increased risk of daily consumption of nut products during pregnancy on childhood asthma outcomes.

How about nut products other than peanut butter?
They did not ask. Only peanut butter was listed as an example of nut products in the questionnaire. Peanut butter is a commonly used spread on sandwiches in the Netherlands whereas the use of other nut spreads is not common. Authors assumed that the largest proportion of nut products is peanut butter.

There was no associations between daily nut product consumption during pregnancy and sensitization to food or inhalant allergens or doctor-diagnosed peanut allergy reported at 8 years of age.

What is so special about peanut better? Any reason why it could increase asthma risk?
Peanut butter contains 20% linoleic acid. Increased intake of linoleic acid may lead to higher levels of cellular arachidonic acid, which increases the capacity to produce prostaglandin E2. PGE2 can alter the balance of Th1 and Th2 cytokines, leading to increased formation of IgE and hence to atopic disease

Daily consumption of 1-2 peanut butter sandwiches may substantially increase the intake of linoleic acid.

But walnuts, Brazil nuts, and pecans contain more linoleic acid than peanuts. Linoleic acid content of peanuts and peanut butter is comparable.

What is lipid hypothesis by Black and Sharpe?
In 1997, Black and Sharpe proposed the so called lipid hypothesis: decreasing antioxidant (fruit and vegetables), increased n-6 polyunsaturated fatty acid (PUFA; (margarine, vegetable oil), and decreased n-3 PUFA (oily fish) intakes may have contributed to the recent increases in asthma and atopic disease.

Conclusion:
Authors concluded that results of this study indicate an increased risk of daily versus rare consumption of nut products (peanut butter) during pregnancy on childhood asthma outcomes. These findings need to be replicated by other studies before dietary advice can be given to pregnant women.

Take home points

Nuts
No effect on child's asthma symptoms

Products of nuts
Peanut butter
Pervasive and persistent (daily) consumption
Probable association with asthma symptoms

References:
Maternal Food Consumption during Pregnancy and the Longitudinal Development of Childhood Asthma. American Journal of Respiratory and Critical Care Medicine Vol 178. pp. 124-131, July, (2008).
A Simple Method for Evaluating the Clinical Literature. Fam Pract Manag 11(5):47-52, 2004.
The prevention and incidence of asthma and mite allergy (PIAMA) birth cohort study: design and first results. Pediatr Allergy Immunol. 2002;13 Suppl 15:55-60.
International Study of Asthma and Allergies in Childhood (ISAAC): rationale and methods. Eur Respir J 1995; 8: 483-491.
Nut Products Consumed During Pregnancy Tied to Childhood Asthma Risk. MedPage Today.
Study Shows Eating Nuts Daily During Pregnancy May Up Kids' Risk of Asthma. WebMD.
Food Allergy: A Short Review. Allergy Cases.
Introduction of cooked egg at 4 to 6 months of age might protect against egg allergy.http://goo.gl/YBf6
Maternal consumption of peanut during pregnancy is associated with peanut sensitization in atopic infants http://goo.gl/rned
Images source: Wikipedia, public domain.
Description of statistics function from Wikipedia, verified with independent sources.

This an excerpt from a Journal Club presented by V. Dimov, M.D. to Creighton University Division of Allergy & Immunology. Faculty adviser: R. Hopp, D.O., Ph.D., Professor, Creighton University Division of Allergy & Immunology.

Updated: 11/01/2010

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