Vegetarian Nutrition

VN: Micronutrients in Pregnancy (2007)

Citation:

Cheng PJ, Chu DC, Chueh HY, See LC, Chang HC, Weng DR. Elevated maternal midtrimester serum free beta-human chorionic gonadotropin levels in vegetarian pregnancies that cause increased false-positive Down syndrome screening results. Am J Obstet Gynecol. 2004 Feb;190(2):442-7.

PubMed ID: 14981387
 
Study Design:
Prospective Cohort Study
Class:
B - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:

To:

  1. Examine whether midtrimester maternal serum free beta-human chorionic gonadotropin (BhCG) and alpha fetoprotein (AFP) levels for Down syndrome screening differed in vegetarian pregnancies and omnivore pregnancies.
  2. Evaluate whether maternal serum vitamin B12 concentration affected these (BhCG and AFP) marker levels.
Inclusion Criteria:

Pregnant women who received prenatal care at the high-risk pregnancy center in Chang Gung Memorial Hospital, Lin-Kou, Taiwan and in the Bureau of Health Promortion, Department of Health, Taiwan, Republic of China during 1999-2001.

No known maternal complications or abnormal outcoms

Classified according to their habitual diets (lactovegetarian or omnivore)

Followed their a consistent dietary pattern for at least 1 year before conception

Exclusion Criteria:
Non-pregnant women
Description of Study Protocol:

Recruitment

Pregnant women who received prenatal care at the high-risk pregnancy center in Chang Gung Memorial Hospital, Lin-Kou, Taiwan and in the Bureau of Health Promortion, Department of Health, Taiwan, Republic of China during 1999-2001.

Signed written consent

Study samples consisted of 98 lactovegetarian; 122 omnivores

Design

Screening was performed between 14 and 18 weeks gestation using maternal serum AFP and free BhCG.

Values were expressed in multiples of the median (MoM) for gestational age.

Reference level of free BhCG and AFP were based on a population of 6312 singleton pregnancies with no known abnormal outcome and no congenital anomalies.

Serum vitamin B12 concentrations were also measured.

Blinding used: NA

Intervention: NA

 

Statistical Analysis

Maternal age, gestational age, maternal weight, free BhCG and AFP between the two study groups were evaluated with a two sample unpaired t test.

Maternal age, gestational age, maternal weight, free BhCG and AFP between the study group and the pregnant population were compared with a one-sample Z test.

ANOVA was made to compare free BhCG and AFP among the omnivore pregnancies, the vegetarian pregnancies with low serum levels of vitamin B12, and the vegetarian group with normal serum levels of vitamin B12.

Scheffe multiple comparison was conducted if significant finding was seen in ANOVA.

Further testing was used to compare the FPR between two study groups or between one study group and the reference pregnancy population, where appropriate.

Data Collection Summary:

Timing of Measurements

Screening was performed between 14 and 18 weeks gestation using maternal serum AFP and free BhCG and vitamin B12 concentrations.

Other measurements included maternal age, gestational age, and maternal weight

Dependent Variables

  • Lactovegetarian diet
  • Omnivore diet

Independent Variables

  • Serum AFP
  • Serum BhCG
  • Serum B12
  • gestational age
  • Maternal body weight
  • maternal age

Confounding Variables

  • Serum B12
Description of Actual Data Sample:

Initial N:

98 lactovegetarians (consumed no meat, fish or poultry, but did not exclude eggs and dairy products)

122 omnivores:  (consumed food of animal and vegetable origin or any type of food indiscriminately)

6312 population of reference singleton pregnancies with no known abnormal outcome and no congenital anomalies.

Attrition (final N): Only mentioned final study sample providing final data

Age:

  • Reference population:  28.71 years
  • Vegetarian group:  28.66 years
  • Omnivore group:  28.46 years

Ethnicity: Of Taiwan and Southern Asian descent

Other relevant demographics: Taiwanese

Location: Chang Gung Memorial Hospital, Lin-Kou, Taiwan and in the Bureau of Health Promortion, Department of Health, Taiwan, Republic of China during 1999-2001.

Summary of Results:

 

Maternal serum free BhCG and AFP MoM differences between vegetarian pregnancies, omnivore pregnancies, and the reference pregnant population

 

Reference pregnant population (n=6312)

Vegetarian pregnancies (n=98)

Omnivore pregnancies (n=122)

P value

Free BhCG

1.00 (0.42)

1.28 (0.80)

1.09 (0.93)

<.011*

.2997**

.0995***

AFP

1.00 (0.33)

1.06 (0.43)

0.98 (0.41)

0.719*

.5032**

.1311***

Values are given as mean (SD)

*Reference pregnant population versus vegetarian pregnancies; 1-sample Z test

**Reference pregnant population versus omnivore pregnancies; 1-sample A test

*** Vegetarian pregnancies versus omnivore pregnancies; 2-sample unpaired t-test

 

Maternal serum free BhCG and AFP MoM values, stratified by maternal serum levels of vitamin B12 in vegetarian pregnancies

 

Reference pregnant population (n=6312)

Vegetarian pregnancies with normal serum levels of vitamin B12 (n=79)

Vegetarian pregnancies with low serum levels of vitamin B12 (n=19)

P value

Free BhCG

1.00 (0.42)

1.09 (0.58)

2.08 (1.08)

.0568*

<.001**

<.001***

AFP

1.00 (0.33)

1.09 (0.45)

0.93 (0.31)

.1530*

.3552**

.1405***

Values are given as mean (SD). Normal serum levels of vitamin B12 are defined as vitamin B12 levels >200pg/ml.  Low serum levels of vitamin B12 are defined as vitamin B12 levels <200 pg/ml.

*Reference pregnant population versus vegetarian pregnancies with normal serum levels of vitamin B12; 1-sample Z test.

**Reference pregnant population versus vegetarian pregnancies with low serum levels of vitamin B12; 1-sample Z test.

***Vegetarian pregnancies with normal serum levels of vitamin B12 versus low serum levels of vitamin B12; 2-sample unpaired t-test.

  •  A statistical significantce was found in the maternal serum free B-hCG MoM levles, but not in the AFP MoM levles between the vegetarian pregnancies and the reference pregnant popultaion (P<0.001 and P=.0719 respectively.
  • No significant difference in the maternal serum-free B-hCG MoM levels or AFP MoM levels between the omnivore pregnancies and the reference pregnant population was observed.
  • However, there were no differences in maternal free B-hCG or AFP between the three study groups.
  • At the cut-off risk of 1:270, the False Positive Rate (FPR) for the reference pregnant population and the omnivore pregnancies group were 5.3% and 5.7% respectively (P=.566)
  • The FPR was 17.3% for the vegetarian pregnancies, which was significantly higher than the omnivore pregnancies group (P=.004) and the reference pregnant population (P<.001)
  • The vegetarian group had a significantly lower mean serum vitamin B12 concentration than that of the omnivore group (P<.001).

Because vegetarian diets are often times lower in vitamin B12, Low serum B12 levels are associated with elevated levels of BhCG.   The study sought to evaluate whether low B12 serum levels could affect maternal serum AFP and hCG levels in Down's syndrome screening.  If this is true, a lowered B12 level could affect the results of the screening to reflect more false positive results.

 

Author Conclusion:

This report describes that maternal serum free BhCG during the second trimester and the overall FPR in the serum screening for Down syndrome is elevated in pregnancies among vegetarian women with low serum levels of vitamin B12.

The authors emphasize the necessity of adequate vitamin B12 nutrition in the maintenance of the health of both mother and embryo.  The investigation of this phenomenon is of importance to avoid redundant invasive confirmation procedures.

For the present, Down syndrome screening in vegetarian pregnancies is more efficient if the screening is carried out by ultrasound markers and nuchal translucency mearsurement instead of the determination of maternal serum AFP and hCG levels before reference biochemical marker levels from vegetarian pregnancies are established.

Funding Source:
Government: Dept. of Health (Taiwan)
University/Hospital: Chang Gung Hospital, Chang Gung University (both Taiwan)
Reviewer Comments:

Strengths:

  • Large study in each group
  • Able to compare to large reference group (n=6312)

 

Weaknesses:

  • Did not look at possible effect of elevated homocysteine levels affecting placental changes.  This has been previously reported in Taiwanese vegetarians.
Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) N/A
 
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? N/A
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? Yes
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? ???
  4.1. Were follow-up methods described and the same for all groups? ???
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) ???
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? ???
  4.4. Were reasons for withdrawals similar across groups? ???
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? Yes
5. Was blinding used to prevent introduction of bias? ???
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) ???
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? ???
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? N/A
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? N/A
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? ???
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes