EAL

VN: Micronutrients in Pregnancy (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

Compare folate intake and status of pregnant women practicing a long term plant-based diet with similar subjects consuming an average Western Diet.

Inclusion Criteria:

Recruitment during 1995-1997.
Pregnant women recruited during any stage of pregnancy through delivery.
Subjects in vegetarian and low meat groups were included only if they had not changed their diet substantially for at least 3 years.

Exclusion Criteria:

Multiple gestations
Those taking vitamin and mineral supplements prior to study
Those that lived greater than 200 km from the study site (Germany)

Description of Study Protocol:

Recruitment 249 pregnant women responded initially to advertisements in magazines. Of those, 22 were not interested and 24 were excluded from participation; 203 were mailed questionnaires; 201 completed questionnaires

Design Women separated into 3 groups based on thier diet patterns

lacto-ovo vegetarian
low meat eaters
typical Western diet

Information of dietary intake was collected for 4 days (prior to blood draw.)

Blood samples (plasma folate, RBC folate, serum B12, serum zinc, serum ferritin)

Data collected once during each trimester of pregnancy.

Blinding: none

Intervention: none

Statistical Analysis

Statistical analyses were performed using SAS 8.2 (SAS Institute). All values are arithmetic means ± SEM or medians with 25th and 75th percentiles in parentheses. BMI was calculated as reported pregravid weight/height (kg/m2).

Generalized estimating equation (GEE) procedure was used. GEE models were generated to allow an appropriate analysis of longitudinal data with repeated measurement and missing values. Logistic regression analysis with repeated measurement design (GEE), and odds ratios and 95% confidence intervals were calculated.

Data Collection Summary:

Timing of Measurements

Information on dietary intake and blood sampleswere collected in each trimester of pregnancy (week 9–12,20–22 and 36–38 of gestation, i.e., postmenstruation).

Dependent Variables

plasma folate
RBC folate levels
serum B12 levels
serum Zinc levels
Serum ferritin levels

Independent Variables

nutritional behavior (questionnaire)
food consumption (semi-quantitative 4 day food frequency list, considering the usual dietary intake before pregnancy)
dietary folate (calculated using the German Food Code and Nutrition Data Base BLS II.3)

Control Variables: none

Description of Actual Data Sample:

Initial N: 109 women; 70 women consuming a plant-based diet (27 ovo-lacto vegetarians, 43 low-meat eaters) and 39 controls.

Attrition (final N): Only 60 subjects were assessed 3 times throughout pregnancy.

Age: (as Means ± SEM measured at beginning of pregnancy)

Lacto-ovo vegetarian 30.8 ± 0.9
Low Meat Eaters 30.6 ± 0.6
Western Diet 29.1 ± 0.6

Ethnicity: Not noted.

Other relevant demographics: Ovo-lacto vegetarians and low-meat eaters had similar mean age and parity as control group, but showed lower prepregnancy BMI and marginal differences in smoking habits.

Location: Germany

Summary of Results:

Median Folate Intake in Pregnant Women

Folate intake during pregnancy (micrograms per day)	Ovo-lacto Vegetarians (OLV) (n=27)	Low Meat Eaters (LME) (n=43)	Average Western Diet (AWD) (n=39)	Significance
Total dietary intake	1545	1551	1489	0.746 (OLV vs. LME) 0.072 (PV vs. AWD)
Bread, cereal, rice and pasta	282	273	277	0.888 (OLV vs. LME) 0.793 (PV vs. AWD)
Whole grain products	193	185	56	0.437 (OLV vs. LME) <0.0001 (PV vs. AWD)
Vegetables	277	280	175	0.647 (OLV vs. LME) <0.0001 (PV vs. AWD)
Potatoes	50	90	83	0.020 (OLV vs. LME) 0.501 (PV vs. AWD)
Fruits	408	337	222	0.114 (OLV vs. LME) <0.0001 (PV vs. AWD)
Juice	100	150	194	0.140 (OLV vs. LME) 0.143 (PV vs. AWD)
Milk, yogurt, cheese	291	328	324	0.303 (OLV vs. LME) 0.647 (PV vs. AWD)
Meat, fish, eggs	14	65	156	<0.0001 (OLV vs. LME) <0.0001 (PV vs. AWD)
Legumes, soy products	13	0	0	0.024 (OLV vs. LME) 0.001 (PV vs. AWD)
Raw food consumption	563	450	294	0.056 (OLV vs. LME) <0.0001 (PV vs. AWD)

Changes in folate intake during pregnancy were not significant within any dietary group (with exclusion of supplemental folate). The estimated average requirement, EAR, (520 micrograms DFE/d) was met by 13% of OLV, 9% of LME, and 5% of the AWD throughout pregnancy.

With the inclusion of supplemental folate, the EAR was met by 33% of OLV, 33% of LME and 36% of AWD.

Dietary Folate Intake (micrograms per 10 MJ)

Trimester	OLV	LME	AWD	P Value OLC vs. LME	P Value Partially Vegetarian vs. AWD
1	226	200	153	0.161	<0.0001
2	235	192	151	0.010	<0.0001
3	203	191	146	0.404	<0.0001
Mean	217	193	149	0.005	<0.0001

Blood Values

Plasma Folate: There were significant differences between OLV, LME and AWD groups, after control for effects of serum B12, supplemental folate and confounding factors.

RBC Folate:

Concentrations highest in OLV, then LME, then AWD groups.
Significant differences observed between OLV vs. AWD but not between LMW vs. AWD
OLV and LME differed significantly
RBC folate was positively related to plasma folate
No significant relation between RBC folate and folate intake
Folate derived from supplements appeared to be the strongest predictors of RBC folate, followed by serum vitamin B12 and also folate derived from fortified juices

Occurrence of folate deficiency

Deficiency defined as RBC folate concentrations <320 nmol/L in nonsupplemented participants
Occurrence of deficiency was lower in OLV and LME groups combined (13%)
AWD deficiency rates was observed at 29%
Odds ratio (with 95% CI) for risk of folate deficiency were lower for OLV and LME compared to the AWD

Author Conclusion:

Long term high consumption of vegetables is associated with improved folate status and therefore may reduce risk of folate deficiency during pregnancy.

This implies that a predominently vegetarian diet consumed on a long term basis with high dietary folate intake can be considered a useful way to optimize folate status and reduce, but not eliminate, risk of folate deficiency during pregnancy.

Funding Source:

Not-for-profit

Foundation associated with industry:

Reviewer Comments:

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
	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
	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
	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)	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
	1.	Was the research question clearly stated?	Yes
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
	1.3.	Were the target population and setting specified?	Yes
	2.	Was the selection of study subjects/patients free from bias?	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
	2.1.	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
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	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?	???
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
	3.	Were study groups comparable?	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
	3.1.	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
	3.2.	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.)	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	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
	3.4.	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
	3.5.	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
	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?	Yes
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	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%.)	Yes
	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%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	Yes
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
	5.	Was blinding used to prevent introduction of bias?	No
5.	Was blinding used to prevent introduction of bias?		No
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	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.)	No
	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.)	No
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	No
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	No
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	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
	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.	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
	6.1.	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?	No
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	No
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	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
	6.4.	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
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	N/A
	6.6.	Were extra or unplanned treatments 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
	6.7.	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
	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.	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
	7.1.	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
	7.2.	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?	N/A
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	N/A
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	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
	7.5.	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
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	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.	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
	8.1.	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
	8.2.	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?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	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
	8.4.	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)?	Yes
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	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
	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.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
	10.	Is bias due to study's funding or sponsorship unlikely?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes