VN: Micronutrients in Pregnancy (2007)

Study Design:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
A nutritional zinc deficiency may be one factor in the slower rate of intrauterine growth of Asian babies and this study was undertaken to explore this possibility.
Inclusion Criteria:
  • Confirmed pregnant women who delivered at Northwick Park Hospital (NPH) in Harrow
[Note: Of this population, 20% are Asians, mainly Hindus of Gujarati descent. This population, along with Europeans in this study, are relatively affluent.]
  • Subjects were recruited from November 1979 through June 1980.
Exclusion Criteria:
  • Non-pregnant women
  • Pregnant women that were carrying multiples
  • Women that had aborted during the study.
Description of Study Protocol:
  • Recruitment: Subjects were recruited from November 1979 through June 1980
  • Design: Based on diet and ethnicity, subjects were placed into one of three different groups: Hindu vegetarians, Hindu meat eaters and European meat eaters. Plasma, urine and hair samples were taken at various intervals in order to measure and assess zinc status.

Statistical Analysis

  • Dietary intake, physicial characteristics and infant birth weight, along with the trace element content of hair were compared between groups using Student's T-test 
  • Multiple regression analyses were conducted to note any differences between groups' biochemical measurements
  • Zinc, copper and other variables were examined for correlations between them and for correlations with dietary intake or pregnancy outcome.
Data Collection Summary:

Timing of Measurements

  • Plasma samples were taken at initial visit, 20 weeks, 28 weeks and 36 weeks
  • 24-hour urine samples were collected at initial visit, 20 weeks and 36 weeks
  • Hair samples were taken at initial visit and 36 weeks.

Dependent Variables

  • Urinary zinc
  • Hair zinc
  • Hair copper
  • Serum albumin
  • Urinary urea
  • Plasma zinc
  • Plasma copper.

Independent Variables

  • Vegetarian diet
  • Non-vegetarian diet.

Control Variables

All subjects were provided daily supplements of 100mg iron and 350Ug of folic acid.

Description of Actual Data Sample:
  • Initial N: 97 Hindus and 53 Europeans initially agreed to take part in the study
  • Age: NA.


  • Of the Hindus, 59 were vegetarian, 33 were meat eaters;
  • 52 European meat eaters.

Other Relevant Demographics

Of this population, 20% are Asians, mainly Hindus of Gujarati descent. This population, along with Europeans in this study, are relatively affluent.


Maternal and infant characteristics in three patient groups.





Meat Eater

Number of subjects




Height (cm)

155.3 (5.8)

156.1 (4.8)

162.3 (5.8)

Maternal weight at 20 weeks gestation

55.1 (9.3)

56.5 (7.6)

63.1 (7.9)

Smokers (N)




Gestational age (weeks)

38.6 (1.5)

38.6 (2.2)

39.5 (1.5)

Birthweight (g)

2905 (517)

2926 (635)

3349 (446)

Pregnancy weight gain (kg/week)

0.445 (0.231)

0.459 (0.172)

0.470 (0.125)

Primiparae (N)




Spontaneous vaginal delivery (N)




Summary of Results:
Dietary Intake in Three Patient Groups
Meat Eaters
Energy (kcal)
1,971 (523)
2,165 (460)
2,033 (260)
Protein (gm)
57.3 (15.6)
75.1 (18.9)
80.3 (19.6)
Iron (mg)
11.1 (4.6)
12.8 (4.0)
10.9 (2.3)
Copper (mg)
1.53 (0.70)
1.80 (0.76)
1.48 (0.30)
Zinc (mg)
7.5 (2.1)
10.2 (3.0)
11.6 (2.8)
Dietary Fiber (g)
23.1 (6.9)
22.8 (6.8)
19.1 (7.4)








Results are means (SD)

  • Within Hindu groups, they had similar levels of energy, iron and copper as did the European sample
  • Vegetarians had significantly lower protein and zinc intakes than meat eaters.

Plasma Zinc and Copper with Serum Albumin Concentrations

Patient Group
Number of Women
Serum Concentrations
Zinc (umol/l)
Albumin (g/l)
Copper (umol/l)
Hindu Vegetarian
Initial visit
8.97 (1.70)
39.5 (3.1)
27.9 (5.4)
20 weeks
8.63 (1.96)
36.3 (2.2)
28.9 (4.4)
28 weeks
8.4 (0.98)
35.4 (2.3)
30.4 (4.1)
36 weeks
7.96 (1.17)
34.2 (2.1)
30.7 (5.5)
Meat Eater
Initial visit
9.22 (2.11)
39.3 (2.8)
28.2 (5.3)
20 weeks
8.72 (1.67)
36.3 (1.5)
28.5 (5.9)
28 weeks
7.94 (1.31)
34.7 (2.1)
29.4 (5.5)
36 weeks
8.22 (1.54)
33.9 (2.1)
29.0 (5.0)
Initial visit
9.59 (1.92)
40.2 (3.0)
24.5 (5.2)
20 weeks
8.95 (1.25)
36.9 (2.2)
28.5 (4.7)
28 weeks
8.91 (1.18)
36.3 (2.2)
28.8 (5.2)
36 weeks
8.46 (1.17)
34.6 (2.5)
27.9 (4.8)
Hindu Vegetarians vs. Hindu Meat Eaters
Not significant
Not significant
Not significant
Europeans vs. Hindus
Not significant

Results are nean (SD)
P-value is the significance of the difference between patient groups , using the four sampling times after adjustment for differences in gestation at bookings.

  • Plasma zinc concentrations were higher for Europeans, but not significantly different between the vegetarians or the meat eaters
  • Serum albumin did not differ significantly between any groups, but in all three groups there was a fall of 13% (P<0.001) and this had a small but significant correlation with the fall in plasma zinc (P<0.05)
  • In contrast, plasma copper concentration rose by 13% (P<0.001) and the ethnic difference was reversed, the Hindus having higher levels than the Europeans (but not significant)
  • No evidence that those with higher copper levels had lower zinc, nor that those with higher copper levels had the greatest fall in zinc.

Excretion of Zinc in 24-Hour Samples in Three Patient Groups

 Patient Group
Number of Women
Serum Concentrations
Urine Weight (kg)
Creatinine (mmol)
Zinc (umol)
Urea (mmol)
Hindu Vegetarians
Initial visit
1.14 (0.43)
7.05 (1.5)
3.96 (1.79)
1.57 (43)
20 weeks
1.31 (0.44)
7.53 (1.8)
3.92 (2.17)
165 (47)
36 weeks
1.22 (0.40)
7.14 (2.0)
4.67 (2.1)
148 (47)
Hindu Meat Eaters
Initial visit
1.31 (0.46)
8.4 (1.9)
4.73 (2.19)
207 (76)
20 weeks
1.23 (0.48)
9.3 (2.3)
5.65 (3.80)
198 (62)
36 weeks
1.35 (0.38)
8.6 (2.2)
6.09 (3.49)
186 (53)
Initial visit
1.37 (0.47)
10.3 (1.9)
5.69 (2.46)
318 (91)
20 weeks
1.33 (0.48)
10.8 (2.6)
5.25 (1.68)
300 (110)
36 weeks
1.41 (0.50)
10.9 (2.2)
7.94 (3.49)
251 (61)
Hindu Vegetarians vs. Hindu Meat Eaters
Not significant
Europeans vs. Hindus
Not significant

Results are Mean (SD)
P-value is the significance of the difference between patient groups using the four sampling times after adjustment for differences in gestation at bookings.

  • Urinary zinc excretion increased during pregancy; plasma zinc decreased during pregnancy
  • Increase in urinary zinc excretion was greatest in Europeans.

Zinc and Copper Concentrations in Hair in Three Patient Groups

 Patient Group
 Number of Women
Concentrations in Hair
Zinc (ug/g) Mean (SD)
Copper (ug/g) Geometric Mean (Range)
Hindu Vegtarian
Initial visit
191 (29.0)
15.4 (8.3-66.1)
36 weeks
187 (25.9)
15.6 (6.9-88.8)
Hindu Meat Eater
Initial visit
198 (22.9)
19.1 (8.7-43.6)
36 weeks
194 (13.7)
16.1 (6.1-51.0)
Initial visit
197 (28.6)
25.5 (9.2-84.6)
36 weeks
189 (30.9)
20.4 (9.1-98.4)

  • No statiscally significant hair zinc measures were noted between groups. There were lower levels of zinc hair measures at 36 weeks vs. initial. This was reflective of a lowered plasma zinc level at later gestation.
  • Europeans tended to have higher copper hair levels at initial visit than Hindus, but this change throughout pregnancy was similar in all groups.
Author Conclusion:
  • The Hindus in this study had an apparently lower zinc status than the Europeans, reflecting a lower average zinc intake
  • There was no evidence that these differences in zinc status and intake were associated with the slower intrauterine growth of their infants or with any other functional deficit
  • Based on this study and in the absence of sound evidence that additional zinc can improve the outcome of pregnancy, routine zinc supplements cannot be recommended for otherwise healthy pregnant women.
Funding Source:
Government: North West Thames Regional Health Authority
University/Hospital: University of California
Foundation associated with industry:
Reviewer Comments:


  • Relatively large groups
  • Ability to obtain multiple biochemical tests in order to better determine zinc status.
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) Yes
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? Yes
  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.) 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
  3.6. 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
  4.1. 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
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? 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
5. Was blinding used to prevent introduction of bias? 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
  5.3. 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? Yes
  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? 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
  7.1. 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? N/A
  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? 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
  8.5. 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? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes