EAL

BF: Dietary Factors, Breast Milk and Infant Outcomes (2008)

Citation:

Helland IB, Smith L, Saarem K, Saugstad OD, Drevon CA. Maternal supplementation with very-long chain n-3 fatty acids during pregnancy and lactation augments children's IQ at four years of age. Pediatrics 2003; 111: e39-44.

PubMed ID: 12509593

Study Design:

Randomized controlled trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

POSITIVE: See Quality Criteria Checklist below.

Research Purpose:

To test the hypothesis that maternal intake of very-long chain n-3 PUFAs is marginal and that the fetus and the newborn infant will benefit (IQ at four years of age) from increasing the mother's intake during pregnancy and lactation.

Inclusion Criteria:

Healthy women with singleton pregnancy, 19-35 years of age, nulli- or primiparous; intend to breastfeed their infants' no supplementation of n-3 fatty acids during pregnancy.

Exclusion Criteria:

Premature births, birth asphyxia, infections, anomalies in infants that required special attention.

Description of Study Protocol:

Recruitment

Not reported. Enrollment at first routine ultrasound scan exam at week 17-19 of pregnancy.

Design

Double-blind, randomized controlled supplementation trial.

Blinding used

Double-blind.

Intervention

Random assignment to receive either 10ml per day cod liver oil or 10ml per day corn oil (Peter Moller, Avd Orkla ASA, Oslo, Norway) or corn oil. Women consumed supplements until three months after delivery.

Statistical Analysis

Two-tailed student's T-test to examine differences between supplementation groups for continuous variables; Chi-square test used for categorical variables. P<0.05 as significant.

Data Collection Summary:

Timing of Measurements

K-ABC (IQ test) given to children at four years of age.

Dependent Variables

Intelligence (IQ): K-ABC - four scales (sequential processing, simultaneous processing, achievement, and non-verbal abilities. Achievement not used in present study).

Independent Variables

Supplementation group (cod liver oil vs. corn oil).

Control Variables

Timing of measurements.

Description of Actual Data Sample:

Initial N

N=48 in cod liver oil and N=36 in corn oil groups.

Age

Four years of age.

Other relevant demographics

NS differences in birth data and baseline characteristics between groups.

Location

Oslo, Norway.

Summary of Results:

Children in cod liver oil group had significantly (P=0.049) higher scores (106.4±7.4) than children in corn oil group (102.3±11.3) on Mental Processing Composite of the K-ABC test at four years of age.
There was a clear tendency to higher scores for sequential processing, simultaneous processing, and non-verbal scales in cod liver oil group, but these differences were not significant.
No correlation was observed between very long chain n-3 PUFAs in umbilical plasma phospholipids and IQ scores, but Mead acid (20:3 n-9) and Osbond acid correlated negatively with IQ scores.
IQ scores at four years of age correlated positively (P=0.03) with plasma phospholipid [DHA] and DHA at four weeks of age. Mental processing skills of children correlated significantly (P=0.03) with maternal intake of EPA and DHA during pregnancy.

Author Conclusion:

Maternal supplementation with very-long chain n-3 PUFAs during pregnancy and lactation improves IQ of children at four years of age. We still do not know whether cod liver oil supplements are important for formula-fed infants, nor whether the length of breastfeeding beyond three months may be important.

Funding Source:

Industry:

Peter Moller, Avd Orkla ASA, Aktieselskabet Freia Chocoladefabriks Medicinske Fond

Food Company:

Not-for-profit

Foundation associated with industry:

Reviewer Comments:

Refer to Helland et al, 2001 for trial specifics; This particular publication focused on IQ at age four (measured by K-ABC).

Only a small portion of children had IQ testing data. The authors stated that the study population did not differ from the population not tested with K-ABC on gestational length, birth weight, birth length, head circumference, placental weight, maternal age, maternal body mass index, maternal or paternal education, or parity.

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?	N/A
	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)	N/A
	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?	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
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?	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?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	Yes
	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.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	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
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?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	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
	6.5.	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?	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)?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	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
	9.1.	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