EAL

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

Citation:

Helland IB, Saugstad OD, Smith L, Saarem K, Solvoll K, Ganes T, Drevon CA. Similar effects on infants of n-3 and n-6 fatty acids supplementation to pregnant and lactating women. Pediatrics 2001; 108: e82.

PubMed ID: 11694666

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 investigate whether dietary supplementation of long chain n-3 fatty acids to pregnant and lactating Norwegian women would affect gestational length, birth weight, and the biochemical status and development of the newborns.

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 (112mg EPA+1,183mg DHA, total n-3 2,632mg, 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

Week 18 of pregnancy: Subject enrollment, begin supplementation, blood sample taken; FFQ
Week 35 of pregnancy: Blood sample taken; FFQ
Upon delivery: Blood sample taken from umbilical cord
Four and 13 weeks post-delivery: Blood sample taken from infants'; milk samples collected from morning feed
Three months post-delivery: Infant diet questionnaire.

Dependent Variables

Fatty acid content of breast milk (gas liquid chromatography)
Infant growth (weight, length, head circumference)
Infant development (EEG readings, Fagan test of infant intelligence)

Independent Variables

Maternal supplementation with either cod liver or corn oil from week 18 of pregnancy through three months post-partum.

Control Variables

Random assignment; double-blind design, timing of measurements

Description of Actual Data Sample:

Initial N

590 mothers randomized

Attrition (final N)

341 mothers (N=175 cod liver oil; N=166 corn oil)

Age

28.6± 3.4 years (cod liver oil); 27.6±3.2 years (corn oil)

Ethnicity

Not reported (Norwegian women)

Other relevant demographics

Anthropometrics

Maternal BMI 22 pre-pregnancy; BMI 28 at birth

Location

Institute for Nutrition Research, Department of Pediatric Research, Institute of Psychology, University of Oslo, Oslo, Norway

Summary of Results:

Fatty acids in breast milk (percent of weight) at four weeks and three months after birth

	Four Weeks		Three Months
Fatty acids (percentage of weight)	Cod Liver Oil (N=145)	Corn Oil (N=138	Cod Liver Oil (N-122)	Corn Oil (N=111)
20:4 n-6	0.38±0.07	0.41±0.07*	0.33±0.06	0.37±0.09*
20:5 n-3	0.43±0.19	0.13±0.09*	0.41±0.22	0.15±0.13*
22:5 n-3	0.36±0.13	0.19±0.09*	0.33±0.12	0.19±0.09*
22:6 n-3	1.37±0.58	0.49±0.32*	1.20±0.57	0.47±0.40*
Total Lipid (mg/100uL)	4.05±1.55	4.40±1.43	3.80±1.71	3.99±1.68

*P<0.001 compared to Cod Liver Oil group

Other Findings

Newborns with a higher DHA concentration in umbilical plasma phospholipids had longer gestational length; no differences found in EEG or Fagan scores (infant development).

Author Conclusion:

This study shows neither clear beneficial nor harmful effects of maternal supplementation of n-3 LCPUFAs regarding infant gestational length, infant growth or development as compared with supplementation with n-6 FAs.

Funding Source:

Industry:

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

Food Company:

Reviewer Comments:

Out of the 590 recruited, 222 women withdrew before giving birth. Most of the women who withdrew did so because of feeling discomfort taking the oil (43.1% and 38.7% in the cod liver oil group and corn oil group, respectively) or lack of compliance (9.5% in the cod liver oil group and 16.1% in the corn oil group.

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?	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?	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?		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?	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
	7.2.	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)?	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
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	Yes
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	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