EAL

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

Citation:

Dunstan JA, Mitoulas LR, Dixon G, Doherty DA, Hartmann PE, Simmer K, Prescott SL. The effects of fish oil supplementation in pregnancy of breast milk fatty acid composition over the course of lactation: A randomized controlled trial. Pediatric Research 20007; 62 (6): 689-694.

PubMed ID: 17957152

Study Design:

Randomized controlled trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

NEUTRAL: See Quality Criteria Checklist below.

Research Purpose:

To explore the potential benefits of fish oil supplementation in pregnancy on subsequent breast milk composition as a continued source of n-3 LCPUFAs for infants over the course of the first six months of lactation.

Inclusion Criteria:

Mothers who delivered after 36 weeks of gestation. All mothers had a history of physician-diagnosed allergic rhinitis or asthma, and one or more positive skin prick tests to common allergens.

Exclusion Criteria:

Smokers, medical problems, normal dietary intake exceeded two meals of fish per week.

Description of Study Protocol:

Recruitment

Women recruited between week 16 and 20 of gestation from antenatal clinics and private OB-GYNs.

Design

Randomized controlled trial; groups block randomized according to parity, pre-pregnancy BMI, age, maternal allergy.

Blinding used

Double-blind.

Intervention

From 20 weeks of gestation until delivery, mothers received either:

Fish oil group: Four 1g fish oil capsules per day: 3.7g of n-3 LCPUFAs with 56% DHA, 27.7% EPA
Control: Four 1g capsules of olive oil per day: 66.6% n-9 oleic acid, <1% n-3 LCPUFAs.

Statistical Analysis

Independent and paired- T-tests; logistic regression; general linear model with repeated measures; Pearson's correlation. P<0.05 level of significance for clinical outcomes; P<0.01 significance level for all FA analysis.

Data Collection Summary:

Timing of Measurements

Three days, six weeks, six months post-partum: Breast milk samples collected (manual expression or pump)
36 weeks gestation, six weeks post-partum: Blood samples collected from mom
One year of age: Blood samples collected from infant; clinical evaluation of allergies and asthma
2.5 years of age: Infant evaluated by psychologist (developmental measures).

Dependent Variables

FA composition of breast milk (gas chromatography)
FA composition of erythrocytes (gas chromatography).

Clinical outcomes: Infant

Infant allergies
Height, weight, head circumference
Developmental measures (Griffiths Mental Development Scales)
Receptive language (Peabody Picture Vocabulary Test IIIA)
Behavior (Child behavior checklist one to five years).

Independent Variables

Treatment assignment (Fish oil vs. control).

Control Variables

Parity, pre-pregnancy BMI, age, maternal allergy (Block randomization).

Description of Actual Data Sample:

Initial N

Fish oil group N=52; Control group: N= 46

Attrition (final N)

N=73 moms total provided breast milk samples at one or more time points; N=50 moms were still breastfeeding at six months post-partum (N=23 in Fish oil and N=27 in control groups).

Maternal Age; Ethnicity; Anthropometrics; Other relevant demographics

No significant differences in characteristics of these groups (reported elsewhere).

Location

Perth, Western Australia.

Summary of Results:

Breast milk FA (% of total FA) at three days (N=33 fish oil, 40 control), six weeks (N=30 fish oil, 37 control), six months (N=23 fish oil, 27 control) post-partum.

Fatty Acids	Three Days (N=33 fish oil, N=40 control)	Six Weeks (N=30 fish oil, N=37 control)	Six Months (N=23 fish oil, N=27 control)	Statistical Significance of Group X Time Interaction
18:1n9	33.32±4.1, 33.55±3.3	33.84±3.1, 34.69±2.9	34.37±3.9, 35.33±3.8	0.155
18:2n6	8.84±2.1, 8.74±1.9	9.91±2.3, 10.71±3.4	10.81±1.9, 10.61±2.7	0.988
18:3n3	0.7±0.3, 0.72±0.3	0.93±0.3, 1.01±0.4	1.16±0.5, 1.09±0.4	0.926
20:2n6	0.45±0.1, 0.44±0.1	0.22±0.1, 0.21±0.1	0.17±0.0, 0.16±0.0	0.389
20:3n6	0.43±0.1*, 0.55±0.1	0.35±0.1, 0.37±0.1	0.25±0.0, 0.24±0.0	0.039
20:4n6	0.55±0.1, 0.61±0.1	0.35±0.1, 0.38±0.1	0.36±0.1, 0.37±0.1	0.098
20:5n3	0.56±0.3*, 0.28±0.1	0.09±0.0^+, 0.07±0.0^	0.10±0.1, 0.10±0.1	0.007
22:5n3	0.56±0.3*, 0.28±0.1	0.20±0.0^, 0.17±0.0^	0.21±0.1+, 0.22±0.2	<0.001
22:6n3	1.15±0.5, 0.5±0.2	0.42±0.2^, 0.25±0.1^	0.38±0.2+, 0.34±0.4	<0.001

*P<0.001, ^P<0.01 between-group difference; +P<0.01 within group changes between time points.

Other Findings

Infant DHA status at one year of age was directly related to DHA levels at three days, six weeks, and six months post-partum (but not to antenatal supplementation).

Both EPA and DHA in breast milk were positively correlated with Griffith's developmental scores including hand-eye coordination.

Cognitive Outcomes From GMDS	Breast Milk Fatty Acids Three Days Post-partum (N=64)			Breast Milk Fatty Acids Six Months Post-partum (N=58)
	EPA	DPA	DHA	EPA	DPA	DHA
Locomotor	0.273*	0.172	0.256*	0.155	0.173	0.231
Social	0.244	0.237	0.271*	0.141	0.094	0.25
Speech and hearing	0.288*	0.239	0.239

*P<0.05

Author Conclusion:

Fish oil supplementation during the second half of pregnancy modified breast milk LCPUFA composition. Breast milk composition (rather than pregnancy levels) contributed to infant n-3 LCPUFA status at one year of age.

In addition to improving neonatal n-3 LCPUFA status, fish oil supplementation in pregnancy has continued effects on infant FA status through effects on breast milk composition.

Funding Source:

Government:

Child health research foundation of W. Australia

Industry:

Reviewer Comments:

The major limitation of this study is that the observed correlation between breast milk EPA/DHA and infant outcomes were for breast-fed infants only; the exclusivity of breastfeeding was not determined. Complete analysis usually causes biases.

The randomization was broken due to complete analysis. Therefore the groups were not comparable anymore.

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?		No
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	No
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	???
	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?		No
	4.1.	Were follow-up methods described and the same for all groups?	No
	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%.)	No
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	No
	4.4.	Were reasons for withdrawals similar across groups?	No
	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?	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?	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?	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