Effect of n-3 long chain polyunsaturated fatty acids during the perinatal period on later body composition

Abstract

A systematic review to identify studies reporting the effects of n-3 long chain polyunsaturated fatty acids (LCPUFA) intake, during pregnancy and postnatally, on infants and young children's body composition was performed. A structured search strategy was performed in the MEDLINE (PubMed), EMBASE, and LILACS databases. Inclusion and exclusion criteria were defined according to the research question. Only those studies addressing the relationship between n-3 LCPUFA exposure during the perinatal period and later adiposity measured in terms of weight, height, body mass index (BMI), skinfold thickness and/or circumferences were included regardless of the study design. Studies quality was scored and were thereafter categorised into those reporting on maternal intake of n-3 LCPUFA during pregnancy or lactation (6 publications) or on infant's n-3 LCPUFA intake (7 publications). Two studies showed inverse associations between maternal n-3 LCPUFA intake and children's later body composition (lower adiposity, BMI or body weight), two showed direct associations and no effects were observed in the remaining two studies. Among those studies focusing on n-3 LCPUFA intake through enriched infant formulas; three observed no effect on later body composition and two showed higher weight and adiposity with increased amounts of n-3 LCPUFA. Reversely, in two studies weight and fat mass decreased. In conclusion, reported body composition differences in infants and young children were not clearly explained by perinatal n-3 LCPUFA intake via supplemented formulas, breastfeeding or maternal intakes of n-3 LCPUFA during pregnancy and lactation. Associated operational mechanisms including n-3 LCPUFA doses and sources applied are not sufficiently explained and therefore no conclusions could be made.

Both intrauterine and early infancy are periods of rapid growth and development during which insufficient supply of energy and nutrients might result to metabolic or body composition alterations. Its relative impact on the different periods has not yet been elucidated⁽¹⁾ but it appears to be modulating early life outcomes and later risk of chronic disease^{(1, 2)}. Specifically, early life nutrition has been shown to significantly contribute to adiposity development variability^(2–4). The fetal-infant programming hypothesis states that increased risk of adiposity later in life is originated from early exposure to detrimental environments including nutritional aspects; however, the mechanisms are still unclear^{(1, 2)}. Therefore, effective preventive measures of the obesity epidemic require knowledge of the dietary risk factors and their consequences which act during critical life periods⁽⁵⁾.

The effects of essential long chain polyunsaturated fatty acids (LCPUFA) supplementation during the perinatal period on neurobehavioral development or visual acuity, infant growth as well as safety monitoring outcomes has been addressed by a number of clinical trials mainly in preterm infant populations^{(6, 7)}. The majority of the studies tested the effect of specific LCPUFA concentrations added to an infant formula on postnatal growth outcomes including body weight and length^{(8, 9)}. Some of the limited reporting effects on body composition and long-term body fat programming, both from animal and human studies, indicate that early availability of LCPUFA might influence development of adipose tissue during fetal life and infancy⁽¹⁰⁾. Eicosanoids derived from arachidonic acid (AA), n-6 LCPUFA, appear to have an adipogenic effect, by providing a molecular link between fatty acid uptake and preadipocytes differentiation during early hyperplasic growth stages of adipose tissue. In contrast, those derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), n-3 LCPUFA, have an antiadipogenic effect^{(11, 12)}. Consequently, fatty acid levels and the ratio between n-6 LCPUFA and n-3 LCPUFA in the maternal diet, during pregnancy and lactation, may play an important role in early adipose tissue development⁽¹³⁾.

The present systematic review presents studies addressing the relationship between n-3 LCPUFA intakes, during pregnancy and postnatally, on early and long-term body composition variability.

Methods

The research question to be answered by the systematic review was if early life n-3 LCPUFA intake (prenatal and early postnatal periods) has any influence on childhood body composition. The flow chart of the process is illustrated in Fig. 1. The search process was not limited to any language, timeframe or country of publication and was performed in three electronic databases (MEDLINE, EMBASE and LILACS). The general search strategy included terms related to the population under question (infants and children), predictor (n-3 LCPUFA intake) and dependent variables (obesity and body composition). The shared terms used in MEDLINE and EMBASE search included (pregnant women [MeSH] OR breastfeeding [MeSH] OR age group [MeSH]) AND (Fatty Acids, Unsaturated [MeSH]) AND (body weight [MesH] OR metabolic syndrome X [MesH]). In LILACS, terms used were slightly different: (Risk groups Nutrition [MeSH] OR feeding behaviour [MeSH] OR age groups [MeSH]) AND (Fatty Acids, Unsaturated [MeSH]) AND (body weight [MesH] OR Nutritional and Metabolic Diseases [MesH]).

Fig. 1 Stages of the systematic review process

The initial search yielded 2605 references after exclusion of duplicates. Additional publications were identified from references listed in the identified original papers reviewed. This secondary search added 47 potential relevant papers (total of 2653). Selected studies were then classified into two different groups: 1) maternal n-3 LCPUFA intake during pregnancy and lactation on infants and young children's body composition; and 2) effects of infant's n-3 LCPUFA intake (from birth or early postnatal period) on later body composition.

The results of the searches were stored in an Endnote XII library. Firstly, references were screened on the basis of title and abstract. Those clearly not meeting the review's criteria were excluded. Selected references in the previous step were all screened based on full text. Reasons for exclusion were registered in the Endnote library. Criteria for inclusion/exclusion are stated in Table 1. References were excluded on the basis of irrelevant health outcome (no adiposity or body composition measurements) and targeted population or dietary exposure (only ALA as n-3 LCPUFA or only n-6 essential fatty acids as LCPUFA supplementations). When in doubt, the team reviewed the papers to ensure alignment and quality control. Only papers fulfilling the inclusion criteria were considered in the present review.

Table 1 Inclusion and exclusion criteria.

Assessment of risk of bias in included studies

The quality and risk of bias were assessed as indicators of validity for identified observational and intervention studies. The studies included in this review were checked for a minimum quality score system developed by EURopean micronutrient RECommendation Aligned (EURRECA -network of excellence-) which was adapted from The Cochrane Handbook⁽¹⁴⁾. Criteria for intervention studies were based on method of sequence generation (adequate randomization procedure) and allocation concealment, blinding, potential funding bias, number of participants at start, number of dropouts and suggested reasons, dose check, dietary intake data reported, and similarities between the most and least exposed groups at baseline. For longitudinal studies criteria were based on number of dropouts and reasons, potential funding bias, lack of other potential threats to validity, inclusion of confounders, and assessment of adequacy of exposure. Concepts were evaluated as of high, low or of uncertain risk of bias. Overall risk of bias was judged as high if more than one of the following concepts were uncertain or inadequately addressed: confounders, exposure assessment, potential funding bias for observational studies and sequence generation, allocation concealment, blinding or potential funding bias for intervention studies. Observational and intervention studies were judged of moderate risk of bias, if reviewed studies had one of the above stated criteria judged as high risk. If there was no risk of bias or the risk of bias was present only in other criteria different from those mentioned above, the overall risk of bias was judged as low.

Results

A total of 13 publications^(15–27) were eventually selected for inclusion in this systematic review. All studies are summarised in Tables 2 and 3 together with extracted information on country where the study was performed, number of participants and age at enrolment, intervention and follow-up duration, intervention details and diet/formula LCPUFA composition, body composition-related outcomes and conclusions. Studies were split into two categories; those reporting data on maternal intake of n-3 LCPUFA during pregnancy or lactation (Table 2)^{(15, 18, 20, 23, 24, 27)} and those assessing infant n-3 LCPUFA intake (beginning during neonatal period) and potential effects on later body composition (Table 3)^{(16, 17, 19, 21, 22, 25, 26)}.

Table 2 Included studies on maternal n-3 polyunsaturated fatty acid intake during pregnancy and lactation and possible effects on infant body composition.

ALA, alpha-linolenic acid; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; AA, araquidonic acid; RCT, randomized controlled trial; LCPUFA, polyunsatured fatty acid; BMI, body mass index.

Table 3 Included studies on infant's n-3 polyunsaturated fatty acid intake and possible effects on body composition

NA, Not applicable; RCT, randomized controlled trial; LA, linoleic acid; ALA, alpha-linolenic acid; LCPUFA, polyunsatured fatty acids; DHA, docosahexaenoic acid; AA, araquidonic acid; PMA, postmenstrual age; EPA, eicosapentaenoic acid; FFM, fat free mass, TBF, total body fat; TOBEC, total body electrical conductivity; DEXA, X-ray absorptiometry; GLA, gamma-linolenic acid; BMI, body mass index

Effects of maternal n-3 LCPUFA intake during pregnancy and lactation on body composition during infancy and childhood

A total of six studies assessed maternal intakes of n-3 LCPUFA, one being an observational and five intervention studies (Table 2).

Only one study⁽¹⁸⁾ addressed longitudinally the relationship between prenatal n-3 fatty acid intake and long term adiposity at 3 years of age. This recently US published study was carried out in a cohort of pregnant women where n-3 LCPUFA maternal intake was measured at 29 weeks of pregnancy (mean) and a month before delivery, using a previously validated food frequency questionnaire. LCPUFA intake was reported as total n-3 fatty acids, alpha-linolenic acid (ALA) and DHA + EPA. Blood samples were obtained at mid-pregnancy and after delivery, from the umbilical cord, for quantification of fatty acids from erythrocyte membranes. Children's body composition parameters (height, weight, skinfold thickness) and dietary intakes were measured at the age of 3. The authors concluded that higher maternal prenatal n-3 intake was associated with lower adiposity in early childhood. They observed that a higher DHA + EPA intake during mid-pregnancy was associated with lower subscapular and triceps skinfold thickness, and with reduced odd of obesity at 3 years (OR = 0·68, 95 % CI = 0·50-0·92). Moreover, higher DHA + EPA concentrations in umbilical cord plasma were similarly associated with lower adiposity (skinfold thickness) and obesity (OR = 0·09, 95 % CI = 0·02-0·52).

Five trials relating infant body composition with pre- and postnatal maternal intake of n-3 LCPUFA were included^{(15, 20, 23, 24, 27)} of which all were double-blinded^{(15, 20, 23, 24)} except one⁽²⁷⁾ where no information was given. All presented results come from European countries (Denmark, Norway and Germany), conducted between 2000 and 2009 with the number of participants varying from 175 to 198 mother-term infant pairs. Body mass index (BMI) was reported in all five trials, skinfold thickness in four^{(15, 23, 27)} and waist circumference in two^{(15, 23)}. Two studies^{(24, 27)} measured head circumference and one⁽²⁷⁾ also calculated weight-for-length and ponderal weight. In order to make possible the comparison of results among intervention studies, sources of n-3 LCPUFA, intervention periods as well as point of time in which the outcomes were measured were considered. In this sense, studies showed some differences (Table 2). Hauner et al. ⁽²⁷⁾ started supplementing pregnant women at 15 weeks of pregnancy till 4 months of lactation and infant's measurements were taken at birth, 6 weeks, 4 months and 12 months postpartum. In Lauritzen et al. ⁽²³⁾, the intervention was carried out during the first 16 weeks of lactation and outcome assessment took place at 9 months and at 2·5 years respectively. The trial of Asserhøj et al. ⁽¹⁵⁾, a follow-up of the Lauritzen et al. ⁽²³⁾ study, described results at 7 years of age. Helland et al. ⁽²⁰⁾, measured BMI as a secondary outcome at 7 years of age, in an intervention trial performed between 18 weeks of pregnancy and 3 months following delivery with either cod liver oil or corn oil differed in the LCPUFA type. In the study by Lucia Bergman et al. ⁽²⁴⁾ pregnant women were supplemented with fish oil DHA (200 mg) from the 21^st week of pregnancy until the 3^rd month of lactation. Infants were measured at birth and thereafter at 1, 3 and 21 months.

Results on the effect of maternal n-3 supplementation on infant's body composition were inconsistent and did no enable the authors' to underpin any relevant conclusion (Table 2). Additionally, the fact that outcomes were assessed at different age points increased difficulties in result's comparison. Lauritzen et al. ⁽²³⁾ observed significantly higher BMI, waist circumference and adipose tissue in the supplemented group at 30 months compared to the control group. These differences, however, disappeared at 7 years in the Asserhøj study⁽¹⁵⁾. Helland et al. ⁽²⁰⁾, reported no significant effect on BMI at 7 years, in the supplemented group however, concentrations of ALA in breast milk 3 months after birth were positively correlated with BMI at 7 years. On the contrary, Donahue et al. ⁽¹⁸⁾ concluded that higher maternal prenatal n-3 intake was associated with lower adiposity in early childhood and Lucia Bergman et al. ⁽²⁴⁾ showed that DHA supplements during pregnancy and lactation may reduce BMI in late infancy. More specifically, lower weight and BMI at 21 months were observed in infants whose mothers were supplemented with DHA, whereas no effects were found for height and head circumference. Hauner et al. ⁽²⁷⁾ however, reported no effect on infants fat mass and growth at ≤  1 year of life between the intervention and the control groups.

Effects of infant's n-3 LCPUFA intake on body composition

A total of seven studies are presented in Table 3^{(16, 17, 19, 21, 22, 25, 26)}. One was an observational cohort study⁽²⁶⁾ and six RCTs^{(16, 17, 19, 21, 22, 25)} four of which performed in North America (mainly in the US)^{(16, 19, 21, 25)} and three in Europe: two in The Netherlands^{(17, 26)}, and one in the UK⁽²²⁾. One was single-blind⁽²⁵⁾ and five were double-blind^{(16, 17, 19, 21, 22)}.

Preterm infants. Four out of seven studies included preterm newborns and varied in sample size (60 to 194 infants)^{(19, 21, 22, 25)}, intervention periods (4 weeks to 12 months) as well as in formula composition with n-3 fatty acid. All used DHA as the main n-3 differential fatty acid with contents ranging from 0·2 % to 0·5 % of total fatty acid weight. The composition of the control formulas differed to that of supplemented formulas in different terms: in two studies LA and ALA but no DHA and AA were added^{(19, 21)}, in one study the control formula did not contain any added n-3 LCPUFA⁽²⁵⁾, and in another the control formula was supplemented with smaller amounts of LA and ALA compared to the supplemented formula⁽²²⁾. Three trials^{(19, 22, 25)} accurately measured body compartments as body fat (BF) and fat-free mass (FFM) although methods of assessment and indicators of body composition varied i.e., skinfolds were assessed in two studies^{(22, 25)}, one measured total body conductivity⁽²⁵⁾, dual X-ray absorptiometry (DEXA) was used in another one⁽¹⁹⁾ and both bioelectrical impedance and deuterium dilution in another study⁽²²⁾.

Results among trials varied in use of supplemented LCPUFA formulas, age and gender groups. Innis et al. ⁽²¹⁾ reported higher weight, length and weight-to-length ratio in infants fed with DHA and AA from algal/fungal oils (0·33 % DHA and 0·60 % AA) supplemented formula for 4 weeks to the controls (formula 21-22 % LA, 3-3·1 % ALA) and those given single-cell algal oil DHA supplemented formula at 40-57 weeks post-menstrual age (PMA). Infants supplemented with DHA and AA formula during 12 months had significantly more FFM and less BF than controls (16-19 % LA and 2·5 % ALA) at 1 year of age; however, no differences were reported for weight, height, and head circumference⁽¹⁹⁾. In preterm infants fed with supplemented formula containing DHA and EPA until 9⁽²²⁾ and 59 weeks postpartum of PMA⁽²⁵⁾, lower FFM and BF in males⁽²⁵⁾ and increased weight and adiposity at 9-11 years among females⁽²³⁾ was observed.

Term infants. Three out of seven studies were RCTs with a sample size of 79⁽¹⁶⁾ and 341⁽¹⁷⁾ infants respectively. One study was a cohort including 244 mother-infant pairs⁽²⁶⁾. The intervention periods with LCPUFA supplemented formulas varied from 2 months⁽¹⁷⁾ to 4 months⁽¹⁶⁾. DHA was used as the main n-3 differential fatty acid for supplementation^{(16, 17)}. No long-term changes in body composition were observed at 1⁽¹⁶⁾ or 9 years of age⁽¹⁷⁾. Reported results in term infants are similarly inconsistent those of preterm infants. No clear relationship between any of the used LCPUFA supplemented formulas and later body composition variability was found. The findings of the cohort study which measured the composition of maternal milk in fatty acids suggested that the n-3 and n-6 LCPUFA content did not have an effect on weight gain or BMI during the first year of life in this group of breast-fed infants⁽²⁶⁾.

Quality of included studies

Table 4 summarizes the method used to assess the quality of the included studies. Different levels of risk of bias among the studies were observed. For intervention studies involving infants' mothers, four studies had a high risk of bias^{(15, 20, 23, 27)} and one had moderate risk⁽²⁴⁾. Repeated reasons for having risk of bias included an inadequate or unclear blinding procedure, inadequate explanation on dropouts, and an inadequate funder and other potential threats of validity. The only observational study included⁽¹⁸⁾ was defined to be of low risk of bias due to insufficient description of dropouts classified as “unclear”. Regarding the studies focused exclusively on children, the observational study⁽²⁶⁾ had a moderate risk of bias because of several threats to validity. Out of the seven RCTs^{(16, 17, 19, 21, 22, 25)}, two^{(17, 25)} were classified at high risk of bias and four^{(16, 19, 21, 22)}at moderate risk of bias. Insufficient description of funding and other potential threats to validity were some of the reasons.

Table 4 Assessment of methodological quality of included RCTs and longitudinal studies.

NA, not applicable

Donahue: Insufficient information on drop-outs.

Lauritzen: Insufficient information on the sequence generation and allocation concealment. Group sizes were based on power calculation for infant visual acuity instead of infant growth which is our main outcome.

Lucia Bergmann: Insufficient information on drop-outs. No explanation on differences between those who completed the study and drop-outs.

Helland: Insufficient information on sequence generation, allocation concealment and blinding procedure. Maternal age and education significantly differed among those mothers included in the study and those who were excluded. The study was co-financed by an enterprise which also provided the supplements. Power calculation of group sizes was based on an infant intelligence questionnaire instead of using infant growth which is our main outcome. Moreover, main outcomes were eventually related to umbilical cord or breast milk concentrations and not to n-3 LCPUFAs intake or supplementation.

Asserhøj: Insufficient information on sequence generation, allocation concealment and blinding procedure. They were not aware of the group allocation at 7y. Maternal age and education significantly differed among those mothers included in the study and those who were excluded. The study was co-financed by an enterprise which also provided the supplements. Power calculation of group sizes was based on an infant intelligence questionnaire instead of using infant growth which is our main outcome.

Hauner: The blinding procedure did not exclude potential bias. Moreover, the study was co-financed by private enterprises.

Birch: The sample size was calculated based on outcome (visual evoked potential) other to the ones examined in this review. Moreover, the supplemented formulas were provided by a private enterprise.

Ryan: No description of blinding method or funding source.

Innis: No description on dropouts. Moreover, supplemented formulas were provided by a private enterprise.

Groh-Wargo: The funder cannot be considered as adequate because the study was partially supported by private enterprise. The fact that subjects were allowed to take supplements but they did not register that information risks study validity.

Scholtens: Mother allocated in the intervention group were highly educated and smoked less often during pregnancy compared to those of the general study population. Moreover, children weight was self-reported.

Kennedy: Gestational age and birth-weight SD scores of dropouts were significantly different from the final included sample. Not controlled intakes of other n-3 LCPUFA. The study was funded by a private enterprise.

DeJong: Sequence generation and allocation concealment were not insufficiently described. The sample size was calculated based on health outcome other to the ones examined in this review. Supplementation period was too short.

Discussion

The aim of this systematic review was to identify and summarize evidence on studies assessing the relationship between n-3 LCPUFA intake on infancy and early childhood body composition across consecutive life stage. A total of 13 studies^(15–27) met the inclusion criteria and were included in this review. A very sensitive search was performed, considering limited availability of literature addressing the topic. References from excluded papers were also reviewed to avoid the omission of any relevant report. Appraised studies were categorised into two groups; those of mothers and infants and to those of infants. It should be taken into consideration that studies carried out in newborns are less solid due to the ethical implications.

The most important strength of the present study is that the review has been performed systematically. On the other hand, the limited number of articles relating intake of n-3 LCPUFA supplemented formulas and short and long-term body composition variability in infants represents the main study weakness. It is difficult to obtain conclusive and comparable results from the scarce existing information. In addition, there is a major discrepancy between the results obtained across the available studies.

Effects of maternal n-3 LCPUFA intake during pregnancy and lactation on body composition during infancy and childhood

All intervention studies had an RCT design. Points which should be considered when interpreting the results of the findings include: geographical location, patterns of intake regarding cold water fish, source of n-3 LCPUFA, and comparability of outcome assessment.

Other important points affecting comparisons and which should be considered include the type of LCPUFA supplemented, formula composition, the different sources of n-3 LCPUFA, the duration of the intervention and the timeframe in which the outcome was measured. The results of this review showed wide variability. The duration of intervention, which ranged from 16 weeks⁽²³⁾ to 36 weeks⁽²⁰⁾, as well as the point in time when the outcome was assessed may have an influence on the outcomes evaluated. While two studies measured body composition at 7 years^{(15, 20)}, in one trial measurements were taken at 1 year⁽²⁷⁾. Three studies^{(20, 24, 27)} comprised both pregnancy and lactation periods; Donahue et al. ⁽¹⁸⁾ only considered pregnancy and two studies evaluated the intake of n-3 LCPUFA exclusively during lactation^{(15, 23)}. That variability on methodology could explain the different findings observed across trials. Two studies^{(20, 27)} did not observe any effect on body composition in terms of fat mass, growth or BMI, although in Hauner et al. ⁽²⁷⁾ outcome measures were obtained much earlier (12 months after birth) than in the other studies. One study⁽²⁴⁾ positively associated n-3 LCPUFA intake with body composition at 2·5y but further measurements at 7y of age⁽¹⁵⁾ did not confirm that association suggesting a time-dependent effect on later body composition. Lucia Bergman et al. ⁽²⁴⁾, however, associated maternal supplementation with DHA with a decrease in children weight and BMI, although no effect was observed on length and head circumference. It is clear that included articles are heterogeneous regarding the interventions as well as the type, sources and doses of n-3 LCPUFA used (see Tables 2 and 3). It is important to remark that exposure time to LCPUFA and EPA/DHA or n-3/n-6 fatty acid ratios might contribute to differential outcome effects.

Literature availability addressing this topic longitudinally is scarce and did not enable conclusion drawing. This is reflected by the nearly non-existent identified literature, since only one paper showing results on the effects of n-3 LCPUFA intake in early periods of life on later adiposity met the inclusion criteria and is presented in this review.

Effects of infant n-3 LCPUFA intake on body composition

Limited literature availability similarly to available evidence on maternal intake should be stressed. Only one paper presented results on the effects of n-3 LCPUFA intake at early life on later body composition in term newborns⁽²⁶⁾. In this study, neither n-3 nor n-6 LCPUFA breast milk content influences weight gain or BMI.

All intervention studies were performed in developed countries. Differences in applied protocols in terms of LCPUFA formula composition or the source of n-3 LCPUFA, target sample, sample size, supplementation design of intervention / control groups intervention and monitoring period duration, outcomes measures and implications of accuracy of body composition assessment should be noted.

Preterm infants supplemented with DHA and AA formula in two studies^{(19, 21)} had significantly higher weight, length, weight-to-length ratio⁽²¹⁾ and FFM but less BF⁽¹⁹⁾ compared with controls at 1 year of age. Although n-3 LCPUFAs may have antiadipogenic effects inhibiting fat development, AA appears to have an adipogenic effect^{(9, 11)}. Recent systematic reviews however, showed that global growth of both term and preterm infants assessed in terms of weight, length and head circumference was unaffected by LCPUFA intake⁽⁸⁾. Despite the lack of evidence on the relationship between changes on body composition and LCPUFA intake, n-3/n-6 LCPUFA ratio as well as doses applied and fatty acid sources are still taken into consideration by the studies^{(22, 25)}. In addition, in preterm infants fed supplemented formulas with fish oil containing DHA and EPA (without AA supplementation) during the first months of life it was observed lower FFM and BF among males⁽²⁵⁾, and higher weight and adiposity at 9-11 years among females⁽²²⁾. These findings are in concordance to those observed by Donahue et al. ⁽¹⁸⁾ where higher prenatal fish intake and exposure to n-3 LCPUFAs were associated with lower adiposity in early childhood. A programming effect could be involved in the modulation of pre-adolescent body composition in subjects with low early adiposity having a different effect in each gender. It should be noted however, that there is a number of studies which failed to show any body composition variations later in life^{(16, 17, 26)}.

Conclusions and final comments

Two studies^{(18, 24)} showed positive effects of n-3 LCPUFA (only DHA or DHA+EPA) maternal intake during pregnancy and lactation on infant and young children's later body composition i.e., decreasing adiposity or BMI. Breastfed infants whose mothers were supplemented with fish oil during lactation had higher BMI, adipose tissue and waist circumference at 2·5 and at 7 years of age^{(15, 23)}. Breast milk n-3 LCPUFA content but not umbilical cord levels were associated with BMI at 7 years of age⁽²⁰⁾. One study did not found any related effect⁽²⁷⁾. Focusing on the perinatal period, three out of seven studies did not observed any effects on later body composition among infants supplemented with n-3 LCPUFA enriched formulas^{(16, 17, 26)}. On the other hand, two studies^{(21, 22)} reported higher weight and adiposity when consuming increased amounts of n-3 LCPUFA (DHA+AA), whereas two^{(19, 25)} showed a decrease in weight and fat mass (DHA+EPA and high ALA intake).

In summary, evidence on the potential relationship between maternal n-3 LCPUFA intake and infant growth or later body composition are not conclusive. In addition, contradictory findings among trials on use of varied supplemented n-3 LCPUFA formulas and on short and long-term effects on body composition or body fat were observed. Results derived from the studies included in this systematic review suggest that mechanisms are not understood and data synthesis is inconclusive. Differences in n-3 LCPUFA formula composition due to the heterogeneity in the type, sources and doses of LCPUFA as well as the timeframe of exposure prevent conclusive findings. Therefore, the association between early n-3 LCPUFA exposure during perinatal period and long-term body composition remains unclear. More studies addressing this relationship are needed.