J Compr Ped
J Compr Ped

article information

Journal of Comprehensive Pediatrics: Vol.13, issue 1; e112148
published online: February 21, 2022
article type: Research Article
received: December 14, 2020
revised: October 31, 2021
accepted: January 14, 2022
DOI: https://doi.org/10.5812/compreped.112148
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Breast Milk Docosahexaenoic Acid and Neonatal Outcome in Preterm Infants: A Cross-sectional Study

authors:

avatar Farnaz Naserly 1 , avatar Minoo Fallahi ORCID 1 , * , avatar Saleheh Tajalli ORCID 2 , avatar Mohammad Kazemian 1 , avatar Mahmoud Hajipour ORCID 3 , avatar Beheshteh Olang ORCID 4 , avatar Shamsollah Noripour 1

Neonatal Health Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Nursing Care Research Center (NCRC), School of Nursing and Midwifery, Iran University of Medical Sciences, Tehran, Iran
Student Research Committee, Epidemiology Department, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Pediatric Gastroenterology, Hepatology and Nutrition Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran

how to cite: Naserly F, Fallahi M, Tajalli S, Kazemian M, Hajipour M, et al. Breast Milk Docosahexaenoic Acid and Neonatal Outcome in Preterm Infants: A Cross-sectional Study. J Compr Ped. 2022;13(1):e112148. https://doi.org/10.5812/compreped.112148.

Abstract

Background:

The usual intake of fish products is not common in Iranian mothers.

Objectives:

Regarding the significant effect of this nutrient material on neonatal outcomes, we aimed to evaluate the breast milk docosahexaenoic acid (DHA) level in mothers with preterm delivery.

Methods:

This cross-sectional study was done in 67 mothers with gestational age lower than 36 weeks during 2018 - 2019. Breast milk samples of 5 - 10 milliliters were evaluated by gas chromatography for DHA level. Then, the correlation between the breast milk DHA levels and neonatal outcomes was assessed.

Results:

A total of 67 mothers were eligible in the study. The mean gestational age and birth weights were 31.54 ± 4.44 weeks and 1707.85 ± 595.83 g, respectively. The mean DHA, as a percentage of total breast milk fatty acids, was 0.29 ± 0.0127%. Statistical analysis showed no significant relationship between the breast milk DHA level and gestational age, birth weight, maternal age, delivery mode, neonatal growth index, and neonatal complications. The relationship between the intake of food materials rich in DHA and breast milk level was not statistically significant.

Conclusions:

We concluded that the breast milk DHA level of mothers with preterm delivery was acceptable, although it revealed no significant correlation with maternal factors and neonatal outcomes.

1. Background

In recent decades, preterm delivery and survival of premature infants have increased (1). A recent WHO report shows a 10.6% preterm birth rate (2, 3). The incidence of preterm delivery worldwide is 6.9%, amounting to 12.9 million premature neonates, with the highest rate in Africa and Asia (12 million neonates) (4). Despite the increased survival rate of premature babies, complications continue to rise in these high-risk neonates. Regarding the increased survival of premature neonates, more complications are expected. One of the most critical issues of the care of preterm neonates is the nutrition quality in the first critical days or weeks of life. Inefficient nutrition leads to growth impairment and neurodevelopmental delay in these high-risk neonates (5).

The best source of nutrition for preterm neonates is breast milk. Much research has revealed the beneficial effects of breast milk feeding on neonatal outcomes. The nutrient content of the breast milk of preterm delivered mothers is proportional to the nutritional needs of their children, such as protein content that is higher in premature birth than in term deliveries (6). Given that the mother's nutrition can change the nutrient content of breast milk, many researchers have studied the effects of maternal diet change on neonatal outcomes. Breast milk's long-chain unsaturated fatty acid (LCPUFA) is an essential nutrient required for normal health. Besides, LCPUFA has significant effects on neonates' neurodevelopmental, cognitive, visual, and immunological systems. Docosahexaenoic acid (DHA) is a kind of alpha-linolenic acid (ALA) and omega-3 essential fatty acid with no endogenous production. Breast milk levels of DHA are determined mainly by maternal intake from DHA supplementation (e.g., omega-3 or fish oil supplements) or fish, which can vary markedly around the world (7-9). Thus, maternal nutrition and breast milk are the only exogenous sources of this material in the first months of the life of preterm infants. This valuable nutrient is essential for both mother and child (10). The mean acceptable level of DHA in breast milk is 0.32% of total fatty acids (11).

In some Iranian research, the mean level of LCPUFA has been reported as 3.52 ± 1.4 and 3.8 ± 1.5 g/dL. Increased lactation duration has been associated with increased DHA levels (10-12). The ratio of DHA to total fatty acids is reported as 0.3 ± 0.2% (11). The blood level of DHA in pregnancy is directly related to the gestational age and fetal growth and inversely related to post-delivery anxiety and depression (12). The blood level of neonatal DHA is directly related to the maternal blood and breast milk DHA levels. The neonatal visual function, brain growth, memory, attention, and immunological state strengthen with DHA intake via breast milk. Improved learning and decreased incidence of atopy are the long-term effects of DHA (11).

Seafood contains LCPUFA and DHA, such as Atlantic mackerel (0.59 gm), salmon (1.24 gm), Dicentrarchus labrax (0.47 gm), oyster (0.23 gm), sardine (0.74 gm), shrimp (0.12 gm), and trout (0.44 gm). Oilseeds consisting of linseed, walnut, egg, and fish liver oil have significant amounts of DHA (13-15). In Iran, the most important fish species in the Caspian Sea are Caspian kutum (R. frisii kutum), mullet (L. aurata and L. saliens), and pikeperch (S. lucioperca). Their total PUFA10 content was 23%, 22%, and 20%, respectively (16).

Regarding the low intake of fish products and medicinal supplements containing LCPUFA during pregnancy in Iranian mothers, there is concern about the low level of DHA in breast milk. Thus, measuring breast milk DHA is essential for providing preterm neonates with the best care.

2. Objectives

Given the limited research on the evaluation of DHA in the breast milk of Iranian mothers and regarding the higher probability of neurodevelopmental and growth disorders in preterm neonates, we planned this study to measure the breast milk DHA level and its effects on neonatal outcomes in preterm deliveries.

3. Methods

This descriptive cross-sectional research was done in mothers with preterm delivery in Mahdieh Medical Center affiliated with Shahid Beheshti University of Medical Sciences during 2018 - 2019. We enrolled the mothers of all preterm neonates admitted from 2018 to 2019 with a gestational age of fewer than 36 weeks or a birth weight of lower than 2,000 g. Then, their breast milk was assessed for the DHA level. All mothers had a normal nutritional status and were not underweight or overweight. If neonates were transferred to other medical centers and missed the follow-up sessions, they were excluded from the study. According to Juber et al.'s study (11), 67 mothers with preterm infants were included in our study.

The Ethics Committee of Shahid Beheshti University of Medical Sciences approved our study with the ethical code of IR.SBMU.MSP.REC.1398.745. Written consent was obtained from mothers before taking breast milk samples. To evaluate the DHA level of breast milk, we sampled 5 - 10 milliliters of breast milk and maintained it at 4°C in a refrigerator for up to seven days before transferring it to the laboratory for DHA measurement with gas chromatography. The correlations between the breast milk DHA levels and gestational age, birth weight, gender, delivery mode, supplementation, maternal age, underlying or gestational disorders, maternal intake of DHA-containing food, neonatal outcomes, such as intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), and necrotizing enterocolitis (NEC), and growth indices, including weight gain, increased height, and head circumferences, were evaluated for four months after discharge from the neonatology clinic based on the available growth curve specific for preterm neonates (Fenton growth chart). Four neonates died during hospitalization, and 63 were followed.

Based on Juber et al.'s study (11), the sample size was calculated as 67 patients, with the mean and standard deviation of 0.22 and 0.13%, respectively, and an error level of 0.325.

The mean and standard deviation were used to analyze quantitative variables. Absolute and relative frequencies were calculated for stratified and ranking data. After assessing the normality of variables, the analysis was done by Spearman and Mann-Whitney U tests using SPSS version 25.

4. Results

A total of 67 mothers were eligible for the study. The mean gestational age and birth weights were 31.54 ± 4.44 weeks (25 - 36 weeks) and 1707.85 ± 595.83 g (760 - 3500 g), respectively. There were 38 (56.7%) males and 29 (43.3%) females. The mean maternal age was 28.47 ± 5.42 years (16 - 40 years). The delivery mode was cesarean sections (C/S) in 46 (68.6%) and normal vaginal delivery (NVD) in 21 (31.3%). The mean age of neonates at breast milk sampling was nine days (2 - 44 days). The mean DHA, as a percentage of total breast milk fatty acids, was 0.29 ± 0.0127%. The minimum and maximum levels were 0.09% and 0.73%, respectively.

Table 1 shows the mean, minimum, maximum, and median DHA levels of breast milk of mothers based on the demographic data of patients and parents. There was no statistical relationship between all the demographic characteristics of patients and parents and breast milk DHA level (Table 1).

Table 1.

Docosahexaenoic Acid Level Based on Demographic Characteristics of Patients

VariablesNumberMeanSDMinimumMaximumMedianIQRP-Value
Sex0.063
Male380.30970.099310.180.570.29500.06
Female290.27030.059370.140.450.27000.14
Delivery mode0.847
NVD210.29570.090640.160.510.26000.09
C/S460.29130.084920.140.570.28000.10
Gestational diabetes0.298
Positive100.31900.107230.180.570.30000.10
Negative570.28810.082100.140.540.28000.13
Preeclampsia0.449
Positive200.30500.118080.140.570.26000.09
Negative470.28740.069140.160.540.28000.12
Place of residency0.140
Tenant330.30850.081210.200.540.29000.10
Another province340.27740.089080.140.570.26000.08
Job of husband0.180
Self-employment300.27800.062770. 140.400.28500.038
Employee170.29710.096810.190.540.28000.06
Manual worker200.31100.105480.200.570.28000.048
Income0.156
Low290.30720.096320.160.570.28000.09
Intermediate370.28410.076360.140.540.28000.12
High10.1900-0.190.190.19000.10
Education of mother0.961
Undergraduate 160.31750.119690.160.570.28000.15
Diploma260.27730.062450.140.400.27500.10
Postgraduate 80.25880.057930.180.350.25000.10
Bachelor120.30920.095200.190.540.29000.06
Masters50.30800.077270.230.400.28000.15
Education of father0.728
Undergraduate 190.29790.085150.210.510.28000.09
Diploma250.27880.085410.140.570.28000.08
Postgraduate100.28500.057590.190.350.30500.10
Bachelor80.35500.106900.250.540.34000.18
Masters50.25800.087580.190.400.23000.15

Table 2 shows the breast milk DHA level based on the mother's diet and the intake of food rich in this valuable material. Although the nutritional resource of DHA is diverse, consisting of animal and plant bases, it seems that the more intake of food rich in DHA increased the level of this material in breast milk. Fortunately, despite the wide range of maternal diets, the same level of DHA in the breast milk of mothers with different socioeconomic levels was detected. The consumption of seafood (P value = 0.37), omega-6 fish liver oil (P value = 0.93), wheat sprouts (P value = 0.44), walnut (P value = 0.20), nuts (P value = 0.49), soya and cotton (P value = 0.33), canola oil (P value = 0.67), and eggs (P value = 0.94) did not affect the DHA level of breast milk.

Table 2.

Docosahexaenoic Acid Level Based on the Diet of Mothers of Neonates

VariablesNumberMeanSDMinimumMaximumMedianIQRP-Value
Use of seafood during last week0.377
Once a week440.28590.078870.140.510.27500.095
Twice a week230.30570.099030.160.570.28000.045
Use of omega-3-6 fish liver oil during last week0.936
Yes460.29330.083270.140.540.28500.092
No210.29140.094090.180.570.26000.05
Wheat sprouts during last week0.446
Yes570.28930.088440.140.570.28000.042
No100.31200.072080.210.450.31500.077
Walnut during last week0.201
Yes180.31500.109450.160.540.28000.053
No490.28450.075440.140.570.28000.042
Nuts during last week0.499
Yes230.30260.101630.160.570.28000.04
No440.28750.077520.140.540.28500.05
Soya and cotton during last week0.336
Yes550.29750.090540.160.570.28000.045
No120.27080.059920.140.340.28500.04
Canola oil during last week0.672
Yes610.29410.086590.140.570.28000.05
No60.27830.087040.210.450.24500.045

Table 3 shows the incidence of neonatal prematurity complications such as IVH, NEC, BPD, and ROP, neonatal growth indices, and mortality based on the DHA level of breast milk in neonates fed by mothers. There was no significant relationship between the DHA level of breast milk and all neonatal complications. Also, statistical analysis showed no significant relationship between gestational age (P value = 0.32), birth weight (P value = 0.59), sex (P value = 0.1), postnatal age (P value = 0.59), maternal age (P value = 0.93), delivery mode (P value = 0.32), neonatal growth index, and neonatal complications. The relationship between the intake of DHA-containing food and breast milk DHA level was not statistically significant (P value = 0.43).

Table 3.

Docosahexaenoic Acid Level Based on Complications of Prematurity

VariablesNumberMeanSDMinimumMaximumMedianIQRP-Value
ROP0.707
Negative540.30170.089750.140.570.29000.05
Positive130.25540.057530.180.400.25000.037
BPD0.275
Negative520.29380.088280.140.570.28000.05
Positive150.28870.080790.190.510.28870.035
NEC0.588
Negative660.29350.086500.140.570.28000.05
Positive10.2400-0.240.240.24000
IVH0.957
Negative 550.29580.091870.140.570.28000.05
Positive120.27830.052540.200.380.27000.032
Appropriate weight gain0.856
No560.29730.091720.140.570.28500.05
Yes70.25000.028280.200.280.25000.025
Appropriate height growth 0.572
No200.28380.064380.180.400.28000.045
Yes430.29670.094730.140.570.28000.05
Appropriate head circumference growth 0.662
No150.28470.060320.190.400.042
Yes480.29540.093620.140.570.05
Mortality0.012
No630.29400.105250.090.730.2800
Yes40.33000.047610.280.380.3300

The associations between the DHA level and our research variables were evaluated with a crude analysis. Multiple logistic regression modeling adjusted for confounding variables did not show any association between the DHA level of breast milk and neonatal complications. However, these results may be due to the low sample size and a single measurement of DHA level during the study.

5. Discussion

The current descriptive cross-sectional research measured the DHA level in mothers' breast milk with preterm delivery and its effect on common neonatal complications in premature babies. Regarding the impact of maternal diet on the level of free fatty acids such as DHA in breast milk, the measurement of this valuable nutrient in breast milk is important. Changing the maternal or neonatal diet or supplementation resulted in an increasing level of DHA in breast milk. Eventually, this resulted in neonatal circulating with an improvement in the neonatal outcome, especially neurodevelopmental and visual acuity. Despite the infrequent seafood intake in Iranian families and regardless of maternal diet, our research revealed that the mean level of DHA in the breast milk of mothers was in the acceptable range: 0.32% of total fatty acids with the minimum and maximum levels of 0.09% and 0.73%, respectively, in comparison with a worldwide global average level of 0.296 ± 1.27% (17). In research by Fu et al., the mean level of DHA in breast milk was 0.37% of total fatty acids. In this study, Asian mothers had the highest level of DHA, and mothers in low-income countries had a higher level of DHA in breast milk than those in other countries (18).

The level of DHA in breast milk did not reveal statistically significant relationships with birth weight, gestational age, postnatal age, delivery mode, age of mother, socioeconomic level of the family, and common neonatal complications such as BPD, IVH, and NEC. Oxidative stress following normal vaginal delivery changes the level of LCPUFA and DHA in the breast milk of mothers. As the findings of many studies show, the mode of delivery affects the level of breast milk DHA. However, the current study showed no significant difference between NVD and C/S in the level of breast milk DHA (P value = 0.32) (19).

In research by Lapillonne et al., the level of breast milk DHA was decreased during the first month of delivery, and they suggested the fortification of breast milk by DHA supplementation for compensating for this deficiency (20). In our research, the sampling time was different in patients and the mean age of neonates at the time of sampling was nine days (2 - 44 days). Although in our research, there was no significant relationship between the time of sampling and DHA level, similar to the Lapillonne et al.’s study, Martin et al.’s study showed that as the baby grows, the amount of DHA decreases, and the low levels of DHA were associated with the increased rate of BPD. In contrast to research by Smith and Rouse, DHA supplementation raised the rate of BPD in preterm infants (10, 20-22).

The current study showed that newborns with more growth in head circumference, height, and body weight had higher levels of DHA in the breast milk of their mothers, although there was no statistically significant relationship between growth indices and DHA levels. Research by Much revealed that LCPUFA of breast milk improved fat mass growth of infants in the first year of life, and the increased protein and amino acid ratio of breast milk caused better growth indicators (23).

Despite the wide range of maternal diets, the same level of DHA in the breast milk of mothers with different socioeconomic levels was detected. The intake of food rich in DHA did not correlate with the level of DHA in breast milk. Some research revealed the positive effect of breast milk DHA on decreasing BPD incidence in preterm babies (24-26).

The finding of our research revealed the higher growth rate of weight, height, and head circumference in neonates fed by a higher level of DHA in breast milk, although not significantly. In research by Smuts et al. in a clinical trial, supplementation of the maternal diet with DHA during pregnancy made no significant change in the birth weight of neonates (26). The results of Oken et al. and Halldorsson et al. in the United States confirmed the mentioned results. They indicated that supplementation with DHA did not correlate with babies' weight gain and growth index (27, 28).

Contrary to research by Ramakrishnan et al. and Olafsdottir et al., supplementation with DHA improved the fetal weight gain in pregnancy (29, 30). In research by Olsen, the weight gain of neonates with the intake of fish oil was higher than that of the control group (31).

In a study by Davoodabadi Farahani and Seyyed Zadeh Aghdam in Arak, Iran, intending to detect the effect of DHA and eicosapentaenoic acid (EPA) in pregnancy on birth weight and duration of pregnancy, there was a statistically significant difference between mothers receiving DHA supplementation and the control group. They found 284 g reduced birth weight in neonates of mothers but no effect on the duration of pregnancy in the group with DHA supplementation (32). They concluded that this negative effect was due to the difference between monitoring the growth index and the guideline of supplementation with DHA.

The current study did not show any difference in gestational age based on the DHA level of breast milk. In research by De Dooy et al., the levels of breast milk unsaturated fatty acids were increased with increasing gestational age (24).

Two clinical trials revealed the correlation between the omega-3 intake of mothers and the duration of pregnancy so that the duration of pregnancy was prolonged with DHA supplementation in the maternal diet. Olsen et al. detected the longer duration of pregnancy as 2.5% in mothers with fish oil supplementation (26, 31). A systematic review by Kar et al. in 2016 revealed a 58% decrease in preterm deliveries of less than 34 weeks and a statistically significant relationship between gestational age and supplementation with DHA in pregnancy (33). In the research by Olsen et al. and Davoodabadi Farahani and Seyyed Zadeh Aghdam, there was no significant relationship between the duration of pregnancy and DHA, EPA, and fish oil supplementation in pregnancy (31, 32).

The inability of preterm neonates to process fatty acids and produce DHA, the low transplacental transfer rate of this fatty acid from the mother, and low intake of this material after birth due to feeding problems are the concerning issues in this regard (34). The administration of intralipids solutions during NICU admission may be an inadequate source of DHA to meet the baby's needs (21, 35). Regarding the mentioned factors, the enrichment of breast milk with DHA seems logical.

Regarding the contribution of inflammatory reactions as an underlying risk factor for neonatal complications such as NEC, BPD, and ROP, DHA with anti-inflammatory properties can decrease the incidence of these complications of prematurity. A longitudinal study by Martin et al. showed the decreased level of DHA in the first months of life concurrent with the progression and severity of chronic lung disease (21). In research by Martin et al., a 1% decrease in DHA from a total of long-chain fatty acids increased the probability of chronic lung disease by 2.5 times (21). Many published studies confirmed the reverse correlation between DHA levels and incidence of BPD in preterm babies (25, 36).

The findings of a clinical trial by Bernabe‐Garcia et al. in Mexico to evaluate the effect of oral DHA with a dose of 75 mg/kg on the severity of ROP showed the positive prophylactic effect of this material on the incidence and severity of ROP (37). Our research evaluated just the effect of breast milk DHA on neonatal complications, with no pharmacological intervention. Similar to the research of Bernabe-Garcia et al., in research by Bernabe in 110 preterm neonates with a birth weight of 1000 - 1500 g, the incidence and severity of ROP were decreased with DHA supplementation (38). In a clinical trial by Collins et al. in Australia, supplementation with DHA with a dose of 60 mg/kg/day in preterm neonates with gestational age lower than 29 weeks did not improve BPD progression (22).

In a study by Fares et al. in Tunisia, supplementation with DHA decreased mortality related to sepsis, IVH, and respiratory distress syndrome (39). However, our research did not show any positive effect of breast milk DHA on neonatal mortality. The single laboratory measurement of this nutrient of breast milk is the most significant limitation of our research, which limited the study results.

The limitations of our research were the low sample size of the study, financial constraints (due to the high cost of laboratory exams), and the measurement of breast milk DHA just in one sample of breast milk and at different times after delivery (2 - 44 days post-delivery). For more conclusive results, larger studies with more sample size and repeated measurements of breast milk DHA or supplementation of the maternal or neonatal diet with this valuable nutrient is recommended.

The current study's findings showed the acceptable levels of DHA in the breast milk of mothers with preterm delivery, although it did not reveal a significant correlation between maternal and neonatal factors and neonatal outcomes. The low sample size and evaluation of just one breast milk sample can justify no significant effects observed. Regarding the well-known beneficial effects of breast milk, research with a higher sample size and repeated measurements of DHA is recommended.

Acknowledgements

References

  • 1.

    Cone S. The Impact of Communication and the Neonatal Intensive Care Unit Environment on Parent Involvement. Newborn Infant Nurs Rev. 2007;7(1):33-8. https://doi.org/10.1053/j.nainr.2006.12.006.

  • 2.

    Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller AB, Narwal R, et al. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet. 2012;379(9832):2162-72. https://doi.org/10.1016/s0140-6736(12)60820-4.

  • 3.

    Chawanpaiboon S, Vogel JP, Moller AB, Lumbiganon P, Petzold M, Hogan D, et al. Global, regional, and national estimates of levels of preterm birth in 2014: a systematic review and modelling analysis. Lancet Glob. Health. 2019;7(1):e37-46. https://doi.org/10.1016/s2214-109x(18)30451-0.

  • 4.

    Howson CP, Merialdi M, Lawn JE, Requejo JH, Say L. March of dimes white paper on preterm birth: the global and regional toll. March of dimes foundation. 2009:13.

  • 5.

    Franz AR, Pohlandt F, Bode H, Mihatsch WA, Sander S, Kron M, et al. Intrauterine, early neonatal, and postdischarge growth and neurodevelopmental outcome at 5.4 years in extremely preterm infants after intensive neonatal nutritional support. Pediatrics. 2009;123(1):e101-9. [PubMed ID: 19117831]. https://doi.org/10.1542/peds.2008-1352.

  • 6.

    Hsu YC, Chen CH, Lin MC, Tsai CR, Liang JT, Wang TM. Changes in preterm breast milk nutrient content in the first month. Pediatr Neonatol. 2014;55(6):449-54. [PubMed ID: 24861533]. https://doi.org/10.1016/j.pedneo.2014.03.002.

  • 7.

    Jensen CL, Maude M, Anderson RE, Heird WC. Effect of docosahexaenoic acid supplementation of lactating women on the fatty acid composition of breast milk lipids and maternal and infant plasma phospholipids. Am J Clin Nutr. 2000;71(1 Suppl):292S-9S. [PubMed ID: 10617985]. https://doi.org/10.1093/ajcn/71.1.292s.

  • 8.

    Cacciari E, Milani S, Balsamo A, Spada E, Bona G, Cavallo L, et al. Italian cross-sectional growth charts for height, weight and BMI (2 to 20 yr). J Endocrinol Invest. 2006;29(7):581-93. [PubMed ID: 16957405]. https://doi.org/10.1007/BF03344156.

  • 9.

    Levant B. N-3 (omega-3) Fatty acids in postpartum depression: implications for prevention and treatment. Depress Res Treat. 2011;2011:467349. [PubMed ID: 21151517]. [PubMed Central ID: PMC2989696]. https://doi.org/10.1155/2011/467349.

  • 10.

    Smith SL, Rouse CA. Docosahexaenoic acid and the preterm infant. Matern Health Neonatol Perinatol. 2017;3:22. [PubMed ID: 29238605]. [PubMed Central ID: PMC5725938]. https://doi.org/10.1186/s40748-017-0061-1.

  • 11.

    Juber BA, Jackson KH, Johnson KB, Harris WS, Baack ML. Breast milk DHA levels may increase after informing women: a community-based cohort study from South Dakota USA. Int Breastfeed J. 2016;12:7. [PubMed ID: 28149321]. [PubMed Central ID: PMC5273852]. https://doi.org/10.1186/s13006-016-0099-0.

  • 12.

    Hubinont C, Savoye T. Maternal and fetal benefits of DHA supplementation during pregnancy. J Pregnancy Reprod. 2017;1(1). https://doi.org/10.15761/jpr.1000103.

  • 13.

    Tur JA, Bibiloni MM, Sureda A, Pons A. Dietary sources of omega 3 fatty acids: public health risks and benefits. Br J Nutr. 2012;107 Suppl 2:S23-52. [PubMed ID: 22591897]. https://doi.org/10.1017/S0007114512001456.

  • 14.

    Lenihan-Geels G, Bishop KS, Ferguson LR. Alternative sources of omega-3 fats: can we find a sustainable substitute for fish? Nutrients. 2013;5(4):1301-15. [PubMed ID: 23598439]. [PubMed Central ID: PMC3705349]. https://doi.org/10.3390/nu5041301.

  • 15.

    Lane K, Derbyshire E, Li W, Brennan C. Bioavailability and potential uses of vegetarian sources of omega-3 fatty acids: a review of the literature. Crit Rev Food Sci Nutr. 2014;54(5):572-9. [PubMed ID: 24261532]. https://doi.org/10.1080/10408398.2011.596292.

  • 16.

    Olang B. Aspects of feeding patterns in the first two years of life in Iranian infants. Sweden: Karolinska Institutet; 2011.

  • 17.

    Brenna JT, Varamini B, Jensen RG, Diersen-Schade DA, Boettcher JA, Arterburn LM. Docosahexaenoic and arachidonic acid concentrations in human breast milk worldwide. Am J Clin Nutr. 2007;85(6):1457-64. [PubMed ID: 17556680]. https://doi.org/10.1093/ajcn/85.6.1457.

  • 18.

    Fu Y, Liu X, Zhou B, Jiang AC, Chai L. An updated review of worldwide levels of docosahexaenoic and arachidonic acid in human breast milk by region. Public Health Nutr. 2016;19(15):2675-87. [PubMed ID: 27056340]. https://doi.org/10.1017/S1368980016000707.

  • 19.

    Makrides M, Best K. Docosahexaenoic Acid and Preterm Birth. Ann Nutr Metab. 2016;69 Suppl 1:29-34. [PubMed ID: 27842314]. https://doi.org/10.1159/000448263.

  • 20.

    Lapillonne A, Groh-Wargo S, Gonzalez CH, Uauy R. Lipid needs of preterm infants: updated recommendations. J Pediatr. 2013;162(3 Suppl):S37-47. [PubMed ID: 23445847]. https://doi.org/10.1016/j.jpeds.2012.11.052.

  • 21.

    Martin CR, Dasilva DA, Cluette-Brown JE, Dimonda C, Hamill A, Bhutta AQ, et al. Decreased postnatal docosahexaenoic and arachidonic acid blood levels in premature infants are associated with neonatal morbidities. J Pediatr. 2011;159(5):743-749 e1-2. [PubMed ID: 21658712]. [PubMed Central ID: PMC3701520]. https://doi.org/10.1016/j.jpeds.2011.04.039.

  • 22.

    Collins CT, Makrides M, McPhee AJ, Sullivan TR, Davis PG, Thio M, et al. Docosahexaenoic Acid and Bronchopulmonary Dysplasia in Preterm Infants. N Engl J Med. 2017;376(13):1245-55. [PubMed ID: 28355511]. https://doi.org/10.1056/NEJMoa1611942.

  • 23.

    Much D, Brunner S, Vollhardt C, Schmid D, Sedlmeier EM, Bruderl M, et al. Breast milk fatty acid profile in relation to infant growth and body composition: results from the INFAT study. Pediatr Res. 2013;74(2):230-7. [PubMed ID: 23715519]. https://doi.org/10.1038/pr.2013.82.

  • 24.

    De Dooy JJ, Mahieu LM, Van Bever HP. The role of inflammation in the development of chronic lung disease in neonates. Eur J Pediatr. 2001;160(8):457-63. [PubMed ID: 11548181]. [PubMed Central ID: PMC7102381]. https://doi.org/10.1007/s004310100785.

  • 25.

    Manley BJ, Makrides M, Collins CT, McPhee AJ, Gibson RA, Ryan P, et al. High-dose docosahexaenoic acid supplementation of preterm infants: respiratory and allergy outcomes. Pediatrics. 2011;128(1):e71-7. [PubMed ID: 21708809]. https://doi.org/10.1542/peds.2010-2405.

  • 26.

    Smuts CM, Huang M, Mundy D, Plasse T, Major S, Carlson SE. A randomized trial of docosahexaenoic acid supplementation during the third trimester of pregnancy. Obstet Gynecol. 2003;101(3):469-79. [PubMed ID: 12636950]. https://doi.org/10.1016/s0029-7844(02)02585-1.

  • 27.

    Oken E, Kleinman KP, Olsen SF, Rich-Edwards JW, Gillman MW. Associations of seafood and elongated n-3 fatty acid intake with fetal growth and length of gestation: results from a US pregnancy cohort. Am J Epidemiol. 2004;160(8):774-83. [PubMed ID: 15466500]. [PubMed Central ID: PMC1994920]. https://doi.org/10.1093/aje/kwh282.

  • 28.

    Halldorsson TI, Meltzer HM, Thorsdottir I, Knudsen V, Olsen SF. Is high consumption of fatty fish during pregnancy a risk factor for fetal growth retardation? A study of 44,824 Danish pregnant women. Am J Epidemiol. 2007;166(6):687-96. [PubMed ID: 17631607]. https://doi.org/10.1093/aje/kwm133.

  • 29.

    Olafsdottir AS, Magnusardottir AR, Thorgeirsdottir H, Hauksson A, Skuladottir GV, Steingrimsdottir L. Relationship between dietary intake of cod liver oil in early pregnancy and birthweight. BJOG. 2005;112(4):424-9. [PubMed ID: 15777439]. https://doi.org/10.1111/j.1471-0528.2005.00477.x.

  • 30.

    Ramakrishnan U, Stein AD, Parra-Cabrera S, Wang M, Imhoff-Kunsch B, Juarez-Marquez S, et al. Effects of docosahexaenoic acid supplementation during pregnancy on gestational age and size at birth: randomized, double-blind, placebo-controlled trial in Mexico. Food Nutr Bull. 2010;31(2 Suppl):S108-16. [PubMed ID: 20715595]. https://doi.org/10.1177/15648265100312S203.

  • 31.

    Olsen SF, Sorensen JD, Secher NJ, Hedegaard M, Henriksen TB, Hansen HS, et al. Randomised controlled trial of effect of fish-oil supplementation on pregnancy duration. Lancet. 1992;339(8800):1003-7. [PubMed ID: 1349049]. https://doi.org/10.1016/0140-6736(92)90533-9.

  • 32.

    Davoodabadi Farahani M, Seyyed Zadeh Aghdam N. [Effect of docosahexaenoic acid and eicosapentaenoic acid supplementation in pregnancy on the birth weight and gestational length]. Complementary Medicine Journal Arak University of Medical Sciences. 2011;1(1):42-50. Persian.

  • 33.

    Kar S, Wong M, Rogozinska E, Thangaratinam S. Effects of omega-3 fatty acids in prevention of early preterm delivery: a systematic review and meta-analysis of randomized studies. Eur J Obstet Gynecol Reprod Biol. 2016;198:40-6. [PubMed ID: 26773247]. https://doi.org/10.1016/j.ejogrb.2015.11.033.

  • 34.

    Baack ML, Norris AW, Yao J, Colaizy T. Long-chain polyunsaturated fatty acid levels in US donor human milk: meeting the needs of premature infants? J Perinatol. 2012;32(8):598-603. [PubMed ID: 22323096]. [PubMed Central ID: PMC3369002]. https://doi.org/10.1038/jp.2011.152.

  • 35.

    Robinson DT, Carlson SE, Murthy K, Frost B, Li S, Caplan M. Docosahexaenoic and arachidonic acid levels in extremely low birth weight infants with prolonged exposure to intravenous lipids. J Pediatr. 2013;162(1):56-61. [PubMed ID: 22878111]. https://doi.org/10.1016/j.jpeds.2012.06.045.

  • 36.

    Collins CT, Gibson RA, Makrides M, McPhee AJ, Sullivan TR, Davis PG, et al. The N3RO trial: a randomised controlled trial of docosahexaenoic acid to reduce bronchopulmonary dysplasia in preterm infants < 29 weeks' gestation. BMC Pediatr. 2016;16:72. [PubMed ID: 27250120]. [PubMed Central ID: PMC4896378]. https://doi.org/10.1186/s12887-016-0611-0.

  • 37.

    Bernabe‐Garcia M, Dominguez‐Vallejo P, Cruz‐Reynoso L, Villavicencio‐Torres A, Villegas‐Silva R, Inda‐Icaza P. Effect of Enteral Docosahexaenoic Acid on Retinopathy of Prematurity During Their Hospital Stay. FASEB J. 2017;31:lb390.

  • 38.

    Bernabe-Garcia M, Villegas-Silva R, Villavicencio-Torres A, Calder PC, Rodriguez-Cruz M, Maldonado-Hernandez J, et al. Enteral Docosahexaenoic Acid and Retinopathy of Prematurity: A Randomized Clinical Trial. JPEN J Parenter Enteral Nutr. 2019;43(7):874-82. [PubMed ID: 30614004]. https://doi.org/10.1002/jpen.1497.

  • 39.

    Fares S, Sethom MM, Kacem S, Khouaja-Mokrani C, Feki M, Kaabachi N. Plasma arachidonic and docosahexaenoic acids in Tunisian very low birth weight infants: status and association with selected neonatal morbidities. J Health Popul Nutr. 2015;33:1. [PubMed ID: 26825799]. [PubMed Central ID: PMC5026025]. https://doi.org/10.1186/s41043-015-0011-3.