{"paper_id":"4094b037-0d5d-4020-a790-42571ca8f114","body_text":"Does antenatal supplementation with omega-3 affect child development and behavior during the first six months of life? 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A randomized double-blind placebo-controlled trial Taciana Maia de Sousa, Luana Caroline dos Santos This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1459246/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose This randomized double-blind placebo-controlled trial aimed to evaluate the effect of antenatal omega-3 supplementation on child development and behavior during the first six months of life. Methods Participants with gestational age between 22–24 weeks were randomized in placebo (olive oil; n = 30) or omega-3 (fish oil; n = 30) groups and supplemented until childbirth. Fish oil capsules provided 1440mg/day of DHA. Child development was assessed using the Survey of Well-being of Young Children in the first, fourth and sixth month of life. Intention-to-treat and per-protocol analyses were performed using Generalized Estimating Equations. Results The comparison between groups showed no differences in the Developmental Milestones score at any time, but when compared to the first month, the omega-3 group showed an increase at the fourth and sixth month. Such increase was not observed in the placebo group. No differences were found between groups for Irritability and Inflexibility scores, however, higher scores for Difficulty with Routine were observed in the placebo group when compared to omega-3 at first, fourth and sixth month. Conclusion There were no differences between groups for child development, but the omega-3 group showed an increase in this score over time. The placebo group had greater difficulty with routine than the omega-3 group, indicating a beneficial effect of antenatal supplementation on child behavior. Trial registration: ReBec U1111-1215-7952 (June 16th 2018). omega-3 pregnancy maternal nutrition child development child behavior randomized controlled trial Figures Figure 1 Figure 2 What is Known Omega-3 fatty acids, especially docosahexaenoic acid (DHA), are found in different cell membranes, but more concentrated in the brain, playing an important role in child’s behavior and development. DHA deficiency in pregnant women may limit neurodevelopment of term infants and dietary intakes are often insufficient, therefore, antenatal supplementation may be necessary to achieve daily recommendation. What is New The omega-3 group had lower difficulty with routine than the placebo group, indicating a beneficial effect of antenatal supplementation on child behavior. The difficulty with routine subscale comprises mostly questions about infant sleep, and DHA supply during the intrauterine period may modify brain phospholipids, resulting in a more mature central nervous system, which is essential for a healthy sleep pattern. Introduction The gestational period is a window of opportunity to promote child adequate growth and development [ 1 ]. During this period, several nutrients are transported to the fetus, therefore, the maternal nutrient intake is important to ensure the adequate supply for their child [ 2 ]. Omega-3 fatty acids are one of the nutrients that increase plasma concentrations during pregnancy, because of an enhanced mobilization of docosahexaenoic acid (DHA) from the maternal adipose tissue to the placenta [ 3 , 4 ]. This nutrient is found in different cell membranes, but is concentrated in the brain, playing an important role in central nervous system development [ 5 ]. The accumulation of DHA in the brain tissue begins during the intrauterine period, around the second pregnancy trimester, when neurodevelopment accelerates [ 4 , 5 ]. Although the DHA have been widely associated to child visual, cognitive, and motor development, previous studies showed mixed results [ 6 – 9 ]. A systematic review reported seven clinical trials that evaluated the effect of omega-3 supplementation during pregnancy on cognition, attention, behavior, language and motor development, however, only one trial showed a positive effect, concluding that further investigations are needed [ 10 ]. On the other hand, a previous study was able to demonstrate that DHA deficiency in pregnant women limited neurodevelopment of term infants [ 8 ], highlighting the importance of adequate omega-3 intake during this period. Also, the need to provide adequate amounts of DHA during pregnancy has become a great concern worldwide, since dietary intakes are insufficient in different populations [ 11 ], therefore, antenatal supplementation may be necessary to achieve daily recommendation. Considering the scenario described above, the present trial aimed to evaluate the effect of antenatal omega-3 supplementation on child development and behavior during the first six months of life. Materials And Methods Design and participants This randomized, double-blind, placebo-controlled trial was conducted with data from the main study entitled “ Omega-3 supplementation during pregnancy to prevent depressive symptoms and possible effect on breastfeeding, child growth and development ”, designed according to CONSORT 2010 recommendations [ 12 ]. The study was approved by the Research Ethics Committee under number 87705018.0.0000.5149 and registered by the Brazilian Registry of Clinical Trials (ReBec) under number U1111-1215-7952 ( http://www.ensaiosclinicos.gov.br/rg / RBR-6gbzw6/). All participants signed a consent form after receiving the necessary information and expressed spontaneous interest to participate in the trial. Low-risk pregnant women attending antenatal care at a public ambulatory in Brazil were recruited. Inclusion criteria were age between 20–40 years old and gestational age between 22–24 weeks. All cases diagnosed by the medical team as high-risk pregnancy, and who reported supplementation with fish oil in the previous month or intolerance to fish/seafood were not included. Women who were under psychiatric treatment or diagnosed with depression were also not included in the sample since they served as exclusion criteria for the main study. Pregnant women were randomized at a proportion of 1:1 in placebo and omega-3 groups using the MATLAB® software. The omega-3 group received fish oil capsules, while the placebo group received olive oil capsules with equivalent caloric content. Both omega-3 and placebo capsules had 1000mg content and were approved according to microbiological safety and nutritional composition. All participants received detailed guidance on how to use and storage the supplement and were instructed to take two capsules a day until delivery (≈ 16 weeks) and no dietary changes were prescribed. The supplementation with two capsules of fish oil a day offered 260mg of EPA (eicosapentaenoic acid) and 1440mg of DHA (docosahexaenoic acid). Women were evaluated at baseline (22–24 gestational weeks) and the mother-child dyad were evaluated at two weeks, one month, four months, and sixth months postpartum (Fig. 1 ). Data collection Sociodemographic data, pregnancy information and food consumption were evaluated. At baseline, women were evaluated in person and after delivery via telephone interviews. Sociodemographic data included maternal age, education, marital status, occupation, parity, and per capita income. Gestational age was calculated based on the first ultrasound and participants were also asked about pregnancy intention. Food consumption was assessed using two 24 hours recall (24hR), applied on non-consecutive days, with a maximum interval of one week between them. Omega-3 composition was computed using Brasil Nutri® software [ 13 ]. Women received a new bottle of supplement capsules once a month during pregnancy, when they were asked whether they had continued supplementation in the previous month and whether there was any intolerance or discomfort. To estimate compliance, the participants referred the number of days not supplemented. Women who discontinued supplementation, or who presented compliance below 80% [ 14 ], were excluded from the analyses. After delivery, women and their respective children were assessed by telephone interview for childbirth information, breastfeeding practice, and child development. Child nutritional status was assessed using weight, length and head circumference at birth collected from medical records, and classified according to gestational age using the INTERGROWTH-21st curves [ 15 ]. Regarding breastfeeding, the participants were asked about breastfeeding in the first hour of life, whether they are currently breastfeeding, and whether they are exclusively breastfeeding and breastfeeding on demand. To assess child development, the Survey of Well-being of Young Children (SWYC) questionnaire was applied in the first, fourth and sixth month of life. For preterm children, the corrected age was adopted. The SWYC is a questionnaire directed for parents of children aged one to 65 months, proposed by Perrin et al. [ 16 ], translated and validated for the Brazilian population by Moreira et al. [ 17 ]. The questionnaire is divided into three domains: developmental, emotional/behavioral, and family context, and was considered suitable for application via telephone interview [ 17 ]. The developmental domain is a checklist containing 10 questions about child motor, language, social and cognitive development; and the emotional/behavioral domain covers the subscales: Irritability, Inflexibility and Difficulty with Routines, with 4 questions each (Fig. 1 ). Parents were also asked whether they have any concerns about their child's behavior or development. Sampling and statistical analyses The sample estimation was performed using the formula for analytical and experimental studies with a continuous outcome variable [ 18 ], considering the standard deviation and expected difference on the development score between groups after the intervention, obtained in a previous study [ 19 ]. The minimum of 14 participants in each group was estimated, considering the statistical power of 80% and the significance level of 5%. Twice the sample estimated was recruited to compensate for an expected loss of 50% during the intervention, according to a clinical trial with similar sample [ 20 ]. The database was built using the Epi Info ™ 3.5.1 program with double typing to enable proper consistency analysis. Statistical Package for the Social Sciences (SPSS) software version 20.0 and Stata® version 13 were used for statistical analyses. Descriptive analyses were performed with the calculation of frequencies and measures of central tendency and dispersion. The adherence of the variables to the normal distribution was assessed using the Shapiro-Wilk test. The difference between women from omega-3 and placebo groups at the baseline, and children at birth, was evaluated using the Chi-square and Student T test. Intention-to-treat and per-protocol analyses were conducted using the Generalized Estimating Equations (GEE) models with the Bonferroni post-hoc test, for analysis of repeated measures considering the effect of time, group and group-time interaction. The analyses were adjusted by breastfeeding practice, considering the effect of this variable on child development and behavior. A significance level of 5% was adopted in all analyses. Results A total of sixty pregnant women were randomized to receive placebo (n = 30) or omega-3 (n = 30). A 43.3% follow-up loss was observed (total: n = 26; omega-3: n = 14; placebo: n = 12), with no differences between the groups (p > 0.05). Follow-up losses are presented in Fig. 2 . Overall, capsules were well accepted by participants. The reason for dropping the study during pregnancy (n = 5) was the interruption of antenatal care at the ambulatory. All women who discontinued supplementation (n = 5) reported often forgetting to take the capsules. Only one woman reported intolerance to supplementation (placebo), presenting nausea and vomiting. Compliance was above 90% and did not differ between placebo (93.94 ± 1.14%) and omega-3 group (94.85 ± 1.22%) (p = 0.589). During the postpartum period, one woman asked to leave the study because of a lack of time to answer the questionnaires, and other losses (n = 10) were due to the impossibility to contact the participant. Women who dropped the study or were excluded from analyses did not differ from those who completed the trial according to age, per capita income, professional occupation, education, marital status, parity, pregestational and current BMI, history of depression, pregnancy intention and fatty acids intake (p > 0,05) (data not shown). Maternal characteristics of omega-3 and placebo groups at baseline are presented in Table 1 . Before the intervention, there were no differences between the groups according to sociodemographic data and pregnancy information (p > 0.05). Also, no differences were found in omega-3 intake by food consumption between groups (placebo: 1.51 ± 0.64g; omega-3: 1.69 ± 0.77g; p = 0.313) (data not shown). Table 1 Maternal characteristics before intervention according to group. Variables Percent (n) p value Placebo Omega-3 Age (years) 20–30 66.7 (20) 70.0 (21) 0.515 31–40 33.1 (10) 30.0 (9) Per capita income (minimum wage) <0.5 27.6 (8) 23.1 (6) 0.782 0.5-1.0 48.3 (14) 57.7 (15) >1.0 24.1 (7) 19.2 (5) Professional occupation Paid work 46.7 (14) 60.0 (18) 0.702 Student 10.0 (3) 10.0 (3) Housewife 30.0 (9) 23.3 (7) Unemployed 13.3 (4) 6.7 (2) Marital status Married/Stable union 82.1 (23) 62.1 (18) 0.092 Single/Divorced 17.9 (5) 37.9 (11) Education Elementary school 6.7 (2) 10.0 (3) 0.799 High school 60.0 (18) 63.3 (19) Higher education 33.3 (10) 26.7 (8) Pregnancy intention Intended 51.7 (15) 41.4 (12) 0.430 Non intended 48.3 (14) 58.6 (17) Parity 0.196 Primiparous 60.0 (18) 43.3 (13) Multiparous 40.0 (12) 56.7 (17) Note: p-value for chi-square test. Minimum wage: ≈ $230 (2018–2019). SD: standard deviation Child characteristics at birth according to groups are presented in Table 2 . There were no differences in sex, gestational age, route of birth and anthropometry between the groups (p > 0.05). Also, no differences were found in breastfeeding, exclusive breastfeeding, and breastfeeding on demand according to group during the first six months of the child's life (Table 3 ) . Table 2 Child characteristics at birth according to group. Variables Percent (n) p value Placebo Omega-3 Sex Female 65.2 (15) 40.0 (8) 0.098 Male 34.8 (8) 60.0 (12) Gestational age Preterm (< 37 weeks) 4.3 (1) 5.0 (1) 0.890 Full-term (≥ 37 weeks) 95.7 (22) 95.0 (19) Route of birth Vaginal 78.3 (18) 60.0 (12) 0.193 Caesarean section 21.7 (5) 40.0 (8) Weight Adequate 82.6 (19) 100.0 (19) 0.188 Low weight 17.4 (4) 0.0 (0) Height Adequate 91.3 (21) 100.0 (19) 0.056 Low height 8.7 (3) 0.0 (0) Head circumference 0.265 Adequate 100.0 (19) 94.7 (18) Small head circumference 0.0 (0) 5.3 (1) Breastfed in the 1st hour of life Yes 82.6 (19) 75.0 (15) 0.541 No 17.4 (4) 25.0 (5) Skin-to-skin contact after birth Yes 91.3 (21) 84.2 (16) 0.480 No 8.7 (2) 15.8 (3) Note: p-value for chi-square test. Table 3 Evolution of breastfeeding practice according to group during the first six months of life. Time Breastfeeding Percent (n) Exclusive breastfeeding Percent (n) Breastfeeding on demand Percent (n) Placebo Omega-3 p value Placebo Omega-3 p value Placebo Omega-3 p value 1st month Yes 100.0 (18) 86.7 (13) 0.110 55.6 (10) 76.9 (10) 0.220 88.9 (16) 100.0 (13) 0.214 No 0.0 (0) 13.3 (2) 44.4 (8) 23.1 (3) 11.1 (2) 0.0 (0) 4th month Yes 87.5 (14) 81.3 (13) 0.626 28.6 (4) 7.7 (1) 0.163 78.6 (11) 69.2 (9) 0.580 No 12.5 (2) 18.8 (3) 71.4 (10) 92.3 (12) 21.4 (3) 30.8 (4) 6th month Yes 88.9 (16) 68.8 (11) 0.050 0.0 (0) 0.0 (0) - 70.6 (12) 63.6 (7) 0.700 No 11.1 (2) 31.2 (5) 100.0 (17) 100.0 (11) 29.4 (5) 36.4 (4) Note: p-value for chi-square test. The comparison between groups showed no differences in the Developmental Milestones score at any time (p > 0.05) (Table 4 ). When compared to the first month, the omega-3 group showed an increase in the Developmental Milestones score at the fourth and sixth month, in both intention-to-treat and per-protocol analysis. Such increase was not observed in the placebo group. Table 4 Intragroup and between groups comparison of child development and behavior score according to linear Generalized Estimating Equation (GEE) models. Item Time Per protocol Intention-to-treat Placebo Mean (95%CI) Omega-3 Mean (95%CI) Placebo Mean (95%CI) Omega-3 Mean (95%CI) Developmental milestones 1st month 14.20 (12.49–15.91) 12.78 (11.08–14.47) A 14.11 (12.72–15.50) 12.76 (11.21–14.32) A 4th month 15.12 (13.85–16.40) 15.73 (14.27–17.19) B 15.42 (14.26–16.59) 15.50 (14.26–16.72) B 6th month 15.20 (13.87–16.53) 16.00 (13.93–17.03) B 15.36 (14.26–16.46) 15.80 (13.94–17.64) B Irritability 1st month 1.79 (0.39–3 .19) 0.54 (0.03–1.05) 1.56 (0.46–2 .65) 0.78 (0.11–1.44) 4th month 1.56 (0.72–2.41) 1.43 (0.52–2.35) 1.82 (0.91–2.72) 1.35 (0.48–2.21) 6th month 1.72 (0.56–2.87) 1.22 (0.69–1.75) 1.78 (0.86–2.70) 1.33 (0.75–1.90) Inflexibility 1st month 2.89 (1.64–4.14) 1.56 (0.32–2.79) 2.89 (1.90–3.88) 1.60 (0.51–2.69) 4th month 2.04 (1.15–2.93) 1.63 (0.81–2.46) 1.84 (0.99–2.69) 1.81 (0.99–2.62) 6th month 1.66 (0.68–2.64) 1.12 (0.32–1.91) 1.59 (0.51–1.93) 1.22 (0.51–1.93) Dificulty with routine 1st month 3.40 (2.33–4.47) a 1.28 (0.10–2.46) b 3.02 (2.06–3.97) a 1.27 (0.24–2.30) b 4th month 3.17 (2.15–4.19) a 1.45 (0.85–2.06) b 2.86 (1.93–3.78) 1.72 (0.92–2.52) 6th month 3.63 (2.15–5.11) a 0.84 (0.62–2.30) b 3.09 (1.85–4.33) a 0.96 (0.26–2.18) b CI: confidential interval. Note: Analysis adjusted by breastfeeding practice. Different uppercase letters indicate intragroup difference and different lowercase letters indicate difference between groups, according to the post-hoc test (Bonferroni). Regarding the Emotional/Behavioral Domain, no differences were found between groups for Irritability and Inflexibility scores at any time (p > 0.05). However, in per-protocol analysis, higher scores for Difficulty with Routine were observed in the placebo group when compared to omega-3 at all times, and at the first and sixth month in intention-to-treat analysis (Table 4 ). Discussion The antenatal supplementation with omega-3 did not promote differences in child development score when compared to the placebo group, however, the omega-3 group showed a significant increase in this score over time. Higher scores for Difficulty with Routine were observed in the placebo group, with no differences for Irritability and Inflexibility scores. Our results are in line with the meta-analysis conducted by Middleton et al. [ 4 ]. According to the study, the antenatal omega-3 supplementation promoted very few differences in cognition and neurodevelopment [ 4 ]. A clinical trial conducted by Ramakrishnan et al. [ 7 ], used the Bayley Scales of Infant Development-II (BSID-II) to evaluate the effect of antenatal supplementation with algal DHA (400mg/day) on offspring development at 18 months of age. The results showed that the supplementation had no effects on child development, although DHA intake attenuated the association between home environment and psychomotor development, suggesting potential benefits for children living in home environments with reduced caregiver interactions and child stimulation [ 7 ]. Similarly, Hurtado et al [ 3 ] recruited pregnant women to take 400 mL/day of a control dairy drink or a DHA–enriched dairy drink (400mg/day) and the BSID-II was used to evaluate the infant development at 12 months. All infants presented normal neurodevelopment for the age, with no significant differences between the groups, but the antenatal supplementation showed a major effect on DHA levels in plasma and erythrocyte membranes of mothers and infants [ 3 ]. In contrast, the maternal plasma DHA concentration was associated with child development in a follow-up study conducted by Mulder et al [ 8 ]. The authors assessed 5–6 years children of mothers who received placebo or DHA (400mg/day) during pregnancy, using the second edition of Kaufman Assessment Battery for Children. Despite finding no differences between groups, maternal DHA plasma concentration was positively related to child performance on language and short-term memory [ 8 ]. The role of omega-3 fatty acids in the development of the fetal central nervous system is well described [ 5 ], however, the effect of supplementation during pregnancy remains unclear in the literature. It is noteworthy that the studies available until now differ regarding the dosage and supplement adopted, sample characteristics, intervention length and development assessment tools, therefore, to systematize the results is very challenging. Despite the lack of differences in the development score between the groups in our trial, the increase in this score over time, observed solely in the omega-3 group, might be an indicator of differences in long-term child development that should be investigated in future studies. Also, children of women who supplemented omega-3 during pregnancy presented less difficulty with routine in our study. Until now, no trials with omega-3 supplementation have been published using SWYC to assess infant development and behavior, which makes it difficult to compare our results with the available literature. However, it is known that alterations in child behavior are strong predictors of developmental deficits throughout childhood [ 17 ]. Additionally, the Difficulty with Routine subscale comprises mostly questions about infant sleep, and previous studies on this subject have found a similar association [ 21 – 23 ]. According to a meta-analysis conducted by Dai et al. [ 23 ], the omega-3 supply during pregnancy may improve infants' sleep organization and maturity, especially reducing the occurrence of active sleep [ 23 ]. Such improvement was demonstrated by Judge et al. [ 22 ], in a trial that aimed to evaluate the effect of using a functional food containing 300mg of DHA during pregnancy, on infant sleep patterning. The authors found lower arousals in quiet and active sleep in the intervention group when compared to placebo, concluding that increased antenatal intake of DHA has a beneficial impact on infant’s sleep organization, and therefore in their routine [ 22 ]. The authors suggested that DHA supply during the intrauterine development may modify brain phospholipids and affect neural function, resulting in a more mature central nervous system, which is essential for a healthy sleep pattern [ 21 – 23 ]. Also, omega-3 intake during pregnancy is associated with an increased gestational length [ 4 ], due to the effect on prostaglandins balance involved in parturition, a fact that may impact the child neurodevelopment, and consequently improve their sleep behavior. Nevertheless, it is important to note that the studies mentioned above were conducted with newborns, and further investigations regarding the effect of antenatal omega-3 supplementation on sleep behavior of older infants are needed. Considering the results found in our study, the use of a higher DHA dosage does not seem to increase the effect of antenatal omega-3 supplementation on child development and behavior. The use of 1440mg/day of DHA did not promote stronger effects when compared to studies that used 300-400mg/day of DHA, as presented above. The mean dietary intake of omega-3 of our sample was above the Adequate Intake (1.4g/day), proposed by Institute of Medicine [ 24 ], which reinforces the hypothesis of the supplementation being more effective for populations with omega-3 deficiency. In addition, our sample consisted of healthy pregnant women, and their offspring consequently had a low risk of inadequate neurodevelopment. However, the increase on development score over time and the lower difficult with routine, observed in the intervention group despite the breastfeeding practice, suggests that the effect of omega-3 on child development and behavior should be further investigated. The lack of omega-3 plasma levels assessment to evaluate compliance and to explain the results of the effect is a limitation of this trial. Despite that, the relevance of the present study is highlighted, considering the investigation of the effect of a higher DHA dosage during pregnancy on child development and behavior. Also, the association of omega-3 supplementation with the sleep behavior (included in the routine) of older infants is an unprecedented result that should be further explored in the future. In conclusion, the antenatal supplementation with a DHA dosage of 1440mg/day did not promote significant differences between groups for child development, but the omega-3 group showed an increase in this score over time. The placebo group had greater difficulty with routine than the omega-3 group, indicating a beneficial effect of antenatal supplementation on child behavior, more specifically in sleep behavior, and this association should be further explored using specific tools to assess children's sleep patterns. Abbreviations CONSORT: Consolidated Standards of Reporting Trials DHA: docosahexaenoic acid EPA: eicosapentaenoic acid GEE: Generalized Estimating Equations IOM: Institute of Medicine ReBec: Brazilian Registry of Clinical Trials SWYC: Survey of Well-being of Young Children Declarations Funding: The current research was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (productivity scholarship - grant number 406644/2016-0). The Conselho Nacional de Desenvolvimento Científico e Tecnológico had no role in the design, analysis or writing of this article. Conflicts of interest/Competing interests: The authors declare that they have no conflict of interest. Availability of data and material: Due to the nature of this research, participants of this study did not agree for their data to be shared publicly, so supporting data is not available. Code availability: Not applicable. Authors' contributions: Sousa TM participated in the project design, bibliographic review, data collection, statistical analysis and article writing. Santos LC acted in the project design and review of the article. Ethics approval: This study was approved by the Research Ethics Committee under number 87705018.0.0000.5149 and registered by the Brazilian Registry of Clinical Trials (ReBec) under number U1111-1215-7952 (http://www.ensaiosclinicos.gov.br/rg / RBR-6gbzw6/). Consent to participate: All participants signed a consent form after receiving the necessary information and expressed spontaneous interest to participate in the trial. Consent for publication: Not applicable. References Christian P, Mullany LC, Hurley KM, Katz J, Black RE (2015) Nutrition and maternal, neonatal, and child health. Semin Perinatol 39:361–372. https://doi.org/10.1053/j.semperi.2015.06.009 Haider BA, Bhutta ZA (2012) Multiple-micronutrient supplementation for women during pregnancy. 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Br J Nutr 119:271–279. https://doi.org/10.1017/S0007114517003531 Ostadrahimi A, Salehi-Pourmehr H, Mohammad-Alizadeh-Charandabi S, Heidarabady S, Farshbaf-Khalili A (2018) The effect of perinatal fish oil supplementation on neurodevelopment and growth of infants: a randomized controlled trial. Eur J Nutr 57:2387–2397. https://doi.org/10.1007/s00394-017-1512-1 Rangel-Huerta OD, Gil A (2018) Effect of omega-3 fatty acids on cognition: an updated systematic review of randomized clinical trials. Nutr Rev 76:1–20. https://doi.org/10.1093/nutrit/nux064 Koletzko B, Cetin I, Brenna JT (2007) Dietary fat intakes for pregnant and lactating women. Br J Nutr 98:873–877. https://doi.org/10.1017/S0007114507764747 Schulz KF, Altman DG, Moher D, for the CONSORT Group (2010) CONSORT 2010 Statement: updated guidelines for reporting parallel group randomized trials. Open Med 4:60–68. https://doi.org/10.1186/1741-7015-8-18 Instituto Brasileiro de Geografia Estatística (IBGE) (2011) Pesquisa de Orçamentos Familiares 2008–2009: análise do consumo alimentar pessoal no Brasil. IBGE, Rio de Janeiro, p 150 Leite SN, Vasconcellos MPC (2003) Adherence to prescribed therapy: points for concepts and presuppositions discussion. Ciênc Saúde Coletiva 8:775–782. https://doi.org/10.1590/S1413-81232003000300011 Villar J, Ismail LC, Victora CG, Ohuma EO, Bertino E, Altman DG et al (2014) International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st). International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross Sectional Study of the INTERGROWTH-21st Project. Lancet 384:857–868 Perrin EC, Sheldrick RC, Henson BS, Merchant S, Survey of Wellbeing of Young hildren (2016) SWYC Forms Portuguese. Available from: https://www.floatinghospital.org/The-Survey-of-Wellbeing-of-Young-Children/Translations.aspx Moreira RS, Magalhães RC, Siqueira CM, Alves CRL (2019) Adaptação Transcultural do instrumento de vigilância do desenvolvimento infantil “Survey of Wellbeing of Young Children (SWYC)” no contexto brasileiro. J Hum Growth Dev 29:28–38. https://doi.org/10.7322/jhgd.145001 Hulley SB, Cummings SR, Browner WS et al (2013) Designing clinical research. Philadelphia: Lippincott Williams & Wilkins; 367p Dunstan JA, Simmer K, Dixon G, Prescott SL (2008) Cognitive assessment of children at age 2(1/2) years after maternal fish oil supplementation in pregnancy: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 93:F45–50. https://doi.org/10.1136/adc.2006.099085 Vaz JDS, Farias DR, Adegboye ARA et al (2017) Omega-3 supplementation from pregnancy to postpartum to prevent depressive symptoms: a randomized placebo-controlled trial. BMC Pregnancy Childbirth 17:180. https://doi.org/10.1186/s12884-017-1365-x Cheruku SR, Montgomery-Downs HE, Farkas SL, Thoman EB, Lammi-Keefe CJ (2002) Higher maternal plasma docosahexaenoic acid during pregnancy is associated with more mature neonatal sleep-state patterning. Am J Clin Nutr 76:608–613. https://doi.org/10.1093/ajcn/76.3.608 Judge MP, Cong X, Harel O, Courville AB, Lammi-Keefe CJ (2012) Maternal consumption of a DHA-containing functional food benefits infant sleep patterning: an early neurodevelopmental measure. Early Hum Dev 88:531–537. https://doi.org/10.1016/j.earlhumdev.2012.12.016 Dai Y, Liu J Omega-3 long-chain polyunsaturated fatty acid and sleep: a systematic review and meta-analysis of randomized controlled trials and longitudinal studies.Nutr Rev, 31:nuaa103. https://doi.org/10.1093/nutrit/nuaa103 Institute of Medicine (IOM) (2005) Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). The National Academies Press, Washington, DC, p 1357 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-1459246\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":92821154,\"identity\":\"1f315efd-ad07-4b09-b07e-4fc640fb7708\",\"order_by\":0,\"name\":\"Taciana Maia de Sousa\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8ElEQVRIiWNgGAWjYJCCA2CSGYg/ADEbOwHlPMhaGGeAtDAToQUOmHlg1uED9uyHHx74ucMumr+d+fFnm1/b5PmYGRg/fMzBYwtPmsHB3jPJuTMOs5lJ5/bdNmxjZmCWnLkNn8NyGA7wtjHnNhxmMGPO7bnNCNTCxsyLTwv/G4aDf9vqc+cfZv/82bLntj1hLRI5DId52w7nbjjMYyDN8ON2ImEtN54ZHJZtO5678TBPmWRvw+3kNmbGZrx+Ye9PfvzxbVt17rzzxzd/+PHntu389uaDHz7i0YIKGNvAZAOx6kHgDymKR8EoGAWjYKQAAJ9IUNmglknWAAAAAElFTkSuQmCC\",\"orcid\":\"https://orcid.org/0000-0002-7387-154X\",\"institution\":\"Universidade Federal de Minas Gerais\",\"correspondingAuthor\":true,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Taciana\",\"middleName\":\"Maia\",\"lastName\":\"de Sousa\",\"suffix\":\"\"},{\"id\":92821155,\"identity\":\"76337d82-639e-4516-9cd4-f39c947e8602\",\"order_by\":1,\"name\":\"Luana Caroline dos Santos\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"UFMG: Universidade Federal de Minas Gerais\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Luana\",\"middleName\":\"Caroline dos\",\"lastName\":\"Santos\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2022-03-16 17:42:37\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-1459246/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-1459246/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":19585171,\"identity\":\"8eee98f0-8c0c-4528-bf11-3d0065ef877d\",\"added_by\":\"auto\",\"created_at\":\"2022-03-24 19:20:45\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":64046,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eParts of the Survey of Well-being of Young Children (SWYC) questionnaire used in the trial.\\u0026nbsp;\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"Fig1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-1459246/v1/dc6535c0012da476e182f4e1.png\"},{\"id\":19585234,\"identity\":\"b6a9db69-5f5d-4b9c-8ad0-09463235105f\",\"added_by\":\"auto\",\"created_at\":\"2022-03-24 19:21:01\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":142669,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eDiagram\\u0026nbsp;of\\u0026nbsp;trial\\u0026nbsp;follow-up.\\u0026nbsp;\\u003c/p\\u003e\\u003cp\\u003e\\u003cbr\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"Fig2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-1459246/v1/2033da84783af540b9518edb.png\"},{\"id\":22431943,\"identity\":\"51985159-55de-4358-9d00-3e492c97ac62\",\"added_by\":\"auto\",\"created_at\":\"2022-06-08 21:54:07\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":628077,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-1459246/v1/d7dba52e-aa88-4c1a-9658-47cff05f076a.pdf\"}],\"financialInterests\":\"\",\"formattedTitle\":\"Does antenatal supplementation with omega-3 affect child development and behavior during the first six months of life? A randomized double-blind placebo-controlled trial\",\"fulltext\":[{\"header\":\"What is Known\",\"content\":\"\\u003cul\\u003e\\n \\u003cli\\u003eOmega-3 fatty acids, especially docosahexaenoic acid (DHA), are found in different cell membranes, but more concentrated in the brain, playing an important role in child\\u0026rsquo;s behavior and development.\\u003c/li\\u003e\\n \\u003cli\\u003eDHA deficiency in pregnant women may limit neurodevelopment of term infants and dietary intakes are often insufficient, therefore, antenatal supplementation may be necessary to achieve daily recommendation.\\u0026nbsp;\\u003c/li\\u003e\\n\\u003c/ul\\u003e\"},{\"header\":\"What is New\",\"content\":\"\\u003cul\\u003e\\n \\u003cli\\u003eThe omega-3 group had lower difficulty with routine than the placebo group, indicating a beneficial effect of antenatal supplementation on child behavior.\\u0026nbsp;\\u003c/li\\u003e\\n \\u003cli\\u003eThe difficulty with routine subscale comprises mostly questions about infant sleep, and DHA supply during the intrauterine period may modify brain phospholipids, resulting in a more mature central nervous system, which is essential for a healthy sleep pattern.\\u003c/li\\u003e\\n\\u003c/ul\\u003e\"},{\"header\":\"Introduction\",\"content\":\"\\u003cp\\u003eThe gestational period is a window of opportunity to promote child adequate growth and development [\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e]. During this period, several nutrients are transported to the fetus, therefore, the maternal nutrient intake is important to ensure the adequate supply for their child [\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eOmega-3 fatty acids are one of the nutrients that increase plasma concentrations during pregnancy, because of an enhanced mobilization of docosahexaenoic acid (DHA) from the maternal adipose tissue to the placenta [\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e]. This nutrient is found in different cell membranes, but is concentrated in the brain, playing an important role in central nervous system development [\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e]. The accumulation of DHA in the brain tissue begins during the intrauterine period, around the second pregnancy trimester, when neurodevelopment accelerates [\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eAlthough the DHA have been widely associated to child visual, cognitive, and motor development, previous studies showed mixed results [\\u003cspan additionalcitationids=\\\"CR7 CR8\\\" citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e]. A systematic review reported seven clinical trials that evaluated the effect of omega-3 supplementation during pregnancy on cognition, attention, behavior, language and motor development, however, only one trial showed a positive effect, concluding that further investigations are needed [\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eOn the other hand, a previous study was able to demonstrate that DHA deficiency in pregnant women limited neurodevelopment of term infants [\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e], highlighting the importance of adequate omega-3 intake during this period. Also, the need to provide adequate amounts of DHA during pregnancy has become a great concern worldwide, since dietary intakes are insufficient in different populations [\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e], therefore, antenatal supplementation may be necessary to achieve daily recommendation.\\u003c/p\\u003e \\u003cp\\u003eConsidering the scenario described above, the present trial aimed to evaluate the effect of antenatal omega-3 supplementation on child development and behavior during the first six months of life.\\u003c/p\\u003e\"},{\"header\":\"Materials And Methods\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eDesign and participants\\u003c/h2\\u003e \\u003cp\\u003eThis randomized, double-blind, placebo-controlled trial was conducted with data from the main study entitled \\u0026ldquo;\\u003cem\\u003eOmega-3 supplementation during pregnancy to prevent depressive symptoms and possible effect on breastfeeding, child growth and development\\u003c/em\\u003e\\u0026rdquo;, designed according to CONSORT 2010 recommendations [\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eThe study was approved by the Research Ethics Committee under number 87705018.0.0000.5149 and registered by the Brazilian Registry of Clinical Trials (ReBec) under number U1111-1215-7952 (\\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttp://www.ensaiosclinicos.gov.br/rg\\u003c/span\\u003e\\u003cspan address=\\\"http://www.ensaiosclinicos.gov.br/rg\\\" targettype=\\\"URL\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e / RBR-6gbzw6/). All participants signed a consent form after receiving the necessary information and expressed spontaneous interest to participate in the trial.\\u003c/p\\u003e \\u003cp\\u003eLow-risk pregnant women attending antenatal care at a public ambulatory in Brazil were recruited. Inclusion criteria were age between 20\\u0026ndash;40 years old and gestational age between 22\\u0026ndash;24 weeks. All cases diagnosed by the medical team as high-risk pregnancy, and who reported supplementation with fish oil in the previous month or intolerance to fish/seafood were not included. Women who were under psychiatric treatment or diagnosed with depression were also not included in the sample since they served as exclusion criteria for the main study.\\u003c/p\\u003e \\u003cp\\u003ePregnant women were randomized at a proportion of 1:1 in placebo and omega-3 groups using the MATLAB\\u0026reg; software. The omega-3 group received fish oil capsules, while the placebo group received olive oil capsules with equivalent caloric content. Both omega-3 and placebo capsules had 1000mg content and were approved according to microbiological safety and nutritional composition. All participants received detailed guidance on how to use and storage the supplement and were instructed to take two capsules a day until delivery (\\u0026asymp;\\u0026thinsp;16 weeks) and no dietary changes were prescribed. The supplementation with two capsules of fish oil a day offered 260mg of EPA (eicosapentaenoic acid) and 1440mg of DHA (docosahexaenoic acid).\\u003c/p\\u003e \\u003cp\\u003eWomen were evaluated at baseline (22\\u0026ndash;24 gestational weeks) and the mother-child dyad were evaluated at two weeks, one month, four months, and sixth months postpartum (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e).\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec4\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eData collection\\u003c/h2\\u003e \\u003cp\\u003eSociodemographic data, pregnancy information and food consumption were evaluated. At baseline, women were evaluated in person and after delivery via telephone interviews.\\u003c/p\\u003e \\u003cp\\u003eSociodemographic data included maternal age, education, marital status, occupation, parity, and per capita income. Gestational age was calculated based on the first ultrasound and participants were also asked about pregnancy intention.\\u003c/p\\u003e \\u003cp\\u003eFood consumption was assessed using two 24 hours recall (24hR), applied on non-consecutive days, with a maximum interval of one week between them. Omega-3 composition was computed using Brasil Nutri\\u0026reg; software [\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eWomen received a new bottle of supplement capsules once a month during pregnancy, when they were asked whether they had continued supplementation in the previous month and whether there was any intolerance or discomfort. To estimate compliance, the participants referred the number of days not supplemented. Women who discontinued supplementation, or who presented compliance below 80% [\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e], were excluded from the analyses.\\u003c/p\\u003e \\u003cp\\u003eAfter delivery, women and their respective children were assessed by telephone interview for childbirth information, breastfeeding practice, and child development.\\u003c/p\\u003e \\u003cp\\u003eChild nutritional status was assessed using weight, length and head circumference at birth collected from medical records, and classified according to gestational age using the \\u003cem\\u003eINTERGROWTH-21st\\u003c/em\\u003e curves [\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eRegarding breastfeeding, the participants were asked about breastfeeding in the first hour of life, whether they are currently breastfeeding, and whether they are exclusively breastfeeding and breastfeeding on demand.\\u003c/p\\u003e \\u003cp\\u003eTo assess child development, the Survey of Well-being of Young Children (SWYC) questionnaire was applied in the first, fourth and sixth month of life. For preterm children, the corrected age was adopted. The SWYC is a questionnaire directed for parents of children aged one to 65 months, proposed by Perrin et al. [\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e], translated and validated for the Brazilian population by Moreira et al. [\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e]. The questionnaire is divided into three domains: developmental, emotional/behavioral, and family context, and was considered suitable for application via telephone interview [\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e]. The developmental domain is a checklist containing 10 questions about child motor, language, social and cognitive development; and the emotional/behavioral domain covers the subscales: Irritability, Inflexibility and Difficulty with Routines, with 4 questions each (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e\\u003cb\\u003e).\\u003c/b\\u003e Parents were also asked whether they have any concerns about their child's behavior or development.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec5\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eSampling and statistical analyses\\u003c/h2\\u003e \\u003cp\\u003eThe sample estimation was performed using the formula for analytical and experimental studies with a continuous outcome variable [\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e], considering the standard deviation and expected difference on the development score between groups after the intervention, obtained in a previous study [\\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e]. The minimum of 14 participants in each group was estimated, considering the statistical power of 80% and the significance level of 5%. Twice the sample estimated was recruited to compensate for an expected loss of 50% during the intervention, according to a clinical trial with similar sample [\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eThe database was built using the Epi Info \\u0026trade; 3.5.1 program with double typing to enable proper consistency analysis. Statistical Package for the Social Sciences (SPSS) software version 20.0 and Stata\\u0026reg; version 13 were used for statistical analyses.\\u003c/p\\u003e \\u003cp\\u003eDescriptive analyses were performed with the calculation of frequencies and measures of central tendency and dispersion. The adherence of the variables to the normal distribution was assessed using the Shapiro-Wilk test. The difference between women from omega-3 and placebo groups at the baseline, and children at birth, was evaluated using the Chi-square and Student T test.\\u003c/p\\u003e \\u003cp\\u003eIntention-to-treat and per-protocol analyses were conducted using the Generalized Estimating Equations (GEE) models with the Bonferroni post-hoc test, for analysis of repeated measures considering the effect of time, group and group-time interaction. The analyses were adjusted by breastfeeding practice, considering the effect of this variable on child development and behavior. A significance level of 5% was adopted in all analyses.\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cp\\u003eA total of sixty pregnant women were randomized to receive placebo (n\\u0026thinsp;=\\u0026thinsp;30) or omega-3 (n\\u0026thinsp;=\\u0026thinsp;30). A 43.3% follow-up loss was observed (total: n\\u0026thinsp;=\\u0026thinsp;26; omega-3: n\\u0026thinsp;=\\u0026thinsp;14; placebo: n\\u0026thinsp;=\\u0026thinsp;12), with no differences between the groups (p\\u0026thinsp;\\u0026gt;\\u0026thinsp;0.05). Follow-up losses are presented in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e.\\u003c/p\\u003e \\u003cp\\u003eOverall, capsules were well accepted by participants. The reason for dropping the study during pregnancy (n\\u0026thinsp;=\\u0026thinsp;5) was the interruption of antenatal care at the ambulatory. All women who discontinued supplementation (n\\u0026thinsp;=\\u0026thinsp;5) reported often forgetting to take the capsules. Only one woman reported intolerance to supplementation (placebo), presenting nausea and vomiting. Compliance was above 90% and did not differ between placebo (93.94\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.14%) and omega-3 group (94.85\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.22%) (p\\u0026thinsp;=\\u0026thinsp;0.589). During the postpartum period, one woman asked to leave the study because of a lack of time to answer the questionnaires, and other losses (n\\u0026thinsp;=\\u0026thinsp;10) were due to the impossibility to contact the participant.\\u003c/p\\u003e \\u003cp\\u003eWomen who dropped the study or were excluded from analyses did not differ from those who completed the trial according to age, \\u003cem\\u003eper capita\\u003c/em\\u003e income, professional occupation, education, marital status, parity, pregestational and current BMI, history of depression, pregnancy intention and fatty acids intake (p\\u0026thinsp;\\u0026gt;\\u0026thinsp;0,05) (data not shown).\\u003c/p\\u003e \\u003cp\\u003eMaternal characteristics of omega-3 and placebo groups at baseline are presented in Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e. Before the intervention, there were no differences between the groups according to sociodemographic data and pregnancy information (p\\u0026thinsp;\\u0026gt;\\u0026thinsp;0.05). Also, no differences were found in omega-3 intake by food consumption between groups (placebo: 1.51\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.64g; omega-3: 1.69\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.77g; p\\u0026thinsp;=\\u0026thinsp;0.313) (data not shown).\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eMaternal characteristics before intervention according to group.\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"4\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003eVariables\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e \\u003cp\\u003ePercent\\u0026nbsp;(n)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003ep\\u0026nbsp;value\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003ePlacebo\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eOmega-3\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eAge (years)\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e20\\u0026ndash;30\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e66.7 (20)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e70.0 (21)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003e0.515\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e31\\u0026ndash;40\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e33.1 (10)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e30.0 (9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cspan type=\\\"BoldItalic\\\" class=\\\"BoldItalic\\\" name=\\\"Emphasis\\\"\\u003ePer capita\\u003c/span\\u003e\\u0026nbsp;\\u003cb\\u003eincome (minimum\\u0026nbsp;wage)\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u0026lt;0.5\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e27.6 (8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e23.1 (6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\" morerows=\\\"2\\\" rowspan=\\\"3\\\"\\u003e \\u003cp\\u003e0.782\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e0.5-1.0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e48.3 (14)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e57.7 (15)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u0026gt;1.0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e24.1 (7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e19.2 (5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eProfessional\\u0026nbsp;occupation\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePaid\\u0026nbsp;work\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e46.7 (14)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e60.0 (18)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\" morerows=\\\"3\\\" rowspan=\\\"4\\\"\\u003e \\u003cp\\u003e0.702\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eStudent\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e10.0 (3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e10.0 (3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eHousewife\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e30.0 (9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e23.3 (7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eUnemployed\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e13.3 (4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e6.7 (2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eMarital status\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eMarried/Stable\\u0026nbsp;union\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e82.1 (23)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e62.1 (18)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003e0.092\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSingle/Divorced\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e17.9 (5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e37.9 (11)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eEducation\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eElementary\\u0026nbsp;school\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e6.7 (2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e10.0 (3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\" morerows=\\\"2\\\" rowspan=\\\"3\\\"\\u003e \\u003cp\\u003e0.799\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eHigh\\u0026nbsp;school\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e60.0 (18)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e63.3 (19)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eHigher\\u0026nbsp;education\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e33.3 (10)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e26.7 (8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003ePregnancy\\u0026nbsp;intention\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eIntended\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e51.7 (15)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e41.4 (12)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003e0.430\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNon\\u0026nbsp;intended\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e48.3 (14)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e58.6 (17)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eParity\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\" morerows=\\\"2\\\" rowspan=\\\"3\\\"\\u003e \\u003cp\\u003e0.196\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePrimiparous\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e60.0 (18)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e43.3 (13)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eMultiparous\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e40.0 (12)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e56.7 (17)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"4\\\"\\u003eNote: p-value for chi-square test. Minimum wage: \\u0026asymp; $230 (2018\\u0026ndash;2019). SD: standard deviation\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003eChild characteristics at birth according to groups are presented in Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e. There were no differences in sex, gestational age, route of birth and anthropometry between the groups (p\\u0026thinsp;\\u0026gt;\\u0026thinsp;0.05). Also, no differences were found in breastfeeding, exclusive breastfeeding, and breastfeeding on demand according to group during the first six months of the child's life (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e\\u003cb\\u003e)\\u003c/b\\u003e.\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab2\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 2\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eChild characteristics at birth according to group.\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"4\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003eVariables\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e \\u003cp\\u003ePercent\\u0026nbsp;(n)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003ep\\u0026nbsp;value\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003ePlacebo\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eOmega-3\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eSex\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eFemale\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e65.2 (15)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e40.0 (8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003e0.098\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eMale\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e34.8 (8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e60.0 (12)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eGestational\\u0026nbsp;age\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePreterm\\u0026nbsp;(\\u0026lt;\\u0026thinsp;37\\u0026nbsp;weeks)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e4.3 (1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e5.0 (1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003e0.890\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eFull-term\\u0026nbsp;(\\u0026ge;\\u0026thinsp;37\\u0026nbsp;weeks)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e95.7 (22)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e95.0 (19)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eRoute\\u0026nbsp;of\\u0026nbsp;birth\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eVaginal\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e78.3 (18)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e60.0 (12)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003e0.193\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCaesarean\\u0026nbsp;section\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e21.7 (5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e40.0 (8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eWeight\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAdequate\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e82.6 (19)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e100.0 (19)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003e0.188\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eLow\\u0026nbsp;weight\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e17.4 (4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.0 (0)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eHeight\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAdequate\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e91.3 (21)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e100.0 (19)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003e0.056\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eLow\\u0026nbsp;height\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e8.7 (3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.0 (0)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eHead\\u0026nbsp;circumference\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\" morerows=\\\"2\\\" rowspan=\\\"3\\\"\\u003e \\u003cp\\u003e0.265\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAdequate\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e100.0 (19)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e94.7 (18)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSmall\\u0026nbsp;head\\u0026nbsp;circumference\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.0 (0)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e5.3 (1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eBreastfed\\u0026nbsp;in\\u0026nbsp;the\\u0026nbsp;1st \\u0026nbsp;hour\\u0026nbsp;of\\u0026nbsp;life\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eYes\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e82.6 (19)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e75.0 (15)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003e0.541\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNo\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e17.4 (4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e25.0 (5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eSkin-to-skin\\u0026nbsp;contact\\u0026nbsp;after\\u0026nbsp;birth\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eYes\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e91.3 (21)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e84.2 (16)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003e0.480\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNo\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e8.7 (2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e15.8 (3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"4\\\"\\u003eNote: p-value for chi-square test.\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab3\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 3\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eEvolution of breastfeeding practice according to group during the first six months of life.\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"10\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c6\\\" colnum=\\\"6\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c7\\\" colnum=\\\"7\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c8\\\" colnum=\\\"8\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c9\\\" colnum=\\\"9\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c10\\\" colnum=\\\"10\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003eTime\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"3\\\" nameend=\\\"c4\\\" namest=\\\"c2\\\"\\u003e \\u003cp\\u003eBreastfeeding\\u003c/p\\u003e \\u003cp\\u003ePercent\\u0026nbsp;(n)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"3\\\" nameend=\\\"c7\\\" namest=\\\"c5\\\"\\u003e \\u003cp\\u003eExclusive\\u0026nbsp;breastfeeding\\u0026nbsp;\\u003c/p\\u003e \\u003cp\\u003ePercent\\u0026nbsp;(n)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"3\\\" nameend=\\\"c10\\\" namest=\\\"c8\\\"\\u003e \\u003cp\\u003eBreastfeeding\\u0026nbsp;on\\u0026nbsp;demand\\u0026nbsp;\\u003c/p\\u003e \\u003cp\\u003ePercent\\u0026nbsp;(n)\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003ePlacebo\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eOmega-3\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003ep\\u0026nbsp;value\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003ePlacebo\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eOmega-3\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003ep\\u0026nbsp;value\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003ePlacebo\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eOmega-3\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c10\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003ep\\u0026nbsp;value\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e1st\\u0026nbsp;month\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eYes\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e100.0 (18)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e86.7 (13)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003e0.110\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e55.6 (10)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e76.9 (10)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003e0.220\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e88.9 (16)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e100.0 (13)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c10\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003e0.214\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNo\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.0 (0)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e13.3 (2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e44.4 (8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e23.1 (3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e11.1 (2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e0.0 (0)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e4th\\u0026nbsp;month\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eYes\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e87.5 (14)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e81.3 (13)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003e0.626\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e28.6 (4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e7.7 (1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003e0.163\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e78.6 (11)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e69.2 (9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c10\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003e0.580\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNo\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e12.5 (2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e18.8 (3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e71.4 (10)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e92.3 (12)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e21.4 (3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e30.8 (4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e6th\\u0026nbsp;month\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eYes\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e88.9 (16)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e68.8 (11)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003e0.050\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.0 (0)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.0 (0)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003e-\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e70.6 (12)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e63.6 (7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c10\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003e0.700\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNo\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e11.1 (2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e31.2 (5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e100.0 (17)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e100.0 (11)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e29.4 (5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e36.4 (4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"10\\\"\\u003eNote: p-value for chi-square test.\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003eThe comparison between groups showed no differences in the Developmental Milestones score at any time (p\\u0026thinsp;\\u0026gt;\\u0026thinsp;0.05) (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab4\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003e). When compared to the first month, the omega-3 group showed an increase in the Developmental Milestones score at the fourth and sixth month, in both intention-to-treat and per-protocol analysis. Such increase was not observed in the placebo group.\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab4\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 4\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eIntragroup and between groups comparison of child development and behavior score according to linear Generalized Estimating Equation (GEE) models.\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"6\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c6\\\" colnum=\\\"6\\\"\\u003e\\u003c/div\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003eItem\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003eTime\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c4\\\" namest=\\\"c3\\\"\\u003e \\u003cp\\u003ePer\\u0026nbsp;protocol\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c6\\\" namest=\\\"c5\\\"\\u003e \\u003cp\\u003eIntention-to-treat\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003ePlacebo\\u003c/b\\u003e\\u003c/p\\u003e \\u003cp\\u003e\\u003cb\\u003eMean\\u0026nbsp;(95%CI)\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eOmega-3\\u003c/b\\u003e\\u003c/p\\u003e \\u003cp\\u003e\\u003cb\\u003eMean\\u0026nbsp;(95%CI)\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003ePlacebo\\u003c/b\\u003e\\u003c/p\\u003e \\u003cp\\u003e\\u003cb\\u003eMean\\u0026nbsp;(95%CI)\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eOmega-3\\u003c/b\\u003e\\u003c/p\\u003e \\u003cp\\u003e\\u003cb\\u003eMean\\u0026nbsp;(95%CI)\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"2\\\" rowspan=\\\"3\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eDevelopmental\\u0026nbsp;milestones\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1st \\u0026nbsp;month\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e14.20 (12.49\\u0026ndash;15.91)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e12.78 (11.08\\u0026ndash;14.47)\\u003csup\\u003eA\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e14.11 (12.72\\u0026ndash;15.50)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e12.76 (11.21\\u0026ndash;14.32)\\u003csup\\u003eA\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e4th \\u0026nbsp;month\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e15.12 (13.85\\u0026ndash;16.40)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e15.73 (14.27\\u0026ndash;17.19)\\u003csup\\u003eB\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e15.42 (14.26\\u0026ndash;16.59)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e15.50 (14.26\\u0026ndash;16.72)\\u003csup\\u003eB\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e6th \\u0026nbsp;month\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e15.20 (13.87\\u0026ndash;16.53)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e16.00 (13.93\\u0026ndash;17.03)\\u003csup\\u003eB\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e15.36 (14.26\\u0026ndash;16.46)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e15.80 (13.94\\u0026ndash;17.64)\\u003csup\\u003eB\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"2\\\" rowspan=\\\"3\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eIrritability\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1st \\u0026nbsp;month\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1.79 (0.39\\u0026ndash;3 .19)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.54 (0.03\\u0026ndash;1.05)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.56 (0.46\\u0026ndash;2 .65)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.78 (0.11\\u0026ndash;1.44)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e4th \\u0026nbsp;month\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1.56 (0.72\\u0026ndash;2.41)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1.43 (0.52\\u0026ndash;2.35)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.82 (0.91\\u0026ndash;2.72)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e1.35 (0.48\\u0026ndash;2.21)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e6th \\u0026nbsp;month\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1.72 (0.56\\u0026ndash;2.87)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1.22 (0.69\\u0026ndash;1.75)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.78 (0.86\\u0026ndash;2.70)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e1.33 (0.75\\u0026ndash;1.90)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"2\\\" rowspan=\\\"3\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eInflexibility\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1st \\u0026nbsp;month\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2.89 (1.64\\u0026ndash;4.14)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1.56 (0.32\\u0026ndash;2.79)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e2.89 (1.90\\u0026ndash;3.88)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e1.60 (0.51\\u0026ndash;2.69)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e4th \\u0026nbsp;month\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2.04 (1.15\\u0026ndash;2.93)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1.63 (0.81\\u0026ndash;2.46)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.84 (0.99\\u0026ndash;2.69)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e1.81 (0.99\\u0026ndash;2.62)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e6th \\u0026nbsp;month\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1.66 (0.68\\u0026ndash;2.64)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1.12 (0.32\\u0026ndash;1.91)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.59 (0.51\\u0026ndash;1.93)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e1.22 (0.51\\u0026ndash;1.93)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"2\\\" rowspan=\\\"3\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eDificulty\\u0026nbsp;with\\u0026nbsp;routine\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1st \\u0026nbsp;month\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e3.40 (2.33\\u0026ndash;4.47)\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1.28 (0.10\\u0026ndash;2.46)\\u003csup\\u003eb\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e3.02 (2.06\\u0026ndash;3.97)\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e1.27 (0.24\\u0026ndash;2.30)\\u003csup\\u003eb\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e4th \\u0026nbsp;month\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e3.17 (2.15\\u0026ndash;4.19)\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1.45 (0.85\\u0026ndash;2.06)\\u003csup\\u003eb\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e2.86 (1.93\\u0026ndash;3.78)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e1.72 (0.92\\u0026ndash;2.52)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e6th \\u0026nbsp;month\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e3.63 (2.15\\u0026ndash;5.11)\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.84 (0.62\\u0026ndash;2.30)\\u003csup\\u003eb\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e3.09 (1.85\\u0026ndash;4.33)\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.96 (0.26\\u0026ndash;2.18)\\u003csup\\u003eb\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"6\\\"\\u003eCI: confidential interval. Note: Analysis adjusted by breastfeeding practice. Different uppercase letters indicate intragroup difference and different lowercase letters indicate difference between groups, according to the post-hoc test (Bonferroni).\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003eRegarding the Emotional/Behavioral Domain, no differences were found between groups for Irritability and Inflexibility scores at any time (p\\u0026thinsp;\\u0026gt;\\u0026thinsp;0.05). However, in per-protocol analysis, higher scores for Difficulty with Routine were observed in the placebo group when compared to omega-3 at all times, and at the first and sixth month in intention-to-treat analysis (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab4\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003e).\\u003c/p\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eThe antenatal supplementation with omega-3 did not promote differences in child development score when compared to the placebo group, however, the omega-3 group showed a significant increase in this score over time. Higher scores for Difficulty with Routine were observed in the placebo group, with no differences for Irritability and Inflexibility scores.\\u003c/p\\u003e \\u003cp\\u003eOur results are in line with the meta-analysis conducted by Middleton et al. [\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e]. According to the study, the antenatal omega-3 supplementation promoted very few differences in cognition and neurodevelopment [\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eA clinical trial conducted by Ramakrishnan et al. [\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e], used the Bayley Scales of Infant Development-II (BSID-II) to evaluate the effect of antenatal supplementation with algal DHA (400mg/day) on offspring development at 18 months of age. The results showed that the supplementation had no effects on child development, although DHA intake attenuated the association between home environment and psychomotor development, suggesting potential benefits for children living in home environments with reduced caregiver interactions and child stimulation [\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eSimilarly, Hurtado et al [\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e] recruited pregnant women to take 400 mL/day of a control dairy drink or a DHA\\u0026ndash;enriched dairy drink (400mg/day) and the BSID-II was used to evaluate the infant development at 12 months. All infants presented normal neurodevelopment for the age, with no significant differences between the groups, but the antenatal supplementation showed a major effect on DHA levels in plasma and erythrocyte membranes of mothers and infants [\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eIn contrast, the maternal plasma DHA concentration was associated with child development in a follow-up study conducted by Mulder et al [\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e]. The authors assessed 5\\u0026ndash;6 years children of mothers who received placebo or DHA (400mg/day) during pregnancy, using the second edition of Kaufman Assessment Battery for Children. Despite finding no differences between groups, maternal DHA plasma concentration was positively related to child performance on language and short-term memory [\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eThe role of omega-3 fatty acids in the development of the fetal central nervous system is well described [\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e], however, the effect of supplementation during pregnancy remains unclear in the literature. It is noteworthy that the studies available until now differ regarding the dosage and supplement adopted, sample characteristics, intervention length and development assessment tools, therefore, to systematize the results is very challenging.\\u003c/p\\u003e \\u003cp\\u003eDespite the lack of differences in the development score between the groups in our trial, the increase in this score over time, observed solely in the omega-3 group, might be an indicator of differences in long-term child development that should be investigated in future studies.\\u003c/p\\u003e \\u003cp\\u003eAlso, children of women who supplemented omega-3 during pregnancy presented less difficulty with routine in our study. Until now, no trials with omega-3 supplementation have been published using SWYC to assess infant development and behavior, which makes it difficult to compare our results with the available literature. However, it is known that alterations in child behavior are strong predictors of developmental deficits throughout childhood [\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eAdditionally, the Difficulty with Routine subscale comprises mostly questions about infant sleep, and previous studies on this subject have found a similar association [\\u003cspan additionalcitationids=\\\"CR22\\\" citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eAccording to a meta-analysis conducted by Dai et al. [\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e], the omega-3 supply during pregnancy may improve infants' sleep organization and maturity, especially reducing the occurrence of active sleep [\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e]. Such improvement was demonstrated by Judge et al. [\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e], in a trial that aimed to evaluate the effect of using a functional food containing 300mg of DHA during pregnancy, on infant sleep patterning. The authors found lower arousals in quiet and active sleep in the intervention group when compared to placebo, concluding that increased antenatal intake of DHA has a beneficial impact on infant\\u0026rsquo;s sleep organization, and therefore in their routine [\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eThe authors suggested that DHA supply during the intrauterine development may modify brain phospholipids and affect neural function, resulting in a more mature central nervous system, which is essential for a healthy sleep pattern [\\u003cspan additionalcitationids=\\\"CR22\\\" citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e]. Also, omega-3 intake during pregnancy is associated with an increased gestational length [\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e], due to the effect on prostaglandins balance involved in parturition, a fact that may impact the child neurodevelopment, and consequently improve their sleep behavior. Nevertheless, it is important to note that the studies mentioned above were conducted with newborns, and further investigations regarding the effect of antenatal omega-3 supplementation on sleep behavior of older infants are needed.\\u003c/p\\u003e \\u003cp\\u003eConsidering the results found in our study, the use of a higher DHA dosage does not seem to increase the effect of antenatal omega-3 supplementation on child development and behavior. The use of 1440mg/day of DHA did not promote stronger effects when compared to studies that used 300-400mg/day of DHA, as presented above. The mean dietary intake of omega-3 of our sample was above the Adequate Intake (1.4g/day), proposed by Institute of Medicine [\\u003cspan citationid=\\\"CR24\\\" class=\\\"CitationRef\\\"\\u003e24\\u003c/span\\u003e], which reinforces the hypothesis of the supplementation being more effective for populations with omega-3 deficiency. In addition, our sample consisted of healthy pregnant women, and their offspring consequently had a low risk of inadequate neurodevelopment. However, the increase on development score over time and the lower difficult with routine, observed in the intervention group despite the breastfeeding practice, suggests that the effect of omega-3 on child development and behavior should be further investigated.\\u003c/p\\u003e \\u003cp\\u003eThe lack of omega-3 plasma levels assessment to evaluate compliance and to explain the results of the effect is a limitation of this trial. Despite that, the relevance of the present study is highlighted, considering the investigation of the effect of a higher DHA dosage during pregnancy on child development and behavior. Also, the association of omega-3 supplementation with the sleep behavior (included in the routine) of older infants is an unprecedented result that should be further explored in the future.\\u003c/p\\u003e \\u003cp\\u003eIn conclusion, the antenatal supplementation with a DHA dosage of 1440mg/day did not promote significant differences between groups for child development, but the omega-3 group showed an increase in this score over time. The placebo group had greater difficulty with routine than the omega-3 group, indicating a beneficial effect of antenatal supplementation on child behavior, more specifically in sleep behavior, and this association should be further explored using specific tools to assess children's sleep patterns.\\u003c/p\\u003e\"},{\"header\":\"Abbreviations\",\"content\":\"\\u003cul\\u003e\\n \\u003cli\\u003eCONSORT: Consolidated Standards of Reporting Trials\\u003c/li\\u003e\\n \\u003cli\\u003eDHA: docosahexaenoic acid\\u003c/li\\u003e\\n \\u003cli\\u003eEPA: eicosapentaenoic acid\\u003c/li\\u003e\\n \\u003cli\\u003eGEE: Generalized Estimating Equations\\u0026nbsp;\\u003c/li\\u003e\\n \\u003cli\\u003eIOM: Institute of Medicine\\u003c/li\\u003e\\n \\u003cli\\u003eReBec: Brazilian Registry of Clinical Trials\\u003c/li\\u003e\\n \\u003cli\\u003eSWYC: Survey of Well-being of Young Children\\u0026nbsp;\\u003c/li\\u003e\\n\\u003c/ul\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eFunding:\\u0026nbsp;\\u003c/strong\\u003eThe current research was supported by Conselho Nacional de Desenvolvimento Cient\\u0026iacute;fico e Tecnol\\u0026oacute;gico (productivity scholarship - grant number 406644/2016-0). The Conselho Nacional de Desenvolvimento Cient\\u0026iacute;fico e Tecnol\\u0026oacute;gico had no role in the design, analysis or writing of this article.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConflicts of interest/Competing interests:\\u0026nbsp;\\u003c/strong\\u003eThe\\u0026nbsp;authors\\u0026nbsp;declare\\u0026nbsp;that\\u0026nbsp;they\\u0026nbsp;have\\u0026nbsp;no\\u0026nbsp;conflict\\u0026nbsp;of\\u0026nbsp;interest.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAvailability of data and material:\\u0026nbsp;\\u003c/strong\\u003eDue to the nature of this research, participants of this study did not agree for their data to be shared publicly, so supporting data is not available.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCode availability:\\u0026nbsp;\\u003c/strong\\u003eNot applicable.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthors\\u0026apos; contributions:\\u0026nbsp;\\u003c/strong\\u003eSousa TM participated in the project design, bibliographic review, data collection, statistical analysis and article writing. Santos LC acted in the project design and review of the article.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eEthics approval:\\u0026nbsp;\\u003c/strong\\u003eThis study was approved by the Research Ethics Committee under number 87705018.0.0000.5149 and registered by the Brazilian Registry of Clinical Trials (ReBec) under number U1111-1215-7952 (http://www.ensaiosclinicos.gov.br/rg / RBR-6gbzw6/).\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConsent to participate:\\u0026nbsp;\\u003c/strong\\u003eAll participants signed a consent form after receiving the necessary information and expressed spontaneous interest to participate in the trial.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConsent for publication:\\u0026nbsp;\\u003c/strong\\u003eNot applicable.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eChristian P, Mullany LC, Hurley KM, Katz J, Black RE (2015) Nutrition and maternal, neonatal, and child health. 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Available from: \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://www.floatinghospital.org/The-Survey-of-Wellbeing-of-Young-Children/Translations.aspx\\u003c/span\\u003e\\u003cspan address=\\\"https://www.floatinghospital.org/The-Survey-of-Wellbeing-of-Young-Children/Translations.aspx\\\" targettype=\\\"URL\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMoreira RS, Magalh\\u0026atilde;es RC, Siqueira CM, Alves CRL (2019) Adapta\\u0026ccedil;\\u0026atilde;o Transcultural do instrumento de vigil\\u0026acirc;ncia do desenvolvimento infantil \\u0026ldquo;Survey of Wellbeing of Young Children (SWYC)\\u0026rdquo; no contexto brasileiro. J Hum Growth Dev 29:28\\u0026ndash;38. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.7322/jhgd.145001\\u003c/span\\u003e\\u003cspan address=\\\"10.7322/jhgd.145001\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eHulley SB, Cummings SR, Browner WS et al (2013) Designing clinical research. Philadelphia: Lippincott Williams \\u0026amp; Wilkins; 367p\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eDunstan JA, Simmer K, Dixon G, Prescott SL (2008) Cognitive assessment of children at age 2(1/2) years after maternal fish oil supplementation in pregnancy: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 93:F45\\u0026ndash;50. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1136/adc.2006.099085\\u003c/span\\u003e\\u003cspan address=\\\"10.1136/adc.2006.099085\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eVaz JDS, Farias DR, Adegboye ARA et al (2017) Omega-3 supplementation from pregnancy to postpartum to prevent depressive symptoms: a randomized placebo-controlled trial. BMC Pregnancy Childbirth 17:180. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1186/s12884-017-1365-x\\u003c/span\\u003e\\u003cspan address=\\\"10.1186/s12884-017-1365-x\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eCheruku SR, Montgomery-Downs HE, Farkas SL, Thoman EB, Lammi-Keefe CJ (2002) Higher maternal plasma docosahexaenoic acid during pregnancy is associated with more mature neonatal sleep-state patterning. Am J Clin Nutr 76:608\\u0026ndash;613. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1093/ajcn/76.3.608\\u003c/span\\u003e\\u003cspan address=\\\"10.1093/ajcn/76.3.608\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eJudge MP, Cong X, Harel O, Courville AB, Lammi-Keefe CJ (2012) Maternal consumption of a DHA-containing functional food benefits infant sleep patterning: an early neurodevelopmental measure. Early Hum Dev 88:531\\u0026ndash;537. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1016/j.earlhumdev.2012.12.016\\u003c/span\\u003e\\u003cspan address=\\\"10.1016/j.earlhumdev.2012.12.016\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eDai Y, Liu J Omega-3 long-chain polyunsaturated fatty acid and sleep: a systematic review and meta-analysis of randomized controlled trials and longitudinal studies.Nutr Rev, 31:nuaa103. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1093/nutrit/nuaa103\\u003c/span\\u003e\\u003cspan address=\\\"10.1093/nutrit/nuaa103\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eInstitute of Medicine (IOM) (2005) Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). The National Academies Press, Washington, DC, p 1357\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"omega-3, pregnancy, maternal nutrition, child development, child behavior, randomized controlled trial \",\"lastPublishedDoi\":\"10.21203/rs.3.rs-1459246/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-1459246/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003ch2\\u003ePurpose\\u003c/h2\\u003e \\u003cp\\u003eThis randomized double-blind placebo-controlled trial aimed to evaluate the effect of antenatal omega-3 supplementation on child development and behavior during the first six months of life.\\u003c/p\\u003e\\u003ch2\\u003eMethods\\u003c/h2\\u003e \\u003cp\\u003eParticipants with gestational age between 22\\u0026ndash;24 weeks were randomized in placebo (olive oil; n\\u0026thinsp;=\\u0026thinsp;30) or omega-3 (fish oil; n\\u0026thinsp;=\\u0026thinsp;30) groups and supplemented until childbirth. Fish oil capsules provided 1440mg/day of DHA. Child development was assessed using the Survey of Well-being of Young Children in the first, fourth and sixth month of life. Intention-to-treat and per-protocol analyses were performed using Generalized Estimating Equations.\\u003c/p\\u003e\\u003ch2\\u003eResults\\u003c/h2\\u003e \\u003cp\\u003eThe comparison between groups showed no differences in the Developmental Milestones score at any time, but when compared to the first month, the omega-3 group showed an increase at the fourth and sixth month. Such increase was not observed in the placebo group. No differences were found between groups for Irritability and Inflexibility scores, however, higher scores for Difficulty with Routine were observed in the placebo group when compared to omega-3 at first, fourth and sixth month.\\u003c/p\\u003e\\u003ch2\\u003eConclusion\\u003c/h2\\u003e \\u003cp\\u003eThere were no differences between groups for child development, but the omega-3 group showed an increase in this score over time. The placebo group had greater difficulty with routine than the omega-3 group, indicating a beneficial effect of antenatal supplementation on child behavior.\\u003c/p\\u003e\\u003ch2\\u003eTrial registration:\\u003c/h2\\u003e \\u003cp\\u003eReBec U1111-1215-7952 (June 16th 2018).\\u003c/p\\u003e\",\"manuscriptTitle\":\"Does antenatal supplementation with omega-3 affect child development and behavior during the first six months of life? 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