Abstract

This paper aims to identify the association between overweight and the nutritional composition of human milk. A systematic review was performed by searching on PubMed, Virtual Health Library (BVS), EMBASE, Web of Science, and SCOPUS databases, from May to June 2018, using keywords “Human Milk” AND “Overweight” OR “Obesity” OR “Body Mass Index”. The bibliographic search returned 435 papers after the duplicates were removed. Of this total, 12 papers were selected for abstract reading, and nine works were incorporated into this systematic review. Eight papers showed that overweight increased the total concentration of lipids or glucose or macronutrient fractions, and only one study found no association between overweight and the nutritional composition of human milk. Most works selected evidenced that obesity changed the total concentration of lipids and their fractions. Thus, we recommend that women’s weight and height be evaluated in the pregestational visit to identify and monitor nutritional deviations, contributing to weight adequacy before pregnancy and assisting in the production of milk with adequate nutritional composition.

Key words
Overweight; Human milk; Nutritional Composition; Systematic Review

Introduction

Human milk is a complex biological fluid containing adequate amounts of essential components for children’s health, growth, and development, such as nutrients¹1 Gidrewicz DA, Fenton TR. A systematic review and meta-analysis of the nutrient content of preterm and term breast milk. BMC Pediatr 2014; 14:216., immunological and trophic factors²2 Fujimori M, França EL, Fiorin V, Morais TC, Honorio-França AC, Abreu LC. Changes in the biochemical and immunological components of serum and colostrum of overweight and obese mothers. BMC Pregnancy Childbirth 2015; 15:166-174^,33 Young BE, Patinkin Z, Palmer C, de la Houssaye B, Barbour LA, Hernandez T, Friedman JE, Krebs NF. Human Milk Insulin is Related to Maternal Plasma Insulin and BMI - But other Components of Human Milk do not Differ by BMI. Eur J Clin Nutr 2017; 71(9):1094-1100., hormones⁴4 De Luca A, Frasquet-Darrieux M, Gaud MA, Christin P, Boquien CY, Millet C, Herviou M, Darmaun D, Robins RJ, In-grand P, Hankard R. Higher Leptin but Not Human Milk Macronutrient Concentration Distinguishes Normal-Weight from Obese Mothers at 1-Month Postpartum. PLoS One 2016; 11(12):e0168568^,55 Kugananthan S, Gridneva Z, Ching TL, Hepworth AR, Mark PJ, Kakulas F, Geddes DT. Associations between Maternal Body Composition and Appetite Hormones and Macronutrients in Human Milk. Nutrients. 2017; 9:252., and essential bacteria for the modulation of the newborn’s intestinal microbiota⁶6 Garcia-Mantrana I, Collado MC. Obesity and overweight: Impact on maternal and milk microbiome and their role for infant health and nutrition. Mol Nutr Food Res 2016; 60(8):1865-1875.. Breastfeeding provides economic and environmental advantages to the health of children, women, and society⁷7 Rollins NC, Lutter CK, Bhandari N, Hajeebhoy N, Horton S, Martines JC, Piwoz EG, Richter LM, Victora CG. Breast-feeding in the 21st century: epidemiology, mechanisms, and lifelong effect. Lancet 2016; 387(10017):475-490. in the short and long term.

Exclusive breastfeeding is recommended in the first six months of life as the only source of nutrients, followed by the introduction of food, however, still based on breastfeeding, which must be maintained for two years or more⁸8 World Health Organization (WHO). Guideline: protecting, promoting and supporting breastfeeding in facilities providing maternity and newborn services. Genebra: WHO; 2017..

Several studies suggest that the nutritional composition of human milk can be modified by different factors such as maternal age⁹9 Alvarez AT, Cluet RI, Rossell PM, Valbuena E, Ugueto E, Acosta L. Macronutrientes en la leche madura de madres adolescentes y adultas. ALAN 2013; 63(1):46-52., lifestyle, maternal food intake¹⁰10 Costa AGV, Sabarense CM. Modulação e composição de ácidos graxos do leite materno. Rev Nutr 2010; 23(3):445-457., lactation stage, type of delivery¹¹11 Cabrera-Rubio R, Collado MC, Laitinen K, Salminen S, Isolauri E, Mira A. The human milk microbiome changes over lactation and is shaped by maternal weight and mode of delivery. Am J Clin Nutr 2012; 96(3):544-551., and maternal disorders (arterial hypertension, and diabetes mellitus)¹²12 Massmann PF, França EL, Souza EG, Souza MS, Brune MFSS, Honorio-França AC. Maternal hypertension induces alterations in immunological factors of colostrum and human milk. Front Life Sci 2013; 7:155-163.^,1313 Dritsakou K, Liosis G, Valsami G, Polychronopoulos E, Skouroliakou M. The impact of maternal and neonatal associated factors on human milk's macronutrients and energy. J Matern Fetal Neonatal Med 2016; 2:1-7..

Besides these factors, women’s overweight has been considered a condition that can modify the nutritional composition of human milk¹⁴14 Fujimori M. Relação do sobrepeso e obesidade materna sobre parâmetros imunológicos, bioquímicos e hormonais do sangue e colostro humano [tese]. São Paulo: Universidade de São Paulo; 2016.. However, there is still no consensus among the studies that aimed to evaluate this association²2 Fujimori M, França EL, Fiorin V, Morais TC, Honorio-França AC, Abreu LC. Changes in the biochemical and immunological components of serum and colostrum of overweight and obese mothers. BMC Pregnancy Childbirth 2015; 15:166-174^,33 Young BE, Patinkin Z, Palmer C, de la Houssaye B, Barbour LA, Hernandez T, Friedman JE, Krebs NF. Human Milk Insulin is Related to Maternal Plasma Insulin and BMI - But other Components of Human Milk do not Differ by BMI. Eur J Clin Nutr 2017; 71(9):1094-1100..

Therefore, this systematic review aims to identify the association between overweight and the nutritional composition of human milk.

Methods

A systematic review of the literature was carried out, which consisted of searching for scientific papers that evaluated the association between overweight and the nutritional composition of human milk. The works were selected from PubMed, Virtual Health Library (BVS), EMBASE, Web of Science, and SCOPUS databases.

The search strategy employed descriptors “Human Milk” AND “Obesity” OR “Overweight” OR “Body Mass Index”. The search for papers was carried out from May 18 to June 4, 2018, by two researchers independently. The reference lists of the selected papers were also examined to identify eligible publications.

All potentially eligible publications were selected for full-text reading. Data extraction and final classification for inclusion in the review were carried out independently, and results were compared. Any disagreement was resolved by consensus between the two reviewers.

The papers were considered on the following inclusion criteria: observational studies that assessed the association between overweight and the nutritional composition of human milk (carbohydrate or fat or protein or fractions of macronutrients or energy).

The publication period was not limited, and the language was not restricted. Studies with rats, different outcomes than those established for this review, which evaluated changes in the microbiota, hormonal composition, and papers with mothers of preterm babies or with any type of malformation were excluded.

The following was recorded in the data extraction table: year of publication, type of study, country of origin, sample size, losses, age of participants, ethnic groups, anthropometric assessment indicators, eligibility criteria, exclusion criteria, analyzed nutritional content, the method used to evaluate the nutritional composition of human milk, milk evaluation period, type of milk evaluated (colostrum, transitional, mature), confounding factors controlled in the analysis, and main results.

A checklist based on the Preferred Reporting Items for Systematic Reviews (PRISMA) guideline was used, which helps authors improve the reports of systematic reviews. The summary of the stages of the selection process of the papers in this systematic review is provided in the flowchart below (Figure 1).

Results

According to the established strategy, the bibliographic search returned 435 papers after excluding duplicates. Of this total, 12 works were selected for abstract reading. In the end, nine papers were selected for this systematic review. No works were added from the reference lists of the papers read.

Table 1 shows the main characteristics of the nine papers included in the ascending order of the study’s publication period. While the publication period was not defined, the selected works were published from 2005 to 2017. Six studies were cross-sectional, and three were cohort. One was carried out in Asia, two in South America, four in Europe, and two in North America.

Regarding the anthropometric assessment of women, only one study measured weight and height to calculate body mass index (BMI), two studies used self-reported data, and six did not inform the method used to calculate BMI. Six studies assessed BMI in the pregestational period, and the others did not specify when the anthropometric assessment was performed.

Table 2 presents the main characteristics of milk, controlled confounding factors, and main results. As for the type of human milk analyzed (colostrum, mature, or transitional), one study looked only at colostrum, six analyzed only mature milk, and two evaluated different lactation stages. There was no standard method for evaluating the composition of macronutrients. A standard method was only used for analyzing fatty acids.

Regarding the confounding factors controlled in the analysis, three papers made adjustments to the analyses.

Concerning the association between overweight and the nutritional content of human milk, of the nine selected papers, five found that women’s overweight altered the concentration of lipid fractions (reduced amount of omega 3¹⁶16 Mäkelä J, Linderborg K, Niinikoski H, Yang B, Lagström H. Breast milk fatty acid composition differs between over-weight and normal weight women: the STEPS Study. Eur J Nutr 2013; 52(2):727-735.

17 Linderborg KM, Kalpio M, Mäkelä J, Niinikoski H, Kallio HP, Lagström H. Tandem mass spectrometric analysis of human milk triacylglycerols from normal weight and overweight mothers on different diets. Food Chem 2014; 146:583-590.

18 Panagos PG, Vishwanathan R, Penfield-Cyr A, Matthan NR, Shivappa N, Wirth MD, Hebert JR, Sen S. Breastmilk from obese mothers has pro-inflammatory properties and decreased neuroprotective factors. J Perinatol 2016; 36(4):284-290.^-1919 Storck Lindholm E, Strandvik B, Altman D, Möller A, Palme Kilander C. Different fatty acid pattern in breast milk of obese compared to normal-weight mothers. Prostaglandins Leukot Essent Fatty Acids 2013; 88(3):211-217., and increased amount of omega 6¹⁵15 Marín MC, Sanjurjo A, Rodrigo MA, Alaniz MJ. Long-chain polyunsaturated fatty acids in breast milk in La Plata, Argentina: relationship with maternal nutritional status. Prostaglandins Leukot Essent Fatty Acids 2005; 73(5):355-360.^,1616 Mäkelä J, Linderborg K, Niinikoski H, Yang B, Lagström H. Breast milk fatty acid composition differs between over-weight and normal weight women: the STEPS Study. Eur J Nutr 2013; 52(2):727-735.^,1919 Storck Lindholm E, Strandvik B, Altman D, Möller A, Palme Kilander C. Different fatty acid pattern in breast milk of obese compared to normal-weight mothers. Prostaglandins Leukot Essent Fatty Acids 2013; 88(3):211-217. and triglycerides¹⁷17 Linderborg KM, Kalpio M, Mäkelä J, Niinikoski H, Kallio HP, Lagström H. Tandem mass spectrometric analysis of human milk triacylglycerols from normal weight and overweight mothers on different diets. Food Chem 2014; 146:583-590.).

Besides the alteration caused by overweight in the lipid fractions, an increase in total fat content was observed in three studies²2 Fujimori M, França EL, Fiorin V, Morais TC, Honorio-França AC, Abreu LC. Changes in the biochemical and immunological components of serum and colostrum of overweight and obese mothers. BMC Pregnancy Childbirth 2015; 15:166-174^,1515 Marín MC, Sanjurjo A, Rodrigo MA, Alaniz MJ. Long-chain polyunsaturated fatty acids in breast milk in La Plata, Argentina: relationship with maternal nutritional status. Prostaglandins Leukot Essent Fatty Acids 2005; 73(5):355-360.^,2020 Hahn WH, Jeong T, Park S, Song S, Kang NM. Content fat and calorie of human milk is affected by interactions between maternal age and body mass index. J Matern Fetal Neonatal Med 2018; 31(10):1385-1388.. As for the protein fraction, only one study found an increase of around 20% in the concentration of branched-chain amino acids in the milk of obese women²¹21 De Luca A, Hankard R, Alexandre-Gouabau MC, Ferchaud-Roucher V, Darmaun D, Boquien CY. Higher concentrations of branched-chain amino acids in breast milk of obese mothers. Nutrition 2016; 31:1295-1298.. Regarding the carbohydrate content, one study observed 2.5 times higher concentration of glucose in the colostrum of obese women compared to eutrophic women²2 Fujimori M, França EL, Fiorin V, Morais TC, Honorio-França AC, Abreu LC. Changes in the biochemical and immunological components of serum and colostrum of overweight and obese mothers. BMC Pregnancy Childbirth 2015; 15:166-174. Only one study showed no significant association between human milk macronutrients and women’s body composition³3 Young BE, Patinkin Z, Palmer C, de la Houssaye B, Barbour LA, Hernandez T, Friedman JE, Krebs NF. Human Milk Insulin is Related to Maternal Plasma Insulin and BMI - But other Components of Human Milk do not Differ by BMI. Eur J Clin Nutr 2017; 71(9):1094-1100..

Discussion

Overweight is a global problem in both developed and developing countries. This issue must be addressed at all stages of life, particularly in women in the reproductive²²22 Correia LL, Silveira DMJ, Silva AC, Campos JS, Machado MMT, Rocha HAL, Cunha AJLA, Lindsay AC. Prevalência e determinantes de obesidade e sobrepeso em mulheres em idade reprodutiva residentes na região semiárida do Brasil. Cien Saude Colet 2011; 16(1):133-145. and gestational²³23 Heerman WJ, Bian A, Shintani A, Barkin SL. Interaction between maternal prepregnancy body mass index and gestational weight gain shapes infant growth. Acad Pediatr 2014; 14(5):463-470. periods due to the several negative consequences of this condition to the mother-child dyad²³23 Heerman WJ, Bian A, Shintani A, Barkin SL. Interaction between maternal prepregnancy body mass index and gestational weight gain shapes infant growth. Acad Pediatr 2014; 14(5):463-470..

Some studies have evaluated the possible impact of overweight on the nutritional composition of human milk²2 Fujimori M, França EL, Fiorin V, Morais TC, Honorio-França AC, Abreu LC. Changes in the biochemical and immunological components of serum and colostrum of overweight and obese mothers. BMC Pregnancy Childbirth 2015; 15:166-174^,2020 Hahn WH, Jeong T, Park S, Song S, Kang NM. Content fat and calorie of human milk is affected by interactions between maternal age and body mass index. J Matern Fetal Neonatal Med 2018; 31(10):1385-1388.. However, their results diverge mainly regarding the nutritional content evaluated, the methods to assess the nutritional composition of milk, the type of milk analyzed (colostrum, transitional, and mature), and the control of confounding factors in the analysis.

Regarding lipids, similar results were observed regarding the association between the women’s overweight and fatty acids based on gas chromatography in the studies conducted by Marin et al.¹⁵15 Marín MC, Sanjurjo A, Rodrigo MA, Alaniz MJ. Long-chain polyunsaturated fatty acids in breast milk in La Plata, Argentina: relationship with maternal nutritional status. Prostaglandins Leukot Essent Fatty Acids 2005; 73(5):355-360., Mäkelä et al.¹⁶16 Mäkelä J, Linderborg K, Niinikoski H, Yang B, Lagström H. Breast milk fatty acid composition differs between over-weight and normal weight women: the STEPS Study. Eur J Nutr 2013; 52(2):727-735., Linderborg et al.¹⁷17 Linderborg KM, Kalpio M, Mäkelä J, Niinikoski H, Kallio HP, Lagström H. Tandem mass spectrometric analysis of human milk triacylglycerols from normal weight and overweight mothers on different diets. Food Chem 2014; 146:583-590., and Storck Lindholm et al.¹⁹19 Storck Lindholm E, Strandvik B, Altman D, Möller A, Palme Kilander C. Different fatty acid pattern in breast milk of obese compared to normal-weight mothers. Prostaglandins Leukot Essent Fatty Acids 2013; 88(3):211-217.. These studies observed an increased proportion of omega 6 compared to omega 3 and reduced omega 3 in overweight women’s human milk. Panagos et al.¹⁸18 Panagos PG, Vishwanathan R, Penfield-Cyr A, Matthan NR, Shivappa N, Wirth MD, Hebert JR, Sen S. Breastmilk from obese mothers has pro-inflammatory properties and decreased neuroprotective factors. J Perinatol 2016; 36(4):284-290. carried out a cohort study to assess newborns’ body composition and a cross-sectional analysis to obtain the nutritional composition of human milk of 42 women at two months of the child’s life. The authors did not identify any difference in the amount of saturated, monounsaturated, and polyunsaturated fatty acids of the omega 6 type in the mature milk of obese women using the modified Folch method. However, this paper’s result was similar to the others cited concerning the lower content of omega 3 in the mature milk of these women. These findings corroborate several studies that have already demonstrated that being overweight generates an inflammatory state marked by an increased amount of omega 6 and a reduced amount of omega 3¹⁶16 Mäkelä J, Linderborg K, Niinikoski H, Yang B, Lagström H. Breast milk fatty acid composition differs between over-weight and normal weight women: the STEPS Study. Eur J Nutr 2013; 52(2):727-735.^,1717 Linderborg KM, Kalpio M, Mäkelä J, Niinikoski H, Kallio HP, Lagström H. Tandem mass spectrometric analysis of human milk triacylglycerols from normal weight and overweight mothers on different diets. Food Chem 2014; 146:583-590.^,1919 Storck Lindholm E, Strandvik B, Altman D, Möller A, Palme Kilander C. Different fatty acid pattern in breast milk of obese compared to normal-weight mothers. Prostaglandins Leukot Essent Fatty Acids 2013; 88(3):211-217..

Unlike the studies mentioned above, the studies conducted by Fujimori et al.²2 Fujimori M, França EL, Fiorin V, Morais TC, Honorio-França AC, Abreu LC. Changes in the biochemical and immunological components of serum and colostrum of overweight and obese mothers. BMC Pregnancy Childbirth 2015; 15:166-174 and Young et al.³3 Young BE, Patinkin Z, Palmer C, de la Houssaye B, Barbour LA, Hernandez T, Friedman JE, Krebs NF. Human Milk Insulin is Related to Maternal Plasma Insulin and BMI - But other Components of Human Milk do not Differ by BMI. Eur J Clin Nutr 2017; 71(9):1094-1100. did not observe statistically significant differences in the concentration of lipids in the milk of overweight women compared to eutrophic women. The study by Fujimori et al.²2 Fujimori M, França EL, Fiorin V, Morais TC, Honorio-França AC, Abreu LC. Changes in the biochemical and immunological components of serum and colostrum of overweight and obese mothers. BMC Pregnancy Childbirth 2015; 15:166-174 differed from the others concerning the type of lipids evaluated (triglycerides), the method used to evaluate the composition of human milk (enzymatic colorimetric), and the type of milk (colostrum). On the other hand, the cohort conducted by Young et al.³3 Young BE, Patinkin Z, Palmer C, de la Houssaye B, Barbour LA, Hernandez T, Friedman JE, Krebs NF. Human Milk Insulin is Related to Maternal Plasma Insulin and BMI - But other Components of Human Milk do not Differ by BMI. Eur J Clin Nutr 2017; 71(9):1094-1100. analyzed the concentration of fat in the transitional and mature milk using the creamatocrit. However, there was no complete milk extraction during the collection, which consequently may have interfered with the fat concentration, as there is a difference in the number of lipids in anterior and posterior milk²⁴24 Ballard O, Morrow AL. Human milk composition, nutrients and bioactive factors. Pediatr Clin N Am 2013; 60:49-74..

In a cross-sectional study with 80 puerperae, Hahn et al.²⁰20 Hahn WH, Jeong T, Park S, Song S, Kang NM. Content fat and calorie of human milk is affected by interactions between maternal age and body mass index. J Matern Fetal Neonatal Med 2018; 31(10):1385-1388. analyzed the concentration of lipids in mature milk using Miris, a piece of equipment already validated for the analysis of human milk²⁵25 García-Lara NR, Escuder-Vieco D, García-Algar O, De la Cruz J, Lora D, Pallás-Alonso C. Effect of Freezing Time on Macronutrients and Energy Content of Breastmilk. Breastfeed Med 2012; 7:295-301.. The authors observed that maternal age and nutritional status changed the composition of lipids in human milk. The authors affirm that overweight women aged 30 years had a higher lipid concentration than eutrophic women of the same age, but did not explain their findings. Argov-Argaman et al.²⁶26 Argov-Argaman N, Mandel D, Lubetzky R, Kedem MH, Cohen BH, Berkovitz Z, Reifen R. Human Milk Fatty acids composition is affected by maternal age. J Matern Fetal Neonatal Med 2017; 30(1):34-37. aimed to assess whether maternal age was associated with changes in fatty acid concentrations in human milk. The authors observed that the lipid content was higher among women over 37 years of age. Lubetzky et al.²⁷27 Lubetzky R, Sever O, Mimouni FB, Mandel D. Human Milk Macronutrients Content: Effect of Advanced Maternal Age. Breastfeed Med 2015; 10(9):433-406. observed that the lipid concentration in transitional milk is higher in women over 35 years of age. However, both highlighted that the mechanism and biological plausibility for such findings are unknown.

Lactose was the most discussed disaccharide among studies, possibly because it is the most significant glycosidic fraction in human milk³3 Young BE, Patinkin Z, Palmer C, de la Houssaye B, Barbour LA, Hernandez T, Friedman JE, Krebs NF. Human Milk Insulin is Related to Maternal Plasma Insulin and BMI - But other Components of Human Milk do not Differ by BMI. Eur J Clin Nutr 2017; 71(9):1094-1100.^,2020 Hahn WH, Jeong T, Park S, Song S, Kang NM. Content fat and calorie of human milk is affected by interactions between maternal age and body mass index. J Matern Fetal Neonatal Med 2018; 31(10):1385-1388.. However, Fujimori et al.²2 Fujimori M, França EL, Fiorin V, Morais TC, Honorio-França AC, Abreu LC. Changes in the biochemical and immunological components of serum and colostrum of overweight and obese mothers. BMC Pregnancy Childbirth 2015; 15:166-174 was the only study that assessed the concentration of glucose in colostrum. The authors observed that the amount of this monosaccharide was higher among obese puerperae. However, the authors did not elucidate the findings. The other studies did not observe differences in the number of carbohydrates in the human milk of overweight women³3 Young BE, Patinkin Z, Palmer C, de la Houssaye B, Barbour LA, Hernandez T, Friedman JE, Krebs NF. Human Milk Insulin is Related to Maternal Plasma Insulin and BMI - But other Components of Human Milk do not Differ by BMI. Eur J Clin Nutr 2017; 71(9):1094-1100.^,1818 Panagos PG, Vishwanathan R, Penfield-Cyr A, Matthan NR, Shivappa N, Wirth MD, Hebert JR, Sen S. Breastmilk from obese mothers has pro-inflammatory properties and decreased neuroprotective factors. J Perinatol 2016; 36(4):284-290.^,2020 Hahn WH, Jeong T, Park S, Song S, Kang NM. Content fat and calorie of human milk is affected by interactions between maternal age and body mass index. J Matern Fetal Neonatal Med 2018; 31(10):1385-1388..

Regarding human milk protein, it was observed that women’s overweight did not change the amount of this macronutrient³3 Young BE, Patinkin Z, Palmer C, de la Houssaye B, Barbour LA, Hernandez T, Friedman JE, Krebs NF. Human Milk Insulin is Related to Maternal Plasma Insulin and BMI - But other Components of Human Milk do not Differ by BMI. Eur J Clin Nutr 2017; 71(9):1094-1100.^,1818 Panagos PG, Vishwanathan R, Penfield-Cyr A, Matthan NR, Shivappa N, Wirth MD, Hebert JR, Sen S. Breastmilk from obese mothers has pro-inflammatory properties and decreased neuroprotective factors. J Perinatol 2016; 36(4):284-290.^,2020 Hahn WH, Jeong T, Park S, Song S, Kang NM. Content fat and calorie of human milk is affected by interactions between maternal age and body mass index. J Matern Fetal Neonatal Med 2018; 31(10):1385-1388.. However, results are different when amino acids are evaluated. De Luca et al.²¹21 De Luca A, Hankard R, Alexandre-Gouabau MC, Ferchaud-Roucher V, Darmaun D, Boquien CY. Higher concentrations of branched-chain amino acids in breast milk of obese mothers. Nutrition 2016; 31:1295-1298. observed that the mature milk of obese women contained 20% more branched-chain amino acids and 30% more tyrosine than eutrophic human milk. Noteworthy is that the increased amount of branched-chain amino acids can modify insulin secretion and sensitivity, resulting in adverse outcomes for women and babies²⁸28 McCormack SE, Shaham O, McCarthy MA, Deik AA, Wang TJ, Gerszten RE, Clish CB, Mootha VK, Grinspoon SK, Fleischman A. Circulating branched-chain amino acid concentrations are associated with obesity and future insulin resistance in children and adolescents. Pediatr Obes 2013; 8(1):52-61..

Concerning the anthropometric assessment of women to perform the nutritional diagnosis, most of the selected papers used pregestational weight and height to calculate BMI. While this measure is used to carry out the nutritional diagnosis in all life stages²⁹29 Brasil. Ministério da Saúde (MS). Vigilância alimentar e nutricional - SISVAN: orientações básicas para a coleta, processamento, análise de dados e informação em serviços de saúde. Brasília: MS; 2004., this index is knowingly not suitable for quantifying body fat⁵5 Kugananthan S, Gridneva Z, Ching TL, Hepworth AR, Mark PJ, Kakulas F, Geddes DT. Associations between Maternal Body Composition and Appetite Hormones and Macronutrients in Human Milk. Nutrients. 2017; 9:252.. Thus, it is vital to assess body composition³⁰30 Marshall NE, Murphy EJ, King JC,Haas KE, Lim JY, Wiedrick J, Thornburg KL, Purnell JQ. Comparison of multiple methods to measure maternal fat mass in late gestation. Am J Clin Nutr 2016; 103(4):1055-1063. and calculate BMI to diagnose the nutritional status.

Regarding the control of potential confounding variables, except for the study conducted by Fujimori et al.²2 Fujimori M, França EL, Fiorin V, Morais TC, Honorio-França AC, Abreu LC. Changes in the biochemical and immunological components of serum and colostrum of overweight and obese mothers. BMC Pregnancy Childbirth 2015; 15:166-174, Mäkelä et al.¹⁶16 Mäkelä J, Linderborg K, Niinikoski H, Yang B, Lagström H. Breast milk fatty acid composition differs between over-weight and normal weight women: the STEPS Study. Eur J Nutr 2013; 52(2):727-735., and Hahn et al.²⁰20 Hahn WH, Jeong T, Park S, Song S, Kang NM. Content fat and calorie of human milk is affected by interactions between maternal age and body mass index. J Matern Fetal Neonatal Med 2018; 31(10):1385-1388., the other selected studies did not focus on the control of potential factors associated with the nutritional composition of human milk. This data must be taken into account since this outcome can be modified by other factors besides women’s nutritional status¹²12 Massmann PF, França EL, Souza EG, Souza MS, Brune MFSS, Honorio-França AC. Maternal hypertension induces alterations in immunological factors of colostrum and human milk. Front Life Sci 2013; 7:155-163.^,1313 Dritsakou K, Liosis G, Valsami G, Polychronopoulos E, Skouroliakou M. The impact of maternal and neonatal associated factors on human milk's macronutrients and energy. J Matern Fetal Neonatal Med 2016; 2:1-7.. Exemplifying the effect of tobacco use and food consumption on the nutritional profile of human milk, Mäkelä et al.¹⁶16 Mäkelä J, Linderborg K, Niinikoski H, Yang B, Lagström H. Breast milk fatty acid composition differs between over-weight and normal weight women: the STEPS Study. Eur J Nutr 2013; 52(2):727-735. observed that smoking decreased omega 3 and increased omega 6 in human milk. Concerning food consumption, only two evaluated the influence of this variable on the lipid quantity in human milk. Noteworthy is that the puerperal diet is pointed out by several studies as a factor associated with changes in lipid concentrations and the profile of long-chain polyunsaturated fatty acids in human milk³¹31 Nyuar KB, Min Y, Ghebremeskel K, Khalil AK, Elbashir MI, Cawford MA. Milk of northern Sudanese mothers whose traditional diet is high in carbohydrate contains low docosahexaenoic acid. Acta Paediatr 2010; 99:1824-1827.^,3232 Valentine CJ, Morrow G, Fernandez S, Gulati P, Bartholomew D, Long D, Welty SE, Morrow AL, Rogers LK. Docosahexaenoic Acid and Amino Acid Contents in Pasteurized Donor Milk are Low for Preterm Infants. J Pediatrics 2010; 157(6):906-910., confirming the need to adjust these and other essential variables in the analyses.

Regarding follow-up losses, only two papers selected for this systematic review reported sample losses¹⁶16 Mäkelä J, Linderborg K, Niinikoski H, Yang B, Lagström H. Breast milk fatty acid composition differs between over-weight and normal weight women: the STEPS Study. Eur J Nutr 2013; 52(2):727-735.^,2121 De Luca A, Hankard R, Alexandre-Gouabau MC, Ferchaud-Roucher V, Darmaun D, Boquien CY. Higher concentrations of branched-chain amino acids in breast milk of obese mothers. Nutrition 2016; 31:1295-1298., and the cohort conducted by Marin et al.¹⁵15 Marín MC, Sanjurjo A, Rodrigo MA, Alaniz MJ. Long-chain polyunsaturated fatty acids in breast milk in La Plata, Argentina: relationship with maternal nutritional status. Prostaglandins Leukot Essent Fatty Acids 2005; 73(5):355-360. did not inform the number of losses. Thus, the association estimates may be compromised by follow-up losses or by not having controlled critical confounding factors.

Even if estimates of the selected studies are compromised, pregestational nutritional surveillance is still paramount, preferably in the preconception visit, so that women start the pregnancy with adequate weight, favoring, among other several aspects, the production of milk with an adequate nutritional profile.

References

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