Evidence for Sexual Dimorphism in the Neonatal Fat Mass Response to Maternal Long-Chain PUFA Intake
This article at a glance 
A recent study has investigated the relationship between maternal LCPUFA intake and fat mass in healthy full-term babies. The study was performed by Pereira-da-Silva and colleagues from the Department of Pediatrics, at the Hospital Dona Estefania, Centro Hospitalar de Lisboa Central, in Lisbon, Portugal, and other research centers in Lisbon, St. John Providence Children’s Hospital, Detroit, MI and Rutgers University Newark, NJ, in the USA. The objective of the study was to examine the effects of maternal LCPUFA intake on the body composition of neonates at birth of full-term appropriate-for-gestational age neonates born to mothers without known potential factors that affect intrauterine growth. Specifically the study employed an accurate and reliable technique to measure adipose fat mass in newborns using air-displacement plethysmography. 
Methods Neonatal anthropomorphic measurements were taken within the first 72 hours after birth. These included weight, length, and midarm circumference. From weight and length measurements, indices were calculated to estimate adiposity, weight/length, body mass index (weight per squared length), and the ponderal index (weight per cubed length, i.e. expressed as 100 x g/cm3) as a measure of leanness. Body composition was determined by air-displacement plethysmography, and a model that permitted calculating fat mass and fat-free mass with a precision of 0.1 g. Maternal diet was assessed by a food-frequency questionnaire validated for pregnant women (Portuguese context), and consumption of individual nutrients calculated based on food composition databases and average portion patterns. The omega-6:omega-3 LCPUFA ratio intake was calculated from the sums of ingested long-chain PUFA. Inclusion criteria were a pregnancy resulting in a singleton birth, and full-term gestation (between 37 and 41 weeks), and appropriate for-gestational-age birth weight. Excluded from the study were pregnant mother-child dyads in the case of ≥5 pregnancies, multiple pregnancies, and small-for-gestational-age, or where mothers had adverse health conditions known to affect intrauterine growth as well as alcohol, tobacco and illicit drugs use. Data were collected on 100 mother-neonate dyads, considered a “convenience” cross-sectional sample from a previously reported study design. Results 
In multivariable regression analysis there was a significant interaction between the estimated omega-6:omega-3 ratio intake and the percentage fat mass of male and female neonates. Further stratification by sex was employed to investigate the effects of maternal LCPUFA intake, pre-pregnancy body mass index, and gestational weight gain, on percentage fat mass and anthropomorphic indices. In female neonates a positive association was found between the n-6:n-3 LCPUFA ratio intake and fat mass and percentage fat mass (corresponding to a 21 g increase in fat mass for each unit increase in n-6:n-3 LCPUFA intake ratio). In boys, a positive association was not found for fat mass and n-6:n-3 LCPUFA, but here the ponderal index was associated with maternal DHA intake, pre-pregnancy body mass index, and with gestational weight gain. After adjustment for body mass index and gestational weight gain of the mother, the ponderal index of male neonates was estimated to be 0.165 g x cm-3 higher when their mothers had an intake ≥200 mg DHA/day, compared to those with mothers with a lower daily DHA intake. Discussion This study provides new indications that at term birth a higher maternal omega-6:omega-3 LCPUFA intake ratio is associated with female offspring having higher fat mass, and fat as percentage of body composition, whereas in male neonates a higher ponderal index is associated with DHA intake above a recommended daily intake of 200 mg/day. Employing measurements within 72 hours after birth, the differences in anthropometry can be ascribed to differences in the prenatal period, in contrast to other studies where effects of post-natal feeding have made it difficult to assign independent effects of variations in LCPUFA supply on intrauterine developing fat depots. A limitation of this study is the reliance on a food frequency questionnaire, sensitive to recall bias, although the authors mention that the quality of the estimated fatty acid intake has been deemed acceptable according to the EURopean micronutrient RECommendations Aligned scoring system. The Portuguese women analyzed in this study had overall relatively high average daily intakes of EPA (115 mg) and DHA (266 mg), and a n-6:n-3 ratio of 7.0. However, almost 40% of women had a daily LCPUFA intake below 200 mg. 
Female neonates are known to have greater fat mass and percent fat mass at birth than males. The results of this study suggest that a relative higher maternal intake of omega-6 compared to omega-3 LCPUFA predisposes to higher adiposity at term birth. With respect to male neonates, it has been suggested that ponderal index as an indicator of body size correlates better with lean mass rather than adiposity, and the authors indicate the possibility that increased ponderal index associated with maternal DHA intake may reflect a higher bone mass than adiposity. Sex differences in the response to omega-3 PUFA intake have also been reported with respect to cognitive performance during childhood with more marked effects for female children. Recognition that increased DHA intake and the relative levels of dietary omega-6 to omega-3 LCPUFA may have differential effects on body composition in male and female neonates is an important observation. The adequate development of fat stores in women throughout fetal development and childhood as a physiological fat storage depot may reflect the location for storage of DHA needed for future delivery of DHA to their respective children. Confirmation of the associations identified here is required to substantiate the observation that maternal LCPUFA intake may have important early effects on the physiology of men and women. Pereira-da-Silva L, Cabo C, Moreira AC, Papoila AL, Virella D, Neves R, Bridges KM, Cordeiro-Ferreira G. The effect of long-chain polyunsaturated fatty acids intake during pregnancy on adiposity of healthy full-term offspring at birth. J. Perinatol. 2015;35(3):177-180. [PubMed] Worth Noting Carlson SE, Colombo J, Gajewski BJ, Gustafson KM, Mundy D, Yeast J, Georgieff MK, Markley LA, Kerling EH, Shaddy DJ. DHA supplementation and pregnancy outcomes. Am. J. Clin. Nutr. 2013;97(4):808-815. [PubMed] EURRECA EURopean micronutrient RECommendations Aligned: http://www.eurreca.org/everyone Hawkes CP, Hourihane JO, L.C. K, Irvine AD, Kiely M, Murray DM. Gender- and gestational age-specific body fat percentage at birth. Pediatrics 2011;128(3):e645-651. [PubMed] Infant body composition measurements: weblink Larqué E, Gil-Sánchez A, Prieto-Sánchez MT, Koletzko B. Omega 3 fatty acids, gestation and pregnancy outcomes. Br. J. Nutr. 2012;107(Suppl 2):S77-84. [PubMed] Lassek WD, Gaulin SJ. Sex differences in the relationship of dietary fatty acids to cognitive measures in American children. Front. Evol. Neurosci. 2011;3(5):1-8. [PubMed] Lassek WD, Gaulin SJ. Changes in body fat distribution in relation to parity in American women: a covert form of maternal depletion. Am. J. Phys. Anthropol. 2006 Oct;131(2):295-302. [PubMed] Ma G, Yao M, Liu Y, Lin A, Zou H, Urlando A, Wong WW, Nommsen-Rivers L, Dewey KG. Validation of a new pediatric air-displacement plethysmograph for assessing body composition in infants. Am. J. Clin. Nutr. 2004;79(4):653-660. [PubMed] Øverby NC, Serra-Majem L, Andersen LF. Dietary assessment methods on n-3 fatty acid intake: a systematic review. Br. J. Nutr. 2009;102(Suppl 1):S56-63. [PubMed] Pereira-da-Silva L, Cabo C, Moreira AC, Virella D, Guerra T, Camoes T, Silva AR, Neves R, Ferreira GC. The adjusted effect of maternal body mass index, energy and macronutrient intakes during pregnancy, and gestational weight gain on body composition of full-term neonates. Am. J. Perinatol. 2014;31(10):875-882. [PubMed] Pinto E, Severo M, Correia S, dos Santos Silva I, Lopes C, Barros H. Validity and reproducibility of a semi-quantitative food frequency questionnaire for use among Portuguese pregnant women. Matern. Child Nutr. 2010;6(2):105-119. [PubMed]
- Omega-3 long-chain polyunsaturated fatty acid (LCPUFA) intake during pregnancy has been associated with a small but significant increase in the average length of a healthy pregnancy, as well as the body weight of a newborn.
- In this study the investigators address the sex-specific effects of maternal LCPUFA intake during pregnancy on body compositon of healthy full-term babies.
- The results suggest that the ratio of omega-6 to omega-3 LCPUFA intake favors development of adipose tissue in newborn girls, and that higher DHA intake is associated with increased ponderal index of males at birth, a measure of larger body size unrelated to fat mass.
A recent study has investigated the relationship between maternal LCPUFA intake and fat mass in healthy full-term babies. The study was performed by Pereira-da-Silva and colleagues from the Department of Pediatrics, at the Hospital Dona Estefania, Centro Hospitalar de Lisboa Central, in Lisbon, Portugal, and other research centers in Lisbon, St. John Providence Children’s Hospital, Detroit, MI and Rutgers University Newark, NJ, in the USA. The objective of the study was to examine the effects of maternal LCPUFA intake on the body composition of neonates at birth of full-term appropriate-for-gestational age neonates born to mothers without known potential factors that affect intrauterine growth. Specifically the study employed an accurate and reliable technique to measure adipose fat mass in newborns using air-displacement plethysmography. 
Methods Neonatal anthropomorphic measurements were taken within the first 72 hours after birth. These included weight, length, and midarm circumference. From weight and length measurements, indices were calculated to estimate adiposity, weight/length, body mass index (weight per squared length), and the ponderal index (weight per cubed length, i.e. expressed as 100 x g/cm3) as a measure of leanness. Body composition was determined by air-displacement plethysmography, and a model that permitted calculating fat mass and fat-free mass with a precision of 0.1 g. Maternal diet was assessed by a food-frequency questionnaire validated for pregnant women (Portuguese context), and consumption of individual nutrients calculated based on food composition databases and average portion patterns. The omega-6:omega-3 LCPUFA ratio intake was calculated from the sums of ingested long-chain PUFA. Inclusion criteria were a pregnancy resulting in a singleton birth, and full-term gestation (between 37 and 41 weeks), and appropriate for-gestational-age birth weight. Excluded from the study were pregnant mother-child dyads in the case of ≥5 pregnancies, multiple pregnancies, and small-for-gestational-age, or where mothers had adverse health conditions known to affect intrauterine growth as well as alcohol, tobacco and illicit drugs use. Data were collected on 100 mother-neonate dyads, considered a “convenience” cross-sectional sample from a previously reported study design. Results 
In multivariable regression analysis there was a significant interaction between the estimated omega-6:omega-3 ratio intake and the percentage fat mass of male and female neonates. Further stratification by sex was employed to investigate the effects of maternal LCPUFA intake, pre-pregnancy body mass index, and gestational weight gain, on percentage fat mass and anthropomorphic indices. In female neonates a positive association was found between the n-6:n-3 LCPUFA ratio intake and fat mass and percentage fat mass (corresponding to a 21 g increase in fat mass for each unit increase in n-6:n-3 LCPUFA intake ratio). In boys, a positive association was not found for fat mass and n-6:n-3 LCPUFA, but here the ponderal index was associated with maternal DHA intake, pre-pregnancy body mass index, and with gestational weight gain. After adjustment for body mass index and gestational weight gain of the mother, the ponderal index of male neonates was estimated to be 0.165 g x cm-3 higher when their mothers had an intake ≥200 mg DHA/day, compared to those with mothers with a lower daily DHA intake. Discussion This study provides new indications that at term birth a higher maternal omega-6:omega-3 LCPUFA intake ratio is associated with female offspring having higher fat mass, and fat as percentage of body composition, whereas in male neonates a higher ponderal index is associated with DHA intake above a recommended daily intake of 200 mg/day. Employing measurements within 72 hours after birth, the differences in anthropometry can be ascribed to differences in the prenatal period, in contrast to other studies where effects of post-natal feeding have made it difficult to assign independent effects of variations in LCPUFA supply on intrauterine developing fat depots. A limitation of this study is the reliance on a food frequency questionnaire, sensitive to recall bias, although the authors mention that the quality of the estimated fatty acid intake has been deemed acceptable according to the EURopean micronutrient RECommendations Aligned scoring system. The Portuguese women analyzed in this study had overall relatively high average daily intakes of EPA (115 mg) and DHA (266 mg), and a n-6:n-3 ratio of 7.0. However, almost 40% of women had a daily LCPUFA intake below 200 mg. 
Female neonates are known to have greater fat mass and percent fat mass at birth than males. The results of this study suggest that a relative higher maternal intake of omega-6 compared to omega-3 LCPUFA predisposes to higher adiposity at term birth. With respect to male neonates, it has been suggested that ponderal index as an indicator of body size correlates better with lean mass rather than adiposity, and the authors indicate the possibility that increased ponderal index associated with maternal DHA intake may reflect a higher bone mass than adiposity. Sex differences in the response to omega-3 PUFA intake have also been reported with respect to cognitive performance during childhood with more marked effects for female children. Recognition that increased DHA intake and the relative levels of dietary omega-6 to omega-3 LCPUFA may have differential effects on body composition in male and female neonates is an important observation. The adequate development of fat stores in women throughout fetal development and childhood as a physiological fat storage depot may reflect the location for storage of DHA needed for future delivery of DHA to their respective children. Confirmation of the associations identified here is required to substantiate the observation that maternal LCPUFA intake may have important early effects on the physiology of men and women. Pereira-da-Silva L, Cabo C, Moreira AC, Papoila AL, Virella D, Neves R, Bridges KM, Cordeiro-Ferreira G. The effect of long-chain polyunsaturated fatty acids intake during pregnancy on adiposity of healthy full-term offspring at birth. J. Perinatol. 2015;35(3):177-180. [PubMed] Worth Noting Carlson SE, Colombo J, Gajewski BJ, Gustafson KM, Mundy D, Yeast J, Georgieff MK, Markley LA, Kerling EH, Shaddy DJ. DHA supplementation and pregnancy outcomes. Am. J. Clin. Nutr. 2013;97(4):808-815. [PubMed] EURRECA EURopean micronutrient RECommendations Aligned: http://www.eurreca.org/everyone Hawkes CP, Hourihane JO, L.C. K, Irvine AD, Kiely M, Murray DM. Gender- and gestational age-specific body fat percentage at birth. Pediatrics 2011;128(3):e645-651. [PubMed] Infant body composition measurements: weblink Larqué E, Gil-Sánchez A, Prieto-Sánchez MT, Koletzko B. Omega 3 fatty acids, gestation and pregnancy outcomes. Br. J. Nutr. 2012;107(Suppl 2):S77-84. [PubMed] Lassek WD, Gaulin SJ. Sex differences in the relationship of dietary fatty acids to cognitive measures in American children. Front. Evol. Neurosci. 2011;3(5):1-8. [PubMed] Lassek WD, Gaulin SJ. Changes in body fat distribution in relation to parity in American women: a covert form of maternal depletion. Am. J. Phys. Anthropol. 2006 Oct;131(2):295-302. [PubMed] Ma G, Yao M, Liu Y, Lin A, Zou H, Urlando A, Wong WW, Nommsen-Rivers L, Dewey KG. Validation of a new pediatric air-displacement plethysmograph for assessing body composition in infants. Am. J. Clin. Nutr. 2004;79(4):653-660. [PubMed] Øverby NC, Serra-Majem L, Andersen LF. Dietary assessment methods on n-3 fatty acid intake: a systematic review. Br. J. Nutr. 2009;102(Suppl 1):S56-63. [PubMed] Pereira-da-Silva L, Cabo C, Moreira AC, Virella D, Guerra T, Camoes T, Silva AR, Neves R, Ferreira GC. The adjusted effect of maternal body mass index, energy and macronutrient intakes during pregnancy, and gestational weight gain on body composition of full-term neonates. Am. J. Perinatol. 2014;31(10):875-882. [PubMed] Pinto E, Severo M, Correia S, dos Santos Silva I, Lopes C, Barros H. Validity and reproducibility of a semi-quantitative food frequency questionnaire for use among Portuguese pregnant women. Matern. Child Nutr. 2010;6(2):105-119. [PubMed]