Abstract

INTRODUCTION

Pregnancy is a condition that involves a metabolic adaptation to satisfy the nutritional support and development of the fetus (¹1 Herrera E. Lipid metabolism in pregnancy and its consequences in the fetus and newborn. Endocrine. 2002;19:55-43.). Since it is a moment of intense maternal hormonal change, the maternal lipid profile (total cholesterol and cholesterol fractions) undergoes physiological changes, increasing throughout the pregnancy (²2 Petraglia F, Dantona D, Lockwood CJ, Snyder PJ, Barss VA. Maternal endocrine and metabolic adaptation to pregnancy. UpToDate, 2012.,³3 Tan EK, Tan EL. Alterations in physiology and anatomy during pregnancy. Best Pract Res Clin Obstet Gynaecol. 2013;27(6):791-802.). The pituitary-stimulating hormones released by the hypothalamus – gonadotropin-releasing hormone (GnRH), corticotropin-releasing hormone (CRH), growth hormone releasing hormone (GHRH), thyrotropin-releasing hormone (TRH) and prolactin – act directly on the pregnancy and reach high circulating levels due to placental stimulation (²2 Petraglia F, Dantona D, Lockwood CJ, Snyder PJ, Barss VA. Maternal endocrine and metabolic adaptation to pregnancy. UpToDate, 2012.). Some studies have shown that significant changes may occur in overweight or obese women (⁴4 Benítez LRY, Bonneau GA, Rascón MSC, López DL, Pedrozo WR. Perfil lipídico por trimestre de gestación en una población de mujeres adultas. Rev Chil Obstet Ginecol. 2010;75:233-27.,⁵5 Neboh EE, Emeh, KJ, Aniebue UU, Ikekpeazu JE, Maduka CI, Ezeugwu OF. Relationship between lipid and lipoprotein metabolism in trimesters of pregnancy in Nigerian women: Is pregnancy a risk factor? J Nat Sci Biol Med. 2012;3:32-7.). The normal physiological increase in circulating lipids allows the mother to have a valuable source of energy for her and for the baby and keeps their metabolic rate steady, enabling the healthy development of the newborn (⁶6 Herrera E, Amusquivar E, López-Soldado I, Ortega H. Maternal lipid metabolism and placental lipid transfer. Horm Res. 2006;65:64-59.). However, during intrauterine development, pathophysiological processes can occur in the metabolism of the lipids leading to abnormal serum concentrations in fetal circulation (⁷7 Herrera E, Amusquivar E. Lipid metabolism in the fetus and the newborn. Diabetes Metab Res Rev. 2000;16(3):202-10.

8 Donegá S, Oba J, Maranhão RC. Concentração sérica de lipídeos e apolipoproteína B em recém-nascidos. Arq Bras Cardiol. 2006;86:419-24.

9 Garver WS, Krishnan K, Gallagos JR, Michikawa M, Francis GA, Heidenreich RA. Niemann-Pick C1 protein regulates cholesterol transport to the trans-Golgi network and plasma membrane caveolae. J Lipid Res. 2002;43(4):579-89.

10 Plosch T, Strate EMEV, Kuipers F. Cholesterol transport by the placenta: placental liver x receptor activity as a modulador of fetal cholesterol metabolism? Placenta. 2007;28:610-04.-¹¹11 Woollett LA. Transport of maternal cholesterol to the fetal circulation. Placenta. 2011;32:s221-s2018.).

The understanding of how the maternal/newborn lipid transport occurs allows us to find out whether lipid alterations are capable of generating permanent changes in the structures and functions of the organs, which may reflect on their metabolism and post-uterine life (³3 Tan EK, Tan EL. Alterations in physiology and anatomy during pregnancy. Best Pract Res Clin Obstet Gynaecol. 2013;27(6):791-802.). Some authors consider the placenta a transport channel for the lipid portions from the mother to the fetus, and this transport can be influenced by maternal diseases associated with lipid metabolism (¹²12 Pac-Kozuchowska E. The concentration of lipid parameters in newborns and in older children. Med Wieku Rozwoj. 2013;17(1):53-63.,¹³13 Higa R, Jawerbaum A. Intrauterine effects of impaired lipid homeostasis in pregnancy diseases. Curr Med Chem. 2013;20(18):2338-50.). Several clinical conditions can influence the serum concentrations of lipids in neonates, and some authors disagree in relation to the transport via placenta (¹⁴14 Meyer BJ, Stewart FM, Brown EA, Cooney J, Nilsson S, Olivecrona G, et al. Maternal obesity is associated with the formation of small dense LDL and hypoadiponectinemia in the third trimester. J Clin Endocrinol Metab. 2013;98(2):643-52.). Changes in circulating lipids – total cholesterol (TC), high-density lipoprotein (HDL-c), low-density lipoprotein (LDL-c) and triglycerides – may be related to maternal/fetal transport mechanisms, in which the supply of fatty acids can be favored or restricted causing serious problems for fetal organs and tissues (¹⁵15 SBC. Sociedade Brasileira de Cardiologia. III Diretrizes Brasileiras sobre Dislipidemias e Diretriz de Prevenção da Aterosclerose do Departamento de Aterosclerose da Sociedade Brasileira de Cardiologia. Arq Bras Cardiol. 2001;77:1-48.

16 SBC. Sociedade Brasileira de Cardiologia. IV Diretriz Brasileira sobre Dislipidemias e Prevenção da Aterosclerose Departamento de Aterosclerose da Sociedade Brasileira de Cardiologia. Arq Bras Cardiol. 2007;88:1-19.

17 Ramasamy I. Recent advances in physiological lipoprotein metabolism. Clin Chem Lab Med. 2014;52(12):1695-727.

18 Soler W, Bravo ML. Perfil lipídico en neonatos. Revista Médica Universidad de Antioquia. 1996;9:110-4.-¹⁹19 Casanueva VE, Cid XC, Milos CG, Chiang MTS, Lama CL, Heredia FJ, et al. Perfil lipídico en recién nacidos normales de ambos sexos. Rev Chil Pediatr. 1994;65:17-20.).

The aim of this study was to evaluate whether there is an association between altered maternal lipid profile and the lipid profile of the newborn in a public maternity hospital in Joinville, Santa Catarina.

SUBJECTS AND METHODS

Design and study population

This is a cross-sectional study, conducted with 435 pairs (mothers and children) attending a public maternity hospital in the city of Joinville-SC, between January and February of 2012. The sample was calculated with the software OpenEpi version 3.02. Based on a prevalence of 6% of macrosomic infants (²⁰20 Tavares JS, Melo ASO, Amorim MMR, Barros VO, Benício MHA, Takito MY, et al. Associação entre o padrão de atividade física materna, ganho ponderal gestacional e peso ao nascer em uma coorte de 118 gestantes no município de Campina Grande, Nordeste do Brasil. Rev Assoc Med Bras. 2009;55(3):335-41.

21 Kac G, Velásquez-Meléndez G. Ganho de peso gestacional e macrossomia em uma coorte de mães e filhos. J Pediat. 2005;81(1):47-53.-²²22 Kerche LTRL, Abbade JF, Costa RAA, Rudge MVC, Calderon IMP. Fatores de risco para macrossomia fetal em gestações complicadas por diabete ou por hiperglicemia diária. Rev Bras Ginecol Obstet. 2005;10:580-7.), for a 95% confidence interval, absolute precision of 2.5% and a population of 7,200 newborns, the estimated sample size was 331 individuals. Assuming a 20% loss, a total of at least 397 participants was required.

This study is part of a larger project which included investigation of socioeconomic, demographic, obstetric, anthropometric and reproductive data of mothers and their newborns. We included in the study all pregnant women in labor, aged 18 years or more, with gestational age classified as “term” (37 to 42 weeks), who did not follow any specific type of diet before or during pregnancy, or at the time of delivery, with a single pregnancy and live births who delivered in the maternity ward. We excluded mothers diagnosed with infectious and contagious diseases (syphilis, human immunodeficiency syndrome, toxoplasmosis and hepatitis) and preeclampsia, and those newborns who presented morphological changes at the time of birth. The study was approved by the Research Ethics Committee of Univille under the number 107/2011.

Biochemical analysis

The blood samples of the newborns, approximately 10 mL, were collected at the time of the delivery by aspiration of the umbilical vein close to the placenta up to 10 minutes after clamping to prevent coagulation. Blood samples of the parturients, approximately 10 mL, were collected by a nurse in the pre-delivery room or soon after the delivery (up to 24 hours). Immediately after collection, the blood was transferred to tubes containing separating gels, then identified and kept at room temperature for 30 minutes. After that, the tubes with the samples were placed in a refrigerator for up to four hours and subsequently centrifuged under 6°C refrigeration at 3,500 rotations per minute for 15 minutes. After separation of the serum, the samples were fractionated in aliquots of 0.5 mL for measurement of TC, HDL-c, LDL-c and triglycerides, and the remainder was stored in a freezer at -75°C.

The concentrations of TC, triglycerides and HDL-c were determined by an enzymatic colorimetric method with Advia Centaur (model 1650, Siemens), using the kits Cholesterol Liquiform (GOD-ANA 2009), Triglycerides Liquiform (GOD-ANA 2009) and D-HDL (Siemens Diagnostics, Tarrytown, USA), respectively. From the TC, triglycerides and HDL-c levels obtained, we determined the values of LDL-c using the Friedewald formula when triglycerides values were below 400 mg/dL (²³23 Friedewald WT, Levy RI, Frederickson DS. Estimation of the concentration of LDL cholesterol in plasma without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499-504.). We considered as reference values for lipids in women above the age of 20 years, those proposed by the “V Brazilian Guideline on Prevention of Dyslipidemia and Atherosclerosis” of the Brazilian Society of Cardiology, which considers as high those values of TC ≥ 240 mg/dL, LDL-c ≥ 160 mg/dL and triglycerides ≥ 200 mg/dL (²⁴24 SBC. Sociedade Brasileira de Cardiologia. V Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose. Arq Bras Cardiol. 2013;101:1-36.). HDL-c was considered low when the values were below 40 mg/dL, according to the “V Brazilian Guideline on Prevention of Dyslipidemia and Atherosclerosis”, which stratifies this variable according to gender (²⁴24 SBC. Sociedade Brasileira de Cardiologia. V Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose. Arq Bras Cardiol. 2013;101:1-36.). For women aged 19 years or younger, we adopted the reference values proposed by the “I Guideline on Prevention of Atherosclerosis in Childhood and Adolescence”, which considers as high those values of TC ≥ 170 mg/dL, LDL-c ≥ 130 mg/dL, HDL-c < 45 mg/dL and triglycerides ≥ 130 mg/dL (²⁵25 SBC. Sociedade Brasileira de Cardiologia. I Diretriz de Prevenção da Aterosclerose na Infância e na Adolescência. Arq Bras Cardiol. 2005;85:1-36.).

Gestational weight gain

Gestational weight gain (GWG) was calculated by subtracting from the weight at the time of hospitalization at the MDV, as evaluated by the screening staff and recorded in the medical chart, the weight reported by the mother before the pregnancy. The adequacy of the GWG was evaluated according to the new recommendations of the Institute of Medicine - IOM (²⁶26 Rasmussen KM, Yaktine AL (eds). Weight Gain during Pregnancy: Reexamining the Guidelines. Institute of Medicine (US) of the National Research Council (US) Committee to Reexamine IOM Pregnancy Weight Guidelines. Washington, DC: National Academy Press; 2009.). Underweight women (BMI < 18.5 kg/m²) should gain between 12.5 and 18 kg; women with adequate BMI (18.5-24.9 kg/m²) between 11.5 and 16.0 kg, overweight women (25.0-29.9 kg/m²) between 7.0 and 11.5 kg, and obese women (BMI ≥ 30.0 kg/m²) between 5.0 and 9.0 kg (²⁶26 Rasmussen KM, Yaktine AL (eds). Weight Gain during Pregnancy: Reexamining the Guidelines. Institute of Medicine (US) of the National Research Council (US) Committee to Reexamine IOM Pregnancy Weight Guidelines. Washington, DC: National Academy Press; 2009.).

Statistical analysis

The data were stored and analyzed by the software SPSS Inc. Released 2008. SPSS Statistics for Windows, Version 17.0. Chicago: SPSS Inc. We calculated measures of central tendency and dispersion for quantitative variables and frequency distributions for categorical variables. The statistical comparison was analyzed using the Mann-Whitney U test for non-parametric variables. Biochemical variables were transformed into the binary modes “NOT ALTERED” and “ALTERED”. Normality was verified using the Kolmogorov-Smirnov test and the significance level adopted was 5%.

RESULTS

Of 529 children born during the period of investigation, 46 did not fulfill the inclusion criteria and 12 were excluded from the study, yielding a total of 471 pairs. Of these, 36 (7.6%) were considered losses, resulting in 435 pairs.

The general characteristics of the 435 parturients and their children are presented in table 1. The mean age of the mothers was 25.9 (SD = 6.0) years and most (56.6%) were ≥ 24 years of age, with ≥ 8 years of education (75.2%), married/in a stable relationship (83.0%) and with a declared household income ≥ 3 times the minimum wage (57.5%). More than one third (37.9%) of the parturients reported having a BMI ≥ 25 kg/m² before the pregnancy. As for the newborns, the male gender was the most prevalent (51.5%), about one third (33.3%) were delivered by cesarean section and 24.4% were categorized as large for gestational age – LGA (Table 1).

Table 2 lists the values of GWG of the 435 investigated parturients. Although the average GWG decreased with increasing BMI, the parturients categorized as being overweight or obese (n = 165; 39.9%) gained more weight than the recommended maximum by the IOM classification (²⁶26 Rasmussen KM, Yaktine AL (eds). Weight Gain during Pregnancy: Reexamining the Guidelines. Institute of Medicine (US) of the National Research Council (US) Committee to Reexamine IOM Pregnancy Weight Guidelines. Washington, DC: National Academy Press; 2009.). When we analyzed only women with BMI ≥ 25 kg/m² (overweight and obese), Spearman’s correlation analysis showed no association between GWG and the lipid profile of the newborns (TC: rho = -0.058, p = 0.467; LDL-c: rho = -0.071,p = 0.376; HDL-c: rho = 0.031, p = 0.701; triglycerides: rho = -0.052, p = 0.518).

The values of the lipid profile of the mothers and their children are presented in table 3. The mean concentrations of TC (208.1 mg/dL) and triglycerides (197.8 mg/dL) of the mothers were classified as altered and borderline, respectively, according to the “V Brazilian Guideline on Prevention of Dyslipidemias and Atherosclerosis” (²⁴24 SBC. Sociedade Brasileira de Cardiologia. V Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose. Arq Bras Cardiol. 2013;101:1-36.).

Table 4 shows the mean values and standard deviations of the concentrations of TC, LDL-c, HDL-c and triglycerides of newborns according to the maternal lipid profile, whether not altered (N) or altered (A). There was no significant difference in the plasma lipid concentrations in newborns in relation to the maternal lipid profile.

DISCUSSION

In this study we demonstrated that with the exception of the maternal variable LDL-c, the other maternal biochemical variables (TC, HDL-c and triglycerides) are not significantly associated with the lipid profile of the newborn.

The relationship of the maternal lipid profile to the lipid profile of the newborn is still not well understood in the scientific literature. Several authors report the occurrence of lipid transport across the placenta, but this transport is not enough to influence the infant’s plasma lipid concentration (¹1 Herrera E. Lipid metabolism in pregnancy and its consequences in the fetus and newborn. Endocrine. 2002;19:55-43.,⁶6 Herrera E, Amusquivar E, López-Soldado I, Ortega H. Maternal lipid metabolism and placental lipid transfer. Horm Res. 2006;65:64-59.,⁷7 Herrera E, Amusquivar E. Lipid metabolism in the fetus and the newborn. Diabetes Metab Res Rev. 2000;16(3):202-10.,¹³13 Higa R, Jawerbaum A. Intrauterine effects of impaired lipid homeostasis in pregnancy diseases. Curr Med Chem. 2013;20(18):2338-50.). The physiological and biochemical mechanisms of the transport of nutrients across the placenta is rather complex (⁹9 Garver WS, Krishnan K, Gallagos JR, Michikawa M, Francis GA, Heidenreich RA. Niemann-Pick C1 protein regulates cholesterol transport to the trans-Golgi network and plasma membrane caveolae. J Lipid Res. 2002;43(4):579-89.

10 Plosch T, Strate EMEV, Kuipers F. Cholesterol transport by the placenta: placental liver x receptor activity as a modulador of fetal cholesterol metabolism? Placenta. 2007;28:610-04.-¹¹11 Woollett LA. Transport of maternal cholesterol to the fetal circulation. Placenta. 2011;32:s221-s2018.). According to some authors, triglycerides are not transferred from the mother to the fetus (⁷7 Herrera E, Amusquivar E. Lipid metabolism in the fetus and the newborn. Diabetes Metab Res Rev. 2000;16(3):202-10.), however, when the placenta presents lipase enzymatic activity and membrane receptors to lipoproteins, essential fatty acids are transported as triglycerides bound to lipoproteins, becoming thus available to the fetus (¹1 Herrera E. Lipid metabolism in pregnancy and its consequences in the fetus and newborn. Endocrine. 2002;19:55-43.,⁶6 Herrera E, Amusquivar E, López-Soldado I, Ortega H. Maternal lipid metabolism and placental lipid transfer. Horm Res. 2006;65:64-59.,⁷7 Herrera E, Amusquivar E. Lipid metabolism in the fetus and the newborn. Diabetes Metab Res Rev. 2000;16(3):202-10.).

During pregnancy, there is an increase in circulating lipids, leading to maternal hyperlipidemia. However, the lipoprotein-specific receptors for the transport of fatty acids in the placenta are metabolized in the fetal plasma (⁶6 Herrera E, Amusquivar E, López-Soldado I, Ortega H. Maternal lipid metabolism and placental lipid transfer. Horm Res. 2006;65:64-59.,⁷7 Herrera E, Amusquivar E. Lipid metabolism in the fetus and the newborn. Diabetes Metab Res Rev. 2000;16(3):202-10.,⁹9 Garver WS, Krishnan K, Gallagos JR, Michikawa M, Francis GA, Heidenreich RA. Niemann-Pick C1 protein regulates cholesterol transport to the trans-Golgi network and plasma membrane caveolae. J Lipid Res. 2002;43(4):579-89.

10 Plosch T, Strate EMEV, Kuipers F. Cholesterol transport by the placenta: placental liver x receptor activity as a modulador of fetal cholesterol metabolism? Placenta. 2007;28:610-04.

11 Woollett LA. Transport of maternal cholesterol to the fetal circulation. Placenta. 2011;32:s221-s2018.-¹²12 Pac-Kozuchowska E. The concentration of lipid parameters in newborns and in older children. Med Wieku Rozwoj. 2013;17(1):53-63.). A study conducted with blood from the umbilical cord of newborns showed a lower concentration of TC and lipid fractions when compared with the concentrations obtained in the first days of life of these same individuals, probably due to the production of TC from the maternal milk. Maternal TC and lipid fractions are transferred to the fetus due to placental permeability (⁹9 Garver WS, Krishnan K, Gallagos JR, Michikawa M, Francis GA, Heidenreich RA. Niemann-Pick C1 protein regulates cholesterol transport to the trans-Golgi network and plasma membrane caveolae. J Lipid Res. 2002;43(4):579-89.

10 Plosch T, Strate EMEV, Kuipers F. Cholesterol transport by the placenta: placental liver x receptor activity as a modulador of fetal cholesterol metabolism? Placenta. 2007;28:610-04.

11 Woollett LA. Transport of maternal cholesterol to the fetal circulation. Placenta. 2011;32:s221-s2018.-¹²12 Pac-Kozuchowska E. The concentration of lipid parameters in newborns and in older children. Med Wieku Rozwoj. 2013;17(1):53-63.). However, at the end of the pregnancy, cholesterol is no longer physiologically important, since it is then synthesized by fetal tissues. Ketone and small amounts of glycerol are also transferred across the placenta, because the fetus uses these elements in their metabolism (¹1 Herrera E. Lipid metabolism in pregnancy and its consequences in the fetus and newborn. Endocrine. 2002;19:55-43.).

Essential fatty acids are required for fetal development, and they are transferred to the fetus with the help of lipoprotein receptors present in the trophoblasts (⁶6 Herrera E, Amusquivar E, López-Soldado I, Ortega H. Maternal lipid metabolism and placental lipid transfer. Horm Res. 2006;65:64-59.). Although the trophoblasts are responsible for the transport of cholesterol to the fetus, these cells express receptors for LDL-c and HDL-c in their membranes, which are responsible for the uptake and transport of cholesterol to the intracellular environment via lysosome. In the lysosome, cholesterol ester is hydrolyzed and then transported by the Niemann-Pick C1 (NPC1) protein, which regulates the transport of cholesterol from the lysosomes to other cellular compartments, making it available to the fetal plasma (⁹9 Garver WS, Krishnan K, Gallagos JR, Michikawa M, Francis GA, Heidenreich RA. Niemann-Pick C1 protein regulates cholesterol transport to the trans-Golgi network and plasma membrane caveolae. J Lipid Res. 2002;43(4):579-89.

10 Plosch T, Strate EMEV, Kuipers F. Cholesterol transport by the placenta: placental liver x receptor activity as a modulador of fetal cholesterol metabolism? Placenta. 2007;28:610-04.-¹¹11 Woollett LA. Transport of maternal cholesterol to the fetal circulation. Placenta. 2011;32:s221-s2018.). Despite the occurrence of this transport of lipoproteins from the mother to the fetus, the maternal concentrations of TC, LDL-c, HDL-c and triglycerides seem not to affect the lipid profile of the newborn, as demonstrated in this study. Additionally, the GWG also showed no relationship with the lipid profile of the newborn, signaling that the nutritional status of the mother seems not to significantly change the lipid profile of the newborn.

Similarly to what has been reported by various authors, there is still limited information on the relationship between the lipid metabolism of the mother and the newborn. Mechanisms of synthesis, degradation and transport of fats, as well as carbohydrate metabolism, need to be better investigated in this group in order to enable the correct monitoring of the maternal plasma lipids during the gestational period.

To conclude, limitations of the present study include: 1) the fact that some parturients were not fasting when the blood was collected, which may have overestimated the values obtained for maternal TC and triglycerides; 2) the absence of a standard reference for the lipid variables TC and cholesterol fractions in children under the age of two years does not allow the assessment of a relationship between the altered lipid profile of the mother and the lipid profile of the child, hindering the understanding of the transport of these substances across the placenta.

Acknowledgments:

we are thankful to the Maternidade Darcy Vargas in Joinville – Santa Catarina, for allowing the collection of the data in their establishment, to the Laboratório de Análises Clínicas Gimenes Ltda., for processing the biochemical analyses, and to the Fundo de Apoio à Pesquisa da Univille for funding the study.

REFERENCES

Publication Dates

History