Maternal Plasma Choline during Gestation and Small for Gestational Age Infants

Abstract

Objective Small for gestational age (SGA) infants are at increased risk for neonatal morbidity and developmental problems in childhood. No current interventions during human pregnancy address this problem. This study investigated the possible relationship between maternal choline concentration during pregnancy and SGA infants.

Study Design Maternal plasma choline concentrations were sampled at 16 and 28 weeks' gestation from women in a public prenatal clinic. Additional factors assessed were maternal age, body mass index, infection, C-reactive protein, hair cortisol, and compliance with prenatal vitamins and folate. Infants below the 10th percentile for gestational age were classified as SGA. Binary logistic regression was used to identify significant associated factors in pregnancies resulting in SGA infants compared with pregnancies resulting in non-SGA infants.

Results Thirteen (8%) of 159 women had SGA infants. Maternal plasma choline concentrations were low for pregnant participants whose infants were SGA, with the 28-week concentration significantly lower compared with other participants. Plasma choline concentrations ≥7 μM at 28 weeks, consistent with a minimally adequate dietary intake of choline-containing foods, were achieved by only 2 (15%) of mothers with SGA infants, compared with 51% of mothers whose infants were not SGA. Choline concentrations <7 μM at 28 weeks' gestation were associated with an odds ratio for SGA of 16.6 (95% confidence interval: 1.5–189.2, p = 0.023). Other significant factors were female sex and maternal C-reactive protein plasma concentration during gestation.

Conclusion This observational study suggests that higher maternal choline levels may influence the risk for SGA. Maternal plasma choline concentrations are not routinely available in clinical laboratories. However, plasma choline levels can be increased by the mothers' intake of choline or phosphatidylcholine supplements. No nutritional intervention is currently recommended to prevent SGA, but the evidence from this study suggests that further consideration of the role of maternal choline may be warranted.

Key Points

• More females are small for gestational age.

• Low maternal choline is related to small infants.

• Maternal choline ≥7 μM at 28 weeks appears optimal.

Keywords

infant - small for gestational age - choline - birth weight - pregnancy - nutrition

Publikationsverlauf

Eingereicht: 22. April 2022

Angenommen: 01. November 2022

Artikel online veröffentlicht:
30. Dezember 2022

• References

• 1 Esih K, Trunk T, Osredkar D. et al. The impact of birthweight on the development of cerebral palsy: a population-based matched case-control study. Early Hum Dev 2022; 165: 105533
• 2 Starikov R, Has P, Wu R, Nelson DM, He M. Small-for-gestational age placentas associate with an increased risk of adverse outcomes in pregnancies complicated by either type I or type II pre-gestational diabetes mellitus. J Matern Fetal Neonatal Med 2022; 35 (09) 1677-1682
• 3 Mehl CV, Hollund IMH, Iversen JM. et al. Health-related quality of life in young adults born small for gestational age: a prospective cohort study. Health Qual Life Outcomes 2022; 20 (01) 49
• 4 Tack LJW, van der Straaten S, Riedl S. et al. Growth, puberty and testicular function in boys born small for gestational age with a nonspecific disorder of sex development. Clin Endocrinol (Oxf) 2022; 96 (02) 165-174
• 5 Martín-Calvo N, Goni L, Tur JA, Martínez JA. Low birth weight and small for gestational age are associated with complications of childhood and adolescence obesity: systematic review and meta-analysis. Obes Rev 2022; 23 (1, suppl 1): e13380
• 6 Melamed N, Baschat A, Yinon Y. et al. FIGO (international Federation of Gynecology and obstetrics) initiative on fetal growth: best practice advice for screening, diagnosis, and management of fetal growth restriction. Int J Gynaecol Obstet 2021; 152 (1, suppl 1): 3-57
• 7 Dy J, Guan H, Sampath-Kumar R, Richardson BS, Yang K. Placental 11beta-hydroxysteroid dehydrogenase type 2 is reduced in pregnancies complicated with idiopathic intrauterine growth Restriction: evidence that this is associated with an attenuated ratio of cortisone to cortisol in the umbilical artery. Placenta 2008; 29 (02) 193-200
• 8 Börzsönyi B, Demendi C, Pajor A. et al. Gene expression patterns of the 11β-hydroxysteroid dehydrogenase 2 enzyme in human placenta from intrauterine growth restriction: the role of impaired feto-maternal glucocorticoid metabolism. Eur J Obstet Gynecol Reprod Biol 2012; 161 (01) 12-17
• 9 Mericq V, Medina P, Kakarieka E, Márquez L, Johnson MC, Iñiguez G. Differences in expression and activity of 11beta-hydroxysteroid dehydrogenase type 1 and 2 in human placentas of term pregnancies according to birth weight and gender. Eur J Endocrinol 2009; 161 (03) 419-425
• 10 Struwe E, Berzl GM, Schild RL. et al. Simultaneously reduced gene expression of cortisol-activating and cortisol-inactivating enzymes in placentas of small-for-gestational-age neonates. Am J Obstet Gynecol 2007; 197 (01) 43.e1-43.e6
• 11 Fu L, Bo QL, Gan Y. et al. Association among placental 11β-HSD2, PPAR-γ, and NF-κB p65 in small-for-gestational-age infants: a nested case-control study. Am J Reprod Immunol 2020; 83 (05) e13231
• 12 Ernst GD, de Jonge LL, Hofman A. et al. C-reactive protein levels in early pregnancy, fetal growth patterns, and the risk for neonatal complications: the Generation R Study. Am J Obstet Gynecol 2011; 205 (02) 132.e1-132.e12
• 13 Amarilyo G, Oren A, Mimouni FB, Ochshorn Y, Deutsch V, Mandel D. Increased cord serum inflammatory markers in small-for-gestational-age neonates. J Perinatol 2011; 31 (01) 30-32
• 14 Trevisanuto D, Doglioni N, Altinier S, Zaninotto M, Plebani M, Zanardo V. High-sensitivity C-reactive protein in umbilical cord of small-for-gestational-age neonates. Neonatology 2007; 91 (03) 186-189
• 15 Yunis KA, Beydoun H, Tamim H, Nassif Y, Khogali M. National Collaborative Perinatal Neonatal Network. Risk factors for term or near-term fetal growth restriction in the absence of maternal complications. Am J Perinatol 2004; 21 (04) 227-234
• 16 Inkster AM, Fernández-Boyano I, Robinson WP. Sex differences are here to stay: relevance to prenatal care. J Clin Med 2021; 10 (13) 3000
• 17 van Lee L, Crozier SR, Aris IM. et al. Prospective associations of maternal choline status with offspring body composition in the first 5 years of life in two large mother-offspring cohorts: the Southampton Women's Survey cohort and the Growing Up in Singapore Towards healthy Outcomes cohort. Int J Epidemiol 2019; 48 (02) 433-444
• 18 Moltó-Puigmartí C, Obeid R, Mommers M, Eussen SJ, Thijs C. Maternal plasma choline and betaine in late pregnancy and child growth up to age 8 years in the KOALA Birth Cohort Study. Am J Clin Nutr 2021; 114 (04) 1438-1446
• 19 van Lee L, Tint MT, Aris IM. et al. Prospective associations of maternal betaine status with offspring weight and body composition at birth: the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort study. Am J Clin Nutr 2016; 104 (05) 1327-1333
• 20 Du YF, Wei Y, Yang J. et al. Maternal betaine status, but not that of choline or methionine, is inversely associated with infant birth weight. Br J Nutr 2019; 121 (11) 1279-1286
• 21 Freedman R, Hunter SK, Law AJ. et al. Higher gestational choline levels in maternal infection are protective for infant brain development. J Pediatr 2019; 208: 198-206.e2
• 22 ACOG (American College of Obstetricians and Gynecologists), Society for Maternal-Fetal Medicine. Guidance 700: methods for estimating the due date. 2017 Accessed November 23, 2022 at: https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/05/methods-for-estimating-the-due-date
• 23 Fenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr 2013; 13: 59
• 24 Ozarda Ilcol Y, Uncu G, Ulus IH. Free and phospholipid-bound choline concentrations in serum during pregnancy, after delivery and in newborns. Arch Physiol Biochem 2002; 110 (05) 393-399
• 25 Abratte CM, Wang W, Li R, Axume J, Moriarty DJ, Caudill MA. Choline status is not a reliable indicator of moderate changes in dietary choline consumption in premenopausal women. J Nutr Biochem 2009; 20 (01) 62-69
• 26 Hoffman MC, D'Anna-Hernandez K, Benitez P, Ross RG, Laudenslager ML. Cortisol during human fetal life: characterization of a method for processing small quantities of newborn hair from 26 to 42 weeks gestation. Dev Psychobiol 2017; 59 (01) 123-127
• 27 Hoffman MC, Karban LV, Benitez P, Goodteacher A, Laudenslager ML. Chemical processing and shampooing impact cortisol measured in human hair. Clin Invest Med 2014; 37 (04) E252-E257
• 28 D'Anna-Hernandez KL, Ross RG, Natvig CL, Laudenslager ML. Hair cortisol levels as a retrospective marker of hypothalamic-pituitary axis activity throughout pregnancy: comparison to salivary cortisol. Physiol Behav 2011; 104 (02) 348-353
• 29 Wu BTF, Dyer RA, King DJ, Richardson KJ, Innis SM. Early second trimester maternal plasma choline and betaine are related to measures of early cognitive development in term infants. PLoS One 2012; 7 (08) e43448
• 30 Orczyk-Pawilowicz M, Jawien E, Deja S, Hirnle L, Zabek A, Mlynarz P. Metabolomics of human amniotic fluid and maternal plasma during normal pregnancy. PLoS One 2016; 11 (04) e0152740
• 31 Resseguie M, Song J, Niculescu MD, da Costa KA, Randall TA, Zeisel SH. Phosphatidylethanolamine N-methyltransferase (PEMT) gene expression is induced by estrogen in human and mouse primary hepatocytes. FASEB J 2007; 21 (10) 2622-2632
• 32 Ozarda Ilçöl Y, Ozyurt G, Kilicturgay S, Uncu G, Ulus IH. The decline in serum choline concentration in humans during and after surgery is associated with the elevation of cortisol, adrenocorticotropic hormone, prolactin and beta-endorphin concentrations. Neurosci Lett 2002; 324 (01) 41-44
• 33 Melbye H, Hvidsten D, Holm A, Nordbø SA, Brox J. The course of C-reactive protein response in untreated upper respiratory tract infection. Br J Gen Pract 2004; 54 (506) 653-658
• 34 Madan JC, Davis JM, Craig WY. et al. Maternal obesity and markers of inflammation in pregnancy. Cytokine 2009; 47 (01) 61-64
• 35 Sharps MC, Baker BC, Guevara T. et al. Increased placental macrophages and a pro-inflammatory profile in placentas and maternal serum in infants with a decreased growth rate in the third trimester of pregnancy. Am J Reprod Immunol 2020; 84 (03) e13267
• 36 Kaitu'u-Lino TJ, Tong S, Walker SP. et al. Maternal circulating SPINT1 is reduced in small-for-gestational age pregnancies at 26 weeks: Growing up in Singapore towards health outcomes (GUSTO) cohort study. Placenta 2021; 110: 24-28
• 37 Wells JC. Natural selection and sex differences in morbidity and mortality in early life. J Theor Biol 2000; 202 (01) 65-76
• 38 Sandman CA, Glynn LM, Davis EP. Is there a viability-vulnerability tradeoff? Sex differences in fetal programming. J Psychosom Res 2013; 75 (04) 327-335
• 39 Clifton VL. Review: Sex and the human placenta: mediating differential strategies of fetal growth and survival. Placenta 2010; 31 (Suppl): S33-S39
• 40 D'Alessandro A, Hay A, Dzieciatkowska M. et al. Protein-L-isoaspartate O-methyltransferase is required for in vivo control of oxidative damage in red blood cells. Haematologica 2021; 106 (10) 2726-2739
• 41 Lips KS, Brüggmann D, Pfeil U, Vollerthun R, Grando SA, Kummer W. Nicotinic acetylcholine receptors in rat and human placenta. Placenta 2005; 26 (10) 735-746
• 42 King JH, Kwan STC, Yan J. et al. Maternal choline supplementation modulates placental markers of inflammation, angiogenesis, and apoptosis in a mouse model of placental insufficiency. Nutrients 2019; 11 (02) E374
• 43 Jensen HH, Batres-Marquez SP, Carriquiry A, Schalinske KL. Choline in the diets of the US population: NHANES, 2003–2004. FASEB J 2007; 21: LB46-LB46
• 44 U.S. Food and Drug Administration (FDA). Nutrition labeling requirements. Accessed March 1, 2020 at: https://www.fda.gov/media/99069/download
• 45 Zeisel SH, Growdon JH, Wurtman RJ, Magil SG, Logue M. Normal plasma choline responses to ingested lecithin. Neurology 1980; 30 (11) 1226-1229
• 46 Fischer LM, da Costa KA, Galanko J. et al. Choline intake and genetic polymorphisms influence choline metabolite concentrations in human breast milk and plasma. Am J Clin Nutr 2010; 92 (02) 336-346
• 47 Cheatham CL, Goldman BD, Fischer LM, da Costa KA, Reznick JS, Zeisel SH. Phosphatidylcholine supplementation in pregnant women consuming moderate-choline diets does not enhance infant cognitive function: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr 2012; 96 (06) 1465-1472
• 48 Ross RG, Hunter SK, McCarthy L. et al. Perinatal choline effects on neonatal pathophysiology related to later schizophrenia risk. Am J Psychiatry 2013; 170 (03) 290-298
• 49 Caudill MA, Strupp BJ, Muscalu L, Nevins JEH, Canfield RL. Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double-blind, controlled feeding study. FASEB J 2018; 32 (04) 2172-2180
• 50 Jacobson SW, Carter RC, Molteno CD. et al. Efficacy of maternal choline supplementation during pregnancy in mitigating adverse effects of prenatal alcohol exposure on growth and cognitive function: a randomized, double-blind, placebo-controlled clinical trial. Alcohol Clin Exp Res 2018; 42 (07) 1327-1341
• 51 Crovetto F, Crispi F, Casas R. et al; IMPACT BCN Trial Investigators. Effects of Mediterranean diet or mindfulness-based stress reduction on prevention of small-for-gestational age birth weights in newborns born to at-risk pregnant individuals: the IMPACT BCN randomized clinical trial. JAMA 2021; 326 (21) 2150-2160
• 52 Baumgartner HK, Trinder KM, Galimanis CE. et al. Characterization of choline transporters in the human placenta over gestation. Placenta 2015; 36 (12) 1362-1369
• 53 Zeisel SH, Epstein MF, Wurtman RJ. Elevated choline concentration in neonatal plasma. Life Sci 1980; 26 (21) 1827-1831
• 54 Hunter SK, Hoffman MC, McCarthy L. et al. Black American maternal prenatal choline, offspring gestational age at birth, and developmental predisposition to mental illness. Schizophr Bull 2021; 47 (04) 896-905