Discovering more benefits of nutrients during pregnancy
Research continues to reveal the impact maternal nutrition can have on the life of the offspring. As various diseases and conditions rise in incidence each year, so to do the links they share with maternal nutrient status. Despite the awareness of prenatal nutrition, insufficiencies in omega-3 fatty acids, iodine, vitamin D and folic acid still exist and as emerging research is illustrating, they offer additional benefits to what was previously thought. Here we take a look at what recent evidence is showing.
Mild iodine deficiencies can impair mental development
Iodine plays an important role in fetal brain development. Its deficiency is the leading cause of preventable mental retardation. Prior to 2009, the incidence of iodine deficiency was 71% in Australian pregnant women with the median urinary iodine concentration around 81-87μg/L which is well below the sufficient level (150μg/L) [1-3]. In 2009 the mandatory fortification of bread with iodized salt was introduced in Australia but recent studies are showing this is only having a mild effect, improving the median urinary iodine concentration in pregnant women from 87μg/L in 2008 to 122μg/L in 2012 (still below the sufficient level) . However, for women who took supplements containing iodine, the median level jumped to 202μg/L . The use of pregnancy supplements containing iodine has increased from 20% to 66% in the last four years .
In another clinical study, pregnant women with mild iodine deficiency were recruited to observe the impact of bread fortification along with supplements containing iodine . The median iodine status of women who did not take supplements remained in the mildly deficient range (<90μg/L) with the fortification of bread only increasing the iodine status by 16μg/L. Conversely, the median iodine status of women who took iodine containing-supplements reached the sufficient level by the end of the trial, increasing the median concentration by 87μg/L. This signifies that the fortification of bread with iodine has only minor benefits, but for the majority with mild iodine deficiencies, supplementation is required. The lack of awareness is a key issue with 78% of pregnant women unaware that iodine deficiency was a problem in Australia and not surprisingly, only 3.7% were aware bread was fortified with iodine .
While the effects of severe iodine deficiency are well established, there is recent evidence to show mild to moderate iodine deficiency during pregnancy can significantly impair offspring mental development. The children of mothers with mild to moderate iodine deficiency displayed significantly higher scores on the problem scales of inhibition and working memory, demonstrating impairment in executive functioning at the age of 4 than children of mothers with sufficient iodine status . Another study showed children at the age of nine, had significantly lower educational outcomes in spelling, grammar and literacy if their mothers had mild-moderate iodine deficiencies during pregnancy than children whose mothers had a sufficient iodine status during gestation. This was observed despite all children having normal iodine levels at the time of the trial .
Supplementation to access the many benefits of omega-3 fatty acids
The essential omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) play a unique role in fetal development and maternal health. Fetal brain development relies on DHA, particularly in the last trimester where it plays a critical role in neurogenesis. After birth, during breastfeeding it is then required for synaptogenesis. Clinical evidence has shown maternal supplementation can improve offspring cognition, mental development, information processing, learning, behaviour, concentration, intellect, attention, problem-solving, motor control and visual acuity . DHA and EPA are also involved in immune regulation and development, where maternal supplementation has been associated with a reduced risk of allergies, asthma and respiratory infections . A concern is that the increasing prevalence of developmental learning and behavioural disorders as well as allergies might be linked to deficiencies in maternal omega-3 levels. Omega-3 fatty acids may also support maternal health by reducing the risk of metabolic syndrome, gestational diabetes and preeclampsia during pregnancy via anti-inflammatory actions and by managing dyslipidemia, decreasing fat stores and increasing fat burning to reduce central obesity and reducing the risk of hypertension and high fasting blood glucose levels [6, 7].
The European consensus, the International Society for the Study of Fatty Acids and Lipids (ISSFAL) and the Omega-3 Centre of Australia & New Zealand recommend women consume 200-300mg/d of DHA during pregnancy and lactation . However pregnant women in Australia are falling well short of this recommendation, averaging 99mg/d of DHA . Fish and seafood are the only substantial dietary sources of DHA, but are typically not consumed on a regular basis, even sparingly for some families. This is further compounded by the fear of heavy metal contamination in seafood during pregnancy, resulting in overall, poor omega-3 fatty acid consumption during this critical life stage. This highlights an important scenario where supplementation can really benefit a group, pregnant/breastfeeding women. Supplements with high DHA levels are particularly beneficial to this group and of great importance to those who don’t eat seafood/fish on a regular basis, which appears to be a large majority of women.
Vitamin D deserves more recognition
Vitamin D has roles beyond skeletal health that are critical during pregnancy and fetal development. Calcitriol, a biologically active form of vitamin D is a neurosteroid that controls brain growth from embryo stage. It regulates genes influencing at least 36 critical brain proteins involved in function and development within the hippocampus and cortex (incl. synaptic plasticity, chaperoning and neurotransmission) . Developmental vitamin D deficiency has also shown shared anomalies with various brain diseases . Furthermore, a low maternal vitamin D status is significantly linked to autism, multiple sclerosis, schizophrenia and impaired neurocognition [10-13]. Vitamin D also plays a key role in activating the innate immune system, whereby a higher maternal vitamin D status is linked to a reduce risk of respiratory tract infections in newborns .
Vitamin D appears important for maintaining maternal health as well. Vitamin D receptors have been found in pancreatic β-cells which assist in insulin secretion . Its immunomodulatory properties control vascular components and it regulates VEGF gene transcription . These mechanisms indicate an important role of vitamin D in reducing two of the most common maternal conditions, gestational diabetes and preeclampsia. A recent meta-analysis systematic review was conducted to observe the effect of vitamin D status on pregnancy outcomes and birth variables . Included in the analysis were ten studies reporting on gestational diabetes (N = 4112), nine on preeclampsia (N = 3191), ten on birth variables (N = 8788) and three on bacterial vaginosis (N = 4462). Analysis revealed that vitamin D insufficiency (<75nmol/L) was associated with a 49% increased risk of gestational diabetes; a 79% increased risk of preeclampsia; an 85% increased risk of small for gestational age infants and a significant increased risk of bacterial vaginosis. These findings highlight the importance of vitamin D in general fetal development and maternal health.
Vitamin D deficiency is a major concern worldwide, particularly during pregnancy. Just in Australia, a perceived sun-loving country, around 43% of women are deficient in vitamin D . Subsequently, the rate and cost of testing vitamin D levels has increased nearly 10-fold in the last 10 years . It is one nutrient that certainly deserves more recognition.
Folic acid can protect against other neurodevelopmental disorders
Preconception and prenatal folic acid supplementation is well recognized to reduce neural tube defects as it plays an important role in rapid cell division during neuronal development as well as aiding DNA synthesis, methylation and repair. Recent evidence suggests that folic acid supplementation can also reduce the risk of autism spectrum disorders (ASDs) which potentially originate in early pregnancy. A prospective population-based study of 85,176 children highlighted that children whose mother took folic acid had a 39% reduced risk of autism than children of mothers unexposed to folic acid supplements . However no association was found with Asperger syndrome and pervasive development disorder-not otherwise specified (PDD-NOS), but statistical power was limited for these disorders. This supports similar findings in which folic acid supplementation has shown to reduce severe language delay . Furthermore, folic acid supplementation is associated with reduced risk of oral cleft and fetal growth restriction . It was also highlighted that a high dose of folic acid (4mg/d) had no additional benefits in fetal growth and oral cleft incidence to the regular dose of folic acid (400μg/d).
Unless there is a history of defects or problems, levels around 400μg/d of folic acid in supplements are sufficient. This is ideally combined with dietary folate from green leafy vegetables and fortified cereals. The problem however is not awareness or compliance as the importance of folic acid during pregnancy is well ingrained in women. The issue is that around 50% of pregnancies are unplanned, who therefore typically miss the opportunity of preconception/early prenatal folic acid supplementation. The focus should be placed on women of child-bearing age to take folic acid supplements.
Targeting adequate prenatal nutrient status is a relatively simple preventative option in relation to the wider implications and burden it has on health, development and the allocated resources for treating the subsequent conditions and diseases that emerge.
- Charlton, K.E., H. Yeatman, E. Brock, C. Lucas, L. Gemming, A. Goodfellow, and G. Ma, (2013) ‘Improvement in iodine status of pregnant Australian women 3years after introduction of a mandatory iodine fortification programme.’ Prev Med. 57(1): p. 26-30.
- Clifton, V.L., N.A. Hodyl, P.A. Fogarty, D.J. Torpy, R. Roberts, T. Nettelbeck, G. Ma, and B. Hetzel, (2013) ‘The impact of iodine supplementation and bread fortification on urinary iodine concentrations in a mildly iodine deficient population of pregnant women in South Australia.’ Nutr J. 12: p. 32.
- Hynes, K.L., P. Otahal, I. Hay, and J.R. Burgess, (2013) ‘Mild iodine deficiency during pregnancy is associated with reduced educational outcomes in the offspring: 9-year follow-up of the gestational iodine cohort.’ J Clin Endocrinol Metab. 98(5): p. 1954-62.
- van Mil, N.H., H. Tiemeier, J.J. Bongers-Schokking, A. Ghassabian, A. Hofman, H. Hooijkaas, V.W. Jaddoe, S.M. de Muinck Keizer-Schrama, E.A. Steegers, T.J. Visser, W. Visser, H.A. Ross, F.C. Verhulst, Y.B. de Rijke, and R.P. Steegers-Theunissen, (2012) ‘Low urinary iodine excretion during early pregnancy is associated with alterations in executive functioning in children.’ J Nutr. 142(12): p. 2167-74.
- Koletzko, B., E. Lien, C. Agostoni, H. Bohles, C. Campoy, I. Cetin, T. Decsi, J.W. Dudenhausen, C. Dupont, S. Forsyth, I. Hoesli, W. Holzgreve, A. Lapillonne, G. Putet, N.J. Secher, M. Symonds, H. Szajewska, P. Willatts, and R. Uauy, (2008) ‘The roles of long-chain polyunsaturated fatty acids in pregnancy, lactation and infancy: review of current knowledge and consensus recommendations.’ J Perinat Med. 36(1): p. 5-14.
- Kulkarni, A., S. Mehendale, H. Pisal, A. Kilari, K. Dangat, S. Salunkhe, V. Taralekar, and S. Joshi, (2011) ‘Association of omega-3 fatty acids and homocysteine concentrations in pre-eclampsia.’ Clin Nutr. 30(1): p. 60-4.
- Saldeen, P. and T. Saldeen, (2006) ‘Omega-3 Fatty acids: structure, function, and relation to the metabolic syndrome, infertility, and pregnancy.’ Metab Syndr Relat Disord. 4(2): p. 138-48.
- Emmett, R., S. Akkersdyk, H. Yeatman, and B.J. Meyer, (2013) ‘Expanding awareness of docosahexaenoic acid during pregnancy.’ Nutrients. 5(4): p. 1098-109.
- Almeras, L., D. Eyles, P. Benech, D. Laffite, C. Villard, A. Patatian, J. Boucraut, A. Mackay-Sim, J. McGrath, and F. Feron, (2007) ‘Developmental vitamin D deficiency alters brain protein expression in the adult rat: implications for neuropsychiatric disorders.’ Proteomics. 7(5): p. 769-80.
- Kocovska, E., E. Fernell, E. Billstedt, H. Minnis, and C. Gillberg, (2012) ‘Vitamin D and autism: Clinical review.’ Res Dev Disabil. 33(5): p. 1541-50.
- McGrath, J.J., T.H. Burne, F. Feron, A. Mackay-Sim, and D.W. Eyles, (2010) ‘Developmental vitamin D deficiency and risk of schizophrenia: a 10-year update.’ Schizophr Bull. 36(6): p. 1073-8.
- Mirzaei, F., K.B. Michels, K. Munger, E. O’Reilly, T. Chitnis, M.R. Forman, E. Giovannucci, B. Rosner, and A. Ascherio, (2011) ‘Gestational vitamin D and the risk of multiple sclerosis in offspring.’ Ann Neurol. 70(1): p. 30-40.
- Whitehouse, A.J., B.J. Holt, M. Serralha, P.G. Holt, M.M. Kusel, and P.H. Hart, (2012) ‘Maternal serum vitamin D levels during pregnancy and offspring neurocognitive development.’ Pediatrics. 129(3): p. 485-93.
- Morales, E., I. Romieu, S. Guerra, F. Ballester, M. Rebagliato, J. Vioque, A. Tardon, C. Rodriguez Delhi, L. Arranz, M. Torrent, M. Espada, M. Basterrechea, and J. Sunyer, (2012) ‘Maternal vitamin D status in pregnancy and risk of lower respiratory tract infections, wheezing, and asthma in offspring.’ Epidemiology. 23(1): p. 64-71.
- Maghbooli, Z., A. Hossein-Nezhad, F. Karimi, A.R. Shafaei, and B. Larijani, (2008) ‘Correlation between vitamin D3 deficiency and insulin resistance in pregnancy.’ Diabetes Metab Res Rev. 24(1): p. 27-32.
- Bodnar, L.M., J.M. Catov, H.N. Simhan, M.F. Holick, R.W. Powers, and J.M. Roberts, (2007) ‘Maternal vitamin D deficiency increases the risk of preeclampsia.’ J Clin Endocrinol Metab. 92(9): p. 3517-22.
- Aghajafari, F., T. Nagulesapillai, P.E. Ronksley, S.C. Tough, M. O’Beirne, and D.M. Rabi, (2013) ‘Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observational studies.’ BMJ. 346: p. f1169.
- Boyages, S. and K. Bilinski, (2012) ‘Seasonal reduction in vitamin D level persists into spring in NSW Australia: implications for monitoring and replacement therapy.’ Clin Endocrinol (Oxf). 77(4): p. 515-23.
- Bilinski, K. and S. Boyages, (2013) ‘Evidence of overtesting for vitamin D in Australia: an analysis of 4.5 years of Medicare Benefits Schedule (MBS) data.’ BMJ Open. 3(6).
- Suren, P., C. Roth, M. Bresnahan, M. Haugen, M. Hornig, D. Hirtz, K.K. Lie, W.I. Lipkin, P. Magnus, T. Reichborn-Kjennerud, S. Schjolberg, G. Davey Smith, A.S. Oyen, E. Susser, and C. Stoltenberg, (2013) ‘Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children.’ JAMA. 309(6): p. 570-7.
- Roth, C., P. Magnus, S. Schjolberg, C. Stoltenberg, P. Suren, I.W. McKeague, G. Davey Smith, T. Reichborn-Kjennerud, and E. Susser, (2011) ‘Folic acid supplements in pregnancy and severe language delay in children.’ JAMA. 306(14): p. 1566-73.
- Wehby, G.L., T.M. Felix, N. Goco, A. Richieri-Costa, H. Chakraborty, J. Souza, R. Pereira, C. Padovani, D. Moretti-Ferreira, and J.C. Murray, (2013) ‘High dosage folic acid supplementation, oral cleft recurrence and fetal growth.’ Int J Environ Res Public Health. 10(2): p. 590-605.