Intelligence and the weight of evidence

The “weight of evidence” is a phrase included in the book The Neuroscience of Intelligence by Richard J. Haier (Cambridge University Press, 2017, New York).  In many areas of study including neuroscience research results may vary somewhat or even give opposite results. The concept of evidence-based medicine suggests we should trust the evidence but – which evidence if there is differing results? The National Clearinghouse Guidelines listed in a recent post were screened for quality of evidence – was there a preponderance of studies that had fairly similar results?

In the last post I mentioned that it was good news that the medical use of magnesium or Epsom salts was mentioned as early as the 17th century and written about in a medical journal in the early 1900’s – it suggests a preponderance of evidence – a “weight of evidence” regarding the medical benefit of magnesium.

In the introduction of the book The Neuroscience of Intelligence the author states that the information in the book is screened and included based on three laws that could be applied to most areas of scientific evidence – paraphrased:

  1. no story about medical evidence is simple;
  2. no one research study is adequate to prove a theory on its own;
  3. it generally takes many years to rule out conflicting and inconsistent research results and establish a weight of evidence. (p xiv, The Neuroscience of Intelligence,  Richard J. Haier)

The book is written for the non-neuroscientist who is interested in gaining an in depth overview of the advances made in the study of the intelligence and the brain for the purpose of general knowledge or for creating policies that are based on realistic expectations of human ability. There have been theories that have not been upheld when larger groups were involved. Intelligence can be affected positively or negatively by early childhood experiences and by better nutrition however  by later adolescence and adulthood years the differences are more affected by genetic potential whether parents were rich or poor, whether schools were average or above average. Many genes are involved however, affecting many pathways throughout the brain. Intelligence and creativity isn’t just located in the frontal area of the brain or in just the right hemisphere.

From a magnesium perspective an interesting point that stood out for me was on page 61. Genes that have been found to be involved in intelligence include several that encode glutamate receptors. Background information: Alzheimer’s disease tends to cause more damage in areas of the brain that have a greater number of glutamate receptors – and adequate magnesium is necessary to help protect brain cells from being overexcited by too much glutamate (an amino acid used in flavoring agents, a commonly known type is MSG, Mono sodium glutamate). Glutamate can open the receptors in the cell membranes while the presence of magnesium inside of the cell can keep them closed. NMDA receptors are discussed on pages 101-102 of the book Magnesium and the Central Nervous System and is mentioned 249 times in the book, (the ebook has a useful search feature). (2) 

Excess calcium being allowed to enter the cell can also overexcite cells to the point of cell death. Too much or too little activity of the NMDA receptors can cause problems with health or damage cells. Overexcitatory activity of the NMDA receptors has been associated with damage from ischemic stroke, traumatic brain injury, neonatal brain injury, and neurodegenerative conditions (which include Alzheimer’s Disease, p 104, (2)). Too much magnesium has been known to cause neonatal brain injury when given intravenously or intramuscularly for the expectant mother during preeclampsia/eclampsia to reduce seizures (3), or for other causes of preterm labor – some magnesium is protective for the fetal brain but too much can negatively affect fetal brain cells. (p103, Mg & the CNS, (2)) 

On page 61 of the book The Neuroscience of Intelligence (1)  genes involved with pathways that influence  glutamate binding with NMDA receptors are mentioned including KNCMA1, NRXN1, POU2F3, and SCRT. (1Both books mention that the NMDA receptors and glutamate as a neurotransmitter are involved with learning and memory. (p101, 2) 

A brief look at what might be known about those genes suggests differences in them may be associated with spasticity, (4), “epilepsy, ataxia, mental retardation, and chronic pain,” (7), alcohol abuse, (5), cervical cancer, (6), – a wide variety of conditions not just learning and memory. Take home point – magnesium is important for learning and memory and general health in an adequate amount, but not excessive amount if given intravenously or intramuscularly.

/Disclosure: This information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes./ 

  1. Richard J. Haier, The Neuroscience of Intelligence, (Cambridge University Press, 2017, New York), http://www.richardhaier.com/the-neuroscience-of-intelligence/ (1)
  2. Robert Vink, Mihai Nechifor, editors, Magnesium in the Central Nervous System, University of Adelaide Press, 2011, adelaide.edu.au, free ebook pdf, https://www.adelaide.edu.au/press/titles/magnesium/magnesium-ebook.pdf  (2) 
  3. Magnesium Sulfate for Seizure Prevention During Pregnancy, American College of Cardiology,  cardiosmart.org,   https://www.cardiosmart.org/healthwise/hw67/281/hw67281 (3)
  4. Baker D., Big conductance calcium-activated potassium channel openers control spasticity without sedation., Queen Mary University of London, https://qmro.qmul.ac.uk/xmlui/bitstream/handle/123456789/24743/BakerBigconductance2017accepted.pdf?sequence=1 (4)
  5. Jill C. Bettinger, Andrew G. Davies, The role of the BK channel in ethanol response behaviors: evidence from model organism and human studies. Front. Physiol., 09 September 2014,   https://www.frontiersin.org/articles/10.3389/fphys.2014.00346/full (5)
  6. Z Zhang, PC Huettner, L Nguyen, M Bidder, MC Funk, J Li, JS Rader, Aberrant promoter methylation and silencing of the POU2F3 gene in cervical cancer, Oncogene vol 25, pp 5436–5445 (31 August 2006), https://www.nature.com/articles/1209530 (6)
  7. C. Contet, S. P. Goulding, D. A. Kuljis, and A. L. Barth, BK Channels in the Central Nervous System, Europe PMC Article,  Int Rev Neurobiol. 2016; 128: 281–342. http://europepmc.org/articles/PMC4902275/ (7)

 

To have optimal Magnesium needs Protein and Phospholipids too

Good news and bad news – magnesium in the form of Epsom salt, magnesium sulfate, has been in use medicinally since the seventeenth century and written about in peer reviewed medical journals since the early nineteenth century. (1) That is both the good and bad news – it is helpful, but it still isn’t used for many conditions where it might be needed. It is not patentable as a pharmaceutical medication because it is a natural substance. It or magnesium chloride and some other forms are in use for a few conditions including preeclampsia, migraines, stroke, and traumatic brain injury. Minor athletic injuries may be treated with Epsom salt soaks (3) and some psychiatric care providers may also recommend the treatment. 

A textbook on the topic of magnesium use for medical conditions reviews the mineral’s role in the body during health and chronic illness or when genetic differences in metabolism are present. It is complex metabolically and just taking a supplement doesn’t always get magnesium to the problem area of the body. Magnesium is primarily found within cells, and most is bound to proteins or phospholipids rather than as free ions, in blood plasma or other extracellular fluid and not all forms can cross the blood brain barrier to help with migraines or other brain injuries.(1) Magnesium sulfate and magnesium chloride have been found helpful for those purposes (1) and both can be used topically which can bypass problems with poor absorption in the digestive system. (3 

Magnesium oxide is a form sometimes used in supplements that has been found to be very poorly absorbed even when the digestive system is in normal health. Only four percent of a dose is likely to be absorbed and the remaining 96% tends to cause loose stools by causing the intestinal muscles to relax too much if the supplement is in a larger dose. (1) Math – a 250 mg supplement of magnesium oxide might only have 10 milligrams absorbed and 240 milligrams pass through in the next bowel movement.  

Magnesium aspartate has been found helpful in some research studies, but the aspartate is an excitatory amino acid that can cause overactivity within brain cells possibly even leading to cell death, so it may not be ideal for people with some conditions such as headaches or brain injury. Other forms of supplements found to typically be well absorbed include magnesium citrate and magnesium glycinate. More recent research is using magnesium threonate as a form that may be more likely to be absorbed through the blood brain barrier. (1) 

Summary points:  

Symptoms of deficiency may include:  

  • Headaches or migraines may be a symptom because magnesium is used within the brain to protect against excess calcium or glutamate entry into brain cells. It is involved in fluid balance so high blood pressure may occur; tiredness and easy weight gain may be symptoms of chronic deficiency as it may cause insulin resistance and is essential within metabolism to turn sugar into a form of usable energy. Muscle cramps are also a common symptom of magnesium deficiency and may include a twitching of the eyelids. Tinnitus, a constant dull ringing sound in the ears, can occur. (1) (2) 

Food sources of magnesium include: 

  • Green leafy vegetables, broccoli, cauliflower, cabbage, sweet potato, squash; fruit, bananas; dark chocolate; beans, tofu; nuts such as cashews & almonds; pumpkin, pomegranate and sesame seeds, tahini; peanuts; brown rice, whole grains; yogurt. (2) 
Magnesium Food Sources and Symptoms of Deficiency.

Topical sources of magnesium include:  

    • Epsom salt, magnesium sulfate, can be used in baths or foot-soaks, or in damp poultices placed on other sore body parts. For a bath, about one cup of salt in a half bath, soak for 20 minutes three times a week, no more than 40 minutes to avoid excess absorption.
      Symptoms of excess absorption can include slowing heart rate, an overly relaxed muscles which can cause loose stools, for up to a day if very excessive. (3)
      An advantage of magnesium sulfate includes the sulfate in a form that doesn’t need sunshine exposure to skin in order for the body to be able to transform sulfur found in foods into the bioactive sulfate form. 
  • Magnesium chloride is available for topical use in body lotions & as an oily feeling liquid solution.People with digestive problems may not be absorbing much magnesium from food or supplements. 
Topical sources of Magnesium and bioactive Sulfate.

Supplemental forms of magnesium may include: 

    • Magnesium citrate, Mg glycinate, Mg L-threonate, Mg lysinate, Mg orotate, Mg malate, and Mg taurate are all fairly well absorbed forms and generally don’t cause side effects when taken in smaller amounts a few times a day (200-250 mg) instead of in a large dose (more than 400 mg in a single dose). People using diuretics or with increased sweat or urine losses for other reasons may need extra magnesium intake to make up for increased loss of magnesium in urine or sweat. People with late stage kidney disease may need to avoid excess Mg intake. (1) (4) 
  • Magnesium sulfate can be taken in water in very small amounts (a few crystals, a very tiny amount) (3), & it or Mg chloride may also be available in capsule form.
    Magnesium aspartate is well absorbed but the aspartate is an excitatory amino acid and may cause headaches for some users. 
  • Magnesium oxide is poorly absorbed (~ only 4%) & may cause loose stools for more users than the other forms. (1) 
Supplemental sources of Magnesium.

 

Food Sources of Phospholipids and other phospho-nutrients:

Hemp seed kernels and oil; Artemisia turanica/wormwood leaf; amaranth seed; asparagus; avocado fruit or the inner kernel, dried and powdered; beans/legumes; cardamom seeds and powder; carrots; celery stalks and leaves; cocoa beans and cocoa powder, baker’s chocolate, dark chocolate and to a lesser amount milk chocolate and chocolate syrup; coconut; cumin seed/powder; fennel seed, flax seed, pine nuts; sesame seeds, pumpkin seed kernels, squash seeds; butternut squash and pumpkin; gingko leaf; grapefruit and orange juice with the pulp; Jerusalem artichoke (this is a root vegetable rather than a green artichoke); lettuce, spinach and mustard leaves and other leafy green vegetables and herbs; nuts/peanuts, cashews, walnuts; oats; okra seeds; onion root, leek leaves, garlic;  parsnip root; pomegranate seeds and pomegranate peel extract;rice, white or brown but the bran is the best source; rosemary; sorghum;  sweet potato or yam; buckwheat (a seed botanically that is not wheat and is gluten free); wheat. (G.26)   

More information about protein and water needs are available in a post about kidney health: Make every day Kidney Appreciation Day.

/Disclosure: This information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes./ 

  1. Robert Vink, Mihai Nechifor, editors, Magnesium in the Central Nervous System, University of Adelaide Press, 2011, adelaide.edu.au, free ebook pdf, https://www.adelaide.edu.au/press/titles/magnesium/magnesium-ebook.pdf  (1
  2. Rachael Link, MS, RD,Top 10 Magnesium-rich Foods, Plus Proven Benefits, DrAxe.com, https://draxe.com/magnesium-deficient-top-10-magnesium-rich-foods-must-eating/ (2
  3. Magnesium sulfate (Epsom salt) – Side Effects Dosage, Interactions, everydayhealth.com https://www.everydayhealth.com/drugs/magnesium-sulfate (3
  4. Magnesium Types Compared: What is the Best Magnesium for You?, swansonvitamins.com, https://www.swansonvitamins.com/blog/chelsea/magnesium-types-compared  (4

Pre-eclampsia means pre convulsions; a life threatening prenatal condition.

Eclampsia is an old medical term for convulsions and has been a known risk with pregnancy for many centuries. (G5.1) In more recent centuries the earlier warning signs of pre-eclampsia have been recognized and include high blood pressure, protein in the urine, and edema – increased swelling in the legs, arms and face. Many women may experience increased puffiness or swelling in the lower legs during later stages of pregnancy and it can be painful to walk with swollen feet. In the more severe condition fluid is also collecting in other areas of the body on the exterior of cells instead of being collected by lymphatic or blood vessels and excreted as urine as in normal health.

Why the condition occurs is not known although some risk factors are known. It is more of a risk for very young women, (G5.3); very young women who are also overweight, (G5.4); overweight women; or women over age 40; women who are pregnant with twins, triplets, or more; women of African ethnicity;  women with a history or currently have high blood pressure; and any women who already had pre-eclampsia during previous pregnancies, or who have a family history of other women in their family (such as the pregnant woman’s sisters or her mother) having had pre-eclampsia. (G5.2) Very low calcium intake may increase risk. (G5.1)

What is known is that the condition or related high blood pressure conditions during pregnancy are a significant cause of maternal deaths, 18% of all maternal deaths in the U.S., and of neonatal/infant deaths, over 10,000 each year in the U.S.. It is also more frequently associated with preterm delivery of infants which can leave the infant more at risk for many other chronic health or development complications. (G5.1)

My health is not great, but it has been worse – I prefer better than worse. On my bucket list is to continue working on collating available research regarding the simple question – Why did simply adding raw shelled pumpkin seeds help my previous prenatal clients prevent the risk of having pre-eclampsia during their later pregnancies.

Possible answers: genetic variations in the TREK 1 potassium ion channels may leave women in some families more at risk for developing preeclampsia due to their membranes being less responsive as normal to changes in acidity or stretch – swelling. (G5.5) The preventative health solution might be too eat a more alkaline promoting diet, a more vegetable based diet rather than excess meats and dairy foods.

Very young women and women of African ethnicity may be more at risk due to less space within the abdomen and pelvic cavity. Young women may be smaller framed than more fully mature women in their twenties and the pelvic shape of women of African ethnicity is slightly narrower than that of other ethnic groups (may be a better shape for running fast though.) A hypothesis suggests a preventative health strategy that includes spending a half hour or so daily or periodically during the day in a position where the head is rested on the arms on a pillow while kneeling so the abdomen is inverted slightly and is above the heart – to help fluid movement and relieve pressure in the area around the baby. (G5.6)

The position that is recommended in the hypothesis article (G5.6) can be seen in this article, see Figure 3, Knee-Chest Position: (G5.7). It would likely help women with a family history of preeclampsia too if TREK 1 variations were involved, to relieve intra-abdominal pressure, or for any prenatal woman in the third trimester. The position can also help promote the infant remaining or moving to a head down position which is safer for delivery (preventing a breech birth delivery).

Pumpkin seeds may be particularly helpful due to being a good source of many nutrients including magnesium, (G5.13), zinc, (G5.11), and phospholipids. (G.26) Cocoa/chocolate is also a good source of magnesium and phospholipids (G.26) and women who report eating chocolate several times per week prenatally has been associated with less risk for preeclampsia. (G5.8)(G5.9) Zinc levels have been found to be significantly lower in women with preeclampsia than in pregnant women not experiencing preeclampsia. (G5.12)  Pumpkin seeds may also help due to omega 3 fatty acid content (G5.11) which has also been found to help reduce risk of preeclampsia. (G5.10Pumpkin seeds  or pumpkin seed oil may help prevent preeclampsia due to increased detoxification and removal of toxins from the body as they may cause a diuretic effect. (G5.11)

Pumpkin seeds are a good source of many minerals. Just two tablespoons provides about 25% of the daily recommendation for magnesium. (G5.13) They are also a source of manganese and other trace minerals including selenium. A larger serving of 100 grams (1/3-1/2 cup) would provide 17% of the daily recommendation for selenium and almost 200% of the recommendation for manganese. (G5.14) Supplements of 100 micrograms of selenium per day  for 6-8 weeks during later pregnancy were found beneficial for preventing pregnancy induced hypertension – high blood pressure in the later part of pregnancy is an early sign of preeclampsia. (G5.15)

Balance of nutrients is important and loss of nutrients due to increased oxidative stress may be the underlying problem rather than deficiency. Selenium, magnesium, and manganese levels were found to be comparable in women who did and did not develop preeclampsia in later pregnancy however the women who did develop the condition had elevated copper levels in early pregnancy. (G5.16) Copper and zinc levels need to be in balance with each other for optimal health.

Why should we care? The risk of complications or death for mothers and infants due to pre-eclampsia is significant and is worse in undeveloped nations. The rate of maternal death has been increasing in the U.S. and now is worse than that of other developed nations. Other developed nations range from four to nine maternal deaths per 100,000 live births while in the U.S. the rate has worsened to 26.4 maternal deaths per 100,000 live births. (G5.17) If 18% of those deaths are due to preeclampsia, (G5.1), then in 2015 when there were 3,978,497 births, (G5.18), approximately 189 families lost a mother due to the dangers of preeclampsia.

This is an introduction to the topic, a longer draft is available here: G5: Preeclampsia & TRP Channels, which does not contain some of the information in this post – yet.

Traveling is fun, I took pictures, but traveling the internet saves gasoline. Bucket list – before I kick the bucket I hope to continue working on ways to help women identify their individual risk factors that may be involved in preeclampsia and identify ways to reduce those risks. Like many problems a similar set of symptoms can have a variety of underlying causes, not just one cause, one set of symptoms. Health requires many things, not just one simple solution.

This may seem melodramatic however my health has been bad enough over the years and more recently to make me very appreciative of health and mental health. Dementia is a very real problem and one that is growing in number of people effected either as patients or as caregivers. I have improved my health but it required many changes in diet and lifestyle habits that  are ongoing, missing a day or two can send me back into negative health symptoms.

Magnesium is an important part of preeclampsia care that may also be needed for dementia. I will also post my initial draft on a magnesium  article I began working on after reading a textbook: Magnesium and the Central Nervous System, (free Magnesium ebook, adelaide.edu.au).  The short message that overlaps with this post is that to have adequate magnesium stores within the cells where it is needed for optimal health then it is likely also essential to have adequate protein intake and phospholipid intake. Something that I have found important that is not included in the text or other current medical articles on the topic is that for some people topical sources of magnesium such as Epsom salt/magnesium sulfate baths or footsoaks or magnesium chloride hand lotions or topical liquid solutions may be needed to bypass problems with intestinal absorption of magnesium.

  • Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.

G.26: Arlen Frank, Chemistry of Plant Phosphorus Compounds, Elsevier, Jun 3, 2013, https://books.google.com/books/about/Chemistry_of_Plant_Phosphorus_Compounds.html?id=6btpFSV1T2YC (G.26)  

Robert Vink, Mihai Nechifor, editors, Magnesium in the Central Nervous System, University of Adelaide Press, 2011, adelaide.edu.au, free ebook pdf, https://www.adelaide.edu.au/press/titles/magnesium/magnesium-ebook.pdf 

  1. John D. MacArthur, Placental Fluorosis: Fluoride and Preeclampsia, Townsend Letter, May 2015; 382:74-79. http://www.townsendletter.com/May2015/placental0515.html (G5.1)
  2. Who is at risk of Preeclampsia?, NICHD, Eunice Kennedy Shriver National Institute of Child Health and Human Development,  https://www.nichd.nih.gov/health/topics/preeclampsia/conditioninfo/Pages/risk.aspx (G5.2)
  3. Priscila E Parra-Pingel, Luis A Quisiguiña-Avellán, Luis Hidalgo, Peter Chedraui, Faustino R Pérez-López, Pregnancy outcomes in younger and older adolescent mothers with severe preeclampsia, Adolesc Health Med Ther. 2017; 8: 81–86. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5476435/ (G5.3)
  4. Mulualem Endeshaw, Fantu Abebe, Solomon Worku, Lalem Menber, Muluken Assress, Muluken Assefa, Obesity in young age is a risk factor for preeclampsia: a facility based case-control study, northwest Ethiopia. BMC Pregnancy Childbirth. 2016; 16: 237. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992278/ (G5.4)
  5. Chad L. Cowles, Yi-Ying Wu, Scott D. Barnett, Michael T. Lee, Heather R. Burkin, Iain L.O. Buxton, Alternatively Spliced Human TREK-1 Variants Alter TREK-1 Channel Function and Localization. Biol Reprod. 2015 Nov; 93(5): 122. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712007/ (G5.5)
  6. Diane J.Sawchuck, Bernd K.Wittmann, Pre-eclampsia renamed and reframed: Intra-abdominal hypertension in pregnancy, Medical Hypotheses, Vol 83, Iss 5, Nov 2014, pp 619-632 
    http://www.sciencedirect.com/science/article/pii/S0306987714002722  (G5.6)
  7. Marybeth Lore, MD, Umbilical Cord Prolapse and Other Cord Emergencies, Citation Lore, M, Glob. libr. women’s med., (ISSN: 1756-2228) 2017; DOI 10.3843/GLOWM.10136 https://www.glowm.com/section_view/heading/Umbilical%20Cord%20Prolapse%20and%20Other%20Cord%20Emergencies/item/136 (G5.7)
  8. Elizabeth W Triche, Laura M Grosso, Kathleen Belanger, Amy S Darefsky, Neal L Benowitz, Michael B Bracken. Chocolate consumption in pregnancy and reduced likelihood of preeclampsia. Epidemiology. 2008 May;19(3):459-64. PMID: 18379424 http://www.greenmedinfo.com/article/chocolate-consumption-during-pregnancy-may-reduce-likelihood-preeclampsia (G5.8)
  9. Audrey F Saftlas, Elizabeth W Triche, Hind Beydoun, Michael B Bracken. Does chocolate intake during pregnancy reduce the risks of preeclampsia and gestational hypertension? Ann Epidemiol. 2010 Aug;20(8):584-91. PMID: 20609337  http://www.greenmedinfo.com/article/chocolate-intake-during-pregnancy-may-reduce-risks-preeclampsia-and-gestationa (G5.9)
  10. M A Williams, R W Zingheim, I B King, A M Zebelman. Omega-3 fatty acids in maternal erythrocytes and risk of preeclampsia. Epidemiology. 1995 May;6(3):232-7. PMID: 7619928 http://www.greenmedinfo.com/article/omega-3-fatty-acid-consumption-may-contribute-reduction-risk-preeclampsia (G5.10)
  11. Pumpkin Seeds versus Pumpkin Seed Oil, Activation Products Blog, https://www.activationproducts.com/blog/pumpkin-seeds-vs-pumpkin-seed-oil/ (G5.11)
  12. Yue Ma, Xiaoli Shen, Dongfeng Zhang, The Relationship between Serum Zinc Level and Preeclampsia: A Meta-Analysis. Nutrients. 2015 Sep; 7(9): 7806–7820. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4586561/ (G5.12)
  13. Megan Ware, RDN, LD, What are the Health Benefits of Pumpkin Seeds?  Jan. 18, 2017, MedicalNewsToday.com, https://www.medicalnewstoday.com/articles/303864.php (G5.13)
  14. Pumpkin Seeds: Nutrition Facts, nutrition-and-you.com, https://www.nutrition-and-you.com/pumpkin-seeds.html (G5.14)
  15. L Han, S M Zhou. Selenium supplement in the prevention of pregnancy induced hypertension. Chin Med J (Engl). 1994 Nov;107(11):870-1. PMID: 7867399 http://www.greenmedinfo.com/article/selenium-supplementation-may-contribute-reduction-risk-pregnancy-induced-hyper (G5.15)
  16. Hiten D. Mistry, Carolyn A. Gill, Lesia O. Kurlak, Paul T. Seed, John E. Hesketh, Catherine Méplan, Lutz Schomburg, Lucy C. Chappell, Linda Morgan, Lucilla Poston, Association between maternal micronutrient status, oxidative stress, and common genetic variants in antioxidant enzymes at 15 weeks׳ gestation in nulliparous women who subsequently develop preeclampsia. Free Radic Biol Med. 2015 Jan; 78: 147–155. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4291148/ (G5.16)
  17. Nina Martin, Renee Montagne, U.S. has the Worst Rate of Maternal Deaths in the Developed World, May 12, 2017, NPR, https://www.npr.org/2017/05/12/528098789/u-s-has-the-worst-rate-of-maternal-deaths-in-the-developed-world (G5.17)
  18. Birth Data, National Vital Statistics System, CDC, https://www.cdc.gov/nchs/nvss/births.htm (G5.18)