One Parent,Two Parents and Child Well-Being

The structure of the family in the United States and other countries is changing. 

This change has occurred over a relatively brief period of time. Data noted in the study I am reviewing today shows that between 1970 and 2013 in the U.S.:

• Percentage of children living with two parents dropped 24%
• Percentage of children living with a single mother increased to 23.7%
• Percentage of children living with a single father quadrupled to 4.1%
• Percentage of children living with a grandparent doubled to 6.2%

It is important to understand how these changes in the structure of family effects children across a variety of domains.

This topic is the focus of an important manuscript published in Population Health Metrics. Patrick Krueger along with four colleagues summarized data related to parental structure and child well-being using the National Health Interview Survey.

They grouped parental structure into nine parental groups. Using married couples (comprising 67% of the sample) as a reference parental unit other structural units in the study included: cohabiting non-married couples, single mother, single father, extended married couple, extended cohabiting couple, extended single mother, extended single mother and skipped generation (care by grandparent). Extended modifiers were added to parental structure when at least one grandparent was available and provided direct care activity to the child.

Children with the various parental structures were compared across multiple variables. The findings that stood out to me included the following:

• Children of married couples generally show higher markers of well-being. However, this effect is reduced but not eliminated when controlling for socioeconomic status
• Children living with a single father fared better than children living with a single mother--fewer ER visits, fewer missed school days, better global health status
• The presence of an extended grandparent did not appear to significantly buffer the effect of single parent on health well-being and other well-being measures
• Learning disabilities and child ADHD rates were highest in children of single mothers and children being raised by grandparents
• Children of single mothers were more likely to be reported as having several medical problems including headaches, ear infections, asthma and anemia 

The findings from this study are important. The most important implication from my perspective is the need to identify at-risk children across all family structure groups. Targeting assessment and intervention assistance in children of single mother and grandparents may produce the highest improvement in well-being and outcome.

The additional services required to address changes in parental structure are evident. Improving access to child medical and mental health care seems to be a key first step. Providing additional financial assistance, assistance with transportation and regular day care support is needed. Expanding early childhood education programs and integrating medical and mental health services with school services may also benefit those most at risk.

There is a load of data in this important paper that readers may want to review in more detail. The free full-text manuscript can be accessed by clicking on the PMID link in the citation below.

Photo of brown pelican is from the author's files.

Follow the author on Twitter WRY999

Krueger PM, Jutte DP, Franzini L, Elo I, & Hayward MD (2015). Family structure and multiple domains of child well-being in the United States: a cross-sectional study. Population health metrics, 13 PMID: 25729332

Infectious disease - Syllabus

10.1  Infectious diseases
10.2  Antibiotics

The infectious diseases studied in this section are caused by pathogens that  are transmitted from one human host  to another. Some, like Plasmodium that  causes malaria, are transmitted by vectors; others are transmitted through water and food or during sexual  activity. An understanding of the biology of the pathogen and its mode of transmission is essential if the disease is to be controlled and ultimately prevented.

Learning outcomes

Candidates should  be able to:

10.1  Infectious diseases

While many  infectious diseases have been successfully controlled in some parts  of the world, many people worldwide are still at risk of these diseases.

a)   define  the term  disease and explain the difference between an infectious disease and a non-infectious disease (limited to sickle cell anaemia and lung cancer)

b)   state the name and type  of causative organism (pathogen) of each  of the following diseases: cholera,  malaria, tuberculosis (TB), HIV/AIDS, smallpox  and measles (detailed  knowledge of structure is not required. For smallpox  (Variola) and measles (Morbillivirus) only the name of genus is needed)

c)   explain how cholera,  measles, malaria, TB and HIV/AIDS are transmitted

d)   discuss the biological, social and economic factors that  need to be considered in the prevention and control of cholera, measles, malaria, TB and HIV/AIDS (a detailed study  of the life cycle of the malarial parasite is not required)

e)   discuss the factors that  influence the global patterns of distribution of malaria, TB and HIV/AIDS and assess the importance of these diseases worldwide

10.2  Antibiotics

The ‘age of antibiotics’  began in the 1940s with the  availability of penicillin. With an increase in antibiotic  resistance is this age about  to come to an end?

a)   outline  how penicillin acts  on bacteria and why antibiotics do not affect  viruses

b)   explain in outline  how bacteria become resistant to antibiotics with reference to mutation and selection

c)   discuss the consequences of antibiotic  resistance and the steps that  can be taken  to reduce its impact

Meat is best for growing brains

There are multiple lines of evidence that an animal-based diet best supports human brain development in infants and young children.

In brief / contents

• Human fetuses and infants rely on ketones for brain building.
• Weaning onto meat increases brain growth.
• The brain is an energy-intensive organ that required an animal-based diet to evolve.
• Because humans wean early, and human brain growth is extended past weaning, the post-weaning diet must support fetal-like brain growth.
• A high-fat animal-based diet best supports brain growth.

Human fetuses and infants rely on ketones for brain building.

In a previous post, we wrote about the known (but little-spoken-of) fact that human infants are in mild ketosis all the time, especially when breastfed. In other words, ketosis is a natural, healthy state for infants. Infancy is a critical time for brain growth, so we expect that ketosis is advantageous for a growing brain. Otherwise, there would have been a selective advantage to reduced ketotis in infancy. This species-critical, rapid brain growth continues well past weaning. For that reason, we suggest in our article that weaning onto a ketogenic diet would probably be preferable to weaning away from ketosis.

In response to that post, a reader sent us a paper called Survival of the fattest: fat babies were the key to evolution of the large human brain. [1]The authors discuss the apparently unique human trait of having extremely fat babies, and explain it in terms of the unique need for growth of extremely large brains.

A key point they make is that a baby's ample fat provides more than simply a large energy supply, (much more than could be stored as glycogen or protein; by their calculations, more than 20 times more), but that ketone bodies are themselves important for human brain evolution.

They repeat the usual unwarranted assumption that adult brains use mainly glucose for brain fuel by default, and that ketone bodies are merely an alternative brain fuel. Nonetheless, when talking about fetuses, they are willing to say that the use of ketones is not merely an "alternative":

In human fetuses at mid-gestation, ketones are not just an alternative fuel but appear to be an essential fuel because they supply as much as 30% of the energy requirement of the brain at that age (Adam et al., 1975).

Second, ketones are a key source of carbon for the brain to synthesize the cholesterol and fatty acids that it needs in the membranes of the billions of developing nerve connections.

[...]

Ketones are the preferred carbon source for brain lipid synthesis and they come from fatty acids recently consumed or stored in body fat. This means that, in infants, brain cholesterol and fatty acid synthesis are indirectly tied to mobilization and catabolism of fatty acids stored in body fat.

In other words, the claim is that ketones are the best source of certain brain-building materials, and specifically, that fetuses use them for that purpose.

Moreover, the thesis is that the extra body fat on human babies is there specifically for the purpose of supporting extra brain growth after birth, through continued use of ketones.

Weaning onto meat increases brain growth.

[ Please note that by convention weaning refers to the gradual process of transitioning from exclusive breastfeeding (starting with the first foods introduced, while breastfeeding is still ongoing), to the end of breastfeeding, not just the end itself. ]

We aren't the only ones who have thought weaning onto meat would be a good idea. A couple of studies have compared weaning onto meat rather than cereal.

One showed a larger increase in head circumference [2], which is a good index of brain growth in infants [3] and young children [4]. Moreover, higher increases in head circumference in infants are correlated with higher intelligence, independently of head circumference at birth [5]. In other words, the amount of brain growth after birth is a better predictor of intelligence than the amount of brain growth in gestation.

That study also found the meat-fed infants to have better zinc status, and good iron status despite not supplementing iron as was done in the cereal arm [2]. Zinc and iron are abundant in the brain, and zinc deficiency is implicated in learning disorders and other brain development problems [6]. Iron deficiency is a common risk in infants in our culture, because of our dietary practices, which is why infant cereal is fortified with it [7].

Another study showed better growth in general in babies weaned onto primarily meat [8].

---

Weaning onto meat is easy.Here's how I did it.

It is believed likely that early humans fed their babies pre-chewed meat [9]. I did that, too, although that wasn't my first weaning step.Influenced by baby-led weaning, I waited until he was expressing clear interest in my food, and then simply shared it with him.At the time this meant:

• Broth on a spoon, increasingly with small fragments of meat in it.
• Bones from steaks and chops, increasingly with meat and fat left on them.
• Homemade plain, unseasoned jerky, which he teethed on, or sucked until it disintegrated.
• Beef and chicken liver, which has a soft, silky texture, and is extremely nutrient-dense.

--Amber

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The brain is an energy-intensive organ that required an animal-based diet to evolve.

In 1995, anthropologists Leslie C. Aiello and Peter Wheeler posed the following problem [10]:

• Brains require an enormous amount of energy.
• Humans have much larger brains than other primates.
• However, human basal metabolic rates are not more than would be predicted by their body mass.

Where do we get the extra energy required to fuel our brains, and how could this have evolved?

Aiello and Wheeler explain this by noting that at the same time as our brains were expanding, our intestines (estimated as comparably energy-intensive) were shrinking, by almost exactly the same amount. thereby freeing up the extra metabolic energy needed for the brain. Both adaptations, a large brain and small guts, independently required them to adopt a "high-quality" diet, for different reasons.

Let's mince no words; "high-quality" means meat [11]. Meat is more nutrient dense than plants, both in terms of protein and vitamins. Plants are simply too fibrous, too low in protein and calories, and too seasonal to have been relied on for such an evolutionary change [11], [12]. It is widely accepted that meat became an important part of our diets during this change. This is the mainstream view in anthropology [13].

Although the need for protein and brain-building nutrients is often cited as a reason for needing meat in the evolutionary diet, energy requirements are also important to consider. It would have been difficult to get caloric needs met from plants (especially before cooking) [13], because they were so fibrous. Herbivores with special guts (such as ruminants like cows with their "four stomachs") and primates with much larger intestines than we have, actually use bacteria in their guts to turn significant amounts of fiber into fat, see eg. [14]. This strategy is not available to a such a small gut [11], [15], which is why we had to find food that was energy dense as is.

Fortunately, insofar as we were already using animal sources to get protein and nutrients, we also had access to an abundance of fat. The animals we hunted were unlikely to have been as lean as modern game. Evidence supports the hypothesis that human hunting was the most likely cause of the extinction of many megafauna (large animals that were much fatter than the leaner game we have left today) [16]. Humans, like carnivores, prefer to hunt larger animals whenever they are available [17]. It has been proposed that the disappearance of the fatter megafauna exerted a strong evolutionary pressure on humans, who were already fat-dependent, to become more skilled hunters of the small game we have today, to rely more on the fat from eating brains and marrow, and to learn to find the fattest animals among the herds [18].

Animal fat and animal protein provided the energy, protein, and nutrients necessary for large brains, especially given the constraint of small guts.

Because humans wean early, and human brain growth is extended past weaning, the post-weaning diet must support fetal-like brain growth.

Humans wean much earlier than other primates, and yet their brains require prolonged growth. Our intelligence has been our primary selective advantage. Therefore it is critical from an evolutionary standpoint that the diet infants were weaned onto was supportive of this brain growth.

In a (fascinating and well-written) paper on weaning and evolution, Kennedy puts it this way:

"[A]lthough this prolonged period of development i.e., ‘‘childhood’’ renders the child vulnerable to a variety of risks, it is vital to the optimization of human intelligence; by improving the child’s nutritional status (and, obviously, its survival), the capability of the adult brain is equally improved. Therefore, a child’s ability to optimize its intellectual potential would be enhanced by the consumption of foods with a higher protein and calorie content than its mother’s milk; what better foods to nourish that weanling child than meat, organ tissues (particularly brain and liver), and bone marrow, an explanation first proposed by Bogin (1997)."

...

"Increase in the size of the human brain is based on the retention of fetal rates of brain growth (Martin, 1983), a unique and energetically expensive pattern of growth characteristic of altricial [ born under-developed ] mammals (Portmann, 1941; Martin, 1984). This research now adds a second altricial trait—early weaning—to human development. The metabolically expensive brain produced by such growth rates cannot be sustained long on maternal lactation alone, necessitating an early shift to adult foods that are higher in protein and calories than human milk."

The only food higher in protein and calories than breast milk is meat.

A high-fat animal-based diet best supports brain growth.

Taking these facts together:

• Even modern fetuses and breastfed infants are in ketosis, which uniquely supports brain growth.
• Infants who are weaned onto meat get essential nutrients to grow brains with: nutrients that are currently deficient in our plant-centric diets today. Moreover, experiments have found that their brains actually grow more than babies fed cereal.
• Human brains continue to grow at a fast rate even past weaning.
• It is likely that in order to evolve such large, capable brains, human babies were weaned onto primarily meat.

A meat-based, inherently ketogenic diet is not only likely to be our evolutionary heritage, it is probably the best way to support the critical brain growth of the human child.

Acknowledgements

We would like to thank Matthew Dalby, a researcher at the University of Aberdeen, for helpful discussions about short-chain fatty acid production in the large intestines.

References

[1]	Hypothesis paper Survival of the fattest: fat babies were the key to evolution of the large human brain. Cunnane SC, Crawford MA. Comp Biochem Physiol A Mol Integr Physiol. 2003 Sep;136(1):17-26.

[2]

Evidence type: experiment Meat as a first complementary food for breastfed infants: feasibility and impact on zinc intake and status. Krebs NF, Westcott JE, Butler N, Robinson C, Bell M, Hambidge KM. J Pediatr Gastroenterol Nutr. 2006 Feb;42(2):207-14. (Emphasis ours) "OBJECTIVE: "This study was undertaken to assess the feasibility and effects of consuming either meat or iron-fortified infant cereal as the first complementary food. "METHODS: "Eighty-eight exclusively breastfed infants were enrolled at 4 months of age and randomized to receive either pureed beef or iron-fortified infant cereal as the first complementary food, starting after 5 months and continuing until 7 months. Dietary, anthropometric, and developmental data were obtained longitudinally until 12 months, and biomarkers of zinc and iron status were measured at 9 months. "RESULTS: "Mean (+/-SE) daily zinc intake from complementary foods at 7 months for infants in the meat group was 1.9 +/- 0.2 mg, whereas that of the cereal group was 0.6 +/- 0.1 mg, which is approximately 25% of the estimated average requirement. Tolerance and acceptance were comparable for the two intervention foods. Increase in head circumference from 7 to 12 months was greater for the meat group, and zinc and protein intakes were predictors of head growth. Biochemical status did not differ by feeding group, but approximately 20% of the infants had low (<60 microg/dL) plasma zinc concentrations, and 30% to 40% had low plasma ferritin concentrations (<12 microg/L). Motor and mental subscales did not differ between groups, but there was a trend for a higher behavior index at 12 months in the meat group. "CONCLUSIONS: "Introduction of meat as an early complementary food for exclusively breastfed infants is feasible and was associated with improved zinc intake and potential benefits. The high percentage of infants with biochemical evidence of marginal zinc and iron status suggests that additional investigations of optimal complementary feeding practices for breastfed infants in the United States are warranted."

[3]

Evidence type: authority [Head circumference and brain development. Growth retardation during intrauterine malnutrition and catch-up growth mechanisms (author's transl)]. [Article in German] Brandt I. Klin Wochenschr. 1981 Sep 1;59(17):995-1007. (Emphasis ours) "Today the close correlation between head circumference growth and brain development in the last weeks of gestation and in the first two years of life is no longer disputed. A recently developed formula even allows for calculations of brain weight based upon head circumference data. Between the ages of 32 postmenstrual weeks and six months after expected date of delivery there is a period of very rapid brain growth in which the weight of the brain quadruples. During this growth spurt there exists an increased vulnerability by unfavorable environmental conditions, such as malnutrition and psychosocial deprivation. The erroneous belief still being prevalent that the brain of the fetus and young infant is spared by malnutrition, can be looked upon as disproved by new research results. Severe malnutrition during the brain growth spurt is thought to be a very important non-genetic factor influencing the development of the central nervous system (CNS) and therewith intellectual performance. In the past a permanent growth retardation of head circumference and a reduced intellectual capacity usually was observed in small-for-gestational age infants (SGA). Nowadays, however, there can be found also proofs of successful catch-up growth of head circumference and normal intellectual development after early and high-energy postnatal feeding of SGA infants. The development of SGA infants of even very low birth weight can be supported in such a way that it takes a normal course by providing good environmental conditions, such as appropriate nutrition - especially during the early growth period - and a stimulating environment with abundant attention by the mother."

[4]

Evidence type: experiment Relationship between head circumference and brain volume in healthy normal toddlers, children, and adults. Bartholomeusz HH, Courchesne E, Karns CM. Neuropediatrics. 2002 Oct;33(5):239-41. (Emphasis ours) "OBJECTIVE: "To quantify the relationship between brain volume and head circumference from early childhood to adulthood, and quantify how this relationship changes with age. "METHODS: "Whole-brain volume and head circumference measures were obtained from MR images of 76 healthy normal males aged 1.7 to 42 years. "RESULTS: "Across early childhood, brain volume and head circumference both increase, but from adolescence onward brain volume decreases while head circumference does not. Because of such changing relationships between brain volume and head circumference with age, a given head circumference was associated with a wide range of brain volumes. However, when grouped appropriately by age, head circumference was shown to accurately predict brain volume. Head circumference was an excellent prediction of brain volume in 1.7 to 6 years old children (r = 0.93), but only an adequate predictor in 7 to 42 year olds. "CONCLUSIONS: "To use head circumference as an accurate indication of abnormal brain volume in the clinic or research setting, the patient's age must be taken into account. With knowledge of age-dependent head circumference-to-brain volume relationship, head circumference (particularly in young children) can be an accurate, rapid, and inexpensive indication of normalcy of brain size and growth in a clinical setting.

[5]

Evidence type: experiment Critical periods of brain growth and cognitive function in children. Gale CR1, O'Callaghan FJ, Godfrey KM, Law CM, Martyn CN. Brain. 2004 Feb;127(Pt 2):321-9. Epub 2003 Nov 25. "Head circumference is known to correlate closely with brain volume (Cooke et al., 1977; Wickett et al., 2000) and can therefore be used to measure brain growth, but a single measurement cannot provide a complete insight into neurological development. Different patterns of early brain growth may result in a similar head size. A child whose brain growth both pre‐ and postnatally followed the 50th centile might attain the same head size as a child whose brain growth was retarded in gestation but who later experienced a period of rapid growth. Different growth trajectories may reflect different experiences during sensitive periods of brain development and have different implications for later cognitive function. "We have investigated whether brain growth during different periods of pre‐ and postnatal development influences later cognitive function in a group of children for whom serial measurements of head growth through foetal life, infancy and childhood were available." [...] "We found no statistically significant associations between head circumference at 18 weeks’ gestation or head circumference at birth SDS and IQ at the age of 9 years." [...] "In contrast, there were strong statistically significant associations between measures of postnatal head growth and IQ. After adjustment for sex, full‐scale IQ rose by 2.59 points (95% CI 0.87 to 4.32) for each SD increase in head circumference at 9 months of age, and by 3.85 points (95% CI 1.96 to 5.73) points for each SD increase in head circumference at 9 years; verbal IQ rose by 2.66 points (95% CI 0.49 to 4.83) for each SD increase in head circumference at 9 months of age, and by 3.76 points (95% CI 1.81 to 5.72) for each SD increase in head circumference at 9 years; performance IQ rose by 2.88 points (95% CI 0.659 to 5.11) for each SD increase in head circumference at 9 months of age, and by 3.16 points (95% CI 1.16 to 5.16) for each SD increase in head circumference at 9 years." [...] "[W]e interpret these findings as evidence that postnatal brain growth is more important than prenatal brain growth in determining higher mental function. This interpretation is supported by the finding that head growth in the first 9 months of life and head growth between 9 months and 9 years of age are also related to cognitive function, regardless of head size at the beginning of these periods."

[6]

Evidence type: review Zinc, the brain and behavior. Pfeiffer CC, Braverman ER. Biol Psychiatry. 1982 Apr;17(4):513-32. "The total content of zinc in the adult human body averages almost 2 g. This is approximately half the total iron content and 10 to 15 times the total body copper. In the brain, zinc is with iron, the most concentrated metal. The highest levels of zinc are found in the hippocampus in synaptic vesicles, boutons, and mossy fibers. Zinc is also found in large concentrations in the choroid layer of the retina which is an extension of the brain. Zinc plays an important role in axonal and synaptic transmission and is necessary for nucleic acid metabolism and brain tubulin growth and phosphorylation. Lack of zinc has been implicated in impaired DNA, RNA, and protein synthesis during brain development. For these reasons, deficiency of zinc during pregnancy and lactation has been shown to be related to many congenital abnormalities of the nervous system in offspring. Furthermore, in children insufficient levels of zinc have been associated with lowered learning ability, apathy, lethargy, and mental retardation. Hyperactive children may be deficient in zinc and vitamin B-6 and have an excess of lead and copper. Alcoholism, schizophrenia, Wilson's disease, and Pick's disease are brain disorders dynamically related to zinc levels. Zinc has been employed with success to treat Wilson's disease, achrodermatitis enteropathica, and specific types of schizophrenia."

[7]

Evidence type: authority From the CDC: "Who is most at risk? Young children and pregnant women are at higher risk of iron deficiency because of rapid growth and higher iron needs. Adolescent girls and women of childbearing age are at risk due to menstruation. Among children, iron deficiency is seen most often between six months and three years of age due to rapid growth and inadequate intake of dietary iron. Infants and children at highest risk are the following groups: Babies who were born early or small. Babies given cow's milk before age 12 months. Breastfed babies who after age 6 months are not being given plain, iron-fortified cereals or another good source of iron from other foods. Formula-fed babies who do not get iron-fortified formulas. Children aged 1–5 years who get more than 24 ounces of cow, goat, or soymilk per day. Excess milk intake can decrease your child's desire for food items with greater iron content, such as meat or iron fortified cereal. Children who have special health needs, for example, children with chronic infections or restricted diets.

[8]

Evidence type: experiment High protein intake from meat as complementary food increases growth but not adiposity in breastfed infants: a randomized trial Minghua Tang and Nancy F Krebs Am J Clin Nutr October 2014 ajcn.088807 (Emphasis ours) "Background: High intake of cow-milk protein in formula-fed infants is associated with higher weight gain and increased adiposity, which have led to recommendations to limit protein intake in later infancy. The impact of protein from meats for breastfed infants during complementary feeding may be different. "Objective: We examined the effect of protein from meat as complementary foods on growths and metabolic profiles of breastfed infants. "Design: This was a secondary analysis from a trial in which exclusively breastfed infants (5–6 mo old from the Denver, CO, metro area) were randomly assigned to receive commercially available pureed meats (MEAT group; n = 14) or infant cereal (CEREAL group; n = 28) as their primary complementary feedings for ∼5 mo. Anthropometric measures and diet records were collected monthly from 5 to 9 mo of age; intakes from complementary feeding and breast milk were assessed at 9 mo of age. "Results: The MEAT group had significantly higher protein intake, whereas energy, carbohydrate, and fat intakes from complementary feeding did not differ by group over time. At 9 mo of age mean (± SEM), intakes of total (complementary feeding plus breast-milk) protein were 2.9 ± 0.6 and 1.4 ± 0.4 g ⋅ kg−1 ⋅ d−1, ∼17% and ∼9% of daily energy intake, for MEAT and CEREAL groups, respectively (P < 0.001). From 5 to 9 mo of age, the weight-for-age z score (WAZ) and length-for-age z score (LAZ) increased in the MEAT group (ΔWAZ: 0.24 ± 0.19; ΔLAZ: 0.14 ± 0.12) and decreased in the CEREAL group (ΔWAZ: −0.07 ± 0.17; ΔLAZ: −0.27 ± 0.24) (P-group by time < 0.05). The change in weight-for-length z score did not differ between groups. Total protein intake at 9 mo of age and baseline WAZ were important predictors of changes in the WAZ (R2 = 0.23, P = 0.01). "Conclusion: In breastfed infants, higher protein intake from meats was associated with greater linear growth and weight gain but without excessive gain in adiposity, suggesting potential risks of high protein intake may differ between breastfed and formula-fed infants and by the source of protein."

[9]

From Wikipedia: "Breastmilk supplement "Premastication is complementary to breastfeeding in the health practices of infants and young children, providing large amounts of carbohydrate and protein nutrients not always available through breast milk,[3] and micronutrients such as iron, zinc, and vitamin B12 which are essential nutrients present mainly in meat.[25] Compounds in the saliva, such as haptocorrin also helps increase B12 availability by protecting the vitamin against stomach acid. "Infant intake of heme iron "Meats such as beef were likely premasticated during human evolution as hunter-gatherers. This animal-derived bioinorganic iron source is shown to confer benefits to young children (two years onwards) by improving growth, motor, and cognitive functions.[26] In earlier times, premastication was an important practice that prevented infant iron deficiency.[27] "Meats provide Heme iron that are more easily absorbed by human physiology and higher in bioavailability than non-heme irons sources,[28][29] and is a recommended source of iron for infants.[30]"

[10]	Hypothesis paper The Expensive-Tissue Hypothesis: The Brain and the Digestive System in Human and Primate Evolution Leslie C. Aiello and Peter Wheeler Current Anthropology, Vol. 36, No. 2 (Apr., 1995), pp. 199-221

[11]

Evidence type: review The critical role played by animal source foods in human (Homo) evolution. Milton K. J Nutr. 2003 Nov;133(11 Suppl 2):3886S-3892S. (The whole paper is worth reading, but these highlights serve our point.) "Without routine access to ASF [animal source foods], it is highly unlikely that evolving humans could have achieved their unusually large and complex brain while simultaneously continuing their evolutionary trajectory as large, active and highly social primates. As human evolution progressed, young children in particular, with their rapidly expanding large brain and high metabolic and nutritional demands relative to adults would have benefited from volumetrically concentrated, high quality foods such as meat." [...] "If the dietary trajectory described above was characteristic of human ancestors, the routine, that is, daily, inclusion of ASF in the diets of children seems mandatory as most wild plant foods would not be capable of supplying the protein and micronutrients children require for optimal development and growth, nor could the gut of the child likely provide enough space, in combination with the slow food turnover rate characteristic of the human species, to secure adequate nutrition from wild plant foods alone. Wild plant foods, though somewhat higher in protein and some vitamins and minerals than their cultivated counterparts (52), are also high in fiber and other indigestible components and most would have to be consumed in very large quantity to meet the nutritional and energetic demands of a growing and active child." [...] "Given the postulated body and brain size of the earliest humans and the anatomy and kinetic pattern characteristics of the hominoid gut, turning increasingly to the intentional consumption of ASF on a routine rather than fortuitous basis seems the most expedient, indeed the only, dietary avenue open to the emerging human lineage (2,3,10,53)." [...] "Given the probable diet, gut form and pattern of digestive kinetics characteristic of prehuman ancestors, it is hypothesized that the routine inclusion of animal source foods in the diet was mandatory for emergence of the human lineage. As human evolution progressed, ASF likely achieved particular importance for small children due to the energetic demands of their rapidly expanding large brain and generally high metabolic and nutritional demands relative to adults."

[12]

Evidence type: review From the ape's dilemma to the weanling's dilemma: early weaning and its evolutionary context. Kennedy GE. J Hum Evol. 2005 Feb;48(2):123-45. Epub 2005 Jan 18. "Although some researchers have claimed that plant foods (e.g., roots and tubers) may have played an important role in human evolution (e.g., O’Connell et al., 1999; Wrangham et al., 1999; Conklin-Brittain et al., 2002), the low protein content of ‘‘starchy’’ plants, generally calculated as 2% of dry weight (see Kaplan et al., 2000: table 2), low calorie and fat content, yet high content of (largely) indigestible fiber (Schoeninger et al., 2001: 182) would render them far less than ideal weaning foods. Some plant species, moreover, would require cooking to improve their digestibility and, despite claims to the contrary (Wrangham et al., 1999), evidence of controlled fire has not yet been found at Plio-Pleistocene sites. Other plant foods, such as the nut of the baobab (Adansonia digitata), are high in protein, calories, and lipids and may have been exploited by hominoids in more open habitats (Schoeninger et al., 2001). However, such foods would be too seasonal or too rare on any particular landscape to have contributed significantly and consistently to the diet of early hominins. Moreover, while young baobab seeds are relatively soft and may be chewed, the hard, mature seeds require more processing. The Hadza pound these into flour (Schoeninger et al., 2001), which requires the use of both grinding stones and receptacles, equipment that may not have been known to early hominins. Meat, on the other hand, is relatively abundant and requires processing that was demonstrably within the technological capabilities of Plio-Pleistocene hominins. Meat, particularly organ tissues, as Bogin (1988, 1997) pointed out, would provide the ideal weaning food."

[13]

Plants can become more nutrient dense through cooking. That is the basis of Wrangham's hypothesis: (From Wikipedia) "Wrangham's latest work focuses on the role cooking has played in human evolution. He has argued that cooking food is obligatory for humans as a result of biological adaptations[9][10] and that cooking, in particular the consumption of cooked tubers, might explain the increase in hominid brain sizes, smaller teeth and jaws, and decrease in sexual dimorphism that occurred roughly 1.8 million years ago.[11] Most anthropologists disagree with Wrangham's ideas, pointing out that there is no solid evidence to support Wrangham's claims.[11][12] The mainstream explanation is that human ancestors, prior to the advent of cooking, turned to eating meats, which then caused the evolutionary shift to smaller guts and larger brains.[13]"

[14]

Evidence type: review The western lowland gorilla diet has implications for the health of humans and other hominoids. Popovich DG1, Jenkins DJ, Kendall CW, Dierenfeld ES, Carroll RW, Tariq N, Vidgen E. J Nutr. 1997 Oct;127(10):2000-5. (Emphasis ours) "We studied the western lowland gorilla diet as a possible model for human nutrient requirements with implications for colonic function. Gorillas in the Central African Republic were identified as consuming over 200 species and varieties of plants and 100 species and varieties of fruit. Thirty-one of the most commonly consumed foods were collected and dried locally before shipping for macronutrient and fiber analysis. The mean macronutrient concentrations were (mean ± SD, g/100 g dry basis) fat 0.5 ± 0.4, protein 11.8 ± 8.2, available carbohydrate 7.7 ± 6.3 and dietary fiber 74.0 ± 12.9. Assuming that the macronutrient profile of these foods was reflective of the whole gorilla diet and that dietary fiber contributed 6.28 kJ/g (1.5 kcal/g), then the gorilla diet would provide 810 kJ (194 kcal) metabolizable energy per 100 g dry weight. The macronutrient profile of this diet would be as follows: 2.5% energy as fat, 24.3% protein, 15.8% available carbohydrate, with potentially 57.3% of metabolizable energy from short-chain fatty acids (SCFA) derived from colonic fermentation of fiber. Gorillas would therefore obtain considerable energy through fiber fermentation. We suggest that humans also evolved consuming similar high foliage, high fiber diets, which were low in fat and dietary cholesterol. The macronutrient and fiber profile of the gorilla diet is one in which the colon is likely to play a major role in overall nutrition. Both the nutrient and fiber components of such a diet and the functional capacity of the hominoid colon may have important dietary implications for contemporary human health." We disagree, of course, with the authors' suggested interpretation that humans, too, could make good use of the same dietary strategy, as we haven't the colons for it.

[15]

The maximum amount of fat humans could get from fermenting fibre in the gut is unknown.The widely cited value of 10% of calories comes from: Energy contributions of volatile fatty acids from the gastrointestinal tract in various species E. N. Bergman Physiological Reviews Published 1 April 1990 Vol. 70 no. 2, 567-590 "The value of 6-10% for humans (Table 3) was calculated on the basis of a typical British diet where 50-60 g of carbohydrate (15 g fiber and 35-50 g sugar and starch) are fermented per day (209). It is pointed out, however, that dietary fiber intakes in Africa or the Third World are up to seven times higher than in the United Kingdom (55). It is likely, therefore, that much of this increased fiber intake is fermented to VFA and even greater amounts of energy are made available by large intestinal fermentation." However, it should not be concluded that SCFA production could rise to 70% of energy requirements! For one thing, as a back-of-the-envelope calculation, you can get up to about 2 kcal worth of SCFA per gram of fermentable carbohydrate.That would come from soluble plant fiber, resistant starch and regular starch that escapes digestion.To get 70% of calories this way on a 2000 kcal/day diet, you'd need to ingest 700g of fibre. Even if you achieved this, it is unlikely you could absorb it all, and in the process of trying, you would experience gastrointestinal distress, including cramping, diarrhea or constipation, gas, and perhaps worse.Indeed, this would probably happen even at 100g/d, which would provide about 10% of energy in a 2000 kcal/d diet.Moreover, it would interfere with mineral absorption, rendering it an unviable evolutionary strategy.Even the ADA, which extols the virtues of fiber, cautions against exceeding their recommendations of 20-35g. See Position of the American Dietetic Association: health implications of dietary fiber.

[16]

Evidence type: review Humans and the Extinction of Megafauna in the Americas DUJS Online May 22, 2009 "As the mathematical models now seem quite plausible and the patterns of survivors versus extinct species seem inexplicable by climate change and easily explicable by hunting (7,11), it is worth considering comparisons to other systems. Barnosky et al. note that on islands, humans cause extinctions through multiple synergistic effects, including predation and sitzkrieg, and “only rarely have island megafauna been demonstrated to go extinct because of environmental change without human involvement,” while acknowledging that the extrapolation from islands to continents is often disputed (7). The case for human contribution to extinction is now much better supported by chronology (both radiometric and based on trace fossils like fungal spores), mathematical simulations, paleoclimatology, paleontology, archaeology, and the traits of extinct species when compared with survivors than when Meltzer and Beck rejected it in the 1990s, although the blitzkrieg model which assumes Clovis-first can be thoroughly rejected by confirmation of pre-Clovis sites. Grayson and Meltzer (12) argue that the overkill hypothesis has become irrefutable, but the patterns by which organisms went extinct (7,11), the timing of megafauna population reductions and human arrival when compared with climate change (5), and the assumptions necessary to make paleoecologically informed mathematical models for the extinctions to make accurate predictions all provide opportunities to refute the overkill hypothesis, or at least make it appear unlikely. However, all of these indicate human involvement in megafauna extinctions as not only plausible, but likely."

[17]

Evidence type: review Linking Top-down Forces to the Pleistocene Megafaunal Extinctions William J. Ripple and Blaire Van Valkenburgh BioScience (July/August 2010) 60 (7): 516-526. "Humans are well-documented optimal foragers, and in general, large prey (ungulates) are highly ranked because of the greater return for a given foraging effort. A survey of the association between mammal body size and the current threat of human hunting showed that large-bodied mammals are hunted significantly more than small-bodied species (Lyons et al. 2004). Studies of Amazonian Indians (Alvard 1993) and Holocene Native American populations in California (Broughton 2002, Grayson 2001) show a clear preference for large prey that is not mitigated by declines in their abundance. After studying California archaeological sites spanning the last 3.5 thousand years, Grayson (2001) reported a change in relative abundance of large mammals consistent with optimal foraging theory: The human hunters switched from large mammal prey (highly ranked prey) to small mammal prey (lower-ranked prey) over this time period (figure 7). Grayson (2001) stated that there were no changes in climate that correlate with the nearly unilinear decline in the abundance of large mammals. Looking further back in time, Stiner and colleagues (1999) described a shift from slow-moving, easily caught prey (e.g., tortoises) to more agile, difficult-to-catch prey (e.g., birds) in Mediterranean Pleistocene archaeological sites, presumably as a result of declines in the availability of preferred prey."

[18]

Evidence type: review Man the fat hunter: the demise of Homo erectus and the emergence of a new hominin lineage in the Middle Pleistocene (ca. 400 kyr) Levant. Ben-Dor M1, Gopher A, Hershkovitz I, Barkai R. PLoS One. 2011;6(12):e28689. doi: 10.1371/journal.pone.0028689. Epub 2011 Dec 9. "The disappearance of elephants from the diet of H. erectus in the Levant by the end of the Acheulian had two effects that interacted with each other, further aggravating the potential of H. erectus to contend with the new dietary requirements: "The absence of elephants, weighing five times the weight of Hippopotami and more than eighty times the weight of Fallow deer (Kob in Table 3), from the diet would have meant that hunters had to hunt a much higher number of smaller animals to obtain the same amount of calories previously gained by having elephants on the menu. "Additionally, hunters would have had to hunt what large (high fat content) animals that were still available, in order to maintain the obligatory fat percentage (44% in our model) since they would have lost the beneficial fat contribution of the relatively fat (49% fat) elephant. This ‘large animal’ constraint would have further increased the energetic cost of foraging." [...] "Comparing the average calories per animal at GBY and Qesem Cave might lead to the conclusion that Qesem Cave dwellers had to hunt only twice as many animals than GBY dwellers. This, however, is misleading as obligatory fat consumption complicates the calculation of animals required. With the obligatory faunal fat requirement amounting to 49% of the calories expected to be supplied by the animal, Fallow deer with their caloric fat percentage of 31% (Kob in Table 3) would not have supplied enough fat to be consumed exclusively. Under dietary constraints and to lift their average fat consumption, the Qesem Cave dwellers would have been forced to hunt aurochs and horses whose caloric fat ratio amounts to 49% (the equivalent of buffalo in Table 3). The habitual use of fire at Qesem Cave, aimed at roasting meat [23], [45], may have reduced the amount of energy required for the digestion of protein, contributing to further reduction in DEE. The fact that the faunal assemblage at Qesem Cave shows significantly high proportions of burnt and fractured bones, typical of marrow extraction, is highly pertinent to the point. In addition, the over-representation of fallow deer skulls found at the site [9], [45] might imply a tendency to consume the brain of these prey animals at the cave. Combined, these data indicate a continuous fat-oriented use of prey at the site throughout the Acheulo-Yabrudian (400-200 kyr). "However, the average caloric fat percentage attributed to the animals at Qesem Cave – 40% – is still lower than the predicted obligatory fat requirements of faunal calories for H. sapiens in our model, amounting to 49% (Table 2). This discrepancy may have disappeared should we have considered in our calculations in Table 3 the previously mentioned preference for prime-age animals that is apparent at Qesem Cave [9], [45]. The analysis of Cordain's Caribou fat data ([124]: Figure 5) shows that as a strategy the selective hunting of prime-age bulls or females, depending on the season, could, theoretically, result in the increase of fat content as the percentage of liveweight by 76% from 6.4% to 11.3%, thus raising the caloric percentage of fat from animal sources at Qesem Cave. Citing ethnographic sources, Brink ([125]:42) writes about the American Indians hunters: “Not only did the hunters know the natural patterns the bison followed; they also learned how to spot fat animals in a herd. An experienced hunter would pick out the pronounced curves of the body and eye the sheen of the coat that indicated a fat animal”. While the choice of hunting a particular elephant would not necessarily be significant regarding the amount of fat obtained, this was clearly not the case with the smaller game. It is apparent that the selection of fat adults would have been a paying strategy that required high cognitive capabilities and learning skills."

The gas exchange system

All organisms take in gases from their environment and release gases to the environment. Animals take in O₂ for aerobic respiration and release CO₂. Plants also respire, but during daylight hours they photosynthesise at a greater rate than they respire, and so take in CO₂ and release O₂.

The body surface across which these gases diffuse into and out of the body is called the gas exchange surface. In mammals, including humans, the gas exchange surface is the surface of the alveoli in the lungs.

The human gas exchange system

The gas exchange surface in the lungs is extensive, very thin, well supplied with blood and well ventilated. The trachea and bronchi provide little resistance to the movement of air to and from the alveoli.

- The gross structure of the human gas exchange system

- Plan diagrams of the structure of the walls of the trachea, bronchi,  bronchioles 

Cartilage in the walls of the trachea and bronchi provides support and prevents the

tubes collapsing when the air pressure inside them is low.

Cillated epithelium is found lining the trachea, bronchi and some bronchioles. It

is a single layer of cells whose outer surfaces are covered with many thin extensions

(cilia) which are able to move. They sweep mucus upwards towards the mouth,

helping to prevent dust particles and bacteria reaching the lungs.

Goblet cells are also found in the ciliated epithelium. They secrete mucus, which

traps dust particles and bacteria.

Smooth muscle cells are found in the walls of the trachea, bronchi and bronchioles.

This type of muscle can contract slowly but for long periods without tiring. When it

contracts, it reduces the diameter of the tubes. During exercise it relaxes, widening

the tubes so more air can reach the lungs.

Elasticc fibres are found in the walls of all tubes and between the alveoli. When

breathing in, these fibres stretch to allow the alveoli and airways to expand. When

breathing out, they recoil, helping to reduce the volume of alveoli and expel air out

of the lungs.

Gas exchange at the alveolar surface

The air inside an alveolus contains a higher concentration of O₂, and a lower concentration of CO₂, than the blood in the capillaries. This blood has been brought to the lungs in the pulmonary artery, which carries deoxygenated blood from the heart. O₂therefore diffuses from the alveolus into the blood capillary, through the thin walls of the alveolus and the capillary. CO₂ diffuses from the capillary into the blood.

The diffusion gradients for these gases are maintained by:

• breathing movements, which draw air from outside the body into the lungs, and then push it out again; this maintains a relatively high concentration of O₂ and low concentration of CO₂ in the alveoli;
• blood flow past the alveolus, which brings deoxygenated blood and carries away
oxygenated blood.

Tidal volume and vital capacity

Air moves by mass flow into and out of the lungs during breathing. This is caused by the contraction and relaxation of external intercostal muscles and muscles in the diaphragm. When these contract, they increase the volume of the thoracic cavity and draw air down through the trachea and into the bronchi and bronchioles. When they relax, the thoracic volume decreases and air flows out, down a pressure gradient.

The volume of air that is moved into or out of the lungs during one breath is called the tidal volume. It is generally about 0,5 dm³. The maximum amount of air that can be moved in or out during the deepest possible breath is called the vital capacity. It is generally somewhere between 3 dm³ and 5 dm³.

Syllabus 2015 (a) [PA] describe the structure of the human gas exchange system, including the microscopic structure of the walls of the trachea, bronchioles and alveoli with their associated blood vessels; (b) [PA] describe the distribution of cartilage, ciliated epithelium, goblet cells and smooth muscle in the trachea, bronchi and bronchioles; (c) describe the functions of cartilage, cilia, goblet cells, mucous glands, smooth muscle and elastic fibres in the gas exchange system; (d) describe the process of gas exchange between air in the alveoli and the blood;

Syllabus:  The gas exchange system is responsible for the uptake of oxygen  into the blood and excreting carbon dioxide. An understanding of this system shows how cells, tissues and organs function  together to exchange these gases between the blood and the environment. The health  of this system and of the cardiovascular system is put at risk by smoking. 9.1    The gas exchange system The gas exchange surface in the lungs is extensive, very thin, well supplied with blood and well ventilated. The trachea and bronchi provide little resistance to the movement of air to and from the alveoli. a)   describe the gross structure of the human gas exchange system b)   observe and draw plan diagrams of the structure of the walls of the trachea, bronchi,  bronchioles and alveoli indicating the distribution of cartilage,  ciliated epithelium, goblet  cells, smooth muscle, squamous epithelium and blood vessels c)   describe the functions of cartilage,  cilia, goblet  cells, mucous glands,  smooth muscle and elastic  fibres and recognise these cells and tissues in prepared slides, photomicrographs and electron micrographs of the gas exchange system d)   describe the process of gas exchange between air in the alveoli and the blood

Parenting Moderates Childhood Brain Stress Response

Child brain development benefits from a positive parenting style and environment.

The mechanism for this positive effect is unclear but moderation of the stress response in the growing child is an area of research interest.

Haroon Sheikh and colleagues from the University of Ontario in Canada recently published results on a study of parenting and brain development in children.

In their study, a cohort of 46 six year old girls underwent brain imaging using a technique known as diffusion tensor imaging or DTI. DTI provides a measure of brain white matter integrity.

This study is informative because all the girls participated in an earlier study of stress reactivity at three years of age. High stress reactivity as measured by serum cortisol response is known to be linked to vulnerability to mood and anxiety disorders.

The key elements in the design of this study including the following:

• Subjects: 45 six year old girls from a larger ongoing longitudinal study of children
• Stress response status: At three years of age participants underwent a two phase study of stress response. A baseline salivary cortisol assay was collected. A second cortisol level was obtained during a stressful task. Subjects were grouped in four categories based on levels of cortisol.
• Parenting assessment: Parents and child participated in a play task. Parents were rated on a measure of parental negative and positive affect.
• MRI scanning: A 3 Telsa brain imaging scan was completed on average two and one-half years following the baseline cortisol and parenting assessment

The main findings from the study included the following:

• High stress reactivity at baseline was linked to lower white matter integrity in prefrontal and basal brain regions (left thalamus, right anterior cingulate cortex and right superior frontal gyrus)
• Positive parental affectivity reduced the brain white matter effects of stress (cortisol) response in the right anterior cingulate cortex and right superior frontal gyrus
• Children with high stress responses at baseline but a positive parental affect environment showed brain integrity findings similar to low stress reactivity children

This is an important study because it suggests an interaction between parental environment and adverse effects of a high stress response in three year old girls. Genetic factors likely contribute to level of stress response in three year old girls. A positive parental style appears to reduce or eliminate adverse effects of high stress reactivity on critical white matter brain development.

The implications of the study are important. High-risk children for mood and anxiety disorders may benefit from early identification and parental training to reduce risk for later psychological morbidity.

Readers with more interest in this study can access the free full-text manuscript by clicking on the PMID link below.

Photo of hawk in flight is from the author's files.

Follow the author on Twitter @WRY999

Sheikh HI, Joanisse MF, Mackrell SM, Kryski KR, Smith HJ, Singh SM, & Hayden EP (2014). Links between white matter microstructure and cortisol reactivity to stress in early childhood: evidence for moderation by parenting. NeuroImage. Clinical, 6, 77-85 PMID: 25379418

Parental Education As Risk Factor For Eating Disorders

Genetic and environmental risk factors contribute to the risk for anorexia nervosa and other eating disorders.

Known risk factors for anorexia nervosa include female gender, young age, family member with anorexia nervosa, weight loss, and participation in weight sensitive sports or activities, i.e. gymnastics, dancing.

There has also been evidence that anorexia nervosa is more common in higher socioeconomic classes. This finding has made it one of the few brain disorders more common with this category.

A recent study using the Swedish medical registry sheds some light on increased risk related to socioeconomic status in anorexia and other eating disorders.

The Swedish medical registry used in this study contained over 2,000,000 records and from this group the research team were able to identify 15,474 girls and women (1.5%) with an inpatient eating disorder diagnosis along with 1051 boys and men (0.1%)

The key findings from the study included:

• Rates of eating disorder diagnosis increased with those born in 1982 and later
• Female eating disorder diagnosis rates were predicted by greater educational level in the father, mother and maternal grandparents
• Rates of anorexia nervosa and bulimia nervosa were nearly doubled in children of parents with post-graduate education compared to those without secondary education
• Parental social class and income were not linked to increased eating disorder risk

The authors note their study results finding links between eating disorders and socioeconomic status may be due to the higher education risk factor.

The authors also note the mechanism for this association is unclear. The speculate that high educational expectations for children may overlap with familial perfectionism, a trait known to increase eating disorder risk. Additionally, they note there is the potential for their study to be confounded by genetic factors.

This is an important study that will prompt further study of the link between parental education and eating disorder risk.

Readers with more interest in this topic can access the free full-text manuscript by clicking on the PMID link below.

Follow the author on Twitter @WRY999 

Photo of black bellied whistling duck is from the author's files.

Goodman A, Heshmati A, & Koupil I (2014). Family history of education predicts eating disorders across multiple generations among 2 million Swedish males and females. PloS one, 9 (8) PMID: 25162402

Smoking in Pregnancy and Child Brain Development

Smoking during pregnancy produces significant and diverse effects on prenatal development.

These adverse effects include dysfunction in prenatal and early childhood brain development.

Hanan El Marroun and colleagues from the Netherlands recently published an important childhood brain imaging study of smoking during pregnancy.

One hundred and thirteen children exposed to tobacco during pregnancy were compared to a control group of unexposed children.

Both groups of children between 6 and 8 years of age were compared on a variety of measures including:

• Nonverbal IQ
• Birth weight and gestational age
• Child Behavior Checklist scores
• Structural brain imaging measures using MRI structural brain imaging

The key findings from this study included the following:

• Birth weight: exposed infants had a significantly lower mean birth weight than non-smoking exposed infants 3194 grams vs 3475 grams (7.04 pounds vs 7.66 pounds)
• Total brain volumes: exposed children showed smaller total brain volumes and smaller brain white matter volumes
• Brain cortex measures: exposed children showed thinner brain cortex measures in multiple brain regions including frontal, temporal and parietal regions
• Behavioral and emotional problems: exposed children had higher measures of mood and anxiety problems at 6 to eight years

An additional important finding was a statistically significant correlation between mood symptoms and thinning of cortical thickness in the superior frontal cortex and the precentral cortex regions.

Children of women who stopped smoking immediately after learning of pregnancy displayed similar brain development as the non-exposed children.

Although key covariates were controlled in this study, the authors do note they cannot rule out a potential contribution of smoking epiphenomenon in their findings. Such potential epiphenomenon linked to the smoking group could include higher parental psychopathology, effect of other substances and differences in paternal nutritional profiles.

This study does support early pregnancy identification in smoking women and aggressive smoking cessation treatment efforts.

Readers with more interest in this study can access the free full-text manuscript by clicking on the PMID link below.

Photo of altamira oriole is from the author's files.

Follow the author on Twitter @WRY999

El Marroun H, Schmidt MN, Franken IH, Jaddoe VW, Hofman A, van der Lugt A, Verhulst FC, Tiemeier H, & White T (2014). Prenatal tobacco exposure and brain morphology: a prospective study in young children. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 39 (4), 792-800 PMID: 24096296