Human Development

Maternal Lifestyle Factors in ADHD Pregnancy Risk / NK Cells Needed for Successful Pregnancy (2012)

Maternal Lifestyle Factors in Pregnancy Risk of Attention Deficit Hyperactivity Disorder (ADHD) and Associated Behaviors: Review of the Current Evidence (2003)

 

Expression of Macrophage Inflammatory Protein-1β in Human Endometrium: Its Role in Endometrial Recruitment of NK Cells
"…The optimal increase of these NK cells at the implantation period is thus essential for successful pregnancy…"  …

 

 

 

 

Maternal Lifestyle Factors in Pregnancy Risk of Attention Deficit Hyperactivity Disorder (ADHD) and Associated Behaviors: Review of the Current Evidence (2003)

 Abstract
OBJECTIVE: The purpose of this review was to examine the literature assessing the relationship between prenatal exposure to nicotine, alcohol, caffeine, and psychosocial stress during pregnancy to the risk of developing behavioral problems related to attention deficit hyperactivity disorder (ADHD) in childhood.

METHOD: PubMed, MEDLINE, EMBASE, and PsycINFO were searched systematically. Studies using DSM diagnostic criteria and other validated diagnostic or screening instruments for ADHD and those examining ADHD symptoms were included. A narrative approach was used because the studies differed too much in methods and data sources to permit a quantitative meta-analysis.

RESULTS: Twenty-four studies on nicotine (tobacco smoking), nine on alcohol, one on caffeine, and five on psychosocial stress were identified. All were published between 1973 and 2002. In spite of inconsistencies, the studies on nicotine indicated a greater risk of ADHD-related disorders among children whose mothers smoked during pregnancy. Contradictory findings were reported in the alcohol studies, and no conclusion could be reached on the basis of the caffeine study. Results from studies on psychological stress during pregnancy were inconsistent but indicated a possible modest contribution to ADHD symptoms in the offspring. Many studies suffered from methodological shortcomings, such as recall bias, crude or inaccurate exposure assessments, low statistical power, and lack of or insufficient control of confounders. A general lack of information on familial psychopathology also limited the interpretations.

CONCLUSIONS: Exposure to tobacco smoke in utero is suspected to be associated with ADHD and ADHD symptoms in children. Other maternal lifestyle factors during pregnancy may also be associated with these disorders. Further studies are needed to reach conclusions.

Attention deficit hyperactivity disorder (ADHD) is one of the most common behavioral disorders in child and adolescent psychiatry. Prevalence varies between 3% and 5% (1), and up to 10% has been reported in recent studies (2). Children with ADHD are characterized by early onset of symptoms of hyperactivity, impulsivity, and poor sustained attention. They show considerable variation in severity of their symptoms, degree of impairment, and presence of comorbid disorders (3). Moreover, the clinical presentation of ADHD varies by gender; boys tend to show more disruptive behavior and a higher frequency of comorbid disorders than girls, which may be one reason boys are overrepresented in clinical settings (4).

Brain imaging suggests that children with ADHD have a dopaminergic midbrain dysfunction at the level of the dopaminergic nuclei (5), decreased regional cerebral blood flow in parts of the prefrontal cortex (6), and alterations in prefrontal cortical asymmetry, right frontal-striatal circuitry, and the cerebellum (7). The mechanisms behind observed differences in the brain and the etiology of ADHD remain unknown (1); however, both genetic and environmental factors have been associated with the severity and maintenance of ADHD (8). Adoption, segregation, and genetic studies suggest an interaction between genetic and environmental factors, such as toxins in utero and pregnancy and delivery complications (1, 9).

According to Barkley (10), as early as 1902 Still proposed that the predisposition to behavioral problems was inherited for some children and a result of prenatal and postnatal injury for others. Pasamanick and co-workers (11) hypothesized that pre- and perinatal injury to the brain could be sufficient to cause childhood behavior disorders. More recently, the programming hypothesis suggests that fetal adaptation to an unfavorable intrauterine environment permanently increases susceptibility to chronic diseases or disorders later in life (12). Apart from the effect of high levels of exposure to alcohol during pregnancy (13), the effects of other agents on brain function remain unknown.

Neurobehavioral changes similar to ADHD symptoms in human children have been found in animals exposed in utero to nicotine, caffeine, ethanol, and stress (14–17). Nicotine, caffeine, and ethanol and its metabolites, as well as stress hormones, cross the placental barrier and reach the human fetal brain. From a public health perspective, it is important to learn to what extent and which of these common lifestyle factors contribute to the development of ADHD and ADHD-related disorders. Preventive actions may limit the poor psychiatric and criminality outcome of ADHD children in adulthood (18, 19).

The purpose of this review is to examine the state of the evidence linking common lifestyle factors during pregnancy such as smoking tobacco, alcohol and caffeine use, and maternal psychological stress to the development of ADHD and ADHD-like symptoms in children.

1 June 2003, The American Journal of Psychiatry, VOL. 160, No. 6,  
Maternal Lifestyle Factors in Pregnancy Risk of Attention Deficit Hyperactivity Disorder and Associated Behaviors: Review of the Current Evidence
Karen Markussen Linnet, M.D.; Søren Dalsgaard, M.D., Ph.D.; Carsten Obel, M.D.; Kirsten Wisborg, M.D., D.M.Sc.; Tine Brink Henriksen, M.D., Ph.D.; Alina Rodriguez, Ph.D.; Arto Kotimaa, B.M.; Irma Moilanen, M.D., Ph.D.; Per Hove Thomsen, M.D., D.M.Sc.; Jørn Olsen, M.D., Ph.D.; Marjo-Riitta Jarvelin, M.D., Ph.D.
Am J Psychiatry 2003;160:1028-1040. 10.1176/appi.ajp.160.6.1028
http://ajp.psychiatryonline.org/article.aspx?articleID=176255

 

Expression of Macrophage Inflammatory Protein-1β in Human Endometrium: Its Role in Endometrial Recruitment of NK Cells

"…The optimal increase of these NK cells at the implantation period is thus essential for successful pregnancy…"

Abstract
Human endometrium is infiltrated by natural killer (NK) cells throughout the menstrual cycle. The number of endometrial NK cells is low in the proliferative phase, but acutely increases after ovulation, and reaches a peak in the late secretory phase, suggesting that endometrium recruits these leukocytes selectively from circulating peripheral blood. We investigated the expression of macrophage inflammatory protein (MIP)-1β, a potential chemoattractant for NK cells, in the endometrium. RT-PCR and ELISA revealed that MIP-1β is expressed in the endometrium throughout the menstrual cycle at both the message and protein levels. MIP-1β expression is stronger in the secretory phase endometrium than in the proliferative phase endometrium.
Immunohistoc

hemistry revealed that MIP-1β is localized in the surface epithelial cells, glandular epithelial cells, and perivascular stromal cells throughout the menstrual cycle. Stromal cells in a wider perivascular area became immunoreactive in the secretory phase. There was a strong correlation between the endometrial MIP-1β concentration and the number of endometrial NK cells. Progesterone significantly induced MIP-1β secretion from cultured endometrial stromal cells, whereas 17β-estradiol had a weak effect. These results suggest that endometrial MIP-1β may be involved in the recruitment of NK cells from circulating peripheral blood…

Although the other leukocyte populations are almost constant, the number of endometrial NK cells fluctuates with the menstrual cycle; their number is low in the proliferative phase, but acutely increases after ovulation, and reaches a peak in the late secretory phase. In the menstrual period, they are shed with other endometrial components (1). Such numerical fluctuation suggests that these leukocytes may be recruited selectively from circulating peripheral blood into the human endometrium…

Discussion

Many studies attempting to characterize endometrial NK cells have been reported, but their exact role at the implantation site yet remains unclear.

Several investigations found that CD16neg CD56bright NK cells are decreased in the secretory phase endometrium in the patients with unexplained recurrent miscarriage (10) and in vitro fertilization-embryo transfer failure (11).
The optimal increase of these NK cells at the implantation period is thus essential for successful pregnancy. Consistent with previous reports (1), we confirmed that the number of endometrial NK cells is higher in the secretory phase than in the proliferative phase.

There may be two possible mechanisms explaining the increase of endometrial NK cells; one is proliferation in the endometrium, and the other is selective recruitment from peripheral blood NK cells. Endometrial NK cells are, at least in part, likely to be proliferating in situ, because 20–70% of them express proliferation-associated nuclear marker Ki-67 (12, 13). Recently, we and other groups reported that the expression of IL-15, a cytokine that has a strong proliferative effect on CD56bright NK cells (14), in the human endometrial stroma corresponds to the number of endometrial NK cells throughout the menstrual cycle and first trimester pregnancy (15, 16, 17). IL-15 therefore may be a candidate for the proliferation of these NK cells. However, it is difficult to explain their drastic increase only by in situ proliferation mechanism…

MIP-1β is one of the CC chemokines that was initially identified in an activated mouse macrophage cell line (4)…

In this study, we demonstrate that MIP-1β is expressed in the human endometrium and its fluctuation with the menstrual cycle corresponds to the number of endometrial NK cells. These results suggest that MIP-1β may be involved in the recruitment of NK cells into the endometrium from circulating peripheral blood.    
[Kotaro Kitaya, Takeshi Nakayama, Tomoharu Okubo, Haruo Kuroboshi, Shinji Fushiki and Hideo Honjo]
[April, 2003, Journal of Clinical Endocrinology & Metabolism, Kitaya et al. 88 (4): 1809, http://jcem.endojournals.org/content/88/4/1809.long]