My Literature Review

Literature Review

Is low birth weight a risk factor for Attention Deficit Hyperactivity Disorder (ADHD) in children? Nazanin Biglarbegi, 24th Oct.2009 International Maternal and Children Health Department, Uppsala University, Sweden

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder.(1) It is the most common cognitive and behavioral childhood disorder which can continue through adolescence and adulthood. (2) The Incidence of this highly prevalent disorder is estimated to be 5-10% in children and 4% in adults.(3) The number of children diagnosed with ADHD has increased remarkably in a way that in 2000 the diagnosis rate was nearly 4times higher than in 1989. (4) Key symptoms of this disorder include impulsivity, hyperactivity and inattention. Having these symptoms for 6 months or more and with a greater degree than children at the same age is needed to be diagnosed with this disorder. (2) However, it is a phenotypically varied disorder in terms of major symptom types and severity and presence of comorbid disorders, particularly Conduct Disorder, which tends to exist more in boys. (1,5) During the last century many different terms have been used to describe this disorder. (6,7) There is not any clear relationships between ADHD and mortality. However, it has been shown that children with ADHD are more likely to take more risky behaviors, such as substance abuse, antisocial behaviors, and being involved in more car accidents (nearly 4times more), which can bring considerable mortality and morbidity.(1,2,8) Besides, Children with ADHD have difficulties in their academic, profession and social life which strongly influence their development.(1) Findings from studies evaluating the quality of life in ADHD children show impairments in all aspects of these children’s daily life.(9) The most common reason for referral to the mental health services is impaired school, peer and home functioning. These negative impacts of ADHD prove that it has a harmful effect on individuals, families and society as a whole.(1) There is no cure for ADHD, but treatments can reduce the symptoms of the disorder. Many different side effects of the medication have been reported and researchers are looking for more effective treatments as well as ways to prevent it. (2)

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The purpose of this literature review is to review the articles and studies attended to assess the relationship between environmental risk factors and ADHD, in order to explore whether low birth weight could be a risk factor for ADHD in children or not. It is broadly known that preterm and low birth weight ( LBW) children are at increased risk for further physical, cognitive and behavioral problems.(10-15) Neurodevelopmental disabilities have been identified in these children specially at school age. (16) LBW, as a early life risk factor for ADHD, can have both biological and psychosocial origins. There is a possibility of a common genetic origin between prematurity and ADHD.(11) Psychosocial environment and parenthood have major influences on developing of a LBW or preterm child, by increasing maternal distress and decreasing positive parent-child interactions. On the other hand, BW(birth weight) itself can be determined by other psychosocial parameter like socioeconomic status and lone parenthood. (14) Some biological explanations can clarify the association between prematurity or low birth weight and ADHD. In a study of children who were born preterm, volumetric measurements of brain regions illustrated smaller volumes of some cortical areas, which have a considerable relationship with an increased rate of ADHD. (16) Also, ischemia-induced release of glutamate in striatum and cingulated-cortical loop leads to hyperactivity, impulsivity and poor attention and the improvements in NICU care and survival rates of premature infants increase the importance of this cause of ADHD. (6) When I was working whit ADHD children as a play therapist, I noticed that most of them were being diagnosed at the school age, when the symptoms and their influences on children’s lives are more visible, however during the pervious years they have already received the negative reactions from parents and society which have harmful effects on their psychosocial development. There is no doubt that the interventions and therapies could be much more effective, if we were able to reach these children earlier. Methods: Different electronic data bases have been searched in order to identify studies for the review, including: Pubmed/Medline, NIMH (national institute of mental health), American Academy of Pediatrics, WHO publications, Libris, ISI (web of science), JAMA (the journal of the American Medical Association).

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Studies were limited by English language and the year of publication. The health outcomes in preterm children is an old question, but the findings have improved and changed during the recent decades due to advances in diagnosis methods. So searching was limited to last 30 years and finally the latest articles among them were selected. Key words include: ADHD, attention deficit, hyperactivity, impulsivity, behavioral problems, low birth weight, very low birth weight, preterm births, premature children, risk factors. The End-note program was used for the reference list, except two website references which were written manually using Vancouver style. Findings and Discussion: The main cause of ADHD is not clear. (2) Studies have proved that a significant part of the etiology is due to genes (around 80%), but like many other illnesses ADHD has a multifactorial etiology. (6) Scientists have found other biological and environmental factors which may contribute to ADHD.(3) One of the possible classification of environmental factors is shown in a table below. (6) Group Genetic acquired

Timing Prenatal

Etiological factors Dopamine deficit, idiopathic Developmental cerebral abnormality, chromosome anomaly, viral exanthema, alcohol, nicotine, lead, cocaine, anemia, hypothyroidism, iodine lack

Genetic acquired

Perinatal

Prematurity, low birth weight, anoxic-ischemic encephalopathy, meningitis, encephalitis

Genetic acquired

Postnatal

Viral meningitis, encephalitis, cerebral trauma, iron deficiency*, fatty acid deficiency*, thyroid dysfunction, otitis media*

* Significance is controversial.

Recently, many studies have attempted to investigate the association between ADHD and these biological and environmental risk factors. (3) The identification of these factors may decrease the physicians dependence on modification of symptoms with medication, which has always been one of the parental concerns and provide more efficient managements. (6) Also, a better knowledge of the etiology of this disorder is valuable for detecting the high risk population as well as targeting earlier prevention and intervention strategies. (1,17) In recent decades, the infant mortality rate has decreased significantly. At the same period there has been an increase in the number of children who have been born preterm with low birth weights.

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(9) As a result of the dramatic developments in perinatal and neonatal care, a great number of these infants have survived. (10,11,16) A quite great number of studies have attempted to examine the association between ADHD or ADHD-related symptoms such as inattention and hyperactivity, and prematurity or low birth weigh. (18) There have been observations of an increased risk (7%-24% or higher) of ADHD in children with very low birth weight. (11,19) While some studies showed a higher prevalence of ADHD in LBW children and adults, (3,8,16,10,12,15,20-23) others haven’t observed a significant statistical relations. (1,11,24-26) Studies which found significant relationships: A perspective follow up which was conducted of birth cohorts and classroom control subjects in UK examined the behavioral and emotional problems in teenagers (15-16 years old) who were born very preterm (< 29 weeks gestation). (10) By using the SDQ (Strengths and Difficulties Questionnaire) they found an increased rate of hyperactivity and peer relationship and emotional problems reported by parents and teachers in preterm teenagers but not conduct problems in consistent with other studies. (11,12,20,25) Also, in a case-control study of preterm children (32-35 weeks gestation) at the age of 7, parents and teachers rated the preterm children as more hyperactive with more difficulties in concentration. (20) In addition, in a recent study trying to assess long-term outcomes of preterm birth in adulthood, a considerable higher incidence of ADHD was reported. (8) In a cross-sectional analysis of 5181 children between 4-15 years old who were randomly selected from a health survey, birth weight was a predictor of hyperactivity in boys and peer problems in girls. (14) There has been a report of an association between moderate low birth weight (1500-2499 g) and a higher incidence of ADHD. (17) Also, a cross-sectional study in 4 countries reported similar higher rates of ADHD in preterm children. (21) Moreover, in a meta-analysis of 227 studies, results confirmed that preterm-born children have a twice higher risk of ADHD. (16) Studies which didn’t find significant relationships A recent study on a population-based sample in Canada aimed to identify the development and prediction of hyperactive symptoms did not found LBW (<2500 g) as a significant predictor. One

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of the possible explanations for this negative result could be the low prevalence of ADHD in the sample (only 2-6 %), which reduced the statistical power. (24) In another study on 356 ADHD children, maternal smoking and social class were found related to the severity of hyperactivity and conduct disorder, while LBW were not. (1) The authors believed that the relation between these environmental risk factors is very complicated because they are strongly related and usually occur at the same time. LBW infants are often born in families with low socioeconomic status where more mothers smoke. (1) There have been an adequate number of studies which are in agreement that in general the predominant symptom in LBW children suffered from ADHD is not the hyperactivity, but it is more inattention which is named “pure” form of ADHD and is less likely to be accompanied by antisocial and conduct disorder. (11,12,20,25) This confirms the distinct phenotype theory ( 1, 11) Although most of the studies have reported some kind of association between LBW and ADHD in children, the persistence of the symptoms in adulthood is not very clear. (11)Usually ADHD decrease with age specifically the hyperactive symptoms, however other impairments, such as inattention and poor ability in concentration, may continue. (11,25) This may be one reason why some studies couldn’t find a higher prevalence of ADHD in LBW adults. Hack et al, found an increased inattention rates reported by parents in VLBW adults, but not higher incidence of ADHD based on the clinical criteria. (25) Strang-Karlsson et al, whose study on adult failed to find a relationship, explained that self-rating questionnaires also are not suitable for exploring these particular features. (11) In sum, an extreme variability has been demonstrated in published data about the importance of the association between LBW and ADHD or ADHD-related behaviors due to: (16) -

Methodological shortcomings ( low statistical powers, recall bias, and inadequate control of confounders).

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Obvious variation in the methods used for the evaluation, which make it difficult to compare the studies.

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Study design problems.

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Nonrepresentative study samples.

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Inadequate demographic data.

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lack of information on familial psychopathology.

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Poor selection of control group.

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Not assessing the medication use during the studies.

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There have been recommendations about using cohorts by gestational age instead of birth weight for investigating the behavioral outcomes in preterm births. (12) Summery of some studies Study

Birth weight(grams) / Gestational Age (week)

Age at assessment (years)

Date

Kelly et al (16) Huddy et al (20) Bhutta et al (11) O’Keeffe (15) Hack et al (25)

Not reported 32-35 w preterm < 37 w Mean BW: 1180 g

4-15 7 Older than 5 14 Adolescence

2000 2001 2002 2003 2003

Higher incidence of ADHD or individual symptoms Yes Yes Yes Yes No

Gardner et al (14) Romano et al (24) Stein et al (12) Langley et al (1) Hall et al (8) Strang-Karlsson et al

Mean GA: 29.7 w < 29 w < 2500 g 1500-2499 g LBW preterm < 1500 g

(20) 15-16 0-11 0-12 6-16 Adolescence Adolescence

2004 2006 2006 2007 2007 2008

Yes No Yes No Yes No

(13) Santo et al (21)

< 37 w - < 2500 g

(18-27) 4-5

2009

Yes

Conclusion: The majority of studies agree on this point that although ADHD is a highly heritable disorder, it is not possible to deny the role of the environmental risk factors. From a public health point of view, it is essential to be aware of different environmental risk factors and their interactions as well as the magnitude of independent effect of each one of them on ADHD phenotypes, in order to be able to make earlier diagnosis and interventions. This suggests the need for future studies to explore whether modifying these factors can bring about effective preventive interventions. Furthermore, it seems that most of the studies supported the theory of “pure” ADHD in LBWSGA children which means that we should not focus only on hyperactivity and antisocial behaviors in these children anymore, since they have impairments in almost all aspects of their daily life. It is really important to detect high risk children with different phenotypes of ADHD (inattention, hyperactivity, impulsivity). Children who suffered from an inattentive kind of the disorder could be easily missed or considered as children with emotional or disciplinary problems. Consequently, adults whose disorder have not been diagnosed would find it extremely challenging to complete even the routine daily tasks such as “getting up in the morning, preparing to leave the house for

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work, arriving at work on time and being productive on the job” and may have negative feelings about themselves as a result. Based on the evidences found in this review, preterm-born children are at a greater risk of ADHD or ADHD-related behaviors. However, the independent role of LBW is not very clear. A few studies have assessed the early predictors which take place during pregnancy or early infancy and their independent effects. Also, we face a gap of how these factors and genes interact and contribute to produce ADHD. However, this knowledge is obviously essential for early detection of high-risk infants because of high prevalence and co-morbidity of this disorder.

--------------------------------------------------------------------References: 1. Langley, K., et al., Effects of low birth weight, maternal smoking in pregnancy and social class on the phenotypic manifestation of Attention Deficit Hyperactivity Disorder and associated antisocial behavior: investigation in a clinical sample. BMC Psychiatry, 2007. 7: p. 26. 2. nimh.nih.gov [ homepage on the internet ]. U.S: The National Institute of Mental Health, Inc.; [ updated 2009 sep 20; cited 2009 sep 25]. Available from: http://www.nimh.nih.gov/health/topics/attention-deficit-hyperactivity-disorder-adhd/index.shtml 3. Banerjee, T.D., F. Middleton, and S.V. Faraone, Environmental risk factors for attention-deficit hyperactivity disorder. Acta Paediatr, 2007. 96(9): p. 1269-74. 4. Mandell, D.S., et al., Trends in diagnosis rates for autism and ADHD at hospital discharge in the context of other psychiatric diagnoses. Psychiatr Serv, 2005. 56(1): p. 56-62. 5. Linnet, K.M., et al., Maternal lifestyle factors in pregnancy risk of attention deficit hyperactivity disorder and associated behaviors: review of the current evidence. Am J Psychiatry, 2003. 160(6): p. 1028-40. 6. Millichap, J.G., Etiologic classification of attention-deficit/hyperactivity disorder. Pediatrics, 2008. 121(2): p. e358-65. 7. emedicine.medscape.com [ homepage on the internet ]. U.S.A: emedicine; c 1994-2009 [updated 2008 Aug 12; cited 2009 sep 25]. Available from: http://emedicine.medscape.com/article/289350-overview 8. Hall, R.W., et al., Long-term deficits of preterm birth: evidence for arousal and attentional disturbances. Clin Neurophysiol, 2008. 119(6): p. 1281-91. 9. Huss, M., [Attention-deficit hyperactivity disorder: risk factors, protective factors, health supply, quality of life. A brief review]. Bundesgesundheitsblatt 10. Stein, R.E., M.J. Siegel, and L.J. Bauman, Are children of moderately low birth weight at increased risk for poor health? A new look at an old question. Pediatrics, 2006. 118(1): p. 217-23. 11. Strang-Karlsson, S., et al., Very low birth weight and behavioral symptoms of attention deficit hyperactivity disorder in young adulthood: the Helsinki study of very-low-birth-weight adults. Am J Psychiatry, 2008. 165(10): p. 1345-53. 12. Gardner, F., et al., Behavioral and emotional adjustment of teenagers in mainstream school who were born before 29 weeks' gestation. Pediatrics, 2004. 114(3): p. 676-82. 13. O'Keeffe, M.J., et al., Learning, cognitive, and attentional problems in adolescents born small for gestational age. Pediatrics, 2003. 112(2): p. 301-7.

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14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26.

Kelly, Y.J., et al., Birthweight and behavioural problems in children: a modifiable effect? Int J Epidemiol, 2001. 30(1): p. 88-94. Anderson, P.J. and L.W. Doyle, Cognitive and educational deficits in children born extremely preterm. Semin Perinatol, 2008. 32(1): p. 51-8. Bhutta, A.T., et al., Cognitive and behavioral outcomes of school-aged children who were born preterm: a meta-analysis. JAMA, 2002. 288(6): p. 728-37. Eddy, L.S., et al., [Attention deficit hyperactivity disorder. A survey to evaluate risk factors, associated factors and parental child rearing behavior]. An Esp Pediatr, 1999. 50(2): p. 145-50. Chapieski, M.L. and K.D. Evankovich, Behavioral effects of prematurity. Semin Perinatol, 1997. 21(3): p. 221-39. Leonard, C.H. and R.E. Piecuch, School age outcome in low birth weight preterm infants. Semin Perinatol, 1997. 21(3): p. 240-53. Huddy, C.L., A. Johnson, and P.L. Hope, Educational and behavioural problems in babies of 32-35 weeks gestation. Arch Dis Child Fetal Neonatal Ed, 2001. 85(1): p. F23-8. do Espirito Santo, J.L., M.W. Portuguez, and M.L. Nunes, Cognitive and behavioral status of low birth weight preterm children raised in a developing country at preschool age. J Pediatr (Rio J), 2009. 85(1): p. 35-41. Valdimarsdottir, M., et al., [The frequency of some factors in pregnancy and delivery for Icelandic children with ADHD]. Laeknabladid, 2006. 92(9): p. 609-14. Saigal, S. and L.W. Doyle, An overview of mortality and sequelae of preterm birth from infancy to adulthood. Lancet, 2008. 371(9608): p. 261-9. Romano, E., et al., Development and prediction of hyperactive symptoms from 2 to 7 years in a population-based sample. Pediatrics, 2006. 117(6): p. 2101-10. Hack, M., et al., Behavioral outcomes and evidence of psychopathology among very low birth weight infants at age 20 years. Pediatrics, 2004. 114(4): p. 932-40. St Sauver, J.L., et al., Early life risk factors for attention-deficit/hyperactivity disorder: a populationbased cohort study. Mayo Clin Proc, 2004. 79(9): p. 1124-31.

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