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 Timing Etiological factors

Dopamine deficit, idiopathic
Genetic Prenatal Developmental cerebral abnormality, chromosome anomaly, viral exanthema,
acquired alcohol, nicotine, lead, cocaine, anemia, hypothyroidism, iodine lack

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

acquired Perinatal encephalitis

Genetic Viral meningitis, encephalitis, cerebral trauma, iron deficiency*, fatty acid
acquired Postnatal 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).
- Obvious variation in the methods used for the evaluation, which make it difficult to
compare the studies.
- Study design problems.
- Nonrepresentative study samples.
- Inadequate demographic data.
- lack of information on familial psychopathology.
- Poor selection of control group.
- 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

Birth weight(grams) / Age at assessment Higher incidence of
Study Gestational Age (week) (years) Date ADHD or individual
symptoms
Kelly et al (16) Not reported 4-15 2000 Yes
Huddy et al (20) 32-35 w 7 2001 Yes
Bhutta et al (11) preterm Older than 5 2002 Yes
O’Keeffe (15) < 37 w 14 2003 Yes
Hack et al (25) Mean BW: 1180 g Adolescence 2003 No
Mean GA: 29.7 w (20)
Gardner et al (14) < 29 w 15-16 2004 Yes
Romano et al (24) < 2500 g 0-11 2006 No
Stein et al (12) 1500-2499 g 0-12 2006 Yes
Langley et al (1) LBW 6-16 2007 No
Hall et al (8) preterm Adolescence 2007 Yes
Strang-Karlsson et al < 1500 g Adolescence 2008 No
(13) (18-27)
Santo et al (21) < 37 w - < 2500 g 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 LBW-
SGA 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.

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