Attention Deficit Disorder with Developmental Coordination Disorders

Arch Dis Child 1998;79:207–212 207 Arch Dis Child: first published as 10.1136/adc.79.3.207 on 1 September 1998. Downloaded from ORIGINAL ARTICLES

Attention deﬁcit disorder with developmental coordination disorders

Magnus Landgren, Bengt Kjellman, Christopher Gillberg

Abstract 6 years.1–4 The term DAMP is used in Nordic Aims—To analyse the contribution of cer- countries as an operational diagnosis for this tain social, familial, prenatal, perinatal, combination of deficits in children who do not and developmental background factors in have mental retardation or cerebral palsy.5 the pathogenesis of deficits in attention, DAMP and ADHD overlap to a considerable motor control, and perception (DAMP). degree.4 All children with DAMP have the Methods—A population based case- combination of attention deficits—amounting control study was carried out with 113 to full ADHD in about half of all cases—and children aged 6 years, 62 diagnosed with motor perceptual deficits (MPD). Some chil- DAMP and 51 controls without DAMP. dren with ADHD do not have MPD.4 The The children’s health and medical records diagnosis of MPD corresponds closely with were studied and their history with regard that of developmental coordination disorder to background factors was taken at an (Kadesjö, Gillberg, unpublished data).2 DAMP interview with the mother using a stand- is conceptualised as a neurodevelopmental ardised schedule. Familial factors, possi- dysfunction syndrome with a high degree of ble non-optimal factors during pregnancy psychiatric comorbidity.67 (including smoking), developmental fac- Several reports have shown an association of tors (including early language develop- specific risk factors and neurodevelopmental– ment), and medical and psychosocial data neuropsychiatric disorders.8–10 In a Swedish were scored in accordance with the re- population study in Gothenburg 20 years ago, duced optimality method. urban children diagnosed as having DAMP were Results—Low socioeconomic class was found to have a variety of socially non-optimal common in the group with DAMP.Famil- familial, prenatal, and perinatal potentially http://adc.bmj.com/ ial language disorder and familial motor brain damaging factors in their histories.11 clumsiness were found at higher rates in We have now carried out an epidemiological the DAMP group. Neuropathogenic risk study of 6 year old children living in a small factors in utero were also more common town with rural surroundings (the municipal- in the children with DAMP. Maternal ity of Mariestad).4 We report here the testing smoking during pregnancy appeared to be of three hypotheses generated in previous an important risk factor. Language prob- studies: (a) hereditary factors play an impor- lems were present in two thirds of the tant part in the pathogenetic chain of events in on September 27, 2021 by guest. Protected copyright. children with DAMP. Sleep problems and DAMP; (b) potentially brain damaging risk gastrointestinal disorders, but not atopy factors, including smoking in pregnancy and or otitis media, were significantly more Table 1 Criteria for deficits in attention, motor control, common in the DAMP group. and perception Conclusions—Prenatal familial and neuropathogenic risk factors contribute to the A. Attention deficit disorder as manifested by: (a) Severe problems in at least one, or moderate problems Department of Child development of DAMP. Primary preven- in at least two, of the following areas: attention span, activity and Adolescent tion, such as improved maternal health level, vigilance, and ability to sit still; and Psychiatry, Göteborg care and early detection or treatment, or (b) Cross situational problems in the areas mentioned University, Annedals under (a) documented at two or more of the following: both, of associated language problems psychiatric, neurological, psychological evaluation, and Clinics, S-413 45 appear to be essential. Gothenburg, Sweden maternal report ( 1998; :207–212) B. Developmental coordination disorder or motor perception C Gillberg Arch Dis Child 79 dysfunction as manifested by severe: Keywords: developmental coordination disorder; atten- (a) gross motor dysfunction according to neurological Department of examination,12 or tion deficit hyperactivity disorder; motor control and Pediatrics, Skövde (b) fine motor dysfunction according to neurological Central Hospital, perception; language; prenatal factors; perinatal factors examination,12 or Skövde, Sweden (c) visuomotor/perceptual dysfunction according to M Landgren testing with the block design and object assembly subtests of the WISC-III13 (a discrepancy of > 15 IQ points on any of B Kjellman Attention deficit hyperactivity disorder these relative to overall IQ) or visuomotor dyscoordination (ADHD) and deficits in attention, motor con- test outlined in Rasmussen et al14 Correspondence to: trol, and perception (DAMP) are common C. Problems not accounted for or associated with mental retardation Professor Gillberg. childhood symptom combinations, each occur- or cerebral palsy Accepted 9 March 1998 ring in about one in 20 Swedish children aged AllofA,B,andChavetobemet. 208 Landgren, Kjellman, Gillberg Arch Dis Child: first published as 10.1136/adc.79.3.207 on 1 September 1998. Downloaded from Table 2 Background factors studied; criteria for reduced previously.4 The screening procedure com- optimality prised: the Conners’ parent questionnaire; a parent psychomotor questionnaire; a preschool Factor Optimal teacher questionnaire; and a standardised Family factors (first degree relatives only) motor examination at the child health Speech/language retardation Absent 15 16 Learning disorder Absent centre. The clinical assessment comprised a Motor clumsiness Absent detailed history, psychiatric and neurodevelop- Left handedness Absent mental examination, neuropsychological test- Mental retardation Absent Epilepsy Absent ing, and speech/language evaluation performed Tics Absent by a multidisciplinary team. The examining Attention deficit Absent doctor was unaware of the results of the assess- Prenatal factors ment performed by his team members. The Smoking No Gestational age (weeks) 37–41 routine paediatric physical examination and Small for gestational age No the neurodevelopmental examination were Large for gestational age No performed by the first author in all instances. Eclampsia/pre-eclampsia Absent Antiepileptic drugs No The methods used have good to excellent Severe infections in pregnancy Absent interrater and test-retest reliability.12 16–18 Alcohol exposure No

Intrapartal factors BACKGROUND FACTORS Apgar score 9–10 Vacuum extraction No The obstetric, child health centre, and medical Twins or multiple birth No records of the children were collected and Breech or foot presentation No Cord prolapse, around neck/knot No scrutinised according to preset standards. Child severely traumatised (fractures, No Table 2 shows the criteria of optimality lots of petechiae) modified from Gillberg and Rasmusen.11 For Neonatal factors each factor with optimal conditions a score of 0 Hypoglycaemia No Septicaemia/meningitis Absent was given and for each factor with non- Respiratory distress Absent optimum conditions a score of 1 was given. Hyperbilirubinaemia not treated Absent Smoking in pregnancy was recorded as present Hyperbilirubinaemia treated Absent DiYculties regulating temperature No in mothers who reported smoking more than Irritable/floppy infant No the occasional cigarette during pregnancy. Postnatal factors Smallness for gestational age and largeness for Encephalitis Absent gestational age were defined as birth weights Meningitis Absent Concussion Absent less than two standard deviations (SDs) and Convulsions Absent greater than two SDs respectively according to 19 Social factors norms of Swedish growth charts. Hyper- Social class I, II, or III20 bilirubinaemia (untreated) was defined as Ethnicity Parent: Swedish/immigrant > 150 mmol/l at birth weights less than 2500 g Family structure Parent: or > 200 mmol/l at birth weights of 2500 g or married/divorced/ more. Hypoglycaemia was defined as blood single http://adc.bmj.com/ Child living with half sugar < 1.5 mmol/l. Pre-eclampsia was defined siblings as comprising at least two of the following: albuminuria, high blood pressure (> 140/90 low birth weight, contribute to the develop- mm Hg), and generalised oedema. Social class ment of DAMP; and (c) early language prob- was rated on the basis of the father’s lems in preschool children predict a diagnosis occupation.20 In single parent families, the rat- of DAMP at the age of 6 years. ing was based on the parent having the main

rearing responsibility for the child. Immigrant on September 27, 2021 by guest. Protected copyright. Subjects status was defined as having at least one parent The DAMP group, 52 boys and 10 girls, com- being born as a non-Swedish citizen. prised all 28 children (25 boys) diagnosed with A language problem was defined as one or DAMP (table 1) in the total population of 589 more of: (a) speech delay according to parents children aged 6 years screened for DAMP in or to child health centre records, or both—that the municipality of Mariestad, and the first 34 is, 8–10 simple words only after the age of 18 children (27 boys) with DAMP recruited after months and intelligible sentences only after the screening covering the surrounding district of age of 3 years; (b) receptive language dysfunc- Skaraborg.4 The children from Mariestad and tion at the age of 6 years according to the those from the rest of the district were similar child’s preschool teacher; (c) limited vocabu- with respect to social class, ethnicity, and lary at the age of 6 years according to the pre- medical background factors. A comparison school teacher; (d) dysarticulation present at group of 6 year old children was randomly assessment at the age of 6 years; and (e) a his- selected (separately for boys and girls) among tory of treatment by a speech therapist. A fam- the children screened and assessed as negative ily history of a language problem was defined as for DAMP and coming from Mariestad and the speech delay, dyslexia, or other learning disor- nearby community; this comprised 39 boys and der in first degree relatives. 12 girls. Certain other medical background factors were studied: infantile colic; a history of one or Methods more middle ear infections; a history of one or SCREENING AND ASSESSMENT more emergency room visits during the first six The screening procedures were identical for all years; a history of, or current, allergy, asthma, children and have been described in detail or atopic dermatitis as defined in several ADD with developmental coordination disorders 209 Arch Dis Child: first published as 10.1136/adc.79.3.207 on 1 September 1998. Downloaded from Table 3 Reduced optimality. Number (%) of subjects with particular background factor and boys yielded significant diVerences for several variables and these are described in the DAMP Comparison (n = 62) (n = 51) Odds ratio (CI) p value text. The IQ score tended to be lower in the Social factors DAMP than in the comparison group, al- Ethnicity—immigrant 6 (10) 5 (10) 1.0 (0.2 to 4.4) 0.767 Family structure—divorced 19 (31) 8 (16) 2.4 (0.9 to 6.9) 0.102 though it was within the normal range in all Social class instances. The complex relation between the I 4 (7) 9 (18) II 12 (19) 22 (43) diagnosis of DAMP, ADHD, and developmen- III 46 (74) 20 (39) 4.5 (1.9 to 10.7) < 0.001 tal coordination disorder (DCD) on the one Mean (SD) 2.7 (0.6) 2.2 (0.7) < 0.0001 hand, and IQ on the other is the subject of a Familial reduced optimality factors* separate report (Landgren et al, unpublished Speech/language retardation 8 (13) 1 (2) 7.7 (0.9 to 348.0) 0.037 Learning disorder 23 (38) 9 (18) 2.9 (1.1 to 8.0) 0.029 data). Briefly, it seems clear that although most Motor clumsiness 20 (33) 6 (12) 3.8 (1.3 to 12.4) 0.014 children with these diagnoses have normal IQs Left handedness 16 (27) 15 (29) 0.9 (0.4 to 2.2) 0.913 and the diagnostic decision is not influenced by Mental retardation or epilepsy 5 (8) 1 (2) 4.5 (0.5 to 215.3) 0.217 Tics 6 (10) 8 (16) 0.6 (0.2 to 2.1) 0.540 the child’s IQ, about one third of children in Attention deficit 10 (17) 3 (6) 3.2 (0.8 to 19.0) 0.137 the DAMP “spectrum” have borderline intel- Presence of one or more reduced lectual functioning and the assignment of a optimality familial factors 49 (80) 3l (61) 2.6 (1.1 to 6.7) 0.038 DAMP/ADHD/DCD diagnoses could be in- *Two boys with DAMP were either living with foster parents or were adopted, and information fluenced by this fact. The general conclusions about their family background was not obtained except one of the boys had a mother and brother regarding background factors are, however, not with epilepsy. aVected by diVerential IQ eVects. previous studies from Skaraborg21 22; current sleep problems (restless sleep, snoring, ob- SOCIAL AND FAMILIAL BACKGROUND FACTORS structive sleep apnoea, and nightmares); and Table 3 gives the social and familial back- gastrointestinal symptoms (recurrent abdomi- ground factors. More boys with DAMP than nal pain, constipation, nausea, and diarrhoea). comparison cases were living in families containing half siblings (29 v 12%; odds ratio STATISTICAL ANALYSIS (OR) 3.1; 95% confidence interval (CI) 1.0 to For univariate analysis of the data, Stat View 10.3; p = 0.045). There was no diVerence in 4.02 (1992–3) and Epi Info 5.00 were used. the use of child care facilities or in the number Group frequency diVerences were analysed of siblings. All neurodevelopmental familial using the ÷2 test with Yates’s correction or factors were grouped together in a cluster and Fisher’s exact test (two tailed) when numbers the combined mean score was significantly in individual cells were less than 5. The various higher in the DAMP group (1.4) than in the mean scores and birth weights were compared comparison group (0.8) (p = 0.001). Familial using the Mann-Whitney U test. Logistic language problems were strongly associated regression analysis was applied to the multi- with DAMP in boys (OR 6.3; 95% CI 2.0 to variate evaluation of the contribution of diVer- 23.5; p = 0.001), but was not an important ent background factors. factor in girls. http://adc.bmj.com/

Results PRENATAL FACTORS SEX AND IQ Table 4 gives the possible prenatal factors. The Subdivision according to sex has not been mean collapsed score of prenatal risk factors made in the tables. Comparison between girls was signiﬁcantly higher in the DAMP group (0.85 v 0.29; p < 0.001). A total of 12 children Table 4 Number (%) of children in the DAMP and comparison groups with one or more (seven of 52 boys and ﬁve of 10 girls) with possibly brain damaging factors

DAMP and two (both boys) in the comparison on September 27, 2021 by guest. Protected copyright. DAMP Comparison group had experienced major prenatal events Risk factor (n = 61) (n = 51) Odds ratio (CI) p value that might have caused brain damage (preterm Prenatal 32 (53) 11 (22) 4.0 (1.6 to 10.2) 0.002 birth or pre-eclampsia) (p = 0.026). Six chil- Intrapartum 14 (23) 4 (8) 3.5 (1.0 to 15.5) 0.039 dren with DAMP (two boys, four girls) and one Neonatal 9 (15) 3 (6) 2.8 (0.6 to 16.7) 0.219 boy in the comparison group had been born to Postnatal 7 (12) 3 (6) 2.1 (0.4 to 13.0) 0.342 Total 41 (67) 15 (29) 4.9 (2.1 to 12.0) <0.001 mothers who had had pre-eclampsia. The diVerence was significant with regard to girls Table 5 Number (%) of children with specific speech and language problems (p = 0.029). Smoking during pregnancy had occurred more often in children with DAMP Problem area DAMP Comparison Odds ratio (CI) p value (36 v 16% in the comparison group; OR 3.0; 95% CI 1.1 to 8.8; p = 0.027). Two mothers Child factors Speech delay 26 (42) 6 (12) 5.4 (1.9 to 17.6) < 0.001 had taken antiepileptic drugs during preg- Present vocabulary* 8 (13) 2 (4) 3.7 (0.7 to 37.0) 0.108 nancy; both children (boys) were in the DAMP Present word understanding* 3 (5) 0 – 0.249 Dysarticulation 31 (50) 3 (6) 16.0 (4.3 to 86.6) < 0.001 group. There was no indication of major alco- Treatment by speech therapist 14 (23) 3 (6) 4.7 (1.2 to 26.6) 0.027 hol exposure or severe infection in pregnancy Any of above five factors 40 (65) 8 (16) 9.8 (3.6 to 27.9) < 0.001 in any of the groups. Mean (SD) number of factors 1.15 (1.1) 0.24 (0.6) < 0.001 The mean (SD) birth weight of the children Familial factors Language disorder in family† 28 (47) 10 (20) 3.6 (1.4 to 9.5) 0.005 with DAMP (3330 (740) g) was significantly Child and familial factors lower than that in the comparison group (3650 Any speech or language problem 50 (83) 11 (28) 9.1 (3.6 to 23.8) < 0.001 (450) g) (p = 0.003). Five of the 62 children with DAMP (8%) and one of the 51 children in *Information about vocabulary and word understanding was missing for one boy with DAMP; †information about language disorder in family was missing for two boys, one adopted and one the comparison group (2%) had a birth weight living with a foster family. less than 2500 g (NS) and 14 children with 210 Landgren, Kjellman, Gillberg Arch Dis Child: first published as 10.1136/adc.79.3.207 on 1 September 1998. Downloaded from Table 6 Influence of various possible risk factors on the enced either neonatal or postnatal major events development of DAMP that might have caused brain damage (septicaemia, hypoglycaemia or bacterial meningitis) Risk factor p value Relative risk (CI) (p = 0.063). The prevalence of non-optimal Motor clumsiness in family 0.025 3.8 (1.2 to 12.1) neonatal and postnatal factors was similar in Language disorder in family 0.06 2.6 (1.0 to 6.7) Maternal smoking in pregnancy 0.10 2.5 (0.8 to 7.3) the DAMP and comparison groups, but eight (Low) birth weight 0.023 – infants (13%) in the DAMP group had been (Low) social class 0.002 4.5 (1.7 to 11.6) admitted to the neonatal ward for observation Divorce >0.30 1.0 (0.3 to 3.3) or treatment compared with two (4%) in the A multivariate logistic regression model with relative risks, 95% comparison group (NS). None of the 113 chil- confidence intervals, and p values. Information about familial dren in the study had needed intubation, artifi- factors and prenatal history was missing for two boys in the DAMP group, 60 children with DAMP and 51 comparison cial ventilation, or had been regarded as children are included in the model. critically ill. Four children in the DAMP group were treated with antibiotics for obvious or DAMP (23%) and four comparison children suspected septicaemia. One of these children (8%) had a birth weight less than 3000 g also had hypoglycaemia and hyperbilirubinae- (p < 0.02). Eight children with DAMP and two mia; another had respiratory distress. A total of comparison children were born preterm. Two eight children (six with DAMP, two compari- children with DAMP and one comparison son) had hyperbilirubinaemia. One child in the child were born small for gestational age and comparison group was hypothermic at birth. four children with DAMP and one comparison After the neonatal period, seven children in child were born large for gestational age. The the DAMP group were admitted for central mean head circumference at birth did not dif- nervous system symptoms: one with bacterial fer across the groups. meningitis; one with symptomatic hypoglycaemia with convulsions; three with mild concus- INTRAPARTUM FACTORS sion; and two with benign convulsions. In the Table 4 gives the intrapartum factors. No child comparison group one child had been admit- in this study had experienced major events that ted for aseptic meningitis and two for benign might have caused brain damage in the convulsions. intrapartum period. The mean collapsed intrapartum score in the DAMP group (0.26) NEUROPATHOGENIC FACTORS was significantly higher than that of the One or more neuropathogenic factors (prena- comparison group (0.10) (p = 0.034). This tal, intrapartum, neonatal, and postnatal fac- diVerence was due to the high proportion of tors combined) occurred significantly more girls with non-optimal intrapartum risk factors: often in the DAMP group (table 4). A history six of 10 girls with DAMP had one or more of major brain damaging events was present in intrapartum risk factors compared with none 16 children with DAMP (26%) compared with of the 12 girls in the comparison group two in the comparison group (4%) (p = 0.003; (p = 0.003). OR 8.7; 95% CI 1.9 to 81.0). The collapsed The only significant single factor was a lower score for reduced optimality in the prenatal, http://adc.bmj.com/ Apgar score in girls with DAMP. Twelve perinatal, and neonatal periods was signifi- children had Apgar scores < 9. Ten of these cantly higher (1.4) in the DAMP than in the were in the DAMP group and five were girls. comparison group (0.5) (p <0.001). This was No girl in the comparison group had an Apgar most pronounced for the girls, of whom all 10 score < 9 (p = 0.010). Four DAMP girls—all with DAMP had a history of one or more neu- exposed to both smoking and maternal pre- ropathogenic risk factors compared with only eclampsia in pregnancy—and no comparison

one of the 12 comparison girls (p < 0.001). In on September 27, 2021 by guest. Protected copyright. group girls were transferred to the neonatal the boys, 31 (61%) had one or more neuro- ward. There was no significant diVerence with pathogenic factors compared with 14 (36%) in respect to twin births (three in total) or delivery the comparison group (p = 0.033). with the help of vacuum extraction (four in total). LANGUAGE FACTORS Table 5 gives the language factors. In total, NEONATAL AND POSTNATAL FACTORS 65% of the DAMP and 16% of the comparison Table 4 gives the possible neonatal and postna- cases had (or had had) a language problem of tal factors. A total of five children with DAMP some kind (OR 9.8; 95% CI 3.6 to 27.9; and none in the comparison group had experi- p < 0.001). A clear diVerence was found in respect of speech delay reported by the parents Table 7 Influence of various possible risk factors on the and verified by child health centre staV,or development of language problems both, but only a few children with language Risk factor p value Relative risk (CI) problems had been detected on the basis of items reported by the preschool teachers (cur- Language disorder in family 0.002 4.0 (1.6 to 9.8) Maternal smoking in pregnancy 0.034 3.0 (1.1 to 8.1) rent vocabulary and receptive language). (Low) birth weight 0.13 – (Low) social class >0.30 1.6 (0.6 to 3.9) UNIVARIATE ANALYSES Divorce 0.17 2.2 (0.7 to 6.4) In univariate analyses, smoking during preg- A multivariate logistic regression model with relative risks, 95% nancy was significantly associated with the confidence intervals, and p values. Information about familial occurrence of DAMP, a higher frequency of factors and prenatal history was missing for two boys in the DAMP group, 60 children with DAMP and 51 comparison DSM-III-R ADHD symptoms, and language children are included in the model. problems. The mean (SD) ADHD score was ADD with developmental coordination disorders 211 Arch Dis Child: first published as 10.1136/adc.79.3.207 on 1 September 1998. Downloaded from Table 8 Ailments of interest studied factors in the child were present in more than 90% of the children with DAMP in both the DAMP Comparison Ailment (n = 62) (n = 51) Odds ratio (CI) p values Gothenburg and Skaraborg studies. Major brain damaging events had occurred in about Infantile colic 19 (31%) 15 (29%) 1.1 (0.4 to 2.6) 0.939 one third of the children with DAMP. There is Atopy 21 (34%) 15 (29%) 1.2 (0.5 to 3.0) 0.762 Otitis media 17 (28%) 15 (29%) 0.9 (0.4 to 2.3) 0.976 evidence for a cause–eVect relation between Emergency visits 17 (27%) 11 (22%) 1.4 (0.5 to 3.7) 0.619 hypoxic–haemodynamic brain injury in utero Sleep disorder 30 (48%) 12 (24%) 3.1 (1.3 to 7.6) 0.012 25 Gastrointestinal disorder 25 (40%) 8 (16%) 3.6 (1.4 to 10.4) 0.008 or neonatally and ADHD. Our results add further support to this suggestion. Boys with DAMP tended towards a stronger familial 6.9 (3.9) in the smoking during pregnancy load, whereas girls had a higher rate of group and 4.8 (3.6) in the non-smoking during potentially brain damaging factors. pregnancy group (p = 0.008). Language problems, DAMP, and ADHD are known to run in families.3 26–29 Children with MULTIVARIATE ANALYSIS The association of smoking during pregnancy DAMP develop reading problems at a high rate.30 31 Speech delay is an important early with DAMP and with language problems was 32 33 also evaluated using logistic regression analysis prognostic sign for later reading disorders. (tables 6 and 7). Early recognition and treatment of language problems seems to be important. It is therefore NON-NEUROLOGICAL SYMPTOMS/DISORDERS disappointing that most children with language Table 8 gives the non-neurological symptoms/ problems had not been detected by the disorders. The most common sleep problem in preschool teachers, in spite of the fact that their the DAMP group was marked nighttime snor- parents had often suspected that something ing (31%). This occurred at a lower rate in the was wrong in this respect in the child’s first comparison group (14%) than in the DAMP three years. group (OR 2.8; 95% CI 1.0 to 8.6; p < 0.057). We found complete agreement between maternal recalled smoking data six to seven Discussion years after pregnancy and maternal health This report is based on a population study of 6 records. The validity of recalled smoking data year old children born in 1986–87 and living in has been reported to be about 90%.34 35 Our a Swedish small town and rural setting. Similar finding of an association of DAMP and a screening and assessment methods have been higher rate of ADHD symptoms with maternal used previously in a Swedish urban sample of 7 smoking during pregnancy agrees with other year old children. The results from that study studies of ADHD and so called minimal brain agree well with the prevalence of DAMP and dysfunction syndrome, a disorder similar to the occurrence of non-optimal background DAMP.36–38 factors in our study.312The similar findings in Smoking covaries with many other factors, an urban and a non-urban population support making a true association of DAMP and other the data as representative of a Swedish popula- developmental disorders diYcult to establish. tion. As the DAMP diagnostic concept is Our data from the regression analyses (tables 6 http://adc.bmj.com/ shared across Scandinavia, there is reason to and 7) indicate an independent eVect of believe that it is also representative of other maternal smoking during pregnancy on the Nordic countries. These findings may also have development of DAMP or language disorder, relevance for children with DSM-III-R ADHD or both. Exposure to maternal smoking during due to the considerable overlap between pregnancy may cause a range of neurobehav- DAMP and ADHD.4 ioural and neuropsychological deficits in 39–44

The IQ score tended to be lower in the group children. Reduced prostacyclin activity is on September 27, 2021 by guest. Protected copyright. with DAMP. A study in progress by our group induced by smoking and might well lead to a suggests that IQ may be a diagnostic con- reduced capacity for sustaining fetal hypoxae- founder in the subgroup (about one third) of mia. In rodents, experimental nicotine expo- the children with DAMP with borderline intel- sure during gestation aVects later behaviour lectual functioning, but that even when IQ and causes a delay in neuronal maturation.45–47 eVects are partialled out, the overall results There is at least one possible alternative expla- with regard to background factors in DAMP nation for the association of smoking in remain unaVected. pregnancy with DAMP, however, and that is The socioeconomic distribution of the chil- genetic.11 Smoking in pregnancy could be taken dren in the comparison group is identical to a as a marker of a genetic trait for DAMP rather cross sectional sample of the general Swedish than an aetiological factor per se. population (Swedish Central Bureau of Statis- Common symptoms in a paediatric popula- tics 1992–93). The reason for the overrepre- tion such as infantile colic, otitis media, and sentation of social class III in DAMP and atopy occurred at similar rates in the DAMP ADHD is unknown.23 One possible contribu- and comparison groups. Sleep and gastrointes- tory factor is non-optimal heredity. Children tinal disorders diVerentiated the groups from with DAMP often have parents who have (or each other, however. The higher rate of snoring once had) DAMP. DAMP and reading skills reported in the DAMP group (31 v 14%) are associated with poor psychosocial might be due to neuromuscular disturbances. adjustment.10 24 The rate of snoring in the comparison group Learning disorders, language problems, or was similar to that reported previously in 4–7 neurological/neurodevelopmental symptoms in year old children.48 The higher rate of gastroin- first degree relatives and/or neuropathogenic testinal disorders recorded in the 6 year old 212 Landgren, Kjellman, Gillberg Arch Dis Child: first published as 10.1136/adc.79.3.207 on 1 September 1998. Downloaded from DAMP children could be due to attention defi- 19 Karlberg P, Priolisi A, Landström T, Selstam U, Clinical analyses of causes of death with emphasis on perinatal cits leading to the postponing of bowel mortality. Monographs in Paediatrics 1977;9:86–120. movements, or deficient bowel motor control 20 Swedish Central Bureau of Statistics. Socioeconomic classification. Örebro: Swedish Central Bureau of Statistics, resulting in constipation and recurrent ab- 1982. dominal pain. 21 Hattevig G, Kjellman B, Björksten B. Clinical symptoms and IgE responses to common food proteins and inhalants in the first 7 years of life. Clin Allergy 1987;17:571–8. CONCLUSIONS 22 Kjellman B, Hesselmar B. Prognosis of asthma in children: This study of background factors in DAMP a cohort study into adulthood. Acta Paediatr 1994;83:854– 61. showed a high rate of familial non-optimal 23 Biederman J, Milberger S, Faraone SV, et al. Family– symptoms and prenatal neuropathogenic fac- environment risk factors for attention-deficit hyperactivity disorder. A test of Rutter’s indicators of adversity. Arch Psy- tors. The impact of prenatal factors on the chiatry 1995;52:464–70. development of DAMP should not be a reason 24 Baker L, Cantwell DP. Factors associated with the develop- for passivity. Improved maternal health care, ment of psychiatric illness in children with early speech/ language problems. J Autism Dev Disord 1987;17:499–510. including the prevention of smoking during 25 Lou HC. Etiology and pathogenesis of attention deficit pregnancy, could lead to a reduction in the rate hyperactivity disorder (ADHD): significance of prematu- rity and perinatal hypoxic–haemodynamic encephalopathy. of language and behaviour problems and a Acta Paediatr 1996;85:1266–71. reduction in DAMP in the general population. 26 Frisk M, Wegelius B, Tenhunen T, Widholm O, Hortling H, The problem of dyslexia in teenage. Acta Paediatr Scand In any event, early detection and remediation 1967;56:333–43. of language problems, isolated or associated 27 Rutter M, MacDonald H, Couteur AL, Harrington R, Bol- ton P, Bailey A. Genetic factors in child psychiatric with DAMP/ADHD, are essential steps to- disorders. II: Empirical findings. J Child Psychol Psychiatry wards the prevention of psychosocially handi- 1990;31:39–83. 28 Gilger JW, Pennington BF, DeFries JC. A twin study of the capping disorders that are otherwise often the etiology of comorbidity: attention-deficit and hyperactivity 49 50 result of untreated language disorders. disorder and dyslexia. J Am Acad Child Adolesc Psychiatry 1992;31:343–8. 29 Stevenson J. Evidence for a genetic etiology in hyperactivity This study was supported by the Swedish National Association in children. Behav Genet 1992;22:337–44. for Disabled Children and Young People, and the Skaraborg 30 Gillberg IC, Gillberg C, Rasmussen P. Three-year follow-up Research Institute. at age 10 of children with minor neurodevelopmental disorders. II. School achievement problems. Dev Med Child 1 American Psychiatric Association. Neuro 1983;25:566–73. Diagnostic and statistical 31 Mason AW. Specific (developmental) dyslexia. manual of mental disorders. 3rd revised ed. Washington: Dev Med American Psychiatric Association, 1987. Child Neurol 1967;9:183–90. 2 American Psychiatric Association. Diagnostic and statistical 32 Mann V. Language problems: a key to early reading manual of mental disorders. 4th ed. Washington: American problems. In: Wong BYL, ed. Learning about learning Psychiatric Association, 1994. disabilities. San Diego: Academic Press, 1991. 3 Gillberg C, Rasmussen P, Carlström G, Svenson B, Walden- 33 Ornoy A, Uriel L, Tennenbaum A. Inattention, hyperactiv- ström E. Perceptual, motor and attentional deficits in ity and speech delay at 2–4 years of age as a predictor for six-year-old children. Epidemiological aspects. J Child Psy- ADD–ADHD syndrome. Israeli Journal of Psychiatry and chol Psychiatry 1982;23:131–44. Related Sciences 1993;30:155–63. 4 Landgren M, Pettersson R, Kjellman B, Gillberg C. ADHD, 34 Krall EA, Valadian I, Dwyer JT, Gardner J. Accuracy of DAMP and other neurodevelopmental/neuropsychiatric recalled smoking data. Am J Public Health 1989;79:200–2. disorders in six-year-old children. Epidemiology and 35 Persson P-G, Norell SE. Retrospective versus original infor- comorbidity. Dev Med Child Neurol 1996;38:891–906. mation on cigarette smoking. Implications for epidemio- 5 Airaksinen E, Bille B, Carlström G, et al. Barn och logical studies. Am J Epidemiol 1989;130:705–12. ungdomar med DAMP/MBD (Children and adolescents 36 Wakschlag LS, Lahey BB, Loeber R, Green SM, Gordon with DAMP/MBD). [In Swedish] Läkartidningen 1990;88: RA, Leventhal BL. Maternal smoking during pregnancy

714. and the risk of conduct disorders in boys. Arch Gen http://adc.bmj.com/ 6 Gillberg C, Perceptual, motor and attentional deficits in Psychiatry 1997;54:670–6. Swedish primary school children. Some child psychiatric 37 Nichols PL, Chen T. Minimal brain dysfunction a prospective aspects. J Child Psychol Psychiatry 1983;24:377–403. study. New Jersey: Lawrence Ehbaum Associates 1981. 7 Hellgren L, Gillberg IC, Bågenholm A, Gillberg C. Children 38 Milberger S, Biederman J, Faraone SV, Chen L, Jones J. Is with deficits in attention, motor control and perception maternal smoking during pregnancy a risk factor for atten- (DAMP) almost grown up: psychiatric and personality dis- tion deficit hyperactivity disorder in children? Am J orders at age 16 years. J Child Psychol Psychiatry Psychiatry 1996;153:1138–42. 1994;35:1255–71. 39 Tong S, McMichael AJ. Maternal smoking and neuropsy- 8 Lindahl E, Michelsson K, Helenius M, Parre M. Neonatal chological development in childhood: a review of the risk factors and later neurodevelopmental disturbances. evidence. Dev Med Child Neurol 1992;34:191–7. Dev Med Child Neurol 1988;30:571–89. 40 Weitzman M, Gortmaker S, Sobol A, Maternal smoking and 9 Hadders-Algra M, Touwen B. Minor neurological dysfunc- behaviour problems of children. Pediatrics 1992;90:342–9. on September 27, 2021 by guest. Protected copyright. tion is more closely related to learning diYculties than to 41 Fergusson DM, Horwood LJ, Lynskey MT. Maternal smok- behavioural problems. Journal of Learning Disabilities 1992; ing before and after pregnancy: eVects of behavioural out- 25:649–57. comes in middle childhood. Pediatrics 1993;92:815–22. 10 Hellgren L, Gillberg C, Gillberg IC. Children with deficits 42 Drews CD, Murphy CC, Yeargin-Allsopp M, Decouflé P. in attention, motor control and perception (DAMP) almost The relationship between idiopathic mental retardation grown up: the contribution of various background factors and maternal smoking during pregnancy. Pediatrics 1996; to outcome at age 16 years. Eur Child Adolesc Psychiatry 97:547–53. 1994;3:1–15. 43 McCartney JS, Fried PA, Watkinson B. Central auditory 11 Gillberg C, Rasmussen P. Perceptual, motor and attentional processing in school-age children prenatally exposed to deficits in seven-year-old children: background factors. Dev cigarette smoke. Neurotoxicol Teratol 1994;16:269–76. Med Child Neurol 1982;24:752–70. 12 Gillberg C, Carlström G, Rasmussen P, Waldenström E. 44 Chew E, Remaley NA, Tamboli A, Zhao J, Podgor MJ, Kle- Perceptual, motor and attentional deficits in seven-year-old banoV M. Risk factors for esotropia and exotropia. Arch children. Neurological screening aspects. Ophthalmol 1994;112:1349–55. Acta Paediatr 45 Ahlsten G, Ewald U, Tuvemo T, Prostacyclin-like activity in Scand 1983;72:119–24. 13 Wechsler D. Wechsler intelligence scale for children. 3rd ed umbilical arteries is dose-dependently reduced by maternal (revised). New York: Psychological Corporation, 1992. smoking and related to nicotine levels. Biol Neonate 14 Rasmussen P, Gillberg C, Waldenström E, Svenson B. Per- 1990;58:271–8. ceptual, motor and attentional deficits in seven-year-old 46 Nordberg A, Zhang X, Fredriksson A, Eriksson P. Neonatal children: neurological and neurodevelopmental aspects. nicotine exposure induces permanent changes in brain Dev Med Child Neurol 1983;25:315–33. nicotine receptors and behaviour in adult mice. Brain Res 15 Conners CK. Rating scales for use in drug studies with chil- Dev Brain Res 1991;63:201–7. dren. Psychopharmacology Bulletin Special Issue, Pharmaco- 47 Roy TS, Sabehrwal U. EVects of prenatal nicotine exposure therapy of Children 1973:24–9. on the morphogenesis of somatosensory cortex. Neurotoxi- 16 Gillberg C, Rasmussen P. Perceptual, motor and attentional col Teratol 1994;16:411–21. deficits in six-year-old children. Screening procedure in 48 Ali NJ, Pitson D, Stradling JR. Natural history of snoring preschool. Acta Paediatr Scand 1982;71:121–9. and related behaviour problems between the ages of 4 and 17 Gillberg IC. Children with minor neurodevelopmental 7 years. Arch Dis Child 1994;71:74–6. disorders. III: Neurological and neurodevelopmental prob- 49 Richman N, Stevenson J, Graham P. Pre-school to school: a lems at age 10. Dev Med Child Neurol 1985;27:3–16. behavioural study. London: Academic Press, 1982. 18 Gillberg IC, Winnergard I, Gillberg C. Screening methods, 50 Levine MD. Neurodevelopmental variation and dysfunction epidemiology and evaluation of intervention in DAMP in among school-aged children. In: Levine MD, Carey WB, preschool children. Eur Child Adolesc Psychiatry 1993;2: Crocker AC, eds. Developmental-behavioural pediatrics. 121–35. Philadelphia: WB Saunders, 1992.