Pnediutric nnd Pninntnl Epidemiology 1992, 6, 403415
Original articles
Effects of maternal smoking upon neuropsychological development in early childhood: importance of taking account of social and environmental factors Peter A. Baghurst', Shi-lu Tongt, Alistair Woodward$ and Anthony J. McMichaelS *CSlRO Division of Human Nutrition, Adelaide, Australia, tDepartment of Special Programmes, National Health Education Institute, Beijing, China, and $Department of Community Medicine, Univenity of Adelaide, Australia
Summary. Data from a prospective study of 548 children followed from birth to 4 years of age were analysed to determine whether maternal smoking during and/or after pregnancy affects children's neuropsychological development. The differences in mean developmental test scores between children whose mothers smoked and those of mothers who did not smoke were slight, with subscale scores only 2.4 to 4.1% lower in children whose mothers smoked. These differences were not statistically significant after adjustment for socio-economic status, quality of home environment and mother's intelligence, suggesting that the social and environmental factors are major confounders of the association of exposure to maternal smoking and neuropsychological development in childhood. In order to gain a better understanding of this area, more precise measures of exposure to environmental tobacco smoke and comprehensive consideration of confounders will be required.
Introduction Although it is generally accepted that exposure of tobacco products from the mother's smoking during pregnancy is associated with both a reduction in Address for correspondence: Peter A. Baghurst, CSIRO Division of Human Nutrition, PO Box 10041Gouger St, Adelaide, South Australia 5000, Australia.
403
404
P.A. Bughurst et al.
birthweight and an increase in perinatal mortality, uncertainties exist about the functional consequences of maternal smoking on offspring. Increasing attention has been paid to studying the relationship between exposure to maternal smoking and neuropsychological development in childhood, extending into early adulthood. Several epidemiological studies have indicated that neuropsychological development in children may be impaired by such exposure, but a justified criticism of the investigations is that few prenatal and postnatal factors, other than social class, have been taken into account in these studies. Thus, the neuropsychological differences between the children of smokers and non-smokers may be attributable to other plausible explanations.1,2 In cohorts followed in Britain, Canada and Finland, associations have been reported between prenatal exposure to maternal smoking and deficits in neuropsychological functioning of school-aged children.= A clinical trial of smoking cessation intervention during pregnancy6 has also indicated that cessation of smoking after becoming pregnant may prevent some cognitive damage to the fetus, which seems to confirm a possible effect of prenatal exposure to tobacco on neuropsychological development in early childhood. Nevertheless, the quality of the studies has vaned widely. Few of the earlier studies have controlled for potential confounders, such as maternal intelligence, psychological status of the parents and postnatal exposure to environmental tobacco smoke. The US Collaborative Perinatal Project,’ which followed 29 889 children from birth to 7 years of age, has provided equivocal evidence of an association of cognitive deficit in children with exposure to maternal smoking. Although, in univariable analysis, the children of mothers who smoked 20 or more cigarettes per day had an increased risk for learning difficulties (LD), hyperkinetic-impulsive behaviour (HI) and neurological ‘soft signs’ (NS), no significant relationship between prenatal exposure to maternal smoking and LD or NS in children was found in the final multiple discriminant model. Mother‘s smoking during pregnancy, in this study, was identified as one of the significant discriminators between children with HI and those who did not have HI. However, the effect of maternal smoking on child’s hyperkinetic-impulsive behaviour was not as large as other factors (such as occurrence of siblings with HI, and head circumferenceat birth). Some participating centres in the US Collaborative Perinatal Project reported inconsistent results. The data collected at the Boston Lying-In Hospital indicated that hyperactivity, short attention span, and lower scores on spelling and reading tests were more frequent for children whose mothers had smoked throughout pregnancy.8 The cognitive decrements were mild, with achievement test scores only 2 to 4% lower in children whose mothers had smoked during pregnancy. Hardy and Mellits reported that, in a matched-pair prospective study conducted in east Baltimore, there was no significant difference in intellectual functioning between children of mothers who smoked during pregnancy and children
Maternal smoking and neuropsychological development
405
whose mothers did not smoke.9 As Donovan pointed out, however, the sample size of the investigation was small (88 pairs), and the statistical power of the investigation was 10w.l~Thus, the results of this study do not exclude the existence of harmful effects of smoking while pregnant. Since the possible long-term effects of maternal smoking on childhood neuropsychological development are of great theoretical and practical importance, the question has emerged of whether the reported lower neuropsychological functioning of children can be attributed to exposure to maternal smoking or to other coexistent aspects of the child's social and environmental circumstances. The results reported in this paper come from a follow-up study of 548 4-yearold children whose mothers were recruited during pregnancy in the Port Pirie Cohort Study. The analyses focus on the associations of the neuropsychological outcome in childhood with maternal smoking, and a number of key social and environmental factors. Evidence is provided that the decrements in children's neuropsychological functioning associated with antenatal or postnatal exposure to maternal smoking are not as large as those attributable to the child's social and environmental factors, and that appropriate adjustment for these factors may explain the mild association between exposure to maternal smoking and neuropsychological development in children.
Methods The Port Pirie Cohort Study is a large collaborativeepidemiological study in which the primary objective has been to examine the relation between exposure to environmental lead and early childhood growth and development. The study population presented an unusual opportunity to evaluate children's neuropsychological development in relation to exposure to maternal smoking, while controlling for other covariates. The study has obtained detailed and formal measures of neuropsychological development in children, as well as measurements of the major social and environmental confounders, and details of the mother's smoking during and after pregnancy. All women living in Port Pirie (population 16000),South Australia, or in the immediately adjoining region, who attended for the first time for antenatal care between May 1979 and May 1982, were encouraged to contact the study coordinator (community health nurse) to discuss participation. The participants completed a baseline questionnaire that included information about their current and pre-pregnancy smoking habits, reproductive histories, sociodemographic and clinical characteristics, intake of alcohol, and diet. The women were defined as non-smokers if they had never smoked or had smoked no more than five cigarettes (total) during this pregnancy. Any changes in smoking status during the pregnancy were recorded in an interview at 32 weeks of gestation. The
406
P.A. Bughurst et al.
information on the child's postnatal exposure to maternal smoking was also obtained by questionnaire-interview. All interviews were carried out by one of four trained nurse-interviewers. A total of 831 pregnant women were recruited into the study. These represented an estimated 90% of all newly occurring pregnancies during this period. Of these 831 pregnancies, 723 were followed to single live births. The number of children remaining in the cohort was 548 at the age of 4 years. The majority (approximately80%) of the children lost to follow-up were in the families that left the Port Pirie district; a smaller number of families (about 20% of those lost to follow-up) simply discontinued their participation. The developmental status of each child was assessed with the use of the Bayley Scales of Infant Development (BSID)at age 2 years and McCarthy Scales of BSID comprises a Mental Scale of Children's Abilities (MSCA)at age 4 163 items and Motor Scale of 81 items. The Mental Scale assesses sensoryperceptual acuities and discriminations, and ability to respond to these; it also assesses acquisition of 'object constancy', memory, learning, problem-solving ability, early language and speech development, and ability to form generalisations and classifications. Results are expressed as a single standard score-the Mental Development Index (MDI). The Motor Scale measures gross and fine motor co-ordination, which is expressed as Psychomotor Development Index (PDI). The MSCA consists of General Cognitive Index (GCI), and two additional subscales of memory and motor performance. The GCI is constructed by combining scores on the verbal, perceptual-performance and quantitative subscales. Both BSID and MSCA are among tests that best predict subsequent neuropsychological development in childhood.11,13 A research psychologist, who was unaware of the child's exposure to maternal smoking, conducted all testing sessions in a clinic setting. Although the psychologist had also assessed the child's abilities (using BSID)at the age of 2 years, he was not aware of that earlier result when the MSCA was conducted. Assessment of socio-economic status, using Daniel's Scale of Prestige of Occupations in A~stralia,'~ was made based on the information obtained from the mother at 16 weeks of gestation. On this Scale of Prestige of Occupation a lower Daniel's score represents greater prestige. Maternal intelligence was estimated with use of the Wechsler Adult Intelligence Scale-Revi~ed.~~This test was administered in full by the research psychologist while the children were in the age range of 3 to 5 years. The care-giving environment, using the Home Observation for Measurement of the Environment (HOME) inventory,16 was assessed during a visit to the children's homes when they were 3 years of age, The detailed description of the measurement procedures has been reported elsewhere. 17,18
Maternal smoking and neuropsychological development
407
Statistical methods Statistical analysis was done by conventional regression techniques included in Genstat (A General Statistical Program).l9 In simple and multiple regression analyses, a dichotomous variable for maternal smoking was used. The effect of maternal smoking was obtained from the regression coefficient on a dummy independent variable which took on a value of zero if the mother was a nonsmoker and one if the mother was a smoker. The regression analyses were conducted only on those children with complete data for all the variables considered.
Results
Maternal smoking and children’s abilities The analyses of children’s scores on the Bayley and McCarthy scales of children’s abilities with postnatal exposure to maternal smoking (Table 1)showed that the children of smokers performed at 2.4 to 4.1% lower level in most of the testing sessions by comparison with those of non-smokers (PG0.03). The mean values of MDI and GCI for children with postnatal exposure to mother‘s smoke were 107.7 (s.e.=l.O) and 105.3(s.e.=1.1) compared to 110.4 (s.e.=0.8) and 108.8 (s.e.=0.8) for children whose mothers did not smoke. The decrements in MDI and GCI scores in the children of smokers were statistically significant (P=0.03and 0.01, respectively).The children with postnatal exposure to maternal smoking also had lower scores for some other subscales of MSCA: the verbal, perceptual-performance and motor subscales ( P S 0.03). Table 1. Children‘s mean scores (standard error) on the Bayley and McCarthy scales of children‘s abilities with exposure to maternal smoking
Prenatal Yes
Postnatal
No
P
Yes
No
P
BSID MDI PDI
n=160 n=420 108.4(1.2) 109.7(0.8) 0.34 105.2(1.1) 105.3(0.7) 0.94
n=232 n=348 107.7(1.0) 110.4(0.8) 104.8(0.9) 105.7(0.8)
0.03 0.46
MSCA GCI Verbal Perceptualperformance Quantitative Memory Motor
n=373 n=148 106.0(1.3) 108.2(0.8) 0.13 52.7(0.8) 53.9(0.5) 0.19
n=190 n=331 105.3(1.1) 108.8(0.8) 52.4(0.7) 54.3(0.6)
0.01 0.03
56.1(0.8) 57.7(0.4) 0.07 SO.O(O.7) Sl.O(O.5) 0.26 47.8(0.6) 48.5(0.5) 0.46 52.9(0.7) 54.3(0.4) 0.10
55.7(0.7) 58.1(0.5) co.01 sO.O(O.7) 51.1(0.5) 0.17 47.5(0.6) 48.8(0.5) 0.10 52.6(0.6)
54.6(0.4)
co.01
408
P.A. Bughurst et al.
However, no significant differences were found between the scores of children with antenatal exposure to maternal smoking and those of children with no antenatal exposure.
Socio-environmental factors and children’s abilities An examination of the relationship of children’s scores on the Bayley and McCarthy scales of children’s abilities to soao-economic status, HOME scores and maternal intelligence indicated that the child’s neuropsychological development was significantly associated with soda1 and environmental factors (Tables 2, 3 Table 2. Children’s mean scores (standard error) on the Bayley and McCarthy scales of children’s abilities with socio-economic status
-
Daniel’s scores a
BSID MDI PDI
n=72 n=195 n=139 n=169 116.0(1.6) 109.6(1.1) llO.O(l.4) 105.7(1.1) 104.9(1.8) 104.3(1.0) 107.3(1.4) 105.0(1.1)
MSCA
n=63 n=170 n=130 n=154 117.8(1.6) 109.0(1.0) 106.3(1.4) 103.0(1.3) 59.4(1.2) 54.3(0.7) 53.1(0.8) 50.9(0.8) 62.4(0.8) 58.4(0.6) 56.6(0.8) 54.5(0.8) 55.7(1.0) 51.3(0.6) 49.9(0.8) 49.0(0.8) 52.7(1.1) 49.4(0.6) 47.4(0.8) 46.1(0.7) 57.7(0.8) 54.8(0.6) 53.3(0.8) 51.8(0.7)
GCI Verbal Perceptual-performance Quantitative Memory Motor
P
Original articles
Effects of maternal smoking upon neuropsychological development in early childhood: importance of taking account of social and environmental factors Peter A. Baghurst', Shi-lu Tongt, Alistair Woodward$ and Anthony J. McMichaelS *CSlRO Division of Human Nutrition, Adelaide, Australia, tDepartment of Special Programmes, National Health Education Institute, Beijing, China, and $Department of Community Medicine, Univenity of Adelaide, Australia
Summary. Data from a prospective study of 548 children followed from birth to 4 years of age were analysed to determine whether maternal smoking during and/or after pregnancy affects children's neuropsychological development. The differences in mean developmental test scores between children whose mothers smoked and those of mothers who did not smoke were slight, with subscale scores only 2.4 to 4.1% lower in children whose mothers smoked. These differences were not statistically significant after adjustment for socio-economic status, quality of home environment and mother's intelligence, suggesting that the social and environmental factors are major confounders of the association of exposure to maternal smoking and neuropsychological development in childhood. In order to gain a better understanding of this area, more precise measures of exposure to environmental tobacco smoke and comprehensive consideration of confounders will be required.
Introduction Although it is generally accepted that exposure of tobacco products from the mother's smoking during pregnancy is associated with both a reduction in Address for correspondence: Peter A. Baghurst, CSIRO Division of Human Nutrition, PO Box 10041Gouger St, Adelaide, South Australia 5000, Australia.
403
404
P.A. Bughurst et al.
birthweight and an increase in perinatal mortality, uncertainties exist about the functional consequences of maternal smoking on offspring. Increasing attention has been paid to studying the relationship between exposure to maternal smoking and neuropsychological development in childhood, extending into early adulthood. Several epidemiological studies have indicated that neuropsychological development in children may be impaired by such exposure, but a justified criticism of the investigations is that few prenatal and postnatal factors, other than social class, have been taken into account in these studies. Thus, the neuropsychological differences between the children of smokers and non-smokers may be attributable to other plausible explanations.1,2 In cohorts followed in Britain, Canada and Finland, associations have been reported between prenatal exposure to maternal smoking and deficits in neuropsychological functioning of school-aged children.= A clinical trial of smoking cessation intervention during pregnancy6 has also indicated that cessation of smoking after becoming pregnant may prevent some cognitive damage to the fetus, which seems to confirm a possible effect of prenatal exposure to tobacco on neuropsychological development in early childhood. Nevertheless, the quality of the studies has vaned widely. Few of the earlier studies have controlled for potential confounders, such as maternal intelligence, psychological status of the parents and postnatal exposure to environmental tobacco smoke. The US Collaborative Perinatal Project,’ which followed 29 889 children from birth to 7 years of age, has provided equivocal evidence of an association of cognitive deficit in children with exposure to maternal smoking. Although, in univariable analysis, the children of mothers who smoked 20 or more cigarettes per day had an increased risk for learning difficulties (LD), hyperkinetic-impulsive behaviour (HI) and neurological ‘soft signs’ (NS), no significant relationship between prenatal exposure to maternal smoking and LD or NS in children was found in the final multiple discriminant model. Mother‘s smoking during pregnancy, in this study, was identified as one of the significant discriminators between children with HI and those who did not have HI. However, the effect of maternal smoking on child’s hyperkinetic-impulsive behaviour was not as large as other factors (such as occurrence of siblings with HI, and head circumferenceat birth). Some participating centres in the US Collaborative Perinatal Project reported inconsistent results. The data collected at the Boston Lying-In Hospital indicated that hyperactivity, short attention span, and lower scores on spelling and reading tests were more frequent for children whose mothers had smoked throughout pregnancy.8 The cognitive decrements were mild, with achievement test scores only 2 to 4% lower in children whose mothers had smoked during pregnancy. Hardy and Mellits reported that, in a matched-pair prospective study conducted in east Baltimore, there was no significant difference in intellectual functioning between children of mothers who smoked during pregnancy and children
Maternal smoking and neuropsychological development
405
whose mothers did not smoke.9 As Donovan pointed out, however, the sample size of the investigation was small (88 pairs), and the statistical power of the investigation was 10w.l~Thus, the results of this study do not exclude the existence of harmful effects of smoking while pregnant. Since the possible long-term effects of maternal smoking on childhood neuropsychological development are of great theoretical and practical importance, the question has emerged of whether the reported lower neuropsychological functioning of children can be attributed to exposure to maternal smoking or to other coexistent aspects of the child's social and environmental circumstances. The results reported in this paper come from a follow-up study of 548 4-yearold children whose mothers were recruited during pregnancy in the Port Pirie Cohort Study. The analyses focus on the associations of the neuropsychological outcome in childhood with maternal smoking, and a number of key social and environmental factors. Evidence is provided that the decrements in children's neuropsychological functioning associated with antenatal or postnatal exposure to maternal smoking are not as large as those attributable to the child's social and environmental factors, and that appropriate adjustment for these factors may explain the mild association between exposure to maternal smoking and neuropsychological development in children.
Methods The Port Pirie Cohort Study is a large collaborativeepidemiological study in which the primary objective has been to examine the relation between exposure to environmental lead and early childhood growth and development. The study population presented an unusual opportunity to evaluate children's neuropsychological development in relation to exposure to maternal smoking, while controlling for other covariates. The study has obtained detailed and formal measures of neuropsychological development in children, as well as measurements of the major social and environmental confounders, and details of the mother's smoking during and after pregnancy. All women living in Port Pirie (population 16000),South Australia, or in the immediately adjoining region, who attended for the first time for antenatal care between May 1979 and May 1982, were encouraged to contact the study coordinator (community health nurse) to discuss participation. The participants completed a baseline questionnaire that included information about their current and pre-pregnancy smoking habits, reproductive histories, sociodemographic and clinical characteristics, intake of alcohol, and diet. The women were defined as non-smokers if they had never smoked or had smoked no more than five cigarettes (total) during this pregnancy. Any changes in smoking status during the pregnancy were recorded in an interview at 32 weeks of gestation. The
406
P.A. Bughurst et al.
information on the child's postnatal exposure to maternal smoking was also obtained by questionnaire-interview. All interviews were carried out by one of four trained nurse-interviewers. A total of 831 pregnant women were recruited into the study. These represented an estimated 90% of all newly occurring pregnancies during this period. Of these 831 pregnancies, 723 were followed to single live births. The number of children remaining in the cohort was 548 at the age of 4 years. The majority (approximately80%) of the children lost to follow-up were in the families that left the Port Pirie district; a smaller number of families (about 20% of those lost to follow-up) simply discontinued their participation. The developmental status of each child was assessed with the use of the Bayley Scales of Infant Development (BSID)at age 2 years and McCarthy Scales of BSID comprises a Mental Scale of Children's Abilities (MSCA)at age 4 163 items and Motor Scale of 81 items. The Mental Scale assesses sensoryperceptual acuities and discriminations, and ability to respond to these; it also assesses acquisition of 'object constancy', memory, learning, problem-solving ability, early language and speech development, and ability to form generalisations and classifications. Results are expressed as a single standard score-the Mental Development Index (MDI). The Motor Scale measures gross and fine motor co-ordination, which is expressed as Psychomotor Development Index (PDI). The MSCA consists of General Cognitive Index (GCI), and two additional subscales of memory and motor performance. The GCI is constructed by combining scores on the verbal, perceptual-performance and quantitative subscales. Both BSID and MSCA are among tests that best predict subsequent neuropsychological development in childhood.11,13 A research psychologist, who was unaware of the child's exposure to maternal smoking, conducted all testing sessions in a clinic setting. Although the psychologist had also assessed the child's abilities (using BSID)at the age of 2 years, he was not aware of that earlier result when the MSCA was conducted. Assessment of socio-economic status, using Daniel's Scale of Prestige of Occupations in A~stralia,'~ was made based on the information obtained from the mother at 16 weeks of gestation. On this Scale of Prestige of Occupation a lower Daniel's score represents greater prestige. Maternal intelligence was estimated with use of the Wechsler Adult Intelligence Scale-Revi~ed.~~This test was administered in full by the research psychologist while the children were in the age range of 3 to 5 years. The care-giving environment, using the Home Observation for Measurement of the Environment (HOME) inventory,16 was assessed during a visit to the children's homes when they were 3 years of age, The detailed description of the measurement procedures has been reported elsewhere. 17,18
Maternal smoking and neuropsychological development
407
Statistical methods Statistical analysis was done by conventional regression techniques included in Genstat (A General Statistical Program).l9 In simple and multiple regression analyses, a dichotomous variable for maternal smoking was used. The effect of maternal smoking was obtained from the regression coefficient on a dummy independent variable which took on a value of zero if the mother was a nonsmoker and one if the mother was a smoker. The regression analyses were conducted only on those children with complete data for all the variables considered.
Results
Maternal smoking and children’s abilities The analyses of children’s scores on the Bayley and McCarthy scales of children’s abilities with postnatal exposure to maternal smoking (Table 1)showed that the children of smokers performed at 2.4 to 4.1% lower level in most of the testing sessions by comparison with those of non-smokers (PG0.03). The mean values of MDI and GCI for children with postnatal exposure to mother‘s smoke were 107.7 (s.e.=l.O) and 105.3(s.e.=1.1) compared to 110.4 (s.e.=0.8) and 108.8 (s.e.=0.8) for children whose mothers did not smoke. The decrements in MDI and GCI scores in the children of smokers were statistically significant (P=0.03and 0.01, respectively).The children with postnatal exposure to maternal smoking also had lower scores for some other subscales of MSCA: the verbal, perceptual-performance and motor subscales ( P S 0.03). Table 1. Children‘s mean scores (standard error) on the Bayley and McCarthy scales of children‘s abilities with exposure to maternal smoking
Prenatal Yes
Postnatal
No
P
Yes
No
P
BSID MDI PDI
n=160 n=420 108.4(1.2) 109.7(0.8) 0.34 105.2(1.1) 105.3(0.7) 0.94
n=232 n=348 107.7(1.0) 110.4(0.8) 104.8(0.9) 105.7(0.8)
0.03 0.46
MSCA GCI Verbal Perceptualperformance Quantitative Memory Motor
n=373 n=148 106.0(1.3) 108.2(0.8) 0.13 52.7(0.8) 53.9(0.5) 0.19
n=190 n=331 105.3(1.1) 108.8(0.8) 52.4(0.7) 54.3(0.6)
0.01 0.03
56.1(0.8) 57.7(0.4) 0.07 SO.O(O.7) Sl.O(O.5) 0.26 47.8(0.6) 48.5(0.5) 0.46 52.9(0.7) 54.3(0.4) 0.10
55.7(0.7) 58.1(0.5) co.01 sO.O(O.7) 51.1(0.5) 0.17 47.5(0.6) 48.8(0.5) 0.10 52.6(0.6)
54.6(0.4)
co.01
408
P.A. Bughurst et al.
However, no significant differences were found between the scores of children with antenatal exposure to maternal smoking and those of children with no antenatal exposure.
Socio-environmental factors and children’s abilities An examination of the relationship of children’s scores on the Bayley and McCarthy scales of children’s abilities to soao-economic status, HOME scores and maternal intelligence indicated that the child’s neuropsychological development was significantly associated with soda1 and environmental factors (Tables 2, 3 Table 2. Children’s mean scores (standard error) on the Bayley and McCarthy scales of children’s abilities with socio-economic status
-
Daniel’s scores a
BSID MDI PDI
n=72 n=195 n=139 n=169 116.0(1.6) 109.6(1.1) llO.O(l.4) 105.7(1.1) 104.9(1.8) 104.3(1.0) 107.3(1.4) 105.0(1.1)
MSCA
n=63 n=170 n=130 n=154 117.8(1.6) 109.0(1.0) 106.3(1.4) 103.0(1.3) 59.4(1.2) 54.3(0.7) 53.1(0.8) 50.9(0.8) 62.4(0.8) 58.4(0.6) 56.6(0.8) 54.5(0.8) 55.7(1.0) 51.3(0.6) 49.9(0.8) 49.0(0.8) 52.7(1.1) 49.4(0.6) 47.4(0.8) 46.1(0.7) 57.7(0.8) 54.8(0.6) 53.3(0.8) 51.8(0.7)
GCI Verbal Perceptual-performance Quantitative Memory Motor
P
