JSLHR
Research Article
Prenatal, Perinatal, and Neonatal Risk Factors for Specific Language Impairment: A Prospective Pregnancy Cohort Study Andrew J. O. Whitehouse,a W. M. R. Shelton,a Caleb Ing,b and John P. Newnhamc
Purpose: Although genetic factors are known to play a causal role in specific language impairment (SLI), environmental factors may also be important. This study examined whether there are prenatal, perinatal, and neonatal factors that are associated with childhood SLI. Method: Participants were members of the Raine Study, a prospective cohort investigation of pregnant women and their offspring. Parent report indicated that 26 children had received a clinical diagnosis of SLI. Data from antenatal and birth medical records were compared between the children with SLI and typically developing comparison children (N = 1,799). Results: There were no statistically significant differences between the SLI and comparison groups in the individual
prenatal, perinatal, and neonatal factors examined. Aggregate risk scores were calculated for each period on the basis of factors known to be associated with neurodevelopmental disorder. There were no group differences in aggregate risk scores in the prenatal and perinatal periods. However, significantly more children in the SLI group (50%) compared with the comparison group (27.6%) experienced 2 or more risk factors during the neonatal period. Conclusion: The vast majority of prenatal, perinatal, and neonatal complications do not play a clear causal role in childhood SLI. However, poor neonatal health may signify increased risk for SLI.
S
diagnostic criteria at 4 years of age (Tomblin, Smith, & Zhang, 1997) and approximately half of these children maintaining a diagnosis in adolescence (Stothard, Snowling, Bishop, Chipchase, & Kaplan, 1998). The broader implications of SLI have been widely documented and include difficulties acquiring literacy, numeracy, and interpersonal relationships, with longer term effects on vocational attainment and mental health (Whitehouse, Line, Watt, & Bishop, 2009; Whitehouse, Watt, Line, & Bishop, 2009). Understanding the causes of SLI has been the focus of a considerable research effort. A genetic basis is supported by clustering in families, higher concordance in monozygotic twins than dizygotic twins, and the recent identification of molecular genetic variants associated with the disorder phenotype (Vernes et al., 2008). However, SLI concordance rates for monozygotic twins range from 39% to 88% depending on case selection criteria (Bishop & Hayiou-Thomas, 2008). Monozygotic twins share 100% of their genes, and therefore a concordance of less than 100% indicates that pre- and postnatal environmental factors may also be involved in the expression of SLI. A substantial body of research has investigated pre-, peri-, and neonatal characteristics associated with a number of neurodevelopmental disorders, such as autism (Glasson et al., 2004) and schizophrenia (Cannon,
pecific language impairment (SLI) is diagnosed when children experience a delay in the development of language that cannot be attributed to low nonverbal ability, hearing impairment, or limited educational opportunities. There is considerable variation in the diagnostic practices for SLI, but a minimum requirement is the standardized assessment of verbal and nonverbal abilities. Diagnosis typically hinges on verbal abilities being significantly below both age expectations and nonverbal ability (American Psychiatric Association, 2013; World Health Organization, 1992). SLI is among the most common of all neurodevelopmental disorders, with around 7% of children meeting
a
Telethon Kids Institute, University of Western Australia, Perth, Western Australia b Columbia University College of Physicians and Surgeons, New York, NY c School of Women’s and Infants’ Health, University of Western Australia, Perth, Western Australia Correspondence to Andrew J. O. Whitehouse: [email protected] Editor: Rhea Paul Associate Editor: Sarita Eisenberg Received July 15, 2013 Revision received October 8, 2013 Accepted December 9, 2013 DOI: 10.1044/2014_JSLHR-L-13-0186
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Key Words: specific language impairment, prenatal, obstetric
Disclosure: The authors have declared that no competing interests existed at the time of publication.
Journal of Speech, Language, and Hearing Research • Vol. 57 • 1418–1427 • August 2014 • A American Speech-Language-Hearing Association
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Jones, & Murray, 2002). A range of risk factors have been identified, including pregnancies complicated by gestational diabetes, antepartum hemorrhage, maternal cigarette smoking or alcohol consumption, longer labors and cesarean deliveries, and poor neonatal health, as indexed by low Apgar scores and time spent in special care units. Less research has examined these and other early factors in relation to the SLI phenotype. The few studies in this area have generally reported negative findings. Tomblin, et al. (1997) obtained the obstetric history of children with SLI and typically developing comparison children ages 4 to 5 years via phone interview with parents. There were no differences between groups in maternal exposure to disease and other teratogens during pregnancy (e.g., cigarette smoking and alcohol consumption), as well as a range of perinatal characteristics, such as the duration of labor and mode of delivery. A subsequent study by Bishop (1997) compared data from obstetric records between a clinical group, comprising 84 twin pairs between 7 and 16 years of age in which one or both twins met criteria for SLI, and a control group of 36 twin pairs with no history of speech-language difficulties. Largely negative results were reported, with the exception of preeclampsia (toxemia), which was more common among women who had a child later diagnosed with SLI. A further case-control study by Merricks, Stott, Goodyer, and Bolton (2004) found no association between SLI status in middle childhood (age range = 6–9 years) and a range of obstetric complications (including preeclampsia) described via parental recall, even after analyses were restricted to children with more severe language difficulties. Although these studies suggest that adverse obstetric and neonatal events do not play an important etiological role in SLI, the null findings may have been influenced by the method of data collection. Both the studies of Tomblin et al. (1997) and Merricks et al. (2004) obtained data on early life event via parent recall. Validation studies indicate that parental recall of distant obstetric events may be unreliable. In particular, underreporting of pregnancy complications has been found to be more common among parents of clinical populations and with low levels of education (Buka, Goldstein, Spartos, & Tsuang, 2004), both of which are relevant to the SLI population (Stanton-Chapman, Chapman, Kaiser, & Hancock, 2004). The Bishop (1997) study did obtain data directly from obstetric records. However, the participants in this study were twin pairs, and pregnancies to twins are known to be at considerably greater risk for obstetric complications (Rao, Sairam, & Shehata, 2004). Conclusions drawn from data obtained from the twin population may not extrapolate to singletons and thus the majority of individuals with SLI. The current study used a prospective longitudinal design to identify risk factors from prenatal, perinatal, and postnatal experience for developing SLI. Participants were members of the Western Australian Pregnancy Cohort (Raine) Study, which is a prospective cohort investigation of pregnant women and their live-born offspring. Children with SLI were identified via parent report at 5, 8, and 10 years of age with a clinical diagnosis of language disorder. Prenatal, perinatal, and neonatal data were obtained prospectively
from direct examination, parent report, and medical records, making this the most methodologically rigorous investigation of early risk factors for SLI to date.
Method Participants The Raine Study recruited pregnant women from the public antenatal clinic at King Edward Memorial Hospital (KEMH) or surrounding private clinics in Perth, Western Australia. Approximately 100 women per month were enrolled from August 1989 to April 1992, with a final sample of 2,979 pregnancies and 2,868 live-born children. Enrollment criteria were a gestational age between 16 and 20 weeks, English language skills sufficient to understand the study demands, an expectation to deliver at KEMH, and an intention to remain in Western Australia to enable future follow-up of their child (Newnham, Evans, Michael, Stanley, & Landau, 1993). Participant recruitment and all follow-ups of the study families were approved by the Human Ethics Committee at KEMH and/or Princess Margaret Hospital for Children in Perth.
Group Selection Criteria At the 5-, 8-, and 10-year follow-ups, caregivers were interviewed regarding their child’s medical and developmental history since the previous follow-up. During this interview, parents were asked to report whether their child had received a clinician-based diagnosis of any neurodevelopmental disorder, including language disorders. Parents were also asked at these time points whether their child had ever received speech therapy. Caregiver responses were then immediately assigned a code according to the International Classification of Diseases, Ninth Revision (ICD-9; Practice Management Information Corporation, 1993). Children who had been diagnosed with Down syndrome, autism, intellectual disability with a known cause, or hearing loss were excluded from the study. Children from a multiple birth or who were born at less than 37 weeks gestation were also not included in the study, given the well-established relationships between preterm birth, obstetric complications, and poor cognitive outcomes (Bhutta, Cleves, Casey, Cradock, & Anand, 2002). Finally, children were excluded from the current study if their parents reported that they spoke a language other than English at home. The SLI-E group in the current study comprised those children who were assigned the code of expressive language disorder (315.31), while the SLI-M group were those children who were given the code for mixed expressive-receptive language disorder (315.32). The participants in these two groups were also combined to form a combined SLI group (SLI-C). The comparison group comprised all of the children who met inclusion criteria for the study and whose parents provided data at the 5-, 8-, or 10-year follow-up indicating that the children did not have a clinical diagnosis of any language disorder.
Psychometric Assessments As part of their involvement in the Raine Study, participants were administered a series of language assessments
Whitehouse et al.: Early Life Complications and SLI
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at several follow-ups throughout childhood. In the first 3 years of life, caregivers completed the Infant Monitoring Questionnaire (IMQ) regarding their children’s behavior (Bricker, Squires, Kaminski, & Mounts, 1988). Different versions of the questionnaire (with items slightly modified according to children’s developmental level) are available for children ages 4 to 36 months. In the Raine Study, parents completed the 12-, 24-, and 36-month IMQ at their child’s 1-, 2-, and 3-year follow-ups, respectively. Each IMQ lists 30 age-appropriate behaviors, divided into five subscales of six items each: Communication, Gross Motor, Fine Motor, Adaptive, and Personal-Social. Parents are asked to rate whether their children demonstrated the behavior described in each item always (1 point), sometimes (0.5 points), or never (zero points). Ratings within each scale are then tallied to provide a score out of 6, with higher scores indicating greater levels of ability. Scales with one missing item were prorated and rounded to the nearest 0.5 to yield a score out of 6. Cutoff scores are provided for each scale at each age to indicate a “clinically significant” delay in the development of that particular skill. “Language delay” cutoff scores for the Communication subscale at 12, 24, and 36 months are 1.87, 3.90, and 4.63, respectively. At the 5- and 10-year follow-up, children were administered the Peabody Picture Vocabulary Test—Revised (PPVT–R; Dunn & Dunn, 1981). The PPVT–R provides a measure of receptive vocabulary, requiring children to select which of four pictures corresponds to an aurally presented word. Raw scores are converted to a Verbal IQ, standardized for age 2 years and above (based around a mean of 100 and a standard deviation of 15). At the 10-year follow-up, children were also administered the Clinical Evaluation of Language Fundamentals— Third Edition (CELF–III; Semel, Wiig, & Secord, 1995), which is an assessment of higher order language semantic, grammatical, and verbal memory abilities. Based on six subtests, the CELF–III generates a summary score for Receptive Language and Expressive Language subscales, both of which are standardized around a mean of 100 and a standard deviation of 15. Nonverbal ability was also assessed at age 10 years with Raven’s Colored Progressive Matrices (RCPM; Raven, 1977), a 36-item multiple choice test that presents a matrixlike arrangement of figural symbols and requires the child to select the missing symbols from a set of six alternatives. Raw scores are converted to percentiles, which provide an indication of a child’s performance relative to same-age peers.
Early Risk Factors Data on prenatal, perinatal, and neonatal risk factors were obtained prospectively from three sources. First, mothers and fathers completed study questionnaires during the 18th and 34th weeks of pregnancy, which provided information on pre-pregnancy weight and height and maternal smoking and alcohol intake during pregnancy. From the height and weight measurements, a body mass index (BMI) was calculated at each time point using the following formula:
(weight in kilograms)/(height in meters2). BMI was dichotomized to identify those women who had pre-pregnancy obesity (BMI > 30.0; World Health Organization, 2004), which has been linked to poor offspring neurodevelopment (Robinson et al., 2013). Sociodemographic data were also collected during pregnancy, including maternal age at conception, maternal level of education, household income (referenced according to $AUD24,000, which was the income “poverty” threshold specified by the Australian government at the time of recruitment), and the presence of the biological father in the family home during pregnancy. Maternal age at conception was dichotomized at 35 years, which is an age previously found to be associated with increased risk for neurodevelopmental disorder among offspring (Maimburg & Vaeth, 2006). Paternal age was not included because of a substantial amount of missing data (i.e., > 50% of cases). Second, pregnancy and labor characteristics were obtained from the mother’s medical record. The information obtained included data on existing and pregnancy-induced health complaints (diabetes, hypertension, hyperemesis, renal tract infection), pregnancy complications (threatened abortion, antepartum hemorrhage), and admittance to hospital. Third, data on delivery and neonatal life were collected from fetal medical records. Data recorded included type of labor onset; fetal presentation at admittance to hospital; presence of maternal fever during labor; presence of abnormal fetal heart rate during labor; maternal administration of oxytocin, prostaglandins, and analgesia (intramuscular narcotics and/or epidural); duration of the first two stages of labor; atypical placental and umbilical cord shape; mode of delivery; birth order; and season of birth. A prolonged first stage of labor was considered to be duration of 10 hr or greater, and a prolonged second stage of labor was considered to be a duration of 120 min or more (Albers, Schiff, & Gorwoda, 1996). Because all participants in the current study were born at term (≥ 37 weeks), we calculated a measure of appropriateness of fetal growth, proportion of optimal birth weight, according to the formula outlined by Blair, Liu, de Klerk, and Lawrence (2005). A proportion of optimal birth weight less than 90% has previously been used as an indication of intrauterine growth restriction (Whitehouse, Mattes, et al., 2012). Neonatal data included indicators of fetal health (time to spontaneous respiration, requirement of resuscitation, evidence of birth trauma, Apgar scores at 1 and 5 min, and admittance to intensive care unit or special care nursery after birth) and complications that can occur during the first few days of life (poor sucking or feeding, hypoglycemia, jaundice, anemia, and difficulty maintaining temperature).
Data Analysis The data obtained were divided into three categories for analysis: prenatal variables, spanning the period from conception to prior to the onset of labor; perinatal variables, covering the period from the onset of labor to the delivery of the offspring; and neonatal variables, spanning the period from the end of delivery until the offspring left hospital.
1420 Journal of Speech, Language, and Hearing Research • Vol. 57 • 1418–1427 • August 2014 Downloaded From: https://jslhr.pubs.asha.org/ by a University of New Mexico User on 04/04/2018 Terms of Use: https://pubs.asha.org/ss/rights_and_permissions.aspx
A chi-square analysis of 2 × 2 matrices was the principal statistical procedure used in this study. The relatively small number of participants in the SLI-E (n = 12) and SLI-M (n = 14) groups raised the possibility that there may be occasions where the expected number of cases in each cell is fewer than 5 (i.e., because of missing data). In response to this, statistical analyses were conducted only on the SLI-C group (n = 26), though we also present data separately for the SLI-E and SLI-M groups. Chi-square analyses first compared sociodemographic characteristics between the comparison group and the participants in the Raine Study who did not contribute data to the current investigation. These same variables were then compared between the SLI-C and comparison groups using chi-square analysis. Psychometric verbal and nonverbal data were also examined using independent-samples t tests to determine the validity of SLI-C and comparison group status. Following this, we used chi-square tests to examine differences between the SLI-C and comparison groups in individual prenatal, perinatal, and neonatal variables. As a final analysis, we calculated aggregate risk scores for the prenatal, perinatal, and neonatal periods by summing the total number of risk factors experienced by each participant. We selected variables a priori in each period that were identified in a recent review of autism research as early risk factors for this disorder (Kolevzon, Gross, & Reichenberg, 2007). This method was used to calculate aggregate risk scores because substantially more studies have investigated early risk factors for autism spectrum disorder (ASD) compared with SLI, and several investigations have identified close links in the etiological pathway between the two disorders (Kjelgaard & Tager-Flusberg, 2001; cf. Whitehouse, Barry, & Bishop, 2007). There were six risk factors in each of the prenatal, perinatal, and neonatal periods that were both described in ASD research and available in the current study. These factors are identified in Tables 3, 4, and 5 and formed the basis of the aggregate risk scores in the prenatal, perinatal, and neonatal periods, respectively. Because these scores constitute ordinal data, chi-square analyses examined between-groups differences in the proportion of children experiencing zero, one, and two or more complications during each period. The null findings of previous studies in this area suggest that any effect of prenatal or obstetric factors on SLI is likely to be small. For this reason and because of the exploratory nature of this study, the analyses adopted an alpha level of p < .05 to denote statistical significance, without correction for multiple comparisons. However, any significant effects were interpreted in light of the number and exploratory nature of the analyses (as recommended by Rothman, 1990).
Results Sample Attrition There were 2,868 live-born children in the Raine Study who were available for follow-up after birth. Children for whom parents reported a clinical diagnosis of Down
syndrome (n = 4), autism spectrum disorder (n = 16), intellectual disability with another known cause (n = 21), or hearing loss (n = 30) were not included in the current study. Further exclusions included 220 additional children who were born prior to 37 weeks, 121 additional children born to a multiple pregnancy, and 71 additional children who spoke a language other than English at home. This left 2,385 children eligible for inclusion in the study. The parents of 1,825 of the 2,385 eligible children (76.5%) had been interviewed when their children were 5, 8, and/or 10 years and provided data on whether their child had received any diagnoses of a neurodevelopmental disorder. There were 12 children with a diagnosis of expressive language disorder and 14 children with a diagnosis of mixed expressive-receptive language disorder. This provided groups of 26 and 1,799 children in the SLI-C and comparison group, respectively. With a sample size of 1,825, chi-square tests have 84.3% power to detect a significant difference between groups, with an effect size of 0.06 (Cramer’s V ) and an alpha level of ( p < .05). Table 1 presents the sociodemographic characteristics of the participant group as well as the children eligible for study inclusion but whose parents were not interviewed at the 5-, 8-, or 10-year follow-up (attrition group; n = 560). Chi-square analyses compared the comparison and the attrition groups and found that the latter group were more likely to have mothers with lower levels of formal education ( p < .01) and have a mother and father who lived separately during the pregnancy ( p < .01) but less likely to have been born into a household living below the poverty threshold ( p < .01). Sociodemographic factors were compared between the SLI-C and comparison groups (Table 1). Participants in the SLI-C group were more likely to be male ( p = .03) and to have mothers who had not completed secondary education at the time of pregnancy ( p = .02).
Sample Validation Independent-samples t tests found that the SLI-C group had significantly lower (worse) scores than the comparison group ( p < .05) on the IMQ at age 2 and 3 years, the PPVT–R at age 5 and 10 years, and the Expressive and Receptive Language subscales of the CELF–III at age 10 years (Table 2). The SLI-C group also had an average percentile score on the RCPM significantly lower than the comparison group at age 10 years. Individual data for all participants with SLI are presented as online supplemental materials. At age 3, 10 children in the SLI-C group (out of 24 with available data) scored below the “language delay” threshold on the IMQ; and at age 5 and 10 years, 8 (out of 21) and 5 (out of 18) children, respectively, scored at least one standard deviation below the mean on the PPVT–R. At age 10 years, 21 children completed the CELF–III. Seven (out of 21) children scored at least one standard deviation below the mean on both the Receptive and Expressive Language subscales of the CELF–III, whereas a further 4 children scored below this threshold on at least one of these scales. In total, 22 of the 26 children with SLI
Whitehouse et al.: Early Life Complications and SLI
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Table 1. Sociodemographic characteristics of SLI cases, comparison participants, and members of the Raine cohort who did not contribute data to the current analyses (attrition). SLI-E
SLI-M
SLI-C
Comparison
Attrition
Sociodemographic characteristic
N
n (%)
N
n (%)
N
n (%)
N
n (%)
N
n (%)
pa
pb
Mother did not complete secondary school Mother and father living separately during pregnancy Household income below poverty threshold Offspring sex Male Female
12
11 (91.7)
14
10 (71.4)
26
21 (80.8)
1,799
1,038 (58.8)
560
420 (75.0)
Research Article
Prenatal, Perinatal, and Neonatal Risk Factors for Specific Language Impairment: A Prospective Pregnancy Cohort Study Andrew J. O. Whitehouse,a W. M. R. Shelton,a Caleb Ing,b and John P. Newnhamc
Purpose: Although genetic factors are known to play a causal role in specific language impairment (SLI), environmental factors may also be important. This study examined whether there are prenatal, perinatal, and neonatal factors that are associated with childhood SLI. Method: Participants were members of the Raine Study, a prospective cohort investigation of pregnant women and their offspring. Parent report indicated that 26 children had received a clinical diagnosis of SLI. Data from antenatal and birth medical records were compared between the children with SLI and typically developing comparison children (N = 1,799). Results: There were no statistically significant differences between the SLI and comparison groups in the individual
prenatal, perinatal, and neonatal factors examined. Aggregate risk scores were calculated for each period on the basis of factors known to be associated with neurodevelopmental disorder. There were no group differences in aggregate risk scores in the prenatal and perinatal periods. However, significantly more children in the SLI group (50%) compared with the comparison group (27.6%) experienced 2 or more risk factors during the neonatal period. Conclusion: The vast majority of prenatal, perinatal, and neonatal complications do not play a clear causal role in childhood SLI. However, poor neonatal health may signify increased risk for SLI.
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diagnostic criteria at 4 years of age (Tomblin, Smith, & Zhang, 1997) and approximately half of these children maintaining a diagnosis in adolescence (Stothard, Snowling, Bishop, Chipchase, & Kaplan, 1998). The broader implications of SLI have been widely documented and include difficulties acquiring literacy, numeracy, and interpersonal relationships, with longer term effects on vocational attainment and mental health (Whitehouse, Line, Watt, & Bishop, 2009; Whitehouse, Watt, Line, & Bishop, 2009). Understanding the causes of SLI has been the focus of a considerable research effort. A genetic basis is supported by clustering in families, higher concordance in monozygotic twins than dizygotic twins, and the recent identification of molecular genetic variants associated with the disorder phenotype (Vernes et al., 2008). However, SLI concordance rates for monozygotic twins range from 39% to 88% depending on case selection criteria (Bishop & Hayiou-Thomas, 2008). Monozygotic twins share 100% of their genes, and therefore a concordance of less than 100% indicates that pre- and postnatal environmental factors may also be involved in the expression of SLI. A substantial body of research has investigated pre-, peri-, and neonatal characteristics associated with a number of neurodevelopmental disorders, such as autism (Glasson et al., 2004) and schizophrenia (Cannon,
pecific language impairment (SLI) is diagnosed when children experience a delay in the development of language that cannot be attributed to low nonverbal ability, hearing impairment, or limited educational opportunities. There is considerable variation in the diagnostic practices for SLI, but a minimum requirement is the standardized assessment of verbal and nonverbal abilities. Diagnosis typically hinges on verbal abilities being significantly below both age expectations and nonverbal ability (American Psychiatric Association, 2013; World Health Organization, 1992). SLI is among the most common of all neurodevelopmental disorders, with around 7% of children meeting
a
Telethon Kids Institute, University of Western Australia, Perth, Western Australia b Columbia University College of Physicians and Surgeons, New York, NY c School of Women’s and Infants’ Health, University of Western Australia, Perth, Western Australia Correspondence to Andrew J. O. Whitehouse: [email protected] Editor: Rhea Paul Associate Editor: Sarita Eisenberg Received July 15, 2013 Revision received October 8, 2013 Accepted December 9, 2013 DOI: 10.1044/2014_JSLHR-L-13-0186
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Key Words: specific language impairment, prenatal, obstetric
Disclosure: The authors have declared that no competing interests existed at the time of publication.
Journal of Speech, Language, and Hearing Research • Vol. 57 • 1418–1427 • August 2014 • A American Speech-Language-Hearing Association
Downloaded From: https://jslhr.pubs.asha.org/ by a University of New Mexico User on 04/04/2018 Terms of Use: https://pubs.asha.org/ss/rights_and_permissions.aspx
Jones, & Murray, 2002). A range of risk factors have been identified, including pregnancies complicated by gestational diabetes, antepartum hemorrhage, maternal cigarette smoking or alcohol consumption, longer labors and cesarean deliveries, and poor neonatal health, as indexed by low Apgar scores and time spent in special care units. Less research has examined these and other early factors in relation to the SLI phenotype. The few studies in this area have generally reported negative findings. Tomblin, et al. (1997) obtained the obstetric history of children with SLI and typically developing comparison children ages 4 to 5 years via phone interview with parents. There were no differences between groups in maternal exposure to disease and other teratogens during pregnancy (e.g., cigarette smoking and alcohol consumption), as well as a range of perinatal characteristics, such as the duration of labor and mode of delivery. A subsequent study by Bishop (1997) compared data from obstetric records between a clinical group, comprising 84 twin pairs between 7 and 16 years of age in which one or both twins met criteria for SLI, and a control group of 36 twin pairs with no history of speech-language difficulties. Largely negative results were reported, with the exception of preeclampsia (toxemia), which was more common among women who had a child later diagnosed with SLI. A further case-control study by Merricks, Stott, Goodyer, and Bolton (2004) found no association between SLI status in middle childhood (age range = 6–9 years) and a range of obstetric complications (including preeclampsia) described via parental recall, even after analyses were restricted to children with more severe language difficulties. Although these studies suggest that adverse obstetric and neonatal events do not play an important etiological role in SLI, the null findings may have been influenced by the method of data collection. Both the studies of Tomblin et al. (1997) and Merricks et al. (2004) obtained data on early life event via parent recall. Validation studies indicate that parental recall of distant obstetric events may be unreliable. In particular, underreporting of pregnancy complications has been found to be more common among parents of clinical populations and with low levels of education (Buka, Goldstein, Spartos, & Tsuang, 2004), both of which are relevant to the SLI population (Stanton-Chapman, Chapman, Kaiser, & Hancock, 2004). The Bishop (1997) study did obtain data directly from obstetric records. However, the participants in this study were twin pairs, and pregnancies to twins are known to be at considerably greater risk for obstetric complications (Rao, Sairam, & Shehata, 2004). Conclusions drawn from data obtained from the twin population may not extrapolate to singletons and thus the majority of individuals with SLI. The current study used a prospective longitudinal design to identify risk factors from prenatal, perinatal, and postnatal experience for developing SLI. Participants were members of the Western Australian Pregnancy Cohort (Raine) Study, which is a prospective cohort investigation of pregnant women and their live-born offspring. Children with SLI were identified via parent report at 5, 8, and 10 years of age with a clinical diagnosis of language disorder. Prenatal, perinatal, and neonatal data were obtained prospectively
from direct examination, parent report, and medical records, making this the most methodologically rigorous investigation of early risk factors for SLI to date.
Method Participants The Raine Study recruited pregnant women from the public antenatal clinic at King Edward Memorial Hospital (KEMH) or surrounding private clinics in Perth, Western Australia. Approximately 100 women per month were enrolled from August 1989 to April 1992, with a final sample of 2,979 pregnancies and 2,868 live-born children. Enrollment criteria were a gestational age between 16 and 20 weeks, English language skills sufficient to understand the study demands, an expectation to deliver at KEMH, and an intention to remain in Western Australia to enable future follow-up of their child (Newnham, Evans, Michael, Stanley, & Landau, 1993). Participant recruitment and all follow-ups of the study families were approved by the Human Ethics Committee at KEMH and/or Princess Margaret Hospital for Children in Perth.
Group Selection Criteria At the 5-, 8-, and 10-year follow-ups, caregivers were interviewed regarding their child’s medical and developmental history since the previous follow-up. During this interview, parents were asked to report whether their child had received a clinician-based diagnosis of any neurodevelopmental disorder, including language disorders. Parents were also asked at these time points whether their child had ever received speech therapy. Caregiver responses were then immediately assigned a code according to the International Classification of Diseases, Ninth Revision (ICD-9; Practice Management Information Corporation, 1993). Children who had been diagnosed with Down syndrome, autism, intellectual disability with a known cause, or hearing loss were excluded from the study. Children from a multiple birth or who were born at less than 37 weeks gestation were also not included in the study, given the well-established relationships between preterm birth, obstetric complications, and poor cognitive outcomes (Bhutta, Cleves, Casey, Cradock, & Anand, 2002). Finally, children were excluded from the current study if their parents reported that they spoke a language other than English at home. The SLI-E group in the current study comprised those children who were assigned the code of expressive language disorder (315.31), while the SLI-M group were those children who were given the code for mixed expressive-receptive language disorder (315.32). The participants in these two groups were also combined to form a combined SLI group (SLI-C). The comparison group comprised all of the children who met inclusion criteria for the study and whose parents provided data at the 5-, 8-, or 10-year follow-up indicating that the children did not have a clinical diagnosis of any language disorder.
Psychometric Assessments As part of their involvement in the Raine Study, participants were administered a series of language assessments
Whitehouse et al.: Early Life Complications and SLI
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at several follow-ups throughout childhood. In the first 3 years of life, caregivers completed the Infant Monitoring Questionnaire (IMQ) regarding their children’s behavior (Bricker, Squires, Kaminski, & Mounts, 1988). Different versions of the questionnaire (with items slightly modified according to children’s developmental level) are available for children ages 4 to 36 months. In the Raine Study, parents completed the 12-, 24-, and 36-month IMQ at their child’s 1-, 2-, and 3-year follow-ups, respectively. Each IMQ lists 30 age-appropriate behaviors, divided into five subscales of six items each: Communication, Gross Motor, Fine Motor, Adaptive, and Personal-Social. Parents are asked to rate whether their children demonstrated the behavior described in each item always (1 point), sometimes (0.5 points), or never (zero points). Ratings within each scale are then tallied to provide a score out of 6, with higher scores indicating greater levels of ability. Scales with one missing item were prorated and rounded to the nearest 0.5 to yield a score out of 6. Cutoff scores are provided for each scale at each age to indicate a “clinically significant” delay in the development of that particular skill. “Language delay” cutoff scores for the Communication subscale at 12, 24, and 36 months are 1.87, 3.90, and 4.63, respectively. At the 5- and 10-year follow-up, children were administered the Peabody Picture Vocabulary Test—Revised (PPVT–R; Dunn & Dunn, 1981). The PPVT–R provides a measure of receptive vocabulary, requiring children to select which of four pictures corresponds to an aurally presented word. Raw scores are converted to a Verbal IQ, standardized for age 2 years and above (based around a mean of 100 and a standard deviation of 15). At the 10-year follow-up, children were also administered the Clinical Evaluation of Language Fundamentals— Third Edition (CELF–III; Semel, Wiig, & Secord, 1995), which is an assessment of higher order language semantic, grammatical, and verbal memory abilities. Based on six subtests, the CELF–III generates a summary score for Receptive Language and Expressive Language subscales, both of which are standardized around a mean of 100 and a standard deviation of 15. Nonverbal ability was also assessed at age 10 years with Raven’s Colored Progressive Matrices (RCPM; Raven, 1977), a 36-item multiple choice test that presents a matrixlike arrangement of figural symbols and requires the child to select the missing symbols from a set of six alternatives. Raw scores are converted to percentiles, which provide an indication of a child’s performance relative to same-age peers.
Early Risk Factors Data on prenatal, perinatal, and neonatal risk factors were obtained prospectively from three sources. First, mothers and fathers completed study questionnaires during the 18th and 34th weeks of pregnancy, which provided information on pre-pregnancy weight and height and maternal smoking and alcohol intake during pregnancy. From the height and weight measurements, a body mass index (BMI) was calculated at each time point using the following formula:
(weight in kilograms)/(height in meters2). BMI was dichotomized to identify those women who had pre-pregnancy obesity (BMI > 30.0; World Health Organization, 2004), which has been linked to poor offspring neurodevelopment (Robinson et al., 2013). Sociodemographic data were also collected during pregnancy, including maternal age at conception, maternal level of education, household income (referenced according to $AUD24,000, which was the income “poverty” threshold specified by the Australian government at the time of recruitment), and the presence of the biological father in the family home during pregnancy. Maternal age at conception was dichotomized at 35 years, which is an age previously found to be associated with increased risk for neurodevelopmental disorder among offspring (Maimburg & Vaeth, 2006). Paternal age was not included because of a substantial amount of missing data (i.e., > 50% of cases). Second, pregnancy and labor characteristics were obtained from the mother’s medical record. The information obtained included data on existing and pregnancy-induced health complaints (diabetes, hypertension, hyperemesis, renal tract infection), pregnancy complications (threatened abortion, antepartum hemorrhage), and admittance to hospital. Third, data on delivery and neonatal life were collected from fetal medical records. Data recorded included type of labor onset; fetal presentation at admittance to hospital; presence of maternal fever during labor; presence of abnormal fetal heart rate during labor; maternal administration of oxytocin, prostaglandins, and analgesia (intramuscular narcotics and/or epidural); duration of the first two stages of labor; atypical placental and umbilical cord shape; mode of delivery; birth order; and season of birth. A prolonged first stage of labor was considered to be duration of 10 hr or greater, and a prolonged second stage of labor was considered to be a duration of 120 min or more (Albers, Schiff, & Gorwoda, 1996). Because all participants in the current study were born at term (≥ 37 weeks), we calculated a measure of appropriateness of fetal growth, proportion of optimal birth weight, according to the formula outlined by Blair, Liu, de Klerk, and Lawrence (2005). A proportion of optimal birth weight less than 90% has previously been used as an indication of intrauterine growth restriction (Whitehouse, Mattes, et al., 2012). Neonatal data included indicators of fetal health (time to spontaneous respiration, requirement of resuscitation, evidence of birth trauma, Apgar scores at 1 and 5 min, and admittance to intensive care unit or special care nursery after birth) and complications that can occur during the first few days of life (poor sucking or feeding, hypoglycemia, jaundice, anemia, and difficulty maintaining temperature).
Data Analysis The data obtained were divided into three categories for analysis: prenatal variables, spanning the period from conception to prior to the onset of labor; perinatal variables, covering the period from the onset of labor to the delivery of the offspring; and neonatal variables, spanning the period from the end of delivery until the offspring left hospital.
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A chi-square analysis of 2 × 2 matrices was the principal statistical procedure used in this study. The relatively small number of participants in the SLI-E (n = 12) and SLI-M (n = 14) groups raised the possibility that there may be occasions where the expected number of cases in each cell is fewer than 5 (i.e., because of missing data). In response to this, statistical analyses were conducted only on the SLI-C group (n = 26), though we also present data separately for the SLI-E and SLI-M groups. Chi-square analyses first compared sociodemographic characteristics between the comparison group and the participants in the Raine Study who did not contribute data to the current investigation. These same variables were then compared between the SLI-C and comparison groups using chi-square analysis. Psychometric verbal and nonverbal data were also examined using independent-samples t tests to determine the validity of SLI-C and comparison group status. Following this, we used chi-square tests to examine differences between the SLI-C and comparison groups in individual prenatal, perinatal, and neonatal variables. As a final analysis, we calculated aggregate risk scores for the prenatal, perinatal, and neonatal periods by summing the total number of risk factors experienced by each participant. We selected variables a priori in each period that were identified in a recent review of autism research as early risk factors for this disorder (Kolevzon, Gross, & Reichenberg, 2007). This method was used to calculate aggregate risk scores because substantially more studies have investigated early risk factors for autism spectrum disorder (ASD) compared with SLI, and several investigations have identified close links in the etiological pathway between the two disorders (Kjelgaard & Tager-Flusberg, 2001; cf. Whitehouse, Barry, & Bishop, 2007). There were six risk factors in each of the prenatal, perinatal, and neonatal periods that were both described in ASD research and available in the current study. These factors are identified in Tables 3, 4, and 5 and formed the basis of the aggregate risk scores in the prenatal, perinatal, and neonatal periods, respectively. Because these scores constitute ordinal data, chi-square analyses examined between-groups differences in the proportion of children experiencing zero, one, and two or more complications during each period. The null findings of previous studies in this area suggest that any effect of prenatal or obstetric factors on SLI is likely to be small. For this reason and because of the exploratory nature of this study, the analyses adopted an alpha level of p < .05 to denote statistical significance, without correction for multiple comparisons. However, any significant effects were interpreted in light of the number and exploratory nature of the analyses (as recommended by Rothman, 1990).
Results Sample Attrition There were 2,868 live-born children in the Raine Study who were available for follow-up after birth. Children for whom parents reported a clinical diagnosis of Down
syndrome (n = 4), autism spectrum disorder (n = 16), intellectual disability with another known cause (n = 21), or hearing loss (n = 30) were not included in the current study. Further exclusions included 220 additional children who were born prior to 37 weeks, 121 additional children born to a multiple pregnancy, and 71 additional children who spoke a language other than English at home. This left 2,385 children eligible for inclusion in the study. The parents of 1,825 of the 2,385 eligible children (76.5%) had been interviewed when their children were 5, 8, and/or 10 years and provided data on whether their child had received any diagnoses of a neurodevelopmental disorder. There were 12 children with a diagnosis of expressive language disorder and 14 children with a diagnosis of mixed expressive-receptive language disorder. This provided groups of 26 and 1,799 children in the SLI-C and comparison group, respectively. With a sample size of 1,825, chi-square tests have 84.3% power to detect a significant difference between groups, with an effect size of 0.06 (Cramer’s V ) and an alpha level of ( p < .05). Table 1 presents the sociodemographic characteristics of the participant group as well as the children eligible for study inclusion but whose parents were not interviewed at the 5-, 8-, or 10-year follow-up (attrition group; n = 560). Chi-square analyses compared the comparison and the attrition groups and found that the latter group were more likely to have mothers with lower levels of formal education ( p < .01) and have a mother and father who lived separately during the pregnancy ( p < .01) but less likely to have been born into a household living below the poverty threshold ( p < .01). Sociodemographic factors were compared between the SLI-C and comparison groups (Table 1). Participants in the SLI-C group were more likely to be male ( p = .03) and to have mothers who had not completed secondary education at the time of pregnancy ( p = .02).
Sample Validation Independent-samples t tests found that the SLI-C group had significantly lower (worse) scores than the comparison group ( p < .05) on the IMQ at age 2 and 3 years, the PPVT–R at age 5 and 10 years, and the Expressive and Receptive Language subscales of the CELF–III at age 10 years (Table 2). The SLI-C group also had an average percentile score on the RCPM significantly lower than the comparison group at age 10 years. Individual data for all participants with SLI are presented as online supplemental materials. At age 3, 10 children in the SLI-C group (out of 24 with available data) scored below the “language delay” threshold on the IMQ; and at age 5 and 10 years, 8 (out of 21) and 5 (out of 18) children, respectively, scored at least one standard deviation below the mean on the PPVT–R. At age 10 years, 21 children completed the CELF–III. Seven (out of 21) children scored at least one standard deviation below the mean on both the Receptive and Expressive Language subscales of the CELF–III, whereas a further 4 children scored below this threshold on at least one of these scales. In total, 22 of the 26 children with SLI
Whitehouse et al.: Early Life Complications and SLI
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Table 1. Sociodemographic characteristics of SLI cases, comparison participants, and members of the Raine cohort who did not contribute data to the current analyses (attrition). SLI-E
SLI-M
SLI-C
Comparison
Attrition
Sociodemographic characteristic
N
n (%)
N
n (%)
N
n (%)
N
n (%)
N
n (%)
pa
pb
Mother did not complete secondary school Mother and father living separately during pregnancy Household income below poverty threshold Offspring sex Male Female
12
11 (91.7)
14
10 (71.4)
26
21 (80.8)
1,799
1,038 (58.8)
560
420 (75.0)
