19]. With respect to anxiety in particular, studies that have distinguished between neurodevelopmental conditions (autism, attention deficit hyperactivity disorder, developmental delay, learning disability) and psychiatric morbidity have found no additional risk of anxiety between term and preterm children. For example, data from the National Survey of Children’s Health (N = 95,677) suggest that increased risk of anxiety is found only among preterm children with comorbid neurodevelopmental conditions [29]. There is journal.pone.0077579 some suggestion from meta-analyses that the relationship between prematurity and emotional problems also varies by the era in which the preterm infant was born, with early studies (<1990) jir.2014.0227 showing an increased risk and later studies (>1998) showing no association [30]. It is likely that biological and Deslorelin solubility environmental pathways operate in concert, where impaired hypothalamic-pituitary-adrenal-axis functioning, in combination with risky extrauterine factors increase the risk of anxiety [4]. Thus, the reduced likelihood of childhood anxiety in preterm infants that we report may be related to the: 1) protective influence of a reduced length of time exposed to a compromised, suboptimal intrauterine environment (fetal programming hypothesis) [14]; in this case, reduced time in-utero may decrease exposure to pathological events, as described in the fetus-at-risk paradigm where the benefit of preterm delivery in terms of ameliorating risk of adverse fetal and neonatal outcomes may exceed that of term delivery [31]; 2) attenuation of risk as a result of early detection and treatment of anxiety symptoms during routine developmental follow-up of preterm infants; or 3) advanced neonatal care that improved neurodevelopmental outcomes in our cohort born 2003?004 [30].Strengths and LimitationsA strength of this study is the inclusion of multiple early life factors from pregnancy to age 5. The population-based sample enhances the study’s generalizability. However, some limitations are inherent in the use of administrative data. We were unable to explore some predictors that others have demonstrated as important (parenting, peers, child temperament [3], child cognitions [21]). Similarly, given that cognitive behavior therapy is BAY1217389MedChemExpress BAY1217389 commonly used to treat mild/ moderate childhood anxiety [24], but not reported in administrative databases, and anxiety in children is often unrecognized and untreated [3], the children we studied likely represent those with greater symptom severity. As such, the findings may not be generalizable to children with less severe anxiety. However, a recent study (N = 1,085) reported that 4-year old children BAY1217389 clinical trials ofPLOS ONE | DOI:10.1371/journal.pone.0129339 July 9,10 /Predictors of Childhood Anxietywomen with both severe and sub-clinical depressive symptoms from pregnancy to 4-years postpartum were more likely to experience emotional difficulties (23 vs 19 , respectively) compared to women with no symptoms (7 ), [20] suggesting that sub-clinical symptoms can also be associated with emotional problems in preschoolers. The prevalence rate of anxiety may have been influenced by: 1) Pepstatin web measuring childhood anxiety by a single diagnostic code, with the possibility that transient cases may be erroneously classified as `childhood anxiety’; 2) anxiolytics that are prescribed for disorders other than anxiety; 3) not capturing children who were prescribed antidepressants (SSRI’s) for anxiety [26]; and under-recognition or false positive diagnose.19]. With respect to anxiety in particular, studies that have distinguished between neurodevelopmental conditions (autism, attention deficit hyperactivity disorder, developmental delay, learning disability) and psychiatric morbidity have found no additional risk of anxiety between term and preterm children. For example, data from the National Survey of Children’s Health (N = 95,677) suggest that increased risk of anxiety is found only among preterm children with comorbid neurodevelopmental conditions [29]. There is journal.pone.0077579 some suggestion from meta-analyses that the relationship between prematurity and emotional problems also varies by the era in which the preterm infant was born, with early studies (<1990) jir.2014.0227 showing an increased risk and later studies (>1998) showing no association [30]. It is likely that biological and environmental pathways operate in concert, where impaired hypothalamic-pituitary-adrenal-axis functioning, in combination with risky extrauterine factors increase the risk of anxiety [4]. Thus, the reduced likelihood of childhood anxiety in preterm infants that we report may be related to the: 1) protective influence of a reduced length of time exposed to a compromised, suboptimal intrauterine environment (fetal programming hypothesis) [14]; in this case, reduced time in-utero may decrease exposure to pathological events, as described in the fetus-at-risk paradigm where the benefit of preterm delivery in terms of ameliorating risk of adverse fetal and neonatal outcomes may exceed that of term delivery [31]; 2) attenuation of risk as a result of early detection and treatment of anxiety symptoms during routine developmental follow-up of preterm infants; or 3) advanced neonatal care that improved neurodevelopmental outcomes in our cohort born 2003?004 [30].Strengths and LimitationsA strength of this study is the inclusion of multiple early life factors from pregnancy to age 5. The population-based sample enhances the study’s generalizability. However, some limitations are inherent in the use of administrative data. We were unable to explore some predictors that others have demonstrated as important (parenting, peers, child temperament [3], child cognitions [21]). Similarly, given that cognitive behavior therapy is commonly used to treat mild/ moderate childhood anxiety [24], but not reported in administrative databases, and anxiety in children is often unrecognized and untreated [3], the children we studied likely represent those with greater symptom severity. As such, the findings may not be generalizable to children with less severe anxiety. However, a recent study (N = 1,085) reported that 4-year old children ofPLOS ONE | DOI:10.1371/journal.pone.0129339 July 9,10 /Predictors of Childhood Anxietywomen with both severe and sub-clinical depressive symptoms from pregnancy to 4-years postpartum were more likely to experience emotional difficulties (23 vs 19 , respectively) compared to women with no symptoms (7 ), [20] suggesting that sub-clinical symptoms can also be associated with emotional problems in preschoolers. The prevalence rate of anxiety may have been influenced by: 1) measuring childhood anxiety by a single diagnostic code, with the possibility that transient cases may be erroneously classified as `childhood anxiety’; 2) anxiolytics that are prescribed for disorders other than anxiety; 3) not capturing children who were prescribed antidepressants (SSRI’s) for anxiety [26]; and under-recognition or false positive diagnose.19]. With respect to anxiety in particular, studies that have distinguished between neurodevelopmental conditions (autism, attention deficit hyperactivity disorder, developmental delay, learning disability) and psychiatric morbidity have found no additional risk of anxiety between term and preterm children. For example, data from the National Survey of Children’s Health (N = 95,677) suggest that increased risk of anxiety is found only among preterm children with comorbid neurodevelopmental conditions [29]. There is journal.pone.0077579 some suggestion from meta-analyses that the relationship between prematurity and emotional problems also varies by the era in which the preterm infant was born, with early studies (<1990) jir.2014.0227 showing an increased risk and later studies (>1998) showing no association [30]. It is likely that biological and environmental pathways operate in concert, where impaired hypothalamic-pituitary-adrenal-axis functioning, in combination with risky extrauterine factors increase the risk of anxiety [4]. Thus, the reduced likelihood of childhood anxiety in preterm infants that we report may be related to the: 1) protective influence of a reduced length of time exposed to a compromised, suboptimal intrauterine environment (fetal programming hypothesis) [14]; in this case, reduced time in-utero may decrease exposure to pathological events, as described in the fetus-at-risk paradigm where the benefit of preterm delivery in terms of ameliorating risk of adverse fetal and neonatal outcomes may exceed that of term delivery [31]; 2) attenuation of risk as a result of early detection and treatment of anxiety symptoms during routine developmental follow-up of preterm infants; or 3) advanced neonatal care that improved neurodevelopmental outcomes in our cohort born 2003?004 [30].Strengths and LimitationsA strength of this study is the inclusion of multiple early life factors from pregnancy to age 5. The population-based sample enhances the study’s generalizability. However, some limitations are inherent in the use of administrative data. We were unable to explore some predictors that others have demonstrated as important (parenting, peers, child temperament [3], child cognitions [21]). Similarly, given that cognitive behavior therapy is commonly used to treat mild/ moderate childhood anxiety [24], but not reported in administrative databases, and anxiety in children is often unrecognized and untreated [3], the children we studied likely represent those with greater symptom severity. As such, the findings may not be generalizable to children with less severe anxiety. However, a recent study (N = 1,085) reported that 4-year old children ofPLOS ONE | DOI:10.1371/journal.pone.0129339 July 9,10 /Predictors of Childhood Anxietywomen with both severe and sub-clinical depressive symptoms from pregnancy to 4-years postpartum were more likely to experience emotional difficulties (23 vs 19 , respectively) compared to women with no symptoms (7 ), [20] suggesting that sub-clinical symptoms can also be associated with emotional problems in preschoolers. The prevalence rate of anxiety may have been influenced by: 1) measuring childhood anxiety by a single diagnostic code, with the possibility that transient cases may be erroneously classified as `childhood anxiety’; 2) anxiolytics that are prescribed for disorders other than anxiety; 3) not capturing children who were prescribed antidepressants (SSRI’s) for anxiety [26]; and under-recognition or false positive diagnose.19]. With respect to anxiety in particular, studies that have distinguished between neurodevelopmental conditions (autism, attention deficit hyperactivity disorder, developmental delay, learning disability) and psychiatric morbidity have found no additional risk of anxiety between term and preterm children. For example, data from the National Survey of Children’s Health (N = 95,677) suggest that increased risk of anxiety is found only among preterm children with comorbid neurodevelopmental conditions [29]. There is journal.pone.0077579 some suggestion from meta-analyses that the relationship between prematurity and emotional problems also varies by the era in which the preterm infant was born, with early studies (<1990) jir.2014.0227 showing an increased risk and later studies (>1998) showing no association [30]. It is likely that biological and environmental pathways operate in concert, where impaired hypothalamic-pituitary-adrenal-axis functioning, in combination with risky extrauterine factors increase the risk of anxiety [4]. Thus, the reduced likelihood of childhood anxiety in preterm infants that we report may be related to the: 1) protective influence of a reduced length of time exposed to a compromised, suboptimal intrauterine environment (fetal programming hypothesis) [14]; in this case, reduced time in-utero may decrease exposure to pathological events, as described in the fetus-at-risk paradigm where the benefit of preterm delivery in terms of ameliorating risk of adverse fetal and neonatal outcomes may exceed that of term delivery [31]; 2) attenuation of risk as a result of early detection and treatment of anxiety symptoms during routine developmental follow-up of preterm infants; or 3) advanced neonatal care that improved neurodevelopmental outcomes in our cohort born 2003?004 [30].Strengths and LimitationsA strength of this study is the inclusion of multiple early life factors from pregnancy to age 5. The population-based sample enhances the study’s generalizability. However, some limitations are inherent in the use of administrative data. We were unable to explore some predictors that others have demonstrated as important (parenting, peers, child temperament [3], child cognitions [21]). Similarly, given that cognitive behavior therapy is commonly used to treat mild/ moderate childhood anxiety [24], but not reported in administrative databases, and anxiety in children is often unrecognized and untreated [3], the children we studied likely represent those with greater symptom severity. As such, the findings may not be generalizable to children with less severe anxiety. However, a recent study (N = 1,085) reported that 4-year old children ofPLOS ONE | DOI:10.1371/journal.pone.0129339 July 9,10 /Predictors of Childhood Anxietywomen with both severe and sub-clinical depressive symptoms from pregnancy to 4-years postpartum were more likely to experience emotional difficulties (23 vs 19 , respectively) compared to women with no symptoms (7 ), [20] suggesting that sub-clinical symptoms can also be associated with emotional problems in preschoolers. The prevalence rate of anxiety may have been influenced by: 1) measuring childhood anxiety by a single diagnostic code, with the possibility that transient cases may be erroneously classified as `childhood anxiety’; 2) anxiolytics that are prescribed for disorders other than anxiety; 3) not capturing children who were prescribed antidepressants (SSRI’s) for anxiety [26]; and under-recognition or false positive diagnose.
