Our analyses of systematically collected information on perinatal and early developmental complications yielded significant differences between children affected with OCD and controls in rates of illness during pregnancy requiring medical care, birth difficulties (such as induced labor, forceps delivery, nuchal cord, or prolonged labor) and needing more formula changes in infancy than did mothers of controls. We also found significant associations between familial (versus sporadic) OCD and age of onset with perinatal risk factors such as accidents and illnesses during pregnancy requiring medical care. Complications during labor, delivery, and the postnatal period also predicted higher frequency of comorbid disorders, including ADHD, chronic tics, anxiety, and major depressive disorder.
Our findings documenting that perinatal complications contribute to the risk of pediatric OCD are consistent with data from genetic studies suggesting that a considerable proportion of the variance in the occurrence of OCD can be explained by nongenetic environmental factors. For example, in a meta-analysis of family studies, Hettema et al. (2001
) found only modest estimated heritability coefficients for OCD of 30%–40%. In a cross-cultural sample of 4246 twin pairs, Hudziak et al. (2004
) used structural equation modeling using an 8-item Obsessive Compulsive Scale (OCS) from the Child Behavior Checklist as a proxy for OCD to examine the influence of both genetic (45%–58%) and unique environmental (42%–55%) factors and concluded that both were about equally important. Even lower estimates of heritability of OCD were reported by Jonnal et al. (2000
) in a population sample of 527 female twin pairs using items from the Padua Inventory. Even if such estimates are inflated due to measurement errors and gene–environment interactions that are not accounted for in the models, these studies support the role of environmental risk factors that could influence the expression of OCD or of symptoms that exist along a dimension of an OC spectrum disorder.
Our results showing that children with OCD differed from controls in rates of several risk factors during pregnancy, birth, and infancy are consistent with the limited literature on this subject. Our findings showing that maternal accidents requiring medical care during pregnancy (perhaps a proxy for prenatal insult) predicted earlier onset of OCD are consistent with those of Lensi et al. (1996
) who also found a significantly greater history of perinatal trauma in males who had an early onset of OCD. Although the reasons for this association are not entirely clear, perinatal insults may disrupt development or migration of neuronal elements in cortical–striatal–thalamic circuits known to be involved in OCD (Fitzgerald et al. 1999
; Rauch and Savage 1997
). In view of the critical importance of the perinatal period as a time of neural growth, it is not surprising that this developmental phase should be an area of scientific interest regarding putative environmental risk factors for psychiatric illness (Burd et al. 1999a
; Burd et al. 1999b
; Klug et al. 2003
Several significant group differences between OCD and control subjects such as “maternal illnesses requiring medical care,” “frequent switching of milk formulas,” and “other infant events (e.g., infection during infancy)” could also suggest a genetic immune vulnerability in both mother and child as another possible etiological mechanism. This hypothesis is supported by the finding of higher rates of illness requiring maternal medical care with familial OCD.
Our hypothesis that perinatal complications would be more in evidence in sporadic cases was not supported by our data. In fact, many if not most cases of OCD arise without
a positive family history of the disorder–so-called “sporadic” cases (Pauls et al. 1995
). Although sporadic occurrences do not rule out a genetic etiology (for example, due to spontaneous mutations), familial and sporadic “subtypes” of OCD have repeatedly been identified (Albert et al. 2002
; Hanna et al. 2005
; Nestadt et al. 2000
; Pauls et al. 1995
), leading to speculation about the differing impact of environmental and genetic factors on familial and sporadic forms of the disorder. It is generally assumed that sporadic cases have less genetic loading (and perhaps more environmental risk factors) than familial cases. However, no perinatal risk factors that we assayed predicted this “subtype” of pediatric OCD.
Our finding that medication use during pregnancy and post-birth complications (incubator post-birth, hospital stay after mother returned home, and excessive crying during infancy) were significantly associated with the presence of co-morbid ADHD and are consistent with other studies of both TD and ADHD. For example, Mathews et al. (2006
) found associations between subject's birth weight and a comorbid ADHD diagnosis in their TD cohort. Reports detailing in utero exposure to alcohol (Brookes et al. 2006
; Knopik et al. 2006
), smoking (Mick et al. 2002
; Rodriguez and Bohlin 2005
; Thapar et al. 2003
), and other complications of pregnancy, delivery, and infancy (Batstra et al. 2003
; Linnet et al. 2003
; Milberger et al. 1997
; Sato et al. 2004
; Sprich-Buckminster et al. 1993
) have been repeatedly shown to be associated with ADHD. Perinatal complications may also influence the trajectories of certain disorders (moderators) through the development of comorbid disorders.
The inclusion of early developmental factors in our analysis, a unique aspect not uniformly assessed in other studies of this nature, yielded several interesting links with co-morbidity in our sample. Although not well operationalized, maternal reports of “sleeping difficulties” and “severe irritability in infancy” predicted later anxiety and depressive disorders. An inability to adapt to changes in the environment is often viewed as one indicator of a rigid, “difficult” temperament that could be a precursor for later behavioral symptoms. Developmental markers such as these, if operationalized and quantified, could create opportunities for early intervention.
While these results indicate the relevance of perinatal complications in the study of nongenetic influences in the expression of OCD, they also demonstrate the difficulties inherent in this type of study. Despite the burgeoning evidence for early environmental triggers of neurodevelopmental disorders, reconciling research findings between studies is frequently limited by their nonuniform characteristics that include selection and publication bias, as well as variable measures, sample sizes, and methods (Glasson et al. 2004
Our results need to be viewed in light of some methodological limitations. Although the retrospective nature of this study could lead to inaccurate or biased recall and reports from mothers, this risk is reduced by collecting information close to illness onset and from mothers rather than subjects. It is possible that greater rates of perinatal complications in children with OCD versus control children could stem from other differences that do not necessarily arise from OCD per se, since our findings do not prove causality but rather show an association. Such evidence would require a prospective study that controlled for all possible factors. Nonetheless, a controlled retrospective analysis such as this may be helpful in identifying particular perinatal events as risk factors worthy of further study. Although most definitions were operationalized (e.g., illness or accidents requiring medical care, weight gain greater than 25 pounds, caffeine intake greater than one cup per day), for some risk factors there is a lack of specificity that may make interpretation of the risk difficult. This is especially so for those early developmental and temperamental behaviors that involve great subjectivity on the part of mothers such as severe irritability in infancy that cannot be easily operationalized, yet may provide useful information. It is plausible that mothers of children with OCD are more anxious than their control counterparts and would report perinatal events as “adverse” more often than mothers of controls. Without prospective data and no corroborating medical information, the predictive value of these items is low.
We also report on some perinatal risk factors that occurred at very low rates making statistical analysis of limited value. Further, if the effect size of a specific risk factor is low, then only larger studies will have sufficient power to detect these as significant. Finally, consistent with the exploratory nature of this study, we tested many relationships increasing the chance for type I errors (false positives). Despite these concerns, our focus on both perinatal and early developmental periods make this study, which is the first to examine links between perinatal factors and pediatric OCD as primary diagnosis, more comprehensive than several other similar efforts.
Despite these considerations, this study shows a significant association between adverse perinatal experiences and the onset and expression of OCD occurring in children and points to the need for further study of nongenetic etiological factors in the development of OCD in youth with attention to familial and sporadic forms of the disorder, age at onset, and comorbid status. Future research that employs prospective methods is needed to better study nongenetic factors in the etiology of OCD and other psychiatric disorders, particularly those with a developmental onset.