To examine the association between ischemic-hypoxic conditions (IHCs) and attention-deficit/hyperactivity disorder (ADHD) by gestational age and race/ethnicity.
Nested case-control study using the Kaiser Permanente Southern California (KPSC) medical records. The study cohort included children aged 5 to 11 years who were delivered and cared for in the KPSC between 1995 and 2010 (N = 308 634). Case children had a diagnosis of ADHD and received ≥2 prescriptions specific to ADHD during the follow-up period. For each case, 5 control children were matched by age at diagnosis. Exposures were defined by using International Classification of Diseases, Ninth Revision codes. A conditional regression model was used to estimate adjusted odds ratios (ORs).
Among eligible children, 13 613 (4.3%) had a diagnosis of ADHD. Compared with control children, case children were more likely to be male and of white or African American race/ethnicity. Case children were more likely to be exposed to IHCs (OR = 1.16, 95% confidence interval [CI] 1.11–1.21). When stratified by gestational age, cases born at 28 to 33, 34 to 36, and 37 to 42 weeks of gestation, were more likely to be exposed to IHCs (ORs, 1.6 [95% CI 1.2–2.1], 1.2 [95% CI 1.1–1.3], and 1.1 [95% CI 1.0–1.2], respectively) compared with controls. IHC was associated with increased odds of ADHD across all race/ethnicity groups.
These findings suggest that IHCs, especially birth asphyxia, respiratory distress syndrome, and preeclampsia, are independently associated with ADHD. This association was strongest in preterm births.
To the editor,
Epidemiologists and statisticians pay a great deal of attention to the homogeneity of the exposures and entities they study 1. Some of us are especially uncomfortable with composite outcomes (such as death or survival with disability) and composite exposures, such as the one offered by Darios Getahun and his colleagues (Pediatrics 2013;131:e53-61.). Under the umbrella term of "ischemic-hypoxic conditions," the authors brought together a heterogeneous group of disorders including placental abruption, birth asphyxia, breech/transverse presentation, dystocia, prolapsed/nuchal cord, respiratory distress syndrome, and preeclampsia,
They unified placental abruption, birth asphyxia, breech/transverse presentation, dystocia, prolapsed/nuchal cord, respiratory distress syndrome, preeclampsia, and perinatal conditions as "ischemic-hypoxic conditions." None of these need produce its adverse effects via ischemia or hypoxia, nor need any of them be accompanied by ischemia or hypoxia capable of contributing to attention-deficit/hyperactivity disorder.
Let's take the entity of birth asphyxia. This is the entity most likely to be considered by some an indicator of ischemia or hypoxia. Yet even here the evidence is weak 2 .
Perhaps the authors are not aware of what contributes to placenta abruption 3, dystocia4, or preeclampsia5. Neither ischemia nor hypoxia appears to characterize these disorders.
We consider it very important for readers of the article by Getahun et al. to be aware of the potentially grossly misleading inferences drawn when placenta abruption, non-vertex presentation, dystocia, respiratory distress syndrome, preeclampsia, and even birth asphyxia are grouped under the construct of "ischemic-hypoxic conditions".
Olaf Dammann Floyd H. Gilles Pierre Gressens Alan Leviton
Citations
1. Fletcher J. What is heterogeneity and is it important? BMJ. 2007;334(7584):94-96. 2. Kurinczuk JJ, White-Koning M, Badawi N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum Dev. 2010;86(6):329-338. 3. Kramer MS, Usher RH, Pollack R, Boyd M, Usher S. Etiologic determinants of abruptio placentae. Obstet Gynecol. 1997;89(2):221-226. 4. Jevitt CM. Shoulder dystocia: etiology, common risk factors, and management. Journal of midwifery & women's health. 2005;50(6):485-497. 5. Redman CW, Sargent IL. Immunology of pre-eclampsia. Am J Reprod Immunol. 2010;63(6):534-543.
Conflict of Interest:
None declared