Eileen A. Curran

Research review: Birth by caesarean section and development of autism spectrum disorder and attention-deficit/hyperactivity disorder: a systematic review and meta-analysis.

BACKGROUND Given the growing prevalence of birth by Caesarean section (CS) worldwide, it is important to understand any long-term effects CS delivery may have on a childs development. We assessed the impact of mode of delivery on autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). METHODS We conducted a systematic review of the literature in PubMed, Embase, CINAHL, PsycINFO and Web of Science up to 28 February 2014. No publication date, language, location or age restrictions were employed. RESULTS Thirteen studies reported an adjusted estimate for CS-ASD, producing a pooled odds ratio (OR) of 1.23 (95% CI: 1.07, 1.40). Two studies reported an adjusted estimate for CS-ADHD, producing a pooled OR of 1.07 (95% CI: 0.86, 1.33). CONCLUSIONS Delivery by CS is associated with a modest increased odds of ASD, and possibly ADHD, when compared to vaginal delivery. Although the effect may be due to residual confounding, the current and accelerating rate of CS implies that even a small increase in the odds of disorders, such as ASD or ADHD, may have a large impact on the society as a whole. This warrants further investigation.

Association Between Obstetric Mode of Delivery and Autism Spectrum Disorder: A Population-Based Sibling Design Study

IMPORTANCE Because the rates of cesarean section (CS) are increasing worldwide, it is becoming increasingly important to understand the long-term effects that mode of delivery may have on child development. OBJECTIVE To investigate the association between obstetric mode of delivery and autism spectrum disorder (ASD). DESIGN, SETTING, AND PARTICIPANTS Perinatal factors and ASD diagnoses based on the International Classification of Diseases, Ninth Revision (ICD-9),and the International Statistical Classification of Diseases, 10th Revision (ICD-10),were identified from the Swedish Medical Birth Register and the Swedish National Patient Register. We conducted stratified Cox proportional hazards regression analysis to examine the effect of mode of delivery on ASD. We then used conditional logistic regression to perform a sibling design study, which consisted of sibling pairs discordant on ASD status. Analyses were adjusted for year of birth (ie, partially adjusted) and then fully adjusted for various perinatal and sociodemographic factors. The population-based cohort study consisted of all singleton live births in Sweden from January 1, 1982, through December 31, 2010. Children were followed up until first diagnosis of ASD, death, migration, or December 31, 2011 (end of study period), whichever came first. The full cohort consisted of 2,697,315 children and 28,290 cases of ASD. Sibling control analysis consisted of 13,411 sibling pairs. EXPOSURES Obstetric mode of delivery defined as unassisted vaginal delivery (VD), assisted VD, elective CS, and emergency CS (defined by before or after onset of labor). MAIN OUTCOMES AND MEASURES The ASD status as defined using codes from the ICD-9 (code 299) and ICD-10 (code F84). RESULTS In adjusted Cox proportional hazards regression analysis, elective CS (hazard ratio, 1.21; 95% CI, 1.15-1.27) and emergency CS (hazard ratio, 1.15; 95% CI, 1.10-1.20) were associated with ASD when compared with unassisted VD. In the sibling control analysis, elective CS was not associated with ASD in partially (odds ratio [OR], 0.97; 95% CI, 0.85-1.11) or fully adjusted (OR, 0.89; 95% CI, 0.76-1.04) models. Emergency CS was significantly associated with ASD in partially adjusted analysis (OR, 1.20; 95% CI, 1.06-1.36), but this effect disappeared in the fully adjusted model (OR, 0.97; 95% CI, 0.85-1.11). CONCLUSIONS AND RELEVANCE This study confirms previous findings that children born by CS are approximately 20% more likely to be diagnosed as having ASD. However, the association did not persist when using sibling controls, implying that this association is due to familial confounding by genetic and/or environmental factors.

A systematic review of the psychobiological burden of informal caregiving for patients with dementia: focus on cognitive and biological markers of chronic stress

Graphical abstract Figure. No caption available. HighlightsMuch research has examined biomarkers of chronic stress in dementia caregivers.Cortisol was increased in dementia caregivers in most studies examining cortisol.Dementia caregivers displayed poorer attention and executive function performance.Interventions to reduce stress in caregivers may improve cognition.Risk of bias was generally low to moderate. &NA; As the physiological impact of chronic stress is difficult to study in humans, naturalistic stressors are invaluable sources of information in this area. This review systematically evaluates the research literature examining biomarkers of chronic stress, including neurocognition, in informal dementia caregivers. We identified 151 papers for inclusion in the final review, including papers examining differences between caregivers and controls as well as interventions aimed at counteracting the biological burden of chronic caregiving stress. Results indicate that cortisol was increased in caregivers in a majority of studies examining this biomarker. There was mixed evidence for differences in epinephrine, norepinephrine and other cardiovascular markers. There was a high level of heterogeneity in immune system measures. Caregivers performed more poorly on attention and executive functioning tests. There was mixed evidence for memory performance. Interventions to reduce stress improved cognition but had mixed effects on cortisol. Risk of bias was generally low to moderate. Given the rising need for family caregivers worldwide, the implications of these findings can no longer be neglected.

Birth by Caesarean Section and the Risk of Adult Psychosis: A Population-Based Cohort Study.

Despite the biological plausibility of an association between obstetric mode of delivery and psychosis in later life, studies to date have been inconclusive. We assessed the association between mode of delivery and later onset of psychosis in the offspring. A population-based cohort including data from the Swedish National Registers was used. All singleton live births between 1982 and 1995 were identified (n= 1,345,210) and followed-up to diagnosis at age 16 or later. Mode of delivery was categorized as: unassisted vaginal delivery (VD), assisted VD, elective Caesarean section (CS) (before onset of labor), and emergency CS (after onset of labor). Outcomes included any psychosis; nonaffective psychoses (including schizophrenia only) and affective psychoses (including bipolar disorder only and depression with psychosis only). Cox regression analysis was used reporting partially and fully adjusted hazard ratios (HR) with 95% confidence intervals (CI). Sibling-matched Cox regression was performed to adjust for familial confounding factors. In the fully adjusted analyses, elective CS was significantly associated with any psychosis (HR 1.13, 95% CI 1.03, 1.24). Similar findings were found for nonaffective psychoses (HR 1.13, 95% CI 0.99, 1.29) and affective psychoses (HR 1.17, 95% CI 1.05, 1.31) (χ(2)for heterogeneityP= .69). In the sibling-matched Cox regression, this association disappeared (HR 1.03, 95% CI 0.78, 1.37). No association was found between assisted VD or emergency CS and psychosis. This study found that elective CS is associated with an increase in offspring psychosis. However, the association did not persist in the sibling-matched analysis, implying the association is likely due to familial confounding by unmeasured factors such as genetics or environment.

The Effect of Hypertensive Disorders of Pregnancy on the Risk of ADHD in the Offspring

Objective: Evidence suggests that perinatal factors may contribute to the development of ADHD. Our objective was to examine the association between hypertensive disorders of pregnancy (HDP) and ADHD, and behavioral difficulties among 7-year-old children. Method: The study cohort consisted of 13,192 children (weighted = 13,500) who participated in the Millennium Cohort Study (MCS) at age 7. HDP (raised blood pressure, preeclampsia, eclampsia, and toxemia) were reported by mothers 9 months postdelivery. ADHD was reported by parents at age 7 years. Weighted logistic regression models were used to assess the association. Results: In all, 1,069 (7.9%) women reported HDP and 166 (1.2%) children had an ADHD diagnosis. There was a significant association between HDP and ADHD (adjusted odds ratio [OR] = 1.78, 95% confidence interval [CI] = [1.03, 3.07]). Conclusion: These findings suggest that HDP is associated with an increased risk of ADHD. It is important to confirm this in larger cohorts and to understand the biological basis of this association.

Birth by caesarean section and school performance in Swedish adolescents- a population-based study

BackgroundOur objective was to assess the impact of obstetric mode of delivery, and in particular birth by Caesarean section (CS), on school performance in adolescents using a large, population-based cohort.MethodsWe extracted data from the Swedish Medical Birth Register and National School Register. We included all live singleton births in Sweden from 1982–1995 (n = 1,489,925). School grades were reported on a scale from 0 to 320, scores less than 160 (i.e. “pass”) were considered to be “poor school performance.” Mode of delivery was categorised as: unassisted vaginal delivery (VD), assisted VD, elective CS and emergency CS. We measured the association between mode of delivery and “poor school performance” using logistic regression. We then used quantile regression to assess the association between mode of delivery and school performance across the distribution of scores. We adjusted for maternal age, parity, small and large for gestational age, gestational age, maternal country of birth, maternal depression, non-affective disorder or bipolar disorder, parental income at time of birth, and parental social welfare at time of birth. We also conducted sensitivity analyses to investigate the association further.ResultsWith logistic regression analysis, the adjusted odds ratio (aOR) of assisted VD and poor school performance, compared to unassisted VD, was 1.06 (95% CI: 1.03–1.08). For elective CS it was 1.06 (95% CI:1.03-1.09) and for emergency CS it was 1.12 (95% CI: 1.09–1.15). With quantile regression, assisted VD showed little difference in scores, when compared to unassisted VD, at any point across the distribution. Elective CS was associated with a 1–3 point decrease in scores, and emergency CS was associated with a 2–5 point decrease in scores.ConclusionA slight association was found between birth by CS and school performance. However, the effect was quite small and given the complex nature of the relationship, should be interpreted with caution.

Sibling Comparisons and Confounding in Autism Epidemiological Studies—Reply

CRP levels reflecting acute inflammation and the likelihood of confounding by medical conditions. In this sample, we found that (1) the somatic and nonsomatic symptom clusters were positively associated with CRP in separate models and (2) only the somatic cluster (sleep disturbance, fatigue, appetite changes, and psychomotor retardation/agitation) remained associated in the model with both symptom clusters. However, our results came with a critical caveat—one size did not fit all. Our examination of race/ethnicity as a moderator revealed some striking results, as the depression-inflammation link was missing in all but 1 group: non-Hispanic white individuals (n = 4858). To our surprise, there were no significant associations between somatic and nonsomatic symptoms and CRP in non-Hispanic black (n = 1978), Mexican American (n = 2260), or other Hispanic (n = 1053) individuals. Inadequate power is not a plausible explanation, given the group sizes. Altogether, our findings suggest that the depressioninflammation association is largely due to the somatic symptoms and may be present only in non-Hispanic white individuals. There is now a clear need to test race/ethnicity as a moderator in depression-inflammation studies. To our knowledge, few such studies exist, and results have been conflicting.5 Determining the role of race/ethnicity is of high potential significance. It could inform the development of novel depression treatments and cardiometabolic disease prevention approaches tailored for specific racial/ethnic groups, which could significantly reduce racial/ethnic disparities in depression, cardiovascular disease, diabetes mellitus, and obesity. In the era of personalized health care, the questions “In whom?” and “For whom?” must remain in the forefront of our minds.