Association of Cesarean Delivery With Risk of Neurodevelopmental and Psychiatric Disorders in the Offspring

Zhang, Tianyang; Sidorchuk, Anna; Sevilla-Cermeño, Laura; Vilaplana-Pérez, Alba; Chang, Zheng; Larsson, Henrik; Mataix‐Cols, David; Cruz, Lorena Fernández de la

doi:10.1001/jamanetworkopen.2019.10236

Cited by 160 publications

(117 citation statements)

References 94 publications

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“…We may hypothesize that these defects depend on the modulation of brain development that itself depends on the complex exposure to perinatal insults such as alterations in the way and/or time of being born, hence explaining the disparities reported in epidemiological studies. Thus, our past and present observations further shed light on the intricacy of deviating from vaginal birth at term, substantiating the recent systematic review and meta-analysis of Zhang and colleagues that evaluated the association between cesarean section delivery with the risk of developing psychiatric disorders [57]. In addition, because the fetus has to be prepared for the imminent onset of parturition, some mechanisms must alert the fetal brain to protect itself from any potential harm induced by hypoxic or hypoglycemic insults during labor.…”

Section: Discussionsupporting

confidence: 86%

Alteration in the time and/or mode of delivery differentially modulates early development in mice

2020

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Delivery is a complex biological process involving hormonal and mechanical stimuli that together condition the survival and development of the fetus out of the womb. Accordingly, changes in the time or way of being born are associated with an alteration of fundamental biological functions and hypothesized to promote the emergence of neurodevelopmental disorders. Hence, the steadily rise in preterm birth and cesarean section (CS) delivery rates over the past years has become a worldwide health concern. In our previous work, we reported that even though no long-term autistic-like deficits were observed, mice born preterm by CS presented early transient neuronal and communicative defects. However, understanding if these alterations were due to an early birth combined with CS delivery, or if prematurity solely could lead to a similar outcome remained to be evaluated. Using mice born either at term or preterm by vaginal or CS delivery, we assessed early life ultrasonic vocalizations and the onset of eye opening. We report that alterations in communicative behaviors are finely attuned and specifically affected either by preterm birth or by the association between CS delivery and preterm birth in mice, while delayed onset of eye opening is due to prematurity. Moreover, our work further underlies a gender-dependent vulnerability to changes in the time and/or way of being born with distinct outcomes observed in males and females. Thus, our results shed light on the intricacy of birth alterations and might further explain the disparities reported in epidemiological studies.

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Section: Discussionsupporting

confidence: 86%

Alteration in the time and/or mode of delivery differentially modulates early development in mice

2020

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“…Although the female fetus is likely to be in a non-cephalic position at birth, other factors, including abnormal fetal heart rate patterns, abnormal labor progress, and macrosomia, may be more influential contributors to an increased risk of cesarean section. In addition to the traditional complications of cesarean section, such as infection, surgical injury, and abnormal placentation in future pregnancies 47 – 49 , cesarean section could cause long-term risks in children, such as allergic disorders, childhood/adolescent obesity, autism spectrum disorders, and attention deficit hyperactivity disorder 50 – 52 . A higher rate of cesarean section among women carrying a male fetus could play some role in these associations.…”

Section: Discussionmentioning

confidence: 99%

Differences in pregnancy complications and outcomes by fetal gender among Japanese women: a multicenter cross-sectional study

Funaki

Ogawa

Ozawa

et al. 2020

Sci Rep

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The association between fetal gender and rare pregnancy complications has not been extensively investigated, and no studies have examined this association in Japanese women. Thus, we used a large Japanese birth registry database to investigate the extent to which fetal gender affects various pregnancy outcomes. We analyzed 1,098,268 women with a singleton delivery with no congenital anomaly at 22 weeks or later between 2007 and 2015. Women carrying a male fetus had a significantly higher risk of placental abruption (adjusted risk ratio [aRR] 1.15, 95% confidence interval (CI) 1.10–1.20)], preterm delivery (aRR 1.20, 95% CI 1.19–1.22), instrumental delivery (aRR 1.27, 95% CI 1.26–1.29), and cesarean delivery (aRR 1.01, 95% CI 1.00–1.02). In contrast, they had a significantly lower risk of preeclampsia (aRR 0.92, 95% CI 0.89–0.94), placenta accreta (aRR 0.90, 95% CI 0.85–0.96), atonic hemorrhage (aRR 0.95, 95% CI 0.93–0.96), and maternal blood transfusion (aRR 0.95, 95% CI 0.92–0.99). Our findings demonstrate a significant association between fetal gender and various pregnancy complications and delivery outcomes among Japanese women.

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“…Interestingly, subjects in the α-ketoglutarate metabotype-positive cluster were more likely to have had a Cesarean delivery (CD). Children born by CD tend to have an increased body mass index [Bernardi et al, 2015], altered microbiome, and immune function [Liu et al, 2018;Wampach et al, 2018], each of which is associated with increased risk of ASD [Healy, Aigner, & Haegele, 2019;Vuong & Hsiao, 2017;Zhang et al, 2019]. Lastly, subjects in the succinate cluster had decreased receptive language scores compared to metabotype-negative subjects.…”

Section: Are There Functional Associations Of the Metabotypes?mentioning

confidence: 99%

A Metabolomics Approach to Screening for Autism Risk in the Children's Autism Metabolome Project

et al. 2020

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Autism spectrum disorder (ASD) is biologically and behaviorally heterogeneous. Delayed diagnosis of ASD is common and problematic. The complexity of ASD and the low sensitivity of available screening tools are key factors in delayed diagnosis. Identification of biomarkers that reduce complexity through stratification into reliable subpopulations can assist in earlier diagnosis, provide insight into the biology of ASD, and potentially suggest targeted interventions. Quantitative metabolomic analysis was performed on plasma samples from 708 fasting children, aged 18 to 48 months, enrolled in the Children's Autism Metabolome Project (CAMP). The primary goal was to identify alterations in metabolism helpful in stratifying ASD subjects into subpopulations with shared metabolic phenotypes (i.e., metabotypes). Metabotypes associated with ASD were identified in a discovery set of 357 subjects. The reproducibility of the metabotypes was validated in an independent replication set of 351 CAMP subjects. Thirty‐four candidate metabotypes that differentiated subsets of ASD from typically developing participants were identified with sensitivity of at least 5% and specificity greater than 95%. The 34 metabotypes formed six metabolic clusters based on ratios of either lactate or pyruvate, succinate, glycine, ornithine, 4‐hydroxyproline, or α‐ketoglutarate with other metabolites. Optimization of a subset of new and previously defined metabotypes into a screening battery resulted in 53% sensitivity (95% confidence interval [CI], 48%–57%) and 91% specificity (95% CI, 86%–94%). Thus, our metabolomic screening tool detects more than 50% of the autistic participants in the CAMP study. Further development of this metabolomic screening approach may facilitate earlier referral and diagnosis of ASD and, ultimately, more targeted treatments. Lay Summary Analysis of a selected set of metabolites in blood samples from children with autism and typically developing children identified reproducible differences in the metabolism of about half of the children with autism. Testing for these differences in blood samples can be used to help screen children as young as 18 months for risk of autism that, in turn, can facilitate earlier diagnoses. In addition, differences may lead to biological insights that produce more precise treatment options. We are exploring other blood‐based molecules to determine if still a higher percentage of children with autism can be detected using this strategy. Autism Res 2020, 13: 1270–1285. © 2020 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals LLC.

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Association of Cesarean Delivery With Risk of Neurodevelopmental and Psychiatric Disorders in the Offspring

Abstract: This systematic review and meta-analysis examines the association between birth by cesarean delivery and risk of neurodevelopmental and psychiatric disorders in the offspring compared with birth by vaginal delivery.

Cited by 160 publications

References 94 publications

Alteration in the time and/or mode of delivery differentially modulates early development in mice

Alteration in the time and/or mode of delivery differentially modulates early development in mice

Differences in pregnancy complications and outcomes by fetal gender among Japanese women: a multicenter cross-sectional study

A Metabolomics Approach to Screening for Autism Risk in the Children's Autism Metabolome Project

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