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The Role of Obstetric Adversities in Neurodevelopmental Conditions: A Sibling Study

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Title: The Role of Obstetric Adversities in Neurodevelopmental Conditions: A Sibling Study
Language: English
Authors: Sandra Gómez-Vallejo (ORCID 0000-0003-0963-6585), Oaia Iriondo-Blanco, Gonzalo Salazar de Pablo, Rosa Calvo Escalona, Luisa Lázaro García
Source: Autism: The International Journal of Research and Practice. 2025 29(12):3072-3082.
Availability: SAGE Publications. 2455 Teller Road, Thousand Oaks, CA 91320. Tel: 800-818-7243; Tel: 805-499-9774; Fax: 800-583-2665; e-mail: journals@sagepub.com; Web site: https://sagepub.com
Peer Reviewed: Y
Page Count: 11
Publication Date: 2025
Document Type: Journal Articles
Reports - Research
Descriptors: Neurodevelopmental Disorders, Predictor Variables, Siblings, Children, Adolescents, Autism Spectrum Disorders, Attention Deficit Hyperactivity Disorder, Comorbidity, Neonates, Pregnancy, Foreign Countries, Individual Characteristics
Geographic Terms: Spain (Barcelona)
DOI: 10.1177/13623613251359317
ISSN: 1362-3613
1461-7005
Abstract: Neurodevelopmental conditions (NDC) are highly heritable. Obstetric complications (OC) have been studied as potential predictors for NDC, although results are inconsistent. Inconsistencies might be related to biases such as family confounders. While some studies using sibling and twin designs have examined the association between OC and NDC, this body of research remains limited, and findings to date remain inconsistent. We used a case-control sibling study including children aged 6--17 years across five groups: those diagnosed with autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), co-occurring ASD + ADHD, their unaffected siblings and a comparison group without NDC. For analytic purposes, we created a combined NDC group including all individuals with ASD, ADHD or both. Participants were recruited between 2021 and 2022 from a tertiary hospital in Spain. We examined the association of NDC and OC using single predictors and cumulative OC. The study adheres to the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines. A total of 238 participants were included (NDC = 117, unaffected siblings = 82, comparison group = 39). We found that NDC individuals showed more neonatal complications than the comparison group ([beta] = 1.73, 95% CI = 1.00-2.98, p = 0.04), which remained significant in the sibling analysis ([beta] = 1.43, 95% CI = 1.02-2.00, p = 0.04). This study supports that the cumulative neonatal complications, rather than specific factors, are associated with increased likelihood of being diagnosed with NDC, beyond familial confounding. Results highlight the neonatal period as a relevant window of vulnerability.
Abstractor: As Provided
Entry Date: 2025
Accession Number: EJ1489400
Database: ERIC
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  Value: <anid>AN0189325695;f9d01dec.25;2025Nov18.00:28;v2.2.500</anid> <title id="AN0189325695-1">The role of obstetric adversities in neurodevelopmental conditions: A sibling study </title> <p>Neurodevelopmental conditions (NDC) are highly heritable. Obstetric complications (OC) have been studied as potential predictors for NDC, although results are inconsistent. Inconsistencies might be related to biases such as family confounders. While some studies using sibling and twin designs have examined the association between OC and NDC, this body of research remains limited, and findings to date remain inconsistent. We used a case-control sibling study including children aged 6–17 years across five groups: those diagnosed with autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), co-occurring ASD + ADHD, their unaffected siblings and a comparison group without NDC. For analytic purposes, we created a combined NDC group including all individuals with ASD, ADHD or both. Participants were recruited between 2021 and 2022 from a tertiary hospital in Spain. We examined the association of NDC and OC using single predictors and cumulative OC. The study adheres to the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines. A total of 238 participants were included (NDC = 117, unaffected siblings = 82, comparison group = 39). We found that NDC individuals showed more neonatal complications than the comparison group (β = 1.73, 95% CI = 1.00–2.98, p = 0.04), which remained significant in the sibling analysis (β = 1.43, 95% CI = 1.02–2.00, p = 0.04). This study supports that the cumulative neonatal complications, rather than specific factors, are associated with increased likelihood of being diagnosed with NDC, beyond familial confounding. Results highlight the neonatal period as a relevant window of vulnerability. The role of complications during pregnancy in neurodevelopmental disorders: a sibling study This study examined the association between complications during pregnancy and autism, attention-deficit/hyperactivity disorder and the combination of both conditions. We compared children with these conditions and their siblings, as well as a group comparison without diagnosed neurodevelopmental disorders. We gathered information through parents' interviews. We found that children with autism or attention-deficit/hyperactivity disorder presented more problems in the first 4 weeks of the child's life than their siblings and the group of comparison. We did not find that children with these conditions present more complications during pregnancy. In addition, we observed that the probability of being diagnosed with these conditions is increased due to cumulative problems rather than specific problems.</p> <p>Keywords: attention-deficit/hyperactivity disorder; autism; neurodevelopmental conditions; obstetric complications; sibling studies</p> <hd id="AN0189325695-2">Introduction</hd> <p>Neurodevelopmental conditions (NDC) are a group of conditions that manifest early in childhood and impact an individual's global functioning ([<reflink idref="bib2" id="ref1">2</reflink>]). NDC currently include intellectual disability, communication disorders, autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), motor disorders, including tic disorders, specific learning disorders and other neurodevelopmental disorders. In this study, we focus on ASD and ADHD due to their high prevalence, frequent co-occurrence and shared genetic and neurobiological features.</p> <p>ASD is a condition characterized by persisting deficits in social communication and restrictive, repetitive patterns of behaviour ([<reflink idref="bib2" id="ref2">2</reflink>]). The prevalence of ASD has been increasing over the last years, with a current estimated prevalence of 1 in 36 ([<reflink idref="bib40" id="ref3">40</reflink>]). ADHD is defined by a persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development ([<reflink idref="bib2" id="ref4">2</reflink>]) with a current estimated prevalence in the United States of 9.8% among children aged 3–17 years ([<reflink idref="bib19" id="ref5">19</reflink>]). Both conditions frequently co-occur, and there is evidence of significant similarities between the two conditions in terms of genetic, phenotypical, behavioural and neuropsychological characteristics ([<reflink idref="bib7" id="ref6">7</reflink>]; [<reflink idref="bib48" id="ref7">48</reflink>]). It is estimated that the co-occurrence of both conditions is around 1.2% among children aged 3–17 years ([<reflink idref="bib10" id="ref8">10</reflink>]).</p> <p>Both conditions are highly heritable. Twin studies have shown that the heritability of ASD and ADHD is over 80% ([<reflink idref="bib14" id="ref9">14</reflink>]; [<reflink idref="bib21" id="ref10">21</reflink>]; [<reflink idref="bib35" id="ref11">35</reflink>]; [<reflink idref="bib49" id="ref12">49</reflink>]; [<reflink idref="bib50" id="ref13">50</reflink>]). Due to the lack of complete concordance, it is likely that environmental factors also contribute to the etiopathogenesis of these conditions.</p> <p>Some of the most studied environmental factors are OC. However, the literature on the association between OC and ASD/ADHD has yielded inconsistent results ([<reflink idref="bib33" id="ref14">33</reflink>], [<reflink idref="bib32" id="ref15">32</reflink>]).</p> <p>These inconsistencies might be explained by multiples biases, such as unmeasured confounding. Family studies are used to examine the effects of genetic, environmental factors and unknown environmental factors on specific conditions. Family members, such as twins, siblings or cousins, share factors that increase their similarity. By comparing the exposure to a specific factor among family members who are discordant for an outcome, it is possible to adjust for familial confounders that are not measured in conventional case-control studies ([<reflink idref="bib18" id="ref16">18</reflink>]).</p> <p>In line with this, several recent studies have used family-based designs—particularly sibling and twin comparisons—to account for genetic and shared environmental confounders, often revealing attenuated or nonsignificant associations compared to population-level estimates ([<reflink idref="bib8" id="ref17">8</reflink>]; [<reflink idref="bib25" id="ref18">25</reflink>]). In the case of ASD, a study in Sweden indicated that children born by C-section had an increased likelihood of ASD. However, this association was nonsignificant when using sibling controls ([<reflink idref="bib17" id="ref19">17</reflink>]). Similarly, Obel et al. found no association between maternal smoking and increased likelihood of ADHD using a sibling design despite previous results in observational studies ([<reflink idref="bib41" id="ref20">41</reflink>]). The results of these studies are of great importance and clinical relevance as they impact decisions made during pregnancy, potentially affecting the health and safety of both the expectant individuals and their babies. For instance, it was recently recommended that pregnant individuals avoid the use of acetaminophen due to the potential likelihood of NDC. However, a later nationwide cohort and a population-based pregnancy cohort studies with sibling control analysis discarded this association ([<reflink idref="bib1" id="ref21">1</reflink>]; [<reflink idref="bib27" id="ref22">27</reflink>]).</p> <p>Exploring how OC relate to neurodevelopmental outcomes is not only important for research and health policy but may also be meaningful to autistic people and families, who often seek to understand the origins and variability of developmental pathways.</p> <p>The current study aims to explore the influence of OC on NDC by comparing five groups: children with ASD, ADHD, co-occurring ASD + ADHD, their unaffected siblings and a comparison group of children without NDC. For analytical purposes, we also examined a combined NDC group including all individuals with ASD, ADHD or both. This design allowed us to investigate both condition-specific and transdiagnostic associations with OC while accounting for familial confounding through sibling comparisons. We hypothesize that children with an NDC will show more OC than the comparison group. Second, we hypothesize that children with an NDC will not show more OC than their unaffected siblings, being the association found between the NDC group and the comparison group due to familial confounding.</p> <hd id="AN0189325695-3">Methods</hd> <p></p> <hd id="AN0189325695-4">Participants</hd> <p></p> <hd id="AN0189325695-5">Case sample</hd> <p>Recruitment of participants was carried out at the outpatient child and adolescent mental health service of Hospital Clinic of Barcelona, a tertiary hospital in Spain, between September 2021 and November 2022. All patients attending this outpatient service with a clinical diagnosis of ASD, ADHD or both, who had at least one sibling, were offered to participate in the study. To be included in the study, participants had to meet the following criteria: a diagnosis of ASD, ADHD or both; being 6–17 years old; having at least one sibling; ongoing follow-up by our service at the time of recruitment; and having provided informed consent (parental and, when applicable, participant assent). Participants with an IQ < 70, a diagnosed genetic syndrome or major congenital malformations were excluded. To avoid potential confounding due to shared obstetric and genetic profiles specific to multiple births, twin siblings were excluded from the sample.</p> <hd id="AN0189325695-6">Comparison group without NDC</hd> <p>For the comparison sample, participants were recruited from the paediatric service of the same hospital. Children without any diagnosed mental conditions who visited for non-psychiatric reasons, such as respiratory or digestive symptoms, were offered to take part in the study. Participants with siblings diagnosed with an NDC were excluded. We also excluded participants with a diagnosed genetic syndrome, neurological disorders, major congenital malformations or an IQ < 70. Twin siblings were excluded.</p> <p>This study followed the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines (see Supplemental Table 1) ([<reflink idref="bib51" id="ref23">51</reflink>]). The project has been reviewed and approved by the institutional review board and ethics committee. All participants aged > 12, and their parents signed a written informed consent. Community members were not involved in developing the research questions or design of this study.</p> <hd id="AN0189325695-7">Measures</hd> <p> <emph>Sociodemographic characteristics.</emph> Sociodemographic characteristics such as age, sex, parents' age, parents' education level, parents' occupation, race and family psychiatric history were gathered. Socioeconomic status (SES) was assessed using the Hollingshead Four-Factor Index of Social Status ([<reflink idref="bib29" id="ref24">29</reflink>]).</p> <p> <emph>Obstetric complications</emph>. Obstetric data were gathered through interviews with parents, using the obstetric enquiry schedule (OES) ([<reflink idref="bib5" id="ref25">5</reflink>]). Details on the scale and its scoring method can be found elsewhere ([<reflink idref="bib25" id="ref26">25</reflink>]). Briefly, three subscales (prenatal, perinatal and neonatal subscales) are calculated by summing the presence of specific medical risk factors during each period, with higher scores indicating an increased number of OC. A detailed list of the specific complications included in each subscale is provided in Supplemental Table 2. Although our primary approach was to examine the cumulative burden of complications, we also analysed certain individual predictors separately. These specific predictors (C-section, physical disorders of the infant, jaundice and phototherapy) were selected because they have been frequently studied as potential predictors for NDC in previous literature and were sufficiently prevalent in our sample (>10%) to allow meaningful statistical analysis. This complementary analysis aimed to explore whether any single predictor showed a particularly strong association with NDC beyond the cumulative burden.</p> <p>In assessing the missing data, Little's Missing Completely at Random (MCAR) test was conducted ([<reflink idref="bib39" id="ref27">39</reflink>]). The test indicated that the missing data across all OES data was random. Thus, we decided to exclude the missing data. To assess the reliability of the OES data, we selected a random sample of 50 participants and compared the gathered information with their medical records. Intra-class correlation (ICC) ([<reflink idref="bib45" id="ref28">45</reflink>]) was used to evaluate the concordance of the two datasets. The value of ICC was 0.82 (95% CI = 0.67–0.91, p < 0.001, absolute-agreement, two-way mixed-effects model), which is indicative of good reliability ([<reflink idref="bib34" id="ref29">34</reflink>]).</p> <p> <emph>NDC assessment</emph>. The diagnostic assessment process is summarized in Figure 1. Participants with an ASD, ADHD or both diagnoses were identified through medical records, and all met criteria for a clinical diagnosis according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (<emph>DSM</emph>-5) or International Classification of Diseases, Tenth Revision (ICD-10). All participants were screened for ASD using the Social Communication Questionnaire (SCQ). The SCQ is a parent-report screening measure for ASD for children over 4 years of age. It was considered positive for those who scored above 15. It has shown good validity ([<reflink idref="bib4" id="ref30">4</reflink>]). Autism Diagnostic Observation Schedule-2 (ADOS-2), Autism Diagnostic Interview-Revised (ADI-R) or both instruments were used to confirm diagnosis for those participants with a previous recorded diagnosis of ASD and those who screened positive on SCQ. A meta-analysis estimated the ADOS-2 sensitivity ranging from 0.89 to 0.92 and specificity ranging from 0.81 to 0.85. The ADI-R pooled sensitivity was estimated to be 0.75, and specificity was 0.82 ([<reflink idref="bib36" id="ref31">36</reflink>]).</p> <p>DIAGRAM: Figure 1. Diagram showing group allocation according to diagnosis.ADI-R: Autism Diagnostic Interview-Revised; ADHD: attention-deficit/hyperactivity disorder; ADOS-2: Autism Diagnostic Observation Schedule-2; ASD: Autism Spectrum Disorder; Conners: Conners 3rd ed parent form; SCQ: Social Communication Questionnaire.</p> <p>All participants were assessed for ADHD using Conner's rating scales ([<reflink idref="bib15" id="ref32">15</reflink>]). This tool assesses the core symptoms of ADHD according to <emph>DSM</emph> and other comorbidities such as conduct disorder and social problems. A T-score of 65 or above was considered clinically significant, following standard interpretive guidelines ([<reflink idref="bib16" id="ref33">16</reflink>]).</p> <p>All the screening and diagnostic assessments described earlier were conducted by the first author (SGV), a child psychiatrist formally trained in the administration of the tools used. Information from all instruments (SCQ, ADI-R, ADOS-2, Conners) was used to determine each participant's diagnosis, as shown in Figure 1.</p> <hd id="AN0189325695-8">Statistical analysis</hd> <p>Descriptive statistics were obtained for all variables, including means, standard deviations and frequencies. Differences regarding sociodemographic and clinical variables between the NDC group and the comparison group were explored using non-parametric tests, as the data was not normally distributed.</p> <p>Then, we analysed the data using generalized linear mixed models (GLMM) to account for siblings' relatedness. This approach allowed us to properly model the non-independence of observations within participants. As ASD and ADHD share genetic factors, we combined the three categories of NDC individuals (ASD, ADHD, co-occurring ASD + ADHD) into an 'NDC group'. We compared both NDC with their unaffected siblings and NDC with the comparison group. Then, we examined each group (ASD, ADHD, co-occurring ASD + ADHD) with their unaffected siblings and the comparison group.</p> <p>The NDC group and each diagnosis category were used as outcome. As fixed predictors, we included in separate analysis the score for prenatal, perinatal and neonatal scales. As birthweight is one of the most replicated predictors for NDC, we also ran an analysis using birthweight as a fixed predictor. As explained previously, only those predictors with a prevalence of more than 10% in our sample were included in the model to analyse separately. The included single predictors were C-section, physical disorders of the infant, jaundice and phototherapy. The Family Identity number (ID) was included in the random effect model to represent the correlation between siblings. By including the random effects, we modelled the clustering of siblings within families, ensuring that the estimates of the fixed effects were not biased by within-family similarities. Hence, we can identify predictors independently of familial confounders. All multivariate models included sex and SES as confounders given their known associations with NDC and access to perinatal care.</p> <p>The data that support the findings of this study are not publicly available due to legal constraints. Materials such as interview schedules are available at https://osf.io/abtd6/.</p> <p>All statistical analyses were conducted using SPSS version 28.0. The level of statistical significance was set at p < 0.05 (two-tailed) for all tests.</p> <hd id="AN0189325695-9">Results</hd> <p>The sample comprised 238 participants with an average age of 11.82 years (±4.60), of which 70.7% were male. It included 43 ASD participants, 46 ADHD participants, 27 co-occurring ASD + ADHD participants, 83 unaffected siblings and 39 from the comparison group. A total of 99 sibling pairs were included. Of these, 83 pairs were discordant for the outcome, meaning that one sibling had a diagnosis of NDC (ASD, ADHD or both), and the other did not. The remaining 16 pairs included siblings both with an NDC. Among the pairs that both had an NDC, three siblings had ASD, nine had ADHD and four presented with both ASD and ADHD. For more sociodemographic and clinical details of the sample, see Table 1.</p> <p>Table 1. Sociodemographic characteristics of participants by diagnostic group (ASD, ADHD, co-occurring ASD + ADHD, combined NDC group and comparison group).</p> <p>Graph</p> <p> <ephtml> <table><colgroup><col align="left" /><col align="char" char="." /><col align="char" char="." /><col align="char" char="." /><col align="char" char="." /><col align="char" char="." /><col align="char" char="." /></colgroup><thead><tr><th /><th align="left">ASD group (<italic>n</italic> = 43)</th><th align="left">ADHD group (<italic>n</italic> = 46)</th><th align="left">Co-occurring ASD + ADHD (<italic>n</italic> = 27)</th><th align="left">NDC group (<italic>n</italic> = 116)</th><th align="left">Comparison group (<italic>n</italic> = 39)</th><th align="left">p</th></tr></thead><tbody><tr><td colspan="7"><italic>Sociodemographic variables</italic></td></tr><tr><td>Gender</td><td /><td /><td /><td /><td /><td>0.03<xref ref-type="table-fn" rid="tfn2">*</xref></td></tr><tr><td> Male (%)</td><td>25 (58.1)</td><td>34 (73.9)</td><td>23 (85.2)</td><td>82 (70.9)</td><td>20 (51.3)</td><td /></tr><tr><td> Female (%)</td><td>18 (41.9)</td><td>12 (26.1)</td><td>4 (14.8)</td><td>34 (29.1)</td><td>19 (48.7)</td><td /></tr><tr><td>Age, mean (s.d.)</td><td>10.63 (4.20)</td><td>12.83 (2.58)</td><td>12.33 (3.22)</td><td>11.91 (3.51)</td><td>10.15 (2.97)</td><td>0.03<xref ref-type="table-fn" rid="tfn2">*</xref></td></tr><tr><td>SES categories</td><td /><td /><td /><td /><td /><td>0.13</td></tr><tr><td> Lower status (%)</td><td>5 (11.6)</td><td>4 (8.7)</td><td>3 (11.1)</td><td>12 (10.3)</td><td>2 (5.1)</td><td /></tr><tr><td> Lower-middle st (%)</td><td>10 (23.3)</td><td>6 (13)</td><td>9 (33.3)</td><td>25 (21.4)</td><td>4 (10.3)</td><td /></tr><tr><td> Middle status (%)</td><td>3 (7)</td><td>4 (8.7)</td><td>3 (11.1)</td><td>10 (8.4)</td><td>2 (5.1)</td><td /></tr><tr><td> Upper-middle st (%)</td><td>11 (25.6)</td><td>18 (39.1)</td><td>4 (14.8)</td><td>33 (28.2)</td><td>10 (25.6)</td><td /></tr><tr><td> Upper status (%)</td><td>14 (32.6)</td><td>14 (30.4)</td><td>8 (29.6)</td><td>36 (31.6)</td><td>21 (53.8)</td><td /></tr><tr><td colspan="7">Parents' education</td></tr><tr><td><italic>Mother's education</italic></td><td /><td /><td /><td /><td /><td>0.001<xref ref-type="table-fn" rid="tfn2">*</xref></td></tr><tr><td>Primary school</td><td>2 (4.7)</td><td>1 (2.2)</td><td>2 (7.4)</td><td>5 (4.3)</td><td>5 (13.2)</td><td /></tr><tr><td>Secondary school</td><td>21 (48.8)</td><td>23 (50)</td><td>12 (44.4)</td><td>56 (47.9)</td><td>6 (15.8)</td><td /></tr><tr><td>University</td><td>20 (46.5)</td><td>22 (47.8)</td><td>13 (48.1)</td><td>55 (47.9)</td><td>28 (71.1)</td><td /></tr><tr><td><italic>Father's education</italic></td><td /><td /><td /><td /><td /><td>0.24</td></tr><tr><td>Primary school</td><td>2 (5.6)</td><td>1 (2.4)</td><td>2 (8)</td><td>5 (4.9)</td><td>2 (5.6)</td><td /></tr><tr><td>Secondary school</td><td>15 (41.7)</td><td>23 (56.1)</td><td>13 (52)</td><td>51 (49.5)</td><td>12 (33.3)</td><td /></tr><tr><td>University</td><td>29 (52.8)</td><td>17 (41.5)</td><td>10 (40)</td><td>56 (45.6)</td><td>22 (61.1)</td><td /></tr><tr><td>Living situation</td><td /><td /><td /><td /><td /><td>0.60</td></tr><tr><td> With both parents (%)</td><td>36 (83.7)</td><td>39 (4.8)</td><td>23 (85.2)</td><td>98 (84.6)</td><td>35 (89.7)</td><td /></tr><tr><td> Only with mother (%)</td><td>7 (16.3)</td><td>7 (15.2)</td><td>4 (14.8)</td><td>18 (15.4)</td><td>4 (10.3)</td><td /></tr><tr><td>Race</td><td /><td /><td /><td /><td /><td>0.20</td></tr><tr><td> Caucasian (%)</td><td>29 (67.4)</td><td>39 (84.8)</td><td>20 (74.1)</td><td>88 (76.1)</td><td>30 (76.9)</td><td /></tr><tr><td> Latino (%)</td><td>9 (20.9)</td><td>4 (8.7)</td><td>5 (18.5)</td><td>18 (15.4)</td><td>7 (17.5)</td><td /></tr><tr><td> Other (%)</td><td>5 (11.6)</td><td>3 (6.5)</td><td>2 (7.4)</td><td>10 (8.5)</td><td>2 (5)</td><td /></tr><tr><td>Maternal age, mean (s.d.)</td><td>33.62 (5.75)</td><td>33.48 (4.63)</td><td>32.56 (4.72)</td><td>33.33 (5.04)</td><td>33.33 (5.42)</td><td>0.99</td></tr><tr><td>Paternal age, mean (s.d.)</td><td>35.74 (7.07)</td><td>35.76 (6.00)</td><td>34.26 (6.06)</td><td>35.42 (6.35)</td><td>35.82 (6.58)</td><td>0.74</td></tr></tbody></table> </ephtml> </p> <p>1 The NDC group includes all participants with a diagnosis of ASD, ADHD or both. Unaffected siblings were not included as they share most of the sociodemographic characteristics with their siblings. ASD: autism spectrum disorder; ADHD: attention-deficit/hyperactivity disorder; NDC: neurodevelopmental conditions; SES: socioeconomic status; s.d.: standard deviation.</p> <p>2 p < 0.05.</p> <p>NDC individuals and the comparison group were similar in terms of SES, parents' education, living situation, race and both maternal and paternal age at birth (all p > 0.05). However, they differed in sex, with a higher proportion of males among the NDC individuals, and age, the comparison group being younger than the NDC individuals (10.15 vs 11.91). In addition, mother's education level significantly differed between groups (p = 0.001), with higher levels of university education observed in the comparison group than in diagnostic groups. Regarding family medical history, excluding siblings, NDC individuals exhibited a significantly higher incidence of ASD and ADHD within the family (p < 0.02 and p < 0.001, respectively). There were no other significant differences between the groups in terms of familial psychiatric history.</p> <hd id="AN0189325695-10">NDC group (ASD, ADHD or both)</hd> <p>The mean score for the subscales of perinatal and neonatal scores was higher for NDC than for the comparison group (Table 2). However, no significant differences were found in the total OES score. The GLMM analysis showed no significant differences between NDC individuals and the comparison group nor their unaffected siblings in the prenatal and perinatal subscale. The neonatal subscale, however, was significantly higher in NDC individuals than in both the comparison group (β =1.73, 95% CI = 1.00–2.98, p = 0.04) and their unaffected siblings (β = 1.43, 95% CI = 1.02–2.00, p = 0.04) (Table 3).</p> <p>Table 2. Clinical variables for the NDC group, unaffected siblings and comparison group.</p> <p>Graph</p> <p> <ephtml> <table><colgroup><col align="left" /><col align="char" char="." /><col align="char" char="." /><col align="char" char="." /></colgroup><thead><tr><th align="left">Clinical variables</th><th align="left">NDC group (<italic>n</italic> = 116)</th><th align="left">Unaffected siblings (<italic>n</italic> = 83)</th><th align="left">Comparison group (<italic>n</italic> = 39)</th></tr></thead><tbody><tr><td>Prenatal scale, mean (s.d.)</td><td>2.83 (1.36)</td><td>2.66 (1.67)</td><td>3.00 (39)</td></tr><tr><td>Perinatal scale, mean (s.d.)</td><td>2.28 (1.38)</td><td>1.97 (1.28)</td><td>2.23 (1.38)</td></tr><tr><td>Neonatal scale, mean (s.d.)</td><td>0.72 (1.11)</td><td>0.37 (0.73)</td><td>0.28 (0.60)</td></tr><tr><td>Total OES, mean (s.d.)</td><td>5.84 (2.56)</td><td>5.01 (2.62)</td><td>5.51 (2.21)</td></tr><tr><td colspan="4"><italic>Single predictors</italic></td></tr><tr><td>Birthweight, mean (s.d.)</td><td>3081.44 (750.01)</td><td>3107.67 (528.50)</td><td>3290.50 (504.30)</td></tr><tr><td>C-section (%)</td><td>33.7</td><td>36.2</td><td>30.8</td></tr><tr><td>Physical disorders in infant (%)</td><td>19.8</td><td>12</td><td>7.7</td></tr><tr><td>Jaundice (%)</td><td>22.4</td><td>15.7</td><td>10.3</td></tr><tr><td>Phototherapy (%)</td><td>10.1</td><td>3.6</td><td>5.1</td></tr><tr><td colspan="4"><italic>Assessments</italic></td></tr><tr><td>SCQ, mean (s.d.)</td><td>12.49 (9.94)</td><td>1.62 (3.42)</td><td>1.08 (0.96)</td></tr><tr><td>Conners – Inattention subscale, mean (s.d.)</td><td>74.77 (12.01)</td><td>63.29 (17.16)</td><td>56.29 (10.08)</td></tr><tr><td>Conners – Hyperactivity subscale, mean (s.d.)</td><td>75.46 (12.53)</td><td>59.18 (17.48)</td><td>54.14 (10.04)</td></tr></tbody></table> </ephtml> </p> <p>3 For Conners inattention and hyperactivity subscale, a T-score > 65 was considered positive. OES: obstetric enquiry schedule; Conners: conners 3<sups>rd</sups> ed parent form; SCQ: Social Communication Questionnaire; s.d.: standard deviation.</p> <p>Table 3. Generalized linear mixed models (GLMM) examining the association between NDC group, comparison group and unaffected siblings.</p> <p>Graph</p> <p> <ephtml> <table><colgroup><col align="left" /><col align="char" char="." /><col align="char" char="." /><col align="char" char="." /><col align="char" char="." /><col align="char" char="." /><col align="char" char="." /><col align="char" char="." /><col align="char" char="." /><col align="char" char="." /></colgroup><thead><tr><th align="left" rowspan="2">Variable</th><th align="left" colspan="3">NDC group vs comparison group</th><th align="left" colspan="3">NDC group vs unaffected siblings</th><th align="left" colspan="3">Comparison group vs unaffected siblings</th></tr><tr><th align="left">β (95% CI)</th><th align="left">t</th><th align="left">p</th><th align="left">β (95% CI)</th><th align="left">t</th><th align="left">p</th><th align="left">β (95% CI)</th><th align="left">t</th><th align="left">p</th></tr></thead><tbody><tr><td>Prenatal subscale</td><td>0.88 (0.65–1.20)</td><td>−0.82</td><td>0.41</td><td>1.08 (0.88–1.32)</td><td>0.76</td><td>0.45</td><td>0.86 (0.67–1.10)</td><td>−1.19</td><td>0.23</td></tr><tr><td>Perinatal subscale</td><td>1.02 (0.76–1.37)</td><td>0.11</td><td>0.91</td><td>1.17 (0.94–1.47)</td><td>1.39</td><td>0.16</td><td>0.85 (0.63–1.15)</td><td>−1.06</td><td>0.29</td></tr><tr><td>Neonatal subscale</td><td>1.73 (1.00–2.98)</td><td>1.99</td><td>0.04<xref ref-type="table-fn" rid="tfn5">*</xref></td><td>1.44 (1.02–2.03)</td><td>2.12</td><td>0.03<xref ref-type="table-fn" rid="tfn5">*</xref></td><td>1.21 (0.66–2.22)</td><td>0.63</td><td>0.53</td></tr><tr><td>Total OES</td><td>1.05 (0.88–1.24)</td><td>0.53</td><td>0.60</td><td>1.12 (0.99–1.27)</td><td>1.90</td><td>0.06</td><td>0.91 (0.78–1.07)</td><td>−1.13</td><td>0.26</td></tr><tr><td colspan="10"><italic>Single predictors</italic></td></tr><tr><td>Birthweight</td><td>0.99 (0.99–1.00)</td><td>−2.01</td><td>0.04<xref ref-type="table-fn" rid="tfn5">*</xref></td><td>1.00 (0.99–1.00)</td><td>−1.63</td><td>0.11</td><td>0.99 (0.99–1.00)</td><td>−1.58</td><td>0.12</td></tr><tr><td>C-section</td><td>0.97 (0.41–2.26)</td><td>0.07</td><td>0.94</td><td>1.12 (0.60–2.09)</td><td>0.36</td><td>0.72</td><td>2.71 (0.64–11.47)</td><td>1.37</td><td>0.17</td></tr><tr><td>Physical disorders in child</td><td>0.33 (0.09–1.21)</td><td>2.79</td><td>0.09</td><td>0.58 (0.25–1.36)</td><td>1.26</td><td>0.21</td><td>0.62 (0.16–2.48)</td><td>−0.68</td><td>0.50</td></tr><tr><td>Jaundice</td><td>0.44 (0.14–1.38)</td><td>1.98</td><td>0.16</td><td>0.78 (0.08–7.91)</td><td>0.22</td><td>0.83</td><td>0.62 (0.18–2.11)</td><td>−0.76</td><td>0.45</td></tr><tr><td>Phototherapy</td><td>0.56 (0.11–2.79)</td><td>0.51</td><td>0.47</td><td>0.32 (0.08–1.29)</td><td>1.61</td><td>0.11</td><td>1.59 (0.24–10.55)</td><td>0.48</td><td>0.63</td></tr></tbody></table> </ephtml> </p> <ulist> <item>4 NDC: neurodevelopmental conditions; OES: obstetric enquiry schedule.</item> <item>5 p < 0.05.</item> </ulist> <hd id="AN0189325695-11">ASD group</hd> <p>No significant differences were found between ASD and either their unaffected siblings or the comparison group in the total, prenatal or perinatal subscale. However, we found a significant difference in the neonatal subscale between the group of participants with ASD and their unaffected siblings (β = 1.53, 95% CI = 1.02–2.29, p = 0.04), but not compared to the comparison group.</p> <hd id="AN0189325695-12">ADHD group</hd> <p>No significant differences were observed in the total, prenatal or perinatal subscale when comparing the ADHD group to either their unaffected siblings or the comparison group. Nevertheless, the neonatal subscale showed significantly higher scores in ADHD individuals than in both their unaffected siblings (β = 1.57, 95% CI = 1.02–2.46, p = 0.04), as well as the comparison group (β = 2.26, 95% CI = 1.09–4.70, p = 0.03).</p> <hd id="AN0189325695-13">Co-occurring ASD + ADHD group</hd> <p>The co-occurring group showed a significantly higher total OES score than their unaffected siblings (β = 1.24, 95% CI = 1.01–1.52, p = 0.04), but not when compared to the comparison group. No significant differences were found in the prenatal subscale. The perinatal subscale was also significantly higher than unaffected siblings (β = 1.56, 95% CI = 1.03–2.38, p = 0.04). No significant differences were observed in the neonatal subscale for this group.</p> <hd id="AN0189325695-14">Comparison between unaffected siblings and comparison group</hd> <p>No significant differences were found between unaffected siblings and the comparison group in any of the OES scale.</p> <hd id="AN0189325695-15">Single predictors</hd> <p>We found significant differences in birthweight between NDC individuals and the comparison group (β = 0.99, 95% CI = 0.99–1.00, p = 0.04). This association did not remain significant when comparing NDC individuals and their unaffected siblings in birthweight (β = 1.00, 95% CI = 0.99–1.00, p = 0.11).</p> <p>No significant differences were observed between ASD, ADHD or co-occurring ASD + ADHD group and their unaffected siblings or the comparison group in birthweight.</p> <p>None of the single predictors examined (C-section, physical disorders of the child, jaundice or phototherapy) were associated with NDC.</p> <hd id="AN0189325695-16">Discussion</hd> <p>The purpose of this study was to examine the association between OC and NDC, comparing NDC individuals with their unaffected siblings and the comparison group. Using a conventional case-control analysis, we found that NDC individuals had more neonatal complications than the comparison group, confirming partially our first hypothesis. In the sibling analysis, this association remained significant, not confirming our second hypothesis, as we predicted that this association would be mediated by familial confounders. Examining each diagnostic category, we found in the sibling analysis that both participants with ADHD as well as ASD presented more neonatal complications than their unaffected siblings.</p> <p>These results suggest that neonatal complications are associated with an increased likelihood of being diagnosed with an NDC, independent of familial confounding. Cumulative adversities in early childhood have been previously associated with ASD and ADHD in sibling studies ([<reflink idref="bib6" id="ref34">6</reflink>]; [<reflink idref="bib20" id="ref35">20</reflink>]; [<reflink idref="bib22" id="ref36">22</reflink>]; [<reflink idref="bib26" id="ref37">26</reflink>]), as well as in twin studies ([<reflink idref="bib9" id="ref38">9</reflink>]; [<reflink idref="bib30" id="ref39">30</reflink>]; [<reflink idref="bib46" id="ref40">46</reflink>]; [<reflink idref="bib52" id="ref41">52</reflink>]). However, most studies have been conducted with ASD participants rather than ADHD participants. Thus, this study provides new insights into the etiopathogenesis of ADHD.</p> <p>When considering specific predictors, however, the findings are less consistent. For instance, some studies suggest that neonatal complications such as respiratory distress or other markers of hypoxia increase the likelihood of ASD and ADHD in sibling and twin studies ([<reflink idref="bib23" id="ref42">23</reflink>]; [<reflink idref="bib28" id="ref43">28</reflink>]). These complications are captured within our neonatal subscale and might contribute to the group differences observed in our study. However others did not find differences among sibling or twin pairs ([<reflink idref="bib24" id="ref44">24</reflink>]; [<reflink idref="bib43" id="ref45">43</reflink>]). Similarly, variables such as low Apgar scores, the need for an incubator or special care also yielded mixed results ([<reflink idref="bib12" id="ref46">12</reflink>]; [<reflink idref="bib24" id="ref47">24</reflink>]). Finally, jaundice has not been associated with ASD or ADHD in sibling studies ([<reflink idref="bib12" id="ref48">12</reflink>]; [<reflink idref="bib20" id="ref49">20</reflink>]; [<reflink idref="bib38" id="ref50">38</reflink>]).</p> <p>However, a twin study found that jaundice was a predictor for ASD only in females ([<reflink idref="bib23" id="ref51">23</reflink>]). In our study, we did not find an association between specific predictors and NDC, but this negative finding could be due to low power in our model. Our findings should also be interpreted in light of previous studies using twin samples. While twin designs are particularly powerful in controlling for familial confounding, they may have limited generalizability to singleton pregnancies due to the distinct obstetric characteristics of multiple births. Our sibling-based design offers a complementary perspective: it also controls for familial factors, while capturing a broader range of naturalistic obstetric exposures.</p> <p>It has already been previously described that environmental factors might increase the likelihood of NDC in a cumulative manner ([<reflink idref="bib47" id="ref52">47</reflink>]), which would explain the lack of consistency in the studies that focus on single environmental factors. In addition, it appears to be a synergistic effect between environmental and genetic factors ([<reflink idref="bib37" id="ref53">37</reflink>]), meaning that the combined effect of environmental and genetic factors is stronger than the sum of their individual effects. Overall, our results and the literature suggest that a higher load of cumulative exposures, rather than specific single events, is associated with an increased likelihood of NDC in individuals with underlying genetic vulnerability.</p> <p>In contrast with neonatal factors, prenatal and perinatal factors were not associated with ASD or ADHD, which is in line with previous findings. Literature examining cumulative complications during the pregnancy, labour and delivery using sibling and twin designs failed to find an association ([<reflink idref="bib3" id="ref54">3</reflink>]; [<reflink idref="bib25" id="ref55">25</reflink>]; [<reflink idref="bib26" id="ref56">26</reflink>]; [<reflink idref="bib28" id="ref57">28</reflink>]). The only two studies reporting positive results were conducted with ASD participants ([<reflink idref="bib28" id="ref58">28</reflink>]; [<reflink idref="bib42" id="ref59">42</reflink>]). This could reflect that obstetrical adversities have a higher impact on ASD than ADHD, or that ASD children also present a higher risk of adversities during pregnancy. Evaluating specific prenatal and perinatal predictors, we did not find any significant association. However, as mentioned previously, the low exposures rates for specific factors might result in a lack of power to detect effects of small size. Previous findings from specific predictors in observational, familial studies and meta-analysis are inconsistent, and when positive, the effect sizes are small, indicating a small modulation by each predictor ([<reflink idref="bib32" id="ref60">32</reflink>]; [<reflink idref="bib33" id="ref61">33</reflink>]).</p> <p>The subgroup of co-occurring ASD + ADHD was associated with perinatal complications, but not prenatal or neonatal complications. The small sample size of this subgroup might have limited the ability to detect a significant association. However, the only sibling study that examined OC in a group of co-occurring ASD + ADHD sample also found that OC did not explain the increased likelihood for these conditions ([<reflink idref="bib42" id="ref62">42</reflink>]).</p> <p>Our findings indicated that lower birthweight increased the likelihood of NDC compared to the comparison group but not with their siblings, suggesting familial confounding as a mediator. This result contrasts with the extensive literature that associates low birthweight, defined as < 2500 g, with NDC ([<reflink idref="bib12" id="ref63">12</reflink>]; [<reflink idref="bib13" id="ref64">13</reflink>]; [<reflink idref="bib42" id="ref65">42</reflink>]). In our sample, as the prevalence of low birthweight was <10%, we used the continuous variable of birthweight. Petterson et al. also used birthweight as a continuous variable to study its association with several mental conditions. Although they found a positive association with ADHD and ASD for low birthweight, this association was not elevated when comparing medium or high birthweight ([<reflink idref="bib44" id="ref66">44</reflink>]), which confirms our results. Furthermore, in another sample of sibling pairs, ADHD was not associated with birthweight ([<reflink idref="bib11" id="ref67">11</reflink>]). Finally, in a twin study, birthweight was significantly associated with ASD and ADHD in monozygotic (MZ) twins but not in dizygotic (DZ) twins ([<reflink idref="bib31" id="ref68">31</reflink>]). As DZ twins share only 50% of their genes, like siblings, the influence of genetics may overshadow non-shared environmental factors in DZ twins, thus observing a stronger association in MZ twins.</p> <p>Finally, it is important to note that some of the neonatal complications or interventions (e.g. phototherapy, floppy infant) may reflect early manifestations of neurodevelopmental vulnerability rather than being causal. For example, subtle behavioural or physiological differences in the foetus or neonate might trigger medical responses or represent early markers of atypical development. Therefore, while our findings indicate a statistically significant association, we cannot infer directionality or causality from these observational data.</p> <p>Although this study does not aim to predict individual outcomes or define likelihood in clinical terms, the observed association between neonatal complications and later neurodevelopmental diagnoses may be of interest to autistic adults and families of autistic children. Understanding patterns of early life experiences may help inform future research on early support, improve obstetric and neonatal care and contribute to a more nuanced understanding of developmental diversity.</p> <hd id="AN0189325695-17">Limitations and strengths</hd> <p>The study has some limitations that should be considered. First, the obstetric data was gathered through interviews with parents, which depends on parental recall of obstetric adversities. Parents' recall may be biased by later child outcome. However, we compared our data with medical health records for a random sample, indicating that our data has a good reliability. Second, the sample was relatively small. The small sample and low frequency rate of specific predictors might have resulted in a limited ability to detect small size effects. Finally, although we conducted separate analyses for ASD, ADHD and co-occurring cases, these group-specific findings should be interpreted with caution, as the relatively small sample sizes – particularly in the co-occurring group – may limit the ability to detect statistically significant associations. Larger studies with sufficient statistical power are needed to better examine potential disorder-specific patterns.</p> <p>A strength of this study is the validity of our diagnosis. We used medical records to include the participants, and then we used several instruments to confirm the diagnosis. This allows us to capture subtle symptoms that did not reach clinical significance to have received a previous diagnosis. Another strength is the use of a sibling design. Sibling-based designs enable the disentanglement of environmental and genetic factors. Thus, this type of design is crucial when trying to establish causal inferences.</p> <hd id="AN0189325695-18">Conclusion</hd> <p>This study supports that cumulative early adversities, particularly in the neonatal period, are associated with a higher likelihood of NDC, beyond familial confounding. Our results indicate that neonatal adversities experienced by the child, rather than pregnancy and labour conditions, are important correlates of later neurodevelopmental conditions. In line with previous research, it stresses the importance to continue using family-design studies when examining environmental factors and their associations with NDC.</p> <hd id="AN0189325695-19">Supplemental Material</hd> <p>Graph: Supplemental material, sj-docx-1-aut-10.1177_13623613251359317 for The role of obstetric adversities in neurodevelopmental conditions: A sibling study by Sandra Gómez-Vallejo, Oaia Iriondo-Blanco, Gonzalo Salazar de Pablo, Rosa Calvo Escalona and Luisa Lázaro García in Autism</p> <ref id="AN0189325695-20"> <title> References </title> <blist> <bibl id="bib1" idref="ref21" type="bt">1</bibl> <bibtext> Ahlqvist V. H., Sjoqvist H., Dalman C., Karlsson H., Stephansson O., Johansson S., Magnusson C., Gardner R. M., Lee B. K. (2024). Acetaminophen use during pregnancy and children's risk of autism, ADHD, and intellectual disability. 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Translational Psychiatry, 7(1), Article e1014. https://doi.org/10.1038/tp.2016.269</bibtext> </blist> </ref> <ref id="AN0189325695-21"> <title> Footnotes </title> <blist> <bibtext> Sandra Gómez-Vallejo</bibtext> </blist> <blist> <bibtext>Graph https://orcid.org/0000-0003-0963-6585</bibtext> </blist> <blist> <bibtext> Sandra Gómez-Vallejo: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Project administration; Writing – original draft.Oaia Iriondo-Blanco: Methodology; Validation; Writing – review & editing.Gonzalo Salazar de Pablo: Methodology; Writing – review & editing.Rosa Calvo Escalona: Conceptualization; Methodology; Supervision; Writing – review & editing.Luisa Lázaro García: Conceptualization; Methodology; Supervision; Writing – review & editing.</bibtext> </blist> <blist> <bibtext> The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: S.G.-V. was supported by a grant from Alicia Koplowitz Foundation. Our special thanks go to the participants and their families.</bibtext> </blist> <blist> <bibtext> The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: G.S.P. has received honoraria from Lundbeck, Janssen Cilag and Menarini.</bibtext> </blist> <blist> <bibtext> Supplemental material for this article is available online.</bibtext> </blist> </ref> <aug> <p>By Sandra Gómez-Vallejo; Oaia Iriondo-Blanco; Gonzalo Salazar de Pablo; Rosa Calvo Escalona and Luisa Lázaro García</p> <p>Reported by Author; Author; Author; Author; Author</p> </aug> <nolink nlid="nl1" bibid="bib40" firstref="ref3"></nolink> <nolink nlid="nl2" bibid="bib19" firstref="ref5"></nolink> <nolink nlid="nl3" bibid="bib48" firstref="ref7"></nolink> <nolink nlid="nl4" bibid="bib10" firstref="ref8"></nolink> <nolink nlid="nl5" bibid="bib14" firstref="ref9"></nolink> <nolink nlid="nl6" bibid="bib21" firstref="ref10"></nolink> <nolink nlid="nl7" bibid="bib35" firstref="ref11"></nolink> <nolink nlid="nl8" bibid="bib49" firstref="ref12"></nolink> <nolink nlid="nl9" bibid="bib50" firstref="ref13"></nolink> <nolink nlid="nl10" bibid="bib33" firstref="ref14"></nolink> <nolink nlid="nl11" bibid="bib32" firstref="ref15"></nolink> <nolink nlid="nl12" bibid="bib18" firstref="ref16"></nolink> <nolink nlid="nl13" bibid="bib25" firstref="ref18"></nolink> <nolink nlid="nl14" bibid="bib17" firstref="ref19"></nolink> <nolink nlid="nl15" bibid="bib41" firstref="ref20"></nolink> <nolink nlid="nl16" bibid="bib27" firstref="ref22"></nolink> <nolink nlid="nl17" bibid="bib51" firstref="ref23"></nolink> <nolink nlid="nl18" bibid="bib29" firstref="ref24"></nolink> <nolink nlid="nl19" bibid="bib39" firstref="ref27"></nolink> <nolink nlid="nl20" bibid="bib45" firstref="ref28"></nolink> <nolink nlid="nl21" bibid="bib34" firstref="ref29"></nolink> <nolink nlid="nl22" bibid="bib36" firstref="ref31"></nolink> <nolink nlid="nl23" bibid="bib15" firstref="ref32"></nolink> <nolink nlid="nl24" bibid="bib16" firstref="ref33"></nolink> <nolink nlid="nl25" bibid="bib20" firstref="ref35"></nolink> <nolink nlid="nl26" bibid="bib22" firstref="ref36"></nolink> <nolink nlid="nl27" bibid="bib26" firstref="ref37"></nolink> <nolink nlid="nl28" bibid="bib30" firstref="ref39"></nolink> <nolink nlid="nl29" bibid="bib46" firstref="ref40"></nolink> <nolink nlid="nl30" bibid="bib52" firstref="ref41"></nolink> <nolink nlid="nl31" bibid="bib23" firstref="ref42"></nolink> <nolink nlid="nl32" bibid="bib28" firstref="ref43"></nolink> <nolink nlid="nl33" bibid="bib24" firstref="ref44"></nolink> <nolink nlid="nl34" bibid="bib43" firstref="ref45"></nolink> <nolink nlid="nl35" bibid="bib12" firstref="ref46"></nolink> <nolink nlid="nl36" bibid="bib38" firstref="ref50"></nolink> <nolink nlid="nl37" bibid="bib47" firstref="ref52"></nolink> <nolink nlid="nl38" bibid="bib37" firstref="ref53"></nolink> <nolink nlid="nl39" bibid="bib42" firstref="ref59"></nolink> <nolink nlid="nl40" bibid="bib13" firstref="ref64"></nolink> <nolink nlid="nl41" bibid="bib44" firstref="ref66"></nolink> <nolink nlid="nl42" bibid="bib11" firstref="ref67"></nolink> <nolink nlid="nl43" bibid="bib31" firstref="ref68"></nolink>
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  Data: The Role of Obstetric Adversities in Neurodevelopmental Conditions: A Sibling Study
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  Data: English
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  Data: <searchLink fieldCode="AR" term="%22Sandra+Gómez-Vallejo%22">Sandra Gómez-Vallejo</searchLink> (ORCID <externalLink term="https://orcid.org/0000-0003-0963-6585">0000-0003-0963-6585</externalLink>)<br /><searchLink fieldCode="AR" term="%22Oaia+Iriondo-Blanco%22">Oaia Iriondo-Blanco</searchLink><br /><searchLink fieldCode="AR" term="%22Gonzalo+Salazar+de+Pablo%22">Gonzalo Salazar de Pablo</searchLink><br /><searchLink fieldCode="AR" term="%22Rosa+Calvo+Escalona%22">Rosa Calvo Escalona</searchLink><br /><searchLink fieldCode="AR" term="%22Luisa+Lázaro+García%22">Luisa Lázaro García</searchLink>
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  Data: <searchLink fieldCode="SO" term="%22Autism%3A+The+International+Journal+of+Research+and+Practice%22"><i>Autism: The International Journal of Research and Practice</i></searchLink>. 2025 29(12):3072-3082.
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  Data: SAGE Publications. 2455 Teller Road, Thousand Oaks, CA 91320. Tel: 800-818-7243; Tel: 805-499-9774; Fax: 800-583-2665; e-mail: journals@sagepub.com; Web site: https://sagepub.com
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  Data: 11
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  Data: 2025
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  Data: Journal Articles<br />Reports - Research
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  Data: <searchLink fieldCode="DE" term="%22Neurodevelopmental+Disorders%22">Neurodevelopmental Disorders</searchLink><br /><searchLink fieldCode="DE" term="%22Predictor+Variables%22">Predictor Variables</searchLink><br /><searchLink fieldCode="DE" term="%22Siblings%22">Siblings</searchLink><br /><searchLink fieldCode="DE" term="%22Children%22">Children</searchLink><br /><searchLink fieldCode="DE" term="%22Adolescents%22">Adolescents</searchLink><br /><searchLink fieldCode="DE" term="%22Autism+Spectrum+Disorders%22">Autism Spectrum Disorders</searchLink><br /><searchLink fieldCode="DE" term="%22Attention+Deficit+Hyperactivity+Disorder%22">Attention Deficit Hyperactivity Disorder</searchLink><br /><searchLink fieldCode="DE" term="%22Comorbidity%22">Comorbidity</searchLink><br /><searchLink fieldCode="DE" term="%22Neonates%22">Neonates</searchLink><br /><searchLink fieldCode="DE" term="%22Pregnancy%22">Pregnancy</searchLink><br /><searchLink fieldCode="DE" term="%22Foreign+Countries%22">Foreign Countries</searchLink><br /><searchLink fieldCode="DE" term="%22Individual+Characteristics%22">Individual Characteristics</searchLink>
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  Data: <searchLink fieldCode="DE" term="%22Spain+%28Barcelona%29%22">Spain (Barcelona)</searchLink>
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1177/13623613251359317
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  Label: ISSN
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  Data: 1362-3613<br />1461-7005
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Neurodevelopmental conditions (NDC) are highly heritable. Obstetric complications (OC) have been studied as potential predictors for NDC, although results are inconsistent. Inconsistencies might be related to biases such as family confounders. While some studies using sibling and twin designs have examined the association between OC and NDC, this body of research remains limited, and findings to date remain inconsistent. We used a case-control sibling study including children aged 6--17 years across five groups: those diagnosed with autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), co-occurring ASD + ADHD, their unaffected siblings and a comparison group without NDC. For analytic purposes, we created a combined NDC group including all individuals with ASD, ADHD or both. Participants were recruited between 2021 and 2022 from a tertiary hospital in Spain. We examined the association of NDC and OC using single predictors and cumulative OC. The study adheres to the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines. A total of 238 participants were included (NDC = 117, unaffected siblings = 82, comparison group = 39). We found that NDC individuals showed more neonatal complications than the comparison group ([beta] = 1.73, 95% CI = 1.00-2.98, p = 0.04), which remained significant in the sibling analysis ([beta] = 1.43, 95% CI = 1.02-2.00, p = 0.04). This study supports that the cumulative neonatal complications, rather than specific factors, are associated with increased likelihood of being diagnosed with NDC, beyond familial confounding. Results highlight the neonatal period as a relevant window of vulnerability.
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        Value: 10.1177/13623613251359317
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        PageCount: 11
        StartPage: 3072
    Subjects:
      – SubjectFull: Neurodevelopmental Disorders
        Type: general
      – SubjectFull: Predictor Variables
        Type: general
      – SubjectFull: Siblings
        Type: general
      – SubjectFull: Children
        Type: general
      – SubjectFull: Adolescents
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      – SubjectFull: Autism Spectrum Disorders
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      – SubjectFull: Attention Deficit Hyperactivity Disorder
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      – SubjectFull: Comorbidity
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      – SubjectFull: Neonates
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      – SubjectFull: Pregnancy
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      – SubjectFull: Foreign Countries
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      – SubjectFull: Individual Characteristics
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      – SubjectFull: Spain (Barcelona)
        Type: general
    Titles:
      – TitleFull: The Role of Obstetric Adversities in Neurodevelopmental Conditions: A Sibling Study
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              Y: 2025
          Identifiers:
            – Type: issn-print
              Value: 1362-3613
            – Type: issn-electronic
              Value: 1461-7005
          Numbering:
            – Type: volume
              Value: 29
            – Type: issue
              Value: 12
          Titles:
            – TitleFull: Autism: The International Journal of Research and Practice
              Type: main
ResultId 1