Hosozawa 2024 Oi 231548 1705094509.26292

Original Investigation | Pediatrics
Maternal Autistic Traits and Adverse Birth Outcomes

Mariko Hosozawa, MD, PhD; Noriko Cable, PhD; Satoyo Ikehara, PhD; Yuri Aochi, PhD; Kanami Tanigawa, PhD; Sachiko Baba, PhD; Kumi Hirokawa, PhD;
Tadashi Kimura, PhD; Tomotaka Sobue, PhD; Hiroyasu Iso, PhD; for the Japan Environment and Children’s Study Group
Abstract Key Points

Question Are self-reported maternal
IMPORTANCE Women with a high level of autistic traits in the general population may experience
autistic traits measured during the
larger health disparities during pregnancy, particularly women diagnosed with autism spectrum
second or third trimester in the general
disorder (ASD), which in turn may be associated with increased risk of adverse birth outcomes.
population associated with adverse
birth outcomes?
OBJECTIVE To investigate the association between maternal autistic traits and the risk of adverse
birth outcomes in the general population. Findings In this cohort study of 87 687
women, a higher level of maternal
DESIGN, SETTING, AND PARTICIPANTS This cohort study included mothers of singletons from a autistic traits was associated with
nationwide, multicenter prospective birth cohort, the Japan Environmental Children’s Study. increased risk of preterm birth,
Expecting mothers were recruited between January 2011 and March 2014. Data were analyzed particularly very preterm birth and small
between June 2021 and November 2023. for gestational age. These risks were
most pronounced for women within the
EXPOSURES Autistic traits were self-reported during the second and third trimesters using the clinical range, although most of them
short form of the Autism-Spectrum Quotient Japanese version (AQ-J10) (score range, 0-10; clinical lacked a formal diagnosis of autism
range, ⱖ7). spectrum disorder.
Meaning Women with a high level of

MAIN OUTCOMES AND MEASURES Data on preterm birth (<37 weeks’ gestation) and neonates
autistic traits in the general population,
born small for gestational age (SGA) were transcribed from medical records. Additional analysis of
particularly those with autistic traits in
gestational age groups (very preterm birth, <32 weeks’ gestation; moderate-to-late preterm birth,
the clinical range, may have an increased
32-36 weeks’ gestation) was also performed.
risk of adverse birth outcomes,
highlighting the need for tailored and
RESULTS Among 87 687 women (mean [SD] age, 31.2 [5.0] years) included in the study, 2350
timely antenatal care support for
(2.7%) had AQ-J10 scores within the clinical range yet only 18 (0.02%) were diagnosed with ASD. A
these women.
higher AQ-J10 score was associated with an increased risk of all birth outcomes, including preterm
births (relative risk [RR] per 1-SD increase, 1.06; 95% CI, 1.03-1.09), moderate-to-late preterm births
(RR per 1-SD increase, 1.05; 95% CI, 1.01-1.08), very preterm births (RR per 1-SD increase, 1.16; 95% + Supplemental content
CI, 1.06-1.26), and child born SGA (RR per 1-SD increase, 1.04; 95% CI, 1.01-1.06) after adjusting for Author affiliations and article information are
maternal and pregnancy-related factors. The risks of all outcomes increased with higher AQ-J10 listed at the end of this article.
scores; compared with women below the clinical range, women within the clinical range had greater
risk of preterm births (RR, 1.16; 95% CI, 1.07-1.26), moderate-to-late preterm births (RR, 1.12; 95%
CI, 1.03-1.22), very preterm births (RR, 1.49; 95% CI, 1.18-1.89), and a child born SGA (RR, 1.11; 95% CI,
1.04-1.19).
CONCLUSIONS AND RELEVANCE In this cohort study, higher level of maternal autistic traits was
associated with increased risk of adverse birth outcomes, particularly very preterm birth.
Acknowledging the risks and providing tailored and timely antenatal care support to women with a
high level of autistic traits in the general population, particularly women with autistic traits within the
clinical range, regardless of formal diagnosis, is warranted.
JAMA Network Open. 2024;7(1):e2352809. doi:10.1001/jamanetworkopen.2023.52809
Open Access. This is an open access article distributed under the terms of the CC-BY License.
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JAMA Network Open | Pediatrics Maternal Autistic Traits and Adverse Birth Outcomes
Introduction
Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition characterized by
differences in social communication and restricted-repetitive behavior.1 Recently, several studies
have indicated that women with ASD may experience significant health disparities during pregnancy,
including inadequate access to health care,2 multiple chronic health conditions,3,4 higher levels of
antenatal psychological distress,5,6 and greater risk of pregnancy complication,7 all of which are
associated with increased risk of adverse birth outcomes, such as preterm birth and child born small
for gestational age (SGA).8-10 Despite women with ASD being susceptible to experiencing adverse
birth outcomes, only a few studies have examined birth outcomes in this population. One study
based on Swedish medical records reported an increased risk of preterm birth among women
diagnosed with ASD.7 Two other studies reported an increased risk of preterm birth among women
with intellectual and developmental disabilities including ASD,11,12 but the associations specific to
ASD were not available, as various conditions were treated together. Furthermore, previous studies
have focused only on women diagnosed with ASD.7,11,12 However, ASD is increasingly viewed as a
spectrum in which autistic traits are continuously distributed across the general population, and
individuals diagnosed with ASD score at the end of the distribution.13,14 It has been reported that
individuals who have a high level of subclinical autistic traits may share similar genetic features14,15
and social and psychological difficulties with those diagnosed with ASD.16,17 Given that women with
an elevated level of autistic traits are less likely to receive a formal diagnosis than men,18,19 which may
create further challenges in gaining support,20 there is a need to investigate the association between
maternal autistic traits in the general population and adverse birth outcomes. This approach will help
identify women who need additional support during pregnancy regardless of having received a
formal diagnosis of ASD, with the potential to improve maternal and child outcomes.21-23
Using data from a nationwide cohort in Japan, this study aimed to examine the association
between maternal autistic traits measured during the second and third trimesters and birth
outcomes (preterm birth and child born SGA). Based on the results of previous studies,7,11,12 we
hypothesized that maternal autistic traits measured using the short form of the Autism-Spectrum
Quotient Japanese version (AQ-J10)24 would be associated with an increased risk of adverse birth
outcomes and that this increase would be particularly pronounced for women with scores in the
clinical range.
Methods
Study Population
This cohort study included participants from the Japan Environmental Children’s Study, a
nationwide, multicenter, prospective birth cohort study funded by the Ministry of the Environment
of Japan that recorded the health and development of children born by 103 060 pregnancies among
women recruited between January 2011 and March 2014.25 Details of the study design are described
elsewhere.26,27 Of the women with singleton live births, those with children with implausible birth
weight for gestational age (±5 SDs) or gestational age older than 42 weeks and those with children
with definitive chromosomal abnormalities reported by the physician at birth were excluded from
the analysis. Cases with missing data on exposure, outcome, or covariates were also excluded
(eFigure 1 in Supplement 1). This study was conducted according to guidelines in the Declaration of
Helsinki.28 The Japan Environmental Children’s Study protocol was reviewed and approved by the
Japan Ministry of the Environment’s Institutional Review Board on Epidemiological Studies, and the
ethics committees of all participating institutions approved all procedures involving participants.
Written informed consent was obtained from all the participants. This study followed the
Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting
guideline in reporting of the results.

Maternal Autistic Traits

Maternal autistic traits were measured during the second or third trimesters using the AQ-J10.24 The
AQ-J10 is a Japanese version of the internationally used self-reported questionnaire that quantifies
autistic traits, mainly autistic social traits, in the general population.24,29,30 The questionnaire
consists of 10 items adapted from the full 50-item AQ,31,32 which is a sensitive measure of autistic
traits in the general population.33,34 Each item is answered on a 4-point Likert scale of “definitely
agree,” “slightly agree,” “slightly disagree,” and “definitely disagree.” The responses were scored either
0 or 1 (responses “strongly agree” and “agree” would be given a score of 1 for responses that indicate
autistic traits) to calculate the total score (range, 0-10). Higher total scores indicated a higher level of
autistic traits. In the Japanese population, a score of 7 was recommended as the clinical threshold,
indicating a potential need for full ASD assessment.24 The sensitivity and specificity of the AQ-J10
were reported as 0.76 and 0.90, respectively.24 The Cronbach α in our study was 0.52, indicating
acceptable internal consistency.
Birth Outcomes
Birth outcomes included preterm birth (<37 weeks’ gestation) and child born SGA (defined as birth
weight less than the tenth percentile of the sex and birth-order specific means for gestational age in
Japan).35 Preterm birth was further classified into moderate-to-late preterm birth (32-36 weeks’
gestation) and very preterm birth (<32 weeks’ gestation). All birth information was transcribed from
the medical records at childbirth.
Covariates
The following variables reported to be associated with the exposure and outcomes were included as
covariates in the present study3,4,8-10,36: maternal age at childbirth, maternal highest level of
education (categorized as a qualification of high school or below, vocational school or junior college,
and university and higher), primiparous or not, smoking during pregnancy (yes vs no), prepregnancy
maternal body mass index, preexisting physical health condition (eMethods in Supplement 1), and
child sex (female or male). Furthermore, we included pregnancy complications (ie, absence or
presence of gestational hypertension and gestational diabetes) for which the risk has been reported
to be high among women with developmental and intellectual disabilities.37 Pregnancy
complications, maternal age, and child sex were transcribed from medical records at childbirth,
whereas all other information was obtained from maternal self-reports during pregnancy.
Statistical Analyses
Statistical analyses were performed between June 2021 and November 2023. Descriptive analysis of
the variables was performed. Sample bias analyses were used to compare whether the individuals
excluded from the analysis differed from those included in this study. In the main analyses, we
applied generalized linear models with Poisson distribution and a log-link function with robust SEs to
obtain relative risks (RRs) for the association between maternal autistic traits and birth outcomes.38
Model 1 was a crude model, model 2 was adjusted for covariates (maternal age at childbirth, maternal
educational level, primiparous or not, smoking during pregnancy, prepregnancy body mass index,
preexisting physical health condition, and child sex), and model 3 was further adjusted for pregnancy
complications (gestational hypertension and gestational diabetes). The effect estimates are
presented per 1-SD increase in maternal autistic traits to aid interpretation. To illustrate the observed
association found in model 3, we performed postestimation analysis and obtained the estimated
marginal probability of the outcomes given all other variables at their mean by each level of maternal
autistic traits using the Stata MP, version 18 (StataCorp LLC) command margins and graphically
presented it using the command marginsplot. To quantify the risk of adverse birth outcomes for
women scoring in the clinical range compared with those scoring below, we derived relative risks
comparing women scoring above vs below the clinical threshold for the AQ-J10 using estimates from
model 3. For this analysis, we first obtained mean risks of outcomes in each group using the

postestimation Stata command margins and then estimated RRs using the Stata command nlcom,
which uses the delta method for calculation.39 All analyses were repeated using gestational age
subgroups (very preterm, <32 weeks’ gestation; moderate-to-late preterm, 32-36 weeks’ gestation)
as outcomes to examine whether the association differed according to gestational age groups.
We conducted 2 sensitivity analyses. First, we adjusted for antenatal psychological distress
measured using the Japanese version of the Kessler Psychological Distress Scale40 administered
during the first trimester to confirm that the association between maternal autistic traits and the
outcomes were not confounded by preceding antenatal psychological distress. Second, to confirm
that the association observed was not influenced by preexisting psychiatric conditions or
psychotropic medication receipt during pregnancy,41,42 we repeated the analyses excluding women
reporting a history of psychiatric conditions or women who used psychotropic medication during
pregnancy (eMethods in Supplement 1).
The proportion of missing data was considerably small in the present study (5.0%); therefore,
the results of a complete case analysis are reported. All analyses were performed using Stata MP,
version 18.0. Tests of statistical significance were based on 2-tailed P values or 95% CIs, and statistical
significance was set at P < .05.
Results
Of 92 944 women with singleton live births in the Japan Environmental Children’s Study, 13 were
excluded because of their children having implausible birth weight for gestational age, 508 because
gestational age was older than 42 weeks, and 144 because of chromosomal abnormalities. A total
Table 1. Descriptive Characteristics of Study Participants

Participants
Characteristic (N = 87 687)a
Maternal age at delivery, mean (SD), y 31.2 (5.0)
Maternal autistic traits, mean (SD), No.b 2.8 (1.7)
Autistic traits in the clinical rangeb 2350 (2.7)
Highest maternal educational level
High school graduate or below 31 529 (36.0)
Vocational school or junior college 36 957 (42.1)
College graduate and above 19 201 (21.9)
Primiparous 38 370 (43.8)
Prepregnancy body mass index, mean (SD)c 21.2 (3.3)
Preexisting physical health condition 18 362 (20.9)
Ever diagnosed with ASD 18 (0.02)
Smoked during pregnancy 4645 (5.3)
Gestational hypertension 2765 (3.2)
Gestational diabetes 2364 (2.7)
Child sex
Female 42 710 (48.7)
Male 44 977 (51.3)
Antenatal psychological distress score, mean (SD)d 3.7 (3.8)
Abbreviation: ASD, autism spectrum disorder.

a
Data are presented as number (percentage) of participants unless otherwise
indicated.
b
Measured using the short form of the Autism-Spectrum Quotient Japanese
version administered during the second and third trimesters. The score ranges
from 0 to 10, and the clinical range was a score at or above the clinical cutoff
of 7.
c
Calculated as weight in kilograms divided by height in meters squared.
d
Measured using the Japanese version of the Kessler Psychological Distress
Scale40 administered during the first trimester, available for 86 414 women.

of 4592 women were excluded because of missing data on exposure, outcome, or covariates, leaving
87 687 women for the analysis. Participants’ descriptive characteristics are presented in Table 1. Of
the 87 687 participating women (mean [SD] age, 31.2 [5.0] years), 38 370 (43.8%) were primiparous,
18 362 (20.9%) had preexisting physical health conditions, and 4645 (5.3%) had smoked during
pregnancy. In the sample, the mean (SD) AQ-J10 score was 2.8 (1.7) and 2350 (2.7%) women scored
above the clinical threshold; however, only 18 (0.02) were diagnosed with ASD. The distribution of
maternal autistic traits is shown in eFigure 2 in Supplement 1. Women scoring within the AQ-J10
clinical range, compared with those scoring below the range, were more likely to be younger and
primiparous and to have attained a lower educational level, smoked during pregnancy, and had
higher antenatal psychological distress scores (eTable 1 in Supplement 1). The sample bias analyses
comparing women included in the analysis with those excluded due to missing responses revealed
that although there were no differences in mean AQ-J10 scores, women scoring in the clinical range
were more likely to be excluded (eTable 2 in Supplement 1). Women who had lower educational
levels, were primiparous, smoked during pregnancy, and had higher antenatal psychological distress
scores were also more likely to be excluded from the study. In addition, more women with a preterm
birth were excluded from this study; however, there were no significant group differences in the
proportion with a child born SGA.
Main Analyses
The main analysis showed that the risks of preterm birth, moderate-to-late preterm birth, very
preterm birth, and child born SGA increased with a higher level of maternal autistic traits (Table 2).
In our crude model, a 1-SD increase in AQ-J10 score was associated with an increased risk of preterm
birth (RR per 1-SD increase, 1.06; 95% CI, 1.03-1.09), moderate-to-late preterm birth (RR per 1-SD
increase, 1.05; 95% CI, 1.01-1.08), very preterm birth (RR per 1-SD increase, 1.16; 95% CI, 1.07-1.26),
and a child born SGA (RR per 1-SD increase, 1.04; 95% CI, 1.02-1.07). These risks showed little change
after adjusting for covariates in model 2 and further adjusting for pregnancy complications in model
3; the highest RR was observed for very preterm birth (RR, 1.16; 95% CI, 1.06-1.26). To further
illustrate the association between maternal autistic traits and outcomes, the estimated marginal
probability of outcomes by the level of maternal autistic traits is shown in Figure. For all outcomes, a
pattern of increasing probability was observed with a higher level of maternal autistic traits.
Furthermore, postestimation analysis indicated that compared with women scoring below the
AQ-J10 threshold, women scoring within the clinical range had a higher risk of preterm birth (RR, 1.16;
95% CI, 1.07-1.26), moderate-to-late preterm birth (RR, 1.12; 95% CI, 1.03-1.22), very preterm birth
(RR, 1.49; 95% CI, 1.18-1.89), and a child born SGA (RR, 1.11; 95% CI, 1.04-1.19) (Table 3).
Table 2. Association Between Maternal Autistic Traits and Risk of Adverse Birth Outcomes
RR (95% CI), per 1-SD increase in AQ-J10 score

Cases, No. (%)
Outcome (gestational age) (N = 87 687) Model 1 Model 2a Model 3b
Preterm birth (<37 wk) 3941 (4.5) 1.06 (1.03-1.09) 1.06 (1.03-1.09) 1.06 (1.03-1.09)
Moderate-to-late preterm 3511 (4.0) 1.05 (1.01-1.08) 1.05 (1.01-1.08) 1.05 (1.01-1.08)
birth (32-36 wk)
Very preterm birth (<32 wk) 430 (0.5) 1.16 (1.07-1.26) 1.16 (1.07-1.27) 1.16 (1.06-1.26)
Child born small for 6722 (7.7) 1.04 (1.02-1.07) 1.04 (1.01-1.06) 1.04 (1.01-1.06)
gestational agec
Abbreviations: AQ-J10, short form of the Autism-Spectrum Quotient Japanese version; RR, relative risk.
a
Adjusted for maternal age at birth, maternal educational level, primiparous status, prepregnancy maternal body mass
index, smoking during pregnancy, preexisting physical health condition, and child sex.
b
Adjusted for the covariates in model 2 and the presence or absence of gestational hypertension and gestational diabetes
derived from medical records at birth.
c
Defined as birth weight below the tenth percentile of sex- and birth order–specific means for gestational age in Japan.

Sensitivity Analysis
In our sensitivity analysis further adjusting for antenatal psychological distress preceding the
measurement of maternal autistic traits, results were not altered (eTable 3 in Supplement 1). Analysis
excluding women with a history of psychiatric conditions and those who took psychotropic
medication during pregnancy yielded similar results (eTable 3 in Supplement 1).
Discussion
In this nationwide prospective birth cohort study, we found that a higher level of maternal autistic
traits in the general population was associated with an increased risk of preterm, moderate-to-late
preterm, and very preterm births and a child born SGA, Risk was most pronounced for very preterm
birth, for which a 1-SD increase in maternal autistic traits was associated with a 1.16-fold increased
risk after adjusting for covariates and pregnancy complications. The risks of all birth outcomes were
higher with a higher level of maternal autistic traits; for example, compared with women below the
clinical range, women within the clinical range had greater risk of preterm births, moderate-to-late
preterm births, very preterm births, and a child born SGA.
Comparison With Previous Studies

To our knowledge, this is the first study to examine the association between maternal autistic traits
and adverse birth outcomes in the general population. A previous study on pregnancy outcomes of
Figure. Estimated Marginal Probability of Adverse Birth Outcomes by Level of Maternal Autistic Traits
10
Small for gestational age

Estimated marginal probability, %
The estimated marginal probability of adverse birth

6 outcomes for each level of maternal autistic traits
Preterm measured using the short form of the Autism-
Moderate-to-late preterm Spectrum Quotient Japanese version (AQ-J10) were
4
derived from a model adjusting for maternal age at
birth, maternal educational level, primiparous status,
2 prepregnancy maternal body mass index, smoking
during pregnancy, preexisting physical health
Very preterm
condition, child sex, gestational hypertension, and
0
0 1 2 3 4 5 6 7 8 9 10 gestational diabetes (model 3). Error bars indicate
AQ-J10 score 95% CIs.
Table 3. Estimated Relative Risks of Adverse Birth Outcomes Comparing Mothers Scoring Above vs Below
the Clinical Threshold for Autistic Traits
Cases, No. (%)a

Below AQ-J10 Within AQ-J10
threshold clinical range
Outcome (gestational age) (n = 85 337) (n = 2350) RR (95% CI)b
Preterm birth (<37 wks) 3824 (4.5) 117 (5.0) 1.16 (1.07-1.26)
Moderate to late preterm (32-36 wks) 3410 (4.0) 101 (4.3) 1.12 (1.03-1.22)
Very preterm (<32 wks) 414 (0.5) 16 (0.7) 1.49 (1.18-1.89)
Child born small for gestational agec 6527 (7.7) 195 (8.3) 1.11 (1.04-1.19)
Abbreviations: AQ-J10, short form of the Autism-Spectrum Quotient Japanese version; RR, relative risk.
a
The AQ-J10 score ranges from 0 to 10, and the clinical range was a score at or above the clinical cutoff of 7.
b
Relative risks and 95% CIs were obtained based on estimations from model 3 using the postestimation Stata command
margins. The model was adjusted for maternal age at birth, maternal educational level, primiparous status, prepregnancy
maternal body mass index, smoking during pregnancy, preexisting physical health condition, child sex, gestational
hypertension, and gestational diabetes.
c
Defined as birth weight below the tenth percentile of sex and birth-order specific means for gestational age in Japan.

women diagnosed with ASD found a 1.3-fold greater risk of preterm birth compared with those
without a diagnosis using a Swedish medical record.7 The study also found a 1.23-fold greater risk of
a child born SGA in autistic women not receiving medication.7 These results generally coincide with
the results of our study. However, our study also showed that the risk of preterm births and a child
born SGA was not limited to those diagnosed with ASD; the risks increased with a higher level of
maternal autistic traits in the general population, with women scoring within the clinical range having
the highest risks. Notably, the present study found that the increased risk of preterm birth was largely
due to the increased risk of very preterm birth, which was not observed in the previous study.7 One
explanation for this difference could be that women in the previous study had a formal ASD
diagnosis, whereas only 18 women (0.02%) in the present study had an ASD diagnosis. Receiving a
formal diagnosis has been reported to be associated with increased access to appropriate support
and health care,43,44 which could have protected women against very preterm births in the previous
study.7 The present study’s results show that women with a high level of autistic traits, particularly
those within the clinical range and without a formal diagnosis, may have a high risk of adverse birth
outcomes and require more attention and support during pregnancy.
Several explanations may account for the observed findings. First, previous studies have shown
that women with developmental and intellectual disabilities, including ASD, were more likely to
experience late entry to prenatal care and receive an inadequate number of hospital visits, which may
be associated with increased risk of adverse birth outcomes.2 Studies on perinatal experiences of
autistic mothers reported multiple barriers to receiving adequate perinatal care, such as
communication barriers with health care practitioners, lack of tailored resources, and
stigmatization.45,46 Women with a high level of autistic traits in the general population may
experience health care disparities similar to those experienced by women diagnosed with ASD.
Second, women with a higher level of autistic traits may experience more antenatal psychological
distress, which if left untreated, is a potential risk factor for adverse birth outcomes.47,48 Compared
with women with a lower level of autistic traits, women with a higher level of autistic traits had higher
prevalence of factors associated with psychological distress, such as increased stressful life events,49
socioeconomic disadvantage,50 less help-seeking for mental health difficulties,51 and lack of social
support during pregnancy.36 Therefore, women with a higher level of autistic traits may be more
likely to experience psychological distress during pregnancy but may not ask for help, leading to an
increased risk of adverse birth outcomes. Finally, a previous study reported that women with a higher
level of autistic traits had inadequate dietary patterns, such as consuming fewer vegetables, fruits,
or fish and less intake of certain nutrients during pregnancy,52 which may lead to fetal growth
restriction and be associated with increased risk of preterm birth.53 Testing these hypotheses was
beyond the scope of this study; however, examining these hypotheses in the future will offer
additional evidence for preventive intervention.
Strengths and Limitations

This study had many strengths, including the large sample size drawn from a nationwide cohort, the
prospective longitudinal design of the study, and the use of medical records to derive data for birth
outcomes, thus reducing the possibility of recall bias. However, this study had several limitations.
First, the observational study design prevented the establishment of causal relationships. Second,
although the proportion of women excluded due to missing responses was relatively small (5.0%) for
a prospective cohort, this could have biased the observed association. Our sample bias analysis
revealed that women scoring in the clinical range of the AQ-J10 and those with preterm births were
more likely to be excluded from this study due to missing data, which could have underestimated the
observed association. Third, although we measured maternal autistic traits using a validated
questionnaire in the Japanese general population,24 reliance on self-report may be prone to response
bias such as social desirability bias.54 We could not replicate the results by limiting the sample to
women diagnosed with ASD because only 18 women reported being diagnosed with ASD in the
present study. We acknowledge that autistic traits in the general population sometimes reflect social

difficulties unrelated to ASD,55 such as those related to psychiatric conditions. However, the
association remained after adjusting for antenatal psychological distress preceding the measurement
of autistic traits or excluding women with a history of psychiatric conditions and those who reported
taking psychotropic medication during pregnancy in our sensitivity analysis. In addition, the level of
autistic traits in the general population is reported to be stable across time and is thus unlikely to be
affected by pregnancy.56 Finally, there may have been unmeasured confounders, including genetic
factors, underlying the observed association between maternal autistic traits and adverse birth
outcomes. However, a previous study showed that maternal polygenetic risk scores for ASD were not
associated with adverse birth outcomes, including preterm birth.57
Conclusions
In this cohort study, a higher level of maternal autistic traits in the general population was associated
with an increased risk of adverse birth outcomes, particularly very preterm birth. Health care
practitioners should acknowledge the significant perinatal health disparity experienced by women
with a high level of autistic traits, particularly those with autistic traits in the clinical range.
Comprehensive antenatal care including the assessment of antenatal psychological distress and
offering timely and tailored support that meets the needs of women should be provided inclusively
regardless of whether a formal diagnosis of ASD is received. If provided, these approaches may
improve maternal well-being with the potential to reduce the risk of adverse birth outcomes and
have a downstream effect on child health and development.
ARTICLE INFORMATION
Accepted for Publication: December 3, 2023.
Published: January 23, 2024. doi:10.1001/jamanetworkopen.2023.52809
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2024 Hosozawa
M et al. JAMA Network Open.
Corresponding Author: Mariko Hosozawa, MD, PhD, Institute for Global Health Policy Research, Bureau of
International Health Cooperation, National Center for Global Health and Medicine,1-21-1 Toyama, Shinjuku-ku,
Tokyo, 162-8655, Japan (mhosozawa@it.ncgm.go.jp).
Author Affiliations: Institute for Global Health Policy Research, Bureau of International Health Cooperation, Na-
tional Center for Global Health and Medicine, Tokyo, Japan (Hosozawa, Iso); Department of Epidemiology and Public
Health, University College London, London, United Kingdom (Cable); Environmental Medicine and Population
Sciences, Department of Social Medicine, Osaka University Graduate School of Medicine, Osaka, Japan (Ikehara,
Aochi, Sobue); Osaka Maternal and Child Health Information Center, Osaka Women’s and Children’s Hospital,
Osaka, Japan (Tanigawa, Baba); Faculty of Societal Safety Sciences, Kansai University, Osaka, Japan (Hirokawa);
Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan (Kimura);
Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Osaka, Japan (Iso).
Author Contributions: Dr Hosozawa had full access to all of the data in the study and takes responsibility for the
integrity of the data and the accuracy of the data analysis.
Concept and design: Hosozawa, Cable, Sobue, Iso.
Acquisition, analysis, or interpretation of data: Hosozawa, Cable, Ikehara, Aochi, Tanigawa, Baba, Hirokawa,
Kimura, Iso.
Drafting of the manuscript: Hosozawa, Cable.
Critical review of the manuscript for important intellectual content: Cable, Ikehara, Aochi, Tanigawa, Baba,
Hirokawa, Kimura, Sobue, Iso.
Statistical analysis: Hosozawa, Ikehara, Aochi.
Obtained funding: Iso.
Administrative, technical, or material support: Ikehara, Baba.
Supervision: Cable, Kimura, Sobue, Iso.

Conflict of Interest Disclosures: Dr Hosozawa reported receiving a grant from the Japan Society for the
Promotion of Science outside the submitted work. Dr Kimura reported receiving grants from Cyugai
Pharmaceutical Co, Ltd; Asuka Pharmaceutical Co, Ltd; Taihou Pharmaceutical Co, Ltd; Takeda Pharmaceutical Co,
Ltd; Nihon Shinyaku Pharmaceutical Co, Ltd; and Fuji Seiyaku Pharmaceutical Co, Ltd outside the submitted work.
Dr Iso reported receiving grants from the Ministry of the Environment, Japan during the conduct of the study and
from the Japan Society for the Promotion of Science and the Ministry of Health and Welfare, Japan outside the
submitted work. No other disclosures were reported.
Funding/Support: This study was funded by the Ministry of the Environment, Japan.
Role of the Funder/Sponsor: The Ministry of the Environment, Japan had no role in the design and conduct of the
study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the
manuscript; and decision to submit the manuscript for publication.
Group Information: The Japan Environment and Children’s Study Group members appear in Supplement 2.
Data Sharing Statement: See Supplement 3.
Additional Contributions: We thank all study participants and Japan Environment and Children’s Study staff
members for their cooperation.
REFERENCES
1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. American
Psychiatric Association Press; 2013.
2. Nishat F, Lunsky Y, Tarasoff LA, Brown HK. Prenatal care adequacy among women with disabilities:
a population-based study. Am J Prev Med. 2022;62(1):39-49. doi:10.1016/j.amepre.2021.05.037
3. Tint A, Brown HK, Chen S, et al. Health characteristics of reproductive-aged autistic women in Ontario:
a population-based, cross-sectional study. Autism. 2021:1362361320982819;25(4):1114-1124. .
4. Kassee C, Babinski S, Tint A, et al. Physical health of autistic girls and women: a scoping review. Mol Autism.
2020;11(1):84. doi:10.1186/s13229-020-00380-z
5. Pohl AL, Crockford SK, Blakemore M, Allison C, Baron-Cohen S. A comparative study of autistic and non-autistic
women’s experience of motherhood. Mol Autism. 2020;11(1):3. doi:10.1186/s13229-019-0304-2
6. Hampton S, Allison C, Aydin E, Baron-Cohen S, Holt R. Autistic mothers’ perinatal well-being and parenting
styles. Autism. 2022;26(7):1805-1820. doi:10.1177/13623613211065544
7. Sundelin HE, Stephansson O, Hultman CM, Ludvigsson JF. Pregnancy outcomes in women with autism:
a nationwide population-based cohort study. Clin Epidemiol. 2018;10:1817-1826. doi:10.2147/CLEP.S176910
8. McCowan L, Horgan RP. Risk factors for small for gestational age infants. Best Pract Res Clin Obstet Gynaecol.
2009;23(6):779-793. doi:10.1016/j.bpobgyn.2009.06.003
9. Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet. 2008;371
(9606):75-84. doi:10.1016/S0140-6736(08)60074-4
10. Vogel JP, Chawanpaiboon S, Moller AB, Watananirun K, Bonet M, Lumbiganon P. The global epidemiology of
preterm birth. Best Pract Res Clin Obstet Gynaecol. 2018;52:3-12. doi:10.1016/j.bpobgyn.2018.04.003
11. Brown HK, Cobigo V, Lunsky Y, Vigod SN. Maternal and offspring outcomes in women with intellectual and
developmental disabilities: a population-based cohort study. BJOG. 2017;124(5):757-765. doi:10.1111/1471-
0528.14120
12. Akobirshoev I, Parish SL, Mitra M, Rosenthal E. Birth outcomes among US women with intellectual and
developmental disabilities. Disabil Health J. 2017;10(3):406-412. doi:10.1016/j.dhjo.2017.02.010
13. Constantino JN, Todd RD. Autistic traits in the general population: a twin study. Arch Gen Psychiatry. 2003;60
(5):524-530. doi:10.1001/archpsyc.60.5.524
14. Robinson EB, Koenen KC, McCormick MC, et al. Evidence that autistic traits show the same etiology in the
general population and at the quantitative extremes (5%, 2.5%, and 1%). Arch Gen Psychiatry. 2011;68(11):
1113-1121. doi:10.1001/archgenpsychiatry.2011.119
15. Bralten J, van Hulzen KJ, Martens MB, et al. Autism spectrum disorders and autistic traits share genetics and
biology. Mol Psychiatry. 2018;23(5):1205-1212. doi:10.1038/mp.2017.98
16. Rai D, Culpin I, Heuvelman H, et al. Association of autistic traits with depression from childhood to age 18 years.
JAMA Psychiatry. 2018;75(8):835-843. doi:10.1001/jamapsychiatry.2018.1323
17. Kanne SM, Christ SE, Reiersen AM. Psychiatric symptoms and psychosocial difficulties in young adults with
autistic traits. J Autism Dev Disord. 2009;39(6):827-833. doi:10.1007/s10803-008-0688-x

18. Lai MC, Szatmari P. Sex and gender impacts on the behavioural presentation and recognition of autism. Curr
Opin Psychiatry. 2020;33(2):117-123. doi:10.1097/YCO.0000000000000575
19. Lord C, Charman T, Havdahl A, et al. The Lancet Commission on the future of care and clinical research in
autism. Lancet. 2022;399(10321):271-334. doi:10.1016/S0140-6736(21)01541-5
20. Belcher HL, Morein-Zamir S, Stagg SD, Ford RM. Shining a light on a hidden population: Social functioning and
mental health in women reporting autistic traits but lacking diagnosis. J Autism Dev Disord. 2023;53(8):3118-3132.
doi:10.1007/s10803-022-05583-2
21. Van den Bergh BRH, van den Heuvel MI, Lahti M, et al. Prenatal developmental origins of behavior and mental
health: the influence of maternal stress in pregnancy. Neurosci Biobehav Rev. 2020;117:26-64. doi:10.1016/j.
neubiorev.2017.07.003
22. Thomason ME, Hect JL, Waller R, Curtin P. Interactive relations between maternal prenatal stress, fetal brain
connectivity, and gestational age at delivery. Neuropsychopharmacology. 2021;46(10):1839-1847. doi:10.1038/
s41386-021-01066-7
23. Fontein-Kuipers YJ, Nieuwenhuijze MJ, Ausems M, Budé L, de Vries R. Antenatal interventions to reduce
maternal distress: a systematic review and meta-analysis of randomised trials. BJOG. 2014;121(4):389-397. doi:10.
1111/1471-0528.12500
24. Kurita H, Koyama T, Osada H. Autism-Spectrum Quotient–Japanese version and its short forms for screening
normally intelligent persons with pervasive developmental disorders. Psychiatry Clin Neurosci. 2005;59(4):
490-496. doi:10.1111/j.1440-1819.2005.01403.x
25. Michikawa T, Nitta H, Nakayama SF, et al; Japan Environment and Children’s Study Group. baseline profile of
participants in the Japan Environment and Children’s Study (JECS). J Epidemiol. 2018;28(2):99-104. doi:10.2188/
jea.JE20170018
26. Kawamoto T, Nitta H, Murata K, et al; Working Group of the Epidemiological Research for Children’s
Environmental Health. Rationale and study design of the Japan Environment and Children’s Study (JECS). BMC
Public Health. 2014;14:25. doi:10.1186/1471-2458-14-25
27. Michikawa T, Nitta H, Nakayama SF, et al; Japan Environment and Children’s Study Group. The Japan
Environment and Children’s Study (JECS): a preliminary report on selected characteristics of approximately
10 000 pregnant women recruited during the first year of the study. J Epidemiol. 2015;25(6):452-458. doi:10.
2188/jea.JE20140186
28. World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical
research involving human subjects. JAMA. 2013;310(20):2191-2194. doi:10.1001/jama.2013.281053
29. Lundin A, Kosidou K, Dalman C. Measuring autism traits in the adult general population with the brief Autism-
Spectrum Quotient, AQ-10: findings from the Stockholm public health cohort. J Autism Dev Disord. 2019;49(2):
773-780. doi:10.1007/s10803-018-3749-9
30. Allison C, Auyeung B, Baron-Cohen S. Toward brief “red flags” for autism screening: the Short Autism
Spectrum Quotient and the Short Quantitative Checklist for Autism in toddlers in 1,000 cases and 3,000 controls
[corrected]. J Am Acad Child Adolesc Psychiatry. 2012;51(2):202-212.e7. doi:10.1016/j.jaac.2011.11.003
31. Wakabayashi A, Tojo Y, Baron-Cohen S, Wheelwright S. The Autism-Spectrum Quotient (AQ) Japanese version:
evidence from high-functioning clinical group and normal adults. Article in Japanese. Shinrigaku Kenkyu. 2004;75
(1):78-84. doi:10.4992/jjpsy.75.78
32. Baron-Cohen S, Wheelwright S, Skinner R, Martin J, Clubley E. The autism-spectrum quotient (AQ): evidence
from Asperger syndrome/high-functioning autism, males and females, scientists and mathematicians. J Autism
Dev Disord. 2001;31(1):5-17. doi:10.1023/A:1005653411471
33. Ruzich E, Allison C, Smith P, et al. Measuring autistic traits in the general population: a systematic review of the
Autism-Spectrum Quotient (AQ) in a nonclinical population sample of 6,900 typical adult males and females. Mol
Autism. 2015;6:2. doi:10.1186/2040-2392-6-2
34. Abu-Akel A, Allison C, Baron-Cohen S, Heinke D. The distribution of autistic traits across the autism spectrum:
evidence for discontinuous dimensional subpopulations underlying the autism continuum. Mol Autism.
2019;10:24. doi:10.1186/s13229-019-0275-3
35. Itabashi K, Miura F, Uehara R, Nakamura Y. New Japanese neonatal anthropometric charts for gestational age
at birth. Pediatr Int. 2014;56(5):702-708. doi:10.1111/ped.12331
36. Hosozawa M, Cable N, Ikeda A, et al. Risk of postpartum depression and very early child mistreatment among
mothers reporting higher autistic traits: evidence from the Japan Environment and Children’s Study. J Affect
Disord. 2021;280(A):11-16.

37. Tarasoff LA, Ravindran S, Malik H, Salaeva D, Brown HK. Maternal disability and risk for pregnancy, delivery,
and postpartum complications: a systematic review and meta-analysis. Am J Obstet Gynecol. 2020;222(1):27.e1-
27.e32. doi:10.1016/j.ajog.2019.07.015
38. Zou G. A modified poisson regression approach to prospective studies with binary data. Am J Epidemiol.
2004;159(7):702-706. doi:10.1093/aje/kwh090
39. Cummings P. Estimating adjusted risk ratios for matched and unmatched data: An update. Stata J. 2011;11(2):
290-298. doi:10.1177/1536867X1101100208
40. Furukawa TA, Kawakami N, Saitoh M, et al. The performance of the Japanese version of the K6 and K10 in the
World Mental Health Survey Japan. Int J Methods Psychiatr Res. 2008;17(3):152-158. doi:10.1002/mpr.257
41. Sujan AC, Rickert ME, Öberg AS, et al. Associations of maternal antidepressant use during the first trimester of
pregnancy with preterm birth, small for gestational age, autism spectrum disorder, and attention-deficit/
hyperactivity disorder in offspring. JAMA. 2017;317(15):1553-1562. doi:10.1001/jama.2017.3413
42. Männistö T, Mendola P, Kiely M, et al. Maternal psychiatric disorders and risk of preterm birth. Ann Epidemiol.
2016;26(1):14-20. doi:10.1016/j.annepidem.2015.09.009
43. Stagg SD, Belcher H. Living with autism without knowing: receiving a diagnosis in later life. Health Psychol
Behav Med. 2019;7(1):348-361. doi:10.1080/21642850.2019.1684920
44. Zuckerman K, Lindly OJ, Chavez AE. Timeliness of autism spectrum disorder diagnosis and use of services
among U.S. elementary school-aged children. Psychiatr Serv. 2017;68(1):33-40. doi:10.1176/appi.ps.201500549
45. Hampton S, Man J, Allison C, Aydin E, Baron-Cohen S, Holt R. A qualitative exploration of autistic mothers’
experiences I: Pregnancy experiences. Autism. 2023;27(5):1271-1282. doi:10.1177/13623613221132435
46. Rogers C, Lepherd L, Ganguly R, Jacob-Rogers S. Perinatal issues for women with high functioning autism
spectrum disorder. Women Birth. 2017;30(2):e89-e95. doi:10.1016/j.wombi.2016.09.009
47. Jarde A, Morais M, Kingston D, et al. Neonatal outcomes in women with untreated antenatal depression
compared with women without depression: a systematic review and meta-analysis. JAMA Psychiatry. 2016;73(8):
826-837. doi:10.1001/jamapsychiatry.2016.0934
48. Stein A, Pearson RM, Goodman SH, et al. Effects of perinatal mental disorders on the fetus and child. Lancet.
2014;384(9956):1800-1819. doi:10.1016/S0140-6736(14)61277-0
49. Roberts AL, Koenen KC, Lyall K, Robinson EB, Weisskopf MG. Association of autistic traits in adulthood with
childhood abuse, interpersonal victimization, and posttraumatic stress. Child Abuse Negl. 2015;45:135-142. doi:10.
1016/j.chiabu.2015.04.010
50. Skylark WJ, Baron-Cohen S. Initial evidence that non-clinical autistic traits are associated with lower income.
Mol Autism. 2017;8:61. doi:10.1186/s13229-017-0179-z
51. Hosozawa M, Yamasaki S, Ando S, et al. Lower help-seeking intentions mediate subsequent depressive
symptoms among adolescents with high autistic traits: a population-based cohort study. Eur Child Adolesc
Psychiatry. 2023;32(4):621-630. doi:10.1007/s00787-021-01895-3
52. Hirokawa K, Kimura T, Ikehara S, et al; Japan Environment & Children’s Study Group. Associations between
broader autism phenotype and dietary intake: a cross-sectional study (Japan environment and children’s study).
J Autism Dev Disord. 2020;50(8):2698-2709. doi:10.1007/s10803-020-04380-z
53. Jain S, Maheshwari A, Jain SK. Maternal nutrition and fetal/infant development. Clin Perinatol. 2022;49(2):
313-330. doi:10.1016/j.clp.2022.02.005
54. Perinelli E, Gremigni P. Use of social desirability scales in clinical psychology: a systematic review. J Clin
Psychol. 2016;72(6):534-551. doi:10.1002/jclp.22284
55. Lord C, Bishop SL. Let’s be clear that “autism spectrum disorder symptoms” are not always related to autism
spectrum disorder. Am J Psychiatry. 2021;178(8):680-682. doi:10.1176/appi.ajp.2021.21060578
56. Taylor MJ, Gillberg C, Lichtenstein P, Lundström S. Etiological influences on the stability of autistic traits from
childhood to early adulthood: evidence from a twin study. Mol Autism. 2017;8:5. doi:10.1186/s13229-017-0120-5
57. Leppert B, Havdahl A, Riglin L, et al. Association of maternal neurodevelopmental risk alleles with early-life
exposures. JAMA Psychiatry. 2019;76(8):834-842. doi:10.1001/jamapsychiatry.2019.0774
SUPPLEMENT 1.
eMethods. Assessment of covariates
eTable 1. Descriptive characteristics by level of maternal autistic traits
eTable 2. Comparison of characteristics of women included the analysis with those excluded

eTable 3. Association between maternal autistic traits and adverse birth outcomes, further adjusted for antenatal
psychological distress (Model S1) and excluding women with a history of psychiatric conditions or who took anti-
psychiatric medication during pregnancy (Model S2)
eFigure 1. Sample flowchart
eFigure 2. Distribution of maternal autistic traits in the study sample
SUPPLEMENT 2.
The Japan Environment and Children’s Study Group
SUPPLEMENT 3.
Data Sharing Statement

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Original Investigation | Pediatrics

Maternal Autistic Traits and Adverse Birth Outcomes

Abstract Key Points

Meaning Women with a high level of

JAMA Network Open. 2024;7(1):e2352809. doi:10.1001/jamanetworkopen.2023.52809

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Maternal Autistic Traits

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Table 1. Descriptive Characteristics of Study Participants

Abbreviation: ASD, autism spectrum disorder.

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RR (95% CI), per 1-SD increase in AQ-J10 score

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Comparison With Previous Studies

Small for gestational age

The estimated marginal probability of adverse birth

Cases, No. (%)a

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Strengths and Limitations

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