Neuropsychiatric Disease and Treatment

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The association of maternal diabetes with

attention deficit and hyperactivity disorder in
offspring: a meta-analysis

Lifeng Zhao, Xuesong Li, Guanying Liu, Baoling Han, Jian Wang & Xia Jiang

To cite this article: Lifeng Zhao, Xuesong Li, Guanying Liu, Baoling Han, Jian Wang & Xia Jiang
(2019) The association of maternal diabetes with attention deficit and hyperactivity disorder in
offspring: a meta-analysis, Neuropsychiatric Disease and Treatment, , 675-684, DOI: 10.2147/
NDT.S189200

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Open Access Full Text Article Original Research

The association of maternal diabetes with attention

deficit and hyperactivity disorder in offspring:
a meta-analysis
This article was published in the following Dove Medical Press journal:
Neuropsychiatric Disease and Treatment

Lifeng Zhao 1 Objective: Recent controversial evidence suggests that maternal diabetes may increase the risk
Xuesong Li 2 of attention deficit and hyperactivity disorder (ADHD) in offspring. To examine this potential
Guanying Liu 1 association, a systematic literature search and meta-analysis was performed.
Baoling Han 1 Methods: OR or risk ratio (RR) from each study was obtained and combined for evaluating
Jian Wang 1 the risk. Six cohort studies and three case-control studies were included in the present study.
Results: The meta-analysis of the highly heterogeneous case-control studies did not find signifi-
Xia Jiang 1
cant association between maternal diabetes and ADHD risk (OR: 1.20, 95% CI: 0.96–1.49). The
1
Department of Endocrinology,
combining of the cohort studies demonstrated that offspring of diabetic mothers were at higher
Tianjin First Center Hospital, Tianjin,
China; 2First Center Clinical Medical risk of ADHD (RR: 1.40, 95% CI: 1.27–1.54); however, publication bias was identified. When
Institute, Tianjin Medical University, exposure was specified as gestational diabetes mellitus (GDM), GDM exposure increased the
Tianjin, China
risk of ADHD for children by 164% (95% CI: 1.25–5.56) in a Caucasian population. Neither
heterogeneity nor publication bias was detected.
Conclusion: Maternal diabetes, especially GDM, is probably a risk factor for ADHD in the
Caucasian population. More studies based on large sample size and different ethnicities are
needed to confirm this association.
Keywords: maternal diabetes, attention deficit hyperactivity disorder, meta-analysis

Introduction
Attention deficit and hyperactivity disorder (ADHD) is an early-onset neurodevel-
opmental disorder combining overactivity and impulsivity with the inability to con-
centrate, resulting in functional impairment in academic, family, and social settings.
A systematic review including 175 studies has demonstrated that ADHD affects up
to 7.2% (95% CI: 6.7–7.8) of children worldwide.1 A recent investigation in the UK
has demonstrated a marked increase in ADHD prevalence, incidence, and medica-
tion.2 Therefore, this disorder is of particular public health concern. The etiology of
ADHD is complex since it is clear that ADHD has a strong genetic component,3 while
environmental risk factors are also implicated.4 For psychiatric disorders in children,
exposure to risk factors in utero plays an important role.5 For example, a hyperglycemic
intrauterine environment may exert a negative impact on the development of fetal brain.6
Correspondence: Lifeng Zhao Diabetes before pregnancy is known as pregestational diabetes mellitus (PGDM).
Department of Endocrinology, Tianjin
First Center Hospital, No 24, Fukang
Gestational diabetes mellitus (GDM) is defined as diabetes diagnosed in the second
Road, Nankai District, Tianjin 300192, and third trimesters of pregnancy. Experiments in animal models of diabetic pregnan-
China
Tel +86 155 2277 9818
cies have demonstrated that maternal hyperglycemia usually creates an inflammatory
Email [email protected] environment by promoting oxidative stress via production of reactive oxygen species

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Zhao et al Dovepress

within the embryo and fetus.7 Intriguingly, it has been maternal diabetes and risk of ADHD in offspring, and
hypothesized that ADHD may be due to central nervous 2) effect size (usually OR or risk ratio [RR]) and its 95% CI
system inflammatory response in the fetus caused by maternal were reported, or the distribution of subjects in each compari-
inflammation and immune response.8 In addition, murine son group was given so that the effect size was able to be cal-
models have showed that maternal diabetes induces imbal- culated. Only English and Chinese literature was included. No
ance in the epigenetic mechanisms, alters transcriptional restriction on diabetes subtype and study design was imposed.
factors and signaling pathways, and thereby contributes to Review, editorial, and conference articles were excluded.
neurodevelopmental disorders.9
In line with the experimental evidence mentioned earlier, Data extraction
population studies have suggested a possible association The following items were extracted independently by two
between maternal diabetes and the risk of ADHD for children. reviewers from each study: first author, publication year,
Several observational studies in the Caucasian and Chinese study design, characteristics of the participants, diagnostic
populations have revealed that maternal diabetes was related criteria of ADHD and maternal diabetes, effect size with its
to higher risk of ADHD among children.10–13 However, some 95% CI (preferentially adjusted effect size), and adjusted
retrospective studies based on large sample size have reported confounders. If the effect size was not reported, it was
statistically insignificant results,8,14 indicating that offspring manually calculated from the original data. Any disagree-
from diabetic mothers may be vulnerable to ADHD. Because ment was resolved by further discussion. Since Caucasian
results from population investigations are currently controver- usually includes modern population of Europe and white
sial, we systematically searched the electronic databases, iden- people in the US, we roughly classified participants from
tified all the relevant studies, and performed meta-analyses Europe and the US into Caucasian population when perform-
to quantitatively synthesize all the available data. This is, to ing subgroup analyses.
our knowledge, the first meta-analysis to study the association
between maternal diabetes and risk of ADHD in offspring. Statistical analyses
The heterogeneity across studies was evaluated with
Materials and methods Q-statistic, and the significance level was defined as 0.1.16
Literature search Heterogeneity was further measured by I 2 value and clas-
This meta-analysis followed the recommended PRISMA sified into high, medium, or low when I 2 $50%, 50%.
guidelines.15 A comprehensive literature search was conducted I 2 $25%, or 25%. I 2, respectively.17 If an I 2 was smaller
on PubMed, Web of Science, Embase, PsycINFO, WanFang, than 25%, Mantel–Hansel’s method in fixed-effect model
and China National Knowledge Infrastructure (CNKI) data- was used to pool outcomes, otherwise data were pooled
base. The most recent search was conducted in November based on Dersimonian and Laird method in random-effect
2018. The detailed search syntax for PubMed was as follows: model.18 The effect size and its lower and higher CIs were
(((maternal OR pregestational OR gestational) AND (diabetes natural logarithm transformed before data combining, and
OR “diabetes mellitus” OR hyperglycemia))) AND (“ADHD” the result was natural exponential transformed and displayed.
OR “attention deficit” OR “hyperactivity syndrome” OR The publication bias was evaluated by the Egger’s linear
“attention deficit hyperactivity disorder”). The corresponding regression test statistically.16 Sensitivity analysis was per-
Chinese characters were used in CNKI database searching. formed with omitting each study and observing whether the
After the primary records were retrieved from databases, synthesized result altered significantly. All statistical analyses
duplicated studies were removed. Then, the remaining records were conducted by Stata 9.0 (StataCorp LP, College station,
were checked according to titles and abstracts. Irrelevant stud- TX, USA). All P-values were two-sided and identified as
ies were excluded during this step. After that, the full texts of significant if ,0.05, unless otherwise specified.
the rest of the studies were obtained and reviewed in detail
for eligibility according to the inclusion criteria. Finally, the Results
qualified studies were included for further analyses. Characteristics of the included studies
As illustrated in Figure 1, a total of nine studies8,10–14,19–21
Inclusion criteria involving 7,218,903 participants were included in the present
The inclusion criteria were established as follows: 1) original analysis. The majority of them8,12–14,19,20 were published in the
observational studies investigating the association between recent 2 years. For baseline information, six studies10–13,19,20

676 submit your manuscript | www.dovepress.com Neuropsychiatric Disease and Treatment 2019:15
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Dovepress Zhao et al

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Figure 1 Flow diagram of the identification of the eligible studies.

were cohort design and used RR or HR to measure the effect case-control studies were conducted among Caucasian popu-
size. The remaining three studies8,14,21 were case-control lation, the findings should be applied to this race exclusively.
studies, using OR to describe the risk. Over half of the stud- High heterogeneity was detected (I 2=74.5%) (Figure 2A).
ies were conducted in Nordic Europe,8,12–14,19 benefiting from Sensitivity analysis indicated that omission of a given
the excellent local nationwide registry system. The rest of study would not reverse the insignificant result (Figure 2B).
the studies were from China,11 Greece,20 Germany,21 and Egger’s test showed that no publication bias existed (t=1.67,
USA.10 Maternal type 1 diabetes (T1D) was investigated in P=0.194) (Table 4).
five studies,8,12–14,19 while four studies did not give the accurate
type of diabetes.10,11,20,21 Only one study recruited mothers Data synthesis of the cohort studies
with type 2 diabetes (T2D).8 Three of the studies10,11,19 did not In terms of cohort studies, 10–13,19,20 the meta-analysis
use multivariate analysis in order to consider the potential bias demon­strated that maternal diabetes increased the risk of
induced by confounders (for details see Table 1). The qual- ADHD in offspring by 40% (RR: 1.40, 95% CI: 1.27–1.54)
ity of each study was assessed in Table 2 using Newcastle- (Figure 2C). Sensitivity analysis confirmed that the results
Ottawa Scale for nonrandomized studies. The overall quality were stable (Figure 2D). Unfortunately, publication bias
levels were evaluated using the GRADE approach in Table 3. was identified according to Egger’s test (t=6.56, P=0.003)
(Table 4), indicating that the estimated effect was probably
Data synthesis of the case-control studies overstated due to publication of positive results. Since only
The pooling of data from case-control studies8,14,21 demon- the Li et al’s11 study investigated the effect of maternal dia-
strated that maternal diabetes was not associated with ADHD betes in Chinese, the remaining studies 10,12,13,19,20 that were
in offspring (OR: 1.20, 95% CI: 0.96–1.49). Since all the conducted in Caucasian population demonstrated the risk in

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 Table 1 Basic information of the included studies

678
Study Ethnicity Study design Exposed/case Unexposed/control Diabetes diagnosis ADHD diagnosis Effect size Confounder adjustment
Zhao et al

Bytoft C A prospective Adolescents with mothers Gender, age, and SES GDM, data from Self-reported use of RR: 14.16, 95% No adjustment
et al, nationwide cohort who had T1D during matched background Danish Diabetes ADHD medication CI: 0.80–250.08
201719 from Denmark 1993–1997 (n=269) individuals (n=293) Association

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Nielsen C A Danish cohort Exposed children born in All unexposed children T1D, ICD-8 code 249 Psychiatric admission RR: 1.36, 95% Age, gender, the interaction
et al, based on nationwide Denmark from 1990 to 2007 born in Denmark and ICD-10 code E10 or outpatient care CI: 1.17–1.56 of gender with age,
201712 register systems (n=190) from 1990 to 2007 for a diagnosis of and parental history of
(n=983,490) ADHD (ICD code psychiatric admission
F90.x+ F98.8)
Daraki C A part of prospective Exposed children had All unexposed children GDM screen between Standardized child RR: 10.18; 95% Child gender, maternal age,

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et al, pregnancy cohort neurodevelopment assessment had neurodevelopment 24 and 28 weeks of scale CI: 0.22–473.43 origin, education, parity,
201720 from Greece at 4 years of age from Oct assessment at 4 years of gestation according to smoking and pre-pregnancy
2011 to Jan 2013 (n=56) age from October 2011 criteria proposed by BMI
to January 2013 (n=716) ADA (2008)
Nomura C A cohort study from Exposed children at 6 years of Unexposed children at GDM, face-to-face Semi-structured child RR: 2.20; 95% No adjustment
et al, New York age (n=21) 6 years of age (n=191) interview psychiatric interview CI: 1.00–4.82
201210
Li et al, A A hospital-based Children exposed to maternal Children unexposed to GDM, blood and oral Standardized child RR: 1.86; 95% No adjustment
201411 cohort study from diabetes and hypertension maternal diabetes and glucose tolerance test scale CI: 1.27–2.73
China (n=302) hypertension (n=668)
Ji et al, C A retrospective Exposed children born in Matched control subjects T1D, ICD-8 code ICD-9 code 314 and HR: 1.35; 95% Year of birth, gender,
201813 cohort study based Denmark from 1970 to 2012 (n=1,380,829) 250, ICD-9 code 250 ICD-10 code F90 CI: 1.18–1.55 parental history of ADHD,
on Swedish register (n=15,615) and ICD-10 code E10 education, income, small for
system gestational age, maternal
smoking, and low Apgar
score
Schmitt C A case control study Children with ADHD (n=660) Children without ADHD Self-reported Medical or OR: 1.91; 95% Age, gender, SES, maternal
and based on German (n=12,828) physician diagnosed psychological CI: 1.21–3.01 smoking, breastfeeding,
Romanos nationwide survey GDM exam reported atopic eczema, and perinatal
201221 in standardized health problems
interview
Hegvik C A cross-sectional Children with ADHD during All remaining individuals T1D, ICD-10 code ADHD medication OR: 1.00; 95% Age and maternal education
et al, study based on a 2004–2015 (n=63,721) (n=2,436,397) E10 or ICPC T89 CI: 0.84–1.20
201814 Norwegian cohort
Instanes C A population-based Children with ADHD during All remaining individuals PGDM, data from ADHD medication T1D: OR: Age, parity, maternal age,
et al, nested case-control 2004–2012 (n=47,944) (n=2,274,713) registry system 1.5; 95% CI: education, marital status,
20178 study based on 1.2–1.9; T2D: ADHD medication, birth
longitudinal OR: 1.1; 95% weight, and gestation age
Norwegian registers CI: 0.7–1.8
Abbreviations: A, Asian; ADA, American Diabetes Association; ADHD, attention deficit hyperactivity disorder; BMI, body mass index; C, Caucasian; GDM, gestational diabetes mellitus; ICD, International Classification of Diseases;

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ICPC, International Classification of Primary Care; PGDM, pregestational diabetes mellitus; RR, risk ratio; SES, socioeconomic status; T1D, type 1 diabetes; T2D, type 2 diabetes.
Dovepress Zhao et al

Table 2 Quality of the included studies

Study Selection score Comparability score Outcome score Total score Quality
Bytoft et al, 2017 19
4 2 3 9 High
Nielsen et al, 201712 3 2 3 8 High
Daraki et al, 2017 20
4 2 3 9 High
Nomura et al, 201210 4 2 3 9 High
Li et al, 2014 11
3 0 2 5 Moderate
Ji et al, 201813 3 2 3 8 High
Schmitt and Romanos, 2012 21
4 2 2 8 High
Hegvik et al, 201814 3 2 3 8 High
Instanes et al, 2017 8
4 2 2 8 High

this race (RR: 1.37, 95% CI: 1.24–1.51). Subgroup analyses should be restricted to this population. Of note, it has been
revealed that T1D increased the risk by 36% (RR: 1.36, 95% suggested that some minority groups, such as obese or older
CI: 1.23–1.50).12,13,19 No heterogeneity between studies were Caucasian women, are at a greater risk for maternal diabetes
found in either overall or subgroup analyses. than the overall Caucasian women.22 This indicates that
management of the high-risk subgroups by maternal DM
Subgroup analysis of the cohort studies intervention could be more beneficial for ADHD prevention.
investigating mothers with GDM On the other hand, cohort studies altogether indicated that
Since the participants in the cohort studies consisted of maternal diabetes was a risk factor for ADHD (RR: 1.40,
mothers with GDM and mothers with a history of diabetes 95% CI: 1.27–1.54). However, this result was not reliable
(the onset of diabetes was not specified), we further nar- considering publication bias was identified.
rowed the scope and investigated the effect of GDM on risk Since higher functions of brain develop during the second
of ADHD for children. The combining of four studies10,11,19,20 half of pregnancy, we hypothesized that GDM may exert
demonstrated that GDM heightened the risk of ADHD by adverse effects on offspring more profoundly in this period.
onefold (RR: 2.00; 95% CI: 1.42–2.81), without detecting When the participants were specified as offspring of moth-
inconsistency between studies (I 2=0%) (Figure 3A). Publi- ers with GDM in Caucasian population from cohort studies,
cation bias was also identified regarding this analysis. We data pooling suggested that they were more vulnerable to
next excluded Li et al’s study11 and ensured all the included ADHD and the risk was increased as much as by 1.64-fold
studies10,19,20 were from Caucasian population. The risk of (95% CI: 1.25–5.56). Although the sample size was relatively
ADHD conferred by GDM in Caucasian was as much as smaller (number of subjects in exposure group was 515,
1.64-fold (95% CI: 1.25–5.56) higher compared with controls number of subjects in non-exposure group was 984,499) in
(Figure 3B). Besides, neither heterogeneity nor publication this subgroup analysis, neither inconsistency nor publication
bias was detected (Table 4). bias was detected, indicating the reliability of this result. This
result emphasizes the importance of good glycemic control
Discussion in diabetic mothers throughout pregnancy and not only in
The present study is, to our knowledge, the first meta- the first trimester.
analysis to evaluate the risk of ADHD for children induced It has been hypothesized that ADHD may be due to
by maternal diabetes. We systematically searched the data- inflammatory response to the central nervous system in the
bases and some of the included studies were nationwide fetus caused by maternal inflammation and immune response.
investigations, and the number of subjects was large enough A nationwide study demonstrated that several immune system
to obtain sufficient study power.12,13 The analyses gener- diseases, including maternal multiple sclerosis, rheumatoid
ally consisted of two parts. On the one hand, combining arthritis, asthma and hypothyroidism, were more frequently
of case-control studies demonstrated that the offspring of observed among mothers of offspring with ADHD com-
diabetic mothers were not at a heightened risk of ADHD pared with mothers of controls.8 Apart from the association
(OR: 1.20, 95% CI: 0.96–1.49). All the case-control stud- regardless of gender, another large cross-sectional study
ies recruited Caucasian participants. Therefore, this finding reported that inflammatory bowel disease was associated

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Table 3 Evaluation of overall quality levels using the GRADE approach
Quality assessment No of patients Effect Quality Importance
No of Design Risk of Inconsistency Indirectness Imprecision Other Case Control Relative Absolute
studies bias considerations (95% CI)
Association between maternal diabetes and ADHD (case-control study)

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3 Observational No serious Seriousa No serious No serious Very strong 2531/112,325 5,53/472,393 RR 1.20 0 more per  Critical
studies risk of bias indirectness imprecision associationb (2.3%) (0.12%) (0.96–1.49) 1,000 (from Moderate
0 fewer to 1
more)
  1.99% 4 more per
1,000 (from
1 fewer to
10 more)
Association between maternal diabetes and ADHD (cohort study)
6 Observational No serious No serious No serious No serious Reporting biasc 2,372/16,453 1,159/23,661 RR 1.40 20 more per  Critical
studies risk of bias inconsistency indirectness imprecision Very strong (14.4%) (4.9%) (1.27–1.54) 1,000 (from Moderate
associationb 13 more to
26 more)
  0.52% 2 more per
1,000 (from
1 more to 3
more)
Association between GDM and ADHD (better indicated by lower values)
4 Observational No serious No serious No serious No serious Reporting biasd 782 984,642 – ES 2.00  Important
studies risk of bias inconsistency indirectness imprecision Very strong higher Moderate
associationb (1.42–2.81
higher)
Notes: aSignificant heterogeneity (I2=76.5%) was observed among the included studies. bA large sample size was observed among the included studies. cPublication bias was identified according to Egger’s test (t=6.56, P=0.003). dPublication
bias was identified regarding this analysis.
Abbreviations: ADHD, attention deficit hyperactivity disorder; ES, effect size; GDM, gestational diabetes mellitus; RR, risk ratio.

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Figure 2 Main results of the meta-analyses.

Notes: (A) Data combination of case-control studies; (B) sensitivity analysis on case-control studies; (C) data combination of cohort studies; and (D) sensitivity analysis on
cohort studies. Weights are from random-effects analysis.
Abbreviations: ES, effect size; GDM, gestational diabetes mellitus; T1D, type 1 diabetes; T2D, type 2 diabetes.

with ADHD, particularly in females.14 Considering that females. Although insignificant findings were shown in both
ADHD has an approximate sex ratio of 3:1 during childhood males and females,14 further studies exploring the difference
and displays sex-specific manifestations,23 a sex-specific between gender are encouraged for a better understanding
mechanism may underlie the relationship between ADHD of ADHD etiology.
and maternal immune disease, such as diabetes. Among the Social factors have been suggested to play a crucial role
included studies, only one investigation14 separately reported on maternal diabetes and glycemic control, thus mediat-
the association of maternal diabetes with ADHD in males and ing the onset of ADHD. Most the included studies8,13,14,20,21

Table 4 Main results of the meta-analyses

Analysis No of Statistical Data pooling Heterogeneity Publication bias Sensitivity
subjects model Effect size t-value P-value I2 (%) P-value t-value P-value analysis

Overall OR 4,836,263 Random 1.20 (0.96–1.49) 1.62 0.105 76.5 0.002 1.67 0.194 Stable
Overall RR 2,382,640 Fixed 1.40 (1.27–1.54) 6.89 ,0.001 31.8 0.197 6.56 0.003 Stable
GDM RR 985,984 Fixed 2.00 (1.42–2.81) 4.00 ,0.001 0.0 0.446 4.99 0.038 Stable
GDM in Caucasian RR 985,014 Fixed 2.64 (1.26–5.56) 2.56 0.011 0.0 0.369 3.30 0.187 Stable
Abbreviations: GDM, gestational diabetes mellitus; RR, risk ratio.

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Zhao et al Dovepress

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Figure 3 Meta-analyses of the subjects from (A) mothers with GDM or (B) Caucasian mothers with GDM.
Abbreviations: ES, effect size; GDM, gestational diabetes mellitus.

considered family socioeconomic status (SES), such as and there is a link between thyroid hormones and diabetes
parental income, occupation, education, and single parent risk.29 In has been observed that thyroid-stimulating hormone
status, as a confounding variable and thereby adjusted the levels are slightly increased among ADHD patients.30 This
result. It is widely accepted that parental socioeconomic dis- finding is further validated by transgenic mouse that expresses
advantage is a risk factor for ADHD in children,24 which is a human mutant thyroid receptor β1, which manifests typical
likely mediated by factors linked to low SES such as parental syndromes of ADHD such as impulsive and inattentive.31
mental disorders. Diabetic mothers, especially for those with The National Institute for Health and Care Excellence
complications, are linked to low SES because those women accredited guidelines for ADHD management emphasized
might have limited ability to work and have lower disposable the importance of a holistic approach to managing ADHD.32
income, resulting in a relatively deprived environment for A comprehensive shared treatment plan should address
children. Apart from socioeconomic deprivation, lifestyle, psychological, behavioral, and occupational or educational
access to health food, regular physical activity, public insur- needs.32 The guideline recommends an ADHD-focused group
ance, etc, are also linked to glycemic control.25 Overall, it parent-training program to parents or carers as first-line treat-
is recommended to record social factors and consider them ment for children under 5 years with ADHD. Pharmacological
as confounders when examining the true effect of maternal medication is offered to children aged 5 years and over, young
diabetes on ADHD in children. So the adjusted results were people, and adults, only if ADHD symptoms are still caus-
extracted and combined if available. ing a significant impairment in interpersonal relationships,
A new insight into the impact of in utero hyperglycemia education and occupational attainment, or risk awareness.32
on fetus brain development emphasizes that maternal diabetes However, a network meta-analysis of randomized trials
may increase the vulnerability to psychiatric disorder later in indicated that the therapeutic effects of cognitive training,
life by interacting with other environmental insult during preg- neurofeedback, antidepressants, antipsychotics, dietary
nancy. Animal model study has demonstrated that GDM and therapy, fatty acids, and other complementary and alterna-
viral infection concurrently produce a novel transcriptional tive medicine were uncertain due to limited evidences.33
profile, and these novel transcriptional changes are associ- The present studies consisted of cohort, cross-sectional,
ated with pathways implicated in psychiatric disorders.26 This and case-control studies. Heterogeneity existed as a significant
finding indicates that GDM may have the potential to prime limitation for this review because of differences in ADHD
the fetus for an exacerbating response to infection, which is definition, ethnicity, type of maternal diabetes, and methodol-
a common environmental stress during pregnancy. ogy used. In order to reduce the heterogeneity between studies
The mechanism of ADHD also has some endocrinologi- included in the review, the studies that were similar regarding
cal components. It has been shown that patients with T1D design and measurement were combined. Another noteworthy
are more likely to receive ADHD diagnosis.27 Interestingly, fact was that we included the studies in which prescriptions
adolescents and young adults with ADHD are reportedly to were used as proxy for the diagnosis of ADHD,8,14,19 and
be more likely than non-ADHD controls to develop T2D in thus selection bias might occur. Due to various health care
later life.28 There is an ongoing discussion whether thyroid systems and policies in different countries, medications are
hormone system is involved in the development of ADHD, accepted by different subgroups of children who may have

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Dovepress Zhao et al

been diagnosed with ADHD. However, medication for ADHD 13. Ji J, Chen T, Sundquist J, Sundquist K. Type 1 diabetes in parents and
risk of attention deficit/hyperactivity disorder in offspring: a population-
does not necessarily mean a clinical diagnosis has been given. based study in Sweden. Diabetes Care. 2018;41(4):770–774.
Therefore, the identification of ADHD cases in further studies 14. Hegvik TA, Instanes JT, Haavik J, Klungsøyr K, Engeland A. Associa-
should be based on a standardized scale so that the selection tions between attention-deficit/hyperactivity disorder and autoimmune
diseases are modified by sex: a population-based cross-sectional study.
bias could be diminished. Eur Child Adolesc Psychiatry. 2018;27(5):663–675.
15. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred
Conclusion reporting items for systematic reviews and meta-analyses: the PRISMA
statement. PLoS Med. 2009;6(7):e1000097.
Maternal diabetes, especially for GDM, is probably a risk 16. Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis
factor for ADHD in Caucasian race. This result emphasizes detected by a simple, graphical test. BMJ. 1997;315(7109):629–634.
17. Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-
the importance of good glycemic control in diabetic mothers analysis. Stat Med. 2002;21(11):1539–1558.
throughout pregnancy and not only in the first trimester. The 18. Dersimonian R, Laird N. Meta-analysis in clinical trials. Control Clin
Trials. 1986;7(3):177–188.
attention on gender difference, the clear record of significant
19. Bytoft B, Knorr S, Vlachova Z, et al. Assessment of attention deficits
confounders, and the accurate diagnosis of ADHD cases are in adolescent offspring exposed to maternal type 1 diabetes. PLoS One.
urgently needed in the further studies. 2017;12(1):e0169308.
20. Daraki V, Roumeliotaki T, Koutra K, et al. Effect of parental obesity
and gestational diabetes on child neuropsychological and behavioral
Disclosure development at 4 years of age: the Rhea mother–child cohort, Crete,
The authors report no conflicts of interest in this work. Greece. Eur Child Adolesc Psychiatry. 2017;26(6):703–714.
21. Schmitt J, Romanos M. Prenatal and perinatal risk factors for attention-
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