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Prenatal maternal infections and early childhood
developmental outcomes: analysis of linked
administrative health data for Greater Glasgow
& Clyde, Scotland
Iain Hardie,
1
Aja Murray,
1
Josiah King,
1
Hildigunnur Anna Hall,
2
Emily Luedecke,
1
Louise Marryat,
3
Lucy Thompson,
4,5
Helen Minnis,
6
Philip Wilson,
4,7
and
Bonnie Auyeung
1
1
Department of Psychology, School of Philosophy, Psychology and Language Sciences, University of Edinburgh,
Edinburgh, UK;
2
Centre for Health Security and Communicable Disease Control, Directorate of Health, Reykjav
ık,
Iceland;
3
School of Health Sciences, University of Dundee, Dundee, UK;
4
Centre for Rural Health, Institute of Applied
Health Sciences, University of Aberdeen, Aberdeen, UK;
5
Gillberg Neuropsychiatry Centre, University of Gothenburg,
Gothenburg, Sweden;
6
School of Health and Wellbeing, University of Glasgow, Glasgow, UK;
7
Centre for Research
and Education in General Practice, University of Copenhagen, Copenhagen, Denmark
Background: Previous research has linked prenatal maternal infections to later childhood developmental outcomes
and socioemotional difficulties. However, existing studies have relied on retrospectively self-reported survey data, or
data on hospital-recorded infections only, resulting in gaps in data collection. Methods: This study used a large
linked administrative health dataset, bringing together data from birth records, hospital records, prescriptions and
routine child health reviews for 55,856 children born in Greater Glasgow & Clyde, Scotland, 2011–2015, and their
mothers. Logistic regression models examined associations between prenatal infections, measured as both
hospital-diagnosed prenatal infections and receipt of infection-related prescription(s) during pregnancy, and
childhood developmental concern(s) identified by health visitors during 6-8 week or 27-30 month health reviews.
Secondary analyses examined whether results varied by (a) specific developmental outcome types (gross-motor-
skills, hearing-communication, vision-social-awareness, personal-social, emotional-behavioural-attention and
speech-language-communication) and (b) the trimester(s) in which infections occurred. Results: After confounder/
covariate adjustment, hospital-diagnosed infections were associated with increased odds of having at least one
developmental concern (OR: 1.30; 95% CI: 1.19–1.42). This was broadly consistent across all developmental outcome
types and appeared to be specifically linked to infections occurring in pregnancy trimesters 2 (OR: 1.34; 95% CI:
1.07–1.67) and 3 (OR: 1.33; 95% CI: 1.21–1.47), that is the trimesters in which foetal brain myelination occurs.
Infection-related prescriptions were not associated with any clear increase in odds of having at least one
developmental concern after confounder/covariate adjustment (OR: 1.03; 95% CI: 0.98–1.08), but were associated
with slightly increased odds of concerns specifically related to personal-social (OR: 1.12; 95% CI: 1.03–1.22) and
emotional-behavioural-attention (OR: 1.15; 95% CI: 1.08–1.22) development. Conclusions: Prenatal infections,
particularly those which are hospital-diagnosed (and likely more severe), are associated with early childhood
developmental outcomes. Prevention of prenatal infections, and monitoring of support needs of affected children,
may improve childhood development, but causality remains to be established. Keywords: Child development;
maternal factors; prenatal; infection; CNS.
Introduction
Maternal health during pregnancy plays an impor-
tant role in later childhood development. One
important aspect of this is maternal infections,
which occur commonly during pregnancy and can
require treatment with prescription drugs, or hospi-
tal admission in more severe cases (Collier
et al., 2009; WHO Global Maternal Sepsis Study
Research Group, 2020). Animal models of prenatal
maternal infection suggest that a mother’s immune
response to an infectious agent (i.e. cytokine signal-
ling, antibody production), which is known as
maternal immune activation (MIA), creates a cascade
of events that can impact upon foetal brain develop-
ment (Garay, Hsiao, Patterson, & McAllister, 2013;
Massrali, Adhya, Srivastava, Baron-Cohen, &
Kotter, 2022; Oskvig, Elkahloun, Johnson, Phillips,
& Herkenham, 2012). Whilst more research is
needed, human studies tend to be consistent with
this (see Han, Patel, Jones, & Dale, 2021).
Most studies examining prenatal infections and
childhood development have focussed on links
between prenatal infections and formal diagnoses of
neurodevelopmental conditions in children. For
example, some research suggests prenatal infections
are associated with diagnosis of autism in children,
particularly among severe maternal infections involv-
ing hospitalisation as these involve higher levels of
MIA (Atladottir et al., 2010; Jiang et al., 2016; Lee
Conflict of interest statement: No conflicts declared.
Ó2024 The Author(s). Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and
Adolescent Mental Health.
This is an open access article under the terms of the Creative Commons Attribution License , which permits use, distribution and reproduction in any
medium, provided the original work is properly cited.
Journal of Child Psychology and Psychiatry 66:1 (2025), pp 30–40 doi:10.1111/jcpp.14028
et al., 2015). Meanwhile, other research has exam-
ined potential links between prenatal infections and
attention-deficit/hyperactivity disorder (ADHD), with
mixed results (e.g. see Ginsberg et al., 2019; Mann &
McDermott, 2011; Werenberg Dreier et al., 2016).
Prenatal infections have also been linked to mental
health conditions in adults such as schizophrenia
and bipolar disorder (Cordeiro, Tsimis, & Burd, 2015;
Khandaker, Zimbron, Lewis, & Jones, 2013;
Parboosing, Bao, Shen, Schaefer, & Brown, 2013).
Whilst most studies focus on neurodevelopmental
or mental health conditions, other research into the
relationship between prenatal infections and a
broader range of early childhood developmental
outcomes (i.e. not necessarily involving any formal
diagnoses) is also important. This is because many
conditions are not diagnosed until late childhood or
adulthood, and understanding outcomes early can
help ensure that any potential support needs are met
as quickly and effectively as possible. To date, only a
few pieces of research on this have been conducted.
One study of linked administrative data from New
South Wales, Australia, found hospital-diagnosed
prenatal maternal infections to be associated with
increased odds of social, emotional, physical, cogni-
tive and communication developmental vulnerabil-
ities in children at age 5 (Green et al., 2018).
Similarly, a cohort study using data from Boston
and Providence, USA, found prenatal bacterial
infections to be associated with reduced cognitive
performance at age 7 (Lee, Papandonatos, Savitz,
Heindel, & Buka, 2020). However, other research,
conducted using data from a UK cohort study, found
no association between hospital-recorded prenatal
infections and childhood socioemotional develop-
mental outcomes at age 3, but did find
self-reported maternal infections to be associated
with increased emotional problems (Hall, Speyer,
Murray, & Auyeung, 2021). Finally, research by
Kwok, Hall, Murray, Lombardo, and Auyeung (2022),
which examined maternal infections in each trimes-
ter of pregnancy and associations with child cogni-
tive outcomes, suggests that infections in the third
trimester could have an effect on cognitive abilities
later in childhood (although effect sizes were small).
There are, however, some important limitations to
these existing pieces of research. Notably, they have
tended to use data on prenatal infections that are
either (a) self-reported, and thus limited by issues
relating to a lack of a strong verification that
infections were present and by the retrospective
nature of reporting (see Hall et al., 2021; Kwok
et al., 2022), or (b) based on hospital records only,
and thus limited by only including a minority of
infections that are most severe (Green et al., 2018).
The present study overcomes some of these limita-
tions by making use of prenatal infections data
from both hospital records and infection-related
prescriptions. These were linked to data on birth
records and routine child health reviews to form a
large linked administrative health dataset covering
children born in 2011–2015 in Greater Glasgow &
Clyde, Scotland. This dataset was used to address
the following aims:
Aim 1: To examine associations between prenatal
maternal infections, measured as both
hospital-diagnosed prenatal infections and receipt
of infection-related prescription(s) during preg-
nancy, and having childhood developmental
concern(s) identified by health visitors during
early routine child health reviews.
Aim 2: To examine whether these associations vary
by (a) specific developmental outcome types (i.e.
gross-motor-skills, hearing-communication, vision-
social-awareness, personal-social, emotional-
behavioural-attention, and speech-language-
communication development) or (b) the trimester(s)
in which infections occurred.
Methods
Data and participants
The linked administrative health dataset –made up of data
from hospital records, birth records, prescriptions and child
health reviews –included children born in the National Health
Service (NHS) health board region of Greater Glasgow & Clyde,
2011–2015. This included all children who had linked
maternal health records and complete records of child
developmental outcomes from child health reviews conducted
(routinely and universally) at ages 6 to 8 weeks and 27–
30 months (for full details of child health reviews, see Public
Health Scotland, 2020; Scottish Government, 2015). In total,
this gave a final sample of 55,856 children and their mothers.
A flowchart providing full details of the sample selection
procedure, and exclusions, is provided in Figure 1.
The exclusions detailed in Figure 1relate to the fact that
although child health reviews are universal in that they are
targeted at all children, they are not taken up by, or recorded
for, everyone. In particular, the following groups are all
excluded for not having outcome data: (a) those whose
parents/carers chose not to take up the reviews, (b) those
who health visitors were unable to make contact with, (c) those
who were born in NHS Greater Glasgow & Clyde but who
moved outside of Scotland before becoming old enough for the
reviews, or (d) those who took part in the reviews but did not
have developmental outcomes assessed.
Childhood developmental outcome measures
The first outcome variable was having any (i.e. at least one)
childhood developmental concerns identified by health visitors
during the 6-8 week or 27-30 month child health review of each
child in the sample (coded: 0 =‘No’, 1 =‘Yes’). These could
relate to either gross-motor-skills, hearing-communication or
vision-social-awareness development measured at 6-8 week
reviews, or personal-social, emotional-behavioural-attention,
or speech-language-communication development measured at
27-30 month reviews. Developmental concerns were defined as
cases where at least one of the above developmental observa-
tions were categorised by health visitors as ‘abnormal’, ‘a
concern’ or ‘doubtful’ (i.e. suggestive of a possible abnormality,
see: Playford, Dibben, & Williamson, 2017) rather than as
‘normal’ or ‘no concerns’. Health visitors make these observa-
tions based on any/all of the following: (a) elicitation of
parental concerns, (b) a structured observation of the child
and/or (c) the results of an ‘Ages and Stages’ questionnaire or
Ó2024 The Author(s). Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for
Child and Adolescent Mental Health.
doi:10.1111/jcpp.14028 Prenatal maternal infections and early childhood development 31
other validated developmental assessment questionnaires (see
Scottish Government, 2015).
In addition, a further set of outcome variables were used in
which the previous overall developmental concerns variable
was disaggregated in order to indicate whether each child
in the sample had developmental concerns identified that
related specifically to (a) gross-motor-skills, (b) hearing-
communication, (c) vision-social-awareness, (d) personal-
social, (e) emotional-behavioural-attention and (f) speech-
language-communication development. These outcomes were
examined as six binary variables (each coded: 0 =‘No’,
1=‘Yes’).
Prenatal maternal infection measures
Two primary measures of prenatal maternal infection were
used as explanatory variables in the analysis. The first was
hospital-diagnosed prenatal infection(s), which indicates
whether, for each mother in the sample, Scotland’s ‘general/
acute inpatient and day case’ hospital records (see Information
Services Division Scotland, 2022d) or ‘maternity inpatient and
day case’ hospital records (see Information Services Division
Scotland, 2022a) show the diagnosis of any maternal infection
during the month of childbirth or in one of the nine preceding
months (coded: 0 =‘No’, 1 =‘Yes’). Infections were identified
using ICD10 codes. As the mechanism(s) behind the relation-
ship between prenatal infections and child development out-
comes is still not fully understood (e.g. whether the mechanism
is related to infection or associated inflammation), a deliber-
ately broad definition of hospital-diagnosed prenatal infection
was used, with all ICD10 codes that were assessed as being
related to either an infection or an inflammation being
included. All postpartum/puerperal infections were excluded
as although these were listed in maternity hospital records
they would have occurred after delivery so are not prenatal
infections. A full list of the ICD10 codes that were included is
provided in Table S1.
The second primary measure used was receipt of
infection-related prescription(s), which indicates whether, for
each mother in the sample, Scotland’s Prescribing Information
System (PIS, see Information Services Division Scotland, 2022b)
records show any receipt of prescriptions that are likely to have
been for an infection during the month of childbirth or in one of
the preceding nine months (coded: 0 =‘No’, 1 =‘Yes’). This
measure was used in order to indicate potential infection rather
than to look at whether the drugs themselves may have potential
effects on child development (this is based on the assumption
that GPs or other physicians would not prescribe drugs known to
be unsafe during pregnancy except in the rare event that the
expected benefits were considered greater than any potential
risks to the foetus). Like in existing literature making similar use
of PIS data related to infections (e.g. Scott et al., 2018),
infection-related prescriptions were defined as prescriptions
included in British National Formulary (BNF) Chapter 5:
Infections (British National Formulary, 2023). A full list of
drugs/prescriptions included is provided in Table S2.
In addition to the above primary explanatory variables, two
further sets of explanatory variables were used in order to
examine whether any potential associations between prenatal
infections and childhood developmental outcomes varied
depending on the trimester in which infections occurred. This
is important to consider because foetal brain myelination does
not begin until the second trimester of pregnancy (with further
growth reinforcements occuring in trimester 3, see Cordeiro
et al., 2015; Kwok et al., 2022). To measure this, the
hospital-diagnosed prenatal infection(s) measure was disag-
gregated into (a) hospital-diagnosed prenatal infection(s) in
trimester 1, (b) hospital-diagnosed prenatal infection(s) in
trimester 2 and (c) hospital-diagnosed prenatal infection(s) in
trimester 3. Similarly, the receipt of infection-related prescrip-
tion measure was disaggregated into (a) receipt of
infection-related prescription(s) during pregnancy trimester
1, (b) receipt of infection-related prescription(s) during preg-
nancy trimester 2 and (c) receipt of infection-related
prescription(s) during pregnancy trimester 3.
Finally, additional sensitivity analysis also included alter-
native measures of hospital-diagnosed prenatal infections and
receipt of infection-related prescriptions, whereby infections/
prescriptions from during the month of childbirth were
excluded. These measures were included because infections
from during the month of childbirth are often those picked up
when mothers are in hospital for the actual delivery/birth,
Importantly, including this type of infection meant the
inclusion of infections like Group B Strep carrier cases and
herpes simplex virus encephalitis picked up when mothers are
in hospital for delivery. These may be harmful for babies but
are unlikely to lead to an immune response in mothers that
would affect foetal development.
Confounders and covariates
The analysis also included a number of potential confounders
and covariates as control variables. Maternal age and
area-based deprivation were included as confounders, as these
factors are known to be potentially associated with both
maternal health during pregnancy and childhood health and
developmental outcomes (Glick, Kadish, & Rottenstreich, 2021;
Lean, Derricott, Jones, & Heazell, 2017; Reijneveld, Brugman,
Verhulst, & Verloove-Vanhorick, 2005; Vinikoor-Imler, Mes-
ser, Evenson, & Laraia, 2011; Yasumitsu-Lovell et al., 2023).
Information on maternal age came from maternity hospital
admissions data and it was defined as maternal age at time of
birth (coded: 0 =≤19, 1 =20–35, 2 =≥36, which is in line with
the ‘optimal’ (20–35) and ‘suboptimal’ (≤19/≥36) maternal age
categorisations for neurodevelopment identified by previous
research (Yasumitsu-Lovell et al., 2023)). Information on
area-based deprivation came from data on Scottish Index of
Multiple Deprivation (SIMD), which was calculated from home
Inclusion Criteria
Sample
(N)
Cases
Excluded
Children born in Greater Glasgow & Clyde from 2011-2015 and
recorded in Scottish Birth Record (SBR) with matched mothers
76,483
0
Children with matched record from 6-8 week routine child health
review
68,631
7,852
Children with matched record from 27-30 month routine child health
review
59,573
9,058
Children with complete data on all childhood developmental
outcomes at 6-8 week and 27-30 month child health reviews
55,856
3,717
Figure 1 Flowchart of sample selection procedure
Ó2024 The Author(s). Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for
Child and Adolescent Mental Health.
32 Iain Hardie et al. J Child Psychol Psychiatr 2025; 66(1): 30–40
postcodes and categorised into quintiles (coded: 1 =most
deprived, 2 =more deprived, 3 =medium deprived, 4 =less
deprived and 5 =least deprived).
In addition, sex of child, maternal history of mental health
hospital admissions and maternal prenatal smoking were
included as covariates as they are potentially heavily associ-
ated with childhood development (Green et al., 2018; National
Advisory Council on Women and Girls, 2022; Wehby, Prater,
McCarthy, Castilla, & Murray, 2011). Sex of child was defined
as a binary variable (coded: 0 =male, 1 =female), with data on
this coming from Scottish birth records. Data on maternal
history of mental health hospital admissions came from
hospital records on mental health inpatient and day case
hospital admissions (see Information Services Division
Scotland, 2022c). It was also defined as a binary variable
(coded 0 =no history of admissions, 1 =history of admissions,
i.e. one or more recorded admissions). Data were not available
on less severe maternal mental health issues (i.e. those not
requiring admission to hospital). Finally, maternal prenatal
smoking was defined as a binary indicator of whether mothers
smoked during pregnancy (coded: 0 =no, 1 =yes), and this
information came from maternity hospital admissions data.
Statistical analysis
The analysis used logistic regression models to measure
associations between the prenatal maternal infection mea-
sures (including the primary measures, secondary measures
and sensitivity analysis measures outlined above) and child-
hood developmental outcome measures (i.e. having any
developmental concerns identified and concerns identified
specifically relating to gross-motor-skills, hearing-
communication, vision-social-awareness, personal-social,
emotional-behavioural-attention and speech-language-
communication development).
Modelling was conducted using a hierarchical approach,
which involved (a) unadjusted models, (b) models which adjust
for confounders only (i.e. maternal age and area-based
deprivation) and (c) models which additionally adjust for
covariates (i.e. sex of child, maternal history of mental health
admissions and maternal prenatal smoking in addition to
maternal age and area-based deprivation). The analysis was
carried out as a complete case analysis because, unlike with
standardised developmental outcomes like SDQ scores (see
SDQ Info, 2024), health visitor judgements on child develop-
mental outcomes do not have set rules for imputing missing
values, and due to the size of the study dataset, it would be too
computationally demanding to impute missing values.
All analyses were conducted using Stata/MP 16 software
within Scotland’s National Safe Haven, with access to all
datasets being facilitated by the electronic Data Research and
Innovation Service (eDRIS) team at Public Health Scotland. The
analysis plan for this study was preregistered using Open
Science Framework (available here: https://osf.io/dx4vb), and
the reporting in this study is consistent with ‘REporting of
studies Conducted using Observational Routinely collected
health Data’ (RECORD) guidelines (see Benchimol et al., 2015).
Results
Descriptive statistics
Descriptive statistics showing the characteristics of
the sample, in terms of prevalence of study vari-
ables, are provided in Table 1. Overall, 21.2% of
children in the sample had at least one develop-
mental concern identified by health visitors. This is
broadly in line with previous estimates of early
Table 1 Descriptive statistics for childhood developmental
outcomes, prenatal infections and confounders/covariates
N%
Primary childhood developmental outcome
Any (i.e. at least one) childhood developmental concerns
identified by health visitors
No 44,026 78.8
Yes 11,830 21.2
Secondary childhood developmental outcomes
Developmental concern: gross-motor-skills development
(6–8 weeks)
No 54,852 98.2
Yes 1,004 1.8
Developmental concern: hearing-communication
development (6–8 weeks)
No 55,598 99.5
Yes 258 0.5
Developmental concern: vision-social-awareness
development (6–8 weeks)
No 55,210 98.8
Yes 646 1.2
Developmental concern: personal-social development
(27–30 months)
No 53,160 95.2
Yes 2,696 4.8
Developmental concern: emotional-behavioural-attention
development (27–30 months)
No 50,003 89.5
Yes 5,853 10.5
Developmental concern: speech-language-communication
development (27–30 months)
No 48,487 86.8
Yes 7,369 13.1
Primary prenatal infection measures
Hospital-diagnosed prenatal infection
No 52,999 94.9
Yes 2,857 5.1
Receipt of infection-related prescription(s) during pregnancy
No 40,774 73.0
Yes 15,082 27.0
Secondary prenatal infection measures
Hospital-diagnosed prenatal infection in trimester 1
No 55,539 99.4
Yes 317 0.5
Hospital-diagnosed prenatal infection in trimester 2
No 55,449 99.3
Yes 407 0.7
Hospital-diagnosed prenatal infection in trimester 3
No 53,600 96.0
Yes 2,256 4.0
Receipt of infection-related prescription(s) during pregnancy
trimester 1
No 50,047 89.6
Yes 5,809 10.4
Receipt of infection-related prescription(s) during pregnancy
trimester 2
No 49,850 89.3
Yes 6,006 10.7
Receipt of infection-related prescription(s) during pregnancy
trimester 3
No 46,980 84.1
Yes 8,876 15.9
Sensitivity analysis prenatal infection measures
Hospital-diagnosed prenatal infection (excluding month of
childbirth)
No 54,369 97.3
Yes 1,487 2.7
(continues)
Ó2024 The Author(s). Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for
Child and Adolescent Mental Health.
doi:10.1111/jcpp.14028 Prenatal maternal infections and early childhood development 33
developmental concerns in Greater Glasgow &
Clyde using similar datasets, although slightly
higher than levels reported at a Scottish population
level (Information Services Division, 2017; Scottish
Government, 2023). Of these, concerns were more
commonly identified for outcomes measured at 27-
to 30-month health reviews, particularly those
relating to speech-language-communication devel-
opment (for which 13.1% of the sample had
concerns identified) and emotional-behavioural-
attention development (for which 10.5% of sample
had concerns identified). Conversely, developmental
concerns at 6- to 8-week child health reviews (i.e.
gross-motor-skills, hearing-communication and
vision-social-awareness development) were rare,
occurring for just 0.5%–1.8% of sample.
5.1% of mothers in the sample had records of
hospital-diagnosed infections, and 27.0% had
records of receiving infection-related prescriptions
during pregnancy, although these figures were lower
(2.7% and 22.9%, respectively) when infections/
prescriptions from the month of childbirth were
excluded (i.e. in the sensitivity analysis prenatal
infection measures). With regard to confounders/
covariates, it is noteworthy that maternal history of
mental health admissions was fairly rare (1.6% of
sample) and that the sample tended to be from more
deprived SIMD quintiles, which reflects the fact that
Glasgow has relatively high levels of deprivation (see
Understanding Glasgow, 2020). In addition to
Table 1, further descriptive statistics showing (a)
variation in prenatal infection measures and con-
founders/covariates across childhood developmen-
tal outcomes, and (b) variation in childhood
developmental outcomes and confounders/covari-
ates across prenatal infection measures, are pro-
vided in Tables S3 and S4.
Prenatal infections and having at least one
childhood developmental concern
Results showing associations between prenatal
infections and having any (i.e. at least one) child-
hood developmental concerns identified by health
visitors at 6–8 weeks or 27–30 months are provided
in Table 2(fully adjusted results for key variables
only) and Table S5a,b (unadjusted, confounder
adjusted and fully adjusted results for all variables).
The results suggest that hospital-diagnosed prena-
tal infections were associated with increased odds
of developmental concerns (OR: 1.43; 95% CI: 1.31–
1.55 in unadjusted model and OR: 1.33; 95% CI:
1.22–1.45 in confounder adjusted model). Even
after adjustment for confounders and covariates,
they were associated with a 1.30 (95% CI: 1.19–
1.42) increase in the odds of having at least one
childhood developmental concern. Meanwhile,
receipt of infection-related prescription(s) during
pregnancy was associated with a small increase in
the odds of having at least one developmental
concern in the unadjusted model (OR: 1.10; 95%
CI: 1.05–1.16), but this was largely attenuated in
the confounder adjusted (OR: 1.03; 95% CI: 0.98–
1.08) and fully adjusted (OR: 1.03; 95% CI: 0.98–
1.08) models.
Prenatal infections and specific types of childhood
developmental concerns
Results showing associations between prenatal
infections and having specific types of childhood
developmental concerns are shown in Table 3(fully
adjusted results for key variables only) and
Table S6a,b (unadjusted, confounder adjusted and
Table 1 (continued)
N%
Receipt of infection-related prescription(s) during pregnancy
(excluding month of childbirth)
No 43,059 77.1
Yes 12,797 22.9
Confounders/Covariates
Maternal age at time of birth
<20 2,472 4.4
20–35 44,524 79.7
>35 8,860 15.9
SIMD quintile
1 (most deprived) 22,245 39.8
2 (more deprived) 10,329 18.5
3 (medium deprived) 8,452 15.1
4 (less deprived) 7,161 12.8
5 (least deprived) 7,669 13.7
Sex of child
Male 28,348 50.7
Female 27,508 49.3
Maternal history of mental health hospital admissions
No 54,970 98.4
Yes 886 1.6
Maternal prenatal smoking
No 47,908 85.8
Yes 7,948 14.2
Table 2 Odds ratios (95% CIs) for fully adjusted associations
between prenatal infection(s) and having any (i.e. at least one)
childhood developmental concern identified by health visitors
Having any (i.e. at least one) childhood
developmental concern identified
Hospital-diagnosed prenatal infection(s)
[No]
Yes 1.30*** (1.19–1.42)
Receipt of infection-related prescription(s) during pregnancy
[No]
Yes 1.03 (0.98–1.08)
Models fully adjust for maternal age at time of birth, SIMD
quintile, sex of child, maternal history of mental health
hospital admissions and maternal prenatal smoking. Refer-
ence categories are shown in square brackets. Childhood
developmental concerns include those measured at both 6- to
8-week and 27- to 30-month routine child health visits.
*p<.05, **p<.01 and ***p<.001.
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Child and Adolescent Mental Health.
34 Iain Hardie et al. J Child Psychol Psychiatr 2025; 66(1): 30–40
fully adjusted results for all variables). The results
suggest that, even after adjustment for confounders
and covariates, hospital-diagnosed prenatal infec-
tions were associated with increased odds of child-
hood developmental concerns relating to gross-
motor-skills (OR:1.30; 95% CI: 1.01–1.67),
hearing-communication (OR: 1.33; 95% CI: 0.82–
2.17) and vision-social-awareness (OR: 1.46; 95%
CI: 1.08–1.96) development at age 6–8 weeks, and
personal-social (OR: 1.34; 95% CI: 1.15–1.56),
emotional-behavioural-attention (OR: 1.36; 95% CI:
1.22–1.52) and speech-language-communication
(OR: 1.33; 95% CI: 1.20–1.47) development at age
27–30 months.
Meanwhile, with regard to infection-related pre-
scriptions the results were less clear.
Infection-related prescriptions did appear to be
associated with a small increase in the odds of
personal-social (OR: 1.12; 95% CI: 1.03–1.22 in fully
adjusted model) and emotional-behavioural-
attention development (OR: 1.15; 95% CI: 1.08–
1.23 in fully adjusted model). However, there were no
clear associations for any of the other types of
developmental concerns examined.
Prenatal infections, by trimester and having at least
one childhood developmental concern
Results showing associations between prenatal
infections, by trimester and having at least one
childhood developmental concern are provided in
Table 4(fully adjusted results for key variables only)
and Table S7a,b (unadjusted, confounder adjusted
and fully adjusted results for all variables). They
highlight that the positive association between
hospital-diagnosed prenatal infections and having
at least one childhood developmental concern
appeared to be specifically linked to infections
occurring in trimesters 2 (OR: 1.34; 95% CI: 1.07–
1.67 in fully adjusted model) and 3 (OR: 1.33; 95%
CI: 1.21–1.47 in fully adjusted model). There was not
a clear association between hospital-diagnosed pre-
natal infections in trimester 1 and having at least
one childhood developmental concern (OR: 1.11;
95% CI: 0.84–1.45 in fully adjusted model). In terms
of infection-related prescriptions, there did not
appear to be much variation in the relationship
between their receipt and having childhood develop-
mental concern(s) by trimester.
Table 3 Odds ratios (95% CIs) for fully adjusted associations between prenatal infections and having specific types of childhood
developmental concerns identified by health visitors
Type of childhood developmental concern identified
6- to 8-week child health review 27- to 30-month child health review
Gross-motor
skills
Hearing-
communication
Vision-social
awareness Personal-social
Emotional-
behavioural-
attention
Speech-language-
communication
Hospital-diagnosed prenatal infection(s)
[No]
Yes 1.30*(1.01–1.67) 1.33 (0.82–2.16) 1.46*(1.08–1.96) 1.34*** (1.15–1.56) 1.36*** (1.22–1.52) 1.33*** (1.20–1.47)
Receipt of infection-related prescription(s) during pregnancy
[No]
Yes 1.05 (0.91–1.21) 1.08 (0.82–1.43) 0.92 (0.77–1.10) 1.12*(1.03–1.22) 1.15*** (1.08–1.22) 0.97 (0.92–1.03)
Models fully adjust for maternal age at time of birth, SIMD quintile, sex of child, maternal history of mental health hospital
admissions and maternal prenatal smoking. Reference categories are shown in square brackets.
*p<.05, **p<.01 and ***p<.001.
Table 4 Odds ratios (95% CIs) for fully adjusted associations
between prenatal infections, by trimester and having any (i.e.
at least one) childhood developmental concern identified by
health visitors
Having any (i.e. at least one) childhood
developmental concern identified
Trimester 1 hospital-diagnosed prenatal infection(s)
[No]
Yes 1.11 (0.84–1.45)
Trimester 2 hospital-diagnosed prenatal infection(s)
[No]
Yes 1.34*(1.07–1.67)
Trimester 3 hospital-diagnosed prenatal infection(s)
[No]
Yes 1.33*** (1.21–1.47)
Trimester 1 receipt of infection-related prescription(s) during
pregnancy
[No]
Yes 1.09*(1.02–1.16)
Trimester 2 receipt of infection-related prescription(s) during
pregnancy
[No]
Yes 1.06*(1.00–1.14)
Trimester 3 receipt of infection-related prescription(s) during
pregnancy
[No]
Yes 1.04 (0.99–1.10)
Models fully adjust for maternal age at time of birth, SIMD
quintile, sex of child, maternal history of mental health
hospital admissions and maternal prenatal smoking. Refer-
ence categories are shown in square brackets. Childhood
developmental concerns include those measured at both 6- to
8-week and 27- to 30-month routine child health visits.
*p<.05, **p<.01 and ***p<.001.
Ó2024 The Author(s). Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for
Child and Adolescent Mental Health.
doi:10.1111/jcpp.14028 Prenatal maternal infections and early childhood development 35
Sensitivity analysis
The results of the sensitivity analysis, which
repeated the main analysis but excluding
hospital-diagnosed infections and infection-related
prescriptions from the month of childbirth, are
provided in Table S8a,b. The results were broadly
in line with the results of the main analysis.
Discussion
This study used linked administrative health data to
examine relationships between prenatal infections,
measured as both hospital-diagnosed infections and
receipt of infection-related prescriptions, and early
childhood developmental outcomes among children
born in NHS Greater Glasgow & Clyde, Scotland,
2011–2015. The findings suggest that, after adjust-
ing for measured confounders and covariates,
hospital-diagnosed prenatal infections were associ-
ated with increased odds of children having at least
one developmental concern identified during 6-8
week or 27-30-month routine child health reviews.
This relationship was broadly consistent across all
developmental outcome types measured and
appeared to be specifically linked to infections
occurring in trimesters 2 and 3 of pregnancy. The
findings also suggest that receipt of infection-related
prescriptions during pregnancy was associated with
increased odds of children having at least one
childhood developmental concern, but this was
attenuated after accounting for confounders
and covariates. There were, however, increased
odds of developmental concerns specifically related
to personal-social and emotional-behavioural-
attention development even after confounder and
covariate adjustment. The relationship between
receipt of infection-related prescriptions and devel-
opmental outcomes did not appear to vary by the
trimester in which prescriptions were received.
Overall, these findings suggest that MIA, or some
other mechanism arising from significant prenatal
infections, is associated with increased likelihood of
adverse childhood developmental outcomes. This is
in line with what is observed in animal models of
maternal prenatal infections (Garay et al., 2013;
Massrali et al., 2022; Oskvig et al., 2012). In
addition, the research findings of the present study
suggest that prenatal infections diagnosed in hospi-
tal had a particularly clear association with devel-
opmental outcomes. This is in line with the results of
some previous human studies such as Green
et al. (2018), but not others, for example Hall
et al. (2021). This most likely reflects the fact that
infections picked up in hospital will typically be more
severe, and more severe infections will, in general,
involve higher levels of MIA (see Hall, Willis, Rodri-
guez, & Schwarz, 2023; Jiang et al., 2016). In
addition, the fact that this association appeared to
be specifically related to infections in the second and
third trimester of pregnancy most likely reflects the
fact that foetal brain myelination occurs in the
second and third trimester, and therefore, this is
the period in which MIA may have the greatest effect
on prenatal brain development (see Cordeiro
et al., 2015; Kwok et al., 2022).
One novel aspect of thisstudy is that, whilst previous
studies on prenatal infections and childhood develop-
ment have relied on retrospectively self-reported
survey data, or data on hospital-recorded infections
only, this study was able to also use data on receipt
of infection-related prescriptions as an additional
indicator of prenatal infection. The finding that
receipt of infection-related prescriptions during
pregnancy was associated with increased odds of
developmental concerns related to personal-social
and emotional-behavioural-attention development
backs up previous research that found maternal
self-reported prenatal infections to be associated
with childhood emotional problems (Hall
et al., 2021). However, the infection-related prescrip-
tion measure used in the present study overcomes
some of the limitations that this previous research
had, in particular, limitations related to its self-
reported data potentially lacking strong verification
that an infection was present and problems arising
from the retrospective nature of its reporting (see Hall
et al., 2021, p. 1647).
The key strength of this study was that it was able
to make use of a large linked administrative health
dataset, which included data on multiple indicators
of prenatal infections, and a range of childhood
developmental outcomes. Nevertheless, there are
some limitations that must be noted. First, it was
beyond the scope of this study to examine variations
in outcomes based on whether infections were
bacterial, viral or other infection types. Moreover,
whilst a range of confounders and covariates were
controlled for, it is possible that there are additional
confounding factors that were not observed in the
dataset. For example, possible unobserved con-
founding mechanisms might be disruption of ante-
natal attachment caused by infection, some genetic
confounding linking susceptibility to infection, or to
a general propensity to receive antibiotic prescrip-
tions, and neurodevelopmental outcomes. In partic-
ular, given the subjective nature of antibiotic
prescribing (see Borek et al., 2020; Public Health
England, 2015), it is possible that unmeasured
confounders with a genetic component (e.g. mild
anxiety) might explain at least part of the observed
association between infection-related prescriptions
(specifically antibiotic prescriptions) during preg-
nancy and poorer child personal-social and
emotional-behavioural-attention developmental out-
comes (see Howie & Bigg, 1980). Also, given that
childhood developmental outcomes are heritable, it
is possible that parental behaviours related to their
own neurodevelopmental outcomes could impact a
mother’s likelihood of receiving a diagnosis of
Ó2024 The Author(s). Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for
Child and Adolescent Mental Health.
36 Iain Hardie et al. J Child Psychol Psychiatr 2025; 66(1): 30–40
infection, for example by affecting their propensity to
consult their GP about a possible infection.
In addition, there are also some limitations related
to the administrative health dataset used in this
study’s analysis. It is well documented that studies
using administrative health data are often not fully
representative of the target population due to
missing data arising from people failing to interact
with health services (e.g. due to barriers such as
housing problems, living in remote areas or a wide
range of other reasons) or due to inaccuracies in data
linkage processes (see Harron et al., 2017; Shaw
et al., 2022). In the case of the present study
specifically, it was conducted as a complete case
analysis, and participation in Scotland’s universal
health visiting pathway (i.e. the routine child health
reviews in which child developmental outcomes were
measured) is known to be lower among those living
in more deprived areas (Horne, Marryat, &
Wood, 2021). This means that the study participants
may not be completely representative of all children
born in Greater Glasgow & Clyde during the analysis
period. More broadly, Greater Glasgow & Clyde is
also unlikely to be representative of Scotland (or the
United Kingdom), as it is a mostly urban area and
has relatively high levels of deprivation (Understand-
ing Glasgow, 2020).
The analysis outlined in this study used hospital-
diagnosed prenatal infections and receipt of
infection-related prescriptions as the main prenatal
infection indicators. As discussed above, this pro-
vides a fuller picture of infections than previous
studies. However, each of these indicators comes
with their own set of strengths and weaknesses. The
strength of using hospital-diagnosed infections is
that they provide a strong verification of the presence
of an infection, as patients will have been thoroughly
examined before a diagnosis is made. However,
infections diagnosed in hospital likely include only
a small proportion of all infections, typically made up
of more severe cases only. Moreover, there can be
nuances in how hospital-diagnosed infections are
coded and in how medical notes/records are inter-
preted by the medical reviewers entering ICD10
codes (Hashimoto, Brodt, Skelly, & Dettori, 2014).
On the other hand, infection-related prescriptions
cover a much larger number of prenatal infections, as
PIS data cover all medicines that are prescribed and
dispensed in the community (Information Services
Division Scotland, 2022b). However, its accuracy in
capturing infections may be affected by geographical
or temporal variations in GP prescribing practices
(see Devine, O’Kane, & Bucholc, 2021; Guthrie
et al., 2022; Pouwels, Dolk, Smith, Smieszek, &
Robotham, 2018b), and there have been known
issues relating to inappropriate prescribing and
overprescribing of antibiotics in the United Kingdom
and elsewhere (e.g. see Pouwels, Dolk, Smith, Robot-
ham, & Smieszek, 2018a; Smieszek et al., 2018).
To conclude, although this study has some
limitations, by including data on both hospital-
diagnosed infections and infection-related prescrip-
tions it provides as full a picture as possible on
prenatal infections. The study provides evidence that
maternal infections during pregnancy, particularly
those which are (a) hospital-diagnosed (i.e. likely
more severe) and (b) occurring in the second and
third trimester of pregnancy, are associated with
early childhood developmental outcomes in children.
As this may be linked to the process of MIA affecting
foetal brain development, prevention of prenatal
infections in the second and third trimester of
pregnancy, alongside monitoring of support needs
of affected children, may improve childhood devel-
opment. However, the findings require confirmation
in experimental study designs, and an important
area for future research is analyses separate by
infection pathogen (i.e. bacterial infection, viral
infection and other infection types) as there may be
difference between pathogens.
Supporting information
Additional supporting information may be found online
in the Supporting Information section at the end of the
article:
Table S1. List of ICD10 codes included in this study’s
hospital-diagnosed prenatal infections definition.
Table S2. List of drugs/prescriptions included in this
study’s receipt of infection-related.
Table S3. Descriptive statistics for prenatal infections
and confounders/covariates by childhood developmen-
tal outcome(s).
Table S4. Descriptive statistics for childhood develop-
mental outcomes and confounders/covariates by pre-
natal infections.
Table S5a. Odds ratios (95% CIs) for unadjusted,
confounder adjusted and fully adjusted associations
between hospital-diagnosed prenatal infections and
having any (i.e. at least one) childhood developmental
concerns identified by health visitors.
Table S5b. Odds ratios (95% CIs) for unadjusted,
confounder adjusted and fully adjusted associations
between receipt of infection-related prescription(s) dur-
ing pregnancy and having any (i.e. at least one)
childhood developmental concerns identified by health
visitors.
Table S6a. Odds ratios (95% CIs) for unadjusted,
confounder adjusted and fully adjusted associations
between hospital-diagnosed prenatal infections and
having specific types of childhood developmental con-
cerns identified by health visitors.
Table S6b. Odds ratios (95% CIs) for unadjusted,
confounder adjusted and fully adjusted associations
between receipt of infection-related prescription(s) dur-
ing pregnancy and having specific types of childhood
developmental concerns identified by health visitors.
Table S7a. Odds ratios (95% CIs) for unadjusted,
confounder adjusted and fully adjusted associations
between hospital-diagnosed prenatal infections, by
Ó2024 The Author(s). Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for
Child and Adolescent Mental Health.
doi:10.1111/jcpp.14028 Prenatal maternal infections and early childhood development 37
trimester, and having any (i.e. at least one) childhood
developmental concerns identified by health visitors.
Table S7b. Odds ratios (95% CIs) for unadjusted,
confounder adjusted and fully adjusted associations
between receipt of infection-related prescription(s), by
trimester, and having any (i.e. at least one) childhood
developmental concerns identified by health visitors.
Table S8a. Odds ratios (95% CIs) for fully adjusted
associations between prenatal infections (with month of
childbirth excluded) and having any (i.e. at least one)
adverse childhood development outcome.
Table S8b. Odds ratios (95% CIs) for fully adjusted
associations between prenatal infections (with month of
childbirth excluded) and having a specific type of
adverse childhood development outcome.
Acknowledgements
I.H. and B.A. were supported by the Economic and
Social Research Council (ES/W001519/1) during the
course of this work. B.A. was additionally supported by
the European Union’s Horizon 2020 research and
innovation programme under the Marie Skłodowska-
Curie grant agreement No.813546, the Baily Thomas
Charitable Fund TRUST/VC/AC/SG/469207686, the
Data Driven Innovation. In addition, the authors would
like to acknowledge the electronic Data Research and
Innovation Service (eDRIS) team at Public Health
Scotland for their support in obtaining approvals, the
provisioning and linking of data and facilitating access
to the National Safe Haven. The authors have declared
that they have no competing or potential conflicts of
interest.
Ethical considerations
This project was approved by the research ethics
committee for the School of Philosophy, Psychology
and Language Sciences (PPLS) at the University of
Edinburgh (reference: 190-1718/2). The project also
received information governance approval from the NHS
Scotland Public Benefit and Privacy Panel for Health
and Social Care (HSC-PBPP, reference: 1617–0314).
Written consent from participants was not required or
obtained. All data used in this study were housed
within Scotland’s National Safe Haven, coordinated by
the electronic Data Research and Innovation Service
(eDRIS) team at Public Health Scotland. The data were
only accessed by approved researchers.
Data availability statement
The administrative health datasets used for this study
are not publicly available, but can be accessed via
successfully applying to the NHS Scotland Public Benefit
and Privacy Panel for Health and Social Care (HSC-
PBPP). The authors of the present study were supported
in applying for approval from HSC-PBPP by the electronic
Data Research and Innovation Service (eDRIS) team at
Public Health Scotland. eDRIS also facilitated access to
the data via Scotland’s National Safe Haven.
Correspondence
Iain Hardie, Department of Psychology, School of Philos-
ophy, Psychology and Language Sciences, University of
Edinburgh, Edinburgh, UK; Email: i.hardie@ed.ac.uk
Key points
•Previous studies suggest that prenatal infections, and the maternal immune activation that comes with
them, are associated with child developmental outcomes. However, research to date has been based on
infection data that is either self-reported or included infections diagnosed in hospital only.
•This study examined associations between prenatal infections, measured by both hospital-diagnosed
infections and receipt of infection-related prescriptions, and child developmental concerns identified by
health visitors at ages 6–8 weeks and 27–30 months.
•Hospital-diagnosed prenatal infections were consistently associated with developmental concerns.
Maternal receipt of infection-related prescriptions during pregnancy was also associated with
developmental concerns, but only those related to personal-social and emotional-behavioural-
attention development.
•This suggests that prenatal infections, particularly severe infections, are associated with early childhood
developmental outcomes.
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