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Maternal mental disorders and neonatal
outcomes: Danish population-based cohort study
Natalie C. Momen*, Hannah Chatwin*, Katrine Holde, Xiaoqin Liu, Trine Munk-Olsen,
Kathrine Bang Madsen and Liselotte Vogdrup Petersen
Background
Previous studies have indicated associations between maternal
mental disorders and adverse birth outcomes; however, these
studies mainly focus on certain types of mental disorders, rather
than the whole spectrum.
Aims
We aimed to conduct a broad study examining all maternal
mental disorder types and adverse neonatal outcomes which is
needed to provide a more complete understanding of the
associations.
Method
We included 1 132 757 liveborn singletons born between
1997 and 2015 in Denmark. We compared children of
mothers with a past (>2 years prior to conception; n=48646),
recent (2 years prior to conception and during pregnancy;
n= 15 899) or persistent (both past and recent; n=10 905)
diagnosis of any mental disorder, with children of mothers
with no mental disorder diagnosis before the index delivery
(n= 1 057 307). We also considered different types of mental
disorders. We calculated odds ratios and 95% CIs of low
birthweight, preterm birth, small for gestational age, low
Apgar score, Caesarean delivery and neonatal death.
Results
Odds ratios for children exposed to past, recent and persistent
maternal mental disorders suggested an increased risk for
almost all adverse neonatal outcomes. Estimates were highest
for children in the ‘persistent’group for all outcomes, with the
exception of the association between persistent maternal men-
tal disorders and neonatal death (odds ratio 0.96, 0.62–1.48).
Conclusions
Our study provides evidence for increased risk of multiple
adverse neonatal outcomes among children of mothers with
mental disorders, highlighting the need for close monitoring and
support for women with mental disorders.
Keywords
Mental disorders; low birthweight; neonatal outcomes; preterm
birth.
Copyright and usage
© The Author(s), 2024. Published by Cambridge University Press
on behalf of Royal College of Psychiatrists. This is an Open
Access article, distributed under the terms of the Creative
Commons Attribution licence (http://creativecommons.org/
licenses/by/4.0/), which permits unrestricted re-use, distribution
and reproduction, provided the original article is properly cited.
The onset of mental disorders tends to occur early in life. Among
women, most mental disorders develop before or during
the child-bearing years,
1
and pregnant women are among those
that are diagnosed with mental disorders. Mental disorders are
common causes of morbidity among pregnant women. In addition
to the impact of mental disorders on the mother, several studies
have highlighted the impact on outcomes in the offspring. Two
reviews
1,2
report associations between maternal mental disorders
and preterm birth, low birthweight, small for gestational age
(SGA) and Caesarean delivery. Adverse neonatal outcomes are, in
turn, associated with detrimental long-term developmental outcomes
in the offspring, including behavioural problems and lower school
performance.
3
Although these associations vary with, for example,
the degree of low birthweight and prematurity, the World Health
Organization has highlighted preterm birth as the leading cause of
perinatal and neonatal morbidity and mortality.
4
Previous studies
on neonatal outcomes have focused on depression,
5
anxiety,
6
schizo-
phrenia
7,8
and eating disorders.
9,10
There is limited research on other
disorders, including personality disorders and developmental/behav-
ioural disorders, which can occur just as frequently as or more fre-
quently than some of the aforementioned disorders. A broad study
examining all mental disorder types would allow for comparison
and provide a more complete understanding of the associations
between maternal mental disorders and adverse neonatal outcomes.
In this study, we used Danish nationwide registers to investigate
adverse neonatal outcomes among offspring whose mothers had
been diagnosed with a mental disorder. Compared with children of
mothers with no mental disorder diagnosis, we considered children
of mothers with (i) a past mental disorder diagnosis (more than
2 years prior to conception), (ii) a recent mental disorder diagnosis
(2 years prior to conception andduring pregnancy) and (iii) a persist-
ent mental disorder diagnosis (both past and recent diagnoses). We
examined the risk of adverse outcomes associated with any mental
disorder, as well as different types of mental disorders.
Method
Study population
We carried out a population-based cohort study using Danish
registers. We identified all liveborn singletons born between 1997
and 2015 (n= 1 159 624) from the Danish Medical Birth Register
(MBR). All residents in Denmark are assigned a unique identifica-
tion number in the Danish Civil Registration System, which allows
linkage of data between different registers.
We excluded 23 676 children with missing or unlikely informa-
tion on outcomes (gestational age <154 or >315 days, or missing;
birthweight <300 or >6400 grams, or missing; missing Apgar
score) and 3191 children with chromosomal abnormalities (ICD-
10 [International Classification of Diseases, 10th revision] codes
Q90–Q99) identified from the Danish National Patient Register.
This resulted in a sample of 1 132 757 singletons born to 663 345
mothers (Fig. 1). The study was approved by the Danish Data
Protection Agency. By Danish law, no informed consent is required
for a register-based study using anonymised data. The research was
carried out according to the Strengthening the Reporting of
* Joint first authors.
The British Journal of Psychiatry (2024)
Page 1 of 8. doi: 10.1192/bjp.2024.164
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https://doi.org/10.1192/bjp.2024.164 Published online by Cambridge University Press
Observational Studies in Epidemiology (STROBE) guidelines (see
Supplementary materials available at https://doi.org/10.1192/bjp.
2024.164).
Ethical approval
The study was approved by the Danish Data Protection Agency.
Consent statement
By Danish law, no informed consent is required for a register-based
study using anonymised data.
Data sharing
No additional data are available. Access to individual-level Denmark
data is governed by Danish authorities. These include the Danish
Data Protection Agency, the Danish Health Data Authority, the
Ethical Committee, and Statistics Denmark. Each scientific project
must be approved before initiation, and approval is granted to a spe-
cific Danish research institution. Researchers at Danish research insti-
tutions may obtain the relevant approval and data. International
researchers may gain data access if governed by a Danish research
institution having needed approval and data access.
Exposure: maternal mental disorder diagnosis
Maternal mental disorders were defined by ICD codes from in-
patient, out-patient and emergency contacts in the Danish
Psychiatric Central Research Register (PCRR) and Danish
National Patient Register (NPR). The PCRR and NPR have
recorded in-patient contacts since 1969 and 1977, respectively, as
well as out-patient and emergency contacts since 1995. The main
analyses examined any maternal mental disorder (ICD-10 codes
F10–F99 and corresponding ICD-8 diagnoses [Supplementary
Table 1]). Diagnoses were only included if they were made after dis-
order-dependent minimum ages of onset (Supplementary Table 1).
We further classified mental disorders into exposure groups defined
by nine ICD-10 subchapter categories (see Supplementary Table 1).
We did not include organic mental disorders (ICD-10 codes
F00–F09) as an exposure group as the onset of these disorders
occur significantly later in life. Children whose mothers had never
been diagnosed with a mental disorder before the index delivery
were classified as unexposed (reference group). Children born to
mothers who had been diagnosed with a mental disorder were
divided into three groups: (i) past maternal mental disorder
group: children born to a mother who had previously but not
recently (more than 2 years prior to conception of the child) been
diagnosed with a mental disorder, (ii) recent maternal mental dis-
order group: children born to a mother who had recently
(between 2 years prior to conception and the birth of the child)
been diagnosed with a mental disorder but did not have a history
of mental disorder, (iii) persistent maternal mental disorder
group: children born to a mother with both recent and past diagno-
ses (between 2 years prior to conception and the birth of the child,
and more than 2 years prior to conception). Conception was ascer-
tained from gestational age based on the first- or second-trimester
ultrasound scan, or when ultrasound data were unavailable, the
first day of the mother’s last menstrual period.
An individual diagnosed with multiple mental disorders could
be classified as exposed in more than one analysis.
Outcomes: neonatal outcomes
We selected seven outcomes relating to labour, delivery and neonatal
complications based on research highlighting these outcomes as asso-
ciated with maternal mental disorders.
1,2
Most outcomes were ascer-
tained using the MBR: preterm birth (gestational age <37 weeks), low
birthweight (birthweight <2500 g), SGA (i.e. birthweight <10th per-
centile for gender and gestational age), low 5-minute Apgar score
(<7) and Caesarean delivery (surgery codes KMCA10-KMCA12).
Neonatal deaths (death from any cause within 28 days of birth)
were identified in the Danish Civil Registration System.
Potential confounders
We adjusted for the following confounders in our main analyses:
maternal age at delivery (<25, 25–34 or ≥35 years); parity (1, 2 or
≥3); maternal marital status at delivery (married/cohabiting or
single/divorced/widowed); maternal highest education at delivery
Excluded (n=26867):
Children with missing or unlikely gestational age
(n= 23 676)
Children who had chromosomal abnormalities
(ICD-10 codes Q90–99) (n= 3191)
Liveborn singletons during 1997–2015 in Denmark (1 159 624)
Singletons born by 663 345 mothers (n= 1 132 757)
Children of mothers never
diagnosed with a mental disorder
in the Central Psychiatric Register
(n= 1 057 307)
Children of mothers with a
previous but not recent mental
disorder diagnosis (i.e. more than
2 years prior to conception of
index child) in the Central
Psychiatric Register (n= 48 646)
Children of mothers with a recent
mental disorder diagnosis (i.e. 2
years prior to conception up to
birth of index child) in the Central
Psychiatric Register (n= 26 804)
Fig. 1 Flowchart showing identification of study population. ICD-10, International Classification of Diseases, 10th revision.
Momen et al
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(elementary school/above elementary school); and calendar year
of delivery (1997–2000, 2001–2005, 2006–2010 or 2011–2015).
We additionally identified three pregnancy-related factors
(Supplementary Fig. 1): number of non-psychiatric hospital visits
during pregnancy (0–1, 2–3or≥4); smoking during pregnancy
(yes/no); pregnancy complications (yes/no for gestational hyperten-
sion/eclampsia [ICD-10 O12–O15], diabetes mellitus during
pregnancy [O24], pregnancy-related renal disease [O26.8] or ante-
partum haemorrhage [O46]). Data on these covariates were
obtained from the aforementioned registers as well as Statistics
Denmark’s registers on socioeconomic status.
Statistical analysis
Using R version 4.1.1 for Windows, we used logistic regression to cal-
culate odds ratios with95% CIs. In the main analyses, we adjusted for
maternal age at delivery, parity, marital status at delivery, highest edu-
cation at delivery andcalendar year of delivery. As the twopregnancy-
related factors could potentially be on the causal pathway, we adjusted
for these in an additional analysis. To account for dependence between
siblings, we used robust variance estimators for correction of standard
errors. The main analyses were repeated for each mental disorder type.
For marital status, smoking and education covariates,0.5, 3.3 and 3.4%
of values were missing, respectively; we applied multivariate logistic
regression imputation by chained equations with 20 imputations to
impute missing values.
Additional analysis
We also considered stillbirth, identified in the MBR. It should be
noted that while the denominator for the neonatal outcomes
included all live born children, the denominator for the outcome
of stillbirth was the sum of all registered stillbirths and live births.
In addition to the broad categorisation of the outcomes, we con-
sidered several of them in more detail to see if results varied with the
outcomes. We considered preterm birth at <32 weeks and 32–26
weeks; low birth weight of <1500 g and 1500–2500 g; SGA in <3 per-
centile and 3–10 percentile; and emergent, planned and unspecified
Caesarean delivery.
We stratified the analyses to investigate whether the risk of
adverse outcomes varied according to whether the mother had
been prescribed and redeemed psychotropic medication during
pregnancy, defined by Anatomic Therapeutic Chemical codes
(N05 Psycholeptics and N06 Psychoanaleptics) in the Danish
National Prescription Register.
We carried out three sensitivity analyses to test the robustness of
our results. First, we assessed the impact of maternal low birthweight
(maternal birthweight <2500 g, obtained from the MBR) as a con-
founder. As there was a relatively high proportion of missing data
on maternal birthweight (partly because some mothers were born
before the start of the MBR in 1973), we restricted these analyses to
children whose mothers had available birthweight data (n= 602 880)
and compared odds ratios with and without the addition of mater-
nal low birthweight as a confounder. Second, we restricted the study
population to firstborn children only (n= 494 354) to compare out-
comes in children with siblings to children without siblings, as it has
previously been demonstrated that parity influences associations
between maternal mental disorders and neonatal outcomes.
11
Third, for the same reason, we restricted the population to one
child per mother, selected at random (n= 663 345).
Results
The characteristics of the mothers of children in the study popula-
tion are shown in Table 1. Among the 1 132 757 children, 48 646
(4.3%) were born to mothers with past mental disorder diagnoses,
15 899 (1.4%) to mothers with recent mental disorder diagnoses
and 10 905 (1.0%) to mothers with persistent mental disorder diag-
noses. Compared to mothers without a mental disorder diagnosis,
mothers in all exposure groups were more likely to be have a
higher number of non-psychiatric hospital visits during pregnancy;
be single, divorced or widowed; not complete education beyond
elementary school; and to have been prescribed a psychotropic
medication during pregnancy. Additionally, mothers with past
diagnoses were more likely to have at least their third child.
Mothers with recent or persistent diagnoses were more likely be
younger and primiparous.
The numbers and proportions of each outcome are shown in
Table 2. The most common mental disorders among mothers
were neurotic disorders (2.6% of children had a mother with a
past diagnosis; 1.0% recent; 0.3% persistent) and mood disorders
(1.2% past; 0.6% recent; 0.2% persistent).
Main analyses
The risk of all adverse neonatal outcomes was elevated for children
of mothers with either past, recent or persistent mental disorders,
compared to the reference group, with the exception of neonatal
death (Fig. 2 and Supplementary Table 2). For preterm birth, low
birthweight, SGA, low Apgar score and Caesarean delivery, the
risks followed the same pattern (to varying extents): highest
among children of mothers with a persistent diagnosis, followed
by children of mothers with a recent diagnosis and then by children
of mothers with a past diagnosis. For example, the adjusted odds
ratio for preterm birth was 1.62 (95% CI 1.51–1.74) for children
of mothers with a persistent disorder, 1.35 (95% CI 1.27–1.44) for
children of mothers with a recent disorder, and 1.27 (95% CI
1.22–1.32) for children of mothers with a past diagnosis. Adding
the pregnancy-related factors resulted in attenuated odds ratios,
with the odds ratios for SGA and neonatal death suggesting
reduced risk (Fig. 2 and Supplementary Table 2).
For neonatal death, a different pattern was observed. The
adjusted odds ratio was highest for children of mothers with a
recent diagnosis (1.20, 95% CI 0.88–1.65), followed by children of
mothers with a past diagnosis (1.02, 95% CI 1.51–1.74). It was
slightly reduced for children of mothers with a persistent mental
disorder (0.96, 95% CI 0⋅62–1.48). Statistical significance was not
reached following any type of exposure.
Analyses by mental disorder type
Results by mental disorder type can be found in the Supplementary
Table 3. No consistent patterns emerged across mental disorders or
outcomes. For past maternal diagnoses, adjusted models demon-
strated that the strongest association was observed for development
disorders and low Apgar score (2.23, 95% CI 0.55–8⋅97). For recent
maternal diagnoses, the strongest association was observed for
schizophrenia and low Apgar score (CI 1.90, 95% CI 0.90–4.01).
For persistent maternal diagnoses, the strongest association was
observed for substance use disorders and low Apgar score (3.22,
95% CI 1.43–7.23). Reduced odds were seen for several pairs, with
statistical significance reached for Caesarean delivery for children
whose mothers had a past eating disorder (0.91, 95% CI 0⋅85–0.98)
Additional analyses
Supplementary Table 4 shows there were 4520 stillbirths in the
period of interest. The risk of stillbirth was increased for recent
mental disorders (odds ratio 1.25, 95% CI 1.01–1.55), but statistical
significance was not reached for past or persistent mental disorders.
Considering the outcomes in more detail suggested some differ-
ences in risks (Supplementary Table 5). For example, the odds ratio
Maternal mental disorders and neonatal outcomes
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for more extreme preterm birth (odds ratio 1.37, 95% CI 1.25–1.51)
was higher than the risk for preterm birth at 32–36 weeks (1.28,
95% CI 1.21–1.35) among those with past mental disorders only.
However the odds ratios for preterm birth at 32–36 weeks gesta-
tional age took higher values among those with recent or persistent
disorders. Odds ratios were slightly higher for planned Caesarean
delivery than emergent Caesarean delivery across exposure groups.
We observed some differences in associations when the sample
was stratified by maternal psychotropic medication use during preg-
nancy (Supplementary Fig. 2 and Table 6). For example, among
children in the recent exposure group whose mothers had taken
psychotropic medication during pregnancy, there was an odds
ratio of 1.60 (95% CI 0.90–2.86) for neonatal death; for those
whose mothers had not taken psychotropic medication during preg-
nancy, the odds ratio was 0.98 (95% CI 0.65–1.46). For the persistent
group, the pattern was in the opposite direction (0.62, 95% CI
0.26–1.48 for those whose mothers did take psychotropic medication
during pregnancy versus 1.11, 95% CI 0.67–1.86 for those whose
mothers did not take psychotropic medication during pregnancy).
The addition of maternal low birthweight as a potential con-
founder changed the results minimally (Supplementary Table 7
and Fig. 3).
Most adjusted odds ratios were all slightly reduced when
restricted to firstborn children (Supplementary Fig. 3 and
Table 8). For neonatal death following past diagnoses, the direction
of association changed (from elevated risk in the main analysis to
reduced risk in this analysis); for recent diagnoses, the odds ratio
was further increased. When the population was limited to one
child per mother, selected at random, several point estimates were
higher than they were for the main analysis for children exposed
to past or persistent mental disorders (Supplementary Table 9).
Discussion
We found that the risk of preterm birth, low birthweight, SGA, low
Apgar score, Caesarean delivery and neonatal death was increased
among children in any of the exposure groups: any past, recent or
persistent maternal mental disorder diagnoses. For these outcomes,
we observed higher point estimates among children whose mothers
had a persistent diagnosis than among children whose mothers had
a past or recent diagnosis. However, neonatal death was increased
only among children whose mothers had a past or recent diagnosis
only, not persistent diagnoses, which appears contradictory.
Table 1 Characteristics of study population according to exposure status, n(%)
Unexposed group
(n= 1 057 307)
Past mental disorders
only (n= 48 646)
Recent mental disorders
only (n= 15 899)
Persistent (past/recent) mental
disorders (n= 10 905)
Characteristics
Maternal age at delivery
<25 years 133 819 (13%) 7709 (16%) 5078 (32%) 2740 (25%)
25–34 years 734 883 (70%) 30 994 (64%) 8703 (55%) 6369 (58%)
≥35 years 188605 (18%) 9943 (20%) 2118 (13%) 1796 (16%)
Parity
1 459 710 (43%) 20 686 (43%) 8295 (52%) 5663 (52%)
2 399 815 (38%) 17 894 (37%) 4636 (29%) 3338 (31%)
≥3 197 782 (19%) 10 066 (21%) 2968 (19%) 1904 (17%)
Number of non-psychiatric hospital visits during pregnancy
0–1 500 446 (47%) 16 121 (33%) 4962 (31%) 2733 (25%)
2–3 416 038 (39%) 20 558 (42%) 6516 (41%) 4577 (42%)
≥4 140 823 (13%) 11 967 (25%) 4421 (28%) 3595 (33%)
Pregnancy complications 87 205 (8.2%) 6140 (13%) 2184 (14%) 1786 (16%)
Maternal smoking during pregnancy
No 860 588 (81%) 34 335 (71%) 9945 (63%) 6373 (58%)
Yes 162 107 (15%) 12 749 (26%) 5346 (34%) 4177 (38%)
Missing 34 612 (3.3%) 1562 (3.2%) 608 (3.8%) 355 (3.3%)
Maternal marital status at delivery
Single, divorced or widowed 74 143 (7%) 7391 (15%) 3638 (23%) 2786 (26%)
Married or cohabiting 977 656 (92%) 41 086 (84%) 12 183 (77%) 8907 (74%)
Missing 5508 (1%) 169 (<1%) 78 (<1%) 22 (<1%)
Maternal highest education at delivery
Elementary schoo l 184 975 (17%) 15 632 (32%) 6888 (43%) 5332 (49%)
Above eleme ntary school 834 896 (79%) 32 209 (66%) 8539 (54%) 5365 (49%)
Missing 37 436 (4%) 805 (2%) 472 (3%) 208 (2%)
Calendar year of delivery
1997–2000 243 698 (23%) 3814 (8%) 2666 (17%) 888 (8%)
2001–2005 290 634 (27%) 9086 (19%) 3894 (24%) 1838 (17%)
2006–2010 279 414 (26%) 15 992 (33%) 4634 (29%) 3359 (31%)
2011–2015 243 561 (23%) 19 754 (41%) 4705 (30%) 4820 (44%)
Redeemed psychotropic
prescriptions during pregnancy
17 621 (2%) 5489 (11%) 4352 (27%) 4325 (40%)
Sex of child
Male 542 501 (51%) 24 888 (51%) 8223 (52%) 5557 (51%)
Female 514 806 (49%) 23 758 (49%) 7676 (48%) 5348 (49%)
Outcomes
Preterm birth (<37 weeks) 50579 (4.8%) 3037 (6.2%) 1135 (7.1%) 937 (8.6%)
Low birthweight (<2500 g) 35 115 (3.3%) 2236 (4.6%) 839 (5.3%) 697 (6.4%)
Small for gestational age 101 615 (9.6%) 5416 (11%) 1994 (13%) 1473 (14%)
Apgar score at 5 min 7263 (0.7%) 378 (0.8%) 150 (0.9%) 141 (1.3%)
Caesarean sec tion 191 614 (18%) 10 614 (22%) 3291 (21%) 2505 (23%)
Neonatal death 1966 (0.2%) 91 (0.2%) 40 (0.3%) 21 (0.2%)
Momen et al
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When the sample was stratified by maternal psychotropic medi-
cation use during pregnancy, for most outcomes, we observed
increased risk among mothers with recent or persistent diagnoses
who had not been prescribed medication compared with mothers
with recent or persistent diagnoses who had been prescribed medi-
cation. These results could reflect mothers with potentially active
and untreated mental disorders or discontinuation of psychotropic
medication. We also note there was between-group variation in
sample size, and thus the prevalence of outcomes when the
sample was stratified by medication use. Sensitivity analyses indi-
cate some differences in odds ratios, though there is no identifiable
pattern of change in results across exposure groups or outcomes.
Comparison with previous literature
While there were no consistent patterns by mental disorder types,
our results support those from studies indicating that some mater-
nal mental disorders are associated with adverse neonatal out-
comes.
1,2
The grouping of diagnoses in this study into past, recent
and persistent makes direct comparison with past research challen-
ging; however, it is possible to identify some differences and similar-
ities. Kelly et al
12
reported that odds ratios for preterm birth and low
birthweight were 1.6 (95% CI 1.4–1.9) and 2.0 (95% CI 1⋅7–2.3),
respectively, among children born to mothers with psychiatric dis-
orders, which are higher than odds ratios found in our study. Unlike
our study, Kelly et al’s definition of psychiatric disorders did not
include substance use disorders, which were examined separately
and revealed even higher odds ratios. Yin et al
13
reported an odds
ratio of 1.31 (95% CI 1.28–1.34) for maternal psychiatric diagnoses
and preterm birth, which was higher than we observed for past diag-
noses, but lower than we observed for recent or persistent diagnoses.
Our results indicate similar increases in risks for preterm birth
and low birthweight compared with studies on substance use
disorders,
12,14
schizophrenia,
7,8,15
mood disorders
5,16
and eating
disorders.
10
Risks of preterm birth and low birthweight were
found to be higher in children exposed to maternal personality dis-
orders but to a slightly lower extent than previous studies.
17,18
Consistent with Jablensky et al,
15
we found an increased risk of
low Apgar score in children exposed to maternal schizophrenia.
For personality disorders, odds ratios for low Apgar score in this
study were below Marshall et al’s
17
pooled effect estimate. For
mood disorders
15,16
and eating disorders,
9,10
the risk of low Apgar
score in our study fell within or close to ranges observed in previous
studies. For recent diagnoses of any mental disorder, the risk of low
Apgar score was similar to a recent Danish study by Heuckendorff
et al
11
(1.49, 95% CI 1.04–1.58), which examined mothers with
mental disorders treated in primary care in the year before child-
birth. Though the population in our study overlaps with
Heuckendorff et al, we have provided novel findings regarding
pre-conception maternal diagnoses, including persistent diagnoses.
Risks for Caesarean delivery were less elevated in our study
compared with previous studies on schizophrenia
7,8,19
and person-
ality disorders.
18
For intellectual disability, we found reduced risk of
Caesarean delivery, whereas an increased risk has previously been
reported.
20
For eating disorders, the reduced risk we observed for
Caesarean delivery was contrary to some previous findings,
10
but
similar to others.
9
For neonatal death, our odds ratios fell around the estimates of
previous studies for substance use
14
and mood disorder.
16
For
schizophrenia and eating disorders, we found a reduced risk of neo-
natal death. A previous study has also indicated reduced risk in
eating disorders,
9
whereas previous studies consistently demon-
strate increased risk in schizophrenia.
7,8,19
It should be noted that
neonatal death is the rarest outcome of those studied, and the
observed odds ratios would result in a small increase in absolute
terms (i.e. neonatal deaths per 100 000 live births: 186 in mothers
with no diagnoses, 187 in mothers with past diagnoses and 228 in
mothers with recent diagnoses).
Table 2 Exposure status of the children in the study population by type of maternal mental disorder
Maternal mental disorder type
Exposure status –Maternal mental disorders
No mental
disorders
Past only mental
disorders
Recent only mental
disorders
Persistent (past and recent)
mental disorders
Any mental disorder 1 057307 (93.3%) 48 646 (4.3%) 15 899 (1.4%) 10 905 (1.0%)
Mental and behavioural disorders due to psychoactive
substance use
Includes use of alcohol, cannabis, cocaine, nicotine,
opioids, sedatives, hypnotics, anxiolytics, etc.
1 127334 (99.5%) 3675 (0.3%) 1296 (0.1%) 452 (<0.1%)
Schizophrenia and related disorders
Includes schizophrenia, schizotypal disorders,
schizoaffective disorders and other psychotic
disorders.
1 127674 (99.6%) 3322 (0.3%) 931 (<0.1%) 830 (<0.1%)
Mood disorders
Includes bipolar disorder, depressive disorders, etc.
1 110590 (98.0%) 13 586 (1.2%) 6423 (0.6%) 2158 (0.2%)
Neurotic, stress-related and somatoform disorders
Includes anxiety disorders, phobias, obsessive-
compulsive disorders, etc.
1 088108 (96.1%) 29 974 (2.6%) 11 131 (1.0%) 3544 (0.3%)
Eating disorders
Includes anorexia nervosa, bulimia nervosa, etc.
1 121189 (99.0%) 8713 (0.8%) 1611 (0.1%) 1244 (0.1%)
Personality disorders
Includes paranoid personality disorder, etc.
1 114493 (98.4%) 12 175 (1.1%) 4004 (0.4%) 2085 (0.2%)
Intellectual disabilities
Includes mild to profound mental intellectual disability
1 132144 (99.9%) 442 (<0.1%) 121 (<0.1%) 50 (<0.1%)
Developmental disorders
Includes autism spectrum disorders
1 132505 (100.0%) 191 (<0.1%) 35 (<0.1%) 26 (<0.1%)
Behavioural disorders
Includes attention-deficit hyperactivity disorder,
conduct disorders, childhood emotional
disorders, etc.
1 126894 (99.5%) 4768 (0.4%) 724 (<0.1%) 371 (<0.1%)
See Supplementary Appendix p. 4 for details of the International Classification of Diseases (ICD)-8 and ICD-10 codes used to define each mental disorder.
Maternal mental disorders and neonatal outcomes
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Mental disorders are associated with various risk factors,
including risky health behaviours.
21
Several of these factors are
also associated with adverse outcomes and may mediate associa-
tions between maternal mental disorders and neonatal outcomes.
Prenatal exposure to tobacco smoke is an obvious covariate of
interest. Women with mental disorders are more likely to continue
smoking throughout pregnancy than women without mental dis-
orders.
22
The effect of smoking during pregnancy is clear, with
evidence consistent that it increases the risk of a range of
adverse birth outcomes.
23
Alternatively, these associations may
be modified by medication use.
24
Whilewewereabletoadjust
for maternal smoking during pregnancy and some other relevant
factors (e.g. education attainment), we do not have data on all
potentially relevant covariates in the Danish registers (e.g. binge
drinking).
Strengths and limitations
This study used Danish register data, which provide nationwide
coverage and minimise selection and reporting biases. Diagnoses
Outcome
Preterm birth
Model Main Analysis
Low birthweight
Small for gestational age
Low Apgar score at 5 min
Caesarean delivery
Neonatal death
No adjustment
Adjusted
Fully adjusted
No adjustment
Adjusted
Fully adjusted
No adjustment
Adjusted
Fully adjusted
No adjustment
Adjusted
Fully adjusted
No adjustment
Adjusted
Fully adjusted
No adjustment
Adjusted
Fully adjusted
0.5 1 1.5 2
Exposure Type Past Only Recent Only Persistent
Fig. 2 Adjusted odds ratios for the associations between maternal mental disorder diagnoses and birth outcomes. Crude: no adjustments.
Adjusted: adjusted for maternal age at delivery; marital status; highest education; calendar year of delivery. Fully adjusted: adjusted for maternal
age at delivery; marital status; highest education; calendar year of delivery; number of non-psychiatric hospital visits during pregnancy; smoking
during pregnancy; pregnancy complications.
Momen et al
6
https://doi.org/10.1192/bjp.2024.164 Published online by Cambridge University Press
in the Danish registers have been validated for several mental disor-
ders. These analyses provide a comprehensive overview of neonatal
outcomes among children of mothers with various mental disor-
ders, which addresses a key knowledge gap. Additionally, this
study provides a clinically meaningful examination of the impact
of past versus recent versus persistent diagnoses.
There are several limitations that should be considered. First,
we relied on register-based diagnoses of mental disorders which
reflect individuals who seek treatment in a hospital setting, and
thus likely represent more severe cases. Diagnosis date is used
as a proxy for mental disorder onset, though it may not reflect
true onset. There is no information within Danish registers
regarding remission; therefore, we do not know whether the
absence of a recent diagnosis reflects a mother no longer requir-
ing treatment or not seeking hospital treatment. Second, our
study focused mainly on live births since we aimed to examine
some postnatal outcomes. We did included stillbirth as an
outcome, but covariate data is missing at a higher rate for still-
births. Third, we were unable to include several potential con-
founders (e.g. planned versus unplanned pregnancy, or stigma
from healthcare professionals) as they are not recorded within
the Danish registers; these should be considered in future popu-
lation-based studies. Fourth, we focused on the magnitude of
estimates rather than statistical significance, but multiple com-
parisons may mean that some associations occurred due to
chance. When adjusting for multiple comparisons, not all asso-
ciations remained statistically significant. Fifth, we did not con-
sider paternal mental disorders. A recent study in the Swedish
population indicates that mental disorder diagnoses in fathers
is associated with preterm birth.
13
Follow-up studies could
compare the impact of maternal versus paternal mental disorders
on neonatal outcomes. Sixth, it was not within the scope of this
study to consider associations between specific mental disorders
and neonatal outcomes in more detail. Future studies could con-
sider past and recent diagnoses of specific mental disorders in
more detail, including stratification by specific medications rele-
vant to each disorder. Finally, while our results support those
reported in previous studies, the generalisability of our results
outside Denmark is unclear.
In conclusion, the results have important research and clinical
implications. Future studies should focus on examining the bio-
logical, psychological and social pathways that mediate associa-
tions between maternal mental disorders and adverse neonatal
outcomes, such that targeted intervention can be implemented
in perinatal and mental healthcare systems to improve outcomes
among mothers and babies. The results indicate an elevated risk
of several adverse outcomes not only in children of mothers
with recent mental disorders, but also in children of mothers
with past mental disorders. This highlights that mothers with
any history of mental disorders, even those in remission, should
receive additional support during the prenatal period. More
broadly, this study underscores the need for improved prevention
and early intervention of maternal mental disorders to mitigate
adverse neonatal outcomes, especially in mothers with recent
diagnoses.
Overall, this study provides evidence for increased risk of
preterm birth, low birthweight, SGA, low Apgar score, Caesarean
delivery and neonatal death among children of mothers with
mental disorders diagnosed at most time points. These results
underscore the need for additional follow-up of these women
during the prenatal period. Further research is needed to identify
modifiable factors that mediate associations between maternal
mental disorders and adverse neonatal outcomes to highlight if,
and when, intervention could potentially mitigate adverse
outcomes.
Natalie C. Momen , PhD, National Centre for Register-based Research, Aarhus
University, Aarhus, Denmark; Hannah Chatwin, PhD, National Centre for Register-
based Research, Aarhus University, Aarhus, Denmark; Katrine Holde, MSc, National
Centre for Register-based Research, Aarhus University, Aarhus, Denmark; Xiaoqin Liu,
PhD, National Centre for Register-based Research, Aarhus University, Aarhus, Denmark;
Trine Munk-Olsen, PhD, National Centre for Register-based Research, Aarhus
University, Aarhus, Denmark; and Department of Clinical Research, University of
Southern Denmark, Odense, Denmark; Kathrine Bang Madsen, PhD, National Centre
for Register-based Research, Aarhus University, Aarhus, Denmark; Liselotte
Vogdrup Petersen, PhD, National Centre for Register-based Research, Aarhus
University, Aarhus, Denmark
Correspondence: Natalie C. Momen. Email: ncm@clin.au.dk
First received 20 Oct 2023, final revision 28 May 2024, accepted 17 Jun 2024
Supplementary material
Supplementary material is available online at https://doi.org/10.1192/bjp.2024.164
Data availability
Access to individual-level Danish data is governed by Danish authorities. These include the
Danish Data Protection Agency, the Danish Health Data Authority, the Ethical Committee
and Statistics Denmark. Each scientific project must be approved before initiation, and approval
is granted to a specific Danish research institution. Researchers at Danish research institutions
may obtain the relevant approval and data. International researchers may gain data access if
governed by a Danish research institution having needed approval and data access.
Author contributions
N.C.M.: investigation, methodology, visualisation, writing –original draft, writing –review &
editing; H.C.: investigation, formal analysis, methodology, visualisation, writing –review &
editing; K.H.: formal analysis, visualisation, writing –review & editing; X.L.: investigation,
methodology, writing –review & editing; T.M.-O.: investigation, methodology, writing –review &
editing; K.B.M.: investigation, methodology, writing –review & editing; L.V.P.: conceptualisation,
investigation, methodology, supervision, writing –review & editing.
Funding
L.V.P. received funding from Lundbeck Foundation (grant no. R276-2018-4581 and iPSYCH grant
R248-2017-2003). The investigators conducted the research independently. The funders had no
role in the design and conduct of the study; collection, management, analysis and interpret-
ation of the data; preparation, review or approval of the manuscript; or the decision to submit
the manuscript for publication.
Declaration of interest
None.
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