Institute of Psychiatry, London
University of Bristol
University of Plymouth
Imperial College School of Medicine, London
Correspondence: Dr T. O'Connor, Institute of Psychiatry, III Denmark Hill, London SE5 8AF, UK. Tel: +44 (0) 20 7848 0873; Fax: +44 (0) 20 7848 0866; e-mail: spjwtoc{at}iop.kcl.ac.uk
Declaration of interest ALSPAC is funded by The Wellcome Trust, the Department of Health, the Department of the Environment, and the Medical Research Council. Support for this analysis was provided by the PPP Healthcare Medical Trust.
See editorial, pp.
478479, this issue.
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ABSTRACT |
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Aims To test the hypothesis that antenatal maternal anxiety predicts behavioural problems at age 4 years.
Method Data were collected on multiple antenatal and postnatal assessments of maternal anxiety and depression, antenatal and obstetric risks, psychosocial risks and children's behavioural/emotional problems (n=7448).
Results Antenatal maternal anxiety predicted behavioural/emotional problems in boys (OR=2.14, 95% CI 1.48-3.10) and girls (OR=1.88, 95% CI 1.3-2.69) after accounting for covariates. When covarying maternal anxiety up to 33 months postnatally, antenatal anxiety continued to predict total problems in boys (OR=1.56, 95% CI 1.02-2.41) and girls (OR=1.51, 95% CI 1.22-2.81).
Conclusions There could be a direct effect of maternal mood on foetal brain development, which affects the behavioural development of the child.
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INTRODUCTION |
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METHOD |
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Data from at least one questionnaire assessment were available on 12 998 women. However, the total sample available for analysis was substantially lower for several reasons. First, data were collected during several assessments in the antenatal and postnatal period. The rate of attrition per questionnaire assessment was acceptable, in the range 5-15%, but the net effect was cumulative over the multiple assessments. Second, exclusion criteria were specified a priori to ensure our ability to evaluate the timing of antenatal stress on offspring outcome. We excluded those individuals who did not complete the antenatal questionnaires in the allotted time frame (for the first assessment, 6% of the total were excluded, the most obvious reason for this being that these pregnant mothers joined the study later in pregnancy; for the second assessment, the allotted time frame was defined as after 22 weeks and before 39 weeks, with 1% of the total excluded; a further 3% were excluded because the questionnaires were completed in overlapping time periods or in the reverse order), children from multiple births and children born before 33 weeks' gestation. The resulting sample size was 7448.
Maternal anxiety and depression were assessed on two occasions in the antenatal period (18 weeks' and 32 weeks' gestation) and at 8 weeks, 8 months, 21 months and 33 months postnatally. Data on covariates used in the analyses were assessed during pregnancy and shortly after birth. Data on children's behavioural/emotional problems were collected at 47 months.
Measures
Maternal anxiety was measured using the anxiety items from the
CrownCrisp index, a validated self-rating inventory
(Birtchnell et al,
1988; Sutherland & Cooper,
1992). There is no well-established clinical cut-off for this
measure; we therefore identified as anxious those mothers who scored in the
top 15% (or as close as possible) at each assessment. In this sample, the
internal consistencies exceeded 0.80. Maternal depression was assessed using
the Edinburgh Postnatal Depression Scale (EPDS), a widely-used 10-item report
questionnaire that has been shown to be valid in and outside of the postnatal
period (Cox et al,
1987; Murray & Carothers,
1990). Internal consistencies exceeded 0.80. A cut-off of 13 was
used because it predicts clinical depression based on diagnostic criteria
(Murray & Carothers,
1990).
Key obstetric factors that were likely to be directly or indirectly related to children's behavioural outcomes were included as covariates. Specific variables were gestational age, birthweight for gestational age (corrected for gender, parity and maternal age and weight), mode of delivery (Caesarean with and without labour, vaginal delivery), and first- or later-born status.
Self-reported smoking and alcohol consumption in early pregnancy were comparatively infrequent. For smoking, risk status was defined as any cigarette or other smoking defined in the 2 weeks prior to completion of the 18-week gestation questionnaire; for alcohol intake, risk status was defined as 1+ units/day in the first 3 months of pregnancy. None of the other measures of smoking and drinking at the later pregnancy assessment improved prediction once these earlier indicators were included in the models, and we therefore retained only the 18-week measures in the analyses.
To control for the possibility that antenatal anxiety was a response to a
known or suspected problem with the foetus (which could also have led to
behavioural disturbance), we asked whether the mother had concerns about the
baby because of a test result in pregnancy. A risk score of 1 was given if the
parent reported that she was affected a lot or fairly
affected by the possibility of an abnormal test result; otherwise a
score of 0 was assigned. Two indicators of socio-economic status, assessed
during pregnancy, were included. A crowding scale, based on the ratio of the
number of persons to the total number of rooms in the house, was used as a
continuous variable. Maternal education was coded on a four-point scale, with
the lowest score indicating minimal educational qualifications and the highest
level indicating a university degree. Maternal age (in pregnancy) was included
as a dichotomous variable, categorised as 20 years or
21 years,
because preliminary analyses showed that only those children of young mothers
were at increased risk for behavioural/emotional problems.
Behavioural adjustment in children at age 4 years was based on parent reports (Goodman & Scott, 1999) using an adaptation of a previously widely used index of psychiatric symptoms in children (Elander & Rutter 1996). This measure, which has three problem behaviour subscales (conduct problems, emotional problems, hyperactivity/inattention), has established links with clinical levels of disturbance (Goodman & Scott, 1999). Internal consistencies of the scales ranged from 0.62 to 0.75. We identified children with difficulties based on statistically high scores, using a cut-off of 2 standard deviations (s.d.) above the mean. Cut-off scores were derived separately for males and females because of the gender differences in mean scores on these measures. Consequently, analyses were conducted separately for males and females.
Data analysis
The analytic aims were twofold. The first was to investigate whether
antenatal anxiety is a risk for behavioural/emotional problems in children. We
therefore examined whether antenatal anxiety predicts behavioural/emotional
problems at age 4 years after controlling for key antenatal, obstetric and
socio-demographic risks. In addition, to determine whether the antenatal risk
for behavioural/emotional problems was specific to maternal antenatal anxiety
or more generally to maternal mental health, we included in the analyses
measures of ante- natal and postnatal depression
(Murray & Cooper, 1997).
The second aim was to examine whether there could be risks linked specifically
to anxiety in the antenatal period. We therefore examined whether maternal
antenatal anxiety predicted behavioural/emotional problems in children after
controlling for multiple postnatal assessments of maternal anxiety. Throughout
the analyses, we begin by reporting the findings for total
behavioral/emotional problems and note if findings differ by specific
behavioural problem sub-scale.
As expected, the large majority of children in this community sample did not exhibit clinically meaningful levels of psychopathology. Consequently, because we were interested in whether the findings were of clinical relevance, we initially report analyses using extreme scores using established cut-off scores (where available) or high scores defined statistically. We follow this approach with analyses of individual differences. As detailed below, the findings are substantively identical. The two approaches require somewhat different analytical methods, however. For analyses based on a dichotomous dependent variable, logistic regression was used and odds ratios (ORs) are reported as the index of association. When we examined the continuous measure of behavioural/emotional problems as the dependent variable, ordinary least-squares regression was used. In both kinds of analyses, a hierarchical approach was used in which the antenatal obstetric and psychosocial covariates were entered at step 1 and the measures of maternal anxiety and depression in pregnancy and the postnatal period were entered at step 2. The estimates reported in Tables 2 and 3 are from the final model, and indicate the effect of each variable controlling for the effects of all other variables in the model.
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RESULTS |
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Preliminary analyses indicated that birthweight, gestational age and mode of delivery were not associated with the outcome measures once we controlled for birthweight for gestational age. Additionally, first and later pregnancies were combined because the effects of antenatal anxiety on offspring outcomes were substantively identical for first- and later-born children.
Maternal anxiety
All pairwise correlations between measures of maternal anxiety exceeded
r=0.50, and the magnitude was inversely associated with the time
interval between assessments. The large sample size made it possible to
identify specific groups with elevated anxiety only at particular times. Using
the categorical distinction of a cut-off for high anxiety of the top 15%,
64.6% experienced no anxiety, 14.6% experienced elevated anxiety on one
occasion only, 7.7% experienced elevated anxiety on two occasions, 5.2%
experienced elevated anxiety on three occasions, 3.6% experienced elevated
anxiety on four occasions, 2.7% experienced elevated anxiety on five occasions
and 1.8% experienced elevated anxiety on all six occasions.
Bivariate associations between maternal anxiety and
behavioural/emotional problems at age 4 years
The findings in Table 1
indicate that mothers who scored in the top 15% of the sample on anxiety at 18
or 32 weeks' gestation were generally 2-3 times more likely to have a child
who scored more than 2 s.d. above the mean in behavioural/emotional
problems.
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Multivariate associations
The next set of analyses provides a stronger test of the effects of
antenatal anxiety by including antenatal, obstetric and psychosocial
covariates, together with postnatal assessments of anxiety and depression at 8
weeks. The results for total problems for boys and girls are shown in
Table 2. The ORs in the models
represent the effect of the variable controlling for the effects of other
variables in the model. Mothers who experienced markedly elevated anxiety at
32 weeks' gestation were more than twice as likely to have children with
markedly elevated behavioural/emotional problems at 4 years of age (OR 2.14
for boys and 1.88 for girls). The effects of antenatal anxiety were equally
strong for boys and girls, although the prediction from other covariates
differed slightly for boys and girls. No significant interactions between late
antenatal anxiety and any of the covariates were detected. The findings for
the specific symptom sub-scales are given in
Table 3. Late antenatal anxiety
significantly predicted later behavioural/emotional problems for four of the
six outcomes.
Previous analyses indicated that the late antenatal anxiety effect was maintained after controlling for postnatal depression. As a test of the specific effects of anxiety in the antenatal period, we included in the model (from Table 2) the assessment of depression in the late antenatal period at 32 weeks' gestation. For neither boys nor girls was the significant effect of late antenatal anxiety reduced to non-significance when antenatal depression was included in the model predicting total problems.
Effects of postnatal anxiety
To determine whether or not the effect of antenatal anxiety could be
distinguished from the cumulative effect of postnatal anxiety throughout the
child's early years, we re-ran the models including maternal anxiety at 8, 21
and 33 months postnatally. Analyses indicated that, for both boys and girls,
the composite measure of total problems remained significantly associated with
late antenatal anxiety even when the effects of antenatal, obstetric and
psychosocial covariates, as well as four measures of postnatal anxiety, were
statistically controlled. In these models, the ORs for maternal anxiety at 32
weeks' gestation were 1.56 (95% CI 1.02-2.41) for boys and 1.51 (95% CI
1.01-2.27) for girls. In addition, for males, late antenatal anxiety was
associated significantly with hyperactivity/inattention at 4 years of age,
even after postnatal self-reports of anxiety at 8 weeks and 8, 21 and 33
months were included in the model (OR 1.85, 95% CI 1.22-2.81). Particularly
notable is the finding that including maternal anxiety in the postnatal period
had virtually no effect on the magnitude of antenatal prediction, and this is
despite the fact that postnatal maternal anxiety also significantly predicted
inattention/ hyperactivity at 4 years of age (only maternal anxiety at 21
months was statistically significant; OR 1.99, 95% CI 1.26-3.15).
Evaluating the robustness of the effect
A final series of analyses was carried out to demonstrate that these
associations held across the range of individual differences rather than only
at the extremes. When less extreme scores of behavioural/emotional problems
were used in the models (based on a cut-off score of 1 s.d. above the mean)
substantively similar results were obtained. For example, for the model
predicting total problems that included all covariates plus postnatal
assessments of anxiety through 33 months, the ORs were 1.39 (1.04-1.84) for
boys and 1.53 (1.12-2.10) for girls. Furthermore, in the most conservative
model that included the covariates plus postnatal assessments of anxiety
through 33 months, the effect of late antenatal anxiety was significant in a
regression analysis when we examined the continuous measure of maternal
anxiety and the continuous measure of behavioural/emotional problems in
children (for boys, ß=0.07, P<0.05; for girls, ß=0.06,
P<0.05).
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DISCUSSION |
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Limitations
The prospective longitudinal design and the large community sample provided
considerable power in assessing the connection between antenatal anxiety and
later child outcomes, but some limitations should be noted. First, the
selective attrition could mean that we are observing associations among the
less severely distrubed individuals. However, it does not seem that the
attrition would have fundamentally influenced the findings in a major way.
That is because the association between antenatal anxiety and outcomes was not
confined to the extreme ends of psychopathology, but was evident within the
normal range of maternal anxiety and children's behaviour. Whether the
obtained effects would have been larger if more of the psychologically
distressed individuals remained in the study is a possibility that we are
unable to test. A second consideration is that the data were based entirely on
maternal report. This is inevitable in large-scale studies, but it does raise
a methodological concern that the ratings of child behavioural/emotional
problems were influenced by reporter bias. That is, anxious mothers might be
more likely to over- (or mis-)report disturbance in their children. However,
if reporter bias were operating, we would not expect to find a
differential prediction from the antenatal period, and certainly not
when covarying multiple postnatal measures of maternal anxiety more
proximal to the assessment of behavioural/emotional problems. Other sources of
data on children's behavioural/emotional problems, notably teacher reports,
were not available at 4 years. Concerns about maternal reports of children's
behavioural/emotional problems must be balanced against the finding that the
effect was obtained across the range of individual differences and that
elevated scores do correspond to clinically documented psychopathology
(Goodman & Scott, 1999). Other explanations could also account for a transmission between maternal
anxiety and child behavioural disturbance, most notably genetic mediation
(Rutter et al, 1999).
However, if genetic mediation were operating it would not be likely to explain
why there is a specific connection between maternal antenatal anxiety
and children's disturbance even when multiple postnatal assessments were
covaried. Thus, the specific antenatal effect is noteworthy both in drawing
direct parallels with previous animal research and in countering alternative
explanations that the effect is due merely to reporter bias or genetic
transmission.
Antenatal anxiety predicts behavioural/emotional problems
Several features of the association between antenatal anxiety and
children's behavioural/emotional disturbance are of interest. First, the
nature of the antenatal risk derived from anxiety/stress rather than from
psychological disturbance more generally, indexed in our study by depression.
This differential finding is especially important given that anxiety rather
than depression is the analogue risk in animal studies and that depression and
anxiety are invariably moderately to highly correlated. Postnatal depression,
especially in the early weeks and months following birth, is a known risk
factor for behavioural/emotional problems in children
(Murray & Cooper, 1997).
Therefore, the finding that the antenatal anxiety effect was maintained when
postnatal depression was included indicates that the effect obtained is
neither mediated through postnatal depression nor explained by general
maternal distress. The apparent specificity of the antenatal anxiety effect is
also inconsistent with a simple reporter bias as an alternative explanation of
the findings.
Second, although there is some suggestion for specificity of risk associated with maternal antenatal mental health, it is far less clear whether the effects on children's behaviour are general or specific. Thus, the bivariate analyses showed that all three sub-scales were associated significantly with antenatal anxiety (Table 1), and this continued to be the case (albeit with two exceptions) when the covariates were included (Table 3). In the analysis that included multiple postnatal assessments of maternal anxiety, the prediction of total problems in both boys and girls from late antenatal anxiety remained significant; the only sub-scale that remained linked significantly with late antenatal anxiety was inattention/hyperactivity (in boys). It could be that the effects were strongest for the composite measure of total problems because this was the most reliable index of problems. The persistent effect on inattention/hyperactivity in boys parallels findings from animal research (Schneider & Moore, 2000).
Third, the results for total problems are consistent with developmental programming, or the notion that experiences in early life can persistently influence how the individual responds to later experiences (Ladd et al, 1996). This is the dominant model derived from the animal research findings, and is based on the finding that antenatal stress can permanently alter the developing HPA axis of the offspring. There are, as yet, few instances of developmental programming found in studies of human behavioural development, and further research on the mechanisms involved (e.g. HPA axis) is clearly needed. It is noteworthy that a model of foetal programming has gained considerable support in the cardiovascular research field (Barker, 1995). Fourth, the connection between antenatal anxiety and children's behavioural/emotional problems was found after controlling for key antenatal and obstetric risks, including birthweight for gestational age. This is an important consideration given that maternal antenatal stress predicts poor obstetric outcome (Hedegaard et al, 1993; Lou et al, 1994; Copper et al, 1996), which could have then increased the risk for behavioural/emotional problems in early childhood.
Finally, although all bivariate associations between antenatal anxiety and behavioural/emotional outcomes were substantial, the effect was partly, and in some cases completely, explained by co-occurring antenatal, obstetric or socio-demographic risks. Controlling for overlapping risks is a prerequisite in the effort to establish causal relationships. However, one side-effect is that we could have actually underestimated the real effect insofar as statistically controlling for socio-demographic risk might also account for a substantial amount of stress and anxiety experienced by mothers; indeed, crowding, one of the covariates used in this study, was the stress imposed in early animal studies (Keeley, 1962). Similarly, by controlling for postnatal anxiety on multiple occasions we could have over-controlled for the effects of antenatal anxiety.
Findings from experimental animal research point to the HPA axis as playing an important role in the connection between maternal antenatal stress and the adjustment of offspring (Clarke et al, 1994; Caldji et al, 2000). Overactive or dysregulated HPA axis activity is implicated in much psychopathology in adults and children, especially depression and anxiety (Chrousos & Gold, 1992). Whether this mechanism also explains the connections observed in this report requires further study.
This study shows a new and additional mode of transmission connecting maternal anxiety and children's behavioural/emotional problems. This should be considered together with other identified risks for psychopathology in children, such as psychosocial and genetic factors. These findings raise the possibility of benefit from an intervention programme targeted specifically at anxiety in pregnant women.
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Clinical Implications and Limitations |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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REFERENCES |
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Received for publication March 7, 2001. Revision received September 11, 2001. Accepted for publication September 11, 2001.
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