Association of Persistent and Severe Postnatal Depression With Child Outcomes

Key Points Question What is the association of differing levels of persistence and severity of postnatal depression with long-term child outcomes? Findings This observational study of 9848 women with varying levels of postnatal depression and 8287 children found that, compared with children of women with postnatal depression that did not persist, of either moderate or severe intensity, children of women with persistent and severe depression are at an increased risk for behavioral problems by age 3.5 years as well as lower mathematics grades and depression during adolescence. Furthermore, women with persistent postnatal depression are likely to experience significant depressive symptoms until at least 11 years after childbirth. Meaning Women with persistent and severe postnatal depression should be prioritized for treatment because they are likely to continue to experience high levels of depressive symptoms and because of the high risk of adverse child development.

P ostnatal depression (PND), also known as postpartum depression, is common, affecting approximately 10% of women in high-income countries, 1 with higher estimates in low-and middle-income countries. 2 Extensive research documents the association of PND with child development, including delayed cognitive and language development, higher rates of behavioral problems, insecure or disorganized attachment, lower school-leaving grades (ie, General Certificate of Secondary Education [GCSE] examinations in the United Kingdom) at 16 years, and higher rates of depression at 16 to 18 years of age. [3][4][5][6] An economic analysis suggests that, in the United Kingdom alone, the long-term costs of perinatal maternal mental health disorders may reach up to £8.1 billion (US $10.8 billion as of December 2017) per year for every 1-year birth cohort, principally because of the impact on the children. 7 Two factors suggested to be important in determining child outcomes in the context of maternal depression are the chronicity and severity of the maternal mood disorder, but data are limited for PND specifically. [8][9][10][11][12][13][14] Campbell and colleagues 15 found an increased risk for the child if PND persisted to 6 months after childbirth, when infants of mothers with persistent depression were less positive during interactions than infants of women with either no depression or remitted depression. Similarly, Petterson and Albers 8 reported that, in a sample of children younger than 5 years, compared with nonexposed children, those exposed to persistent maternal depression had lower cognitive scores (a decrement of 0.47 SDs for girls and 0.36 for boys). Beyond the perinatal period, the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Child studies, which examined depression in mothers of schoolaged children, have shown that the risk of offspring depression increased markedly with both the chronicity and severity of maternal depression. 16 In summary, evidence suggests that both persistent PND and severe PND raise the risk of adverse child outcomes. 3,[8][9][10] However, PND that is both severe and persistent has not been well described in the literature, as highlighted by a recent report for the US Preventive Services Task Force. 17 Studies have generally included small sample sizes, had shortterm follow-up periods, and examined a limited range of outcomes. Systematic research into this question is therefore required to establish the precise duration and symptom thresholds of significance for compromised child functioning. Elucidating the relative magnitude of the consequences for children of different levels of PND severity and persistence could help with targeting intervention resources, thereby limiting the time children are exposed to maternal depression and potentially compromised parenting.
Using participants in the Avon Longitudinal Study of Parents and Children (ALSPAC), we investigated the sequelae of PND on subsequent maternal depression and child outcome. The ALSPAC involves multiple assessments of maternal depression over the first 18 years of offspring life, including 2 postnatal assessments. Our study had 2 aims: (1) to examine the natural course of different levels of PND severity identified at 2 and 8 months after childbirth using growth curve modeling and (2) to examine the association of PND persistence and severity with child behavioral problems at 3.5 years of age, GCSE mathematics grades at 16 years of age, and self-reported depression at 18 years of age. These 3 offspring outcomes have been shown to be associated with maternal PND in this sample. [18][19][20] We hypothesized that (1) women with persistent and severe PND would continue to show elevated levels of depression at the following assessments and (2) children of women with persistent and severe PND would be at an increased risk for behavioral problems, lower mathematics grades, and higher rates of depression.

Sample
Our study sample comprised participants in the ALSPAC cohort (see the eAppendix in the Supplement for full details). 21 Ethical approval for the study was obtained from the ALSPAC Law and Ethics Committee and the local research ethics committees. All participants provided written informed consent. Data analysis was conducted from July 12, 2016, to February 8, 2017.
We had complete data on maternal depression in the postnatal year for 9848 mothers and at 11 years after childbirth for 6182 mothers. Data were available on child behavioral problems at 3.5 years of age for 8419 children, on GCSE mathematics grades at 16 years of age for 5198 children, and on offspring depression at 18 years of age for 3613 children.

Depression Measures
Maternal depression was measured using the self-rated Edinburgh Postnatal Depression Scale (EPDS; score range: 0-30, with higher scores indicating more severe depressive symptoms). 19,22 We defined 3 levels of PND severity: 13 to 14 points indicating moderate depression; 15 to 16 points, marked depression; and 17 or more points, severe depression. These threshold levels are consistent with those in previous analyses 23 and have been shown to have high specificity and positive predictive value for major depressive disorder (for ≥13

Key Points
Question What is the association of differing levels of persistence and severity of postnatal depression with long-term child outcomes?
Findings This observational study of 9848 women with varying levels of postnatal depression and 8287 children found that, compared with children of women with postnatal depression that did not persist, of either moderate or severe intensity, children of women with persistent and severe depression are at an increased risk for behavioral problems by age 3.5 years as well as lower mathematics grades and depression during adolescence. Furthermore, women with persistent postnatal depression are likely to experience significant depressive symptoms until at least 11 years after childbirth.
Meaning Women with persistent and severe postnatal depression should be prioritized for treatment because they are likely to continue to experience high levels of depressive symptoms and because of the high risk of adverse child development.
Postnatal depression was identified as persistent when an individual scored above the EPDS threshold at both the 2-and 8-month postnatal assessment. Postnatal depression was considered not persistent when someone scored above the threshold only at the 2-month postnatal assessment. In this way, we were able to examine the association of chronicity with the outcomes at different levels of PND severity.
We examined the association of PND with the outcomes for the following 7 mutually exclusive groups: (1) no depressionreference group (EPDS score of <13 points in the postnatal year), (2) moderate but not persistent depression (EPDS score of 13-14 points at 2 months; EPDS score of <13 points at 8 months), (3) marked but not persistent depression (EPDS score of 15-16 points at 2 months; EPDS score of <15 points at 8 months), (4) severe but not persistent depression (EPDS score of ≥17 points at 2 months; EPDS score of <17 points at 8 months), (5) moderate and persistent depression (EPDS score of 13-14 points at 2 months; EPDS score of ≥13 points at 8 months), (6) marked and persistent depression (EPDS score of 15-16 points at 2 months; EPDS score of ≥15 points at 8 months), and (7) severe and persistent depression (EPDS score of ≥17 points at 2 and 8 months).

Maternal Measures
Mothers participating in the ALSPAC indicated their highest education level on a questionnaire, which was sent out in their last trimester of pregnancy (eAppendix in the Supplement). Mothers with education continuing beyond 16 years of age were categorized as having high education (3841 [39%] of the sample), and those with education up to 16 years of age were categorized as having low education (6007 [61%]).

Child Measures
Rutter Total Problems Scale Child behavioral problems at 3.5 years of age were assessed by maternal report using the total problems scale (sum of hyperactivity and emotional and conduct problems) of the Rutter revised preschool questionnaire. 25 The measure was split into quartiles.

School-Leaving Mathematics Grades
Grades achieved in mathematics were extracted from records of the GCSE, which are external national public examinations taken at 16 years of age at the end of high school in the United Kingdom. The accepted binary coding was the achievement of an A* to a C grade (coded as 0) or no such achievement (coded as 1).

Offspring Depression
Offspring depression was assessed at 18 years of age using the Clinical Interview Schedule-Revised, a self-administered com-puterized interview. 26 A binary variable indicating a diagnosis of depression on the Clinical Interview Schedule-Revised or no such diagnosis was the outcome measure (eAppendix in the Supplement).

Confounding Variables
Owing to the relatively small sample size of mothers with PND that was persistent and marked (n = 75) or severe (n = 83), it was important to maintain the sample size and minimize the complexity of statistical models. Therefore, in the adjusted models, we controlled only for maternal education, the only variable in this sample shown to considerably influence the association between PND and child outcomes. 3,19 Statistical Analysis We explored the EPDS trajectories of women across 6 repeated assessments from 21 months to 11 years after childbirth using linear growth modeling and controlling for maternal education (Stata command: xtmixed, using mixed-effects maximum likelihood regression and unstructured covariance matrix; Stata, version 13 [StataCorp LLC]). We compared both the intercepts (overall mean EPDS scores across the repeated measures) and the slopes (the extent to which the scores increased or decreased over time, achieved by exploring the interaction between the PND and time variables). We present EPDS means and SDs at 21 months, 33 months, and 11 years.
We performed logistic and ordered logistic regressions, controlling for maternal education, to investigate the association between PND and the 3 child outcomes 18-20 (child behavioral problems at 3.5 years of age, GCSE mathematics grades at 16 years of age, and offspring depression at 18 years of age). We examined different levels of severity and persistence to elucidate the contribution of these factors and to explore a potential dose-response relationship.

Results
For the 9848 mothers in the sample, the mean (SD) age at delivery was 28.5 (4.7) years. Of the 8287 children, 4227 (51%) were boys and 4060 (49%) were girls. Table 1 presents means and SDs of EPDS scores for the 3 levels of PND severity (moderate, marked, and severe) at 21 months, 33 months, and 11 years for mothers with PND that did or did not persist to 8 months.

Long-term Course of Depression
Mean scores remained relatively stable from 21 months to 11 years for women with persistent PND. The mean EPDS score of women with persistent moderate PND remained high at subsequent times: 12.52 (5.00) points at 21 months and 12.45 (5.64) points at 11 years. Similarly, the mean EPDS score for women with persistent severe PND remained high with little improvement even up to 11 years after childbirth: 16.29 (4.98) points at 21 months and 14.49 (6.13) points at 11 years. Table 2 shows the analysis of the linear growth modeling indicating the mean EPDS scores across 6 time points (measured approximately yearly from 21 months to 11 years after childbirth) and the influence of PND severity and persistence on these trajectories. For the sample as a whole, the models indicate that, after the postnatal year, there was little change in the mean EPDS scores over time; mean EPDS scores rose by 0.004 points (95% CI, −0.02 to 0.03) at each repeated assessment. Compared with women who were not above the threshold in the postnatal year (EPDS score <13 points), all other groups had consistently higher EPDS scores up to 11 years after childbirth that progressed in a stepwise function. Compared with women in the reference group, women with an EPDS score of 13 to 14 points at 2 months only (moderate but not persistent PND) had higher EPDS scores of, on average, 3.46 points (95% CI, 2.86-4.05); women whose EPDS scores were 17 or more points at 2 months only (severe but not persistent PND) had higher EPDS scores of, on average, 5.84 points (95% CI, 5.13-6.55); women whose EPDS scores were 13 to 14 points at both 2 and 8 months (moderate and persistent PND) had higher EPDS scores of, on average, 6.91 points (95% CI, 5.98-7.83); and women whose EPDS scores were 17 or more points at both 2 and 8 months (severe and persistent PND) had higher EPDS scores of, on average, 9.90 points (95% CI, 8.73-11.08).
There was no evidence that the change in scores (the slope) differed between women with depression that did not persist and women with depression that did persist, suggesting that EPDS scores did not improve over time and were consistently higher compared with women with no depression (Table 2). Table 3 presents the odds ratios (ORs) of adverse child outcomes using the 3 thresholds of PND severity for women whose PND did or did not persist.

Nonpersistent PND
For mothers with PND that was not persistent (ie, depression only at 2 months after childbirth), the risk of child behavioral disturbance at 3.5 years of age was somewhat raised; this risk was similar whatever PND severity threshold was applied. Thus, the OR for child behavioral disturbance for the maternal group with moderate PND was 2.22 (95% CI, 1.74-2.83), for the group with marked PND was 1.91 (95% CI, 1.36-2.68), and for the group with severe PND was 2.39 (95% CI, 1.78-3.22). For the outcomes of GCSE mathematics grades at 16 years of age and offspring depression at 18 years of age, PND that was not persistent was not associated with increased risk. Furthermore, risk did not differ substantially between levels of severity with the exception of the group of mothers with marked PND, with offspring showing higher rates of depression at 18 years of age (OR, 2.34; 95% CI, 1.03-5.29).

Persistent PND
Children of women with persistent PND of moderate (OR, 3.04; 95% CI, 2.10-4.38) or marked severity (OR, 2.84; 95% CI, 1.71-4.71) were at higher risk of behavioral problems at 3.5 years of age compared with children of women with PND that was not persistent at any level of severity. The ORs for lower mathematics grades at 16 years of age and depression at 18 years of age were not substantially elevated in the context of either moderate or marked PND.

Discussion
We used a longitudinal prospective sample from a study with multiple assessments (ALSPAC) to examine the long-term course of PND and the association of PND at varying levels of severity and chronicity with child development. The adverse consequences on child development of severe and persistent PND is of particular note given the long-term follow-up of the children.
Using linear growth modeling, the data indicate that depression scores from 21 months to 11 years show relative stability. The data also indicate a step function, with higher mean depression scores for women whose PND persisted from 2 to 8 months after childbirth compared with women who scored below the threshold and those whose PND was not persistent. Further analysis indicated that, although the intercepts were higher for those with persistent PND, the slopes did not differ, suggesting that women with PND did not improve over time and women with persistent PND consistently remained at relatively higher EPDS scores. We found elevated risks for adverse outcomes for children of women who had persistent PND compared with women whose PND did not persist, and this association was especially pronounced in the group with persistent and severe PND. Postnatal depression that was not persistent either at moderate or marked severity level did not increase the risk in children for lower GCSE mathematics grades or offspring depression.  In practice, perinatal depression data are routinely collected in the United Kingdom, as recommended by the National Institute for Health and Clinical Excellence guidelines. 27 Our results show that women who meet criteria for PND both early and late in the postpartum year are at an increased risk for prolonged depression. In addition, PND is most likely to raise the risk for adverse child development when PND is severe and persistent. Health care professionals should identify these women for further referral because early and effective treatment could reduce the continued exposure of the child. Owing to the frequent contact with health care professionals in the perinatal period, it is possible to identify women with persistent PND during this period. Identification of women with PND may be associated with increased treatment costs, but the overall cost to the public sector of perinatal mental health problems is 5 times more than the cost of improving services, 7 further highlighting that early intervention and effective treatment of perinatal depression are a public health priority.
To date, the literature is mixed on whether treating maternal depression leads to positive child outcomes, particularly for depression in the early years of life. Treatments for PND have been relatively brief in duration and moderate in intensity; therefore, it is perhaps unsurprising that such interventions have not shown long-term benefits for either the mother or the child. [28][29][30][31] A limited number of interventions targeting the mother-child relationship have shown some short-term benefits for outcomes, such as attachment and behavior. 32-34 This finding highlights the complex issue of treatment recommendations, which may be further compounded by persistent and severe PND, which may in itself require more intensive treatment.

Strengths and Limitations
A particular strength of our analysis is the large sample, which allowed us to categorize depressive symptoms in a stepwise function. However, the higher thresholds of marked and severe PND do not invariably reflect clinically severe depression, and thus further research using diagnostic instruments is needed. Other strengths of this study include the longterm follow-up and the inclusion of different outcomes at different ages, all of which confirm the increased risk for children of women with persistent and severe PND symptoms.
Our study was also subject to some limitations, including a relatively small number of women meeting criteria for persistent and severe PND. The ALSPAC has high attrition, especially during the later time points. The patterns of missing data suggest that children most disadvantaged and more likely to have mothers with depression are overrepresented in the group with missing data 20 ; however, previous imputation analysis of the association between PND and mathematics grades and depression revealed that these associations did not attenuate following imputation. 19,20 Women experiencing significant levels of depression may be more likely to opt out of the study. Therefore, our report on the proportion of women who experience severe and persistent PND may be an underestimate. Owing to the small sample size of women with persistent and severe PND, we decided a priori to control for maternal education only, as this is the demographic variable that has consistently been shown to influence the association between PND and child outcomes. Previous analyses showed no attenuation of the association between PND and child outcomes by including other potential confounders. [18][19][20] The ALSPAC study did not collect information on whether women received psychological treatment, but the availability of such treatment at the time was severely limited. The available information indicates that less than 1% of the sample used antidepressants, which is too small a subsample for a subgroup analysis. Finally, women experiencing severe depressive symptoms may be more likely to report child behavioral problems. 35 This observation is a potential limitation for 1 of our outcomes; however, we present objective and selfreported outcomes at 16 and 18 years of age indicating a similar pattern of risk when PND is persistent and severe.

Conclusions
The analyses we conducted highlight that women with persistent depression in the postnatal year continue to experience elevated levels of depressive symptoms until at least 11 years after childbirth. Children of women with persistent PND, especially when it is severe, are at an increased risk for a number of adverse outcomes. Screening both early and late in the first postpartum year will enable the identification of women with persistent PND and thus the offer of appropriate treatment. 36