(2024) 22:284
KC et al. BMC Medicine
https://doi.org/10.1186/s12916-024-03501-0

BMC Medicine

RESEARCH ARTICLE

Open AccessA longitudinal multi-centric cohort study
assessing infant neurodevelopment delay
among women with persistent postpartum
depression in Nepal
Ashish KC1* , Jaya Chandna2, Ankit Acharya3, Rejina Gurung3,4 , Carin Andrew4   and Alkistis Skalkidou4   

Abstract
Background Infant neurodevelopment in the first years after birth is determined by multiple factors, including parental care and maternal mental wellbeing. In this study, we aim to assess the impact of persistent maternal
depressive symptoms during the first 3 months postpartum on infant neurodevelopment at 6 months.
Methods Using a longitudinal cohort design, 1253 mother-infant pairs were followed up at 7, 45, and 90 days
to assess postpartum depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS); infants were followed up at 6 months to assess neuro-developmental status using the WHO’s Infant and Young Child Development(IYCD) tool. A generalized linear regression model was used to assess the association between persistent postpartum depressive symptoms and infant neurodevelopmental delay at 6 months. A generalized linear mixed model(GLMM) with a hospital as a random intercept was used to assess the persistent postpartum depressive symptoms
with an IYCD score. Linear regression was used to compare the IYCD scores between exposure groups.
Results In the study population, 7.5% of mothers had persistent depressive symptoms, and 7.5% of infants had
neurodevelopmental delay. Infants born to mothers with persistent depressive symptoms had a higher proportionof neurodevelopmental delay than infants born to women without persistent symptoms (48.6% vs 5.1%; p < 0.001).
In the adjusted regression model, infants whose mothers had persistent depressive symptoms at 7, 45, and 90 days
had a 5.21-fold increased risk of neurodevelopmental delay (aRR, 5.21; 95% CI, 3.17, 8.55). Mean scores in the motor
domain (12.7 vs 15.2; p < 0.001) and language domain (6.4 vs 8.5; p < 0.001) were significant when a mother had persistent depression vs. no depression. Mean scores in the general behavioral domain (5.9 vs 10.4, p < 0.001) and the socioemotional domain (15.4 vs 17.7; p < 0.001) were significantly different when a mother had persistent depression vsno persistent depression.
Conclusions Our results suggest that 6-month-old infants are at higher risk for neurodevelopment delays if theirmother reports persistent symptoms of depression from 7 to 90 days postpartum. The neurodevelopmental delay
can be observed in all functional domains. Preventive intervention to reduce maternal postpartum depression may
reduce the impact on infant developmental delay.

*Correspondence:
Ashish KC
ashish.kc@gu.se
Full list of author information is available at the end of the article© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which
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KC et al. BMC Medicine(2024) 22:284

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Keywords Infant’s delayed neurodevelopment, Postpartum depression, Infant young child development (IYCD)
domain, Nepal

Background
Maternal depression is a global health problem, with anestimated 23.4 million mothers experiencing postpartum depressive symptoms each year and a prevalence
rate of 17.2% [1]. Depressive episodes during the postpartum period range from sadness, changes in sleepand eating patterns, despair, crying spells, anxiety, irritability, feelings of isolation, mental liability, thoughtsof hurting oneself and/or the infant, and even suicidal thoughts [1]. In South Asia, the rate of maternal
depression is 22.2%, with the prevalence rate varying
according to the timing and duration of breastfeeding, maternal education, income, life stress, gestational
age at birth, and infant illness [1–4]. Infant and earlychildhood development is a maturational and interactive process that progressively develops perceptual,
motor, cognitive, language, socio-emotional, and selfregulatory skills [5]. Parental psychopathology has beenfound to be a consistent and robust correlate of child
maladjustment, particularly maternal depression [6–9].
More than 250 million children under the age of 5
were estimated to have developmental delays in LMICs(low- and middle-income countries) worldwide in 2015[10], highlighting the need to improve access to multisectoral interventions that include health, nutrition,
security and safety, responsive care, and early learningfor parents [11]. Parents need support to provide nurturing care; they need learning materials and resources
to support their children’s neurodevelopment [12]. The
fundamental promotive childhood experiences comefrom the nurturing care and protection received fromparents, family, and community, which have lifelong
benefits [13].
There are consistent findings linking maternal depression to deficits in both socio-emotional and instrumental
functioning. A landmark study conducted by the National
Institute of Child Health and Early Development showedthat children whose mothers reported depressive symptoms had poorer cognitive functioning and school readiness compared to children who mothers never reported
depressive symptoms [14]. Although the literature provides both theoretical and limited empirical support fora reciprocal effects model between maternal depression
and child development, a key question remains about thetiming of these effects. Children whose mothers reported
feeling depressed performed worse on measures of cognitive-linguistic functioning and were rated as less cooperative and more problematic [15, 16].

In Nepal, studies have shown that the population prevalence of maternal postpartum depressive symptoms
ranges from 28 to 33% [17, 18], indicating that one-thirdof the women have depressive symptoms, which is higher
than estimates (20% prevalence) made for mothers in
LMIC [19]. Given the high burden of postpartum depressive symptoms in Nepal and the link between infant neurodevelopment and maternal mental health, this study
aims to assess the impact of persistent maternal depressive symptoms during the first 3 months of the postpartum period on infant neurodevelopment at 6 months.

Methods
DesignThis is a longitudinal cohort study design nested within
an ongoing quality improvement study in 9 surveillancesite hospitals in Nepal. From the women-infant pairs
enrolled in the ongoing quality improvement study, asample of women-infant pairs was selected and followed
up until 6 months postpartum. The sample of women
who delivered between April and July 2023 were assessedfor depressive symptoms between April 28 and September 29, 2020, and developmental assessment follow-up at
6 months was conducted between October 10, 2020 andJanuary 29, 2021 [20, 21].
Study setting

The nine public referral hospitals included in the study
represented the seven administrative provinces and the
population of the country. Seti Provincial Hospital andDadeldhura Hospital represented the marginalized population in the far western province; Surkhet Provincial
Hospital catered service to the mid-western hilly population; Bheri, Lumbini, Janakpur, and Koshi Hospitals represented the population in the Southern plain province ofthe country; and Kaski Hospital represented the central
hilly population of the country.
Inclusion criteria

Mothers who had singleton live born infants were eligible for inclusion in the study and were approached forconsent [22]. Mothers who experienced birth trauma
and understood the Nepali language were also eligible
to participate. Mothers who consented to the study
were followed up at 7, 45, and 90 days for depressive
symptoms using the Edinburgh Postpartum Depression Scale (EPDS), and infant neuro-developmentalKC et al. BMC Medicine(2024) 22:284

assessment was conducted at 6 months (180 days)
using the World Health Organization’s Infant andYoung Child Development (IYCD) tool.
SampleWe randomly selected 10% of the mothers enrolled
in the quality improvement study in the nine hospitals for this longitudinal cohort study using random
sequence generation in an Excel spreadsheet with allparticipants. Of the 2022 mothers enrolled, longitudinal follow-up was conducted at 7, 45, 90, and 180 days
(Fig. 1).

Fig. 1 Study flow diagram

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MeasureExposure

Symptoms of postpartum depression were measured
using the EPDS. EPDS is a validated self-reported
10-question self-report questionnaire with a scale of 0 to
3 to measure depressive symptoms in postpartum mothers [23, 24], and for this study, a score of ≥ 12 was used tocategorize mothers with depressive symptoms. Persistentdepressive symptoms were defined as scores ≥ 12 at all
three time points (7, 45, and 90 days).
OutcomeInfant neurodevelopment was measured using the WHO’s
IYCD, an open-access, validated, mother-reported toolKC et al. BMC Medicine(2024) 22:284

for child development in the domains of motor, languagecognitive, social-emotional, and general behavior [25,26]. The IYCD was a 100-item parent report tool (40fine motor and gross motor, 30 language, 20 socioemotional, and 10 unscored behavioral items). Delayed
infant neurodevelopment at 6 months was based on a
centile score of 10 or less, based on previous literature[25, 26].
Covariates
Ethnicity

In Nepal, the social class system determines the social
access to resources. For the purpose of this study, ethnicity was divided into two social groups, first a disadvantaged social group which included janjati, muslim,
madeshi, and dalit ethnic groups and an advantagedsocial group such as chettri-brahmin. Maternal education was categorized as uneducated (illiterate and unable
to read and write) and educated (primary education andabove).
Preterm birth

Based on the date of last menstrual cycle date, preterm
birth was defined as birth occurring before 37 weeks
of gestation; low birth weight was defined as birthweight < 2500 g, and infant sex was categorized as boy or
girl.
Data collection

The hospital research surveillance team approached eligible women, informed them of the study, and enrolled
those who provided written consent. The trained
research surveillance team conducted telephone followups at 7, 45, 90, and 180 days after delivery. During thetelephone follow-up with the mother, sociodemographic,obstetric, postpartum depression (EPDS 10), and infant
neurodevelopment (IYCD) data were collected using
a semi-structured questionnaire from a tablet-based
application.
Data management and analysis

Descriptive statistics on the prevalence of maternal
depressive symptoms at 7, 45, and 90 days and persistentdepressive symptoms were calculated in Additional file 1:
Table S1. The IYCD as a score for a global developmental
domain and subdomains was analyzed using percentile
cut-offs calculated in Additional file 1: Table S2. Differences in the population characteristics (maternal ethnicity, maternal education), birth characteristics (preterm
birth, LBW, and infant sex), maternal depression (exposure), and infants with developmental delay (outcome)were analyzed using Pearson’s chi-square, and Fisher’s
exact test was done in Tables 2 and 3. We used three

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different statistical models to assess the causal relationship between maternal depression and infant neurodevelopment. In the first statistical model, a generalized
linear regression model was used to assess the association between maternal depression at 7, 45, and 90 days
and persistent postpartum depressive symptoms withan infant’s neurodevelopmental delay at 6 months, as
shown in Additional file 1: Table S3. In the second statistical model, the generalized linear mixed model (GLMM)
with the hospital as a random intercept was used. In thismodel, because there were not enough children with
developmental problems in all the hospitals, we decided
not to use a binary outcome and instead modeled theoutcome as a continuous variable (IYCD6 continuous)
using a mixed effects linear regression model with thehospital as a random intercept in Table 4. In the third
statistical model, the mean score with standard deviationof IYCD and functional domain of infants whose mothers had persistent depression compared to infants whose
mothers did not have persistent depression using linear
regression model in Fig. 2 and Additional file 1: Table S2.
The sociodemographic factors (ethnicity and maternal
education) and biological factors (infant sex and prematurity) that differed in the exposure population were
adjusted in all three statistical models. Statistical analysis was performed using IBM SPSS Statistics SPSS 28.0.2
version for generating supplementary tables and R program-4.3.3 version for generating main text tables andthe “glmm” package for GLMM regression [27, 28]. Missing data for any exposure or outcome of interest were
excluded at the pairwise level.

Results
During the recruitment period, a total of 24,912 mothers delivered at the nine study hospitals. Of those who
gave birth, 21,805 were eligible for enrollment, and 10%of them were randomly selected for this study. Of the2022 mothers enrolled in this study, 1253 were successfully contacted during the 7 days follow-up to assess
depressive symptoms, 961 were successfully followed up
at 45 days (292 lost to follow-up), and 1201 were successfully followed up at 90 days (52 lost to follow-up). Of themothers who were followed, 946 were successfully contacted at all three time points (307 were lost to follow-up
at all three time points). At 6 months, 1253 mothers had
a successful postnatal interview to assess the infant neurodevelopmental status using the IYCD reporting tool(Fig. 1).
Maternal depression and population characteristics

Among the follow-up study cohort, the prevalence ofmothers with depressive symptoms at 7, 45, and 90 days
was 10.1% (n = 127), 11.6% (n = 111), and 9.6% (n = 115)

KC et al. BMC Medicine(2024) 22:284

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Fig. 2 Scores in different functional domains among infants at 6 months born to mothers with/without depressive symptoms

respectively. The prevalence of mothers with persistentdepressive symptoms was 7.5% (n = 71) (Additional
file 1: Table S1). There was a statistical difference inthe persistent depressive symptoms among mothers bysocial group (p < 0.001), maternal education (p < 0.001),
and infant’s prematurity (p < 0.001) (Table 1).

Infant neurodevelopmental delay and population
characteristics

Among the infants, the IYCD development score atthe 10th, 50th, and 95th percentiles were 44, 53, and 59
respectively (Additional file 1: Table S2). In the population, 7.5% of the infants had a total IYCD score ≤ 44 andTable 1 Sociodemographic and obstetric characteristics of mothers with or without persistent depressive symptoms (n = 946)
Persistent depressive symptom
No, n (%) 875 (92.5%)

Yes, n (%) 71 (7.5%)

p-values

Relatively ­advantageda (313)309 (98.7%)

4 (1.3%)< 0.001*

Relatively ­disadvantagedb (633)566 (89.4%)

67 (10.6%)

Maternal ethnicity (social group)

Maternal education

0

1

Educated (799)761 (95.2%)

38 (4.8%)

Not educated (101)71 (70.3%)

30 (29.7%)< 0.001**

Sex of infantGirl (390)362 (92.8%)

28 (7.2%)

Boy (555)

512 (92.3%)

43 (7.7%)

0.774**

Preterm birth
No (779)741 (95.1%)

38 (4.9%)

Yes (167)

134 (80.2%)

33 (19.8%)< 0.001**

Low birth weight of infant
No (855)786 (91.9%)

69 (8.1%)

Yes (91)

89 (97.8%)

2 (2.2%)< 0.056*

Data provided as n (%), percentages refer to column values (values in columns add up to 100); p-value were obtained from *Fisher’s exact test, **Pearson’s chi-square
test; cut-off value for depressive symptoms was ≥ 12arelatively advantaged—brahmin and Chettrib

relatively disadvantaged—janjati, dalit, madeshi, and muslim

KC et al. BMC Medicine(2024) 22:284

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were classified as having neurodevelopmental delay.
There was a statistical difference in infant neurodevelopment delayed among mothers stratified by socialgroup (p < 0.001), maternal education (p < 0.001), infantsex (p < 0.05), and prematurity (p < 0.001). Infants bornto mothers with persistent depressive symptoms had ahigher proportion of neurodevelopmental delay than
infants born to women without persistent depressive
symptoms (47.9% vs 4.6%, p < 0.001) (Table 2).
Statistical model using generalized linear regression

After adjustment for sociodemographic (social group andmaternal education) and birth characteristics (infant’s
sex and prematurity), infants whose mothers had depressive symptoms at 7 days had a 4.19-fold increased risk ofneurodevelopmental delay compared with infants whose

mothers did not have depressive symptoms (aRR, 4.19;
95% CI; 2.79, 6.30; p < 0.001). In the adjusted model, infants
whose mothers had depressive symptoms at 90 days had
a 3.32-fold increased risk of neurodevelopmental delay(aRR, 3.32; 95% CI; 2.15, 5.13; p < 0.001). In the adjusted
model, infants whose mothers had persistent depressive
symptoms had a 5.21-fold increased risk of neurodevelopmental delay compared with infants whose mothers did
not have persistent depressive symptoms (aRR, 5.21; 95%
CI, 3.17, 8.55; p < 0.001) (Additional file 1: Table S3).
Statistical model using GLMM with the hospital as random
intercept

In this model, with adjustment for sociodemographic andbirth characteristics, with each increase in EPDS score atday 7, the IYCD score decreased by 0.13 (p = 0.005). With

Table 2 Distribution of the co-variates for delayed infant neuro-development at 6 months using IYCD (n = 1253)
Delayed development at 6-monthNo, n (%) 1159 (92.5%)

Yes, n (%) 94 (7.5%)

p-value

Relatively ­advantageda (423)409 (96.7%)

14 (3.3%)< 0.001

Relatively ­disadvantagedb (830)750 (90.4%)

80 (9.6%)

Ethnicity (social groups)

Maternal education
Educated (1050)

996 (94.9%)

54 (5.1%)

Uneducated (135)

100 (74.1%)

35 (25.9%)< 0.001

Infant’s sex
Boys (724)498 (94.3%)

30 (5.7%)

Girl (528)660 (91.2%)

64 (8.8%)

0.052

Low birth weight of infant
No (968)894 (92.4%)

74 (7.6%)

Yes (285)

265 (93.0%)

20 (7.0%)0.468

Preterm birth
No (1210)

984 (94.1%)

62 (5.9%)

Yes (43)

175 (84.5%)

32 (15.5%)< 0.001

Depressive symptom at 7
Yes (127)

87 (68.5%)

40 (31.5%)

No (1126)

1072 (95.2%)

54 (4.8%)< 0.001

Depressive symptom at 45
Yes (111)

69 (62.2%)

42 (37.8%)

No (850)812 (95.5%)

38 (4.5%)< 0.001

Depressive symptom at 90 days
Yes (115)

79 (68.7%)

36 (31.3%)

No (1086)

1030 (94.8%)

56 (5.2%)< 0.001

Persistent symptom
Yes (71)

37 (52.1%)

34 (47.9%)

No (875)835 (95.4%)

40 (4.6%)< 0.001

Data provided as n (%), percentages refer to column values (values in columns add up to 100%), level of significance = 0.05; p-value were obtained from χ2 test. Cut-off
value for developmental delay is total IYCD score ≤ 44arelatively advantaged—brahmin and Chettrib

relatively disadvantaged—janjati, dalit, madeshi, and muslim

KC et al. BMC Medicine(2024) 22:284

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each increase in depressive score at all three time points(7, 45, and 90 days), the IYCD score decreased by − 0.19
(β coefficient =  − 0.19; p = 0.019) (Table 3).
Statistical model using linear regression for individual
neurodevelopmental domains

There was a difference in the mean IYCD score between
infants born to mothers with persistent depressive symptoms and those born to non-depressive mothers (40.7 vs
51.9; p < 0.001). The mean score and adjusted regression
score in the motor domain were significant when a motherhad persistent depression compared to no depression (12.7
vs 15.2; β coefficient =  − 1.92; p < 0.001). The mean scoreand adjusted regression scores in the language domain werealso significant between the two groups (6.4 vs 8.5; β coefficient =  − 1.80; p < 0.001). The mean score and adjusted
regression score in the socio-emotional domain werealso significant between the groups (15.4 vs 17.7; β coefficient =  − 3.96; p < 0.001). Mean score and adjusted regression
score in the general behavior domain were significant whena mother had persistent depression vs no depression (5.9 vs
10.4; β coefficient =  − 3.96; p < 0.001) (Table 4 and Fig. 2).

Discussion
In this study, the prevalence of postpartum depressive
symptoms persisted at 7, 45, and 90 days with similarprevalence rates, indicating that maternal stress remains
Table 3 Mixed effects linear regression model with hospital
as a random intercept on the postpartum depressive score atdifferent time points on IYCD score
Beta ­coefficienta (95% CI)

Characteristics

p-value

EPDS 7 day− 0.13 (− 0.22, − 0.04)

0.005

EPDS 45 day− 0.07 (− 0.17, 0.03)

0.14

EPDS 90 day− 0.05 (− 0.16, 0.06)

0.4

EPDS at all three points− 0.19 (− 0.36, − 0.03)

0.019

a

Adjusted for ethnicity, maternal education, infant’s sex, and pre-term birthhigh during the postpartum period. In the study cohort,one in nine infants had neurodevelopmental delay at
6 months, and the risk increased fivefold for infants bornto mothers with persistent depressive symptoms up to
90 days. Due to the persistence of maternal depressive
symptoms, the infants were delayed in all four functional domains, but more so in the general behavioral andsocial-emotional domains. Delayed infant neurodevelopment was higher among women who were from sociallydisadvantaged populations, had no maternal education,
and were born preterm.
As the study result shows, the early infancy is a timeof major transition in terms of physical and social maturation, which is influenced by the presence of maternal
depression [29]. Persistent maternal depression may
affect breastfeeding behavior and hinder infant stimulation and mother–child attachment, in line with our study,
where the infant’s social-emotional domain and generalbehavior among those born to mothers with persistentdepression were affected; a study in the United States
reported that exposure to maternal depression was associated with difficulties in the development of infant’ssocial competence and emotional maturity [30]. Children
exposed to maternal depression before the age of 5 had ahigher risk of developmental vulnerability at school entry
than children not exposed to maternal depression before
the age of 5. A study in a Finnish cohort of 270 mother–child pairs showed that maternal postnatal depressive
symptoms predicted low social competence in children.
The children of mothers with depressive symptoms had
lower problem-solving and externalizing scores thanthose of mothers without depression [31].
Similar to our findings of poor child development andbehavioral problems in children born of mothers with
postpartum depression, cohort studies in LMICs havereported similar results. A study in South Africa showedthat children whose mothers had postpartum depression
were more likely to have mental health problems later inlife [32]. The study also showed that children from poor

Table 4 Linear regression analysis of the association between persistent maternal postnatal depression and infant neurodevelopment(individual domain) (n = 946)
Persistent depression

Regression score

No (875)

Yes (71)

Mean score (SD)

Mean score (SD)β coefficient, 95% CI

p-value

Adjusted β ­coefficienta, 95% CI

p-value

51.9 (5.7)

40.7 (10.9)− 11.22 (− 12.72, − 9.72)< .001− 9.72 (− 11.32, − 8.12)< .001

Motor domain

15.2 (2.0)

12.7 (3.6)− 2.37 (− 2.89, − 184)

< .001− 1.92 (− 2.49, − 136)

< .001

language domain

8.5 (2.2)

6.4 (2.7)− 2.15 (− 2.68, − 1.63)< .001− 1.80 (− 2.37, − 1.24)< .001Social emotional

17.7 (1.3)

15.4 (2.6)− 2.21 (− 2.53, − 1.88)< .001− 2.03 (− 2.36, − 1.69)< .001

General behavior

10.4 (2.9)

5.9 (3.3)− 4.49 (− 5.18, − 3.81)< .001− 3.96 (− 4.70, − 3.23)< .001a

Adjusted for ethnicity, maternal education, infant’s sex and pre-term birthKC et al. BMC Medicine(2024) 22:284

social groups had more social-emotional difficulties thanthose from relatively better social groups, which was also
reported in our study. A study in Ethiopia showed thatcaretakers’ mental health had negative effects on personalsocial, fine and gross motor, and language development[33]. The study also showed the difference in neurodevelopmental outcomes according to the sex of the infant asshown in our study. A country neighboring Nepal withsimilar study settings, India, has shown delayed neurodevelopment in infants whose mothers had postpartum
depression [34]. This study in India also showed, as highlighted in our study, that prematurity and birth weightaffect infant neurodevelopment, highlighting fetal growth
as an important covariate for later development.
In settings such as Nepal, the early screening for postpartum depression has not been recommended in postpartum clinical care, resulting in early detection andmanagement of postpartum depressive symptoms not
being routine care [35]. Similarly, the system for detection
and management of children with developmental delay is
still under development in countries like Nepal, whichmainly requires close interaction between the health andeducation sectors [36]. The World Health Organization
recognizes maternal depression as a key health issue andrecommends countries for early screening, referral, andmanagement as part of routine postpartum care [37].
There is also a need to assess how improving the management of maternal depression reduces the risk of delayed
early childhood development.

Methodological considerations
The maintenance of a cohort of mother-infant pairs who
were observed at birth during the COVID-19 pandemic
is one of the major strengths of the study. The enrolled
mother-infants came from diverse populations representing different hospitals and community settings, which
helped to generalize the result. To our knowledge, thisis one of the largest cohort studies assessing persistentmaternal depression in Southeast Asia, which contributes
to the generalizability of the findings. The study did notcollect data on breastfeeding status at the time of IYCD
assessment at 6 months, which was a major limitation,
as breastfeeding, especially exclusive breastfeeding, is ameditator to maternal postpartum depression and infant
neurodevelopmental status. A major limitation is that we
did not assess maternal antepartum depression, which isa strong correlate of postpartum depression and has also
been associated with neurodevelopmental delays [38].
Third, the IYCD is a mother-reported measure of infant
neurodevelopment function and has a lower sensitivity
than developmental assessment conducted using structured tools such as the Malawi Development Assessment

Page 8 of 10

Tool (MDAT) [39]. Finally, attrition from 2022 participants enrolled to 1253 followed up at 6 months may haveintroduced to sampling bias. However, when we compared the population characteristics between those lost
to follow-up and those who were followed up, there wasno difference in maternal ethnicity, maternal age, birthcomplications, and prematurity, but there was difference
in infant sex (Additional file 1: Table S4).

Conclusions
The burden of persistent maternal depression and its
interlinkage with delayed infant neurodevelopment will
have an unprecedented societal public health impact. The
vicious cycle between poor maternal mental health andpoor child developmental outcomes will be detrimental to the family and society. There is a need to further
develop interventions to improve both maternal mental
health and infant development through a common clinical setting so that mothers attending postpartum followup are screened for depressive symptoms, while infants
are screened for functional neurodevelopment.
Abbreviations
aRR	Adjusted risk ratio
CI	Confidence interval
EPDS	Edinburgh Postnatal Depression Scale
GLM	Generalized linear modeling
IYCD	Infant and Young Child Develop Tool
LMIC	Low- and middle-income countries
MDAT	Malawi Development Assessment Tool
SDG	Sustainable development goal

Supplementary Information
The online version contains supplementary material available at https://​doi.​
org/​10.​1186/​s12916-​024-​03501-0.
Additional file 1.
Acknowledgements
We would like to thank Omkar Banset, Honey Malla, Avinash K Sunny, Prajwal
Paudel, and Pratiksha Paudel and surveillance officers, the hospital manager,
the nurse in charge, all the nurses, and support staff working in the labor anddelivery unit during this unprecedented time. We would like to thank Richard
White for his statistical advice and revision of the statistics.
Authors’ contributions
AKC and AS conceptualized the study. AA conducted the first draft of theanalysis, and AKC conducted the second draft of the analysis. AKC conducted
the first draft of the manuscript. AS, RG, JC, and CA authors provided input inthe first draft. AS and AKC conducted the third and final draft of the analysis.
All authors read and approved the final manuscript.
Authors’ X handles@Ashish_K_C, @jayachandna, @RejinaGurung3, @ASkalkidou.
Funding
Open access funding provided by University of Gothenburg. For this study, nofunding was available.
Availability of data and materials
The dataset generated and analyzed is available and provided on request.

KC et al. BMC Medicine(2024) 22:284

Declarations
Ethics approval and consent to participate
The study was approved by the ethical committee of the Nepal HealthResearch Council (439/2020). Written consents were obtained from all women
before participation in the study.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Author details
1
School of Public Health and Community Medicine, Sahlgrenska Academy, University of Gothenburg, Medicinargatan 18, Gothenburg, Sweden.
2
MARCH Center, London, School of Hygiene and Tropical Medicine, London,
UK. 3 Research Division, Golden Community, Lalitpur, Nepal. 4 Department
of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden.
Received: 20 August 2023 Accepted: 26 June 2024

References
1. Wang ZY, Liu JY, Shuai H, Cai ZX, Fu X, Liu Y, Xiao X, Zhang WH, Krabbendam E, Liu S, et al. Mapping global prevalence of depression amongpostpartum women. Transl Psychiatry. 2021;11(1):543.
2. Al-Abri K, Edge D, Armitage CJ. Prevalence and correlates of perinatal
depression. Soc Psychiatry Psychiatr Epidemiol. 2023;58(11):1581-90.
3. Bhusal BR, Bhandari N. Identifying the factors associated with depressive
symptoms among postpartum mothers in Kathmandu, Nepal. Int J Nurs
Sci. 2018;5(3):268–74.
4. Khadka R, Hong SA, Chang YS. Prevalence and determinants of poor
sleep quality and depression among postpartum women: a communitybased study in Ramechhap district, Nepal. Int Health. 2020;12(2):125–31.
5. Sameroff A. The transactional model of development: how children andcontexts shape each other. American Psychological Association; 2009.
6. Brentani A, Fink G. Maternal depression and child development: evidence
from Sao Paulo’s Western Region Cohort Study. Rev Assoc Med Bras
(1992). 2016;62(6):524–9.
7. Comaskey B, Roos NP, Brownell M, Enns MW, Chateau D, Ruth CA, Ekuma O.
Maternal depression and anxiety disorders (MDAD) and child development:a Manitoba population-based study. PLoS One. 2017;12(5):e0177065.
8. Koutra K, Roumeliotaki T, Kyriklaki A, Kampouri M, Sarri K, Vassilaki M, Bitsios P, Kogevinas M, Chatzi L. Maternal depression and personality traits inassociation with child neuropsychological and behavioral developmentin preschool years: mother-child cohort (Rhea Study) in Crete, Greece. J
Affect Disord. 2017;217:89–98.
9. Rogers A, Obst S, Teague SJ, Rossen L, Spry EA, Macdonald JA, Sunderland
M, Olsson CA, Youssef G, Hutchinson D. Association between maternal
perinatal depression and anxiety and child and adolescent development:
a meta-analysis. JAMA Pediatr. 2020;174(11):1082–92.
10. Black MM, Walker SP, Fernald LCH, Andersen CT, DiGirolamo AM, Lu
CL, McCoy DC, Fink G, Shawar YR, Shiffman J, et al. Early childhood
development coming of age: science through the life course. Lancet.
2017;389(10064):77–90.
11. Richter LM, Daelmans B, Lombardi J, Heymann J, Boo FL, Behrman JR, Lu
CL, Lucas JE, Perez-Escamilla R, Dua T, et al. Investing in the foundationof sustainable development: pathways to scale up for early childhood
development. Lancet. 2017;389(10064):103–18.
12. Shonkoff JP, Radner JM, Foote N. Expanding the evidence base to drive moreproductive early childhood investment. Lancet. 2017;389(10064):14–6.
13. Britto PR, Lye SJ, Proulx K, Yousafzai AK, Matthews SG, Vaivada T, PerezEscamilla R, Rao N, Ip P, Fernald LCH, et al. Nurturing care: promoting earlychildhood development. Lancet. 2017;389(10064):91–102.
14. National Inst of Child Health & Human Development, Early Child Care
Research Network. (1999). Chronicity of maternal depressive symptoms,
maternal sensitivity, and child functioning at 36 months. Dev Psychol.
1999;35(5):1297–1310.

Page 9 of 10

15. Slomian J, Honvo G, Emonts P, Reginsteri JY, Bruyere O. Consequences ofmaternal postpartum depression: a systematic review of maternal andinfant outcomes. Womens Health. 2019;15:1745506519844044.
16. Beck CT. The effects of postpartum depression on child development: ameta-analysis. Arch Psychiat Nurs. 1998;12(1):12–20.
17. Singh DR, Sunuwar DR, Adhikari S, Singh S, Karki K. Determining factors
for the prevalence of depressive symptoms among postpartum mothers
in lowland region in southern Nepal. PloS One. 2021;16(1):e0245199.
18. Giri RK, Khatri RB, Mishra SR, Khanal V, Sharma VD, Gartoula RP. Prevalence
and factors associated with depressive symptoms among post-partum
mothers in Nepal. BMC Res Notes. 2015;8:111.
19. Fisher J, Cabral de Mello M, Patel V, Rahman A, Tran T, Holton S, Holmes W.
Prevalence and determinants of common perinatal mental disorders inwomen in low- and lower-middle-income countries: a systematic review.
Bull World Health Organ. 2012;90(2):139G-149G.
20. Gurung R, Gurung A, Basnet O, Eilevstjonn J, Myklebust H, Girnary S,
Shrestha SK, Singh D, Bastola L, Paudel P, et al. REFINE (Rapid Feedback for
quality Improvement in Neonatal rEsuscitation): an observational study of
neonatal resuscitation training and practice in a tertiary hospital in Nepal.
BMC Pregnancy Childbirth. 2020;20(1):756.
21. Gurung R, Jha AK, Pyakurel S, Gurung A, Litorp H, Wrammert J, Jha BK,
Paudel P, Rahman SM, Malla H, et al. Scaling Up Safer Birth Bundle ThroughQuality Improvement in Nepal (SUSTAIN)-a stepped wedge cluster randomized controlled trial in public hospitals. Implement Sci. 2019;14(1):65.
22. Kc A, Acharya A, Bhattarai P, Basnet O, Shrestha A, Rijal G, Skalkidou A.
Association of disrespectful care after childbirth and COVID-19 exposure
with postpartum depression symptoms- a longitudinal cohort study in
Nepal. BMC Pregnancy Childbirth. 2023;23(1):145.
23. Bhusal BR, Bhandari N, Chapagai M, Gavidia T. Validating the Edinburgh
Postnatal Depression Scale as a screening tool for postpartum depressionin Kathmandu, Nepal. Int J Ment Health Sy. 2016;10:71.
24. Ho-Yen SD, Bondevik GT, Eberhard-Gran M, Bjorvatn B. The prevalence ofdepressive symptoms in the postnatal period in Lalitpur district, Nepal.
Acta Obstet Gyn Scan. 2006;85(10):1186–92.
25. Lancaster GA, McCray G, Kariger P, Dua T, Titman A, Chandna J, McCoy D,
Abubakar A, Hamadani JD, Fink G, et al. Creation of the WHO Indicators ofInfant and Young Child Development (IYCD): metadata synthesis across
10 countries. BMJ Glob Health. 2018;3(5):e000747.
26. Gladstone M, Lancaster G, McCray G, Cavallera V, Alves CRL, Maliwichi L,
Rasheed MA, Dua T, Janus M, Kariger P. Validation of the infant and young
child development (IYCD) indicators in three countries: Brazil, Malawi andPakistan. Int J Environ Res Public Health. 2021;18(11):6117.
27. IBM Corp. Released. IBM SPSS Statistics for Windows, Version 29.0.2.0
Armonk: IBM Corp; 2023.
28. R Core Team. _R: A Language and Environment for Statistical Computing_. Vienna: R Foundation for Statistical Computing; 2023.
29. Culp AM. The transactional model of development: how children andcontexts shape each other. Infant Ment Health J. 2010;31(1):115–7.
30. Wall-Wieler E, Roos LL, Gotlib IH. Maternal depression in early childhood and developmental vulnerability at school entry. Pediatrics.
2020;146(3):e20200794.
31. Luoma I, Tamminen T, Kaukonen P, Laippala P, Puura K, Salmelin R, Almqvist F.
Longitudinal study of maternal depressive symptoms and child well-being.
J Am Acad Child Adolesc Psychiatry. 2001;40(12):1367–74.
32. Verkuijl NE, Richter L, Norris SA, Stein A, Avan B, Ramchandani PG.
Postnatal depressive symptoms and child psychological development at
10 years: a prospective study of longitudinal data from the South African
Birth to Twenty cohort. Lancet Psychiatry. 2014;1(6):454–60.
33. Hadley C, Tegegn A, Tessema F, Asefa M, Galea S. Parental symptoms ofcommon mental disorders and children’s social, motor, and language
development in sub-Saharan Africa. Ann Hum Biol. 2008;35(3):259–75.
34. Patel V, DeSouza N, Rodrigues M. Postnatal depression and infant growthand development in low income countries: a cohort study from Goa,
India. Arch Dis Child. 2003;88(1):34–7.
35. Cavallera V, Tomlinson M, Radner J, Coetzee B, Daelmans B, Hughes R,
Perez-Escamilla R, Silver KL, Dua T. Scaling early child development: what
are the barriers and enablers? Arch Dis Child. 2019;104:S43–50.
36. Milner KM, Salazar RB, Bhopal S, Brentani A, Britto PR, Dua T, Gladstone
M, Goh E, Hamadani J, Hughes R, et al. Contextual design choices andpartnerships for scaling early child development programmes. Arch Dis
Child. 2019;104:S3–12.

KC et al. BMC Medicine(2024) 22:284

37. The Lancet. Adolescence: a second chance to tackle inequities, The
Lancet. 2013;382(9904):1535
38. Fransson E, Sorensen F, Kallak TK, Ramklint M, Eckerdal P, Heimgartner M,
Krageloh-Mann I, Skalkidou A. Maternal perinatal depressive symptoms
trajectories and impact on toddler behavior ? the importance of symptom duration and maternal bonding. J Affect Disorders. 2020;273:542–51.
39. Gladstone M, Lancaster GA, Umar E, Nyirenda M, Kayira E, van den Broek
NR, Smyth RL. The Malawi Developmental Assessment Tool (MDAT): thecreation, validation, and reliability of a tool to assess child development
in rural African settings. PloS Medicine. 2010;7(5):e1000273.

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