Introduction
Maternal prenatal and postnatal psychological distress, including depressive symptoms and anxiety, is known to affect the children’s neurodevelopment, including cognitive development, motor development, mental health, and temperament, influencing the developing fetus up to infancy (first 1000 days from conception). This process is commonly known as the “Developmental Origins of Health and Disease hypothesis.” Reference Gentile1–Reference Oyetunji and Chandra4
However, inconsistencies exist in the clinical periods from pregnancy to postpartum that are vulnerable to the effects of maternal psychological distress on children’s neurodevelopment. Reference van den Bergh, van den Heuvel and Lahti2,Reference Aoyagi and Tsuchiya3,Reference Rees, Channon and Waters5 When focusing solely on the pregnancy period, reports indicated higher susceptibility in the early term, while others suggest increased susceptibility in the mid or late term of pregnancy. In a comparison between pregnancy and postpartum periods, some studies report higher susceptibility in the postpartum period than in the pregnancy period, while others find greater susceptibility during the pregnancy period than in the postpartum period. Reference van den Bergh, van den Heuvel and Lahti2,Reference Aoyagi and Tsuchiya3,Reference Rees, Channon and Waters5
Furthermore, inconsistencies exist in the sex differences regarding vulnerability to maternal psychological distress effects on children’s neurodevelopment. Generally, reports suggest boys are more susceptible than girls. Conversely, some reports show girls as more susceptible, particularly in aspects of temperament. Reference Gentile1,Reference van den Bergh, van den Heuvel and Lahti2,Reference Rees, Channon and Waters5
In Japan, the Japan Environment and Children Study (JECS), a nationwide birth cohort study of approximately 100,000 pairs of parents and children, was launched in 2011. Reference Kawamoto, Nitta and Murata6,Reference Michikawa, Nitta and Nakayama7 JECS is ongoing and will continue until the participating children turn 40 years old. As a Sub-Cohort Study of the JECS, trained testers have conducted evaluations of the cognitive development of approximately 5,000 children randomly selected from the sample. In the present study, we used this dataset to evaluate the association between maternal prenatal/postnatal psychological distress trajectories and cognitive development in 4-year-old children, considering sex differences.
Methods
Design and participants
The JECS protocol was reviewed and approved by the Ministry of the Environment’s Institutional Review Board on Epidemiological Studies (no. 100910001) and have been approved by the Ethics Committees of all participating institutions. JECS recruitment occurred between January 2011 and March 2014 and included pregnant women nationwide. Participants were recruited from 15 Regional Centers. Written informed consent was obtained from all participants. In the JECS Main Study, the eligibility criteria for participants (expecting mothers) are as follows: (1) they must reside in the study areas at the time of recruitment and are expected to continue residing in Japan for the foreseeable future; (2) they must be capable of participating in the study without difficulty, i.e., they must be able to comprehend the Japanese language and complete the self-administered questionnaire. Reference Kawamoto, Nitta and Murata6
From the JECS Main Study, a Sub-Cohort Study, which included 5% of the participating children who were randomly selected for each Regional Centre at regular intervals, was extracted. Reference Sekiyama, Yamazaki and Michikawa8 The eligibility criteria were as follows: (1) children born after April 1, 2013; (2) all questionnaire and medical record data from children and their mothers collected from the first half of pregnancy to 6 months of age; and (3) biospecimens (except umbilical cord blood) from children and their mothers collected at the first to the second half of pregnancy and delivery. Reference Sekiyama, Yamazaki and Michikawa8 For this Sub-Cohort Study, extended outcome measurements were planned, including face-to-face interviews with specialized staff to evaluate neurological development based on the Kyoto Scale of Psychological Development 2001 (KSPD) for 4-year-old children. Reference Sekiyama, Yamazaki and Michikawa8
The present study used the jecs-qa-20210401 dataset, which was released in April 2021 and revised in April 2023. It contains the cognitive developmental results of 4-year-old children based on the KSPD. As this study included children from singleton pregnancies, multiple-birth children were excluded. Children with congenital anomalies were also excluded from the analysis. Reference Mezawa, Tomotaki and Yamamoto-Hanada9 Congenital anomalies were assessed by physicians who diagnosed them immediately after delivery and during the first month at a regular checkup. Participants who had congenital anomalies reported either at delivery or at 1-month data collection were excluded from the analysis. Reference Mezawa, Tomotaki and Yamamoto-Hanada9
Maternal psychological distress
The JECS administered the six-item version of the Kessler Psychological Distress Scale (K6) during the first (M-T1) and second (M-T2) half of pregnancy and at one year postpartum (C-1y). K6 is widely used to assess psychological distress during perinatal and postnatal periods. Reference Kessler, Andrews and Colpe10,Reference Kessler, Barker and Colpe11 It is a self-administered questionnaire comprising six questions that evaluate depressive mood and anxiety according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), over the preceding 4 weeks on a scale of 0 to 4. The total score is the sum of the scores of the six items, with a possible range of 0 to 24. We used a Japanese version of K6 with a cutoff score of ≥ 5 to identify cases of psychological distress, as used in previous studies of populations and affected communities in Japan. Reference Furukawa, Kawakami and Saitoh12–Reference Mori, Nishigori and Ogata15
We analyzed the data to determine the association between K6 scores of ≥ 5 and cognitive development in 4-year-old children.
We classified participants into eight trajectory groups based on K6 scores ≥ 5 and K6 scores ≤ 4 at M-T1, M-T2, and C-1y (Table 1).
Characteristics of participants (total = 3287)
Abbreviations: Kyoto Scale of Psychological Development 2001(KSPD), developmental quotient (DQ), cognitive-adaptive (C-A), language-social (L-S), standard deviation (SD), interquartile range (IQR), the 6-item Kessler Psychological Distress Scale (K6; total point scores ranged from 0 to 24),1 year postpartum (C-1y).
Cognitive development in 4-year-old children
The KSPD, a standardized developmental assessment tool for Japanese children, covers the cognitive-adaptive (C-A) and language-social (L-S) areas of development. Reference Koyama, Osada, Tsujii and Kurita16–Reference Nishigori, Nishigori and Obara18 The C-A and L-S areas correspond to nonverbal and verbal cognitive development, respectively. Scores were combined to form the developmental quotient (DQ), which was calculated, in days, by dividing the developmental age in days by the chronological age and multiplying the quotient by 100. Administrative procedures and evaluations were strictly standardized to ensure tester reliability in this survey. To ensure the reliability of the administration, the testers received rigorous training before they were certified to conduct the testing. Specifically, the testers' training included general lectures by instructors, technique confirmation through watching actual examination videos, learning techniques by observing and conducting examinations, confirming correct evaluations via examination videos, and undergoing evaluation by performing examinations on mock children. The JECS and Kyoto International Social Welfare Exchange Centre certified the testers. As sex-specific differences in children’s cognitive development have been suggested, we examined this issue separately for boys and girls. Reference van den Bergh, van den Heuvel and Lahti2
Statistical analysis and covariables
We compared the characteristics of mothers and their children with data on cognitive development to those obtained with an analysis of variance (ANOVA). Bivariate and multiple regression analyses were then used to assess the association between maternal psychological distress and children’s cognitive development.
First, multiple regression analyses were adjusted for maternal age at delivery, whether the pregnancy was unplanned, use of infertility treatment, marital status, highest level of education (maternal and paternal), smoking during pregnancy (maternal and paternal), alcohol consumption during pregnancy, annual household income, whether the mother had any neuropsychiatric disorders, psychoactive drug use during pregnancy, pregnancy complications, obstetric labor complications, mode of delivery, children’s birth weight, gestational week of delivery, feeding method at 6 months postpartum, family structure, number of children (including the subject), children’s age at the time of beginning attendance at a daycare center, location of the Regional Center, and children’s sex. Information regarding maternal neuropsychiatric disorders, pregnancy complications, obstetric labor complications, mode of delivery, children’s birth weight, and gestational week of delivery was transcribed from physicians’ records. All other information was obtained from participants’ responses to the questionnaire, which was not validated. These covariate factors were mostly chosen with reference to previous relevant studies. Reference Gentile1–Reference Oyetunji and Chandra4,Reference Mori, Nishigori and Ogata15 No multicollinearity was found in this analysis (VIF < 2), except for parity and number of children.
Second, multiple regression analyses were adjusted for variables selected through a stepwise method, with the significance level for entry into the model set at 0.20 and for staying in the model at 0.15.
All analyses were performed using the SAS statistical software (version 9.4; SAS Institute Inc., Cary, NC, USA).
Results
Of the 104,059 records in this dataset, records from 3,287 children were analyzed (Fig. 1). Table 1 shows the characteristics of the participants as evaluated by the KSPD. In total, there were 1,630 boys and 1,657 girls.
Flow chart depicting research participants’ selection.
In the group of boys, at M-T1, the maternal prenatal K6 score was estimated at 14.6 (interquartile range (IQR) 12.0–18.1) weeks of gestation; at M-T2, it was estimated at 27.4 (IQR 25.3–30.3) weeks of gestation. In the group of girls, at M-T1, the maternal prenatal K6 score was estimated at 14.4 (IQR 11.9–17.7) weeks of gestation; at M-T2, it was estimated at 27.0 (IQR 25.1–29.9) weeks of gestation.
Boys
The participants were divided into eight trajectory groups (Table 1). Table 2 depicts the one-way ANOVA results of maternal K6 and KSPD. Table 3 depicts the bivariate analysis of maternal K6 and KSPD.
ANOVA of Maternal K6 and KSPD in eight trajectories groups.
Abbreviations: Kessler Psychological Distress Scale (K6), Kyoto Scale of Psychological Development 2001(KSPD), developmental quotient (DQ), cognitive-adaptive (C-A), language-social (L-S), interquartile range (IQR),1 year postpartum (C-1y).
M-T1; Overall median 14.6 (IQR 11.9–17.9), Boys median 14.6 (IQR 12.0–18.1), Girls median 14.4 (IQR 11.9–17.7) pregnant week.
M-T2; Overall median 27.3 (IQR 25.1–30.0), Boys median 27.4 (IQR 25.3–30.3), Girls median 27.0 (IQR 25.1–29.9) pregnant weeks.
Bivariate analysis of Maternal K6 and KSPD in eight trajectories groups.
Abbreviations: Kessler Psychological Distress Scale (K6), Kyoto Scale of Psychological Development 2001(KSPD), developmental quotient (DQ), cognitive-adaptive (C-A), language-social (L-S), partial regression coefficient (B), confidence interval (CI), standardized partial regression coefficients (β), interquartile range (IQR),1 year postpartum (C-1y).
M-T1; Overall median 14.6 (IQR 11.9–17.9), Boys median 14.6 (IQR 12.0–18.1), Girls median 14.4 (IQR 11.9–17.7) pregnant weeks. M-T2; Overall median 27.3 (IQR 25.1–30.0), Boys median 27.4 (IQR 25.3–30.3), Girls median 27.0 (IQR 25.1–29.9) pregnant weeks.
Multiple regression analysis without the stepwise method showed significantly lower scores with maternal K6 scores ≥ 5 at both M-T1 and M-T2 and C-1y for the L-S DQ (partial regression coefficient (B): −4.09, 95% confidence interval [CI]: −6.88 – −1.31, β: −0.075, p = 0.004) areas, compared to those with maternal K6 scores ≤ 4 at both M-T1 and M-T2 and C-1y (Table 4). The groups with maternal K6 scores ≤ 4 at any one or two periods during M-T1, M-T2, and C-1y were not significantly different from those with maternal K6 scores ≤ 4 at both M-T1 and M-T2 and C-1y (Table 4). There were no significant differences in the C-A DQ area (Table 4).
Multiple regression analysis of Maternal K6 and KSPD in eight trajectories groups.
Abbreviations: Kyoto Scale of Psychological Development 2001(KSPD), developmental quotient (DQ), cognitive-adaptive (C-A), language-social (L-S), partial regression coefficient (B), confidence interval (CI), standardized partial regression coefficients (β), interquartile range (IQR),1 year postpartum (C-1y).
M-T1; Overall median 14.6 (IQR 11.9–17.9), Boys median 14.6 (IQR 12.0–18.1), Girls median 14.4 (IQR 11.9–17.7) pregnant weeks.
M-T2; Overall median 27.3 (IQR 25.1–30.0), Boys median 27.4 (IQR 25.3–30.3), Girls median 27.0 (IQR 25.1–29.9) pregnant weeks.
Adjusted for age of mother at the delivery, unplanned pregnancy, infertility treatment, marital status, maternal highest level of education, paternal highest level of education, maternal smoking during pregnancy, paternal smoking during pregnancy, maternal alcohol consumption during pregnancy, annual household income, maternal neuropsychiatric disorders, psychoactive drug use during pregnancy, pregnancy complications, obstetric labor complications, mode of delivery, birth weight of children, gestational week of delivery, feeding method at 6 months postpartum, family structure, number of children included subject, attendance age of daycare center, location of regional center, and sex of children for overall.
Multiple regression analysis with the stepwise method showed significantly lower scores with maternal K6 scores ≥ 5 at both M-T1 and M-T2 and C-1y for the L-S DQ (partial regression coefficient (B): −3.70, 95% confidence interval [CI]: −6.41 – −0.98, β: −0.068, p = 0.008) areas, compared to those with maternal K6 scores ≤ 4 at both M-T1 and M-T2 and C-1y (Table 5). The groups with maternal K6 scores ≤ 4 at any one or two periods during M-T1, M-T2, and C-1y were not significantly different from those with maternal K6 scores ≤ 4 at both M-T1 and M-T2 and C-1y (Table 5). There were no significant differences in the C-A DQ area (Table 5).
Multiple regression analysis with stepwise method of Maternal K6 and KSPD in eight trajectories groups.
Abbreviations: Kyoto Scale of Psychological Development 2001(KSPD), developmental quotient (DQ), cognitive-adaptive (C-A), language-social (L-S), partial regression coefficient (B), confidence interval (CI), standardized partial regression coefficients (β), interquartile range (IQR),1 year postpartum (C-1y).
M-T1; Overall median 14.6 (IQR 11.9–17.9), Boys median 14.6 (IQR 12.0–18.1), Girls median 14.4 (IQR 11.9–17.7) pregnant weeks.
M-T2; Overall median 27.3 (IQR 25.1–30.0), Boys median 27.4 (IQR 25.3–30.3), Girls median 27.0 (IQR 25.1–29.9) pregnant weeks.
Overall; C-A DQ: Adjusted for unplanned pregnancy, marital status, maternal highest level of education, paternal highest level of education, paternal smoking during pregnancy, annual household income (×1000 yen/year) during pregnancy, maternal neuropsychiatric disorders, sex of children, birth weight of children (grams), attendance at daycare center (attendance age), Regional Center.
Overall; L-S DQ: Adjusted for maternal highest level of education, paternal highest level of education, paternal smoking during pregnancy, annual household income (×1000 yen/year) during pregnancy, pregnancy complications, sex of children, birth weigt of children (grams), feeding method at postpartum 6 months, number of children included subject, attendance at daycare center (attendance age), Regional Center.
Boys; C-A DQ: Adjusted for marital status, maternal highest level of education, paternal highest level of education, paternal smoking during pregnancy, annual household income (×1000 yen/year) during pregnancy, birth weight of children (grams), number of children included subject, Regional Center.
Boys; L-S DQ: Adjusted for age of mother at the delivery (years), maternal highest level of education, paternal highest level of education, paternal smoking during pregnancy, annual household income (×1000 yen/year) during pregnancy, birth weight of children (grams), gestation week of delivery, number of children included subject, Regional Center.
Girls; C-A DQ: Adjusted for marital status, maternal highest level of education, paternal highest level of education, paternal smoking during pregnancy, annual household income (×1000 yen/year) during pregnancy, maternal neuropsychiatric disorders, mode of delivery, birth weight of children (grams), gestation week of delivery, feeding method at postpartum 6 months, family structure, attendance at daycare center (attendance age), Regional Center.
Girls; L-S DQ: Adjusted for maternal highest level of education, paternal highest level of education, annual household income (×1000 yen/year), during pregnancy, maternal neuropsychiatric disorders, obstetric labor complications, feeding method at postpartum 6 months, number of children included subject, attendance at daycare center (attendance age), Regional Center.
Girls
The participants were divided into eight trajectory groups (Table 1). Table 2 depicts the one-way ANOVA results of maternal K6 and KSPD. Table 3 depicts the bivariate analysis of maternal K6 and KSPD.
Multiple regression analysis without the stepwise method showed no significant differences in maternal K6 scores ≥ 5 at both M-T1 and M-T2 and C-1y for the L-S DQ (B: −2.22, 95% CI: −4.60 − 0.17, β: −0.045, p = 0.07) areas, compared to maternal K6 scores ≤ 4 at both M-T1 and M-T2 and C-1y (Table 4). The groups with maternal K6 scores ≤ 4 at any one or two periods during M-T1, M-T2, and C-1y were also not significantly different compared to those with maternal K6 scores ≤ 4 at both M-T1 and M-T2 and C-1y (Table 4). There were no significant differences in the C-A DQ area (Table 4).
Multiple regression analysis with the stepwise method showed no significant differences in maternal K6 scores ≥ 5 at both M-T1 and M-T2 and C-1y for the L-S DQ (B: −2.24, 95% CI: −4.58 – 0.10, β: −0.046, p = 0.06) areas, compared to maternal K6 scores ≤ 4 at both M-T1 and M-T2 and C-1y (Table 5). The groups with maternal K6 scores ≤ 4 at any one or two periods during M-T1, M-T2, and C-1y were also not significantly different compared to those with maternal K6 scores ≤ 4 at both M-T1 and M-T2 and C-1y (Table 5). There were no significant differences in the C-A DQ area (Table 5).
Overall
Multiple regression analysis without the stepwise method showed significantly low scores with maternal K6 ≥ 5 at both M-T1 and M-T2 and C-1y for the C-A DQ (B: −2.00, 95% CI: −3.65 − −0.35, β: −0.043, p = 0.02) and L-S DQ areas (B: −3.14, 95% CI: −4.96 − −1.33, β: −0.061, p = 0.001), compared to those with maternal K6 scores ≤ 4 at both M-T1 and M-T2 and C-1y (Table 4). The groups with maternal K6 scores ≤ 4 at any one or two periods during M-T1, M-T2, and C-1y were also not significantly different from those with maternal K6 scores ≤ 4 at both M-T1 and M-T2 and C-1y (Table 4).
Multiple regression analysis with the stepwise method showed significantly low scores with maternal K6 ≥ 5 at both M-T1 and M-T2 and C-1y for the C-A DQ (B: −2.01, 95% CI: −3.65 − −0.38, β: −0.043, p = 0.02) and L-S DQ areas (B: −3.27, 95% CI: −5.04 − −1.50, β: −0.063, p = 0.0003), compared to those with maternal K6 scores ≤ 4 at both M-T1 and M-T2 and C-1y (Table 5). The groups with maternal K6 scores ≤ 4 at any one or two periods during M-T1, M-T2, and C-1y were also not significantly different from those with maternal K6 scores ≤ 4 at both M-T1 and M-T2 and C-1y (Table 5).
Discussion
In the present study of 4-year-old children, persistent maternal psychological distress (K6 scores ≥ 5) from the first half of pregnancy to 1 year postpartum tended to be associated with lower verbal cognitive development in boys, but not in girls. In contrast, in the group without persistent maternal psychological distress from the first half of pregnancy to 1 year postpartum, no significant impact was observed on verbal cognitive development, regardless of the children’s sex.
Sex-specific differences
Our study showed that maternal perinatal psychological distress tended to lead to lower verbal cognitive development in boys, but not in girls, at 4 years of age. At present, the reasons and mechanisms behind this phenomenon remain unknown, and further research is warranted. It is worth noting that although not specific to verbal cognitive development, several studies have found sex-specific effects, suggesting that boys are more vulnerable to maternal perinatal stress than girls. Reference Gentile1,Reference van den Bergh, van den Heuvel and Lahti2,Reference Rees, Channon and Waters5 King et al. reported a linear decline in IQ with increasing maternal prenatal objective stress exposure among boys. However, no such effect was observed among girls aged 11 years. Reference King, Dancause, Turcotte-Tremblay, Veru and Laplante19 Simcock et al. reported that higher levels of objective flood exposure predicted a more irritable temperament in boys, but not girls, at the age of 6 months. Reference Simcock, Elgbeili and Laplante20 Gerardin et al. reported that infants of mothers with prenatal depression presented higher scores on generalized anxiety, activity/impulsivity, and sleep problems than controls, particularly boys aged 1 year. Reference Gerardin, Wendland and Bodeau21 Loomans et al. reported that prenatal maternal anxiety was associated with hyperactivity/inattention in boys aged 5 years. Reference Loomans, van der Stelt and Van Eijsden22 Li et al. reported that prenatal maternal exposure to severe stress increases the risk of attention-deficit/hyperactivity disorder (ADHD) in boys. Reference Li, Olsen, Vestergaard and Obel23 Zhu et al. also reported that in mothers who experienced severe stressful prenatal life events, there was an increased risk for ADHD in boys, but not in girls. Reference Zhu, Hao and Tao24 Fineberg et al. reported that maternal daily-life stress during pregnancy was associated with significantly increased odds of schizophrenia spectrum disorders in boys. Reference Fineberg, Ellman and Schaefer25 Glasheen et al. reported that maternal prenatal and postnatal anxiety was associated with a higher risk of conduct disorder among boys; however, it was less likely in girls aged 16 years. Reference Glasheen, Richardson and Kim26
Others have found girls to be more vulnerable, particularly to emotional problems. Buss et al. reported that higher maternal cortisol levels during early gestation were associated with more affective problems in girls aged 7.5 years. Reference Buss, Davis and Shahbaba27 Braithwaite et al. reported that girls exposed to high levels of maternal prenatal cortisol were more emotionally negative than boys at 2 months of age. Reference Braithwaite, Murphy, Ramchandani and Hill28,Reference Braithwaite, Pickles and Sharp29 Wright et al. reported that an elevated maternal prenatal cortisol level was associated with lower callous-unemotional traits in girls, but not in boys, at 2.5–5.0 years of age. Reference Wright, Pickles, Braithwaite, Sharp and Hill30 As this study was based solely on K6 points based on the questionnaire and did not examine cortisol levels, future studies are needed to determine how the effects of K6 trajectories and cortisol levels on children differ by sex.
Sex differences have been observed in rodents. For example, Weinstock found that male rats subjected to prenatal stress had greater learning deficits than did female rats, with greater long-term hippocampal potentiation, hippocampal neurogenesis, and reduced dendritic spine density in the prefrontal cortex. Reference Weinstock31–Reference Zagron and Weinstock33 These sex differences may be due to the developing brain regions' sensitivity to stress hormones. Decreased testosterone and aromatase activity combined with the effects of other corticosteroids may contribute to learning deficits in male rats. Reference Weinstock34 In contrast, estrogen has protective effects on brain regions associated with learning and memory in rats and mice. Reference Liu, Day and Muñiz35–Reference Weinstock37
Clinical periods vulnerable to the effect of maternal psychological distress trajectories
Our study examined maternal psychological distress during three periods: the first half of pregnancy at approximately 14 weeks, the second half of pregnancy at approximately 27 weeks, and 1 year postpartum. We observed that persistent maternal psychological distress from the first half of pregnancy to 1 year postpartum had a negative association with verbal cognitive development in boys. Even overall, persistent maternal psychological distress from the first half of pregnancy to 1 year postpartum had a disadvantageous association with verbal and nonverbal cognitive development. No such association was noted in mothers who were not psychologically distressed (K6 scores ≤ 4) at any one or two of these three periods.
In a similar study that focused specifically on children’s cognitive development, Lin et al. reported that children’s cognitive development may be more susceptible to prenatal exposure to maternal emotional stress than postnatal emotional stress, at the age of 24–30 months. Reference Lin, Xu and Huang38
Although not specific to cognitive development, several studies have reported clinical periods associated with children’s vulnerability to the effects of maternal psychological distress trajectories on their neurodevelopment. Van der Waerden et al. reported that children whose mothers had persistent depressive symptoms, either intermediate or severe, from pregnancy to the postpartum period, had the greatest emotional and behavioral difficulties at the age of 5 years. Reference van der Waerden, Galéra and Larroque39 Fransson et al. reported that maternal prenatal and postpartum depression is associated with more behavioral problems in children. Girls are affected to a greater degree at 18 months of age. Reference Fransson, Sörensen and Kunovac Kallak40 Lin et al. reported that children’s temperamental development may be more susceptible to postnatal exposure to maternal emotional stress than to prenatal exposure, at the age of 24–30 months. Reference Lin, Xu and Huang38
For reference, although the research design blended prenatal and postpartum periods, Srinivasan et al. reported that children of mothers who experience depression in the perinatal period are more likely to report psychotic experiences at 18 years of age. Reference Srinivasan, Pearson, Johnson, Lewis and Lewis41 Oh et al. also reported that maternal perinatal depression up to 2 years postpartum affects childhood behavioral problems and executive function at 9 years of age. Reference Oh, Joung, Baek and Yoo42
Clinical implications
Undoubtedly, prenatal and postpartum maternal depression, anxiety, and stress negatively affect neurodevelopment, including cognitive performance, in children.
In our previous study using JECS data, persistent maternal psychological distress from the first to the second half of pregnancy was a risk factor for autism spectrum disorder among children. Reference Nishigori, Hashimoto and Mori14 Our current study also suggests that persistent maternal psychological distress from the first half of pregnancy to the first year postpartum had a negative effect on boys' verbal cognitive development at 4 years of age. In light of this finding, assessing the mental health of pregnant women during the early stages of pregnancy is essential. For women who experience psychological distress during early pregnancy, appropriate interventions to prevent continued psychological distress throughout the pregnancy and at least in the postpartum period are important.
Limitations
This study has several limitations. First, K6 is a self-administered questionnaire; therefore, the mothers’ psychological distress was not medically diagnosed. However, this questionnaire can be used because previous studies have shown reasonable results with it. Reference Furukawa, Kawakami and Saitoh12,Reference Sakurai, Nishi, Kondo, Yanagida and Kawakami13 Second, the Sub-Cohort Study was based on 5,000 participants (5%) who were selected from the total births. In reality, 3,287 participants (3.3%) were analyzed in this study. There may be an intrinsic bias in the sub-sample used for the study.
Strengths of the study
This was a large prospective birth cohort study in which certified testers objectively assessed the cognitive development of 3,287 children at 4 years of age.
Conclusion
Persistent maternal psychological distress from the first half of pregnancy to 1 year postpartum had a disadvantageous association with verbal cognitive development in boys, but not in girls, at 4 years of age. The JECS is a prospective study that plans to follow and evaluate the development of the targeted children until they reach 40 years of age. In the future, we plan to further evaluate children’s neurodevelopment, including changes in the effects of maternal prenatal and postnatal psychological distress on children’s development.
Data availability statement
Data are unsuitable for public deposition due to ethical restrictions and the legal framework of Japan. It is prohibited by the Act on the Protection of Personal Information (Act No.57 of 30 May 2003, amendment on 9 September 2015) to publicly deposit data containing personal information. Ethical Guidelines for Epidemiological Research enforced by the Japan Ministry of Education, Culture, Sports, Science and Technology and the Ministry of Health, Labour and Welfare also restricts the open sharing of epidemiologic data. All inquiries regarding access to data should be sent to: pj.og.sein@ne-scej. The person responsible for handling enquiries sent to this email address is Dr Shoji F. Nakayama, JECS Programme Office, National Institute for Environmental Studies.
Acknowledgments
The authors are grateful to all the participants of the study. Members of the JECS group as of 2023 are as follows: Michihiro Kamijima (principal investigator, Nagoya City University, Nagoya, Japan), Shin Yamazaki (National Institute for Environmental Studies, Tsukuba, Japan), Yukihiro Ohya (National Center for Child Health and Development, Tokyo, Japan), Reiko Kishi (Hokkaido University, Sapporo, Japan), Nobuo Yaegashi (Tohoku University, Sendai, Japan), Koichi Hashimoto (Fukushima Medical University, Fukushima, Japan), Chisato Mori (Chiba University, Chiba, Japan), Shuichi Ito (Yokohama City University, Yokohama, Japan), Zentaro Yamagata (University of Yamanashi, Chuo, Japan), Hidekuni Inadera (University of Toyama, Toyama, Japan), Takeo Nakayama (Kyoto University, Kyoto, Japan), Tomotaka Sobue (Osaka University, Suita, Japan), Masayuki Shima (Hyogo Medical University, Nishinomiya, Japan), Seiji Kageyama (Tottori University, Yonago, Japan), Narufumi Suganuma (Kochi University, Nankoku, Japan), Shoichi Ohga (Kyushu University, Fukuoka, Japan), and Takahiko Katoh (Kumamoto University, Kumamoto, Japan).
Author contribution
Hidekazu Nishigori and Toshie Nishigori are contributed equally to this work.
Financial support
This study was funded by the Ministry of the Environment, Japan. The findings and conclusions of this article are solely the responsibility of the authors and do not represent the official views of the above government.
Competing interests
None.
Ethical standards
The authors assert that all procedures contributing to this work comply with the ethical standards of the Ministry of the Environment’s Institutional Review Board on Epidemiological Studies (no. 100910001) and with the Helsinki Declaration of 1975, as revised in 2008, and have been approved by the institutional committees of all participating institutions. Written informed consent was obtained from all participants.
