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Original Studies

Maternal Mental Disorders and Pediatric Infectious Diseases

A Retrospective Cohort Study

Auger, Nathalie MD, MSc, FRCPC*,†,‡; Monnier, Maëva MPH†,§; Low, Nancy MD, MSc, FRCPC; Lee, Ga Eun MScPH*,†; Bilodeau-Bertrand, Marianne MSc; Luu, Thuy Mai MD, MSc, FRCPC

Author Information
The Pediatric Infectious Disease Journal: August 2021 - Volume 40 - Issue 8 - p 697-703
doi: 10.1097/INF.0000000000003108

Abstract

Infectious diseases are the most frequent reason for hospital stays in children,1 but maternal risk factors remain largely unknown. Mental disorders are common in women of reproductive age, and have the potential to be an important determinant of pediatric infections.2 Major depressive disorder affects up to 16% and psychosocial stress up to 78% of pregnant women.3 Depression and stress may increase susceptibility to infection by influencing the developing offspring immune system.4 Neonates and infants rely on maternal IgG to protect against infectious pathogens.5 Animal studies suggest that maternal stress hampers transplacental transfer of IgG antibodies.6 Depression and stress are risk factors for prematurity and low birthweight,2,7 birth outcomes associated with reduced transfer of IgG antibodies.5,8 Mental disorders may additionally affect breast-feeding and childcare, furthering the risk of infection.9,10

Previous studies suggest that children of women with prenatal depression and stress have higher rates of ear, respiratory and gastrointestinal infections.4,11–16 A study of 107,587 children in the United Kingdom reported that maternal depression during pregnancy or 6 months postpartum was associated with a 27% higher risk of lower respiratory tract infection and 40% higher risk of gastrointestinal infection up to 4 years of age.11 Studies of children under 2 years found higher rates of otitis media and recurrent respiratory infection when mothers had prenatal symptoms of depression, anxiety and stress.4,12,13 Other studies indicate that stressful life events during pregnancy such as financial hardship or familial death are associated with infectious diseases in offspring.14–16 However, there is a dearth of evidence for conditions such as schizophrenia, bipolar disorder and personality disorder.17 To better understand how maternal mental disorders affect the risk of childhood infections, we assessed the extent to which a range of mental disorders in women before and during pregnancy were associated with the risk of infection hospitalization before 13 years of age in a large cohort of Canadian children.

MATERIALS AND METHODS

We conducted a retrospective cohort study of 832,290 infants born between 2006 and 2016 in hospitals of the province of Quebec, Canada. Information on the cohort was available from hospital discharge abstracts compiled in the Maintenance and Use of Data for the Study of Hospital Clientele registry.18 Discharge abstracts contain clinical information on up to 41 diagnoses coded using the International Classification of Diseases and 35 procedures coded using the Canadian Classification of Health Interventions. Infants are linked with their mothers in the registry, enabling us to obtain data on maternal exposures and morbidities. Using encrypted health insurance numbers, we followed infants from birth until the end of the study on March 31, 2019 to identify hospitalizations for infection in childhood. The cohort is population-based as almost all deliveries in Quebec occur in hospital (98%). The cohort did not include 3296 stillbirths.

Maternal Mental Disorders

The primary exposure in this study was any maternal mental disorder diagnosed before or during pregnancy, including depression, bipolar disorder, stress- and anxiety-related disorders, schizophrenia and delusional disorder, personality disorder and drug- or alcohol-related substance use disorders (see Table, Supplemental Digital Content 1, http://links.lww.com/INF/E330 for International Classification of Diseases codes).18 We identified mental disorders that were present during pregnancy using diagnostic codes from the delivery discharge abstract, which contains information on any prenatal mental disorder that required ambulatory treatment.19 We also had information on mental disorders that required hospitalization before pregnancy. Thus, we had data on both outpatient mental disorders during pregnancy and mental disorders requiring inpatient treatment before pregnancy. We identified the total number of hospitalizations for mental disorders. Women with no documented mental disorder were the comparison group.

Childhood Infection

The main outcome measure was defined as pediatric infections that required hospitalization between birth and 13 years of age. We included respiratory (acute upper respiratory, influenza, tonsillitis, bronchitis, bronchiolitis and pneumonia), gastrointestinal (infectious enteritis and appendicitis), otitis media, central nervous system (meningitis and encephalitis), urinary tract, carditis (myocarditis, endocarditis and pericarditis), septic arthritis and osteomyelitis, skin infections, septicemia, perinatal infections before 28 days of age and other infections (see Table, Supplemental Digital Content 1, http://links.lww.com/INF/E330). We included a category for vaccine-preventable infections defined as measles, mumps, rubella, varicella, rotavirus, poliomyelitis, hepatitis A, hepatitis B, diphtheria, tetanus, whooping cough, Haemophilus influenzae, Streptococcus pneumoniae and meningococcal infection.

Confounders

We considered characteristics that had the potential to affect the association between maternal mental disorders and childhood infections. Covariates included maternal age (<25, 25–34 and ≥35 years), parity (0, 1, 2 or more previous deliveries), maternal comorbidity including tobacco use, obesity, preexisting or gestational diabetes, dyslipidemia and preexisting or pregnancy-related hypertension (see Table, Supplemental Digital Content 1, http://links.lww.com/INF/E330), infant sex (male and female), socioeconomic disadvantage (the poorest fifth of the population, not disadvantaged and unknown), and time period of birth (2006–2009, 2010–2012 and 2013–2016).

Data Analysis

We calculated the incidence of infection hospitalization per 1000 person-years and plotted cumulative incidence curves from birth to 13 years of age. We used Cox proportional hazards regression models to compute the hazard ratio (HR) and 95% confidence interval (CI) for the association between maternal mental disorders and childhood infections, adjusted for confounders. We used a Cox model with robust sandwich estimators to account for correlation of survival data in children with the same mother. We expressed the follow-up time in days, from birth to the first hospitalization for infection, death or the end of the study. We accounted for death as a competing event that prevented children from developing future infections. Children who were never hospitalized for infection were censored.

We examined associations by type and severity of mental disorder and type of infection. We further assessed whether associations differed by age of infection hospitalization, including <1, 1–2, 3–4 and 5 years and older. In sensitivity analyses, we examined whether excluding preterm, low birthweight or small-for-gestational age children modified the associations and whether findings differed in sex-stratified models. We performed analyses using SAS version 9.4 for Windows (SAS Institute Inc., Cary, NC). As health insurance numbers were scrambled and patients could not be identified, the institutional review board of the University of Montreal Hospital Centre waived the need for consent and ethics review.

RESULTS

This study included 832,290 children followed from birth to 13 years of age (see Figure, Supplemental Digital Content 2, http://links.lww.com/INF/E331). Maternal mental disorders were present for 43,179 children (5.2%) (Table 1). The incidence of any pediatric infection hospitalization was higher for maternal mental disorders compared with no disorder (66.1 vs. 41.1 cases per 1000 person-years). Incidence rates were higher for stress- and anxiety-related disorders (70.4 per 1000 person-years), personality disorders (72.2 per 1000 person-years), and for women with 2 or more admissions for mental disorders (76.0 per 1000 person-years).

TABLE 1. - Incidence of Childhood Infection Hospitalization According to Maternal and Child Characteristics
No. Infants No. Infection Hospitalization Total Person-years Incidence Rate per 1000 Person-years (95% CI)
Maternal mental disorder*
 Any 43,179 14,174 214,279 66.1 (65.4–66.9)
 Depression 9776 3232 49,058 65.9 (64.3–67.5)
 Bipolar 2423 745 12,026 62.0 (58.9–65.2)
 Stress and anxiety 25,412 8765 124,423 70.4 (69.4–71.5)
 Schizophrenia 1702 432 9180 47.1 (44.0–50.3)
 Personality 9889 3466 48,023 72.2 (70.5–73.9)
 Substance use 15,722 5051 76,366 66.1 (64.9–67.4)
 No mental disorder 789,111 194,016 4,717,189 41.1 (41.0–41.3)
No. admissions for mental disorder
 ≥2 9182 3290 43,264 76.0 (74.2–77.9)
 1 33,997 10,884 171,015 63.6 (62.8–64.5)
 0 789,111 194,016 4,717,189 41.1 (41.0–41.3)
Age at delivery, yrs
 <25 135,222 37,485 777,559 48.2 (47.9–48.6)
 25–34 553,362 140,574 3,303,635 42.6 (42.4–42.7)
 ≥35 143,706 30,131 850,274 35.4 (35.2–35.7)
Maternal comorbidity
 Yes 122,396 33,414 655,987 50.9 (50.6–51.3)
 No 709,894 174,776 4,275,481 40.9 (40.7–41.0)
Parity
 0 410,989 96,462 2,468,335 39.1 (38.9–39.3)
 1 287,922 76,654 1,695,531 45.2 (45.0–45.4)
 ≥2 133,379 35,074 767,603 45.7 (45.4–46.0)
Infant sex
 Male 426,510 118,065 2,456,549 48.1 (47.9–48.3)
 Female 405,780 90,125 2,474,920 36.4 (36.2–36.6)
Socioeconomic deprivation
 Yes 166,118 41,554 956,118 43.5 (43.2–43.8)
 No 631,315 158,124 3,789,944 41.7 (41.6–41.9)
Time period
 2006–2009 329,964 85,654 2,570,291 33.3 (33.2–33.5)
 2010–2012 253,466 63,659 1,467,532 43.4 (43.1–43.6)
 2013–2016 248,860 58,877 893,646 65.9 (65.5–66.3)
Total 832,290 208,190 4,931,468 42.2 (42.1–42.3)
*Not mutually exclusive.
Tobacco use, obesity, preexisting and gestational diabetes, dyslipidemia, hypertension and preeclampsia.

At 13 years of age, the cumulative incidence of infection hospitalization for any maternal mental disorder was 378.0 per 1000 children compared with 281.9 per 1000 for no mental disorder (Fig. 1). Differences in incidence were apparent from birth and increased rapidly before 2 years of age. The difference was more marked for personality disorders.

FIGURE 1.
FIGURE 1.:
Maternal mental disorders and cumulative incidence of pediatric infection hospitalization before 13 years of age. The solid line indicates mental disorder and the dotted line indicates no mental disorder.

Maternal mental disorders were associated with most types of pediatric infection (Table 2). Compared with no mental disorder, maternal mental disorders overall were associated with otitis media, bronchitis, infectious enteritis, encephalitis, urinary tract infections, carditis, skin infections, septicemia, perinatal infections and vaccine-preventable infections. Maternal mental disorders were not associated with appendicitis and infections of the bone and joints.

TABLE 2. - Association Between Maternal Mental Disorders Overall and Hospitalizations for Specific Pediatric Infections
Incidence Rate per 1000 Person-years (95% CI) HR (95% CI)
Mental Disorder (N = 43,179) No Mental Disorder (N = 789,111) Unadjusted Adjusted*
Any infection 66.2 (65.4–66.9) 41.1 (41.0–41.3) 1.48 (1.45–1.51) 1.41 (1.38–1.44)
Otitis media 27.1 (26.6–27.5) 17.9 (17.9–18.0) 1.42 (1.39–1.46) 1.38 (1.35–1.42)
Respiratory 27.5 (27.1–28.0) 15.5 (15.5–15.6) 1.64 (1.60–1.68) 1.51 (1.47–1.55)
 Acute upper respiratory 11.2 (10.9–11.5) 6.62 (6.58–6.67) 1.59 (1.53–1.65) 1.49 (1.44–1.55)
 Tonsillitis 1.02 (0.94–1.10) 0.68 (0.67–0.70) 1.45 (1.29–1.63) 1.41 (1.26–1.59)
 Influenza 2.07 (1.96–2.19) 1.01 (0.99–1.02) 1.97 (1.81–2.15) 1.76 (1.61–1.92)
 Bronchiolitis 9.51 (9.26–9.77) 4.96 (4.92–5.00) 1.77 (1.70–1.84) 1.55 (1.48–1.61)
 Bronchitis 1.12 (1.04–1.21) 0.51 (0.50–0.53) 2.05 (1.83–2.30) 1.89 (1.68–2.12)
 Pneumonia 9.83 (9.57–10.1) 5.37 (5.33–5.41) 1.72 (1.65–1.79) 1.56 (1.50–1.62)
Gastrointestinal 6.53 (6.32–6.74) 3.90 (3.86–3.93) 1.62 (1.54–1.70) 1.58 (1.50–1.66)
 Infectious enteritis 5.95 (5.76–6.15) 3.34 (3.30–3.37) 1.69 (1.61–1.78) 1.65 (1.57–1.74)
 Appendicitis 0.60 (0.54–0.67) 0.58 (0.56–0.59) 1.14 (0.98–1.32) 1.10 (0.94–1.28)
Central nervous system 0.59 (0.53–0.66) 0.40 (0.39–0.41) 1.42 (1.22–1.66) 1.33 (1.14–1.55)
 Meningitis 0.50 (0.45–0.56) 0.34 (0.33–0.35) 1.41 (1.20–1.67) 1.31 (1.11–1.55)
 Encephalitis 0.11 (0.09–0.14) 0.07 (0.06–0.07) 1.69 (1.19–2.40) 1.65 (1.16–2.35)
Urinary tract 3.60 (3.45–3.76) 2.15 (2.12–2.17) 1.58 (1.48–1.68) 1.49 (1.39–1.59)
Carditis 0.07 (0.06–0.10) 0.04 (0.04–0.05) 1.72 (1.11–2.66) 1.60 (1.03–2.47)
Septic arthritis and osteomyelitis 0.19 (0.16–0.23) 0.21 (0.20–0.22) 0.88 (0.68–1.15) 0.85 (0.65–1.11)
Integument 2.16 (2.05–2.28) 1.43 (1.41–1.45) 1.44 (1.32–1.56) 1.31 (1.21–1.42)
Septicemia 0.51 (0.46–0.57) 0.34 (0.33–0.35) 1.43 (1.22–1.69) 1.28 (1.09–1.51)
Perinatal 7.44 (7.22–7.66) 4.61 (4.57–4.65) 1.50 (1.44–1.57) 1.42 (1.36–1.49)
Vaccine preventable 1.52 (1.42–1.63) 0.99 (0.97–1.00) 1.44 (1.30–1.59) 1.41 (1.28–1.56)
Other infection 4.58 (4.41–4.76) 2.67 (2.64–2.70) 1.63 (1.54–1.72) 1.51 (1.42–1.60)
*Adjusted for maternal age, parity, maternal comorbidity, sex, socioeconomic deprivation and time period.

All types of mental disorders were associated with the risk of childhood infection, but the associations were stronger for stress- and anxiety-related disorders, as well as personality disorders (Table 3). The associations were particularly strong for gastrointestinal infection. A history of 2 or more admissions for mental disorders was more strongly associated with the risk of gastrointestinal infection than a single admission, compared with no mental disorder. Maternal schizophrenia was not associated with the risk of childhood infections.

TABLE 3. - Association Between Type of Mental Disorder With Hospitalizations for Leading Childhood Infections
HR (95% CI)*
Any Infection Otitis Media Respiratory Gastrointestinal
Type of mental disorder
 Depression 1.42 (1.37–1.48) 1.41 (1.34–1.49) 1.56 (1.48–1.64) 1.71 (1.55–1.89)
 Bipolar 1.37 (1.27–1.47) 1.32 (1.18–1.47) 1.45 (1.30–1.61) 1.39 (1.11–1.73)
 Stress and anxiety 1.49 (1.46–1.53) 1.51 (1.46–1.56) 1.58 (1.53–1.64) 1.75 (1.64–1.85)
 Schizophrenia 1.11 (1.00–1.23) 1.05 (0.91–1.22) 1.13 (0.98–1.32) 1.22 (0.92–1.62)
 Personality 1.55 (1.49–1.61) 1.54 (1.46–1.62) 1.68 (1.60–1.77) 1.81 (1.65–1.99)
 Substance use 1.39 (1.35–1.43) 1.28 (1.23–1.34) 1.52 (1.46–1.58) 1.39 (1.28–1.51)
 None Reference Reference Reference Reference
No. admissions for mental disorder
 ≥2 1.61 (1.55–1.67) 1.57 (1.49–1.65) 1.81 (1.72–1.90) 1.90 (1.73–2.09)
 1 1.36 (1.33–1.39) 1.34 (1.30–1.38) 1.43 (1.39–1.47) 1.49 (1.41–1.58)
 0 Reference Reference Reference Reference
*Adjusted for maternal age, parity, maternal comorbidity, sex, socioeconomic deprivation and time period.

Associations were more prominent before 1 year and weakened slightly with age (Table 4). Maternal mental disorders were associated with 54% greater risk of any infection hospitalization before 1 year (95% CI: 1.50–1.58), 35% greater risk between 1 and 2 years (95% CI: 1.31–1.39), 29% greater risk between 3 and 4 years (95% CI: 1.22–1.37) and 23% greater risk between 5 and 13 years of age (95% CI: 1.15–1.32). For most types of infection, associations tended to weaken with increasing age. Associations nonetheless persisted after 5 years of age for otitis media, respiratory infection, gastrointestinal infection and urinary tract infection.

TABLE 4. - Association Between Maternal Mental Disorder and Hospitalization for Infections by Child Age
HR (95% CI)*
<1 yr 1–2 yrs 3–4 yrs ≥5 yrs
Any infection 1.54 (1.50–1.58) 1.35 (1.31–1.39) 1.29 (1.22–1.37) 1.23 (1.15–1.32)
Otitis media 1.63 (1.54–1.72) 1.35 (1.31–1.40) 1.27 (1.19–1.35) 1.29 (1.17–1.41)
Respiratory 1.58 (1.52–1.63) 1.45 (1.39–1.51) 1.42 (1.30–1.54) 1.42 (1.28–1.59)
Gastrointestinal 1.85 (1.70–2.01) 1.54 (1.43–1.67) 1.57 (1.38–1.79) 1.27 (1.13–1.43)
Central nervous system 1.39 (1.14–1.70) 1.05 (0.65–1.71) 1.42 (0.90–2.26) 1.04 (0.63–1.74)
Urinary tract 1.44 (1.33–1.55) 1.64 (1.43–1.88) 1.44 (1.11–1.87) 1.57 (1.21–2.04)
Carditis 2.31 (1.32–4.03) 3.77 (1.62–8.78)
Septic arthritis and osteomyelitis 0.73 (0.35–1.54) 0.93 (0.63–1.36) 0.52 (0.23–1.18) 1.03 (0.61–1.75)
Integument 1.45 (1.20–1.75) 1.65 (1.44–1.89) 1.19 (0.95–1.50) 1.20 (0.95–1.51)
Septicemia 1.11 (0.86–1.44) 1.83 (1.33–2.53) 0.96 (0.51–1.83) 1.28 (0.72–2.31)
Vaccine preventable 1.51 (1.30–1.76) 1.32 (1.12–1.54) 1.59 (1.16–2.18) 1.11 (0.72–1.69)
Other infection 1.48 (1.36–1.62) 1.57 (1.42–1.73) 1.51 (1.28–1.78) 1.23 (1.02–1.49)
*HR for maternal mental disorder versus no mental disorder, adjusted for maternal age, parity, maternal comorbidity, sex, socioeconomic deprivation and time period.

In sensitivity analyses where we excluded preterm children, associations with maternal mental disorders weakened slightly for all types of infection (see Table, Supplemental Digital Content 3, http://links.lww.com/INF/E332). Results did not change substantially when we excluded low birthweight and small-for-gestational age children. There was no noticeable difference in the risk of infection hospitalization between male and female children in sex-stratified analyses.

DISCUSSION

In this cohort study of >800,000 children followed from birth to 13 years of age, maternal mental disorders were associated with an increased risk of infectious disease hospitalization in childhood. Maternal depression, bipolar disorder and substance use disorders were all associated with offspring infections, but associations were more elevated for stress- and anxiety-related disorders as well as personality disorders. The risk of pediatric infection hospitalization was also elevated for women with multiple admissions for mental disorders. Associations were strongest the first year of life and weakened with increasing age of children. The findings suggest that maternal mental disorders before and during pregnancy may contribute to the risk of infectious diseases in offspring. Women with mental disorders may benefit from closer psychosocial support to reduce infectious disease morbidity in their children.

Current data on prenatal mental disorders and offspring infections are limited to maternal depression and psychologic stress.4,11–16 Using data obtained from primary healthcare records, a cohort study of 107,587 children reported that perinatal depression was associated with 1.4 times the risk of gastrointestinal infection and 1.3 times the risk of respiratory infection.11 Studies of self-reported prenatal symptoms of depression, stress and anxiety have found associations with ear and respiratory infections.4,12,13 Stressful life events in the prenatal period including financial problems, serious accidents and familial death are also associated with increased risks of child infections.14–16 For example, the Norwegian Mother and Child Cohort Study of 74,801 children found that stressful life events 1 year before and during pregnancy were associated 1.1 times the risk of infections in infants under 1 year.14 In our study of children up to 13 years of age, associations were present with prenatal depression and stress- and anxiety-related disorders as well as with understudied mental disorders including bipolar and personality disorders. Maternal schizophrenia was not associated with childhood infection hospitalization, but power for this analysis was low and women with schizophrenia may be more likely to have alternate childcare arrangements.17

Both bipolar disorder and personality disorders were associated with the same infections as depression and stress- and anxiety-related disorders. Bipolar disorder is a complex mental condition characterized by episodic mood episodes, potentially accompanied by psychosis.17 Symptoms of bipolar disorder may affect caregiving or factors that increase the risk of infections in offspring.10 Mothers in an acute mood or psychotic bipolar episode may have considerable mental health symptoms and face challenges in infection prevention.10,17 Some personality disorders may make it difficult for mothers to be responsive to their child before infectious symptoms become severe.10,20 Infectious diseases may have a greater chance of progressing before healthcare is obtained, which may increase the need for hospitalization to treat advanced infections.

Maternal mental disorders were associated with otitis media, all types of respiratory infections, and vaccine-preventable infections in our data. While the risks of acquiring these infections can be reduced with the use of preventive services, there is conflicting evidence that maternal mental disorders may be associated with decreased participation in well-child visits.21 There is, however, more evidence that women with mental health problems may start vaccination schedules late.22 A recent study of 479,949 children demonstrated that maternal mental disorders were associated with a 14% lower likelihood of completing vaccinations by 5 years of age.22 Smoking is also common in women with mental disorders.16 Passive smoking is a risk factor for otitis media and respiratory infections in children.23 Tobacco smoke impairs airway function and mucociliary clearance, increasing susceptibility to pathogens.23

Maternal mental disorders were strongly associated with infectious enteritis. Risk factors for infectious enteritis are similar to other childhood infections, although diet and hygiene may be greater determinants.11,24,25 Poor diet may lower immunity and encourage pathogen invasion.24 In addition, unhealthy gut microbiota can be associated with poor behavioral outcomes in children.26 Handwashing and toothbrushing reduce the risk of infections, and studies have found that these behaviors may be less common in individuals with mental disorders.25 Poor hygiene practices may also be adopted by children.16 Breast-feeding is another factor protective against gastrointestinal infection, and infections overall.27 However, maternal mental disorders may be associated with shorter duration of breast-feeding.9 Women using lithium for bipolar disorder may also be advised against breast-feeding to avoid toxicity in infants.17,28

It is unclear if exposure to psychiatric drugs in utero is linked with future infection risk in offspring. During pregnancy, women with severe mental disorders may require psychiatric drugs that can cross the placenta and be present in amniotic fluid.28 Mood stabilizers such as sodium valproate are associated with a risk of teratogenicity, but the extent to which psychiatric drugs could affect the fetal immune system is uncertain.28 Psychiatric drugs are known to have immunomodulatory effects.29 Lithium may influence cytokine levels in patients with bipolar disorder.29 Maternal mental disorders are associated with increased use of illicit drugs and alcohol,28 which can pass to the fetus through the placenta and contribute to the risk of infections.30 Some data suggest that cocaine suppresses the fetal T lymphocyte response,31 and that alcohol impairs the development of innate immunity in the fetal lung.32

In our study, associations between maternal psychiatric disorders and pediatric infectious diseases weakened over time, reinforcing the possibility of a perinatal origin. Associations were the strongest before 1 year of age. Titers of placentally transferred IgG antibodies are highest in the first months of life, and protect neonates as their immune systems mature.5 In macaques, maternal stress impairs the transplacental transfer of IgG antibodies.6 Mental disorders are also associated with preterm birth, low birthweight and small-for-gestational age birth,2,7,10 adverse birth outcomes associated with lower levels of maternal IgG.5,8 When we excluded these children from the analysis, associations weakened mostly for preterm birth, suggesting that gestational length and immaturity may be more important than growth-related pathways. Preterm infants have immature immune systems and may require more time to develop immunity.33 Moreover, preterm birth is associated with chronic lung diseases which may further the risk of respiratory infections. Preterm infants also have a suboptimal gut microbiota compared with term infants.34 A balanced microbiome is necessary for the normal development of the immune system.34

Maternal mental disorders may also cluster with emotional stress due to financial hardship, unsafe neighborhoods and limited social resources.14–16 These stressful life events can activate the hypothalamic-pituitary-adrenocortical axis and lead to elevated levels of cortisol.13 Recent data suggest that high levels of prenatal cortisol may disrupt the maternal gut microbiota and the transmission of microbiota to the infant during delivery.26 Activation of the maternal hypothalamic-pituitary-adrenocortical axis may affect the programming of the offspring immune system.14 The immune system continues to develop during infancy and childhood, and is vulnerable to environmental insults including stress.35 Effects of stress have the potential to persist after birth, and may partly explain why we found associations between maternal mental disorders and infections later in childhood.

There were limitations in this study. We captured infections requiring hospitalization but not mild infections that resolved spontaneously or were treated in outpatient settings. We could not determine if the motive for hospitalization was the infectious disease or concerns about potentially compromised childcare. We had data on maternal mental disorders during pregnancy and severe disorders before pregnancy, but not mental disorders that only appeared after birth of the child. Moreover, mental disorders may be underreported, especially substance use disorders. We did not have information on the type of treatment for mental disorders, including psychiatric drugs or their dosage. We censored patients with short follow-up time due to missing health insurance numbers (5.5%) and accounted for deaths as competing events (0.3%), but do not know the extent to which selection bias may have affected the results. Excluding these children from analyses led to similar results. However, we could not include stillbirths. Residual confounding may be present as we did not have information on daycare attendance, diet, breast-feeding, probiotic or antibiotic use, immunization status and lifestyle factors; however, we adjusted for known confounders. Coding errors may have attenuated the associations. We did not account for multiple comparisons to minimize the chance of not capturing associations. It is unlikely that the findings were due to chance alone because findings were consistent between outcomes. The data are representative of a large Canadian province with a multicultural population, but the findings may differ in substantially different regions.

In this population-based study of over 800,000 children, we found that maternal mental disorders before or during pregnancy were associated with the risk of pediatric infections. Associations were strongest for women with stress- and anxiety-related disorders as well as personality disorders, and for women with multiple admissions for mental disorders. Associations persisted throughout childhood, suggesting that maternal mental disorders may be an important contributor to infectious disease morbidity in children. Future studies are merited to elucidate the underlying factors driving this relationship and to identify strategies for prevention.

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Keywords:

bipolar disorders; mental disorder; respiratory tract infections; schizophrenia; vaccine-preventable infections

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