Characteristics of the studies included in the meta-analysis
| First author [ref.] | Subjects n | Design | Psychological stress | Gestational age at exposure | Measurement of psychological stress | Exposure included | Respiratory health | Age at assessment/diagnosis | Measurement of respiratory health | Outcome measure included | Most relevant effect size# | Quality assessment: NOS |
| Alton [30] | 791 | Follow-up study of a prenatal care trial | Maternal distress | Gestational weeks 7 and 32–34 | Symptom Questionnaire (anxiety, depression, somatic, hostility scales). | Severe maternal distress (sum score of Symptom Questionnaire) versus no stress | Wheeze | 3 years of age | Maternal report of a diagnosis of chronic breathing problems made by a healthcare worker. | Wheeze/no wheeze | Severe prenatal stress: OR 2.62 (95% CI 0.92–7.43)¶ | 6 |
| Beijers [31] | 174 | Cohort study | General anxiety and stress; pregnancy-related anxiety and stress | Last trimester (mean: 37 weeks of pregnancy) | STAI (general anxiety); Alledaagse Problemen Lijst [Everyday Problem Checklist]; pregnancy-specific anxieties questionnaire revised; Pregnancy Experience Scale. | Sum of all questionnaires | Respiratory health | First 12 months of life | Mothers reported on their infant's illnesses and health complaints in semi-structured interviews at monthly intervals (three in person, nine by telephone). The health data were coded using ICD-10 and summed over 12 months. | Respiratory health (upper versus lower quartile) | Anxiety during pregnancy (STAI)+: B=1.465, β=0.132, R2model=0.232, Fchange=5.614, R2change=0.093 | 5 |
| Chiu [32] | 653 | Cohort study | Negative life events (NLEs) | Within 2 weeks of enrolment; mid-to-late pregnancy (28.4±7.9 week) | Crisis in Family Systems - Revised survey: measuring life events experienced across 11 domains in the past 6 months. | Prenatal NLEs | Wheeze | From birth to 2 years of age | Child wheeze reported by mother at telephone and face-to-face interviews at ∼3-month intervals. Mothers were asked, “Since we last spoke with you on [date], has your infant/child had wheezing or whistling in the chest?” Repeated wheeze was defined as two or more episodes. | Repeated wheeze: more than two episodes versus less than two episodes | NLE score ≥5; OR 3.79 (95% CI 1.39–10.3)§ | 7 |
| Cookson [33] | 5810 | Cohort study | Anxiety; maternal depression; life events | Gestational weeks 18 and 32 | Crown Crisp Experiential Index; Edinburgh Postnatal Depression Scale; Life Events Inventory. | Anxiety during pregnancy (4th quartile at 18 or 32 weeks) | Asthma; wheeze | 7.5 years | Current asthma was defined as a report via questionnaire of a doctor's diagnosis of asthma-ever and either reported symptoms of wheeze or treatment for asthma in the previous 12 months. | Asthma/no asthma; wheeze/no wheeze | Maternal anxiety 4th quartile Asthma 32 weeks: OR 1.65 (95% CI 1.30–2.08)ƒ Asthma 18 weeks: OR 1.53 (95% CI 1.22–1.93)## | 7 |
| De Marco [34] | 3854 | Survey | Stressful life events | Any time during pregnancy (retrospectively assessed) | One question: “During pregnancy, did the mother experience any situations of loss or uneasiness (mourning, loss of her or her husband's job, separation/divorce)?” | Stressful life events during pregnancy Yes/No | Asthma; wheeze | 3–14 years of age (mean±sd 8.5±3.2) | A child was considered to have wheeze/asthma based on the following questions: “Has your child ever had wheezing or whistling in his/her chest at any time in the past?”; “Has your child ever had asthma?” | Asthma/no asthma; wheeze/no wheeze | Asthma: OR 1.71 (95% CI 1.02–2.89)¶¶ Wheezing: adjusted OR 1.41 (95% CI 1.03–1.94) | 5 |
| Guxens [35] | 4848 | Cohort study | Psychological distress | 20 weeks of gestation | Brief Symptom Inventory | Overall measure, anxiety## depression## | Wheeze; asthma | Wheeze was assessed at 1, 2, 3 and 4 years of age, asthma at 6 years of age | Adapted questionnaire (ISAAC): 1) no wheezing; 2) early wheezing; 3) late wheezing; 4) preschool persistent wheezing. Physician-diagnosed ever-asthma obtained using questionnaires. | Asthma/no asthma; wheeze (transient + late onset + persistent)/no wheeze | Asthma: overall distress-adjusted OR 1.45 (95% CI 0.91–2.31)++ Wheezing: overall distress-adjusted OR 1.60 (95% CI 1.32–1.93) | 7 |
| Khashan [27] | 3 193 033 | Cohort study | Bereavement | First (0–12 weeks), second (13–24 weeks) and third (25 weeks- birth) trimester | Death of a spouse or child. | Exposed/unexposed during pregnancy | Asthma | All ages and additional analysis at >6 years of age | Hospital discharges from the National Patient Register. The primary outcome measure was defined according to the ICD codes of asthma (ICD-8, ICD-9 and ICD-10) from hospitalised patients. | Asthma/no asthma | Adjusted RR age of children >6 years of age: 2.01 (95% CI 1.16–3.49)§§ Adjusted RR all ages: 1.43 (95% CI 1.06–1.92) | 6 |
| Lefevre [36] | 247 | Case–control study | Depression, anxiety | Anytime during pregnancy (retrospectively assessed) | Doctor's diagnosis, recorded at the hospital in “cases” and reported using a standardised questionnaire in “controls”. In both, diagnoses and troubles were confirmed during an interview with a trained psychologist. | Anxiety during pregnancy, depression during pregnancy## | Wheeze | Before 2 years of age | More than three dyspnoeic episodes with wheezing, whatever the age of onset. | Wheeze (more than three episodes)/no wheeze | Anxiety: adjusted OR 1.98 (95% CI 0.69–5.68)ƒƒ Depression: adjusted OR 1.55 (95% CI 0.12–19.8)## | 5 |
| Reyes [37] | 279 | Cohort study | Maternal demoralisation | Third trimester | PERI-D | High (score >1.55) versus low demoralisation | Wheeze | Every 3 months in the first 0–2 years, and every 6 months at 2–5 years | Mother/caregiver asked a binary question: “In the last 3 months has your child had wheezing or whistling in the chest?” Divided into: transient, late-onset and persistent wheezers. | Wheeze (transient + late onset + persistent)/no wheeze | Adjusted OR 1.66 (95% CI 1.29–2.14)### | 5 |
| Wood [38] | 515 | Cohort study | Internal stress; external stress | 60% in third trimester, most of the remainder in the second trimester | Internal stressors: Pregnancy Anxiety Scale, EPDS, PSS. External stressors: difficult life circumstances, financial strain, neighbourhood violence, housing problems. | External stress (cumulative stress score), internal stress## | Wheeze | From birth until 12 months | Wheeze in the first 12 months (zero, one or more than two episodes of wheezing) assessed by telephone surveys performed every 3 months using the Respiratory and Allergy Symptoms questionnaire and during telephone calls at the time of illnesses, from records of hospitalisations caused by respiratory tract illnesses, and from physical examinations at scheduled study visits. | Wheeze (one or more episode)/no wheeze | Multiple wheeze: External stress: adjusted OR 1.11 (p=0.10)¶¶¶ Mean EPDS score: adjusted OR 1.37 (p<0.01)## Mean PSS score: adjusted OR 1.59 (p=0.01)## | 5 |
#: effect sizes in bold are included in the adjusted meta-analysis. ¶: adjusted for prenatal maternal alcohol use, smoking and vitamin use, postnatal smoking, preterm birth, duration exclusive breastfeeding, maternal education level and out-of-home childcare. +: variables in initial regression model: maternal educational level, smoking during pregnancy, alcohol ingestion during pregnancy, birth weight, 5-min Apgar score, sex, number of siblings, postnatal anxiety, postnatal daily hassles, daily hassles, fear of giving birth, fear of bearing a child with disabilities and evening cortisol. Adjusted for duration of breastfeeding, child care attendance, pregnancy-specific hassles and cortisol decline. §: adjusted for child's sex, season of birth, race/ethnicity, education and self-reported maternal history of atopy, prenatal traffic-related air pollution (black carbon), household cockroach allergen and neighbourhood disadvantage index. ƒ: adjusted for sex, preterm delivery, multiple birth, number of siblings, maternal age, maternal education, maternal history of asthma and allergy, prenatal tobacco smoke exposure and problems during pregnancy (diabetes, hypertension, steroid intake). ##: analysed exploratively as alternative measures in meta-analyses. ¶¶: adjusted for sex, age, of foreign descent (both non-Italian parents), parental education, parental smoking, parental asthma, person who filled in the questionnaire, residential area, traffic level near home, exposure to industrial pollution, exposures to mould, farm animals, bedroom sharing with older siblings, ever had a cat at home, ever had a dog at home, pregnancy conditions (hypertension, pre-eclampsia, risk of miscarriage or premature delivery, infection-induced fever, gynaecological infection, use of paracetamol), birth conditions (mother's age at delivery, birth weight, preterm birth, caesarean birth) and breastfeeding.++: adjusted for maternal age, body mass index, smoking during pregnancy, educational level, ethnicity, parity, parental history of asthma or atopy, pet keeping, children's sex, preterm birth, birth weight, breastfeeding, daycare attendance, secondhand smoke at home, eczema and lower respiratory tract infections. §§: adjusted for calendar year and age as time-dependent variables, family history of allergy, maternal age, infant sex and maternal level of education. ƒƒ: adjusted for propensity score, child's age, maternal asthma, maternal smoking habit during pregnancy and birthplace (Paris/outside Paris (France)). ###: maternal (age at pregnancy, ethnicity, education, history of asthma and IgE) and child characteristics (sex, exposure to secondhand smoke and wheeze reported during the cold and flu season). ¶¶¶: adjusted for study site, birth season of the child and child's sex. NOS: Newcastle-Ottawa Scale; STAI: Stait-Trait Anxiety Inventory; ICD-8, -9 and -10: International Classification of Diseases, 8th, 9th and 10th revision; B: regression coefficient; β: standardised regression coefficient; R2model: total explained variance by the model; Fchange: F statistic corresponding to R2change; R2change: partial explained variable by added predictors; ISAAC: International Study of Asthma and Allergies in Childhood; RR: relative risk; PERI-D: Psychiatric Epidemiology Research Interview Demoralisation Scale; EPDS: Edinburgh Postnatal Depression Scale; PSS: Perceived Stress Scale.