Mode of delivery and offspring atopic dermatitis in a Swedish nationwide study.

BACKGROUND: Atopic dermatitis is a common chronic childhood disease associated with significant morbidity and healthcare costs. There is a known association between caesarean section and asthma, but the relationship between caesarean section and offspring atopic dermatitis remains uncertain. METHODS: We conducted a register-based nationwide cohort study including children born in Sweden between January 2006 and December 2018. Data on health and socioeconomic variables were extracted from the national registers for children aged ≤5 years. Time-to-event analyses were used to calculate hazard ratios (HR) with 95% confidence intervals (CI) adjusting for confounders and familial factors. RESULTS: 1,399,406 children were included (6,029,542 person-years at risk). Atopic dermatitis was observed in 17.2% of the 1,150,896 children born by vaginal delivery and 18.3% of the 248,510 born by caesarean section. The mean age of onset of atopic dermatitis was 2.72 years (SD 1.8). Birth by caesarean section was associated with a higher risk of atopic dermatitis (adj-HR 1.12, 95% CI: 1.10-1.14). A higher risk of atopic dermatitis was found in children born by instrumental vaginal delivery (adj-HR 1.10, 1.07-1.13); emergency caesarean section (adj-HR 1.12, 1.10-1.15), and elective caesarean section (adj-HR 1.13, 1.10-1.16) than uncomplicated vaginal delivery in children <1 year of age. Similar hazards were observed in those ≥1 year of age. In sibling control analysis, greater risks remained in children aged <1 year but not in age ≥1 year. CONCLUSIONS: In our study population, it was observed that children born by caesarean section or instrumental vaginal delivery were at higher risk of early childhood atopic dermatitis. Although familial confounding attenuates the risk in children aged ≥1 year, this was not observed in the first year of life.

Associations Between Maternal Distress, Cortisol Levels, and Perinatal Outcomes.

OBJECTIVE: Stress during pregnancy may decrease gestational age at birth and birth size. We aimed to investigate the associations between maternal subjective stress measures, salivary cortisol, and perinatal outcomes. METHODS: A cohort of pregnant women (n = 1693) was recruited from eight antenatal care clinics in Stockholm, Sweden. Questionnaires on subjective distress (perceived stress, worry, depression symptoms, sleep quality) and saliva samples for cortisol measurement (morning and evening) were collected in early and late pregnancy. Perinatal outcomes were birth weight, birth length, gestational age, and birth weight for gestational age. We used linear regression to estimate associations adjusted for maternal characteristics. RESULTS: All associations between subjective distress and cortisol levels were close to null and nonsignificant, for example, exp(ß) = 1.001 (95% confidence interval = 0.995 to 1.006) for the morning cortisol level and perceived stress in early pregnancy. Likewise, most associations between distress (subjective and cortisol) and perinatal outcomes were weak and not statistically significant, for example, ß = 1.95 (95% confidence interval = -4.16 to 8.06) for perceived stress in early pregnancy and birth weight. An exception was a statistically significant association between birth weight for gestational age and depression symptoms in early pregnancy, with somewhat higher weight with more symptoms (ß = 0.08; 95% CI = 0.04 to 0.13). The results were similar for stress in early and late pregnancy. CONCLUSIONS: We found no association between subjective distress and cortisol measures irrespective of when in pregnancy the measures were taken. Furthermore, we found no evidence for a longitudinal association between psychological measures of stress or cortisol with lower birth weight, birth weight for gestational age, or gestational age.

Maternal asthma and early fetal growth, the MAESTRO study.

BACKGROUND: Several maternal conditions can affect fetal growth, and asthma during pregnancy is known to be associated with lower birth weight and shorter gestational age. OBJECTIVE: In a new Swedish cohort study on maternal asthma exposure and stress during pregnancy (MAESTRO), we have assessed if there is evidence of early fetal growth restriction in asthmatic women or if a growth restriction might come later during pregnancy. METHODS: We recruited women from eight antenatal clinics in Stockholm, Sweden. Questionnaires on background factors, asthma status and stress were assessed during pregnancy. The participants were asked to consent to collection of medical records including ultrasound measures during pregnancy, and linkage to national health registers. In women with and without asthma, we studied reduced or increased growth by comparing the second-trimester ultrasound with first-trimester estimation. We defined reduced growth as estimated days below the 10th percentile and increased growth as days above the 90th percentile. At birth, the weight and length of the newborn and the gestational age was compared between women with and without asthma. RESULTS: We enrolled 1693 participants in early pregnancy and collected data on deliveries and ultrasound scans in 1580 pregnancies, of which 18% of the mothers had asthma. No statistically significant reduced or increased growth between different measurement points were found when women with and without asthma were compared; adjusted odds ratios for reduced growth between first and second trimester 1.11 95% CI (0.63-1.95) and increased growth 1.09 95% CI (0.68-1.77). CONCLUSION AND CLINICAL RELEVANCE: In conclusion, we could not find evidence supporting an influence of maternal asthma on early fetal growth in the present cohort: Although the relatively small sample size, which may enhance the risk of a type II error, it is concluded that a potential difference is likely to be very small.

Parental asthma and risk of autism spectrum disorder in offspring: A population and family-based case-control study.

BACKGROUND: Associations between parental asthma and prenatal exposure to asthma medications with offspring autism spectrum disorder (ASD) have been reported. However, the associations might be confounded by unmeasured (genetic and shared environmental) familial factors. OBJECTIVE: We investigated the association between (a) maternal/paternal asthma and offspring ASD, and (b) prenatal exposures to ß2-agonists, other asthma medications and offspring ASD using cases and controls selected from the population as well as biological relatives with different degrees of relatedness. METHODS: We included all children (N = 1 579 263) born in Sweden 1992-2007. A nested case-control design was used to compare 22 894 ASD cases identified from the National Patient Register to (a) 228 940 age-, county- and sex-matched controls randomly selected from the population, (b) their eligible full-siblings (n = 1267), (c) half-siblings (n = 1323), (d) full-cousins (n = 11 477) and (e) half-cousins (n = 3337). Conditional logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for ASD in children differentially exposed to parental asthma or prenatal asthma medications. RESULTS: Maternal asthma was associated with increased risk of offspring ASD (OR 1.43, 95% CI 1.38-1.49); there was a weaker association for paternal asthma (OR 1.17, 95% CI 1.11-1.23). The risk of offspring ASD in mothers with asthma showed similar estimates when adjusting for shared familial factors among paternal half-siblings (OR 1.20, 95% CI 0.80-1.81), full-cousins (OR 1.28, 95% CI 1.16-1.41) and half-cousins (OR 1.30, 95% CI 1.10-1.54), albeit with wider confidence intervals. Prenatal exposure to asthma medications among subjects whose mothers had asthma was not associated with subsequent ASD. CONCLUSIONS AND CLINICAL RELEVANCE: In this large observational study, parental asthma was associated with slightly elevated risk of ASD in offspring. More specifically, the increased risk by maternal asthma did not seem to be confounded by familial factors. There was no evidence of an association between asthma medications during pregnancy and offspring ASD.

Pre-eclampsia and risk of early-childhood asthma: a register study with sibling comparison and an exploration of intermediate variables.

BACKGROUND: We aimed to study whether pre-eclampsia is associated with childhood asthma, allergic and non-allergic asthma, accounting for family factors and intermediate variables. METHODS: The study population comprised 779 711 children born in 2005-2012, identified from Swedish national health registers (n = 14 823/7410 exposed to mild/moderate and severe pre-eclampsia, respectively). We used Cox regression to estimate the associations of mild/moderate and severe pre-eclampsia with incident asthma, before and after age 2 years. Cox regressions were controlled for familial factors using sibling comparisons, then stratified on high and low risk for intermediate variables: caesarean section, prematurity and small for gestational age. We used logistic regression for allergic and non-allergic prevalent asthma at 6 years as a measure of more established asthma. RESULTS: The incidence of asthma in children was 7.7% (n = 60 239). The associations varied from adjusted hazard ratio (adjHR) 1.11, 95% confidence interval (CI): 1.00, 1.24 for mild/moderate pre-eclampsia and asthma at >2 years age, to adjHR 1.78, 95% CI: 1.64, 1.95 for severe pre-eclampsia and asthma at <2 years age. Sibling comparisons attenuated most estimates except for the association between severe pre-eclampsia and asthma at <2 years age (adjHR 1.45, 95% CI: 1.10, 1.90), which also remained when stratifying for the risk of intermediates. Mild/moderate and severe pre-eclampsia were associated with prevalent non-allergic (but not allergic) asthma at 6 years, with adjusted odds ratio (adjOR) 1.17, 95% CI: 1.00, 1.36 and adjOR 1.51, 95% CI: 1.23, 1.84, respectively. CONCLUSIONS: We found evidence that severe, but not mild/moderate, pre-eclampsia is associated with asthma regardless of familial factors and confounders.

Effect of maternal asthma exacerbations on perinatal outcomes: a population-based study.

BACKGROUND: Although there is a growing body of literature about the impact of asthma exacerbations during pregnancy on adverse perinatal outcomes, it is still unclear whether asthma exacerbations themselves or asthma severity are the driving factor for negative outcomes. This study aimed to estimate the associations between maternal asthma exacerbations and perinatal outcomes, and whether this differed by asthma treatment regime as a proxy for severity. METHODS: We included births of women with asthma in Sweden from July 2006 to November 2013 (n=33 829). Asthma exacerbations were defined as unplanned emergency visits/hospitalisations or a short course of oral corticosteroids. Adjusted odds ratios (aOR) were estimated for the associations between exacerbations during pregnancy and perinatal outcomes (small for gestational age (SGA), preterm birth, birthweight and mode of delivery), stratified by preconception treatment regime. RESULTS: Exacerbations occurred in 1430 (4.2%) pregnancies. Exacerbations were associated with reduced birthweight (aOR 1.45, 95% CI 1.24-1.70), and elective (aOR 1.50, 95% CI 1.25-1.79) and emergency caesarean section (aOR 1.35, 95% CI 1.13-1.61). Multiple exacerbations were associated with a 2.6-fold increased odds of SGA (95% CI 1.38-4.82). Amongst women treated prepregnancy with combination therapy (proxy for moderate-severe asthma), exacerbators were at increased odds of elective (aOR 1.69, 95% CI 1.30-2.2) and emergency (aOR 1.62, 95% CI 1.26-2.08) caesarean section, and SGA (aOR 1.74, 95% CI 1.18-2.57) versus non-exacerbators. CONCLUSION: Maternal asthma exacerbations increase the risk of SGA and caesarean sections, particularly in women with multiple exacerbations or moderate-severe asthma. Adequate antenatal asthma care is needed to reduce exacerbations and reduce risks of poor outcomes.

Maternal anxiety, depression and asthma and adverse pregnancy outcomes - a population based study.

To evaluate associations between maternal anxiety or depression and adverse pregnancy outcomes, taking possible familial confounding and interaction with asthma into account, we conducted a cohort study of all singleton births in Sweden 2001-2013. We retrieved information about pregnancy, diagnoses of anxiety/depression, asthma, and prescribed medication from the Swedish Medical Birth, National Patient, and Prescribed Drug Registers. We estimated associations with regression models, performed cousin and sibling comparisons, and calculated interactions. In 950 301 identified pregnancies; 5.9% had anxiety/depression and 4.0% had asthma. Anxiety/depression was associated with adverse pregnancy outcomes (e.g. preeclampsia, adjusted Odds Ratio 1.17 (95% Confidence Interval 1.12, 1.22), instrumental delivery (1.14 (1.10, 1.18)), elective (1.62 (1.57, 1.68)) and emergency (1.32 (1.28, 1.35)) caesarean section (CS)). Their children had lower birth weight (-54 g (-59, -49)) and shorter gestational age (-0.29 weeks (-0.31, -0.28)). Associations were not confounded by familial factors and asthma did not modify the effect of anxiety/depression for outcomes other than elective CS, p < 0.001. In women with anxiety/depression diagnosis, untreated women had higher odds of elective CS compared to women on medication (1.30 (1.17, 1.43)). In conclusion, anxiety/depression should be considered when evaluating pregnant women's risk of complications such as preeclampsia and non-vaginal deliveries.

Adverse Pregnancy Outcomes in Asthmatic Women: A Population-Based Family Design Study.

BACKGROUND: Asthma is associated with several adverse pregnancy and perinatal outcomes. Familial factors may confound these associations. OBJECTIVE: To examine the role of measured and unmeasured confounding by conducting a study that compared differentially exposed cousins and siblings from the same families. METHODS: We retrieved data on adverse pregnancy outcomes, prescribed drugs, and physician-diagnosed asthma from nationwide registers for all women in Sweden with singleton births between 2001 and 2013. Logistic and linear regression estimated the association between maternal asthma and several outcomes in the whole population and within differently exposed pregnant relatives. RESULTS: In total, 1,075,153 eligible pregnancies were included and 10.1% of the study population had asthma. We identified 475,200 cousin and 341,205 sister pregnancies. Women with asthma had increased risks for preeclampsia (adjusted odds ratio [aOR], 1.17; 95% CI, 1.13-1.21), emergency cesarean section (aOR, 1.24; 95% CI, 1.22-1.27), and having a child small for gestational age (aOR, 1.18; 95% CI, 1.12-1.23). In the conditional regression analyses, after adjustment for familial factors, the associations remained: preeclampsia in cousins (aOR, 1.16; 95% CI, 1.07-1.25) and siblings (aOR, 1.23; 95% CI, 1.08-1.38), emergency cesarean section in cousins (aOR, 1.28) and siblings (aOR, 1.21), and small for gestational age in cousins (aOR, 1.17) and siblings (aOR, 1.13). CONCLUSIONS: Factors shared by siblings and cousins do not seem to explain the observed association between maternal asthma and adverse pregnancy outcomes. This implies that targeting the asthma disease will continue to be important in reducing risks for adverse outcomes in pregnancy.

Asthma during pregnancy in a population-based study--pregnancy complications and adverse perinatal outcomes.

BACKGROUND: Asthma is one of the most common chronic diseases, and prevalence, severity and medication may have an effect on pregnancy. We examined maternal asthma, asthma severity and control in relation to pregnancy complications, labour characteristics and perinatal outcomes. METHODS: We retrieved data on all singleton births from July 1, 2006 to December 31, 2009, and prescribed drugs and physician-diagnosed asthma on the same women from multiple Swedish registers. The associations were estimated with logistic regression. RESULTS: In total, 266 045 women gave birth to 284 214 singletons during the study period. Maternal asthma was noted in 26 586 (9.4%) pregnancies. There was an association between maternal asthma and increased risks of pregnancy complications including preeclampsia or eclampsia (adjusted OR 1.15; 95% CI 1.06-1.24) and premature contractions (adj OR 1.52; 95% CI 1.29-1.80). There was also a significant association between maternal asthma and emergency caesarean section (adj OR 1.29; 95% CI 1.23-1.34), low birth weight, and small for gestational age (adj OR 1.23; 95% CI 1.13-1.33). The risk of adverse outcomes such as low birth weight increased with increasing asthma severity. For women with uncontrolled compared to those with controlled asthma the results for adverse outcomes were inconsistent displaying both increased and decreased OR for some outcomes. CONCLUSION: Maternal asthma is associated with a number of serious pregnancy complications and adverse perinatal outcomes. Some complications are even more likely with increased asthma severity. With greater awareness and proper management, outcomes would most likely improve.

Parental socioeconomic status, childhood asthma and medication use--a population-based study.

BACKGROUND: Little is known about how parental socioeconomic status affects offspring asthma risk in the general population, or its relation to healthcare and medication use among diagnosed children. METHODS: This register-based cohort study included 211,520 children born between April 2006 and December 2008 followed until December 2010. Asthma diagnoses were retrieved from the National Patient Register, and dispensed asthma medications from the Prescribed Drug Register. Parental socioeconomic status (income and education) were retrieved from Statistics Sweden. The associations between parental socioeconomic status and outcomes were estimated by Cox proportional hazard regression. RESULTS: Compared to the highest parental income level, children exposed to all other levels had increased risk of asthma during their first year of life (e.g. hazard ratio, HR 1.19, 95% confidence interval, CI 1.09-1.31 for diagnosis and HR 1.17, 95% CI 1.08-1.26 for medications for the lowest quintile) and the risk was decreased after the first year, especially among children from the lowest parental income quintile (HR 0.84, 95% CI 0.77-0.92 for diagnosis, and HR 0.80, 95% CI 0.74-0.86 for medications). Further, compared to children with college-educated parents, those whose parents had lower education had increased risk of childhood asthma regardless of age. Children with the lowest parental education had increased risk of an inpatient (HR 2.07, 95% CI 1.61-2.65) and outpatient (HR 1.32, 95% CI 1.18-1.47) asthma diagnosis. Among diagnosed children, those from families with lower education used fewer controller medications than those whose parents were college graduates. CONCLUSIONS: Our findings indicate an age-varying association between parental income and childhood asthma and consistent inverse association regardless of age between parental education and asthma incidence, dispensed controller medications and inpatient care which should be further investigated and remedied.