Adverse neonatal outcomes in pregnant women with asthma: An updated systematic review and meta-analysis.

BACKGROUND: A systematic review and meta-analysis from 2013 reported increased risks of congenital malformations, neonatal death and neonatal hospitalization amongst infants born to women with asthma compared to infants born to mothers without asthma. OBJECTIVE: Our objective was to update the evidence on the associations between maternal asthma and adverse neonatal outcomes. SEARCH STRATEGY: We performed an English-language MEDLINE, Embase, CINAHL, and COCHRANE search with the terms (asthma or wheeze) and (pregnan* or perinat* or obstet*). SELECTION CRITERIA: Studies published from March 2012 until September 2023 reporting at least one outcome of interest (congenital malformations, stillbirth, neonatal death, perinatal mortality, neonatal hospitalization, transient tachypnea of the newborn, respiratory distress syndrome and neonatal sepsis) in a population of women with and without asthma. DATA COLLECTION AND ANALYSIS: The study was reported following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Quality of individual studies was assessed by two reviewers independently using the Newcastle-Ottawa Scale. Random effects models (≥3 studies) or fixed effect models (≤2 studies) were used with restricted maximum likelihood to calculate relative risk (RR) from prevalence data and the inverse generic variance method where adjusted odds ratios (aORs) from individual studies were combined. MAIN RESULTS: A total of 18 new studies were included, along with the 22 studies from the 2013 review. Previously observed increased risks remained for perinatal mortality (relative risk [RR] 1.14, 95% confidence interval [CI]: 1.05, 1.23 n = 16 studies; aOR 1.07, 95% CI: 0.98-1.17 n = 6), congenital malformations (RR 1.36, 95% CI: 1.32-1.40 n = 17; aOR 1.42, 95% CI: 1.38-1.47 n = 6), and neonatal hospitalization (RR 1.27, 95% CI: 1.25-1.30 n = 12; aOR 1.1, 95% CI: 1.07-1.16 n = 3) amongst infants born to mothers with asthma, while the risk for neonatal death was no longer significant (RR 1.33, 95% CI: 0.95-1.84 n = 8). Previously reported non-significant risks for major congenital malformations (RR1.18, 95% CI: 1.15-1.21; aOR 1.20, 95% CI: 1.15-1.26 n = 3) and respiratory distress syndrome (RR 1.25, 95% CI: 1.17-1.34 n = 4; aOR 1.09, 95% CI: 1.01-1.18 n = 2) reached statistical significance. CONCLUSIONS: Healthcare professionals should remain aware of the increased risks to neonates being born to mothers with asthma.

Breastfeeding and wheeze-related outcomes in high-risk infants: A systematic review and meta-analysis.

BACKGROUND: The risk of wheezing is high in infancy and is heightened in infants with a family history of asthma/atopy. The role of breastfeeding in influencing respiratory health for these high-risk infants is unclear. OBJECTIVES: To systematically appraise evidence for the association between breastfeeding and wheeze incidences and severity in high-risk infants. METHODS: Studies identified through electronic databases and reference lists were eligible if they assessed breastfeeding and respiratory outcomes in infants with a family history of asthma/atopy. The primary outcome was wheeze incidences in the first year of life. Secondary outcomes were wheeze incidences in the first 6 months of life, indicators of wheeze severity (recurrent wheeze, health-care utilization, and medication use), and other wheeze-related outcomes [bronchiolitis, pneumonia, croup, and incidence of lower respiratory tract infection (LRTI)] up to 12 months old. Meta-analyses were conducted where possible. RESULTS: Of 1843 articles screened, 15 observational studies met the inclusion criteria. Breastfeeding was associated with 32% reduced odds of wheezing during the first year of life (ever vs. never: OR, 0.68; 95% CI: 0.53, 0.88; n = 9 studies); this association was even stronger in the first 6 months (OR, 0.45; 95% CI: 0.27, 0.75; n = 5 studies). Breastfeeding for a "longer" versus "shorter" time (approximately longer vs. shorter than 3 months) was associated with 50% reduced odds of wheezing at the age of 6 months (OR, 0.50; 95% CI: 0.39, 0.64; n = 3 studies). CONCLUSIONS: Breastfeeding was associated with reduced odds of wheezing in high-risk infants, with the strongest protection in the first 6 months. More research is needed to understand the impact of breastfeeding intensity on wheezing and to examine additional respiratory outcomes, including wheeze severity. This review was registered at PROSPERO as CRD42019118631.

The Impact of Sample Type on Vitamin D Quantification and Clinical Classification during Pregnancy.

Measurement of vitamin D status has significant use in clinical and research settings, including during pregnancy. We aimed to assess the agreement of total 25-hydroxyvitamin D (25(OH)D) concentration, and its three analytes (25-hydroxyvitamin D3 (25(OH)D3), 25-hydroxyvitamin D2 (25(OH)D2) and Epi-25-hydroxyvitamin D3 (Epi-25(OH)D3)), in plasma and serum samples collected during pregnancy, and to examine the proportion of women who change vitamin D status category based on sample type. Matching samples were collected from n = 114 non-fasting women between 12-25 weeks gestation in a clinical trial in Newcastle, Australia. Samples were analysed by liquid chromatography-tandem mass-spectrometry (LC-MS/MS) to quantify total 25(OH)D and its analytes and examined using Bland-Altman plots, Pearson correlation (r), intraclass correlation coefficient and Cohen's Kappa test. Serum total 25(OH)D ranged from 33.8-169.8 nmol/L and plasma ranged from 28.6-211.2 nmol/L. There was a significant difference for total 25(OH)D based on sample type (measurement bias 7.63 nmol/L for serum vs plasma (95% Confidence Interval (CI) 5.36, 9.90, p ≤ 0.001). The mean difference between serum and plasma concentrations was statistically significant for 25(OH)D3 (7.38 nmol/L; 95% CI 5.28, 9.48, p ≤ 0.001) and Epi-25(OH)D3 (0.39 nmol/L; 95% CI 0.14, 0.64, p = 0.014). Of 114 participants, 28% were classified as vitamin D deficient (<50 nmol/L) or insufficient (<75 nmol/L) based on plasma sample and 36% based on serum sample. Nineteen (16.7%) participants changed vitamin D status category based on sample type. 25-hydroxyvitamin D quantification using LC-MS/MS methodology differed significantly between serum and plasma, yielding a higher value in plasma; this influenced vitamin D status based on accepted cut-points, which may have implications in clinical and research settings.

Serum 25 Hydroxyvitamin D Levels During Pregnancy in Women with Asthma: Associations with Maternal Characteristics and Adverse Maternal and Neonatal Outcomes.

Low 25-hydroxyvitamin D (25(OH)D) levels are common in pregnancy and associated with adverse maternal/neonatal outcomes. In pregnant women with asthma, this study examined the association of lifestyle- and asthma-related factors on 25(OH)D levels and maternal/neonatal outcomes by vitamin D status. Serum 25(OH)D was measured at 16 and 35 weeks gestation in women with asthma (n = 103). Body mass index (BMI), gestational weight gain (GWG), smoking status, inhaled corticosteroid (ICS) use, asthma control, airway inflammation, and exacerbations, and maternal/neonatal outcomes were collected. Baseline and change (Δ) in 25(OH)D were modelled separately using backward stepwise regression, adjusted for season and ethnicity. Maternal/neonatal outcomes were compared between low (25(OH)D < 75 nmol/L at both time points) and high (≥75 nmol/L at one or both time points) vitamin D status. Fifty-six percent of women had low vitamin D status. Obesity was significantly associated with lower baseline 25(OH)D (Adj-R2 = 0.126, p = 0.008); ICS and airway inflammation were not. Excess GWG and season of baseline sample collection were significantly associated with Δ25(OH)D (Adj-R2 = 0.405, p < 0.0001); asthma-related variables were excluded (p > 0.2). Preeclampsia was more common in the low (8.6%) vs. high (0%) vitamin D group (p < 0.05). Obesity and excess GWG may be associated with gestational 25(OH)D levels, highlighting the importance of antenatal weight management.

Maternal asthma, breastfeeding, and respiratory outcomes in the first year of life.

Maternal asthma increases the risk of infant wheeze. Breastfeeding may offer protection but there is limited evidence in this high-risk group. We examined associations between breastfeeding and respiratory outcomes, in infants born to women with asthma. This study was a secondary analysis of two prospective cohorts of pregnant women with asthma, and their infants, conducted between 2007 and 2018. At 6 ± 1 (T1) and 12 ± 1 (T2) months post-partum, mothers reported breastfeeding patterns and infant wheeze (primary outcome), bronchiolitis, and related medication use and healthcare utilization, via a validated questionnaire; a subgroup completed face-to-face interviews. χ2 tests and logistic regression models, adjusting for confounders, were utilized. Data were complete for 605 participants at T1 and 486 (80%) at T2. Of 605 participants: 89% initiated breastfeeding and 38% breastfed for more than 6 months. Breastfeeding for more than 6 months vs "never" was associated with a reduced adjusted relative risk of infant wheeze at T1 (0.54, 95% confidence interval, 0.30-0.96). Bronchiolitis risk was reduced at T1 and T2 with more tha 6 months of breastfeeding vs "never." Breastfeeding duration of 1 to 3 months, 4 to 6 months, and more than 6 months were associated with a reduced risk of infant healthcare utilization (all P < .05, vs "never"), but not medication use (P > .05). Breastfeeding for more than 6 months was associated with a reduced risk of wheeze, bronchiolitis, and wheeze-related healthcare utilization in infants at risk due to maternal asthma. Notably, breastfeeding for shorter durations was associated with a reduced risk of healthcare utilization compared with none. Larger cohorts are needed to further examine the impact of breastfeeding exposure on respiratory health in infants exposed to maternal asthma.