Maternal folic acid use during pregnancy, methylenetetrahydrofolate reductase gene polymorphism, and child's lung function and asthma.

BACKGROUND: Folic acid supplement use during pregnancy might affect childhood respiratory health, potentially mediated by methylenetetrahydrofolate reductase polymorphism C677T (MTHFR-C677T) carriership. OBJECTIVES: We examined the associations of maternal folic acid supplement use and folate, vitamin B12 and homocysteine concentrations during pregnancy with childhood lung function and asthma. METHODS: This study was embedded in a population-based prospective cohort study among 5653 children. Folic acid supplement use was assessed by questionnaires. Folate, vitamin B12 and homocysteine plasma concentrations were measured in early pregnancy and at birth. At age 10 years, forced expiratory volume in 1 second (FEV1 ), forced vital capacity (FVC), FEV1 /FVC, forced expiratory flow between 25% and 75% (FEF25-75 ), at 75% of FVC (FEF75 ), and asthma were examined. RESULTS: Maternal folic acid supplement use during pregnancy was associated with higher childhood FEV1 and FVC and with a lower FEV1 /FVC, compared with no folic acid supplement use. Among mothers carrying MTHFR-C677T variants, preconceptional start of folic acid supplement use was associated with lower FEV1 /FVC (-0.17 [-0.32, -0.02]) and FEF25-75 (-0.24 [-0.40, -0.07]). Among children carrying MTHFR-C677T wild-type, a higher vitamin B12 level at birth was associated with a lower FEV1 (-0.07 [-0.12, -0.01]) and FVC (-0.09 [-0.15, -0.04]). Folate and homocysteine concentrations were not consistently associated with lower childhood lung function or asthma. CONCLUSIONS: Preconceptional start of maternal folic acid supplement use and higher vitamin B12 concentrations at birth might adversely affect childhood lung function depending on MTHFR-C677T carriership. The clinical implications need to be evaluated.

Maternal psychiatric symptoms during pregnancy and risk of childhood atopic diseases.

BACKGROUND: Maternal psychiatric symptoms during pregnancy might affect the developing immune system and subsequent risk of childhood atopic diseases. OBJECTIVE: Our aim was to examine the associations of maternal psychiatric symptoms during pregnancy with allergic sensitization, allergy and eczema in children until age 10 years. METHODS: This study among 5205 children was performed in a population-based prospective cohort from foetal life onwards. We assessed maternal and paternal psychiatric symptoms (overall, depressive, anxiety) during pregnancy and at 36 months after delivery, and maternal psychiatric symptoms at 2 and 6 months after delivery using the Brief Symptom Inventory. Inhalant and food allergic sensitization were measured by skin prick tests, and physician-diagnosed inhalant and food allergy or eczema by questionnaires from birth until age 10 years. We used multivariate logistic regression, multinomial logistic regression or generalized estimating equation models where appropriate. RESULTS: We observed no association of maternal psychiatric symptoms during pregnancy with allergic sensitization. Maternal overall psychiatric, depressive and anxiety symptoms during pregnancy were associated with an increased risk of inhalant allergy only (adjusted odds ratio (95% confidence interval) 1.96 (1.44, 2.65), 1.58 (1.25, 1.98) and 1.61 (1.27, 2.03), respectively, per 1-unit increase). Maternal overall psychiatric and anxiety symptoms during pregnancy were associated with an increased risk of eczema (1.21 (1.05, 1.39) and 1.15 (1.02, 1.29), respectively, per 1-unit increase). Effect estimates did not materially change when maternal psychiatric symptoms after delivery, or paternal psychiatric symptoms during pregnancy and after delivery were taken into account. CONCLUSIONS AND CLINICAL RELEVANCE: Maternal psychiatric symptoms during pregnancy were associated with increased risks of childhood inhalant allergy and eczema, independent of maternal psychiatric symptoms after delivery and of paternal psychiatric symptoms.

Duration and exclusiveness of breastfeeding and risk of childhood atopic diseases.

BACKGROUND: Breastfeeding may have immune modulatory effects that influence the development of childhood allergic sensitization and atopic diseases. We aimed to examine the associations of breastfeeding with childhood allergic sensitization, inhalant or food allergy and eczema, and whether any association was affected by disease-related modification of the exposure or modified by maternal history of allergy, eczema, or asthma. METHODS: This study among 5828 children was performed in a population-based prospective cohort from fetal life onwards. We collected information on duration (<2 months, 2-4 months, 4-6 months, and ≥6 months) and exclusiveness (nonexclusive vs exclusive for 4 months) of breastfeeding in infancy by postal questionnaires. At age 10 years, inhalant allergic sensitization and food-allergic sensitization were measured by skin prick tests, and physician-diagnosed inhalant and food allergy by a postal questionnaire. Data on parental-reported eczema were available from birth until age 10 years. RESULTS: We observed no association of breastfeeding with any allergic sensitization, physician-diagnosed allergy, or combination of these outcomes. Shorter breastfeeding duration was associated with an overall increased risk of eczema (P-value for trend <.05). Nonexclusively breastfed children had an overall increased risk of eczema (adjusted odds ratio [95% confidence interval]: 1.11 [1.01, 1.23]), compared with children exclusively breastfed for 4 months. Risk period-specific sensitivity analyses, additional adjustment for ointment use for eczema at age 2 months, and cross-lagged modeling showed no consistent results for disease-related modification of the exposure. Results were not modified by maternal history of allergy, eczema, or asthma (lowest P-value for interaction=.13). CONCLUSION: Shorter duration or nonexclusiveness of breastfeeding is associated with a weak overall increased risk of eczema but not allergic sensitization or physician-diagnosed allergy at age 10 years.

Associations of maternal and fetal 25-hydroxyvitamin D levels with childhood lung function and asthma: the Generation R Study.

BACKGROUND: Exposure to low levels of vitamin D in fetal life might be a risk factor for childhood asthma. OBJECTIVE: We examined whether 25-hydroxyvitamin D levels in mid-gestation and at birth were associated with higher airway resistance and inflammation, and increased risks of wheezing and asthma in school-age children. METHODS: We performed a population-based prospective cohort study among 3130 mothers and their children. Maternal blood samples in mid-gestation and umbilical cord blood samples at birth were used to determine 25-hydroxyvitamin D levels. At age of 6, airway resistance (Rint) was measured by interrupter technique and airway inflammation by fractional exhaled nitric oxide (FENO) using NIOX chemiluminescence analyser. Wheezing and asthma were prospectively assessed by annual questionnaires until age 6. RESULTS: Maternal levels of 25-hydroxyvitamin D in mid-gestation were not associated with Rint, FeNO, wheezing patterns, or asthma. Children in the lowest tertile of 25-hydroxyvitamin D levels at birth had a higher Rint (Z-score (95% confidence interval [95% CI]): -0.42 (-0.84, -0.01), P-value for trend< 0.05), compared to those in the highest tertile group. The effect estimate attenuated when child's current 25-hydroxyvitamin D level was taken into account [Z-score (95% CI): -0.55 (-1.08, 0.01)]. CONCLUSION AND CLINICAL RELEVANCE: Low levels of 25-hydroxyvitamin D at birth were associated with a higher airway resistance in childhood. Additional adjustment for child's current 25-hydroxyvitamin D level reduced the effect size of the association. Further studies are needed to replicate these findings and to examine mechanisms underlying the observed association and the long-term consequences.

Maternal fatty acid levels during pregnancy, childhood lung function and atopic diseases. The Generation R Study.

BACKGROUND: Maternal fatty acid status during pregnancy might influence foetal immunological development and subsequently the risk of childhood atopic diseases. OBJECTIVE: To examine the associations of maternal fatty acid levels during pregnancy with airway resistance and inflammation, asthma and eczema, in school-age children. METHODS: This study among 4976 subjects was embedded in a population-based prospective cohort study. We measured maternal plasma glycerophospholipid fatty acid levels by gas chromatography during the second trimester of pregnancy (mean gestational age: 20.7 (± 1.1) weeks). At the age of 6 years, airway resistance and inflammation were measured by interrupter technique (Rint) and fractional exhaled nitric oxide (FeNO), and current physician-diagnosed asthma and eczema were assessed by ISAAC-based questionnaires. Multiple linear and logistic regression models were adjusted for socio-demographic, lifestyle and anthropometric factors. RESULTS: We did not observe consistent associations of maternal total polyunsaturated fatty acid (PUFA), total n-6 PUFA, total n-3 PUFA levels and n-6/n-3 PUFA ratio during pregnancy with child's Rint and FeNO. Higher maternal total PUFA and total n-6 PUFA levels were associated with a decreased risk of childhood asthma (odds ratios (95% confidence interval): 0.76 (0.60, 0.97) and 0.71 (0.52, 0.96) per standard deviation score (SDS) increase of total PUFA and total n-6 PUFA levels, respectively) and with an increased risk of childhood eczema (1.16 (1.05, 1.28) and 1.21 (1.07, 1.37)). The observed associations were partly explained by Linoleic acid (LA, C18:2n-6) levels. Maternal total n-3 PUFA levels and n-6/n-3 PUFA ratio were not associated with current asthma and eczema. The observed associations were not explained by child's PUFA intake. CONCLUSIONS AND CLINICAL RELEVANCE: Higher maternal total PUFA and total n-6 PUFA levels during pregnancy seem to influence the risk of atopic diseases in childhood. The underlying mechanisms need to be further explored.