Supplementary Table S1. Comparison of subject ...



Polyunsaturated fatty acid status at birth and childhood allergy-related phenotypes: a pooled analysis of the MEFAB and RHEA birth cohorts Nikos Stratakis, Marij Gielen, Katerina Margetaki, Renate H. M. de Groot, Maria Apostolaki, Georgia Chalkiadaki, Marina Vafeiadi, Vasiliki Leventakou, Roger W. Godschalk, Manolis Kogevinas, Euripides G. Stephanou, Maurice P. Zeegers, Leda Chatzi.Table of Contents TOC \o "1-3" \h \z \u Supplementary Table S1. Comparison of subject characteristics in MEFAB and RHEA between those included and not included in the main analyses PAGEREF _Toc487485914 \h 2Supplementary Table S2. Associations of primary PUFAs (polyunsaturated fatty acids) of interest with asthma ever at 6-7 years of age in MEFAB and RHEA cohorts, separately and in pooled analysis PAGEREF _Toc487485915 \h 3Supplementary Table S3. Associations of primary PUFAs (polyunsaturated fatty acids) of interest with current rhinitis and eczema at 6-7 years of age in MEFAB and RHEA cohorts, separately and in pooled analysis PAGEREF _Toc487485916 \h 4Supplementary Table S4. Associations (pooled analysis) of primary PUFAs (polyunsaturated fatty acids) of interest with allergy-related phenotypes at 6-7 years of age after adjusting only for child sex and age PAGEREF _Toc487485918 \h 5Supplementary Table S5. Associations of secondary PUFAs (polyunsaturated fatty acids) of interest with current wheeze and asthma at 6-7 years of age in MEFAB and RHEA cohorts, separately and in pooled analysis PAGEREF _Toc487485920 \h 6Supplementary Table S6. Associations of secondary PUFAs (polyunsaturated fatty acids) of interest with current rhinitis and eczema at 6-7 years of age in MEFAB and RHEA cohorts, separately and in pooled analysis PAGEREF _Toc487485921 \h 7Supplementary Table S7. Associations of primary PUFAs (polyunsaturated fatty acids) of interest with current wheeze symptoms at 9 months and 4 years of age in the RHEA cohort PAGEREF _Toc487485922 \h 8Supplementary Table S8. Associations (pooled analysis) of primary PUFAs (polyunsaturated fatty acids) of interest with allergic disease-related phenotypes at 6-7 years of age after including birth weight and gestational age in multivariable models PAGEREF _Toc487485923 \h 9Supplementary Table S9. Assessment of effect measure modification by parent atopy in the association of the total n-3:n-6 PUFA ratio with current symptoms of asthma, rhinitis, and eczema at 6-7 years in the pooled dataset PAGEREF _Toc487485924 \h 10Supplementary Table S10. Assessment of effect measure modification by sex in the association of the total n-3:n-6 PUFA ratio with current symptoms of asthma, rhinitis, and eczema at 6-7 years in the pooled dataset PAGEREF _Toc487485925 \h 11Supplementary Fig. S1. Flow chart of the MEFAB participants PAGEREF _Toc487485926 \h 12Supplementary Fig. S2. Flow chart of the RHEA participants PAGEREF _Toc487485927 \h 13Supplementary Fig. S3. Directed acyclic graph for the association of fatty acid status at birth with allergic disease-related symptoms in childhood. PAGEREF _Toc487485929 \h 14Text accompanying Supplementary Fig. S3 PAGEREF _Toc487485930 \h 15Supplementary Table S1. Comparison of subject characteristics in MEFAB and RHEA between those included and not included in the main analyses(Mean values and standard deviations; number of subjects and percentages)MEFABRHEASubjects not included (n 910)Subjects included (n 293)Subjects not included (n 1150)Subjects included (n 213)n%n%P*n%n%P*Parental characteristicsMaternal age at birth (years)0·010·56Mean29·129·829·629·8SD4·34·25·04·8Maternal BMI at study entry (kg/m2)0·060·28Mean24·223·625·225·7SD4·23·94·65·8Gestational weight gain (kg)0·060·68Mean11·611·114·113·8SD4·64·06·06·1Maternal smoking in pregnancy22626·36723·30·3115119·42913·70·06Parity at birth, multiparous20323·48729·70·0365456·911654·50·53Area-based socio-economic status at birth, high?25338·29436·30·10---Parental education, high -----28236·49142·90·12Child characteristicsSex, female 40945·013144·70·9358050·49042·30·03Gestational age (weeks)0·920·46Mean39·939·938·338·2SD1·71·61·51·5Birth weight (grams)0·480·61Mean3271329632083191SD511516454434Breastfeeding, yes-----65685·117886·30·53Cord blood n-3 PUFAs (wt %)0·870·25Mean6·906·895·255·38SD1·581·591·291·12Cord blood n-6 PUFAs (wt %)0·520·11Mean32·0832·1632·4432·06SD1·681·693·032·35wt %, weight percentage of total fatty acids measured.* P values for difference were estimated using Student’s t test for continuous and Pearson's χ2 test for categorical variables.? Area-based socio-economic status at birth was determined based on the postal code of the place of residence. Supplementary Table S2. Associations of primary PUFAs (polyunsaturated fatty acids) of interest with asthma ever at 6-7 years of age in MEFAB and RHEA cohorts, separately and in pooled analysis?(Relative risks (RRs) and 95% confidence intervals)Asthma ever§MEFAB (n 293) RHEA (n 213)Pooled (n 506)RR95% CIRR95% CIRR95% CIALA0·470·24, 0·93*1·020·66, 1·580·790·57, 1·09??EPA+DHA0·670·46, 0·98*0·590·39, 0·89*0·650·49, 0·86**?Total n-3 PUFAs 0·660·46, 0·96*0·600·40, 0·92*0·650·49, 0·86**?LA1·481·01, 2·17*0·900·56, 1·441·170·90, 1·52?AA1·280·85, 1·930·890·57, 1·411·060·78, 1·43?Total n-6 PUFAs1·270·86, 1·870·790·52, 1·191·020·77, 1·36?Total n-3:n-6 ratio0·640·44, 0·93*0·700·44, 1·110·670·49, 0·90**?AA, arachidonic acid (C20:4n-6); ALA, a-Linolenic acid (C18:3n-3); DHA, docosahexaenoic acid (C22:6n-3); EPA, eicosapentaenoic acid (C20:5n-3); LA, linoleic acid (C18:2n-6); total n-3 (n-6) PUFAs, the sum of n-3 (n-6) PUFAs present in the chromatogram. P value for PUFA exposure-outcome association: *P<0·05; **P<0·01.P value for PUFA exposure-cohort interaction: ?P for interaction >0.10; ??P for interaction =0.07.? Relative risks (RRs) and their 95% CIs were calculated using generalized linear models for binary outcomes (modified Poisson) adjusted for maternal age, maternal BMI at study entry, gestational weight gain, maternal smoking during pregnancy, parity, parental education, parent atopy, child age at outcome assessment, child sex, and for the pooled estimate, a cohort indicator. Effect estimates correspond to a standard deviation score (SDS) increase in PUFAs and to a unit increase in the total n-3:n-6 ratio.§ Asthma ever was defined as ever-reported doctor diagnosis of asthma.Supplementary Table S3. Associations of primary PUFAs (polyunsaturated fatty acids) of interest with current rhinitis and eczema at 6-7 years of age in MEFAB and RHEA cohorts, separately and in pooled analysis?(Relative risks (RRs) and 95% confidence intervals)Current rhinitis§Current eczema||MEFAB (n 293) RHEA (n 213)Pooled (n 506)MEFAB (n 293) RHEA (n 213)Pooled (n 506)RR95% CIRR95% CIRR95% CIRR95% CIRR95% CIRR95% CIALA1·020·86, 1·211·060·57, 1·961·020·87, 1·21?0·820·59, 1·131·210·67, 2·190·920·73, 1·17?EPA+DHA0·880·68, 1·140·640·32, 1·300·840·66, 1·07?0·990·74, 1·330·820·46, 1·460·940·73, 1·22?Total n-3 PUFAs 0·870·68, 1·130·650·32, 1·310·840·65, 1·07?0·980·73, 1·330·830·46, 1·490·940·73, 1·22?LA1·010·77, 1·331·280·79, 2·071·100·84, 1·44?1·000·74, 1·371·380·98, 1·961·160·91, 1·47?AA1·070·80, 1·430·920·49, 1·741·050·80, 1·39?1·040·74, 1·470·730·49, 1·100·960·74, 1·26?Total n-6 PUFAs1·100·83, 1·451·130·71, 1·801·110·87, 1·42?0·980·71, 1·361·200·74, 1·941·050·80, 1·38?Total n-3:n-6 ratio0·880·67, 1·150·630·33, 1·210·820·64, 1·06?1·000·73, 1·360·770·45, 1·310·920·71, 1·20?AA, arachidonic acid (C20:4n-6); ALA, a-Linolenic acid (C18:3n-3); DHA, docosahexaenoic acid (C22:6n-3); EPA, eicosapentaenoic acid (C20:5n-3); LA, linoleic acid (C18:2n-6); PUFA, polyunsaturated fatty acid; total n-3 (n-6) PUFAs, the sum of n-3 (n-6) PUFAs present in the chromatogram. P value for PUFA exposure-cohort interaction: ?P for interaction >0·10.? Relative risks (RRs) and their 95% CIs were calculated using generalized linear models for binary outcomes (modified Poisson) adjusted for maternal age, maternal BMI at study entry, gestational weight gain, maternal smoking during pregnancy, parity, parental education, parent atopy, child age at outcome assessment, child sex, and for the pooled estimate, a cohort indicator. Effect estimates correspond to a standard deviation score (SDS) increase in PUFAs and to a unit increase in the total n-3:n-6 ratio.§ Current rhinitis was defined as presence of sneezing or a runny or blocked nose in the last 12 months without common cold or flu.|| Current eczema was defined presence of an itchy rash in the last 12 months that affected any of the following places: the folds of the elbows, behind the knees, in front of the ankles, under the buttocks, or around the neck, ears or eyes.Supplementary Table S4. Associations (pooled analysis; n 506) of primary PUFAs (polyunsaturated fatty acids) of interest with allergy-related phenotypes at 6-7 years of age after adjusting only for child sex and age?(Relative risks (RRs) and 95% confidence intervals)Current wheeze§Current asthma||Current rhinitis?Current eczema??RR95% CIRR95% CIRR95% CIRR95% CIALA0·910·69, 1·20?0·610·32, 1·17?1·020·85, 1·22?0·920·73, 1·16?EPA+DHA0·590·44, 0·79***?0·510·32, 0·79**?0·860·68, 1·09?0·980·77, 1·25?Total n-3 PUFAs 0·580·43, 0·78***?0·490·31, 0·76**?0·860·68, 1·09?0·980·76, 1·26?LA1·321·08, 1·61**?1·401·01, 1·94*?1·100·85, 1·42?1·100·87, 1·40?AA1·330·99, 1·80??1·270·84, 1·93?1·060·82, 1·38?0·950·73, 1·23?Total n-6 PUFAs1·621·16, 2·27**?1·450·98, 2·16?1·120·88, 1·41?1·030·80, 1·34?Total n-3:n-6 ratio0·520·38, 0·72***?0·440·27, 0·70**?0·850·66, 1·08?0·960·75, 1·24?AA, arachidonic acid (C20:4n-6); ALA, a-Linolenic acid (C18:3n-3); DHA, docosahexaenoic acid (C22:6n-3); EPA, eicosapentaenoic acid (C20:5n-3); LA, linoleic acid (C18:2n-6); total n-3 (n-6) PUFAs, the sum of n-3 (n-6) PUFAs present in the chromatogram. P value for PUFA exposure-outcome association: *P<0·05; **P<0·01; *** P<0·001.P value for PUFA exposure-cohort interaction: ?P for interaction >0.10; ??P for interaction <0.05.? Relative risks (RRs) and their 95% CIs were calculated using generalized linear models for binary outcomes (modified Poisson) adjusted for child age at outcome assessment, child sex, and a cohort indicator. Effect estimates correspond to a standard deviation score (SDS) increase in PUFAs and to a unit increase in the total n-3:n-6 ratio.§ Current wheeze was defined as presence of wheezing or whistling in the chest in the last 12 months.|| Current asthma was defined as a positive answer to both ever-reported doctor diagnosis of asthma and presence of wheezing or whistling in the chest in the last 12 months.? Current rhinitis was defined as presence of sneezing or a runny or blocked nose in the last 12 months without common cold or flu.?? Current eczema was defined presence of an itchy rash in the last 12 months that affected any of the following places: the folds of the elbows, behind the knees, in front of the ankles, under the buttocks, or around the neck, ears or eyes.Supplementary Table S5. Associations of secondary PUFAs (polyunsaturated fatty acids) of interest with current wheeze and asthma at 6-7 years of age in MEFAB and RHEA cohorts, separately and in pooled analysis?(Relative risks (RRs) and 95% confidence intervals)Current wheeze§Current asthma||MEFAB (n 293) RHEA (n 213)Pooled (n 506)MEFAB (n 293) RHEA (n 213)Pooled (n 506)RR95% CIRR95% CIRR95% CIRR95% CIRR95% CIRR95% CIn-3 DPA0·680·41, 1·11----0·600·31, 1·16----n-6 GLA1·120·70, 1·791·260·91, 1·741·110·84, 1·46?1·060·57, 1·961·530·86, 2·721·110·72, 1·72?n-6 DGLA0·670·43, 1·041·230·87, 1·740·920·67, 1·27??0·400·23, 0·72**1·670·97, 2·900·740·43, 1·28??n-6 Osbond acid0·630·37, 1·09----0·790·41, 1·53----DGLA, dihomo-γ-linolenic acid (C20:3n-6); DPA, docosapentaenoic acid (C22:5n-3); GLA, γ-Linolenic acid (C18:3n-6); Osbond acid, C22:5n-6.P value for PUFA exposure-outcome association: **P<0·01. P value for PUFA exposure-cohort interaction: ?P for interaction > 0·10; ??P for interaction <0·05.? Relative risks (RRs) and their 95% CIs were calculated using generalized linear models for binary outcomes (modified Poisson) adjusted for maternal age, maternal BMI at study entry, gestational weight gain, maternal smoking during pregnancy, parity, parental education, parent atopy, child age at outcome assessment, child sex, and for the pooled estimate, a cohort indicator. Effect estimates correspond to a standard deviation score (SDS) increase in PUFAs and to a unit increase in the total n-3:n-6 ratio.§ Current wheeze was defined as presence of wheezing or whistling in the chest in the last 12 months.|| Current asthma was defined as a positive answer to both ever-reported doctor diagnosis of asthma and presence of wheezing or whistling in the chest in the last 12 months.Supplementary Table S6. Associations of secondary PUFAs (polyunsaturated fatty acids) of interest with current rhinitis and eczema at 6-7 years of age in MEFAB and RHEA cohorts, separately and in pooled analysis?(Relative risks (RRs) and 95% confidence intervals)Current rhinitis§Current eczema||MEFAB (n 293) RHEA (n 213)Pooled (n 506)MEFAB (n 293) RHEA (n 213)Pooled (n 506)RR95% CIRR95% CIRR95% CIRR95% CIRR95% CIRR95% CIn-3 DPA0·80·62, 1·03----1·040·74, 1·45----n-6 GLA1·351·06, 1·72*0·670·39, 1·171·100·89, 1·36???0·930·69, 1·261·461·05, 2·04*1·080·84, 1·4??n-6 DGLA1·090·82, 1·440·880·54, 1·431·010·79, 1·29?0·870·68, 1·131·410·99, 2·011·010·81, 1·26???n-6 Osbond acid0·860·64, 1·15----0·980·74, 1·31----DGLA, dihomo-γ-linolenic acid (C20:3n-6); DPA, docosapentaenoic acid (C22:5n-3); GLA, γ-Linolenic acid (C18:3n-6); Osbond acid, C22:5n-6.P value for PUFA exposure-outcome association: *P<0·05. P value for PUFA exposure-cohort interaction: ?P for interaction > 0·10; ??P for interaction =0·07; ???P for interaction <0·05.? Relative risks (RRs) and their 95% CIs were calculated using generalized linear models for binary outcomes (modified Poisson) adjusted for maternal age, maternal BMI at study entry, gestational weight gain, maternal smoking during pregnancy, parity, parental education, parent atopy, child age at outcome assessment, child sex, and for the pooled estimate, a cohort indicator. Effect estimates correspond to a standard deviation score (SDS) increase in PUFAs and to a unit increase in the total n-3:n-6 ratio.§ Current rhinitis was defined as presence of sneezing or a runny or blocked nose in the last 12 months without common cold or flu.|| Current eczema was defined presence of an itchy rash in the last 12 months that affected any of the following places: the folds of the elbows, behind the knees, in front of the ankles, under the buttocks, or around the neck, ears or eyes.Supplementary Table S7. Associations of primary PUFAs (polyunsaturated fatty acids) of interest with current wheeze symptoms at 9 months and 4 years of age in the RHEA cohort (n 213)*(Relative risks (RRs) and 95% confidence intervals)Current wheeze?9 months (n 228)4 years (n 222)RR (95% CI)RR (95% CI)ALA0·99 (0·76, 1·28)1·57 (0·68, 3·60)EPA+DHA1·00 (0·79, 1·28)0·74 (0·38, 1·44)Total n-3 PUFAs 1·02 (0·80, 1·29)0·75 (0·39, 1·44)LA0·90 (0·71, 1·15)1·57 (0·98, 2·53)AA1·08 (0·86, 1·35)0·54 (0·29, 1·01)Total n-6 PUFAS1·03 (0·79, 1·34)0·86 (0·35, 2·11)Total n-3:n-6 ratio1·02 (0·79, 1·31)0·84 (0·41, 1·72)AA, arachidonic acid (C20:4n-6); ALA, a-Linolenic acid (C18:3n-3); DHA, docosahexaenoic acid (C22:6n-3); EPA, eicosapentaenoic acid (C20:5n-3); LA, linoleic acid (C18:2n-6); total n-3 (n-6) PUFAs, the sum of n-3 (n-6) PUFAs present in the chromatogram. * Relative risks (RRs) and their 95% CIs were calculated using generalized linear models for binary outcomes (modified Poisson) adjusted for maternal age, maternal BMI at study entry, gestational weight gain, maternal smoking during pregnancy, parity, parental education, parent atopy, child age at outcome assessment, and sex. Effect estimates correspond to a standard deviation score (SDS) increase in PUFAs and to a unit increase in the total n-3:n-6 ratio.? Current wheeze was defined as presence of wheezing or whistling in the chest since birth at 9 months of age (n/N= 62/228) and in the last 12 months at 4 years of age (n/N=10/222).Supplementary Table S8. Associations (pooled analysis; n 506) of primary PUFAs (polyunsaturated fatty acids) of interest with allergic disease-related phenotypes at 6-7 years of age after including birth weight and gestational age in multivariable models?(Relative risks (RRs) and 95% confidence intervals)Current wheeze?Current asthma§Current rhinitis||Current eczema?RR95% CIRR95% CIRR95% CIRR95% CIALA0·910·70, 1·180·590·29, 1·171·030·87, 1·210·900·70, 1·15EPA+DHA0·610·44, 0·84**0·470·27, 0·80**0·830·64, 1·080·860·66, 1·13Total n-3 PUFAs 0·600·44, 0·83**0·440·26, 0·75**0·820·63, 1·070·860·65, 1·13LA1·180·92, 1·511·280·83, 1·971·090·81, 1·451·200·94, 1·52AA1·340·98, 1·841·380·89, 2·151·060·80, 1·400·930·71, 1·21Total n-6 PUFAs1·491·05, 2·13*1·420·94, 2·151·100·86, 1·411·070·81, 1·40Total n-3:n-6 ratio0·550·39, 0·78**0·400·23, 0·70**0·810·62, 1·070·840·63, 1·12AA, arachidonic acid (C20:4n-6); ALA, a-Linolenic acid (C18:3n-3); DHA, docosahexaenoic acid (C22:6n-3); EPA, eicosapentaenoic acid (C20:5n-3); LA, linoleic acid (C18:2n-6); total n-3 (n-6) PUFAs, the sum of n-3 (n-6) PUFAs present in the chromatogram. P value for PUFA exposure-outcome association: *P<0·05; **P<0·01.? Relative risks (RRs) and their 95% CIs were calculated using generalized linear models for binary outcomes (modified Poisson) adjusted for maternal age, maternal BMI at study entry, gestational weight gain, maternal smoking during pregnancy, parity, birth weight, gestational age, parental education, parent atopy, child age at outcome assessment, sex, and a cohort indicator. Effect estimates correspond to a standard deviation score (SDS) increase in PUFAs and to a unit increase in the total n-3:n-6 ratio.? Current wheeze was defined as presence of wheezing or whistling in the chest in the last 12 months.§ Current asthma was defined as a positive answer to both ever-reported doctor diagnosis of asthma and presence of wheezing or whistling in the chest in the last 12 months.|| Current rhinitis was defined as presence of sneezing or a runny or blocked nose in the last 12 months without common cold or flu.? Current eczema was defined presence of an itchy rash in the last 12 months that affected any of the following places: the folds of the elbows, behind the knees, in front of the ankles, under the buttocks, or around the neck, ears or eyes.Supplementary Table S9. Assessment of effect measure modification by parent atopy in the association of the total n-3:n-6 PUFA ratio with current symptoms of asthma, rhinitis, and eczema at 6-7 years in the pooled datasetnCurrent asthmaCurrent rhinitisCurrent eczemaRR95% CIP valueRR95% CIP valueRR95% CIP valueParent atopy, no2830·480·28, 0·820·010·840·59, 1·210·360·900·58, 1·380·63Parent atopy, yes2230·380·17, 0·830·020·820·59, 1·150·250·970·69, 1·360·86Measure of effect modification on multiplicative scale:For current asthma: RR = 0·94 (95% CI 0·38, 2·34); P=0·90For current rhinitis: RR = 0·92 (95% CI 0·56, 1·51); P=0·74For current eczema: RR = 1·02 (95% CI 0·60, 1·73); P=0·94Measure of effect modification on additive scale:For current asthma: RERI = -0·31 (95% CI -1·87, 1·26); P= 0·70For current rhinitis: RERI = 0·04 (95% CI -0·88, 0·95); P= 0·94For current eczema: RERI = 0·21 (95% CI -1·04, 1·46); P= 0·74Effect estimates were adjusted for maternal age, maternal BMI at study entry, gestational weight gain, maternal smoking during pregnancy, parity, parental education, child age at outcome assessment, child sex, and a cohort indicator.Supplementary Table S10. Assessment of effect measure modification by sex in the association of the total n-3:n-6 PUFA ratio with current symptoms of asthma, rhinitis, and eczema at 6-7 years in the pooled datasetnCurrent asthmaCurrent rhinitisCurrent eczemaRR95% CIP valueRR95% CIP valueRR95% CIP valueChild sex, male2850·470·27, 0·80<0·011·000·72, 1·390·980·950·67, 1·350·77Child sex, female2210·270·17, 0·43<0·0010·610·37, 1·010·060·840·53, 1·340·47Measure of effect modification on multiplicative scale:For current asthma: RR = 0·80 (95% CI 0·38, 1·69); P=0·56For current rhinitis: RR = 0·57 (95% CI 0·32, 1·01); P=0·06For current eczema: RR = 0·88 (95% CI 0·52, 1·49); P=0·63Measure of effect modification on additive scale:For current asthma: RERI = 0·58 (95% CI -0·09, 1·26); P= 0·09For current rhinitis: RERI = -1·83 (95% CI -5·60, 1·94); P= 0·34For current eczema: RERI = -0·41 (95% CI -1·89, 1·07); P= 0·59Effect estimates were adjusted for maternal age, maternal BMI at study entry, gestational weight gain, maternal smoking during pregnancy, parent atopy, parity, parental education, child age at outcome assessment, and a cohort indicator.Supplementary Fig. S1. Flow chart of the MEFAB participantsSupplementary Fig. S2. Flow chart of the RHEA participantsSupplementary Fig. S3. Directed acyclic graph for the association of fatty acid status at birth with allergic disease-related symptoms in childhood.Text accompanying Supplementary Fig. S3In our models, selection of covariates for adjustment was based on a directed acyclic graph (DAG) approach. A DAG is a graphical tool that enables the visualization of the associations among the exposure of interest, the outcome(s) being studied, and all other related characteristics. It represents a conceptual model, and provides a structured way to present an overview of the research question and its context, therefore aiding in identifying the presence of confounding and ways to resolve it ADDIN EN.CITE <EndNote><Cite><Author>Shrier</Author><Year>2008</Year><RecNum>147</RecNum><DisplayText><style face="superscript">(1)</style></DisplayText><record><rec-number>147</rec-number><foreign-keys><key app="EN" db-id="fwtd50td9s2p0uets25xdavltwrazdwsewrf" timestamp="1499717155">147</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Shrier, I.</author><author>Platt, R. W.</author></authors></contributors><auth-address>Centre for Clinical Epidemiology and Community Studies, SMBD-Jewish General Hospital, McGill University, Montreal, Canada. ian.shrier@mcgill.ca</auth-address><titles><title>Reducing bias through directed acyclic graphs</title><secondary-title>BMC Med Res Methodol</secondary-title></titles><periodical><full-title>BMC Med Res Methodol</full-title></periodical><pages>70</pages><volume>8</volume><keywords><keyword>*Bias (Epidemiology)</keyword><keyword>*Computer Graphics</keyword><keyword>*Confounding Factors (Epidemiology)</keyword><keyword>Humans</keyword><keyword>Models, Statistical</keyword></keywords><dates><year>2008</year><pub-dates><date>Oct 30</date></pub-dates></dates><isbn>1471-2288 (Electronic)&#xD;1471-2288 (Linking)</isbn><accession-num>18973665</accession-num><urls><related-urls><url>;(1). Below, we use some illustrative examples for the reader who has not previous experience with DAGs. For those who are more interested in the concept of DAGs, there are some excellent reviews on this topicPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HcmVlbmxhbmQ8L0F1dGhvcj48WWVhcj4xOTk5PC9ZZWFy

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ADDIN EN.CITE.DATA (1,2,3). Arrows in DAGs represent direct effects of one factor on another, either protective or harmful. Moreover, arrows should follow time order, or else the diagram contradicts the basic principle that causes must precede their effects. The arrows and their direction are drawn based on prior knowledge. For instance, in Supplemental Figure 3, parental education, as a proxy of SES status, can affect both prenatal fatty acid exposurePEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XZW5uYmVyZzwvQXV0aG9yPjxZZWFyPjIwMTI8L1llYXI+

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ADDIN EN.CITE.DATA (7,8). Hence, gestational age is not a cause of prenatal PUFA exposure, but prenatal PUFAs can be regarded as a cause of gestational age.?Additionally, the arrow from gestational age to child allergy indicates that gestational age predicts child allergy symptoms; an association that is supported by good epidemiological evidencePEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Tb25uZW5zY2hlaW4tdmFuIGRlciBWb29ydDwvQXV0aG9y

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ADDIN EN.CITE.DATA (9). Gestational age is therefore in the causal pathway between fatty acid status and child allergy. In our study, the DAG was drawn using DAGitty () ADDIN EN.CITE <EndNote><Cite><Author>Textor</Author><Year>2011</Year><RecNum>109</RecNum><DisplayText><style face="superscript">(10)</style></DisplayText><record><rec-number>109</rec-number><foreign-keys><key app="EN" db-id="fwtd50td9s2p0uets25xdavltwrazdwsewrf" timestamp="1499688786">109</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Textor, J.</author><author>Hardt, J.</author><author>Knuppel, S.</author></authors></contributors><titles><title>DAGitty: a graphical tool for analyzing causal diagrams</title><secondary-title>Epidemiology</secondary-title></titles><periodical><full-title>Epidemiology</full-title></periodical><pages>745</pages><volume>22</volume><number>5</number><keywords><keyword>Algorithms</keyword><keyword>*Causality</keyword><keyword>*Computer Graphics</keyword><keyword>*Data Interpretation, Statistical</keyword><keyword>*Software</keyword><keyword>User-Computer Interface</keyword></keywords><dates><year>2011</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1531-5487 (Electronic)&#xD;1044-3983 (Linking)</isbn><accession-num>21811114</accession-num><urls><related-urls><url>;(10), a user friendly software that allows the instant identification of minimum but sufficient sets of factors to control for in the analysis in order to resolve confounding. The adjustment set in our study included the following covariates: maternal age, maternal BMI at study entry, gestational weight gain, maternal smoking during pregnancy, parental education, parity, parent atopy, child age and sex. Through this adjustment set, the backdoor paths from fatty acid status at birth towards child allergy are blocked. Below, we present references for the assumed relationships in our DAG (Supplementary Fig. 3):Parental education → prenatal PUFA status:PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XZW5uYmVyZzwvQXV0aG9yPjxZZWFyPjIwMTI8L1llYXI+

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ADDIN EN.CITE.DATA (6) → smoking during pregnancy: ADDIN EN.CITE <EndNote><Cite><Author>Vardavas</Author><Year>2010</Year><RecNum>121</RecNum><DisplayText><style face="superscript">(11)</style></DisplayText><record><rec-number>121</rec-number><foreign-keys><key app="EN" db-id="fwtd50td9s2p0uets25xdavltwrazdwsewrf" timestamp="1499693970">121</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Vardavas, C. I.</author><author>Patelarou, E.</author><author>Chatzi, L.</author><author>Roumeliotaki, T.</author><author>Sarri, K.</author><author>Murphy, S.</author><author>Koutis, A.</author><author>Kafatos, A. G.</author><author>Kogevinas, M.</author></authors></contributors><auth-address>Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece. vardavas@edu.med.uoc.gr</auth-address><titles><title>Factors associated with active smoking, quitting, and secondhand smoke exposure among pregnant women in Greece</title><secondary-title>J Epidemiol</secondary-title></titles><periodical><full-title>J Epidemiol</full-title></periodical><pages>355-62</pages><volume>20</volume><number>5</number><keywords><keyword>Adult</keyword><keyword>Age Factors</keyword><keyword>Cohort Studies</keyword><keyword>Educational Status</keyword><keyword>Female</keyword><keyword>Greece/epidemiology</keyword><keyword>Humans</keyword><keyword>Maternal Exposure/*statistics &amp; numerical data</keyword><keyword>Pregnancy</keyword><keyword>Risk Factors</keyword><keyword>Smoking/*epidemiology</keyword><keyword>Smoking Cessation/*statistics &amp; numerical data</keyword><keyword>Surveys and Questionnaires</keyword><keyword>*Tobacco Smoke Pollution</keyword></keywords><dates><year>2010</year></dates><isbn>1349-9092 (Electronic)&#xD;0917-5040 (Linking)</isbn><accession-num>20595782</accession-num><urls><related-urls><url>;(11)→ child BMI:PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NdXRodXJpPC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48

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ADDIN EN.CITE.DATA (12)Maternal age→ smoking during pregnancy: ADDIN EN.CITE <EndNote><Cite><Author>Vardavas</Author><Year>2010</Year><RecNum>121</RecNum><DisplayText><style face="superscript">(11)</style></DisplayText><record><rec-number>121</rec-number><foreign-keys><key app="EN" db-id="fwtd50td9s2p0uets25xdavltwrazdwsewrf" timestamp="1499693970">121</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Vardavas, C. I.</author><author>Patelarou, E.</author><author>Chatzi, L.</author><author>Roumeliotaki, T.</author><author>Sarri, K.</author><author>Murphy, S.</author><author>Koutis, A.</author><author>Kafatos, A. G.</author><author>Kogevinas, M.</author></authors></contributors><auth-address>Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece. vardavas@edu.med.uoc.gr</auth-address><titles><title>Factors associated with active smoking, quitting, and secondhand smoke exposure among pregnant women in Greece</title><secondary-title>J Epidemiol</secondary-title></titles><periodical><full-title>J Epidemiol</full-title></periodical><pages>355-62</pages><volume>20</volume><number>5</number><keywords><keyword>Adult</keyword><keyword>Age Factors</keyword><keyword>Cohort Studies</keyword><keyword>Educational Status</keyword><keyword>Female</keyword><keyword>Greece/epidemiology</keyword><keyword>Humans</keyword><keyword>Maternal Exposure/*statistics &amp; numerical data</keyword><keyword>Pregnancy</keyword><keyword>Risk Factors</keyword><keyword>Smoking/*epidemiology</keyword><keyword>Smoking Cessation/*statistics &amp; numerical data</keyword><keyword>Surveys and Questionnaires</keyword><keyword>*Tobacco Smoke Pollution</keyword></keywords><dates><year>2010</year></dates><isbn>1349-9092 (Electronic)&#xD;0917-5040 (Linking)</isbn><accession-num>20595782</accession-num><urls><related-urls><url>;(11)→ child BMI: ADDIN EN.CITE <EndNote><Cite><Author>Savage</Author><Year>2013</Year><RecNum>153</RecNum><DisplayText><style face="superscript">(13)</style></DisplayText><record><rec-number>153</rec-number><foreign-keys><key app="EN" db-id="fwtd50td9s2p0uets25xdavltwrazdwsewrf" timestamp="1503921408">153</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Savage, T.</author><author>Derraik, J. G.</author><author>Miles, H. L.</author><author>Mouat, F.</author><author>Hofman, P. L.</author><author>Cutfield, W. S.</author></authors></contributors><auth-address>Liggins Institute, University of Auckland, Auckland, New Zealand.</auth-address><titles><title>Increasing maternal age is associated with taller stature and reduced abdominal fat in their children</title><secondary-title>PLoS One</secondary-title></titles><periodical><full-title>PLoS One</full-title></periodical><pages>e58869</pages><volume>8</volume><number>3</number><edition>2013/03/26</edition><keywords><keyword>*Abdominal Fat</keyword><keyword>Adult</keyword><keyword>Anthropometry</keyword><keyword>Birth Weight</keyword><keyword>Blood Glucose</keyword><keyword>Body Composition</keyword><keyword>*Body Height</keyword><keyword>Body Mass Index</keyword><keyword>Child</keyword><keyword>Child, Preschool</keyword><keyword>Cholesterol/blood</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Insulin/metabolism</keyword><keyword>Male</keyword><keyword>*Maternal Age</keyword><keyword>Pregnancy</keyword><keyword>Somatomedins/metabolism</keyword><keyword>Young Adult</keyword></keywords><dates><year>2013</year></dates><isbn>1932-6203 (Electronic)&#xD;1932-6203 (Linking)</isbn><accession-num>23527040</accession-num><urls><related-urls><url>;(13) → gestational age/birthweight:PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MYXdsb3I8L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFyPjxS

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ADDIN EN.CITE.DATA (15)→ gestational age/birthweight: ADDIN EN.CITE <EndNote><Cite><Author>Nohr</Author><Year>2008</Year><RecNum>116</RecNum><DisplayText><style face="superscript">(16)</style></DisplayText><record><rec-number>116</rec-number><foreign-keys><key app="EN" db-id="fwtd50td9s2p0uets25xdavltwrazdwsewrf" timestamp="1499691980">116</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Nohr, E. A.</author><author>Vaeth, M.</author><author>Baker, J. L.</author><author>Sorensen, TIa</author><author>Olsen, J.</author><author>Rasmussen, K. M.</author></authors></contributors><auth-address>Department of Epidemiology, Institute of Public Health, University of Aarhus, Aarhus, Denmark. ean@soci.au.dk</auth-address><titles><title>Combined associations of prepregnancy body mass index and gestational weight gain with the outcome of pregnancy</title><secondary-title>Am J Clin Nutr</secondary-title></titles><periodical><full-title>Am J Clin Nutr</full-title><abbr-1>The American journal of clinical nutrition</abbr-1></periodical><pages>1750-9</pages><volume>87</volume><number>6</number><keywords><keyword>Adult</keyword><keyword>*Body Mass Index</keyword><keyword>Cohort Studies</keyword><keyword>Denmark</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Interviews as Topic</keyword><keyword>Obesity/physiopathology</keyword><keyword>Overweight/physiopathology</keyword><keyword>Parity</keyword><keyword>Pregnancy/*physiology</keyword><keyword>*Pregnancy Outcome</keyword><keyword>Pregnancy Trimester, Second</keyword><keyword>Pregnancy Trimester, Third</keyword><keyword>*Weight Gain</keyword></keywords><dates><year>2008</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>1938-3207 (Electronic)&#xD;0002-9165 (Linking)</isbn><accession-num>18541565</accession-num><urls><related-urls><url>;(16)→ child BMI: ADDIN EN.CITE <EndNote><Cite><Author>Yu</Author><Year>2013</Year><RecNum>117</RecNum><DisplayText><style face="superscript">(17)</style></DisplayText><record><rec-number>117</rec-number><foreign-keys><key app="EN" db-id="fwtd50td9s2p0uets25xdavltwrazdwsewrf" timestamp="1499692196">117</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yu, Z.</author><author>Han, S.</author><author>Zhu, J.</author><author>Sun, X.</author><author>Ji, C.</author><author>Guo, X.</author></authors></contributors><auth-address>State Key Laboratory of Reproductive Medicine, Department of Pediatrics, Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, China.</auth-address><titles><title>Pre-pregnancy body mass index in relation to infant birth weight and offspring overweight/obesity: a systematic review and meta-analysis</title><secondary-title>PLoS One</secondary-title></titles><periodical><full-title>PLoS One</full-title></periodical><pages>e61627</pages><volume>8</volume><number>4</number><keywords><keyword>Birth Weight/*physiology</keyword><keyword>*Body Mass Index</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Infant, Newborn</keyword><keyword>Obesity/*epidemiology</keyword><keyword>Overweight/*epidemiology</keyword><keyword>Pregnancy</keyword></keywords><dates><year>2013</year></dates><isbn>1932-6203 (Electronic)&#xD;1932-6203 (Linking)</isbn><accession-num>23613888</accession-num><urls><related-urls><url>;(17)→ child allergy-related symptoms:PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Gb3JubzwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJl

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ADDIN EN.CITE.DATA (18)Gestational weight gain→ gestational age/birthweight: ADDIN EN.CITE <EndNote><Cite><Author>Nohr</Author><Year>2008</Year><RecNum>116</RecNum><DisplayText><style face="superscript">(16)</style></DisplayText><record><rec-number>116</rec-number><foreign-keys><key app="EN" db-id="fwtd50td9s2p0uets25xdavltwrazdwsewrf" timestamp="1499691980">116</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Nohr, E. A.</author><author>Vaeth, M.</author><author>Baker, J. L.</author><author>Sorensen, TIa</author><author>Olsen, J.</author><author>Rasmussen, K. M.</author></authors></contributors><auth-address>Department of Epidemiology, Institute of Public Health, University of Aarhus, Aarhus, Denmark. ean@soci.au.dk</auth-address><titles><title>Combined associations of prepregnancy body mass index and gestational weight gain with the outcome of pregnancy</title><secondary-title>Am J Clin Nutr</secondary-title></titles><periodical><full-title>Am J Clin Nutr</full-title><abbr-1>The American journal of clinical nutrition</abbr-1></periodical><pages>1750-9</pages><volume>87</volume><number>6</number><keywords><keyword>Adult</keyword><keyword>*Body Mass Index</keyword><keyword>Cohort Studies</keyword><keyword>Denmark</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Interviews as Topic</keyword><keyword>Obesity/physiopathology</keyword><keyword>Overweight/physiopathology</keyword><keyword>Parity</keyword><keyword>Pregnancy/*physiology</keyword><keyword>*Pregnancy Outcome</keyword><keyword>Pregnancy Trimester, Second</keyword><keyword>Pregnancy Trimester, Third</keyword><keyword>*Weight Gain</keyword></keywords><dates><year>2008</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>1938-3207 (Electronic)&#xD;0002-9165 (Linking)</isbn><accession-num>18541565</accession-num><urls><related-urls><url>;(16)→ child BMI:PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Nb3VydGFrb3M8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFy

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ADDIN EN.CITE.DATA (22)→ child allergy-related symptoms: ADDIN EN.CITE <EndNote><Cite><Author>Gilliland</Author><Year>2001</Year><RecNum>127</RecNum><DisplayText><style face="superscript">(23)</style></DisplayText><record><rec-number>127</rec-number><foreign-keys><key app="EN" db-id="fwtd50td9s2p0uets25xdavltwrazdwsewrf" timestamp="1499696141">127</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gilliland, F. D.</author><author>Li, Y. F.</author><author>Peters, J. M.</author></authors></contributors><auth-address>Keck School of Medicine, Department of Preventive Medicine, University of Southern California, Los Angeles, California 90033, USA. gillilland@hsc.usc.edu</auth-address><titles><title>Effects of maternal smoking during pregnancy and environmental tobacco smoke on asthma and wheezing in children</title><secondary-title>Am J Respir Crit Care Med</secondary-title></titles><periodical><full-title>Am J Respir Crit Care Med</full-title></periodical><pages>429-36</pages><volume>163</volume><number>2</number><keywords><keyword>Adolescent</keyword><keyword>Asthma/*etiology</keyword><keyword>California</keyword><keyword>Child</keyword><keyword>Child, Preschool</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Infant</keyword><keyword>Infant, Newborn</keyword><keyword>Male</keyword><keyword>Pregnancy</keyword><keyword>Respiratory Sounds/*etiology</keyword><keyword>Risk Factors</keyword><keyword>Smoking/*adverse effects</keyword><keyword>Tobacco Smoke Pollution/*adverse effects</keyword></keywords><dates><year>2001</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1073-449X (Print)&#xD;1073-449X (Linking)</isbn><accession-num>11179118</accession-num><urls><related-urls><url>;(23)Parity→ prenatal PUFA status: ADDIN EN.CITE <EndNote><Cite><Author>Hornstra</Author><Year>2000</Year><RecNum>50</RecNum><DisplayText><style face="superscript">(24)</style></DisplayText><record><rec-number>50</rec-number><foreign-keys><key app="EN" db-id="fwtd50td9s2p0uets25xdavltwrazdwsewrf" timestamp="1479230715">50</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hornstra, G.</author></authors></contributors><auth-address>Department of Human Biology, Maastricht University, Maastricht, Netherlands. g.hornstra@hb.unimaas.nl</auth-address><titles><title>Essential fatty acids in mothers and their neonates</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>Am J Clin Nutr</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title><abbr-1>The American journal of clinical nutrition</abbr-1></periodical><alt-periodical><full-title>Am J Clin Nutr</full-title><abbr-1>The American journal of clinical nutrition</abbr-1></alt-periodical><pages>1262S-9S</pages><volume>71</volume><number>5 Suppl</number><keywords><keyword>Dietary Fats/*administration &amp; dosage</keyword><keyword>Fatty Acids, Unsaturated/*metabolism</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Infant, Newborn/*physiology</keyword><keyword>Nutritional Requirements</keyword><keyword>Pregnancy/*physiology</keyword></keywords><dates><year>2000</year><pub-dates><date>May</date></pub-dates></dates><isbn>0002-9165 (Print)&#xD;0002-9165 (Linking)</isbn><accession-num>10799400</accession-num><urls><related-urls><url>;(24)→ child allergy-related symptoms:PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYWxsPC9BdXRob3I+PFllYXI+MjAwMDwvWWVhcj48UmVj

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ADDIN EN.CITE.DATA (25,26)Parent atopy→ prenatal PUFA status: ADDIN EN.CITE <EndNote><Cite><Author>Duchen</Author><Year>2001</Year><RecNum>139</RecNum><DisplayText><style face="superscript">(27)</style></DisplayText><record><rec-number>139</rec-number><foreign-keys><key app="EN" db-id="fwtd50td9s2p0uets25xdavltwrazdwsewrf" timestamp="1499698969">139</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Duchen, K.</author><author>Bjorksten, B.</author></authors></contributors><auth-address>Division of Pediatrics, Department of Health and Environment, Linkoping University Hospital, Linkoping, Sweden. KarDu@ihm.liu.se</auth-address><titles><title>Polyunsaturated n-3 fatty acids and the development of atopic disease</title><secondary-title>Lipids</secondary-title></titles><periodical><full-title>Lipids</full-title></periodical><pages>1033-42</pages><volume>36</volume><number>9</number><keywords><keyword>Child, Preschool</keyword><keyword>Fatty Acid Desaturases/genetics/metabolism</keyword><keyword>Fatty Acids, Omega-3/immunology/*metabolism</keyword><keyword>Fatty Acids, Omega-6</keyword><keyword>Fatty Acids, Unsaturated/metabolism</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Hypersensitivity/etiology</keyword><keyword>Hypersensitivity, Immediate/metabolism/*physiopathology</keyword><keyword>Linoleoyl-CoA Desaturase</keyword><keyword>Milk, Human/immunology/metabolism</keyword><keyword>Phospholipids/blood/chemistry/*metabolism</keyword><keyword>Triglycerides</keyword></keywords><dates><year>2001</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0024-4201 (Print)&#xD;0024-4201 (Linking)</isbn><accession-num>11724455</accession-num><urls><related-urls><url>;(27)→ child allergy-related symptoms: ADDIN EN.CITE <EndNote><Cite><Author>Alford</Author><Year>2004</Year><RecNum>140</RecNum><DisplayText><style face="superscript">(28)</style></DisplayText><record><rec-number>140</rec-number><foreign-keys><key app="EN" db-id="fwtd50td9s2p0uets25xdavltwrazdwsewrf" timestamp="1499699040">140</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Alford, S. H.</author><author>Zoratti, E.</author><author>Peterson, E. L.</author><author>Maliarik, M.</author><author>Ownby, D. R.</author><author>Johnson, C. C.</author></authors></contributors><auth-address>The Henry Ford Health System, One Ford Place #5C, Detroit, MI 48202, USA.</auth-address><titles><title>Parental history of atopic disease: disease pattern and risk of pediatric atopy in offspring</title><secondary-title>J Allergy Clin Immunol</secondary-title></titles><periodical><full-title>J Allergy Clin Immunol</full-title></periodical><pages>1046-50</pages><volume>114</volume><number>5</number><keywords><keyword>Adult</keyword><keyword>Child</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Hypersensitivity/etiology/*genetics</keyword><keyword>Male</keyword><keyword>Parents</keyword><keyword>Risk Factors</keyword></keywords><dates><year>2004</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0091-6749 (Print)&#xD;0091-6749 (Linking)</isbn><accession-num>15536408</accession-num><urls><related-urls><url>;(28)Prenatal PUFA status→ birthweight/gestational age:PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Hcm9vdGVuZG9yc3QtdmFuIE1pbDwvQXV0aG9yPjxZZWFy

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ADDIN EN.CITE.DATA (30)→ allergy-related symptoms: ADDIN EN.CITE <EndNote><Cite><Author>Almqvist</Author><Year>2008</Year><RecNum>78</RecNum><DisplayText><style face="superscript">(31)</style></DisplayText><record><rec-number>78</rec-number><foreign-keys><key app="EN" db-id="fwtd50td9s2p0uets25xdavltwrazdwsewrf" timestamp="1497988277">78</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Almqvist, C.</author><author>Worm, M.</author><author>Leynaert, B.</author><author>working group of, G. A. L. E. N. W. P. Gender</author></authors></contributors><auth-address>Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden.</auth-address><titles><title>Impact of gender on asthma in childhood and adolescence: a GA2LEN review</title><secondary-title>Allergy</secondary-title></titles><periodical><full-title>Allergy</full-title></periodical><pages>47-57</pages><volume>63</volume><number>1</number><keywords><keyword>Adolescent</keyword><keyword>Asthma/*epidemiology/*physiopathology</keyword><keyword>Child</keyword><keyword>Child, Preschool</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Incidence</keyword><keyword>Male</keyword><keyword>Prevalence</keyword><keyword>Prognosis</keyword><keyword>Risk Factors</keyword><keyword>Severity of Illness Index</keyword><keyword>Sex Distribution</keyword><keyword>Sex Factors</keyword></keywords><dates><year>2008</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>1398-9995 (Electronic)&#xD;0105-4538 (Linking)</isbn><accession-num>17822448</accession-num><urls><related-urls><url>;(31)Gestational age/birth weight→ child allergy-related symptoms:PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NZWJyYWh0dTwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+

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ADDIN EN.CITE.DATA (32,33)Child BMI→ allergy-related symptoms: ADDIN EN.CITE <EndNote><Cite><Author>Gilliland</Author><Year>2003</Year><RecNum>143</RecNum><DisplayText><style face="superscript">(34)</style></DisplayText><record><rec-number>143</rec-number><foreign-keys><key app="EN" db-id="fwtd50td9s2p0uets25xdavltwrazdwsewrf" timestamp="1499699480">143</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gilliland, F. D.</author><author>Berhane, K.</author><author>Islam, T.</author><author>McConnell, R.</author><author>Gauderman, W. J.</author><author>Gilliland, S. S.</author><author>Avol, E.</author><author>Peters, J. M.</author></authors></contributors><auth-address>Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. gillilan@usc.edu</auth-address><titles><title>Obesity and the risk of newly diagnosed asthma in school-age children</title><secondary-title>Am J Epidemiol</secondary-title></titles><periodical><full-title>Am J Epidemiol</full-title></periodical><pages>406-15</pages><volume>158</volume><number>5</number><keywords><keyword>Adolescent</keyword><keyword>Asthma/*epidemiology</keyword><keyword>Body Mass Index</keyword><keyword>California/epidemiology</keyword><keyword>Child</keyword><keyword>Cohort Studies</keyword><keyword>Comorbidity</keyword><keyword>Female</keyword><keyword>Follow-Up Studies</keyword><keyword>Humans</keyword><keyword>Incidence</keyword><keyword>Longitudinal Studies</keyword><keyword>Male</keyword><keyword>Multivariate Analysis</keyword><keyword>Obesity/*epidemiology</keyword><keyword>Prospective Studies</keyword><keyword>Reference Values</keyword><keyword>Risk Factors</keyword><keyword>Sex Distribution</keyword></keywords><dates><year>2003</year><pub-dates><date>Sep 01</date></pub-dates></dates><isbn>0002-9262 (Print)&#xD;0002-9262 (Linking)</isbn><accession-num>12936895</accession-num><urls><related-urls><url>;(34)References ADDIN EN.REFLIST 1. 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