Comparison of the performances of survival analysis regression models for analysis of conception modes and risk of type-1 diabetes among 1985–2015 Swedish birth cohort

The goal is to examine the risk of conception mode-type-1 diabetes using different survival analysis modelling approaches and examine if there are differentials in the risk of type-1 diabetes between children from fresh and frozen-thawed embryo transfers. We aimed to compare the performances and fitness of different survival analysis regression models with the Cox proportional hazard (CPH) model used in an earlier study. The effect of conception modes and other prognostic factors on type-1 diabetes among children conceived either spontaneously or by assisted reproductive technology (ART) and its sub-groups was modelled in the earlier study. We used the information on all singleton children from the Swedish Medical Birth Register hosted by the Swedish National Board of Health and Welfare, 1985 to 2015. The main explanatory variable was the mode of conception. We applied the CPH, parametric and flexible parametric survival regression (FPSR) models to the data at 5% significance level. Loglikelihood, Akaike and Bayesian information criteria were used to assess model fit. Among the 3,138,540 singletons, 47,938 (1.5%) were conceived through ART (11,211 frozen-thawed transfer and 36,727 fresh embryo transfer). In total, 18,118 (0.58%) of the children had type-1 diabetes, higher among (0.58%) those conceived spontaneously than the ART-conceived (0.42%). The median (Interquartile range (IQR)) age at onset of type-1 diabetes among spontaneously conceived children was 10 (14–6) years, 8(5–12) for ART, 6 (4–10) years for frozen-thawed embryo transfer and 9 (5–12) years for fresh embryo transfer. The estimates from the CPH, FPSR and parametric PH models are similar. There was no significant difference in the risk of type-1 diabetes among ART- and spontaneously conceived children; FPSR: (adjusted Hazard Ratio (aHR) = 1.070; 95% Confidence Interval (CI):0.929–1.232, p = 0.346) vs CPH: (aHR = 1.068; 95%CI: 0.927–1.230, p = 0.361). A sub-analysis showed that the adjusted hazard of type-1 diabetes was 37% (aHR = 1.368; 95%CI: 1.013–1.847, p = 0.041) higher among children from frozen-thawed embryo transfer than among children from spontaneous conception. The hazard of type-1 diabetes was higher among children whose mothers do not smoke (aHR = 1.296; 95%CI:1.240–1.354, p<0.001) and of diabetic mothers (aHR = 6.419; 95%CI:5.852–7.041, p<0.001) and fathers (aHR = 8.808; 95%CI:8.221–9.437, p<0.001). The estimates from the CPH, parametric models and the FPSR model were close. This is an indication that the models performed similarly and any of them can be used to model the data. We couldn’t establish that ART increases the risk of type-1 diabetes except when it is subdivided into its two subtypes. There is evidence of a greater risk of type-1 diabetes when conception is through frozen-thawed transfer.Publisher PDFPeer reviewe

Cardiovascular disease, obesity, and type 2 diabetes in children born after assisted reproductive technology: A population-based cohort study

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Long-term outcome of children born after Assisted Reproductive Technology

Background: While the short-term outcome after assisted reproductive technology (ART) is broadly examined, studies on the long-term outcome of ART children are limited. Aim: To examine the long-term outcome in children born after ART and study whether different ART techniques affect the outcome in the children differently. Material and methods: All papers were national population-based register studies, performed by cross-linking national ART registers with health data registers. Paper I-III included all singletons born in Sweden: after ART (n=8 323) and spontaneous conception (SC) (n=1 499 667) between 1985 and 2001 (Paper I), after intracytoplasmic sperm injection (ICSI) (n=6 953), standard in vitro fertilization (IVF) (n=11 713) and SC (n=2 022 995) between 1985 and 2006 (Paper II) and after ART (n=47 938) and SC (n=3 090 602) between 1985 and 2015 (Paper III). In Paper IV all singletons born after ART (n=122 429) and SC (n=7 574 685) in Sweden, Norway, Finland and Denmark between 1984 and 2015 were included. The primary outcomes were school performance (Paper I and II), type 1 diabetes (Paper III), cardiovascular disease (ischemic heart disease, cardiomyopathy, heart failure or cerebrovascular disease), obesity and type 2 diabetes (Paper IV). Results: Paper I: ART children had significantly better school results than SC children in the crude analyses. After adjustment, a small but significant difference was observed in total scores in favour of SC children (adjusted mean difference percentiles -0.72; 95% confidence interval -1.31 to -0.12; p=0.018). Paper II: ICSI children had similar school performance as IVF and SC children in the ninth grade. In the third grade, ICSI children had lower chance of passing all the subtests in mathematics and Swedish compared to SC children. Paper III: ART children had no increased risk of type 1 diabetes after adjustment for important covariates. In a subgroup analysis, children born after frozen embryo transfer had increased risk of type 1 diabetes compared to children born after fresh embryo transfer and SC. Paper IV: No increased risk of cardiovascular disease or type 2 diabetes were found among ART children in the adjusted analyses. A small but significantly increased risk of obesity was found. Conclusion: School performance up to ninth grade is reassuring for ART children. Cardiometabolic outcomes in ART children are also generally reassuring. However, the number of events were limited for several diseases and small negative differences were observed in a few analyses. Previous studies of ART children have repeatedly suggested small differences in cardiometabolic surrogate outcomes, emphasizing a need for further studies

A Suggestion of how The Parent Report Instrument, The Swedish Communicative Development Inventories (SCDI-III) Can Be Validated : A Pilot Study

I denna studie ett förslag till validering av föräldraskattningsformuläret SCDI-III baserad på en genomförd pilotstudie. Studiens syfte är att undersöka hur väl föräldrars och förskolepedagogers skattning av deltagande barns språkförmåga med skattningsinstrumentet SCDI-III överensstämmer med resultaten av ett test som studieförfattarna utformade. Testmaterialet speglar direkt de frågor som ställs till vårdnadshavarna och förskolepedagoger i SCDI-III.  Tio barn i åldersgruppen 2;5–3;10 år med svenska som starkaste språk, tio vårdnadshavare och tio förskolepedagoger deltog i studien. Studieförfattarna utformade ett eget testmaterial som i så hög grad som möjligt speglar frågeställningarna i föräldraskattsformuläret SCDI-III. Bildbenämning användes för ordförrådsdelen och BUSS-sagan användes för bedömning av meningskomplexitet och meningsbyggnad. Testningen av sju av barnen utfördes i det digitala mötesrummet Zoom och tre barn testades delvis på förskolan. Vårdnadshavarna och förskolepedagogerna fyllde i föräldraskattningsformuläret SCDI-III, varefter resultaten jämfördes.   Resultatet visade generellt på en hög överensstämmelse mellan samtliga bedömargrupper. Det förelåg endast små skillnader mellan grupperna och dessa var förutom två ord (“förstå” och “dum”) inte statistiskt signifikanta.   Slutsatsen var att deltagande vårdnadshavare och förskolepedagoger kunde skatta barnens språkliga förmåga i hög utsträckning. Studiens resultat pekar därmed på att föräldraskattningen SCDI-III kan vara värdefull som kompletterande information gällande barnets språkliga förmåga. Förslag på hur en större valideringsstudie kan genomföras diskuteras. In the present study, a suggestion is provided of how the parent report instrument, The Swedish Communicative Development Inventories (SCDI-III) can be validated. The suggestion is based on a conducted pilot study. The purpose of the study is to investigate how well parents and preschool teachers assessment of participating children’s language ability with the assessment instrument SCDI-III corresponds with the results of a test designed by the study authors. The test material directly reflects the questions asked to the guardians and preschool teachers in SCDI-III.  Ten children in the age group 2;5-3;10 years old with Swedish as their strongest language, ten guardians and ten preschool teachers participated in the study. The study authors designed a test material which as closely as possible mirrored the content in the questions asked in the parent report SCDI-III. Picture-naming was used for the vocabulary part and the BUS-story test was used for the assessment of sentence complexity and sentence construction. The screening of seven of the children was performed in the digital meeting room Zoom, and three children were partially tested at the preschool. The guardians and preschool teachers filled in the parent report SCDI-III, and the results were compared.   The results generally showed a high degree of agreement between all the assessment groups. There were only small differences between the groups and these, apart from two words ("understand" and "stupid") were not statistically significant.   The conclusion was that participating guardians and preschool teachers could estimate the children’s language ability to a great extent. The results of the study indicate that the parent report SCDI-III, can be valuable as supplementary information regarding the children’s language ability. Suggestions on how a larger validation study may be carried out are discussed.

A Suggestion of how The Parent Report Instrument, The Swedish Communicative Development Inventories (SCDI-III) Can Be Validated : A Pilot Study

I denna studie ett förslag till validering av föräldraskattningsformuläret SCDI-III baserad på en genomförd pilotstudie. Studiens syfte är att undersöka hur väl föräldrars och förskolepedagogers skattning av deltagande barns språkförmåga med skattningsinstrumentet SCDI-III överensstämmer med resultaten av ett test som studieförfattarna utformade. Testmaterialet speglar direkt de frågor som ställs till vårdnadshavarna och förskolepedagoger i SCDI-III.  Tio barn i åldersgruppen 2;5–3;10 år med svenska som starkaste språk, tio vårdnadshavare och tio förskolepedagoger deltog i studien. Studieförfattarna utformade ett eget testmaterial som i så hög grad som möjligt speglar frågeställningarna i föräldraskattsformuläret SCDI-III. Bildbenämning användes för ordförrådsdelen och BUSS-sagan användes för bedömning av meningskomplexitet och meningsbyggnad. Testningen av sju av barnen utfördes i det digitala mötesrummet Zoom och tre barn testades delvis på förskolan. Vårdnadshavarna och förskolepedagogerna fyllde i föräldraskattningsformuläret SCDI-III, varefter resultaten jämfördes.   Resultatet visade generellt på en hög överensstämmelse mellan samtliga bedömargrupper. Det förelåg endast små skillnader mellan grupperna och dessa var förutom två ord (“förstå” och “dum”) inte statistiskt signifikanta.   Slutsatsen var att deltagande vårdnadshavare och förskolepedagoger kunde skatta barnens språkliga förmåga i hög utsträckning. Studiens resultat pekar därmed på att föräldraskattningen SCDI-III kan vara värdefull som kompletterande information gällande barnets språkliga förmåga. Förslag på hur en större valideringsstudie kan genomföras diskuteras. In the present study, a suggestion is provided of how the parent report instrument, The Swedish Communicative Development Inventories (SCDI-III) can be validated. The suggestion is based on a conducted pilot study. The purpose of the study is to investigate how well parents and preschool teachers assessment of participating children’s language ability with the assessment instrument SCDI-III corresponds with the results of a test designed by the study authors. The test material directly reflects the questions asked to the guardians and preschool teachers in SCDI-III.  Ten children in the age group 2;5-3;10 years old with Swedish as their strongest language, ten guardians and ten preschool teachers participated in the study. The study authors designed a test material which as closely as possible mirrored the content in the questions asked in the parent report SCDI-III. Picture-naming was used for the vocabulary part and the BUS-story test was used for the assessment of sentence complexity and sentence construction. The screening of seven of the children was performed in the digital meeting room Zoom, and three children were partially tested at the preschool. The guardians and preschool teachers filled in the parent report SCDI-III, and the results were compared.   The results generally showed a high degree of agreement between all the assessment groups. There were only small differences between the groups and these, apart from two words ("understand" and "stupid") were not statistically significant.   The conclusion was that participating guardians and preschool teachers could estimate the children’s language ability to a great extent. The results of the study indicate that the parent report SCDI-III, can be valuable as supplementary information regarding the children’s language ability. Suggestions on how a larger validation study may be carried out are discussed.

Comparison of the performances of survival analysis regression models for analysis of conception modes and risk of type-1 diabetes among 1985–2015 Swedish birth cohort

The goal is to examine the risk of conception mode-type-1 diabetes using different survival analysis modelling approaches and examine if there are differentials in the risk of type-1 diabetes between children from fresh and frozen-thawed embryo transfers. We aimed to compare the performances and fitness of different survival analysis regression models with the Cox proportional hazard (CPH) model used in an earlier study. The effect of conception modes and other prognostic factors on type-1 diabetes among children conceived either spontaneously or by assisted reproductive technology (ART) and its sub-groups was modelled in the earlier study. We used the information on all singleton children from the Swedish Medical Birth Register hosted by the Swedish National Board of Health and Welfare, 1985 to 2015. The main explanatory variable was the mode of conception. We applied the CPH, parametric and flexible parametric survival regression (FPSR) models to the data at 5% significance level. Loglikelihood, Akaike and Bayesian information criteria were used to assess model fit. Among the 3,138,540 singletons, 47,938 (1.5%) were conceived through ART (11,211 frozen-thawed transfer and 36,727 fresh embryo transfer). In total, 18,118 (0.58%) of the children had type-1 diabetes, higher among (0.58%) those conceived spontaneously than the ART-conceived (0.42%). The median (Interquartile range (IQR)) age at onset of type-1 diabetes among spontaneously conceived children was 10 (14–6) years, 8(5–12) for ART, 6 (4–10) years for frozen-thawed embryo transfer and 9 (5–12) years for fresh embryo transfer. The estimates from the CPH, FPSR and parametric PH models are similar. There was no significant difference in the risk of type-1 diabetes among ART- and spontaneously conceived children; FPSR: (adjusted Hazard Ratio (aHR) = 1.070; 95% Confidence Interval (CI):0.929–1.232, p = 0.346) vs CPH: (aHR = 1.068; 95%CI: 0.927–1.230, p = 0.361). A sub-analysis showed that the adjusted hazard of type-1 diabetes was 37% (aHR = 1.368; 95%CI: 1.013–1.847, p = 0.041) higher among children from frozen-thawed embryo transfer than among children from spontaneous conception. The hazard of type-1 diabetes was higher among children whose mothers do not smoke (aHR = 1.296; 95%CI:1.240–1.354, p&lt;0.001) and of diabetic mothers (aHR = 6.419; 95%CI:5.852–7.041, p&lt;0.001) and fathers (aHR = 8.808; 95%CI:8.221–9.437, p&lt;0.001). The estimates from the CPH, parametric models and the FPSR model were close. This is an indication that the models performed similarly and any of them can be used to model the data. We couldn’t establish that ART increases the risk of type-1 diabetes except when it is subdivided into its two subtypes. There is evidence of a greater risk of type-1 diabetes when conception is through frozen-thawed transfer.<br/

Cardiovascular disease, obesity, and type 2 diabetes in children born after assisted reproductive technology: A population-based cohort study

Background Some earlier studies have found indications of significant changes in cardiometabolic risk factors in children born after assisted reproductive technology (ART). Most of these studies are based on small cohorts with high risk of selection bias. In this study, we compared the risk of cardiovascular disease, obesity, and type 2 diabetes between singleton children born after ART and singleton children born after spontaneous conception (SC). Methods and findings This was a large population-based cohort study of individuals born in Norway, Sweden, Finland, and Denmark between 1984 and 2015. Data were obtained from national ART and medical birth registers and cross-linked with data from national patient registers and other population-based registers in the respective countries. In total, 122,429 children born after ART and 7,574,685 children born after SC were included. Mean (SD) maternal age was 33.9 (4.3) years for ART and 29.7 (5.2) for SC, 67.7% versus 41.8% were primiparous, and 45.2% versus 32.1% had more than 12 years of education. Preterm birth (<37 weeks 0 days) occurred in 7.9% of children born after ART and 4.8% in children born after SC, and 5.7% versus 3.3% had a low birth weight (<2,500 g). Mean (SD) follow-up time was 8.6 (6.2) years for children born after ART and 14.0 (8.6) years for children born after SC. In total, 135 (0.11%), 645 (0.65%), and 18 (0.01%) children born after ART were diagnosed with cardiovascular disease (ischemic heart disease, cardiomyopathy, heart failure, or cerebrovascular disease), obesity or type 2 diabetes, respectively. The corresponding values were 10,702 (0.14%), 30,308 (0.74%), and 2,919 (0.04%) for children born after SC. In the unadjusted analysis, children born after ART had a significantly higher risk of any cardiovascular disease (hazard ratio [HR] 1.24; 95% CI 1.04–1.48; p = 0.02), obesity (HR 1.13; 95% CI 1.05–1.23; p = 0.002), and type 2 diabetes (HR 1.71; 95% CI 1.08–2.73; p = 0.02). After adjustment, there was no significant difference between children born after ART and children born after SC for any cardiovascular disease (adjusted HR [aHR]1.02; 95% CI 0.86–1.22; p = 0.80) or type 2 diabetes (aHR 1.31; 95% CI 0.82–2.09; p = 0.25). For any cardiovascular disease, the 95% CI was reasonably narrow, excluding effects of a substantial magnitude, while the 95% CI for type 2 diabetes was wide, not excluding clinically meaningful effects. For obesity, there was a small but significant increased risk among children born after ART (aHR 1.14; 95% CI 1.06–1.23; p = 0.001). Important limitations of the study were the relatively short follow-up time, the limited number of events for some outcomes, and that the outcome obesity is often not considered as a disease and therefore not caught by registers, likely leading to an underestimation of obesity in both children born after ART and children born after SC. Conclusions In this study, we observed no difference in the risk of cardiovascular disease or type 2 diabetes between children born after ART and children born after SC. For obesity, there was a small but significant increased risk for children born after ART