Patterns of Gestational Hypertension or Preeclampsia Across 2 Pregnancies in Relationship to Chronic Hypertension Development: A Retrospective Cohort Study.

BACKGROUND: Gestational hypertension (GHTN) and preeclampsia are established risk indicators for chronic hypertension. While recurrence is associated with a greater risk, it is unclear whether there are differences in risk when these gestational complications occur for the first time in an earlier pregnancy versus first occurrence in a subsequent one. We hypothesized that the absence of recurrence reflects a transition toward a lower hypertension risk trajectory, whereas a new occurrence in a later pregnancy indicates a transition toward elevated risk. METHODS AND RESULTS: We analyzed linked data in Quebec, Canada, from public health care insurance administrative databases and birth, stillbirth, and death registries. Our retrospective cohort study included mothers with 2 singleton deliveries between April 1990 and December 2012. The primary exposure was patterns of GHTN or preeclampsia across 2 pregnancies (GHTN/preeclampsia in neither, first only, second only, or both). The outcome was incident chronic hypertension. We performed an adjusted multivariable Cox regression analysis. Among 431 980 women with 2 singleton pregnancies, 27 755 developed hypertension during the follow-up period. Compared with those without GHTN/preeclampsia, those with GHTN/preeclampsia only in the first pregnancy had a 2.7-fold increase in hazards (95% CI, 2.6-2.8), those with GHTN/preeclampsia only in the second had a 4.9-fold increase (95% CI, 4.6-5.1), and those with GHTN/preeclampsia in both pregnancies experienced a 7.3-fold increase (95% CI, 6.9-7.6). Patterns and estimates were similar when we considered GHTN and preeclampsia separately. CONCLUSIONS: The magnitude of hypertension risk is associated with the number and sequence of GHTN/preeclampsia-affected pregnancies. Considering both allows more personalized risk estimates.

Incident Diabetes in Women With Patterns of Gestational Diabetes Occurrences Across 2 Pregnancies.

Importance: Gestational diabetes is a type 2 diabetes risk indicator, and recurrence further augments risk. In women with a single occurrence across 2 pregnancies, it is unclear whether first- vs second-pregnancy gestational diabetes differ in terms of risk. Objective: To compare the hazards of incident diabetes among those with gestational diabetes in the first, in the second, and in both pregnancies with women without gestational diabetes in either. Design, Setting, and Participants: This was a retrospective cohort study with cohort inception from April 1, 1990, to December 31, 2012. Follow-up was April 1, 1990, to April 1, 2019. Participants were mothers with 2 singleton deliveries between April 1, 1990, and December 31, 2012, without diabetes before or between pregnancies, who were listed in public health care insurance administrative databases and birth, stillbirth, and death registries in Quebec, Canada. Data were analyzed from July to December 2023. Exposure: Gestational diabetes occurrence(s) across 2 pregnancies. Main outcomes and measures: Incident diabetes from the second delivery until a third pregnancy, death, or the end of the follow-up period, whichever occurred first. Results: The 431 980 women with 2 singleton deliveries studied had a mean (SD) age of 30.1 (4.5) years at second delivery, with a mean (SD) of 2.8 (1.5) years elapsed between deliveries; 373 415 (86.4%) were of European background, and 78 770 (18.2%) were at the highest quintile of material deprivation. Overall, 10 920 women (2.5%) had gestational diabetes in their first pregnancy, 16 145 (3.7%) in their second, and 8255 (1.9%) in both (12 205 incident diabetes events; median [IQR] follow-up 11.5 [5.3-19.4] years). First pregnancy-only gestational diabetes increased hazards 4.35-fold (95% CI, 4.06-4.67), second pregnancy-only increased hazards 7.68-fold (95% CI, 7.31-8.07), and gestational diabetes in both pregnancies increased hazards 15.8-fold (95% CI, 15.0-16.6). Compared with first pregnancy-only gestational diabetes, second pregnancy-only gestational diabetes increased hazards by 76% (95% CI, 1.63-1.91), while gestational diabetes in both pregnancies increased it 3.63-fold (95% CI, 3.36-3.93). Conclusions and relevance: In this retrospective cohort study of nearly half a million women with 2 singleton pregnancies, both the number and ordinal pregnancy of any gestational diabetes occurrence increased diabetes risk. These considerations offer greater nuance than an ever or never gestational diabetes dichotomy.

Differences in excess mortality by recipient sex after heart transplant: An individual patient data meta-analysis.

BACKGROUND: Identification of differences in mortality risk between female and male heart transplant recipients may prompt sex-specific management strategies. Because worldwide, males of all ages have higher absolute mortality rates than females, we aimed to compare the excess risk of mortality (risk above the general population) in female vs male heart transplant recipients. METHODS: We used relative survival models conducted separately in SRTR and CTS cohorts from 1988-2019, and subsequently combined using 2-stage individual patient data meta-analysis, to compare the excess risk of mortality in female vs male first heart transplant recipients, accounting for the modifying effects of donor sex and recipient current age. RESULTS: We analyzed 108,918 patients. When the donor was male, female recipients 0-12 years (Relative excess risk (RER) 1.13, 95% CI 1.00-1.26), 13-44 years (RER 1.17, 95% CI 1.10-1.25), and ≥45 years (RER 1.14, 95% CI 1.02-1.27) showed higher excess mortality risks than male recipients of the same age. When the donor was female, only female recipients 13-44 years showed higher excess risks of mortality than males (RER 1.09, 95% CI 1.00-1.20), though not significantly (p = 0.05). CONCLUSIONS: In the setting of a male donor, female recipients of all ages had significantly higher excess mortality than males. When the donor was female, female recipients of reproductive age had higher excess risks of mortality than male recipients of the same age, though this was not statistically significant. Further investigation is required to determine the reasons underlying these differences.

A Multinational Cohort Study Examining Sex Differences in Excess Risk of Death With Graft Function After Kidney Transplant.

BACKGROUND: Kidney transplant recipients show sex differences in excess overall mortality risk that vary by donor sex and recipient age. However, whether the excess risk of death with graft function (DWGF) differs by recipient sex is unknown. METHODS: In this study, we combined data from 3 of the largest transplant registries worldwide (Scientific Registry of Transplant Recipient, Australia and New Zealand Dialysis and Transplant Registry, and Collaborative Transplant Study) using individual patient data meta-analysis to compare the excess risk of DWGF between male and female recipients of a first deceased donor kidney transplant (1988-2019), conditional on donor sex and recipient age. RESULTS: Among 463 895 individuals examined, when the donor was male, female recipients aged 0 to 12 y experienced a higher excess risk of DWGF than male recipients (relative excess risk 1.68; 95% confidence interval, 1.24-2.29); there were no significant differences in other age intervals or at any age when the donor was female. There was no statistically significant between-cohort heterogeneity. CONCLUSIONS: Given the lack of sex differences in the excess risk of DWGF (other than in prepubertal recipients of a male donor kidney) and the known greater excess overall mortality risk for female recipients compared with male recipients in the setting of a male donor, future study is required to characterize potential sex-specific causes of death after graft loss.

Influence of donor sex and age on graft outcome in kidney transplantation.

BACKGROUND: There is a known recipient sex-dependent association between donor sex and kidney transplant survival. We hypothesized that donor age also modifies the association between donor sex and graft survival. METHODS: First, deceased donor kidney transplant recipients (1988-2019, n = 461 364) recorded in the Scientific Registry of Transplant Recipients, the Australia and New Zealand Dialysis and Transplant Registry and the Collaborative Transplant Study were analyzed. We used multivariable Cox regression models to estimate the association between donor sex and death censored graft loss, accounting for the modifying effects of recipient sex and donor age; donor age was categorized as 5-19, 20-34, 35-49, 50-59 and ≥60 years. Results from cohort-specific Cox models were combined using individual patient data meta-analysis. RESULTS: Among female recipients of donors aged <60 years, graft loss hazards did not differ by donor sex; recipients of female donors ≥60 years showed significantly lower graft loss hazards than recipients of male donors of the same age [combined adjusted hazard ratio (aHR) 0.90, 95% CI 0.86-0.94]. Among male recipients, female donors aged <50 years were associated with significantly higher graft loss hazards than same-aged male donors (5-19 years: aHR 1.11, 95% CI 1.02-1.21; 20-34 years: aHR 1.08, 95% CI 1.02-1.15; 35-49 years: aHR 1.07, 95% CI 1.04-1.10). There were no significant differences in graft loss by donor sex among male recipients of donors aged ≥50 years. CONCLUSION: Donor age modifies the association between donor sex and graft survival. Older female donors were associated with similar or lower hazards of graft failure than older male donors in both male and female recipients, suggesting a better functional reserve of older female donor kidneys.

School-based vaccination program against HPV and Hepatitis B: A longitudinal analysis of vaccine coverage between 2015 and 2021 in Quebec.

BACKGROUND: HPV vaccination prevents cancers, including 90% of cervical cancer. Since 2008, a school-based HPV vaccination program has been implemented in Quebec, but vaccine coverage is suboptimal. The COVID-19 pandemic disrupted school-based vaccination programs. This study aimed to assess variation in HPV vaccination coverage in the school-based program between 2015 and 2022 in Quebec and to identify sociodemographic characteristics associated with non-vaccination. METHODS: HPV vaccine coverage data were extracted from the Quebec Immunization Registry for students in Grade 4 and matched to the 2016 Canadian census sociodemographic data. Descriptive analysis was conducted to explore individual-level vaccine coverage according to sociodemographic data. A Generalized Estimating Equations model assessed the independent association between non-vaccination and students' sociodemographic characteristics. RESULTS: HPV vaccine coverage (at least one dose) was 84% in 2018-2019 and 85% in 2019-2020. A decrease was observed during the pandemic. In 2020-2021, the HPV vaccine coverage (at least one dose) was 52% (at the end of the school year) and rose to 84% with intense catch-up activities. In 2021-2022, the coverage was slightly lower than before the pandemic (81%). Factors in the dissemination area were statistically significantly associated with non-vaccination: material (p-value = 0.0001) and social deprivation index (p-value = 0.0048), the proportion of immigration (p-value < 0.0001), and the language spoken at home (English (p-value = 0.0318), other than French or English (p-value = 0.0001). CONCLUSION: School-based vaccination programs offer equitable access to vaccination, and our analysis showed that some groups have consistently lower vaccine acceptance and uptake. Strategies to improve HPV vaccine coverage should target children living in areas with a higher proportion of immigrants, non-French speakers, and people from underprivileged backgrounds. Although it is too early to assess the full impact of COVID-19 on school-based programs in Quebec, it remains important to ensure that catch-up strategies are implemented for missed doses.

Considering gestational diabetes and gestational hypertension history across two pregnancies in relationship to cardiovascular disease development: A retrospective cohort study.

AIMS: Gestational diabetes (GDM) and hypertension (GHTN) occurrences signal elevated cardiovascular disease (CVD) risk. There is little study of occurrence and recurrence of these conditions in relationship to CVD. Among women with two singleton pregnancies, we aimed to quantify CVD risk in relationship to the number of GDM/GHTN occurrences. METHODS: In this Quebec-based retrospective cohort study (n = 431,980), we ascertained the number of GDM/GHTN occurrences over two pregnancies and assessed for CVD over a median of 16.4 years (cohort inception 1990-2012, outcomes 1990-2019). We defined CVD as a composite of myocardial infarction, stroke, and angina, requiring hospitalization and/or causing death. We adjusted Cox proportional hazards models for offspring size, preterm/term birth status, maternal age group, time between deliveries, ethnicity, deprivation level, and co-morbid conditions. RESULTS: Compared to absence of GDM/GHTN in either pregnancy, one GDM/GHTN occurrence increased CVD hazards by 47% (hazard ratio [HR] = 1.47, 95% confidence interval [CI] 1.35-1.61), two occurrences nearly doubled hazards (HR = 1.91, 95% CI 1.68-2.17), and three or more approximately tripled CVD hazards (HR = 2.93, 95% CI 2.20-3.90). Individual components of the composite demonstrated similar findings. CONCLUSIONS: Health care providers and mothers should consider a complete history of GDM/GHTN occurrences to ascertain the importance and urgency of preventive action.

Associations of free sugars from solid and liquid sources with cardiovascular disease: a retrospective cohort analysis.

BACKGROUND: The World Health Organization recommends a 10% total energy (TE%) limit for free sugars (i.e., added sugars and naturally occurring sugars in fruit juice, honey, and syrups) based on evidence linking higher intakes with overweight and dental caries. Evidence for cardiovascular disease (CVD) is limited. Impacts may differ by sex, age group, and solid vs. liquid sources; liquids may stimulate more adverse CVD profiles (due to their rapid absorption in the body along along with triggering less satiety). We examined associations of consuming total free sugars ≥ 10 TE% with CVD within four sex and age-defined groups. Given roughly equal free sugar intakes from solid and liquid sources, we also evaluated source-specific associations of free sugars ≥ 5 TE% thresholds. METHODS: In this retrospective cohort study, we estimated free sugars from 24-h dietary recall (Canadian Community Health Survey, 2004-2005) in relationship to nonfatal and fatal CVD (Discharge Abstract and Canadian Mortality Databases, 2004-2017; International Disease Classification-10 codes for ischemic heart disease and stroke) through multivariable Cox proportional hazards models adjusted for overweight/obesity, health behaviours, dietary factors, and food insecurity. We conducted analyses in separate models for men 55 to 75 years, women 55 to 75 years, men 35 to 55 years, and women 35 to 55 years. We dichotomized total free sugars at 10 TE% and source-specific free sugars at 5 TE%. RESULTS: Men 55 to 75 years of age had 34% higher CVD hazards with intakes of free sugars from solid sources ≥ 5 TE% vs. below (adjusted HR 1.34, 95% CI 1.05- 1.70). The other three age and sex-specific groups did not demonstrate conclusive associations with CVD. CONCLUSIONS: Our findings suggest that from a CVD prevention standpoint in men 55 to 75 years of age, there may be benefits from consuming less than 5 TE% as free sugars from solid sources.

A multinational cohort study uncovered sex differences in excess mortality after kidney transplant.

Worldwide and at all ages, males have a higher mortality risk than females. This mortality bias should be preserved in kidney transplant recipients unless there are sex differences in the effects of transplantation. Here we compared the excess risk of mortality (risk above the general population) in female versus male recipients of all ages recorded in three large transplant databases. This included first deceased donor kidney transplant recipients and accounted for the modifying effects of donor sex and recipient age. After harmonization of variables across cohorts, relative survival models were fitted in each cohort separately and results were combined using individual patient data meta-analysis among 466,892 individuals (1988-2019). When the donor was male, female recipients 0-12 years (Relative Excess Risk 1.54, 95% Confidence Interval 1.20-1.99), 13-24 years (1.17, 1.01-1.34), 25-44 years (1.11, 1.05-1.18) and 60 years and older (1.05, 1.02-1.08) showed higher excess mortality risks than male recipients of the same age. When the donor was female, the Relative Excess Risk for those over 12 years were similar to those when the donor was male. There is a higher excess mortality risk in female than male recipients with differences larger at younger than older ages and only statistically significant when the donor was male. While these findings may be partly explained by the known sex differences in graft loss risks, sex differences in the risks of death with graft function may also contribute. Thus, higher risks in females than males suggest that management needs to be modified to optimize transplant outcomes among females.

Differences in medication adherence by sex and organ type among adolescent and young adult solid organ transplant recipients.

BACKGROUND: Identification of differences in medication adherence by sex or organ type may help in planning interventions to optimize outcomes. We compared immunosuppressive medication adherence between males and females, and between kidney, liver and heart transplant recipients. METHODS: This multicenter study of prevalent kidney, liver and heart transplant recipients 14-25 years assessed adherence 3 times (0, 3, 6 months post-enrollment) with the BAASIS self-report tool. At each visit, participants were classified as adherent if they missed no doses in the prior 4 weeks and non-adherent otherwise. Adherence was also assessed using the coefficient of variation (CV) of tacrolimus trough levels; CV < 30% was classified as adherent. We used multivariable mixed effects logistic regression models adjusted for potential confounders to compare adherence by sex and by organ. RESULTS: Across all visits, males (n = 150, median age 20.4 years, IQR 17.2-23.3) had lower odds of self-reported adherence than females (n = 120, median age 19.8 years, IQR 17.1-22.7) (OR 0.41, 95% CI 0.21-0.80) but higher odds of adherence by tacrolimus CV (OR 2.50, 95% CI 1.30-4.82). No significant differences in adherence (by self-report or tacrolimus CV) were noted between the 184 kidney, 58 liver, and 28 heart recipients. CONCLUSION: Females show better self-reported adherence than males but greater variability in tacrolimus levels. Social desirability bias, more common in females than males, may contribute to better self-reported adherence among females. Higher tacrolimus variability among females may reflect biologic differences in tacrolimus metabolism between males and females rather than sex differences in adherence. There were no significant differences in adherence by organ type.

Differences in medication adherence between preemptive and post-dialysis young kidney transplant recipients.

BACKGROUND: The mechanisms underlying the superior graft survival associated with preemptive kidney transplantation, compared with transplantation following a period of dialysis, are unknown. We aimed to compare medication adherence between preemptively transplanted young kidney transplant recipients and those who received a transplant after an interval of dialysis. METHODS: This was a secondary analysis of the Teen Adherence in Kidney transplant Effectiveness of Intervention Trial (TAKE-IT), in which adherence was assessed with electronic monitoring over 15 months among 11-24-year-old transplant recipients. Adherence scores were calculated for each day as 0%, 50%, or 100% (intake of none, half, or all prescribed doses). We used ordinal logistic regression, with generalized estimating equations to account for repeated measures within each participant, to estimate the association between preemptive transplantation and adherence. The model was adjusted for sex, age at transplant, time since transplant, primary kidney disease, race, donor source, medication insurer, household income, and adherence intervention. RESULTS: There were 43 preemptive transplant recipients and 103 who had been treated with dialysis. The median adherence score was 85.1% (IQR 81.3-88.9) for those preemptively transplanted, and 80.0% (IQR 76.7-83.4) for those transplanted after dialysis. Preemptively transplanted recipients had significantly higher odds of adherence than those dialyzed before transplantation (adjusted OR 1.76 95% CI 1.21-2.55; p = 0.003). CONCLUSIONS: Preemptively transplanted patients showed significantly better adherence than those treated with dialysis before transplantation. This suggests that the superior outcomes observed among preemptive kidney transplant recipients may reflect selection of patients more likely to adhere to therapy. A higher resolution version of the Graphical abstract is available as Supplementary information.

Age-dependent Sex Differences in Graft Loss After Kidney Transplantation.

BACKGROUND: Sex differences in kidney graft loss rates were reported in the United States. Whether these differences are present in other countries is unknown. METHODS: We estimated the association between recipient sex and death-censored graft loss in patients of all ages recorded in the Scientific Registry of Transplant Recipients, Australia and New Zealand Dialysis and Transplant Registry, and Collaborative Transplant Study registries who received a first deceased donor kidney transplant (1988-2019). We used multivariable Cox regression models, accounting for the modifying effects of donor sex and recipient age, in each registry separately; results were combined using individual patient data meta-analysis. RESULTS: We analyzed 438 585 patients. Young female patients 13-24 y old had the highest crude graft loss rates (female donor: 5.66; male donor: 5.50 per 100 person-years). Among young recipients of male donors, females showed higher graft loss risks than males (0-12 y: adjusted hazard ratio [aHR] 1.42, (95% confidence interval [CI], 1.17-1.73); 13-24 y: 1.24 (1.17-1.32); 25-44 y: 1.09 (1.06-1.13)). When the donor was female, there were no significant differences by recipient sex among those of age <45 y; however, the aHR for females was 0.93 (0.89-0.98) in 45-59 y-old and 0.89 (0.86-0.93) in ≥ 60 y-old recipients. Findings were similar for all 3 registries in most age intervals; statistically significant heterogeneity was seen only among 13-24-y-old recipients of a female donor (I2 = 71.5%, P = 0.03). CONCLUSIONS: There is an association between recipient sex and kidney transplantation survival that is modified by recipient age and donor sex.

Associations of overweight and gestational diabetes mellitus with free sugars from solid and liquid sources: cross-sectional and nested case-control analyses.

BACKGROUND: Sugar-sweetened beverages have obesogenic and diabetogenic effects ascribed to free sugars. These include added sugars and naturally occurring sugars in juices. A meta-analysis indicates that some foods with added sugars are associated with lower type 2 diabetes rates. To expand the evidence relevant to free sugars from solid sources, we examined a young to middle-aged population with respect to overweight and gestational diabetes (GDM) outcomes. METHODS: We studied female participants (12-50 years old) from the 2004-2005 Canadian Community Health Survey 2.2 (CCHS) with data linked to the hospital Discharge Abstract Database (DAD) until 2017, providing 13 years of follow-up. We estimated free sugars by solid and liquid sources from 24-h dietary recalls as percent total energy intake (TE%), and computed body mass index (BMI). We applied ICD-10 diagnostic codes for deliveries and GDM to DAD. We conducted multivariable logistic regression analyses to evaluate associations between free sugars with overweight at baseline (cross-sectional component) and, in those who delivered, with GDM during follow-up (nested case control component). We compared those with consumption above versus below various thresholds of intake for free sugars, considering solid and liquid sources separately (2.TE%, 5TE%, 10TE% and 15TE% thresholds). RESULTS: Among 6305 participants, 2505 (40%) were overweight, defined as BMI ≥ 85th percentile below 18 years and BMI ≥ 25 kg/m2 for adults. Free sugars from solid sources were associated with lower odds of overweight above versus below the 2.5TE% (adjusted odds ratio [adjOR] 0.80, 95%CI 0.70-0.92), 5TE% (adjOR 0.89, 95%CI 0.79-0.99), and 10TE% (adjOR 0.86, 95%CI 0.75-0.97) thresholds. Free sugars from liquid sources were associated with greater odds of overweight across the 2.5TE% (adjOR 1.20, 95%CI 1.07-1.36), 10TE% (adjOR 1.17, 95%CI 1.02-1.34), and 15TE% (adjOR 1.43, 95%CI 1.23-1.67) thresholds. There were 113 cases of GDM among the 1842 women who delivered (6.1%). Free sugars from solid sources were associated with lower odds of GDM above versus below the 5TE% threshold (adjOR 0.56, 95%CI 0.36-0.85). CONCLUSIONS: Our findings support limiting free sugars from liquid sources, given associations with overweight. We did not identify adverse associations of free sugars from solid sources across any of the thresholds examined.

Differences in Heart Graft Survival by Recipient Sex.

We aimed to characterize patterns of differences in heart graft failure rates by recipient sex, accounting for modifying effects of donor sex and recipient age. METHODS: We evaluated 69 246 first heart transplant recipients (1988-2019; Scientific Registry of Transplant Recipients). We used multivariable time-varying Cox models, considering recipient sex by donor sex by recipient age interaction and adjusting for potential confounders. Using the hazard ratio (HR) from the models and a fixed profile of recipient and donor characteristics, we also compared fitted absolute failure rates by recipient sex. RESULTS: Among recipients of male donors, female recipients of all ages had higher failure rates than males (0-12 y: HR 1.36 (95% confidence interval [CI], 1.03-1.81); 13-24 y: 1.43 [1.09-1.88]; 25-44 y: 1.22 [0.95-1.57]; ≥45 y: 1.16 [1.06-1.27]); differences were statistically significant in all age intervals except 25-44 y. When the donor was male, 13 to 24-y-olds showed the largest absolute difference in fitted absolute failure rates, with rates higher by 11.3 failures per 1000 person-y in female than male recipients. Among recipients of female donors, there were no statistically significant differences in graft failure rates between female and male heart recipients of any age. Although point estimates suggested higher failure rates in female than male recipients <25 y (0-12 y: HR 1.19 [95% CI, 0.85-1.66]; 13-24 y: 1.17 [0.84-1.63]), these were not statistically significant. CONCLUSIONS: Female recipients tended to have poorer outcomes than males, particularly at younger ages and when the donor was male, consistent with observations in kidney transplants.

Care processes and structures associated with higher medication adherence in adolescent and young adult transplant recipients.

BACKGROUND: We aimed to identify care processes and structures that were independently associated with higher medication adherence among young transplant recipients. METHODS: We conducted a prospective, observational cohort study of 270 prevalent kidney, liver, and heart transplant recipients 14-25 years old. Patients were ≥3 months post-transplant, ≥2 months post-discharge, and followed in one of 14 pediatric or 14 adult transplant programs in Canada. Patients were enrolled between June 2015 and March 2018 and followed for 6 months. Adherence was assessed at baseline, 3, and 6 months using the BAASIS© self-report tool. Patients were classified as adherent if no doses were missed in the prior 4 weeks. Transplant program directors and nurses completed questionnaires regarding care organization and processes. RESULTS: Of the 270 participants, 99 were followed in pediatric programs and 171 in adult programs. Median age was 20.3 years, and median time since transplant was 5 years. At baseline, 71.5% were adherent. Multivariable mixed effects logistic regression models with program as a random effect identified two program-level factors as independently associated with better adherence: minimum number of prescribed blood draws per year for those >3 years post-transplant (per 1 additional) (OR 1.12 [95% CI 1.00, 1.26]; p = .047), and average time nurses spend with patients in clinic (per 5 additional minutes) (OR 1.15 [1.03, 1.29]; p = .017). CONCLUSION: Program-level factors including protocols with a greater frequency of routine blood testing and more nurse time with patients were associated with better medication adherence. This suggests that interventions at the program level may support better adherence.

Differences in Liver Graft Survival by Recipient Sex.

We aimed to characterize patterns of differences in liver graft failure rates by recipient sex, accounting for the modifying effects of donor sex and recipient age. METHODS: We evaluated 144 212 first deceased donor liver transplant recipients [1988-2019; Scientific Registry of Transplant Recipients (SRTR)]. We used multivariable time-varying Cox models, considering a recipient sex by donor sex by recipient age (0-12, 13-24, 25-44, ≥45 y) interaction. RESULTS: Among recipients of male donors, females <45 y had higher graft failure rates than males of the same age, but none of these differences were statistically significant [0-12 y: adjusted hazard ratio (aHR) 1.17 (0.98, 1.40); 13-24 y: aHR 1.18 (0.96, 1.46); 25-44 y: aHR 1.11 (0.96, 1.28)]; there was no material or statistically significant difference between female and male recipients ≥45 y [aHR 1.01 (0.97, 1.06)]. When the donor was female, recipients <45 y showed no statistically significant differences in graft outcomes by recipient sex [0-12 y: aHR 0.91 (0.74, 1.11); 13-24 y: aHR 0.98 (0.77, 1.25); 25-44 y: aHR 0.86 (0.73, 1.01)], whereas female recipients ≥45 y had significantly lower graft failure rates [aHR 0.85 (0.81, 0.89)] than males of the same age. CONCLUSIONS: Among recipients of female donors, female recipients ≥45 y had significantly better outcomes than males of the same age; there were no clear differences by recipient sex in younger recipients. When the donor was male, there was no material or statistically significant difference in graft failure rates between males and females ≥45 y; among younger recipients point estimates suggested higher failure rates in females than males recipients, but confidence intervals were wide making firm conclusions impossible. Larger studies combining multiple datasets are needed.

Perinatal health among foreign versus native-born mothers in Canada: variations across outcomes and cohorts.

BACKGROUND: To examine perinatal health differences between foreign-born and native-born mothers in Canada across multiple outcomes and two cohorts 10 years apart. METHODS: Using 94 896 and 131 271 births in the 1996 and 2006 Canadian Census-Birth Cohort, respectively, we estimated risk ratios and risk differences of preterm birth (PTB), small-for-gestational age (SGA), large-for-gestational age (LGA), stillbirth and infant mortality between foreign-born and Canadian-born mothers. RESULTS: In the 1996 cohort, we observed no important differences in adverse outcomes between foreign-born and native-born mothers. In the 2006 cohort, however, foreign-born mothers had lower risks of PTB, LGA, stillbirth, and infant mortality and a higher risk of SGA on both the relative and absolute scales. Lowered risk of PTB among foreign-born mothers in the 2006 cohort was also observed within Caucasian, East Asian, Southeast Asian and South Asian mothers. Favourable outcomes associated with foreign-born status in the 2006 cohort were negatively graded by duration of residence in Canada among immigrant mothers. CONCLUSIONS: Differences in perinatal health by maternal foreign-born status varied across cohorts and a more pronounced 'healthy migrant' effect was observed among more recent migrants. The native-born mothers' perinatal health over time and a more restrictive/selective immigration policy in recent years would explain our results.

Associations of atopic dermatitis and asthma with child behaviour: Results from the PROBIT cohort.

BACKGROUND: Conflicting findings from studies evaluating associations of allergic disease with child behaviour require longitudinal studies to resolve. OBJECTIVE: To estimate the magnitude of associations of atopic dermatitis (AD) in infancy, and symptoms of asthma and AD at 6.5 years, with child behaviour at 6.5 years. METHODS: Secondary cohort analysis of the Promotion of Breastfeeding Intervention Trial (PROBIT). PROBIT enrolled 17 046 infants at birth and followed them up at 6.5 years (n = 13 889). Study paediatricians collected data on infantile AD at repeated follow-up examinations during the first year of life. At 6.5 years, paediatricians performed skin prick tests and parents reported asthma and AD symptoms during the prior year. In addition, parents and teachers completed the Strength and Difficulties Questionnaire, which includes scales on hyperactivity/inattention, emotional problems, conduct problems, peer problems and prosocial behaviours. RESULTS: Physician-diagnosed AD in the first year of life was not associated with increased risk for behavioural problems at 6.5 years. Emotional problems at 6.5 years were more common among children with AD symptoms (OR: 2.24, 95% CI: 1.62-3.12) and asthma symptoms (OR: 1.45; 95% CI: 1.07-1.96) during the past year at 6.5 years and ORs for children with symptoms of more severe AD and asthma were also higher. AD in the past year was also associated with probable hyperactivity/inattention disorder at 6.5 years (OR: 2.05; 95% CI: 1.09-3.84). Other subscales of the SDQ were not related to asthma or AD symptoms during the past year. CONCLUSIONS AND CLINICAL RELEVANCE: Children with AD symptoms were at higher risk for concomitant hyperactivity/inattention and emotional disorder, and children with asthma symptoms were at higher risk of having concomitant emotional problems. However, AD during infancy did not predict childhood behaviours.

Gestational diabetes associated with incident diabetes in childhood and youth: a retrospective cohort study.

BACKGROUND: Indicators of childhood- and youth-onset diabetes may be useful for early detection of diabetes; there is a known association between composite exposure of parental type 2 diabetes and gestational diabetes mellitus with childhood- and youth-onset diabetes. We examined associations between gestational diabetes mellitus and incidence of childhood- and youth-onset diabetes in offspring. METHODS: Using public health insurance administrative databases from Quebec, Canada, we randomly selected singleton live births with maternal gestational diabetes mellitus (1990-2007) and matched them 1:1 with singleton live births without gestational diabetes mellitus. Follow-up was to Mar. 31, 2012. We examined associations of diabetes in offspring with maternal gestational diabetes mellitus through unadjusted and adjusted Cox proportional hazards models. In secondary analyses, we separately considered age groups ranging from birth to age 12 years, and age 12 to 22 years. RESULTS: Incidence of pediatric diabetes (per 10 000 person-years) was higher in offspring born to mothers with gestational diabetes mellitus (4.52, 95% confidence interval [CI] 4.47-4.57) than in mothers without gestational diabetes mellitus (2.4, 95% CI 2.37-2.46). In an adjusted Cox proportional hazards model, maternal gestational diabetes mellitus was associated with development of pediatric diabetes overall (birth to age 22 yr: hazard ratio [HR] 1.77, 95% CI 1.41-2.22), during childhood (birth to age 12 yr: HR 1.43, 95% CI 1.09-1.89), and in youth (age 12 to 22 yr: HR 2.53, 95% CI 1.67-3.85). INTERPRETATION: Gestational diabetes mellitus is associated with incident diabetes in offspring during childhood and adolescence. Future studies are needed to examine longer-term outcomes in patients with pediatric diabetes with a maternal history of gestational diabetes mellitus, to ascertain how they compare with other patients with childhood- or youth-onset diabetes, in terms of disease severity and outcomes.

Infant feeding and growth: putting the horse before the cart.

Background: Previous observational studies have consistently shown slower weight and length gains in infants with prolonged breastfeeding than in those who were formula-fed from birth or breastfed for a shorter duration. These studies inferred that prolonged breastfeeding causes slower growth in infancy. Objective: We compared infant growth associated with ≥12 mo of breastfeeding with a shorter duration of breastfeeding on the basis of 3 different analytic approaches to the same data from a randomized trial: intention-to-treat (ITT; "as randomized"), observational ("as fed"), and instrumental variable (IV; by using randomization as an "instrument" to achieve ≥12 mo of breastfeeding). Design: This was a cluster-randomized trial of a breastfeeding-promotion intervention. Anthropometric measurements were obtained at birth and at 1, 2, 3, 6, 9, and 12 mo. Results: The 3 analytic approaches yielded different results. The ITT approach showed more rapid growth in the first 2 mo among infants randomly assigned to the breastfeeding-promotion intervention than among control infants, with a decreasing difference over the ensuing months and nearly identical weight, length, and body mass index by 12 mo. The observational analysis showed a different trend: higher weight and length in infants who were breastfed ≥12 mo than in those who were breastfed <12 mo during the first 3 mo and no difference by 6 mo, while infants who were breastfed <12 mo showed increasingly higher weight and length from 6 to 12 mo. The IV analysis showed a temporal pattern that was similar to that seen in the ITT analysis, but with larger (and less precise) differences between infants breastfed for ≥12 compared with <12 mo. Conclusions: We observed major differences in experimental (ITT and IV) compared with observational approaches to analyzing data obtained from the same children. These approaches lead to opposite causal inferences about the relation between infant feeding and growth and underline the importance of ensuring that the postulated cause (feeding) temporally precedes its hypothesized effect (growth). This trial is registered at http://www.isrctn.org/ as ISRCTN37687716.