Drug repositioning and ovarian cancer, a study based on Mendelian randomisation analysis.

Background: The role of drug repositioning in the treatment of ovarian cancer has received increasing attention. Although promising results have been achieved, there are also major controversies. Methods: In this study, we conducted a drug-target Mendelian randomisation (MR) analysis to systematically investigate the reported effects and relevance of traditional drugs in the treatment of ovarian cancer. The inverse-variance weighted (IVW) method was used in the main analysis to estimate the causal effect. Several MR methods were used simultaneously to test the robustness of the results. Results: By screening 31 drugs with 110 targets, FNTA, HSPA5, NEU1, CCND1, CASP1, CASP3 were negatively correlated with ovarian cancer, and HMGCR, PLA2G4A, ITGAL, PTGS1, FNTB were positively correlated with ovarian cancer. Conclusion: Statins (HMGCR blockers), lonafarnib (farnesyltransferase inhibitors), the anti-inflammatory drug aspirin, and the anti-malarial drug adiponectin all have potential therapeutic roles in ovarian cancer treatment.

Maternal pre-pregnancy overweight or obesity and risk of birth defects in offspring: Population-based cohort study.

INTRODUCTION: Maternal obesity, a health condition increasingly prevalent worldwide, has been suggested to be associated with a higher risk of birth defects in offspring, whereas evidence from population-based data from China was largely lacking. Additionally, the role of gestational diabetes in the association between maternal obesity and birth defects remains unclear. We aimed to investigate the association of maternal pre-pregnancy overweight or obesity with any and different types of birth defects in offspring and the interaction between pre-pregnancy overweight or obesity and gestational diabetes. MATERIAL AND METHODS: We conducted a population-based cohort study including 257 107 singletons born between 2015 and 2021 in Longgang District, Shenzhen, China, using data from the Shenzhen Maternal and Child Health Management System. Poisson regression was conducted to estimate the associations of maternal pre-pregnancy overweight or obesity, as well as the interaction between pre-pregnancy overweight or obesity and gestational diabetes, with the risk of birth defects. Models were adjusted for maternal age at delivery, educational level, type of household registration, and gravidity. RESULTS: Maternal pre-pregnancy overweight was associated with a higher risk of any birth defect (risk ratio [RR] 1.21, 95% confidence interval [CI] 1.12 to 1.31) as well as of congenital malformations of the circulatory system (RR 1.26, 95% CI 1.12 to 1.41), eye/ear/face/neck (RR 1.42, 95% CI 1.04 to 1.94), and musculoskeletal system (RR 1.21, 95% CI 1.01 to 1.44). Maternal pre-pregnancy obesity was associated with a higher risk of any birth defect (RR 1.38, 95% CI 1.18 to 1.63) and congenital malformations of the circulatory system (RR 1.61, 95% CI 1.30 to 1.98). Infants born to overweight or obese mothers with gestational diabetes had a higher risk of congenital malformations of the circulatory system than infants born to overweight or obese mothers without gestational diabetes. CONCLUSIONS: Maternal pre-pregnancy overweight or obesity was associated with a higher risk of birth defects, particularly congenital malformations of the circulatory system, in offspring. Gestational diabetes interacts additively with pre-pregnancy overweight or obesity on modifying the risk of congenital malformations of the circulatory system. The importance of improving weight management and assessment of glucose and metabolic functions was emphasized among women planning for pregnancy who are overweight or obese.

Neurological development in children born moderately or late preterm: national cohort study.

OBJECTIVE: To assess long term neurodevelopmental outcomes of children born at different gestational ages, particularly 32-33 weeks (moderately preterm) and 34-36 weeks (late preterm), compared with 39-40 weeks (full term). DESIGN: Nationwide cohort study. SETTING: Sweden. PARTICIPANTS: 1 281 690 liveborn singleton children without congenital malformations born at 32+0 to 41+6 weeks between 1998 and 2012. MAIN OUTCOME MEASURES: The primary outcomes of interest were motor, cognitive, epileptic, hearing, and visual impairments and a composite of any neurodevelopmental impairment, diagnosed up to age 16 years. Hazard ratios and 95% confidence intervals were estimated using Cox regression adjusted for parental and infant characteristics in the study population and in the subset of full siblings. Risk differences were also estimated to assess the absolute risk of neurodevelopmental impairment. RESULTS: During a median follow-up of 13.1 years (interquartile range 9.5-15.9 years), 75 311 (47.8 per 10 000 person years) liveborn singleton infants without congenital malformations had at least one diagnosis of any neurodevelopmental impairment: 5899 (3.6 per 10 000 person years) had motor impairment, 27 371 (17.0 per 10 000 person years) cognitive impairment, 11 870 (7.3 per 10 000 person years) epileptic impairment, 19 700 (12.2 per 10 000 person years) visual impairment, and 20 393 (12.6 per 10 000 person years) hearing impairment. Children born moderately or late preterm, compared with those born full term, showed higher risks for any impairment (hazard ratio 1.73 (95% confidence interval 1.60 to 1.87) and 1.30 (1.26 to 1.35); risk difference 4.75% (95% confidence interval 3.88% to 5.60%) and 2.03% (1.75% to 2.35%), respectively) as well as motor, cognitive, epileptic, visual, and hearing impairments. Risks for neurodevelopmental impairments appeared highest from 32 weeks (the earliest gestational age), gradually declined until 41 weeks, and were also higher at 37-38 weeks (early term) compared with 39-40 weeks. In the sibling comparison analysis (n=349 108), most associations remained stable except for gestational age and epileptic and hearing impairments, where no association was observed; for children born early term the risk was only higher for cognitive impairment compared with those born full term. CONCLUSIONS: The findings of this study suggest that children born moderately or late preterm have higher risks of adverse neurodevelopmental outcomes. The risks should not be underestimated as these children comprise the largest proportion of children born preterm. The findings may help professionals and families achieve a better risk assessment and follow-up.

Association of maternal snuff use and smoking with Sudden Infant Death Syndrome: a national register study.

BACKGROUND: The aim was to study whether non-combustible nicotine (Swedish snuff) use in pregnancy is associated with elevated risk of post neonatal mortality, Sudden Infant Death Syndrome (SIDS), and Sudden Unexpected Infant Death (SUID) and to study how cessation before the antenatal booking influenced these risks. METHODS: This was a population-based register study of all infants with information on tobacco exposure in early pregnancy born in Sweden 1999-2019, n = 2,061,514. Self-reported tobacco use in early pregnancy was categorized as nonuse, snuff use, and moderate and heavy smoking. Multiple logistic regression models were used to estimate crude and adjusted odds ratios (aORs) with 95% confidence intervals (CIs). RESULTS: Maternal snuff use was associated with increased risks of post neonatal mortality, SIDS, and SUID. The risks of snuff use and moderate smoking were of similar magnitude. Heavy smoking was associated with the highest risks. Cessation of smoking and snuff use before the antenatal booking was associated with lower risks of SIDS and SUID compared to that of continuous usage. CONCLUSIONS: Maternal snuff use was associated with increased risks of post neonatal mortality, SIDS, and SUID. Nicotine is the common substance in cigarette smoke and snuff. These findings support the hypothesis that nicotine contributes to an elevated risk of SIDS. IMPACT: Maternal snuff use and smoking in early pregnancy were associated with increased risks of post neonatal mortality, SIDS, and SUID. Cessation of smoking and snuff use before the first antenatal visit was associated with reduced risks of SIDS and SUID. The common substance in cigarette smoke and snuff is nicotine. Our findings suggest that nicotine contributes to an elevated risk of SIDS and SUID. The implication of our findings is that all forms of nicotine should be avoided in pregnancy.

Amplicon sequencing-based carrier screening for 170 monogenic disorders among children with abnormal LC-MS/MS results.

BACKGROUND: Next-generation sequencing (NGS) has been suggested as a second-tier diagnostic test for newborn screening, which could help identify the carrier status of hundreds monogenic disorders with wider spectrum and earlier stage. METHODS: Among the 1087 children (age from 27 min to 14 years old) underwent liquid chromatography-tandem mass spectrometry (LC-MS/MS), 290 individuals who had at least one abnormal value of LC-MS/MS measurements were sent for amplicon sequencing-based carrier screening (targeting 141 genes for 170 monogenic disorders). Multiplex polymerase chain reaction was used for amplicon capture and library preparation, the NextSeq 500 NGS platform (Illumina PE150) was used for sequencing. The identified clinical significant variants were further validated by Sanger sequencing. RESULTS: Only 89 children carry none of clinical significant variants, other 201 individuals carry 1-4 variants in 63 genes (132 types; 317 in total: 171 pathogenic, 37 likely pathogenic, 29 variants of unknown significance, and 80 disease-associated functional polymorphisms). Besides the three missing samples with 4 variants, 91.1 % of identified variants (285 variants in 54 genes) were completely validated by Sanger sequencing. The most common genetic variants were in UGT1A1, GJB2, PAH, G6PD, and SLC25A13 (top 5 genes), which corresponding to Gilbert/Crigler-Najjar symdrome (n = 89), autosomal recessive hearing loss type 1A (n = 58), phenylketonuria (n = 12), glucose-6-phosphate dehydrogenease deficiency (n = 11) and Citrin deficiency (n = 9). More than 42 children present higher phenylalanine in LC-MS/MS, but only 12 of them were identified to carry clinical significant variants in PAH gene. CONCLUSION: The amplicon sequencing-based carrier screening in our study could further clarify the abnormal LC-MS/MS results, which could also discover more monogenic disorders uncovered by LC-MS/MS screening.

Impact of gestational age on risk of cerebral palsy: unravelling the role of neonatal morbidity.

BACKGROUND: The contribution of adverse consequences of preterm birth to gestational-age-related risk of cerebral palsy (CP) has rarely been studied. We aimed to assess the potential mediating roles of neonatal morbidity on the association between gestational age and risk of CP. METHODS: In this Swedish population-based study, 1 402 240 singletons born at 22-40 gestational weeks during 1998-2016 were followed from day 28 after birth for a CP diagnosis until 2017. Potential mediators included asphyxia, respiratory-related, infection-/inflammatory-related and neurological-related diseases within 0-27 days of life. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Causal mediation analysis was performed to estimate the proportion of the association mediated through pathways involving the four sequential mediators. RESULTS: We found an inverse dose-response relationship between gestational age and risk of CP, where the strongest association was observed for 22-24 weeks (HR 47.26, 95% CI 34.09-65.53) vs 39-40 weeks. Compared with non-diseased peers, children with neonatal morbidity, particularly those with neurological-related diseases (HR 31.34, 95% CI 26.39-37.21), had a higher risk of CP. The increased risk of CP was, at 24 weeks, almost entirely explained by neonatal morbidity (91.7%); this proportion decreased to 46.1% and 16.4% at 32 and 36 weeks, respectively. Asphyxia was the main mediating pathway from 22 to 34 weeks, and neurological-related neonatal diseases led the mediating pathways from 34 weeks onwards. CONCLUSION: Neonatal morbidity mediates a large proportion of the effect of preterm birth on CP, but the magnitude declines as gestational age increases.

Mediterranean diet and depression: a population-based cohort study.

BACKGROUND: Depression imposes immense public health burden, demonstrating an urgent need of the identification of modifiable risk factors. Only a few cohort studies have analyzed the association between Mediterranean dietary pattern (MDP) and depression but with mixed results. We examined the impact of MDP on clinically ascertained depression in a large population-based dataset. METHODS: In 1991/92, detailed information on diet, using a food frequency questionnaire, and potential confounding factors (body weight, height, educational attainment, smoking, previous diabetes and hypertension, and physical activity) was collected, in a random sample of 49,261 Swedish women aged 29-49. Adherence to MDP was calculated. Clinical depression was extracted from the National Patient Register. Study participants were followed up through 2012. RESULTS: During an average follow-up of 20.4 years, 1677 incident cases of depression were diagnosed. We observed a lower risk of depression for medium (score 4-5) and high (6-9) adherence to MDP, compared with low (0-3) adherence (Medium: hazard ratio (HR) = 0.90, 95% confidence interval (CI) = 0.81-1.00; High: HR = 0.82, 95%CI = 0.71-0.94). Per unit increase of adherence, the risk of depression was reduced by 5% (HR = 0.95, 95%CI = 0.92-0.98). The association became stronger when restricting to severe form of depression (HR = 0.51, 95%CI = 0.33-0.76). The HRs were higher from age 50 onward both over the first and the second 10-year follow-up period, compared with before age 50, indicating stronger association with increasing age. Results remained after extensive sensitivity analyses. CONCLUSION: Higher adherence to a Mediterranean diet at middle age was associated with a lower risk of depression later in life among Swedish women.

Neonatal Morbidities in Infants Born Late Preterm at 35-36 Weeks of Gestation: A Swedish Nationwide Population-based Study.

OBJECTIVE: To assess risk for neonatal morbidities among infants born late preterm at 35-36 gestational weeks, early term (37-38 weeks), and late-term (41 weeks) infants, compared with full-term (39-40 weeks) infants. STUDY DESIGN: This nationwide population-based cohort study included 1 650 450 non-malformed liveborn singleton infants born at 35-41 weeks between 1998 and 2016 in Sweden. The relative risks for low Apgar score (0-3) at 5 minutes; respiratory, metabolic, infectious, and neurologic morbidities; and severe neonatal morbidity (composite outcome) were adjusted for maternal, pregnancy, delivery, and infant characteristics. RESULTS: Compared with infants born at 39-40 weeks, the adjusted relative risks and proportions of infants born at 35-36 weeks were higher for metabolic morbidity 7.79 (95%, 7.61 to 7.97; 33.75% vs 3.11%), respiratory morbidity 5.54 (95% CI, 5.24 to 5.85; 5.49% vs 0.75%), severe neonatal morbidity 2.42 (95% CI, 2.27 to 2.59; 3.40% versus 1.03%), infectious morbidity 1.98 (95% CI, 1.83 to 2.14; 2.53% vs 0.95%), neurologic morbidity 1.74 (95% CI, 1.48 to 2.03; 0.54% vs 0.23%), and low Apgar score 2.07 (95% CI, 1.72 to 2.51; 0.42% vs 0.12%). The risks for respiratory, severe neonatal morbidity, infectious, neurologic morbidities, and low Apgar score were highest at 35 weeks, gradually decreased until 39 weeks, and increased during 39-41 weeks. CONCLUSIONS: Infants born late preterm at 35-36 weeks of gestation are at increased risk of neonatal morbidities, although the absolute risks for severe neonatal morbidities are low. Our findings reinforce the need of preventing late preterm delivery to decrease the burden of neonatal morbidity and help professionals and families with a better risk assessment.

Chinese pediatric Tuina on children with acute diarrhea: a randomized sham-controlled trial.

BACKGROUND: Pediatric Tuina has been widely used in children with acute diarrhea in China. However, due to the lack of high-quality clinical evidence, the benefit of Tuina as a therapy is not clear. We aimed to assess the effect of pediatric Tuina compared with sham Tuina as an add-on therapy in addition to usual care for 0-6-year-old children with acute diarrhea. METHODS: Eighty-six participants aged 0-6 years with acute diarrhea were randomized to receive pediatric Tuina plus usual care (n = 43) or sham Tuina plus usual care (n = 43). The primary outcomes were days of diarrhea from baseline and times of diarrhea on day 3. Secondary outcomes included a global change rating (GCR) and the number of days when the stool characteristics returned to normal. Adverse events were assessed. RESULTS: Pediatric Tuina was associated with a reduction in times of diarrhea on day 3 compared with sham Tuina in both ITT (crude RR, 0.73 [95% CI, 0.59-0.91]) and PP analyses (crude RR, 0.66 [95% CI, 0.53-0.83]). However, the results were not significant when we adjusted for social demographic and clinical characteristics. No significant difference was found between groups in days of diarrhea, global change rating, or number of days when the stool characteristics returned to normal. CONCLUSIONS: In children aged 0-6 years with acute diarrhea, pediatric Tuina showed significant effects in terms of reducing times of diarrhea compared with sham Tuina. Studies with larger sample sizes and adjusted trial designs are warranted to further evaluate the effect of pediatric Tuina therapy. TRIAL REGISTRATION: Clinicaltrials.gov, Identifier: NCT03005821 , Data of registration: 2016-12-29.

Association between telomere length and Parkinson's disease: a Mendelian randomization study.

In this study, we examined the potential association of telomere length with Parkinson's disease (PD) using the publicly available genome-wide association study summary statistics from the International Parkinson's Disease Genomics Consortium involving up to 37,688 patients with PD and 449,056 controls in Mendelian randomization framework. The Mendelian randomization approach has the potential to investigate a causal relationship between a risk factor and a disease, avoiding confounding and reverse causation that often present in conventional epidemiological studies. We did not find that longer telomeres were associated with higher risks of PD (odds ratio: 1.18, 95% confidence interval: 0.94, 1.48, p = 0.15). Our study, therefore, did not provide evidence to support a potential causal relationship between telomere length and PD.

Maternal body mass index in early pregnancy and severe asphyxia-related complications in preterm infants.

BACKGROUND: Little is known about the associations between maternal body mass index (BMI) and asphyxia-related morbidity in preterm infants (<37 weeks). We aimed to investigate associations between maternal BMI in early pregnancy and severe asphyxia-related neonatal complications in preterm infants (<37 weeks) and to examine whether possible associations were mediated by overweight- or obesity-related complications. METHODS: In this Swedish population-based cohort of 62 499 singleton non-malformed preterm infants born from 1997 to 2011, risks of low Apgar scores (0-3) at 5 and 10 minutes, neonatal seizures and intraventricular haemorrhage (IVH) were estimated through two analytical approaches. In the conventional approach, the denominator for risk was all live births at a given gestational age. In the fetuses-at-risk (FAR) approach, the denominator for risk was ongoing pregnancies at a given gestational age. RESULTS: Using the conventional approach, adjusted risk ratios per 10-unit BMI increase were 1.32 [95% confidence interval (CI) 1.13-1.54] and 1.37 (95% CI 1.12-1.67) for low Apgar scores at 5 and 10 minutes, respectively; 1.28 (95% CI 1.00-1.65) for neonatal seizures; and 1.18 (95% CI 1.01-1.37) for IVH. Using the FAR approach, corresponding risks were higher. These associations varied by gestational age (<32 and 32-36 weeks). Associations between maternal BMI and asphyxia-related outcomes were partly mediated through lower gestational age. CONCLUSIONS: Increasing maternal BMI in early pregnancy is associated with increased risks of severe asphyxia-related complications in preterm infants. Our findings add to the evidence to support interventions to reduce obesity in woman of reproductive age.

Pregnancy As a Risk Factor for Small Bowel Obstruction After Laparoscopic Gastric Bypass Surgery.

OBJECTIVE: To evaluate whether pregnancy is associated with increased risk for small bowel obstruction after laparoscopic gastric bypass surgery. BACKGROUND: Small bowel obstruction is a common and feared long-term complication to laparoscopic gastric bypass surgery that may be more common during pregnancy. It is unclear if the risk truly increases during pregnancy. METHODS: Women, 18 to 55 years, operated with a primary laparoscopic gastric bypass procedure from 2010 until 2015 were identified through the Scandinavian Obesity Surgery Registry (n = 25,853). Through record-linkage to the Medical Birth Registry, the National Patient Registry, and review of hospital charts, information on pregnancy periods and outcome were obtained. The main outcome was operation due to small bowel obstruction after the laparoscopic gastric bypass procedure. RESULTS: Pregnancy was associated with increased risk for small bowel obstruction following laparoscopic gastric bypass surgery (incidence rates 46.5, 95% CI 38.0-56.9/1000 person-years, vs 20.9 95% CI 19.9-22.0; adjusted-HR 1.72, 95% CI 1.39-2.12, P < 0.001). While no excess risk was observed during the first trimester, the second (adjusted-HR 1.67, 95% CI 1.17-2.39, P = 0.005) and third (adjusted-HR 2.69, 95% CI 2.02-3.59, P < 0.001) conferred increased risk. The incidence rate of small bowel obstruction during pregnancy was 42.9 (95% CI 32.4-57.0/1000 person-years) among women for whom the mesenteric defects had been closed during the primary procedure, and 53.2 (95% CI 38.9-72.8/1000 person-years) for women in whom they had been left open. CONCLUSION: Pregnancy is associated with increased risk for small bowel obstruction after laparoscopic gastric bypass surgery during the second and third trimesters.

No increased risk of short-term complications after radical cystectomy for muscle-invasive bladder cancer among patients treated with preoperative chemotherapy: a nation-wide register-based study.

PURPOSE: Preoperative chemotherapy is underused in conjunction with radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) due to concerns for complications and delay of surgery. Prospective data on short-term complications from population-based settings with frequent use of preoperative chemotherapy and standardised reporting of complications is lacking. METHODS: We identified 1,340 patients who underwent RC between 2011 and 2015 in Sweden due to MIBC according to the Swedish Cystectomy Register. These individuals were followed through linkages to several national registers. Propensity score adjusted logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for complications and death within 90 days of surgery, comparing patients receiving preoperative chemotherapy or not. RESULTS: Minimum two cycles of preoperative chemotherapy were given to 519 (39%) of the patients, who on average tended to be younger, have higher education, better physical status, and more advanced bladder cancer than patients not receiving chemotherapy. After adjusting for these and other parameters, there was no association between treatment with preoperative chemotherapy and short-term complications (OR 1.06 95% CI 0.82-1.39) or mortality (OR 0.75 95% CI 0.36-1.55). We observed a risk reduction for gastrointestinal complications among patients who received preoperative chemotherapy compared with those who did not (OR 0.49 95% CI 0.30-0.81). CONCLUSION: This nation-wide population-based observational study does not suggest that preoperative chemotherapy, in a setting with high utilisation of such treatment, is associated with an increased risk of short-term complications in MIBC patients treated with radical cystectomy.

Marital status, telomere length and cardiovascular disease risk in a Swedish prospective cohort.

OBJECTIVE: To investigate if marital status is associated with risk of cardiovascular disease (CVD) and to explore the potential influence of leucocyte telomere length (LTL), a marker of biological ageing, on such association. DESIGN: Population-based prospective cohort study SETTINGS: Swedish Twin Registry. PARTICIPANTS: Based on the Screening Across the Lifespan Twin Study from the Swedish Twin Registry, we included 10 058 twins born between 1900 and 1958 who underwent an interview between 1998 and 2002 during which information about marital status was collected. Blood samples from these participants were subsequently collected between 2004 and 2008 and used for LTL assessment using quantitative PCR technique. MAIN OUTCOME MEASURES: Incident cases of CVD were identified through the Swedish Patient Register and Causes of Death Register through December 31, 2016. Multivariable linear regression and Cox proportional hazards regression models were used to estimate the regression coefficients (ßs) and HRs with 95% CIs respectively. Potential confounders included age, sex, educational attainment and body mass index. RESULTS: A total of 2010 participants were diagnosed with CVD during a median follow-up of 9.8 years. LTL was shorter among individuals living singly, including those who were divorced or separated (ß:-0.014, 95% CI: -0.035, 0.007), widowed (ß:-0.035, 95% CI: -0.061, -0.010), or living alone (ß:-0.033, 95% CI: -0.052, -0.014), than individuals who were married or cohabitating. One SD increase of LTL was associated with a lower risk of CVD (HR: 0.79, 95% CI: 0.66, 0.93). Individuals who were divorced or separated, widowed, or living alone had a higher risk of CVD than individuals who were married or cohabitating. The summary HR of CVD was 1.21 (95% CI: 1.08, 1.35) when comparing individuals who were living singly, regardless of reason, with the individuals who were married or cohabitating. LTL appeared to mediate little of the association between marital status and CVD (HR additionally adjusted for LTL: 1.20; 95% CI: 1.08, 1.34). CONCLUSIONS: Living singly, regardless of reason, was associated with a shorter LTL and a higher risk of CVD. The association between marital status and CVD was however not greatly attributable to telomere shortening.

Risk of intellectual disability in children born appropriate-for-gestational-age at term or post-term: impact of birth weight for gestational age and gestational age.

Children born small for gestational age have a higher risk of intellectual disability. We investigated associations of birth weight for gestational age percentile and gestational age with risk of intellectual disability in appropriate-for-gestational-age (AGA) children. We included 828,948 non-malformed term or post-term AGA singleton children (including 429,379 full siblings) born between 1998 and 2009 based on data from the Swedish Medical Birth Register. Diagnosis of intellectual disability after 3 years of age was identified through the Patient Register. Using Cox regression models, we calculated hazard ratios (HRs) with 95% confidence intervals (CIs) of intellectual disability among children with different birth weight percentiles and gestational age in the whole population and in a subpopulation of full siblings. A total of 1688 children were diagnosed with intellectual disability during follow-up. HRs (95% CIs) of intellectual disability for the low birth weight percentile groups (10th-24th and 25th-39th percentiles, respectively) versus the reference group (40th-59th percentiles) were 1.43 (1.22-1.67) and 1.28 (1.10-1.50) in population analysis and 1.52 (1.00-2.31) and 1.44 (1.00-2.09) in sibling comparison analysis. The increased risk for low birth weight percentiles in population analysis was stable irrespective of gestational age. A weak U-shaped association between gestational age and intellectual disability was observed in population analysis, although not in sibling comparison analysis. These findings suggest that among AGA children born at term or post-term, lower birth weight percentiles within the normal range are associated with increased risk of intellectual disability, regardless of gestational age.

Low stress resilience in late adolescence and risk of smoking, high alcohol consumption and drug use later in life.

BACKGROUND: While compromised stress resilience constitutes a recognised risk factor for somatic and psychiatric disease development in general, the knowledge about how individual variation in vulnerability to stress may specifically influence the long-term risks of disadvantageous health behaviours is limited. METHODS: In this Swedish cohort study, we aimed to investigate the association between stress resilience in late adolescence and adult use of addictive substances. We included 9381 men with information on psychological stress resilience measured during military conscription examinations, who later responded to an extensive health survey (mean age 34.0±7.2 years) including detailed information on substance use. We modelled continuous outcomes using linear regression, binary outcomes with logistic regression and other categorical outcomes with multinomial logistic regression. RESULTS: We found that low stress resilience in adolescence conferred increased risks of all studied measures of addictive behaviour. After adjusting for childhood socioeconomic information, low stress resilience was associated with adult current regular smoking (relative risk ratio: 5.85, 95% CI 4.32 to 7.93), higher nicotine dependence scores (beta: 0.76, 95% CI 0.29 to 1.23), hazardous use of alcohol (>14 alcoholic drink-equivalents per week, OR: 1.72, 95% CI 1.37 to 2.16), DSM-IV criteria for alcohol dependence (OR: 1.74, 95% CI 1.35 to 2.25), and drug use (OR: 1.77, 95% CI 1.51 to 2.08). The results remained largely unchanged after further adjustments for adult educational attainment and occupation as well as for additional conscription covariates. CONCLUSION: Low stress resilience in late adolescence appears to be associated with an increased risk of disadvantageous and addictive health behaviours in adulthood.

Impact of parental cancer on IQ, stress resilience, and physical fitness in young men.

BACKGROUND: A parental cancer diagnosis is a stressful life event, potentially leading to increased risks of mental and physical problems among children. This study aimed to investigate the associations of parental cancer with IQ, stress resilience, and physical fitness of the affected men during early adulthood. MATERIALS AND METHODS: In this Swedish population-based study, we included 465,249 men born during 1973-1983 who underwent the military conscription examination around the age of 18 years. We identified cancer diagnoses among the parents of these men from the Cancer Register. IQ, stress resilience, and physical fitness of the men were assessed at the time of conscription and categorized into three levels: low, moderate, and high (reference category). We used multinomial logistic regression to assess the studied associations. RESULTS: Overall, parental cancer was associated with higher risks of low stress resilience (relative risk ratio [RRR]: 1.09 [95% confidence interval (CI) 1.04-1.15]) and low physical fitness (RRR: 1.12 [95% CI 1.05-1.19]). Stronger associations were observed for parental cancer with a poor expected prognosis (low stress resilience: RRR: 1.59 [95% CI 1.31-1.94]; low physical fitness: RRR: 1.45 [95% CI 1.14-1.85]) and for parental death after cancer diagnosis (low stress resilience: RRR: 1.29 [95% CI 1.16-1.43]; low physical fitness: RRR: 1.40 [95% CI 1.23-1.59]). Although there was no overall association between parental cancer and IQ, parental death after cancer diagnosis was associated with a higher risk of low IQ (RRR: 1.11 [95% CI 1.01-1.24]). CONCLUSION: Parental cancer, particularly severe and fatal type, is associated with higher risks of low stress resilience and low physical fitness among men during early adulthood. Men who experienced parental death after cancer diagnosis also have a higher risk of low IQ.

Childhood Bereavement and Lower Stress Resilience in Late Adolescence.

PURPOSE: Although childhood traumatic experiences are recognized as important determinants for adolescent psychiatric health in general, our objective was to explore the specific influence of childhood bereavement on the stress resilience development trajectory. METHODS: In this national register-based cohort study, we identified 407,639 men born in Sweden between 1973 and 1983, who underwent compulsory military enlistment examinations in late adolescence, including measures of psychological stress resilience. We defined exposure as loss of a first-degree family member in childhood, and estimated relative risk ratios (RRRs) for reduced (moderate or low), compared with high, stress resilience with 95% confidence intervals (CIs) using multinomial logistic regression. RESULTS: Loss of a parent or sibling in childhood conferred a 49% increased risk of subsequent low stress resilience (RRR, 1.49, 95% CI, 1.41-1.57) and an 8% increased risk of moderate stress resilience (RRR, 1.08, 95% CI, 1.03-1.13) in late adolescence. There was also a graded increase in risk with increasing age at loss; teenagers were at higher risk for low resilience (RRR, 1.64, 95% CI, 1.52-1.77) than children aged 7-12 (RRR, 1.47, 95% CI, 1.34-1.61) and ≤6 years (RRR, 1.16 95% CI, 1.02-1.32). The excess risk was observed for all causes of death, including suicide and unexpected deaths as well as deaths due to other illnesses. The associations remained after exclusion of parents with a history of hospitalization for psychiatric diagnoses. CONCLUSIONS: The long-term consequences of childhood bereavement may include lower stress resilience in late adolescence.

Psychiatric disorders among children of parents with cancer: A Swedish register-based matched cohort study.

OBJECTIVE: To investigate the risk of psychiatric disorders among children of parents with cancer in a nationwide population-based setting. METHODS: Based on Swedish national registers, the study included 101 339 children with parental cancer diagnosed either during pregnancy (N = 1047) or after birth (N = 100 292) that were born during 1983 to 2000. For each exposed child, we randomly selected 10 unexposed children from the general population after individual matching by year of birth and sex. The matched cohort was followed during 2001 to 2010. Clinical diagnoses of psychiatric disorders and use of prescribed psychiatric medications were identified for all children. Cox regression and logistic regression were used to evaluate the associations of parental cancer with psychiatric disorder diagnosis and psychiatric medication use, respectively. RESULTS: Parental cancer during pregnancy was not associated with the risk of psychiatric disorders overall, although paternal cancer during pregnancy was associated with a higher risk of psychiatric medication use among females. Parental cancer after birth was associated with higher risks of psychiatric disorder diagnoses, particularly stress reaction and adjustment disorders (males: hazard ratio [HR]: 1.24, 95% confidence interval [CI], 1.08-1.43; females: HR: 1.27, 95% CI, 1.14-1.41), and use of psychiatric medication (males: odds ratio [OR]: 1.09, 95% CI, 1.04-1.13; females: OR: 1.14, 95% CI, 1.10-1.18). The positive associations were stronger for parental cancer with poor expected survival and for parental death after cancer diagnosis. CONCLUSIONS: Parental cancer, primarily the life-threatening cancer, might confer a higher risk of psychiatric disorders among children. These findings have potential implications for health care professionals in providing targeted support to children living with a parent with cancer.