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Thyroid cancer has peak incidence among women of reproductive age, and growth factors, which have procarcinogenic properties, may play an important etiologic role. However, the association between fetal growth rate during a woman's pregnancy and her subsequent risk of thyroid cancer has not been previously examined. We conducted a national cohort study of 1,837,634 mothers who had a total of 3,588,497 live-births in Sweden in 1973-2008, followed up for thyroid cancer incidence through 2009. There were 2,202 mothers subsequently diagnosed with thyroid cancer in 36.8 million person-years of follow-up. After adjusting for maternal age, height, weight, smoking, and sociodemographic factors, high fetal growth (birth weight standardized for gestational age and sex) was associated with a subsequent increased risk of thyroid cancer in the mother (incidence rate ratio [IRR] per additional 1 standard deviation, 1.05; 95% CI, 1.01-1.09; p = 0.02). Each 1,000 g increase in the infant's birth weight was associated with a 13% increase in the mother's subsequent risk of thyroid cancer (IRR, 1.13; 95% CI, 1.05-1.22; p = 0.001). These findings appeared to involve both papillary and follicular subtypes, and did not vary significantly by the mother's height, weight or smoking status. In this large national cohort study, high fetal growth during a woman's pregnancy was independently associated with a subsequent increased risk of her developing thyroid cancer. If confirmed, these findings suggest an important role of maternal growth factors in the development of thyroid cancer, and potentially may help facilitate the identification of high-risk subgroups of women., (© 2015 UICC.)

Background: High birth weight has been associated with subsequent increased risk of breast cancer in the infant's mother, possibly related to maternal estrogen and growth factor pathways. However, its association with maternal risk of colorectal cancer, the third most common cancer among women, is unknown., Methods: We conducted a national cohort study of 1,838,509 mothers who delivered 3,590,523 babies in Sweden in 1973-2008, followed up for colorectal cancer incidence through 2009., Results: There were 7,318 mothers diagnosed with colorectal cancer in 36.8 million person-years of follow-up. After adjusting for maternal age, body mass index, diabetes, and other potential confounders, high fetal growth was associated with a subsequent increased risk of colorectal cancer in the mother [incidence rate ratio (IRR) per additional 1 SD relative to mean birth weight for gestational age and sex, 1.05; 95% confidence intervals (CI), 1.03-1.07; P < 0.0001]. Each 1,000 g increase in the infant's birth weight was associated with a 12% increase in the mother's subsequent risk of colorectal cancer (IRR, 1.12; 95% CI, 1.07-1.17; P < 0.0001). Multiple gestation was also independently associated with increased maternal risk of colorectal cancer (IRR for twin or higher order vs. singleton, 1.22; 95% CI, 1.04-1.44; P = 0.02)., Conclusion: In this large cohort study, high fetal growth and multiple gestation were independently associated with subsequent higher maternal risk of colorectal cancer. These findings warrant further investigation of maternal growth factor and estrogen pathways in the etiology of colorectal cancer., Impact: If confirmed, our findings may help identify subgroups of women at high risk of colorectal cancer., (©2015 American Association for Cancer Research.)

Objective: Several studies have reported associations between restricted fetal development, as shown by birth weight or birth length, and later ischaemic heart disease (IHD). However, few studies have examined the importance of these perinatal factors when taking into account gestational age at birth, hereditary factors, sociodemographic factors and comorbidities. This study investigated the importance of perinatal risk factors for premature IHD and myocardial infarction (MI) in a large Swedish cohort., Setting and Participants: National cohort study of 1,970,869 individuals who were live-born in Sweden in 1973 through 1992, and followed up to 2010 (ages 18-38 years)., Primary and Secondary Outcome Measures: The main outcome was IHD, and the secondary outcome was MI., Results: A total of 668 individuals were diagnosed with IHD in 18.8 million person-years of follow-up. After adjusting for gestational age at birth, sociodemographic factors, comorbidities and family history of IHD, low fetal growth was associated with increased risk of IHD (HR for <-2 vs -1 to <1 SD, 1.54; 95% CI 1.15 to 2.07; p=0.004) and increased risk of MI (HR for <-2 vs -1 to <1 SD, 2.48; 95% CI 1.66 to 3.71; p<0.001) in young adulthood. In contrast, gestational age at birth was not associated with the risk of IHD or MI., Conclusions: In this large national cohort, low fetal growth was strongly associated with IHD and MI in young adulthood, independently of gestational age at birth, sociodemographic factors, comorbidities and family history of IHD., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Perinatal factors including high birth weight have been found to be associated with acute lymphoblastic leukemia (ALL) in case-control studies. However, to the best of our knowledge, these findings have seldom been examined in large population-based cohort studies, and the specific contributions of gestational age and fetal growth remain unknown., Methods: The authors conducted a national cohort study of 3,569,333 individuals without Down syndrome who were born in Sweden between 1973 and 2008 and followed for the incidence of ALL through 2010 (maximum age, 38 years) to examine perinatal and familial risk factors., Results: There were 1960 ALL cases with 69.7 million person-years of follow-up. After adjusting for potential confounders, risk factors for ALL included high fetal growth (incidence rate ratio [IRR] per additional 1 standard deviation, 1.07; 95% confidence interval [95% CI], 1.02-1.11 [P =.002]; and IRR for large vs appropriate for gestational age, 1.22; 95% CI, 1.06-1.40 [P =.005]), first-degree family history of ALL (IRR, 7.41; 95% CI, 4.60-11.95 [P<.001]), male sex (IRR, 1.20; 95% CI, 1.10-1.31 [P<.001]), and parental country of birth (IRR for both parents born in Sweden vs other countries, 1.13; 95% CI, 1.00-1.27 [P =.045]). These risk factors did not appear to vary by patient age at the time of diagnosis of ALL. Gestational age at birth, season of birth, birth order, multiple birth, parental age, and parental education level were not found to be associated with ALL., Conclusions: In this large cohort study, high fetal growth was found to be associated with an increased risk of ALL in childhood through young adulthood, independent of gestational age at birth, suggesting that growth factor pathways may play an important long-term role in the etiology of ALL., (© 2014 American Cancer Society.)

Perinatal risk factors including high birth weight have been associated with Wilms tumor in case-control studies. However, these findings have seldom been examined in large cohort studies, and the specific contributions of gestational age at birth and fetal growth remain unknown. We conducted the largest population-based cohort study to date consisting of 3,571,574 persons born in Sweden in 1973-2008, followed up for Wilms tumor incidence through 2009 to examine perinatal risk factors. There were 443 Wilms tumor cases identified in 66.3 million person-years of follow-up. After adjusting for gestational age and other perinatal factors, high fetal growth was associated with increased risk of Wilms tumor among girls (hazard ratio per 1 standard deviation (SD), 1.36; 95% CI 1.20-1.54; P < 0.001), but not boys (1.10; 95% CI 0.97-1.25; P = 0.14) (P interaction = 0.02). Among girls, high fetal growth was associated with disease onset before age 5 years (odds ratio per 1 SD, 1.47; 95% CI 1.28-1.69; P < 0.001), but not beyond (1.00; 95% CI 0.76-1.31; P = 0.99). No clear associations were found for gestational age at birth or other perinatal factors. In this large cohort study, high fetal growth was associated with Wilms tumor before age 5 years among girls. These findings suggest that early-life growth factor pathways for Wilms tumor may be more common among girls than boys. Further elucidation of these mechanisms may reveal better targets for prevention or treatment of specific subtypes of Wilms tumor.

The incidence of Hodgkin lymphoma has increased among adolescents and young adults in recent decades, but the relevant risk factors in early life are still unknown. A national cohort study was conducted of 3,571,574 individuals born in Sweden in 1973-2008 and followed up for Hodgkin lymphoma incidence through 2009, to examine perinatal and family risk factors for Hodgkin lymphoma in childhood through young adulthood (ages 0-37 years). There were 943 Hodgkin lymphoma cases identified in 66.3 million person-years of follow-up. High fetal growth was associated with an increased risk of Hodgkin lymphoma after adjustment for gestational age at birth and other potential confounders (P(trend) = 0.005). Family history of Hodgkin lymphoma in a sibling or parent also was strongly associated with an increased risk, with adjusted hazard ratios = 8.83 (95% confidence interval: 3.67, 21.30) and 7.19 (95% confidence interval: 3.58, 14.44), respectively. No association was found between gestational age at birth, birth order, twinning, parental age, or parental education and Hodgkin lymphoma. These findings did not vary by age at Hodgkin lymphoma diagnosis. Similar associations were found for nodular sclerosis and mixed cellularity subtypes. These findings suggest that perinatal factors including possible growth factor pathways may contribute to the risk of Hodgkin lymphoma in childhood through young adulthood.

Background: The incidence of non-Hodgkin lymphoma (NHL) in early life has increased in recent decades, but the relevant risk factors remain largely unknown. We examined perinatal and family risk factors for NHL in childhood through young adulthood., Methods: We conducted a national cohort study of 3 571 574 individuals born in Sweden in 1973-2008 who were followed for incidence of NHL through 2009 (ages 0-37 years). Detailed information on perinatal and family characteristics and NHL diagnoses were obtained from national birth and cancer registries. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between perinatal and family variables and NHL; P values are from two-sided tests., Results: There were 936 NHL case patients identified in 66.3 million person-years of follow-up. Independent risk factors for NHL included family history of NHL in either a sibling (adjusted HR = 9.84; 95% CI = 2.46 to 39.41; P = .001) or parent (adjusted HR = 2.36; 95% CI = 1.27 to 4.38; P = .007); high fetal growth (for ≥ 2 SDs relative to 0 to <1 SD from the mean: adjusted HR = 1.64; 95% CI = 1.19 to 2.25; P = .002); older maternal age (adjusted HR for each 5-year increment = 1.11; 95% CI = 1.04 to 1.19; P (trend) = .004); low birth order (adjusted HR for each increment of one birth = 0.91; 95% CI = 0.84 to 0.99; P (trend) = .02); and male sex (adjusted HR = 1.58; 95% CI = 1.38 to 1.80; P < .001). Male sex was associated with onset of NHL before 15 years of age but not with later-onset NHL, whereas the other risk factors did not vary by age at diagnosis. No association was found between gestational age at birth, twinning, paternal age, or parental education and NHL., Conclusion: In this large national cohort study, family history of NHL, high fetal growth, older maternal age, low birth order, and male sex were independent risk factors for NHL in early life.

Background: Adverse perinatal exposures have been associated with psychiatric disorders and suicidal behaviours later in life. However, the independent associations of gestational age at birth or fetal growth with suicide death, potential sex-specific differences, and causality of these associations are unclear.Methods: A national cohort study was conducted of all 2 440 518 singletons born in Sweden during 1973-98 who survived to age 18 years, who were followed up through 2016. Cox regression was used to compute hazard ratios (HRs) for suicide death associated with gestational age at birth or fetal growth while mutually adjusting for these factors, sociodemographic characteristics and family history of suicide. Co-sibling analyses assessed the influence of unmeasured shared familial (genetic and/or environmental) factors.Results: In 31.2 million person-years of follow-up, 4470 (0.2%) deaths by suicide were identified. Early preterm birth (22-33 weeks) was associated with an increased risk of suicide among females [adjusted hazard ratio (HR), 1.97; 95% confidence interval CI), 1.29, 3.01; P = 0.002) but not males (0.90; 0.64, 1.28; P = 0.56), compared with full-term birth (39-41 weeks). Small for gestational age was associated with a modestly increased risk of suicide among females (adjusted HR, 1.27; 95% CI, 1.08, 1.51; P = 0.005) and males (1.14; 1.03, 1.27; P = 0.02). However, these associations were attenuated and non-significant after controlling for shared familial factors.Conclusions: In this large national cohort, preterm birth in females and low fetal growth in males and females were associated with increased risks of suicide death in adulthood. However, these associations appeared to be non-causal and related to shared genetic or prenatal environmental factors within families. [ABSTRACT FROM AUTHOR]

Perinatal factors, including high birth weight, have been associated with childhood brain tumors in case-control studies. However, the specific contributions of gestational age and fetal growth remain unknown, and these issues have never been examined in large cohort studies with follow-up into adulthood. We conducted a national cohort study of 3,571,574 persons born in Sweden in 1973-2008, followed up for brain tumor incidence through 2010 (maximum age 38 years) to examine perinatal and familial risk factors. There were 2,809 brain tumors in 69.7 million person-years of follow-up. After adjusting for potential confounders, significant risk factors for brain tumors included high fetal growth [incidence rate ratio (IRR) per additional 1 SD, 1.04; 95% confidence interval (CI), 1.01-1.08, P = 0.02], first-degree family history of a brain tumor (IRR, 2.43; 95% CI, 1.86-3.18, P < 0.001), parental country of birth (IRR for both parents born in Sweden vs. other countries, 1.21; 95% CI, 1.09-1.35, P < 0.001), and high maternal education level (Ptrend = 0.01). These risk factors did not vary by age at diagnosis. The association with high fetal growth appeared to involve pilocytic astrocytomas, but not other astrocytomas, medulloblastomas, or ependymomas. Gestational age at birth, birth order, multiple birth, and parental age were not associated with brain tumors. In this large cohort study, high fetal growth was associated with an increased risk of brain tumors (particularly pilocytic astrocytomas) independently of gestational age, not only in childhood but also into young adulthood, suggesting that growth factor pathways may play an important long-term role in the etiology of certain brain tumor subtypes. [ABSTRACT FROM AUTHOR]

Background: Ultraviolet radiation (UVR) exposure is the main risk factor for cutaneous malignant melanoma (CMM), but its specific effect in infancy is unknown. We examined whether season of birth, a proxy for solar UVR exposure in the first few months of life, is associated with CMM in childhood through young adulthood.Methods: National cohort study of 3 571 574 persons born in Sweden in 1973–2008, followed up for CMM incidence through 2009 (maximum age 37 years) to examine season of birth and other perinatal factors.Results: There were 1595 CMM cases in 63.9 million person-years of follow-up. We found a sinusoidal pattern in CMM risk by season of birth (P = 0.006), with peak risk corresponding to birthdates in spring (March–May). Adjusted odds ratios for CMM by season of birth were 1.21 [95% confidence interval (CI), 1.05–1.39; P = 0.008] for spring, 1.07 (95% CI, 0.92–1.24; P = 0.40) for summer and 1.12 (95% CI, 0.96–1.29; P = 0.14) for winter, relative to fall. Spring birth was associated with superficial spreading subtype of CMM (P = 0.02), whereas there was no seasonal association with nodular subtype (P = 0.26). Other CMM risk factors included family history of CMM in a sibling (>6-fold) or parent (>3-fold), female gender, high fetal growth and high paternal education level.Conclusions: In this large cohort study, persons born in spring had increased risk of CMM in childhood through young adulthood, suggesting that the first few months of life may be a critical period of UVR susceptibility. Sun avoidance in early infancy may play an important role in the prevention of CMM in high-risk populations. [ABSTRACT FROM PUBLISHER]

OBECTIVE--Previous studies have suggested that preterm birth is associated with diabetes later in life. These studies have shown inconsistent results for late preterm births and have had various limitations, including the inability to evaluate diabetic outpatients or to estimate risk across the full range of gestational ages. Our objective was to determine whether preterm birth is associated with diabetes medication prescription in a national cohort of young adults. RESEARCH DESIGN AND METHODS--This was a national cohort study of 630,090 infants born in Sweden from 1973 through 1979 (including 27,953 born preterm, gestational age <37 weeks), followed for diabetes medication prescription in 2005-2009 (ages 25.5-37.0 years). Medication data were obtained from all outpatient and inpatient pharmacies throughout Sweden. RESULTS--Individuals born preterm, including those born late preterm (gestational age 35-36 weeks), had modestly increased odds ratios (ORs) for diabetes medication prescription relative to those born full term, after adjusting for fetal growth and other potential confounders. Insulin and/or oral diabetes medications were prescribed to 1.5% of individuals born preterm compared with 1.2% of those born full term (adjusted OR 1.13 [95% CI 1.02-1.261). Insulin without oral diabetes medications was prescribed to 1.0% of individuals born preterm compared with 0.8% of those born full term (1.22 [1.08-1.39]). CONCLUSIONS--Preterm birth, including late preterm birth, is associated with a modestly increased risk of diabetes in young Swedish adults. These findings have important public health implications given the increasing number of preterm births and the large disease burden of diabetes, particularly when diagnosed in young adulthood. [ABSTRACT FROM AUTHOR]

Previous studies have reported an association between preterm birth and elevated blood pressure in adolescence and young adulthood. These studies were based on single-day blood pressure measurements and had limited ability to estimate risk of hypertension measured over a longer period and across the full range of gestational ages. The authors conducted a national cohort study of all infants born in Sweden from 1973 through 1979 (n = 636,552), including 28,220 born preterm (<37 weeks), followed to ages 25.5–37.0 years to determine whether individuals born preterm were more likely to be prescribed antihypertensive medications in 2005–2009 than those born full term. Antihypertensive medication data were obtained from all outpatient and inpatient pharmacies throughout Sweden. Young adults who were born preterm had an increased relative rate of antihypertensive medication prescription that increased monotonically by earlier gestational age and that was independent of fetal growth. The adjusted odds ratio for ≥1 antihypertensive medications/year ranged from 1.25 (95% confidence interval: 1.12, 1.39) for those born near term (35–36 weeks) to 2.51 (95% confidence interval: 1.11, 5.68) for those born extremely preterm (23–27 weeks) relative to those born full term. These findings suggest that preterm birth is strongly associated with hypertension in young adulthood, including an increased risk among those born near term. [ABSTRACT FROM PUBLISHER]

Abstract: Objective: The majority of ovarian tumors in girls and young women are nonepithelial in origin. The etiology of nonepithelial ovarian tumors remains largely unknown, and intrauterine exposures may play an important role. We examined the association of perinatal factors with risk of nonepithelial ovarian tumors in girls and young women. Methods: National cohort study of 1,536,057 women born in Sweden during 1973–2004 and followed for diagnoses of nonepithelial ovarian tumors through 2009 (attained ages 5–37years). Perinatal and maternal characteristics and cancer diagnoses were ascertained using nationwide health registry data. Results: 147 women were diagnosed with nonepithelial ovarian tumors in 31.6million person-years of follow-up, including 94 with germ cell tumors and 53 with sex-cord stromal tumors. Women born preterm (<37weeks of gestation) had a significantly increased risk of developing nonepithelial ovarian tumors (adjusted hazard ratio 1.86, 95% CI 1.03–3.37; p=0.04). Histological subgroup analyses showed that preterm birth was associated with increased risk of sex-cord stromal tumors (4.39, 2.12–9.10; p<0.001), but not germ cell tumors (0.68, 0.21–2.15; p=0.51). No significant associations were found with fetal growth, birth order, and maternal age at birth. Conclusions: This large cohort study provides the first evidence that preterm birth is a risk factor for developing sex cord-stromal tumors. Ovarian hyperstimulation in response to high gonadotropin levels in preterm girls could mediate disease risk through the proliferative and steroidogenic effects of FSH and LH on granulosa and theca cells, from which most sex-cord stromal tumors are derived. [Copyright &y& Elsevier]