Gestational age at birth and mortality from infancy into mid-adulthood: a national cohort study.

BACKGROUND: Breakthroughs in the treatment of preterm birth approximately 40 years ago have enabled a generation of preterm survivors to now reach mid-adulthood. Understanding their health sequelae is essential for guiding their long-term care. We did a study to examine preterm birth in relation to mortality into mid-adulthood. METHODS: A national cohort study was done of all 4 296 814 singleton livebirths in Sweden between 1973 and 2015, who were followed up for mortality through Dec 31, 2017 (maximum age 45 years). Cox regression was used to examine gestational age at birth in relation to all-cause and cause-specific mortality, and cosibling analyses assessed for potential confounding by shared familial (genetic or environmental) factors. FINDINGS: In 103·5 million person-years of follow-up, 43 916 (1·0%) deaths were reported. Gestational age at birth was inversely associated with mortality from infancy to mid-adulthood. Relative to full-term birth (39-41 weeks), the adjusted hazard ratios for mortality associated with gestational age at birth were: 66·14 (95% CI 63·09-69·34) for extremely preterm (22-27 weeks), 8·67 (8·32-9·03) for very preterm (28-33 weeks), 2·61 (2·52-2·71) for late preterm (34-36 weeks), and 1·34 (1·30-1·37) for early term (37-38 weeks), from birth to age 45 years; and 2·04 (0·92-4·55) for extremely preterm, 1·48 (1·17-1·87) for very preterm, 1·22 (1·07-1·39) for late preterm, and 1·16 (1·08-1·25) for early term, at ages 30-45 years. Preterm birth accounted for more deaths among males than females (additive interaction p<0·001). Multiple underlying causes were identified, including congenital anomalies; respiratory, endocrine, cardiovascular, and neurological diseases; cancer; and external causes. Cosibling analyses suggested that the observed associations were not due to shared genetic or environmental factors in families. INTERPRETATION: Preterm and early term birth should be recognised as chronic conditions that require long-term follow-up for adverse health sequelae in adulthood. FUNDING: National Heart, Lung, and Blood Institute at the National Institutes of Health.

Fetal growth and subsequent maternal risk of thyroid cancer.

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.

Fetal growth and subsequent maternal risk of colorectal cancer.

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.

Perinatal risk factors for acute myeloid leukemia.

Infectious etiologies have been hypothesized for acute leukemias because of their high incidence in early childhood, but have seldom been examined for acute myeloid leukemia (AML). We conducted the first large cohort study to examine perinatal factors including season of birth, a proxy for perinatal infectious exposures, and risk of AML in childhood through young adulthood. A national cohort of 3,569,333 persons without Down syndrome who were born in Sweden in 1973-2008 were followed up for AML incidence through 2010 (maximum age 38 years). There were 315 AML cases in 69.7 million person-years of follow-up. We found a sinusoidal pattern in AML risk by season of birth (P < 0.001), with peak risk among persons born in winter. Relative to persons born in summer (June-August), incidence rate ratios for AML were 1.72 (95 % CI 1.25-2.38; P = 0.001) for winter (December-February), 1.37 (95 % CI 0.99-1.90; P = 0.06) for spring (March-May), and 1.27 (95 % CI 0.90-1.80; P = 0.17) for fall (September-November). Other risk factors for AML included high fetal growth, high gestational age at birth, and low maternal education level. These findings did not vary by sex or age at diagnosis. Sex, birth order, parental age, and parental country of birth were not associated with AML. In this large cohort study, birth in winter was associated with increased risk of AML in childhood through young adulthood, possibly related to immunologic effects of early infectious exposures compared with summer birth. These findings warrant further investigation of the role of seasonally varying perinatal exposures in the etiology of AML.

Perinatal and familial risk factors for acute lymphoblastic leukemia in a Swedish national cohort.

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.

Perinatal and familial risk factors for brain tumors in childhood through young adulthood.

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.

Season of birth and risk of Hodgkin and non-Hodgkin lymphoma.

Infectious etiologies have been hypothesized for Hodgkin and non-Hodgkin lymphoma (HL and NHL) in early life, but findings to date for specific lymphomas and periods of susceptibility are conflicting. We conducted the first national cohort study to examine whether season of birth, a proxy for infectious exposures in the first few months of life, is associated with HL or NHL in childhood through young adulthood. A total of 3,571,574 persons born in Sweden in 1973-2008 were followed up through 2009 to examine the association between season of birth and incidence of HL (943 cases) or NHL (936 cases). We found a sinusoidal pattern in NHL risk by season of birth (p = 0.04), with peak risk occurring among birthdates in April. Relative to persons born in fall (September-November), odds ratios for NHL by season of birth were 1.25 [95% confidence interval (CI), 1.04-1.50; p = 0.02] for spring (March-May), 1.22 (95% CI, 1.01-1.48; p = 0.04) for summer (June-August) and 1.11 (95% CI, 0.91-1.35; p = 0.29) for winter (December-February). These findings did not vary by sex, age at diagnosis or major subtypes. In contrast, there was no seasonal association between birthdate and risk of HL (p = 0.78). In this large cohort study, birth in spring or summer was associated with increased risk of NHL (but not HL) in childhood through young adulthood, possibly related to immunologic effects of delayed infectious exposures compared with fall or winter birth. These findings suggest that immunologic responses in early infancy may play an important role in the development of NHL.

Perinatal risk factors for Wilms tumor in a Swedish national cohort.

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.

Intrauterine factors and risk of nonepithelial ovarian cancers.

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 5-37 years). Perinatal and maternal characteristics and cancer diagnoses were ascertained using nationwide health registry data. RESULTS: 147 women were diagnosed with nonepithelial ovarian tumors in 31.6 million person-years of follow-up, including 94 with germ cell tumors and 53 with sex-cord stromal tumors. Women born preterm (<37 weeks 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.

Season of birth and other perinatal risk factors for melanoma.

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.

Comorbidities and mortality in bipolar disorder: a Swedish national cohort study.

IMPORTANCE: Bipolar disorder is associated with premature mortality, but the specific causes and underlying pathways are unclear. OBJECTIVE: To examine the physical health effects of bipolar disorder using outpatient and inpatient data for a national population. DESIGN, SETTING, AND PARTICIPANTS: National cohort study of 6,587,036 Swedish adults, including 6618 with bipolar disorder. MAIN OUTCOMES AND MEASURES: Physical comorbidities diagnosed in any outpatient or inpatient setting nationwide and mortality (January 1, 2003, through December 31, 2009). RESULTS: Women and men with bipolar disorder died 9.0 and 8.5 years earlier on average than the rest of the population, respectively. All-cause mortality was increased 2-fold among women (adjusted hazard ratio [aHR], 2.34; 95% CI, 2.16-2.53) and men (aHR, 2.03; 95% CI, 1.85-2.23) with bipolar disorder, compared with the rest of the population. Patients with bipolar disorder had increased mortality from cardiovascular disease, diabetes mellitus, chronic obstructive pulmonary disease (COPD), influenza or pneumonia, unintentional injuries, and suicide for both women and men and cancer for women only. Suicide risk was 10-fold among women (aHR, 10.37; 95% CI, 7.36-14.60) and 8-fold among men (aHR, 8.09; 95% CI, 5.98-10.95) with bipolar disorder, compared with the rest of the population. Substance use disorders contributed only modestly to these findings. The association between bipolar disorder and mortality from chronic diseases (ischemic heart disease, diabetes, COPD, or cancer) was weaker among persons with a prior diagnosis of these conditions (aHR, 1.40; 95% CI, 1.26-1.56) than among those without a prior diagnosis (aHR, 2.38; 95% CI, 1.95-2.90; P(interaction) = .01). CONCLUSIONS AND RELEVANCE: In this large national cohort study, patients with bipolar disorder died prematurely from multiple causes, including cardiovascular disease, diabetes, COPD, influenza or pneumonia, unintentional injuries, and suicide. However, chronic disease mortality among those with more timely medical diagnosis approached that of the general population, suggesting that better provision of primary medical care may effectively reduce premature mortality among persons with bipolar disorder.

Comorbidities and mortality in persons with schizophrenia: a Swedish national cohort study.

OBJECTIVE: Schizophrenia is associated with premature mortality, but the specific causes and pathways are unclear. The authors used outpatient and inpatient data for a national population to examine the association between schizophrenia and mortality and comorbidities. METHOD: This was a national cohort study of 6,097,834 Swedish adults, including 8,277 with schizophrenia, followed for 7 years (2003-2009) for mortality and comorbidities diagnosed in any outpatient or inpatient setting nationwide. RESULTS: On average, men with schizophrenia died 15 years earlier, and women 12 years earlier, than the rest of the population, and this was not accounted for by unnatural deaths. The leading causes were ischemic heart disease and cancer. Despite having twice as many health care system contacts, schizophrenia patients had no increased risk of nonfatal ischemic heart disease or cancer diagnoses, but they had an elevated mortality from ischemic heart disease (adjusted hazard ratio for women, 3.33 [95% CI=2.73-4.05]; for men, 2.20 [95% CI=1.83-2.65]) and cancer (adjusted hazard ratio for women, 1.71 [95% CI=1.38-2.10; for men, 1.44 [95% CI=1.15-1.80]). Among all people who died from ischemic heart disease or cancer, schizophrenia patients were less likely than others to have been diagnosed previously with these conditions (for ischemic heart disease, 26.3% compared with 43.7%; for cancer, 73.9% compared with 82.3%). The association between schizophrenia and mortality was stronger among women and the employed. Lack of antipsychotic treatment was also associated with elevated mortality. CONCLUSIONS: Schizophrenia patients had markedly premature mortality, and the leading causes were ischemic heart disease and cancer, which appeared to be underdiagnosed. Preventive interventions should prioritize primary health care tailored to this population, including more effective risk modification and screening for cardiovascular disease and cancer.

Perinatal and family risk factors for Hodgkin lymphoma in childhood through young adulthood.

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.

Perinatal and family risk factors for non-Hodgkin lymphoma in early life: a Swedish national cohort study.

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.

Gestational age at birth and risk of testicular cancer.

Most testicular germ cell tumors originate from carcinoma in situ cells in fetal life, possibly related to sex hormone imbalances in early pregnancy. Previous studies of association between gestational age at birth and testicular cancer have yielded discrepant results and have not examined extreme preterm birth. Our objective was to determine whether low gestational age at birth is independently associated with testicular cancer in later life. We conducted a national cohort study of 354,860 men born in Sweden in 1973-1979, including 19,214 born preterm (gestational age < 37 weeks) of whom 1,279 were born extremely preterm (22-29 weeks), followed for testicular cancer incidence through 2008. A total of 767 testicular cancers (296 seminomas and 471 nonseminomatous germ cell tumors) were identified in 11.2 million person-years of follow-up. Extreme preterm birth was associated with an increased risk of testicular cancer (hazard ratio = 3.95; 95% confidence interval = 1.67-9.34) after adjusting for other perinatal factors, family history of testicular cancer and cryptorchidism. Only five cases (three seminomas and two nonseminomas) occurred among men born extremely preterm, limiting the precision of risk estimates. No association was found between later preterm birth, post-term birth or low or high fetal growth and testicular cancer. These findings suggest that extreme but not later preterm birth may be independently associated with testicular cancer in later life. They are based on a small number of cases and will need confirmation in other large cohorts. Elucidation of the key prenatal etiologic factors may potentially lead to preventive interventions in early life.

Preterm birth and risk of epilepsy in Swedish adults.

OBJECTIVE: To determine whether preterm birth is associated with epilepsy in a national cohort of adults aged 25-37 years. METHODS: We conducted a national cohort study of 630,090 infants born in Sweden from 1973 through 1979, including 27,953 born preterm (<37 weeks), followed from 2005 to 2009 for 1) hospitalization for epilepsy and 2) outpatient and inpatient prescription of antiepileptic drugs. Epilepsy diagnoses and medication data were obtained from all hospitals and pharmacies throughout Sweden. RESULTS: We found a strong association between preterm birth and epilepsy that increased by earlier gestational age. After adjusting for fetal growth and potential confounders, odds ratios for hospitalization for epilepsy were 4.98 (95%confidence interval [CI] 2.87-8.62) for those born at 23-31 weeks, 1.98 (95% CI 1.26-3.13) for those born at 32-34 weeks, and 1.76 (95% CI 1.30-2.38) for those born at 35-36 weeks, relative to those born full-term (37-42 weeks). A similar but slightly weaker trend was observed for the association between preterm birth and antiepileptic drug prescription. These associations persisted after excluding individuals with cerebral palsy, inflammatory diseases of the CNS, cerebrovascular disease, and brain tumors. CONCLUSIONS: These findings suggest that preterm birth, including late preterm birth, is strongly associated with epilepsy in Swedish adults aged 25-37 years. This association was independent of fetal growth and was not mediated by cerebral palsy or other comorbidities.

Gestational age at birth and mortality in young adulthood.

CONTEXT: Preterm birth is the leading cause of infant mortality in developed countries, but the association between gestational age at birth and mortality in adulthood remains unknown. OBJECTIVE: To examine the association between gestational age at birth and mortality in young adulthood. DESIGN, SETTING, AND PARTICIPANTS: National cohort study of 674,820 individuals born as singletons in Sweden in 1973 through 1979 who survived to age 1 year, including 27,979 born preterm (gestational age <37 weeks), followed up to 2008 (ages 29-36 years). MAIN OUTCOME MEASURES: All-cause and cause-specific mortality. RESULTS: A total of 7095 deaths occurred in 20.8 million person-years of follow-up. Among individuals still alive at the beginning of each age range, a strong inverse association was found between gestational age at birth and mortality in early childhood (ages 1-5 years: adjusted hazard ratio [aHR] for each additional week of gestation, 0.92; 95% CI, 0.89-0.94; P < .001), which disappeared in late childhood (ages 6-12 years: aHR, 0.99; 95% CI, 0.95-1.03; P = .61) and adolescence (ages 13-17 years: aHR, 0.99; 95% CI, 0.95-1.03; P = .64) and then reappeared in young adulthood (ages 18-36 years: aHR, 0.96; 95% CI, 0.94-0.97; P < .001). In young adulthood, mortality rates (per 1000 person-years) by gestational age at birth were 0.94 for 22 to 27 weeks, 0.86 for 28 to 33 weeks, 0.65 for 34 to 36 weeks, 0.46 for 37 to 42 weeks (full-term), and 0.54 for 43 or more weeks. Preterm birth was associated with increased mortality in young adulthood even among individuals born late preterm (34-36 weeks, aHR, 1.31; 95% CI, 1.13-1.50; P < .001), relative to those born full-term. In young adulthood, gestational age at birth had the strongest inverse association with mortality from congenital anomalies and respiratory, endocrine, and cardiovascular disorders and was not associated with mortality from neurological disorders, cancer, or injury. CONCLUSION: After excluding earlier deaths, low gestational age at birth was independently associated with increased mortality in early childhood and young adulthood.

Physician advice on exercise and diet in a U.S. sample of obese Mexican-American adults.

PURPOSE: To document the prevalence of obese Mexican-Americans never advised by health professionals regarding exercise and diet, and to determine risk factors for no advice. METHODS: Data came from 1787 obese Mexican-American adults (body mass index ≥30; age ≥18 years) in the Medical Expenditure Panel Survey. The survey included self-reported receipt of health care provider advice on exercise and diet as well as sociodemographic, health-related, and provider-related factors. Multivariable logistic regression models were performed separately for advice regarding exercise and advice regarding diet. RESULTS: Overall, 45% of respondents reported that they had never received advice from a doctor or health care professional to exercise more, and 52% reported that they have received advice to eat fewer higher-fat/high-cholesterol foods. Men, nonmarried respondents, lower-educated respondents, those who preferred to speak Spanish at home, and those without comorbid chronic conditions were less likely to receive advice. DISCUSSION: Results suggest that obese Mexican-Americans are insufficiently advised by health care providers regarding exercise and diet. Given the seriousness of obesity-related health risks and the increasing prevalence of overweight status and obesity among Mexican-Americans, it is vital that providers are involved in finding ways to effectively educate and/or treat overweight patients.

Predictors of trying to lose weight among overweight and obese Mexican-Americans: a signal detection analysis.

OBJECTIVE: Signal detection analysis, a form of recursive partitioning, was used to identify combinations of sociodemographic and acculturation factors that predict trying to lose weight in a community-based sample of 957 overweight and obese Mexican-American adults (ages 18-69 years). DESIGN: Data were pooled from the 2004 and 2006 Behavioral Risk Factor Surveillance System conducted in a low-income, semi-rural community in California. RESULTS: Overall, 59 % of the population reported trying to lose weight. The proportion of adults who were trying to lose weight was highly variable across the seven mutually exclusive groups identified by signal detection (range 30-79 %). Significant predictors of trying to lose weight included BMI, gender, age and income. Women who were very overweight (BMI > 28.5 kg/m2) were most likely to be trying to lose weight (79 %), followed by very overweight higher-income men and moderately overweight (BMI = 25.0-28.5 kg/m2) higher-income women (72 % and 70 %, respectively). Moderately overweight men, aged 28-69 years, were the least likely to be trying to lose weight (30 %), followed by moderately overweight lower-income women (47 %) and very overweight lower-income men (49 %). The latter group is of particular concern since they have characteristics associated with medical complications of obesity (low education and poor access to medical care). CONCLUSIONS: Our findings highlight opportunities and challenges for public health professionals working with overweight Mexican-American adults - particularly lower-income adults who were born in Mexico - who are not trying to lose weight and are therefore at high risk for obesity-related co-morbidities.

Evaluation of risk factors and a community intervention to increase control and treatment of asthma in a low-income semi-rural California community.

To better understand risk factors associated with current asthma in a low-income, ethnically diverse population, we analyzed pooled data from the 2004-2006 Behavioral Risk Factor Surveillance System survey conducted in Salinas, CA. We were particularly interested in modifiable risk factors, as the survey was conducted as part of a large community-based intervention that addresses asthma, obesity, and diabetes. We also conducted semi-structured interviews with key informants involved with the clinical, school, and community aspects of the intervention to inform the intervention's progress, and adapt practices and programs to reach those most in need. Of the 4925 adults in this analysis, 51% were Mexican-American and 32% lacked a high-school diploma; 227 women and 84 men had current asthma, and 194 were parents of children with current asthma; prevalences of 7.7%, 4.3%, and 7.0% respectively. Over 20% of women and men with asthma were current smokers and/or exposed to passive smoking, more than 50% reported less than the recommended 60 minutes or more of physical activity per day, and approximately 40% were obese or morbidly obese (42% of women and 36% of men compared to 26% of adults without asthma). Two of the strongest modifiable risk factors associated with current asthma and identified by the stepwise multiple regression models were: could not afford prescription medication(s) in the past 12 months (OR 2.5, p < 0.001 for adults with asthma, OR 1.8, p < 0.01 for parents of children with asthma) and morbid obesity (OR 3.4, p < 0.001 for adults with asthma). Among adults who reported one or more episodes of asthma in the past 30 days, 28% of women and 30% of men had not used a preventive medication, and 48% of women and 57% of men had not used a prescription asthma inhaler (20% had not used either). This study adds to the scarce body of literature on the prevalence of asthma and related risk factors in a predominately Mexican-American, semi-rural community, and illustrates how survey and key informant data can enhance knowledge of local study populations and guide interventions to improve asthma control and treatment.