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1.
Artigo em Inglês | MEDLINE | ID: mdl-32133682

RESUMO

BACKGROUND: Risks of neonatal and long-term neurological outcomes are influenced by metabolic acidosis at birth and by reduced Apgar scores, even within the normal range (7-10). OBJECTIVE: To analyse associations between metabolic acidosis at birth and risks of reduced Apgar scores within the normal range. METHODS: In a Swedish cohort of term non-malformed infants born between 2008 and 2013, we included 81 861 infants with information from cord blood gas analyses and Apgar score values of 7-10 at 1, 5, and 10 minutes. Poisson log-linear regression analyses were used to examine associations between metabolic acidosis at birth (defined as pH <7.05 or <7.10 and base deficit ≥12) and Apgar scores of 7, 8, and 9. Adjusted risk ratios (RRs) and risk differences (RDs) were calculated, using 95% confidence intervals (CI). RESULTS: Compared with infants without metabolic acidosis, the adjusted RR of an Apgar score of 9 at 5 minutes was 3.14 (95% CI 2.57, 3.84) in infants with metabolic acidosis (pH <7.05 as cut-off), and 10.13 (95% CI 7.63, 13.45) and 7.60 (95% CI 3.54, 16.33) for Apgar scores of 8 and 7, respectively. Corresponding RRs of Apgar scores at 10 minutes were also substantially increased. The magnitude of RDs varied, but was consistently increased. Both reduced Apgar scores and metabolic acidosis (pH <7.10) influenced neonatal morbidity. CONCLUSIONS: Metabolic acidosis is associated with increased risks of reduced Apgar scores within the normal range. Due to international variations in the assessment of Apgar score, our findings need to be confirmed in other populations.

2.
Fertil Steril ; 113(3): 524-532, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32081362

RESUMO

OBJECTIVE: To assess infant (<1 year) and childhood (1-18 years) mortality in singletons conceived through assisted reproductive techniques (ART) versus naturally conceived singletons. DESIGN: Nationwide prospective study. SETTING: Sweden. PATIENT(S): All singleton liveborn infants born from 1983 to 2012 in Sweden identified using the Medical Birth Register (N = 2,847,108), of whom 43,506 were conceived through ART treatments including in vitro fertilization with and without intracytoplasmic sperm injection. INTERVENTION(S): None. MAIN OUTCOME MEASURES(S): Infant (<1 year) and childhood (1-18 years) mortality. RESULT(S): Data on ART treatment and covariates were retrieved from population-based registers using the unique personal identity number assigned to all permanent residents in Sweden. Cox proportional hazards models estimated the hazard ratios (HRs) with 95% confidence intervals (CIs) as measures of association between ART treatments and death. The analyses were adjusted for maternal characteristics, infertility, child sex, and birth cohort and were restricted to individuals with complete information on covariates for fully adjusted analysis. Compared with naturally conceived singletons, higher infant mortality risks were seen in infants conceived through ART (adjusted HR 1.45; 95% CI, 1.19-1.77), especially after transfer of cryopreserved embryos (adjusted HR 2.30; 95% CI, 1.46-3.64). Early neonatal mortality risk (deaths during the first week) was increased in children born after transfer of blastocysts (HR 2.40; 95% CI, 1.05-5.48). No increased mortality risk was observed between the ages of 1 and 18 years. CONCLUSION(S): Singletons conceived through ART had an increased risk of infant mortality from birth up to 1 year of life, predominantly in the early neonatal period and in pregnancies after transfer of frozen and thawed embryos.

3.
BMJ ; 368: l7057, 2020 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996343

RESUMO

OBJECTIVE: To study the impact of maternal smoking during pregnancy on fractures in offspring during different developmental stages of life. DESIGN: National register based birth cohort study with a sibling comparison design. SETTING: Sweden. PARTICIPANTS: 1 680 307 people born in Sweden between 1983 and 2000 to women who smoked (n=377 367, 22.5%) and did not smoke (n=1 302 940) in early pregnancy. Follow-up was until 31 December 2014. MAIN OUTCOME MEASURE: Fractures by attained age up to 32 years. RESULTS: During a median follow-up of 21.1 years, 377 970 fractures were observed (the overall incidence rate for fracture standardised by calendar year of birth was 11.8 per 1000 person years). The association between maternal smoking during pregnancy and risk of fracture in offspring differed by attained age. Maternal smoking was associated with a higher rate of fractures in offspring before 1 year of age in the entire cohort (birth year standardised fracture rates in those exposed and unexposed to maternal smoking were 1.59 and 1.28 per 1000 person years, respectively). After adjustment for potential confounders the hazard ratio for maternal smoking compared with no smoking was 1.27 (95% confidence interval 1.12 to 1.45). This association followed a dose dependent pattern (compared with no smoking, hazard ratios for 1-9 cigarettes/day and ≥10 cigarettes/day were 1.20 (95% confidence interval 1.03 to 1.39) and 1.41 (1.18 to 1.69), respectively) and persisted in within-sibship comparisons although with wider confidence intervals (compared with no smoking, 1.58 (1.01 to 2.46)). Maternal smoking during pregnancy was also associated with an increased fracture incidence in offspring from age 5 to 32 years in whole cohort analyses, but these associations did not follow a dose dependent gradient. In within-sibship analyses, which controls for confounding by measured and unmeasured shared familial factors, corresponding point estimates were all close to null. Maternal smoking was not associated with risk of fracture in offspring between the ages of 1 and 5 years in any of the models. CONCLUSION: Prenatal exposure to maternal smoking is associated with an increased rate of fracture during the first year of life but does not seem to have a long lasting biological influence on fractures later in childhood and up to early adulthood.


Assuntos
Fraturas Ósseas , Gestantes/psicologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar , Adulto , Fatores Etários , Criança , Correlação de Dados , Feminino , Fraturas Ósseas/diagnóstico , Fraturas Ósseas/epidemiologia , Humanos , Lactente , Masculino , Gravidez , Sistema de Registros/estatística & dados numéricos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologia , Suécia/epidemiologia
4.
BMJ ; 367: l6398, 2019 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801789

RESUMO

OBJECTIVE: To evaluate the associations between maternal diabetes diagnosed before or during pregnancy and early onset cardiovascular disease (CVD) in offspring during their first four decades of life. DESIGN: Population based cohort study. SETTING: Danish national health registries. PARTICIPANTS: All 2 432 000 liveborn children without congenital heart disease in Denmark during 1977-2016. Follow-up began at birth and continued until first time diagnosis of CVD, death, emigration, or 31 December 2016, whichever came first. EXPOSURES FOR OBSERVATIONAL STUDIES: Pregestational diabetes, including type 1 diabetes (n=22 055) and type 2 diabetes (n=6537), and gestational diabetes (n=26 272). MAIN OUTCOME MEASURES: The primary outcome was early onset CVD (excluding congenital heart diseases) defined by hospital diagnosis. Associations between maternal diabetes and risks of early onset CVD in offspring were studied. Cox regression was used to assess whether a maternal history of CVD or maternal diabetic complications affected these associations. Adjustments were made for calendar year, sex, singleton status, maternal factors (parity, age, smoking, education, cohabitation, residence at childbirth, history of CVD before childbirth), and paternal history of CVD before childbirth. The cumulative incidence was averaged across all individuals, and factors were adjusted while treating deaths from causes other than CVD as competing events. RESULTS: During up to 40 years of follow-up, 1153 offspring of mothers with diabetes and 91 311 offspring of mothers who did not have diabetes were diagnosed with CVD. Offspring of mothers with diabetes had a 29% increased overall rate of early onset CVD (hazard ratio 1.29 (95% confidence interval 1.21 to 1.37); cumulative incidence among offspring unexposed to maternal diabetes at 40 years of age 13.07% (12.92% to 13.21%), difference in cumulative incidence between exposed and unexposed offspring 4.72% (2.37% to 7.06%)). The sibship design yielded results similar to those of the unpaired design based on the whole cohort. Both pregestational diabetes (1.34 (1.25 to 1.43)) and gestational diabetes (1.19 (1.07 to 1.32)) were associated with increased rates of CVD in offspring. We also observed varied increased rates of specific early onset CVDs, particularly heart failure (1.45 (0.89 to 2.35)), hypertensive disease (1.78 (1.50 to 2.11)), deep vein thrombosis (1.82 (1.38 to 2.41)), and pulmonary embolism (1.91 (1.31 to 2.80)). Increased rates of CVD were seen in different age groups from childhood to early adulthood until age 40 years. The increased rates were more pronounced among offspring of mothers with diabetic complications (1.60 (1.25 to 2.05)). A higher incidence of early onset CVD in offspring of mothers with diabetes and comorbid CVD (1.73 (1.36 to 2.20)) was associated with the added influence of comorbid CVD but not due to the interaction between diabetes and CVD on the multiplicative scale (P value for interaction 0.94). CONCLUSIONS: Children of mothers with diabetes, especially those mothers with a history of CVD or diabetic complications, have increased rates of early onset CVD from childhood to early adulthood. If maternal diabetes does have a causal association with increased CVD rate in offspring, the prevention, screening, and treatment of diabetes in women of childbearing age could help to reduce the risk of CVD in the next generation.


Assuntos
Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus/fisiopatologia , Diabetes Gestacional/fisiopatologia , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Adulto , Doenças Cardiovasculares/etiologia , Dinamarca/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Adulto Jovem
5.
Eur J Epidemiol ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31788734

RESUMO

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.

6.
PLoS One ; 14(12): e0227120, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31887199

RESUMO

BACKGROUND: Interferon-beta (IFN-beta) is a commonly used treatment for multiple sclerosis (MS). Current guidelines recommend cessation of treatment during pregnancy, however the results of past studies on the safety of prenatal exposure to IFN-beta have been conflicting. A large scale study of a population of MS women is therefore warranted. OBJECTIVES: To assess whether, among those born to women with MS, infants prenatally exposed to IFN-beta show evidence of smaller size at birth relative to infants which were not prenatally exposed to any MS disease modifying drugs. METHODS: Swedish and Finnish register data was used. Births to women with MS in Sweden and Finland between 2005-2014 for which a birth measurement for weight, height, and head circumference was available were included. The exposure window was from 6 months prior to LMP to the end of pregnancy. RESULTS: In Sweden, 411 pregnancies were identified as exposed to IFN-beta during the exposure window, and 835 pregnancies were counted as unexposed to any MS DMD. The corresponding numbers for Finland were 232 and 331 respectively. Infants prenatally exposed to interferon-beta were on average 28 grams heavier (p = 0.17), 0.01 cm longer (p = 0.95), and had head circumferences 0.14 cm larger (p = 0.13) in Sweden. In Finland, infants were 50 grams lighter (p = 0.27), 0.02 cm shorter (p = 0.92) and had head circumferences 0.22 cm smaller (p = 0.15) relative to those unexposed. CONCLUSIONS: This study provides evidence that exposure to IFN-beta during pregnancy does not influence birth weight, length, or head circumference.

7.
BMJ Open ; 9(8): e028866, 2019 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-31467051

RESUMO

PURPOSE: The Uppsala-Stockholm Assisted Reproductive Techniques (UppStART) study is a prospectively recruited sample of couples undergoing assisted reproduction in Stockholm and Uppsala county in Sweden. The study was initiated to (1) investigate possible changes in the epigenetic profile of infants inferred through the ART procedures and their consequence and (2) to assess the impact of lifestyle and health exposures on treatment outcome. PARTICIPANTS: Recruitment took place between September 2011 and December 2013, and in vitro fertilisation (IVF) cycles initiated and pregnancies conceived during this time were followed until December 2014. The cohort includes 971 participants (n= 514 women; n= 457 men), and 129 pregnancies were achieved from the first IVF cycle included in the study. FINDINGS TO DATE: Self-reported demographic, health and lifestyle data were collected from a baseline questionnaire, and to assess changes to lifestyle, a follow-up questionnaire was issued at the time of oocyte retrieval, and at subsequent IVF cycles. Questionnaire data were linked to data extracted from medical records. Biological samples were collected at baseline: blood for extraction of serum, plasma and DNA, morning and evening saliva samples for cortisol measurement and at delivery including samples of maternal blood, placenta and amniotic fluid, and cord blood for epigenetic analysis. FUTURE PLANS: Through the unique identification number assigned to each Swedish citizen at birth or immigration, UppStART study participants will be linked to the Swedish population-based national and quality registers to provide data from prenatal, obstetrical, neonatal and infant care, and subsequent updates will provide data on childhood health and educational outcomes. Collaboration and use of UppStART data is encouraged, and more information about access can be found at www.ki.se/meb/uppstart.

8.
PLoS Med ; 16(6): e1002831, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31199800

RESUMO

BACKGROUND: Socioeconomic disparities in infant mortality have persisted for decades in high-income countries and may have become stronger in some populations. Therefore, new understandings of the mechanisms that underlie socioeconomic differences in infant deaths are essential for creating and implementing health initiatives to reduce these deaths. We aimed to explore whether and the extent to which preterm birth (PTB) and small for gestational age (SGA) at birth mediate the association between maternal education and infant mortality. METHODS AND FINDINGS: We developed a population-based cohort study to include all 1,994,618 live singletons born in Denmark in 1981-2015. Infants were followed from birth until death, emigration, or the day before the first birthday, whichever came first. Maternal education at childbirth was categorized as low, medium, or high. An inverse probability weighting of marginal structural models was used to estimate the controlled direct effect (CDE) of maternal education on offspring infant mortality, further split into neonatal (0-27 days) and postneonatal (28-364 days) deaths, and portion eliminated (PE) by eliminating mediation by PTB and SGA. The proportion eliminated by eliminating mediation by PTB and SGA was reported if the mortality rate ratios (MRRs) of CDE and PE were in the same direction. The MRRs between maternal education and infant mortality were 1.63 (95% CI 1.48-1.80, P < 0.001) and 1.19 (95% CI 1.08-1.31, P < 0.001) for low and medium versus high education, respectively. The estimated proportions of these total associations eliminated by reducing PTB and SGA together were 55% (MRRPE = 1.27, 95% CI 1.15-1.40, P < 0.001) for low and 60% (MRRPE = 1.11, 95% CI 1.01-1.22, P = 0.037) for medium versus high education. The proportions eliminated by eliminating PTB and SGA separately were, respectively, 46% and 11% for low education (versus high education) and 48% and 13% for medium education (versus high education). PTB and SGA together contributed more to the association of maternal educational disparities with neonatal mortality (proportion eliminated: 75%-81%) than with postneonatal mortality (proportion eliminated: 21%-23%). Limitations of the study include the untestable assumption of no unmeasured confounders for the causal mediation analysis, and the limited generalizability of the findings to other countries with varying disparities in access and quality of perinatal healthcare. CONCLUSIONS: PTB and SGA may play substantial roles in the relationship between low maternal education and infant mortality, especially for neonatal mortality. The mediating role of PTB appeared to be much stronger than that of SGA. Public health strategies aimed at reducing neonatal mortality in high-income countries may need to address socially related prenatal risk factors of PTB and impaired fetal growth. The substantial association of maternal education with postneonatal mortality not accounted for by PTB or SGA could reflect unaddressed educational disparities in infant care or other factors.


Assuntos
Escolaridade , Retardo do Crescimento Fetal/mortalidade , Mortalidade Infantil/tendências , Vigilância da População , Nascimento Prematuro/mortalidade , Adolescente , Adulto , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Retardo do Crescimento Fetal/diagnóstico , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Nascimento Prematuro/diagnóstico , Fatores de Risco , Adulto Jovem
9.
Clin Epidemiol ; 11: 285-298, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31118817

RESUMO

Purpose: Postpartum psychosis is a rare but severe complication following childbirth, with unknown etiology. This study investigated whether the death of a close family member - a source of severe stress - the year before or during pregnancy was associated with an increased risk of psychotic illness in the postpartum period among women without and with a history of psychiatric disorder. Methods: We studied live births in Denmark during 1978-2008 and births in Sweden during 1973-2006 (n=5,246,978). Information on death of women's relatives and partners and sociodemographic, health-, and pregnancy-related factors was obtained through linkage with nationwide registries. Results: The death of a close relative the year before or during pregnancy was not associated with psychotic illness during the first 90 days postpartum among women without (adjusted HR 1.02, 95% CI 0.76-1.37) or with a history of psychiatric disorder (HR 0.96, 95% CI 0.74-1.25). Similarly, there was no association between bereavement and risk of postpartum psychosis according to the timing of the loss (the year before or during pregnancy), the relative's cause of death (natural or unnatural), or the woman's relationship to the deceased (parent/sibling or partner/older child). Conclusions: Death of a close relative, one of the most severe sources of stress, before or during pregnancy was not associated with postpartum psychosis. Therefore, these data do not support the hypothesis that severely stressful life events, such as bereavement around the time of pregnancy, are associated with postpartum psychosis.

10.
BMJ Open ; 9(5): e027655, 2019 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-31072859

RESUMO

OBJECTIVES: We investigated the associations between Apgar scores at 1 and 5 min, across the entire range of score values, and child developmental health at 5 years of age. SETTING: British Columbia, Canada PARTICIPANTS: All singleton term infants without major congenital anomalies born between 1993 and 2009, who had a developmental assessment in kindergarten between 1999 and 2014. MAIN OUTCOMES AND MEASURES: Developmental vulnerability on one or more domains of the Early Development Instrument and special needs requirements. Adjusted rate ratios (aRRs) and 95% CIs were estimated using log-linear regression. RESULTS: Of the 150 081 children in the study, 45 334 (30.2%) were developmentally vulnerable and 3644 (2.5%) had special needs. There was an increasing trend in developmental vulnerability and special needs with decreasing 1 min and 5 min Apgar scores. Compared with children with an Apgar score of 10 at 5 min, the aRR for developmental vulnerability increased steadily with decreasing Apgar score from 1.02 (95% CI 1.00 to 1.04) for an Apgar score of 9 to 1.57 (95% CI 1.03 to 2.39) for an Apgar score of 2. Among children with 1 min Apgar scores in the 7-10 range, changes in Apgar scores between 1 and 5 min were associated with significant differences in developmental vulnerability. Compared with children who had an Apgar score of 9 at 1 min and 10 at 5 min, children with an Apgar score of 9 at both 1 and 5 min had higher rates of developmental vulnerability (aRR 1.03, 95% CI 1.01 to 1.05). Compared with infants with an Apgar of 10 at both 1 and 5 min, infants with a 1 min score of 10 and a 5 min score of <10 had higher rates of developmental vulnerability (aRR 1.53, 95% CI 1.08 to 2.17). CONCLUSION: Risks of adverse developmental health and having special needs at 5 years of age are inversely associated with 1 min and 5 min Apgar scores across their entire range.

11.
BMJ ; 365: l1656, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-31064770

RESUMO

OBJECTIVE: To investigate associations between Apgar scores of 7, 8, and 9 (versus 10) at 1, 5, and 10 minutes, and neonatal mortality and morbidity. DESIGN: Population based cohort study. SETTING: Sweden. PARTICIPANTS: 1 551 436 non-malformed live singleton infants, born at term (≥37 weeks' gestation) between 1999 and 2016, with Apgar scores of ≥7 at 1, 5, and 10 minutes. EXPOSURES: Infants with Apgar scores of 7, 8, and 9 at 1, 5, and 10 minutes were compared with those with an Apgar score of 10 at 1, 5, and 10 minutes, respectively. MAIN OUTCOME MEASURES: Neonatal mortality and morbidity, including neonatal infections, asphyxia related complications, respiratory distress, and neonatal hypoglycaemia. Adjusted odds ratios (aOR), adjusted rate differences (aRD), and 95% confidence intervals were estimated. RESULTS: Compared with infants with an Apgar score of 10, aORs for neonatal mortality, neonatal infections, asphyxia related complications, respiratory distress, and neonatal hypoglycaemia were higher among infants with lower Apgar scores, especially at 5 and 10 minutes. For example, the aORs for respiratory distress for an Apgar score of 9 versus 10 were 2.0 (95% confidence interval 1.9 to 2.1) at 1 minute, 5.2 (5.1 to 5.4) at 5 minutes, and 12.4 (12.0 to 12.9) at 10 minutes. Compared with an Apgar score of 10 at 10 minutes, the aRD for respiratory distress was 9.5% (95% confidence interval 9.2% to 9.9%) for an Apgar score of 9 at 10 minutes, and 41.9% (37.7% to 46.4%) for an Apgar score of 7 at 10 minutes. A reduction in Apgar score from 10 at 5 minutes to 9 at 10 minutes was also associated with higher odds of neonatal morbidity, compared with a stable Apgar score of 10 at 5 and 10 minutes. CONCLUSIONS: In term non-malformed infants with Apgar scores within the normal range (7 to 10), risks of neonatal mortality and morbidity are higher among infants with lower Apgar score values, and also among those experiencing a reduction in score from 5 minutes to 10 minutes (compared with infants with stable Apgar scores of 10).


Assuntos
Índice de Apgar , Mortalidade Infantil , Doenças do Recém-Nascido/mortalidade , Mães/estatística & dados numéricos , Adulto , Índice de Massa Corporal , Escolaridade , Feminino , Inquéritos Epidemiológicos , Humanos , Lactente , Mortalidade Infantil/tendências , Recém-Nascido , Masculino , Idade Materna , Razão de Chances , Gravidez , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Suécia/epidemiologia , Nascimento a Termo , Fatores de Tempo , Adulto Jovem
12.
J Am Coll Cardiol ; 73(1): 44-53, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30621950

RESUMO

BACKGROUND: Congenital heart defects are more frequent in offspring of mothers with overweight or obesity. However, associations between maternal overweight and obesity, and risks of complex and specific heart defects are not clear. OBJECTIVES: This study sought to analyze associations between maternal overweight and obesity severity and rates of complex and specific heart defects. METHODS: This was a population-based cohort study in Sweden, including 2,050,491 live singleton infants born between 1992 and 2012. Data on maternal and infant characteristics, and diagnoses of congenital heart defects were retrieved from nationwide registries. Maternal body mass index (BMI) was categorized as underweight (BMI <18.5 kg/m2), normal weight (BMI 18.5 to <25 kg/m2), overweight (BMI 25 to <30 kg/m2), obesity class I (BMI 30 to <35 kg/m2), class II (BMI 35 to <40 kg/m2), and class III (BMI ≥40 kg/m2). Outcomes included complex heart defects (tetralogy of Fallot, transposition of the great arteries, atrial septal defects [ASD], aortic arch defects, and single-ventricle heart) and subgroups of specific heart defects diagnosed up to 5 years of age. The authors calculated adjusted prevalence rate ratios (PRRs) with 95% confidence intervals. RESULTS: A total of 28,628 (1.40%, N = 2,050,491) children had at least 1 congenital heart defect. PRRs of aortic arch defects increased with maternal obesity severity. Compared with offspring of normal weight mothers, PRRs of aortic arch defects and transposition of the great arteries were doubled in offspring of mothers with severe obesity. PRRs of ASD and persistent ductus arteriosus in term infants increased with maternal BMI. CONCLUSIONS: PRRs of aortic branch defects, ASD, and persistent ductus arteriosus increase with maternal obesity severity.


Assuntos
Cardiopatias Congênitas/epidemiologia , Obesidade/epidemiologia , Complicações na Gravidez/epidemiologia , Adolescente , Adulto , Índice de Massa Corporal , Criança , Estudos de Coortes , Feminino , Cardiopatias Congênitas/diagnóstico , Humanos , Recém-Nascido , Gravidez , Prevalência , Sistema de Registros , Fatores de Risco , Suécia/epidemiologia , Adulto Jovem
13.
Int J Epidemiol ; 48(1): 297-306, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30239740

RESUMO

BACKGROUND: Small-for-gestational-age (SGA) birth is commonly used as a proxy for fetal growth restriction, but also includes constitutionally small infants. Genetic factors account for almost half of the risk of SGA birth. We estimated perinatal risks of SGA birth using both population-based and within-sibling analyses, where the latter by design controls for shared genetic factors and maternal environmental factors that are constant across pregnancies. METHODS: This was a prospective nationwide cohort study of 2 616 974 singleton infants born in Sweden between January 1987 and December 2012, of whom 1 885 924 were full siblings. We estimated associations between severe or moderate SGA (<3rd percentile and 3rd to <10th percentiles, respectively) and risks of stillbirth, neonatal mortality and morbidity, using both population-based and within-sibling analyses. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated in stillbirth analyses, whereas relative risks (RRs) were used for analyses of neonatal outcomes. RESULTS: Compared with non-SGA births (>10th percentile), the HR (95% CI) of stillbirth was 18.5 (95% CI 17.4-19.5) among severe SGA births in the population analysis and 22.5 (95% CI 18.7-27.1) in the within-sibling analysis. In non-malformed infants, RRs for neonatal mortality in moderate and severe SGA infants were similarly increased in both population and within-sibling analyses. In term non-malformed infants (≥37 weeks), SGA-related RRs of several neonatal morbidities were higher in within-sibling than in population analyses. CONCLUSIONS: Perinatal risks associated with fetal growth restriction are more accurately estimated from analyses of SGA in which genetic factors are accounted for.


Assuntos
Retardo do Crescimento Fetal/epidemiologia , Mortalidade Infantil/tendências , Recém-Nascido Pequeno para a Idade Gestacional , Natimorto/epidemiologia , Peso ao Nascer , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Gravidez , Estudos Prospectivos , Irmãos , Suécia/epidemiologia
14.
Epidemiology ; 30(2): 234-242, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30516650

RESUMO

BACKGROUND: Observational cohort studies have consistently shown that maternal weight gain in pregnancy is positively associated with fetal size, but it is unknown whether the association is causal. This study investigated the effect of pregnancy weight gain on fetal growth using a sibling comparison design to control for unmeasured confounding by genetic and shared environmental factors. METHODS: Our study population included 44,457 infants (21,680 women) with electronic medical records in the Stockholm-Gotland Obstetrical Database, 2008-2014. We standardized pregnancy weight gain into gestational age-specific z-scores. Fetal size was classified as birthweight (gram), and as small- and large-for-gestational-age birth (birthweight <10th or >90th percentiles, respectively). Our sibling comparison analyses used multivariable linear fixed effects models for birthweight and hybrid logistic fixed effects models for small- and large-for-gestational-age birth (SGA and LGA). We repeated analyses using conventional (unmatched) regression models. RESULTS: Sibling comparison analyses showed a clinically meaningful association between weight gain and fetal size (e.g., adjusted difference of +89 g birthweight [95% CI = 82, 95 g]; adjusted risk ratios [aRR] for SGA of 0.80 [95% CI = 0.75, 0.86] per 1 z-score increase in weight gain for a woman of body mass index [BMI] = 25). These findings were consistent across the range of BMI. Estimates were only modestly attenuated compared with conventional approach (+97 g [95% CI = 92, 102 g], aRR for SGA of 0.70 [95% CI = 0.67, 0.73] per 1 z-score increase in weight gain). CONCLUSION: The positive association between pregnancy weight gain and fetal size we found using a sibling comparison design suggests that this relation has minimal confounding by familial factors that remain constant between pregnancies.


Assuntos
Peso ao Nascer , Desenvolvimento Fetal , Ganho de Peso na Gestação , Índice de Massa Corporal , Estudos de Coortes , Registros Eletrônicos de Saúde , Feminino , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Razão de Chances , Gravidez , Fatores de Risco , Irmãos , Suécia/epidemiologia
15.
PLoS Med ; 15(12): e1002717, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30562348

RESUMO

BACKGROUND: Small for gestational age (SGA) has been associated with increased risks of stillbirth and neonatal mortality, but data on long-term childhood mortality are scarce. Maternal antenatal care, including globally reducing the risk of SGA birth, may be key to achieving the Millennium Development Goal of reducing under-5 mortality. We therefore aimed to examine the association between SGA and mortality from 28 days to <18 years using a population-based and a sibling control design. METHODS AND FINDINGS: In a Swedish population study, we identified 3,795,603 non-malformed singleton live births and 2,781,464 full siblings born from January 1, 1973, to December 31, 2012. We examined the associations of severe (<3rd percentile) and moderate (3rd to <10th percentile) SGA with risks of death from 28 days to <18 years after birth. Children born SGA were first compared to non-SGA children from the population, and then to non-SGA siblings. The sibling-based analysis, by design, features a better control for unmeasured factors that are shared between siblings (e.g., socioeconomic status, lifestyle, and genetic factors). Hazard ratios (HRs) were calculated using Cox proportional hazards and flexible parametric survival models. During follow-up (1973-2013), there were 10,838 deaths in the population-based analysis and 1,572 deaths in sibling pairs with discordant SGA and mortality status. The crude mortality rate per 10,000 person-years was 5.32 in children born with severe SGA, 2.76 in children born with moderate SGA, and 1.93 in non-SGA children. Compared with non-SGA children, children born with severe SGA had an increased risk of death in both the population-based (HR = 2.58, 95% CI = 2.38-2.80) and sibling-based (HR = 2.61, 95% CI = 2.19-3.10) analyses. Similar but weaker associations were found for moderate SGA in the population-based (HR = 1.37, 95% CI = 1.28-1.47) and sibling-based (HR = 1.38, 95% CI = 1.22-1.56) analyses. The excess risk was most pronounced between 28 days and <1 year of age but remained throughout childhood. The greatest risk increase associated with severe SGA was noted for deaths due to infection and neurologic disease. Although we have, to our knowledge, the largest study sample so far addressing the research question, some subgroup analyses, especially the analysis of cause-specific mortality, had limited statistical power using the sibling-based approach. CONCLUSIONS: We found that SGA, especially severe SGA, was associated with an increased risk of childhood death beyond the neonatal period, with the highest risk estimates for death from infection and neurologic disease. The similar results obtained between the population- and sibling-based analyses argue against strong confounding by factors shared within families.


Assuntos
Mortalidade da Criança/tendências , Mortalidade Infantil/tendências , Recém-Nascido Pequeno para a Idade Gestacional , Nascimento Vivo/epidemiologia , Vigilância da População , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/fisiologia , Masculino , Vigilância da População/métodos , Fatores de Risco , Suécia/epidemiologia
16.
BMC Pregnancy Childbirth ; 18(1): 358, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30269686

RESUMO

BACKGROUND: The reported positive association between opiatic drug use during pregnancy and adverse pregnancy outcomes might be confounded by other factors related to high-risk behaviors, including the use of other harmful substances. In rural areas of Iran, opium use during pregnancy is relatively common among women who otherwise do not have a hazardous lifestyle, which reduces the risk of residual confounding and increasing the possibility to identify its effects. We aimed to examine the association of antenatal exposure to opium with risks of small for gestational age, short birth length, and small head circumference at birth. METHOD: In this cohort study in the rural area of the Golestan province, Iran, we randomly selected 920 women who were exposed to opium during pregnancy and 920 unexposed women during 2008-2010. Log-binomial regression was used to estimate risk ratios (RR) and 95% confidence intervals (CI) for the associations between prenatal exposure to opium and risks of small for gestational age, short birth length, and small head circumference at birth. RESULTS: Compared with non-use of opium and tobacco during pregnancy, using opium only and dual use of opium and tobacco were associated with increased risks of small for gestational age at births (RR = 1.71; 95% CI 1.34-2.18 and RR = 1.62; 95% CI 1.13-2.30, respectively). Compared with non-use of opium and tobacco, exposure to only opium or dual use of opium and tobacco were also associated with more than doubled increased risks of short birth length, and small head circumference in term infants. CONCLUSION: Maternal opium use during pregnancy is associated with increased risks of giving birth to a small for gestational age infant, as well as a term infant with short birth length or small head circumference.


Assuntos
Peso ao Nascer , Recém-Nascido Pequeno para a Idade Gestacional , Comportamento Materno , Dependência de Ópio/epidemiologia , Resultado da Gravidez/epidemiologia , Adulto , Estudos de Coortes , Comorbidade , Feminino , Humanos , Recém-Nascido , Irã (Geográfico) , Gravidez , Nascimento Prematuro/epidemiologia , Efeitos Tardios da Exposição Pré-Natal , Assunção de Riscos , Fatores Socioeconômicos , Adulto Jovem
17.
PLoS Med ; 15(7): e1002609, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30020924

RESUMO

BACKGROUND: There is evidence for long-lasting effects of birth characteristics on cognitive ability in childhood and adulthood. Further, low cognitive ability throughout the lifetime has been linked to age-related cognitive decline and dementia risk. However, little is known about the effects of birth characteristics on cognitive dysfunction late in life. Here we explore potential associations between birth characteristics (weight, head circumference, length, and gestational age), adjusted and not adjusted for gestational age, and cognitive impairment and dementia late in life. METHODS AND FINDINGS: Data from twins in the Swedish Twin Registry born 1926-1960 were merged with information from the Swedish birth, patient, and cause of death registries, resulting in a sample of 35,191 individuals. A subsample of 4,000 twins aged 65 years and older also participated in a telephone cognitive screening in 1998-2002. Associations of birth characteristics with registry-based dementia diagnoses and on telephone-assessed cognitive impairment were investigated in the full sample and subsample, respectively. The full sample contained 907 (2.6%) individuals with a dementia diagnosis (an incidence rate of 5.9% per 100,000 person-years), 803 (2.4%) individuals born small for gestational age, and 929 (2.8%) individuals born with a small head for gestational age. The subsample contained 569 (14.2%) individuals with cognitive impairment. Low birth weight for gestational age and being born with a small head for gestational age were significant risk factors for cognitive dysfunction late in life, with an up to 2-fold risk increase (p < 0.001) compared to infants with normal growth and head size, even after controlling for familial factors, childhood socioeconomic status, and education in adulthood. In line with this, each additional 100 g birth weight and each additional millimeter head circumference significantly reduced the risk for dementia (hazard ratio 0.98, 95% confidence interval 0.97 to 0.99, p = 0.004) and cognitive impairment (odds ratio 0.99, 95% confidence interval 0.99 to 1.00, p = 0.004), respectively. Within-pair analyses of identical twins, though hampered by small sample size, suggested that the observed associations between birth characteristics and dementia are likely not due to underlying shared genetic or environmental etiology. A limitation of the present study is that registry-based dementia diagnoses likely miss some of the true dementia cases in the population. Further, a more precise measure of cognitive reserve early in life as well as a date of onset for the cognitive impairment measure in the subsample would have been favorable. CONCLUSIONS: In this study, we found that infants of smaller birth size (i.e., low birth weight or small head circumference adjusted and unadjusted for gestational age) have a significantly higher risk of age-related cognitive dysfunction compared to those with normal growth, highlighting the importance of closely monitoring the cognitive development of such infants and evaluating the potential of early life interventions targeted at enhancing cognitive reserve.


Assuntos
Peso ao Nascer , Transtornos Cognitivos/psicologia , Cognição , Envelhecimento Cognitivo , Demência/psicologia , Cabeça/anatomia & histologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Cefalometria , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/epidemiologia , Demência/diagnóstico , Demência/epidemiologia , Feminino , Idade Gestacional , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Medição de Risco , Fatores de Risco , Suécia/epidemiologia
18.
Pediatrics ; 142(2)2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30021856

RESUMO

OBJECTIVES: Adverse early-life experience may affect preterm delivery later in life through priming of stress response. We aim to investigate the links between out-of-home care (OHC) experience in childhood, as a proxy of severe adversities, on subsequent risk of preterm delivery. METHODS: A register-based national cohort of all women born in Sweden between 1973 and 1977 (N = 175 821) was crosslinked with information on these women's subsequent deliveries as recorded in the Swedish medical birth register. During 1986-2012, 343 828 livebirths of these women were identified. The associations between women's OHC experience and her risk of preterm delivery were analyzed through logistic regression models, adjusting for women's own preterm birth, intrauterine growth, and childhood socioeconomic situation. RESULTS: Compared with women that never entered OHC, women with OHC experience up to and after age 10 were both associated with increased risks of preterm delivery (adjusted odds ratio [aOR] = 1.23 [95% confidence interval 1.08-1.40] and aOR = 1.29 [1.13-1.48], respectively). Women who experienced OHC before or at 10 years of age had increased risk of both spontaneous and medically indicated preterm delivery (aOR = 1.19 [1.03-1.38] and aOR = 1.27 [1.02-1.59], respectively). Women who experienced OHC after age 10 had a more pronounced risk of medically indicated preterm delivery (aOR = 1.76 [1.44-2.16]) than for spontaneous preterm delivery (aOR = 1.08 [0.92-1.27]). CONCLUSIONS: Women who were placed in OHC in childhood had increased risk of preterm delivery independent from their own perinatal history. Stress response, as 1 consequence of early life adversities, may take its toll on women's reproductive health and their offspring, calling for integrative efforts in preventing early life adversity.


Assuntos
Experiências Adversas da Infância/tendências , Criança Acolhida/psicologia , Relação entre Gerações , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/psicologia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Nascimento Prematuro/diagnóstico , Sistema de Registros , Fatores de Risco , Estresse Psicológico/diagnóstico , Estresse Psicológico/epidemiologia , Estresse Psicológico/psicologia , Suécia/epidemiologia , Adulto Jovem
19.
Int J Eat Disord ; 51(8): 906-913, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30051496

RESUMO

BACKGROUND: The etiology of anorexia nervosa is poorly understood. Although genetic factors play a major role, maternal factors, and obstetric complications are possible environmental causes. We investigated the association between maternal overweight and obesity in early pregnancy and risk of anorexia nervosa in daughters. METHODS: A retrospective cohort study including all live singleton females born in Sweden from 1992 through 2002. Anorexia nervosa diagnosis was identified by using the nation-wide Swedish Patient and Cause of Death Registers. Multivariable Cox hazards regression was used to estimate adjusted hazard ratios (aHRs) and 95% CIs, adjusting for confounders. Stratified Cox regressions were applied to data on siblings to adjust for unmeasured familial confounding. RESULTS: Among 486,688 live singleton females, 2,414 (0.50%) were diagnosed with anorexia nervosa through 2012. The aHR of anorexia nervosa decreased linearly by maternal BMI (p-value for trend < .001). When compared with daughters of normal weight mothers (body mass index [BMI] 18.5-24.9), aHRs (95%CI) of anorexia nervosa were 0.74 (0.65-0.84) in daughters of overweight mothers (BMI 25-29.9) and 0.61 (0.47-0.78) in daughters of mothers with obesity Grade I (BMI 30-34.9). In sibling control analysis, no associations were observed between maternal BMI and aHRs of anorexia nervosa in offspring. CONCLUSIONS: The rate of anorexia nervosa decreased with maternal overweight and obesity in a dose-response manner. However, the sibling control analysis suggests that these findings are not consistent with causals effects of maternal BMI on anorexia nervosa in offspring.


Assuntos
Anorexia Nervosa/diagnóstico , Índice de Massa Corporal , Obesidade/complicações , Sobrepeso/complicações , Adulto , Anorexia Nervosa/patologia , Feminino , Humanos , Masculino , Mães , Núcleo Familiar , Gravidez , Estudos Retrospectivos , Adulto Jovem
20.
Acta Obstet Gynecol Scand ; 97(11): 1373-1380, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29900536

RESUMO

INTRODUCTION: Oral moist snuff is widely used in Sweden including during pregnancy. Maternal snuff use has been associated with increased risks of adverse pregnancy outcomes in epidemiological studies. Self-reported maternal snuff use has not been validated previously. The main objective of this study was to validate self-reported snuff use in pregnancy in a prospective cohort study and in the Medical Birth Register. MATERIAL AND METHODS: A prospective Swedish cohort study, 2005-2011, in which 572 women were asked to participate. Of 474 recruited women, 381 non-smokers (263 snuff users and 118 non-tobacco users) were included in the main analyses. Participants prospectively reported snuff use through questionnaires. Medical Birth Register data on the participants was obtained. Maternal urine cotinine was collected in late pregnancy and was used as a biomarker. RESULTS: Cotinine levels in maternal urine confirmed a high validity of self-reported snuff use through questionnaires in late pregnancy; sensitivity and specificity values were 98% and 96%, respectively. In the Medical Birth Register, 45% of the snuff users were misclassified as nonusers in late pregnancy. There were significant differences in median cotinine levels between users of mini pouches and users of standard pouches, but there was a great difference of cotinine levels among users with similar number of pouches used daily. CONCLUSIONS: Self-reported snuff use through questionnaires has high validity. In the Medical Birth Register, in late pregnancy, many snuff users were misclassified as nonusers. As a consequence, there is a risk of underestimating the harmful effects of snuff use when using late pregnancy Medical Birth Register data.


Assuntos
Cotinina/urina , Autorrelato , Uso de Tabaco/epidemiologia , Tabaco sem Fumaça , Adulto , Biomarcadores/urina , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Estudos Prospectivos , Sistema de Registros , Sensibilidade e Especificidade , Suécia/epidemiologia , Uso de Tabaco/metabolismo
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