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1.
BMJ ; 368: m331, 2020 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-32075790

RESUMEN

OBJECTIVE: To assess the association between macrolide antibiotics prescribing during pregnancy and major malformations, cerebral palsy, epilepsy, attention deficit hyperactivity disorder, and autism spectrum disorder in children. DESIGN: Population based cohort study. SETTING: The UK Clinical Practice Research Datalink. PARTICIPANTS: The study cohort included 104 605 children born from 1990 to 2016 whose mothers were prescribed one macrolide monotherapy (erythromycin, clarithromycin, or azithromycin) or one penicillin monotherapy from the fourth gestational week to delivery. Two negative control cohorts consisted of 82 314 children whose mothers were prescribed macrolides or penicillins before conception, and 53 735 children who were siblings of the children in the study cohort. MAIN OUTCOME MEASURES: Risks of any major malformations and system specific major malformations (nervous, cardiovascular, gastrointestinal, genital, and urinary) after macrolide or penicillin prescribing during the first trimester (four to 13 gestational weeks), second to third trimester (14 gestational weeks to birth), or any trimester of pregnancy. Additionally, risks of cerebral palsy, epilepsy, attention deficit hyperactivity disorder, and autism spectrum disorder. RESULTS: Major malformations were recorded in 186 of 8632 children (21.55 per 1000) whose mothers were prescribed macrolides and 1666 of 95 973 children (17.36 per 1000) whose mothers were prescribed penicillins during pregnancy. Macrolide prescribing during the first trimester was associated with an increased risk of any major malformation compared with penicillin (27.65 v 17.65 per 1000, adjusted risk ratio 1.55, 95% confidence interval 1.19 to 2.03) and specifically cardiovascular malformations (10.60 v 6.61 per 1000, 1.62, 1.05 to 2.51). Macrolide prescribing in any trimester was associated with an increased risk of genital malformations (4.75 v 3.07 per 1000, 1.58, 1.14 to 2.19, mainly hypospadias). Erythromycin in the first trimester was associated with an increased risk of any major malformation (27.39 v 17.65 per 1000, 1.50, 1.13 to 1.99). No statistically significant associations were found for other system specific malformations or for neurodevelopmental disorders. Findings were robust to sensitivity analyses. CONCLUSIONS: Prescribing macrolide antibiotics during the first trimester of pregnancy was associated with an increased risk of any major malformation and specifically cardiovascular malformations compared with penicillin antibiotics. Macrolide prescribing in any trimester was associated with an increased risk of genital malformations. These findings show that macrolides should be used with caution during pregnancy and if feasible alternative antibiotics should be prescribed until further research is available. TRIAL REGISTRATION: ClinicalTrials.gov NCT03948620.


Asunto(s)
Anomalías Inducidas por Medicamentos/etiología , Antibacterianos/efectos adversos , Macrólidos/efectos adversos , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Anomalías Inducidas por Medicamentos/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/inducido químicamente , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno del Espectro Autista/inducido químicamente , Trastorno del Espectro Autista/epidemiología , Anomalías Cardiovasculares/inducido químicamente , Anomalías Cardiovasculares/epidemiología , Parálisis Cerebral/inducido químicamente , Parálisis Cerebral/epidemiología , Estudios de Cohortes , Bases de Datos Factuales , Prescripciones de Medicamentos/estadística & datos numéricos , Epilepsia/inducido químicamente , Epilepsia/epidemiología , Femenino , Humanos , Recién Nacido , Embarazo , Primer Trimestre del Embarazo , Efectos Tardíos de la Exposición Prenatal/epidemiología , Estudios Retrospectivos , Sensibilidad y Especificidad , Reino Unido/epidemiología
2.
BMJ ; 368: m237, 2020 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-32075794

RESUMEN

OBJECTIVE: To evaluate the risk of adverse maternal and infant outcomes following in utero exposure to duloxetine. DESIGN: Cohort study nested in the Medicaid Analytic eXtract for 2004-13. SETTING: Publicly insured pregnancies in the United States. PARTICIPANTS: Pregnant women 18 to 55 years of age and their liveborn infants. INTERVENTIONS: Duloxetine exposure during the etiologically relevant time window, compared with no exposure to duloxetine, exposure to selective serotonin reuptake inhibitors, exposure to venlafaxine, and exposure to duloxetine before but not during pregnancy. MAIN OUTCOME MEASURES: Congenital malformations overall, cardiac malformations, preterm birth, small for gestational age infant, pre-eclampsia, and postpartum hemorrhage. RESULTS: Cohort sizes ranged from 1.3 to 4.1 million, depending on the outcome. The number of women exposed to duloxetine varied by cohort and exposure contrast and was around 2500-3000 for early pregnancy exposure and 900-950 for late pregnancy exposure. The base risk per 1000 unexposed women was 36.6 (95% confidence interval 36.3 to 36.9) for congenital malformations overall, 13.7 (13.5 to 13.9) for cardiovascular malformations, 107.8 (107.3 to 108.3) for preterm birth, 20.4 (20.1 to 20.6) for small for gestational age infant, 33.6 (33.3 to 33.9) for pre-eclampsia, and 23.3 (23.1 to 23.4) for postpartum hemorrhage. After adjustment for measured potential confounding variables, all baseline characteristics were well balanced for all exposure contrasts. In propensity score adjusted analyses versus unexposed pregnancies, the relative risk was 1.11 (95% confidence interval 0.93 to 1.33) for congenital malformations overall and 1.29 (0.99 to 1.68) for cardiovascular malformations. For preterm birth, the relative risk was 1.01 (0.92 to 1.10) for early exposure and 1.19 (1.04 to 1.37) for late exposure. For small for gestational age infants the relative risks were 1.14 (0.92 to 1.41) and 1.20 (0.83 to 1.72) for early and late pregnancy exposure, respectively, and for pre-eclampsia they were 1.12 (0.96 to 1.31) and 1.04 (0.80 to 1.35). The relative risk for postpartum hemorrhage was 1.53 (1.08 to 2.18). Results from sensitivity analyses were generally consistent with the findings from the main analyses. CONCLUSIONS: On the basis of the evidence available to date, duloxetine is unlikely to be a major teratogen but may be associated with an increased risk of postpartum hemorrhage and a small increased risk of cardiac malformations. While continuing to monitor the safety of duloxetine as data accumulate over time, these potential small increases in risk of relatively uncommon outcomes must be weighed against the benefits of treating depression and pain during pregnancy in a given patient. TRIAL REGISTRATION: EUPAS 15946.


Asunto(s)
Clorhidrato de Duloxetina/efectos adversos , Complicaciones del Embarazo/tratamiento farmacológico , Resultado del Embarazo/epidemiología , Inhibidores de Captación de Serotonina y Norepinefrina/efectos adversos , Anomalías Inducidas por Medicamentos/epidemiología , Anomalías Inducidas por Medicamentos/etiología , Adolescente , Adulto , Estudios de Cohortes , Clorhidrato de Duloxetina/uso terapéutico , Femenino , Cardiopatías Congénitas/inducido químicamente , Cardiopatías Congénitas/epidemiología , Humanos , Recién Nacido Pequeño para la Edad Gestacional , Persona de Mediana Edad , Hemorragia Posparto/inducido químicamente , Hemorragia Posparto/epidemiología , Preeclampsia/inducido químicamente , Embarazo , Complicaciones del Embarazo/epidemiología , Nacimiento Prematuro/inducido químicamente , Nacimiento Prematuro/epidemiología , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/epidemiología , Inhibidores de Captación de Serotonina y Norepinefrina/uso terapéutico , Estados Unidos/epidemiología , Adulto Joven
3.
BMJ ; 368: l7057, 2020 01 29.
Artículo en Inglés | MEDLINE | ID: mdl-31996343

RESUMEN

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.


Asunto(s)
Fracturas Óseas , Mujeres Embarazadas/psicología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Fumar , Adulto , Factores de Edad , Niño , Correlación de Datos , Femenino , Fracturas Óseas/diagnóstico , Fracturas Óseas/epidemiología , Humanos , Lactante , Masculino , Embarazo , Sistema de Registros/estadística & datos numéricos , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Factores de Riesgo , Fumar/efectos adversos , Fumar/epidemiología , Suecia/epidemiología
4.
BMC Public Health ; 20(1): 15, 2020 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-31906901

RESUMEN

BACKGROUND: Short-term starvation has been related to hyperuricemia. However, little is known about the long-term effect of early-life exposure to famine on hyperuricemia risk in adulthood. METHODS: The analysis included 2383 participants from the China Health and Retirement Longitudinal Study in 2015. Hyperuricemia was diagnosed as serum uric acid ≥7 mg/dL in men and serum uric acid ≥6 mg/dL in women. Famine exposure subgroups were defined as unexposed (born between October 1, 1962, and September 30, 1964), fetal-exposed (born between October 1, 1959, and September 30, 1961), and early-childhood exposed (born between October 1, 1956, and September 1, 1958). The association between early-life famine exposure and hyperuricemia risk was assessed using multivariate logistic regression. RESULTS: The prevalence of hyperuricemia in the unexposed, fetal-exposed, and early-childhood exposed participants was 10.7, 14.1, 11.1%, respectively. Compared with unexposed and early-childhood exposed participants combined as an age-balanced control, fetal-exposed participants showed an increased risk of hyperuricemia in adulthood (OR = 1.41; 95% CI: 1.06-1.88), after adjusting for gender, marital status, famine severity, residence, smoking, drinking, BMI, hypertension, and diabetes. The famine effect on hyperuricemia was accentuated by overweight or obesity (P for interaction = 0.042). Compared with unexposed and BMI < 24 kg/m2 participants, the OR (95%CI) of hyperuricemia was 3.66 (2.13-6.30) for fetal-exposed and overweight/obesity participants. However, combined unexposed and early-childhood exposed participants as an age-balanced control, the interaction of famine exposure and BMI was not statistically significant (P for interaction = 0.054). CONCLUSION: Famine exposure in the fetal stage was associated with an increased risk of hyperuricemia in adulthood.


Asunto(s)
Experiencias Adversas de la Infancia/estadística & datos numéricos , Hiperuricemia/epidemiología , Efectos Tardíos de la Exposición Prenatal/epidemiología , China/epidemiología , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Embarazo , Factores de Riesgo
5.
Environ Pollut ; 256: 113340, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31662257

RESUMEN

BACKGROUND: Evidence of health effects following early life exposure to short-to-medium duration of high pollution levels is extremely limited. OBJECTIVES: We aimed to evaluate the associations between: 1. intrauterine exposure to fine particulate matter (PM2.5) from coal mine fire emissions and the frequencies of general practitioner attendances and dispensations of prescribed asthma inhalers, steroid skin creams, and antibiotics during the first year of life; 2. infant exposure and those outcomes during the year following the fire. METHODS: All participants were recruited from the Latrobe Valley of Victoria, Australia. Participants' 24-h average and hourly peak mine fire-specific PM2.5 exposures from 09/02/2014 to 31/03/2014 were estimated using chemical transport modelling. Outcome data were obtained from the Australian Medicare Benefits Schedule and Pharmaceutical Benefits Scheme from each child's birth to 31/12/2016. We used negative binomial and logistic regression models to independently assess risks of the outcomes associated with every 10 and 100 µg m-3 increase in average or peak PM2.5 exposure, respectively, while adjusting for potential confounders. RESULTS: We included 286 of 311 children whose parents consented to be linked, comprising 77 with no exposure, 88 with intrauterine exposure and 121 with exposure in infancy. 10- and 100- µg m-3 increases in average and peak PM2.5 exposure during infancy were associated with greater incidence of antibiotics being dispensed during the year following the fire: the adjusted incidence rate ratios were 1.24 (95% CI 1.02, 1.50, p = 0.036) and 1.14 (1.00, 1.31, p = 0.048) respectively. No other significant associations were observed. CONCLUSION: Exposure to coal mine fire emissions during infancy was associated with increased dispensing of antibiotics. This could reflect increased childhood infections or increased prescriptions of antibiotics in the year following the fire.


Asunto(s)
Contaminación del Aire/análisis , Asma/epidemiología , Infecciones Bacterianas/epidemiología , Dermatitis Atópica/epidemiología , Utilización de Medicamentos/estadística & datos numéricos , Exposición a Riesgos Ambientales/análisis , Efectos Tardíos de la Exposición Prenatal/epidemiología , Contaminantes Atmosféricos/análisis , Asma/terapia , Infecciones Bacterianas/terapia , Niño , Minas de Carbón , Dermatitis Atópica/terapia , Prescripciones de Medicamentos/estadística & datos numéricos , Femenino , Fuego , Humanos , Incidencia , Lactante , Masculino , Material Particulado/análisis , Embarazo , Efectos Tardíos de la Exposición Prenatal/terapia , Factores de Tiempo , Victoria/epidemiología
6.
Environ Pollut ; 256: 113307, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31733973

RESUMEN

BACKGROUND: The number of children diagnosed with autism spectrum disorder (ASD) has been increasing. Previous studies suggested potential association between pregnancy air pollution exposure and ASD. This systematic review and meta-analysis is intended to summarize the association between maternal exposure to outdoor air pollution and ASD in children by trimester based on recent studies. METHODS: A systematic literature search in 3 databases (Medline, Embase, and Web of Science) was performed using subject headings related to ASD and air pollution since 2007. Eligible studies were screened and evaluated based on predetermined criteria. For meta-analyses, the studies were grouped by air pollutant and exposure time (prenatal period and trimesters). Within-group studies were standardized by log odds ratio (OR) and then combined by three meta-analysis methods: frequentist fixed and random effects models, and Bayesian random effects model. RESULTS: Initial search identified 1564 papers, of which 25 studies remained for final analysis after duplicates and ineligible studies were removed. Of the 25 studies, 13, 14, 12, and 7 studies investigated ASD in children associated with PM2.5, PM10, NO2, and ozone, respectively. The frequentist and Bayesian random effects models resulted in different statistical significance. For prenatal period, frequentist meta-analysis returned significant pooled ORs with 95% confidence intervals, 1.06(1.01,1.11) for PM2.5 and 1.02(1.01,1.04) for NO2, whereas Bayesian meta-analysis showed similar ORs with wider 95% posterior intervals, 1.06(1.00,1.13) for PM2.5 and 1.02(1.00,1.05) for NO2. Third trimester appeared to have higher pooled ORs for PM2.5, PM10, and ozone, but patterns in the time-varying associations over the trimester were inconsistent. CONCLUSIONS: For positive association between maternal exposure to ambient air pollution and ASD in children, there is some evidence for PM2.5, weak evidence for NO2 and little evidence for PM10 and ozone. However, patterns in associations over trimesters were inconsistent among studies and among air pollutants.


Asunto(s)
Contaminantes Atmosféricos/toxicidad , Contaminación del Aire/efectos adversos , Trastorno del Espectro Autista/epidemiología , Exposición Materna/efectos adversos , Efectos Tardíos de la Exposición Prenatal/epidemiología , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Teorema de Bayes , Niño , Femenino , Humanos , Oportunidad Relativa , Ozono/análisis , Ozono/toxicidad , Material Particulado/análisis , Material Particulado/toxicidad , Embarazo
7.
BJOG ; 127(1): 39-45, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31444892

RESUMEN

OBJECTIVE: To explore the relation between famine exposure in early life and subsequent pregnancy loss, including stillbirth, and spontaneous abortion in adulthood. DESIGN: A population-based, partly ecological study. SETTING AND POPULATION: Individual data of 58 601 females born around the time of the Great Chinese Famine in 1959-1961. METHODS: Associations between the famine exposure in early life and pregnancy loss (stillbirth and spontaneous abortion) in adulthood were analysed using negative binomial regression, with the non-exposure group as reference, adjusting for region, highest education, monthly income, alcohol consumption, tobacco use, body mass index in 25-year-olds and metabolic equivalent. Further analyses were stratified by rural versus urban region. MAIN OUTCOME MEASURES: Continuous variables of times of stillbirths and spontaneous abortions were used according to the individual self-reported reproductive history. RESULTS: No association was found between famine exposure and spontaneous abortion. In contrast, females experiencing the famine during their prenatal period (incidence rate ratio = 1.15, 95% CI 1.00-1.33) or infant period (incidence rate ratio = 1.27, 95% CI 1.12-1.44) were more likely to report stillbirth in later adult life. Such an association appeared stronger in women living in rural regions. CONCLUSIONS: Early life exposure of famine was associated with an increased risk of stillbirth but not spontaneous abortion in adulthood. The strength of such an association appeared stronger in rural areas. Given the high potential for unmeasured confounding, these associations must be interpreted with caution. Regarding the potential implication that undernutrition in the fetal period is related to reproductive outcome in adulthood, fetal nutritional supply may play an important role in human reproduction. TWEETABLE ABSTRACT: Exposure to famine in early life was associated with increased pregnancy loss in adulthood.


Asunto(s)
Aborto Espontáneo/epidemiología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Mortinato/epidemiología , Adulto , Anciano , Índice de Masa Corporal , China/epidemiología , Femenino , Humanos , Estilo de Vida , Persona de Mediana Edad , Embarazo , Salud Rural
8.
BJOG ; 127(1): 8-16, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31529594

RESUMEN

BACKGROUND: With expanding recreational cannabis legalisation, pregnant women and their offspring are at risk of potentially harmful consequences. OBJECTIVES: To assess the prevalence of recreational cannabis use among pregnant women, health outcomes associated with prenatal recreational cannabis use, and the potential impact of recreational cannabis legalisation on this population. SEARCH STRATEGY: Five databases and the grey literature were systematically searched (2000-2019). SELECTION CRITERIA: Human studies published in English or French reporting on the prevalence of prenatal recreational cannabis use in high-income countries. DATA COLLECTION AND ANALYSIS: Data on study characteristics, prenatal substance use, and health outcomes were extracted and qualitatively synthesised. MAIN RESULTS: Forty-one publications met our inclusion criteria. The overall prevalence of prenatal cannabis use varied substantially (min-max: 0.24-22.6%), with the greatest use in the first trimester. In the three studies with temporal data available, rates of prenatal cannabis use increased across years. Only 7/41 and 5/41 studies provided information on gestational age of exposure and frequency of use, respectively. The concomitant use of alcohol, illicit drugs, and tobacco was higher among cannabis users than nonusers. Prenatal cannabis use was associated with select neonatal, but not maternal, health outcomes. There were insufficient data to compare prenatal cannabis use between the pre- and post-legalisation periods. CONCLUSION: Cannabis use among pregnant women is prevalent and may be associated with adverse neonatal outcomes. Future studies should assess the gestational age and frequency of cannabis exposure, and usage patterns prior to and following legalisation. TWEETABLE ABSTRACT: Women who consume cannabis during pregnancy could risk predisposing their newborns to poor birth outcomes.


Asunto(s)
Uso de la Marihuana/efectos adversos , Complicaciones del Embarazo/etiología , Países Desarrollados , Métodos Epidemiológicos , Femenino , Edad Gestacional , Humanos , Renta , Recién Nacido de Bajo Peso , Cuidado Intensivo Neonatal/estadística & datos numéricos , Uso de la Marihuana/epidemiología , Uso de la Marihuana/legislación & jurisprudencia , Salud Materna , Embarazo , Complicaciones del Embarazo/epidemiología , Resultado del Embarazo/epidemiología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Efectos Tardíos de la Exposición Prenatal/etiología
9.
Int J Gynaecol Obstet ; 148(1): 6-13, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31691277

RESUMEN

OBJECTIVE: To assess the risk of adverse fetal outcomes after exposure to oral antifungal agents during pregnancy. SEARCH STRATEGY: PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched up to October 2018. SELECTION CRITERIA: Cohort studies and case-control studies investigating fetal outcomes following maternal exposure to oral antifungal agents. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed studies for inclusion, assessed risk of bias, and extracted data. Pooled estimates were calculated for the frequency of adverse fetal outcomes. MAIN RESULTS: Overall, eight cohort studies and one case-control study were included. The oral antifungal agents used during pregnancy were fluconazole and itraconazole. The data indicated that oral fluconazole exposure during pregnancy might slightly increase the risk of congenital heart defects and limb defects relative to the general population; oral itraconazole during pregnancy might increase the risk of eye defects. No difference was found between oral fluconazole/itraconazole exposure and non-exposure in the risk of other birth defects, spontaneous abortion, or stillbirth. CONCLUSION: Oral fluconazole or itraconazole may not increase the risk of birth defects. Nonetheless, the risk of congenital heart defects and limb defects after fluconazole exposure and eye defects after itraconazole exposure should be cautiously investigated.


Asunto(s)
Antifúngicos/efectos adversos , Fluconazol/efectos adversos , Itraconazol/efectos adversos , Aborto Espontáneo/epidemiología , Aborto Espontáneo/etiología , Estudios de Casos y Controles , Estudios de Cohortes , Anomalías Congénitas/epidemiología , Anomalías Congénitas/etiología , Femenino , Humanos , Embarazo , Efectos Tardíos de la Exposición Prenatal/epidemiología , Mortinato/epidemiología
10.
BMJ ; 367: l6398, 2019 12 04.
Artículo en Inglés | MEDLINE | ID: mdl-31801789

RESUMEN

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.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Diabetes Mellitus/fisiopatología , Diabetes Gestacional/fisiopatología , Exposición Materna/efectos adversos , Efectos Tardíos de la Exposición Prenatal/epidemiología , Adulto , Enfermedades Cardiovasculares/etiología , Dinamarca/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/etiología , Adulto Joven
11.
Environ Health Prev Med ; 24(1): 74, 2019 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-31812162

RESUMEN

BACKGROUND: There have been inconsistent findings reported on maternal passive smoking during pregnancy and child risk of ADHD. In this study, ADHD symptoms at pre-school age children in association with prenatal passive and active tobacco smoke exposure determined by maternal plasma cotinine levels in the third trimester were investigated. METHODS: This was a follow-up study of the birth cohort: the Hokkaido Study on Environment and Children's Health. Children whose parents answered Strengths and Difficulties Questionnaire (SDQ) to identify child ADHD symptoms (hyperactivity/inattention and conduct problems) and total difficulties at age 5 years with available maternal plasma cotinine level at the third trimester were included (n = 3216). Cotinine levels were categorized into 4 groups; ≦ 0.21 ng/ml (non-smoker), 0.22-0.51 ng/ml (low-passive smoker), 0.52-11.48 ng/ml (high-passive smoker), and ≧ 11.49 ng/ml (active smoker). RESULTS: Maternal cotinine levels of active smokers were significantly associated with an increased risk of total difficulties (OR = 1.67) and maternal low- and high-passive smoking also increased the risk (OR = 1.11, 1.25, respectively) without statistical significance. Similarly, maternal cotinine levels of active smokers were associated with an increased risk of hyperactivity/inattention (OR = 1.49). Maternal low- and high-passive smoking and active smoking increased the risk of hyperactivity/inattention (OR = 1.45, 1.43, and OR = 1.59, respectively) only in boys. CONCLUSION: Our findings suggested that maternal active smoking during pregnancy may contribute to the increased risk of child total difficulties and hyperactivity/inattention at pre-school age. Pregnant women should be encouraged to quit smoking and avoid exposure to tobacco smoke.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/etiología , Exposición Materna/efectos adversos , Efectos Tardíos de la Exposición Prenatal/etiología , Fumar Tabaco/efectos adversos , Adulto , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Trastorno por Déficit de Atención con Hiperactividad/psicología , Preescolar , Cotinina/sangre , Femenino , Estudios de Seguimiento , Humanos , Japón/epidemiología , Masculino , Madres , Embarazo , Tercer Trimestre del Embarazo , Efectos Tardíos de la Exposición Prenatal/epidemiología , Riesgo , Factores Sexuales , Fumar Tabaco/epidemiología
12.
Medicine (Baltimore) ; 98(44): e17672, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31689782

RESUMEN

BACKGROUND: Previous studies investigated the relation of prenatal exposure to bisphenol A (BPA) and birth outcomes, but these results were inconsistent. The aim of this study was to investigate the relation of prenatal exposure to BPA and birth outcomes, provide comprehensive results based on current studies. METHODS: The PubMed, Cochrane databases, and Web of Science databases were searched systematically by two researchers respectively from their inceptions to Oct. 2018, using the following keywords "bisphenol A, birth weight, birth length, head circumference, gestational age, birth outcomes". We extracted ß coefficient and 95% confidence interval (CI) or ß coefficient and standard deviation (SD) from included study. The subgroup analysis was performed to evaluate the potential heterogeneity between studies. We conducted sensitivity analysis by excluding the each individual study to assess the results whether were stable. Finally, the publication bias was performed by accumulative forest plot. RESULTS: Seven studies with 3004 participants met the inclusion criteria. BPA had significant positively association with birth weight (ß = 21.92, 95%CI: 1.50-42.35, P = .04). No significant associations were found between BPA and birth length, head circumference and gestational age (All of P > .05). CONCLUSION: This meta-analysis demonstrated that the BPA was positively associated with birth weight. Therefore, further studies are needed to investigate the critical sensitive period of influencing fetal development and to investigate the difference on gender.


Asunto(s)
Compuestos de Bencidrilo , Peso al Nacer , Fenoles , Resultado del Embarazo/epidemiología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Femenino , Desarrollo Fetal , Edad Gestacional , Humanos , Embarazo
13.
BMC Public Health ; 19(1): 1412, 2019 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-31739791

RESUMEN

BACKGROUND: Maternal exposure to air pollution is related to fetal dysplasia. However, the association between maternal exposure to air pollution and the risk of congenital hypothyroidism (CH) in the offspring is largely unknown. METHODS: We conducted a national database based study in China to explore the association between these two parameters. The incidence of CH was collected from October 1, 2014 to October 1, 2015 from the Chinese Maternal and Child Health Surveillance Network. Considering that total period of pregnancy and consequently the total period of particle exposure is approximately 10 months, average exposure levels of PM2.5, PM10 and Air Quality Index (AQI) were collected from January 1, 2014 to January 1, 2015. Generalized additive model was used to evaluate the association between air pollution and the incidence of CH, and constructing receiver operating characteristic (ROC) curve was used to calculate the cut-off value. RESULTS: The overall incidence of CH was 4.31 per 10,000 screened newborns in China from October 1, 2014 to October 1, 2015. For every increase of 1 µg/m3 in the PM2.5 exposure during gestation could increase the risk of CH (adjusted OR = 1.016 per 1 µg/m3 change, 95% CI, 1.001-1.031). But no significant associations were found with regard to PM10 (adjusted OR = 1.009, 95% CI, 0.996-1.018) or AQI (adjusted OR = 1.012, 95% CI,0.998-1.026) and the risk of CH in the offspring. The cut-off value of prenatal PM2.5 exposure for predicting the risk of CH in the offspring was 61.165 µg/m3. CONCLUSIONS: The present study suggested that maternal exposure to PM2.5 may exhibit a positive association with increased risk of CH in the offspring. We also proposed a cut-off value of PM2.5 exposure that might determine reduction in the risk of CH in the offspring in highly polluted areas.


Asunto(s)
Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Hipotiroidismo Congénito/inducido químicamente , Exposición Materna/efectos adversos , Material Particulado/análisis , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Niño , Preescolar , China/epidemiología , Hipotiroidismo Congénito/epidemiología , Bases de Datos Factuales , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/epidemiología
14.
Pediatrics ; 144(6)2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31744890

RESUMEN

BACKGROUND AND OBJECTIVES: Fetal alcohol spectrum disorders (FASD) comprise the continuum of disabilities associated with prenatal alcohol exposure. Although infancy remains the most effective time for initiation of intervention services, current diagnostic schemes demonstrate the greatest confidence, accuracy, and reliability in school-aged children. Our aims for the current study were to identify growth, dysmorphology, and neurodevelopmental features in infants that were most predictive of FASD at age 5, thereby improving the timeliness of diagnoses. METHODS: A cohort of pregnant South African women attending primary health care clinics or giving birth in provincial hospitals was enrolled in the project. Children were followed longitudinally from birth to 60 months to determine their physical and developmental trajectories (N = 155). Standardized protocols were used to assess growth, dysmorphology, and development at 6 weeks and at 9, 18, 42, and 60 months. A structured maternal interview, including estimation of prenatal alcohol intake, was administered at 42 or 60 months. RESULTS: Growth restriction and total dysmorphology scores differentiated among children with and without FASD as early as 9 months (area under the receiver operating characteristic curve = 0.777; P < .001; 95% confidence interval: 0.705-0.849), although children who were severely affected could be identified earlier. Assessment of developmental milestones revealed significant developmental differences emerging among children with and without FASD between 18 and 42 months. Mothers of children with FASD were significantly smaller, with lower BMIs and higher alcohol intake during pregnancy, than mothers of children without FASD. CONCLUSIONS: Assessment of a combination of growth, dysmorphology, and neurobehavioral characteristics allows for accurate identification of most children with FASD as early as 9 to 18 months.


Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/psicología , Trastornos del Espectro Alcohólico Fetal/diagnóstico , Trastornos del Espectro Alcohólico Fetal/psicología , Efectos Tardíos de la Exposición Prenatal/diagnóstico , Efectos Tardíos de la Exposición Prenatal/psicología , Consumo de Bebidas Alcohólicas/epidemiología , Preescolar , Estudios de Cohortes , Femenino , Trastornos del Espectro Alcohólico Fetal/epidemiología , Humanos , Lactante , Recién Nacido , Estudios Longitudinales , Masculino , Valor Predictivo de las Pruebas , Embarazo , Efectos Tardíos de la Exposición Prenatal/epidemiología , Factores de Riesgo , Sudáfrica/epidemiología
15.
Artículo en Inglés | MEDLINE | ID: mdl-31623306

RESUMEN

This study aimed to investigate the association between environmental exposure to tobacco smoke (ETS) during early life and astigmatism in Chinese preschool children. In this cross-sectional study, information concerning prenatal and postnatal ETS exposure at three stages of early life (during pregnancy, from birth to one year and from one to three years), visual problems of children and parents (including a confirmed diagnosis of astigmatism), socio-demographics and perinatal characteristics were obtained from 27,890 parent-reported questionnaires. Logistic regression analyses were undertaken to yield adjusted odds ratios (OR) for assessing their associations. After adjusting for the potential confounders, children were more likely to exhibit astigmatism when they were exposed to ETS during pregnancy + from one to three years [OR (95% CI) = 1.37 (1.02, 1.84)], or from birth to one year + from one to three years [OR (95% CI) = 1.36 (1.11, 1.66)], or during pregnancy + from birth to one year + from one to three years old [OR (95% CI) = 1.29 (1.16, 1.45)], compared to children without ETS exposure at any stage of early life. In Chinese preschool children, prenatal and postnatal astigmatism was associated with ETS exposure; the greater the ETS dose, the greater the astigmatism risk.


Asunto(s)
Astigmatismo/etiología , Efectos Tardíos de la Exposición Prenatal/etiología , Contaminación por Humo de Tabaco/efectos adversos , Astigmatismo/epidemiología , Astigmatismo/fisiopatología , Preescolar , China/epidemiología , Estudios Transversales , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/epidemiología , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Contaminación por Humo de Tabaco/estadística & datos numéricos
16.
BJOG ; 126(13): 1588-1597, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31529591

RESUMEN

OBJECTIVE: To examine the association of prenatal alcohol exposure (PAE) on cognitive abilities and behaviour profiles of 4-year-old children. DESIGN: Prospective cohort study. SETTING: Cape Town, South Africa. POPULATION: A cohort of 500 children. METHODS: Children from the Safe Passage Study, which prospectively collected PAE, were included. Cognition and behavioural profiles were assessed. Children with and without PAE were compared. Mean scores were compared, with P ≤ 0.05 considered significant. Results were adjusted for confounding factors. MAIN OUTCOME MEASURES: The Kaufman Assessment Battery for children measured intellectual and mental ability; the NEPSY-II instrument assessed neurocognitive performance. The caregiver completed the Preschool Child Behaviour checklist to rate the child's problem behaviours and competencies. RESULTS: Two hundred children had no PAE, 117 children had mild to moderate PAE (with no binge episodes), 113 children had heavy PAE (with one or two binge episodes), and 70 children had very heavy PAE (with three or more binge episodes). Women who binge drank had significantly higher rates of smoking, marijuana use, and methamphetamine use. Low to moderate PAE had no effect on cognitive ability and behaviour. Very heavy PAE was associated with problems performing simultaneous as well as sequential functions, lower scores in the language and sensorimotor domain, and more attention and pervasive developmental problems. CONCLUSIONS: Low to moderate PAE was not associated with cognitive processing or developmental problems. Women who had many binge drinking episodes during pregnancy were the most at risk for cognitive processing, neurocognitive, and behaviour problems in their children at 4 years of age. TWEETABLE ABSTRACT: Low to moderate prenatal alcohol use was not associated with cognitive or behavioural problems in 4-year-olds.


Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Desarrollo Infantil/fisiología , Trastornos del Neurodesarrollo/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Preescolar , Femenino , Estudios de Seguimiento , Encuestas Epidemiológicas , Humanos , Masculino , Trastornos del Neurodesarrollo/epidemiología , Pruebas Neuropsicológicas , Embarazo , Efectos Tardíos de la Exposición Prenatal/epidemiología , Estudios Prospectivos , Sudáfrica/epidemiología
17.
MMWR Morb Mortal Wkly Rep ; 68(36): 777-783, 2019 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-31513558

RESUMEN

Since 1999, the rate of opioid use disorder (OUD) has more than quadrupled, from 1.5 per 1,000 delivery hospitalizations to 6.5 (1), with similar increases in incidence of neonatal abstinence syndrome (NAS) observed for infants (from 2.8 per 1,000 live births to 14.4) among Medicaid-insured deliveries (2). CDC's response to the opioid crisis involves strategies to prevent opioid overdoses and related harms by building state capacity and supporting providers, health systems, and payers.* Recognizing systems gaps in provision of perinatal care and services, CDC partnered with the Association of State and Territorial Health Officials (ASTHO) to launch the Opioid Use Disorder, Maternal Outcomes, and Neonatal Abstinence Syndrome Initiative Learning Community (OMNI LC). OMNI LC supports systems change and capacity building in 12 states.† Qualitative data from participating states were analyzed to identify strategies, barriers, and facilitators for capacity building in state-defined focus areas. Most states focused on strategies to expand access to and coordination of quality services (10 of 12) or increase provider awareness and training (nine of 12). Fewer states focused on data, monitoring, and evaluation (four of 12); financing and coverage (three of 12); or ethical, legal, and social considerations (two of 12). By building capacity to strengthen health systems, state-identified strategies across all focus areas might improve the health trajectory of mothers, infants, and families affected by the U.S. opioid crisis.


Asunto(s)
Síndrome de Abstinencia Neonatal/terapia , Trastornos Relacionados con Opioides/terapia , Complicaciones del Embarazo/terapia , Efectos Tardíos de la Exposición Prenatal/terapia , Femenino , Humanos , Lactante , Recién Nacido , Síndrome de Abstinencia Neonatal/epidemiología , Trastornos Relacionados con Opioides/epidemiología , Periodo Posparto , Embarazo , Complicaciones del Embarazo/epidemiología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Estados Unidos/epidemiología
18.
Medicine (Baltimore) ; 98(31): e16665, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31374040

RESUMEN

BACKGROUND: The aim of this study was to summarize current evidence evaluating the association between antenatal infection and intraventricular hemorrhage (IVH) in preterm infants. MATERIALS AND METHODS: We searched for published articles on antenatal infection and IVH in 3 English (PubMed, the Cochrane Library, and EBSCO) and 3 Chinese (VEIPU, CNKI, and WANFANG) databases on May 19, 2019. In addition, the references of these articles were screened. The included studies had to meet all of the following criteria: preterm infants (<37 weeks); comparing antenatal infection with no infection; the outcomes included IVH (all grades), mild IVH, or sereve IVH; the type of study was randomized controlled trial or cohort study. RESULTS: A total of 23 cohort studies involving 13,605 preterm infants met our inclusion criteria. Antenatal infection increased the risk of IVH (odds ratios ([OR] 2.18, 95% confidence intervals [CI] 1.58-2.99), mild IVH (OR 1.95, 95% CI 1.09-3.49) and severe IVH (OR 2.65, 95% CI 1.52-4.61). For type of antenatal infection, the ORs and 95% CI were as follows: 2.21 (1.60-3.05) for chorioamnionitis, 2.26 (1.55-3.28) for histologic chorioamnionitis, 1.88 (1.22-2.92) for clinical chorioamnionitis, and 1.88 (1.14-3.10) for ureaplasma. CONCLUSIONS: Antenatal infection may increase the risk of developing IVH in the preterm infant. The evidence base is however of low quality and well-designed studies are needed.


Asunto(s)
Hemorragia Cerebral Intraventricular/epidemiología , Recien Nacido Prematuro , Resultado del Embarazo/epidemiología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Peso al Nacer , Corioamnionitis/epidemiología , Femenino , Edad Gestacional , Humanos , Embarazo , Índice de Severidad de la Enfermedad
19.
Environ Res ; 177: 108630, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31421446

RESUMEN

There is increasing evidence that several metals are endocrine disrupting chemicals (EDCs). In utero development and adolescence are critical windows of susceptibility to EDC exposure. With the exception of a few heavy metals, few human studies have evaluated the impact of metal exposure on pubertal development. Our aim was to investigate measures of in utero and peripubertal metal exposure in relation to reproductive hormone levels and sexual maturation and progression among girls from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohorts. We measured urinary concentrations of aluminum (Al), arsenic (As), barium (Ba), cadmium (Cd), cobalt (Co), copper (Cu), iron (Fe), manganese (Mn), molybdenum (Mo), nickel (Ni), antimony (Sb), selenium (Se), and zinc (Zn) in samples collected from women during their third trimester of pregnancy and from their female children at 8-13 years (n = 132). We measured serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG) at age 8-13, and assessed Tanner stages for sexual maturation (breast, pubic hair development, and menarche status), at two time points (8-13, 14-18 years). We used linear regression to independently examine in utero and peripubertal metal concentrations as predictors of peripubertal hormones. In a longitudinal analysis using generalized estimation equations, we evaluated Tanner stage and menarche progression in relation to individual in utero and peripubertal metal concentrations. We found that higher in utero Zn was associated with increased inhibin B. Several metals at 8-13 years were associated with higher DHEA-S and estradiol, while Ni was positively but Cu was negatively associated with testosterone. In utero Ni, Al, and Cd were associated with slower progression of breast development after adjustment for child age and BMI z-score. For example, an IQR increase in in utero Al exposure was associated with 0.82 times lower odds of progressing to a higher Tanner stage for breast development per year (95% CI: 0.68, 0.99). Peripubertal concentrations of Ba and Al were also associated with being at a higher pubic hair Tanner stage and menarche at 8-13, but lower odds of progressing to the next stage at 14-18 years. We used Bayesian kernel machine regression (BKMR) to model the joint effect of multiple metals while accounting for correlated exposures, as well as potential non-linear relationships between metals and outcomes of interest, which yielded results similar to individual analyses. These findings suggest that female reproductive development may be vulnerable to the effects of metal exposure, and using both Tanner stages and hormone levels may provide clues about underlying mechanisms in two sensitive periods of development.


Asunto(s)
Disruptores Endocrinos/efectos adversos , Hormonas Esteroides Gonadales/sangre , Metales Pesados/efectos adversos , Efectos Tardíos de la Exposición Prenatal/epidemiología , Maduración Sexual , Adolescente , Teorema de Bayes , Niño , Ciudades , Sulfato de Deshidroepiandrosterona/sangre , Disruptores Endocrinos/orina , Estradiol/sangre , Femenino , Humanos , Inhibinas/sangre , Metales Pesados/orina , México , Embarazo , Globulina de Unión a Hormona Sexual/análisis , Testosterona/sangre
20.
Eur J Epidemiol ; 34(10): 927-938, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31451995

RESUMEN

Self-selection into prospective cohort studies and loss to follow-up can cause biased exposure-outcome association estimates. Previous investigations illustrated that such biases can be small in large prospective cohort studies. The structural approach to selection bias shows that general statements about bias are not possible for studies that investigate multiple exposures and outcomes, and that inverse probability of participation weighting (IPPW) but not adjustment for participation predictors generally reduces bias from self-selection and loss to follow-up. We propose to substantiate assumptions in structural models of selection bias through calculation of genetic correlations coefficients between participation predictors, outcome, and exposure, and to estimate a lower bound for bias due to self-selection and loss to follow-up by comparing effect estimates from IPP weighted and unweighted analyses. This study used data from the Norwegian Mother and Child Cohort Study and the Medical Birth Registry of Norway. Using the example of risk factors for ADHD, we find that genetic correlations between participation predictors, exposures, and outcome suggest the presence of bias. The comparison of exposure-outcome associations from regressions with and without IPPW revealed meaningful deviations. Assessment of selection bias for entire multi-exposure multi-outcome cohort studies is not possible. Instead, it has to be assessed and controlled on a case-by-case basis.


Asunto(s)
Trastornos Generalizados del Desarrollo Infantil/epidemiología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Sesgo de Selección , Sesgo , Trastornos Generalizados del Desarrollo Infantil/etiología , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Noruega/epidemiología , Embarazo , Estudios Prospectivos , Factores de Riesgo
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