| 1. |
- Class, Quetzal A., et al.
(författare)
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Outcome-dependent associations between short interpregnancy interval and offspring psychological and educational problems : a population-based quasi-experimental study
- 2018
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Ingår i: International Journal of Epidemiology. - Stockholm : Oxford University Press. - 0300-5771 .- 1464-3685. ; 47:4, s. 1159-1168
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Tidskriftsartikel (refereegranskat)abstract
- Background: Causal interpretation of associations between short interpregnancy interval (the duration from the preceeding birth to the conception of the next-born index child) and the offspring's psychological and educational problems may be influenced by a failure to account for unmeasured confounding.Methods: Using population-based Swedish data from 1973-2009, we estimated the association between interpregnancy interval and outcomes [autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), severe mental illness, suicide attempt, criminality, substance-use problem and failing grades] while controlling for measured covariates. We then used cousin comparisons, post-birth intervals (the interval between the second-and third-born siblings to predict second-born outcomes) and sibling comparisons to assess the influence of unmeasured confounding. We included an exploratory analysis of long interpregnancy interval.Results: Interpregnancy intervals of 0-5 and 6-11 months were associated with higher odds of outcomes in cohort analyses. Magnitudes of association were attenuated following adjustment for measured covariates. Associations were eliminated for ADHD, severe mental illness and failing grades, but maintained magnitude for ASD, suicide attempt, criminality and substance-use problem in cousin comparisons. Post-birth interpregnancy interval and sibling comparisons suggested some familial confounding. Associations did not persist across models of long interpregnancy interval.Conclusions: Attenuation of the association in cousin comparisons and comparable post-birth interval associations suggests that familial genetic or environmental confounding accounts for a majority of the association for ADHD, severe mental illness and failing grades. Modest associations appear independently of covariates for ASD, suicide attempt, criminality and substance-use problem. Post-birth analyses and sibling comparisons, however, show some confounding in these associations.
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| 2. |
- D'Onofrio, Brian M., et al.
(författare)
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Translational Epidemiologic Approaches to Understanding the Consequences of Early-Life Exposures
- 2016
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Ingår i: Behavior Genetics. - New York, USA : Springer. - 0001-8244 .- 1573-3297. ; 46:3, s. 315-328
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Forskningsöversikt (refereegranskat)abstract
- Prominent developmental theories posit a causal link between early-life exposures and later functioning. Yet, observed associations with early exposures may not reflect causal effects because of genetic and environmental confounding. The current manuscript describes how a systematic series of epidemiologic analyses that combine several genetically-informative designs and statistical approaches can help distinguish between competing theories. In particular, the manuscript details how combining the use of measured covariates with sibling-comparisons, cousin-comparisons, and additional designs can help elucidate the sources of covariation between early-life exposures and later outcomes, including the roles of (a) factors that are not shared in families, including a potential causal effect of the exposure; (b) carryover effects from the exposure of one child to the next; and (c) familial confounding. We also describe key assumptions and how they can be critically evaluated. Furthermore, we outline how subsequent analyses, including effect decomposition with respect to measured, plausible mediators, and quantitative genetic models can help further specify the underlying processes that account for the associations between early-life exposures and offspring outcomes.
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| 3. |
- Sujan, Ayesha C., et al.
(författare)
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A Genetically Informed Study of the Associations Between Maternal Age at Childbearing and Adverse Perinatal Outcomes
- 2016
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Ingår i: Behavior Genetics. - New York, USA : Springer. - 0001-8244 .- 1573-3297. ; 46:3, s. 431-456
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Tidskriftsartikel (refereegranskat)abstract
- We examined associations of maternal age at childbearing (MAC) with gestational age and fetal growth (i.e., birth weight adjusting for gestational age), using two genetically informed designs (cousin and sibling comparisons) and data from two cohorts, a population-based Swedish sample and a nationally representative United States sample. We also conducted sensitivity analyses to test limitations of the designs. The findings were consistent across samples and suggested that, associations observed in the population between younger MAC and shorter gestational age were confounded by shared familial factors; however, associations of advanced MAC with shorter gestational age remained robust after accounting for shared familial factors. In contrast to the gestational age findings, neither early nor advanced MAC was associated with lower fetal growth after accounting for shared familial factors. Given certain assumptions, these findings provide support for a causal association between advanced MAC and shorter gestational age. The results also suggest that there are not causal associations between early MAC and shorter gestational age, between early MAC and lower fetal growth, and between advanced MAC and lower fetal growth.
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| 4. |
- Sujan, Ayesha C., et al.
(författare)
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A population-based study of concurrent prescriptions of opioid analgesic and selective serotonin reuptake inhibitor medications during pregnancy and risk for adverse birth outcomes
- 2021
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Ingår i: Paediatric and Perinatal Epidemiology. - : Blackwell Science Ltd.. - 0269-5022 .- 1365-3016. ; 35:2, s. 184-193
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pregnant women with painful conditions often have mental health problems, including depression and anxiety. Co-morbid conditions may cause pregnant women to use multiple medications, although safety of such practice is poorly understood.OBJECTIVES: We investigated the influence of combined prescriptions of opioid analgesics and selective serotonin reuptake inhibitors (SSRIs) during pregnancy on two adverse birth outcomes.METHODS: We analysed Swedish population-based births (n = 688 914) between 2007 and 2013. Using national registers, we obtained data on filled medication prescriptions, birth outcomes, and a wide range of parental characteristics. We estimated preterm birth and small-for-gestational-age risk following independent or combined prescriptions of the two medications compared with no filled prescriptions for either medication. We adjusted for confounders using inverse probability of treatment weights.RESULTS: After adjusting for confounders, preterm birth risk was higher among women with opioid analgesic prescriptions only (5.9%; risk ratio [RR] 1.27, 95% confidence interval [CI] 1.22, 1.33), SSRIs only (6.2%; RR 1.34, 95% CI 1.27, 1.42), and both medications (7.8%; RR 1.70, 95% CI 1.47, 1.96) compared with unexposed women (4.6%). The interaction between the medications on preterm birth was small (risk difference [RD] 0.4%, 95% CI -0.8%, 1.6%); relative excess risk due to interaction [RERI] 0.09, 95% CI -0.17, 0.34; RR 1.00, 95% CI 0.85, 1.17). For small for gestational age, risk was approximately 2% across all groups, and there was no interaction between the medications (RD 0.3%, 95% CI -0.4%, 1.1%); RERI 0.15, 95% CI -0.16, 0.47; RR 1.15, 95% CI 0.87, 1.52).CONCLUSIONS: Compared with unexposed pregnancies, those with either medication alone had a small increased risk for preterm birth but no increased risk for small for gestational age. The magnitude of associations with combined exposure to both medications were not greater than the sum of the associations with each medication considered individually.
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| 5. |
- Sujan, Ayesha C, et al.
(författare)
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Associations of maternal antidepressant use during the first trimester of pregnancy with preterm birth, small for gestational age, autism spectrum disorder, and attention-deficit/hyperactivity disorder in offspring
- 2017
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Ingår i: JAMA. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0098-7484 .- 1538-3598.
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Prenatal antidepressant exposure has been associated with adverse outcomes. Previous studies, however, may not have adequately accounted for confounding. Objective: To evaluate alternative hypotheses for associations between first-trimester antidepressant exposure and birth and neurodevelopmental problems. Design, Setting, and Participants: This retrospective cohort study included Swedish offspring born between 1996 and 2012 and followed up through 2013 or censored by death or emigration. Analyses controlling for pregnancy, maternal and paternal covariates, as well as sibling comparisons, timing of exposure comparisons, and paternal comparisons, were used to examine the associations. Exposures: Maternal self-reported first-trimester antidepressant use and first-trimester antidepressant dispensations. Main Outcomes and Measures: Preterm birth (<37 gestational weeks), small for gestational age (birth weight <2 SDs below the mean for gestational age), and first inpatient or outpatient clinical diagnosis of autism spectrum disorder and attention-deficit/hyperactivity disorder in offspring. Results: Among 1580629 offspring (mean gestational age, 279 days; 48.6% female; 1.4% [n = 22544] with maternal first-trimester self-reported antidepressant use) born to 943776 mothers (mean age at childbirth, 30 years), 6.98% of exposed vs 4.78% of unexposed offspring were preterm, 2.54% of exposed vs 2.19% of unexposed were small for gestational age, 5.28% of exposed vs 2.14% of unexposed were diagnosed with autism spectrum disorder by age 15 years, and 12.63% of exposed vs 5.46% of unexposed were diagnosed with attention-deficit/hyperactivity disorder by age 15 years. At the population level, first-trimester exposure was associated with all outcomes compared with unexposed offspring (preterm birth odds ratio [OR], 1.47 [95% CI, 1.40-1.55]; small for gestational age OR, 1.15 [95% CI, 1.06-1.25]; autism spectrum disorder hazard ratio [HR], 2.02 [95% CI, 1.80-2.26]; attention-deficit/hyperactivity disorder HR, 2.21 [95% CI, 2.04-2.39]). However, in models that compared siblings while adjusting for pregnancy, maternal, and paternal traits, first-trimester antidepressant exposure was associated with preterm birth (OR, 1.34 [95% CI, 1.18-1.52]) but not with small for gestational age (OR, 1.01 [95% CI, 0.81-1.25]), autism spectrum disorder (HR, 0.83 [95% CI, 0.62-1.13]), or attention-deficit/hyperactivity disorder (HR, 0.99 [95% CI, 0.79-1.25]). Results from analyses assessing associations with maternal dispensations before pregnancy and with paternal first-trimester dispensations were consistent with findings from the sibling comparisons. Conclusions and Relevance: Among offspring born in Sweden, after accounting for confounding factors, first-trimester exposure to antidepressants, compared with no exposure, was associated with a small increased risk of preterm birth but no increased risk of small for gestational age, autism spectrum disorder, or attention-deficit/hyperactivity disorder.
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| 6. |
- Sujan, Ayesha C., et al.
(författare)
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Associations of Maternal Antidepressant Use During the First Trimester of Pregnancy With Preterm Birth, Small for Gestational Age, Autism Spectrum Disorder, and Attention-Deficit/Hyperactivity Disorder in Offspring
- 2017
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Ingår i: Obstetrical and Gynecological Survey. - : Lippincott Williams & Wilkins. - 0029-7828 .- 1533-9866. ; 72:9, s. 523-524
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Tidskriftsartikel (refereegranskat)abstract
- While antidepressant use during pregnancy has been associated with adverse birth and neurodevelopmental outcomes, these associations may be attributed to confounding factors, such as genetic influences, maternal stress, or poor health practices during pregnancy. This study used 4 observational designs to investigate these associations, including sibling and paternal information.The study used multiple national Swedish registries. First-trimester exposures, defined as at least 1 dispensation between 90 days before estimated conceptions and 90 days after estimated conception, to any antidepressants and selective serotonin reuptake inhibitors, reported through either maternal self-report or dispensation records, were the main exposures evaluated. The main outcomes were small for gestational age, defined as birth weight less than 2 SDs below the mean for gestational age; preterm birth, defined as less than 37 gestational weeks; and diagnosis of autism spectrum disorder or attention-deficit/hyperactivity disorder (ADHD). Maternal and paternal covariates included age of childbearing, highest level of completed education, history of criminal conviction, history of psychiatric illnesses, history of suicide attempts, and country of origin (Sweden or outside Sweden). Parity and year of birth were pregnancy covariates. Population-wide baseline models were assessed adjusting only for pregnancy covariates. Then, population-wide associations were adjusted for maternal and paternal covariates as well. A third model compared exposure-and outcome-discordant offspring within families.After exclusion of multiple births, missing father identifiers, or other missing information, a final cohort of 1,580,629 offspring born to 943,776 was used. Of these, 26,477 offspring had first-trimester maternal antidepressant dispensations, 22,125 of which were selective serotonin reuptake inhibitor dispensations. Preterm births accounted for 6.98% of exposed and 4.78% of unexposed offspring. In the baseline models, first-trimester exposure was associated with all 4 outcomes (preterm birth odds ratio [OR], 1.47; 95% confidence interval [CI], 1.40-1.55]; small for gestational age OR, 1.15 [95% CI, 1.06-1.25]; ADHD HR, 2.21 [95% CI, 2.04-2.39]). After adjusting for pregnancy and maternal and paternal traits and comparing sibling data, first-trimester antidepressant exposure was associated with only a small increased risk of preterm birth (OR, 1.34 [95% CI, 1.18-1.52]) and was not associated with small for gestational age (OR, 1.01 [95% CI, 0.81-1.25]), ADHD (HR, 0.99 [95% CI, 0.79-1.25]), or autism spectrum disorder (HR, 0.83 [95% CI, 0.62-1.13]).Unexposed and exposed siblings were found to be at equal risk of small for gestational age, ADHD, and autism spectrum disorder as one another, whereas exposed siblings had a slightly increased risk of preterm birth. Both autism spectrum disorder and ADHD were associated with paternal first-trimester antidepressant dispensations, supporting the idea that familial confounding may explain associations between exposure and neurodevelopmental disorders.
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| 7. |
- Sujan, Ayesha C., et al.
(författare)
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Maternal prescribed opioid analgesic use during pregnancy and associations with adverse birth outcomes : A population-based study
- 2019
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 16:12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Published research on prescribed opioid analgesic (POA) use during pregnancy and birth outcomes is limited in scope and has not adequately adjusted for potential confounding factors. To help address these gaps, we estimated associations between maternal POAs during pregnancy and two adverse birth outcomes using a large population-based dataset, multiple definitions of POA exposure, and several methods to evaluate the influence of both measured and unmeasured confounding factors.METHODS AND FINDINGS: We obtained data by linking information from several Swedish registers and conducted a retrospective cohort study on a population-based sample of 620,458 Swedish births occurring between 2007 and 2013 (48.6% female; 44.4% firstborn). We evaluated associations between prenatal POA exposure and risk for preterm birth (PTB; <37 gestational weeks) and small for gestational age (SGA; birth weight 2 standard deviations below the expected weight for gestational age or lower). We evaluated the influence of confounding by adjusting for a wide range of measured covariates while comparing exposed and unexposed infants. Additionally, we adjusted for unmeasured confounding factors by using several advanced epidemiological designs. Infants exposed to POAs anytime during pregnancy were at increased risk for PTB compared with unexposed infants (6.4% exposed versus 4.4% unexposed; adjusted odds ratio [OR] = 1.38, 95% confidence interval [CI] 1.31-1.45, p < 0.001). This association was attenuated when we compared POA-exposed infants with acetaminophen-exposed infants (OR = 1.18, 95% CI 1.07-1.30, p < 0.001), infants born to women who used POAs before pregnancy only (OR = 1.05, 95% CI 0.96-1.14, p = 0.27), and unexposed siblings (OR = 0.99, 95% CI 0.85-1.14, p = 0.92). We also evaluated associations with short-term versus persistent POA use during pregnancy and observed a similar pattern of results, although the magnitudes of associations with persistent exposure were larger than associations with any use or short-term use. Although short-term use was not associated with SGA (adjusted ORsingle-trimester = 0.95, 95% CI 0.87-1.04, p = 0.29), persistent use was associated with increased risk for SGA (adjusted ORmultiple-trimester = 1.40, 95% CI 1.17-1.67, p < 0.001) compared with unexposed infants. The association with persistent exposure was attenuated when we used alternative comparison groups (e.g., sibling comparison OR = 1.22, 95% CI 0.60-2.48, p = 0.58). Of note, our study had limitations, including potential bias from exposure misclassification, an inability to adjust for all sources of confounding, and uncertainty regarding generalizability to countries outside of Sweden.CONCLUSIONS: Our results suggested that observed associations between POA use during pregnancy and risk of PTB and SGA were largely due to unmeasured confounding factors, although we could not rule out small independent associations, particularly for persistent POA use during pregnancy.
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