| 1. |
- 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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| 2. |
- 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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| 3. |
- Iliadou, Anastasia N., et al.
(författare)
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The Uppsala-Stockholm Assisted Reproductive Techniques (UppStART) study
- 2019
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Ingår i: BMJ Open. - : BMJ PUBLISHING GROUP. - 2044-6055. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- 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
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| 4. |
- Li, Lin, 1989-, et al.
(författare)
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Associations of Prescribed ADHD Medication in Pregnancy with Pregnancy-Related and Offspring Outcomes : A Systematic Review
- 2020
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Ingår i: CNS Drugs. - : Adis International. - 1172-7047 .- 1179-1934. ; 34:7, s. 731-747
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Increasing numbers of reproductive-aged women are using attention-deficit/hyperactivity disorder (ADHD) medications. Findings from studies exploring the safety of these medications during pregnancy are mixed, and it is unclear whether associations reflect causal effects or could be partially or fully explained by other factors that differ between exposed and unexposed offspring.OBJECTIVES: The aim of this systematic review was to evaluate the adverse pregnancy-related and offspring outcomes associated with exposure to prescribed ADHD medication during pregnancy with a focus on how studies to date have handled the influence of confounding.METHODS: We searched PubMed, Embase, PsycINFO, and Web of Science up to 1 July 2019 without any restrictions on language or date of publication. We included all observational studies (e.g., cohort studies, case-control studies, case-crossover studies, cross-sectional studies, and registry-based studies) with pregnant women of any age or from any setting who were prescribed ADHD medications and evaluated any outcome, including both short- and long-term maternal and offspring outcomes. Two independent authors then used the Newcastle-Ottawa Scale to rate the quality of the included studies.RESULTS: Eight cohort studies that estimated adverse pregnancy-related and offspring outcomes associated with exposure to ADHD medication during pregnancy were included in the qualitative review. The included studies had substantial methodological differences in data sources, type of medications examined, definitions of studied pregnancy-related and offspring outcomes, types of control groups, and confounding adjustment. There was no convincing evidence for teratogenic effects according to the relative risk of pregnancy-related and offspring outcomes, and the observed differences in absolute risks were overall small in magnitude. Adjustment for confounding was inadequate in most studies, and none of the included studies adjusted for ADHD severity in the mothers.CONCLUSION: The current evidence does not suggest that the use of ADHD medication during pregnancy results in significant adverse consequences for mother or offspring. However, the data are too limited to make an unequivocal recommendation. Therefore, physicians should consider whether the advantages of using ADHD medication outweigh the potential risks for the developing fetus according to each woman's specific circumstances. Future research should attempt to triangulate research findings based on a combination of different designs that differ in their underlying strengths and limitations and should investigate specific confounding factors, the potential impact of timing of exposure, and potential long-term outcomes in the offspring.
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| 5. |
- Sujan, Ayesha C., et al.
(författare)
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A nation-wide Swedish study of opioid analgesic prescribing patterns during pregnancy and associated preexisting mental health conditions
- 2022
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Ingår i: The Journal of Maternal-Fetal & Neonatal Medicine. - : Informa Healthcare. - 1476-7058 .- 1476-4954. ; 35:25, s. 5161-5167
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Research has consistently shown individuals with mental health conditions are more likely to be prescribed opioid analgesic medications and to engage in heavier utilization. However, it is unclear whether these findings apply to pregnant women.STUDY DESIGN: We explored opioid analgesic prescription in 689,400 pregnancies occurring in Sweden between 2007 and 2013. We investigated prescription patterns across time and type of source clinic for any opioid analgesic and for strong and weak opioid analgesics. We further evaluated the extent to which receipt of opioid analgesic medications was associated with previous mental health diagnoses and prescriptions of other psychoactive medications.RESULTS: The prevalence of pregnant women who filled prescriptions for opioid analgesics (4.5%) was relatively stable across the assessed years. However, among pregnant women who filled opioid analgesic prescriptions, there was a large increase in strong opioid analgesic prescriptions-from 6.1% in 2007 to 17.1% in 2013. The main source of opioid analgesic prescriptions were primary care and obstetrics and gynecology clinics-38.7% of all filled prescriptions originated from primary care providers and 25.3% from obstetrics and gynecology practitioners. Compared to pregnant women who did not fill any opioid analgesic prescriptions, those who did were more likely to have a wide range of pre-existing mental health diagnoses (e.g., anxiety disorder odds ratio[OR] = 3.13, 95% confidence interval[CI]:2.98,3.29) and to utilize a wide range of other psychoactive medications (e.g., benzodiazepines OR =4.26, 95% CI:4.10,4.43). Similarly, those who received strong opioids were more likely to have a wide range of mental health diagnoses and be prescribed a wide range of psychoactive medications compared to those who received weak opioids.CONCLUSIONS: These results highlight the need for physicians treating pregnant women and women of childbearing age for painful conditions to obtain detailed histories of mental health problems, screen for symptoms of mental health problems, and facilitate integrated care and evidence-based mental health interventions if needed.
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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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| 8. |
- Wiggs, Kelsey K., et al.
(författare)
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A nationwide study of initiation of antidepressant pharmacotherapy and the risk of seizures
- 2023
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Ingår i: Epilepsy Research. - : Elsevier. - 0920-1211 .- 1872-6844. ; 192
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The present study aimed to examine whether antidepressant initiation increases the risk of hospitalizations and unplanned outpatient visits for seizures. Research has provided conflicting evidence as to whether antidepressant initiation causes seizures. Because epilepsy and depression are comorbid, this remains an important question, particularly in the care of those already at-risk for seizures.METHODS: We used Swedish-register data, including 658,766 antidepressant initiators and 1:1 age-, region-, and sex-matched non-initiators, ages 12-65. We used filled prescriptions to identify any antidepressant and serotonergic antidepressant and inpatient hospitalizations and unplanned outpatient (to avoid coding routine epilepsy maintenance as a seizure) visits to identify seizures, respectively. We first compared seizure visit incidence between antidepressant-initiators and matched non-users in the year following initiation from 2006 to 2013. To examine seizure risk over months pre- and post-initiation, within-individual analyses compared risk during the month one year prior to initiation with all subsequent months. We examined associations for any antidepressant and serotonergic antidepressants, as well as for any initiator and initiators with a history of seizures.RESULTS: Our matched-cohort results showed higher incidence of seizure visits among antidepressant users compared with non-users (e.g., adjusted incidence rate ratio [IRR]=3.14, 95% confidence interval [CI]=2.83-3.49). In within-individual analyses, the months after initiation were associated with higher incidence of seizure visits when compared with the month one year prior to initiation (e.g., one month after initiation IRR=1.96, 95%CI=1.64-2.34), but in individuals with a seizure history we observed weaker or no associations in the months after initiation (e.g., two months after initiation IRR=1.12, 95%CI=0.87-1.45). Notably, irrespective of potential seizure history, the months preceding initiation were associated with the greatest risk (e.g., one month before initiation IRR=2.86, 95% CI=2.42-3.38).CONCLUSIONS: Our findings suggest that there may be an elevated risk of seizures during antidepressant treatment, though the period of highest risk was before the initiation of antidepressants. Risk for seizure visits was lower among individuals with a history of prior seizures, which may be reassuring for the clinical care of these patients or indicate lack of treatment seeking following seizures. This study highlights the need to consider seizure risk across time; the failure to account for these dynamics may help account for discrepant findings in previous studies.
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| 9. |
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