Carryover Effects in Sibling Comparison Designs

Sjölander, Arvid; Frisell, Thomas; Kuja‐Halkola, Ralf; Öberg, Sara; Zetterqvist, Johan

doi:10.1097/ede.0000000000000541

Cited by 106 publications

(123 citation statements)

References 8 publications

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“…In addition to the pregnancies having to be exchangeable with respect to covariates, there can also be no carry‐over effect of the exposure itself . The extent to which this assumption holds for sibling comparison studies of interpregnancy intervals is unclear, and it is worth noting that the design was intended primarily for transient or acute exposures. One could speculate that any effects of close pregnancy spacing mediated through nutritional status could differ if there was a cumulative effect of nutritional depletion over three, rather than two, pregnancies .…”

Section: Sibling Comparison Studiesmentioning

confidence: 99%

Good practices for the design, analysis, and interpretation of observational studies on birth spacing and perinatal health outcomes

Hutcheon

Moskosky

Ananth

et al. 2018

Paediatric Perinatal Epid

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Background Meta‐analyses of observational studies have shown that women with a shorter interpregnancy interval (the time from delivery to start of a subsequent pregnancy) are more likely to experience adverse pregnancy outcomes, such as preterm delivery or small for gestational age birth, than women who space their births further apart. However, the studies used to inform these estimates have methodological shortcomings. Methods In this commentary, we summarise the discussions of an expert workgroup describing good practices for the design, analysis, and interpretation of observational studies of interpregnancy interval and adverse perinatal health outcomes. Results We argue that inferences drawn from research in this field will be improved by careful attention to elements such as: (a) refining the research question to clarify whether the goal is to estimate a causal effect vs describe patterns of association; (b) using directed acyclic graphs to represent potential causal networks and guide the analytic plan of studies seeking to estimate causal effects; (c) assessing how miscarriages and pregnancy terminations may have influenced interpregnancy interval classifications; (d) specifying how key factors such as previous pregnancy loss, pregnancy intention, and maternal socio‐economic position will be considered; and (e) examining if the association between interpregnancy interval and perinatal outcome differs by factors such as maternal age. Conclusion This commentary outlines the discussions of this recent expert workgroup, and describes several suggested principles for study design and analysis that could mitigate many potential sources of bias.

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Section: Sibling Comparison Studiesmentioning

confidence: 99%

Good practices for the design, analysis, and interpretation of observational studies on birth spacing and perinatal health outcomes

Hutcheon

Moskosky

Ananth

et al. 2018

Paediatric Perinatal Epid

View full text Add to dashboard Cite

show abstract

“…Such designs, while informative, are not without potential limitations (e.g. carryover effects) and do not completely rule out a causal effect of pre‐pregnancy obesity. Continued research using a variety of study designs such as these and others (e.g.…”

Section: Discussionmentioning

confidence: 99%

Maternal pre‐pregnancy obesity and child neurodevelopmental outcomes: a meta‐analysis

et al. 2017

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This review examined evidence of the association between maternal pre-pregnancy overweight/obesity status and child neurodevelopmental outcomes. PubMed and PsycINFO databases were systematically searched for empirical studies published before April 2017 using keywords related to prenatal obesity and children's neurodevelopment. Of 1483 identified papers, 41 were included in the systematic review, and 32 articles representing 36 cohorts were included in the meta-analysis. Findings indicated that compared with children of normal weight mothers, children whose mothers were overweight or obese prior to pregnancy were at increased risk for compromised neurodevelopmental outcomes (overweight: OR = 1.17, 95% CI [1.11, 1.24], I = 65.51; obese: OR = 1.51; 95% CI [1.35, 1.69], I = 79.63). Pre-pregnancy obesity increased the risk of attention deficit-hyperactivity disorder (OR = 1.62; 95% CI [1.23, 2.14], I = 70.15), autism spectrum disorder (OR = 1.36; 95% CI [1.08, 1.70], I = 60.52), developmental delay (OR = 1.58; 95% CI [1.39, 1.79], I = 75.77) and emotional/behavioural problems (OR = 1.42; 95% CI [1.26, 1.59], I = 87.74). Given the current obesity prevalence among young adults and women of childbearing age, this association between maternal obesity during pregnancy and atypical child neurodevelopment represents a potentially high public health burden.

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“…First, the sibling-controlled design does not rule out factors that vary between siblings, correlate with exposure within families, or correlate with the outcome [39, 40]. The inclusion of an estimated PS in the sibling analyses accounting for the observed factors shown to be associated with BZD and z-hypnotics use helped control for these factors in the current study.…”

Section: Discussionmentioning

confidence: 99%

Association of prenatal exposure to benzodiazepines and child internalizing problems: A sibling-controlled cohort study

et al. 2017

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BackgroundDuring pregnancy, many women experience sleep problems and anxiety that require treatment. The long-term safety for the child of maternal benzodiazepine (BZD) and z-hypnotic use during pregnancy remains controversial.MethodWe conducted a cohort and a sibling control study using data from the Norwegian Mother and Child Cohort Study. Data on use of BZD and z-hypnotics, internalizing and externalizing outcomes, and covariates were collected from mothers at gestational weeks 17 and 30 and when children were 0.5, 1.5, and 3 years of age. The total sample consisted of 71,996 children (19,297 siblings) at 1.5 years and 55,081 children (13,779 siblings) at 3 years. Short-term use was defined as use in one pregnancy period only. Long-term use was defined as use in two or more pregnancy periods. Linear full cohort random-effect and sibling-matched fixed-effect regression models were used to compare internalizing and externalizing behavior in children prenatally exposed compared to those unexposed in the full cohort of pregnancies accounting for family clusters, as well as within sibling clusters comparing pregnancies with discordant exposures. Propensity score (PS) adjustment included variables on indication for use (sleep problems, symptoms of anxiety and depression) and other potential confounding factors.ResultsLong-term prenatal exposure to BZD or z-hypnotics was associated with increased internalizing behavior in crude cohort analyses and at age 1.5 years after PS adjustment in sibling-matched fixed-effect models [β 0.60, 95% confidence interval 0.17–0.95]. Analyses on specific drug groups showed that prenatal exposure to BZD-anxiolytics was associated with increased internalizing problems at both 1.5 years [β 0.25, 0.01–0.49] and 3 years [β 0.26, 0.002–0.52] while exposure to z-hypnotics was not associated with any adverse outcomes after adjustment.ConclusionThe findings suggest a moderate association between BZD-anxiolytic exposure and child internalizing problems that is not likely due to stable familial confounding factors.

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Carryover Effects in Sibling Comparison Designs

Cited by 106 publications

References 8 publications

Good practices for the design, analysis, and interpretation of observational studies on birth spacing and perinatal health outcomes

Good practices for the design, analysis, and interpretation of observational studies on birth spacing and perinatal health outcomes

Maternal pre‐pregnancy obesity and child neurodevelopmental outcomes: a meta‐analysis

Association of prenatal exposure to benzodiazepines and child internalizing problems: A sibling-controlled cohort study

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