Mediation Analysis in Sibling Designs: An Application to the Effect of Prenatal Antidepressant Exposure on Toddler Depression Mediated by Gestational Age at Birth

Abstract Background: Mediation analysis requires strong assumptions of no unmeasured confounding. Sibling designs offer a method for controlling confounding shared within families, but no previous research has done mediation analysis using sibling models. Methods: We demonstrate the validity of the sibling mediation approach using simulation, and show its application using the example of prenatal antidepressant exposure and toddler anxiety and depression, with gestational age at birth as a mediator. We used data from the Norwegian Mother and Child Cohort Study, a cohort comprising 41% of births in Norway between 1999 and 2008 to identify 91,333 pregnancies, of which 25,776 were part of sibling groups. Results: In simulations, sibling models were less biased than cohort models in cases where non-shared confounding was weaker than shared confounding, and when stronger non-shared confounding was controlled, but more biased otherwise. In the full cohort, the estimated mean difference in depression/anxiety scale z-scores for natural direct effects (NDE) were 0.31 (95% confidence interval 0.23 to 0.39) and 0.14 (95% CI 0.03 to 0.24), without and with adjustment for non-shared confounders, respectively. The natural indirect effect was 0.01 (95% CI 0.00 to 0.02) after adjustment. Adjustment for shared and non-shared confounding showed similar point estimates with wider confidence intervals (NDE 0.18, 95% CI -0.21 to 0.47; NIE -0.01, 95% CI -0.06 to 0.06).Conclusions: Findings suggest that the modest association between prenatal antidepressant exposure and anxiety/depression is not mediated by gestational age and is likely explained by both shared confounders and non-shared confounders, and chance.

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Mediation analysis in sibling designs: an application to the effect of prenatal antidepressant exposure on toddler depression mediated by gestational age at birth

10.1101/2020.06.11.20128496 ◽

2020 ◽

Author(s):

Mollie E. Wood ◽

Espen Eilertsen ◽

Eivind Ystrom ◽

Hedvig Nordeng ◽

Sonia Hernandez-Diaz

Keyword(s):

Gestational Age ◽

Mediation Analysis ◽

Full Cohort ◽

Point Estimates ◽

Mother And Child ◽

Sibling Models ◽

Z Scores ◽

Gestational Age At Birth ◽

Anxiety Depression ◽

Age At Birth

AbstractBackgroundMediation analysis requires strong assumptions of no unmeasured confounding. Sibling designs offer a method for controlling confounding shared within families, but no previous research has done mediation analysis using sibling models.MethodsWe demonstrate the validity of the sibling mediation approach using simulation, and show its application using the example of prenatal antidepressant exposure and toddler anxiety and depression, with gestational age at birth as a mediator. We used data from the Norwegian Mother and Child Cohort Study, a cohort comprising 41% of births in Norway between 1999 and 2008 to identify 91,333 pregnancies, of which 25,776 were part of sibling groups.ResultsIn simulations, sibling models were less biased than cohort models in cases where non-shared confounding was weaker than shared confounding, and when stronger non-shared confounding was controlled, but more biased otherwise. In the full cohort, the estimated mean difference in depression/anxiety scale z-scores for natural direct effects (NDE) were 0.31 (95% confidence interval 0.23 to 0.39) and 0.14 (95% CI 0.03 to 0.24), without and with adjustment for non-shared confounders, respectively. The natural indirect effect was 0.01 (95% CI 0.00 to 0.02) after adjustment. Adjustment for shared and non-shared confounding showed similar point estimates with wider confidence intervals (NDE 0.18, 95% CI −0.21 to 0.47; NIE −0.01, 95% CI −0.06 to 0.06).ConclusionsFindings suggest that the modest association between prenatal antidepressant exposure and anxiety/depression is not mediated by gestational age and is likely explained by both shared confounders and non-shared confounders, and chance.

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Cost Comparison of Prenatal Myelomeningocele Closure Versus Postnatal Closure for Both Mother and Child at 1 year of Life

Neurosurgery ◽

10.1093/neuros/nyz310_199 ◽

2019 ◽

Vol 66 (Supplement_1) ◽

Author(s):

Brice A Kessler ◽

Carolyn Quinsey ◽

William Goodnight ◽

Scott Elton

Keyword(s):

Gestational Age ◽

The United States ◽

Cost Of Care ◽

Cost Comparison ◽

Charge Ratio ◽

Hospital Perspective ◽

Shunt Placement ◽

Mother And Child ◽

Gestational Age At Birth ◽

Age At Birth

Abstract INTRODUCTION Prenatal myelomeningocele (MMC) closure has been performed in the United States for 2 decades, though economic impact in terms of cost to the hospital when comparing prenatal to postnatal MMC closure is unclear. METHODS A prospective database of patients undergoing prenatal and postnatal MMC closure between 2011 and 2018 with 1 yr follow up was reviewed. Charge data for relevant admissions was converted to a cost estimate using our institution's Medicare hospital-specific cost-to-charge ratio and corrected to the 2018 US dollar. Children, mothers, and mother/child pairs were considered separately. Additional data included length of stay (LOS), gestational age at birth, readmission, and need for ventriculoperitoneal shunt placement. RESULTS Average cost to prenatal MMC closure children was $67,331.49 (median $58,406.71), compared to $89,502.01 (median $49,889.95) for postnatal MMC closure children (P = .28). Cost to prenatal MMC closure mothers was $28,476.12 (median $24,548.29), compared to $5039.27 (median $5,087.30) (P < .001). Cost of care for prenatal MMC closure mother/child pairs was $95,803.11 (median $102,377.75), compared to $94,541.28 (median $55,667.82) (P = .45). Prenatal MMC closure children had shorter gestational age at birth (235.81 d vs 265.77 d, P < .001), fewer readmissions (33.3% vs 72.7%, P < .001), and shunt placement was less common (33.3% vs 90.9%, P < .001). Prenatal MMC closure mothers had longer total LOS (15.92 d vs 4.68 d, P < .001) and more readmissions (18.5% vs 0.0%, P = .06). Total LOS for prenatal MMC closure mother/child pairs was 43.70 d compared to 30.41 d, though not significant (P = .09). CONCLUSION Cost of prenatal versus postnatal MMC closure did not significantly differ from a hospital perspective at 1 yr. When considering the mother alone, prenatal MMC closure was costlier. Future work is needed assessing cost from a patient and societal perspective both at 1 yr and beyond.

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Gestational Age at Birth, 1994 and 2004

PsycEXTRA Dataset ◽

10.1037/e411542008-001 ◽

2006 ◽

Keyword(s):

Gestational Age ◽

Gestational Age At Birth ◽

Age At Birth

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Faculty Opinions recommendation of Effects of gestational age at birth on health outcomes at 3 and 5 years of age: population based cohort study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.14264188.15777343 ◽

2012 ◽

Author(s):

Mark Sullivan

Keyword(s):

Cohort Study ◽

Health Outcomes ◽

Gestational Age ◽

Population Based ◽

Gestational Age At Birth ◽

Age At Birth

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Prenatal household air pollutant exposure is associated with reduced size and gestational age at birth among a cohort of Ghanaian infants

Environment International ◽

10.1016/j.envint.2021.106659 ◽

2021 ◽

Vol 155 ◽

pp. 106659

Author(s):

Ashlinn K. Quinn ◽

Irene Apewe Adjei ◽

Kenneth Ayuurebobi Ae-Ngibise ◽

Oscar Agyei ◽

Ellen Abrafi Boamah-Kaali ◽

...

Keyword(s):

Gestational Age ◽

Air Pollutant ◽

Gestational Age At Birth ◽

Age At Birth

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Coeliac disease presenting atypically: A much wider spectrum

Tropical Doctor ◽

10.1177/0049475521991348 ◽

2021 ◽

pp. 004947552199134

Author(s):

Avinash Lomash ◽

Abhinaya Venkatakrishnan ◽

Meenakshi Bothra ◽

Bhavna Dhingra ◽

Praveen Kumar ◽

...

Keyword(s):

Coeliac Disease ◽

Gestational Age ◽

Dermatitis Herpetiformis ◽

Mode Of Delivery ◽

Gastrointestinal Symptoms ◽

Stunted Growth ◽

Significant Difference ◽

High Index Of Suspicion ◽

Gestational Age At Birth ◽

Age At Birth

Atypical coeliac disease in young children is frequently missed when it presents atypically as non-gastrointestinal presentations to different specialties. There was a greater delay (54 months) in establishing the diagnosis in those with atypical coeliac disease (p < 0.001). No difference was observed in the mode of delivery or duration of breast feeding, but significant difference was observed between gestational age at birth (p < 0.001). Most cases showed stunted growth and underweight. Irritability, anaemia, rickets, dermatitis herpetiformis, alopecia and intussusception were other common predictors of atypical coeliac disease. Because of a myriad spectrum of non-gastrointestinal symptoms, at any age with diverse presentation, a high index of suspicion is therefore required.

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Maternal biological age assessed in early pregnancy is associated with gestational age at birth

Scientific Reports ◽

10.1038/s41598-021-94281-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Eva E. Lancaster ◽

Dana M. Lapato ◽

Colleen Jackson-Cook ◽

Jerome F. Strauss ◽

Roxann Roberson-Nay ◽

...

Keyword(s):

Risk Factors ◽

Preterm Birth ◽

Early Pregnancy ◽

Gestational Age ◽

Cellular Aging ◽

Biological Age ◽

Potential Candidate ◽

A Genome ◽

Gestational Age At Birth ◽

Age At Birth

AbstractMaternal age is an established predictor of preterm birth independent of other recognized risk factors. The use of chronological age makes the assumption that individuals age at a similar rate. Therefore, it does not capture interindividual differences that may exist due to genetic background and environmental exposures. As a result, there is a need to identify biomarkers that more closely index the rate of cellular aging. One potential candidate is biological age (BA) estimated by the DNA methylome. This study investigated whether maternal BA, estimated in either early and/or late pregnancy, predicts gestational age at birth. BA was estimated from a genome-wide DNA methylation platform using the Horvath algorithm. Linear regression methods assessed the relationship between BA and pregnancy outcomes, including gestational age at birth and prenatal perceived stress, in a primary and replication cohort. Prenatal BA estimates from early pregnancy explained variance in gestational age at birth above and beyond the influence of other recognized preterm birth risk factors. Sensitivity analyses indicated that this signal was driven primarily by self-identified African American participants. This predictive relationship was sensitive to small variations in the BA estimation algorithm. Benefits and limitations of using BA in translational research and clinical applications for preterm birth are considered.

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