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National Center on Birth Defects and Developmental Disabilities Autism Spectrum Disorder and Birth Spacing: Findings from the Study to Explore Early Development LA Schieve, LH Tian, C Drews-Botsch, GC Windham, C Newschaffer, JL Daniels, LC Lee, LA Croen, MD Fallin Interagency Autism Coordinating Committee Meeting October 24, 2017

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Page 1: E ] } v o v } v ] Z ( v À o } u v o ] ] o ] ] µ ] u^ µ u ... · } ] ] } v Á v ^ v ] v r P v v Ç ] v À o. d u ] Z U ^ Á ] Z Z ] P Z À ] Ç } Further analyses indicated associations

National Center on Birth Defects and Developmental Disabilities

Autism Spectrum Disorder and Birth Spacing: Findings from the Study to Explore Early Development

LA Schieve, LH Tian, C Drews-Botsch, GC Windham, C Newschaffer, JL Daniels, LC Lee, LA Croen, MD Fallin

Interagency Autism Coordinating Committee Meeting

October 24, 2017

Page 2: E ] } v o v } v ] Z ( v À o } u v o ] ] o ] ] µ ] u^ µ u ... · } ] ] } v Á v ^ v ] v r P v v Ç ] v À o. d u ] Z U ^ Á ] Z Z ] P Z À ] Ç } Further analyses indicated associations

Background and Study Objective

Previous studies reported associations between ASD and birth spacing. But they had some limitations– Case definitions based on non-standardized diagnostic coding– Limited assessment of phenotypic case subtypes – No assessment of other (non-ASD) developmental disabilities– Little examination of possible underlying mechanisms for associations

SEED was able to address these limitations– Rigorous case classification based on gold standard instruments– Extensive developmental data to characterize phenotypic subtypes– Second non-ASD DD case group enrolled– Detailed maternal health data allowed exploration of possible

mechanisms

Page 3: E ] } v o v } v ] Z ( v À o } u v o ] ] o ] ] µ ] u^ µ u ... · } ] ] } v Á v ^ v ] v r P v v Ç ] v À o. d u ] Z U ^ Á ] Z Z ] P Z À ] Ç } Further analyses indicated associations

Methods Analysis sample: children who were 2nd or later births

Inter-pregnancy interval (IPI) -- time between mother’s previous birth and conception of the study child’s birth– Short birth spacing: IPI <18 months (16% POP controls)– Long birth spacing: IPI >60 months (33% POP controls)

Case groups compared to POP controls– ASD (total) – ASD + intellectual disability (ID) vs ASD w/out ID– ASD with high symptom severity score vs ASD w/ lower symptom severity score

(measured on ADOS)

– DD (total)– DD + ID vs DD w/out ID– DD with ASD features vs DD without ASD features (measured on SCQ)

Page 4: E ] } v o v } v ] Z ( v À o } u v o ] ] o ] ] µ ] u^ µ u ... · } ] ] } v Á v ^ v ] v r P v v Ç ] v À o. d u ] Z U ^ Á ] Z Z ] P Z À ] Ç } Further analyses indicated associations

Methods

Odds ratios derived from multivariable logistic regression– adjusted for child sex, maternal age, education, race-ethnicity

Analyses run for total sample and sample limited to children born at term (37 or more weeks gestation) to eliminate competing risks caused by preterm birth

Several factors possibly related to the underlying mechanism also assessed

Page 5: E ] } v o v } v ] Z ( v À o } u v o ] ] o ] ] µ ] u^ µ u ... · } ] ] } v Á v ^ v ] v r P v v Ç ] v À o. d u ] Z U ^ Á ] Z Z ] P Z À ] Ç } Further analyses indicated associations

Adjusted odds ratios and 95% confidence intervals: Association between ASD and inter-pregnancy interval <18 months

1.3 1.4 1.3

1.8

1.1

1.5 1.6 1.4

2.0

1.3

0

0.5

1

1.5

2

2.5

3

3.5

Total Sample Term Births

All cases ASD + ID ASD w/o ID ASD, high ASD, low severity All cases ASD + ID ASD w/o ID ASD, high ASD, low severity severity severity

• Modest association between ASD and short birth spacing • Slightly more pronounced among term births • Much more pronounced among ASD cases with high ASD symptom severity

Page 6: E ] } v o v } v ] Z ( v À o } u v o ] ] o ] ] µ ] u^ µ u ... · } ] ] } v Á v ^ v ] v r P v v Ç ] v À o. d u ] Z U ^ Á ] Z Z ] P Z À ] Ç } Further analyses indicated associations

1.4 1.3 1.4 1.5

1.2

1.5 1.4 1.5

1.8

1.3

0

0.5

1

1.5

2

2.5

3

3.5

Total Sample Term Births

Adjusted odds ratios and 95% confidence intervals: Association between ASD and inter-pregnancy interval >60 months

All cases ASD + ID ASD w/o ID ASD, high ASD, low severity All cases ASD + ID ASD w/o ID ASD, high ASD, low severity severity severity

• Modest association between ASD and long birth spacing • Slightly more pronounced among term births • Much more pronounced among ASD cases with high ASD symptom severity

Page 7: E ] } v o v } v ] Z ( v À o } u v o ] ] o ] ] µ ] u^ µ u ... · } ] ] } v Á v ^ v ] v r P v v Ç ] v À o. d u ] Z U ^ Á ] Z Z ] P Z À ] Ç } Further analyses indicated associations

Cubic spline analysis demonstrating a U-shaped association between ASD and inter-pregnancy interval

Term Births, ASD with high severity score

Page 8: E ] } v o v } v ] Z ( v À o } u v o ] ] o ] ] µ ] u^ µ u ... · } ] ] } v Á v ^ v ] v r P v v Ç ] v À o. d u ] Z U ^ Á ] Z Z ] P Z À ] Ç } Further analyses indicated associations

Further analyses indicated associations were NOT explained by:

– Unplanned pregnancy

– Maternal infertility disorders

– Maternal complications during pregnancy – hypertension, diabetes

Page 9: E ] } v o v } v ] Z ( v À o } u v o ] ] o ] ] µ ] u^ µ u ... · } ] ] } v Á v ^ v ] v r P v v Ç ] v À o. d u ] Z U ^ Á ] Z Z ] P Z À ] Ç } Further analyses indicated associations

Cubic spline analysis demonstrating no association between other DDs and inter-pregnancy interval

Page 10: E ] } v o v } v ] Z ( v À o } u v o ] ] o ] ] µ ] u^ µ u ... · } ] ] } v Á v ^ v ] v r P v v Ç ] v À o. d u ] Z U ^ Á ] Z Z ] P Z À ] Ç } Further analyses indicated associations

Conclusion

ASD is associated with both short and long birth spacing, particularly ASD with the highest symptom severity

Association not explained by unplanned pregnancy, mother’s underlying infertility disorders, or hypertension or diabetes during pregnancy

Two areas to investigate further are maternal nutrition and inflammation

Page 11: E ] } v o v } v ] Z ( v À o } u v o ] ] o ] ] µ ] u^ µ u ... · } ] ] } v Á v ^ v ] v r P v v Ç ] v À o. d u ] Z U ^ Á ] Z Z ] P Z À ] Ç } Further analyses indicated associations

National Center on Birth Defects and Developmental Disabilities

Many thanks to all the families who participated in SEED and made this work possible!

The findings and conclusions of this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.


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