Neural Tube Defects

Disease Description

Neural tube defects occur when the neural tube fails to close completely during development. The GBD 2017 case definition includes spina bifida, in which part of the spinal cord and/or meninges are uncovered by skin; encephalocele, a congenital defect characterized by sac-like protrusions of the brain and meninges through openings in the skull; and anencephaly, the absence of a major portion of the brain, skull, and scalp. Spina bifida occulta, a much less severe form of spina bifida where the defect in vertebral column remains covered by skin, is excluded from the GBD case definition of spina bifida.

All infants born with anencephaly die during the first few weeks of life, as there is no remission and no cure for this condition. Infants born with spina bifida or encephalocele typically require surgical intervention during the first few weeks of life, and thereafter may experience a range of neural and motor complications. The GBD 2017 case definitions of spina bifida and encephalocele do not consider surgical intervention for either condition as remission.

Spina bifida corresponds to the ICD-10 codes Q05.0, Q05.4,Q05.6, Q05.7, Q05.8, and Q05.9. Encephalocele corresponds to the ICD-10 codes Q01.2, Q01.8, and Q01.9. Anencephaly corresponds to the ICD-10 codes Q00.0 and Q00.2. [GBD-2017-YLD-Capstone-Appendix-1-Neural-Tube-Defects]

Todo

Add more information and references. In particular, find data about global prevalence and relation to folic acid during pregnancy.

Modeling Neural Tube Defects in GBD 2017

Congenital Anomalies in GBD 2017

GBD 2017 uses similar modeling strategies to estimate the prevalence and resulting disability and mortality of the following eight categories of congenital anomalies: neural tube defects; congenital heart anomalies; orofacial clefts; chromosomal disorders; congenital musculoskeletal anomalies; congenital urogenital anomalies; congenital digestive anomalies; and other congenital birth defects.

The GBD case definition of congenital anomalies includes any condition present at birth that is a result of abnormalities of embryonic development, excluding those that are directly the result of infections or substance abuse (e.g. fetal alcohol syndrome, congenital syphilis) and excludes minor anomalies as they are defined by EUROCAT. Further, our GBD case definition includes only live births and excludes all terminations of pregnancy following prenatal diagnosis and stillbirths.

Modeling Strategy for Neural Tube Defects

In GBD 2017, spina bifida, encephalocele, and anencephaly are each modeled separately and then fit to a total model of all neural tube defects.

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Add relevant detail about NTD modeling process from [GBD-2017-YLD-Capstone-Appendix-1-Neural-Tube-Defects] and from the CoD Capstone Appendix [GBD-2017-CoD-Appendix-1-Neural-Tube-Defects].

Cause Hierarchy

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Make cause hierarchy diagram.

cause id = c642
level = 4
parent = congenital_birth_defects (c641)
grandparent = other_non_communicable_diseases (c640)
great-grandparent = non_communicable_diseases (c409)
great-great-grandparent = all_causes (c294)

Sequelae and health states associated with Neural Tube Defects

The Neural Tube Defects cause has 85 sequelae, which can be summarized as follows:

  • All infants with anencephaly are assigned the health state of severe motor and cognitive impairment, so there is 1 sequela for anencephaly.

  • Cases of spina bifida are split into every combination of mild, moderate and severe motor impairment, all 6 severities of intellectual disability (none, borderline, mild, moderate, severe, profound), and presence or absence of urinary incontinence. Thus, there are \(3\times 6\times 2 =36\) sequelae for spina bifida.

  • Cases of encephalocele are split into every combination of motor impairments (none, mild, moderate, severe), all 6 severities of intellectual disability (none, borderline, mild, moderate, severe, profound), and presence or absence of urinary incontinence. Thus, there are \(4\times 6\times 2 =48\) sequelae for encephalocele, and the total number of sequelae for all 3 subcategories of neural tube defects is \(1+36+48=85\).

  • The proportions of the various sequelae were calculated using a pooled analysis of available literature on the long-term outcomes in cohorts of individuals born with each sub-type of neural tube defects.

  • The distribution of health states associated with encephalocele was derived separately from the distribution of health states associated with spina bifida, although these two categories of neural tube defects are associated with the same list of long-term outcome sequela.

Cause Model Diagram

There are two possible states for this cause, with-condition for people born with neural tube defects, and free-of-condition for people born without neural tube defects:

../../../_images/neural_tube_defects_cause_model_diagram.svg

There is no transition between the states; each person is born into one state or the other and permanently stays in that state. Thus, incidence and remission rates are zero.

Data Description

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Decide on section headings and structure. E.g. should this whole section be called “State and Transition Data Tables” instead of “Data Description”? Is there anything else that belongs in a section titled “Data Description”?

State and Transition Data Tables

State Definitions

State

State Name

Definition

C

With Condition

Born with neural tube defects

F

Free of Condition

Born without neural tube defects
State Data

State

Measure

Value

Notes

C

prevalence

prevalence_c642

C

birth prevalence

birth_prevalence_c642

C

excess mortality rate

\(\frac{\text{deaths\_c642}}{\text{population} \,\times\, \text{prevalence\_c642}}\)

= \(\frac{\text{cause-specific mortality rate}}{\text{prevalence}}\)

C

disability weight

\(\displaystyle{\sum_{s\in \text{sequelae\_c642}}} \scriptstyle{\text{disability\_weight}_s \,\times\, \text{prevalence}_s}\)

= average disability weight over all sequelae

F

prevalence

1 – prevalence_c642

F

birth prevalence

1 – birth_prevalence_c642

F

excess mortality rate

0

F

disability weight

0

All

cause-specific mortality rate

\(\frac{\text{deaths\_c642}}{\text{population}}\)
Transition Data

Transition

Source State

Sink State

Value

Notes

N/A

N/A

N/A

N/A

N/A
Data Sources and Definitions

Value

Source

Description

Notes

prevalence_c642

como

Prevalence of neural tube defects

birth_prevalence_c642

como

Birth prevalence of neural tube defects

deaths_c642

codcorrect

Deaths from neural tube defects

population

demography

Mid-year population for given age/sex/year/location

sequelae_c642

gbd_mapping

List of 85 sequelae for neural tube defects

prevalence_s{sid}

como

Prevalence of sequela with id sid

disability_weight_s{sid}

YLD Appendix

Disability weight of sequela with id sid

Model Assumptions and Limitations

Restrictions

The following table describes any restrictions on the effects of this cause (such as being only fatal or only nonfatal), as well as restrictions on the age and sex of simulants to which different aspects of the cause model apply.

Restrictions

Restriction Type

Value

Notes

Male only

False

Female only

False

YLL only

False

YLD only

False

YLL age group start

Early neonatal

GBD age group id 2

YLL age group end

60 to 64

GBD age group id 17

YLD age group start

Early neonatal

GBD age group id 2

YLD age group end

95 plus

GBD age group id 235

Scope

This model is designed to be used for estimating DALYs due to neural tube defects that are averted from an intervention that directly reduces the birth prevalence of neural tube defects, such as large-scale fortification of flour with folic acid, or targeted folic acid supplementation during pregnancy.

This model groups together all three severities of neural tube defects (anencephaly, encephalocele, and spina bifida), weighted by prevalence. Thus it is unable to capture any differential effects of an intervention that affects the birth prevalence of the different subtypes of neural tube defects at different rates.

Todo

Describe more assumptions and limitations of the model.

Validation Criteria

Todo

Describe tests for model validation.

References