Neonatal encephalopathy due to birth asphyxia and birth trauma

Disease Overview

Neonatal encephalopathy (NE) due to birth asphyxia and birth trauma, also called hypoxic-ischaemic encephalopathy, is defined as injury to the brain in the first few moments or days of life in an infant born at term. NE has multiple aetiologies and is defined more by its symptoms – abnormal neurological function, including reduced level of consciousness, seizures, depression of tone and reflexes, or difficulty maintaining respiration – than its origin. NE can occur when an infant is deprived of oxygen during delivery or sustains physical trauma to the head, among other causes.

GBD 2021 Modeling Strategy

We focus on only the mortality due to this cause, which is estimated together with all other cause-specific mortality through the CODEm process.

The nonfatal part is described here: GBD 2021 Non-fatal Neonatal Infections Modeling Strategy (pages 13-21).

Cause Hierarchy

  • All causes (c_294) [level 0]

    • Communicable, maternal, neonatal, and nutritional diseases (c_295)

      • Maternal and neonatal disorders (c_962)

        • Neonatal disorders (c_380)

          • Neonatal encephalopathy due to birth asphyxia and birth trauma (c_382) [level 4]

Restrictions

The following table describes restrictions on the effects of this cause (such as being only fatal), 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

True

YLD only

False

YLL age group start

Early neonatal

GBD age group id 2

YLL age group end

Post neonatal

GBD age group id 4

Vivarium Modeling Strategy

Scope

The Level 4 neonatal conditions included in the MNCNH Portfolio model are closely linked to the Overall Neonatal Disorders Model. Since the LBWSG Risk Factor has an effect on overall neonatal mortality, this subcause will define a birth-weight- and gestational-age-specific cause specific mortality rate that the Overall Neonatal Disorders Model can use. This risk-specific CSMR might then be further individualized based on treatment coverage and efficacy, to ensure that individuals who have access to a treatment like emergency C-section have a lower risk of mortality from neonatal encephalopathy than those who do not.

Assumptions and Limitations

Focusing solely on YLLs will likely underestimate the total burden of this cause and, consequently, the DALYs averted by interventions that reduce prevalence and mortality due to it. However, we anticipate this underestimation to be less than 10%.

We assume that the relationship between LBWSG and encephalopathy CSMR follow the relationship between LBWSG and all-cause mortality during the neonatal period, and could be refined with additional data.

Cause Model Decision Graph

We are not modeling Neonatal Encephalopathy dynamically as a finite state machine, but we can draw an directed graph to represent the collapsed decision tree representing this cause. Unlike a state machine representation, the values on the transition arrows represent decision probabilities rather than rates per unit time. Note that these probabilities are not used directly in the model and are included here only for clarity. If they end up being more confusing than enlightening, we should delete them.

digraph NN_encephalopathy_decisions { rankdir = LR; lb [label="live birth", style=dashed] nn_alive [label="neonate did not die\nof encephalopathy"] nn_dead [label="neonate died of\nencephalopathy"] lb -> nn_alive [label = "1 - csmrisk"] lb -> nn_dead [label = "csmrisk"] }

State Definitions

State

Definition

live birth

The parent simulant has given birth to a live child simulant (which is determined in the intrapartum step of the pregnancy model)

neonate did not die of encephalopathy

The child simulant did not die of encephalopathy within the first 28 days of life

neonate died of encephalopathy

The child simulant died of encephalopathy within the first 28 days of life
Transition Probability Definitions

Symbol

Name

Definition

csmrisk

encephalopathy mortality risk

The probability that a simulant who was born alive dies from this cause during the neonatal period

Modeling Strategy

The Neonatal Encephalopathy submodel requires only the birth-weight- and gestation-age-stratified cause specific mortality risk during the early and late neonatal periods.

The way these CSMRisks are used is the same for all subcauses, and therefore is included in the Overall Neonatal Disorders Model page. This page describes the birth-weight- and gestational-age-specific cause specific mortality risks that are used for this cause on that page, \(\text{CSMR}^{\text{encephalopathy}}_{\text{BW},\text{GA}}\). The formula is:

\[\begin{aligned} \text{CSMRisk}_{\text{BW},\text{GA}} &= \text{CSMRisk} \cdot \text{RR}_{\text{BW},\text{GA}} \cdot Z \end{aligned}\]

where \(\text{CSMRrisk}\) is the cause-specific mortality risk for encephalopathy, \(\text{RR}_{\text{BW},\text{GA}}\) is the relative risk of all-cause mortality for a birth weight of \(\text{BW}\) and gestational age of \(\text{GA}\), and \(Z\) is a normalizing constant selected so that \(\int_{\text{BW}} \int_{\text{GA}} \text{RR}_{\text{BW},\text{GA}} \cdot Z = 1\).

Note

the choice to use \(\text{RR}_{\text{BW},\text{GA}}\) in this equation is essentially arbitrary, and it could be replaced by any other nonnegative “weight function” \(w(\text{BW},\text{GA})\) as long it doesn’t lead to a negative “other causes” mortality risk. But with this choice, \(Z\) is equal to the \(1-\text{PAF}\) of LBWSG on all-cause mortality.

Each individual simulant \(i\) has their own \(\text{CSMRisk}_i\) that might be different from \(\text{CSMRisk}_{\text{BW}_i,\text{GA}_i}\) (meaning the average birth-weight- and gestational-age-specific CSMRisk for simulants with the birth weight and gestational age matching simulant \(i\). We recommend implementing this as a pipeline eventually because it will be modified by interventions (or access to interventions) relevant to this subcause. (Until we implement those, we will have \(\text{CSMRisk}_{i} = \text{CSMRisk}_{\text{BW}_i,\text{GA}_i}\), though.)

The following table shows the data needed for these calculations.

Data Tables

Note

All quantities pulled from GBD in the following table are for a specific year, sex, age group, and location.

Data values and sources

Variable

Definition

Value or source

Note

enn_all_cause_death_count

Count of deaths due to all causes in the early neonatal age group

GBD: source=’codcorrect’, metric_id=1, cause_id=294

enn_death_count

Count of deaths due to cause neonatal encephalopathy in the early neonatal age group

GBD: source=’codcorrect’, metric_id=1, cause_id=382

lnn_death_count

Count of deaths due to cause neonatal encephalopathy in the late neonatal age group

GBD: source=’codcorrect’, metric_id=1, cause_id=382

live_birth_count

Count of live births

GBD: covariate_id = 1106

csmrisk_enn

neonatal encephalopathy mortality risk in the early neonatal age group

enn_death_count / live_birth_count

csmrisk_lnn

neonatal encephalopathy mortality risk in the late neonatal age group

lnn_death_count / (live_birth_count - enn_all_cause_death_count)

\(\text{CSMRisk}\)

neonatal encephalopathy mortality risk

either csmrisk_enn or csmrisk_lnn depending on the simulant’s age group

\(\text{RR}_{\text{BW},\text{GA}}\)

Relative Risk of all-cause mortality for a birth weight of BW and gestational age of GA

interpolated from GBD data

See Low Birth Weight and Short Gestation (LBWSG) page for details.

\(Z\)

Normalizing constant

calculated from \(\text{RR}_{\text{BW},\text{GA}}\) and LBWSG exposure distribution.

see above for details.

Calculating Burden

Years of life lost

The years of life lost (YLLs) due to Neonatal Encephalopathy are calculated assuming age \(a=14 \text{ days}\), and equals \(\operatorname{TMRLE}(a) - a\), where \(\operatorname{TMRLE}(a)\) is the theoretical minimum risk life expectancy for a person of age \(a\).

Years lived with disability

For simplicity, we will not include YLDs in this model.

Validation Criteria

  • Neonatal Encephalopathy mortality risk in simulation should match GBD estimates.

  • Relative Risk of Neonatal Encephalopathy death due to LBWSG should match overall neonatal mortality RR.

References

GBD 2021 Non-fatal Neonatal Infections Modeling Strategy (pages 13-21).

GBD 2021 Neonatal Encephalopathy Factsheet.