الفهرس 
INTRODUCTION AND AIM OF THE STUDYOnly 14 pages are availabe for public view
 |  | from | 118 |  |  |
| | | from | 118 | | |
Abstract
Child mortality has long been recognized as a worldwide measure of health, hence it is important to delineate its causes. There has been a decrease in child deaths from acquired causes with a relative increase in deaths of genetic origin. In developed countries, genetic disorders and malformations have emerged as the leading cause of infant mortality.
There is a scarcity of studies on the contribution of genetic disorders to child deaths in Egypt and with no doubt, the existence of studies on genetic diseases will help health care providers in planning and implementing strategies to control child deaths due to this cause. Therefore, the present study aimed to determine the contribution of genetic disorders to post-neonatal under-five mortality at AUCH and identify the factors associated with child deaths related to genetic disorders.
The main results of the present study could be summarized as follows:
More than two-thirds (69.2%) of under-five deaths occurred during infancy. Moreover, the most common causes of death in the age group 1-59 months at Alexandria University Children’s Hospital were congenital malformations (28.1%) followed by infectious diseases (27.8%) and genetic disorders (22.6%). More than half of the post-neonatal under-five mortality had an underlying genetic element (54.7%) including chromosomal disorders (5.1%), single gene disorders (17.1%), multifactorial disorders (26.0%), mitochondrial disorders (0.4%) and diseases with uncertain genetic inheritance (6.1%).
Factors associated with mortality from genetic disorders:
Mortality and age: Children dying between 1 – 12 months were 3 times more likely to have died from a genetic cause than age group 48 - 60 months (OR= 3.06; 95% CI, 1.04 – 8.99; p = 0.002).
Mortality and weight: Deceased children who weighed less than the 3rd centile for age and sex were almost 3 times more likely to have died from a genetic cause compared to those who had an appropriate weight. (OR= 2.92; 95% CI, 2.05 – 4.17; p < 0.001).
Mortality and duration of hospital stay: Deceased children who stayed at the hospital for more than 30 days were 11 times more likely to have died from a genetic cause compared to those who stayed for less than two days (OR= 11.11; 95% CI, 4.61 - 26.76; p < 0.001).
Mortality and prematurity: Deceased children who were born preterm were 1.68 times more likely to have died from a genetic cause compared to those who were born at full term (OR = 1.68; 95% CI, 1.06 – 2.64; p = 0.025).
Mortality and maternal history of other child deaths: Children who died from genetic causes were twice as likely to have a maternal history of other child deaths than those who died from non-genetic causes (OR = 2.01; 95% CI, 1.13 - 3.56, p = 0.015).
Mortality and maternal reproductive wastage: Children who died from genetic causes were around 5 times more likely to have maternal reproductive wastage of 2 or more compared to those who died from a non-genetic cause (OR = 4.76; 95% CI, 1.83 - 12.33, p = 0.002).
Factors associated with mortality from chromosomal, single gene, and multifactorial disorders:
Mortality and weight: Deceased children who weighed less than the 3rd centile for age and sex were 3.5 times more likely to have died from chromosomal aberrations (OR= 3.52; 95% CI, 1.34 – 9.24; p = 0.025) and around 1.6 times more likely to have died from multifactorial disorders compared to those who had an appropriate weight (OR= 1.61; 95% CI, 1.10 – 2.34; p = 0.005).
Mortality and duration of hospital stay: Deceased children who stayed at the hospital for more than 30 days were 5.4 more likely to have died from a multifactorial disease compared to those who stayed for less than two days. (OR= 5.42; 95% CI, 3.03 – 9.70; p < 0.001).
Mortality and prematurity: Deceased children who were born preterm were 1.6 times more likely to have died from a multifactorial disorder compared to those who were born at full term (OR = 1.64; 95% CI, 1.08 – 2.51; p = 0.021).
Mortality and birth order: Children who died from chromosomal disorders were almost 6 times more likely to have had a birth order of 5+ than those who died from other causes (OR = 5.81; 95% CI, 2.06 – 16.38; p = 0.010).
Mortality and maternal gravidity: Children who died from chromosomal disorders were 4 times more likely to have had maternal gravidity of 5+ (OR = 4.35; 95% CI, 1.57 – 12.03; p = 0.011) and those who died from multifactorial disorders were twice as likely to have had maternal gravidity of 5+ (OR = 2.18; 95% CI, 1.17 – 4.07; p = 0.009) than those who died from other causes.
Mortality and maternal parity: Children who died from chromosomal disorders were almost 6 times more likely to have had maternal parity of 5+ (OR = 5.70; 95% CI, 2.00 – 16.30; p = 0.006) and those who died from multifactorial disorders were twice as likely to have had maternal parity of 5+ (OR = 2.22; 95% CI, 1.09 – 5.58; p = 0.048) than those who died from other causes.
Mortality and maternal history of other child deaths: Children who died from single gene disorders were 4 times more likely to have had maternal history of other child deaths (OR = 4.45; 95% CI, 2.66 – 7.45; p < 0.001) and those with multifactorial disorders were 2.6 times more likely to have had maternal history of other child deaths (OR = 2.62; 95% CI, 1.37 – 4.99; p = 0.003) than those who died from other causes.
Mortality and maternal reproductive wastage: Children who died from single gene disorders were around 5 times more likely to have maternal history of reproductive wastage of 2+ (OR = 4.67; 95% CI, 2.43 – 8.97; p < 0.001) and those who had multifactorial disorders were around twice as likely to have maternal history of reproductive wastage of 2+ (OR = 1.98; 95% CI, 1.05 – 3.73; p = 0.020) than those who died from other causes.
Binary Logistic Regression:
The following variables were included in the logistic regression model: male sex, maternal and paternal ages at conception, parental consanguinity, history of affected relatives/siblings and history of maternal abortions/stillbirths.
Predictors of mortality from genetic disorders: The odds of dying from genetic disorders was twice as likely among children with a positive family history of an affected sibling/relative than those without a family history (AOR = 2.14, 95% CI, 1.19 – 3.86).
Predictors of mortality from chromosomal disorders: The odds of dying from chromosomal disorders was 4 times as likely among children with mothers more than 35 years of age at the time of conception than those with mothers 20 – 35 years of age (AOR = 4.11, 95% CI, 1.06 – 15.98).
Predictors of mortality from single gene disorders: The odds of dying from single gene disorders was almost twice as likely among children with consanguineous parents (AOR = 1.92, 95% CI, 1.18 – 3.12) and 4.3 times as likely among children with family history of affected siblings/relatives (AOR = 4.33, 95% CI, 3.54 – 7.39).
Predictors of mortality from multifactorial disorders: The odds of dying from a multifactorial disorder was 1.5 times as likely among males than females (AOR = 1.53, 95% CI, 1.05 – 2.25), 1.8 times as likely among children with consanguineous parents than non-consanguineous parents (AOR = 1.84, 95% CI, 1.24 – 1.75), twice as likely among children with family history of affected siblings/relatives (AOR = 2.17, 95% CI, 1.14 – 4.14).
6.2 Conclusion:
The present study provides evidence for the burden of genetics underlying post-neonatal infant and child mortality. A considerable proportion of the post-neonatal under-five mortality had an underlying genetic element (54.7%) including chromosomal disorders (5.1%), single gene disorders (17.1%), multifactorial disorders (26.0%), mitochondrial disorders (0.4%) and diseases with uncertain genetic inheritance (6.1%). The most common causes of death in the age group 1-59 months at AUCH were congenital malformations (28.1%) followed by infectious diseases (27.8%) and genetic disorders (22.6%).
Different predictors were identified for the mortality from genetic disorders and its subtypes. Such predictors can prove useful in identifying high risk couples. Positive family history of an affected sibling/relative was the single most important predictor of mortality from genetic disease. Moreover, the highest frequency of genetic deaths occurred during infancy. Deceased children were more likely to have been underweight, have a longer duration of hospital stay and have been born prematurely. They were also more likely to be associated with maternal history of other child deaths and a maternal total reproductive wastage more than 2.
Among genetic deaths, the most important predictor of mortality from chromosomal disorders was advanced maternal age. It was also associated with weight less than the third percentile and birth order/maternal gravidity/parity of 5 or more.
As regards single gene disorders, positive family history of an affected sibling/relative was the most significant predictor of mortality followed by parental consanguinity. It was also associated with increased frequency of death during infancy, increased duration of hospital stay, maternal history of other child deaths and a maternal total reproductive wastage more than one.
Positive family history of an affected sibling/relative was the most significant predictor of mortality from multifactorial disorders followed by parental consanguinity and male sex. Other factors associated with mortality from multifactorial disorders included increased frequency of death during infancy, weight less than the third percentile, increased duration of hospital stay, prematurity, maternal gravidity/parity of 3 or more, maternal history of other child deaths and a maternal total reproductive wastage more than one.
6.3 Recommendations:
Policies and strategies for the prevention and management of genetic disorders should be nationally prioritized, emphasized, implemented, and integrated into health-care systems through:
1- Premarital and pre-conceptional counseling services for genetic disorders especially among high-risk couples.
2- Increasing public awareness about genetic disorders, risk factors, consequences, and screening programs through health education campaigns.
3- Improvement of hospital records/filing systems as well as creating a national registry for common genetic disorders and malformations in Egypt for guiding research and enhancing policies.
4- Continuous educational and training activities to update physicians’ knowledge and skills regarding early diagnosis, management, and follow-up of genetic disorders as well as proper reporting of those diseases in relevant records, registries, and statistics.
5- Provision of modern and advanced techniques for genetic testing to confirm clinical diagnoses and to diagnose uncertain cases.
6- Initiate the Egyptian Human Genome project in order to understand the magnitude of the most common genetic disorders in Egypt and guide research on how to control them.
7- Further research is needed to:
Identify the cause-specific mortality especially mortality from genetic disorders on a national level in order to guide policies for the improvement of child survival.
Improve diagnostic approaches to include cytogenetic testing of those with unknown diagnosis or those suspected of having genetic disease in order to confirm the diagnosis and estimate the true burden of genetic disorders in under-five mortality.
Study and understand the influence of early recognition of genetic disorders on under-five survival and health.