Monogenic diseases that result in early pregnancy loss or neonatal death are genetically and phenotypically highly variable. This often poses significant challenges in arriving at a molecular diagnosis for reproductive planning. Molecular autopsy by proxy (MABP) refers to the genetic testing of relatives of deceased individuals to deduce the cause of death. Here, we specifically tested couples who lost one or more children/pregnancies with no available DNA. We developed our testing strategy using whole exome sequencing data from 83 consanguineous Saudi couples. We detected the shared carrier state of 50 pathogenic variants/likely pathogenic variants in 43 families and of 28 variants of uncertain significance in 24 families. Negative results were seen in 16 couples after variant reclassification. In 10 families, the risk of more than one genetic disease was documented. Secondary findings were seen in 10 families: either genetic variants with potential clinical consequences for the tested individual or a female carrier for X-linked conditions. This couple-based approach has enabled molecularly informed genetic counseling for 52% (43/83 families). Given the predominance of autosomal recessive causes of pregnancy and child death in consanguineous populations, MABP can be a helpful approach to consanguineous couples who seek counseling but lack molecular data on their deceased offspring.

Introduction: A significant proportion of parents are still reluctant to have their children vaccinated against COVID-19. This study aimed to determine what factors influence parents' decision to get COVID-19 vaccine for the children of age group 5-11 years. Methodology: A cross-sectional study was conducted in the region Qassim of Saudi Arabia, by using a self-administered, pre-tested questionnaire to assess the predicting factors of caregivers’ readiness to get their children vaccinated against COVID-19. Results: Two-thirds of the caregivers surveyed were unwilling to get their children vaccinated against COVID-19. The factors that influence the parents’ decision to get their young children (5-11 years old) vaccinated against COVID-19 were: having secondary school education (p = 0.019), family members infected with SARS-CoV-2 (p = 0.016), caregivers completed the three doses of vaccination (p = 0.003) and those who received additional flu vaccine (p = 0.014), and not experiencing the side effects of COVID-19 vaccine (p = 0.0001). Additionally, no history of COVID-19 vaccine adverse events in older 12-18 year old children (p = 0.011) and no chronic diseases in the 5-11 year old children (p = 0.001) were predictors. Conclusions: Caregivers' preferences about the children’s vaccination were influenced by multiple factors, including educational level, having family members infected with SARS-CoV-2, caregivers completing three doses of COVID-19 vaccine, receiving additional flu vaccine with no or mild adverse events, and history of chronic diseases in the child. Understanding these factors can help determine the likelihood of the caregivers getting their child vaccinated.

Objectives We aimed to report our 10-year experience of treating short children born small for gestational age (SGA) by comparing the long-term growth, metabolic safety, and cost-effectiveness of recombinant human growth hormone (rhGH) therapy in short children born SGA with those in rhGH-treated children with growth hormone deficiency (GHD) and Turner syndrome. Methods We performed a 10-year retrospective cohort study at King Saud University Medical City. We included children aged 3–16 years who received rhGH for GHD, SGA, or Turner syndrome for >1 year. Results A total of 166 children received rhGH therapy for GHD, 58 for SGA, and 16 for Turner syndrome. During the last study visit, the average height change was 21 cm for GHD children and 14 cm for children born SGA (p-value <0.001). The height SDS change was 0.84 for GHD children and 0.55 for SGA children (p-value=0.004). The average cost-effectiveness ratios for treating GHD and SGA children were USD 1,717.22 and USD 1,157.19 per centimeter gained, respectively. Moreover, the mean incremental cost-effectiveness ratio for GHD vs. SGA patients was USD 2,820.39 per centimeter gained. Dysglycemia developed in 70 patients: 43 (36.44%), 22 (40.74%), and 5 (13%) in the GHD, SGA, and Turner syndrome groups, respectively. Conclusions rhGH is effective in height improvement of short children. However, pursuing rhGH treatment for children born SGA requires a shared decision-making approach to balance the modest benefit of final adult height gain with the long-term metabolic effects, considering the acceptable costs on the Saudi healthcare system.

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