Preterm birth (PTB) and early term birth (ETB) are associated with high risks of perinatal mortality and morbidity. While extreme to very PTBs have been extensively studied, studies on infants born at later stages of pregnancy, particularly late PTBs and ETBs, are lacking. In this study, we aimed to assess the incidence, risk factors, and feto-maternal outcomes of PTB and ETB births in Qatar. We examined 15,865 singleton live births using 12-month retrospective registry data from the PEARL-Peristat Study. PTB and ETB incidence rates were 8.8% and 33.7%, respectively. PTB and ETB in-hospital mortality rates were 16.9% and 0.2%, respectively. Advanced maternal age, pre-gestational diabetes mellitus (PGDM), assisted pregnancies, and preterm history independently predicted both PTB and ETB, whereas chromosomal and congenital abnormalities were found to be independent predictors of PTB but not ETB. All groups of PTB and ETB were significantly associated with low birth weight (LBW), large for gestational age (LGA) births, caesarean delivery, and neonatal intensive care unit (NICU)/or death of neonate in labor room (LR)/operation theatre (OT). On the other hand, all or some groups of PTB were significantly associated with small for gestational age (SGA) births, Apgar < 7 at 1 and 5 min and in-hospital mortality. The findings of this study may serve as a basis for taking better clinical decisions with accurate assessment of risk factors, complications, and predictions of PTB and ETB.

Currently, there is no evidence in the literature to support the routine supplementation of all parenterally fed premature infants with l-carnitine. In our study, we found that about 8.56% of extremely preterm neonates are diagnosed with carnitine deficiency secondary to malnutrition, either due to reduced stores at birth or related to total parenteral nutrition (TPN). Our two step approach of performing newborn screening (NBS) again at 32 weeks gestational age (GA) equivalent helps to diagnose 81.4% more preterm babies with carnitine deficiency—who would otherwise be missed—and supplement them with l-carnitine for optimal growth. We performed a retrospective cohort study to diagnose carnitine deficiency related to malnutrition in two groups: those presenting at birth and those presenting later in life. We found that there was a statistically significant difference in the median GA and birth weight (BW) between the two groups, but there was no difference in the free carnitine levels.

Background: Newborn screening is an essential public health strategy that aims to detect a range of conditions, including inborn errors of metabolism, in neonates shortly after birth. The timely identification is crucial due to the asymptomatic nature of many conditions at birth, but which can lead to significant health complications if left untreated. Through this study, we aimed to investigate the incidence of IEMs screened by the Qatar National Newborn Screening Program. Methods: We retrospectively analyzed a total of 351,223 newborns screened from 2010 to 2023. The incidence for the studied IEMs was calculated and correlated with demographics, consanguinity, and family history. In addition, the diagnostic yield of different tests utilized was assessed. Results: Our study revealed a total of 318 positive cases with IEMs, and a significantly high incidence of 1:1105 for IEMs in Qatar. Classical Homocystinuria was the most frequently detected condition, with a cumulative incidence of 1:6754 live births, linked to the founder variant p. Arg336Cys in the CBS gene. Aminoacidopathies were the most prevalent category, followed by fatty acid oxidation disorders, organic acidurias, biotinidase deficiency, and urea cycle disorders. Genetic testing showed a high diagnostic yield of 90%. Of the 60 cases that underwent targeted variant testing, 98% were confirmed, while 90% of the 59 cases tested by single gene testing were confirmed. Conclusions: Our study provides the incidence rates of IEMs in Qatar and novel insights that could facilitate setting up/developing IEM incidence-reducing strategies and improving outcomes for affected newborns and their families.

Malonic aciduria is a rare autosomal recessive organic acid disorder. With the widespread use of tandem mass spectrometry for analysis of the amino acid/acylcarnitine profile on dried blood spots for newborn screening (NBS), this condition can be readily diagnosed and can be included in the organic acid screen in NBS programs. In Qatar, we report the first case of an asymptomatic baby screened and diagnosed with malonic aciduria through NBS. This patient has a genetic variant of malonyl-CoA decarboxylase that has not been previously reported in the literature. This condition should be differentiated from a similar disorder, combined malonic and methylmalonic aciduria. The clinical phenotype of malonic aciduria is variable and the pathophysiology is not fully understood. There is no established guidance or recommendations regarding the appropriate treatment regimen, dietary therapy or regular follow-up of these patients. Most available evidence for treatment is based on a single study or case report.

Background: Biotinidase deficiency (BD) is a common autosomal recessive metabolic disorder in Qatar and the Arab world. It is treatable if detected early, making it essential to understand the genetic variants involved. This study aimed to investigate the carrier frequency of BD-related variants in a healthy Qatari population, reflecting the genetic landscape of the broader Middle Eastern region; classify them using bioinformatics tools; and compare findings with global datasets. Methods: Whole-genome sequencing data from 14,669 participants in the Qatar Genome Program (QGP), a multiethnic cohort including Qatari nationals and long-term residents (≥15 years), were analyzed to identify BTD variants. A total of 723, including 653 single-nucleotide polymorphisms (SNPs) and 70 structural variants (SVs) in BTD associated with BD, were screened against the Qatari cohort and compared with international data. In silico tools were used to assess variant pathogenicity, conservation, and protein stability. Molecular dynamics (MD) simulations were performed to evaluate structural and functional changes in the BTD. Results: A total of 80 SNPs and 3 SVs were identified, among which 21 variants (19 SNPs and 2 SVs) were classified as pathogenic or likely pathogenic, according to ClinVar. The carrier frequency of BTD-related variants in Qatar was 1:20, primarily driven by rs13078881 (D444H). Molecular dynamics (MD) simulations revealed significant conformational changes with H323R, D444H, and P497S, which demonstrated increased flexibility (higher RMSD/RMSF and PCA trace values). Additionally, R209C and D444H showed reduced compactness (higher Rg) and distinct energy minima, suggesting altered conformational states. Conclusions: This study demonstrates a high carrier frequency of pathogenic BTD variants in the Qatari population, underscoring the need to integrate these SNPs and SVs into the national genomic neonatal screening program (gNBS) for enhanced early detection and treatment strategies. The mild structural deviations observed in the D444H mutant through MD simulations may explain its association with milder clinical phenotypes of BTD, offering valuable insights for personalized therapeutic approaches.