Incidence of newborn screening disorders among 56632 infants in Central Saudi Arabia. A 6-year study.

OBJECTIVES: To determine the incidence of newborn screening (NBS) disorders and to study the key performance indicators of the program. METHODS: This retrospective single-center study enrolled all infants who underwent NBS from January 2012 to December 2017 at Prince Sultan Military Medical City, Riyadh, Saudi Arabia. We screened 17 NBS disorders. Blood samples were collected 24 hours after birth. If the initial result was positive, a second sample was collected. True positive cases were immediately referred for medical management. Data were extracted from laboratory computerized and non-computerized records using case report forms. RESULTS: During the study period, 56632 infants underwent NBS with a coverage rate of 100%. Thirty-eight cases were confirmed. The incidence of congenital hypothyroidism was 1:3775. The positive predictive value for the detection of congenital hypothyroidism was 11.8%. Propionic aciduria was the most common metabolic disorder, with an incidence of 1:14158. Very long-chain acyl CoA dehydrogenase deficiency and glutaric aciduria type 1 had an incidence of 1:18877 each. Phenylketonuria, biotinidase deficiency, maple syrup urine disease, and citrullinemia had an incidence of 1:28316 each. However, galactosemia and 3-methyl crotonyl carboxylase deficiency had the lowest incidence of 1:56632. CONCLUSION: The NBS coverage rate at our facility was 100%. Congenital hypothyroidism was the most frequently detected disorder with an incidence that matches worldwide figures. The incidence of other inherited disorders was consistent with regional figures.

Prenatal Diagnosis and Management of a Rare Central Tendon Defect Type of Congenital Diaphragmatic Hernia with a Massive Pericardial Effusion.

The central tendon defect type of congenital diaphragmatic hernia (CDH) is extremely rare and usually associated with a significant pericardial effusion. Prenatal diagnostic ultrasound features of this quite rare entity remain often overlooked or misdiagnosed. There is a dearth of literature about the role of prenatal intervention, often through an elective pericardiocentesis, for the prevention of lung hypoplasia and to decrease the overall neonatal morbidity and mortality. To the best of our knowledge, till date, there is only one case that was subjected to a prenatal intervention. Here, we present a second case of a central tendon defect type of CDH with a large pericardial effusion that was subjected to a prenatal transthoracic pericardiocentesis. Although smooth intubation and ventilation were performed immediately after birth, the infant suffered for several months from respiratory instability. Laparoscopic central tendon hernia repair was performed, and neonate was discharged home at seven months of age. Although prenatal pericardiocentesis may facilitate smoother postnatal intubation and ventilation, its broader effect on respiratory function is uncertain and still remains elusive.

Congenital anomalies and associated risk factors in a Saudi population: a cohort study from pregnancy to age 2 years.

OBJECTIVE: To assess the three key issues for congenital anomalies (CAs) prevention and care, namely, CA prevalence, risk factor prevalence and survival, in a longitudinal cohort in Riyadh, Saudi Arabia. SETTING: Tertiary care centre, Riyadh, Saudi Arabia. PARTICIPANTS: Saudi women enrolled during pregnancy over 3 years and their 28 646 eligible pregnancy outcomes (births, stillbirths and elective terminations of pregnancy for foetal anomalies). The nested case-control study evaluated the CA risk factor profile of the underlying cohort. All CA cases (1179) and unaffected controls (1262) were followed through age 2 years. Referred mothers because of foetal anomaly and mothers who delivered outside the study centre and their pregnancy outcome were excluded. PRIMARY OUTCOME MEASURES: Prevalence and pattern of major CAs, frequency of CA-related risk factors and survival through age 2 years. RESULTS: The birth prevalence of CAs was 412/10 000 births (95% CI 388.6 to 434.9), driven mainly by congenital heart disease (148 per 10 000) (95% CI 134 to 162), renal malformations (113, 95% CI 110 to 125), neural tube defects (19, 95% CI 25.3 to 38.3) and chromosomal anomalies (27, 95% CI 21 to 33). In this study, the burden of potentially modifiable risk factors included high rates of diabetes (7.3%, OR 1.98, 95% CI 1.04 to 2.12), maternal age >40 years (7.0%, OR 2.1, 95% CI 1.35 to 3.3), consanguinity (54.5%, OR 1.5, 95% CI 1.28 to 1.81). The mortality for live births with CAs at 2 years of age was 15.8%. CONCLUSIONS: This study documented specific opportunities to improve primary prevention and care. Specifically, folic acid fortification (the neural tube defect prevalence was >3 times that theoretically achievable by optimal fortification), preconception diabetes screening and consanguinity-related counselling could have significant and broad health benefits in this cohort and arguably in the larger Saudi population.

Crisponi/CISS1 syndrome: A case series.

Crisponi/CISS1 syndrome (MIM#272430) is a rare autosomal recessive disease characterized by major feeding difficulties, camptodactyly, and anhidrosis in early childhood; and the subsequent development of paradoxical cold-induced sweating and scoliosis later in life. The syndrome is caused by biallelic mutations in CRLF1 or, much less commonly, CLCF1. Although genotype/phenotype correlation has been elusive, it has been suggested that the level of the mutant protein may correlate with the phenotypic severity. However, we show in this series of 12 patients from four families, all previously unpublished, that the homogeneity of the recently described c.983dupG (p.Ser328Argfs∗2) mutation in CRLF1 was associated with a highly variable degree of severity, and that the phenotype significantly overlaps with the recently described COG6-related anhidrosis syndrome (MIM#615328). Another fifth previously unpublished family is also described with a novel mutation in CRLF1, c.605delC (p.Ala202Valfs*32). In Saudi Arabia the prevalence of the syndrome is probably underestimated due to the difficulty in making the diagnosis considering the complex phenotype with typical neonatal and evolutive features.

Patterns of folic acid use in pregnant Saudi women and prevalence of neural tube defects - Results from a nested case-control study.

BACKGROUND: Although the role of folic acid (FA) in preventing neural tube defects (NTDs) is well documented, its optimal intake in pregnant women is still low in many countries. Here, we prospectively studied the prevalence of NTDs in the newborns and the patterns of FA intake in pregnant Saudi mothers. METHODS: This case-control study was nested within a 3-year project (July 2010 to June 2013) to study the patterns of birth defects in the offspring of Saudi women who received their antenatal care and delivered at Prince Sultan Military Medical City, Riyadh-Saudi Arabia. Enrolled mothers were divided into 4 groups: group 1 (FA taken before pregnancy and continued regularly after conception), group 2 (FA taken post-conception), group 3 (no FA intake), and group 4 (did not remember or were unsure of taking FA). Control mothers were randomly selected from those with normal first obstetrical ultrasound scan at 18-22 weeks of gestation. RESULTS: The cohort included 30,531 mothers giving birth to 28,646 infants. We studied 1179 mothers of babies with birth defects (BDs) and 1262 control mothers. There were 237 (9.7%) mothers in-group 1; 2001 (82%) in-group 2; 154 (6.3%) in-group 3; and 49 (2%) in-group 4. There were 49 babies with NTDs, a prevalence of 1.7/1000 total births. Among the studied mothers 2274 (93%) took FA either full or partial course. CONCLUSION: The high prevalence of NTDs and the low optimal FA intake highlight the need for a strict implementation of staple food fortification and health education program for Saudi women.

Effect of consanguinity on birth defects in Saudi women: results from a nested case-control study.

BACKGROUND: The role of consanguinity in the etiology of structural birth defects outside of chromosomal and inherited disorders has always been debated. We studied the independent role of consanguinity on birth defects in Saudi women with a high prevalence of consanguineous marriages. METHODS: This case and control study was nested within a 3-year prospective cohort study to examine patterns of fetal and neonatal malformations in Saudi women at Prince Sultan Military Medical City (PSMMC), Riyadh -Saudi Arabia. Consanguineous marriages were defined as marriages with first or second cousins (related); unions beyond second cousins (distant relatives) were considered unrelated for this study. RESULTS: During the 3-year study (July 2010 through June 2013), there were 28,646 total births; of these, we included 1,179 babies with major birth defects, and 1,262 babies as their controls. The consanguinity prevalence for all included women was 49.6%. The consanguinity among babies with major Birth Defects (BDs) was 54.5% and 45.2% for controls (P < 0.0002). The prevalence of major birth defects was 41.1 per 1000 total births. Univariate analysis showed that consanguinity had a statistically significant contribution in babies born with genetic syndromes, isolated renal defects, and isolated other defects (P < 0.05). Multivariate logistic regression analyses showed that consanguinity was an independent risk factor for this high prevalence of birth defects in the study population (P < 0.0002). CONCLUSION: The prevalence of major birth defects in the study population is higher than what is reported from European countries. Consanguinity is a significant independent risk factor for the high prevalence of birth defects.

Ciliary genes TBC1D32/C6orf170 and SCLT1 are mutated in patients with OFD type IX.

Clinical syndromes caused by defects in the primary cilium are heterogeneous but there are recurrent phenotypic manifestations that define them as a collective group known as ciliopathies. Dozens of genes have been linked to various ciliopathies but large patient cohorts have clearly revealed the existence of additional genetic heterogeneity, which is yet to be fully appreciated. In our search for novel ciliopathy-linked genes through the study of unmapped ciliopathy phenotypes, we have identified two simplex cases with a severe ciliopathy phenotype consistent with oro-facio-digital syndrome type IX featuring midline cleft, microcephaly, and colobomatous microphathalmia/anophthalmia. In addition, there was variable presence of polydactyly, absent pituitary, and congenital heart disease. The autozygome of each index harbored a single novel truncating variant as revealed by exome sequencing, and the affected genes (SCLT1 and TBC1D32/C6orf170) have established roles in centrosomal biology and ciliogenesis. Our findings suggest a previously unrecognized role of SCLT1 and TBC1D32 in the pathogenesis of ciliopathy in humans.

Effects of body position on thermal, cardiorespiratory and metabolic activity in low birth weight infants.

BACKGROUND: Low birth weight (LBW) infants sleeping prone are known to exhibit many physiological differences from those sleeping supine, including lower energy expenditure (heat production) and higher surface temperature. This apparent increase in heat storage suggests that heat loss may be inhibited in the prone position which, in turn, might influence cardiorespiratory activity. AIMS: To determine the effects of body position (prone vs. supine) on absolute surface temperature profile (heat storage), central-peripheral (C-P) thermal gradients (vasomotor response), cardiorespiratory activity and metabolic gas exchange in growing LBW infants. METHODS: Six-hour continuous recordings of absolute surface temperature profiles, cardiorespiratory activity and O2 and CO2 exchange, along with minute-to-minute assessment of behavioral sleep states were performed in 32 healthy growing LBW infants (birth weight 805-1590 g, gestational age 26-35 weeks and postconceptional age at study 33-38 weeks). Each infant was randomly assigned to the prone or supine position for the first 3 h of the study and then reversed for the second 3 h. Surface temperatures were recorded from 4 sites (forehead, flank, forearm and leg) and averaged each minute. Central (forehead and flank)-to-peripheral (forearm and leg) and forehead-to-environment (H-E) thermal gradients were calculated from the surface temperatures. Corresponding sleep states were aligned with minute averages obtained from the temperature and cardiorespiratory measurements. Data were then sorted for prone and supine positions during quiet (QS) and active sleep (AS) and compared using paired t-tests. RESULTS: In the prone position during both AS and QS, infants had higher forehead, flank, forearm and leg surface temperatures, narrower C-P gradients, higher heart rates and respiratory frequency, and lower heart rate and respiratory variability. Despite similar environmental temperatures, the H-E gradient was higher in the prone position. In the prone position infants demonstrated lower O2 consumption and CO2 production and a higher respiratory quotient. CONCLUSIONS: Despite thermoregulatory adjustments in cardiorespiratory function, infants sleeping prone have relatively higher body temperature. The cardiorespiratory responses to this modest increase in temperature indicate that thermal and metabolic control of cardiac and respiratory pumps seem to work in opposition. The consequences of any attendant changes in blood gas activity (e.g. hypocapnia and/or increased mixed venous oxygen concentration) due to this override of metabolic control remains speculative.

Pattern of neonatal and postneonatal deaths over a decade (1995--2004) at a Military Hospital in Saudi Arabia.

OBJECTIVE: To describe and monitor the causes of neonatal and postneonatal deaths in the Neonatal Intensive Care Unit (NICU) over a 10-year-period. METHODS: This is a descriptive study of all infants who died in the NICU from January 1995 until December 2004 at Riyadh Military Hospital, Riyadh, Kingdom of Saudi Arabia. Data were collected prospectively on all infants admitted to NICU. The cause of death for each infant was discussed and determined by at least 2 consultant neonatologists. Deaths were classified according to the modified Wigglesworth's classification of perinatal death. RESULTS: During the study period, there were 79871 live births and 526 deaths, in which 446 (84.2%) were inborn deaths and 80 (15.8%) were outborn. Of the inborn deaths, 251 infants died between 1-6 days, 103 died between 7-27 days, and 92 died after 27 days. Lethal malformations led to death in 36%, prematurity and its complications in 42%, hypoxic ischemic encephalopathy in 5%, while other specific diagnoses, combined, led to death in 17% of the cases. CONCLUSION: Prematurity and its complications followed by congenital malformations were the leading causes of death.

Variables associated with the early failure of nasal CPAP in very low birth weight infants.

OBJECTIVE: To identify risk factors and neonatal outcomes associated with the early failure of "bubble" nasal continuous positive airway pressure (CPAP) in very low birth weight (VLBW) infants with respiratory distress syndrome (RDS). STUDY DESIGN: Following resuscitation and stabilization at delivery, a cohort of 261 consecutively inborn infants (birth weight < or = 1250 g) was divided into three groups based on the initial respiratory support modality and outcome at 72 hours of age: "ventilator-started" group, "CPAP-failure" group, and "CPAP-success" group. RESULTS: CPAP was successful in 76% of infants < or = 1250 g birth weight and 50% of infants < or = 750 g birth weight. In analyses adjusted for postmenstrual age (PMA) and small for gestational age (SGA), CPAP failure was associated with need for positive pressure ventilation (PPV) at delivery, alveolar-arterial oxygen tension gradient (A-a DO2) >180 mmHg on the first arterial blood gas (ABG), and severe RDS on the initial chest x-ray (adjusted odds ratio [95% CI] = 2.37 [1.02, 5.52], 2.91 [1.30, 6.55] and 6.42 [2.75, 15.0], respectively). The positive predictive value of these variables ranged from 43% to 55%. In analyses adjusted for PMA and severe RDS, rates of mortality and common premature morbidities were higher in the CPAP-failure group than in the CPAP-success group. CONCLUSION: Although several variables available near birth were strongly associated with early CPAP failure, they proved weak predictors of failure. A prospective controlled trial is needed to determine if extremely premature spontaneously breathing infants are better served by initial management with CPAP or mechanical ventilation.

Is the new definition of bronchopulmonary dysplasia more useful?

OBJECTIVE: To determine the incidence of bronchopulmonary dysplasia (BPD) in low birth weight (LBW) infants <1251 g managed with early bubble nasal continuous positive airway pressure (NCPAP) and a gentle ventilation strategy using the newly proposed definition for BPD and the previous definitions. METHODS: Needs for supplemental oxygen and positive pressure (positive pressure ventilation or NCPAP) during initial hospitalization were evaluated in 266 inborn LBW infants (birth weight <1251 g). The data were categorized in three weight groups, <751, 751 to 1000 and 1001 to 1250 g and the incidence of BPD was computed in survivors based on oxygen need at 28 days, 36 weeks postmenstrual age (PMA) and the new severity of BPD criteria, that is, mild BPD: need for supplemental oxygen > or =28 days, but not at 36 weeks PMA; moderate BPD: need for supplemental oxygen > or =28 days and <30% at 36 weeks PMA and severe BPD: need for supplemental oxygen > or =28 days, and >30% at 36 weeks PMA and/or positive pressure at 36 weeks PMA. Further, BPD-associated comorbidities and short-term outcome data during hospitalization were compared among the groups, defined by severity of BPD. RESULTS: Among LBW infants <1251 g, the incidences of BPD at 28 days and 36 weeks PMA were 21.1 and 7.4% respectively. Using the newly defined criteria, the incidences of mild, moderate and severe BPD were 13.5, 4.8 and 2.6%, respectively. In total, 64.6% of these infants had mild BPD and 70.8% weighed <751 g at birth. Associated comorbidities correlated significantly with grades of underlying pulmonary disease. Also, significantly longer hospital stay, discharge at a higher PMA and lower growth velocity was observed with increasing grades of BPD. CONCLUSIONS: The new system for grading the severity of BPD offers a better description of underlying pulmonary disease and correlates with the infant's maturity, growth and overall severity of illness. Whether it will have a role in predicting long-term outcome remains to be determined.

Subcutaneous emphysema and pneumomediastinum as presenting manifestations of neonatal tracheal injury.

Neonatal tracheal injury/perforation is an uncommon complication of traumatic deliveries or endotracheal intubation. We present a case of neonatal tracheal injury following delivery at term that presented with subcutaneous emphysema and pneumomediastinum before any attempt at intubation. The clinical course, treatment, and outcome are described.

Uses and abuses of sodium bicarbonate in the neonatal intensive care unit.

Despite the lack of evidence for its effectiveness in the treatment of acid-base disturbances in critically ill patients of all ages, and despite several lines of evidence that indicate it might be dangerous, bicarbonate therapy is used routinely in many neonatal intensive care units. The justification for the persistent use of this controversial therapy comes from a variety of sources, many based more in philosophy than in science. Clinicians contemplating the use of bicarbonate therapy should consider what they expect the intervention to accomplish and what evidence exists that their therapeutic objective will be met. Without rigorous scientific support for this therapy, it should be considered of unproven value and, therefore, experimental.