Significance of Intermittent Hypoxic Episodes in Premature Infants Prior to Discharge.

Objective The aim of this study was to determine the rate and severity of intermittent hypoxic episodes in premature infants who underwent overnight pulse oximetry prior to discharge. Methods Preterm infants with a birth weight of 1500 grams or less and who underwent overnight pulse oximetry prior to discharge were included. Maternal and neonatal demographic data and complications of prematurity were recorded. All infants underwent overnight pulse oximetry prior to discharge and the McGill score was used to categorize the degree of desaturations (categories 1-4; normal, mildly, moderately, and severely abnormal). Results Fifty infants underwent the overnight pulse oximetry The McGill score showed that 2% had no hypoxia, 50% had mild hypoxia, 20% had moderate hypoxia, and 28% had severe hypoxia. The frequency of desaturations (62.5%) was found more in infants with a birth weight of 1000 grams or less. The results showed that the O2 requirement at discharge was significant (p = 0.0341), and increased values of O2 at discharge were associated with more severe hypoxia. As a result of these findings, 40% of infants were discharged home on oxygen and 26% were discharged on caffeine. Fifty-two percent of infants were initially diagnosed to have stages 1 & 2 retinopathy of prematurity (ROP), 14% had stage 3, and 2% had stage 4 ROP. Eight percent of infants required surgical intervention for ROP. Conclusions Clinically inapparent significant episodes of intermittent hypoxia (IH) are frequent in preterm infants in the early postnatal age, and they may persist post-discharge. Knowledge of the association between IH and morbidity among all neonatal intensive care unit (NICU) caregivers would be of great benefit. Indications for screening preterm infants at risk of severe IH should be reconsidered.

Exposure of preterm neonates receiving total parenteral nutrition to phthalates and its impact on neurodevelopment at the age of 2 months.

This prospective study assessed the exposure to phthalates of preterm neonates who received total parenteral nutrition (TPN) during their stay in the neonatal intensive care unit (NICU) and the risk of neurodevelopment delays at the age of 2 months. Our study recruited 33 preterm neonates who required TPN upon NICU admission. Urine samples for analyzing phthalate metabolites were obtained at admission and then daily until the last day of receiving TPN. Phthalates in the daily TPN received by the preterm neonates were analyzed. The neurodevelopment of the neonates was assessed using the Ages and Stages Questionnaire Edition 3 (ASQ-3). Diethyl phthalate and butyl benzyl phthalate were found in all TPN samples, while 27% and 83% contained dibutyl phthalate and di-(2-ethylhexyl) phthalate (DEHP), respectively. Yet, the daily dose of each phthalate that our preterm neonates received from TPN was much lower than the recommended tolerable limit. Urinary levels of monobenzyl phthalate and four metabolites of DEHP [i.e., mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP)] and the sum of four DEHP metabolites (∑4DEHP) increased significantly in preterm neonates before discharge. However, these levels were not correlated with their phthalate parent compounds in TPN, suggesting other sources of exposure in the NICU. At 2 months, we found that urinary levels of mono-iso-butyl phthalate (MiBP), MECPP, MEHP, and ∑4DEHP were inversely related to fine motor skills. After adjusting for head circumference, the inverse relationships remained significant, suggesting direct effects from phthalates. Given the extreme vulnerability of our population, it is critical to minimize exposure to phthalates during their NICU stay.

Exposure of preterm neonates to toxic metals during their stay in the Neonatal Intensive Care Unit and its impact on neurodevelopment at 2 months of age.

BACKGROUND: Premature neonates might be exposed to toxic metals during their stay in the neonatal intensive care unit (NICU), which could adversely affect neurodevelopment; however, limited evidence is available. The present study was therefore designed to assess the exposure to mercury, lead, cadmium, arsenic, and manganese of preterm neonates who received total parenteral nutrition (TPN) and/or red blood cell (RBC) transfusions during their NICU stay and the risk of neurodevelopment delay at the age of 2 months. METHODS: We recruited 33 preterm neonates who required TPN during their NICU admission. Blood samples were collected for metal analysis at two different time points (admission and before discharge). Metals in the daily TPN received by preterm neonates were analyzed. Neurodevelopment was assessed using the Ages and Stages Questionnaire Edition 3 (ASQ-3). RESULTS: All samples of TPN had metal contamination: 96% exceeded the critical arsenic limit (0.3 µg/kg body weight/day); daily manganese intake from TPN for preterm neonates exceeded the recommended dose (1 µg/kg body weight) as it was added intentionally to TPN solutions, raising potential safety concerns. All samples of RBC transfusions exceeded the estimated intravenous reference dose for lead (0.19 µg/kg body weight). Levels of mercury, lead and manganese in preterm neonates at discharge decreased 0.867 µg/L (95% CI, 0.76, 0.988), 0.831 (95%CI, 0.779, 0.886) and 0.847 µg/L (95% CI, 0.775, 0.926), respectively. A decrease in ASQ-3-problem solving scores was associated with higher levels of blood lead in preterm neonates taken at admission (ß = -0.405, 95%CI = -0.655, -0.014), and with plasma manganese (ß = -0.562, 95%CI = -0.995, -0.172). We also observed an association between decreased personal social domain scores with higher blood lead levels of preterm neonates before discharge (ß = -0.537, 95%CI = -0.905, -0.045). CONCLUSION: Our findings provide evidence to suggest negative impacts on the neurodevelopment at 2 months of preterm infants exposed to certain metals, possibly related to TPN intake and/or blood transfusions received during their NICU stay. Preterm neonates may be exposed to levels of metals in utero.

The cumulative risk assessment of phthalates exposure in preterm neonates.

Phthalates are widely used plasticizers in various consumer products and medical devices, with some reporting as having estrogenic and anti-androgenic endocrine-disrupting effects. Premature neonates may be exposed to high levels of specific phthalates during hospitalization in the neonatal intensive care unit (NICU) because of reliance on multiple medical procedures that pose a possible health risk. The present study utilized seven urinary phthalate metabolites of dibutyl phthalate isomers [(di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP)], butylbenzyl phthalate (BBzP), and di(2-ethylhexyl) phthalate (DEHP) that had been previously measured in 33 preterm neonates sampled at hospital admission (N = 23) and daily during their NICU stay (N = 260). We aimed to perform: (1) cumulative risk assessment (CRA) using the volume and creatinine-adjusted models; (2) examine the temporal variability of CRA from repeated measures and (3) estimate the risk of cumulative exposure to phthalates based on their anti-androgenic and/or estrogenic properties. We multiplied the relative activity of individual phthalates exhibiting estrogenic or anti-androgenic effects by daily intake. For each preterm neonate, CRA was assessed based on the hazard index (HI) metric [the sum of hazard quotients] based on three reference doses for anti-androgenicity: the tolerable daily intake (TDI) from the European Food Safety Authority, the reference dose (RfD-AA) published in 2010 and newly revised published in 2020 (NRfD-AA). The metabolites of BBzP and DEHP were 2-23 fold higher in preterm neonates during their NICU stay. Median HIs increased in the order of HINRfDAA > HIRfDAA > HITDI. In the creatinine-based model, 87% (92%), 87% (96%), and 100% (100%) of preterm neonates at admission (during NICU stay) showed HITDI, HIRfD-AA, and HINRfD-AA exceeding 1, respectively with DEHP the most prevalent. The temporal reproducibility of HI (based on three reference doses) during preterm neonate stay in the NICU was high, with intra-class correlation coefficients ranging between 0.77 and 0.97, suggesting persistent exposure to phthalates. The four phthalates that preterm neonates were exposed to in the NICU exhibited estrogenic binding and anti-androgenic effects with median values (creatinine-based) of 98.7 and 56.9 µg/kg body weight/day, respectively. This was especially true for DEHP. The results indicate that preterm neonates in this NICU setting are probably at high risk of cumulative phthalate exposure with anti-androgenic properties that may have long-term adverse reproductive and developmental effects.

Observational cohort study of perinatal outcomes of women with COVID-19.

BACKGROUND: Understanding the impact of SARS-CoV-2 infection on pregnancy outcomes and of pregnancy on COVID-19 outcomes is critical for ensuring proper prenatal and antenatal care. No similar studies have been published in Saudi Arabia. METHODS: We performed a prospective cohort study of pregnant women with confirmed SARS-CoV-2 infection who presented at King Faisal Specialist Hospital and Research Center (KFSHRC) in Riyadh, Kingdom of Saudi Arabia. COVID-19 staging was performed, pregnancy-related complications were assessed, and neonatal infection was evaluated. RESULTS: We enrolled 81 patients (mean age 31.75 years, SD 5.25) of which there were 17 cases in the first trimester, 20 in the second trimester, and 34 in the third trimester. The distribution of COVID-19 severity was 40 patients with Stage A, 36 with Stage B, 4 with Stage C, and 1 with Stage D. Complications were pregnancy loss in 2 patients (one in each first and second trimester) and 1 fetal death after 20 weeks of pregnancy, 7 patients with fetal growth restriction, and 8 with pre-term delivery. CONCLUSIONS: We did not observe an unusual frequency of pregnancy-related complications due to SARS-CoV-2 infection in this high-risk obstetric population and there was no evidence of vertical transmission in newborns from women who delivered while positive for the virus.

Randomised trial estimating length of endotracheal tube insertion using gestational age or nasal-tragus length in newborns: a study protocol.

INTRODUCTION: Endotracheal tube (ETT) insertion depth estimation is important for optimal placement of ETT tip and balanced ventilation of the lungs. Various methods are available to determine the ETT insertion depth. The Neonatal Resuscitation Programme recommends the gestational age and nasal-tragus length (NTL) methods for estimating ETT insertion depth during cardiopulmonary resuscitation. However, the prospective data comparing these two methods is lacking. METHODS AND ANALYSIS: This is an open-label multi-centre randomised controlled trial, where gestational age and NTL methods will be used to determine the initial ETT insertion depth in term and preterm infants that are less than 28 days old, requiring oral intubation in the delivery room or neonatal intensive care unit (NICU). SITES AND SAMPLE SIZE: The trial is aimed to recruit 454 infants over 3 years across tertiary level NICUs. OUTCOMES: The primary outcome includes an optimally positioned ETT, defined as an ETT tip between the upper border of the first thoracic vertebra and the lower border of the second thoracic vertebra. The outcome is assessed by a paediatric radiologist, who will be masked to the group assignment. Secondary outcomes are malpositioned ETT tips, pneumothorax, ETT repositioning, chronic lung disease, invasive ventilation days, and death. ANALYSIS: Data will be analysed using the intention-to-treat principle. The primary and categorical secondary outcomes will be compared using the χ2 test. Adjusted risk ratios of outcomes will be calculated along with 95% CIs through multivariable logistic regression analysis, including covariates deemed biologically to influence the outcomes. ETHICS AND DISSEMINATION: The study has been approved by the PNU Research Ethics Board (20-0148) and the respective ethical review boards of the participating centres. The results will be disseminated through conference meetings, social media platforms, and publications in scientific journals. TRIAL REGISTRATION NUMBER: NCT04393337.

Effects of Probiotics and Lactoferrin on Necrotizing Enterocolitis in Preterm Infants.

Background Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in neonates. Despite intensive research, the etiology and pathophysiology of NEC is still obscure. Evidence from recent studies and meta-analyses showed a significant role of probiotics as a prophylactic measure in reducing NEC, sepsis, and mortality. However, obstacles against the generalization of the results still remain. The aim of the study was to evaluate the role of prophylactic administration of probiotics and lactoferrin in reducing the rate of NEC in preterm infants. Methods In this retrospective cohort study, all medical records of infants born with a birth weight of 1,500 g and less who were born between 2012 and 2017 were reviewed. The enrolled infants were divided into two groups: group 1 included infants born between January 2012 and August 2014, a period before probiotics were started in our unit, and group 2 included infants born between January 2014 and December 2017 after starting probiotics and lactoferrin. Multiple variables were collected including maternal data, neonatal data, and risk factors for NEC. Results Medical records of 284 infants who met our inclusion criteria were reviewed. Of the 284 infants, 134 were in group 1 and 150 infants were in group 2. There were no significant statistical differences between group 1 and group 2 in neonatal and maternal demographic data and clinical data. Of 134 infants who received probiotics and lactoferrin, 11 developed NEC, while 26 of the 150 infants in group 2 developed NEC, and the difference was statistically significant (p = 0.023). Conclusion Probiotics and lactoferrin given orally to very low birth weight preterm infants were associated with a decreased rate of NEC.

Decisions and outcome for infants born near the limit of viability.

BACKGROUND: Initiation or withholding life support at birth on infants born prematurely near the limit of viability is not an easy decision, with wide variation in practice around the world. Our aim was to review the outcome of preterm infants born near the limit of viability at 23-25 weeks gestation in our institution, with regard to resuscitation decision, survival, and major outcome measures. METHODS: We included all live newborn infants born prematurely at 23-25 weeks gestation at King Faisal Specialist Hospital and Research Centre from January 2006 to December 2015. We collected data on resuscitation decisions, survival, and major neonatal morbidities such as severe brain injury, severe retinopathy of prematurity, and bronchopulmonary dysplasia. RESULTS: Between January 1, 2006 and December 31, 2015, 97 infants with a gestational age (GA) of 23-25 weeks gestation were admitted; 23, 42, and 32 infants were born at 23, 24, and 25 weeks gestation, respectively. At 23 weeks gestation, full support was initiated in 87% of patients and later on support was withheld in 17.4% of patients, finally 13% of patients survived to discharge. At 24 weeks, full support was initiated in 97.6% of patients, then withheld in 7.1% of patients, and ultimately 59.5% survived. At 25 weeks, full support was initiated in 93.8% of patients, then withheld in 15.6% of patients, and ultimately 62.5% survived. In terms of survival with and without the three major neonatal morbidities, at 23 weeks gestation, no infant survived without any morbidity as compared to 7.1% and 28.1% at 24 and 25 weeks, respectively. The incidence of survival with 1 major morbidity was 8.7%, 30.9%, and 34.4% at 23, 24, and 25 weeks, respectively, the incidence of survival with 2 major morbidities was 0%, 19%, and 0% at 23, 24, and 25 weeks, respectively, and the incidence of survival with 3 major morbidities was 4.3%, 2.4%, and 0% at 23, 24, and 25 weeks, respectively. CONCLUSION: In our patient cohort, survival and survival without major neonatal morbidity were very low at 23 weeks gestation, but it improved gradually as gestational age advanced.

Maternal Vitamin D Levels and Its Correlation With Low Birth Weight in Neonates: A Tertiary Care Hospital Experience in Saudi Arabia.

Introduction A meta-analysis showed that 63.6% of the Saudi population have vitamin D deficiency, including many pregnant women. Studies showed that maternal vitamin D deficiency during pregnancy is a risk factor for low birth weight (LBW) in neonates. Neonatal LBW is a risk factor for multiple neonatal complications including respiratory distress syndrome, necrotizing enterocolitis, chronic renal disorders, seizures, and sepsis. Our objective in this study is to determine a correlation between low maternal vitamin D level and neonatal LBW in Saudi Arabia. Methods Neonates (n = 119) were divided based on their gestational age (GA) into full-term neonates (≥37 weeks) and preterm neonates (< 37 weeks) and based on birth weight into normal birth weight neonates (full-term = 2,500-3,500 g or preterm > 10th percentile) and LBW neonates (full-term < 2,500 g or preterm < 10th percentile). Vitamin D deficiency is defined as 25- hydroxyvitamin D level less than 50 nmol/L. Results Correlating neonatal birth weight with maternal vitamin D level during pregnancy was statistically insignificant for both full-term neonates and preterm neonates. In contrast, comparing the mean maternal vitamin D levels in each neonatal group showed that the mean were higher in mothers of neonates with normal birth weight. Conclusion Because 87.4% of mothers had low vitamin D levels during their pregnancy, correlation between maternal vitamin D level and LBW in neonates could not be found. However, mean maternal vitamin D levels were higher in mothers with normal birth weight neonates. Therefore, further detailed studies are required to establish local guidelines about the treatment of vitamin D deficiency during pregnancy.

Kangaroo mother care practice, knowledge, and perception among NICU nurses in Riyadh, Saudi Arabia.

BACKGROUND: The imapct of Kangaroo Mother Care (KMC) in neonates is positively reported in the literature. However,several challenges hindered the wide-scale application of this practice. OBJECTIVES: To assess the levels of knowledge and competency of kangaroo mother care (KMC) among nurses and to identify the potential barriers to practice. METHODOLOGY: Structured web-based questionnaires were submitted to nurses working at neonatal intensive care units (NICUs) located in Riyadh, Saudi Arabia. The participants were asked to answer 23 questions distributed in four main domains, namely, demographic data, knowledge about KMC, practice levels, and barriers to KMC practice. For answers to the knowledge and barriers to practice domains, the mean scores (standard deviations) were calculated to present participants' perceptions and beliefs from 1 (strongly disagree) to 5 (strongly agree). RESULTS: Two hundred nine NICU nurses responded (95.2% females, 89.5% working in a government hospital, 69.9% obtained a Bachelor's degree). The majority of respondents perceived KMC as promoting maternal-infant bonding (4.47 ± 1.3) and enhancing successful breastfeeding (4.44 ± 0.9), while there were considerable uncertainties about KMC application in infants weighing < 1000 g (2.21 ± 1.2). Most of the nurses encouraged parents to perform KMC (92.8%) and provided sufficient information to optimize practice (90%). However, several barriers were apparent, including fear of accidental extubation, lack of time due to workload, familial reluctance to initiate KMC, and lack of privacy during KMC practice. CONCLUSION: There is reasonable knowledge among NICU nurses, and most of them are actively engaged in practice. There is an urgent need to address the reported barriers through the implementation of clear practice guidelines, provision of suitable educational programs, optimization of staff numbers, and financial support for the development of areas conducive to KMC.

Congenital Central Hypoventilation Syndrome Presenting with Seizures.

Congenital central hypoventilation syndrome (CCHS) is a critical and rare autosomal dominant disorder that was first described by Robert Mellins in 1970. CCHS is defined to be an autonomic nervous system (ANS) dysfunction that usually presents in the neonatal period with hypoventilation and dysregulated autonomic homeostasis on a multi-system level. Classically, CCHS presents with normal ventilation while awake, and hypoventilation with normal respiratory rate during sleep. CCHS has been causally linked to the paired-like homeobox 2B (PHOX2B) gene. We report the case of a full-term male infant diagnosed with CCHS at two months of age with repeated extubation failure secondary to CCHS. The patient was discharged at five months of age with a home ventilator.

Use of high noninvasive respiratory support pressures in preterm neonates: a single-center experience.

PURPOSE: To describe the incidence, indications and clinical outcomes following high pressures on noninvasive respiratory support (NRS) in preterm neonates. STUDY DESIGN: Retrospective cohort study of all neonates with BW <1.500 g admitted from July 2012 to June 2014 and placed on high noninvasive respiratory support (NRS), defined as mean airway pressure ≥10 cm H2O for at least 12 continuous hours using nasal continuous positive airway pressure (NCPAP) and/or nasal high-frequency ventilation (NIHFV). Clinical and physiological outcomes following high NRS were ascertained. Median (IQR) and percentages were used to describe continuous and categorical data, respectively. RESULTS: There were 131 instances of high NRS use in 70 of 315 eligible infants. Most common indication was post-extubation, observed in 37% (49/131) of high NRS instances. Intubation was avoided in 71% (93/131) of instances in the first 7 days following high NRS initiation. There were no physiological perturbations in heart rate, blood pressure or oxygen requirement. Furthermore, there were no instances of lung hyperinflation, pneumothoraces or spontaneous intestinal perforation following high NRS. CONCLUSION: The use of high NRS pressure was followed by avoidance of intubation in the majority of cases without adverse effects. Further research on high NRS use including its indications, clinical outcomes and safety profile is warranted.