Short-term outcome of very low-birth-weight infants in a tertiary care hospital in Saudi Arabia over a decade.

BACKGROUND: Knowledge on short-term outcomes of preterm infants is important for quality control. Our objective was to analyze the outcomes of very low birth weight infants admitted to our neonatal intensive care unit over a ten years' period and to compare the results with internationally published data. METHODS: We analyzed the outcome measures for all live born infants with birth weight (BW) of 400-1500 grams and gestational age (GA) of 23-32 weeks born at King Faisal Specialist Hospital & Research Centre between 2006 and 2015. Results were compared to data from four international neonatal networks. RESULTS: During the study period, we admitted 528 infants born at a gestational age of≥23 and≤32 weeks with a very low birth weight (VLBW) of 400-1500 grams. Mean (SD) GA was 28 (2.4) weeks and mean (SD) BW was 1007 (290) grams. A hundred and twenty-nine (24.4%) infants were small for gestational age and major congenital anomalies were present in 56 (10.6 %) infants. The rate of bronchopulmonary dysplasia (BPD) was 24.4 %, necrotizing enterocolitis (NEC) 9.1%, patent ductus arteriosus (PDA) 29.9%, severe intraventricular hemorrhage (IVH)10.8 %, periventricular leukomalacia (PVL) 5.7%, severe retinopathy of prematurity (ROP) 8%, and late-onset sepsis was 18.8%. The incidences of major neonatal outcomes such as CLD, NEC, severe IVH and severe ROP were comparable to the international cohorts. CONCLUSION: In our population of preterm infants, survival rates and complications of prematurity were comparable to international data.

Positive distending pressure produced by heated, humidified high flow nasal cannula as compared to nasal continuous positive airway pressure in premature infants.

OBJECTIVE: our objective is to assess the positive distending pressure generated by high flow nasal cannula and nasal continuous positive airway pressure by measuring the end esophageal pressure in premature infants. STUDY DESIGN: This is a pilot, non-randomized, open label, uncontrolled, crossover assignment study that included neonates born with a birth weight of 1750 grams or less and receiving nCPAP ventilatory support for 24 hrs or more and requiring FiO2 21-50% on nCPAP. Each infant was started on nCPAP at 4, 6 and 8 cm H2O then on three levels of HHHFNC, 4 L/min, 6 L/min and 8 L/min with 4 hours interval on each flow level. Esophageal pressure (EP), apnea of prematurity, FiO2 requirements and bradycardia were recorded during the different levels of CPAP and HHHFNC use. RESULTS: The study showed that there were no complications observed during the study such as pneumothorax. It showed that EP created by the three different levels of HHHFNC were slightly higher than that EPs created by the three different levels of nCPAP, but statistically not significant. There was no significant change in the FiO2 requirements during the study. There was a trend towards the improvement of oxygen saturation in HHHFNC at different levels and it was statistically significant when 8 L/min was used (P 0.0214). The rates of bradycardia and apnea in nCPAP and HHHFNC were low and statistically were not significant, however the episodes of bradycardia were less in HHHFNC and they were statistically significant at the level of 6 L/min. CONCLUSIONS: HHHFNC in premature infants was well-tolerated with no adverse side effects such as pneumothorax, desaturation, apnea and bradycardia. The study also showed that HHHFNC was able to deliver distending pressure equal to nCPAP. Moreover, we have observed a significant improvement in oxygen saturation when higher levels of HHHFNC was used, most probably due to the improvement of infant comfort which is a noticeable feature of HHHFNC.

Neonatal short-term outcomes of gestational diabetes mellitus in saudi mothers: a retrospective cohort study.

BACKGROUND: Gestational diabetes mellitus (GDM) affects up to 10% of all pregnancies and results in significant maternal and neonatal morbidities. OBJECTIVES: Our main objective was to investigate retrospectively the rate of neonatal intensive care unit (NICU) admissions and significant neonatal complications in pregnant mothers with gestational diabetes. MATERIALS AND METHODS: A retrospective cohort study was conducted. The medical records of King Khalid University Hospital (KKUH) were reviewed from January till December 2007. All pregnant women with GDM along with their offsprings were included and matched with healthy pregnant women. The primary outcome was the rate of NICU admission, hypoglycemia, birth weight and length of hospital stay. RESULTS: A total of 766 mothers (419 GDM mothers and 347 controls) with their term babies were included. Infants born to GDM mothers had significantly higher risk of NICU admissions [OR 2.7 (95% CI 1.5, 4.9), P value 0.0004], longer hospital stay and higher rates of hypoglycemia. Newborns of GDM mothers had higher rates of perinatal distress and macrosomia; however, the difference did not reach statistical significance. CONCLUSION: GDM remains a significant morbidity to newborns resulting in increased intensive care admission, prolongation of hospital stay and higher rates of neonatal hypoglycemia. More efforts to assure early recognition and strict sugar control during pregnancy are still needed.

Caffeine metabolism in premature infants.

Caffeine has been used frequently in the treatment and prevention of apnea of prematurity. The metabolism of caffeine depends on the activities of the hepatic enzymes that vary from one infant to another. The objective of this study was to determine the influence of postnatal age (PNA), birth weight (BW), study weight (SW), gestational age (GA), postconceptual age (PCA), and gender on the maturation of caffeine metabolism in premature infants. The caffeine base was administered orally as a loading dose of 10 mg/kg, followed by a maintenance dose of 2 mg/kg every 24 hours. The steady-state concentration of caffeine and metabolites was measured in plasma taken on the 5th-day postloading dose. The molar concentration ratios for the N3 (N3-), N7 (N7-), N1 (N1-), and all methyl (Nall-) demethylation processes; clearance (CL); and the percentage of molar concentration of caffeine found in plasma to that of the total caffeine and metabolites (%CAF) were calculated from samples collected from 80 neonatal infants. The 48 male and 32 female premature infants had median (range) BW (g), GA (weeks), SW (g), PCA (weeks), and PNA (days) of 1300 (650-2260), 30 (24-34), 1630 (980-2670), 34 (29-40), and 28 (5-60), respectively. The median (range) of the ratios for the %CAF, CL, and the N3-, N7-, N1-, and Nall- were 86.9 (52.9-99.0), 0.127 (0.046-0.503) ml.kg-1.min-1, 0.032 (0-0.438), 0.070 (0.007-0.471), 0.026 (0-0.283), and 0.0463 (0.003-0.303), respectively. When the patients were stratified into four PNA age groups, each older group showed a consistently higher level of caffeine metabolic activity for the N3-, N7-, and Nall- pathways with a corresponding decrease in the %CAF, whereas no significant differences were seen for the N1-pathway or for CL. No pattern of significant differences between the demethylation process ratios, %CAF, or CL was seen between groups of infants when they were stratified according to BW, SW, PCA, or GA. The female infants were found to have significantly higher rates of caffeine metabolism as shown by %CAF, N1-, N3-, and Nall- processes but not the N7-. Multivariate linear regression analysis by two methods demonstrated that PNA is significantly related to %CAF and Nall-, whereas the female patients had higher levels of metabolic activity for the %CAF and N1- process. The authors conclude that the N7-demethy-lation process is the predominate caffeine metabolic process in premature infants. Furthermore, the maturation of the caffeine metabolism in premature infants with a PNA of less than 60 days increases with postnatal age, regardless of birth weight, gestational age, postconceptual age, and study weight. The female neonatal patients demonstrated a higher rate of caffeine metabolism than the males.

The use of L-arginine [correction of F-arginine] and phosphodiesterase inhibitor (dipyridamole) to wean from inhaled nitric oxide.

A full-term, female neonate developed acute hypoxemic respiratory failure complicated by persistent pulmonary hypertension of the newborn (PPHN), and responded to high-frequency oscillatory ventilation (HFOV) and inhaled nitric oxide (iNO). Discontinuation of iNO was attempted three times and was followed by severe desaturation due to right-to-left shunt through the patent ductus arteriosus and patent foramen ovale. As a result of iNO dependency state and rebound pulmonary hypertension, the neonate was maintained on iNO therapy for dipyridamole alone was unsuccessful. However, successful discontinuation of iNO therapy was achieved by combination of L-Arginine and dipyridamole. Exogeous NO may lead to down regulation of endogenous NO production, and further lead to rapid hydrolization of cyclic guanosine 3', 5' monophosphate (cGMP), the smooth muscle relaxant, by the enzyme phosphodiesterase. Moreover L-Arginine, the precursor for the formation of endogenous NO, has been found to be deficient in neonates with PPHN, so we speculated that by inhibiting phosphodiesterase and administrating L-Arginine smooth muscle relaxation occurred, and consequent weaning from iNO was achieved.

The use of indomethacin for the prevention of intraventricular brain hemorrhage in high-risk neonates.

OBJECTIVE: The objective of this study was to determine the effect of indomethacin on reducing the incidence of intraventricular hemorrhage in premature infants treated in our units at King Faisal Specialist Hospital and Research Centre. METHODS: This historical cohort study included 45 infants born with birth weights of 1250 g or less and received indomethacin in the first 12 hours of life for intraventricular hemorrhage prevention. The treated infants were compared to 33 other infants with birth weights of 1250 g or less who did not receive indomethacin for intraventricular hemorrhage prevention. Data collected included demographic, complications of prematurity, renal function and maternal data. RESULTS: Mean birth weight (grams) and gestational age (week) were 928.6+/-34, 1066.2+/-38.9, 27.2+/-0.37 and 29+/-0.42 for the treated and the control infants. Overall incidence of intraventricular hemorrhage decreased significantly in the treated infants in comparison to the controls (P=0.0169). There was no infant with Grade 3-4 intraventricular hemorrhage found in the treated group while 2 developed grade 3-4 intraventricular in the control group which was insignificant. There were no statistically significant differences between the groups in terms of the complications of prematurity, Apgar scores at 5 minutes, airleak syndrome and the use of umbilical catheters. The total fluid intake in the first 4 days after starting the treatment was comparable between the groups. There were no significant differences between the groups in urine output in day 1, 3 and 4. However the urine output decreased significantly in day 2 in the treated group (P = 0.0349). There were no statistically significant differences in serum urea and creatinine between the groups. CONCLUSION: Low dose indomethacin given in the first 12 hours of life was shown to be associated with a decrease in intraventricular hemorrhage in premature infants and it was not associated with significant adverse effect.

The use of indomethacin for the prevention of intraventricular brain hemorrhage in high-risk neonates.

OBJECTIVE: The objective of this study was to determine the effect of indomethacin on reducing the incidence of intraventricular hemorrhage in premature infants treated in our units at King Faisal Specialist Hospital and Research Centre. METHODS: This historical cohort study included 45 infants born with birth weights of 1250g or less and received indomethacin in the first 12 hours of life for intraventricular hemorrhage prevention. The treated infants were compared to 33 other infants with birth weights of 1250g or less who did not receive indomethacin for intraventricular hemorrhage prevention. Data collected included demographic, complications of prematurity, renal function and maternal data. RESULTS: Mean birth weight (grams) and gestational age (week) were 928.4+/-34, 1066.2+/-38.9, 27.2+/-0.37 and 29+/-0.42 for the treated and the control infants. Overall incidence of intraventricular hemorrhage decreased significantly in the treated infants in comparison to the controls (P=0.0169). There was no infant with Grade 3-4 intraventricular hemorrhage found in the treated group while 2 developed grade 3-4 intraventricular in the control group which was insignificant. There were no statistically significant differences between the groups in terms of the complications of prematurity, Apgar scores at 5 minutes, airleak syndrome and the use of umbilical catheters. The total fluid intake in the first 4 days after starting the treatment was comparable between the groups. There were no significant differences between the groups in urine output in day 1, 3 and 4. However the urine output decreased significantly in day 2 in the treated group (P = 0.0349). There were no statistically significant differences in serum urea and creatinine between the groups CONCLUSION: Low dose indomethacin given in the first 12 hours of life was shown to be associated with a decrease in intraventricular hemorrhage in premature infants and it was not associated with significant adverse effect.

Late hyporegenerative anemia in neonates with rhesus hemolytic disease.

This study was conducted to determine the risk factors of the late hyporegenerative anemia in Rh-isoimmunized infants. Data on 36 infants with rhesus hemolytic disease were analyzed. The mean gestational age and birth weight were 36 +/- 1.3 weeks and 2837 +/- 403 grams respectively. Twenty-seven infants (75%) received between 2 and 8 intravascular intrauterine blood transfusions. Fourteen infants (39%) required simple packed red blood cell transfusions and 11 infants (31%) required exchange blood transfusion in the immediate postnatal period. Thirty infants (83%) developed late anemia and required blood transfusions at a mean postnatal age of 43.3 +/- 15.7 days. Sixty-four percent of infants who had exchange blood transfusions did not develop late anemia, while 92% of infants who did not require exchange blood transfusion developed late anemia, and the difference was statistically significant (P = 0.035). Serum erythropoietin levels were determined in 8 infants immediately before simple transfusion for late anemia. The media serum erythropoietin level was 21.2 mU/ml, ranging between less than 10 to 114.2 mU/ml. We conclude that late hyporegenerative anemia is common among Rh isoimmunized infants, regardless of the intravascular intrauterine transfusion. Exchange blood transfusion was associated with less occurrence of late anemia.

Inhaled nitric oxide in persistent pulmonary hypertension of the newborn refractory to high-frequency ventilation.

BACKGROUND: This study was designed to evaluate the effect of nitric oxide (NO) on the management of neonates with severe persistent pulmonary hypertension refractory to high-frequency oscillatory ventilation. METHODS: The birth weight and the gestational age of infants were 3125.5 +/- 794 g (mean +/- SD) and 39 +/- 2.4 weeks, respectively. All neonates were ventilated for an average of 137.5 min (range 90-180 min) prior to NO therapy. The mean oxygenation index (OI) of all neonates prior to NO was 46.3 +/- 5 (mean +/- SEM). NO was initially administered at 20 parts per million (ppm) for at least 2 h and increased gradually by 2 ppm to a maximum of 80 ppm. RESULTS: Eighteen infants (75%) responded and six (25%) did not respond to the treatment. Three neonates died in the responding group, while all the non-responders died (P = 0.0001). The survival rate was 62.5% among all neonates. NO significantly decreased OI (P < 0.0001) and improved the arterial/alveolar (a/A) oxygen ratio (P < 0.0001) within the first 2 h of NO therapy in 61.1% of the responders. However, the OI and the a/A oxygen ratio remained almost the same throughout the treatment in the non-responders and the non-survivors. CONCLUSION: Inhaled NO at 20 ppm, following adequate ventilation for 2 h without significant response, could be used to identify the majority of the non-responders in order to seek other alternatives.

Congenital diaphragmatic hernia: A local experience.

BACKGROUND: The objective of this study was to review infants with congenital diaphragmatic hernia (CDH) from the clinical and surgical aspects, and to analyze the risk factors affecting the outcome. PATIENTS AND METHODS: The records of 33 infants with CDH who were admitted to the Neonatal Intensive Care Unit (NICU) from January 1989 to July 1996 were retrospectively reviewed. The mean gestational age was 38.87A+/-2.6 weeks and the mean birth weight was 2896A+/-700 g. The male to female ratio was 2:1. Twenty-six infants had left-sided and seven had right-sided CDH. All infants required mechanical ventilation within six hours of being born. RESULTS: Nineteen infants survived until hospital discharge and 14 infants died, giving an overall mortality rate of 43%. We noted that pH of less than 7.3, PaCO2 of more than 45 mm Hg, or peak inspiratory pressure of more than 25 cm, were associated with high mortality. A higher risk of mortality was also seen in infants with persistent pulmonary hypertension of the newborn (PPHN). Survival rate was observed to be slightly higher in infants who had surgical repair beyond 48 hours of age. Survivors and nonsurvivors were comparable in terms of a 5-minute Apgar score, sex, mode of delivery, PaCO2 at presentation, the site of diaphragmatic defect, air leak syndrome, associated congenital heart disease, and the presence of stomach or viscera in the thorax. CONCLUSION: High ventilatory support and moderate-to-severe respiratory acidosis at presentation and PPHN during hospital course were found to be associated with high mortality.

Liposomal amphotericin B in neonates with invasive candidiasis.

Liposomal amphotericin B (L-Amp B), a novel formulation of amphotericin B, is effective for the treatment of invasive fungal infections in children and adults and is associated with less toxicity than the conventional preparation. Data on the use of Liposomal amphotericin B in neonates is scarce. We describe the clinical course of two premature infants who were treated with Liposomal amphotericin B (one infant had candidemia, and the other had candidemia and meningitis), and provide a summary of previously published experience on this topic. Liposomal amphotericin B may be an option for therapy of invasive candidiasis in neonates who are at high risk of nephrotoxicity and other amphotericin-related reactions, but clinical trials are necessary to document its safety and efficacy in this age group.

Liposomal amphotericin B in neonates with invasive candidiasis.

Liposomal amphotericin B L-Amp B, a novel formulation of Amp B, is effective for the treatment of invasive fungal infections in children and adults and is associated with less toxicity than the conventional preparation. Data on the use of L-Amp B in neonates is scarce. We describe the clinical course of two premature infants who were treated with L-Amp B (one infant had candidemia, and the other had candidemia and meningitis), and provide a summary of previously published experience on this topic. L-Amp B may be an option for therapy of invasive candidiasis in neonates who are at high risk of nephrotoxicity and other amphotericin-related reactions, but clinical trials are necessary to document its safety and efficacy in this age group.

Theophylline concentration following equal doses of intravenous aminophylline and oral theophylline in preterm infants.

Steady-state serum theophylline concentrations following equal doses of intravenous aminophylline and oral theophylline were compared in 30 preterm infants with gestational age of 29.2 +/- 2.9 weeks. The result showed no significant statistical difference between the mean serum concentration of theophylline (8.2 +/- 2.2 micrograms/mL vs. 8.4 +/- 1.9 micrograms/mL; p = 0.483). This indicates that a dose reduction of 20%, which is currently recommended, is not required when changing from intravenous aminophylline to oral theophylline. We conclude that in preterm infants, equal doses of intravenous aminophylline and oral theophylline maintain the same serum theophylline concentration.

Fiberoptic, conventional and combination phototherapy for treatment of nonhemolytic hyperbilirubinemia in neonates.

The objective of this prospective, randomized study was to compare the effectiveness of fiberoptic, conventional and a combination phototherapy in decreasing bilirubin concentrations in neonatal nonhemolytic hyperbilirubinemia. Forty-six infants who were 36 weeks' gestation and more were randomly assigned to fiberoptic phototherapy (n=16) (Biliblanket, Ohmeda), conventional daylight phototherapy (n=15) and combination phototherapy (n=15) (fiberoptic and conventional). The groups were similar in clinical characteristics at study entry in terms of birth weight, age and bilirubin concentration. There were no statistically significant differences in the duration of treatment among the three groups (P=0.83). There were also no statistically significant differences among the three groups in the serum bilirubin concentrations at 24 hours, 48 hours, end of phototherapy, and 24 hours postphototherapy. We concluded that the decrease in serum bilirubin concentration was comparable among fiberoptic, conventional and combination phototherapy groups.

The use of phosphodiesterase inhibitor (dipyridamole) to wean from inhaled nitric oxide.

A full-term, male neonate developed persistent pulmonary hypertension, and responded to high-frequency oscillatory ventilation and inhaled nitric oxide (INO). Discontinuation of INO was attempted three times and was followed by severe desaturations due to right-to-left shunt through the patent ductus arteriosus and patent foramen ovale. As a result of this rebound pulmonary hypertension, the neonate was maintained on INO therapy for 6 days. Successful discontinuation was achieved by using the phosphodiesterase inhibitor, dipyridamole. We speculate that during exogenous INO therapy, endogenous nitric oxide was inhibited, thus cyclic guanosine 3',5'-monophophate, the smooth muscle relaxant, was rapidly hydrolyzed. By inhibiting phosphodiesterase, smooth muscle relaxation occurred, and consequently weaning from INO was achieved.