Effect of Prophylactic Caffeine on Noninvasive Respiratory Support in Preterm Neonates Weighing 1250-2000 g: A Randomized Controlled Trial.

BACKGROUND: Caffeine is commonly used to prevent or treat apnea in preterm neonates. The present trial was designed to determine the effect of caffeine on reducing the time required for nasal continuous positive airway pressure (NCPAP) in neonates with respiratory distress syndrome (RDS). METHODS: In a randomized controlled trial, a total of 90 neonates (birth weight between 1250 and 2000 g) who were clinically diagnosed with RDS were subjected to random assignment to one of the two groups of caffeine (n=45) or control (n=45). Infants in the caffeine group received 20 mg/kg caffeine as the initial dose, and then 10 mg/kg daily as the maintenance dose. Infants in the control group did not receive any placebo or similar drugs. The primary outcome was the duration time of respiratory support with NCPAP. RESULTS: The mean (SD) duration of NCPAP differed significantly and was shorter among the infants in the caffeine group than those assigned to the control group (41.53 (43.25) versus 78.48 (114.25) hours, respectively; mean difference: -36.95; 95%CI: -73.14, -0.76; P = 0.04). Apnea of prematurity (AOP) occurred in 2 (4.4%) newborns in the caffeine group and in 9 (20%) of the infants in the control condition [proportion difference: -15.6% (-29.8,-1.8); (P = 0.02)]. The incidence of intraventricular hemorrhage (IVH) was higher in the control group than in the caffeine group after one week (P = 0.03). The incidence of chronic lung disease (CLD), infection, necrotizing enterocolitis (NEC), seizure, vomiting and pneumothorax was similar in the two groups. CONCLUSION: The results suggest that preventative caffeine can reduce the duration of NCPAP support in neonates with RDS.

Heated Humidified High Flow Nasal Cannula (HHHFNC) is not an effective method for initial treatment of Respiratory Distress Syndrome (RDS) versus nasal intermittent mandatory ventilation (NIMV) and nasal continuous positive airway pressure (NCPAP).

BACKGROUND: Noninvasive respiratory support techniques are widely used to treat respiratory distress syndrome (RDS) in preterm infants, and the effectiveness of these methods should be compared. In the current study, nasal continuous positive airway pressure (NCPAP), nasal intermittent mandatory ventilation (NIMV), and heated humidified high-flow nasal cannula (HHHFNC) were compared. MATERIALS AND METHODS: In the current bicenter clinical trial, 109 preterm infants with RDS not treated with surfactant were randomly assigned to three groups: NCPAP, NIMV, and HHHFNC. The initial outcomes including the failure of treatment within the first initial 72 h, and the duration of RDS treatment, and the secondary outcomes including the need for intubation, the need for surfactants, the duration of oxygen dependency, the incidence of pneumothorax, the patent ductus arteriosus, intraventricular hemorrhage, length of stay, and mortality were compared among the groups. RESULTS: The frequency of HHHFNC treatment failure (54.3%) was significantly higher compared with those of NIMV (21.6%) (P < 0.001, hazard ratio [HR] = 9.12, 95% confidence interval [CI] = 2.59 - 32.07) and NCPAP (35.1%) (P = 0.004, HR = 21.25, 95% CI = 2.51-180.08). The median duration of RDS treatment was longer (40 h) in the HHHFNC group, although it was not significantly different from those of NIMV (31.16 h) and NCPAP (38.91 h). CONCLUSION: Based on the high prevalence of failure of HHHFNC treatment than the other two methods (NCPAP and NIMV), HHHFNC is not recommended as the initial treatment of RDS.

Nasal high-frequency oscillatory ventilation (nHFOV) versus nasal continuous positive airway pressure (NCPAP) as an initial therapy for respiratory distress syndrome (RDS) in preterm and near-term infants.

BACKGROUND: Currently, various forms of non-invasive respiratory support have been used in the management of respiratory distress syndrome (RDS) in preterm neonates. However, nasal high-frequency oscillatory ventilation (nHFOV) has not yet been applied commonly as an initial treatment. OBJECTIVES: This study was designed to investigate the efficacy and safety of nHFOV compared with nasal continuous positive airway pressure (NCPAP) in preterm and near-term infants with RDS. METHODS: In a randomised clinical trial, a total of 68 neonates (gestational age (GA) between 30 and 36 weeks and 6 days) with a clinical diagnosis of RDS were randomly assigned to either the NCPAP (n=34) or the nHFOV (n=34) group. The primary outcome was the duration of non-invasive respiratory support (duration of using NCPAP or nHFOV). RESULT: The median (IQR) duration of non-invasive respiratory support, was significantly shorter in the nHFOV group than that in the NCPAP group (20 (15-25.3) versus 26.5 (15-37.4) hours, respectively; p=0.02). The need for a ventilator occurred in 4 out of 34 (11.8%) neonates in the NCPAP group and in none of the neonates in the nHFOV group (p=0.03). In addition, intraventricular haemorrhage (IVH) occurred in nine cases (6.9%) in the NCPAP group and two cases (3.3%) in the nHFOV group, which showed a significant difference (p=0.04). The incidence of pneumothorax, chronic lung disease, pulmonary haemorrhage and necrotising enterocolitis was similar between the two groups. CONCLUSION: This study showed that nHFOV significantly reduced the duration of non-invasive respiratory support and decreased the need for intubation compared with NCPAP in infants with RDS. Furthermore, nHFOV seems to reduce the incidence of IVH without increasing other complications. TRIAL REGISTRATION NUMBER: IRCT2017062734782N1.

Caffeine Administration to Prevent Apnea in Very Premature Infants.

BACKGROUND: Apnea intervals frequently occur in premature infants. Periods of apnea occur more often with decreases in gestational age. Periods of apnea can cause damage to the infant's developing brain and other organs. This study was designed to investigate the preventive effects of caffeine on apnea incidence in higher-risk neonates. METHODS: In this single-center randomized control trial study, premature infants with a birth weight of ≤1200 g were eligible for enrollment. Twenty-six infants were randomly assigned to receive 20 mg/kg caffeine, as the loading dose, which was followed by 5 mg/kg daily as the maintenance dose until the 10th day of life; these infants were compared with 26 infants in the control group. Primary outcomes were incidence of apnea, bradycardia, and cyanosis. RESULTS: Fifty-two infants were enrolled (26 in the caffeine group and 26 in the control group). The preventive effect of caffeine on apnea was significant in these infants. The relative risk for incidence of apnea in preterm neonates with a birth weight of <1200 g was 0.250 (95% confidence interval, 0.097-0.647). Only four infants (15.4%) in the caffeine group developed apnea, compared with 16 (61.5%) in the control group (p = 0.001). CONCLUSION: It seems that preventative effects of caffeine on apnea become apparent by using the drug in very premature infants.

Comparison of long chain polyunsaturated fatty acid content in human milk in preterm and term deliveries and its correlation with mothers' diet.

BACKGROUND: Human milk (HM) is the main food for infants, and phospholipids, especially long chain polyunsaturated fatty acids (LCPUFAs), play an essential role in the growth and brain development. This study was designed to evaluate the fatty acid composition in HM of mothers with preterm and full-term newborns and to determine the relationships of dietary intake of docosahexaenoic acid (DHA) and arachidonic acid (AA) of mothers and the content of these fatty acids in their milks. MATERIALS AND METHODS: The AA and DHA of HM were determined by gas chromatography at the 3(rd) day after birth from mothers of 59 term and 58 preterm infants. Mothers were selected from those who delivered in Shahid Beheshti Hospital, a referral teaching hospital affiliated to Isfahan University of Medical Sciences, Isfahan, Iran. Dietary fat composition of mothers was examined by a food-frequency questionnaire. Total fat content, and DHA and AA levels of HM were compared in both groups. The correlation of dietary DHA and AA with DHA and AA of HM was determined in both groups. RESULTS: We found that maternal age, body mass index (BMI), and self-reported food-frequency questionnaire did not differ in the two groups. The mean AA (0.19 ± 0.10 mg/ml and 0.16 ± 0.09 mg/ml, respectively), DHA (0.10 ± 0.06 mg/ml and 0.08 ± 0.05 mg/ml, respectively), and total fat content (2.58 ± 2.16 g/dl and 2.06 ± 1.22 g/dl, respectively) of HM of mothers with preterm neonates were non-significantly higher than in mothers with term neonates. The percentage of DHA in the HM fat of preterm and term groups (0.45 ± 0.16% and 0.45 ± 0.18%, respectively) and the percentage of AA (0.85 ± 0.26% and 0.84 ± 0.20%, respectively) were comparable with worldwide standards. No correlations were documented between DHA and AA intake and DHA and AA content of HM in both groups. CONCLUSION: Although DHA and AA content of HM in preterm group was higher than in term group, this difference were not significant. In Isfahan, the percentage of DHA and AA was acceptable in the milk fat of mothers with term and preterm neonates.

A study on lipid content and fatty acid of breast milk and its association with mother's diet composition.

INTRODUCTION: The aim of our study was to determine the content of fat and fatty acid composition of breast milk, and its association with the mother's diet. MATERIALS AND METHODS: This cross-sectional study was conducted among pregnant mothers who came to health care centers for last prenatal care in Isfahan, Iran. Eight to 72 hours after delivery, 2 to 5 ml of colostrum was collected by hand into tubes. They were kept in an ice box and sent within half an hour to the collaborating health centre for freezing at -20°C until analysis, which was performed at the laboratory of NNFTRI in Tehran. The milk samples were homogenized by Vortex (Heidolph Vortex Shaker REAX 1. 220 V. 30 W Germany) at 2400 rpm for 30 sec. RESULTS: The data of 86 out of 91 samples were complete. The mean maternal age and gestational age was 28.37 ± 5.55 years old and 38.7 ± 1.2 weeks, respectively. The content of fat was 2.17 ± 1.22 g/100 ml breast milk. Arachidonic acid (AA, 20:4n-6) and docosohexaanoic acid DHA (22:6n-3) made 0.8 ± 0.4% and 0.3 ± 0.2% of total fatty acids. Although the AA/DHA ratio in our study is suitable, but the content of DHA is nearly low. CONCLUSION: Dietary habits of women in reproductive age group should be improved, with special emphasis on the fatty acid content of breast milk. This may have long-term impact on health promotion and disease prevention.

Comparison of Two Phototherapy Methods (Prophylactic vs Therapeutic) for Management of Hyperbilirubinemia in Very Low Birth Weight Newborns.

OBJECTIVE: Preterm and low birth weight (LBW) infants are at greater risk of developing bilirubin-associated brain damage compared with term infants. Certainly, phototherapy, if used appropriately, is capable of controlling the bilirubin levels in LBW infants; but there is not a unique phototherapy treatment strategy in LBW infants. This study was designed to compare the prophylactic phototherapy and late treatment of jaundiced newborns weighing 1000-1500 grams. METHODS: Sixty newborns with birth weight 1000-1500 g were studied. They were divided into two groups: the "Prophylactic" group, in which phototherapy started within six hours after birth and continued for at least 96 hours, and the "Treatment" group, which received phototherapy when indicated according to birth weight and suspended when bilirubin level fell below 50% of bilirubin level for blood exchange. Mean value of daily transcutaneous bilirubin (TCB), duration of phototherapy, the need for blood exchange, and the highest TCB value in both groups were analyzed. FINDINGS: In the prophylactic group, the highest daily mean rate of TCB was 7.71±1.84 mg/dl, which happened on the third day. In the treatment group, it was 8.74±1.72 mg/dl on the fourth day after birth. The TCB values in prophylactic group were significantly less than those of the treatment group only on the fourth and fifth days after birth (P<0.001). Although the median duration of phototherapy in the treatment group was shorter than that of the prophylactic group (137.60±57.39 vs 168.71±88.01 hours, respectively), this difference was not statistically significant. Only one neonate needed blood exchange in the treatment group. CONCLUSION: The prophylactic phototherapy treatment for babies weighing 1000-1500 g significantly decreases bilirubin levels on the fourth and fifth days after birth but the clinical course of hyperbilirubinemia does not alter in LBW infant, as indicated by the non-significant change in the duration of phototherapy.

Nephrocalcinosis in very low birth weight infants.

To determine the incidence and risk factors of nephrocalcinosis in preterm infants, we studied in a prospectively 64 preterm infants of birth weight :5 1500 g from February 2006 to November 2007. Data were collected on gestation, birth weight, gender and family history of renal calculi, respiratory support, and use of nephrotoxic drugs. The parameters of mineral metabolism were assessed in blood and spot urine samples at the end of 2 nd and 4 th weeks of age. Forty-nine babies completed the study, and nephrocalcinosis was observed in 13 (26.5%) babies and was bilateral in 7 (14.3%) infants. The mean age of diagnosis of nephrocalcinosis was 52.58 days (range 30-123 days). Gestational age, birth weight, and sex were not significantly associated with increased risk of nephrocalcinosis. The mean duration of ventilation was significantly less in babies with than without nephrocalcinosis (P= 0.020), and the mean levels of urine calcium and phosphate at 4 weeks of age, respectively (P= 0.013, P= 0.048). There were also significant differences in urine calcium/creatinine ratio (P= 0.001), mean plasma levels of calcium at 2 weeks of age (P= 0.047) and plasma levels of phosphate at 4 weeks of age (P= 0.016) between babies with and without nephrocalcinosis. Using logistic regression analysis, family history of renal stone (P= 0.002) and urine calcium/creatinine ratio (P= 0.011) were significant predictors of nephrocalcinosis. However, there were no significant differences in the length of stay in the intensive care unit, duration of total parenteral nutrition, and duration and cumulative doses of nephrotoxic drugs between these two groups. We conclude that the incidence of nephrocalcinosis was similar in our population to the previous studies. Family history of renal stone and urine calcium/ creatinine ratio are the major risk factors of nephrocalcinosis in very low birth weight neonates.

Assessing the effect of high school students' training program on peers performance suffering from asthma.

BACKGROUND: Asthma is the most common disease in childhood which is considered as the forerunner of the acute diseases and simply can cause disability among the children. Since childhood and adolescence are the most important periods of growth and perfection and incidence of asthma can bring about distortion in this process, the present study done aimed to assess the effect of conducting high school training program on peers' performance with asthma. METHODS: This was a quasi-experimental study in which the performance rate of the students at the time of artificial attack of asthma was directly observed, assessed and compared through demographic data questionnaire and performance assessment check list. Eighty individuals from the second grade of high school students in 2010 in Isfahan City were randomly selected to participate in the present study, among which, 40 individuals were entered in the test group and 40 of them also were placed in the control group. After conducting the training program for the test group, which had been designed both by direct method (in person and face to face by asking and answering and group discussion) and by indirect method (using pamphlet and other educational materials), the level of the training effectiveness was assessed on the students' performance. RESULTS: The findings of the present study indicated that the performance of students at the test group increased from 2.2 (0.6) to 91.8 (1.3) which emphasized that the training program for the young adolescent peers had a positive effect on promoting their health. CONCLUSIONS: Considering the results of the present study and regarding to the importance and role of students as the future makers of the country, and also the cost-effectiveness of the training programs and the positive effect of peers on increasing the level of health among the students with asthma and consequently decreasing the school absence, it obviously seems necessary to generalize and expand these training programs.

Comparison of maternal and umbilical cord blood selenium levels in term and preterm infants.

OBJECTIVE: Selenium is an essential trace element and has a main role in cellular antioxidant defense system. In very preterm babies, low selenium is associated with an increased risk of complications such as chronic neonatal lung disease and retinopathy of prematurity. This study was designed to determine and compare maternal and umbilical cord blood selenium levels in term and preterm infants. METHODS: From February 2008 to April 2008, 30 term (gestational age>37 weeks) and 30 preterm infants (gestational age<34 weeks) and their mothers were enrolled. Selenium concentrations in umbilical cord and maternal venous blood were measured by atomic absorption spectrometry. RESULTS: The mean selenium concentration in term infants was higher than in preterm infants (124.80+/-13.72 microg/L vs 100.30+/-11.72 microg/L, P=0.0001). The mean selenium concentration in mothers of term and preterm infants was not significantly different (117.03+/-17.15 microg/L vs 110.56+/-17.49 microg/L, P=0.15). Cord selenium concentrations were strongly correlated with gestational age and birth weight (r=0.66, p<0.0001 and r=0.59, p<0.0001, respectively) when the data of all infants were analyzed together. None of the 60 women had a serum selenium level below the laboratory lower limit of normal (70.0 microg/L). Maternal selenium levels were correlated with cord selenium levels in their infants (r=0.40, p<0.001) when data of all newborn infants and mothers were considered together. CONCLUSIONS: Mothers have a relatively good selenium status and serum selenium is not a significant predictor of preterm delivery in Isfahan. The cord selenium concentration in term infants is significantly higher than in preterm infants, but the cord selenium concentrations in both groups are in a suggested normal range.

Permanent and transient congenital hypothyroidism in Isfahan-Iran.

OBJECTIVES: To determine the prevalence of permanent and transient congenital hypothyroidism (CH) in Isfahan, Iran. METHODS: In 256 primarily diagnosed CH patients identified through the neonatal screening programme from May 2002 to February 2005, treatment was discontinued for 4 weeks and T4 and thyroid stimulating hormone (TSH) were measured. Permanent or transient CH was determined from the results of the thyroid function tests and the radiologic findings. Patients with TSH levels >6 (mIU/l) were diagnosed with permanent CH. RESULTS: Results were available from 204 patients, of whom 122 patients were diagnosed with permanent CH (59.8%) (prevalence 1:748 births), and 82 with transient hypothyroidism (prevalence 1:1114). Permanent CH was associated with higher initial TSH levels than transient hypothyroidism (P < 0.05). The most common aetiology of CH was dyshormonogenesis. CONCLUSION: The rates of both permanent and transient CH in our study were higher than the comparable worldwide rates. The transient group had low T4 levels, suggesting that iodine contamination should be investigated. The aetiology of CH was also different from that recorded in many other studies.

Newborn screening for glucose-6-phosphate dehydrogenase deficiency in Isfahan, Iran: a quantitative assay.

OBJECTIVES: To determine the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Isfahan, the central state of Iran. METHODS: From February to March 2006, a total of 2501 samples were screened for the quantitative measurement of G6PD activity by enzymatic colorimetric assay by a commercial kit (GAMMA, Belgium). The neonates were referred from 17 delivery units to the Isfahan neonatal screening center at 3-7 days after birth. Any neonate with a value < 6.4 U/gHb was considered G6PD deficient. RESULTS: Of the 2501 newborns (1307 males, 1194 females) screened, 79 neonates were found to have G6PD deficiency (67 males, 12 females). The overall incidence of G6PD deficiency was 3.2%. Frequency in male population was 5.1 % (67 out of 1307 male neonates) and in female population was 1% (12 out of 1194 female neonates).The female:male ratio was 1:5.5 (P = 0.0001). The mean enzyme activity in deficient patients was 3.22 +/- 1.8 U/gHb (male deficient group; 3.17 +/- 1.74 U/gHb, female deficient group; 3.49 +/- 2.17 U/gHb, P = 0.58). CONCLUSION: Routine neonatal screening in Isfahan, Iran with a relatively high prevalence of G6PD deficiency is justified and meets the World Health Organization recommendation.

Comparison of blood lead levels of mothers and cord blood in intrauterine growth retarded neonates and normal term neonates.

OBJECTIVE: To compare the blood lead levels of mothers and cord blood in intrauterine growth retarded (IUGR) neonates and normal term neonates. METHODS: From April to December 2005, we carried out a cross-sectional, prospective study in Isfahan University of Medical Sciences, Isfahan, Iran. Blood lead levels were measured in the umbilical cord and maternal venous blood samples in 32 mother-infant pairs with IUGR full term neonates, and 34 mother-infant pairs with normal full term neonates. Blood-lead levels were analyzed by atomic absorption spectrometry. RESULTS: The mean lead concentration in neonates of IUGR and normal groups was not significantly different (107.47 +/- 16.75 versus 113.08 +/- 19.08 micrometer/L, p=0.2). The mean lead concentration in mothers of IUGR group was lower than normal groups, but this difference was not significant (124.56 +/- 19.71 versus 135.26 +/- 26.91 micrometer/L, p=0.07). Maternal lead levels were strongly related with cord blood in both IUGR and normal groups (r=0.8, p<0.0001). Maternal and cord blood lead levels was not correlated with birth weight of newborns in either group. Overall, 65.6% of IUGR neonates and 76.4% of normal neonates was above the critical level defined for lead poisoning as >100 micrometer/L by the centers for disease control; however, this was not statistically different between the groups. CONCLUSION: Our results indicate that the mean lead level was not higher in IUGR neonates, and the whole blood lead was not related to the birth weight. In addition, maternal and cord blood lead levels were strongly correlated, and there were remarkable lead burdens on both the mothers and their neonates in this industrial area.

Rate of recalls in congenital hypothyroidism based upon a regional survey in Isfahan, Iran, using serum T4 and TSH analyses: comparison of two different recall methods.

AIMS: To evaluate and compare the recall rate in congenital hypothyroidism screening project in Isfahan, first using an approach involving measures of both TSH and T4 and then using TSH alone. METHODS: From June 2002 to January 2005, serum TSH and T4 level of referred neonates were measured at 3rd to 7th day of birth through venous sampling. If neonates' serum TSH was >20 mIU/l or T4 was <6.5 microg/dl by the first protocol, or TSH was >20 mIU/l by the second protocol, they were recalled. TSH and T4 were measured using an immunoradiometric assay and radioimmunoassay, respectively. Neonates with TSH > 10 and T4 < 6.5 on their second measurement were considered as congenitally hypothyroid. RESULTS: Serum T4 and TSH of 29,425 neonates by first and 57,235 neonates by second recall approach were measured. Recall rate was higher in the first protocol (2.2% vs. 0.6%, p < 0.05). Most of the recalled neonates in the first protocol were recalled for low T4 level (p < 0.05). The prevalence of CH was 1 in 350 livebirths. CONCLUSION: Although the recall rate was in the acceptable range by either approach, the TSH alone protocol seems to be a more sensitive and practical approach with the least recall burden and considering the high prevalence of CH in our region merit adaptation of widespread screening for CH using TSH measurements from heel stab blood spotted on filter paper.

Prevalence of congenital hypothyroidism in Isfahan, Iran: results of a survey on 20,000 neonates.

AIMS: To evaluate the prevalence of congenital hypothyroidism (CH) in a screening program performed for the first time in Isfahan, Iran. METHODS: From May 2002 to December 2002, T4 and TSH serum concentrations of 20,000 3- to 7-day-old newborns, born in all 17 hospitals of the city, were measured by radioimmunoassay and immunoradiometric assay, respectively. The newborns with abnormal screening results (TSH >20 mIU/l, T4 <6.5 microg/dl and based on the weight) were re-examined. RESULTS: Of 531 recalled subjects (recall rate 2.6%), 54 were confirmed to be hypothyroid, showing a prevalence of 1:370 for CH. CONCLUSION: Considering the high frequency of CH, the necessity of implementing a routine screening program in the healthcare system of Isfahan Province is emphasized.

Comparison of urinary iodine excretion in neonates and their mothers in Isfahan, Iran.

OBJECTIVE: To determine the urinary iodine excretion of neonates (28 days of age or younger) and their mothers in Isfahan, a centrally located city in Iran, in 1997 after 8 years of iodized salt distribution in an effort to ameliorate iodine deficiency. METHODS: Through a cross-sectional study and by means of convenient sampling, 146 mother-neonate pairs were selected among neonates born in Shahid Sadoughi Hospital in Isfahan. In order to eliminate the effect of povidone-iodine on breast milk and urinary iodine, Savlon antiseptic solution was used in normal vaginal delivery and on the umbilical cord. Normal values of urinary iodine concentration for the mothers and their neonates were > or = 10.0 microg/dL and >5.0 microg/dL, respectively. The data were analyzed and compared by the Student t test and Pearson correlation coefficient in SPSS software. P values <0.05 were considered statistically significant. RESULTS: In only 3% of the neonates and 14% of the mothers, urinary iodine excretion was below the normal range. No mother or neonate had severe iodine deficiency. In 2% of the mothers and 2% of the neonates, mild iodine deficiency was found. The mean urinary iodine concentration of neonates whose mothers were iodine deficient was significantly lower than that of neonates whose mothers were iodine sufficient (17.34 +/- 7.83 microg/dL versus 22.21 +/- 7.57 microg/dL; P<0.01). A direct significant correlation was noted between the urinary iodine excretion of neonates and that of their mothers (r = 0.37; P<0.01). CONCLUSION: The urinary iodine excretion in mothers paralleled the urinary iodine concentration of their neonates. If urinary iodine concentration is considered an index of total body iodine content, this study demonstrated that prolonged iodized salt intake has minimized the occurrence of iodine deficiency in Isfahan.