Comparison of ketorolac and indomethacin for the closure of patent ductus arteriosus among preterm infants born at the Philippine General Hospital: A randomized controlled crossover design

@#<p style="text-align: justify;"><strong>Background.</strong> Indomethacin has been the gold standard for the closure of patent ductus arteriosus (PDA). Still, the availability of the intravenous (IV) form has been a big issue precluding its use in the Philippines. IV ketorolac is another non-steroidal anti-inflammatory drug (NSAID) that is cheaper and more available in our country and used for post-cardiac surgery pain management among neonates.</p><p style="text-align: justify;"><strong>Objectives.</strong> To compare the efficacy of ketorolac versus indomethacin in the closure of patent ductus arteriosus among preterm infants.</p><p style="text-align: justify;"><strong>Methods.</strong> We conducted a randomized controlled, double-blind, crossover design, non-inferiority trial on the use of iindomethacin versus ketorolac among preterm infants with PDA. We enrolled preterm infants at 5-12 days postnatal life, diagnosed with PDA by echocardiography at the Philippine General Hospital (PGH). We excluded infants with upper gastrointestinal bleeding, renal failure, birthweight < 500 grams, septic shock, and lethal anomalies. Patients were randomly allocated between two treatment groups (indomethacin versus ketorolac). The primary outcome measure was PDA closure measured after the treatment course. Adverse events like oliguria and bleeding were recorded.</p><p style="text-align: justify;"><strong>Results.</strong> A total of 27 preterm infants were randomly assigned to the indomethacin (0.2 mg/kg/dose) and ketorolac (0.6 mg/kg/dose) group. Ketorolac has a 60% success rate for PDA closure (9/15) compared to indomethacin 41.67% (5/12) (p=0.154). No renal insufficiency and bleeding diathesis were noted. Five patients died in the study, four in the group initially allocated in ketorolac and one in indomethacin. Causes of death were late-onset sepsis, bronchopulmonary dysplasia, and congenital adrenal hyperplasia.</p><p style="text-align: justify;"><strong>Conclusion.</strong> The success rate of PDA closure between IV ketorolac and IV indomethacin was not significantly different. There was neither oliguria nor bleeding observed in both groups.</p>

Kangaroo mother care implementation at the Philippine General Hospital: A quality assurance initiative

Background@#The Philippine General Hospital (PGH) implemented the Kangaroo Mother Care (KMC) Program in 2014, recognizing its benefits in helping low birth weight (LBW) infants survive. @*Objective@#To determine the acceptability and compliance of the stakeholders to the KMC program after one year from implementation. @*Method@#Data were obtained from the NICU Annual statistics, KMC data forms, logbooks, and questionnaires to the stakeholders-doctors rotating at the NICU, NICU nurses, and mothers enrolled in the KMC program. @*Results@#One year into the KMC program implementation, the KMC enrollment increased from 57% in 2014 to 75% in 2015. All mothers enrolled in the program said that they received their KMC knowledge from the health providers and firmly believed that KMC benefited them and their infants. The mothers also became more confident in taking care of their babies after each KMC encounter. Although only 50% said they would continue KMC at home, 85% proceeded. Furthermore, both doctors and nurses believed that KMC was beneficial to both mothers and infants, decreased hospital cost and nursing workload. KMC provision was 0.5-6 hours/day. Also, less than half of the data forms were accomplished. The KMC program was acceptable to all stakeholders who believed in the benefits of KMC to preterm infants. The mothers were very receptive and continued KMC even after discharge. However, there was sub-optimal engagement provided by the health providers with the mothers. There was also low adherence to recommended duration of KMC per day provided by the mothers. KMC data records were frequently not accomplished. PGH has instituted strategies to improve the KMC implementation by providing dedicated KMC rooms and supplying meals to mothers to increase KMC duration and frequency. A computer-based program for data entry was developed for the health providers, and a dedicated encoder was assigned. @*Conclusion@#KMC acceptability was high among stakeholders. Compliance increased after one year, with enrolment going up to 75%. However, adherence to the recommended KMC duration per day and accomplishment of data forms were still sub-optimal.

A meta-analysis on the effect of kangaroo mother care on preterm mortality

Background@#Kangaroo mother care (KMC) is a low-cost but high-impact intervention for preterm and low birth weight (LBW) infants. @*Objectives@#To determine the effect of KMC on in-hospital mortality among preterm and LBW infants, taking into consideration their gestational age, birth weight, income category of the country of birth, and medical stability. @*Materials and Methods@#A comprehensive search of several databases, as well as local listings of research papers, was performed to look for randomized controlled studies with KMC as intervention, and mortality and length of hospitalization as outcome measures. The risk of bias and publication bias was assessed. We did subgroup analyses based on income category of the country of birth, gestational age, birth weight, and medical stability of the infants. @*Results@#Sixteen randomized controlled trials (RCTs) with 1738 infants in the KMC group and 1674 infants in the control group were included. Based on the GRADE approach, although all the studies were RCTs, the evidence is assessed as moderate certainty due to the nature of the intervention (KMC) that prevented blinding. There was a 41% reduction in risk of dying among preterm and low birth weight infants who received KMC compared to conventional medical care (3.86%% vs 6.87%; RR = 0.59, 95% CI 0.44, 0.79; I2 = 0%; number needed to treat for additional benefit (NNTB) = 34; 16 RCTs; 3,412 infants). Furthermore, there were also reductions in the risk of dying among infants who were <34 weeks AOG (KMC: 4.32% vs CMC: 8.17%, RR = 0.55, 95% CI 0.38, 0.79; I2 = 0%; NNTB = 26; 10 RCTs; 1795 infants), with birthweight of >1500 g (KMC: 3.97% vs CMC: 6.83%, RR = 0.60; 95% CI 0.45, 0.82; I2 = 0%; NNTB = 35; 10 RCTs; 2960 infants), and born in low- and middle income countries (LMIC) (3.77% vs 6.95%; RR = 0.57, 95% CI 0.43, 0.77; I2 = 0%; NNTB = 32; 14 RCTs; 3281 infants). There was a significant reduction in mortality (KMC: 11.05% vs CMC: 20.94%; RR = 0.54; 95% CI 0.34, 0.87; I2 = 0%; NNTB = 11; 5 RCTs; 387 infants) even among medically unstable infants who received KMC compared to those who did not. The length of hospitalization did not significantly differ between the KMC and the control groups. Due to high heterogeneity, subgroup analyses were performed, which showed a trend towards a shorter length of hospital stay among preterm infants <34 weeks AOG, with birthweight ≥1500 g, medically unstable during admission, and belonging to LMIC but did not reach statistical significance. @*Conclusion@#There was moderate certainty evidence that KMC can decrease mortality among preterm and LBW infants. Furthermore, KMC was beneficial among relatively more premature, bigger, medically unstable preterm infants and born in low to middle-income countries.

Effectiveness of kangaroo mother care in intubated preterm neonates 28 to 36 weeks gestational age, weighing 600 to 2000 grams at birth: A randomized controlled trial

Background@#Kangaroo Mother Care (KMC) is the standard of care for stable low birth weight infants. Provision of KMC to intubated preterm infants may also be beneficial, but strong evidence is still lacking. @*Objective@#To determine the effectiveness of KMC in decreasing mortality among intubated preterm neonates. @*Study Design@#This is a non-blinded, parallel, non-inferiority randomized controlled trial. @*Methodology@#All intubated, preterm admissions, 28-36 weeks gestation, weighing 600-2000 grams, with respiratory distress were included. They were randomized to the intervention group who received KMC for 2-4 hours daily while intubated and the control group who received care inside an incubator. Participants’ physiologic status – before, during, and after the intervention – was recorded. The primary outcome was mortality. Secondary outcomes included comorbidities, days intubated, and hospital stay. @*Results@#There was a total of 32 patients. The risk of dying in the KMC group (n=16) was significantly reduced by 78% (RR 0.22; 95% CI 0.06 - 0.87 p=0.009). The KMC patients were also less likely to have hypothermia, nosocomial pneumonia, NEC, and late-onset neonatal sepsis (p<0.05). The KMC group had higher blood sugar levels (110 vs. 58, p=0.001) and required fewer days of intubation (3.5 vs.1.5 days, p<0.000) compared to the control group. There was no difference in the duration of the hospital stay. @*Conclusion@#KMC is effective in decreasing mortality among intubated preterm neonates. Other comorbidities and days of intubation were also reduced.

Effectiveness of kangaroo mother care in reducing morbidity and mortality among preterm neonates on nasal continuous positive airway pressure: A randomized controlled trial

Background@#Prematurity is a major cause of neonatal death. Continuous positive airway pressure (CPAP) is the recognized initial intervention among preterm neonates in respiratory distress. Kangaroo mother care (KMC) may help improve neonatal outcomes. @*Objective@#To determine the effectiveness of KMC in reducing morbidity and mortality among preterm neonates on CPAP via RAM nasal cannula (nCPAP). @*Methods@#A prospective, non-blinded, randomized controlled trial was conducted on eligible preterm neonates requiring nCPAP due to respiratory distress. They were randomly allocated to either KMC (n=35) or conventional care groups (n=35). Outcome measures included duration of nCPAP and oxygen support, physiologic parameters, morbidity, mortality, and length of hospital stay. @*Results@#The durations of nCPAP and oxygen support were both significantly shorter in the KMC group. Morbidities (air leak syndrome, necrotizing enterocolitis, and late-onset sepsis) were also significantly lower in the KMC group. Although the mortality rate and the hospital stay were lower in the KMC group, these were not statistically significant. @*Conclusion@#KMC effectively decreased the duration of nCPAP and oxygen support, as well as the incidence of neonatal morbidities. There were trends towards reduced mortality and length of hospital stay in the neonates who received KMC.

Effectiveness of reverse kangaroo mother care position in decreasing adverse physiological events and pain during screening of premature infants for Retinopathy of prematurity

Background@#Retinopathy of prematurity (ROP) screening is uncomfortable and even painful in preterm infants. @*Objective@#To determine the effectiveness of the Reverse-Kangaroo Mother Care (R-KMC) position compared with the conventional position in decreasing adverse physiological events and pain during ROP screening. @*Methods@#This was a parallel randomized controlled trial with two arms- R-KMC position and conventional position (control). The primary outcomes included increased oxygen saturation, decreased heart and respiratory rates, and decreased pain intensity measured by Prematurity Infant Pain Profile (PIPP). @*Results@#There were 100 preterm infants recruited. There were no differences in baseline characteristics, mean ROP screening duration, mean physiological parameters after the mydriatic application and during ROP screening between the two. Only the mean respiratory rates were significantly lower among the R-KMC group during the application of mydriatric agent. (50.26 ± 6.18 vs. 51.6 ± 8.35; p=0.0191). Relative risk (RR) in the control group is 37 to 84 versus 40 to 68 in the R-KMC group. The R-KMC group had a significantly lower mean PIPP score (6.5±2.06 vs. 8.8±2.80; p<0.0001) after mydriatic application and during ROP screening (7.6±2.05 vs. 9.8±2.90; p<0.0001) compared with control. No apnea was observed after mydriatic application, but one apneic episode was in control during ROP screening. 26% of the ROP screeners recommended the R-KMC position during ROP screening, while a majority (70%) was neutral. @*Conclusion@#R-KMC position, a low-cost intervention, significantly reduces pain during ROP screening. It is recommended as a position of choice during ROP screening.

Kangaroo mother care versus incubator in transporting stable preterm neonates: A randomized controlled trial

Background@#Transporting preterm neonates soon after birth entails risks. Only one study among many about the beneficial effects of Kangaroo Mother Care (KMC) had cited it as a safe and effective alternative to transport incubators. @*Objective@#To determine if KMC transport could be an alternative to transport incubators by comparing the physiological outcomes of the two transport methods. @*Methods@#This is a parallel non-blinded randomized-controlled trial funded by KMC Foundation, Philippines, Inc, of physiologically stable preterm neonates weighing ≤ 2200 grams delivered at a tertiary government hospital from September 10, 2011, to April 18, 2012. After obtaining written consent from their mothers, participants were randomly assigned to either the intervention or control group. The intervention groups were transported from the delivery room to the NICU while on skin-to-skin contact with the caregiver. In contrast, those in the control group were placed in a transport incubator. Vital signs, oxygen saturation, and blood glucose were measured before transport and upon NICU arrival. Adverse effects were monitored. Data were recorded using a standard database. @*Results@#Ninety-two participants were recruited, forty-six in each arm. Two dropped out. The mean change in heart rate in the KMC transport decreased by 1.6 beats per minute; respiratory rate decreased by 0.18 breaths per minute, the temperature increased by 0.01°C, oxygen saturation decreased by 0.07%, blood glucose decreased by 5.07 mg/dL. The measured physiological parameters were not statistically significant between the two groups. In the KMC transport, there was a decreasing trend in the incidence of hypothermia, hypoglycemia, tachypnea, and tachycardia. @*Conclusion@#There are no significant differences in the heart rate, respiratory rate, temperature, oxygen saturation, and blood glucose levels among preterm neonates on KMC transport compared with preterm neonates on transport incubators, which is the current standard of care. The study showed that KMC transport is equally effective as a transport incubator. Hence, in low-resource settings, KMC transport may be used as a safe and effective neonatal transport.

Effect of kangaroo mother care on maternal anxiety and depression states at the neonatal ICU: A prospective cohort study

Objectives@#To determine the effect of kangaroo mother care (KMC) on anxiety and depression of mothers of low-birth-weight neonates during the immediate newborn period. @*Method@#Eligible participants were mothers of low-birth-weight infants (birth weight ≤2500 grams) admitted at a tertiary hospital's neonatal intensive care unit. Mothers were instructed on providing KMC daily to their infants during the study period (first seven days of life). @*Main Outcome Measure(s)@#The primary study outcome was the effect of KMC in improving maternal anxiety and depression scores in the immediate postpartum period using the locally validated Hospital Anxiety and Depression Scale-Pilipino (HADS/HADS-P). @*Results@#A total of 171 mothers were enrolled in the study. Only 79 mothers provided KMC, and the rest (92) did not provide KMC. The anxiety and depression scores improved significantly from day 1 to 7 postpartum in both groups (p<0.05). Frequency of mothers categorized as having severe anxiety significantly decreased over time whether they provided KMC or not (KMC: 40.5%, 13.9%, 7.6% at Day 1 and 7 postpartum and day of discharge; No KMC: 35.9% and 27.2% at Day 1 and Day 7 postpartum). There was a significant reduction in the percentage of mothers categorized in the depressed group from Day 1 to Day 7 postpartum, among those who rendered KMC compared with those who did not (KMC: 7.6%, 2.5%, 0% at Day 1 and 7 postpartum and at the day of discharge vs. No KMC: 7.6% and 10.9% at Day 1 and 7 postpartum). There were no significant differences in the anxiety and depression scores at any period between mothers who rendered KMC > 6 hours and KMC ≤ 6 hours/day. @*Conclusion@#Anxiety and depression scores significantly decreased over time in both mothers who rendered and did not render KMC to their infants. However, there was a significant reduction in the percentage of mothers categorized as having severe depression over time among those who rendered KMC compared to those who did not. Other factors aside from KMC may affect the maternal anxiety and depression states, such as instability of the infant.

Effect of kangaroo mother care on the likelihood of breastfeeding from birth up to 6 months of age: A meta-analysis

Background@#One of the World Health Organization (WHO) nutrition target by 2025 is 50% exclusive breastfeeding rate among infants until age 6 months. Kangaroo mother care (KMC) known to increase breastfeeding rates, especially in preterm and low birth weight (LBW) infants. @*Objectives@#This study determined the effect of KMC to the rate of exclusive breastfeeding among preterm and LBW infants at 6 months of age. @*Methods@#Conducted searches in MEDLINE and CENTRAL databases, likewise hand searched local publications December 1996 until June 2018. Included several randomized controlled trials and prospective observational studies comparing KMC and conventional care among preterm and LBW infants. The primary outcome was exclusive breastfeeding of infants at six months of age. Two authors independently assessed trial quality and extracted data the statistical analysis applied using Review Manager version 5.3. @*Results@#Identified nine eligible trials involving 1,202 neonates. All studies had low-to-moderate risk of bias. KMC significantly noted to increase the likelihood of exclusive breastfeeding by 1.9 times at birth up to 6 months (OR 1.93 [1.18,3.17], p=0.009). @*Conclusion@#KMC can increase exclusive breastfeeding among preterm and LBW infants from birth up to 6 months of age.

Prolactin level and breastmilk production among mothers of low-birth-weight Infants admitted to level II Neonatal Intensive Care Unit

Background@#Kangaroo mother care (KMC) has been proven by several studies to promote breastfeeding, but many of the studies focus on the success of exclusive breastfeeding, and less on its galactogenic effects. @*Objective@#We aim to determine the maternal serum prolactin levels and breastmilk volume of mothers who rendered KMC to their infants. @*Materials and Methods@#This is a randomized controlled, open-labeled, interventional study in the Neonatal Intensive Care Unit of a tertiary government hospital. Infants weighing < 2000 grams admitted in NICU Level II, together with medically stable mothers and no contraindication for breastfeeding were simultaneously enrolled. Primary outcome measures were maternal serum prolactin levels and expressed milk volume on day 3 and day 7 postpartum. Two-sample t-test was used to compare groups, and paired t-test to compare within groups. Tests were two-tailed, with a p-value of < 0.05 considered statistically significant. @*Trial Registration@#Australia-New Zealand Clinical Trial Registry ID ACTRN12614000218695 @*Results@#Fifty mother-infant dyads were equally allocated into KMC and control groups (p < 0.001). There was significantly larger milk volume on the third day (29.6 ± 27.8 mL vs 16.3 ± 26.1 mL; p < 0.001) and seventh post-partum day (72.4 ± 62.3 mL vs 47.3 ± 43.8 mL; p < 0.000). There were increased serum prolactin levels compatible with post-partum state. The increase was more evident in the KMC (5244 ± 2702 mIU/L, on the 3rd postpartum day versus 4969 ± 2426 mIU/L, on the 7th postpartum day, p = 0.996) compared to control group (4129 ± 2485 mIU/L on the 3rd postpartum day versus 3705 ± 2731 mIU/L on the 7th postpartum day, p = 0.301). @*Conclusion@#We noted a significantly larger milk volume in the KMC group. There was also a greater increase in the prolactin levels in the KMC group, but this did not reach statistical significance. Further studies should be done to determine mechanism of galactogenesis through KMC.

Effect of continuous versus intermittent Kangaroo Mother Care on weight gain and duration of hospital stay among low-birth-weight admitted at a level II NICU: A randomized control trial

Background@#The Neonatal Intensive Care Unit (NICU) admission at the Philippine General Hospital (PGH) exceeds total bed capacity. Decreasing admissions to the NICU would prevent overcrowding of patients, improve patient care, reduce hospital stay, and reduce predisposition to hospital-acquired infections. @*Objective@#To determine the effect of continuous versus intermittent Kangaroo Mother Care (KMC) on weight gain and duration of hospital stay among low birth weight (LBW) neonates weighing 1,800 - 2,220 grams. @*Methods@#Forty-six (46) stable LBW were randomized to either continuous (≥12 hours in the maternity ward) or intermittent (≤6 hours in the NICU step-down unit) KMC groups. Daily weight and weekly length, head and chest circumference until discharge, and duration of hospital stay were measured. Data were analyzed using the Mann-Whitney U-test and Fisher's exact test. @*Results@#Infants in continuous KMC had an average weight gain of 50 grams/day (p=0.509) and had an average duration of hospital stay of 3 days (p=0.218). Results were not statistically different from intermittent KMC. @*Conclusion@#There was no evidence to show that weight gain and duration of hospital stay among infants in continuous KMC were significantly different from those in the intermittent KMC group.

The physiologic status of low-birth-weight infants before and after kangaroo mother care sessions: A retrospective study

Objective@#To compare the physiologic status of infants before and after receiving kangaroo mother care (KMC) through assessment of their heart rate (HR), respiratory rate (RR), temperature, oxygen saturation, and pain scores. @*Methods@#We conducted a retrospective study by chart review of all low-birth weight (LBW) infants enrolled in the KMC program of a tertiary medical center. Significance is defined by lower HR, RR, PIPP score and FLACC scale, and significant increase in temperature and oxygen saturation (within normal range) after 4 hours after each KMC session. @*Results@#Out of the 46 LBW weight infants enrolled in the KMC program, only 23 infants had complete chart entries. A total of 99 KMC sessions were analyzed. There was no significant difference in the HR (p = 0.331), RR (p = 0.453), oxygen saturation (p = 0.839), and PIPP (p = 0.387)/FLACC (p = 0.13) scores among the LBW infants before and after the KMC session. However, there was a significantly higher axillary temperature (within normal range) four hours after KMC (p = 0.044). @*Conclusions@#KMC is associated with better thermoregulation even at four hours after the KMC session compared to four hours before. Other physiologic parameters such as heart rate, respiratory rate, oxygen saturation and pain scores were similar four hours before and after the KMC session.

A randomized controlled trial of intermittent kangaroo mother care versus conventional care in increasing the rate of weight gain among low-birth-weight neonates

Objective@#To determine the effectiveness of Kangaroo Mother Care (KMC) in increasing the rate of weight gain and decreasing hypothermia, apnea, and sepsis rate, and shorten hospital stay among low-birth-weight infants. @*Methods@#Very low birth weight (VLBW) infants (≤1500 grams) were randomized to either the KMC or conventional care group. KMC provided skin-to-skin contact at least 6 hours per day while the conventional group received the usual care in the newborn intensive care unit (NICU). Daily weight measurements and weekly measurements of length, head, and chest circumference were recorded until discharge. Occurrence of hypothermia, apnea, sepsis, and length of stay was noted. @*Results@#KMC group had a higher mean weight gain per day (p=0.0102). There was no difference in the length, head, and chest circumference between the two groups. Sepsis and apnea rates were not significant between the two groups. Significantly more neonates experience hypothermia in the control group (p<0.0069). @*Conclusion@#KMC is effective in increasing the weight per day compared with the control group. KMC protects the neonates against hypothermia. There is not enough evidence to show a difference in the incidence of sepsis, apnea, and the length of hospital stay between the two groups.