Postnatal Maturation of Amplitude Integrated Electroencephalography (aEEG) in Preterm Small for Gestational Age Neonates

Objective: The primary objective was to evaluate the postnatal maturation pattern on aEEGduring first two weeks of life in clinically stable and neurologically normal preterm small forgestational age (PSGA) and gestation matched (1 week) preterm appropriate for gestationalage (PAGA) neonates born between 300/7 and 346/7 weeks of gestation. Methods: SerialaEEG tracings were recorded on 3rd, 7th and 14th day of life. The primary outcome wastotal aEEG maturation score. Three blinded assessors assigned the scores. Results: Weanalyzed a total of 117 aEEG recordings in 40 (19 PSGA and 21 PAGA) neonates. Thebaseline characteristics were comparable except for birthweight [1186 (263) vs 1666(230) g]. There was no difference in the mean (SD) total scores on day 3 (9.0 (1.8) vs. 9.5(1.1), P=0.32) and day 14 of life, but was lower in PSGA infants on day 7 (8.6 (2.4) vs. 10.1(1.1), P=0.02). On multivariate analysis, maturation of PSGA neonates was found to besignificantly delayed at any point of life from day 3 to day 14 (mean difference, -0.8, 95 % CI:-1.6 to -0.02, P=0.04). Conclusion: Lower aEEG maturation score on day 7 possiblyindicates delayed maturation in PSGA neonates in the first week of life.

Target Oxygen Saturation Among Preterm Neonates on Supplemental Oxygen Therapy: A Quality Improvement Study

Objective: To avoid excessive oxygen exposure and achieve target oxygen saturation(SpO2) within intended range of 88%-95% among preterm neonates on oxygen therapy.Methods: 20 preterm neonates receiving supplemental oxygen in the first week of lifewere enrolled. The percentage of time per epoch (a consecutive time interval of 10 hours/day) spent by them within the target SpO2 range was measured in phase 1 followed byimplementation of a unit policy on oxygen administration and targeting in phase 2. In phase 3,oxygen saturation histograms constructed from pulse-oximeter data were used as dailyfeedback to nurses and compliance with oxygen-targeting was measured again. Results:48 epochs in phase 1 and 69 in phase 3 were analyzed. The mean (SD) percent time spentwithin target SpO2 range increased from 65.9% (21.4) to 76.5% (12.6) (P=0.001).Conclusion: Effectiveimplementation of oxygen targeting policy and feedback usingoxygen saturation histograms may improve compliance with oxygen targeting.

Assisted Physical Exercise and Stress in Preterm Neonates

Objective: To evaluate the markers of stress before and after a session of assisted physicalexercise in infants born before 35 weeks’ gestation. Methods: 25 infants born at 280/7 to 346/7weeks were subjected to assisted physical exercise daily for about 10-15 min at one week ofpostnatal age or 33 weeks of post menstrual age, whichever was later. Primary outcome wassalivary cortisol and secondary outcome was Premature infant pain profile (PIPP) score.Outcomes were measured, on day 5 (±1) of exercise. Results: There was no difference insalivary cortisol between baseline and immediately after (P=0.16), at 90 min (P=0.6) or 120min (P=0.7) after exercise. Salivary cortisol was lower at 30 min after exercise as compared tobaseline (mean difference -0.08 ?g/dL; 95% CI -0.16 to -0.002; P=0.04). The median (IQR)PIPP score was significantly higher at 5 min into exercise (4 (3-6) vs 4 (3-5); P=0.04) and atcompletion of exercise 6 (4-8) vs 4 (3-5); P<0.01), as compared to baseline. Conclusion:Assisted physical exercise does not seem to result in stress in premature infants

Assisted Physical Exercise for Improving Bone Strength in Preterm Infants Less than 35 Weeks Gestation: A Randomized Controlled Trial

Objective: To compare the efficacy of daily assisted physicalexercise (starting from one week of postnatal age) on bonestrength at 40 weeks of post menstrual age to no intervention ininfants born between 27 and 34 weeks of gestation.Design: Open-label randomized controlled trial.Setting: Tertiary-care teaching hospital in northern India from 16May, 2013 to 21 November, 2013.Participants: 50 preterm neonates randomized to Exercisegroup (n=26) or Control group (n=24).Intervention: Neonates in Exercise group underwent onesession of physical exercise daily from one week of age, whichincluded range-of-motion exercises with gentle compression,flexion and extension of all the extremities with movements ateach joint done five times, for a total of 10-15 min. Infants inControl group underwent routine care and were not subjected toany massage or exercise Outcome measures:Primary: Bone speed of sound of lefttibia measured by quantitative ultrasound at 40 weeks postmenstrual age. Secondary:Anthropometry (weight length andhead circumference) and biochemical parameters (calcium,phosphorus, alkaline phosphatase) at 40 weeks post menstrualage.Results:The tibial bone speed of sound was comparablebetween the two groups [2858 (142) m/s vs. 2791 (122) m/s;mean difference 67.6 m/s; 95% CI - 11 to 146 m/s; P=0.38]. Therewas no difference in anthropometry or biochemical parameters.Conclusion:Daily assisted physical exercise does not affectthe bone strength, anthropometry or biochemical parameters inpreterm (27 to 34 weeks) infants.

Description and Validation of a Novel Method of Measuring Pharyngeal Pressure in New-born.

Study background: Measurement of delivered pharyngeal pressure during continuous positive airway pressure (CPAP) therapy is not in routine practice due to lack of a simple and affordable technique of intrapharyngeal pressure measurement. To overcome the lack of the gold standard solid-state catheter-tip pressure measurement technology in our set up, we improvised a novel method of pressure measurement and tested its validity in a simulated pharynx. Methods: A low-cost pressure transducer was improvised by attaching an orogastric tube to its one end. The other end of the orogastric tube was sealed into an artificial pharynx - a 20 ml syringe. The pressure transducer readings were compared with that obtained by a digital manometer attached to the tip of the syringe. Bland-Altman statistic was used to quantify the measurement reliability of the novel method against the digital manometer. Effect of tube length on the measurement agreement was also studied. The developed technique was applied in new-borns. Results & conclusion: Pressures measured by this technique were in good agreement with that obtained using a digital manometer. This technique has the potential to be used as an alternative to catheter-tip pressure transducers for bedside pharyngeal pressure measurement in new-born babies, especially in underresourced setups.

Association between household air pollution and neonatal mortality: an analysis of Annual Health Survey results, India.

Background: In India, household air pollution (HAP) is one of the leading risk factors contributing to the national burden of disease. Estimates indicate that 7.6% of all deaths in children aged under 5 years in the country can be attributed to HAP. This analysis attempts to establish the association between HAP and neonatal mortality rate (NMR). Methods: Secondary data from the Annual Health Survey, conducted in 284 districts of nine large states covering 1 404 337 live births, were analysed. The survey was carried out from July 2010 to March 2011 (reference period: January 2007 to December 2009). The primary outcome was NMR. The key exposure was the use of firewood/crop residues/cow dung as fuel. The covariates were: sociodemographic factors (place of residence, literacy status of mothers, proportion of women aged less than 18 years who were married, wealth index); health-system factors (three or more antenatal care visits made during pregnancy; institutional deliveries; proportion of neonates with a stay in the institution for less than 24 h; percentage of neonates who received a check-up within 24 h of birth); and behavioural factors (initiation of breast feeding within 1 h). Descriptive analysis, with district as the unit of analysis, was performed for rural and urban areas. Bivariate and multivariable linear regression analysis was carried out to investigate the association between HAP and NMR. Results: The mean rural NMR was 42.4/1000 live births (standard deviation [SD] = 11.4/1000) and urban NMR was 33.1/1000 live births (SD=12.6/1000). The proportion of households with HAP was 92.2% in rural areas, compared to 40.8% in urban areas, and the difference was statistically significant (P < 0.001). HAP was found to be strongly associated with NMR after adjustment (β = 0.22; 95% confidence interval [CI] = 0.09 to 0.35) for urban and rural areas combined. For rural areas separately, the association was significant (β = 0.30; 95% CI = 0.13 to 0.45) after adjustment. In univariable analysis, the analysis showed a significant association in urban areas (β = 0.23; 95% CI = 0.12 to 2.34) but failed to demonstrate an association in multivariable analysis (β = 0.001; 95% CI = –0.15 to 0.15). Conclusion: Secondary data from district level indicate that HAP is associated with NMR in rural areas, but not in urban areas in India.

A Micro-costing Model of Neonatal Intensive Care from a Tertiary Indian Unit: Feasibility and Implications for Insurance.

Objective: To calculate and compare costs of neonatal intensive care by micro-costing and gross-costing methods. Methods: The costs of resources of a tertiary care neonatal intensive care unit were estimated by the two methods to arrive at specific costs per diagnosis related categories for 33 neonates followed-up prospectively. Results: Grosscosting as compared to micro-costing resulted in higher cost per bed (Rs 6315 vs. Rs 4969) and wide variations of costs (-34.8% to +13.4%). Intensity of interventions, relative stay in neonatal intensive care unit compared to the step-down nursery, and total length of hospital admission accounted for these variations. Conclusions: Estimates based on micro-costing arrived in this study may be used as a starting point in developing assumptions for insurance models covering neonatal intensive care.

Evaluation of Phototherapy Devices Used for Neonatal Hyperbilirubinemia.

Objective: To compare phototherapy devices based on their physical and photo-biological characteristics viz spectral properties, maximum and mean irradiance, treatable percentage of body surface area, decay of irradiance over time and in vitro photoisomerisation of bilirubin. Design: In vitro experimental study. Setting: Ocular pharmacy laboratory at a tertiary care hospital. Methodology: All the characteristics were measured at a fixed distance of 35 cm from one compact fluorescent lamp (CFL) and three light emitting diode (LED) phototherapy devices in a dark room with an irradiance of <0.1μW/cm2/nm. Estimation of products of in vitro photoisomerisation was done using liquid chromatography - tandem mass spectroscopy (LC-MS/ MS). Results: The emission spectral data were comparable between the phototherapy devices. The devices, however, differed in their maximum irradiance with the spot and indigenous LED units having the highest and lowest values, respectively (56.5 and 16.8μW/cm2/nm). The mean irradiance – measured in 5x5cm grids falling within the silhouette of a term baby – of the spot and improvised LED devices were low (26.8μW/cm2/nm and 11.5μW/cm2/ nm, respectively) possibly due to unevenness in the irradiance of light falling within the silhouette. There was a significant difference in the amount of bilirubin left after exposure to light over a 2-hour time period (% reduction of bilirubin) among the four devices (P=0.001); at 120 minutes after exposure, the amount of bilirubin left was lowest for the CFL (16%) and spot LED (17%) devices and highest for the indigenous LED unit (41%). Conclusions: The four phototherapy devices differed markedly in their physical and photobiological characteristics. Since the efficacy of a device is dependent not only on the maximum irradiance but also on the mean irradiance, rate of decay of irradiance, and treatable surface area of the foot print of light, each phototherapy device should have these parameters verified and confirmed before being launched for widespread use.

Burden, Differentials, and Causes of Child Deaths in India.

Objective To review the current information on trends, burden, differentials, causes, and timing of under five (U5) child deaths in India. Methods We reviewed and analyzed data on child deaths in India from official government sources, reports, surveys, and from the published literature. The secondary analyses were carried out to provide additional insight. Results An estimated 1.84 million under 5 child deaths, including approx 1.44 million infant and 940,000 neonatal deaths occurred in India during 2007. More than 60% of these Under 5 child deaths occurred in 5 states: Uttar Pradesh (27.0%), Bihar (11.3%), Madhya Pradesh (9.9%), Rajasthan (8.0%) and Andhra Pradesh (5.7%). Approximately 41% of all Under 5 child deaths happen in the first week of life and the risk of deaths during neonatal period was at least 68 times higher than the rest of childhood. The children living in rural areas, in the central Indian states, in the lowest 20% of wealth index have the highest risk of death in India. The mortality rates in under 5, infant, neonates and early neonatal period in India declined by 43.5%, 31.2%, 32.1%, and 21.6%, respectively, between 1990 to 2007. However, the rate of reduction has slowed in last 4 years (2003–2007), with negative trend in the early neonatal mortality rate. Neonatal conditions (33%), pneumonia (22%) and diarrhea (14%) are the leading causes of under 5 deaths in India. Sepsis, pneumonia (30.4%), birth asphyxia (19.5%), and pre-maturity (16.8%) are the 3 commonest causes of neonatal deaths (0–27 days). Conclusions The reduction in under 5 child mortality in India during 1990–2007 has been insufficient to attain Millennium Development Goal 4 (MDG4). However, there have been variable declines in early neonatal, neonatal, infant and child mortality. Despite the well known importance of neonatal survival to attain MDG4, our data suggest the early neonatal mortality rate in India may be increasing in the recent years, which is a cause for serious concern. Achievement of MDG4 in India will require further acceleration in the reduction of the under 5 mortality rate, particularly, in the 5 highest burden states: Uttar Pradesh, Bihar, Madhya Pradesh, Rajasthan and Andhra Pradesh.

Management of Neonatal Seizures.

Seizures in the newborn period constitute a medical emergency. Subtle seizures are the commonest type of seizures occurring in the neonatal period. Myoclonic seizures carry the worst prognosis in terms of long-term neurodevelopmental outcome. Hypoxic-ischemic encephalopathy is the most common cause of neonatal seizures. Multiple etiologies often co-exist in neonates and hence it is essential to rule out common causes such as hypoglycaemia, hypocalcemia, and meningitis before initiating specific therapy. A comprehensive evidence based approach for management of neonatal seizures has been described in this protocol.

Hypocalcemia in the Newborn.

Hypocalcemia is a frequently observed clinical and laboratory abnormality in neonates. Ionic calcium is crucial for many biochemical processes including blood coagulation, neuromuscular excitability, cell membrane integrity, and many of the cellular enzymatic activities. Healthy term infants undergo a physiological nadir in serum calcium levels by 24-48 h of age. This nadir may drop to hypocalcemic levels in high-risk neonates including infants of diabetic mothers, preterm infants and infants with perinatal asphyxia. The early onset hypocalcemia which presents within 72 h requires treatment with calcium supplementation for at least 72 h. In contrast, late onset hypocalcemia usually presents after 7 days and requires longer term therapy.

Management of Polycythemia in Neonates.

Polycythemia is defined as a venous hematocrit above 65%. The hematocrit in a newborn peaks at 2 h of age and decreases gradually after that. The relationship between hematocrit and viscosity is almost linear till 65% and exponential thereafter. Increased viscosity of blood is associated with symptoms of hypo-perfusion. Clinical features related to hyperviscosity may affect all organ systems. Neonates born small for gestational age (SGA), infants of diabetic mothers (IDM), and multiple births are at risk for polycythemia. They should therefore undergo screening at 2, 12, and 24 h of age. Polycythemia may be symptomatic or asymptomatic and guidelines for the management of both types based on the current evidence are provided in the protocol.

Kangaroo mother care--an alternative to conventional care.

The term kangaroo mother care (KMC) is derived from practical similarities to marsupial care-giving, i.e., the premature infant is kept warm in the maternal pouch and close to the breasts for unlimited feeding. It is a gentle and effective method that avoids agitation routinely experienced in a busy ward with preterm infants. An important main stay of kangaroo mother care is breastfeeding encouragement. Observational studies have shown reduction in mortality after institution of KMC. Preterm babies exposed to skin to skin contact showed a better mental development and better results in motor tests. It also improves thermal care. All stable LBW babies are candidate for KMC. Often this is desirable, until the baby's gestation reaches term or the weight is around 2500 g. The mother and family members are encouraged to take care of the baby in KMC and should be counseled to come for follow-up visits regularly.

Feeding of low birth weight infants.

Optimal feeding of low birth weight (LBW) infants improves their immediate survival and subsequent growth and development. Being a heterogeneous group comprising term and preterm neonates, their feeding abilities, fluid and nutritional requirements are quite different from normal birth weight infants. A practical approach to feeding a LBW infant including choice of initial feeding method, progression of oral feeds, and nutritional supplementation based on her oral feeding skills and nutritional requirements is being discussed in this protocol. Growth monitoring, management of feed intolerance, and the essential skills involved in feeding them have also been described in detail.

Protocol for administering continuous positive airway pressure in neonates.

Continuous positive airway pressure (CPAP) is a simple, inexpensive and gentle mode of respiratory support in preterm very low birth weight (VLBW) infants. It helps by preventing the alveolar collapse and increasing the functional residual capacity of the lungs. Since it results in less ventilator induced lung injury than mechanical ventilation, it should theoretically reduce the incidence of chronic lung disease in VLBW infants. Various devices have been used for CPAP generation and delivery. The relative merits and demerits of these devices and the guidelines for CPAP therapy in neonates are discussed in this protocol.

Follow-up of high risk neonates.

The improvement in perinatal care has led to increase in survival as well as reduction of morbidity in sick newborns. These babies need to be followed up regularly to assess growth and neurodevelopmental outcome and for early stimulation and rehabilitation. We present a protocol describing the various components of a follow up program, and services.

Parenteral nutrition.

Nutritional insufficiency, leading to early growth deficits has long-lasting effects, including short stature and poor neurodevelopmental outcomes. Early enteral feeding is commonly limited by immaturity of gastrointestinal motor function in preterm neonates. To ensure that a stressed premature infant receives an adequate but not excessive amount of glucose, the amount of carbohydrate delivered in the form of dextrose is commonly initiated at the endogenous hepatic glucose production and utilization rate of 4 to 6 mg/kg/min; and 8 to 10 mg/kg/min in ELBW infants. The early provision of protein is critical to attain positive nitrogen balance and accretion as premature babies lose approximately 1% of their protein stores daily. Aminoacid can be used at concentrations of 3-3.5 g/kg/day and lipid at 3.5-4 g/kg/day as long as the fat intake remains less than 60% of nonprotein calories. Sodium, potassium, chloride, calcium, magnesium and phosphorus need to be provided in PN solution as per their daily needs. Hospital-acquired infection (HAI) is a major complication of PN. All efforts should be made to avoid it.

Chronic lung disease in newborns.

Chronic lung disease (CLD) or bronchopulmonary dysplasia (BPD) occurs in preterm infants who require respiratory support in the first few days of birth. Apart from prematurity, oxygen therapy and assisted ventilation, factors like intrauterine/postnatal infections, patent ductus arteriosus, and genetic polymorphisms also contribute to its pathogenesis. The severe form of BPD with extensive inflammatory changes is rarely seen nowadays; instead, a milder form characterized by decreased alveolar septation due to arrest in lung development is more common. A multitude of strategies, mainly pharmacological and ventilatory, have been employed for prevention and treatment of BPD. Unfortunately, most of them have not been proved to be beneficial. A comprehensive protocol for management of BPD based on the current evidence is discussed here.

Acute renal failure in neonates.

Acute renal failure (ARF) is a common condition seen in neonatal intensive care units. It is broadly classified into prerenal, intrinsic renal and post renal failure. There is no consensus on the definition of neonatal ARF. Of utmost importance is to differentiate prerenal from intrinsic renal failure. The most common causes of neonatal ARF are hypovolemia, hypotension and, hypoxia. Among several indices that are available for differentiating prerenal failure from intrinsic renal failure, fractional excretion of sodium is the preferred index. Diagnostic fluid challenge with or without frusemide is a bed side method for differentiating prerenal failure from intrinsic renal failure. Babies with ARF have to be monitored for several metabolic derangements like hyponatremia, hyperkalemia, hypocalcemia, and acidosis and have to be managed accordingly. Fluid balance should be precise in order to avoid fluid overload. It is difficult to provide adequate calories due to fluid restriction. Dialysis has to be instituted to preempt complications. Peritoneal dialysis is the easiest and safest modality. These babies need long term follow up as they are prone for long term complications.