Dr Mehar Varghes
ABSTRACT
Neonatal hypoglycemia remains a critical concern in the care of newborns,presenting significant challenges in early detection and management.This condition,defined as low blood glucose levels in the first few days of life,can lead to neurologic impairment if not promply identified and treated.Management typically involves early detection through screening protocols,followed by interventions such as feeding,or glucagon administration if necessary.While conventional medicine provides established protocols for diagnosis and management.While homoeopathy offers individualised treatments tailored to symptoms.Homoeopathy presents an intriguing adjunctive therapy warranting research into its efficacy and safety.This article highlights on the definition,pathophysiology, etiology,Clinical features, investigations,and current management strategies underscoring the evolving role of homoeopathy in addressing neonatal hypoglycemia.
Keywords : Neonatal Hypoglycemia,Hypoxic ischemic encephalitis, Keton bodies,Insulin
INTRODUCTION
As many as 5 to 15% of apparently healthy neonates suffer with neonatal hypoglycemia which is more common in nations with low resources. Low blood glucose levels are a common occurrence in the neonatal era and can be a significant cause of brain damage. Neonatal hypoglycemia occurs soon after birth as newborns adapt from continuous umbilical glucose to intermittent feeding. Hypoglycemia in neonatal period may be asymptomatic or severe and prolonged. In the neonatal population hypoglycemia may be associated with seizure activity and abnormal neurologic outcomes.Approximately half of the patients with newborn hypoglycemia have hypoxic-ischemic encephalopathy (HIE). HIE might exacerbate the long-term brain damage brought on by hypoglycemia . Hence,neonatal hypoglycemia should always be given urgent attention.
Treatment delays frequently lead to poor neurological outcomes .Despite limited evidence, concerns about severe neurologic consequences have driven the creation of screening guidelines to identify and manage neonates at risk for hypoglycemia, focusing on those with specific risk factors shortly after birth.According to recent research, using dextrose gel for treatment is both safe and effective, and it may even aid to promote breastfeeding.
This article outlines pathophysiology of neonatal hypoglycaemia,discuss on the current dilemmas in clinical management,and describes some recent research that is beginning to indicate the potential for a more evidence-based approach to the diagnosis and treatment and outcome of neonatal hypoglycaemia.
DEFINITION
It is difficult to define hypoglycemia in neonates because of several reason. Over time, the definition of hypoglycemia has altered. In the 1960s, blood glucose (BG) values as low as 20 mg/dL were considered acceptable; in the 1970s, levels as high as 40 mg/dL were considered acceptable; and starting in 1988, many neonatologists began to accept BG concentrations as low as 47 mg/dL (2.6 mmol/L). Neonates of various gestation ages have variable maturity of nervous system and varable capacity to manifest the signs and symptoms of hypoglycemia.It is currently unknown what the crucial blood glucose level is necessary to maintain the integrity of newborn brain function.
Low blood glucose levels, or hypoglycemia, are a screening test for neuroglycopenia or insufficient brain supply of glucose, and, in rare cases, an indication of an underlying endocrine or metabolic problem. However, hypoglycemia is not a diagnosis in and of itself. In the first 24 to 48 hours after birth, blood glucose levels in the healthy newborn population are typically lower than those in the populations of older children and adults. Hence, it is difficult to identify any particular levels of plasma glucose values that define pathologic hypoglycemia.
PATHOPHYSIOLOGY
The primary source of nutrition for the fetus is the transplacental transfer of nutrients, particularly glucose.A constant intravenous glucose supply is given to the fetus before to delivery. This glucose diffuses from the mother’s blood across the placenta through carrier-mediated facilitated diffusion hence, the blood glucose concentrations in the fetus are marginally lower than those in the mother. In a prenatal organism, endogenous glucose synthesis is not physiological.Even though the human fetus’s primary energy substrate is glucose, but a part of maternal glucose is converted by the placenta to lactate, which is released into the fetal and maternal circulation in 1:3 ratio
Stress hormones including catecholamines and glucocorticoids are secreted during labor and delivery, which raises fetal blood glucose levels and frequently results in high cord blood glucose concentrations.After cord clamping, the abrupt cessation of the mother’s glucose supply causes a fast decrease in the blood glucose concentration of the newborn. The high rate of glycogenolysis leads to hastened depletion of hepatic glycogen stores, especially in preterm infants in which liver glycogen deposits are limited. The newborn brain has a 5–40 fold greater capacity to utilize ketone bodies than that of an infant or adult brain. Lactate appears to be important for neonates in the immediate postnatal life. Ketone bodies and lactate serve as important alternative fuels for maintaining cerebral energy supply of the brain.
The exogenous glucose supply stops when the umbilical chord is severed, and blood glucose levels drop. A decrease in insulin production and an increase in counter-regulator hormones including glucagon, catecholamines, and glucocorticoids are the outcomes of this drop in blood glucose.These modifications work together to start the fetal body’s natural process of producing glucose through gluconeogenesis and glycogenolysis, which stabilizes blood glucose levels.Failure of this sequence of physiological changes can lead to hypoglycaemia, which is most common in the first few hours after birth.
Transitional hypoglycemia, is temporary in most infants and usually recovers within a few hours to days. Fewer neonates have hypoglycemia that lasts for several days or weeks. Of these, some will develop permanent neonatal hyperinsulinism, which require further treatments.
BRAIN INJURY AND GLUCOSE METABOLISM
The brain relies on a regulated supply of glucose for energy, managed by glucose transporters like GLUT-1 and GLUT-3. Once glucose enters brain cells, it’s converted into glucose-6-phosphate, a step crucial for further energy production. This glucose is then directed into pathways like glycolysis, where it’s broken down to generate ATP, the cell’s energy currency.
Excess glucose can be stored as glycogen, mainly in astrocytes within the brain, serving as a reserve energy source. When needed, glycogen can be broken down back into glucose-6-phosphate to fuel energy production.Brain function disruptions caused by hypoglycemia seem to initiate prior to any observable decline in overall brain ATP levels. Neuronal activity might be subdued as a means of conserving energy. ATP, produced through glycolysis under normal glucose levels (euglycemia), plays a key role in upholding glutamatergic neurotransmission.When blood glucose levels drop, cerebral blood flow initially increases to bolster glucose delivery to the brain.
During the early metabolic shifts in hypoglycemia, the focus is on preserving cerebral energy levels by utilizing alternative fuels and starting glycogenolysis. Alongside lactate and ketone bodies, amino acids may serve as alternative substrates, as their concentrations decline notably alongside rising brain ammonia levels.Thus, even in the early stages of hypoglycemia, consciousness levels may decline despite relatively preserved ATP levels. This phenomenon can elucidate the discrepancy between cerebral energy metabolism and neuronal functions during hypoglycemia in certain instances.
However, the newborn brain exhibits relative resilience to neuronal damage caused by hypoglycemia. This resilience may be attributed to lower cerebral energy requirements, increased cerebral blood flow during the initial phases of hypoglycemia, the neonatal brain’s enhanced capacity to utilize alternative fuels, and comparatively minor effects on the cardiovascular system due to ample endogenous carbohydrate reserves compared to adults.
If hypoglycemia persists, cells experience an energy deficit. Under these circumstances, the energy-dependent Na+/K+-ATPase fails, causing neurons to lose their capacity to uphold typical ionic gradients. Consequently, there are alterations in intracellular calcium and extracellular potassium concentrations ultimately lead to cellular damage.Continued hypoglycemia can lead to additional complications such as hypoxia, ischemia, and seizures, exacerbating the insult to the brain.
Hypoglycemia often occurs alongside other health issues, resulting in distinct patterns of brain injury. Specifically, hypoglycemia triggers apoptotic cell death in oligodendrocyte precursor cells and impedes their maturation and myelination process. The consequences of hypoglycemic brain injury manifest as microcephaly, widened sulci, atrophic gyri, reduced cerebral white matter, and enlarged lateral ventricles.
ETIOLOGY FOR NEONATAL HYPOGLYCEMIA
The physiological reasons behind hypoglycemia in neonates encompass factors such as depleted hepatic glycogen reserves, insufficient muscle stores as a source of amino acids for gluconeogenesis, and inadequate lipid reserves for fatty acid utilization.
Other serious causes of persistent Neonatal hypoglycemia include;
- Inadequate glycogen stores and inadequate substrate source for gluconeogenesis seen in conditions like Prematue birth, Small for gestational age, Intrauterine growth restriction, Perinatal stress (sepsis, asphyxia), Polycythemia.
- Hyperinsulinima :Is the other important cause for neonatal hypoglycemia.Transitional hypoglycemia exhibit relatively high insulin levels compared to older individuals due to incomplete suppression of insulin, and tend to retain their limited glycogen reserves inappropriately when facing hypoglycemia.
- Growth hormone deficiency Adrenal insufficiency encompasses a range of congenital and acquired conditions leading to insufficient production of steroid hormones. These conditions may coincide with deficiencies in other hormones.
- Inborn errors of metabolism, or other congenital reasons for hypoglycemia, can lead to severe and prolonged hypoglycemia,this condition may be associated with central nervous system symptoms, particularly in recently born infants.
CLASSIFICATION
Early Transitional Adaptive Hypoglycemia : This condition typically emerges within the first 6 to 12 hours after birth, triggered by the sudden halt in maternal blood supply. Neonates affected by this condition struggle to initiate appropriate metabolic adjustments in the immediate postnatal period. It has been noted that the glycolytic and gluconeogenic responses of the neonate are diminished, while insulin secretion increases if the mother receives excessive glucose via intravenous fluids during labor. This type of hypoglycemia is typically short-lived and mild in severity. Treatment responses are generally positive.
Secondary Associated Hypoglycemia: This variant of hypoglycemia is connected with conditions other than hypoglycemia, notably involving the central nervous system, such as birth asphyxia and intracranial hemorrhage, as well as congenital anomalies and systemic disorders.This type of hypoglycemia is short-lived, mild, and usually responds promptly to treatment.
Classical Transient Neonatal Hypoglycemia : This group mainly comprises infants born small for their gestational age, often accompanied by polycythemia. Hypoglycemia in this case usually appears later in the first day. It tends to be more severe and prolonged, often requiring high infusion rates of glucose for treatment.
Severe Recurrent Hypoglycemia : This variant is characterized by recurrent or persistent hypoglycemia seen in term neonates who are appropriate for their gestational age, and it is often linked to endocrinopathies or hereditary metabolic defects. This hypoglycemia is usually severe and poses challenges in treatment.
CLINICAL FEATURE
The excerpt provides insights from a study on neonatal hypoglycemia, focusing on its clinical presentation and associated risk factors. It notes common symptoms observed in affected neonates, including jitteriness, cyanosis, temperature instability, lethargy, and respiratory abnormalities.
In the investigation by C.D. Dhananjaya et al., the clinical presentation of patients with hypoglycemia revealed lethargy in 81.25% and jitteriness in 75% of cases, whereas respiratory abnormalities were observed in 37.5%, cyanosis in 18.75%, and seizures in 31.25%. Neonatal risk factors identified in the current study included low birth weight (49%), small gestational age (26%), macrodome (11%), respiratory distress (32%), sepsis (20%), hypothermia (25%), congenital cardiac abnormalities (4%), endocrine disorders (4%), family history of metabolic disorders (7%), inborn errors of metabolism (4%), rhesus hemolytic disease (5%), erythroblastosis fetalis (1%), inadequate feeding (35%), and neonates without any factors accounted for 6%.
Additionally, the study delves into the underlying mechanisms behind hypoxia, hypothermia, shock, respiratory distress, and sepsis, which can either increase glucose consumption or decrease glucose production, exacerbating the hypoglycemic condition in neonates.
This underscores the importance of promptly identifying and managing both the clinical symptoms and underlying risk factors associated with neonatal hypoglycemia to ensure optimal outcomes for affected infants.
INVESTIGATION AND DIAGNOSIS
Screening for Neonatal Hypoglycemia
Biochemical measurement of blood glucose provides a more precise assessment compared to clinical evaluation alone. Plasma glucose levels typically register 10–18% higher than whole blood values. According to recommendations from the Pediatric Endocrine Society (PES) and the American Academy of Pediatrics (AAP), glucose levels of ≥40 mg/dL (mmol/L) are recommended within the first 4 hours after birth, and levels of ≥45 mg/dL (mmol/L) are advised after feeding from 4 to 24 hours post-birth. Values of ≤40 mg/dL (mmol/L) should be treated parenterally.
Blood Glucose Monitoring
Neonate who are predisposed for higher insulin level,become symptomatic very early in postnatal life.IDM and severily intrauterine growth retarded neonate deverse screening right from cord blood.The gold standard method of blood glucose determination is by laboratory examination.
Intermittent Glucose Monitoring
A prevalent approach for assessing glucose levels in neonates involves heel-prick blood sampling, which is then analyzed using point-of-care non-enzymatic glucometers. These devices offer rapid results, are cost-effective, easily accessible in neonatal units, user-friendly, and necessitate only small blood volumes.
These devices,can be influenced by various factors that fluctuate significantly in newborns, such as bilirubin concentrations and hematocrit levels. Their accuracy diminishes notably at low glucose concentrations, with estimated false positive and false negative rates ranging from 10% to 30%. Consequently, they are not recommended as the sole method for diagnosing neonatal hypoglycemia.
Continuous Interstitial Glucose Monitoring: It consist of a sensor implanted beneath the skin and a recording device, typically situated remotely from the sensor. These monitors typically offer readings every 5 minutes, furnishing comprehensive data on glycemic control, including details regarding the duration, frequency, and severity of hypoglycemia.
Continuous glucose monitors have various limitations. They need to be calibrated against blood glucose concentrations at least every 12 hours, so they do not remove the necessity for blood tests. Despite these challenges, continuous glucose monitoring (CGM) holds immense promise for enhancing the management of neonatal hypoglycemia.
Neuroradiological investigations: Employing different MRI techniques to examine the anatomical region affected by hypoglycemia-induced brain injury consistently show cortical abnormalities, particularly in the posterior cerebral cortex, either with or without accompanying subcortical or periventricular damage.In rare instances, thalamic involvement or injury to the basal ganglia may occur. Therefore, it is advisable to conduct follow-up MRI studies in cases with a history of prolonged and severe hypoglycemia.
The Babies and Blood Sugars study: (BABIES) examined the impact of hypoglycemia on EEG by utilizing bedside amplitude-integrated electroencephalography (aEEG) to evaluate real-time neuronal damage caused by hypoglycemia.
The most effective timing and frequency for screening newborns for hypoglycemia remain unclear. Current protocols generally suggest screening shortly(1- 4 hr) after birth and at regular intervals every 3 or 4 hr until blood sugar levels stabilize.
DIAGNOSIS
Obtaining a comprehensive history related to pregnancy, delivery, gestational age, and birth weight is crucial. This includes information about diabetes during pregnancy, dietary habits, and insulin use. Additionally, details regarding the delivery, such as occurrences of asphyxia, are important. Gestational age, whether the infant is small for gestational age (SGA) or large for gestational age (LGA), and birth weight (whether low birth weight or macrosomia) are significant factors to consider.
Family history plays a vital role in diagnosing the cause of hypoglycemia. A history of diabetes, whether gestational or pregestational, may suggest mutations in the HNF4α gene. Parental consanguinity may indicate a recessively inherited cause of hypoglycemia.
Furthermore, a history of siblings experiencing infantile seizures could indicate hypoglycemia as a potential cause of the condition. This information underscores the importance of a thorough medical history in diagnosing and managing hypoglycemia in infants.
Performing a thorough physical examination of the infant is invaluable in diagnosing hypoglycemia. Infants who are late preterm (34–36+6 weeks), large for gestational age (LGA), or small for gestational age (SGA) are at increased risk for hypoglycemia.
Certain physical characteristics may suggest specific underlying conditions. For example, macrosomia, macroglossia, ear pits, hemihypertrophy, and omphalocele may indicate Beckwith–Wiedemann syndrome. On the other hand, midline defects, micropenis, and hypoglycemia may be indicative of congenital hypopituitarism.
TREATMENT
Treating neonatal hypoglycemia is indeed crucial for preventing potential brain injury. The primary approach typically involves feeding the baby to raise their glucose levels. This can be done through either formula or breast milk.Early establishment of feeding and maintaining normothermia is essential. Feed volume and frequency can be increased as tolerated in asymptomatic infants, if they are able to tolerate oral feeds, with monitoring of blood glucose.
However, when glucose levels fall below a critical threshold, usually <18–25 mg/dl (1.0–1.4 mmol/l), intravenous dextrose administration becomes necessary.
The standard protocol often involves administering a bolus of 200 mg/kg of dextrose, followed by an infusion at a rate of around 4–8 mg/kg per minute to maintain glucose levels within an acceptable range. This regimen aims to swiftly elevate and sustain blood glucose concentrations, safeguarding the neonate’s developing brain from potential harm due to hypoglycemia.Nevertheless, the administration of intravenous dextrose requires admission to the neonatal intensive care unit (NICU), a costly and invasive measure that separates mothers from their babies. This separation can escalate maternal anxiety and hinder the establishment of breastfeeding.
Oral dextrose gel 200 mg/kg (0.5 ml/kg of 40% dextrose), in combination with feeding, is increasingly recommended as a first-line treatment for asymptomatic neonatal hypoglycemia.It is simple, safe, effective, and allows mother and baby to be together and establish breast-feeding early.
HOMOEOPATHIC MANAGEMENT
URANIUM NITRATE : Is especially recommended in hepatogenic diabetes, with defective digestion and assimilation and plentiful deposit of sugar in the urine. The child is languid,debilitated and in a generally unwholesome condition. It has purulent conjunctivitis and an offensive nasal and aural discharge.
PHOSPHORIC ACID : Is especially indicated in glycosuria of nervous origin, with debility from a loss of vital forces.The urine is thick ,like milk,and contains much sugar.Furuncles,onychia and sluggish sores add to the child’s discomfort,and its weakness and emaciation are extreme.
TEREBINTHINA : In which the disease-casts appear in the urine,is homoeopathic to pathology of the disease. The child is intensely thirsty, its features are sunken, its gums spongy, its lips cracked and bleeding, and its state generally miserable,irritable and peevish.The child is compelled to urinate often,and albumin is seen in connection with sugar.
SYZYGIUM : Is highly recommended in the tincture and lower attenuation, as capable of diminishing the quantity of urine secreted and causing the disappearence of sugar in the urine.
NATRUM SULPHURICUM : Is useful in hydrogenoid conditions with pancreatic symptoms,and general disturbance of the gastro-intestinal canal.The food is not assimilated, the patient is jaundiced and sallow.There is dryness of the mouth and throat,great thirst for cold drinks,and intestinal dyspepsia with fetid flatulence and continued sensation of chilliness.
ARSENICUM ALBUM : Presents the usual physiognomy of this drug in diabetic subjects.The face is pale and puffy; there is thirst and irritability of the stomach,diarrhea,neuralgic symptoms,palpitation of the heart,and the characteristic Arsenicum restlessness and anxiety.The urine is increased in quantity and as it becomes copious thirst is unquanchable.
Synthesis Repertory
GENERALS – LABORATORY findings – blood – glucose – decreased: (10) acip-tm.bwd1 betamtf0 dulc.dgt,dgt0 gluca.mtf Lac-ac.vml3 lact-stj*dgt0 mag-m.dgt0 oplo-hr.dpl1 rumx.dgt0 sacch.dgt0
CONCLUSION
The primary objective of this review article is to identify the persistent or recurrent hypoglycemia in a neonate and initiate therapy promptly to avert brain damage. Low blood sugar might also be a red flag for more complicated illnesses. Clinical and supplementary laboratory results may reveal the potential cause of hypoglycemia, allowing for cause-specific treatment. In the medical system of homoeopathy, the basis for treatment is a symptom’s similarity.It is possible to effectively handle situations by choosing a comparable cure based on the entirety of the symptoms.
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Dr.Mehar Varghese
MD Part-1 Scholar
mehar.varghese@gmail.com
Under the Guidence of Dr.Jyoshna Shivaprasad HOD Department of peadiatrics,
Father Muller Homoeopathic Medical College and Hospital,Mangalore,Karnataka,India.
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