Neonatal The options for treatment in infants born at

Neonatalhypoglycemia affects up to 15% of newborns (Harding et al., 2015). Risk factorsinclude preterm delivery, infant born from a diabetic mother, and those of highor low birth weight. Untreated neonatal hypoglycemia can cause brain damage andeven death. The options for treatment in infants born at risk of hypoglycemiamay involve interventions such as increasing feeds with breast milk, infantformula, Neonatal Intensive Care Unit (NICU) admission and or administration ofintravenous dextrose therapy to avoid developmental delays later in life.

Thiscourse of action is not only expensive but can also reduce the mother’s vitaltime spent bonding and breastfeeding (Harding et al., 2015). The purpose of this paper is to discuss thedefinition of neonatal hypoglycemia, its causes, adverse effects, implications,and possible effective treatment alternatives.A consistent and accepted definition of hypoglycemiadoes not exist for the first two days of life (Uettwiller et al., 2015); thisis because there is no consensus on a specific level or range of value thatdefine hypoglycemia in the first 48 hours, or when to treat and how muchtreatment to provide. A number of methods have attempted to recognize thethreshold blood glucose concentration at which there is a substantiallikelihood of functional brain impairment. One approach is an epidemiologicalmethod, which defines blood glucose concentrations in cohorts of healthyinfants and uses the mean or an empirically derived cutoff value, such as <2 s.

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ds (standard deviation) below the mean. Any single value is unlikely torepresent a threshold of abnormality, as the data represent a continuum fromnormal (Adamkin & Polin, 2015). It has long been known that plasma glucoseconcentrations are lower in the first one to three days of life in normalnewborn infants than at later ages. In normal newborns immediately followingbirth, the mean plasma glucose concentrations drop by 25–30 mg/dL (1.4–1.7mmol/L) to a nadir of about 55–60 mg/dL (3–3.

3 mmol/L) by one to two hours ofage; glucose levels then steadily rise over the first few days of life toreturn to the normal range for infants, children, and adults (70–100 mg/dL3.9–5.6 mmol/L) (Stanley et  al.,2015).As for thecauses of neonatal hypoglycemia, these vary, occurring in both very low birthweight (VLBW) babies and also affecting approximately 8-30% of babies born tomothers with diabetes (Alemu, Olayinka,Baydoun, Hoch, & Elci, 2017).

VLBW neonates develop hypoglycemiamore readily due to limited reserves of fat and glycogen, which is generallycomposed during the third quarter of pregnancy (Uetwiller et al., 2015); incomparison, infants born to mothers with diabetes have a higher risk thanbabies born to non-diabetic mothers.The full extent of the individual risk factors of hypoglycemia remains unclear,but clinical risk factors include infant-related and mother-related riskfactors. The previously identified infant-related risk factors are varied,ranging from pondered index and male, to macrosomia, small for gestation age,prematurity and lower cord blood index.

Risk factors relating to the motherinclude maternal diabetes and maternal HbA1c, hyperglycemia, ethnic origin,diabetes diagnosed prior to 28 weeks gestation, blood glucose and apre-pregnancy BMI of ? 25 kg/m2 (Alemu et al., 2017).Adverse effects of neonatalhypoglycemia are serious, ranging from brain damage to neuro-developmental delay, visual impairment andbehavioural problems.

Between 5 and 15% of otherwise healthy babies becomehypoglycemic (Harris et al., 2017), and the prevalence is rising due to theincreasing occurrence of preterm birth and maternal diabetes. Screening isrecommended for babies with known risk factors, as half are likely to becomehypoglycemic. In relation to neuro-developmental delays, impairment is definedas mild (mild cerebral palsy or Bayley-III motor composite score one to two SDbelow the mean or mild developmental delay), moderate (moderate cerebral palsyor a Bayley-III motor composite score two to three SD below the mean ormoderate developmental delay or deaf), or severe (severe cerebral palsy thechild is not ambulant at two years and likely to remain so or Bayley-III motorcomposite score more than three SD (standard deviation) below the mean orsevere developmental delays or blindness) (Harris et al.

, 2017). In terms ofvisual impairments, children are considered to have a vision problem if theyhave any one of the following: internal ocular health problem, external ocularhealth problem, strabismus, abnormal ocular motility, no measurable stereopsis,or binocular visual acuity > 0.5 LogMAR or immeasurable (Harris et al.,2017).The AmericanPediatric Endocrine Society (PES) recently published guidelines for evaluationand management of hypoglycemia in neonates, infants and children, including theprovision of recommendations for recognizing neonates that require diagnosisand treatment during the first days of life.

This includes disorders causingsevere and persistent hypoglycemia. Developing accurate screening for newbornsis essential for the diagnosis of persistent or genetic hypoglycemia disorders toprevent and reduce the risk of hypoglycemia-induced brain injury. PES suggeststhat mean plasma glucose levels are initially maintained at approximately 55 to65 mg dl (deciliters) but then increase to 470 mg dl by twoto three days of life (Adamkin & Polin, 2016). Using these initial meanplasma glucose levels may lead to many more infants being evaluated and treatedfor asymptomatic hypoglycemia. Over screening, over diagnosing and overtreating are matters of concern when a ‘lower limit threshold’ is set too high(Adamkin & Polin, 2016).Treatment of hypoglycemic episodes varies considerablyin infants. A randomized trial of dextrose gel massaged into the buccal mucosafor treatment of neonatal hypoglycemia was the focus of “The Sugar Babies Study,”conducted in New Zealand by Hegarty et al.

(2016). This study determined thatbabies who received dextrose gel instead of placebo were not only less likelyto remain hypoglycemic, but also less likely to be admitted to NICU forhypoglycemia, and receive nourishment other than formula at two weeks of age.Dextrose gel is considered safe, inexpensive, simple to administer, and can beused in almost any setting. Dextrose gel is now being used in some areas asfirst-line treatment for neonatal hypoglycemia; however, because neonatalhypoglycemia is known to cause brain injury, it is also vital to determinewhether using dextrose gel is either beneficial or causes any adverse effectslater in life.

Therefore, children who had participated in the Sugar BabiesStudy were invited to participate in a follow-up study with the primary aim todetermine whether treatment of hypoglycemic babies with dextrose compared toplacebo gel altered the rate of neuro-sensory impairment or processingdifficulties at two years’ corrected age (Harris et al., 2016).In another studyconducted by Uettwiller et al. (2015), the glucose level was monitored eitherby real-time continuous glucose monitoring system (RT-CGMS), or by anintermittent capillary glucose testing (IGM-group) associated with a blindstudy to detect retrospectively missed hypoglycemia. Following a dose of oralglucose (30% dextrose solution) and a local anesthesia of lidocaine, the twodevices, both made up of a sensor connected to a transmitter and used to manageglucose levels in the interstitial tissue, were inserted into the child’ssubcutaneous thigh tissue. After withdrawing the needle, the sensor wasconnected to the transmitter.

The use of RT-CGMS real-time readout of glucoselevels employed by continuous glucose monitoring indicate much higher number ofhypoglycemic episodes than those repeated with capillary blood glucose testingas demonstrated by the IGM-group. The hypoglycemia risk was not predictable inthe patients who had the glucose supply increased prematurely at the time ofhypoglycemia, and no distinction was found between patients who received higherintakes of glucose a few days after birth, from VLBW babies experiencingdifferent prenatal characteristics or demographics. Thus, the use of RT-CGMSenabled the identification of these neonates and provided the opportunity foran individual management of the glucose supply, closest to their needs.

In summation, between5 and 15% of otherwise healthy babies become hypoglycemic, and the prevalenceis growing due to the increasing incidence of preterm birth and maternaldiabetes. Screening is recommended for babies with known risk factors, of whomhalf are likely to become hypoglycemic (Harris et al., 2016). There remains noevidence that identification and treatment of infants with low glucose levelsborn to diabetic mothers improves their outcomes.

). While a single dose ofprophylactic oral dextrose gel is shown to reduce the occurrence of neonatalhypoglycemia in those babies born with a higher chance of developing thecondition, more research is required to determine if oral dextrose gel also lowersNICU admission and neuro-developmental impairment. Other than encouraging earlyfeeding, there are no effective prophylactic interventions for infants at riskof neonatal hypoglycemia (Hegarty et al.

, 2016). Further research and educationare required to better equip mothers in recognizing the signs and symptoms ofhypoglycemic episodes in neonates and the need for consistent definition inwhat constitutes as hypoglycemia in infants.