infant of diabetic mother2

IDMIDM

Many infants of insulin dependent diabetics Many infants of insulin dependent diabetics have an uneventful clinical coursehave an uneventful clinical course

Even more infants of gestational diabetics Even more infants of gestational diabetics do welldo well

Over the past decade, perinatal mortality Over the past decade, perinatal mortality has approached that of neonate of has approached that of neonate of nondiabetic ( except for congenital nondiabetic ( except for congenital anomalies)anomalies)

HYPOGLYCEMIA DEFINEDHYPOGLYCEMIA DEFINED

In term infants, glucose values are rarely < In term infants, glucose values are rarely < 35 mg% between 1-3 hrs of life, < 40 mg% 35 mg% between 1-3 hrs of life, < 40 mg% from 3-24 hrs and < 45 mg% after 24 hrsfrom 3-24 hrs and < 45 mg% after 24 hrs

Old concept of lower levels in preterms not Old concept of lower levels in preterms not substantiated by newer studiessubstantiated by newer studies

Currently recommended to view glucose < Currently recommended to view glucose < 50 mg% to be viewed with suspicion and 50 mg% to be viewed with suspicion and treated especially after 2-3 hrs of lifetreated especially after 2-3 hrs of life

GLUCOSE HOMEOSTASISGLUCOSE HOMEOSTASIS

Under nonstressed conditions fetal glucose Under nonstressed conditions fetal glucose is derived entirely from mother and is derived entirely from mother and concentrations are slightly lower than concentrations are slightly lower than mother’smother’s

Fetal stress releases catecholamines Fetal stress releases catecholamines mobilizes fetal glucose and FFAs from liver mobilizes fetal glucose and FFAs from liver and fat and may inhibit fetal insulin +/- and fat and may inhibit fetal insulin +/- stimulate glucagon releasestimulate glucagon release


After birth, mobilisation of glucose occurs After birth, mobilisation of glucose occurs by 3 factors by 3 factors

1) Changes in hormones1) Changes in hormones 2) Changes in their receptors2) Changes in their receptors 3) Changes in key enzyme activity3) Changes in key enzyme activity


3-5 fold abrupt increase in glucagon within 3-5 fold abrupt increase in glucagon within minutes to hours of birthminutes to hours of birth

Insulin level falls initially and remains basal Insulin level falls initially and remains basal for several days without the usual brisk for several days without the usual brisk response to stimuliresponse to stimuli

Dramatic surge in spontaneous Dramatic surge in spontaneous catecholamines secretioncatecholamines secretion

GH levels increased at birth, partly due to GH levels increased at birth, partly due to epinephrineepinephrine


Gluconeogenesis (from alanine – from Gluconeogenesis (from alanine – from muscle) and glycolysismuscle) and glycolysis

Lipolysis (from lipid stores) and Lipolysis (from lipid stores) and ketogenesis ketogenesis

Depletion of liver glycogen within hoursDepletion of liver glycogen within hours FFA and ketones rise, sparing glucose for FFA and ketones rise, sparing glucose for

brain utilization and providing CoA and brain utilization and providing CoA and NADH from hepatic fat oxidation favoring NADH from hepatic fat oxidation favoring neoglucogenesisneoglucogenesis


Rapid fall in glycogen synthetase activityRapid fall in glycogen synthetase activity Sharp increase in phosphorylase activitySharp increase in phosphorylase activity Sharp increase in Phosphoenolpyruvate Sharp increase in Phosphoenolpyruvate

carboxykinase – rate limiting enzyme for carboxykinase – rate limiting enzyme for neoglucogenesisneoglucogenesis

HYPOGLYCEMIAHYPOGLYCEMIA

Pedersen originally proposed fetal Pedersen originally proposed fetal hyperglycemia causing hyperinsulinemiahyperglycemia causing hyperinsulinemia

Defective counter regulation by Defective counter regulation by catecholamines and glucagoncatecholamines and glucagon

Stern proposed adrenal medullary Stern proposed adrenal medullary exhaustionexhaustion

Newborns may have blunted response to Newborns may have blunted response to epinephrineepinephrine

Factors influencing Factors influencing HypoglycemiaHypoglycemia

Duration and severity Duration and severity of maternal diabetesof maternal diabetes

Prior maternal glucose Prior maternal glucose homeostasishomeostasis

Maternal glycemia Maternal glycemia during deliveryduring delivery

HYPERINSULINEMIAHYPERINSULINEMIA

Fetal hyperglycemia causes hypertrophy and Fetal hyperglycemia causes hypertrophy and hyperplasia of the pancreatic islets with a hyperplasia of the pancreatic islets with a disproportionate increase in disproportionate increase in ß cellsß cells

Insulin acts as primary anabolic hormone of fetal Insulin acts as primary anabolic hormone of fetal growth and development causing visceromegaly growth and development causing visceromegaly (especially heart and liver, not kidney and brain) (especially heart and liver, not kidney and brain) and macrosomia and macrosomia

Increase fat synthesis and deposition, mainly 3Increase fat synthesis and deposition, mainly 3 rdrd trimester and increased muscle masstrimester and increased muscle mass

HYPERINSULINEMIAHYPERINSULINEMIA

Hyperinsulinemia and hyperglycemia Hyperinsulinemia and hyperglycemia produce fetal acidosis – stillbirthproduce fetal acidosis – stillbirth

Lower FFA Lower FFA Fasting glucose production and utilization Fasting glucose production and utilization

diminisheddiminished Response to glucose is abnormally prompt Response to glucose is abnormally prompt

and assimilation is more rapidand assimilation is more rapid

CLINICAL FEATURESCLINICAL FEATURES

Large and plump with “steroid” faciesLarge and plump with “steroid” facies May be normal/low birth weight if mother has May be normal/low birth weight if mother has

vascular diseasevascular disease Hypertrichosis is characteristicHypertrichosis is characteristic Head circumference corresponds to GA rather Head circumference corresponds to GA rather

than birth weightthan birth weight Tend to be jumpy,tremulous and hyperexcitable Tend to be jumpy,tremulous and hyperexcitable

during first 3 daysduring first 3 days May have hypotonia,lethargy, poor suckingMay have hypotonia,lethargy, poor sucking

CLINICAL FEATURESCLINICAL FEATURES

Early appearance of signs more related to Early appearance of signs more related to hypoglycemia, later to hypocalcemiahypoglycemia, later to hypocalcemia

Tachypnoea in first 2 days (Hypo glycemia, Tachypnoea in first 2 days (Hypo glycemia, hypothermia,polycythemia,TTN,CCF,cerebhypothermia,polycythemia,TTN,CCF,cerebral edema,RDS)ral edema,RDS)

Cardiomegaly in 30% CCF in 5% (ASH)Cardiomegaly in 30% CCF in 5% (ASH) Immature neurological developmentImmature neurological development

NEONATAL MORBIDITIESNEONATAL MORBIDITIES

AsphyxiaAsphyxia Birth injuryBirth injury Caudal regressionCaudal regression Congenital anomaliesCongenital anomalies Heart failureHeart failure HyperbilirubinemiaHyperbilirubinemia HypocalcemiaHypocalcemia HypoglycemiaHypoglycemia HypomagnesemiaHypomagnesemia

Increased blood volumeIncreased blood volume MacrosomiaMacrosomia Neurological instabilityNeurological instability OrganomegalyOrganomegaly PolycythemiaPolycythemia Renal vein thrombosisRenal vein thrombosis RDSRDS ASH, TGA, ASH, TGA,

Truncus,DORVTruncus,DORV Small left colon syndromeSmall left colon syndrome Transient hematuriaTransient hematuria

INVESTIGATIONSINVESTIGATIONS

Prenatal evaluation of fetal maturity and Prenatal evaluation of fetal maturity and biophysical profilebiophysical profile

Asymptomatic infants- blood glucose Asymptomatic infants- blood glucose within 1 hr of birth, every hour for 6-8 hrs, within 1 hr of birth, every hour for 6-8 hrs, then 4-6 hrly until 234 hours of lifethen 4-6 hrly until 234 hours of life

Symptomatic every 2 hrs after initiating Symptomatic every 2 hrs after initiating therapy until several values> 40 mg%, then therapy until several values> 40 mg%, then every 4-6 hrs until glucose normal and baby every 4-6 hrs until glucose normal and baby Asymptomatic for 24-48 hrsAsymptomatic for 24-48 hrs

TREATMENTTREATMENT

Normoglycaemic – Normoglycaemic – early feeding, (? 3 hrly early feeding, (? 3 hrly intervals)intervals)

If not feeding well, IV If not feeding well, IV glucose at 4-8 glucose at 4-8 mg/kg/minmg/kg/min

Hypoglycemia to be Hypoglycemia to be treated even if treated even if asymptomaticasymptomatic

TREATMENTTREATMENT

In sick infants, bolus of 200 mg/kg glucose In sick infants, bolus of 200 mg/kg glucose ( 2 ml/kg 10%)( 2 ml/kg 10%)

If convulsing, double the doseIf convulsing, double the dose Follow with infusion @ 8 mg/kg/minFollow with infusion @ 8 mg/kg/min

PROGNOSISPROGNOSIS

Subsequent incidence of DM in IDM Subsequent incidence of DM in IDM increased compared to general populationincreased compared to general population

Physical development normal but may be Physical development normal but may be predisposed to childhood obesitypredisposed to childhood obesity

? Slightly increased risk of intellectual ? Slightly increased risk of intellectual development unrelated to hypoglycemiadevelopment unrelated to hypoglycemia

THANK YOUTHANK YOU

infant of diabetic mother2

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