The infant of a The infant of a diabetic motherDr.A.ShiraniDr.A.Shirani

:INTRODUCTION

Diabetes in pregnancy is associated with an increased risk of fetal,neonatal,and long- term complications in offspring.maternaldiabetes may be pregestational(ie,type1 or diabetes may be pregestational(ie,type1 or type2 diabetes diagnosed before pregnancy with a prevalence rate of aboute 7.5%) or gestational.The outcome is generally related to the onset and duration of the mothers diabetes.

HHyperglycemiayperglycemia in the mother in the mother results inresults inhyperglycemia in the fetus, which hyperglycemia in the fetus, which in turn causes in turn causes hypertrophyhypertrophyof the fetal of the fetal pancreatic islets pancreatic islets and and of the fetal of the fetal pancreatic islets pancreatic islets and and beta cells increased secretion of beta cells increased secretion of insulin.insulin..

The newborn IDM, as evidencedby increased levels of insulininsulinandCC peptide peptide in theumbilical blood.

resulting inmacrosomiamacrosomia, cardiomegalycardiomegaly, , and macrosomiamacrosomia, cardiomegalycardiomegaly, , and an increase in adipose tissue.adipose tissue.

Chronic fetal Chronic fetal hyperinsulinemiahyperinsulinemia results in results in an an increaseincrease in the in the metabolic ratemetabolic rateand and oxygen consumption, oxygen consumption, leading to leading to relative hypoxemiarelative hypoxemia,,which in turn results in an increase in the which in turn results in an increase in the synthesis ofsynthesis ofsynthesis ofsynthesis oferythropoietinerythropoietin and an increase in red and an increase in red blood cell mass andblood cell mass andpolycythemiapolycythemia.

hyperinsulinemiahyperinsulinemia has beenhas beenshown to shown to suppresssuppress the the production of production of surfactantsurfactant in thein thelung and thus predispose to lung and thus predispose to respiratory distress respiratory distress syndromesyndromerespiratory distress respiratory distress syndromesyndrome..

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The The increasedincreased concentrationconcentrationof these of these nutrientsnutrients in the fetal circulation in the fetal circulation

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ExcessiveExcessivetransport of other nutrients (i.e., transport of other nutrients (i.e., amino acidsamino acids and and lipidslipids).).

of these of these nutrientsnutrients in the fetal circulation in the fetal circulation stimulates fetalstimulates fetalinsulin secretioninsulin secretion, which in turn , which in turn stimulates stimulates excessive fetaexcessive fetallgrowthgrowth.

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lack of lack of aa countercounter--regulatory regulatory hormonal response. Thehormonal response. Thelatter is confirmed by the lack of latter is confirmed by the lack of an increase in circulatingan increase in circulatingglucagonglucagon andand catecholamine catecholamine glucagonglucagon andand catecholamine catecholamine levels in IDMs levels in IDMs duringduringhypoglycemiahypoglycemia

Clinical ManifestationsMacrosomia: At At birth, these infants arebirth, these infants are obeseobese, , plethoricplethoric,,and large for gestational age and large for gestational age ((LGALGA) ) and show evidenceand show evidence((LGALGA) ) and show evidenceand show evidenceof of excessive fat excessive fat as well as as well as visceromegalyvisceromegaly in the formin the formof a of a large liverlarge liver, , spleenspleen, and , and heartheart

GGrowth rowth of the of the brainbrain and possibly and possibly the the kidneykidney is notis notdependent on insulin, these two dependent on insulin, these two organs are normal inorgans are normal insize.size.

Management Management of maternal of maternal metabolism tendsmetabolism tendsto to reducereduce the incidence of the incidence of macrosomiamacrosomia but but does notdoes notprevent it.prevent it.

Congenital anomalies:Increased Increased twofold to threefold twofold to threefold in in thetheinfants infants of insulinof insulin--dependent dependent diabetic mothers compareddiabetic mothers comparedwith the normal population. The with the normal population. The with the normal population. The with the normal population. The frequency of congenitalfrequency of congenitalanomalies is anomalies is not increased in the not increased in the infants of infants of gestationallygestationallydiabetic mothers diabetic mothers or in those of or in those of diabetic fathers.diabetic fathers.

A number of congenitalA number of congenitalanomalies: anomalies: TThehe HHearteart, MusculoskeletalMusculoskeletalsystem, and system, and GenitourinaryGenitourinarysystemsystem,. ,. Caudal agenesis Caudal agenesis or or dysplasiadysplasiaagenesis or hypoplasia agenesis or hypoplasia of the of the femora femora in conjunction within conjunction withfemora femora in conjunction within conjunction withagenesis of the lower vertebrae agenesis of the lower vertebrae , neural tubeneural tubeDefects and Defects and sacrumsacrum

Immediately after birth, there isImmediately after birth, there isa significant decrease in plasma a significant decrease in plasma glucose concentration,glucose concentration,reaching a nadir between reaching a nadir between 3030 and and 9090 minutes and followedminutes and followedby a by a spontaneous recovery spontaneous recovery in most in most by a by a spontaneous recovery spontaneous recovery in most in most infantsinfants

MostMost of these infants of these infants areareasymptomaticasymptomatic.

HHypoglycemia ypoglycemia in the newborn in the newborn does not necessarilydoes not necessarilyreflect the magnitude of reflect the magnitude of antepartum metabolic control ofantepartum metabolic control ofthe mother and may simply be the the mother and may simply be the consequence of hyperglycemiaconsequence of hyperglycemiaconsequence of hyperglycemiaconsequence of hyperglycemiaduring labor and deliveryduring labor and delivery.

HypocalcemiaHypocalcemia and and HypomagnesemiaHypomagnesemia::Alterations in calcium and Alterations in calcium and magnesium homeostasismagnesium homeostasisoccur in about occur in about 5050% % of infants born of infants born to insulinto insulin--dependentdependentdiabetic mothersdiabetic mothers.diabetic mothersdiabetic mothers.between between 48 48 and and 72 72 hours hours after after birth birth ..

HypocalcemiaHypocalcemia has been has been related torelated tothe the severityseverity and and durationduration of of maternal diabetesmaternal diabetes.

::Mechanisms Mechanisms of of HHypocalcemiaypocalcemia

Failure Failure ofofthe IDM to mount an appropriate the IDM to mount an appropriate parathyroid hormoneparathyroid hormone(PTH) response(PTH) response, persistently , persistently highhighlevels of calcitoninlevels of calcitonin, and, andpossible possible alterations in vitamin D alterations in vitamin D metabolismmetabolism.

Improve spontaneously. Improve spontaneously. ..

Other Other clinical clinical problemsproblems:

Polycythemia Polycythemia

HyperbilirubinemiaHyperbilirubinemia

trombosistrombosis Renal Renal veinvein trombosistrombosis Renal Renal veinvein

SeptalSeptal Hypertrophy of the Hypertrophy of the Heart:Heart:Despite Despite good metabolic control, good metabolic control, cardiaccardiachypertrophy developed in late hypertrophy developed in late gestation (gestation (3434--40 40 weeks).weeks).

Management Management of the Diabeticof the Diabetic Mother:Mother: PreconceptionalPreconceptional and and earlyearlypostconceptionalpostconceptionalmetabolic metabolic control control decreasedecreasecongenital congenital malformationsmalformations.

Improving maternalImproving maternalcompliancecompliance, , preventingpreventingketoacidosisketoacidosis, and recognizing, and recognizingand treating pregnancyand treating pregnancy--induced induced hypertension hypertension and and pyelonephritis pyelonephritis are importantare important.

MMaternal aternal fastingfasting plasma glucose valuesplasma glucose valuesat at less than less than 80 80 mg/mg/dLdL and and 22--hour hour postprandialpostprandial plasmaplasmaglucose values at glucose values at less than less than 120 120 mg/mg/dLdL.

Early Early screeningscreening:: maternal maternal serumserum

alphaalpha--fetoproteinfetoprotein level for open neural level for open neural alphaalpha--fetoproteinfetoprotein level for open neural level for open neural tube defects andtube defects anda a level II ultrasound level II ultrasound at at 18 18 to to 20 20 weeks weeks of gestationof gestation

second trimester (second trimester (2828--3232):):

Daily Daily fetal movement fetal movement counts andcounts andbiweekly biophysical testing biweekly biophysical testing (non(non--stress testing, biophysicalstress testing, biophysicalprofile, or both) or profile, or both) or nonnon--stress testing stress testing combined withcombined withan amniotic fluid indexan amniotic fluid indexan amniotic fluid indexan amniotic fluid index

Vaginal delivery Vaginal delivery isispreferred, but obstetric factors may justify preferred, but obstetric factors may justify cesarean deliverycesarean delivery

DuringDuringllaborabor, glucose and insulin therapy should , glucose and insulin therapy should be adjusted tobe adjusted tomaintainmaintain normoglycemianormoglycemia in the mother.in the mother.

Delivery should take place in Delivery should take place in a hospitala hospital

Glucose values areGlucose values arechecked during the checked during the first first 3 3 hours hours after after birth birth (typically(typicallybetween between 30 30 and and 60 60 minutes)minutes), , sporadically sporadically before feedingsbefore feedings,,and and any time symptoms are any time symptoms are and and any time symptoms are any time symptoms are suspectedsuspected.

Feedings mayFeedings maybe started be started as soon as as soon as the infant is the infant is stable, usually withinstable, usually within

2 2 to to 4 4 hours hours after after birth and birth and continued every continued every 33--44hh

Prognosis:Prognosis:

Control of maternal metabolismmaternal metabolism,and maternal educationeducation have all resulted in reduced perinatalmortalitymortality and morbiditymorbidity.

control ofmaternal metabolism during the maternal metabolism during the periconceptionalpericonceptional periodhas resulted in a decreaseddecreased incidence of congenitalcongenital malformationsmalformationsin IDMs.

Howeverhypoglycemiahypoglycemia, macrosomiamacrosomia, and polycythemiapolycythemia, persist.

Children of diabeticmothers, with and without macrosomia in the newbornperiod, had higher body mass indexeshigher body mass indexes, higher blood pressures,blood pressures,and higher glucose and insulin levels higher glucose and insulin levels on glucoseand higher glucose and insulin levels higher glucose and insulin levels on glucosetolerance testing when evaluated at age age 18 18 to to 26 26 years.

NNeurodevelopmental outcome:eurodevelopmental outcome:Is confounded by the contribution of perinatalperinataleventsevents such as perinatal asphyxia perinatal asphyxia and metabolic acidosismetabolic acidosisin addition to chronic metabolic insults and iron deficiencyiron deficiency..and iron deficiencyiron deficiency..

IntellectualIntellectualdelaydelay at ages 3 3 and and 5 5 years years in infants born to womenwith acetonuriaacetonuria (a marker of poor metabolic control) hasbeen observed.

Congenital anomaliesCongenital anomalies• • Heart failure and Heart failure and septalseptal hypertrophy of hearthypertrophy of heart• • Surfactant deficiency respiratory distress syndrome, Surfactant deficiency respiratory distress syndrome, transienttransienttachypnea of the newborn, persistent pulmonarytachypnea of the newborn, persistent pulmonaryhypertensionhypertension• • HyperbilirubinemiaHyperbilirubinemia• • Hypoglycemia, Hypoglycemia, hypocalcemiahypocalcemia, , hypomagnesemiahypomagnesemia• • MacrosomiaMacrosomia, nerve injury related to birth trauma, nerve injury related to birth trauma• • MacrosomiaMacrosomia, nerve injury related to birth trauma, nerve injury related to birth trauma• • Renal vein thrombosisRenal vein thrombosis• • Small left colonSmall left colon• • Unexplained intrauterine demiseUnexplained intrauterine demise• • PolycythemiaPolycythemia• • VisceromegalyVisceromegaly• • Predisposition to laterPredisposition to later--life obesity, insulin resistance,life obesity, insulin resistance,and diabetesand diabetesBOX BOX 9595--3 3 MORBIDITY IN INFANTS OFMORBIDITY IN INFANTS OFDIABETIC