INTRA UTERINE INTRA UTERINE GROWTH GROWTH

RESTRICTION and RESTRICTION and intrauterine fetal intrauterine fetal

DeathDeath

King Khalid University HospitalKing Khalid University HospitalDepartment of Obstetrics & GynecologyDepartment of Obstetrics & Gynecology

Course 482Course 482

objectivesobjectives DefinitionsDefinitions EtiologyEtiology ManagementManagement PreventionPrevention

IUGRIUGR is failure of a fetus to reach its genetic is failure of a fetus to reach its genetic growth potentialgrowth potential

-- The best guide is to establish fetal size The best guide is to establish fetal size early in gestationearly in gestation

-- Estimated fetal weight can be Estimated fetal weight can be calculated calculated from from ultrasoundultrasound measurementsmeasurements-- Abdominal circumference Abdominal circumference is affected is affected

early in growth restriction owing to early in growth restriction owing to decreased glycogen storage in the liverdecreased glycogen storage in the liver..

Low Birth weight and Small for gestation ageLow Birth weight and Small for gestation age

LBWLBW is defined by the WHO as birth is defined by the WHO as birth weight < 2.5 kg, so does not correct weight < 2.5 kg, so does not correct for gestation.for gestation.

SGASGA is used is used postnatallypostnatally to describe a to describe a fetus or neonate with growth fetus or neonate with growth parameters (e.g EFW, AC, parameters (e.g EFW, AC, birthweight) below a given centile for birthweight) below a given centile for gestational age.gestational age.

Implications of Growth RestrictionImplications of Growth RestrictionGrowth restricted fetusesGrowth restricted fetuses Have a higher risk of Have a higher risk of still birthstill birth and and

mortality mortality Are most at risk of Are most at risk of

hypothermiahypothermiahypoglycaemiahypoglycaemiapulmonary haemorrhagepulmonary haemorrhageinfectioninfectionencephalopathyencephalopathynecrotising enterocolitisnecrotising enterocolitis

Incidence of fetal heart rate abnormalitiesIncidence of fetal heart rate abnormalities Higher incidence of operative deliveryHigher incidence of operative delivery

AetiologyAetiologyThere is a wide range of associations:There is a wide range of associations:

FetalFetalMaternalMaternalPlacentalPlacental

-- These in turn may have a genetic or These in turn may have a genetic or environmental basisenvironmental basis

Fetal CausesFetal Causes(a)(a) ChromosomalChromosomal

Abnormal fetal karyotype can be Abnormal fetal karyotype can be responsible for up to responsible for up to 20% of growth 20% of growth restricted fetusrestricted fetus-- Early pregnancy, triploidy – 58%Early pregnancy, triploidy – 58%

Trisomy - 46%Trisomy - 46%Trisomy 21 and Turners – Trisomy 21 and Turners –

second second trimestertrimesterThe reason is probably because of lack The reason is probably because of lack

of cell division or cell growth in of cell division or cell growth in either the fetus or placentaeither the fetus or placenta

(b)(b) Structural anomaliesStructural anomaliesStructural defectsStructural defects1.1. Central nervous systemCentral nervous system2.2. Cardiovascular systemCardiovascular system3.3. Gastro intestinal systemGastro intestinal system4.4. Genito urinary systemGenito urinary system5.5. Muskilo skeletalMuskilo skeletal

Are associated with an increased Are associated with an increased risk of IUGRrisk of IUGR

(c)(c) Infection:Infection:1.1. MalariaMalaria – major cause of – major cause of

IUGR – its treatment IUGR – its treatment reduces reduces the incidence of IUGRthe incidence of IUGR

2.2. RubellaRubella3.3. CytomegalovirusCytomegalovirus4.4. ToxoplasmosisToxoplasmosis5.5. SyphilisSyphilis

Can affect cell division and have all Can affect cell division and have all been implicatedbeen implicated

Nutrient SupplyNutrient SupplyInadequate maternal nutrition can Inadequate maternal nutrition can

restrict growth in the 3restrict growth in the 3rdrd trimester trimester-- examples are the Dutch Famine examples are the Dutch Famine

Glucose, amino acids and lactate are Glucose, amino acids and lactate are the major substrates for the fetusthe major substrates for the fetus-- Oxygen : Babies born at higher Oxygen : Babies born at higher altitude are smaller than those altitude are smaller than those born born at sea levelat sea level

Placental CausesPlacental Causes Lack of conversion of spiral arteries into Lack of conversion of spiral arteries into

utero placental arteriesutero placental arteries The low-resistance circulation thus created The low-resistance circulation thus created

allows high blood flow to the placenta.allows high blood flow to the placenta.

In normal pregnancies, end diastolic flow is In normal pregnancies, end diastolic flow is usually present usually present (umbilical arteries by the (umbilical arteries by the early second trimesterearly second trimester

And increases until termAnd increases until term Growth restricted fetuses often have absent Growth restricted fetuses often have absent

or reversed end-diastolic flow in the or reversed end-diastolic flow in the umbilical arteryumbilical artery – this suggests increased – this suggests increased resistance in the feto-placental circulationresistance in the feto-placental circulation

Maternal CausesMaternal Causes(a)(a) SmokingSmoking

-- Active and passive smoking Active and passive smoking is a is a major cause of IUGRmajor cause of IUGR

-- Such babies weigh between Such babies weigh between 100-100-300gm less than other babies300gm less than other babies-- > 10 cigarettes/ day is > 10 cigarettes/ day is significantsignificant-- Male fetus more affected than Male fetus more affected than femalesfemales-- Mechanism is probably via the Mechanism is probably via the higher higher levels of carboxy levels of carboxy haemoglobin in such haemoglobin in such fetuses.fetuses.

(b) Alcohol:(b) Alcohol:-- Moderate to heavy alcohol Moderate to heavy alcohol consumption consumption can reduce fetal weight by up can reduce fetal weight by up to 500 gm.to 500 gm.

(c)(c) DrugsDrugsHeroin and methadone use are associated with Heroin and methadone use are associated with growth restriction <490 gm and 280 gm growth restriction <490 gm and 280 gm respectively.respectively.

(d)(d) Chronic DiseasesChronic Diseases1. 1. Congenital heart disease Congenital heart disease – especially if – especially if cyanoticcyanotic2.2. Chest disease Chest disease e.g. cystic fibrosis, e.g. cystic fibrosis, bronchitasis, bronchitasis, kyphoscoliosm and asthma in kyphoscoliosm and asthma in severe cases where severe cases where there is marked there is marked respiratory compromis.respiratory compromis.3.3. Chronic renal diseases Chronic renal diseases – especially if there is – especially if there is hypertension, proteinuriahypertension, proteinuria4.4. Diabetes mellitus Diabetes mellitus – if there is renal disease – if there is renal disease and and vascular disease.vascular disease.

Screening:Screening:Clinical ExaminationClinical Examinationa.a. PalpationPalpationb.b. Symphyseal – fundal height – higher Symphyseal – fundal height – higher

sensitivities than palpationsensitivities than palpationUltrasoundUltrasound

-- Has a better detection rate for Has a better detection rate for IUGR than clinical examinationIUGR than clinical examination

MANAGEMENTMANAGEMENTThe terms symmetric and asymmetric The terms symmetric and asymmetric

growth restrictions are descriptivegrowth restrictions are descriptive-- growth restriction detected at growth restriction detected at any any gestation gestation without associated without associated anomaly anomaly is most likely to is most likely to represent represent true true growth restriction as a result growth restriction as a result of of utero utero placental dysfunctionplacental dysfunction-- The earlier the gestation the The earlier the gestation the more more likely the fetus is to be likely the fetus is to be aneuploid aneuploid or infected.or infected.

The gestational age should be checked The gestational age should be checked using the last menstrual period and using the last menstrual period and any early scans.any early scans.-- diagnosis of IUGR should be diagnosis of IUGR should be made made on serial scans – every 2 on serial scans – every 2 weeksweeks-- thorough survey of the fetus for thorough survey of the fetus for

associated anomalies is associated anomalies is undertakenundertaken-- liquor volume should be liquor volume should be quantified quantified (amniotic fluid index)(amniotic fluid index)-- doppler waveforms of the uterine doppler waveforms of the uterine

and and umbilical artery should be umbilical artery should be obtainedobtained..

EARLY –ONSET GROWTH EARLY –ONSET GROWTH RESTRICTION (<32 WEEKS)RESTRICTION (<32 WEEKS)

The principle differential diagnosis The principle differential diagnosis are:are:

(a)(a) Chromosomal abnormality or some other Chromosomal abnormality or some other genetic problemgenetic problem

(b)(b) Congenital infectionCongenital infection(c)(c) Utero placental dysfunctionUtero placental dysfunction

Findings that would make a chromosomal Findings that would make a chromosomal problem more likely include:problem more likely include:-- Normal uterine artery doppler Normal uterine artery doppler findingsfindings-- Normal liquor volumeNormal liquor volume-- Presence of a structural abnormalityPresence of a structural abnormality

The commonest infection The commonest infection associated with IUGR is associated with IUGR is cytomegalovirus (CMV)cytomegalovirus (CMV)-- Mother may have complained Mother may have complained

of flu-like illnessof flu-like illness-- Fetus has sonographic Fetus has sonographic findings findings compatible with CMV compatible with CMV (e.g. (e.g. microcephaly and microcephaly and cerebral cerebral calcification).calcification).

Utero placental dysfunction is a Utero placental dysfunction is a diagnosis of exclusion. Factors diagnosis of exclusion. Factors supporting this are:supporting this are:-- a history of growth restriction a history of growth restriction in a previous pregnancyin a previous pregnancy-- reduced liquor volumereduced liquor volume-- abnormal uterine umbilical abnormal uterine umbilical artery waveformsartery waveforms

LATE-ONSET GROWTH RESTRICTION LATE-ONSET GROWTH RESTRICTION (>32 WEEKS)(>32 WEEKS)-- most likely cause is most likely cause is utero utero placental placental insufficiencyinsufficiency, often , often associated with the associated with the development development of of pre-eclampsiapre-eclampsia

FETAL MONITORINGFETAL MONITORINGMonitoring the growth-restricted fetus Monitoring the growth-restricted fetus

involves serial fetal measurementinvolves serial fetal measurement Abdominal circumferenceAbdominal circumference Amniotic fluid indexAmniotic fluid index CardiotocographyCardiotocography Doppler ultrasoundDoppler ultrasound

Fetuses with absent end-diastolic flow are Fetuses with absent end-diastolic flow are hypoxaemic, these changes may hypoxaemic, these changes may appear up appear up to 5 weeks before demiseto 5 weeks before demise

Reversed end-diastolic flow is suggestive of Reversed end-diastolic flow is suggestive of preterminal compromise ; the preterminal compromise ; the fetus may die fetus may die within 1-2 days if not deliveredwithin 1-2 days if not delivered..

AMNIOTIC FLUID INDEXAMNIOTIC FLUID INDEX Reduction in amniotic fluid index (the Reduction in amniotic fluid index (the

sum of the four deepest vertical pools sum of the four deepest vertical pools in each quandrant) is associated with in each quandrant) is associated with an increase in perinatal mortality.an increase in perinatal mortality.

Fetal urine production is significantly Fetal urine production is significantly lower in the SGA fetus than in the lower in the SGA fetus than in the AGA fetus.AGA fetus.

Decreased renal perfusion results in Decreased renal perfusion results in oligohydramniosoligohydramnios

BIOPHYSICAL PROFILEBIOPHYSICAL PROFILEBreathingBreathingToneToneMovementMovementAmniotic fluid volumeAmniotic fluid volumeCardiotocographyCardiotocography

-- requires about 40 mins requires about 40 mins observation of observation of fetal breathing fetal breathing movements.movements.-- a persistently abnormal a persistently abnormal biophysical biophysical score is associated score is associated with absence of with absence of end-diastolic end-diastolic flowflow

PREVENTION:PREVENTION: All women should be encouraged to All women should be encouraged to

stop smoking stop smoking since it is the since it is the commonest risk factorcommonest risk factor

Even passive smoking is harmful – Even passive smoking is harmful – husbands should be persuaded to husbands should be persuaded to stop.stop.

Early aspirin treatment Early aspirin treatment before 17 before 17 weeks (100-150mg) for patients with weeks (100-150mg) for patients with previous IUGR babies (possible role of previous IUGR babies (possible role of placental thrombosis)placental thrombosis)

LABOUR AND DELIVERYLABOUR AND DELIVERY In the preterm failure to delilver poses the In the preterm failure to delilver poses the

risk of chronic hypoxia while delivery risk of chronic hypoxia while delivery exposes the neonate to the risks of exposes the neonate to the risks of prematurityprematurity

Most fetuses follow a decompesation Most fetuses follow a decompesation cascade:cascade:

absent end-diastolic flowabsent end-diastolic flowdecelerative decelerative CTG CTG reversed end diastolic flow reversed end diastolic flow

fetal deathfetal death IUGR fetus is more likely to become more IUGR fetus is more likely to become more

hypoxic in labourhypoxic in labour With AEDF or reversed EDF, delivery should With AEDF or reversed EDF, delivery should

be by caesarean sectionbe by caesarean section

IUFDIUFDThe term IUFD (Intra uterine fetal death) The term IUFD (Intra uterine fetal death)

embraces embraces before the 28before the 28th or 24 thth or 24 th week week of of pregnancy (delayed) miscarriage) and those pregnancy (delayed) miscarriage) and those occuring later which result in occuring later which result in macerated macerated stillbirth.stillbirth.

MacerationMaceration is a destructive process which first is a destructive process which first reveals itself by blistering and peeling of the reveals itself by blistering and peeling of the fetal skin. This appears between 12 and 24 fetal skin. This appears between 12 and 24 hours after fetal death. The ligaments are hours after fetal death. The ligaments are softened and the vertebral column is liable softened and the vertebral column is liable to sag. The skull bones overlap each other to sag. The skull bones overlap each other at the sutures because of the shrinkage of at the sutures because of the shrinkage of the brain (the brain (Spalding’s signSpalding’s sign). It takes several ). It takes several days for Spalding’s sign to appear after days for Spalding’s sign to appear after intrauterine death, usually a week or moreintrauterine death, usually a week or more..

CAUSES:CAUSES:1.1. One of the commonest is One of the commonest is pre-eclampsiapre-eclampsia

-- hypertensive spasm of the utero hypertensive spasm of the utero placental vessels which results into placental vessels which results into reduced oxygen supply to the fetus.reduced oxygen supply to the fetus.

2.2. Chronic hypertensionChronic hypertension3.3. Chronic nephritisChronic nephritis

-- fetus dies from placental infarction fetus dies from placental infarction and hypoxia even before the age of and hypoxia even before the age of viabilityviability

4.4. Hyperpyrexia Hyperpyrexia – a body temperature over – a body temperature over 39.439.400C can kill the fetus directlyC can kill the fetus directly

5.5. Diabetes in pregnancyDiabetes in pregnancy6.6. Fetal malformationFetal malformation7.7. Placental insufficiencyPlacental insufficiency8.8. IdiopathicIdiopathic

MANAGEMENT:MANAGEMENT:1.1. Conservative – await spontaneous Conservative – await spontaneous

labourlabour2.2. Induction of labourInduction of labour

-- Prostin EProstin E22 (Vaginal pessary) (Vaginal pessary)-- IV NaladorIV Nalador-- OxytocinOxytocinExclude coagulation disorderExclude coagulation disorder-- generally hypofibrinogenaemia generally hypofibrinogenaemia does not set in until after about 4 does not set in until after about 4 weeks after the IUFD.weeks after the IUFD.

Thank youThank you