INTRAUTERINE GROWTH RESTRICTION: RISK FACTORS AND PATHOGENESIS

Joserizal Serudji

Introduction

FETAL GROWTH

genetic

maternalplacental

FETUSHEALTHY NEWBORN

& APPR- SIZENormal circumstances

InheritanceGrowth

potential

Introduction

Growth potential

Environ-ment

Ability to reach optimal birth weight

Introduction

Introduction

Slow Growth

0 to 15-16 weeks

Less than 10 grams/weeks

Accelerating Growth

10-17 to 26-27 weeks

85 grams/weeks

Maximum Growth

26-27 to 37-38 weeks

200 grams/week

Decelerating Growth

37-38 to 44 weeks

More than 70 grams/week

The normal rate of fetal growth in an ideal cases is limited by its internal constraints (genetic in nature)

Introduction

Introduction

Oxygen

Glucose

Amino

Acids

Fetal requirement

Introduction

Oxygen

Glucose

Amino Acids

Simple Diffusion

Facilitated Diffusion

Active Transport

Chemical energy (ATP)

Synthesis of lypids, glycogen, nucleoti des and

other molecules

Synthesis of protein

• Persistent decrease in availability of any of these substrates limit the ability of the fetus to reach its growth potential

• Persistent and severe substrate deficiency threaten the ability of the fetus to survive

• So many factors associated with reducing substrates supplies to the fetus

Terminology

Intrauterine Growth Retardation

Intrauterine Growth Restriction

Abnormal Mental Function Slow Growth or Ceases

•Fetal weight ≤ 10th percentile for gestational age and sex/SGA•Present of pathological process

SGA is defined as birth weight:• At 10th or less percentile, or• At 5th or less percentile, or• At 3rd or less percentile, or• 2 SDs below the mean for gestational age

The lower cut-off incidence and morbidity and mortality

Cut-off 10th percentile:

• SGA : 3—7 %• IUGR: 3 quarter (failed to achieve its potential

growth)• Non-IUGR: 1 quarters (constitutionally small)

Risk factorsIUGR occurs when gas exchange and nutrient delivery

to the fetus are not sufficientThe process occur primariliy because of:• Maternal disease causing decreased oxygen-carrying

capacity• A dysfunctional oxygen delivery system secondary to

maternal vascular desease• Placental damage resulting from maternal diseaseMany factors: fetoplacental fac tors and maternal

factors

Risk Factors

Constitutionally small mother• Small women have smaller baby• Reduced intrauterine growth of mother reduced intrauterine

growth of her children• Environment more important than genetic contribution

Poor maternal weight gain and nutrition• Lack of weight gain in the second trimester associated with

fetal growth restriction

Social deprivation• Associated to lifestyle factors such as smoking, alcohol or other

substances abuse and poor nutrition

Risk Factors

Fetal infections• Viral, bacterial, protozoon, and spirochaetal implicated on

fetal growth restriction• CMV direct cytolysis and loss functional cells• Rubella vascular deficiency• Another infection affect fetal growth : hepatitis A and B,

Listeriosis, TB, Syphilis, Toxoplasmosis and Congenital Malaria

Congenital malformations• More severe malformation more likely fetus to be small• Espescially with chromosomal abnormalities or serious

cardiovascular malformations

Risk Factors

Chromosomal abnormalities• Autosomal trisomies related togrowth restriction• Trisomy 18, 13 and 21• Not seen in Turner or Klinefelter Syndrome

Trisomi 16• Patches of trisomy 16 confined placental mosaicism

placental insufficiency fetal growth restriction

Primary disorders of cartilage and bone• Osteogenesis imperfecta• Various chondrodystrophies

Risk Factors

Chemical teratogens• Anticonvulsants (phenitoin, trimethadione)• Cigarette• Narcotics• Alcohol• Cocaine

Vascular disease• Chronic vascular disease especially when further complicated by

superimposed preeclampsia

Chronic renal disease• Renal disease maybe accompanied by restricted fetal growth

Risk Factors

Chronic hypoxia• Women in high altitude• Cyanotic heart disease

Maternal anemia• Anemia does not cause growth restriction (in most

cases)• Except : • sickle cell disease• inherited anemia with serious maternal disease• deficient total blood volume early in pregnancy

Risk Factors

Placental and cord abnormalities• Chronic partial placental separation• Extensive infarction• Chorioangioma• Marginal insertion of the cord• Velamentous insertion of the cord

Multiple fetuses• Two or more fetuses more likely complicated by

diminished growth of one or both fetuses compared with normal singleton

Risk Factors

Antiphospholipid antibody syndrome• Two classes of antiphospholipid antibodies :

• Anticardiolipin antibodies• Lupus anticoagulant

• Pathophysiological mechanism maternal platelet aggregation & placental thrombosis

Extrauterine pregnancy• Fetus gestated outside uterus is usually growth

restricted• Also some maternal uterine malformations

Pathogenesis & Categories

• There are standards and averages in weight according to gestational age (weeks)

• Using a fetal growth curve derived from one population and applyng to another over- or underestimation of true incidence of SGA

• A population of smaller individual will have smaller babies the difference lies in genetic growth potential

Normal intrauterine growth pattern:• 1st stage: 4—20 weeks gestation, rapid cell division and

multiplication (hyperplasia)• 2nd stage: 20—28/32 weeks gestation, cell division

(hyperplasia) and cells increase in size (hypertrophy)• 3rd stage: 28/32—40 weeks gestation, rapid increase in cell

size, rapid accumulation of fat, muscle and connective tissue

95% offetal weight gain occurs during the last 20 weeksIf development and weight gain is disturbed or

interrupted restricted growth

Fetal weight below tenth percentile

Pathological process present

IUGR

Increased Risk of Perinatal Mortality & Morbidity

Pathogenesis & Categories

IUGR

First StageHyperplactic Stage

Symmetric

Stage 2Hyperplastic and

Hypertrophic Stage

Stage 3Hypertrophic Stage

Asymmetric

Pathogenesis & Categories

Pathogenesis & Categories

Pathogenesis & Categories

Symmetrical Growth Restriction• Growth inhibition during first stage undersized

fetus with fewer cells but normal size• Weight, head and length < 10th percentile

proportionally small• Condition associated include genetic

(constitutional, chromosomal and single gene defect, deletion disorders and inborn error of metabolism), congenital anomalies, intrauterine infections, and therapeutic iradiation

Pathogenesis & Categories

Asymmetrical Growth Restriction• Growth inhibition during stage 2 and 3

decreased of cell size and fetal weight with less effect on total cell number fetal length and fetal head circumference

• Implies fetus who is undernourished and directing most of its energy to maintainaning growth of vital organs such as brain and heart at the expensive of the liver, muscle and fat role of brain sparing effect (redistribution mechanism)

Pathogenesis & Categories

Asymmetrical Growth Restriction• Normal head but small abdominal

circumference, scrawny limbs and thinned skin• Condition associated include uteroplacental

insufficiency (chronis hypertension or preeclampsia), chronis renal disease, cyanotic heart disease, hemoglobinopathies, placental infarcs, abruptio placenta, multiple gestation, velamentous insertion, cirmcumvallate placenta and high altitude

Perinatal Complication

Antepartum Complications

• Stillbirth• Oligohydramnios• Intrapartum fetal

acidosis

Perinatal Complication

Neonatal Complications

• Meconium aspiration syndrome• Persistent fetal circulation• Hypoxic-ischemic encephalopathy• Hypoglicemia• Hypocalcemia• Hyperviscosity syndrome• Deficient temperature controle

Conclusion

IUGR is a part of SGA with present of pathological process

Growth restricted fetus have a great chance to suffer from many prenatal and/or neonatal complications

Many factors should be recognized

Impaired substrates supply may reduce cellular process resulting in symmetrical or asymmetrical IUGR

Take home message

The most important thing in efforts to comprehensively overcome IUGR

issues is the early detection of its risk factor(s), -- eg. Premarital, preconception, or as early as

possible in pregnancy

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