Published on March 11, 2014
IUGR by La Lura White MD Maternal Fetal Medicine
IUGR • Fetal growth restriction, (IUGR), is a common complication of pregnancy. • Pathologic condition where there is a restriction of growth in utero, and the fetus does not attain its full growth potential. • Complicates ≈5-10% of pregnancies • Third leading cause of perinatal mortality after anomalies and prematurity • 40% of all stillbirths are IUGR
IUGR • Problems in making the diagnosis because there is a lack of consensus regarding terminology, etiology, and diagnostic criteria for fetal growth restriction. • Difficult in differentiating between the fetus that is SGA vs. IUGR sometimes leading to misdiagnosis. • Uncertainty surrounding the optimal management and timing of delivery for the growth-restricted fetus.
IUGR • Often literature will use varying percentiles, 10%, 5% and even 3%. • Perinatal mortality inversely proportional to percentile growth: 1.5% <10% 2.5% < 5th %
IUGR • Most accepted definition fetuses with IUGR is an estimated fetal weight that is less than the 10th percentile for gestational age. • 70% of fetuses <10% are SGA • 30% are IUGR
IUGR 70% 20% 10% Uteroplacental insuffiency:assymetrical Chrosomal,structural, early infection:symmetrical Constitutionally small
IUGR • Types of IUGR • Symmetric IUGR: weight, length and head circumference are all below the 10 th percentile • Asymmetric IUGR: weight is below the 10 th percentile and head circumference and length are preserved, “head sparing” and the abdomen is small.
IUGR • Normal Rate of Fetal Growth • 15 weeks = 5 grams/day • 20 weeks = 10 grams/day • 30 weeks = 25 grams/day • 35 weeks = 35 grams/day • 40 weeks = 15 grams/day • May vary by race, gender, multiple gestation
IUGR • Normal cellular development • Cellular hyperplasia • Cellular hypertrophy
IUGR • Stage I (Hyperplasia) • - 4 to 20 weeks • - Rapid mitosis • - Increase of DNA content • Stage II (Hyperplasia & Hypertrophy) • - 20 to 28 weeks • - Declining mitosis. • - Increase in cell size.
IUGR • Stage III ( Hypertrophy) • - 28 to 40 weeks • - Rapid increase in cell size. • - Rapid accumulation of fat, muscle and connective tissue. • 95% of fetal weight gain occurs during last 20 weeks of gestations.
IUGR • Growth inhibition in stage I: • - Undersized fetus with fewer cells. • - Normal cell size. • Result in symmetric IUGR. (1/3) • Associated conditions: • - Genetic • - Congenital anomalies • - Intrauterine infections • - Substance abuse • - Cigarette smoking • - Therapeutic irradiation
IUGR • Growth Inhibition in Stage II/III • -Decrease in cell size and fetal weight • - Less effect on total cell numeric, fetal length, head circumferance. • Result in asymmetric IUGR.(2/3) • Associated Conditions: • - Uteroplacental insufficiency.
IUGR • Etiology of IUGR • Maternal • Fetal • Placental
IUGR • Maternal • Chronic disorder that is associated with vascular disease • Pregnancy-related hypertensive diseases: (pre-eclampsia with or without chronic hypertension) Impaired trophoblastic arteriolar invasion Atherosis and necrosis Reduced utero-placental blood flow • Antiphospholipid syndrome, an acquired immune-meditated thrombophilia (not seen in hereditary thrombophilia)
IUGR • Maternal • Pregestational diabetes mellitus • Renal insufficiency • Autoimmune disease (eg, systemic lupus erythematous) • Cyanotic cardic disease • Substance use and abuse (eg, tabacco, alcohol, cocaine, or narcotics) • Teratogen exposure (eg, cyclophosphamide, valproic acid, or antithrombotic drugs) • Infectious disease (eg, malaria cytomegalovirus rubella, toxoplasmosis, or syphilis)
IUGR • Fetal • Multiple gestation • Congential heart disease • Gastroschisis • Genetic and structural disorder trisomy 13 trisomy 18
IUGR • Placental • Small placenta • Fetal/Placental weight ratio >10 • Placental chronic abruption • Post-term
IUGR Cord anomalies Velementous insertion of the cord. Major umbilical vessels separate in the fetal membranes before reaching the placental disk.
IUGR • Cord anomalies • Battledore placenta: • The cord is attached to the margin of the placenta.
IUGR • Epidemiologic studies have revealed that growth-restricted fetuses are predisposed to the development of cognitive delay in childhood and diseases in adulthood. • Barker hypothesis: Increased risk of adult metabolic syndrome • Obesity • Type 2 diabetes mellitus • Coronary artery disease • Stroke
IUGR • Growth Restriction Intervention Trial • Only published randomized trial to assess the timing of delivery of the early preterm (less than 34 weeks of gestation) growth-restricted fetus. • Randomized to either the early delivery group (delivery within 48 hours) or to the expectant management group (with antepartum surveillance until it was felt that delivery should not be delayed any longer) • Betamethasone administration were the same in both groups
IUGR • Perinatal survival was similar, and at the 6–12-year follow-up there were no differences in cognitive, language, behavior, or motor abilities
IUGR • Disproportionate Intrauterine Growth Intervention Trial at Term • Women with singleton gestations at or beyond 36 weeks with suspected fetal growth restriction (defined as an estimated fetal weight less than the 10th percentile) were randomized to undergo delivery or expectant management • Delivery only if indicated • There were no differences in composite neonatal outcome between these two groups (study cohort was not large enough)
IUGR • Screening for Fetal Growth Restriction • Fundal height measured in centimeters (between 24–38 weeks of gestation) approximates the gestational age • Up to 85% sensitivity 32-34 weeks • Ultrasound: • Biometric measures ( biparietal diameter, head circumference, abdominal circumference, femur length) yield EFW and % growth • EFW may deviate from the birth weight by up to 20% in 95% of cases • Standard BW curves will underestimate preterm SGA
IUGR • AC most sensitive • 3616 preg >25 wks gestation • Single us within two wks delivery • Predicted <10th%ile for GA with • Sens 61% • Spec 95% • Ppv 86% • Npv 83%
IUGR • Ultrasound • amniotic fluid assessment • <5 oligo
IUGR • Doppler: • Blood flowing through the umbilical arteries originates from the fetus and enters the placenta. • The flow of blood through the arteries is dependent upon the strength of the fetal heart contraction and the health of the placenta. • Blood returning from the placenta goes through the umbilical vein to the fetus.
IUGR • Doppler principle based on changes in sound waves related to the flow velocity of blood traveling through these vessels. • The umbilical artery was first used to study this flow velocity in in 1977. • The umbilical arterial waveform usually has a "saw tooth" type pattern with flow always in the forward direction
IUGR The umbilical artery is evaluated by measuring the blood flow velocity at peak systole (maximal contraction of the heart) and peak diastole (maximal relaxation of the heart). • These values are then computed to derive a ratio.
IUGR • As GA advances, increase blood flow at diastole means placenta less resistant.
IUGR • In growth-retarded fetuses and fetuses developing intra- uterine distress, there is more placental resistance and the umbilical artery blood velocity waveform usually changes in a progressive manner. • Increased resistance, absent end diastolic flow, reverse flow.
IUGR • Increasing RI values , PI values and S:D ratios if blood flow during diastole is decreased.
IUGR • absent end diastolic flow
IUGR • reversal of end diastolic flow (REDF) :
IUGR • notching in late in pregnancy is an indicator of increased uterine vascular resistance and impaired uterine circulation’ Mild Severe
IUGR • Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction (IUGR) (PORTO STUDY) • OBJECTIVE: • National prospective observational multicenter study • Evaluate which sonographic findings were associated with perinatal morbidity and mortality in pregnancies affected by growth restriction (defined as estimated fetal weight (EFW) <10th centile) • Am J Obstet Gynecol. 2013 Apr;208(4)
IUGR • STUDY DESIGN: • Over 1100 consecutive ultrasound-dated singleton pregnancies with EFW <10th centile were recruited from January 2010 through June 2012. • A range of IUGR definitions were used, including EFW or abdominal circumference <10th, <5th, or <3rd centiles • with or without oligohydramnios • with or without abnormal umbilical arterial Doppler • Adverse perinatal outcomes included intraventricular hemorrhage, periventricular leukomalacia, hypoxic ischemic encephalopathy, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, and death • Am J Obstet Gynecol. 2013 Apr;208(4)
IUGR • RESULTS: • N=1116 fetuses • 312 (28%) were admitted to neonatal intensive care unit • 58 (5.2%) were affected by adverse perinatal outcome including 8 mortalities (0.7%) • The presence of abnormal umbilical Doppler was significantly associated with adverse outcome, irrespective of EFW or abdominal circumference measurement. • The only sonographic weight-related definition consistently associated with adverse outcome was EFW <3rd centile (P = .0131), all mortalities had EFW <3rd centile. • Presence of oligohydramnios was clinically important when combined with EFW <3rd centile (P = .0066). • Am J Obstet Gynecol. 2013 Apr;208(4)
IUGR • CONCLUSION: • Abnormal umbilical artery Doppler and EFW <3rd centile were strongly and most consistently associated with adverse perinatal outcome. • Stricter IUGR cutoffs may be warranted and future studies should comparing various definitions of IUGR and management strategies
IUGR • Management • Serial US q 2-4 weeks as indicated • Antenatal surveillance with umbilical artery Doppler velocimetry and antepartum testing (NST,BPP) • Delivery depends on the underlying etiology and estimated gestational age
IUGR • Eunice Kennedy Shriver National Institute of Child Health and Human Development/Society for Maternal-Fetal Medicine/American College of Obstetricians and Gynecologists Joint Conference • Dx fetal growth restriction: • Delivery at 38 0/7–39 6/7 weeks of gestation isolated fetal growth restriction • Delivery at 34 0/7–37 6/7 weeks of gestation in cases of fetal growth restriction with additional risk factors for adverse outcome (eg, oligohydramnios, abnormal umbilical artery Doppler velocimetry results, maternal risk factors, or co- morbidities)
IUGR • Delivery for fetal growth restriction before 34 weeks: • Planned at a center with a neonatal intensive care unit and consultation with a maternal–fetal specialist. • Antenatal corticosteroids should be administered • For cases in which delivery occurs before 32 weeks: • Magnesium sulfate should be considered for fetal and neonatal neuroprotection.
IUGR Neonatal Complications • Low Apgar scores/cord ph • Asphyxia • Meconium aspiration • Hypoglycemia • Hypocalcemia • Polycythemia • Thrombocytopenia • Hyperbilirubinemia • Hypothermia • Intraventricular hemorrhage • Necrotizing enterocolitis, • Less RDS (?)
IUGR • Way of characterizing the relationship of height to mass for an individual. • PI = 1000 x cubed root of Mass (kgs) • Height (cms) • Typical values are 20 to 25. • PI is normal in symmetric IUGR. • PI is low in asymmetric IUGR
IUGR • Heads are disproportionately large for their trunks and extremities • Facial appearance has been likened to that of a “wizened old man”. • Long nails. • Scaphoid abdomen
IUGR • Way of characterizing the relationship of height to mass for an individual. • PI = 1000 x cubed root of Mass (kgs) Height (cms) • Typical values are 20 to 25. • PI is normal in symmetric IUGR. • PI is low in asymmetric IUGR
IUGR • Long-term Sequale: • Up to 50% cognitive disability • Increased risk of cerebral palsy • <50% will have chronic growth lag • <10th percentile at 8 years • Early IUGR less likely to catch up
IUGR “ I AM A FETUS IN THE WOMB I FEAR IT MAY BECOME MY TOMB IF ONLY I COULD GIVE A SHOUT TO MAKE MY DOCTOR GET ME OUT!” UNKNOWN MEDICAL STUDENT DUBLIN, UK 1982
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