6/14/2019 Disclosures • I have nothing to disclose Update on Fetal Growth Restriction Brian L. Shaffer, MD Associate Professor Maternal Fetal Medicine Doernbecher Fetal Therapy June 13, 2019 Disclosures Objectives: Update on Fetal Growth Restriction • Definition/Terminology • I have nothing to disclose – Prenatal vs. Neonatal • Outcomes associated with FGR • Diagnosis • Etiology • Work-up • Surveillance/Management • Treatment? 1
6/14/2019 Fetal growth restriction: Birthweight? FGR: Scope of the issue Birthweight: Sum of physiologic & pathologic processes Stillbirth: 1.5% 2.5% at <5 th % during gestation – growth potential +/- environment - Greatest risk (severe, early onset) - Absolute risk of SGA ↑ with decreasing GA Influences on Birthweight: Many! Morbidity: IVH, NEC, RDS, Asphyxia, Pulmonary HTN, - Maternal characteristics: Height & Weight, Parity, Geo Seizures, Hypoglycemia, Hyperbilirubinemia, Hypothermia ancestry, Social, Nutrition, etc. Neonatal Mortality - ↑ preterm, ↑<5 th , ↑↑<3 rd - Paternal genes, Conflict between maternal/paternal - Intrinsic fetal characteristics – Genetics, Fetal Sex Childhood: Neurodevelopment - ↓ Motor, Cognitive & Language performance - Others: Altitude, Air quality, Pollution Adult onset: HTN, ↑ Lipids, CAD, DM, Obesity - Medical (Maternal/Fetal/Placental) – Etiology SGA: Define in Neonates? SGA: Define in Neonates? Small for Gestational Age (SGA) - Neonatal Birthweight Small for Gestational Age (SGA) - Neonatal Birthweight Who is at risk for poor outcome? Who is at risk for poor outcome? - <10 th for GA (most common) - <10 th for GA (most common) - Importance of - Importance of Gestational age Gestational age - 2500gm NICU - 2500gm NICU - Controversy! - Controversy! Buene 2017 J Pediatrics Buene 2017 J Pediatrics 2
6/14/2019 FGR: Methods of Screening FGR: Screening Fundal Height: FH >3cm from GA – measuring 33 at 37 weeks FH Chart - Intergrowth-21 st - International cohort to determine norms for FH - Low risk, normal outcome pregnancies Limitations: multiples, obesity, fibroids US Papageorghiou AT BMJ 2016 FGR: Definition for Fetal Growth Restriction FGR: Geo Ancestry Prenatal US: <10 th centile – most common 5 th % (grams) US: Fetal biometry-EFW: HC, BPD, AC, FL, +/- HL White 2790 Number of different growth charts (e.g., Hadlock) Hispanic 2633 Rationale: Timely intervention to ↓ morbidity & mortality Black 2622 Screening Intervention (monitoring/IOL), Anxiety, $, F+ Asian 2621 Does not take into account: White curve - Any maternal biometric characteristics, maternal/paternal 15% - IUGR (<5th) BW, geographic ancestry, etc. - Any measure for constitutionally small vs. restricted growth potential Buck Louis. Am J Obstet Gyencol 2015 3
6/14/2019 FGR: Geo FGR: Rationale & Challenges of screening via US Ancestry Traditional screening: fail to identify ~80% Definition <10 th centile (US) - EFW 25 th % - “programmed” for 85 th % -- Miss - EFW ↓ from 68 th 17 th % from 28-32 weeks -- Miss - EFW 10 th – constitutionally 10 th – False Positive No clear evidence of benefit Buck Louis. Am J Obstet Gyencol 2015 Gardosi J 2011 Paediatr Perinat Epidemiol; Figueras F 2011 AJOG FGR: Rationale & Challenges of screening via US FGR: Challenges with parental screening via US Customized growth chart? Difficult? Maternal height, pre-pregnancy weight, parity, ethnicity, fetal sex Fetal growth potential Rationale: Distinguish FGR from Constitutional Improve detection? Lower unnecessary intervention? Very Promising No clear evidence of benefit Not recommended by ACOG/SMFM Gardosi J 2011 Paediatr Perinat Epidemiol; Figueras F 2011 AJOG Berkley E, et al. for SMFM AJOG 2012 4
6/14/2019 FGR: Importance of Centile/Fluid and Doppler FGR: Importance of Symmetry <10 th vs. <5 th vs. <3 rd (PORTO) Symmetrical: ~20-30% Prospective, n>1100, 5% FGR, ~25% went to NICU All biometry restricted Adverse Outcomes: IVH/PVL, NEC, HIE, BPD, Sepsis, Death (2.5%) - Potential global impairment early in gestation 3 rd -10 th % 2% adverse outcomes, no mortality Asymmetrical: ~70-80% <3 rd % 6% adverse outcomes, 1% mortality Response late in gestation to pathologic process Fetus <3 rd & Oligo 10% adverse outcomes favors vital organs – redistributed nutrients (brain/heart) <3 rd & Abnl UA 17% adverse outcome rather than abdominal (Liver, fat, kidneys) Abnl UA - ↑ PI, Absent EDF PORTO Unterscheider J 2015 AJOG FGR - Etiology Audience Poll 29 yo G2P1001 at initial prenatal visit. LMP c/w 8 weeks sono. Maternal Intrinsic Fetal Maternal Prior pregnancy with FGR and SGA at 37 weeks. Neonate spent 14 days in NICU. What is chance of recurrence? A. 2-5% if there are no modifiable risk factors 42% Environment 37% B. 10-12% and if so your child will have neurodev delays C. Can’t determine that until 20 weeks 12% ultrasound 7% 2% D. 18-20% if there are no modifiable risk factors Placenta E. 35-40% if normal maternal/paternal size & BW 5
6/14/2019 FGR - Etiology FGR - Etiology Placenta Intrinsic Fetal Genetic – Aneuploidy (T13 & T18), Single Aneuploidy gene, UPD, Syndromes (Russel-Silver) Confined placental mosaicism Infection – CMV, Toxo, HSV, Varicella, Placental mesenchymal dysplasia Malaria (worldwide), Rubella, Syphilis. Ischemic placental disease Structural malformation – gastroschisis, Infection – CMV, Malaria omphalocele, CDH, congenital cardiac Cord – Velamentous, Marginal, SUA malformation Structural –Bilobate, circumvallate, hemangioma (weak association) Morbidly adherent placenta/previa not associated with FGR FGR: Work-up & Management – 2 nd Trimester FGR - Etiology Maternal Diagnostic Medical – Numerous Maternal US +/- Echocardiogram cHTN, CRI, DM, Lupus, APA - Fetal Survey Structural malformation, Aneuploidy, Syndrome syndrome, Cardiac, Pulmonary, Anemia, Sickle cell, Uterine Amniocentesis, PUBs, Cord blood – CMA, Karyotype, Gene Malformation, Radiation - Early (20-24 wks), Severe (<5th), Symmetric Obstetric – Pre-e, Abruption, Multiples - Soft marker(s), Structural malformation (Cardiac, CDH) Substance – Tobacco, EtOH, drugs, Pollution Serum Screening: cf DNA (high suspicion for trisomy 18) Teratogen – Medications, Radiation Weight/Nutrition – Poor gain, Nutrition Infection: Maternal hx, US features Serum/Amniocentesi s Risk – ART, Interpregnancy interval, - CMV, toxoplasmosis, rubella, varicella, malaria, zika Altitude, Age, Biochemical markers - Titers, PCR amniotic fluid SGA not associated with thrombophilia 6
6/14/2019 FGR: Work-up & Management 3 rd trimester FGR: Management 3 rd trimester – FGR/Uteroplacental insufficiency Dopplers Ultrasound Umbilical Artery Assess for structural malformations Ductus Venosus Serial biometry q2-4 weeks Surveillance Umbilical Vein BPP &/or NST/AFI Middle Cerebral Artery Doppler – Umbilical artery, +/- Ductus Venosus Management: Admit/BMZ/More frequent surveillance Delivery timing APA: <34 (Placental insufficiency, Pre-eclampsia) Kennedy AM 2019 Radiographics Audience Poll FGR: Management 31 yo G1 at 37 weeks with FGR. EFW is <10% (7 th centile) Ultrasound-Doppler with normal UA S:D ratios/PI index, no structural Normal Umbilical Artery (S:D ratio, Pulsatility Index) malformations. AFI is 6cm with 2.1cm pocket, – low likelihood of adverse outcome (1-2%) Please choose optimal management 64% A. A: Continue weekly UA doppler and NST/AFI, 39 Features with greater rates of adverse outcome/death wk IOL UA: Absent EDF or reversal 25% B. B: IOL now - oligohydramnios DV waveform abnormalities C. C: Counsel regarding low risk of adverse 4% 4% 3% outcome, expectant management until 41 weeks MCA – Possible adjunct / Cerebro Placental Ratio – CPR D. D: NST/BPP – NPO for Cesarean if ≤8/10 PI MCA/PI UA E. E: Contraction stress test – CD if positive nonreactive 7
6/14/2019 FGR: Management FGR: Management Ultrasound-Doppler Features with greater rates of adverse outcome/death Normal Umbilical Artery (S:D ratio, Pulsatility Index) UA: Absent EDF or reversal DV waveform abnormalities – low likelihood of adverse outcome (1-2%) MCA – Possible adjunct / Cerebro Placental Ratio - CPR Features with greater rates of adverse outcome/death UA: Absent EDF or reversal DV waveform abnormalities MCA – Possible adjunct / Cerebro Placental Ratio - CPR Kennedy AM 2019 Radiographics FGR: Management FGR: Management Features with greater rates of adverse outcome/death Features with greater rates of adverse outcome/death UA: Absent EDF or reversal DV waveform abnormalities DV waveform abnormalities MCA – Possible adjunct / Cerebro Placental Ratio - CPR MCA – Possible adjunct / Cerebro Placental Ratio - CPR Kennedy AM 2019 Radiographics Kennedy AM 2019 Radiographics 8
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