Severe early onset IUGR Dorothy Ting Nepean Hospital

JE-Antenatal history 22yo primip BMI 31 Regional centre, EDD 2/5/15 A positive, serology NAD Cholecystectomy 12/40 PMHx: depression, PCOS, tramadol use FHx: deletion on chromosome 20p3 (nephew+sister) Non smoker

JE-Antenatal history Low risk NT 20+4 US symmetrically small = 18/40. Normal FAS +amniotic fluid 21+2 Amniocentesis. Normal results 24+4 US EFW 383g = 20.5/40. Dilatation of right heart and fluid within bowel. REDF. Normal AFI. Self-referred to Nepean

JE-Antenatal history: first visit 25+5 EFW 383g REDF. Normal anatomy 25+5 NICU meeting: steroids, ASA, clexane Investigation: PET, thrombophilia, TORCH, HbA1c, FGTT, TFT-NAD 28+6 EFW 444g AFI 4.9 REDF, normal MCA+DV 29+4 EFW 472g AFI 7.7 AEDF, normal MCA+DV. Reduced FM on US. 29+4 NICU meeting: surveillance and daily CTG 29+6 NICU meeting: US MWF, daily CTG, CS 31-32/40. Repeat PET Ix

JE-Antenatal US

JE-Antenatal history 30+4: EFW 494g AFI 11.8 AEDF, normal MCA and DV 30+6 and 31+0: Rescue steroids 31+1: Admission 31+2: MgSO4 loading

JE-Delivery 31+2: LSCS of LFI, respiratory effort notes Birthweight 630g Apgar 6 at 1min, 8 at 5min IPPV and suction Venous gas: pH 7.32, lactate 3 Arterial gas: pH 7.21, lactate 2.9 Pt discharge day 2 post op

JE-Placenta Weight 149g (3rd-5th centile) Cord 5-8mm diameter Variable appearance of villi- oedematous stroma, syncytial knotting Avascular sclerotic villi Suggestive of fetal thrombotic vasculopathy MCS no significant growth Sent for FISH: Mosaic Monosomy X (36%), probe for chromosome 16 not available

Challenging dilemma Extreme prematurity at diagnosis Early onset, severe IUGR Aetiology of IUGR Risks in utero vs perinatal Timing of delivery Surveillance

Severe early onset IUGR 0.4% of pregnancies Varying outcomes EFW <501g, GA< 30/40 and AREDF: FDIU 53%, overall survival 14%, good intact survival TRUFFLE EFW<550g Placental dysfunction is amenable to intervention Delivery 2% median survival gained per day between 24-27/40 GA 29+2 best predictor for intact survival Multinodal foetal surveillance

Foetal surveillance Baschat AA. Arterial and venous Doppler in the diagnosis and management of early onset fetal growth restriction. Early Human Development 2005: 81: 877-887

Foetal surveillance and delivery Perinatal mortality is 5.5x higher if both FH and DV PI affected (SB 1/52 after) Monitoring: raised UA 2/52, brain sparing 1/52, AEDV 2x/52, 2-3x/7 raised DV PI Thresholds for delivery for 27/40 and EFW<500g vs 27-37/40 (DV, bPP, FHR) Steroids

Confined placental mosaicism At least two cell lines with different chromosomal complements Only placenta affected Occurs 1-2% viable pregnancies studied by CVS (50% confirmed in placenta) Mostly autosomal trisomy

Pathogenesis Kalousek DK and Vekemans M. 1996. Confined Placental mosaicism. J Med Genet 33:529-533

Outcomes Conflicting Likely depends on genomic imprinting, number of placental cells, specific chromosome Association with idiopathic IUGR 35% of CPM if high aneuploidy 20% of idiopathic IUGR have CPM Prenatal loss-MC, FDIU, perinatal (22%) Long term studies: short stature

Specific CPM Monosomy X: normal phenotype, (45X/46XX/46Xi(Xq), 45X/46XY, 45X/47XYY) Trisomy 16: severe IUGR, pre-eclampsia, fetal anomalies Other chromosome associated with IUGR 2, 3, 7, 8, 12, 13, 15, 18, 22 Monosomy X: first case was CVS diagnosis with female XX 3600g, second TOP with foetal cells 46XY, third TOP with foetal cells 47XYY