Fetal growth restriction

Fetal Growth restriction includes definition, various types , diagnosis and management

1. FETAL GROWTH RESTRICTION.. What the evidence says?! Dr. Kirtan Vyas M. S. (Ob/Gy) Assistant Professor, P.D.U. Medical College, Rajkot

2. Gujarat Uni. First-Gold medallist Gujarat Public Service Commission(GPSC) first Fellow in Gynec Endoscopy(Mumbai) Fellow in Ultrasonography(FOGSI) Publications in various International Journals Presented Scientific Papers and Chaired Sessions at State and National conferences Faculty at State and National Conferences Local Joint Secretary of SOGOG-Gujarat State Org of Ob Gy 2015 Organizing Secretary for the First Rajkot Obstetrics and Gynec Society Annual Conference 2015 and Committee Member at State and National conferences Organizing secretary for the West Zone Yuva Fogsi 2016, Rajkot Faculty at FOGSI-JOGI PICSEP Scientific Program 2016 at Rajkot Presently an Assistant Professor at P.D. U. Medical College, Rajkot Dr. Kirtan Vyas M.S.(Ob/Gy) Dr. Kirtan Vyas # 9825407702

3. The major concern in IUGR is not the small size of the fetus, but the possibility of life threatening fetal compromise Timely identification is difficult but crucial for proper management and a favorable neonatal outcome as it is the second leading cause of perinatal mortality after prematurity Dr. Kirtan Vyas # 9825407702

4. Baffles the researchers in the most controversial way Extensively studied, still confusing!! Dr. Kirtan Vyas # 9825407702

5. To compare and contrast the used terminology and definitions To evaluate screening approaches To critically review proposed management Surveillance regimens Recommendations for timing and mode of delivery Risk of Recurrence , preventative strategies Postnatal management Dr. Kirtan Vyas # 9825407702

6. DEFINITION IUGR : A condition where the fetus fails to achieve its genetic growth potential and consequently is at risk of increased perinatal morbidity & mortality SGA : Infant with weight < 10 th percentile of those born at the same gestational age or > 2 SDs below mean for Gestational Age Dr. Kirtan Vyas # 9825407702

7. Easiest way to think about these terms are IUGR : is a term used by Obstetrician to describe a pattern of growth over a period of time SGA : is a term used by Pediatrician to describe a single point on a growth curve Dr. Kirtan Vyas # 9825407702

8. V/S Preterm gestation and small Term gestation and small Healthy but small – Constitutionally small Pathologically small – IUGR Dr. Kirtan Vyas # 9825407702

9. Thus 2 essential components for IUGR are Birth weight <10 th percentile Pathologic process that inhibits normal growth potential (intrinsic) 30 % And the 2 essential components for SGA are Birth weight <10 th percentile Absence of pathologic process 70 % Dr. Kirtan Vyas # 9825407702

10. In 2013, 3 major obstetric colleges in the UK , Canada, and the USA have published their clinical recommendations for pregnancies with FGR RCOG February 2013 SGA ACOG May 2013 FGR SOGC August 2013 IUGR Dr. Kirtan Vyas # 9825407702

11. All guidelines use a different terminology All do agree that an EFW < 10th centile for gestation should be used to alert clinicians to small fetal size Dr. Kirtan Vyas # 9825407702

12. INCIDENCE 3 - 5% of all pregnancies 20 % of still borns are growth restricted 1/3 of infants with BW < 2750 gms are growth restricted and not premature Only 20-30% of growth restricted fetuses are small due to pathological restriction of growth Perinatal mortality is 8 - 10 times higher for these fetuses * Peleg D et al Dr. Kirtan Vyas # 9825407702

13. NORMAL INTRAUTERINE GROWTH PATTERN 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 Dr. Kirtan Vyas # 9825407702

14. NORMAL INTRAUTERINE GROWTH PATTERN 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 Dr. Kirtan Vyas # 9825407702

15. 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

16. MATERNAL PLACENTAL FETAL Chronic disease Cyanotic heart disease DM (class F or above) Chronic respiratory disease Chronic hypertension Chronic renal disease General Malnutrition Malabsorption syndrome High attitude Constitutionally small mother Substances abuse Smoking Alcohol Other disorders Severe anemia Hemoglobinopathies Antiphospholipid antibody syndrome Recurrent APH Abnormal placentation Abruptio Infarction Circumvallate Placenta Chorioangioma Placenta accreta Placenta previa Chromosomal Trisomy 13, Triploidy 21 Turner syndrome Structural abnormality Congenital Heart disease NTD Collagen and musculoskeletal. Fetal infection CMV Rubella Herpes Toxoplasmosis Teratogens Anti- convulsant Anticoagulant Alcohol Narcotic Multiple gestation (10 times more common) Dr. Kirtan Vyas # 9825407702

17. RELATIVE FREQUENCY OF DIFFERENT ETIOLOGIES Placental insufficiency -80% Tobacco /Smoking -5% Fetal Chromosomal -5% Fetal Infections -1-2% Dr. Kirtan Vyas 98254 07702

18. CLASSIFICATION Based on evaluation & USG examination small fetuses are divided into two categories Healthy SGA or True IUGR or C onstitutionally small Pathologically growth restricted TYPE –I TYPE –II Symmetrical IUGR Asymmetrical IUGR Intrinsic IUGR Extrinsic IUGR * Campbell S and Thomas A Dr. Kirtan Vyas # 9825407702

19. FETAL GROWTH - A COMPLEX PHENOMENON Besides these there occurs a delicate interplay between fetal adaptation to the maternal metabolism by modulating placental function This means that an adequate maternal nutritional status does not ensure adequate supply to the fetus, it requires a normal placental function also Dr. Kirtan Vyas 98254 07702

20. Comparison between PFGR and Normal SGA Pathological Growth Restriction Normal, Small for gestation Age Birth weight usaully <10% but may be <25% Birth weight <10% Birth weight usaully <2500gms but may be larger Birth weight <2500gms Low Ponderal Index Normal Ponderal Index Decreased subcutaneous fat Normal subcutaneous fat Elevated nucleated blood red cells & thrombocytopenia Normal nucleated blood red cells & thrombocytopenia Complicated neonatal period Uneventful neonatal period usually

21. FGR is a pathologic process associated with additional features abnormal placental morphology oligohydramnios or abnormal uteroplacental or fetoplacental doppler Dr. Kirtan Vyas # 9825407702

22. PRIOR H/O IUGR HAS 4FOLD INCREASE INCIDENCE Lagging fundal measurement of 3cms with the estimated gestational age Poor maternal weight gain of <5 kg by 24 wks or 8 kg by 32 wks (for women with BMI<30) EFW <10 percentile HC/ AC ratio>1 AFI ≤ 5 Grade 3 placenta before 34 wks Decrease DFMC Dr. Kirtan Vyas 98254 07702

23. COMPARISON BETWEEN PFGR AND NORMAL SGA PATHOLOGICAL GROWTH RESTRICTION NORMAL, SMALL FOR GESTATION AGE Birth weight usually <10% but may be <25% Birth weight usually <2500gms but may be larger Birth weight <10% Birth weight <2500gms Hypoglycemia, Hypocalcemia , Hyperbilirubinemia , Polycythemia - present Usually absent Low Ponderal Index Normal Ponderal Index Decreased subcutaneous fat Normal subcutaneous fat Elevated nucleated blood red cells & thrombocytopenia Normal nucleated blood red cells & thrombocytopenia Complicated neonatal period Uneventful neonatal period usually Dr. Kirtan Vyas # 9825407702

24. EFFECTS OF IUGR The study by Bernstein et al (2000) done on 20,000 neonates born IUGR without major anomaly described the following RR Dr. Kirtan Vyas # 9825407702 Death 2.77 RDS 1.19 IVH 1.13 Intravascular hemorrhage 1.27 NEC 1.27

25. LONG TERM MORBIDITIES Cerebral palsy (Goldenberg RL et al. 1998) Hypertension ( Hannsens M et al 1996), D y slipidemia ( Gogate S. 2001 ) Diabetes Melitus ( Mukhopadhyay S et al 2001 ) B reast cancer ( LeMarchand L et al 1998) P rostate cancer ( Ekbom A et al 1996 ) M ental health problems, academic impairment and poorer general health Dr. Kirtan Vyas # 9825407702

26. IUGR SCREENING Whom to screen ? Ideally Symphysis Fundal Height (SFH) performed regularly for all pregnancies SFH in cms = weeks of gestation High risk cases will need ultrasound for growth, liquor volume, umbilical artery Doppler and Biophysical Profile Umbilical Artery Doppler is the best test! Dr. Kirtan Vyas # 9825407702

27. There are FOUR TESTING MODALITIES which are helpful Daily fetal movement count (DFMC) Non-Stress Test (NST) Amniotic Fluid Index (AFI) Doppler of the Umbilical Artery Biophysical Profile (BPP) C ombination of tests are better than an isolated test Dr. Kirtan Vyas # 9825407702

28. DIAGNOSIS CLINICAL BIOPHYSICAL BIOCHEMICAL Ultrasonography MSAFP & hCG in 2 nd trimester Erythropoietin level in cord blood is high in IUGR Dr. Kirtan Vyas # 9825407702

29. DIAGNOSIS - CLINICALLY Maternal weight gain Stationary or falling during second half of pregnancy Palpation of uterus SFH-Normally increases by 1 cm per week between 14 and 32 wks - A lag in fundal height of 4 wks s/o moderate IUGR and over 6 wks s/o severe IUGR Abdominal girth – stationary or decreasing Liquor volume - less Dr. Kirtan Vyas # 9825407702

30. BIOCHEMICAL MARKERS IN IUGR ERYTHROPOIETIN (EPO) An elevated HCG and amniotic fluid EPO has been found which supports the concept of early damage of placenta sufficient to cause erythroblastic response ( Seppo Heinonen et al 1999 ) High levels of EPO were also found in hypoxic and growth restricted neonates ( Ostlund E at al 2000 ) PAPPA A positive co-relation of PAPPA with femur length and abdominal circumference in second trimester ( Leung TY et al 2006 ) Dr. Kirtan Vyas # 9825407702

31. SERIAL ULTRASOUND BIOMETRY AND DOPPLER STUDIES FORM THE MAINSTAY OF DIAGNOSIS The greater the risk of IUGR based on clinical findings, the greater is the positive predictive value of USG It must be borne in mind that each measurement has an error potential of about 1 week up to 20 weeks gestation, 2 weeks from 20-36 weeks and 3 weeks thereafter Dr. Kirtan Vyas # 9825407702

32. USG Abdominal circumference (AC) T he most sensitive indicator Sensitivity is 95% if it measures below 2.5 th percentile HC/AC ratio drops almost linearly from 1.2 to 1.0 between 20-36 weeks normally It is elevated in asymmetric IUGR and is normal in symmetric IUGR FL/AC ratio elevated to >2.4 in IUGR Dr. Kirtan Vyas # 9825407702

33. Remember that we shall not switch to color doppler directly when patient is referred for color doppler First go for biometry & precisely define type of growth retardation by plotting the finding in growth charts, assess fetus for malformation. Assess Amniotic fluid & biophysical activity & then switch on the color doppler Dr. Kirtan Vyas # 9825407702

34. IMPORTANCE OF COLOUR DOPPLER THE ACCURACY OF DOPPLER VELOCIMETRY IN CONJUNCTION WITH 2D ULTRASOUND AND COLOR FLOW MAPPING IS NOW REGARDED AS AN INDISPENSABLE COMPONENT OF A PREGNANCY SONOGRAM Dr. Kirtan Vyas # 9825407702

35. PERSPECTIVE OF COLOUR DOPPLER EXCLUDE FETAL ANOMALIES EVALUATE FETAL SIZE QUANTIFY LIQUOR AMNII ASSESS PLACENTA, CORD & CERVIX Dr. Kirtan Vyas # 9825407702

36. Quantitative analysis Doppler indices Dr. Kirtan Vyas # 9825407702

37. DOPPLER VESSELS TO BE STUDIED MATERNAL SIDE Uterine artery PLACENTAL SIDE Umbilical artery FETAL SIDE Arterial: MCA, renal and others Venous: ductus, hepatic, umbilical Fetal echocardiography Dr. Kirtan Vyas # 9825407702

38. UTERO PLACENTAL CIRCULATION Conversion of spiral artery into utero placental vessel Brosens et al Dr. Kirtan Vyas # 9825407702

39. UTERINE ARTERY Normal impedance to flow the uterine arteries in 1º trimester Normal impedance to flow the uterine arteries in early 2ºtrimester Normal impedance to flow the uterine arteries in late 2º and 3º trimester UTERO PLACENTAL CIRCULATION Dr. Kirtan Vyas # 9825407702

40. UTERINE ARTERY FACTS More accurate for screening in high risk- early onset cases At a place, where UtA crosses the EIA B/L notch or U/L notch on the side of placenta is significant Best GA is 22-24 weeks High negative predictive value Dr. Kirtan Vyas 98254 07702

41. Progressive rise in the end-diastolic velocity Decrease in the pulsatility index ADVANCING GESTATION UMBILICAL ARTERY

42. UMBILICAL ARTERY FLOW Whether at fetal end, placental end or in between – no difference S/D ratio : 2-3 in 2 nd & 3 rd trimester PI : 1.5 – 2.0 in 2 nd trimester1.0 – 1.5 in 3 rd trimester RI : decreases with gest. In late 2 nd and 3 rd it is around 0.5 Dr. Kirtan Vyas # 9825407702

43. UMBILICAL ARTERY FLOW- WHAT DOES IT TELL US ?? First sign of hypoxia & growth retardation Dr. Kirtan Vyas # 9825407702

44. NORMAL UMBILICAL ARTERY 1º trimester Absent Diastolic Flow early 2ºtrimester Low Diastolic Flow late 2º and 3º trimester Resistance further reduce, more diastolic flow

45. UMBILICAL ARTERY - ABNORMAL Umbilical arteries - normal Umbilical arteries - high pulsatility index Umbilical arteries - Absent end diastolic velocity - very high pulsatility index. - pulsation in the umbilical vein Umbilical arteries reversal of end diastolic Dr. Kirtan Vyas # 9825407702

46. UMBILICAL ARTERY & CTG Umbilical artery 90% more sensitive to CTG Interval between absence of end diastolic flow & onset of late deceleration was 3-12 days Bekedam DJ et al. Early Hum Dev 1990;24:79–89 High Resistance Dr. Kirtan Vyas # 9825407702

47. MIDDLE CEREBRAL ARTERIES Reflects : cerebral flow End points : rising PI after a nadir More than 1.45 before term Fall down to 1 If less than 1- peak of redistribution

48. MCA 22-28 weeks- no EDF in MCA 28w to term- some EDF seen- normal Increased EDF ( low PI) suggests ‘brain sparing’ redistribution in IUGR Worsening hypoxia- fetal acidemia - paradoxical rise in resistance (high PI) CPR increases – this is indicative of IUGR

49. MANNING’S BPP NST FBM FM FT AFI Maximum score 10 - Minimum 0 Oligohydramnios indicates abnormal BPP regardless of the total score of others

50. MANAGEMENT D epends on the severity of growth restriction and how early the problem began in pregnancy Earlier the onset, more severe is the IUGR and greater the risk to fetus Management is based on the following Prevention Diagnosis of IUGR Antenatal vigilance. Treatment of the cause, if found to be present. Delivery Neonatal management Dr. Kirtan Vyas # 9825407702

51. MATERNAL BED REST This is the initial approach for the treatment of IUGR Adequate bed rest in left lateral position results in increased blood flow to the uterus & placenta

52. ASPIRIN THERAPY The use of aspirin to treat foetus with IUGR is still controversial If aspirin is used , it may be advantageous if given to patients before 20 weeks of gestation It is minimal to limited benefit if given at the time of diagnosis (third trimester)

53. However it is beneficial in cases with history of thrombotic disease hypertension pre-eclampsia The Maternal- Fetal Medicine Network randomized 3135 women to receive 60mg/d aspirin or placebo and found no significant difference in incidence of IUGR Dr. Kirtan Vyas # 9825407702

54. HYPEROXYGENATION Fetal oxygenation is crucial for fetal growth A positive response to maternal oxygen therapy found by decreased resistance in placental circulation is marker of good prognosis and lack of response is an indication of poor outcome ( Bilardo et al 1991) Dr. Kirtan Vyas # 9825407702

55. OTHERS…. Other forms of treatment that have been studied are maternal hyperalimantation by aminoacids , nutritional supplementation, zinc supplementation , fish oil and hormones Maternal volume expansion may be helpful in improving placental perfusion Limited studies are available regarding the use of these modalities in the treatment of IUGR Dr. Kirtan Vyas # 9825407702

56. JUDGE OPTIMUM TIME OF DELIVERY Risk of PREMATURITY Difficult extra uterine existence Risk of IUD hostile intra uterine environment Dr. Kirtan Vyas # 9825407702

57. MANAGEMENT ACCORDING TO GESTATIONAL AGE Less than 24 weeks of gestational age Antenatal surveillance with Umbilical & D uctus venous doppler study is reliable ٠ If UmA diastolic flow + nt ٠ If UmA –RDF ٠ DV – Uninterrupted ٠ DV– Interrupted forward flow forward flow Fetal Acidosis& Hypoxia Expectant Management Imminent Fetal Death Termination

58. 26 to 34 weeks gestational age Antenatal surveillance with NST and Umbilical A, Middle cerebral A, Ductus venous doppler 1. NST-REACTIVE UmA Doppler-Reassuring Repeat in 1wk UmA Doppler-Non reassuring Ductus venous Doppler Reassuring--Repeat 1wk Non reassuring—Deliver Dr. Kirtan Vyas # 9825407702

59. 2. NST-NON REACTIVE UmA Doppler—follow as above Or Biophysical profile ≥8 UmA doppler ≤4 Deliver 6 Repeat in 6-24hrs wait till ≥36wks Deliver

60. 34 TO 37 WEEKS GESTATIONAL AGE Antenatal surveillance with FHR monitoring by NST AND COLOR DOPPLER VELOCIMERY. 1. Both the tests reassuring Repeat in 1 week Test for lung maturity Immature Mature Repeat in 1 wk Deliver 2.Either test non reassuring Deliver

61. MODE OF DELIVERY Labour is a stressful process for the fetus Every contraction reduces oxygenation, though briefly and it recovers Prolonged difficult labors should be avoided! Continuous fetal monitoring is a MUST! Elective LSCS for severe IUGR, abnormal presentation, oligohydramnios, abnormal CTG/ NST Dr. Kirtan Vyas # 9825407702

62. AMNIOINFUSION Amnioinfusion refers to the instillation of fluid into the amniotic cavity This procedure is typically performed during labor through an intrauterine pressure catheter introduced transcervically after rupture of the fetal membranes Alternatively , fluid can be infused through a needle transabdominally , the reverse process of amniocentesis Dr. Kirtan Vyas # 9825407702

63. Randomised trial of Amnioinfusion during labour with meconium stained amniotic fluid (BJOG Jan 2002) Conclusion- Amnioinfusion in an under resourced labour ward decreases caesarean section rates and fetal morbidity Dr. Kirtan Vyas # 9825407702

64. OUTCOME Symmetric vs. Asymmetric IUGR - symmetric has poor outcome compare to asymmetric Preterm IUGR has high incidence of abnormalities IUGR with chromosomal disease has 100% incidence of handicap Congenital infection has poor outcome - handicap rate > 50% IUGR has higher rate of learning disability Dr. Kirtan Vyas # 9825407702

65. CONCLUSION Currently USG measurements are used to confirm small fetal size, whereas, BPP is used to assess fetal function . Based on BPP one can consider the safety of continuing pregnancy. Unequivocal cessation of ultrasound growth would also constitute fetal grounds for delivery Risk of elective delivery after 37 weeks is very small, suspicion of fetal compromise from any abnormal fetal welfare study may precipitate decision for undertaking prompt delivery LSCS is used increasingly for the compromised fetus because of high risk of fetal distress in labour However, in the Indian setup, facilities for NICU are not uniformly available. Hence, the decision for time and mode of delivery needs to be individualized as the management of such a neonate is a real challenge. If possible, the mother should be transferred to a center with a well-equipped neonatal care unit to minimize the risks involved in transfer of the newborn baby Dr. Kirtan Vyas # 9825407702

66. 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

67. 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