Intrauterine growth retardation (IUGR)

Intrauterine growth retardation and low birth weight baby- OBG

1. IUGR and care of Low birth weight baby Roll no 0954

2. Intrauterine growth restriction is said to be present in those babies whose birth weight is below the tenth percentile of the average for gestational age. Definition It can occur in preterm, term or post-term babies Disparity of >= 2 weeks- Mild IUGR Disparity of >=4 weeks- severe IUGR

3. Incidence Dysmaturity comprises about one-third of LBW babies. In developed countries, its overall incidence is about 3-10% Term babies- 5% Post-term babies-15%

4. Relationship between birthweight percentile and perinatal mortality and morbidity in small-for-gestational-age fetuses. A progressive increase in both mortality and morbidity is observed as birthweight percentile falls.

5. Nomenclature SGA and IUGR are too often used synonymously though there is a degree of overlap. SGA fetus is not necessarily growth retarded . Baby may be constitutionally small  not at increased risk. Late onset of pathological cessation of growth may produce a baby with typical features of IUGR  increased perinatal mortality and morbidity

6. Normal fetal growth cellular hyperplasia ( upto 16 weeks ) hyperplasia and hypertrophy ( 16 to 32 weeks ) hypertrophy ( after 32 weeks ) Most of fetal weight gain (2/3) occurs beyond 24 th week of pregnancy

7. T ypes Based on clinical evaluation and US examination- Fetuses those are small and healthy . Birth weight is less than 10 th percentile for gestational age They have normal ponderal index, normal subcutaneous fat and usually have uneventful neonatal course

8. (ii) Fetuses where growth is restricted by pathological process (true IUGR) Depending on relative size of their head, abdomen and femur, they are subdivided into Symmetrical or type I Asymmetrical or type II

9. Symmetrical (20%) Affected from noxious effect very early in the phase of cellular hyperplasia Total cell no is less Most often caused by structural or chromosomal abnormalities or congenital infection(TORCH) Pathological process is intrinsic to fetus and involves all organs including head

10. Asymmetrical (80%) Affected in later months during cellular hypertrophy Total cell no remains same but size is smaller Pathological process is often maternal disease extrinsic to fetus Diseases alter fetal size by reducing uteroplacental flow or by restricting oxygen and nutrient transfer or by reducing placental size. preferential shunting of oxygen and nutrients to the brain

11. Symmetrical Asymmetrical Uniformly small Head larger than abdomen Ponderal index (birth wt/Crown-heel length 3 ) normal Low HC: AC and FL:AC –normal Elevated Etiology: genetic disease or infection (Intrinsic to fetus) Chronic placental insufficiency (extrinsic to fetus) Total cell no- less Cell size- normal Normal Smaller Neonatal course- complicated with poor prognosis Usually uncomplicated having good prognosis

12. Etiology 1. Maternal Constitutional - Small women, maternal genetic and racial background Not at increased risk Pre-pregnancy weight less than 100 pounds- 2-fold risk Reduced intrauterine growth of the mother is a risk factor Maternal nutrition before and during pregnancy -Glucose, amino acids and oxygen are deficient during pregnancy Social Deprivation effects of associated lifestyle factors such as smoking, alcohol or other substance abuse, and poor nutrition.

13. Maternal diseases Anemia(sickle cell disease, hereditary anemias ), hypertension, thrombotic diseases, heart diseases, chronic renal disease, collagen vascular disease Toxins Alcohol, smoking, cocaine, heroin, drugs Antiphospholipid Antibody Syndrome - anticardiolipin antibodies and lupus anticoagulant -maternal platelet aggregation and placental thrombosis. Extrauterine Pregnancy

14. 2. Fetal Substrate not utilised by fetus Structural anomalies - cardiovascular, renal Chromosomal abnormality 8-12% growth retarded infants Triploidy , aneuploidy Trisomies ( 13, 18, 21), Turner’s syndrome Disorders of bone and cartilage - osteogenesis imperfecta , chondrodystrophies

15. 3 . Infection TORCH and malaria Cytomegalovirus : direct cytolysis and loss of functional cells. Rubella : vascular insufficiency by damaging the endothelium of small vessels. ,reduces cell division Hepatitis A and B, Listeriosis , tuberculosis, and syphilis Paradoxically, with syphilis, the placenta is almost always increased in weight and size due to edema and perivascular inflammation 4. Multiple pregnancy Mechanical hindrance to growth and excessive fetal demand 5. Chronic Hypoxia high altitude ,maternal cyanotic heart disease

16. 3. Placental Poor uterine blood flow to placental site for a long time This leads to chronic placental insufficiency with inadequate substrate transfer Placenta praevia , Abruption, circumvallate , infarction, mosaicism 4. Unknown - 40%

17. Pathophysiology Reduced availability of nutrients in mother Reduced transfer by placenta to fetus Reduced utilisation by fetus Brain size (asymmetric) as well as cell no (symmetric) are reduced Liver glycogen content is reduced Renal and pulmonary contribution to amniotic fluid are diminished due to reduced blood flow  Oligohydramnios Risk of intrauterine hypoxia and acidosis  death if severe

18. Accelerated Maturation accelerated fetal pulmonary maturation in complicated pregnancies associated with growth restriction fetus responds to a stressed environment by increasing adrenal glucocorticoid production, which leads to earlier or accelerated fetal lung maturation

19. Diagnosis Clinical Palpation of uterus Fundal height Liqour volume Fetal mass SFH Closely correlates with gestational age after 24 weeks Lag of 4 cm or more- IUGR Fairly sensitive (30-80%) Serial measurement is important Maternal weight gain- stationary or falling during second half of pregnancy Abdominal girth- stationary or falling

20. Investigations Hemoglobin Blood group- ABO, Rh Urine- sugar, albumin, microscopy, culture and sensitivity HIV, STS TSH HbSAg OGTT

21. Biophysical First examination(16-20 weeks) should confirm gestational age, anomalies USG - 2-3 weekly diagnosis of IUGR, type Head circumference/ Abdominal circumference ratios >1- before 32 weeks =1 - 32-34 weeks <1- after 34 weeks Elevated - asymmetrical IUGR Normal –asymmetrical IUGR 85% IUGR fetuses are detected AC -Single most sensitive parameter

22. Correlation of fetal weight estimation using abdominal circumference (AC) with actual birthwt

23. Serial measurements of AC and estimation of fetal weight are more diagnostic Femur length Not affected in asymmetric IUGR FL/AC =22 from 21 weeks to term FL/AC> 23.5- IUGR Amniotic fluid volume Vertical pocket of amniotic fluid <1 cm suggests IUGR Four quadrant technique –measuring vertical diameter of largest pockets of fluid found in each of 4 quadrants of uterus. The sum of results is AFI AFI 5 to 25 cm- normal AFI< 5 cm- oligohydramnios Anatomical survey: To exclude fetal abnormalities Bi-parietal diameter

24. Placental grading grade 0 :  < 18 weeks :  uniform echogenicity smooth chorionic plate grade I : 18 - 29 weeks :  occasional parenchymal calcification / hyper-echoic areas grade II : > 30 weeks :  occasional basal calcification  / hyper-echoic areas may also have comma type densities at the chorionic plate. grade III : > 39 weeks :  significant basal calcification  chorionic plate interrupted by indentations an early progression to a grade III placenta is sometimes associated with placental insufficiency

25. Ultrasound doppler parameters Doppler velocimetry Elevated uterine artery S/D ratio (>2.6) presence of diastolic notch Diastolic notch suggests incomplete invasion of placental trophoblasts to uterine spiral arteries Also predicts possible development of pre- eclampsia Normally, diastolic flow increases as pregnancy progresses. Reduced/ absent/ reversed diastolic flow in umbilical artery indicates fetal jeopardy and poor perinatal outcome

26. Normal flow velocity waveform from the uterine artery at 24 weeks of gestation. Flow velocity waveform from the uterine artery at 24 weeks of gestation in a pregnancy with impaired placentation ; in early diastole there is a notch (yellow arrow) and in late diastole there is decreased flow (orange arrow).

27. Umbilical arterial Doppler velocimetry studies, ranging from normal to markedly abnormal. A. Normal velocimetry pattern with an S/D ratio of <30. B. The diastolic velocity approaching zero reflects increased placental vascular resistance. C. During diastole, arterial flow is reversed (negative S/D ratio), which is an ominous sign that may precede fetal demise

28. Middle cerebral artery Increased diastolic velocity(brain sparing effect) in compromised fetus Cerebro -Placental Doppler ratio [ RI (mca)/ RI (umb. a.)] is decreased The normal ratio is > 1. PI Degree of fetal wasting judged (birth weight/Crown-heel length 3 ) <10 th percentile –IUGR Reduction of fetal facial fat stores- IUGR

29. Color doppler and spectral waveform of the middle cerebral artery shows increased diastolic flow in the brain suggesting a "fetal brain sparing" effect, whereby, the fetal cerebral vessels "open up", lowering the cerebral vascular resistance to increase flow to the brain thus diverting blood to the important organs in a state of overall hypoxia.

30. Doppler spectral waveform of the ductus venosus shows not just absent diastolic flow, but actual flow reversal during diastole. This is an ominous sign and suggest severe fetal compromise ( ie : hypoxia).

31. Biochemical markers Elevated levels of MSAFP and hCG level in second trimester are markers of abnormal placentation and risks of IUGR

32. Physical features at birth Weight deficit- 600 g below the minimum in percentile standard Length - unaffected Head circumference – relatively larger than body in asymmetric IUGR Alert, active, normal cry. Eyes- open Reflexes- normal

33. Dry and wrinkled skin because of less subcutaneous fat, scaphoid abdomen, thin meconium stained vernix caseosa and thin umbilical cord – “ old man look” Pinna - cartilaginous ridges. Plantar creases- well defined

34. Complications Fetal Antenatal- chronic fetal distress, fetal death, diminished amniotic fluid volume increases the likelihood of cord compression Intranatal –hypoxia, acidosis After birth- immediate -late

35. Immediate Asphyxia , bronchopulmonary dysplasia and RDS Hypoglycemia due to shortage of glycogen reserve in liver because of chronic hypoxia Meconium aspiration syndrome Microcoagulation leading to DIC Hypothermia Pulmonary haemorrhage Polycythaemia , anaemia , thrombocytopenia Hyperviscosity thrombosis Necrotising enterocolitis due to reduced intestinal blood flow IVH

36. Electrolyte abnormalities , hyperphosphataemia , hypokalemia due to impaired renal function Multiorgan failure Increased perinatal mortality and morbidity

37. Late Symmetrical growth retarded baby is likely to grow slowly after birth Asymmetrical - catch up growth in early infancy retarded neurologic and intellectual development in infancy Worst prognosis- congenital infection, congenital abnormalities, chromosomal defects 2. Increased risk- metabolic syndrome in adult life: obesity, hypertension, diabetes, coronary heart disease

38. 3. altered orexigenic mechanism that causes increased appetite and reduced satiety 4. Reduced no of nephrons - renal vascular hypertension

39. Maternal Per se IUGR does not cause any harm to mother Underlying disease process like pre- eclampsia , heart disease, malnutrition may be life threatening Risk of having another growth retarded infant is two fold Immediate neonatal mortality- 6 times more than normal newborn or even similar weight appropriate to shorter gestational age Most babies –die within 24 hours Morbidity rises to 50%

40. Management Constitutionally small- no intervention symmetric IUGR - investigated for anomalies, infections, genetic syndromes -No effective therapy Placental disease or reduced placental blood flow May be given some treatment

41. General No proven therapy for reversing IUGR once it has established Adequate bed rest specially in left lateral position Correct malnutrition by balanced diet- 300 extra calories per day Appropriate therapy for complicating factors likely to produce IUGR Avoidance of smoking, alcohol Maternal hyperoxygenation at the rate of 2.5 mL /min by nasal prong ,for short term prolongation of pregnancy Low dose aspirin (50 mg daily) in selected cases with history of thrombotic disease, hypertension, pre- eclampsia or IUGR

42. Antepartum evaluation Serial evaluations of fetal growth and assessment of well being should be done USG - intervals of 3-4 weeks for assessment of BPD, HC/AC, fetal weight and AFI Fetal well being- kick count, NST, biophysical profile, amniotic fluid volume and cordocentesis for blood gases Doppler ultrasound parameters

43. Time of delivery Factors to be considered: Presence of fetal abnormality Duration of pregnancy Degree of growth restriction Associated complicating factor Degree of fetal compromise Previous obstetric history Availability of NICU

44. Beyond 37 weeks Delivery should be done Before 37 weeks Uncomplicated mild IUGR: General treatment Placental function may improve pregnancy is allowed to continue till at least 37 weeks

45. (b) Severe degree of IUGR If lung maturation is achieved Presence of phosphatidyl glycerol and L:S ratio at least 2 from amniotic fluid study  termination Lung maturation not yet achieved problems- prematurity, growth restriction Preterm IUGR requires highest level of NICU Betamethasone therapy - <34 week Corticosteroid reduce risk of neonatal HMD and IVH

46. Methods of delivery Route and time decided considering: Severity of IUGR Maternal condition Any other obstetric complication Low rupture of membranes followed by oxytocin Beyond 34 weeks with favourable cervix and head is deep in pelvis PGE2 gel when cervix unfavourable Intrapartum monitoring by clinical , continuous electronic and scalp blood sampling is needed as risk of intrapartum asphyxia is high

47. Care during vaginal delivery Equipped institution where intensive intranatal monitoring (clinical and electronic) is possible and having facilities for NICU. precautions Caesarean section without a trial of labour - when risks of vaginal delivery are more( fetal acidemia , absent or reversed diastolic flow in umbilical artery or unfavourable cervix)

48. First stage Ensure adequate fetal oxygenation by giving oxygen to mother by mask Epidural analgesia is of choice Labour carefully monitored preferably with continuous EFM Second stage Birth should be gentle and slow to avoid rapid compression and decompression of head Episiotomy may be done to minimise head compression Tendency to delay is curtailed by low forceps Cord is to be clamped immediately at birth

49. Management protocol of IUGR To confirm IUGR and type To exclude cong malformation To treat specific cause if found Fetal surveillance Daily fetal movement count Cardiotocography , NST Biophysical profile Doppler US parameters, ductus venosus , umbilical vein Pregnancy >= 37 weeks Delivery Pregnancy <37 weeks Severe IUGR Mild IUGR

50. Mild IUGR Increased rest Folic acid Increased fliud intake General management Fetal monitoring till 37 weeks Delivery Dual problem Prematurity dysmaturity Equipped centre Centre with limited facilities In utero transfer to a referral centre Severe IUGR Fetal surveillance Reassuring fetal status Non-reassuring fetal status Doppler after 1 week

51. Assess lung maturity L:S ratio Phosphatidyl glycerol level Not mature Mature Betamethasone therapy Delivery Delivery Non-reassuring fetal status

52. Low birth weight WHO has defined LBW “as one whose birth weight is less than 2500 g (irrespective of gestational age” Very low birth weight - <=1500 g Extremely low birth weight- <=1000 g

53. LBW Preterm Birth occurs before completion of 37 weeks of gestation regardless of birth weight Growth potential is normal and appropriate for gestational period(10-90 th percentile) SGA Birth weight< 10 th percentile or <2 SD for gestational age May be constitutionally small(70%) or due to pathologic process(30%)

54. Incidence Highest in those countries where mean birth weight is low 5%-40% of live births India- 1/3 Factors- short gestational period, socio-economic status, nutritional and intrauterine environment, ethnic background, genetic control

55. Care of low birth weight baby IMMEDIATE MANAGEMENT FOLLOWING BIRTH - The cord is to be clamped quickly to prevent hypervolaemia and development of hyperbilirubinemia Cord length is kept long ( 10-12 cm) in case exchange transfusion is required

56. Air passage should be cleared of mucus promptly and gently using a mucus sucker Adequate oxygenation through mask or nasal catheter in concentration not exceeding 35% Baby should be wrapped including head in a sterile warm towel (36.5-37.5 ⁰C) Aqueous solution of vitamin K 1 mg is to be injected i.m . to prevent haemorrhagic manifestations

57. Hypothermia and sequelae : Hypoxia Hypoglycemia Anaerobic metabolism Metabolic acidosis

58. INTENSIVE CARE PROTOCOL Those requiring special care are judged by: Inability to suckle the breast and to swallow Incapacity to regulate temperature within limited range 96⁰-99⁰F (35.6⁰- 37.2⁰ C) Inability to control cardio-respiratory function without cyanotic attacks

59. Maintaining body temperature Delivery room dept warm, dry With mother- skin to skin contact Best placed in incubator where temperature and humidity(50%) can be better stabilised

60. Under radiant warmer with protective plastic covers. Baby is placed naked. If not possible to maintain for entire room, cot is kept warm( 30 ⁰C). Rubber hot water ( not boiling) bottles stoppered and well covered with clothings

61. Respiratory support To tide over initial cyanotic phase, air passage is cleared Placed in incubator with oxygen running / Baby’s head kept in oxygen head box for prolonged oxygen therapy Some may require endotracheal intubation and mechanical ventilation

62. Pulse oximeter - continuous O 2 monitoring (90-92%) Arterial blood gas values: PaO 2 55-65 mm Hg PaCO 2 35-45 mm Hg pH 7.35-7.45 Surfactant replacement therapy is indicated in HMD

63. Infection Respiratory tract, GIT, skin, umbilicus Poor defensive power of neonates with low WBC count and poor phagocytic activity make baby more vulnerable Prophylactic antibiotic therapy in premature rupture of membranes Every precaution to prevent infection Ampicillin 100 mg/kg per day or amikacin 10-15 mg/kg per day i.v . in 2 divided doses for 5-7 days

64. Nutrition Enteral feeding depending on gestation age and vigour May require gavage feeding/ parenteral nutrition Human milk is 1st choice Colostrum , foremilk, hindmilk and preterm milk help faster growth

65. Commencement 1/2-1 hours of birth Eliminates hypoglycaemia , lowers serum bilirubin and neurological sequelae Intervals- hourly in extreme prematurity to 3 hourly in birth after 36 weeks

66. Methods Start i.v . fluids if <1200 g (<30 weeks) gradually tube feeding after 1-3 days Spoon after 2-4 weeks 1200-1800 g(30-34 weeks) started with tube feeding and gradually spoon and breast feeding >1800 g (>34 weeks)- breast feed

67. Tube/ Gavage : Fine polythene tube 0.5 mm internal diameter Through nose down to oesophagus Expressed milk is started with small volume and gradually build up. Continued for about 7 days Calculated amount is injected with syringe by gravitation/pressure

68. Pipette, dropper, katori and spoon- where baby can swallow but fails to suck Bottle - when baby can suck and swallow but can’t manage to express milk from the breast I.v . fluids- neonates within incubator/radiant warmer Net reqt = 60-80 mL /kg/day of 10% dextrose water on 1 st day, increase by 15 mL /kg/day More amount(10%) if phototherapy used Monitoring by body weight, urine output, specific gravity and serum sodium

69. Position- when in cot, placed on one side with head raised a little to prevent regurgitation Nature of food- undiluted breast milk expressed from mother or pooled is ideal Diluted cow’s milk 1:1 for 1 st month and 2:1 during second month One tsp glucose added to 50 mL milk prepared for 1 st 10 days ,then reduced to 1 tsp to 100 mL Alternately, half cream powder milk with glucose in full strength

70. Calorie reqt More than mature counterpart because of greater loss of heat from body surface 60 cal/kg/d on 7 th day 100 cal/kg/d on 14 th day 120-150 cal/kg/d on 21 st day Food volume Amount of milk to be given is given slowly and progressively increased 1 st day- 80mL/kg Increased by 15 mL /kg /d to reach 200 mL /kg/d by 8-10 day Small stomach capacity, weak cardiac sphincter, poor cough reflex  small feeds at shorter intervals

71. Additional supplements Started after 2 weeks Vitamin A 2500 IU, vitamin D 400 IU,vitamin C 50 mg, folic acid 65 µg, vitamin B1 0.5 mg Iron - liquid preparation 2-4 mg/kg/d in 2 divided doses calcium , phosphate I.v . gamma globulin therapy(400 mg/kg/dose) to prevent infections <1200 g- parenteral nutrition with a.a , lipids with dextrose and multivitamins

72. Adequate nursing care 1 nurse-2 or 3 infants Temperature –twice daily Weight daily- over or underhydrated Constant supervision during 1 st 48 hours Mother should be allowed to her baby in the nursery Mother taught general care and manual expression of milk

73. Favourable signs of progress Colour of skin remains pink all the time Smooth and regular breathing Increasing vigour –movements of limb, cry Progressive gain in weight. Loss of 1-2% everyday for 5-7 days, gain 1-1.5% daily, regains birth wt by 10-14 days

74. Discharge When they attain sufficient weight Attain good vigour Able to suck the breast successfully Advice About feeding schedule Prescribe suitable multivitamin and oral iron preparation To attend child welfare clinic for subsequent check up, immunisation and guidance Supervision continued at home by public health nurses or health visitors if possible.