Approach to Intrauterine growth restriction IUGR Neonatology monitoring of a growth-restricted fetus Fetal growth restriction FGR

1. Seminar on IUGR
Dr. Anurakkhi Barua
Resident, year 3, neonatology
Dr. Habibur Rahman Bhuiyan
Resident, year 4, neonatology

2. Presentation Outline
• Definition
• Epidemiology
• Classification
• Pathophysiology
• Diagnosis
• Complications
• Prognosis
• Prevention

3. • A fetus with IUGR is one that has failed to achieve its
genetically determined growth potential, owing to one or more
pathological factors .
• SGA: when its estimated fetal weight is below a specific
percentile for its gestation (10th percentile) for a given
population.
Definition
WHO

4. • SGA baby having a higher rate of adverse outcome than
average for gestational age babies.
• up to 70% of fetuses identified as SGA are
‘constitutionally small.
• IUGR fetus has at least a 10-fold increased risk of
perinatal mortality
SGA vs IUGR

5. Epidemiology
• IUGR is the commonest cause of stillbirth.
• the second leading cause of perinatal mortality, after preterm
birth.
• recent reports shows undiagnosed IUGR associated with 50%
of stillbirths in the UK.
• 30% of babies born before 35 weeks have IUGR
• 4.5% of babies born at term have IUGR
• SGA is 6 times higher in babies born preterm than term

6. • At least 10% of singleton pregnancies are SGA.
• SGA is 20% in dichorionic and 30% of monochorionic twins.
• IUGR occurs in 30–40% of pregnancies affected by pre-
eclampsia.
• In women who had a previous IUGR pregnancy the recurrence
rate is about 20%
• This is increased to approximately 50% in women with
previous early IUGR
Incidence

7. • Nationwide data is not available.
• At NICU, BSMMU 2021
• SGA 11.8%
• IUGR 9.54%
• Symmetrical IUGR 7%
• Asymmetrical IUGR 2.54%
Many IUGR cases remain undetected.
Incidence at Bangladesh perspective

8. Classification
According to symmetry of growth:
1. Symmetrical IUGR
2. Asymmetrical IUGR
According to onset:
1. Early onset (onset before 32 weeks)
2. Late onset (onset after 32 weeks)

9. Symmetrical IUGR
• Head circumference, length, and weight are all proportionally
reduced for gestational age (below 10th percentile).
• When insufficiency appearing early in pregnancy.
• Fetal weight is reduced out of proportion to length and head
circumference .
• Head sparing IUGR.
When insufficiency appearing late in pregnancy.
Asymmetrical IUGR

10. Normal Fetal Growth
• upto 16 weeks = Cellular hyperplasia
• 16 to 32 weeks= Hyperplasia &
hypertrophy
• After 32 weeks = Hypertrophy
• Two third of fetal weight gain occurs
beyond 24 th week of pregnancy

12. Fetal Risk Factors
• Chromosomal anomaly: triploidy, trisomies (21,18,13),
Turner syndrome etc
• Genetic abnormalities and syndromes
• Congenital anomalies
• Fetal infections: TORCHs, malaria, human
immunodeficiency virus, Epstein–Barr virus
• Multiple pregnancies: monochorionic gestation, twin-
to-twin transfusion

13. Maternal Risk Factors
• Past obstetric history: previous intrauterine growth restriction,
stillbirth, preterm birth
• Social/environmental/nutritional:
• extreme reproductive age
• short pregnancy interval
• poor diet
• anorexia nervosa
• body mass index <20
• high altitude
• active inflammatory bowel
disease
• Smoking, substance abuse
• self-neglect and/or psychiatric
illness
• medication (β-blockers,
overtreatment of hypertension)

14. Maternal Risk Factors (cont)
• Vasculopathy: chronic hypertension, pre-eclampsia,
sickle-cell disease, antiphospholipid syndrome, SLE
• Hypoxia: severe anaemia, chronic lung disease, severe
asthma, cyanotic heart disease, Reduced plasma volume
expansion
• Renal disease: glomerulonephritis, lupus nephritis,
chronic renal failure
• Thrombophilia

15. Placental Risk Factors
• Abnormalities of the umbilical cord: single umbilical
artery, velamentous insertion of the cord, overcoiled umbilical
cord
• Tumours: chorioangiomatosis, placental mesenchymal
dysplasia
• Vascular: vascular malformations, fetal thrombotic
vasculopathy, placental abruption
• Abnormal placental development: placenta praevia,
circumvallate placenta, abnormal trophoblast invasion,
recurrent bleeding, confined placental mosaicism

16. Other Risk Factors
• Uterine factors
• Uterine abnormality, uterine fibroids, assisted reproductive
techniques
• Endocrine factors
• Vascular endothelial growth factor, placental growth factor,
pregnancy-associated plasma protein A, insulin-like growth
factor

17. Insulin
• Anabolic hormone
• It controls the cell number because of direct mitogenic
effects.
• It leads to glucose uptake and consumption by body
tissues and decreases protein breakdown.
• Fetal insulin acts as a signal of nutrient availability for
growth and insulin deficiency will lead to IUGR.
• In insulin deficiency, IUGR results because of reduced
uptake and utilization of nutrients.

18. IGF-I
• It has mitogenic properties inducing somatic cell growth and
proliferation.
• It influences the transport of glucose and amino acids across
the placenta.
• IGF-I also has positive effect on brain growth,
1. increase in oligodendrocytes
2. neuronal number and neuronal outgrowth,
3. increases dendritic branching
4. increases axon terminal fields.

19. Thyroid hormone
Thyroid hormone triggers discrete developmental events in the
fetal brain and somatic tissues from early in gestation.
Fetal hypothyroxinaemia leads to developmental abnormalities
such as-
• decreased oxygen consumption and
• decreased oxidation of glucose
• leading to decreased fetal energy supply for growth.

20. Others
• Glucocorticoid hormone- development and maturation of
fetal organs.
• Insulin-like growth factor-II (IGF-II) -intrauterine
programming of adipose tissue
• Insulin-like growth factor binding protein-2 (IGFBP-2)
developmental Neurotropic and Regenerative Functions IN
CNS - binds (IGFs)
• Insulin-like growth factor binding protein-3 (IGFBP-3)
• vasoactive intestinal polypeptide (VIP) signaling is critical
for the modulation of appetite/satiety and body mass
phenotype

21. Stress
Primary adaptive response
Secondary adaptive response
Progressive decompensation
Death
Chronic respiratory and nutritional insufficiency
Decrease fetal growth rate
• Fetal energy conservation
Decreased fetal movement
Decreased fetal heart rate reactivity
• Circular redistribution
Falling cerebral flow impedance
Rising umbilical and aortic impedence
• Fetal growth preferred over placental growth
• Increased efficiency of placental exchange
• Polycythemia- Greater O2 carrying capacity
• Hypoxia → metabolic acidosis
• High impedance in fetoplacental circulation → absent end diastolic flow in umbilical arteries
• Declining amniotic fluid volume → Oligohydroamnios
• Loss of fetal movement
• Loss of fetal heart rate activity
• Further detoriation
Pathophysiology

22. Adapted from Sharma D, Farahbakhsh N, Shastri S, Sharma P. Intrauterine growth restriction–part 2.

23. Diagnosis of IUGR
1. Proper history taking
2. Establishing gestational age
3. Fetal assessment
A) Clinical diagnosis
B) Ultrasonography
-Estimated fetal weight
-Ratio of head and abdominal circumference
-Femur length
-Placental morphology and amniotic fluid
-Placental volume measurements
C) Biophysical profile
D) Doppler study

24. Clinical Diagnosis
Symphysio Fundal height (SFH)
Closely correlates with gestational age after 24 weeks
Lag of 4 cm or more –IUGR
Sensitivity 21-27%
Specificity 80-90%
Serial measurement is important.

25. Biophysical profile
8-10 Normal, 6 = equivocal, <4 abnormal - induction of labor

26. Biophysical profile score
• BPP <2 is 100% sensitive to
detect fetal acidemia
• However, BPP is less sensitive
to detect fetal detoriation
• Cardiotocography (CTG).
It is a component of BPP and
is limited when used alone.

27. USG of Pregnancy profile
• To assess for FGR, 4 biometric measures are commonly used:
1. abdominal circumference
2. biparietal diameter
3. head circumference
4. femur length
• The liver is the first organ suffers due to redistribution
of ductus venosus blood flow to the heart
• a decrease in glycogen deposition in the liver.
• Reduced abdominal circumference (<5 mm/wk) is the
earliest sign

28. • In the second trimester,
• the head circumference>abdominal circumference.
• 32 to 36 weeks =1:1
• after 36 weeks, the abdominal circumference ↑↑
• If the ration is <1 suggestive of IUGR.
• Femur length: Serial measurements of femur length are as
effective as head measurements for detecting early-onset FGR.
Ratio of head circumference to abdominal circumference

29. Placental morphology
• Placental morphology and amniotic fluid assessment
helps in differentiating a constitutional small fetus from
a growth-restricted fetus.
• Placental aging with oligohydramnios suggests FGR
• Placental volume measurements FGR with
decreased placental size is more likely to be associated
with fetal acidosis.

30. Doppler study
• used to detect, monitor, and optimize time of delivery
• Doppler studies are more helpful in diagnosing moderate to
severe FGR than mild FGR.
• The various groups of vessels used are as follows:
• Uterine artery Doppler
• Umbilical artery Doppler
• Middle cerebral artery Doppler
• Cerebro-placental ratio (CPR)
• Ductus venosus Doppler
• Aortic isthmus Doppler.

31. • Uterine arteries > maternal circulation
• Umbilical arteries > fetal circulation
• Middle cerebral arteries > fetal compensation
• Ductus venosus Doppler > reflects fetal cardiac status

32. Quantitive analysis:
• Pulsatility index (PI)
• Resistance Index (RI)
• Systolic/diastolic ratio (SD ratio)
Qualitative analysis
• Uterine artery: presence or absence
of early diastolic notch
• Umbilical artery(UA): normal with
reduced diastolic flow
• Absent End diastolic flow
• Reversed EDF

34. Pulsatility Index chart

35. • Uterine artery flow abnormalities
• Used to predict FGR as early as 12 to 14 weeks.
• A persistent abnormality at 23 to 24 weeks has an approximate
75% sensitivity in predicting early FGR.

36. Umbilical artery flow abnormalities
• Normally, the umbilical artery resistance declines with pregnancy.
• Increased pulsatility index (PI),
• decreased end-diastolic velocity (EDV)
• absent EDV (AEDV)
• reversed EDV (REDV)
• AEDV and REDV are associated with 20% to 68% mortality.
• Decreased EDV is seen when 30% of placental flow is attenuated
• AEDV/REDV is noted when 60% to 70% of placental flow is affected.
• AEDV and REDV are associated with a 4.0- and 10.6-fold increased
risk of mortality.

37. Fetal cerebaral arterial flow
• Usually studied in the MCA as a Pulsatility index and MCA peak
systolic velocity (MCA PSV).
• With worsening FGR, MCA PSV increases.
• decreased MCA resistance is associated with worse perinatal
outcomes.
• MCA Doppler changes better identify late-onset FGR

38. Cerebroplacental ratio
The CPR quantifies the redistribution of cardiac output by
dividing the Doppler PI of the MCA with that of the UA.
CPR = MCA PI/UA PI.
• Adverse outcomes = CPR ratio of <1 or <1.08.
• CPR can be affected in about 25% of term SGA fetuses.
A decrease in expected CPR measurement after 28 weeks
gestation is highly sensitive in diagnosing late onset FGR.

39. FREQUENCY OF MONITORING IN EARLY AND LATE FGR
BPP: biophysical profile; CPR, cerebroplacental ratio; CTG, cardiotocography; DV, ductus venosus; EDV, end-diastolic
flow; FGR, fetal growth restriction; FHR, fetal heart rate; MCA, middle cerebral artery; PI, pulsatility index;

40. Decreased amniotic fluid index
Increased uterine artery resistance with EDV
Decreased MCA resistance (brain sparing)
Absent UA EDV
Increased resistance in DV-reversed EDV in
UA
Reversed flow in DV and pulsatile flow in
Umbilical vein
Early Changes
(2-3 Weeks before
nonreactive FHR)
Initial changes
Late changes (6 days
before nonreactive FHR)
Very late changes (24
hours before changes in
BPP)
Sequential changes of doppler studies in decompensating
fetal growth restriction

43. Comparision between normal and abnormal
uterine artery Doppler velocimetry

52. International Archives of Integrated Medicine, 2019; 6(1): 118-127
In the present study, PIH was found to be the commonest
(50.9%) cause of IUGR. Abnormal Doppler Indices in Umbilical
and MCA correlated statistically with lower birth weight, higher
rates of caesarean delivery, oligohydramnios, lower Apgar
scores, perinatal death, and higher admissions to NICU.
AEDF/REDF was associated with highest perinatal loss, poor perinatal
outcome.

53. Ponderal index
• to diagnose impaired fetal growth
• to identify soft tissue mass is
below normal for skeletal
development.
• The higher the score, the higher
the level of body fat.
• Normal range: 2.2 to 3.0 g/cm3
.
• A ponderal index of <2 or <10%
is suggestive of asymmetrical FGR

54. Placental magnetic resonance
imaging
• severity of FGR can be assessed by
placental thickness-to volume ratio.
• Fetal demise can also be predicted
by a
• abnormal vasodilatation
• mesenteric vasoconstriction
• preferential shunting through the
foramen ovale etc

55. stages condition findings Intervention
Stage I mild placental
insufficiency
Abnormal
Doppler studies
Carefull monitoring
Stage II severe uteroplacental
insufficiency
There is absent
EDV in the UA
after 34 weeks
Stage III fetal deterioration, low
suspicion of fetal
acidosis
Risks of stillbirth
reversal of EDV in
the UA or DV PI
>95th percentile
around 32 weeks
Stage IV fetal acidosis
reversal of atrial flow on
DV
Imminent risk of
fetal demise
Deliver immediately
Timing of delivery

56. • Early Antenatal diagnosis
• Early admission of mother
• Mode of delivery
• Antenatal Corticosteroid
• Delivery and Resuscitation
• Prevention of heat loss
• Prevention of hypoglycemia
• Feeding protocol
• Infection control
• Management of complications
Management

57. Neonatal Assesment
Anthropometry
• Reduced birth weight for
gestational age.
• Appropriate growth charts
should be used.
• Ponderal index˂ 10th
percentile.
• Ballard scoring

58. • Heads are dis proportionately
large for their trunks and
extremities
• Facial appearance has been
likened to that of a “wizened
old man”.
• Thin loose, peeling skin
• Long nails.
• Scaphoid abdomen
Physical appearance

59. Gestation < 35 weeks
Gestation ≤ 29 weeks
If tolerating well
Start MEN * after 24 hours
if no contraindication
@10ml/kg/day
Birth weight ≥1250g
Birth weight <1250g
increase feeds @10-
20 ml/kg/day
increase feeds
@ 20-30 ml/kg/day
Start MEN on day 1 if no
contraindication
@10-20 ml/kg/day
Gestation ≥ 29 weeks
Continue MEN for 48
hours then increase feeds
@10ml/kg/day
Add fortification once baby tolerates 100ml/kg/day of feeds and increase
feeds till 150-180ml/kg/day AIIMS protocol 2019
Feeding algorithm
for absent or
reverse end
diastolic flow
*MEN minimal entral neutrition

60. • Dysmorphic facies
• Congenital anomalies
• Features of infection
• Microcephaly
• Petechiae
• cardiac defect
• Hepatosplenomegaly
• intracranial calcification
• Chorioretinitis
• Cataracts).
Physical appearance cont

61. Nine parameters (hair, cheeks, neck
and chin, arms, legs, back, buttocks,
chest, and abdomen)
The maximum score is 36
Each category ranges 1-4 marks
<25 is considered to be malnourished.
Clinical Assessment of Nutrition Score (CAN Score):

62. It is the ratio of the
head circumference
(HC) to body weight
• higher cephalization
index reflects greater
degree of brain
vulnerability and
• increased risk of
cerebral palsy and
severe psychomotor
retardation.
Cephalization Index

63. 1. Intrapartum:
• Fetal death
• Acute-on-chronic hypoxia
• Metabolic acidosis
• Meconium aspiration
Consequences of intrauterine growth restriction

64. 2. Neonatal:
• Hypoxic–ischaemic
encephalopathy
• Seizures
• Respiratory distress syndrome
• Hypotension
• Heart failure
• Pulmonary haemorrhage
• Pulmonary hypertension
• Renal failure
• Hypoglycaemia/Hyperglycaemia
• Hypothermia
• Polycythaemia
•Hyperviscosity
•Renal vein thrombosis
•Thrombocytopenia
•Hyperbilirubinaemia
•Feeding intolerance
•Necrotising enterocolitis
•Coagulopathy
•Infection
•Congenital abnormality
•Adrenal insufficiency
•Retinopathy of prematurity
•Neonatal death
Consequences of IUGR

66. 66
Long term:
Bronchopulmonary dysplasia
Cognitive delay
Cerebral palsy dysplasia
Consequences of intrauterine growth restriction cont

67. They found that, despite a median difference of 3 weeks in
gestational age at birth between IUGR and AGA infants, neonatal
mortality was 35% higher in neonates who had experienced fetal
growth restriction, and that IUGR was five times more predictive
of CLD than was AGA.
Neonatology 2014;106:304–310

68. 68
Adulthood:
Diabetes
Obesity
Hypertension
Dyslipidaemia
Cardiac disease
Stroke
Bronchitis
Early menopause
Consequences of IUGR

71. Thrifty Phenotype (Barker Hypothesis)
• This metabolic programming (epigenetic modification ie,
those molecular mechanisms affecting gene expression
patterns without causing alterations in DNA base sequence)
occurs at the critical time window of fetal development
• These epigenetic changes become permanent or
“programmed” in the genes of the fetus.

72. Antenatal epigenetic changes
•Postnatal mismatched (normal or excessive nutrition)
•Suboptimal environment (sedentary life, less physical activity,
and sedentary life habits)
•Child’s genetics
Developmental origin of health and diseases (DoHaD)

73. Prognosis
• Mortality decreases by 48% for each week that the fetus
remains in utero before 30 weeks’ gestation
• At 24 to 26 weeks gestation, survival is around 50%
• survival improves to >90% by 32 weeks.
• The total brain volume is also reduced by 10% particularly in
the hippocampal, parietal, and parietooccipital areas.
• Infants with congenital rubella or cytomegalovirus infection with
microcephaly have a poor outcome, with a disability rate >50%.
• increased prevalence of elevated fasting glucose and metabolic
syndrome in childhood and adolescence.

74. • Neurodevelopmental morbidities are 5 to 10 times more often
in FGR
• minimal brain dysfunction, including hyperactivity, short
attention span, and learning problems.
• shows early neurobehavioral functions, such as attention-
interaction capacity and cognitive and memory dysfunction.
• Increased risk of cerebral palsy, learning disabilities, mental
retardation, and neuropsychiatric disorders.
• Growth may be hampered, growth hormone therapy (started
before 8 years of age and continued for >7 years) can augment
growth parameters.

75. A higher incidence of almost 50% in poorer neurodevelopmental
scores during early childhood ages (from 15 to 24 months)
among infants born after a pregnancy complicated by IUGR.
results showed that the developmental outcome for children with
IUGR was not influenced by birth weight, GA, gender, or type of
IUGR, suggesting that IUGR is an independent variable for poor
neurodevelopmental outcome.
2018

76. Prevention of IUGR
• Prepregnancy counselling and proper health education
• Balanced protein energy and micronutrients supplementation
with healthy life style.
• Ensure planned pregnancy at right age
• Ensure regular antenatal check up
• Treating chronic disease and pregnancy-induced disorders
accordingly
• Development a strong surveillance system with skilled
manpower at all level

77. Key Messages
• IUGR is a major concern in worldwide.
• Proper history, antenatal, natal and postnatal assessment in
necessary for diagnosis.
• Better to follow up with Doppler study and ensure proper
mode and timing of delivery
• Early diagnosis and prompt management may reduce
complication and unexpected consequences
• These infants need to be monitored for long time with
appropriate intervention.

78. Thank You