• Chairperson Elect ICOG –Indian College of OB/GY
• National Corresponding Editor-Journal of OB/GY of India JOGI
• National Corresponding Secretary Association of Medical Women, India
• Founder Patron & President –ISOPARB Vidarbha Chapter
• Chairperson-IMS Education Committee 2021-23
• President-Association of Medical Women, Nagpur AMWN 2021-24
• Nagpur Ratan Award @ hands of Union Minister Shri Nitinji Gadkari
• Received Bharat excellence Award for women’s health
• Received Mehroo Dara Hansotia Best Committee Award for her work as
Chairperson HIV/AIDS Committee, FOGSI 2007-2009
• Received appreciation letter from Maharashtra Government for her work in the
field of SAVE THE GIRL CHILD
• Senior Vice President FOGSI 2012
• President Menopause Society, Nagpur 2016-18
• President Nagpur OB/GY Society 2005-06
• Delivered 11 orations and 450 guest lectures
• Publications-Thirty National & Eleven International
• Sensitized 2 lakh boys and girls on adolescent health issues
Dr. Laxmi Shrikhande
MBBS; MD(OB/GY);
FICOG; FICMU; FICMCH
Medical Director-
Shrikhande Fertility Clinic
Nagpur, Maharashtra

OVERVIEW OF IUGR

What do we mean by FGR ?
 Fetal growth restriction (FGR, also called IUGR) is the term used to
describe a fetus that has not reached its growth potential because of
environmental factors.
 The origin of the problem may be fetal, placental, or maternal, with
significant overlap among these entities.

Definition
The most common obstetric definition of FGR is based on
sonography: an estimated fetal weight below the 10th percentile for
gestational age; however, other definitions using a variety of criteria
have been proposed.
Society for Maternal-Fetal Medicine (SMFM). Electronic address: pubs@smfm.org, Martins JG, Biggio
JR, Abuhamad A. Society for Maternal-Fetal Medicine Consult Series #52: Diagnosis and
management of fetal growth restriction: (Replaces Clinical Guideline Number 3, April 2012). Am J
Obstet Gynecol 2020; 223:B2.

FGR: Screening and diagnosis-What's new ?
 Fetal abdominal circumference <10th percentile for diagnosis of
growth restriction (March 2021)
 Updated guidance from the Society for Maternal-Fetal Medicine and
the American College of Obstetricians and Gynecologists now
considers abdominal circumference <10th percentile for gestational
age another acceptable threshold for suspecting FGR .
 Note that the lower the percentile, the more likely the diagnosis of
FGR rather than a constitutionally small fetus.
American College of Obstetricians and Gynecologists Committee on Practice Bulletins—Obstetrics,
Society for Maternal-Fetal Medicine Publications Committee. Fetal Growth Restriction: ACOG
Practice Bulletin, Number 227. Obstet Gynecol 2021; 137:e16.

Limitations
 The use of a percentile to define FGR is problematic because it does
not distinguish among fetuses who are constitutionally small versus
SGA.
 As many as 70 percent of fetuses estimated to weigh below the
10th percentile for gestational age are small simply due to
constitutional factors (eg, maternal ethnicity, parity, or body mass
index) and are not at high risk of perinatal mortality and morbidity .
 There is a real possibility of misclassifying these normally nourished,
healthy, but constitutionally small, fetuses as growth restricted.
Manning FA. Intrauterine growth retardation. In: Fetal Medicine: Principal an
d Practice, Appleton & Lange, Norwalk, CT 1995. p.317.

Limitations
 An additional problem is that use of percentiles requires an
appropriate reference, but there is little consensus on which
reference should be used.
 Ultrasound-based standards avoid this bias but are limited by the
inaccuracy and imprecision of ultrasound-EFW.
Zhang J, Merialdi M, Platt LD, Kramer MS. Defining normal and abnormal fetal growth:
promises and challenges. Am J Obstet Gynecol 2010; 202:522.
Ananth CV, Brandt JS, Vintzileos AM. Standard vs population reference curves in obstetrics:
which one should we use? Am J Obstet Gynecol 2019; 220:293.

Classification
Regardless of the FGR definition used, FGR may be classified as early or
late and as symmetric or asymmetric:
 Early FGR refers to diagnosis before 32 weeks of gestation, in the
absence of congenital anomalies.
 Late FGR refers to diagnosis at ≥32 weeks of gestation, in the absence
of congenital anomalies.

Classification
 Symmetric FGR comprises 20 to 30 percent of FGR and refers to a growth pattern
in which all fetal organs are decreased proportionally due to global impairment of
cellular hyperplasia early in gestation.
 Symmetric FGR is thought to result from a pathologic process manifesting early in
gestation.
 Asymmetric FGR comprises the remaining 70 to 80 percent of the FGR population
and is characterized by a relatively greater decrease in abdominal size (eg, liver
volume and subcutaneous fat tissue) than in head circumference.
 Asymmetric fetal growth is thought to result from the capacity of the fetus to
adapt to a pathologic environment late in gestation by redistributing blood flow
in favor of vital organs (eg, brain, heart, placenta) at the expense of nonvital fetal
organs (eg, abdominal viscera, lungs, skin, kidneys) .
 Undoubtedly, some overlap exists between these two entities.
Uerpairojkit B, Chan L, Reece AE, et al. Cerebellar Doppler velocimetry in the appropriate- and small-for-gestational-age fetus. Obstet Gynecol
1996; 87:989.
Bahado-Singh RO, Kovanci E, Jeffres A, et al. The Doppler cerebroplacental ratio and perinatal outcome in intrauterine growth restriction. Am J
Obstet Gynecol 1999; 180:750.

Screening
 Rationale — Ideally, prenatal detection of FGR will provide an opportunity
to employ interventions to reduce the morbidity and mortality associated
with this problem.
 Adverse outcomes include fetal demise, preterm birth, perinatal asphyxia,
poor thermoregulation, hypoglycemia, polycythemia/hyperviscosity,
impaired immune function, neonatal death, neurodevelopmental delay,
and some adult-onset disorders.
 the ability of screening and appropriate intervention to reduce the
frequency of any of these outcomes has not been proven.
 Harms of screening include overdiagnosis of FGR, leading to parental
anxiety and unnecessary, costly, and/or potentially harmful interventions
(eg, antenatal fetal testing, induction of labor, iatrogenic preterm delivery).

How to screen ?

Symphysis-fundal height measurement with
selective ultrasonography —
 The first suspicion of FGR often arises when this length is noted to be
discordant with the expected size for dates.
 Discordancy has been defined in various ways; the most common criterion
is a fundal height in centimeters that is at least 3 centimeters less than the
gestational age in weeks (eg, fundal height 32 cm at 36 weeks of gestation)
 Alternatively, a fundal height measurement below the 3rd or
10th percentile for gestational age can be used: The INTERGROWTH-
21st Project International published printable symphysis-fundal height
measurement standards for the 3rd, 10th, 50th, 90th, and 97th percentiles
using eight urban populations of healthy, well-nourished women.
Papageorghiou AT, Ohuma EO, Gravett MG, et al. International standards for symphysis-fundal height based on
serial measurements from the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project:
prospective cohort study in eight countries. BMJ 2016; 355:i5662.

Symphysis-fundal height measurement with
selective ultrasonography —
 The performance of fundal height measurements for screening for FGR is
controversial.
 A systematic review concluded evidence was inadequate (one randomized
trial) to evaluate the effectiveness of this technique versus abdominal
palpation for detecting abnormal fetal growth .
 Robert Peter J, Ho JJ, Valliapan J, Sivasangari S. Symphysial fundal height (SFH) measurement in pregnancy
for detecting abnormal fetal growth. Cochrane Database Syst Rev 2015; :CD008136.
 Observational studies using symphysis pubis-fundal height measurements
have reported a wide range of sensitivities: 13 to 86 percent of small
fetuses were detected . Factors that may affect sensitivity include maternal
body mass index, bladder volume, parity, and ethnic group.
Goetzinger KR, Tuuli MG, Odibo AO, et al. Screening for fetal growth disorders by
clinical exam in the era of obesity. J Perinatol 2013; 33:352.

Symphysis-fundal height measurement with
selective ultrasonography —
• This technique appears to perform best when all of the
measurements are obtained by the same clinician using the
unmarked side of the tape (to reduce bias ) and plotted to reflect fetal
growth for the individual patient ("customized"), rather than against a
standardized norm .
Roex A, Nikpoor P, van Eerd E, et al. Serial plotting on customised fundal height charts results in doubling of
the antenatal detection of small for gestational age fetuses in nulliparous women. Aust N Z J Obstet
Gynaecol 2012; 52:78.

Universal ultrasonography
 Routine universal performance of ultrasound examination is an
alternative method of screening for FGR.
 There is no consensus on the timing or number of screening
examinations.
Deter RL, Lee W, Yeo L, et al. Individualized growth assessment: conceptual framework and
practical implementation for the evaluation of fetal growth and neonatal growth outcome. Am J
Obstet Gynecol 2018; 218:S656.

Universal ultrasonography
 In general, if two screening examinations are performed after the 18-
to 22-week fetal anatomic survey, they are obtained at approximately
32 and 36 weeks of gestation .
 If one examination is obtained, it is obtained between 32 and 36
weeks of gestation, and the predictive performance is higher nearer
to 36 weeks .
Bricker L, Medley N, Pratt JJ. Routine ultrasound in late pregnancy (after 24 weeks' gestation). Cochrane Database Syst Rev
2015; :CD001451.
Ciobanu A, Khan N, Syngelaki A, et al. Routine ultrasound at 32 vs 36 weeks' gestation: prediction of small-for-gestational-
age neonates. Ultrasound Obstet Gynecol 2019; 53:761.

Approach to screening for fetal growth restriction in
singleton pregnancies in the third trimester

Evidence — Universal ultrasonography
 In a 2019 meta-analysis of 21 cohort studies of screening ultrasound at ≥32
weeks of gestation in low-risk or non selected singleton pregnancies,
Modeled sensitivities of AC and EFW <10th percentile at a 10 percent false-
positive rate were 78 and 54 percent, respectively.
 In a meta-analysis of 13 controlled trials including nearly 35,000 women,
perinatal mortality was similar for patients undergoing routine versus
no/concealed/selective ultrasonography (risk ratio 1.01, 95% CI 0.67-1.54);
none of the trials reported on neurodevelopmental outcomes at age 2 .
 A subsequent prospective study reported sensitivity for detection of small
for gestational age infants was higher with universal than with selective
ultrasound screening, but this did not lead to a significant reduction in
composite severe adverse perinatal outcome .
Caradeux J, Martinez-Portilla RJ, Peguero A, et al. Diagnostic performance of third-trimester ultrasound for the prediction of late-onset fetal
growth restriction: a systematic review and meta-analysis. Am J Obstet Gynecol 2019; 220:449.
Sovio U, White IR, Dacey A, et al. Screening for fetal growth restriction with universal third trimester ultrasonography in nulliparous women in
the Pregnancy Outcome Prediction (POP) study: a prospective cohort study. Lancet 2015; 386:2089.

Special populations- sub optimally dated
pregnancies
 When the gestational age is not known with reasonable certainty, a
single ultrasound examination may not be able to distinguish a small
for gestational age fetus from an appropriately grown fetus that is less
far along in gestation than expected from menstrual dates.
 Serial sonographic examinations at two-week intervals can be useful
when pregnancy dating is suboptimal.
Deter RL, Lee W, Kingdom JCP, Romero R. Fetal growth pathology score: a novel ultrasound
parameter for individualized assessment of third trimester growth abnormalities. J Matern
Fetal Neonatal Med 2018; 31:866.

Special populations- Multiple gestation
 Growth in multiple gestations diverges from that in singletons in the
late second or early third trimester.
 Smallness of one or both fetuses of a multiple gestation can be
related to any of the disorders that cause FGR in singleton
pregnancies, as well as disorders unique to multiple gestations, such
as unequal placental sharing or twin-twin transfusion.

Fetal growth restriction:
Evaluation and management

Initial approach- Confirm the diagnosis
Characteristics that support a diagnosis of a constitutionally small fetus
include:
 Modest smallness (ie, EFW between the 5th and 10th percentiles)
 Normal growth velocity across gestation
 Normal physiology (ie, normal amniotic fluid volume and umbilical
artery Doppler)
 Abdominal circumference growth velocity above the 10th percentile
 Appropriate size in relation to maternal characteristics (height,
weight, race/ethnicity)
Society for Maternal-Fetal Medicine (SMFM). Electronic address: pubs@smfm.org, Martins JG, Biggio JR, Abuhamad A. Society for
Maternal-Fetal Medicine Consult Series #52: Diagnosis and management of fetal growth restriction: (Replaces Clinical Guideline
Number 3, April 2012). Am J Obstet Gynecol 2020; 223:B2.
Dubinsky TJ, Sonneborn R. Trouble With the Curve: Pearls and Pitfalls in the Evaluation of Fetal Growth. J Ultrasound Med 2020; 39:1839.

Initial approach- Confirm the diagnosis
 Maternal characteristics have a major influence on fetal growth
potential.
 For example, when race/ethnicity was taken into account, the
5th percentiles for White, Hispanic, Black, and Asian women were
2790, 2633, 2622, and 2621 grams, respectively, in a prospective
study of over 2300 healthy women with low-risk, singleton
pregnancies from 12 medical centers in the United States .
Buck Louis GM, Grewal J, Albert PS, et al. Racial/ethnic
standards for fetal growth: the NICHD Fetal Growth
Studies. Am J Obstet Gynecol 2015; 213:449.e1.

Initial approach- Confirm the diagnosis
 Using a lower threshold to define FGR may help distinguish the small
fetus at increased risk of adverse outcome from the small fetus at low
risk.
 Use of a lower threshold for defining pathologic FGR is supported by
several studies.
Unterscheider J, Daly S, Geary MP, et al. Optimizing the definition of intrauterine growth restriction:
the multicenter prospective PORTO Study. Am J Obstet Gynecol 2013; 208:290.e1.
Mlynarczyk M, Chauhan SP, Baydoun HA, et al. The clinical significance of an estimated fetal weight
below the 10th percentile: a comparison of outcomes of <5th vs 5th-9th percentile. Am J Obstet
Gynecol 2017; 217:198.e1.

Initial approach- Confirm the diagnosis
 In a retrospective study, composite fetal morbidity at <5th percentile
versus 5th to 10th percentile was 39 and 13 percent, respectively (odds
ratio 2.41, 95% CI 1.5-3.8) .
 Although using <5th percentile as a threshold for FGR captures the
group of fetuses at highest risk for adverse outcome, those at the
5th to 10th percentile still need to be monitored closely since not all
are constitutionally small.
Mlynarczyk M, Chauhan SP, Baydoun HA, et al. The clinical significance of an estimated fetal weight
below the 10th percentile: a comparison of outcomes of <5th vs 5th-9th percentile. Am J Obstet
Gynecol 2017; 217:198.e1.

Determine the cause —
 The genetically predetermined growth potential of the fetus can be
impaired as a result of maternal, placental, or fetal processes .
 To determine the cause of FGR, a complete history and physical
examination is performed to assess for maternal disorders that have
been associated with restricted fetal growth.
 In addition, obstetric imaging and laboratory evaluations are
performed to look for fetal and placental etiologies.
 However, the reason(s) for growth impairment cannot always be
determined ante natally.
Mateus J, Newman RB, Zhang C, et al. Fetal growth patterns in pregnancy-associated
hypertensive disorders: NICHD Fetal Growth Studies. Am J Obstet Gynecol 2019;
221:635.e1.

Fetal survey –
 A detailed fetal anatomic survey should be performed in all cases
since approximately 10 percent of FGR is accompanied by congenital
anomalies and 20 to 60 percent of malformed infants are SGA .
 Anomalies associated with FGR include omphalocele, gastroschisis,
diaphragmatic hernia, skeletal dysplasia, and some congenital heart
defects.
 A fetal echocardiogram is indicated if results of an expert (level II)
ultrasound examination suggest any uncertainty that the heart is
normal.

Fetal genetic studies –
Fetal genetic studies are indicated in any of the following settings because of
the increased risk of an abnormality:
 FGR that is all of the following: Early (<24 weeks), severe (<5th percentile),
and symmetrical.
 FGR with major fetal structural abnormalities.
 FGR with soft ultrasound markers associated with an increased risk of
aneuploidy, such as thickened nuchal fold/choroid plexus cyst and
abnormal hand positioning.
 Placental findings suggestive of a partial molar pregnancy: Enlarged, cystic
spaces ("Swiss cheese pattern") and/or increased echogenicity of chorionic
villi.

Fetal genetic studies –
 The American College of Obstetricians and Gynecologists suggests
genetic counseling and offering diagnostic testing for patients with
diagnosis of FGR before 32 weeks or FGR in combination with
polyhydramnios or fetal malformation .
 Ultrasound examination has high sensitivity for identifying trisomy 18,
as high as 100 percent, when performed by an experienced
ultrasonographer at 19 to 20 weeks of gestation in a fetus with
multiple structural anomalies characteristic of the syndrome.
American College of Obstetricians and Gynecologists Committee on Practice Bulletins—
Obstetrics, Society for Maternal-Fetal Medicine Publications Committee. Fetal Growth
Restriction: ACOG Practice Bulletin, Number 227. Obstet Gynecol 2021; 137:e16.

Fetal genetic studies –
 Although the finding of symmetrical FGR prior to 24 weeks of gestation is
associated with a high risk of aneuploidy, this is no longer the case later in
gestation .
 After 24 weeks, we do not screen for fetal genetic abnormalities if anatomy
is normal and FGR is asymmetric since the yield would be low, the etiology
is most likely a maternal or placental disorder, and pregnancy termination
is generally not an option.
 In a systematic review of 14 observational cohort studies including 874
apparently isolated FGR cases, the mean rate of chromosome anomalies
was 6.4 percent (range 0 to 26 percent), and no abnormal karyotypes were
found in the two studies of apparently isolated FGR diagnosed in the third
trimester (32 pregnancies).
Meler E, Sisterna S, Borrell A. Genetic syndromes associated with isolated fetal growth restriction. Prenat
Diagn 2020; 40:432.
Sagi-Dain L, Peleg A, Sagi S. Risk for chromosomal aberrations in apparently isolated intrauterine growth
restriction: A systematic review. Prenat Diagn 2017; 37:1061.

Work-up for infection –
 Infections associated with FGR include cytomegalovirus, toxoplasmosis, rubella,
and varicella. Amniotic fluid DNA testing can also be performed for specific
infections when indicated by the clinical setting.
 Malaria in pregnancy can also cause FGR and should be considered in endemic
areas
 Maternal COVID-19 does not appear to be associated with an increased
prevalence of FGR . However, data on perinatal outcomes when the infection is
acquired in early pregnancy are limited, and any condition that results in
prolonged maternal hypoxia places the fetus at risk for growth restriction.
Dashraath P, Wong JLJ, Lim MXK, et al. Coronavirus disease 2019 (COVID-19) pandemic and pregnancy.
Am J Obstet Gynecol 2020; 222:521.
Di Mascio D, Khalil A, Saccone G, et al. Outcome of coronavirus spectrum infections (SARS, MERS, COVID-
19) during pregnancy: a systematic review and meta-analysis. Am J Obstet Gynecol MFM 2020;
2:100107.

Work-up for antiphospholipid syndrome –
 Although early-onset placental insufficiency is one of the clinical
criteria for the diagnosis of APS by expert consensus , a link between
antiphospholipid antibodies alone and FGR has not been established,
and there is insufficient evidence to support screening all women
with FGR for these antibodies.
 Indications for screening include a past history of fetal loss and prior
unexplained arterial or venous thromboembolism.
Committee on Practice Bulletins—Obstetrics, American College of Obstetricians and
Gynecologists. Practice Bulletin No. 132: Antiphospholipid syndrome. Obstet Gynecol 2012;
120:1514. Reaffirmed 2019.

Pregnancy management
 Pregnancy management of FGR in structurally and chromosomally
normal fetuses-
 Most of these cases are caused by uteroplacental insufficiency.
 Management of FGR associated with congenital or chromosomal
anomalies depends on the specific abnormality and is beyond the
scope of this presentation.

Pregnancy management
The optimal management of the pregnancy with suspected growth
restriction related to uteroplacental insufficiency consists of serial
ultrasound evaluation of:
 Fetal growth velocity
 Fetal behavior (biophysical profile [BPP])
 Impedance to blood flow in fetal arterial and venous vessels (Doppler
velocimetry)

Pregnancy management
The purpose is to identify those fetuses who are at highest risk of
perinatal demise and who may benefit from delivery.
Hugh O, Williams M, Turner S, Gardosi J. Reduction of stillbirths in England from 2008 to 2017
according to uptake of the Growth Assessment Protocol: 10-year population-based cohort
study. Ultrasound Obstet Gynecol 2021; 57:401.

Ambulatory monitoring —
 Women with pregnancies complicated by FGR may maintain normal activities
and are usually monitored as outpatients.
 There are no data on which to base indications for hospitalization.
 consider hospitalization for selected women who need daily or more frequent
maternal or fetal assessment (eg, daily BPP score because of reversed diastolic
flow).
 Hospitalization provides convenient access for daily fetal testing and allows
prompt evaluation and intervention in the event of decreased fetal activity or
other complications, but there is no evidence that hospitalization or bed rest
improves fetal growth or outcome .
Lausman A, McCarthy FP, Walker M, Kingdom J. Screening, diagnosis, and management of intrauterine
growth restriction. J Obstet Gynaecol Can 2012; 34:17.

Ambulatory monitoring —
 Although decisions about selecting women for ambulatory versus in-
hospital care should be made on a case-by-case basis, we generally
admit women with absent/reversed flow of the umbilical artery and
estimated fetal weight (EFW) >350 grams.
 This cutoff is based on our experience of good short- and long-term
outcomes in such cases.
 However, the cutoff weight for monitoring varies among institutions.
Gülmezoglu AM, Hofmeyr GJ. Bed rest in hospital for suspected impaired fetal growth.
Cochrane Database Syst Rev 2000; :CD000034.

Antenatal corticosteroids —
 Ideally, a course of antenatal betamethasone is given to pregnancies
<34+0 weeks of gestation in the week before preterm delivery is
anticipated.
 Administration at 34+0 to 36+6 weeks does not appear to decrease
the need for respiratory support and increases the rate of neonatal
hypoglycemia but is recommended by some guidelines .
 Timing is estimated based on multiple factors, including the severity
of FGR, Doppler findings, comorbid conditions, and rate of
deterioration in fetal status.
Bitar G, Merrill SJ, Sciscione AC, Hoffman MK. Antenatal corticosteroids in the late preterm period for
growth-restricted pregnancies. Am J Obstet Gynecol MFM 2020; 2:100153.

Maternal interventions —
 There is no convincing evidence that any intervention in healthy
women improves the growth of growth-restricted fetuses.
 Numerous approaches have been tried in small randomized trials,
including maternal nutritional supplementation, oxygen therapy, and
interventions to improve blood flow to the placenta, such as plasma
volume expansion, low-dose aspirin, bed rest, and anticoagulation .
Gülmezoglu AM, Hofmeyr GJ. Maternal nutrient supplementation for suspected impaired fetal
growth. Cochrane Database Syst Rev 2000; :CD000148.
Gülmezoglu AM, Hofmeyr GJ. Maternal oxygen administration for suspected impaired fetal
growth. Cochrane Database Syst Rev 2000; :CD000137.

Maternal interventions —Sildanafil
 appeared promising and was under investigation.
 However, a multicenter Dutch trial of sildenafil for treatment of poor
prognosis early-onset FGR was halted early because of a higher than
expected rate of pulmonary hypertension in the intervention group
with no benefit in the primary outcome (perinatal mortality or major
neonatal morbidity) at the time the trial was stopped.
 A concurrent trial in Australia and New Zealand reported sildenafil
had no effect on fetal growth velocity after diagnosis of growth
restriction before 30 weeks but no adverse effects on newborns.
Pels A, Derks J, Elvan-Taspinar A, et al. Maternal Sildenafil vs Placebo in Pregnant Women With Severe
Early-Onset Fetal Growth Restriction: A Randomized Clinical Trial. JAMA Netw Open 2020; 3:e205323.
Groom KM, McCowan LM, Mackay LK, et al. STRIDER NZAus: a multicentre randomised controlled
trial of sildenafil therapy in early-onset fetal growth restriction. BJOG 2019; 126:997.

Maternal interventions —
 In hypertensive pregnant women, antihypertensive therapy does not
improve fetal growth .
 In smokers, an intensive smoking cessation program may be of value
and has other pregnancy and health benefits .
Abalos E, Duley L, Steyn DW. Antihypertensive drug therapy for mild to moderate hypertension during
pregnancy. Cochrane Database Syst Rev 2014; :CD002252.
Figueras F, Meler E, Eixarch E, et al. Association of smoking during pregnancy and fetal growth
restriction: subgroups of higher susceptibility. Eur J Obstet Gynecol Reprod Biol 2008; 138:171.
Aagaard-Tillery KM, Porter TF, Lane RH, et al. In utero tobacco exposure is associated with modified
effects of maternal factors on fetal growth. Am J Obstet Gynecol 2008; 198:66.e1.

Timing delivery —GRIT Trial
 There is little consensus about the optimum time to deliver the growth-restricted fetus.
 The following key trials attempted to answer the question of when to intervene in these
pregnancies, without a clear conclusion:
 The Growth Restriction Intervention Trial (GRIT) randomly assigned pregnant women
between 24 and 36 weeks with FGR to immediate (n = 296) or delayed (n = 291) delivery
if their obstetrician was uncertain about when to intervene . Forty percent of these
pregnancies had absent or reversed end-diastolic umbilical artery flow. In the delayed
delivery group, delivery occurred when the obstetrician was no longer uncertain about
intervening, which took a median 4.9 days.
 The immediate delivery group had fewer stillbirths (2 versus 9 with delayed delivery) but
more neonatal and infant deaths (27 versus 18), especially when randomization occurred
before 31 weeks. Follow-up data up to age 13 years showed no differences between
groups in cognition, language, motor, or parent-assessed behavior scores on
standardized tests; follow-up was achieved in approximately 70 percent of survivors .
Cognition scores were close to the standardized normal range.
Walker DM, Marlow N, Upstone L, et al. The Growth Restriction Intervention Trial: long-term
outcomes in a randomized trial of timing of delivery in fetal growth restriction. Am J Obstet
Gynecol 2011; 204:34.e1.

Timing delivery —DIGITAT Trial
 The Disproportionate Intrauterine Growth Intervention Trial At Term trial
(DIGITAT) randomly assigned 650 pregnant women over 36.0 weeks of gestation
with suspected FGR to induction of labor or expectant monitoring .
 The primary outcome was a composite measure of adverse neonatal outcome
(death before hospital discharge, five-minute Apgar score <7, umbilical artery pH
<7.05, or admission to the intensive care unit) . Neonatal morbidity was analyzed
separately using Morbidity Assessment Index for Newborns (MAIN) score .
 The authors concluded that both approaches were reasonable, and the choice
should depend on patient preference. However, in a sub analysis of the data, they
also reported that neonatal admissions were lower when growth restricted
fetuses were delivered after 38 weeks of gestation , which suggests a benefit of
deferring delivery until 38 weeks of gestation, as long as the fetus is closely
monitored and in the absence of other indications for an early delivery.
Boers KE, van Wyk L, van der Post JA, et al. Neonatal morbidity after induction vs expectant
monitoring in intrauterine growth restriction at term: a subanalysis of the DIGITAT RCT. Am J
Obstet Gynecol 2012; 206:344.e1.

Timing delivery —TRUFFLE Study
 TRUFFLE assessed whether changes in the fetal ductus venosus Doppler
waveform could be used to guide timing of delivery of growth-restricted fetuses
with a high umbilical artery Doppler pulsatility index (>95th percentile) instead of
the conventional approach using cardiotocography short-term variation (STV) .
 The primary outcome measure was survival without neurodevelopmental
impairment at two years of age. Pregnancies were randomly assigned to one of
three monitoring approaches: cardiotocography with delivery for reduced STV,
ductus venosus monitoring with delivery for early ductus venosus changes
(pulsatility index >95th percentile), or ductus venosus monitoring with delivery for
late ductus venosus changes (a-wave indicating absent or reversed flow).
 Their observations clearly demonstrate the need for additional study of the most
appropriate methods to determine delivery timing in the very preterm (<32
weeks of gestation) FGR fetus.
Visser GHA, Bilardo CM, Derks JB, et al. Fetal monitoring indications for delivery and 2-year
outcome in 310 infants with fetal growth restriction delivered before 32 weeks' gestation in the
TRUFFLE study. Ultrasound Obstet Gynecol 2017; 50:347.

Route of delivery —
 An unfavorable cervix is not a reason to avoid induction.
 In a secondary analysis of data from the DIGITAT and HYPITAT trials (pregnancies
complicated by FGR and hypertension), induction of labor at term in women with median
Bishop scores of 3 (range 1 to 6) was not associated with a higher rate of cesarean
delivery than expectant management, and approximately 85 percent of women in both
groups achieved a vaginal delivery . Prostaglandins or a balloon catheter was used for
cervical ripening.
 In a meta-analysis of observational studies of labor induction
with misoprostol, dinoprostone, or mechanical methods in FGR, mechanical methods
appeared to be associated with a lower occurrence of adverse intrapartum outcomes,
but a direct comparison among methods could not be performed.
 However, when the indication for delivery is persistent reversed flow of the umbilical
artery, we give patients the option of a scheduled cesarean birth, especially when the
cervix is unfavorable, because many of these fetuses will not tolerate labor and we wish
to avoid adding an acute insult on a chronic hypoxic fetus.
Bernardes TP, Broekhuijsen K, Koopmans CM, et al. Caesarean section rates and adverse neonatal outcomes after induction of labour versus
expectant management in women with an unripe cervix: a secondary analysis of the HYPITAT and DIGITAT trials. BJOG 2016; 123:1501.
Familiari A, Khalil A, Rizzo G, et al. Adverse intrapartum outcome in pregnancies complicated by small for gestational age and late fetal growth
restriction undergoing induction of labor with Dinoprostone, Misoprostol or mechanical methods: A systematic review and meta-analysis. Eur
J Obstet Gynecol Reprod Biol 2020; 252:455.

Intrapartum management
 It is important to optimize the timing of delivery, perform continuous
intrapartum fetal monitoring to detect non reassuring fetal heart rate
patterns suggestive of progressive hypoxia during labor, and provide
skilled neonatal care in the delivery room . Umbilical cord blood
analysis should be considered as a component of establishing
baseline neonatal status
 If antenatal testing (non stress test or biophysical profile) is normal, a
trial of labor with continuous intrapartum monitoring is reasonable .
 However, the frequency of cesarean delivery for non reassuring fetal
heart rate tracing is increased, given the increased prevalence of
chronic hypoxia and oligohydramnios among these fetuses.
Werner EF, Savitz DA, Janevic TM, et al. Mode of delivery and neonatal outcomes in preterm, small-for-gestational-age newborns. Obstet
Gynecol 2012; 120:560.
Chauhan SP, Weiner SJ, Saade GR, et al. Intrapartum Fetal Heart Rate Tracing Among Small-for-Gestational Age Compared With
Appropriate-for-Gestational-Age Neonates. Obstet Gynecol 2018; 132:1019.

Intrapartum management
• For fetuses less than 32 weeks of gestation, magnesium sulfate is
given before delivery for neuroprotection.
• When use of magnesium sulfate was studied specifically in
pregnancies with growth-restricted fetuses, a decrease in significant
neurodevelopmental impairment and death was observed.
Stockley EL, Ting JY, Kingdom JC, et al. Intrapartum magnesium sulfate is associated with
neuroprotection in growth-restricted fetuses. Am J Obstet Gynecol 2018; 219:606.e1.

Prognosis
 Fetal, newborn, and childhood outcomes — Fetal demise, neonatal death,
neonatal morbidity, and abnormal neurodevelopmental outcome are more
common in growth-restricted fetuses than in those with normal growth .
 The prognosis worsens with early-onset FGR, increasing severity of growth
restriction , and absent or reversed end-diastolic flow on umbilical artery
Doppler .
 In a systematic review of studies of FGR diagnosed before 32 weeks of
gestation (n = 2895 pregnancies delivered after 2000), the frequencies of
fetal and neonatal death were 12 and 8 percent, respectively . The most
common neonatal morbidities were respiratory distress syndrome (34
percent), retinopathy of prematurity (13 percent), and sepsis (30 percent).
Chauhan SP, Rice MM, Grobman WA, et al. Neonatal Morbidity of Small- and Large-for-Gestational-
Age Neonates Born at Term in Uncomplicated Pregnancies. Obstet Gynecol 2017; 130:511.

Prognosis-Fetal & Newborn
 Fetal, newborn, and childhood outcomes — Among children who
underwent neurodevelopmental assessment, 12 percent were
diagnosed with cognitive impairment and/or cerebral palsy. The
quality of evidence was generally rated as very low to moderate,
except for three large, well-designed, randomized trials.
 When all pregnancies with FGR are considered, regardless of
gestational age at diagnosis, the risk of fetal death is approximately
1.5 percent at <10th percentile and 2.5 percent at <5th percentile for
gestational age
Delorme P, Kayem G, Lorthe E, et al. Neurodevelopment at 2 years and umbilical artery Doppler in cases of very
preterm birth after prenatal hypertensive disorder or suspected fetal growth restriction: EPIPAGE-2 prospective
population-based cohort study. Ultrasound Obstet Gynecol 2020; 56:557.
Pels A, Beune IM, van Wassenaer-Leemhuis AG, et al. Early-onset fetal growth restriction: A systematic review on
mortality and morbidity. Acta Obstet Gynecol Scand 2020; 99:153.

Prognosis-Childhood
 Longer term outcomes — An association has been observed between poor fetal
growth, early accelerated postnatal growth, and later development of obesity,
metabolic dysfunction, insulin sensitivity, type 2 diabetes, and cardiovascular and
renal diseases (eg, coronary heart disease, hypertension, chronic kidney disease).
 This association has been attributed to partial resetting of fetal metabolic
homeostasis and endocrine systems in response to in utero nutritional
deprivation. The combination of prematurity and severe FGR increases the risk of
long-term neurodevelopmental abnormalities and decreased cognitive
performance.
Youssef L, Miranda J, Paules C, et al. Fetal cardiac remodeling and dysfunction is associated with both
preeclampsia and fetal growth restriction. Am J Obstet Gynecol 2020; 222:79.e1.
Timpka S, Macdonald-Wallis C, Hughes AD, et al. Hypertensive Disorders of Pregnancy and Offspring
Cardiac Structure and Function in Adolescence. J Am Heart Assoc 2016; 5.

Prognosis-Maternal
 Maternal — The birth of a newborn with idiopathic growth restriction
may be predictive of an increased long-term maternal risk for
cardiovascular disease (coronary artery disease, myocardial infarction,
coronary revascularization, peripheral arterial disease, transient
ischemic attack, stroke).
 A systematic review of 10 cohort studies found a consistent trend of
an increased risk of cardiovascular disease-related morbidity and
mortality in patients with a history of birth of an SGA infant compared
to those with no such history (range of odds ratios 1.09 to 3.50) .
 Pooling was not performed because of variations in the exposure
definition among studies.
Grandi SM, Filion KB, Yoon S, et al. Cardiovascular Disease-Related Morbidity and Mortality in
Women With a History of Pregnancy Complications. Circulation 2019; 139:1069.

Recurrence risk
 There is a tendency to repeat small for gestational age (SGA) deliveries in
successive pregnancies.
 A prospective national cohort study from the Netherlands reported that the risk
of a non anomalous SGA birth (<5th percentile) in the second pregnancy of
women whose first delivery was "SGA" versus "not SGA" was 23 and 3 percent,
respectively .
 The association between the birth of an SGA infant in a first pregnancy and
stillbirth in a subsequent pregnancy was illustrated by analysis of data from the
Swedish Birth Register ; subsequent studies from the United States and Australia
reported similar findings .
 The highest risk of stillbirth was in women who delivered a preterm SGA infant.
 Another series suggested a sibling delivered after the birth of an SGA infant
(even if mildly SGA) was at increased risk of sudden infant death syndrome.
Gordon A, Raynes-Greenow C, McGeechan K, et al. Stillbirth risk in a second pregnancy. Obstet Gynecol 2012; 119:509.
Smith GC, Wood AM, Pell JP, Dobbie R. Sudden infant death syndrome and complications in other pregnancies. Lancet 2005; 366:2107.

Prevention in subsequent pregnancies —
 Address any potentially treatable causes of FGR (eg, cessation of smoking and
alcohol intake, chemoprophylaxis and mosquito avoidance in areas where malaria
is prevalent, balanced energy/protein supplementation in women with significant
nutritional deficiencies.
 Avoiding a short or long interpregnancy interval may also be beneficial.
 Low-dose aspirin may be effective when FGR is secondary to preeclampsia since
aspirin appears to reduce the risk of developing preeclampsia in women at
moderate to high risk of developing the disorder.
 In a meta-analysis of 45 randomized trials of low dose aspirin for prevention of
preeclampsia and FGR in women at high risk, aspirin prophylaxis markedly
reduced the incidence of FGR (relative risk [RR] 0.56, 95% CI 0.44-0.70) compared
with placebo/no treatment .
 Low-dose aspirin is not recommended in the absence of risk factors for PIH
Roberge S, Nicolaides K, Demers S, et al. The role of aspirin dose on the prevention of preeclampsia
and fetal growth restriction: systematic review and meta-analysis. Am J Obstet Gynecol 2017;
216:110.
ACOG Committee Opinion No. 743: Low-Dose Aspirin Use During Pregnancy. Obstet Gynecol 2018;
132:e44.

Prevention in subsequent pregnancies —
 Anticoagulation with unfractionated heparin or low molecular weight heparin does not
reduce the risk of recurrent placenta-mediated late pregnancy complications, such as
growth restriction.
 In a 2016 meta-analysis using individual patient data from randomized trials of low
molecular weight heparin (LMWH) therapy versus no LMWH for women with any prior
placenta-mediated pregnancy complications, the intervention did not significantly reduce
the incidence of the primary composite outcome (early-onset or severe preeclampsia,
SGA <5th percentile, abruption, pregnancy loss ≥20 weeks of gestation): 62/444 (14
percent) versus 95/443 (22 percent), RR 0.64, 95% CI 0.36-1.11 .
 These data support avoidance of anticoagulation in women with previous placenta-
mediated disease, given the lack of clear benefit and potential risks of anticoagulation,
cost, and inconvenience. The combination of low dose aspirin and LMWH does not
appear to be more effective than aspirin alone .
 Dietary changes and supplements, antihypertensive therapy of hypertensive women,
beta-mimetics, and bedrest do not prevent FGR .
Rodger MA, Gris JC, de Vries JIP, et al. Low-molecular-weight heparin and recurrent placenta-mediated pregnancy complications: a meta-
analysis of individual patient data from randomised controlled trials. Lancet 2016; 388:2629.
Groom KM, McCowan LM, Mackay LK, et al. Enoxaparin for the prevention of preeclampsia and intrauterine growth restriction in women
with a history: a randomized trial. Am J Obstet Gynecol 2017; 216:296.e1.

Management of subsequent pregnancies —
 Accurate dating by early ultrasonography is important to establish
gestational age and intermittent ultrasound examinations are used to
monitor fetal growth.
 Otherwise, prenatal management is routine.
 If fetal growth is normal, FGR in a previous pregnancy is not an
indication for antepartum fetal surveillance with non stress tests,
biophysical profiles, or umbilical artery Doppler velocimetry.
Morris RK, Malin G, Robson SC, et al. Fetal umbilical artery Doppler to predict compromise of
fetal/neonatal wellbeing in a high-risk population: systematic review and bivariate meta-analysis.
Ultrasound Obstet Gynecol 2011; 37:135.

Summary and recommendations-overview
Evaluation and management of suspected fetal growth restriction (FGR)
involves:
Accurate determination of gestational age
Confirming the diagnosis
Distinguishing between the constitutionally small and the growth-
restricted fetus
onitoring the fetal weight trajectories
Managing maternal comorbidities
Serial assessment of fetal well-being
Preterm delivery when indicated

The more you give, the more you
will get.
Then life will become a sheer dance
of love.
H. H. Sri. Sri. Ravishankar
The Art of Living
Thank you