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European Journal of Obstetrics & Gynecology and Reproductive Biology 193 (2015) 1018

Contents lists available at ScienceDirect

European Journal of Obstetrics & Gynecology and


Reproductive Biology
journal homepage: www.elsevier.com/locate/ejogrb

Fetal growth restriction and intra-uterine growth restriction:


guidelines for clinical practice from the French College of
Gynaecologists and Obstetricians
C. Vayssie`re a,b,*, L. Sentilhes c, A. Ego d,e,f, C. Bernard g, D. Cambourieu h, C. Flamant i,
G. Gascoin j, A. Gaudineau k, G. Grange l, V. Houfin-Debarge m, B. Langer k, V. Malan n,
P. Marcorelles o, J. Nizard p, F. Perrotin q, L. Salomon r, M.-V. Senat s, A. Serry g, V. Tessier s,
P. Truffert t, V. Tsatsaris l, C. Arnaud b, B. Carbonne u
a
Service de Gynecologie-Obstetrique, CHU Toulouse Hopital Paule de Viguier, Toulouse, France
b
INSERM UMR1027, Universite Toulouse III, Toulouse, France
c
Service de Gynecologie-Obstetrique, CHU Angers, Angers, France
d
Universite Grenoble Alpes, TIMC-IMAG, Grenoble, France
e
CNRS, TIMC-IMAG, Grenoble, France
f
CHU Grenoble, Pole Sante Publique, Grenoble, France
g
Collectif Interassociatif Autour de la Naissance, Paris, France
h
Cabinet medical, Lyon, France
i
Service de reanimation et medecine neonatales, hopital me`re-enfant, CHU de Nantes, Nantes, France
j
Service de reanimation et medecine neonatales, pole femme-me`re-enfant, CHU dAngers, Angers, France
k
Departement de gynecologie-obstetrique, hopitaux universitaires de Strasbourg, Strasbourg, France
l
Maternite Port-Royal, groupe hospitalier Cochin hotel-Dieu, Paris, France
m
Clinique dobstetrique, pole femme me`re-nouveau-ne, hopital Jeanne-de-Flandre, CHRU de Lille, Lille, France
n
Cytogenetique, hopital universitaire Necker-Enfants-Malades, Paris, France
o
Service danatomie pathologique, pole biologie pathologie, hopital Morvan, CHRU de Brest, Brest, France
p
Service de gynecologie obstetrique, CHU Pitie-Salpetrie`re, Paris, France
q
Pole de gynecologie obstetrique, medecine ftale, medecine et biologie de la reproduction, centre Olympe de Gouges, CHRU de Tours, Tours, France
r
Maternite, hopital universitaire Necker-Enfants-Malades, Paris, France
s
Service de gynecologie-obstetrique, hopital Bicetre, Le Kremlin-Bicetre, France
t
Service de reanimation neonatale, hopital Jeanne-de-Flandre, CHRU de Lille, Lille, France
u
Unite dobstetrique maternite, hopital Trousseau, Assistance Publique Hopitaux de Paris, universite Pierre-et-Marie-Curie-Paris 6, France

A R T I C L E I N F O A B S T R A C T

Article history: Small for gestational age (SGA) is dened by weight (in utero estimated fetal weight or birth weight)
Received 4 October 2014 below the 10th percentile (professional consensus). Severe SGA is SGA below the third percentile
Received in revised form 22 April 2015 (professional consensus). Fetal growth restriction (FGR) or intra-uterine growth restriction (IUGR)
Accepted 25 June 2015
usually correspond with SGA associated with evidence indicating abnormal growth (with or without
abnormal uterine and/or umbilical Doppler): arrest of growth or a shift in its rate measured
Keywords: longitudinally (at least two measurements, 3 weeks apart) (professional consensus). More rarely, they
Small for gestational age
may correspond with inadequate growth, with weight near the 10th percentile without being SGA (LE2).
Fetal growth restriction
Birthweight curves are not appropriate for the identication of SGA at early gestational ages because of
Adjusted fetal weight curves
the disorders associated with preterm delivery. In utero curves represent physiological growth more
reliably (LE2). In diagnostic (or reference) ultrasound, the use of growth curves adjusted for maternal
height and weight, parity and fetal sex is recommended (professional consensus). In screening, the use of
adjusted curves must be assessed in pilot regions to determine the schedule for their subsequent
introduction at national level. This choice is based on evidence of feasibility and the absence of any proven
benets for individualized curves for perinatal health in the general population (professional consensus).
Children born with FGR or SGA have a higher risk of minor cognitive decits, school problems and
metabolic syndrome in adulthood. The role of preterm delivery in these complications is linked.

* Corresponding author at: Hopital Paule de Viguier, CHU Toulouse, 330 av de Grande Bretagne, 31059 Toulouse, France. Tel.: +33 567771216; fax: +33 567771219.
E-mail address: christophe.vayssiere@gmail.com (C. Vayssie`re).

http://dx.doi.org/10.1016/j.ejogrb.2015.06.021
0301-2115/ 2015 Elsevier Ireland Ltd. All rights reserved.
C. Vayssie`re et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 193 (2015) 1018 11

The measurement of fundal height remains relevant to screening after 22 weeks of gestation
(Grade C). The biometric ultrasound indicators recommended are: head circumference (HC),
abdominal circumference (AC) and femur length (FL) (professional consensus). They allow calculation
of estimated fetal weight (EFW), which, with AC, is the most relevant indicator for screening. Hadlocks
EFW formula with three indicators (HC, AC and FL) should ideally be used (Grade B). The ultrasound
report must specify the percentile of the EFW (Grade C). Verication of the date of conception is
essential. It is based on the crownrump length between 11 and 14 weeks of gestation (Grade A). The
HC, AC and FL measurements must be related to the appropriate reference curves (professional
consensus); those modelled from College Francais dEchographie Fetale data are recommended
because they are multicentere French curves (professional consensus).
Whether or not a work-up should be performed and its content depend on the context (gestational
age, severity of biometric abnormalities, other ultrasound data, parents wishes, etc.) (professional
consensus). Such a work-up only makes sense if it might modify pregnancy management and, in
particular, if it has the potential to reduce perinatal and long-term morbidity and mortality (professional
consensus).
The use of umbilical artery Doppler velocimetry is associated with better newborn health status in
populations at risk, especially in those with FGR (Grade A). This Doppler examination must be the rst-
line tool for surveillance of fetuses with SGA and FGR (professional consensus). A course of
corticosteroids is recommended for women with an FGR fetus, and for whom delivery before 34
weeks of gestation is envisaged (Grade C). Magnesium sulphate should be prescribed for preterm
deliveries before 3233 weeks of gestation (Grade A). The same management should apply for preterm
FGR deliveries (Grade C). In cases of FGR, fetal growth must be monitored at intervals of no less than 2
weeks, and ideally 3 weeks (professional consensus).
Referral to a Level IIb or III maternity ward must be proposed in cases of EFW <1500 g, potential birth
before 3234 weeks of gestation (absent or reversed umbilical end-diastolic ow, abnormal venous
Doppler) or a fetal disease associated with any of these (professional consensus). Systematic caesarean
deliveries for FGR are not recommended (Grade C). In cases of vaginal delivery, fetal heart rate must be
monitored continuously during labour, and any delay before intervention must be faster than in low-
risk situations (professional consensus). Regional anaesthesia is preferred in trials of vaginal delivery,
as in planned caesareans.
Morbidity and mortality are higher in SGA newborns than in normal-weight newborns of the same
gestational age (LE3). The risk of neonatal mortality is two to four times higher in SGA newborns than
in non-SGA preterm and full-term infants (LE2). Initial management of an SGA newborn includes
combatting hypothermia by maintaining the heat chain (survival blanket), ventilation with a
pressure-controlled insufator, if necessary, and close monitoring of capillary blood glucose
(professional consensus).
Testing for antiphospholipids (anticardiolipin, circulating anticoagulant, anti-beta2-GP1) is
recommended in women with previous severe FGR (below third percentile) that led to birth before
34 weeks of gestation (professional consensus). It is recommended that aspirin should be prescribed to
women with a history of pre-eclampsia before 34 weeks of gestation, and/or FGR below the fth
percentile with a probable vascular origin (professional consensus). Aspirin must be taken in the evening
or at least 8 h after awakening (Grade B), before 16 weeks of gestation, at a dose of 100160 mg/day
(Grade A).
2015 Elsevier Ireland Ltd. All rights reserved.

Methods [13] available data using the working framework dened by the French
Health Authority (HAS) as follows.
The sponsor, the French College of Gynaecologists and
Obstetricians, appointed an organization committee (see Quality of evidence assessment
Appendix A) to dene the exact questions to put to a group of
expert authors, to choose these experts, follow them up and draft LE1: very powerful randomized comparative trials, meta-
the synthesis of recommendations resulting from their work. The analysis of randomized comparative trials.
experts analyzed the scientic literature on the subject in order to LE2: not very powerful randomized trials, well-run non-
answer the questions raised. MEDLINE and the Cochrane Library randomized comparative studies, cohort studies.
were searched for relevant literature up to mid-2013. The search LE3: casecontrol studies.
was restricted to articles published in English and French. Priority LE4: non-randomized comparative studies with large biases,
was given to articles reporting results of original research, retrospective studies, transversal studies, series of cases.
although review articles and commentaries were also consulted. A synthesis of recommendations was drafted by the organizing
Guidelines of the American College of Obstetricians and Gynecol- committee based on the replies given by the expert authors. Each
ogists [4] and the Royal College of Obstetricians and Gynaecol- recommendation for practice was allocated a level dened by the
ogists [5], a comparison of these two guidelines [6], and guidelines HAS as follows.
of the World Association of Perinatal Medicine [7] were reviewed,
and additional studies were located by reviewing the bibliogra- Classication of recommendations
phies of identied articles.
For each question, each overview of validated scientic date Grade A: recommendations based on good and consistent
was associated with a level of evidence according to the quality of scientic evidence.
12 C. Vayssie`re et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 193 (2015) 1018

Grade B: recommendations based on limited or inconsistent Choice of curves


scientic evidence.
Grade C: recommendations based primarily on consensus and  Birthweight curves are not appropriate for the identication of
expert opinion. SGA at early gestational ages because of the disorders associated
Professional consensus: in the absence of any conclusive with preterm delivery. In utero curves represent physiological
scientic evidence, some practices have nevertheless been growth more reliably (LE2).
recommended on the basis of agreement between the members  Fetal sex, maternal height and weight at the beginning of
of the working group (professional consensus). pregnancy, parity and ethnic origin inuence fetal weight
All texts were reviewed by experts in maternal-fetal medicine signicantly; fetal sex is the predominant factor (LE2). The use
who were not involved in the work [i.e. practitioners in the various of a curve undifferentiated by sex leads to the preferential
specialties (see Appendix A) concerned and working in various suspicion of SGA in girls (false positives) and to ignoring SGA in
situations (public, private, university or non-university establish- boys (false negatives) (LE3).
ments)]. Following completion of the review process, changes  Individual adjusted curves of fetal growth combine in utero
were made, if appropriate, considering assessment of the quality of growth and adjustment for maternal height and weight, parity
evidence. and fetal sex. SGA dened solely according to a curve in the
The texts are cited [313], but the individual references general population does not present an increased perinatal risk,
included in each text are not reported here due to space and seems simply to indicate that the infant is constitutionally
constraints. small. SGA babies dened solely according to individual adjusted
fetal weight curves have an excess risk of perinatal death of 2
Denitions, choice of growth curves [8] 10% (LE3). Overall, 5% of all children are reclassied, including
25% of SGA babies (LE3).
All professionals working with women during the perinatal
 Overall, the homogeneous adoption of new growth curves for
period are involved in the management of fetal or intra-uterine prenatal and postnatal periods is necessary for all professionals
growth restriction (FGR/IUGR), and must understand the pro-
involved in perinatal care (obstetricians, midwives, ultrasono-
cesses involved. All professionals will also benet from the graphers, paediatricians, etc.) (professional consensus).
adoption of a common language based on specic denitions.
 In diagnostic (or reference) ultrasound, the use of growth curves
The clearest possible information must be provided to parents to adjusted for maternal height and weight, parity and fetal sex is
enable their informed involvement in medical decisions before
recommended (professional consensus).
and after the birth.  In screening, the use of adjusted curves must be assessed in pilot
The denition of abnormal growth and the choice of a weight
regions to determine the schedule for their subsequent
curve are the main determinants of screening for, and diagnosis introduction at national level. This choice is based on evidence
of, FGR.
of feasibility, and the absence of any proven benets for
individualized curves for perinatal health in the general
Denitions
population (professional consensus).

The following terminology is proposed for use both before and


after birth. Risk factors for SGA [9]

 Small for gestational age (SGA) (used most often as an adjective,  A history of SGA increases the risk of another SGA child four-fold
to be read as small size for gestational age when used as a noun) (LE2).
is dened by weight (in utero estimated weight or birth weight)  Maternal age >35 years triples the risk of SGA compared with
below the 10th percentile (professional consensus). Severe SGA women aged 2030 years (LE2).
is SGA below the third percentile (professional consensus).  Primiparity and grand multiparity double the risk of SGA (LE23).
 FGR/IUGR usually corresponds with SGA associated with  Hypertensive disorders increase the frequency of SGA: chronic
evidence indicating abnormal growth (with or without abnor- hypertension (by a factor of 2), pre-eclampsia (by a factor of 5
mal uterine and/or umbilical Doppler): arrest of growth or a 12, varying by severity and by study) and pregnancy-related
shift in its rate measured longitudinally (at least two hypertension (by a factor of 2) (LE2).
measurements, 3 weeks apart) (professional consensus). More  Pre-existing diabetes before pregnancy with vascular damage is
rarely, FGR/IUGR may correspond with inadequate growth, associated with SGA (risk multiplied by 6) (LE3).
with weight near the 10th percentile without being SGA  Smoking 10 cigarettes/day during pregnancy doubles the risk of
(LE2). IUGR is appropriate when there is evidence that a fetus, SGA, with a doseeffect relationship (LE2).
placenta and amniotic uid are all growth restricted; however,  Drinking alcohol also doubles the risk of SGA (LE2).
when (as is usually the case) the diagnosis is based on birth  Use of illegal drugs during pregnancy triples the risk of SGA (LE2).
weight, FGR is more appropriate.  Other risk factors, including underweight, obesity and disadvan-
taged socio-economic status, increase the risk of SGA by a factor
Comments of less than 2 (LE2).

 When SGA is diagnosed based on a single measurement, the Long-term consequences for children born SGA or FHR [10]
existence of signs of impaired fetal well-being (reduced fetal
movement, Doppler abnormalities, oligohydramnios) must The principal difculty in determining these consequences lies
suggest FGR (professional consensus). in dissociating the intermediate and long-term effects of FGR or
 SGA children are either constitutionally small or authentically SGA from the effects due to preterm birth.
growth restricted (LE2).
 Terms such as hypotrophic or symmetrically or asymmetrically  Neurodevelopmental scores at 2 years of age are lower in these
growth restricted should be removed from the medical children, whether born preterm or at term, and the effect is more
vocabulary (professional consensus). marked in FGR children compared with SGA children (LE3).
C. Vayssie`re et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 193 (2015) 1018 13

 Recent interventional studies regarding the time and type  The ultrasound report must specify the percentile of the EFW
of delivery in this population have not succeeded in identifying (Grade C).
effects on development at 2 years or at 613 years of age (LE2).  It should be borne in mind that a fetus whose biometric
 As with normal-sized children, the mothers wish to breast feed measurements are all at or above the 10th percentile can still
must be supported. Development appears best in these children have an EFW below the 10th percentile.
when they are breast fed, despite their poorer weight/height  Verication of the date of conception is essential. This is based on
growth curve (breastfeeding paradox) (LE3). the crownrump length between 11 and 14 weeks of gestation
 SGA/FGR children have a higher risk of minor cognitive (Grade A).
deciencies, symptoms of hyperactivity and attention decit  HC, AC and FL measurements must be related to the appropriate
at 5 years of age, and a higher risk of school problems at 8 years of reference curves (professional consensus). From 18 to 41 weeks
age (LE3). In children born before 28 weeks of gestation, the of gestation, the curves recommended are those modelled from
effects due to prematurity are more marked than those due to Colle`ge Francais dechographie Ftale data because these are
growth restriction (LE3). multicentre French curves (professional consensus).
 SGA/FGR children are at higher risk of cardiovascular diseases,  Professional practice evaluation of the techniques and distribu-
hypertension, glucose intolerance, diabetes, dyslipidaemia and tion of measurements of ultrasound indicators must be
obesity in adulthood (LE2). encouraged (professional consensus).
 Most SGA/FGR children have caught up in weight and height by 6  A routine supplementary ultrasound at the end of pregnancy (in
months and 1 year, respectively (LE3). Catch-up growth (both additon to the third-trimester ultrasound) is not necessary (Grade
height and weight) that is too rapid may be a supplementary A), except when clinical evidence indicates a need (Grade C).
factor in the onset of hypertension (LE2).  In a population at low risk of SGA and in the framework of
 Studies of adults born SGA have not shown repercussions in ultrasound screening, a referral must be offered when the EFW is
terms of quality of life, employability or self-esteem (LE3). below the third percentile, even in the absence of any other
 In conclusion, FGR or SGA children have a higher risk of minor clinical or ultrasound anomaly. In this case, specicity is
cognitive decits, school problems and metabolic syndrome in favoured over sensitivity (professional consensus).
adulthood. The role of preterm delivery in these complications is  For populations at risk of SGA or when a clinical or ultrasound
linked. (including Doppler) anomaly is present, the threshold of the 10th
percentile is chosen for referrals. In this case, sensitivity is
Modalities of screening and diagnosis of SGA fetuses [11] favoured over specicity (professional consensus).
 An expert opinion is also recommended for a non-SGA fetus with
The performance of ultrasound for screening for SGA is low in inadequate growth between two examinations (e.g. no change in
France, with a sensitivity of 22%. EFW over a 3-week period) (professional consensus).
 After 24 weeks of gestation, management is more urgent because
Clinical screening of fetal viability.
 If the biometric examination must be repeated to help diagnose
FGR, the minimum interval is 3 weeks (Grade B). This interval
 The measurement of fundal height remains relevant to screening
can be shorter if the EFW has an important role in the decision
after 22 weeks of gestation (Grade C).
for possible medically indicated early delivery (professional
 This measurement can help screen for SGA because a growth
consensus).
defect may appear between the 22- and 32-week ultrasounds,
or after 32 weeks of gestation (Grade C). An abnormal fundal
height justies a supplementary ultrasound (professional
Causal work-up for FGR [12]
consensus).

 Whether or not a work-up should be performed and its content


Ultrasound screening depend on the context (term, severity of biometric abnormali-
ties, other ultrasound data, parents wishes, etc.) (professional
 Fetal biometry must be interpreted according to the clinical and consensus).
ultrasound context (Grade C).  Such a work-up only makes sense if it might modify pregnancy
 The biometric ultrasound indicators dened by the Ultrasound management and, in particular, if it has the potential to reduce
Advisory Committee are recommended: head circumference perinatal and long-term morbidity and mortality (professional
(HC), abdominal circumference (AC) and femur length (FL) consensus).
(professional consensus).  These additional investigations have two principal objectives: to
 HC, AC and FL measurements enable calculation of estimated assess fetal vitality and the possibilities for continuing the
fetal weight (EFW), which, together with AC, is the most relevant pregnancy in conditions that are safe for both mother and fetus;
indicator for screening. Hadlocks EFW formula with three and to determine the cause of SGA. This work-up should be
indicators (HC, AC and FL) should ideally be used (Grade B). EFW envisaged when the EFW is below the 10th percentile or below
has demonstrated its usefulness in populations at high and low the fth percentile (or at least when the abdominal circumfer-
risk of SGA. For 95% of women, EFW has a maximum error of ence is below the 10th percentile) (professional consensus).
20%. This means that the difference between EFW and real fetal  Coordination and homogenization of practices within care
weight exceeds 20% for 5% of women (LE2). networks are recommended, working with the prenatal diag-
 EFW is used for screening in order to improve performance and nostic centre (professional consensus).
to make practices more consistent (and results more compara-  Management (and, where appropriate, the work-up) must be
ble) (Grade C). performed on an emergency basis in the case of maternal vascular
 EFW has the advantage of sharing a common language with symptoms or a Doppler umbilical artery velocimetry anomaly
paediatricians and facilitating communication with parents such as absent diastole or reverse ow (professional consensus).
(provided that it is clearly stated that it is only an estimate  The work-up must review the principal items in the history and
and the margins of error are mentioned). clinical ndings (professional consensus).
14 C. Vayssie`re et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 193 (2015) 1018

 An ultrasound will be performed to conrm and specify the Modalities of surveillance and management
biometric abnormalities and to search for other abnormalities of
the fetus, amniotic uid, placenta and Doppler results.  Hospitalization is not indicated routinely for surveillance of
 Screening for maternalfetal cytomegalovirus infections by a fetuses with SGA/FGR. This decision depends on the organization
simple maternal serology test can be offered at the outset in the of care at each facility (Grade C).
absence of evidence of a vascular cause.  A course of corticosteroids is recommended for patients with FGR
 The principal difculty is deciding whether invasive sampling fetuses and for whom delivery before 34 weeks of gestation is
(usually amniocentesis) must be performed. This sample will envisaged (Grade C).
undergo, depending on the case, assessment for infection,  Magnesium sulphate should be prescribed for preterm deliveries
chromosomal and/or gene analysis, or other more specic before 3233 weeks of gestation (Grade A). There is no evidence
assays. to justify a different attitude for preterm FGR deliveries (Grade
 Amniocentesis is not indicated routinely for a work-up for SGA C). This administration should ideally take place in the hours
or FGR, and must be discussed with the prenatal diagnostic before the birth.
centre.  In cases of FGR, fetal growth must be monitored at intervals of no
less than 2 weeks, and ideally 3 weeks (professional consensus).
 In practice, the principal factors suggesting that invasive
 If the Doppler umbilical artery velocimetry shows normal
sampling would be useful are:
diastole, it should be repeated every 23 weeks and combined
 early and/or severe biometric anomaly;
with a cerebral artery Doppler and biometric measurements. The
 association with an excessive quantity of amniotic uid;
frequency of this surveillance should be adjusted to the severity
 association with one or more morphological anomalies;
of FGR (professional consensus).
 absence of a Doppler abnormality;
 If the umbilical artery Doppler velocimetry is abnormal but
 absence of another evident cause;
diastole is still positive, and if early delivery is not envisaged,
 parental desire for a prenatal diagnosis; and
surveillance by umbilical and cerebral artery Doppler veloci-
 results that might modify the management.
metry and FHR should be repeated weekly or more often,
depending on the severity of FGR. For cerebral artery Doppler,
Prenatal surveillance and indications for delivery in cases of a cerebroplacental Doppler ratio <1 or below the fth
isolated vascular FGR [13] percentile is considered routinely for management. This
surveillance can be performed on an outpatient basis (profes-
Prenatal surveillance sional consensus).
 In the case of absent diastole or reverse ow on the umbilical
The modalities of fetal surveillance must be appropriate for the artery Doppler velocimetry, hospitalization must be considered
severity of FGR, the gestational age and the Doppler ndings to administer a course of corticosteroids and organize surveil-
(professional consensus). lance, or even delivery. FHR should then be performed daily
(professional consensus).
Available surveillance tools

 Umbilical artery Doppler velocimetry and fetal cardiotocography Indications for immediate delivery
are the rst-line surveillance tools to be implemented in cases
with a diagnosis of FGR (professional consensus).  Before 32 weeks (Fig. 1).
 Conventional FHR, despite the strong interobserver variability in  Induced preterm delivery has major consequences that justify
its analysis, remains an essential element in surveillance of SGA/ conservative treatment even in cases with abnormal umbilical
FGR fetuses (professional consensus). artery Dopplers (Grade B).
 At present, there is insufcient evidence to recommend for or  Isolated arrested fetal growth (with normal fetal Doppler results
against routine surveillance of short-term variability, even and normal FHR) is not, in itself, an indication for immediate
before 32 weeks of gestation (Grade C). Nonetheless, in view delivery (professional consensus).
of its objective and reproducible nature, short-term vari-  A pulsatility index of the ductus venosus above the 95th
ability can provide decision support about the need to deliver percentile and FHR abnormalities (short-term variability
FGR infants before 32 weeks of gestation (professional <3 ms or rhythm with little oscillation or repeated decelera-
consensus). tions) are independent criteria for delivery of infants with FGR
 The use of umbilical artery Doppler velocimetry is associated <32 weeks of gestation. Delivery must be envisaged when
with better newborn health status in populations at risk, and either of these two indicators is persistently abnormal
especially in those with FGR (Grade A). This Doppler examination (professional consensus).
must be the rst-line tool for surveillance of fetuses with SGA
 After 32 weeks (Fig. 2).
and FGR (professional consensus).
 Despite the absence of randomized trials to demonstrate  The two possible options are delivery or expectant management
potential clinical benets, the high predictive value of a cerebral (Grade B).
Doppler examination, compared with examination of the  In cases of reverse ow or permanent absent diastole on the
umbilical artery alone, makes it possible to offer it routinely umbilical artery Doppler velocimetry after 34 weeks of gestation,
for fetuses with suspected FGR, regardless of whether or not the delivery should be envisaged (Grade C).
umbilical artery Doppler is normal (Grade C).  In the case of abnormal umbilical artery Doppler velocimetry
 Pregnancies with FGR fetuses do not always follow the standard with positive diastolic ow, enhanced surveillance should
sequence, in which deterioration occurs rst in the arterial include umbilical and cerebral artery Doppler velocimetry and
Doppler index, then the venous Doppler index and nally in the FHR several times a week. Surveillance on an outpatient basis is
cardiotocographic tracing. possible (professional consensus).
 The venous Doppler must only be performed by trained  Birth can be envisaged from 37 weeks of gestation, based on
operators and only in pregnancies with FGR in which delivery the EFW, quantity of amniotic uid and Doppler measurements.
before 32 weeks of gestation is envisaged (Grade C). The route of delivery will take maternal and obstetric
C. Vayssie`re et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 193 (2015) 1018 15

Gestational age
EFW
AFI
Umbilical and Cerebral Artery Doppler

Normal UAD

Biometry and UAD


every 2 to 3 weeks
Reduced end-diastolic flow in the UA

Normal CAD Abnormal CAD

UAD and CAD UAD


FHR and/or Computerized FHR with STV FHR and/or Computerized FHR with STV
1 / week 1 / week or more

UAD, umbilical artery doppler; EFW, estimated fetal weight; AFI, amniotic fluid index; CAD,
cerebral artery Doppler; FHR, fetal heart rate; STV, short-term variability.

Fig. 1. Management of fetal growth restriction before 32 weeks of gestation without absent or reversed end-diastolic ow in the umbilical artery. UAD, umbilical artery
doppler; EFW, estimated fetal weight; AFI, amniotic uid index; CAD, cerebral artery Doppler; FHR, fetal heart rate; STV, short-term variability.

Gestational age
EFW
AFI
UAD and CAD
Absent or reversed end-diastolic flow in the UA

+/- Hospitalization
Corticosteroids

Visual FHR and Computerized FHR with STV every day


Ductus Venosus numerous times a week

Normal FHR Decreased Variability


Normal STV < 5 mn > 40 mn STV < 3 ms ARED on DV
Normal DV and/or
Repeat Decelerations

Continue Cesarean Delivery


surveillance

EFW, estimated fetal weight; AFI, amniotic fluid index; UAD, umbilical artery Doppler; CAD,
cerebral artery Doppler; FHR, fetal heart rate; STV, short-term variability; DV, ductus
venosus.

Fig. 2. Management of fetal growth restriction before 32 weeks of gestation with absent or reversed end-diastolic (ARED) ow in the umbilical artery. EFW, estimated fetal
weight; AFI, amniotic uid index; UAD, umbilical artery Doppler; CAD, cerebral artery Doppler; FHR, fetal heart rate; STV, short-term variability; DV, ductus venosus.

characteristics (parity, previous caesarean, body mass index,  when fetal prognosis appears so compromised that the newborns
local cervical condition) into account (Grade C). chances of survival in good conditions appear very low; and
 when the mothers life is endangered, most often because of pre-
eclampsia.
Role of termination of pregnancy and palliative care in cases of
Gestational age and weight are two major prognostic criteria
fetal or intra-uterine vascular growth restriction [14]
(LE1).

Two circumstances can raise the question of termination of  The prognostic assessment is based essentially on ultrasound,
pregnancy in vascular FGR: which must be performed by a senior physician. EFW, growth
16 C. Vayssie`re et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 193 (2015) 1018

rate, fetal Doppler ndings and signs of chronic hypoxia (e.g.  There is no evidence to contraindicate induction of labour for
hyperechoic intestines, oligohydramnios) must all be considered FGR, even before term and/or with an unripe cervix (Grade C).
(professional consensus).  When the cervix is not ripe, intracervical or intravaginal
 An interval of at least 2 weeks (ideally 3 weeks) should elapse prostaglandins or an intracervical balloon can be used, except
between two examinations to minimize the error associated in very-high-risk situations (very early term and/or reverse ow
with the imprecision of EFW (professional consensus). on the umbilical artery Doppler) (professional consensus).
 In some cases, in utero death can occur during this interval  After placement of the prostaglandins or of an intracervical
necessary for diagnosis and prognosis; this risk must be balloon, surveillance must continue beyond the rst 2 h
explained to the parents (professional consensus). (professional consensus).
 Collaboration between the obstetrician and paediatrician is  Use of an oxytocin test before induction for FGR is not
essential, and they should jointly provide the parents with recommended (professional consensus).
information (professional consensus).  Neither a routine instrumental intervention nor a systematic
episiotomy is recommended (professional consensus).
When the fetal prognosis appears reserved, several approaches
can be considered with the parents.
Breech presentation
 They may move towards an expectant approach, aware that
death in utero may occur, in a time period that is difcult to  There is no evidence in the literature to contraindicate vaginal
predict (professional consensus). delivery for a woman in labour with a fetus with FGR in breech
 The couple may also prefer active management with immedi- presentation (professional consensus).
ate delivery, postnatal assessment and the possibility of  Vaginal delivery must be assessed according to the extent of FGR
secondary development towards support with palliative care and the obstetric conditions (professional consensus).
(professional consensus). It nonetheless exposes the mother to
both the short- and long-term morbidity associated with a Mode of anaesthesia during labour and in caesarean deliveries
caesarean that most often involves incision into the uterine
body.  Regional anaesthesia is preferred in trials of vaginal delivery, as
 Finally, the couple may choose to request a medically indicated in planned caesareans.
termination of pregnancy. In such a case, the request must be  In caesareans under spinal anaesthesia, adequate anaesthetic
presented to a multidisciplinary prenatal diagnosis centre, management must endeavour to maintain blood pressure at its
regardless of whether the indication is fetal or maternal. normal value. It appears desirable to shorten the delay between
Exemption from this regulatory obligation is only possible in induction of anaesthesia and actual fetal delivery (the obstetri-
maternal emergencies (and then the exemption is only to the cian should be available immediately) (Grade B).
advance request for authorization).
 Regardless of the couples decision, they must receive support.
Psychological support must be offered to them both before and
Management of SGA newborns and early outcome [16]
after the birth (professional consensus).
The principal early complications of SGA differ notably from
Modalities of birth of fetuses with FGR [15] those for term newborns and preterm newborns who are not SGA.

Interventions and place of birth of fetuses with FGR Assessment of the cause

 The diagnosis of a fetus with FGR justies referral to an


 The investigation always includes a clinical examination with an
appropriate maternity ward able to provide obstetric, neonatal
HC measurement. Additional investigations depend on those
and possibly maternal management, in compliance with
already performed during the prenatal period and on the
the regional perinatal care network protocols (professional
likelihood of a non-vascular disease (professional consensus).
consensus).
 Referral to a Level IIb or III maternity ward must be proposed in
cases of EFW <1500 g, potential birth before 3234 weeks of Complications associated with low birth weight
gestation (absent umbilical ow diastolic end ow or reverse
ow, Doppler venous anomaly) or a fetal disease associated with  Morbidity and mortality are higher in SGA newborns than in
any of these (professional consensus). normal-weight newborns of the same gestational age (LE3).
 The risk of neonatal mortality is two to four times higher in SGA
Route of delivery of SGA/FGR fetuses newborns than in non-SGA preterm and full-term infants (LE2).
 The risks are simultaneous for perinatal (especially perinatal
 Systematic caesarean deliveries for FGR are not recommended anoxia-ischaemia in term newborns), early postnatal (particu-
(Grade C). larly hypothermia and hypoglycaemia) and later consequences
 In cases of vaginal delivery, fetal heart rate must be recorded (e.g. bronchopulmonary dysplasia, pulmonary hypertension and
continuously during labour, and any delay before intervention enteropathy in preterm SGA newborns).
must be faster than in low-risk situations (professional consen-  The risk of hyaline membrane disease is not signicantly higher
sus). in SGA than non-SGA newborns (LE2).
 Caesareans are habitual at early term or in cases of severe  From the neurological perspective, periventricular leukomalacia
abnormalities of the umbilical artery Doppler velocimetry is not more frequent, but the results for severe intraventricular
(absent diastolic index or reverse ow), although no data are haemorrhage and retinopathy of prematurity are controversial
available about trial of vaginal delivery in favourable situations (expert opinion).
(ripened permeable cervix, multiparity, cephalic presentation)  The increased risk of poor adaptation to extra-uterine life in SGA
(professional consensus). newborns must be anticipated by a paediatric consultation
C. Vayssie`re et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 193 (2015) 1018 17

before birth for infants with severe SGA (below third percentile), During pregnancy, to avoid the onset of FGR
given that that fetal weight is estimated and thus subject to
inherent margins of error (professional consensus). In cases without chronic maternal disease
 Initial management of an SGA newborn includes combatting
hypothermia by maintaining the heat chain (survival blanket),  It is recommended to comply with the weight objectives
ventilation with a pressure-controlled insufator, if necessary, recommended by the Institute of Medicine as a function of
and close monitoring of capillary blood glucose (professional preconceptional body mass index (Grade B).
consensus).  Women must be encouraged to stop smoking and consuming any
 Transfer to a special unit, especially in a different facility, other toxic substances as early as possible in the pregnancy
depends on the infants weight and adaptation to extra-uterine (professional consensus).
life; promoting proximity between mother and child remains  There is no evidence to support recommending rest for
important (professional consensus). prevention of FGR (professional consensus).
 Routine iron supplementation does not reduce the risk of FGR
(LE1).
Pathological examination of the placenta [17] In cases of chronic maternal disease

 A pathological examination of the placenta should be performed  For diabetes that preceded pregnancy, it is recommended that
in the case of FGR or IUGR at or below the third percentile glycaemic objectives should be maintained in avoiding hypo-
(professional consensus). glycaemia (Grade B).
 The request form for examination of the placenta must  For chronic hypertension, it is recommended that systolic
include information about the pregnancy, delivery and child. blood pressure should be maintained between 140 and
A standard information form accompanying the request 160 mmHg, and diastolic blood pressure should be maintained
facilitates the transmission of these data (professional between 90 and 110 mmHg; this can require that treatment
consensus). for hypertension be stopped during the pregnancy (profes-
 The most common placental lesions in IUGR are those compati- sional consensus).
ble with placental vascular insufciency of maternal origin:
 infarction;
For pregnant women with a history of FGR
 decidual arterial disease;
 syncytial clusters; and
 It is recommended to test for antiphospholipids (anticardiolipin,
 villous chorangiosis.
circulating anticoagulant, anti-beta-GP1) in women with previ-
 These lesions are variable, non-specic and most suggestive ous severe FGR (below third percentile) that led to birth before
when they are found together (expert opinion). 34 weeks of gestation (professional consensus).
 There are other placental diseases that can cause IUGR, including  There is no evidence to support testing for other thrombophilias
abnormalities of the conguration of the placenta, cord in women with a history of FGR (professional consensus).
abnormalities and diseases of the placental parenchyma, which  An interval of 1823 months between two pregnancies seems to
must be diagnosed microscopically (expert opinion). be associated with a lower rate of FGR (expert opinion).
 This is particularly the case for fetal thrombotic vasculopathy,
chronic villitis and chronic histiocytic intervillositis. These can
Role of aspirin
recur and have notable clinical implications for mother and child
(expert opinion).
 It is recommended that aspirin should be prescribed to women
with a history of pre-eclampsia before 34 weeks of gestation and/
Prevention of FGR [18] or FGR below the fth percentile with a probable vascular origin
(professional consensus).
Before a rst pregnancy  Aspirin must be taken in the evening or at least 8 h after
awakening (Grade B), before 16 weeks, at a dose of 100160 mg/
Due to the risk factors for FGR, it is recommended: day (Grade A).
 Some diseases are associated with a increased risk of vascular FGR;
 to encourage women planning to become pregnant to aim to nonetheless, there is no evidence in the literature on which to base
reach a preconceptional body mass index <30 kg/m2 and a recommendation for prescribing aspirin in these situations
>18 kg/m2 (professional consensus); (professional consensus): chronic hypertension, pregestational
 to encourage them to stop smoking (Grade A) and offer them diabetes, lupus, chronic nephropathy and sickle cell anaemia.
assistance in doing so (professional consensus). The same is true
for alcohol and drugs (professional consensus); and
 to limit multiple pregnancy in cases of assisted reproductive Condensation
technology (Grade A).
Guidelines for clinical practice from the French College of
Gynaecologists and Obstetricians on fetal growth restriction/intra-
Among women at increased risk of FGR
uterine growth restriction.
 Some chronic maternal diseases (diabetes, lupus and chronic
hypertension) are associated with an increased risk of FGR, Appendix A
especially for women with kidney damage (LE4).
 A multidisciplinary consultation before conception is particular- A.1. Steering committee
ly indicated to assess these risks, adjust treatments to the
attempt to become pregnant, and plan the pregnancy for the B. CARBONNE, President (gynaecologist/obstetrician, Hopital
best moment of the disease (professional consensus). Trousseau, Paris, France), C. VAYSSIERE, Coordinator (gynaecologist/
18 C. Vayssie`re et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 193 (2015) 1018

obstetrician, CHU Toulouse, Toulouse, France), L. SENTILHES, Coordi- Mourier, Colombes, France), R. KUTNAHORSY (gynaecologist/obste-
nator (gynaecologist/obstetrician, CHU Angers, Angers, France), trician, CH Colmar, Colmar, France), H. LAURICHESSE (gynaecologist/
C. ARNAUD, Methodologist (epidemiologist, INSERM U1027, Toulouse, obstetrician, CHU Clermont-Ferrand, Clermont-Ferrand, France), A.
France), D. COMBOURIEU (Colle`ge Francais dechographie Ftale, Lyon, LEREBOURS-BARBIER (gynaecologist/obstetrician, Vannes, France),
France), V. TESSIER (midwife, CNSF, CHU Bicetre, Le Kremlin-Bicetre, M. MARTINEZ (midewife, CHU Montpellier, Montpellier, France), E.
France), B. LANGER (gynaecologist/obstetrician, Societe Francaise de MASCITTI-HUMBERT (midwife, CH Chaumont, Chaumont, France), C.
Medecine Perinatale, CHU Hautepierre, Strasbourg, France), P. TRUF- MORIN (midewife, CHU Bordeaux, Bordeaux, France), M. MORIN
FERT (neonatologist, Societe Francaise de Neonatologie, CHRU Lille, (midwife, CHU Toulouse, Toulouse, France), I. NISAND (gynaecologist/
France), A. SERRY (Collectif Interassociatif Autour de la Naissance, Paris, obstetrician, CHU Hautepierre, Strasbourg, France), M. PERINEAU
France) and C. BERNARD (Collectif Interassociatif Autour de la (gynaecologist/obstetrician, Clinique Sarrus-Teinturiers, Toulouse,
Naissance, Paris, France). France), A. RICBOURG (gynaecologist/obstetrician, CHU Lariboisie`re,
Paris, France), V. RIGOURD (paediatrician, Paris, France), C. ROUIL-
A.2. Working group LARD (midwife, CHU Angers, Angers, France), P. ROZENBERG
(gynaecologist/obstetrician, CHI Poissy, Poissy, France), B. SCHAUB
A. EGO (epidemiologist, INSERM U953, CHU Grenoble, Grenoble, (gynaecologist/obstetrician, CHU, de Fort de France, Fort de France,
Paris), C. FLAMANT (paediatrician, CHU Nantes, Nantes, France), A. France), J. SEROR (sonographist, Paris, France), O. THIEBAUGEORGES
GAUDINEAU (gynaecologist/obstetrician CHU Strasbourg, Strasbourg, (gynaecologist/obstetrician, Clinique Sarrus-Teinturiers, Toulouse,
France) G. GASCOIN (paediatrician, CHU Angers, Angers, France), G. France), E. VERSPYCK (gynaecologist/obstetrician, CHU Rouen, Rouen,
GRANGE (gynaecologist/obstetrician, CHU Cochin, Paris France), V. France), J. ZEITLIN (epidemiologist, INSERM U953, Paris, France).
HOUFFLIN-DEBARGE (gynaecologist/obstetrician, CHRU Jeanne de
Flandre, Lille, France), V. MALAN (genetician, CHU Necker,
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