Fetal Growth Restriction. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/080, October 2024)

Abstract

Purpose The purpose of this official guideline, updated and published by the German Society for Gynecology (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG) and coordinated by the joint guidelines program of the DGGG, Austrian Society for Gynecology and Obstetrics (Österreichische Gesellschaft für Gynäkologie und Geburtshilfe, OEGGG) and Swiss Society for Gynecology and Obstetrics (Schweizerische Gesellschaft für Gynäkologie und Geburtshilfe, SGGG) is to provide a consensus-based overview of the diagnosis and management of intrauterine growth restriction based on an evaluation of the relevant literature.

Methods This S2k-guideline is the result of a structured consensus of representative members from various medical professions. It was compiled at the request of the guidelines commission of the DGGG.

Recommendations The guideline provides recommendations on the diagnosis, management, counseling, prophylaxis, and screening of fetal growth restriction.

 

MissingLinkText

Keywords

guideline - fetal growth restriction - FGR

I  Guideline Information

Guidelines program of the DGGG, OEGGG and SGGG

More information on the program is available at the end of the guideline.

 

MissingLinkText

Citation format

Fetal Growth Restriction. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/080, October 2024). Geburtsh Frauenheilk 2025. DOI: 10.1055/a-2535-0528

 

MissingLinkText

Guideline documents

The complete long version in German and a slide version of this guideline together with a list of the conflicts of interest of all the authors is available on the homepage of the AWMF: http://www.awmf.org/leitlinien/detail/ll/015-080.html

 

MissingLinkText

Guideline authors

See [Tables 1] and [2].

Table 1 Lead and/or coordinating guideline author.

Author	AWMF medical society
Prof. Dr. Sven Kehl	DGGG

Table 2 Contributing guideline authors.

Author Mandate holder	DGGG working group/AWMF/non-AWMF medical society/ organization/association
Prof. Dr. med. Franz Bahlmann	ARGUS
Prof. Dr. med. Jörg Dötsch	DGKJ
Prof. Dr. med. Ursula Felderhoff-Müser	GNPI
Prof. Dr. med. Tanja Groten	DGGG/AGG
Prof. Dr. med. Gwendolin Manegold-Brauer	SGGG
Prof. Dr. med. Kurt Hecher	DEGUM
Prof. Dr. med. Sven Kehl	DGGG/AGG
Prof. Dr. med. Philipp Klaritsch	OEGGG, ÖGUM
Prof. Dr. med. Silvia Lobmaier	DEGUM
Prof. Dr. med. Ulrich Pecks	DGPM
Prof. Dr. med. Luigi Raio	SGGG
Priv.-Doz. Dr. med. Dietmar Schlembach	DGPGM
Priv.-Doz. Dr. med. Dagmar Schmitz	AEM

The following medical societies/working groups/organizations/associations wanted to contribute to the guideline text and participate in the consensus conference and nominated representatives to attend the consensus conference ([Table 2]).

Prof. Dr. med. Constantin von Kaisenberg (AWMF-certified guideline advisor/moderator) moderated the structured consensus conferences.

 

MissingLinkText

Abbreviations

AED: absent end-diastolic

AEDF: absent end-diastolic flow

ARED: absent or reversed end-diastolic

ASA: acetylsalicylic acid

BPP: biophysical profile

CPR: cerebroplacental ratio

CRL: crown-rump length

CTG: cardiotocography

FGR: fetal growth restriction

GW: week(s) of gestation

ICSI: intracytoplasmic sperm injection

IUFD: intrauterine fetal death

IVF: in vitro fertilization

MCA: middle cerebral artery

NO: nitrogen monoxide

PI: pulsatility index

RED: reversed end-diastolic

REDF: reversed end-diastolic flow

RI: resistance index

SGA: small for gestational age

SDP: single deepest pocket

s./p.: status post

STV: short-term variation

UA: umbilical artery

UCR: umbilicocerebral ratio

UtA: uterine arteries
 

 

MissingLinkText

 

MissingLinkText

II  Guideline Application

Purpose and objectives

The purpose of this guideline is to provide a summary of the current knowledge about fetal growth restriction (FGR), focusing on the definition, diagnosis and management of care to determine the best time to deliver the fetus.

 

MissingLinkText

Targeted areas of care

• Inpatient care

• Day-patient care

• Outpatient care

 

MissingLinkText

Target user groups/target audience

This guideline is aimed at the following groups of people:

• Gynecologists and obstetricians

• Neonatologists

• Pediatricians

 

MissingLinkText

Adoption and period of validity

The validity of this guideline was confirmed by the executive boards/representatives of the participating professional medical societies, working groups, organizations, and associations as well as the boards of the DGGG, the DGGG Guidelines Commission, the OEGGG and the SGGG in September 2024 and was thereby approved in its entirety. This guideline is valid from 1 October 2024 through to 30 September 2029. Because of the contents of this guideline, this period of validity is only an estimate. The guideline can be reviewed and updated earlier if urgently necessary. Similarly, if the guideline still reflects the current state of knowledge, its period of validity can be extended.

 

MissingLinkText

 

MissingLinkText

III  Method

Basic principles

The method used to prepare this guideline was determined by the class to which this guideline was assigned. The AWMF Guidance Manual (version 1.0) has set out the respective rules and requirements for different classes of guidelines. Guidelines are differentiated into lowest (S1), intermediate (S2), and highest (S3) class. The lowest class is defined as consisting of a set of recommendations for action compiled by a non-representative group of experts. In 2004, the S2 class was divided into two subclasses: a systematic evidence-based subclass (S2e) and a structural consensus-based subclass (S2k). The highest S3 class combines both approaches.

This guideline was classified as: S2k

 

MissingLinkText

Grading of recommendations

The grading of evidence based on the systematic search, selection, evaluation, and synthesis of an evidence base which is then used to grade the recommendations of the guideline is not envisaged for S2k guidelines. The individual statements and recommendations are only differentiated by syntax, not by symbols ([Table 3]).

Table 3 Grading of recommendations (based on Lomotan et al., Qual Saf Health Care 2010).

Description of binding character	Expression
Strong recommendation with highly binding character	must/must not
Regular recommendation with moderately binding character	should/should not
Open recommendation with limited binding character	may/may not

 

MissingLinkText

Statements

Expositions or explanations of specific facts and circumstances, or problems without any direct recommendations for action included in this guideline are referred to as “statements.” It is not possible to provide any information about the level of evidence for these statements.

 

MissingLinkText

Achieving consensus and level of consensus

At structured NIH-type consensus conferences (S2k/S3 level), authorized participants attending the session vote on draft statements and recommendations. The process is as follows. A recommendation is presented, its contents are discussed, proposed changes are put forward, and all proposed changes are voted on. If a consensus (> 75% of votes) is not achieved, there is another round of discussions, followed by a repeat vote. Finally, the level of consensus is determined, based on the number of participants ([Table 4]).

Table 4 Level of consensus based on extent of agreement.

Symbol	Level of consensus	Extent of agreement in percent
+++	Strong consensus	> 95% of participants agree
++	Consensus	> 75 – 95% of participants agree
+	Majority agreement	> 50 – 75% of participants agree
–	No consensus	< 51% of participants agree

 

MissingLinkText

Expert consensus

As the term already indicates, this refers to consensus decisions relating specifically to recommendations/statements issued without a prior systematic search of the literature (S2k) or where evidence is lacking (S2e/S3). The term “expert consensus” (EC) used here is synonymous with terms used in other guidelines such as “good clinical practice” (GCP) or “clinical consensus point” (CCP). The strength of the recommendation is graded as previously described in the chapter Grading of recommendations but without the use of symbols; it is only expressed semantically (“must”/“must not” or “should”/“should not” or “may”/“may not”).

 

MissingLinkText

 

MissingLinkText

IV  Guideline

1  Definition

Consensus-based statement 1.S1
Expert consensus	Level of consensus +++
UA-AEDF: umbilical artery (UA) with AEDF (absent end-diastolic flow) UtA-PI: pulsatility index of the uterine arteries (UtA) UA-PI: pulsatility index of the umbilical artery (UA)
Early fetal growth restriction (FGR) is present if the gestational age is < 32 + 0 GW, there are no congenital anomalies and the following findings are present: abdominal circumference/estimated fetal weight < 3rd percentile or UA-AEDF OR abdominal circumference/estimated fetal weight < 10th percentile AND UtA-PI > 95th percentile and/or UA-PI > 95th percentile
Statement: new

Consensus-based statement 1.S2
Expert consensus	Level of consensus +++
CPR: cerebroplacental ratio UA-PI: pulsatility index of the umbilical artery
Late fetal growth restriction (FGR) is present if the gestational age is ≥ 32 + 0 GW, there are no congenital anomalies, and the following criteria are present: abdominal circumference/estimated fetal weight < 3rd percentile OR At least two of these three findings are present: abdominal circumference/estimated fetal weight < 10th percentile slowed growth of abdominal circumference/estimated fetal weight (decrease > 2 quartiles) CPR < 5th percentile or UA-PI > 95th percentile
Statement: new

The definitions of constitutionally small and growth-restricted fetuses are very heterogeneous and definitions in international guidelines differ [1], [2], [3], [4].

A fetus or neonate is considered small for gestational age (SGA) if the estimated fetal weight or the birth weight is less than the 10th percentile. A diagnosis of SGA only describes a fetal weight which is at the lower end of the normal growth distribution, but this is not directly associated with pathological growth. It also includes constitutionally small children who will not necessarily be affected with higher perinatal morbidity. However, the lower the percentile, the greater the likelihood of a real FGR situation.

Depending on the gestational age at diagnosis, clinicians differentiate between early FGR (< 32 + 0 GW) and late FGR (≥ 32 + 0 GW) [2], [5]. There are relevant differences in the clinical course of early and late FGR and these must be taken into account (see chapter 6: Management of FGR).

 

MissingLinkText

2  Epidemiology and etiology

Consensus-based recommendation 2.E1
Expert consensus	Level of consensus +++
All pregnant women must be evaluated for potential risk factors for FGR by taking their detailed medical history. If risk factors are found to be present, further diagnostic examinations must be considered or offered.
Recommendation: new

FGR is a condition which affects about 5 – 10% of all pregnancies [6], [7]. The etiology of FGR is roughly divided into maternal, placental and fetal causes ([Table 5]) [8]. Although the underlying pathophysiological mechanisms may differ, they often result in the same endpoint: suboptimal uteroplacental perfusion with suboptimal provision of nutrients to the fetus.

Table 5 Risk factors for developing fetal growth restriction. Common risk factors are highlighted in bold.

Maternal causes	Alcohol abuse [10] Maternal hypertensive disease in pregnancy (preeclampsia, gestational hypertension) [11] Drug/nicotine abuse [12], [13] Embryotoxic or fetotoxic medications [14] Maternal age (≥ 35/>40 years) [15] Maternal weight (high or very low BMI) [16] Low socioeconomic status [17], [18] Nulliparity [19] Subclinical cardiovascular dysfunction [20] s./p. hypertensive disease in a previous pregnancy s./p. IUFD [11] s./p. SGA/FGR [11] Preexisting maternal disease which could result in reduced uteroplacental perfusion or reduced oxygenation of maternal blood, e.g., chronic respiratory disease chronic hypertension [21] chronic renal disease [22] diabetes mellitus with vascular disease [23] cyanotic heart disease [24] severe anemia systemic lupus erythematosus and antiphospholipid syndrome [25]
Uteroplacental causes	Placental abruption [26] Velamentous cord insertion Placental infarction [27] Disorders of placentation with insufficient invasion of the trophoblast and high maternal risk of preeclampsia [28] Placental tumors Singular umbilical artery [29]
Fetal causes	Chromosomal disorders and syndromal diseases [30], [31] Fetal infections (esp. cytomegalovirus, toxoplasmosis, rubella, varicella-zoster virus) Multiple pregnancy [32]

It is essential that the mother is asked in detail about her medical history. This helps to identify pregnancies with a higher risk of FGR which will require close monitoring [9].

 

MissingLinkText

3  Diagnostic workup to evaluate for possible FGR

In addition to the information obtained from the motherʼs medical history, a clinical examination with instrument-based diagnostic procedures must be carried out to exclude or confirm FGR. This is an important aspect of antenatal care as the majority of FGR cases are not detected prenatally [33] and undetected FGR has an 8 times higher risk of intrauterine fetal death [34].

3.1  Clinical examination

Consensus-based recommendation 3.E2
Expert consensus	Level of consensus +++
Clinical examinations to screen for FGR are of limited use. If abnormalities are suspected, an examination must be carried out based on ultrasound biometry.
Recommendation: confirmed

 

MissingLinkText

3.2  Sonography

3.2.1  Crown-rump length

Consensus-based recommendation 3.E3
Expert consensus	Level of consensus +++
The maternal history-based gestational age must be verified by measuring the crown-rump length in early pregnancy and must be corrected if there is a discrepancy of more than 7 days. In Switzerland, the due date is corrected if there is a discrepancy of more than 5 days, in accordance with the requirements of the SGUM guidelines.
Recommendation: new

When carrying out a diagnostic workup to exclude or confirm possible FGR, it is essential to review the maternal history-based gestational age. Estimating the gestational age by measuring the crown-rump length (or the biparietal diameter) in early pregnancy in accordance with maternity guidelines provides the most reliable data compared to all other methods [9], [10], [11]. Unless the date of conception was fixed (e.g., ICSI), the gestational age must always be corrected if the maternal history-based gestational age deviates from the sonographically determined age by at least 7 days [35], [36], [37].

However, if screening is carried out in the first trimester of pregnancy, the guideline “First Trimester Diagnosis and Therapy in Weeks 11 – 13⁺⁶ of Gestation” (AWMF Registry No. 085/002, Level: S2e) and its recommendation 4.1 should be consulted [38]:

When carrying out first trimester screening in accordance with the guideline, specific reference curves based on crown-rump length must be used to determine the gestational age. In this setting, if the exact date of conception (e.g., ICSI) is not known, the crown-rump length must always be used to determine gestational age.

 

MissingLinkText

3.2.2  Measurement of the fetus

Consensus-based recommendation 3.E4
Expert consensus	Level of consensus +++
Further diagnostic evaluations must be carried out if the estimated fetal weight/abdominal circumference is less than the 10th percentile.
Recommendation: confirmed

Fetal abdominal circumference is the most important indicator of FGR in addition to estimated weight. A discrepancy between fetal abdominal and fetal head circumference may also be an indication of FGR.

Evaluating the estimated fetal weight should also take maternal and paternal characteristics into consideration. Parental height, weight, and ethnicity affect fetal weight, which is why growth curves which were adapted to take account of these factors may be useful [39], [40], [41], [42].

As FGR is not limited to a weight below the 10th percentile, repeat measurement of the fetus may be useful, especially if risk factors are present; however, repeat measurements should be carried out two weeks later at the earliest to minimize the methodological bias of weight formulas as much as possible.

 

MissingLinkText

3.2.3  Amniotic fluid

Consensus-based recommendation 3.E5
Expert consensus	Level of consensus +++
The amniotic fluid volume should be evaluated when investigating for possible FGR.
Recommendation: new

 

MissingLinkText

3.2.4  Detailed sonographic investigation (further, more differentiated, diagnostic examination of organs)

Consensus-based recommendation 3.E6
Expert consensus	Level of consensus +++
When investigating for possible SGA/FGR, the detailed diagnostic examination should include sonography.
Recommendation: confirmed

 

MissingLinkText

 

MissingLinkText

3.3  Doppler sonography

Consensus-based recommendation 3.E7
Expert consensus	Level of consensus +++
Doppler sonography must be done to investigate for possible FGR.
Recommendation: confirmed

 

MissingLinkText

3.4  Cardiotocography (CTG)

Cardiotocography (CTG) is known to have a high false-positive rate for the prediction of poor outcomes and is better at detecting acute hypoxic conditions than identifying a chronic course [43]. The usefulness of CTG to investigate for possible FGR is therefore somewhat limited but it should be carried out as recommended in maternity guidelines in the context of standard antenatal screening if there is a suspicion of placental insufficiency [44].

 

MissingLinkText

 

MissingLinkText

4  Differential diagnostics for a SGA/FGR fetus

4.1  Genetic investigation

Consensus-based recommendation 4.E8
Expert consensus	Level of consensus ++
A genetic investigation should be recommended in cases with severe FGR (estimated fetal weight < 3rd percentile, early FGR) when sonography findings indicate a genetic cause and these findings are expected to affect management of the condition.
Recommendation: new

 

MissingLinkText

4.2  Investigation for infection

Consensus-based recommendation 4.E9
Expert consensus	Level of consensus ++
An investigation for infection should considered if the fetus is SGA or has FGR.
Recommendation: confirmed

 

MissingLinkText

 

MissingLinkText

5  Summary: diagnosis of FGR

The differential diagnostic procedures used to arrive at a diagnosis of FGR are shown in [Fig. 1].

Fig. 1 Diagnosis of fetal growth restriction. Abbreviations: AEDF, absent end-diastolic flow; CPR, cerebroplacental ratio; FGR, fetal growth restriction; PI, pulsatility index; REDF, reversed end-diastolic flow; SGA, small for gestational age; UA, umbilical artery; UA-AEDF, umbilical artery with absent end-diastolic flow; UtA, uterine arteries. [rerif]

 

MissingLinkText

6  Management of FGR

There is very little evidence on the most suitable method for prenatal monitoring of FGR [45]. A single monitoring method is not able to effectively predict the outcome of FGR, which is why a combination of different methods to monitor growth-restricted fetuses is recommended. Sonography, especially Doppler sonography, is essential to monitor FGR and improve perinatal outcomes.

6.1  Diagnostic monitoring of changes over time

Diagnostic monitoring of changes over time facilitates the differential diagnosis of any placental function disorders and provides a more exact prognostic assessment of the perinatal risk. Most importantly, a combination of biometry and Doppler sonography may reduce perinatal mortality.

6.1.1  Clinical examination

Consensus-based recommendation 5.E10
Expert consensus	Level of consensus +++
It is important to watch out for preeclampsia, especially in cases with FGR from uteroplacental causes.
Recommendation: new

 

MissingLinkText

6.1.2  Sonography (measurement of the fetus)

Consensus-based recommendation 5.E11
Expert consensus	Level of consensus +++
Serial sonographic assessments of fetal growth must be carried out if FGR is present or suspected.
Recommendation: confirmed

Consensus-based recommendation 5.E12
Expert consensus	Level of consensus +++
The interval between individual sonographic assessments of fetal growth should be at least two weeks.
Recommendation: confirmed

 

MissingLinkText

6.1.3  Sonography (amniotic fluid)

Consensus-based recommendation 5.E13
Expert consensus	Level of consensus +++
Sonographic assessment of the amniotic fluid volume must only be interpreted in the context of other monitoring methods.
Recommendation: confirmed

Consensus-based recommendation 5.E14
Expert consensus	Level of consensus +++
The SDP (single-deepest-pocket) method should be used to assess amniotic fluid volumes.
Recommendation: confirmed

 

MissingLinkText

6.1.4  Doppler sonography (umbilical artery)

Consensus-based recommendation 5.E15
Expert consensus	Level of consensus +++
Doppler sonography of the umbilical artery must be carried out as part of the management of FGR, as the use of Doppler sonography may reduce perinatal mortality in high-risk pregnancies.
Recommendation: confirmed

Consensus-based statement 5.S3
Expert consensus	Level of consensus +++
Unremarkable Doppler sonography findings of the umbilical artery are associated with a lower risk of a poor perinatal outcome in cases with early FGR.
Statement: confirmed

Consensus-based statement 5.S4
Expert consensus	Level of consensus +++
Diastolic absent-end flow (AED flow), especially reverse diastolic blood flow (RED flow) in the umbilical artery is often associated with a poor perinatal outcome in cases with FGR.
Statement: confirmed

Consensus-based recommendation 5.E16
Expert consensus	Level of consensus +++
The intervals between Doppler sonography assessments must always be adapted to the severity of FGR and the Doppler sonography findings.
Recommendation: new

Consensus-based statement 5.S5
Expert consensus	Level of consensus +++
If Doppler sonography findings of the umbilical artery are unremarkable, repeat assessments appear to be sufficient in cases with early FGR. It may be useful to carry out assessments more often in cases with severe FGR.
Statement: confirmed

Consensus-based recommendation 5.E17
Expert consensus	Level of consensus +++
It is not clear what the intervals between Doppler sonography assessments should be if Doppler sonography findings of the umbilical artery are pathological. Assessments should be carried out at least once a week in cases with a high pulsatility index (PI > 95th percentile) and assessments should be carried out even more often in cases with ARED flow.
Recommendation: confirmed

Consensus-based recommendation 5.E18
Expert consensus	Level of consensus +++
Doppler sonography assessment of additional vessels (middle cerebral artery, ductus venosus) should be carried out, especially if Doppler sonography findings of the umbilical artery are abnormal.
Recommendation: confirmed

 

MissingLinkText

6.1.5  Doppler sonography (middle cerebral artery)

Consensus-based recommendation 5.E19
Expert consensus	Level of consensus +++
Doppler sonography of the middle cerebral artery should be carried out in addition to Doppler sonography of the umbilical artery in cases with FGR.
Recommendation: confirmed

Consensus-based statement 5.S6
Expert consensus	Level of consensus +++
Pathological Doppler sonography findings of the middle cerebral artery (PI < 5th percentile) in cases with late FGR at the due date increase the risk of delivery by caesarean section and a poor perinatal outcome.
Statement: confirmed

 

MissingLinkText

6.1.6  Doppler sonography (cerebroplacental ratio, CPR)

Consensus-based statement 5.S7
Expert consensus	Level of consensus +++
It is currently not possible to conclusively establish the value of the cerebroplacental ratio (CPR), i.e., the ratio of the PI of the middle cerebral artery and the PI of the umbilical artery, for monitoring FGR. We will have to await the results of current ongoing studies.
Statement: new

 

MissingLinkText

6.1.7  Doppler sonography (ductus venosus)

Consensus-based statement 5.S8
Expert consensus	Level of consensus +++
Lack of an a-wave or reverse flow of the a-wave on Doppler sonography of the ductus venosus are indications of imminent or already existing acidosis and the risk of fetal death.
Statement: confirmed

Consensus-based recommendation 5.E20
Expert consensus	Level of consensus +++
Doppler sonography of the ductus venosus must be part of monitoring early FGR.
Recommendation: confirmed

 

MissingLinkText

6.1.8  Doppler sonography (other vessels)

The predictive value of Doppler sonography of the uterine arteries in the last third of pregnancy is not clear as there are no evidence-based data. Doppler sonography of other arteries (e.g., fetal aorta) and veins (e.g., umbilical vein, inferior vena cava) is currently only recommended in the context of medical research because evidence for this is still lacking.

 

MissingLinkText

6.1.9  Cardiotocography (CTG)

Consensus-based recommendation 5.E21
Expert consensus	Level of consensus +++
Cardiotocography (CTG) must not be the only method used to monitor FGR.
Recommendation: confirmed

 

MissingLinkText

6.1.10  Computerized CTG (Oxford CTG)

Consensus-based recommendation 5.E22
Expert consensus	Level of consensus +++
In cases with FGR, analysis of short-term variation must be done using computerized CTG (Oxford CTG).
Recommendation: new

 

MissingLinkText

6.1.11  Biophysical profile

Carrying out a BPP is time-consuming and the results are unclear in 15 – 20% of cases, especially for severe SGA fetuses [46]. Moreover, the use of BPP in high-risk pregnancies does not provide a more precise prediction of fetal acidosis [47], [48] nor is it associated with reduced perinatal mortality [49]. BPP has a high false-negative rate in these cases [48].

Other studies have even reported that the caesarean section rate increased when BPP was done but did not improve the perinatal outcomes [49], which is why the BPP score is not generally used in German-speaking countries.

 

MissingLinkText

 

MissingLinkText

6.2  Antenatal corticosteroids

Consensus-based recommendation 5.E23
Expert consensus	Level of consensus +++
A single administration of antenatal corticosteroids should be done in a case with FGR between 24 + 0 GW and 34 + 0 GW if delivery of the infant is expected within the next 7 days.
Recommendation: confirmed

 

MissingLinkText

6.3  Magnesium sulfate for neuroprotection

Consensus-based recommendation 5.E24
Expert consensus	Level of consensus +++
Magnesium sulfate may be administered for neuroprotection when a preterm birth is expected < 32 + 0 GW as there is some evidence that it has a neuroprotective effect.
Recommendation: confirmed

 

MissingLinkText

6.4  Delivery

6.4.1  Place of birth

Consensus-based recommendation 5.E25
Expert consensus	Level of consensus +++
If FGR is present, the infant must be born in a perinatal center with a neonatal intensive care unit with an experienced team present to ensure immediate continuous care.
Recommendation: confirmed

 

MissingLinkText

6.4.2  Time of birth

Consensus-based recommendation 5.E26
Expert consensus	Level of consensus +++
Early FGR and late FGR must be assessed differently. Increasing deterioration in a case of early FGR is reflected in abnormalities of venous Doppler sonography parameters and, in cases with late FGR, mainly in the cerebral Doppler sonography findings.
Recommendation: confirmed

Consensus-based recommendation 5.E27
Expert consensus	Level of consensus +++
When planning the time of birth, the risks of preterm birth must be weighed up against the risks of remaining in utero.
Recommendation: confirmed

Consensus-based statement 5.S9
Expert consensus	Level of consensus +++
Gestational age is a significant factor affecting survival without morbidities.
Statement: confirmed

Consensus-based recommendation 5.E28
Expert consensus	Level of consensus +++
If there are recurrent treatment-resistant decelerations of the CTG, active management must include delivery of the infant.
Recommendation: new

Given that there is a high false-positive rate, the general rule for active management (= maximum therapy) is that the infant must be delivered in cases with recurrent, treatment-resistant decelerations in the CTG [50]. According to the classification of the FIGO, the definition of repeated decelerations is when they occur in more than 50% of contractions [51]. More than two decelerations per hour were classified as recurrent decelerations in a cohort of early FGR [52].

Consensus-based recommendation 5.E29
Expert consensus	Level of consensus +++
If there is a short-term variation (STV) < 2.6 ms between week 26 + 0 and week 28 + 6 of gestation or a STV < 3 ms between 29 + 0 and 31 + 6 GW, delivery of the infant must be considered.
Recommendation: confirmed

Consensus-based recommendation 5.E30
Expert consensus	Level of consensus +++
The infant must be delivered if the a-wave (AEDF) is repeatedly absent or there is reversed a-wave flow (REDF) on Doppler sonography of the ductus venosus.
Recommendation: new

Consensus-based recommendation 5.E31
Expert consensus	Level of consensus +++
The infant should be delivered by 32 + 0 GW at the latest if reversed end-diastolic flow (REDF) is detected on Doppler sonography of the umbilical artery.
Recommendation: confirmed

Consensus-based recommendation 5.E32
Expert consensus	Level of consensus +++
The infant should be delivered by 34 + 0 GW at the latest if absent end-diastolic flow (AEDF) is detected on Doppler sonography of the umbilical artery.
Recommendation: confirmed

Consensus-based recommendation 5.E33
Expert consensus	Level of consensus +++
Delivery of the infant from week 37 + 0 of gestation should be aimed for if increased pulsatility (PI > 95th percentile) is found on Doppler sonography of the umbilical artery.
Recommendation: confirmed

Consensus-based recommendation 5.E34
Expert consensus	Level of consensus ++
Delivery of the infant from week 37 + 0 of gestation may be offered in cases with repeated, isolated, decreased pulsatility on Doppler sonography of the middle cerebral artery (PI < 5th percentile).
Recommendation: new

Consensus-based recommendation 5.E35
Expert consensus	Level of consensus +++
Delivery of the infant from week 37 + 0 of gestation may be aimed for if the CPR (cerebroplacental ratio) is low.
Recommendation: confirmed

Calculation of the CPR (cerebroplacental ratio), the ratio of the PI (or RI) of the middle cerebral artery, and the PI (or RI) of the umbilical artery is useful when deciding when to terminate a FGR pregnancy. However, there is no evidence of a precise CPR threshold value which reliably predicts a poor perinatal outcome. Values of < 1 or < 5th percentile are often considered pathological [53]. In a Delphi process, the final consensus was that a CPR < 5th percentile was an important diagnostic criterion for FGR (see chapter 1: Definition) [5]. This threshold value has also been included in international recommendations [2].

Because of concerns about interobserver reliability during Doppler measurement (PI of the middle cerebral artery, CPR, UCR, and ductus venosus), measurements should be repeated within 24 hours for confirmation if the initial findings were pathological to avoid false-positive results, especially if the time of delivery depends on these findings.

Consensus-based recommendation 5.E36
Expert consensus	Level of consensus +++
In the case of an isolated SGA fetus (unremarkable Doppler sonography findings, no additional risks), delivery may be considered from week 39 + 0 of gestation.
Recommendation: new

Consensus-based recommendation 5.E37
Expert consensus	Level of consensus +++
An isolated SGA fetus (unremarkable Doppler sonography findings, no additional risks) must not be delivered later than the due date.
Recommendation: confirmed

The parents must be involved in all decisions and the consequences of the different options must be explained. The higher risk of intrauterine fetal death when an observant approach is taken must be set against the higher mortality and morbidity risks of preterm delivery. Close collaboration with the neonatologist is required to provide the parents with sufficient information.

 

MissingLinkText

6.4.3  Mode of delivery

Consensus-based statement 5.S10
Expert consensus	Level of consensus +++
Not every pregnant woman with FGR will require caesarean section.
Statement: new

Consensus-based recommendation 5.E38
Expert consensus	Level of consensus +++
Delivery may be induced in cases with FGR and unremarkable Doppler sonography findings or a higher pulsatility of the umbilical artery (> 95th percentile), but not for cases with ARED flow, with the aim of achieving a vaginal birth. However, the high risk of complications must be considered and continuous intrapartum monitoring is required.
Recommendation: confirmed

 

MissingLinkText

6.4.4  Other recommendations

Outpatient or inpatient care

Consensus-based recommendation 5.E39
Expert consensus	Level of consensus +++
The decision whether a pregnant woman with FGR should receive inpatient or outpatient care should be made on a case-by-case basis.
Recommendation: confirmed

 

MissingLinkText

Bed rest

Consensus-based recommendation 7.E40
Expert consensus	Level of consensus +++
Limiting physical activity and bed rest should not be recommended as part of the management of FGR.
Recommendation: new

 

MissingLinkText

Nutrition

Dietary changes, dietary measures or the intake of additional food supplements (e.g., calcium [54]) showed no benefit [55] and are therefore not recommended.

 

MissingLinkText

Abstaining from smoking

Consensus-based recommendation 5.E41
Expert consensus	Level of consensus +++
All pregnant women must be given the recommendation to stop smoking.
Recommendation: new

 

MissingLinkText

Progesterone

There is insufficient evidence that progesterone reduces FGR [56] and it should therefore not be used for this purpose.

 

MissingLinkText

Maternal oxygen administration

The studies on the benefits of maternal oxygen administration are inadequate and some of them are not methodologically strong. The studies were evaluated in an older Cochrane analysis which found that the evidence to assess the benefits and risks of maternal oxygen administration is insufficient [57]; maternal oxygen administration should therefore not be carried out.

 

MissingLinkText

Other therapies

Many interventions in pregnancy which aim to improve blood flow to the placenta have been investigated [58]. However, neither an increase in plasma volume nor the administration of low-dose ASA [59] or sildenafil [60], [61] were found to be beneficial to prevent FGR and they are therefore not recommended.

Antihypertensive therapy to treat pregnant women with hypertensive disease does not affect fetal growth [62], [63] and should therefore not be used, and nitric oxide donors or vasodilatative substances, both of which have still not been investigated sufficiently, are also not recommended [64]. Irrespective of the above, medication to control maternal blood pressure when the mother has hypertension is useful to prevent maternal morbidity (see guideline “Hypertensive Disorders in Pregnancy: Diagnostics and Therapy”, AWMF Registry No. 015 – 018, Level: S2k).

 

MissingLinkText

 

MissingLinkText

 

MissingLinkText

 

MissingLinkText

7  Summary: management of FGR

The management of FGR is shown in [Fig. 2].

Fig. 2 Management of fetal growth restriction. Abbreviations: AEDF, absent end-diastolic flow; CPR, cerebroplacental ratio; CTG, cardiotocography; cCTG, computerized CTG; FGR, fetal growth restriction; GW, week(s) of gestation; PI, pulsatility index; REDF, reversed end-diastolic flow. [rerif]

 

MissingLinkText

8  Information and counseling

A detailed explanatory and advisory consultation on FGR as a complication of pregnancy should be held with the pregnant woman or the expectant parents and must cover the individual course and further implications. It also needs to be explained that in the current case the infant might only be constitutionally small, which is not inevitably associated with higher perinatal morbidity. The discussion should involve an interdisciplinary group and include specialists for antenatal medicine/obstetricians and neonatologists. Depending on the fetal pathology, pediatricians or human geneticists may be additionally called in. In addition to information about possible causes, the information provided should also include short and long-term consequences, the risk of recurrence in a subsequent pregnancy and, where necessary, possible diagnostic examinations.

The pregnant woman must be advised about the increased maternal and infant risk of cardiovascular disease [65]. Intrauterine fetal death, preterm death, neonatal mortality and morbidity and reduced neurological development are more common in FGR fetuses, both in a current pregnancy and in any subsequent pregnancies [66], [67].

The risk of FGR occurring in any subsequent pregnancy is higher [11], [68], [69], especially if there are additional hypertensive complications [6]. A prospective study found that women with FGR in a previous pregnancy had a significantly higher risk of FGR in a second pregnancy compared to women with no previous pregnancy with FGR (23% versus 3%) [70].

 

MissingLinkText

9  Prophylaxis

A number of different medical constellations and insufficient placental perfusion over the course of pregnancy are associated with an increased risk of developing FGR. The risk of recurrence of FGR after a previous pregnancy with FGR is between 20 and 30% [71]. A number of different prophylactic approaches have been previously evaluated, only a few of which were found to have any evidence-based benefit.

9.1  Acetylsalicylic acid (ASA)

Consensus-based recommendation 7.E42
Expert consensus	Level of consensus +++
In cases with an increased risk of uteroplacental dysfunction and a risk of FGR, the mother should take low-dose ASA (150 mg) prophylactically from ≤ 16 GW.
Recommendation: new

 

MissingLinkText

9.2  Nutrition

Consensus-based recommendation 7.E43
Expert consensus	Level of consensus +++
There is no evidence that special diets or nutritional supplements provide any benefit and they should therefore not be recommended as preventive measures against FGR.
Recommendation: confirmed

 

MissingLinkText

9.3  Heparin

Consensus-based statement 7.S11
Expert consensus	Level of consensus +++
The evidence for the administration of low-weight molecular heparin is insufficient and it should therefore not be recommended, especially in view of possible severe side effects.
Statement: new

 

MissingLinkText

9.4  Nicotine

Consensus-based recommendation 5.E44
Expert consensus	Level of consensus +++
All pregnant woment must be given the recommendation to stop smoking.
Recommendation: confirmed

 

MissingLinkText

9.5  Nitric oxide (NO donors)

The first study on the efficacy of NO donors in pregnancies at risk for FGR was published by Lees in 1998 [72]. A pilot study of 111 women with a higher risk of FGR and preeclampsia showed that the NO donor pentaerythritol tetranitrate (PETN) was able to reduce the risk of severe FGR and perinatal death by 39% and of preterm birth before the 32nd week by 70% [64]. A subsequent prospective, randomized, double-blind multicenter study based on the initial study was unable to confirm these findings but nevertheless showed that PETN intake was associated with a less severe course in high-risk pregnancies [73]. Follow-up examinations of the children at the age of 12 months additionally showed better outcomes for the children born to mothers who had taken PETN [74]. But the preventive effect of PETN on FGR has not yet been definitively established and the long-term results of the children born in this German study who are now six years old are not yet available.

 

MissingLinkText

 

MissingLinkText

10  Screening

Early detection of FGR is essential as FGR not only significantly affects the course of pregnancy but also affects the neonatal outcome [33], [75].

10.1  Medical history

Taking a detailed medical history which particularly focuses on potential risk factors for FGR (see chapter 2: Epidemiology and etiology) is very important. By identifying cases with a higher risk of FGR it is possible to initiate suitable measures to closely monitor at-risk mothers and infants [9].

 

MissingLinkText

10.2  Clinical examination

(see chapter 3.1: Clinical examination)

 

MissingLinkText

10.3  Sonography

Precise determination of the due date using crown-rump length (chapter 3.2.1) is a prerequisite for effective screening. In addition, similar to screening for preeclampsia in the 1st trimester of pregnancy, a combination of different markers (maternal medical history, Doppler sonography of the uterine arteries, mean arterial pressure, PAPP-A, free β-hCG, PlGF, PP13, ADAM 12, and NT) may be used to screen for SGA/FGR [38]. Detection rates of 73% have been reported for FGR with delivery before 37 GW and 46% for FGR in infants delivered after 37 GW have been reported [7], [76].

The last sonography screening in week 29 to 32 of gestation as required by maternity guidelines can detect early FGR but not late FGR. If there is a high risk of FGR, regular growth monitoring and Doppler sonography should be carried out as the pregnancy progresses.

 

MissingLinkText

10.4  Doppler sonography

Consensus-based recommendation 8.E45
Expert consensus	Level of consensus +++
Abnormal Doppler sonography findings of the uterine artery such as high pulsatility (PI > 95th percentile) should be followed by regular growth monitoring with sonography and Doppler sonography of the umbilical artery.
Recommendation: confirmed

 

MissingLinkText

 

MissingLinkText

 

MissingLinkText

 

MissingLinkText

Conflict of Interest/Interessenkonflikt

The conflicts of interest of all the authors are listed in the long, German-language version of the guideline.

• References/Literatur

• 1 Unterscheider J, Daly S, Geary MP. et al. Definition and management of fetal growth restriction: a survey of contemporary attitudes. Eur J Obstet Gynecol Reprod Biol 2014; 174: 41-45
• 2 Lees CC, Stampalija T, Baschat A. et al. ISUOG Practice Guidelines: diagnosis and management of small-for-gestational-age fetus and fetal growth restriction. Ultrasound Obstet Gynecol 2020; 56: 298-312
• 3 Society for Maternal-Fetal Medicine (SMFM). Martins JG, Biggio JR. et al. 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-B17
• 4 American College of Obstetricians and Gynecologistsʼ Committee on Practice Bulletins–Obstetrics and the Society forMaternal-FetalMedicin. ACOG Practice Bulletin No. 204: Fetal Growth Restriction. Obstet Gynecol 2019; 133: e97-e109
• 5 Gordijn SJ, Beune IM, Thilaganathan B. et al. Consensus definition of fetal growth restriction: a Delphi procedure. Ultrasound Obstet Gynecol 2016; 48: 333-339
• 6 Parker SE, Werler MM. Epidemiology of ischemic placental disease: a focus on preterm gestations. Semin Perinatol 2014; 38: 133-138
• 7 Albu AR, Anca AF, Horhoianu VV. et al. Predictive factors for intrauterine growth restriction. J Med Life 2014; 7: 165-171
• 8 Mayer C, Joseph KS. Fetal growth: a review of terms, concepts and issues relevant to obstetrics. Ultrasound Obstet Gynecol 2013; 41: 136-145
• 9 Gaudineau A. [Prevalence, risk factors, maternal and fetal morbidity and mortality of intrauterine growth restriction and small-for-gestational age]. J Gynecol Obstet Biol Reprod (Paris) 2013; 42: 895-910
• 10 Jaddoe VW, Bakker R, Hofman A. et al. Moderate alcohol consumption during pregnancy and the risk of low birth weight and preterm birth. The generation R study. Ann Epidemiol 2007; 17: 834-840
• 11 Ananth CV, Peltier MR, Chavez MR. et al. Recurrence of ischemic placental disease. Obstet Gynecol 2007; 110: 128-133
• 12 Kramer MS, Platt R, Yang H. et al. Are all growth-restricted newborns created equal(ly)?. Pediatrics 1999; 103: 599-602
• 13 Gouin K, Murphy K, Shah PS. et al. Effects of cocaine use during pregnancy on low birthweight and preterm birth: systematic review and metaanalyses. Am J Obstet Gynecol 2011; 204: 340.e1-340.e12
• 14 Maulik D. Fetal growth restriction: the etiology. Clin Obstet Gynecol 2006; 49: 228-235
• 15 Odibo AO, Nelson D, Stamilio DM. et al. Advanced maternal age is an independent risk factor for intrauterine growth restriction. Am J Perinat 2006; 23: 325-328
• 16 Gardosi J, Francis A. Adverse pregnancy outcome and association with small for gestational age birthweight by customized and population-based percentiles. Am J Obstet Gynecol 2009; 201: 28.e1-28.e8
• 17 Blumenshine P, Egerter S, Barclay CJ. et al. Socioeconomic disparities in adverse birth outcomes: a systematic review. Am J Prev Med 2010; 39: 263-272
• 18 Kleijer ME, Dekker GA, Heard AR. Risk factors for intrauterine growth restriction in a socio-economically disadvantaged region. J Matern Fetal Neonatal Med 2005; 18: 23-30
• 19 Shah PS. Knowledge Synthesis Group on Determinants of LBWPT births. Parity and low birth weight and preterm birth: a systematic review and meta-analyses. Acta Obstet Gynecol Scand 2010; 89: 862-875
• 20 Yinon Y, Kingdom JCP, Odutayo A. et al. Vascular dysfunction in women with a history of preeclampsia and intrauterine growth restriction: insights into future vascular risk. Circulation 2010; 122: 1846-1853
• 21 Allen VM, Joseph K, Murphy KE. et al. The effect of hypertensive disorders in pregnancy on small for gestational age and stillbirth: a population based study. BMC Pregnancy Childbirth 2004; 4: 17
• 22 Fink JC, Schwartz SM, Benedetti TJ. et al. Increased risk of adverse maternal and infant outcomes among women with renal disease. Paediatr Perinat Epidemiol 1998; 12: 277-287
• 23 Howarth C, Gazis A, James D. Associations of Type 1 diabetes mellitus, maternal vascular disease and complications of pregnancy. Diabet Med 2007; 24: 1229-1234
• 24 Drenthen W, Pieper PG, Roos-Hesselink JW. et al. Outcome of pregnancy in women with congenital heart disease: a literature review. J Am Coll Cardiol 2007; 49: 2303-2311
• 25 Yasuda M, Takakuwa K, Tokunaga A. et al. Prospective studies of the association between anticardiolipin antibody and outcome of pregnancy. Obstet Gynecol 1995; 86: 555-559
• 26 Costa SL, Proctor L, Dodd JM. et al. Screening for placental insufficiency in high-risk pregnancies: is earlier better?. Placenta 2008; 29: 1034-1040
• 27 Laurini R, Laurin J, Marsal K. Placental histology and fetal blood flow in intrauterine growth retardation. Acta Obstet Gynecol Scand 1994; 73: 529-534
• 28 Salafia CM, Minior VK, Pezzullo JC. et al. Intrauterine growth restriction in infants of less than thirty-two weeksʼ gestation: associated placental pathologic features. Am J Obstet Gynecol 1995; 173: 1049-1057
• 29 Battarbee AN, Palatnik A, Ernst LM. et al. Association of Isolated Single Umbilical Artery With Small for Gestational Age and Preterm Birth. Obstet Gynecol 2015; 126: 760-764
• 30 Khoury MJ, Erickson JD, Cordero JF. et al. Congenital malformations and intrauterine growth retardation: a population study. Pediatrics 1988; 82: 83-90
• 31 Eydoux P, Choiset A, Le Porrier N. et al. Chromosomal prenatal diagnosis: study of 936 cases of intrauterine abnormalities after ultrasound assessment. Prenat Diagn 1989; 9: 255-269
• 32 Powers WF, Kiely JL. The risks confronting twins: a national perspective. Am J Obstet Gynecol 1994; 170: 456-461
• 33 Chauhan SP, Beydoun H, Chang E. et al. Prenatal detection of fetal growth restriction in newborns classified as small for gestational age: correlates and risk of neonatal morbidity. Am J Perinat 2014; 31: 187-194
• 34 Gardosi J, Madurasinghe V, Williams M. et al. Maternal and fetal risk factors for stillbirth: population based study. BMJ 2013; 346: f108
• 35 Rempen A. [Standards in ultrasound examination in early pregnancy. Recommendation of DEGUM Stage III of the German Society of Ultrasound in Medicine (Gynecology and Obstetrics Section) and ARGUS (Working Group of Ultrasound Diagnosis of DGGG). December 2000 revision]. Z Geburtshilfe Neonatol 2001; 205: 162-165
• 36 Standards zur Ultraschalluntersuchung in der Frühschwangerschaft. Leitlinie der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (S1-Level, AWMF-Register Nr. 015/032, August 2010).
• 37 Kehl S, Hösli I, Pecks U. et al. Induction of Labour. Guideline of the DGGG, OEGGG and SGGG (S2k, AWMF Registry No. 015-088, December 2020). Geburtshilfe Frauenheilkd 2021; 81: 870-895
• 38 AWMF 085-002 S2e LL Ersttrimester Diagnostik und Therapie @ 11–13 + 6 Schwangerschaftswochen. 2024. Accessed January 22, 2024 at: https://register.awmf.org/de/leitlinien/detail/085-002
• 39 Groom KM, Poppe KK, North RA. et al. Small-for-gestational-age infants classified by customized or population birthweight centiles: impact of gestational age at delivery. Am J Obstet Gynecol 2007; 197: 239.e1-239.e5
• 40 Figueras F, Figueras J, Meler E. et al. Customised birthweight standards accurately predict perinatal morbidity. Arch Dis Child Fetal Neonatal Ed 2007; 92: F277-F280
• 41 Unterscheider J, Geary MP, Daly S. et al. The customized fetal growth potential: a standard for Ireland. Eur J Obstet Gynecol Reprod Biol 2013; 166: 14-17
• 42 Gardosi J, Chang A, Kalyan B. et al. Customised antenatal growth charts. Lancet 1992; 339: 283-287
• 43 Evertson LR, Gauthier RJ, Schifrin BS. et al. Antepartum fetal heart rate testing. I. Evolution of the nonstress test. Am J Obstet Gynecol 1979; 133: 29-33
• 44 Richtlinien des Gemeinsamen Bundesausschusses über die ärztliche Betreuung während der Schwangerschaft und nach der Entbindung („Mutterschafts-Richtlinien“). Accessed September 20, 2017 at: https://www.g-ba.de/downloads/62-492-1223/Mu-RL_2016-04-21_iK-2016-07-20.pdf
• 45 Grivell RM, Wong L, Bhatia V. Regimens of fetal surveillance for impaired fetal growth. Cochrane Database Syst Rev 2012; (06) CD007113
• 46 Baschat AA, Galan HL, Bhide A. et al. Doppler and biophysical assessment in growth restricted fetuses: distribution of test results. Ultrasound Obstet Gynecol 2006; 27: 41-47
• 47 Turan S, Turan OM, Berg C. et al. Computerized fetal heart rate analysis, Doppler ultrasound and biophysical profile score in the prediction of acid-base status of growth-restricted fetuses. Ultrasound Obstet Gynecol 2007; 30: 750-756
• 48 Kaur S, Picconi JL, Chadha R. et al. Biophysical profile in the treatment of intrauterine growth-restricted fetuses who weigh < 1000 g. Am J Obstet Gynecol 2008; 199: 264.e1-264.e4
• 49 Lalor JG, Fawole B, Alfirevic Z. et al. Biophysical profile for fetal assessment in high risk pregnancies. Cochrane Database Syst Rev 2008; 2008 (01) CD000038
• 50 Lees CC, Marlow N, van Wassenaer-Leemhuis A. et al. 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial. Lancet 2015; 385: 2162-2172
• 51 AWMF 015/083 (S3). Die vaginale Geburt am Termin. AWMF 2020. Accessed March 29, 2021 at: https://www.awmf.org/uploads/tx_szleitlinien/015-083k_S3_Vaginale-Geburt-am-Termin_2021-01_1.pdf
• 52 Wolf H, Gordijn SJ, Onland W. et al. Computerized fetal heart rate analysis in early preterm fetal growth restriction. Ultrasound Obstet Gynecol 2020; 56: 51-60
• 53 DeVore GR. The importance of the cerebroplacental ratio in the evaluation of fetal well-being in SGA and AGA fetuses. Am J Obstet Gynecol 2015; 213: 5-15
• 54 Hofmeyr GJ, Lawrie TA, Atallah AN. et al. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database Syst Rev 2014; (06) CD001059
• 55 Say L, Gülmezoglu AM, Hofmeyr GJ. Maternal nutrient supplementation for suspected impaired fetal growth. Cochrane Database Syst Rev 2003; (01) CD000148
• 56 Meher S, Duley L. Progesterone for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev 2006; 2006 (04) CD006175
• 57 Say L, Gülmezoglu AM, Hofmeyr GJ. Maternal oxygen administration for suspected impaired fetal growth. Cochrane Database Syst Rev 2003; (01) CD000137
• 58 Nozaki AM, Francisco RP, Fonseca ES. et al. Fetal hemodynamic changes following maternal betamethasone administration in pregnancies with fetal growth restriction and absent end-diastolic flow in the umbilical artery. Acta Obstet Gynecol Scand 2009; 88: 350-354
• 59 Newnham JP, Godfrey M, Walters BJ. et al. Low dose aspirin for the treatment of fetal growth restriction: a randomized controlled trial. Aust N Z J Obstet Gynaecol 1995; 35: 370-374
• 60 Lausman A, Kingdom J. MATERNAL FETAL MEDICINE COMMITTEE. Intrauterine growth restriction: screening, diagnosis, and management. J Obstet Gynaecol Can 2013; 35: 741-748
• 61 von Dadelszen P, Dwinnell S, Magee LA. et al. Sildenafil citrate therapy for severe early-onset intrauterine growth restriction. BJOG 2011; 118: 624-628
• 62 Gülmezoglu AM, Hofmeyr GJ. Betamimetics for suspected impaired fetal growth. Cochrane Database Syst Rev 2001; (04) CD000036
• 63 Abalos E, Duley L, Steyn DW. Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database Syst Rev 2014; (02) CD002252
• 64 Schleussner E, Lehmann T, Kahler C. et al. Impact of the nitric oxide-donor pentaerythrityl-tetranitrate on perinatal outcome in risk pregnancies: a prospective, randomized, double-blinded trial. J Perinat Med 2014; 42: 507-514
• 65 Smith GC, Pell JP, Walsh D. Pregnancy complications and maternal risk of ischaemic heart disease: a retrospective cohort study of 129,290 births. Lancet 2001; 357: 2002-2006
• 66 Gordon A, Raynes-Greenow C, McGeechan K. et al. Stillbirth risk in a second pregnancy. Obstet Gynecol 2012; 119: 509-517
• 67 Surkan PJ, Stephansson O, Dickman PW. et al. Previous preterm and small-for-gestational-age births and the subsequent risk of stillbirth. N Engl J Med 2004; 350: 777-785
• 68 Evers AC, van Rijn BB, van Rossum MM. et al. Subsequent pregnancy outcome after first pregnancy with normotensive early-onset intrauterine growth restriction at < 34 weeks of gestation. Hypertens Pregnancy 2011; 30: 37-44
• 69 Bakketeig LS, Bjerkedal T, Hoffman HJ. Small-for-gestational age births in successive pregnancy outcomes: results from a longitudinal study of births in Norway. Early Hum Dev 1986; 14: 187-200
• 70 Voskamp BJ, Kazemier BM, Ravelli AC. et al. Recurrence of small-for-gestational-age pregnancy: analysis of first and subsequent singleton pregnancies in The Netherlands. Am J Obstet Gynecol 2013; 208: 374.e1-374.e6
• 71 Blue NR, Page JM, Silver RM. Recurrence Risk of Fetal Growth Restriction: Management of Subsequent Pregnancies. Obstet Gynecol Clin North Am 2021; 48: 419-436
• 72 Lees C, Valensise H, Black R. et al. The efficacy and fetal-maternal cardiovascular effects of transdermal glyceryl trinitrate in the prophylaxis of pre-eclampsia and its complications: a randomized double-blind placebo-controlled trial. Ultrasound Obstet Gynecol 1998; 12: 334-338
• 73 Groten T, Lehmann T, Städtler M. et al. Effect of pentaerythritol tetranitrate (PETN) on the development of fetal growth restriction in pregnancies with impaired uteroplacental perfusion at midgestation-a randomized trial. Am J Obstet Gynecol 2023; 228: 84.e1-84.e12
• 74 Groten T, Lehmann T, Städtler M. et al. Pentaerythrityl tetranitrate improves the outcome of children born to mothers with compromised uterine perfusion-12-months follow-up and safety data of the double-blind randomized PETN trial. Am J Obstet Gynecol MFM 2024; 6: 101332
• 75 Lindqvist PG, Molin J. Does antenatal identification of small-for-gestational age fetuses significantly improve their outcome?. Ultrasound Obstet Gynecol 2005; 25: 258-264
• 76 Karagiannis G, Akolekar R, Sarquis R. et al. Prediction of small-for-gestation neonates from biophysical and biochemical markers at 11–13 weeks. Fetal Diagn Ther 2011; 29: 148-154

Publication History

Received: 22 January 2025

Accepted: 03 February 2025

Article published online:
07 July 2025