Fetal growth restriction requiring maternal medical care (fetal growth restriction): clinical guidelines

List of Abbreviations

Terms and Definitions

Fetal growth restriction (FGR) is a term describing a pathologically small fetus that has failed to reach its growth potential and carries a high risk of perinatal complications (noted as a significant deceleration in the growth rates of estimated fetal weight (EFW) and/or abdominal circumference (AC) <10th percentile combined with abnormal blood flow on Doppler ultrasound, or EFW and/or AC values <3rd percentile).

Small for gestational age fetus (SGA, small for gestational age, SGA) is a heterogeneous group of fetuses with dimensions below a predefined threshold for the corresponding gestational age, but with a low risk of perinatal complications (a fetus with EFW/AC values between the 3rd and 9th percentiles combined with normal blood flow parameters on Doppler ultrasound and normal growth dynamics of EFW and/or AC) and constitutionally small fetuses.

Percentile (= centile) is a statistical parameter that determines what a measured indicator (height, body weight, body mass index (BMI), etc.) is in individuals of the same age and sex among the entire population. The value of the indicator reflects an individual's position compared to their peers. Each percentile expresses one-hundredth of the frequency of manifestation in the general population

Fetal cardiotocography (CTG) is a method for functional assessment of the fetus's condition during pregnancy and labor based on recording its heart rate and changes in response to uterine contractions, external stimuli, or the fetus's own activity. CTG is an essential part of the comprehensive fetal assessment along with ultrasound examination and Doppler ultrasonography.

Dawes-Redman criteria are cardiotocographic criteria used to assess fetal condition, which additionally include values of short-term variation (STV) and long-term variation (LTV).

Non-stress test (NST): a natural non-invasive functional fetal test characterizing its antenatal condition. It is usually sufficient during CTG to account for the presence of accelerations caused by fetal movement. The test is considered positive (reactive, normal) if at least 2 accelerations are recorded on the CTG during 20 minutes of observation. If 2 accelerations are recorded in a shorter period (less than 20 minutes), the test is terminated and considered reactive.

Short-term variation (STV, English short term variation STV) is an index of the difference between mean pulse intervals recorded during the preceding and succeeding periods equal to 1/16 of a minute (4 s). Normal STV ranges from 4 to 10 ms.

Long-term variability (LTV, English long-term variability LTV) is an index characterizing fetal heart rate variability, calculated as the mean difference between the minimum and maximum pulse intervals for each minute or, in the case of prolonged acceleration, between the maximum amplitude and the baseline level. The normal LTV value in a physiological pregnancy corresponds to 50 ms, which is almost equivalent to 17 bpm. The lower limit of normal LTV values is 30 ms.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Fetal growth restriction (FGR) is a term characterizing a pathologically small fetus that has not reached its growth potential and has a high risk of perinatal complications (there is a significant deceleration in the growth rates of estimated fetal weight (EFW) and/or abdominal circumference (AC) <10th percentile combined with abnormal blood flow according to Doppler ultrasound, or EFW and/or AC values <3rd percentile).

Small for gestational age fetus (SGA, English small for gestational age, SGA) is a heterogeneous group of fetuses with dimensions below a predetermined threshold for the corresponding gestational age but with a low risk of perinatal complications (a fetus with an estimated fetal weight / abdominal circumference between the 3rd and 9th percentiles combined with normal blood flow parameters according to ultrasound Doppler studies and normal growth velocity of the estimated fetal weight and/or abdominal circumference), as well as constitutionally small fetuses.

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

The causes leading to the development of FGR can be divided into 4 groups: maternal, placental, fetal, and genetic [1–6]. Despite their different pathophysiology, they all ultimately lead to the same result: decreased uteroplacental perfusion and fetal nutrition [7, 8]. There is evidence of a possible negative impact of STIs, as well as cytomegalovirus infection in the fetus [9]. The frequency of chromosomal abnormalities such as trisomy 13 (Patau syndrome), 18 (Edwards syndrome), and 21 (Down syndrome) in FGR is higher than in the general population and can reach 7-19% [10, 11]. Risk factors for FGR are given in Appendix A3.3.

1.3 Epidemiology of the Disease or Condition

The prevalence of FGR is 5-10% [12–14], and 10–25% in cases of burdened obstetric and gynecological history and complicated pregnancy [15]. The frequency of FGR is inversely proportional to term gestation and can reach 60% among preterm infants [16].

With a fetal mass (birth weight) of less than the 10th percentile, there is a higher risk of perinatal mortality [17–21], including stillbirth [17, 22]. The highest risk of these complications was observed in fetuses with a birth weight of less than the 3rd percentile [17, 18].

FGR is a risk factor for intranatal complications [23, 24], as well as various, often severe neurological and mental deficits after birth [25, 26].

1.4 Features of Coding the Disease or Condition

O36.5 – Fetal malnutrition and retarded growth, requiring care of mother.

P05 – Slow fetal growth and fetal malnutrition.

P07 – Disorders related to short gestation and low birth weight, not elsewhere classified.

O43 – Placental disorders.

1.5 Classification of the disease or condition

Depending on the time of onset, two main phenotypes of FGR are distinguished: early (when diagnosed before 32 weeks of gestation) and late (when diagnosed after 32 weeks), which differ significantly, primarily in fetal prognosis (Appendix A3.1) [27–30]. In clinical practice, criteria (clinical, echographic, and pathological Doppler ultrasound characteristics) developed by international consensus reached within the Delphi protocol are universally used (Appendix A3.2) [31–33].

Diagnostic criteria for FGR vary depending on guidelines and author groups [34]. The criteria proposed by the international Delphi consensus are the most recognized [31]. Criteria based on EFW <10th percentile using the growth standard developed by Hadlock et al. are also used [30, 35]. Both criteria have comparable characteristics, while the application of Delphi criteria is associated with a better prognosis of adverse neonatal outcomes.

The terms "symmetric form" and "asymmetric form" of FGR are currently not recommended for use, as they are considered not to provide additional information regarding etiology or fetal prognosis [32, 33].

1.6 Clinical presentation of the disease or condition

There is no specific clinical picture for FGR, but FGR is often combined with preeclampsia [36, 37], and FGR must be excluded upon the onset of preeclampsia.

2. Diagnostics, medical indications and contraindications for diagnostic methods

Fetal growth (physical development of the fetus) is a dynamic process; identifying its disorders requires multiple monitoring of fetal growth rates throughout pregnancy. Physical parameters (sizes) of the fetus are determined by measuring head circumference (HC), biparietal diameter (BPD), AC, femur length (FL), and/or EFW calculated using various formulas. These clinical guidelines use terminology for describing deviations in fetal growth/development given in Table 2. Identifying FGR is often difficult because fetal growth cannot be assessed by a single measurement of its dimensions, and growth potential is a hypothetical concept [32].

Table 2 Definitions of SGA and FGR [22, 23, 38, 39]

2.1 Complaints and Anamnesis

2.2 Physical Examination

Physical examination during pregnancy must comply with the clinical guidelines "Normal Pregnancy"¹

Comment: despite low sensitivity and specificity, determination of weight-height parameters and SFH are the only generally available methods of routine physical examination. It is necessary to measure SFH and enter the data into individual charts - gravidity charts (see Appendix A3.8); diagnose suboptimal fetal growth using McDonald's rule, when the height of the uterine fundus is less than ≥ 3 cm of the corresponding gestational age in weeks [46].

Comment: measuring symphysis-fundal height (SFH) starting from 22 weeks can help detect small-for-gestational-age (SGA) fetuses in a timely manner, as growth restriction may appear both between ultrasound examinations at 22 and 32 weeks and after 32 weeks of gestation. An SFH that does not correspond to the gestational age, as well as a BMI > 35 kg/m², large uterine myomas, polyhydramnios, etc., are indications for an additional ultrasound examination.

¹ https://yadi.sk/i/6WWXSxDEH7sjow

2.3 Laboratory Diagnostics

The list of laboratory diagnostic tests during pregnancy must comply with the clinical guidelines for "Normal Pregnancy".¹

Comments: cytomegalovirus infection is the most frequently detected condition. Patients with suspected congenital infections should be referred to an appropriate regional maternal-fetal medicine center for further evaluation.

• Pregnant women in the high-risk group are recommended to undergo serum pregnancy-associated plasma protein A (PAPP-A) and/or serum PlGF testing as part of the 1st trimester screening to identify a high risk of developing SGA and FGR [24, 48–53].

FoR ALevel of Recommendation A (Level of Evidence – 1).

Comment: PAPP-A is a biomarker of placental function in the first trimester, despite its limited prognostic value [51, 52].

If available, when FGR is suspected between viability and 36 weeks, determine PlGF alone or the sFlt1/PlGF ratio [45].

Comment: according to some studies, the use of the ratio of placental growth factor (PlGF) to soluble fms-like tyrosine kinase-1 (sFlt-1) in blood serum may be useful in the differential diagnosis of SGA and FGR [41, 53–57]. However, the lack of convincing interventional clinical trials currently precludes recommending these markers as an additional diagnostic criterion to ultrasound.

¹ https://yadi.sk/i/6WWXSxDEH7sjow

2.4 Instrumental Diagnostics

The list of instrumental diagnostic tests during pregnancy must comply with the clinical guidelines for "Normal Pregnancy".¹

Ultrasound examination

The importance of ultrasound in early pregnancy has been confirmed by many researchers [33, 48, 58–63].

• Pregnant women included in the high-risk group are recommended to undergo a fetal ultrasound at 30–34 weeks of gestation for the timely diagnosis of FGR [1, 31, 42, 43, 66–70] (Appendix A3.9).

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comment: for earlier or later manifestation of FGR, the patient may be scheduled for additional ultrasounds. Fetal ultrasound should include the assessment of abdominal circumference (AC), head circumference (HC), biparietal diameter (BPD), femur length (FL), estimated fetal weight (EFW), and measurement of the deepest vertical pocket (DVP) of amniotic fluid. Oligohydramnios is diagnosed when the DVP of fluid is less than 2 cm and the amniotic fluid index is less than 5 cm [67, 71, 72]. The ultrasound report must indicate the EFW percentile. In 95% of cases, a deviation (calculation error) of the EFW up to 20% from the birth weight is possible [42, 65] (Appendices A3.5, A3.6).

Currently, the INTERGROWTH-21 standards and WHO centile charts are used to assess deviations in the physical development of the newborn. WHO centile values are more sensitive for identifying small-for-gestational-age fetuses, and all recent publications recommend using WHO values if customized standards are not available [77]. If the birth weight and/or length is below the 10th percentile and abnormal Doppler ultrasound characteristics are present, the infant is diagnosed with FGR. Values below the 3rd percentile indicate moderate or severe FGR [40, 78–81].

Doppler ultrasound of uteroplacental blood flow

Comment: Doppler signals in the umbilical arteries are usually abnormal in early-onset placental-mediated fetal growth restriction and usually normal in late-onset placental-mediated fetal growth restriction. Umbilical artery Doppler results may be abnormal if growth restriction is due to aneuploidy (e.g., trisomy 18, trisomy 21, etc.) or other congenital fetal malformations [45].

Comment: after 32 weeks of gestation, patients with SGA and abnormal PI in the uterine arteries are at risk of developing FGR [82].

Comment: currently, in the management of a patient with late FGR, CPR is one of the most important parameters. If the umbilical artery PI is > 95th percentile, monitoring of CPR at least once or twice a week is indicated (see Appendix B) [27]. Evaluation of CPR and middle cerebral artery (MCA) blood flow in pregnancies up to 32 weeks does not affect the timing of delivery or the prediction of adverse outcomes [91–93].

• In cases of FGR with impaired blood flow in the ductus venosus (zero and/or reversed a-wave), it is recommended to perform color Doppler ultrasound of the uteroplacental blood flow including: UA PI, ductus venosus every 24 hours. CTG: twice daily [48, 97–101].

GCR ALoE 2Grade of Recommendation A (Level of Evidence – 2).

Comment: decreased fetal motor activity combined with abnormal blood flow in the DV may indicate the presence of acidosis (fetal umbilical cord pH <7.20) [91, 102].

Fetal Cardiotocography (CTG)

• If FGR or SGA is suspected, it is recommended to refer the pregnant patient for fetal CTG starting from 28 weeks of gestation [94, 100, 103].

GCR ALoE 2Grade of Recommendation A (Level of Evidence – 2).

Comment: despite the high rate of false-positive results in predicting adverse fetal condition, fetal CTG remains a valuable method for diagnosing acute conditions [94, 100, 103].

It is preferable to perform cCTG with short-term variation (STV) assessment as the primary parameter. Pathological cCTG parameters include: STV <2.6 ms regardless of gestational age, and STV <3 ms at 29 weeks or more, as well as spontaneous repetitive decelerations [32, 48].

If cCTG is not available, standard visual CTG assessment (non-stress test (NST)) is used (Appendix A3.7).

• A pregnant patient with FGR is not recommended to undergo fetal functional state assessment using the biophysical profile (BBP) due to its low prognostic value [27, 28, 95].

GPP ALOE 1Grade of Recommendation A (Level of Evidence – 1).

Comment: BBP assessment is the combined result of two methods for monitoring the mother-placenta-fetus system: ultrasound and CTG. Ultrasound monitoring includes assessing the amniotic fluid volume and several types of fetal motor activity (generalized body movements, breathing movements, muscle tone). CTG monitoring allows the evaluation of fetal heart rate variability. Pathological BBP results are used to predict fetal acidemia in countries where color Doppler ultrasound of uteroplacental blood flow is not routinely used [94].

¹ https://yadi.sk/i/6WWXSxDEH7sjow

2.5 Other Procedures

The list of other diagnostic examinations during pregnancy must comply with the clinical guidelines "Normal Pregnancy"¹.

¹ https://yadi.sk/i/6WWXSxDEH7sjow

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

Non-pharmacological and pharmacological methods for managing pregnancy-related complaints, as well as the prescription of vitamins and dietary supplements during pregnancy, must comply with the clinical guidelines "Normal Pregnancy"¹.

3.1. Delivery

The physician's algorithm of action is presented in Appendix B.

• If labor pre-induction is necessary in a pregnant woman with FGR, it is recommended to use mechanical methods (Foley catheter, laminaria, etc.) to reduce the risk of hyperstimulation [109].

GPP ALOE 1Grade of Recommendation A (Level of Evidence – 1).

• A parturient with early-onset FGR is recommended regional anesthesia, as it is preferred both for vaginal delivery and elective cesarean section [32].

GOR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

3.2. Pharmacotherapy

¹ https://yadi.sk/i/6WWXSxDEH7sjow

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Not applicable.

5. Prevention and Dispensary Observation

Methods for preventing complications during pregnancy must comply with the clinical guidelines "Normal Pregnancy"¹.

• At the preconception counseling stage or during the 1st antenatal visit, it is recommended to assess FGR risk factors [12, 13, 45, 129]. FGR risk factors are listed in Appendix A3.3.

GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).

Comments: diagnostic value is attributed to 1 risk factor with an odds ratio (OR) greater than 2.0 or a combination of 3 or more factors with an odds ratio (OR) of less than 2.0. These patients should be classified into the high-risk group for FGR.

• A pregnant patient with a risk of FGR and preeclampsia is recommended to be prescribed oral #acetylsalicylic acid** from 12 weeks of gestation to 36 weeks of gestation at 150 mg/day [102, 130, 131].

GPP ALOE 1Grade of Recommendation A (Level of Evidence – 1).

Comment: an analysis of priority publications has convincingly demonstrated the benefits of evening administration (at bedtime) of low-dose aspirin (150 mg) initiated before 16 weeks and continued until 36 weeks of gestation to reduce the risk of early-onset FGR identified based on expanded combined 1st-trimester screening results [102, 130, 131]. Low-molecular-weight heparin in combination with low-dose aspirin may be used to prevent fetal growth restriction associated with preeclampsia [45].

• In pregnant patients with risk factors for fetal growth restriction (FGR) and obesity or underweight, it is recommended to achieve a BMI <30 kg/m² and >18 kg/m², respectively [12, 132, 133].

Level of recommendation C (LoR C)Level of evidence 4 (LoE 4)Level of recommendation C (level of reliable evidence – 4).

• In pregnant patients with risk factors for FGR, smoking cessation is recommended [12, 132, 134].

Level of recommendation C (LoR C)Level of evidence 4 (LoE 4)Level of recommendation C (level of reliable evidence – 4).

• Pregnant patients with diabetes mellitus are recommended to maintain target glycemic levels to prevent hypoglycemia [47].

Level of recommendation C (LoR C)Level of evidence 5 (LoE 5)Level of recommendation C (level of reliable evidence – 5).

• Pregnant patients with a history of severe FGR (below the 3rd percentile) and induced preterm birth at less than 34 weeks of gestation are recommended to have blood antiphospholipid antibody testing for the diagnosis and timely management of antiphospholipid syndrome as a potential etiological factor for FGR [6].

Level CLevel 3Level of recommendation evidence C (reliability level of evidence – 3).

¹ https://yadi.sk/i/6WWXSxDEH7sjow

² Order No. 1130n dated October 20, 2020 – "Approval of the Procedure for Providing Medical Care in the Field of Obstetrics and Gynecology"

6. Organization of Medical Care

Indications for admission to a Level III hospital:

1. FGR combined with abnormal Doppler parameters and/or oligohydramnios;

2. compromised fetal condition according to cardiotocography (CTG) data.

Indications for discharge from the hospital:

- positive dynamics of the parameters that served as the indication for hospitalization.

7. Additional Information

Not applicable.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Zulfiya S. Khodzhaeva – D.Sc. (Medicine), Professor, Deputy Director for Research at the Institute of Obstetrics, Professor at the Department of Obstetrics and Gynecology, Department of Professional Education, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). No conflict of interest.

2. Nataliya V. Dolgushina – D.Sc. (Medicine), Professor, Deputy Director – Head of the Department of Scientific Activity Organization, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). No conflict of interest.

3. Natalia E. Kan – D.Sc. (Medicine), Professor, Deputy Director for Research, Director of the Institute of Obstetrics, Professor at the Department of Obstetrics and Gynecology, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow).

4. Vladimir A. Klimov – Ph.D. (Medicine), Head of Service, Head of the Medical Care Organization Department, Medical Care Organization and Information Service, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow), Chief Freelancer Specialist of the Russian Ministry of Health. No conflict of interest.

5. Aleksandr I. Gus – D.Sc. (Medicine), Professor, Head of the Ultrasound and Functional Diagnostics Department, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). No conflict of interest.

6. Kamilla T. Muminova – Ph.D. (Medicine), Researcher at the 1st Department of Obstetrics and Pregnancy Pathology, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). No conflict of interest.

7. Natalya V. Protopopova – Head of the Department of Obstetrics and Gynecology, Institute of Postgraduate Medical Education - branch of the Russian Medical Academy of Continuing Professional Education, Chief Freelancer Specialist in Obstetrics and Gynecology of the Russian Ministry of Health in the Irkutsk Region, D.Sc. (Medicine), Professor, Honored Doctor of the Russian Federation. No conflict of interest.

8. Leila V. Adamyan – Academician of the Russian Academy of Sciences, D.Sc. (Medicine), Professor, Deputy Director of the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health, Chief Freelancer Specialist in Obstetrics and Gynecology of the Russian Ministry of Health (Moscow). No conflict of interest.

9. Natalya V. Artymuk – D.Sc. (Medicine), Professor, Head of the Professor G.A. Ushakov Department of Obstetrics and Gynecology, Kemerovo State Medical University of the Russian Ministry of Health, Chief Freelancer Specialist in Obstetrics and Gynecology of the Russian Ministry of Health in the Siberian Federal District (Kemerovo). No conflict of interest.

10. Baranov Igor Ivanovich – D.Sc. (Medicine), Professor, Head of the Department of Scientific and Educational Programs, Department of Research Organization, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health. There is no conflict of interest.

11. Stanislav V. Pavlovich – Ph.D. (Medicine), Associate Professor, Scientific Secretary of the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health, Professor at the Department of Obstetrics, Gynecology, Perinatology and Reproductology, Institute of Professional Education, I.M. Sechenov First Moscow State Medical University (Moscow). No conflict of interest.

12. Nadezhda V. Bashmakova – D.Sc. (Medicine), Professor, Chief Researcher at the Ural Research Institute of Maternity and Infancy Protection, Chief Freelancer Specialist in Obstetrics and Gynecology of the Russian Ministry of Health in the Ural Federal District (Yekaterinburg). No conflict of interest.

13. Vitaly F. Bezhenar – D.Sc. (Medicine), Professor, Head of the Departments of Obstetrics, Gynecology and Neonatology/Reproductology, Head of the Clinic of Obstetrics and Gynecology, Academician I.P. Pavlov First Saint Petersburg State Medical University of the Russian Ministry of Health, Chief Freelancer Specialist in Obstetrics and Gynecology of the Healthcare Committee of the Government of Saint Petersburg (Saint Petersburg). No conflict of interest.

14. Tatyana E. Belokrinitskaya – D.Sc. (Medicine), Professor, Head of the Department of Obstetrics and Gynecology, Faculty of Advanced Training and Professional Retraining, Chita State Medical Academy of the Russian Ministry of Health, Honored Doctor of the Russian Federation, Chief Freelancer Specialist in Obstetrics and Gynecology of the Russian Ministry of Health in the Far Eastern Federal District (Chita). No conflict of interest.

15. Kseniya A. Gorina – Ph.D. (Medicine), Junior Researcher at the 1st Department of Obstetrics and Pregnancy Pathology, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). No conflict of interest.

16. Gagayev Chelebi Gadaevich – D.Sc. (Medicine), Professor at the Department of Obstetrics and Gynecology with a Course in Perinatology, Medical Institute, Peoples' Friendship University of Russia of the Ministry of Science and Higher Education of the Russian Federation. No conflict of interest.

17. Sergey V. Martirosyan – Candidate of Medical Sciences, Chief Physician, Yekaterinburg Clinical Perinatal Center; Associate Professor, Department of Obstetrics and Gynecology, Faculty of General Medicine and Preventive Care, Ural State Medical University (Yekaterinburg). No conflict of interest.

18. Anna I. Malyshkina – Doctor of Medical Sciences, Professor, Director, V.N. Gorodkov Ivanovo Research Institute of Motherhood and Childhood; Head of the Department of Obstetrics and Gynecology, Medical Genetics, Faculty of General Medicine, Ivanovo State Medical Academy of the Russian Ministry of Health; Chief Non-Resident Specialist in Obstetrics and Gynecology of the Russian Ministry of Health in the Central Federal District (Ivanovo). No conflict of interest.

19. Anton V. Mikhailov – Doctor of Medical Sciences, Professor, Chief Non-Resident Specialist in Obstetrics and Gynecology for the Northwestern Federal District (Saint Petersburg). No conflict of interest.

20. Anastasia V. Nikolaeva – Candidate of Medical Sciences, Chief Physician, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow).

21. Anton S. Olenev – Candidate of Medical Sciences, Chief Non-Resident Specialist in Obstetrics and Gynecology, Moscow Healthcare Department; Head of the Perinatal Center Branch, City Clinical Hospital No. 24 of the Moscow Healthcare Department; Associate Professor, Department of Obstetrics and Gynecology with a Course in Perinatology, Medical Institute, RUDN University. No conflict of interest.

22. Vasily A. Petrukhin – MD, Professor, Honored Doctor of the RF, Director of the Moscow Regional Research Institute of Obstetrics and Gynecology (MONIIAG) (Moscow). No conflict of interest.

23. Viktor E. Radzinsky – Doctor of Medical Sciences, Professor, Corresponding Member of the Russian Academy of Sciences, Head of the Department of Obstetrics and Gynecology with a Course in Perinatology, Peoples' Friendship University of Russia (Moscow). No conflict of interest.

24. Vladimir N. Serov – Academician of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Honored Scientist of the Russian Federation, President of the Russian Society of Obstetricians and Gynecologists, Chief Researcher, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). No conflict of interest.

25. Viktor L. Tyutyunnik – Doctor of Medical Sciences, Professor, Leading Researcher, Center for Scientific and Clinical Research, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). No conflict of interest.

26. Ildar F. Fatkullin – Doctor of Medical Sciences, Professor, Head of the Prof. V.S. Gruzdev Department of Obstetrics and Gynecology, Kazan State Medical University; Chief Non-Resident Specialist in Obstetrics and Gynecology of the Russian Ministry of Health in the Volga Federal District (Kazan). No conflict of interest.

27. Zarine V. Khachatryan – Candidate of Medical Sciences, Physician at the Perinatal Center, European Medical Center JSC, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). No conflict of interest.

28. Alexey M. Kholin – Head of the Telemedicine Department, Ultrasound Diagnostics Physician, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). No conflict of interest.

29. Roman G. Shmakov – Doctor of Medical Sciences, Professor of the Russian Academy of Sciences, Director of the Academician V.I. Krasnopolsky Moscow Regional Research Institute of Obstetrics and Gynecology; Head of the Department of Obstetrics and Gynecology, M.F. Vladimirsky Moscow Regional Research Clinical Institute (Moscow). No conflict of interest.

30. Tamara A. Yarygina – Candidate of Medical Sciences, Head of the Department of Ultrasound Diagnostics, Academician V.I. Krasnopolsky Moscow Regional Research Institute of Obstetrics and Gynecology; Researcher at the Perinatal Cardiology Center, A.N. Bakulev National Medical Research Center for Cardiovascular Surgery of the Russian Ministry of Health (Moscow). No conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. Obstetricians-gynecologists

2. Midwives

Table 1. Levels of Evidence (LoE) grading scale for diagnostic methods (diagnostic interventions)

Table 2. Levels of Evidence (LE) rating scale for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table 3. Scale for grading grades of recommendation (GoR) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, rehabilitation interventions)

Appendix A3. Reference Materials

Appendix A3.1. Main characteristics of early and late fetal growth restriction [31, 32]

Appendix A3.2. Diagnostic criteria for early- and late-onset fetal growth restriction based on international Delphi consensus criteria [31]

Appendix A3.3. Risk factors for FGR/small for gestational age (SGA) * [10, 42]

Appendix A3.4. Protocol for ultrasound Doppler study of uteroplacental blood flow

Note: * Evaluated according to indications.

Appendix A3.5. Examples of assessing the dynamics of estimated fetal weight measurements for growth restriction and/or inadequate growth

Inadequate dynamics of fetometric parameter growth, defined as a slowed growth rate of estimated fetal weight (EFW) or abdominal circumference (AC) when EFW and AC percentiles cross two quartile lines on individual growth charts [31], was officially included in the diagnostic criteria for FGR for the first time.

Quartiles are values corresponding to the 25th percentile (lower (first) quartile), the 50th percentile (median, essentially the middle (second) quartile), and the 75th percentile (upper (third) quartile). They divide the initial dataset into 4 equal parts, each corresponding to 25%.

To establish a slowed growth rate of EFW and AC, a difference between two measurements exceeding 2 quartiles is required (i.e., a difference exceeding 50% on the percentile chart).

An example of such a slowed EFW growth rate can be seen in Fig. G3.1 and G3.2, which show that the EFW at 26 weeks of gestation corresponds to the 75th percentile, and at 34 weeks to the 20th percentile (the difference between measurements is 55 (75 – 20 = 55)).

Figures G3.1 and G3.2. Example of an individual EFW growth chart, expressed in grams, with a slowed growth rate. Markers (+) indicate individual values at various stages of pregnancy [81].

Figures G3.3 and G3.4. demonstrate an example of EFW dynamics that correspond to the 75th percentile at 26 weeks of gestation and the 30th percentile at 34 weeks of gestation (the difference between measurements is 45 (75 – 30 = 45)), meaning that such a case cannot be classified as slowed growth dynamics according to consensus data.

Figures G3.3 and G3.4. Example of an individual EFW growth chart, expressed in grams, with non-slowed growth dynamics. Markers (+) indicate individual values at various stages of pregnancy [81].

Figure G3.5. Patterns of estimated fetal weight measurements indicative of fetal growth restriction.

Figure G3.6. Examples of observations on estimated fetal weight dynamics demonstrating a normal growth trajectory. Patients do not require further growth monitoring after 38 weeks and can be monitored in the SGA low-risk group.

Appendix A3.6. Methods for determining exact gestational age:

• When a patient undergoes an ultrasound examination in the 1st trimester of pregnancy, the gestational age is established using the fetal CRL [33, 61, 62, 78]. The international standard for establishing gestational age is the fetal crown-rump length (CRL) at 9 + 0 – 13 + 6 weeks [33, 61, 62, 78].

• When a patient undergoes an ultrasound examination at 14–26 weeks, gestational age is established taking into account the fetal head circumference and femur length [63]. Measurement of additional parameters (biparietal diameter, occipitofrontal diameter, abdominal circumference) does not increase the accuracy of gestational age determination [63].

• During ultrasound, head and abdominal circumferences should be measured using an ellipse, placing calipers on the outer contours of the fetal soft tissues [33].

• It is recommended to use international standards for fetometric parameters and fetal weight, created prospectively in compliance with strict methodology on a large sample of healthy patients (e.g., INTERGROWTH-21st standards) [43]. To date, a large international, multinational, multi-ethnic prospective study of fetal and newborn growth and development has been conducted as part of the INTERGROWTH-21st project, which includes three major studies: the Fetal Growth Longitudinal Study (FGLS), the Newborn Cross-Sectional Study (NCSS), and the Postnatal Follow-up Study of Preterm Infants (PRSN). The main conclusion of the INTERGROWTH-21st project is that indicators of longitudinal fetal skeletal growth and newborn growth at birth are strikingly similar worldwide, provided that maternal health, social conditions, and nutrition are optimal and women have access to evidence-based medical care during pregnancy and childbirth [79]. The developed population-based scale of fetometric and growth parameters is the most optimal for assessing deviations in the physical development of the newborn child and should also be used for children born with FGR. Unlike WHO standards, it takes into account not only the child's sex but also their gestational age (24–42 weeks). If the body weight and/or length is below the 10th percentile, the child is diagnosed with FGR. Values below the 3rd percentile indicate severe FGR.

Appendix A3.7. Parameters for assessing the non-stress test (NST)

When performing antepartum CTG, an evaluation of the non-stress test is necessary. Periodic accelerations usually coincide with fetal movements; these changes begin to be detected from the beginning of the second trimester, and the amplitude and duration of these changes increase with gestational age.

Acceleration during a non-stress test is an increase in fetal heart rate of at least 15 beats per minute and 15 seconds in duration. If there are two or more accelerations, the test is considered reactive.

It must be remembered that the frequency of test reactivity increases from 50% at 24–28 weeks to 85% at 28–32 weeks, and it is advisable to use other acceleration criteria at earlier gestational ages, namely an increase in fetal heart rate of at least 10 beats per minute and 10 seconds in duration.

A non-reactive non-stress test is the absence of accelerations over 40 minutes.

Appendix A3.8. International standards for assessing symphysis-fundal height during pregnancy [80]

International standards for assessing symphysis-fundal height [40]

Appendix A3.9. International standards for assessing fetal growth during pregnancy using percentile charts and tables for estimated fetal weight and abdominal circumference as an example [80]

International fetal growth standards. Estimated fetal weight [150][79]

International fetal growth standards. Fetal abdominal circumference [79]

Appendix A3.10. Table of reference values for ultrasound Doppler parameters of umbilical artery pulsatility index and cerebroplacental ratio

Appendix A3.11. Table of reference values for ultrasound Doppler parameters of uterine artery pulsatility index (arithmetic mean of the right and left uterine artery pulsatility indices)

Appendix B. Physician Action Algorithms

Monitoring, timing, and mode of delivery in FGR and SGA

Appendix C. Patient Information

The pregnant woman or future parents must receive detailed information and comprehensive counseling regarding FGR as a pregnancy complication, as well as the individual clinical course and consequences of FGR. The mother / future parents should also be informed that the baby may be constitutionally small, which can lead to an increased risk of perinatal morbidity. These discussions should be conducted by a multidisciplinary team including a prenatal medicine specialist / obstetrician and a neonatologist. Depending on the fetal pathology identified, consultations with pediatricians and medical geneticists should also be arranged. In addition to information on possible causes, details regarding short-term and long-term consequences, recurrence risk, and, where appropriate, potential diagnostic tests should be provided.

Individual medical, psychological, and social questions of the pregnant woman or future parents regarding the diagnosis should be addressed during a comprehensive multidisciplinary medical consultation. All necessary decisions must be made through a shared decision-making process. The most important outcomes of the informational and counseling sessions must be documented in the perinatal board protocols.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Information is not available.