Medical care for the mother in established or suspected fetal anomalies and injuries, and antepartum fetal death: clinical guidelines

List of Abbreviations

BP – blood pressure.

ALT – alanine aminotransferase

AST – aspartate aminotransferase

WHO – World Health Organization.

CS – caesarean section.

CTG – cardiotocography.

ICD – International Classification of Diseases.

PPH – postpartum hemorrhage.

abruptio placentae – placental abruption.

PT – preterm birth.

PROM – premature rupture of membranes.

US – ultrasound.

HR – heart rate.

Terms and Definitions

Congenital malformation of the fetus – a combination of deviations from the normal structure of the organism arising during intrauterine development.

Chromosomal abnormality of the fetus – a hereditary disease caused by a change in the number or structure of chromosomes.

Preterm birth (PT) – delivery occurring between 22 and 36⁶ weeks of gestation, where the gestational age is determined based on the date of the 1st day of the last menstrual period (in regular menstrual cycles) and fetal ultrasound performed in the 1st trimester.

Delivery by caesarean section (CS) – a method of delivery in which the birth of the child occurs through surgical intervention with incision of the pregnant uterus wall, extraction of the fetus and placenta, and subsequent restoration of uterine integrity.

Term birth – delivery at 37⁰–41⁶ weeks of gestation.

Fetocide – a medical procedure resulting in intrauterine fetal demise.

Intranatal fetal demise – cessation of fetal cardiac activity at a gestational age of more than 22 weeks after the onset of labor until the moment of separation of the fetus from the maternal organism via birth [1].

Stillbirth – the moment of separation of the fetus from the maternal organism via birth at a gestational age of 22 weeks or more with a newborn body weight of 500 grams or more (or less than 500 grams in multiple pregnancies) or, if the birth weight of the child is unknown, with a newborn body length of 25 cm or more in the absence of signs of live birth in the newborn [1].

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Antenatal fetal demise – cessation of fetal cardiac activity at a gestational age of more than 22 weeks before the onset of labor [1].

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

Main etiological factors of intrauterine fetal demise:

A. Direct causes: fetal distress syndrome;

B. Indirect causes (in descending order of significance) [2]:

• unknown causes;

• placental dysfunction;

• congenital malformations of the fetus;

• Rh-factor and ABO blood group incompatibility;

• antiphospholipid syndrome;

• bleeding during pregnancy and childbirth;

• umbilical cord pathology;

• intrauterine infections;

• extragenital maternal diseases (diabetes mellitus, acute and chronic kidney diseases; maternal heart defects, etc.) leading to placental insufficiency;

• pregnancy complications (preeclampsia, eclampsia, placental abruption, etc.) leading to impaired fetoplacental hemodynamics [3];

• labor complications.

Risk factors for antenatal fetal demise [3–5]:

• maternal age over 35 years [4, 5];

• low socioeconomic status [3];

• harmful working conditions of the mother [6];

• bad habits (smoking, alcohol, substance abuse) [7, 8];

• amniotic fluid volume abnormalities (especially oligohydramnios) [9–11];

• history of antenatal fetal demise [12];

• fetal growth restriction syndrome.

Risk factors for intranatal fetal demise:

• nuchal cord with two or more loops;

• short umbilical cord;

• true knot of the umbilical cord;

• large, macrosomic fetus;

• anatomically narrow pelvis;

• congenital malformations of the fetus;

• iatrogenic labor management defects (absence of intrapartum fetal monitoring, untimely decision-making regarding operative delivery) [13, 14].

There are no unified pathophysiological mechanisms of intrauterine fetal death. In the vast majority of cases, it is not possible to establish the true cause of intrauterine fetal death. The direct cause of antenatal or intranatal fetal death is fetal distress syndrome during pregnancy [15].

1.3 Epidemiology of the Disease or Condition

Every year, over 5 million cases of perinatal death and 2.6 million stillbirths are registered worldwide; therefore, a major goal of international public health efforts is to reduce the incidence of preventable stillbirth and neonatal mortality. Even in highly developed countries of Europe and North America, the stillbirth rate does not drop below 1.3‰ [1, 16]. Over the past 9 years, the perinatal mortality rate in the Russian Federation has shown a clear downward trend (2014: 8.81‰, 2022: 6.7‰). The stillbirth rate in the Russian Federation in 2022 was 5.5‰ (2014: 6.02‰), with a maximum regional value of 9.52‰ per 1,000 live births and stillbirths, and a minimum of 3.44‰. At the same time, antenatal fetal death accounted for 93.1% of all stillbirth cases (ranging from 79.5 to 100% across various regions). In the structure of stillbirth in the Russian Federation, the ratio of term to preterm newborns was 1:2. Delivery of patients with antenatal fetal death at the 1st level of medical care in the Russian Federation accounted for 5.3%, at the 2nd level: 43.6%, and at the 3rd level: 51.1%. However, in a number of regions, 25 to 35% of patients with antenatal fetal death are delivered at the 1st level of medical care [17].

It should be noted separately that the frequency of established congenital malformations and chromosomal abnormalities of the fetus incompatible with life, at a gestational age of more than 22 weeks at the time of diagnosis, reaches 0.1% of all pregnancies. Meanwhile, statistics on the frequency of fetocide procedures in this group of pregnant women are lacking [17].

1.4 Features of Coding the Disease or Condition

O35.0 – Congenital malformations of the central nervous system in the fetus requiring maternal medical care

O35.1 – Chromosomal abnormalities in the fetus (suspected) requiring maternal medical care

O35.2 – Hereditary diseases in the fetus (suspected) requiring maternal medical care

O35.3 – Fetal injury (suspected) resulting from maternal viral disease requiring maternal medical care

O35.4 – Fetal damage (suspected) resulting from alcohol exposure requiring maternal medical care

O35.5 – Fetal damage (suspected) resulting from drug use requiring maternal medical care

O35.6 – Fetal damage (suspected) resulting from radiation requiring maternal medical care

O35.7 – Fetal damage (suspected) resulting from other medical procedures requiring maternal medical care

O35.8 – Other fetal abnormalities and damage (suspected) requiring maternal medical care

O35.9 – Fetal abnormality and damage requiring maternal medical care, unspecified

O36.4 – Intrauterine death requiring maternal medical care

O83.4 – Destructive operation for delivery

1.5 Classification of the disease or condition

• Antenatal fetal death.

  - early stillbirth (22–27 weeks of gestation);

  - late stillbirth (28–36 weeks);

  - stillbirth at term (37 weeks and more)

• Intranatal fetal death.

1.6 Clinical presentation of the disease or condition

Characteristic clinical symptoms of intrauterine fetal death:

1. Absence of fetal movements.

2. Pulling pain in the lower abdomen and increased uterine tone are possible.

3. In 25% of patients, bloody discharge from the genital tract (ranging from slight to moderate, usually recurrent in nature).

4. Lagging of the uterine fundal height compared to the estimated gestational age.

5. Increased uterine tone [18].

A decrease in the frequency of fetal movements is observed in 70% of antenatal fetal death cases 1–3 days prior to its occurrence. Prolonged retention of a dead fetus in the uterine cavity (more than 7 days) sharply increases the risk of coagulopathic complications and the incidence of purulent-septic complications in labor and the postpartum period [19, 20].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria suggesting intrauterine fetal death:

1) absence of fetal movements;

2) appearance of intermittent bloody discharge from the genital tract;

3) absence of fetal heart sounds on auscultation or cardiotocography;

4) increased uterine tone.

Criteria for establishing the diagnosis/condition:

The presence of antenatal fetal death prior to delivery is confirmed by fetal ultrasound based on the absence of visualization of fetal heart contractions and blood flow in its vessels during color Doppler imaging.

Indications for medical termination of pregnancy after 22 weeks of gestation are determined in the presence of fetal congenital syndromes and/or malformations by a perinatal council involving specialist physicians from 3rd-level obstetric medical organizations. When the council establishes the presence of congenital fetal malformations incompatible with life, or combined fetal malformations with an unfavorable prognosis for life and health, leading to permanent loss of bodily functions due to the severity and extent of the lesion in the absence of effective correction methods, the pregnant woman is provided with information about the possibility of artificial termination of pregnancy for medical reasons and is informed about the medical organization where this can be performed. Based on the collected medical information, the council invites the patient to make a decision on further prolongation or termination of pregnancy. The result of the perinatal council is the final diagnosis and conclusion. The council conclusion is signed by all members of the council, approved by the signature of the head of the medical organization, and certified by its seal. The pregnant woman is invited to endorse the council conclusion with her own signature. The council conclusion is drawn up in three copies (one remains in the medical organization where the perinatal council was held, while the second and third are issued to the pregnant woman for presentation to medical organizations providing antenatal care and subsequent medical assistance [21].

2.1 Complaints and Anamnesis

• When taking the obstetric and gynecological history for timely care, it is recommended to pay attention to decreased fetal motor activity in the II–III trimesters of pregnancy as one of the characteristic complaints preceding antenatal fetal death [4, 19, 20, 22–25].

LeveL of Recommendation BGrade of Evidence 2LeveL of Recommendation B (Grade of Evidence - 2).

2.2 Physical Examination

• Upon admission to the hospital, it is recommended to determine the gestational age and expected date of delivery based on the date of the last menstruation and fetal ultrasound data (optimally, 1st-trimester ultrasound) to determine patient management tactics [30].

GCR BLEL 3Recommendation Grade B (Level of Evidence — 3).

Comments: in the absence of 1st-trimester ultrasound and lack of information on the date of the last menstruation, gestational age and expected date of delivery can be established using other ultrasound data. If the gestational age calculated from the last menstrual period differs from the 11–14 weeks ultrasound by more than 5 days, gestational age should be established based on ultrasound data [31].

• Upon admission to the hospital of a patient with suspected antenatal fetal death, it is recommended to measure body temperature for the purpose of diagnosing infectious and inflammatory complications of pregnancy [34–38].

GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).

• Upon admission to the hospital, it is recommended to perform fetal auscultation using a fetal Doppler or obstetric stethoscope for the timely diagnosis of intrauterine fetal compromise or antenatal death [33].

Level of Recommendations CEvidence Level 5Level of recommendations C (evidence level - 5).

• Upon admission to the hospital, it is recommended to perform a bimanual vaginal examination to assess the state of the birth canal [39].

GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).

2.3 Laboratory Diagnostics

Comments: As part of the general clinical biochemical blood test (determination of bilirubin level (medical service code: A09.05.021, A09.05.022, A09.05.022.001, A09.05.022.002), ALT, AST, creatinine, urea, total protein, electrolytes (K⁺, Mg²⁺, Na⁺, Cl^-)), as part of the hemostasis study (determination of fibrinogen level, D-dimer, activated partial thromboplastin time, international normalized ratio, prothrombin time in maternal blood plasma [2, 40–42].

2.4 Instrumental Diagnostics

• Fetal cardiotocography is recommended in pregnant patients to diagnose fetal distress syndrome and possible antenatal death. Diagnostic criteria for this condition are determined by clinical guidelines for fetal growth restriction and distress. The absence of fetal heartbeat on cardiotocography requires a fetal ultrasound examination for reliable diagnosis of possible intrauterine fetal death [45, 46].

GCR CLOE 4Grade of Recommendation C (Level of Evidence - 4).

• Fetal ultrasound examination is recommended as the most reliable method for diagnosing intrauterine fetal death when antenatal death is suspected [41].

GPP CLoE 5Level of Evidence/Grade of Recommendation C (level of evidence - 5).

Comments: a reliable criterion for intrauterine fetal death is the absence of visualized heart contractions and umbilical artery blood flow on ultrasound and Doppler examination. To reliably diagnose antenatal fetal death when suspected, fetal ultrasound and cardiotocography must be performed in the admission department [48].

2.5 Other Procedures

Comments: upon admission of a patient with suspected antenatal fetal death, the examination by an obstetrician-gynecologist should be performed as quickly as possible in the admission department of the medical facility.

Comment: the presence of signs of fetal maceration does not allow for a reliable assessment of the time elapsed since intrauterine fetal death occurred, as its development time depends on the cause of antenatal death [51].

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

3.1 Preparation for delivery (Appendix B).

• Patients with antenatal fetal death are at high risk for bleeding during pregnancy, labor, and the postpartum period, as well as purulent-septic and thromboembolic complications; therefore, their prevention is recommended in accordance with current clinical guidelines [52].

GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).

Comment: see clinical guidelines: "Venous complications during pregnancy and the postpartum period. Obstetric thromboembolism", "Postpartum hemorrhage".

• When delivering patients with intrauterine fetal death, it is recommended to actively manage the third stage of labor. It is recommended to administer uterotonic drugs intravenously slowly after the delivery of the fetus [54].

GPP ALE 2Grade of Recommendations A (Level of Evidence 2).

Comment: Management of labor in intrauterine fetal death according to the clinical guidelines "Normal labor. Singleton labor, spontaneous delivery in occipital presentation". Instrumental curettage of the uterine cavity in the early postpartum period is contraindicated due to the high risk of coagulopathic bleeding and septic complications [55].

• During artificial termination of pregnancy at a gestational age ≥22 weeks, amniotomy is recommended to induce labor once full cervical ripening is achieved (8 points or more on the Bishop score - see Appendix G) to shorten the time interval to delivery [56].

GCR CLOE 4Grade of Recommendation C (Level of Evidence - 4).

Comments: Amniotomy with a ripe cervix does not increase the risk of Cesarean section, but shortens the time interval to delivery by an average of 5 hours.

Comment: Fetal elimination is performed under aseptic conditions and with continuous ultrasound guidance. For fetal analgesia, #fentanyl** is administered into the umbilical vein at a dose of 10 mcg/kg. To arrest cardiac activity, administration of a 10% solution of #potassium chloride** into the fetal heart ventricle is indicated. After aspiration of fetal blood to confirm correct needle placement, 2-3 ml of #potassium chloride** solution is administered. If cardiac arrest does not occur, repeated administration of #potassium chloride** is recommended after 30-60 seconds [59, 62]. Asystole should be documented for at least 2 minutes. A follow-up ultrasound examination of the fetus is performed after 30–60 minutes to ensure the absence of fetal heartbeats. Potassium chloride** is a chemical compound, an inorganic compound with the formula KCl. It is a neutral potassium salt of hydrochloric acid. Cardiocentesis may be associated with certain technical difficulties due to the density of the thoracic bone structures. An alternative method is cordocentesis to gain access to the fetal systemic circulation. For fetal analgesia, #fentanyl** is administered into the umbilical vein at a dose of 10 mcg/kg of the estimated fetal weight, and after 3 minutes, to arrest fetal cardiac activity, #lidocaine** is administered at a dose of 100 mg/kg of the estimated fetal weight [60]. Taking a sample of fetal blood for subsequent karyotyping to verify the results of previously performed prenatal diagnosis is mandatory. Another method of arresting fetal cardiac activity can be intrathoracic or intraamniotic administration of #digoxin** (1 mg) [63, 64]. However, intraamniotic administration of #digoxin** is less effective [59, 62]. Digoxin** is a cardiac glycoside that blocks transport Na+/K+-ATPase, resulting in an increase in Na+ content in the cardiomyocyte, which leads to the opening of Ca2+-channels and the entry of Ca2+ into cardiomyocytes. Excess Na+ also leads to accelerated release of Ca2+ from the sarcoplasmic reticulum. An increase in Ca2+ concentration leads to the inhibition of the troponin complex, which exerts an inhibitory effect on the interaction of actin and myosin. The increase in the force and speed of myocardial contraction occurs via a mechanism different from the Frank-Starling mechanism (independent of the degree of preliminary myocardial stretch). As a result of the increased myocardial contractility, the stroke volume of blood flow and cardiac output (CO) increase. It decreases the end-systolic volume and end-diastolic volume of the heart, which, along with an increase in myocardial tone, leads to a reduction in its size and thus a decrease in myocardial oxygen demand. In order to shorten the interval between the time of fetal cardiac activity cessation and the termination of pregnancy, it is advisable to perform the invasive procedure immediately before the first dose of #misoprostol** in the medical termination of pregnancy regimen for medical indications.

Comments: For medical termination of pregnancy at 22⁰-27⁶ weeks for labor induction after fetal cardiac arrest, it is recommended to administer #mifepristone once orally at a dose of 200 mg, followed (after 24 hours) by #misoprostol** 800 mcg vaginally or sublingually, then in the absence of labor activity after 3 hours – #misoprostol** repeatedly 400 mcg sublingually every 3 hours until pregnancy termination (maximum 4 doses) or vaginally 400 mcg every 4 hours until pregnancy termination.

For medical termination of pregnancy at a gestational age of ≥28 weeks for labor induction after fetal cardiac arrest and assessment of the Bishop score (see Appendix G), it is recommended to prescribe #mifepristone once orally at a dose of 200 mg, followed (after 24 hours) by #misoprostol** 25 mcg vaginally every 6 hours or 25 mcg orally every 2 hours (maximum 4 doses) until 2 contractions per 10 minutes are achieved [63, 69].

Comments: Mifepristone is a synthetic oral steroid drug. Currently, mifepristone, a progesterone receptor antagonist widely used for medical abortion, is approved in more than 40 countries. Possessing high affinity for progesterone receptors, mifepristone acts as its antagonist. The mechanism of the abortifacient action of mifepristone is based on its antiprogestogenic effect, caused by blocking the action of progesterone at the receptor level in the endometrium and myometrium, which in turn leads to the suppression of trophoblast development, damage and rejection of the decidua, the onset of uterine contractions, and the development of menstrual-like bleeding, clinically manifested as a medical abortion [21]. Misoprostol** is a synthetic analogue of prostaglandin E1. The mechanism of abortifacient action is associated with the initiation of myometrial smooth muscle contraction and cervical dilation. The ability of misoprostol** to stimulate uterine contractions facilitates cervical ripening and the evacuation of the uterine cavity. Misoprostol** increases the frequency and strength of myometrial contractions while exerting a mild stimulating effect on the smooth muscles of the gastrointestinal tract [21, 72, 73]. The drug should be used for termination of pregnancy in combination with mifepristone only in specialized facilities staffed by appropriately trained medical personnel [21, 32, 63, 65, 66, 74].

Comments: early delivery in multiple pregnancies is indicated only when both fetuses are diagnosed with congenital malformations incompatible with life or combined fetal malformations with an unfavorable prognosis for their life and health, leading to permanent loss of bodily functions due to the severity and extent of the lesion in the absence of effective treatment methods. In all other cases, the possibility of selective fetal reduction of the abnormally developing fetus should be discussed. In multiple pregnancies, the basis for making an adequate management decision is the unambiguous establishment of chorionicity. If one of the fetuses is found to have congenital malformations incompatible with life, or combined fetal malformations with an unfavorable prognosis for its life and health, leading to permanent loss of bodily functions due to the severity and extent of the lesion in the absence of effective treatment methods, selective fetal reduction may be performed to prevent the live birth of an abnormal fetus and reduce the risks of carrying a multiple pregnancy [76–78].

• In the absence of mifepristone, it is recommended to induce abortion with high doses of oxytocin** [21, 32, 63, 66].

GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).

• In the 2nd–3rd trimester of pregnancy, on the day of pregnancy termination (but no earlier than 4 hours later), it is recommended to administer bromocriptine** or cabergoline according to the manufacturer's instructions to suppress/prevent lactation [79, 80].

LeveL of Recommendation BGrade of Evidence 2LeveL of Recommendation B (Grade of Evidence - 2).

3.2 Selection of the delivery method

• Vaginal delivery is recommended to be considered the optimal method of delivery in cases of antenatal fetal death [81–83].

LoR CGoE 4Level of Recommendation C (Grade of Evidence - 4).

• Delivery via CS is not recommended in intrauterine fetal death, except in situations where vaginal delivery carries a higher risk than CS. Indications for CS in intrauterine fetal death include: complete placenta previa and placenta accreta, two or more previous CSs; myomectomy (FIGO types 2–5 or unknown location of the myomatous node) [26, 27], history of hysterotomy (uterine perforation, excision of the tubal corner, excision of a rudimentary horn, history of classical CS, T-shaped or J-shaped incision), presence of an obstruction in the birth canal to fetal delivery (large uterine myoma in the lower segment or cervix; cervical cancer, except for preinvasive and microinvasive forms of cervical cancer) [65], progressive premature detachment of a normally positioned placenta [42], threatening, incipient, or complete uterine rupture [42], eclamptic seizure during labor [83, 86–90].

LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)

3.3 Postpartum period

• In the management of the postpartum period in patients with intrauterine fetal death, it is recommended to closely monitor the patient's condition, implement prevention of postpartum hemorrhage and purulent-septic complications, see the clinical guidelines "Postpartum Infectious Complications" [92].

LoR CGoE 4Level of Recommendation C (Grade of Evidence - 4).

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Comments: antenatal fetal death is a distressing event for parents, who frequently report symptoms of post-traumatic stress for several years; sometimes even 5–6 years after antenatal fetal death, mothers hold a negative perception of their perinatal period [93].

5. Prevention and Dispensary Observation

There is no specific prevention for antenatal fetal death.

Comments: maintaining an interdelivery interval of at least 6 months is optimal.

Comments: at every visit of a pregnant patient after 20 weeks of gestation [98].

Comments: the probability of developing gestational diabetes mellitus is four times higher in patients with a history of stillbirth of unknown etiology [100, 101]. If normal values are recorded at the initial visit, a repeat OGTT is performed at 24–28 weeks [99].

Comments: in the presence of complications in the current pregnancy, the timing of delivery should be individualized, balancing maternal and fetal/neonatal intervention risks against the risks associated with expectant management [100, 101].

6. Organization of Medical Care

To address the viability of the fetus and the necessity of medical termination of pregnancy after 22 weeks of gestation, the patient is referred to a perinatal board. The perinatal board is organized at level III (group) medical facilities. The perinatal board must include an obstetrician-gynecologist, an ultrasound diagnostics physician, a geneticist, a neonatologist, and a pediatric specialist in the field (pediatric cardiologist, surgeon, orthopedist, or neuroologist) corresponding to the fetal condition or disease that serves as the medical indication for artificial termination of pregnancy. To ensure comprehensive medical and social care, the perinatal board may also include a psychologist and a lawyer. Specialist participation may be conducted remotely using modern data transmission and telecommunication facilities.

At the pregnant woman's request, her spouse/partner and other legal representatives may participate in the board.

The board provides the pregnant woman with comprehensive medical information regarding the results of her examination and the nature of the identified fetal developmental anomalies. Based on current medical knowledge, it provides information on the prognosis for fetal life and health both before and after birth, potential treatment methods and associated risks, and potential medical prenatal and postnatal interventions along with their short- and long-term outcomes.

When the board establishes the presence of congenital fetal anomalies requiring specialized, including high-tech, medical care for the fetus or newborn in the perinatal period, the pregnant woman is provided with information regarding a medical organization licensed to provide this type of care, both within the constituent entity and across the Russian Federation.

When the board establishes the presence of congenital fetal anomalies incompatible with life, or combined developmental anomalies with an unfavorable prognosis for life and health leading to permanent loss of bodily functions due to the severity and extent of the lesion in the absence of effective treatment methods, the pregnant woman is provided with information regarding the possibility of medical termination of pregnancy and is informed of the medical organization where it can be performed.

In the event of an informed refusal by the patient to terminate the pregnancy in the presence of congenital fetal anomalies or other combined malformations incompatible with life, information is provided regarding her further management plan in accordance with the Procedure for the Provision of Medical Care to Women during Pregnancy.

Based on the totality of the medical information obtained, the board invites the patient to make a decision regarding the further continuation or termination of pregnancy.

The outcome of the perinatal board consists of a final diagnosis and a conclusion. The conclusion of the board is signed by all board members, approved by the signature of the head of the medical organization, and certified by its seal. The pregnant woman is invited to endorse the board conclusion with her own signature.

The board conclusion is drawn up in three copies (one remains in the medical organization where the perinatal board was held, while the second and third are issued to the pregnant woman for submission to medical organizations providing antenatal care and subsequent medical assistance).

Determination of the medical organization for artificial termination of pregnancy for medical indications

In the event of the pregnant woman's voluntary informed consent and the perinatal board's conclusion regarding the presence of indications for artificial termination of pregnancy for medical indications, the patient is referred: for pregnancies up to 22 weeks — to the gynecology department; for pregnancies of 22 weeks or more — artificial termination of pregnancy (delivery) is performed in a level III (group) obstetric inpatient facility.

When the perinatal board is held in a medical facility other than the one where the artificial termination of pregnancy for medical indications will be performed, a medical commission is established at the latter. The personal composition of the commission and its operational procedure are determined by the head of the medical organization. Upon confirmation of indications, exclusion of contraindications, and determination of the method of artificial termination of pregnancy, the Commission approves a conclusion certified by the signatures of the Commission members and the seal of the medical organization.

The medical commission determines the method of artificial termination of pregnancy and, in the event of prescribing medications at gestational ages not specified in the drug instructions, in accordance with Order of the Ministry of Health of the Russian Federation No. 502n dated May 5, 2012, "On Approval of the Procedure for the Establishment and Activities of a Medical Commission of a Medical Organization", reflects this prescription in the conclusion, which constitutes an integral part of the medical/obstetric history. Information regarding the session and conclusion of the Medical Commission is entered into the "Logbook of Clinical and Expert Work of the Healthcare Facility", accounting form No. 035/u-02.

Diagnosed antenatal fetal death is an indication for emergency hospitalization in an obstetric inpatient facility. Delivery of patients with antenatal fetal death verified prior to the onset of labor is carried out in level II and III perinatal care inpatient facilities. The transportation of patients with a diagnosed antenatal fetal death is carried out by medical transport accompanied by medical personnel prepared to provide emergency care in the event of complications. Delivery of patients with antenatal fetal death is performed taking into account the high risk of complications (obstetric hemorrhage, purulent-septic complications) by a team of physicians including an obstetrician-gynecologist and an anesthesiologist-resuscitologist with sufficient skills to provide emergency care. Availability of a reserve of transfusiological media and readiness to perform surgical intervention in the event of complications are mandatory. When performing the procedure of feticide and artificial termination of pregnancy at a gestational age of ≥22 weeks, hospitalization in the gynecology department of a multidisciplinary hospital or a level III obstetric inpatient facility is indicated.

Discharge of postpartum women from the obstetric inpatient facility is carried out according to general rules with mandatory ultrasound examination of the uterus and pelvic organs under the following conditions:

1) absence of hyperthermia (above 37.2°C) and an uncomplicated postoperative course;

2) absence of pathological changes on ultrasound of the uterus and appendages;

3) absence of signs of mastitis and lactostasis;

4) absence of signs of inflammation in the suture area.

Discharge is possible with non-absorbable suture material followed by suture removal at the place of residence.

7. Additional Information

Factors influencing maternal pregnancy outcomes in antenatal fetal death include [13, 65]:

• gestational age;

• duration of antenatal fetal death prior to seeking medical care;

• condition of the pregnant woman;

• presence of bleeding;

• state of the hemostatic system (presence of coagulopathy).

Maternal outcome is determined not only by the severity of the condition, but also by the timeliness of qualified care.

7.1 Principles of interaction with the patient and her partner

1. Do not underestimate patients' complaints and concerns upon admission, and do not offer false hope in advance.

2. It must be remembered that a parent's reaction to loss is unique and can represent a spectrum of different emotions ranging from sadness to anger and denial. Parents usually found it difficult to realize what had happened. The consequences of perinatal loss are felt not only in the actual loss of a desired child, but also in the loss of self-esteem, the parental role, and confidence in the ability to give birth to a healthy child. The emotional experience creates an atmosphere of despair and confusion in families expecting a joyful event. Medical staff should be aware of this normal range of reactions, allow parents to express their feelings, and support them during this time.

3. Emotional support and acknowledgment of the birth and death of the child are an important part of providing bereavement care.

4. The best way a healthcare professional can support a grieving family is to show impartiality, a deep sense of care, and personal involvement.

5. Do not hide behind "performing" your job, distancing yourself, and staying silent (especially before and during ultrasound); provide honest and timely information and time for decision-making (if possible), support the desire to participate in decision-making, and explain what is happening—your actions and those of other staff members.

6. Communication with parents is preferably conducted in a private setting.

7. One should not argue with parents or evade questions; answer questions honestly and do not avoid eye contact. The patient may request information about why this happened. They should be informed that examinations and tests will be offered to answer this question, but gathering the necessary information may take several weeks.

8. Do not use complex professional terms; explain things in simple, understandable phrases. Clear, easily understandable, and structured information provided delicately and at the appropriate time helps parents.

9. Do not say: "You will have another child," "It's for the best," "It could have been worse," "You can still have children," "Time heals," "It's good that the child died before you got used to them." It is better to use phrases such as: "I am so sorry," "I am sorry," "I wish things had turned out differently," "I don't know what to say," "I feel sad," "I sympathise with you," "Do you have any questions?," "We can talk about this again a little later."

10. Show respect for the child by calling them by name (if one has already been chosen).

11. Spiritual support should be provided, and the cultural background and beliefs of the parents should be respected.

12. Non-verbal confirmation of the diagnosis is desirable, such as showing ultrasound results.

13. It is necessary to explain how and why delivery will be performed. Parents do not expect to go through a vaginal delivery; most expect their child to be born via Caesarean section. It is important to explain the options and the reasons why one option might be better in their individual circumstances. With a vaginal delivery, parents need information, advice, and support at every stage. Looking back, women report that vaginal delivery gave them strength.

14. Autopsy counseling should be conducted in a respectful manner, and the family should understand its purpose and timeframe. Written information should additionally be provided to help them make an informed decision regarding fetal autopsy, as well as information on stillbirth and fetal death rates.

15. The advantages and disadvantages of pain relief options should be thoroughly discussed.

16. Encourage parental contact with the deceased. Do not aggressively urge parents to contact the child. However, parents who choose not to see or hold their child often regret this decision later. Parents should be informed of this and offered this opportunity more than once. The parents' choice should be supported by the staff, and the time spent with the child should be determined by the parents themselves. It is worth explaining in advance what their child will look like.

17. Keep in mind that parents would like space to support each other in private; seeing and hearing other mothers and infants can exacerbate parents' suffering. At the same time, do not ignore them or avoid visiting them; staff involvement improves the experience.

18. Notify key staff of medical organizations currently and future involved in providing care about the situation. Also consider using special stickers, for example, on the door of a bereaved mother's room, so that staff are aware of her condition.

19. Avoid sedatives.

20. If possible and with the parents' consent, provide a memory box including, for example, photographs, first clothes, a bracelet, an identification tag, a lock of hair, and leaflets about the grief process and bereavement support groups.

21. Parents often blame their own actions for the stillbirth and feel guilty. Parents must be assured that they were not the cause.

22. The woman and her partner must be informed that each of them may have completely different coping mechanisms, which will require mutual respect and understanding.

23. Complete information about the postpartum period must be provided (including in written form):

a. Physical symptoms — lactation period, pain afterpains, bleeding;

b. Psychological symptoms — risks of developing depression, postpartum depression, anxiety, post-traumatic stress disorder;

c. Risk factors for psychological problems after stillbirth;

d. How often the emotional reactions of men and women differ;

e. Financial considerations and rights – maternity benefits, maternity leave;

f. Support groups and services;

g. Stillbirth certificates and registration;

h. Follow-up care.

24. When discussing the results of the fetal autopsy, it is desirable that medical professionals who previously interacted with the parents be present.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Vladimir A. Klimov – Cand. of Sci. (Med.), Head of the Medical Care Organization and Information Service Department, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). There is no conflict of interest.

2. Anton V. Mikhailov – Chief freelance specialist in obstetrics and gynecology of the Ministry of Health of the Russian Federation in the North-Western Federal District, Chief Physician of Maternity Hospital No. 17 of St. Petersburg, Chief Researcher at the Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott, Professor of the Departments of Obstetrics, Gynecology and Reproductology at the First Pavlov St. Petersburg State Medical University and I.I. Mechnikov North-Western State Medical University, Dr. of Sci. (Med.), Professor. There is no conflict of interest.

3. Elrad Yu. Amiraslanov – Cand. of Sci. (Med.), Head of the Obstetric Department, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). There is no conflict of interest.

4. Nadezhda V. Bashmakova – Dr. of Sci. (Med.), Professor, Chief Researcher at the Ural Research Institute of Maternity and Infancy, Chief freelance specialist in obstetrics and gynecology of the Russian Ministry of Health in the Ural Federal District (Yekaterinburg). There is no conflict of interest

5. Dmitry M. Belousov – Cand. of Sci. (Med.), Head of Clinical Work at the Department of Ultrasound and Functional Diagnostics, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). There is no conflict of interest.

6. Natalia E. Kan – Dr. of Sci. (Med.), Professor, Deputy Director, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). There is no conflict of interest.

7. Sergey V. Martirosyan – Cand. of Sci. (Med.), Deputy Chief Physician for Obstetric and Gynecological Care, City Clinical Hospital No. 67 (Moscow). There is no conflict of interest.

8. Anastasia V. Nikolaeva – Cand. of Sci. (Med.), Chief Physician, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). There is no conflict of interest.

9. Inna A. Ushakova – Cand. of Sci. (Med.), Head of the 2nd Obstetric Department, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). There is no conflict of interest.

10. Roman G. Shmakov – Doctor of Medical Sciences, Professor of the Russian Academy of Sciences, Director of the Institute of Obstetrics, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). There is no conflict of interest.

11. Olga I. Mikhailova – Researcher at the 2nd Physiological Department, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). There is no conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. Obstetricians-gynecologists.

2. Students; residents, postgraduate students in obstetrics and gynecology

3. Faculty members, researchers

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

Table 2. Scale for grading levels of evidence certainty (LEC) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table 3. Grade of Recommendation (GoR) scale for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines.

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

1. Federal Law No. 323-FZ "On the Fundamentals of Protecting Citizens' Health in the Russian Federation" dated November 21, 2011.

2. Collection of the Federal Research Institute for Health Organization and Informatics of the Russian Ministry of Health, "Main indicators of maternal and child health, the activities of the child and maternity welfare services in the Russian Federation", Moscow, 2019.

3. Order of the Ministry of Health of the Russian Federation No. 203n dated May 10, 2017 "On Approval of Criteria for Assessing the Quality of Medical Care".

4. Order of the Ministry of Health of the Russian Federation No. 1130n dated October 20, 2020, "On Approval of the Procedure for Providing Medical Care in the Field of Obstetrics and Gynecology".

5. Order of the Russian Ministry of Health No. 804n dated October 13, 2017 (as amended on April 16, 2019) "On Approval of the Nomenclature of Medical Services".

6. Order of the Ministry of Health of the Russian Federation No. 1687r dated December 27, 2011, "On Medical Criteria for Birth, the Form of the Birth Certificate, and the Procedure for Its Issuance"

7. ACOG Practice Bulletin No. 202: Gestational Hypertension and Preeclampsia.

8. ACOG Committee Opinion Number 712, August 2017: Intrapartum Management of Intraamniotic Infection.

9. ACOG committee opinion No. 433: optimal goals for anesthesia care in obstetrics. ACOG Committee on Obstetric Practice.

10. ACOG. Intrapartum Fetal Heart Rate Monitoring: Nomenclature, Interpretation, and General Management Principles Replaces Practice Bulletin Number 70, December 2005. Reaffirmed 2017

11. ASA Committee on Occupational Health Task Force on Infection Control. 2007.

12. Commissioned by the National Institute for Health and Clinical Excellence «Caesarean section» National Collaborating Centre for Women’s and Children’s Health. Commissioned by the National Institute for Health and Clinical Excellence. November 2011

13. ACOG Committee Opinion No. 382: Fetal Monitoring Prior to Scheduled Cesarean Delivery. Committee on Obstetric Practice.

14. NICE Caesarean section Clinical guideline Published: 23 November 2011Last updated August 2019

15. RCOG. Classification of urgency of caesarean section: a continuum of risk. Good Practice No. 11, April 2010

16. The Cochrane Collaboration. Techniques for assisting difficult delivery at caesarean section (Review) 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

17. Guidelines for Perinatal Care. 8th Edition. ACOG&AAP, 2017

18. Antenatal Care. Routine care for the Healthy Pregnant Woman. NICE&NCCWCH, RCOG Press 2008.

Appendix B. Physician Action Algorithms

Algorithm for fetocide and pregnancy termination at 220–276 weeks of gestation

Algorithm for labor induction in antenatal fetal death or after elimination – cardiac arrest of the fetus, at a gestational age of 22 weeks + 0 days – 27 weeks + 6 days in patients without a uterine scar:

Day 1: Assessment of the obstetric situation, administration of #mifepristone 200 mg orally. Intracervical administration of osmotic dilators.

Day 2: administration of #misoprostol** 200 mcg vaginally or sublingually. Thereafter – in the same dose every 6 hours (up to a maximum of 5 doses).

With the onset of regular labor contractions, neuroaxial analgesia is advisable. Amniotomy is performed after entering the active phase of labor (with cervical dilation of 3 cm or more).

Algorithm for labor induction in antenatal fetal death or after elimination – cardiac arrest of the fetus, at a gestational age of 28 weeks + 0 days in patients without a uterine scar.

With the onset of regular labor contractions, neuroaxial analgesia is advisable.

Algorithm for labor induction in antenatal fetal death or after elimination – cardiac arrest of the fetus, at a gestational age of 22 weeks + 0 days in patients with a uterine scar (low risk of uterine scar rupture)

Low risk of uterine scar rupture (uterine scar after lower segment cesarean section, unknown uterine incision type during previous cesarean section)

Given the low risks of uterine rupture and the high rate of vaginal delivery, in this cohort of patients, delivery by cesarean section due to antenatal fetal death or after elimination – cardiac arrest of the fetus, should be avoided, since cesarean section is associated with potential maternal morbidity and mortality without fetal benefit.

Prostaglandins are not used for labor induction in the presence of a uterine scar after a cesarean section due to the high risk of uterine rupture.

With the onset of regular labor contractions, neuroaxial analgesia is advisable.

Algorithm for labor induction in antenatal fetal death or after elimination – cardiac arrest of the fetus, at a gestational age of 22 weeks + 0 days in patients with a uterine scar (high risk of uterine scar rupture)

High risk of uterine scar rupture:

• uterine scar after classical, fundal, T-shaped, J-shaped cesarean section;

• history of prior uterine rupture;

• unintentional extension of the uterine incision during previous cesarean section

• uterine scar after >1 lower segment cesarean section,

• history of preterm abdominal delivery before 28 weeks

• myomectomy (FIGO type 2-5 or unknown location of the myoma node)

• History of hysterotomy.

In patients at high risk of uterine scar rupture with antenatal fetal death or after elimination – cardiac arrest of the fetus, delivery by cesarean section is indicated. If the patient wishes to attempt a vaginal delivery, careful counseling about the risks associated with this method of delivery and close monitoring of the patient during labor are necessary.

The algorithm for labor induction upon refusal of cesarean section is similar to the induction algorithm in patients at low risk of uterine scar rupture.

Pregnancy termination in multiple pregnancy

Pregnancy termination in multiple pregnancy is indicated only when both fetuses are found to have congenital malformations incompatible with life or combined fetal malformations with an unfavorable prognosis for their life and health, leading to permanent loss of bodily functions due to the severity and extent of the lesion in the absence of effective treatment methods. In all other cases, the possibility of selective cardiac arrest of the abnormally developing fetus should be discussed.

In multiple pregnancy, the basis for making an adequate management decision is the unambiguous determination of the chorionicity type.

When congenital malformations incompatible with life or combined fetal malformations with an unfavorable prognosis for its life and health, leading to permanent loss of bodily functions due to the severity and extent of the lesion in the absence of effective treatment methods, are detected in one of the fetuses, selective fetal elimination may be performed to prevent the live birth of the anomalous fetus and reduce the risks of carrying a multiple pregnancy.

In heterochorial heteroamniotic multiple pregnancy, due to the presence of independent hemocirculatory systems of the fetuses, cardiac arrest of the anomalous fetus can be performed using techniques applied for this purpose before pregnancy termination for medical indications in singleton pregnancy.

In monochorionic multiples, vascular anastomoses are always present in the placenta between the circulatory systems of the fetuses. Therefore, prior to the delivery of the healthy fetus, the use of medications to terminate the cardiac activity of the abnormally developed fetus is contraindicated. In monochorionic multiples, to arrest the development of fetuses with congenital life-threatening anomalies or combined fetal anomalies with an unfavorable prognosis for life and health—leading to permanent loss of bodily functions due to the severity and extent of the lesion in the absence of effective treatments—antenatal fetoscopic surgical techniques may be used: laser coagulation of umbilical cord vessels and major vessels (twin-reversed arterial perfusion sequence), electrosurgical occlusion, cord clamping or ligation, or intraoperative antenatal arrest of the cardiac activity of the abnormally developed fetus after the delivery of the healthy twin.

Appendix C. Patient Information

Antenatal fetal death is the intrauterine death of a fetus, which can be diagnosed at any stage of pregnancy. This condition occurs due to infections, chronic somatic diseases, hemostatic disorders, and a number of other factors. The direct cause of death is fetal distress syndrome. This encompasses all impairments in the functional state of the fetus, primarily its movements and heartbeat.

The process of intrauterine fetal death is not always accompanied by changes in the woman's well-being. Sometimes the pregnant woman notes more frequent fetal movements, followed later by their complete cessation. This indicates acute fetal hypoxia, which is a decrease in oxygen content in the body. However, the baby's death often occurs unnoticed by the mother and physician, leading to late diagnosis of antenatal fetal death.

During the first three days following the baby's death, the patient may notice changes in her condition:

• fetal movements cease;

• mammary glands decrease in size and become less tense;

• the abdomen stops increasing in volume;

• weakness, malaise, and a feeling of heaviness in the lower abdomen occur.

If several weeks have passed since the fetal death in utero, signs of an inflammatory reaction may appear: fever up to 38℃; severe drawing pains in the lower abdomen; headache and dizziness; drowsiness; impaired consciousness.

After the woman consults a doctor complaining of malaise and the absence of fetal movements, the doctor refers the patient for diagnostic examination. This makes it possible to establish an accurate diagnosis.

Diagnosis of intrauterine fetal death includes the following stages of examination:

• auscultation of fetal heart tones using a special stethoscope. It is impossible to hear the heartbeat in this case with a conventional medical stethoscope. A wooden obstetrical stethoscope is used for this purpose. It features a wide bell that is firmly applied to the pregnant woman's abdomen.

• auscultation of heart tones with a fetal audiodoppler and/or monitor. A fetal doppler can be used even at home, starting from the 12th week of pregnancy. To do this, the woman needs to lie on her back and, to obtain a clear signal, apply gel to the areas of the abdomen that will contact the probe. The doppler itself should be moved slowly, without sudden movements. The duration of the examination is 3-7 minutes.

• ultrasound examination (ultrasound) of the fetus. This method is one of the most reliable for diagnosing intrauterine fetal death. With its help, the physician confirms the absence of a heartbeat in the baby.

For any woman, the death of an unborn child is a serious psychological trauma, but such a situation can be avoided.

If antenatal fetal death is confirmed as a result of the diagnostic examination, a series of urgent measures will be required to eliminate the consequences.

With a confirmed diagnosis of antenatal fetal death, emergency hospitalization and a decision on the method and timing of delivery are indicated. The shorter the interval between the established diagnosis and delivery, the lower the risk of complications during and after childbirth.

The choice of method is determined individually, based on clinical data and the characteristics of the obstetric situation. The optimal delivery option for antenatal fetal death is vaginal delivery. However, a cesarean section is sometimes performed, for example, in cases of early placental abruption from the uterine walls, or profuse or ongoing vaginal bleeding.

In the delivery of pregnant women with antenatal fetal death complicated by a septic condition, emergency surgical intervention is indicated. The extent of the surgery is decided individually; removal of the uterus with the fetus (hysterectomy) is possible.

After delivery, it is important to carefully monitor the condition of the parturient woman, prevent postpartum hemorrhage and purulent-septic complications. Attention must be paid to vaginal discharge (purulent or bloody), body temperature, the onset of chills, weakness, and drawing pains in the lower abdomen.

In all cases of intrauterine fetal death, a pathoanatomical examination of the fetus and placenta (its membranes) is indicated. Refusal of the examination at the request of relatives is processed in accordance with the norms of current legislation.

The most difficult question remains when the fetal death occurred. Previously, it was believed that the determination of the time of death was based on assessing the severity of maceration processes—softening and loosening of fetal tissues. However, the presence of signs of maceration does not always reliably indicate the time elapsed since death, as the rate of its development depends on the causes of the baby's death.

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

Bishop score

Russian title: Bishop score

Original title (if available): Bishop score

Source (official developer website, publication with

validation): Wormer K. C., Bauer A., Williford A. E. Bishop score. – 2017., Calculator B. S. Perinatology. com //internet].[fecha de acceso 12 de junio del 2017] URL Disponible en: http://perinatology. com/calculators/exbiometry. Htm, Bishop EH Pelvic scoring for elective induction.Obstet Gynecol. 1964 Aug;24:266-8

Type: rating scale.

Purpose: assessment of cervical ripeness.

Contents:

Interpretation:

Notes:

Fill out before each stage of cervical pre-induction/induction of labor.

The Bishop score is the best available tool for assessing cervical ripeness.

Ripe cervix – clinical signs of cervical readiness for labor (8 points or more).

Insufficiently ripe cervix – clinical signs of insufficient cervical readiness for labor (6-7 points).

Unripe cervix – absence of clinical signs of cervical readiness for labor (5 points or less).