Intrauterine fetal death

　　Causes of fetal death The causes of fetal death are mainly the following factors:

　　1. Chromosomal abnormalities:In the late 1960s, Carr in Canada and Boues in France clarified under a light microscope that chromosomal abnormalities are an important cause of fetal death in humans. Now, a large number of studies have elaborated in detail on the relationship between specific fetal chromosomal abnormalities and gestational age, parental age, obstetric history, and fetal morphology. Compared to rodents, the incidence of human chromosomal abnormalities during pregnancy is very high, leading to embryonic/fetal death. The incidence of chromosomal diseases decreases sharply as the gestational age extends. The highest incidence can reach 15% in miscarriages from 6 to 15 weeks, accounting for 6% in stillbirths (after 20 weeks), and only 0.5% in neonatal deaths. Therefore, only a few chromosomal diseases can be seen in live-born newborns.

　　2. Non-chromosomal fetal malformations:Approximately 1/4 of fetal deaths are accompanied by malformations, and nearly 50% of these malformations are caused by non-chromosomal abnormalities, which are also the main cause of spontaneous abortion and stillbirth. However, not all malformations can be diagnosed before birth, and the detection rate of malformations is only 22.3%. Single malformations such as anencephaly or other neural tube defects can be diagnosed relatively easily, but 12% of neural tube defects are part of multiple congenital malformation syndromes. Table 2 lists malformations caused by non-chromosomal abnormalities related to stillbirth.

　　The average stillbirth rate in all the above cases is 30%. Congenital heart disease is the most common malformation, with an incidence rate of about 8/1000, and 3 out of 8 cases are severe malformations. The perinatal mortality rate of congenital heart disease is quite high, with most deaths occurring in utero or in the early postpartum period. If the mother has systemic diseases such as diabetes, the incidence rate of congenital heart disease increases by a factor of 2. If the mother has phenylketonuria, the incidence rate also increases. If the pregnant woman had a previous child with congenital heart disease, the recurrence rate is 1% to 3%, and if two children are congenital heart disease patients, it rises to 10%.

　　3. The next most common is neural tube defects:The highest incidence rate can reach 1.5/1000, accounting for about 27%. The stillbirth rate of spina bifida is 10%, and that of anencephaly is 72%. The incidence rate of neural tube defects in China varies greatly, with significant differences between the north and south regions. The incidence rate in the north is 6‰ to 7‰, accounting for 40% to 50% of all malformations, while in the south it is 1‰. This kind of malformation is mainly a polygenic genetic disease, closely related to the environment. If caused by malnutrition (deficiency of vitamins or folic acid), its incidence rate can be significantly reduced after improvement. In the United States, it is recommended that all pregnant women take 0.4mg of folic acid daily, and if the previous delivery had a fetus with a neural tube defect, it should be 4mg/d, starting 3 months before pregnancy. Research has shown that the incidence rate can be reduced by at least 70%. Many other reports suggest that neural tube defects are related to gender, with a higher incidence rate in female fetuses, mainly anencephaly and upper spinal bifida, and lower spinal bifida in male fetuses, which may be related to insufficient chorionic gonadotropin (HCG) or insensitivity of embryonic receptor cells to HCG.

　　4. Umbilical hernia, abdominal wall defects, and hydrocephalus are common clinical malformations:However, they may be associated with other diseases or syndromes. Umbilical hernia accounts for 1/3000 of all newborns, 1/4167 of live births, and abdominal wall defects for 1/8000 and 1/12328. The total incidence rate of these two malformations is 1/3448, with a stillbirth rate of 33% to 50%. The occurrence of hydrocephalus is related to neural tube defects, with an incidence rate of 1/1000, a stillbirth rate of 12% to 28%, and hydrocephalus accounts for 32% of multiple malformations. Umbilical hernia and abdominal wall defects each account for 24% and 50%, respectively. Unbalanced dwarfism often also has a stillbirth rate of 23%. In prenatal diagnosis, the main reliance is on specific skeletal X-ray examination, including three most common lethal dwarfisms - thanatophoric dwarfism, osteochondrodysplasia, and osteogenesis imperfecta type II.

　　5. Joint flexion is another important disease:The incidence rate is 1/5000 to 1/10000, but the mortality rate of stillbirths cannot be accurately estimated. Any syndrome with multiple joint flexions or abductions in the uterus can increase the risk of incomplete lung development in the fetus. Many fetuses with joint flexions often die due to neurological abnormalities if they also have such abnormalities. Pena-Shokeir, Iethalpterygium, and Neu-Laxova syndromes are three rare joint flexion syndromes, but they have a very high mortality rate.

　　6. Other rare or rare (occurring in 8.6% cases, then 22.4%):(1) Patients with vascular complications, such as nephropathy (F grade), with proteinuria >3g/24h, serum creatinine >132.6μmol/L (1.5mg/dl), anemia (hematocrit 0.25), hypertension [mean arterial pressure >107mmHg (14.3kPa)] before 20 weeks, perinatal outcomes are poor, nearly 50% have perinatal death or neonatal weight <50%; (2) The activity of SLE for several months before pregnancy: if SLE is in clinical activity phase 6 months before pregnancy, the live birth rate is only 64%, while it is 88% if it is in a stationary phase; (3) Patients with latent nephritis, the fetal mortality rate is 7.5%, and it is related to the degree of renal damage, such as serum creatinine ≥132.6μmol/L (1.5mg/dl), indicating moderate to severe renal insufficiency, 50% of 10 cases of fetal loss, with proteinuria (>300mg/24h) or creatinine clearance.

　　1. Coordinated uterine contractions:Also known as hypotonic uterine inertia. Its characteristics are that uterine contractions have rhythm, polarity, and symmetry, but the contraction force is weak, the intrauterine pressure is low, the duration is short and the interval is long, and the uterus does not bulge during the peak of contraction. The muscle at the bottom of the uterus can still be indented with a finger. It is not enough to dilate the cervix at a normal speed, resulting in prolonged or停滞 of labor. According to the period when uterine inertia occurs, it is divided into:

　　(1) Primary uterine inertia: It refers to the uterine inertia from the beginning of labor. The main cause is malposition of the pelvis and fetus. Clinically, it often manifests as prolonged latent phase. It must be distinguished from false labor. The method of differentiation is to give strong sedatives, such as drugs that can stop uterine contractions are false labor, and those that cannot stop are primary uterine inertia.

　　(2) Secondary uterine inertia: It refers to the normal uterine contractions in the early stage of labor, but the intensity of contractions weakens after the labor progresses to the active phase, which leads to prolonged or停滞 of labor. This situation often occurs in narrow pelvis, persistent occipito-transverse position and occipito-posterior position.

　　2. Incoordination of uterine contractions:Also known as hypertonic uterine inertia. Its characteristics are the lack of symmetry, rhythm, especially polarity. The excitation points of uterine contractions can occur in one or more places in the uterus, even inverted polarity. Although the intrauterine pressure continues to rise, the presenting part of the fetus does not descend, and the cervix cannot be normally dilated, which is an ineffective contraction. Because the uterine wall does not relax completely during the intercontraction period, the resting intrauterine pressure increases. Clinical manifestations include the产妇 feeling continuous pain in the lower abdomen, refusing to be pressed, restlessness, dehydration, electrolyte disorder, intestinal distension, and urinary retention. Examination: tenderness in the lower abdomen, unclear palpation of the fetal position, irregular fetal heart rate, slow or no dilation of the cervix, delayed or stationary descent of the presenting part, and prolonged labor.

　　1, Symptoms

　　The most common complaints of pregnant women after fetal death are: (1) disappearance of fetal movement; (2) weight gain or loss; (3) breast retraction; (4) others: such as feeling discomfort, bloody or watery vaginal discharge, bad odor in the mouth, etc.

　　2, Signs

　　(1) Regular follow-up examinations, finding that the uterus does not increase with gestational weeks.

　　(2) Fetal heart sound is not heard.

　　(3) Fetal movement is not palpated.

　　(4) Abdominal palpation does not palpate elastic and solid fetal parts.

　　After the death of the fetus, the pregnant woman feels the cessation of fetal movement, the cessation of uterine growth, and the inaudibility of fetal heart sound during examination. The uterus is smaller than the gestational weeks, which can be considered as a dead fetus, and B-ultrasound can confirm this.

　　According to the cessation of spontaneous fetal movement, the cessation of uterine growth, the inaudibility of fetal heart sound, the uterus being smaller than the gestational weeks, it can be considered as a dead fetus. The commonly used auxiliary examinations include: B-ultrasound finding the disappearance of fetal heart and movement is a reliable basis for diagnosing dead fetus. If death is prolonged, there may be cranial plate collapse, skull overlap, and bag-like deformation, which can be diagnosed as a dead fetus: the Doppler fetal heart sound can assist in diagnosis, and in the late pregnancy, the 24-hour urine estrone content of pregnant women is below 3mg (recently measured within the normal range) also suggests that the fetus may die, and the significantly increased alpha-fetoprotein value in amniotic fluid can be detected.

　　In 1950, Weiner and others first discovered that Rh-negative pregnant women with dead fetuses can develop coagulation system diseases. Subsequent studies have shown that during normal pregnancy, fibrinogen increases from 3g/L (300mg/dl) at non-pregnant levels to 4.5g/L (450mg/dl), and coagulation factors I, VII, VIII, IX, and X all increase. However, after 20 weeks of pregnancy, fetal death occurs, and the fetal tissue thromboplastin stimulates the maternal exogenous coagulation system, causing widespread microthrombosis in the blood vessels, leading to the consumption of coagulation factors, mainly factors V, VIII fibrinogen, thrombin, and platelets secondary to fibrinolysis, coagulation, hemorrhage, and tissue necrosis, and the changes of disseminated intravascular coagulation (DIC). Hypofibrinogenemia is related to the retention time of dead fetus in the uterus. Those delivered within 4 weeks of fetal death almost never have coagulation system diseases; 25% of pregnant women develop hypofibrinogenemia 4 weeks later, with a slow linear decrease in plasma fibrinogen levels (25-85mg/(dl·week)) until delivery, which is often restored to normal within 48 hours after delivery. Low-dose heparin can be used for prevention before the dead fetus is removed.

　　With the continuous advancement of medical technology, it is now possible to accurately and promptly diagnose fetal death in utero, reducing the occurrence of maternal complications. Combined with regular prenatal monitoring, it is possible to prevent fetal death. Confirming the risk of fetal death in utero, providing appropriate and timely obstetric intervention in the late pregnancy period, and ensuring the completeness of neonatal rescue facilities can all reduce the mortality rate of fetal death in utero. Because 85% of stillbirths are caused by fetal lethal malformations and hypoxia, this is the key to prediction and assessment.

　　1. Thoroughly understand the medical history of the mother. Based on the investigation of the pregnant woman's medical, social, and economic status, divide the population into high-risk and low-risk groups, with fetal intrauterine mortality rates of 5.4% and 1.3% respectively. Therefore, strengthening the monitoring of high-risk pregnant women can also reduce some fetal deaths.

　　2. Fetal movement is one of the simplest, most economical, and convenient means of monitoring, which can be self-monitored by the pregnant woman. If the fetal movement is less than 10 times in 12 hours or decreases by more than 50% per day, consider intrauterine fetal distress. In high-risk pregnancies, a decrease in placental function can cause a decrease in fetal movement before changes in fetal heart rate (sedatives or magnesium sulfate and other drugs should be excluded). If the fetal activity suddenly increases and then stops, it often indicates acute intrauterine hypoxia and death of the fetus, often caused by umbilical cord compression or placental abruption.

　　3. The pregnancy chart was first used by Westin of Sweden in 1972 to observe the growth of the fetus in utero. It does so by dynamically observing indicators such as the weight, abdominal circumference, and uterine height of the pregnant woman, and promptly identifying developmental abnormalities in the fetus, such as IUGR, malformed infants, oligohydramnios, etc. It is generally recorded from the 16th week of pregnancy. If the parameters gradually increase within the normal range, it indicates that the fetus is developing normally, and 84% to 86% can deliver a normal weight baby. If the parameters remain unchanged, increase or decrease too slowly for 2 or 3 consecutive times in the warning zone, it suggests fetal abnormalities and further ultrasound or biochemical tests are needed.

　　4. Biochemical examination (1) Estrone (E3) in maternal urine: It continues to increase during pregnancy, but begins to decrease within 24-48 hours after fetal death. This is because most of the precursors of E3, such as dehydroepiandrosterone sulfate and 16-hydroxydehydroepiandrosterone sulfate, come from the functional fetal kidney and liver. If the content of 24h E3 is measured repeatedly,

　　1. Before delivery

　　(1) Peripheral blood smear examination of fetal red blood cells.

　　(2) Cultivation of cervical secretion.

　　(3) Urine virus isolation/culture.

　　(4) Maternal blood virus isolation, checks for toxoplasmosis, etc.

　　(5) Indirect Coombs test.

　　(6) Fasting blood glucose or glycosylated hemoglobin.

　　(7) Antiphospholipid antibodies, antigen-antibody.

　　(8) Lupus anticoagulant.

　　(9) Blood routine.

　　(10) If the death time exceeds 4 weeks, determine fibrinogen and platelets weekly until delivery.

　　(11) Amniocentesis: Perform karyotype analysis and culture of viruses, aerobic, and anaerobic bacteria.

　　2. Postpartum

　　(1) Mother: Evaluate coagulation function (platelets, APTT, fibrinogen).

　　(2) Placenta:

　　① Bacterial culture on the fetal and maternal faces.

　　② Viral isolation from placental tissue, karyotype analysis.

　　③ Placental tissue pathological examination, such as circumvallate placenta, placental abruption, abnormal umbilical cord attachment, and abnormal placental size.

　　④ Umbilical cord blood culture.

　　(3) Fetus:

　　① Bacterial culture of the oropharynx, external ear, and anus.

　　② Fetal autopsy.

　　3. Imaging examination

　　X-ray examination

　　The earliest diagnosis of intrauterine fetal death was in 1922. In the early stage of fetal death, X-ray examination may show no abnormalities; until the fetus deforms, four main X-ray signs can be seen in the abdomen, among which the formation of gas from fetal blood decomposition is the only reliable X-ray diagnostic sign.

　　(1) Gas formation: This phenomenon occurs 6 to 10 hours after fetal death, with gas accumulation in the fetal great vessels or soft tissue. Reports show that 13% to 84% of cases have this phenomenon, and it only occurs in late fetal death. It may be mistakenly attributed to excessive gas accumulation in the mother, and diagnosis may be more difficult.

　　(2) Haze sign around the fetal head: It is the first sign to appear within 48 hours of fetal death, due to the accumulation of subcutaneous fluid under the fetal galea aponeurotica, which lifts the subcutaneous fat to form a halo. This phenomenon can occur in 38% to 90% of cases, but it must sometimes be distinguished from fetal edema.

　　(3) Fetal cranial plate collapse: It usually appears after 7 days of death, and almost all cases can be seen after 10 days, mainly due to the decrease in intracranial pressure after fetal death, causing cranial deformation.

　　(4) Angular deformity of the spine: After fetal death, the decrease or disappearance of spinal tension leads to an angular deformation backward.

　　4. Ultrasound examination

　　The time of fetal death varies, and the ultrasound imaging also varies accordingly. If the death time is short, only the disappearance of fetal heartbeat can be seen, with the blood flow in the fetal organs, umbilical cord blood flow stops, the body tension and bones, subcutaneous tissue echo is normal, and there are no abnormal changes in the amniotic fluid echo-free zone. If the death time is longer, the ultrasound imaging of fetal maceration is similar to radiological imaging, showing strong echo rings in the fetal skull, overlapping and deformation of the skull; the accumulation of subcutaneous fluid around the fetal scalp can cause scalp edema and general edema; fluid accumulation in serous cavities such as the pleural cavity, abdominal cavity; the abdominal cavity can show irregular strong echoes due to the expansion of the intestinal tract; a small amount of gas accumulation may not produce ultrasound shadowing. If the dead fetus remains in the uterus, further maceration and deformation may occur, making the outline blurred and possibly difficult to identify. At this time, it is necessary to be careful to prevent the occurrence of disseminated intravascular coagulation (DIC) in pregnant women. Occasionally, ultrasound examination can also find the cause of fetal death, such as multiple malformations.

　　Try to eat well, sleep well, pay attention to increasing nutrition, enhance the body's resistance to diseases, promote the early repair of damaged organs, and eat more fish, meat, eggs, and bean products rich in protein and fresh vegetables rich in vitamins after abortion, in order to accelerate the recovery of the body. Food supplementation should be done immediately; it is not advisable to eat cold and spicy foods. If possible, dietary references can be made to the diet after normal childbirth. In addition, in life, follow the taboos after childbirth, do not take a bath in a basin, do not drink cold drinks, keep warm clothes, and avoid catching a cold.

　　I. Treatment

　　1. Handling of fetal death in a singleton pregnancy at 28 weeks: Bishop cervical score

　　2. The method of dealing with the death of one fetus in a multiple pregnancy In a multiple pregnancy, due to the death of one fetus, the survival rate of the multiple organs of the surviving fetus increases due to thrombosis or low perfusion, especially brain injury. The survival of newborns depends on gestational age and fetal weight. Delivery after 28 weeks, if corticosteroids are used before delivery, surfactants and new treatments such as high-frequency oscillating ventilators after delivery, the prognosis of newborns is better. Literature reports that only 6% of newborns die, because if it is clear that it is a monozygotic twin and the gestational age is ≥28 weeks, pregnancy should be terminated. If the gestational age is below 28 weeks, various factors need to be considered, such as fetal weight, lung maturity, survival rate, the attitude of the pregnant woman and her family, and then make a decision. Generally, the mortality rate of newborns delivered before 28 weeks is 28.5%.

　　3. Abortion (1) Direct abortion:

　　① Abortion induction by intraperitoneal injection of drugs, commonly used is Yizhayan. Contraindicated in patients with incomplete liver and kidney function; ② oral ethinyl estradiol for 3 to 5 days, then induce labor with oxytocin; ③ misoprostol combined with prostaglandin abortion.

　　(2) Indirect abortion: If the dead fetus exceeds 3 weeks, the coagulation function should be checked. If fibrinogen

　　II. Prognosis

　　After the fetus dies, it can become a softened fetus, a flattened fetus, or a paper-like fetus. If it has not been expelled after 3 weeks, DIC can occur, leading to uncontrollable massive bleeding.