I. Twin-twin transfusion syndrome
Overview】Twin-twin transfusion syndrome (TTTS) is a complication that occurs specifically in monochorionic twin fetuses. TTTS is a continuous but balanced transfusion between monochorionic twin fetuses via anastomotic vessels, but in 10-15% of monochorionic twin fetuses an imbalance in the development of the vascular network results in TTTS, often occurring between 15-26 weeks.TTTS is a unidirectional transport of blood from artery to vein through an arterial-venous anastomotic branch between the placenta, with one fetus becoming the donor and the other the recipient. One fetus becomes a donor and the other is a recipient, resulting in light weight, small length, anemia, dehydration, low urine, low amniotic fluid, low blood volume, and finally death due to ischemia; while the recipient dies of congestive heart failure due to excessive blood volume, cardiomegaly, enlarged liver and kidneys, rapid weight gain, fetal edema, excessive amniotic fluid, and finally also congestive heart failure. If untreated during pregnancy, fetal death in utero occurs in 80% to 100% of TTTS. Current studies suggest that in addition to the interplacental arteriovenous anastomoses that cause TTTS, placental hemodynamics and hormones such as the renin-angiotensin system also play a role in the development of TTTS. Prior to the use of ultrasound in clinical diagnosis, TTTS could only be diagnosed by careful examination of the placental vasculature and observation of placental vascular traffic based on inconsistent fetal growth at delivery. With the rapid development of fetal medicine, TTTS can not only be diagnosed prenatally, but also further treated, but there are still near and long-term complications and neonatal neurological sequelae.
[Diagnostic criteria
1. Diagnosis of twin pregnancy chorionicity in early and mid pregnancy
(1) Ultrasound monitoring of twin fetuses in early pregnancy if there are 2 separate gestational sacs.
(2) If there are 2 amniotic sacs in one chorionic villus cavity with a T-shaped structure between the amnion and chorionic villus, it is a single chorionic villus twin fetus; it is a “bimodal” structure with “λ”. (2) A double chorionic villus twin fetus.
(3) The presence of two placentas and a septum 2 mm or thicker on ultrasound can assist in the diagnosis of bichorionic twins.
(4) The sex of the two fetuses is different as dizygotic twins.
2. Diagnostic criteria of TTTS.
(1) Two fetuses of the same sex with a single placenta.
(2) Inconsistent growth of the two fetuses, with an estimated difference in weight of 20% or more and abdominal circumference of 20 mm or more, with differences not always apparent in acute cases.
(3) Low amniotic fluid in the donor fetus: ultrasound maximum amniotic segment ≤ 2 cm.
(4) Excessive amniotic fluid in the recipient fetus: ultrasound maximal amniotic segment ≥ 8 cm before 20 weeks of gestation and ≥ 10 cm between 20 and 26 weeks.
(5) Difference in hemoglobin between two fetuses ≥ 5 g/L. Confirmation of diagnosis by invasive prenatal diagnosis of umbilical cord puncture to obtain fetal blood samples.
(6) Fetal ultrasound Doppler abnormalities: disappearance or regurgitation of end-diastolic blood flow in the umbilical artery of the blood donor at stage III, or abnormal venous Doppler images of the blood recipient, such as intravenous regurgitation or pulsatile blood flow in the umbilical vein.
3.Postnatal diagnosis of TTTS
Newborns of the same sex, weight difference >20%, same blood type, hemoglobin difference >5g/L, pale anemic appearance in the blood donor, red face and bruising in the blood recipient, etc. The two placentas are fused, with some placental lobules sharing in the middle, with fine vessels connected, or with larger vessels communicating, and amniotic membrane can be seen in the middle.
4.Stage diagnosis of TTTS
Traditional Quintero staging.
Stage I: Excessive amniotic fluid or too little amniotic fluid, blood supplying fetal bladder is visible.
Stage II: Blood supplying fetal bladder is not filled.
Stage III: Loss of end-diastolic flow or regurgitation in the umbilical artery of the donor fetus, or abnormal venous Doppler images in the recipient fetus, such as intraventricular regurgitation or pulsatile blood flow in the umbilical vein.
Stage IV: Fetal edema.
Stage V: one or two fetal deaths.
5.Differential diagnosis
Differentiate from twin fetuses with inconsistent growth, see related chapter.
【Treatment plan】.
In mid to late gestation, for the diagnosis of uncomplicated monochorionic twin fetus, ultrasound examination of fetal health status should be performed every 3-4 weeks. Once TTTS is diagnosed, ultrasound examination of fetal status needs to be performed every 2 weeks or even every 1 week. As it often occurs before 28 weeks of gestation, it is prone to intrauterine death and preterm delivery of one fetus and requires transfer of the mother to a tertiary care facility.
1.Expectant therapy
Patients with early TTTS around 28 weeks of gestation (before Quintero stage II) and patients with uncertain diagnosis and no conditions for surgery can be followed up regularly to prolong the pregnancy to terminate at the right time for a viable neonate.
2. Treatment of TTTS in mid-pregnancy: Applicable to pregnant women with TTTS at all stages.
(1) Amniocentesis reduction: to prevent preterm delivery and correct hemodynamic imbalance.
(2) Amniotic diaphragm perforation: laser perforation of the amniotic diaphragm or perforation with a perforating needle under fetoscopy.
(3) Fetoscopic laser electrocoagulation vascular anastomosis: a riskier procedure than amniotic fluid reduction and must be undertaken by a physician with specialized training.
(4) Blocking the umbilical cord for selective reduction: some scholars suggest it for TTTS stage III and IV.
3. Complications of TTTS treatment
(1) Intraoperative complications: amniotic fluid leakage, bleeding, loss of instruments in the amniotic cavity, infection, fetal membrane detachment, placental abruption, loss of fetal heart, abortion, incomplete blockage of vascular traffic branches, or omission, accidental injury to normal vessels.
(2) Near-term and long-term complications: two fetal hearts disappear one after another a few hours after surgery, miscarriage occurs, especially in patients with stage III TTTS with end-diastolic loss of umbilical artery S/D or regurgitation, high rate of recent miscarriage; preterm delivery; premature rupture of fetal membranes; in the distant future, low amniotic fluid, fetal growth restriction, and intrauterine fetal death may also occur.
(3) Neonatal neurological sequelae: surviving children have different degrees of neurological sequelae and impaired intelligence, which are related to whether the fetus is severely ischemic and hypoxic at the time of surgery; the earlier the surgery, the fewer the sequelae.
4. Close follow-up after surgery to prevent miscarriage, premature birth and fetal death in utero.
5.Timely termination of pregnancy and mode of delivery
For patients with late TTTS after 28 weeks of gestation, the mode of delivery is the same as obstetric management, and the maturity of the fetal lung needs to be evaluated and fetal lung maturation needs to be promoted before termination of pregnancy.
6.After the birth of the newborn, obstetrics, neonatology and anesthesiology collaborate to perform timely and necessary resuscitation and resuscitation, and transfer to NICU for further treatment according to the situation.
Efficacy assessment
The diagnosis and treatment of TTTS requires high professional and technical ability of medical institutions. A team of obstetrics specialists, ultrasound specialists, maternal-fetal medicine specialists, anesthesia specialists and nursing specialists should be organized to establish a regional fetal medicine center and develop treatment measures. TTTS treatment methods in mid-pregnancy carry a risk of preterm delivery, miscarriage and intrauterine fetal death and neurological sequelae for the fetus. The primary criterion for efficacy assessment is survival of at least one fetus to 6 months of gestation and the secondary criterion is absence of neurological damage in the surviving fetus; or delivery after TTTS treatment and survival of both fetuses or at least one neonate for 28 days is the gold standard for treatment efficacy, according to which the efficacy of surgical treatment can be compared globally.
B. Twin fetuses with one dead and one alive (one of the twin fetuses died)
The risk is highest in twin pregnancies of the same sex, with inconsistent growth, severe malformations, and TTTS also increasing the risk of stillbirth. TTTS also increases the risk of stillbirth, with one fetal death in utero and the risk of death of the other surviving fetus being six times higher in same-sex twins than in opposite-sex twins. Death of one fetus early in pregnancy is a vanishing twin, and stillbirths in mid-trimester can be paper-like. Late gestational death of one fetus causes coagulation disorders in the mother, but is rarely reported in the literature and may be associated with delivery soon after several weeks. In twin sIUFD, the surviving fetus is at significantly increased risk for both neurological abnormalities and preterm delivery, and the risk of neurological abnormalities is significantly higher in monochorionic twins than in bichorionic twins.
[Diagnostic criteria
1. Most fetal deaths occur in early gestation, and the diagnosis mostly relies on the initial ultrasound examination suggesting two gestational sacs, followed by the finding of the disappearance of one gestational sac. sIUFD should be diagnosed when a definite fetal remnant is found or when subsequent ultrasound examinations confirm the death of one fetus or the disappearance of one of the previously surviving fetuses.
2. Mid to late gestation: ultrasound monitoring of one fetal heart disappearance in both fetuses.
【Treatment plan
1.Expectant therapy
Depending on the risk of twin chorionicity and surviving fetus, prevention of preterm delivery and miscarriage.
If the surviving fetus is in good condition at the time of fetal death of one of the twin chorionic fetuses, immediate treatment is not necessary. Fetal monitoring and biophysical assessment of the surviving fetus are performed regularly to monitor the growth and development of the surviving fetus.
If one fetus is in good condition at the time of death of a monochorionic twin, regular ultrasound Doppler monitoring of umbilical blood flow and middle cerebral artery blood flow is required, and vaginal ultrasound and MRI can also be used to examine brain damage in the surviving fetus.
2. Termination of pregnancy
(1) In late pregnancy, if the fetus is viable but preterm, glucocorticoid therapy should be given to promote fetal lung maturation.
(2) Full-term gestation at the time of fetal death of one fetus: termination of pregnancy should generally be chosen to save the other fetus without expectant treatment. The choice of delivery method should be decided according to the condition of the mother and the size, fetal position and whether the fetus can tolerate vaginal delivery.
3. Monitor the maternal coagulation status before termination of pregnancy.
4. Transfer the newborn to the NICU for further treatment after birth according to the situation.
Evaluation of efficacy
The surviving fetus was closely monitored and the newborn was born alive with no near or long-term complications.
Uneven development of twin fetuses (inconsistent growth of twin fetuses)
The difference between the birth weight of newborns >20% can be used as a diagnostic criterion. It can be divided into discordant growth of twin chorionic fetuses and discordant growth of single chorionic fetuses, and the size inconsistency is often defined by the larger fetus of the twins. Twin fetal growth inconsistencies usually occur at the end of mid-trimester and the beginning of late pregnancy and are often disproportionate, with the possibility of large malformations in the smaller fetus occurring in early pregnancy. The likelihood of both fetuses being small for gestational age (SGA) is twice as high in monochorionic twins as in dichorionic twins. Inconsistent growth has been reported to be associated with inadequate placental perfusion in dichorionic twins and with placental hemodynamic imbalance in monochorionic twins. The risk of inconsistent growth is similar to that of singleton fetuses, with increased neonatal morbidity and mortality after birth.
[Diagnostic criteria].
The diagnosis of twin fetal growth inconsistency is based on the measurement of each parameter of the fetus, and the diagnosis of twin fetal inconsistency after birth has more confirmatory value.
1. Clinical manifestations
The difference of neonatal weight after birth is >20%.
2.Auxiliary examination
(1) The difference in abdominal circumference between the two fetuses is 20mm on prenatal ultrasound.
(2) Prenatal ultrasound monitoring of fetal weight difference >20%, fetal weight based on fetal biparietal diameter and abdominal circumference or femoral length and abdominal circumference measurements into the computer assessment, can assist in diagnosis.
(3) Ultrasonic Doppler measurement of fetal umbilical artery flow ratio (S/D) difference >15% and diastolic regurgitation can assist in the diagnosis.
3.Diagnosis by category
(1) Inconsistent growth of two fetuses of appropriate gestational age.
(2) Inconsistent growth of two fetuses less than gestational age.
(3) Inconsistent growth of a fetus of appropriate gestational age and a fetus younger than gestational age.
4.Differential diagnosis
Differentiate from TTTS.
(1) The growth-restricted fetus with inconsistent growth of both fetuses looks like an “adherent fetus” because of low amniotic fluid, but the normal growth of fetus has normal amniotic fluid volume. In TTTS, there is too much amniotic fluid in the recipient fetus and too little amniotic fluid in the donor fetus.
(2) TTTS can be differentiated from growth inconsistency by indicators such as bladder filling and cardiac changes in both fetuses.
【Treatment plan】.
Close monitoring should be done during pregnancy to prevent fetal death in utero and to choose the right time to terminate the pregnancy.
1.Monitoring during pregnancy
(1) Ultrasound assessment of fetal growth and development.
Ultrasound assessment is recommended every 3-4 weeks in the middle and late stages of twin pregnancies. The assessment includes ultrasound monitoring of fetal abdominal circumference, biparietal diameter, head circumference, femoral length, amniotic fluid volume and fetal weight, as well as monitoring changes in the S/D ratio of umbilical artery blood flow.
In cases of inconsistent growth or S/D abnormalities in both fetuses, closer monitoring should be performed according to the condition.
(2) Strengthen the monitoring of fetal heart rate and biophysical score to evaluate whether the fetus is in good condition.
2. Terminate pregnancy at the right time
(1) Inconsistent growth of twin fetuses does not require routine interventional termination of pregnancy.
(2) In late pregnancy, if there is intrauterine hypoxia and other obstetric indications for termination of pregnancy, the obstetric management should be the same, and the maturation of fetal lung should be clarified before termination of pregnancy.
[Efficacy assessment].
The fetal growth and development should be evaluated regularly in the middle and late stages of pregnancy, and the pregnancy should be terminated at the right time, and the newborn should be born healthy and free of near and long-term complications.
One of the twin fetuses combined with malformation
Overview】One twin malformation includes structural anomalies, chromosomal malformations and monochorionic twin-specific malformation Twin reverse artery perfusion (TRAP). The risk of chromosomal malformation in one twin can be calculated by adding the age-related risk (e.g., 1/100 + 1/100 = 1/50 for a 40-year-old woman), and the incidence of structural anomalies in one twin is 2-3 times higher per fetus than in a single fetus. This rare phenomenon is known as monozygotic dizygotic twins with different karyotypes. Monochorionic twin chromosomal anomalies can cause preterm delivery of the other fetus, and monochorionic twin chromosomal anomalies can cause preterm delivery, brain damage and intrauterine death of the other fetus, most of the anomalies are found in midtrimester.
Diagnostic criteria
1, Ultrasound diagnosis of twin chorionic villous sex in early to mid-term pregnancy (see TTTS chapter).
2, The screening method for chromosomal abnormalities in twin pregnancies is not exact: nuchal translucency (NT) ultrasound measurements in early pregnancy can be used to screen for chromosomal abnormalities in twin pregnancies.
3, Ultrasound screening of twin fetuses can be carried out at 18-20 weeks of gestation to clarify whether there is an abnormality in one of the twin fetuses and to dynamically monitor the amniotic fluid volume.
4. Invasive prenatal screening for twin fetuses to confirm chromosomal abnormalities.
Fetal karyotype determination is performed by invasive tests amniocentesis or chorionic villus biopsy (CVS), which are technically demanding and therefore usually recommended to be performed in prenatal diagnostic centers of tertiary health care institutions. The choice of invasive test depends on the risks associated with this operation and the accuracy of the results obtained from the fetus and the technique, and the rate of miscarriage is currently not exact.
Either dizygotic twin amniocentesis or chorionic villus biopsy (CVS) may be used, usually sampling both fetuses. Amniocentesis is preferred in monozygotic twins because CVS is rarely able to diagnose monozygotic twins with different karyotypes.
Treatment options]
1.Expectant treatment
When one of the twin fetuses has not affected normal fetal health, the fetal growth and development should be monitored regularly.
2. Selective fetal reduction and selective termination of pregnancy: in the early and middle stages of pregnancy, must be performed in a qualified tertiary care institution.
Indications for surgery: the presence of conditions that threaten normal fetal health. If one of the twin fetuses is anencephalic, causing progressive pathological hyperhydramnios, which may lead to preterm delivery of the other fetus.
(1) Selective reduction or elective termination of pregnancy in a twin chorionic twin is performed by intracardiac or spinal injection of potassium chloride under continuous ultrasound monitoring. It is extremely important to identify the target fetus to be killed by differentiating the sex, identifying obvious structural abnormalities, placental positioning and umbilical cord attachment.
(2) Monochorionic twins It is not possible to determine which method of selective fetal reduction is best. The use of laser/bipolar electrocoagulation to occlude the umbilical cord or perform cord ligation is recommended for selective termination at fetal medicine centers that perform intrauterine fetal treatment.
(3) Complications of the procedure: The risks of elective reduction or elective termination of pregnancy are miscarriage, preterm delivery, maternal infection, bleeding during pregnancy and diffuse intravascular coagulation.
3. Monitor the status of the surviving fetus and maternal well-being after elective reduction or elective termination of pregnancy.
4. Terminate pregnancy at the right time
After 28 weeks of gestation, the treatment is the same as the obstetric indications.
5.Prevention of postpartum hemorrhage
Use contractions promptly after delivery.
6.Transfer the newborn to NICU for further treatment after birth according to the situation.
Evaluation of efficacy
Close monitoring of fetal growth and safety in utero, healthy fetus born alive, no recent or long-term complications.