| disease | Multiple Pregnancy |
A pregnancy with two or more fetuses at the same time is called a multiple pregnancy. Multiple pregnancies have more complications during pregnancy and childbirth, with higher perinatal and neonatal mortality rates, making them high-risk pregnancies. To improve pregnancy outcomes, in addition to early diagnosis, it is essential to strengthen prenatal care and pay attention to the management of the childbirth period.
bubble_chart Etiology
1. Genetic factors: Multiple pregnancies have a familial tendency. If either spouse has a family history of multiple childbirths, the incidence of multiple pregnancies increases. Monozygotic twins are not related to genetics, while dizygotic twins have a clear hereditary pattern. If a woman is one of dizygotic twins herself, the probability of giving birth to twins is higher than if the husband is one of dizygotic twins, suggesting that the mother's genotype has a greater influence than the father's.
2. Age and parity: Age has no significant effect on the incidence of monozygotic twins. Hauser et al. found that the incidence of monozygotic twins was 3% in women under 20 years old and 4.5% in those over 40. The incidence of dizygotic twins increases significantly with age, rising from 2.5% in the 15–19 age group to 11.5% in the 30–34 age group. The incidence of twins also increases with parity. Chai et al. (1988) reported that the rate was 21.3% in primiparous women and 26% in multiparous women.
3. Endogenous gonadotropins: Spontaneous dizygotic twinning is associated with higher levels of follicle-stimulating hormone (FSH). Mastin et al. (1984) found that women who gave birth to twins had significantly higher blood FSH levels in the early follicular phase than those who gave birth to singletons. The rate of dizygotic twinning increases when conception occurs within one month after discontinuing contraceptive pills, possibly due to increased pituitary secretion of gonadotropins, leading to the maturation of multiple primordial follicles.
4. Use of ovulation-inducing drugs: Multiple pregnancies are a major complication of drug-induced ovulation, related to individual response differences and excessive doses. During treatment with human menopausal gonadotropin (HMG), ovarian hyperstimulation is prone to occur, leading to multiple ovulation and increasing the chance of twins by 20–40%.bubble_chart Clinical Manifestations
In multiple pregnancies, early pregnancy symptoms are more severe and last longer. After 10 weeks of pregnancy, the uterine size is significantly larger than in singleton pregnancies, and it grows even more rapidly after 24 weeks. In the advanced stages of pregnancy, the excessively enlarged uterus pushes the diaphragm upward, compressing the lungs and reducing diaphragmatic movement, often leading to difficulty breathing. The enlarged uterus also compresses the inferior vena cava and pelvis, obstructing venous return, which commonly causes edema in the lower limbs and abdominal wall, as well as varicose veins in the lower limbs and vulvovaginal area. Additionally, complications are much more frequent in multiple pregnancies, including both general and specific complications.
Based on medical history and obstetric examination, the diagnosis of multiple pregnancy is not difficult to establish. When in doubt, auxiliary examinations such as B-mode ultrasound imaging can be utilized.
1. Medical history: A family history of multiple childbirths on both sides; treatment with ovulation-inducing drugs prior to conception; severe early pregnancy reactions; significant weight gain and lower abdominal discomfort after entering the intermediate stage [second stage] of pregnancy.
(1) The uterine volume is significantly larger than the corresponding gestational week.
(2) Three or more fetal poles are palpated; the fetal head is relatively small and disproportionate to the uterine volume; multiple fetal limbs are present in various parts of the uterine cavity.
(3) Fetal heart sounds with a frequency difference of more than 10 beats per minute are heard in different parts of the uterus; or if the fetal heart rates are similar, there is a silent zone between the two fetal heart sounds.
3. Auxiliary examinations
(1) B-mode ultrasound examination: This is currently the primary method for diagnosing multiple pregnancy. Using a B-mode ultrasound imaging device transabdominally, as early as 6 days of pregnancy, the number of gestational sacs implanted in different parts of the uterus can be displayed, with each sac and its surrounding decidua forming a fluid halo with double-ring characteristics. By the end of the 7th week, rhythmic pulsations of the primitive heart tube appear within the embryonic bud. After 12 weeks of pregnancy, the fetal head becomes visible, and the biparietal diameter of each fetal head can be measured. The diagnostic accuracy increases with gestational age, reaching 100%. Therefore, if multiple pregnancy is clinically suspected, follow-up should continue until the number of fetuses is fully confirmed.
(2) Doppler ultrasound examination: After 12 weeks of pregnancy, fetal heart sounds with varying frequencies can be heard using a Doppler fetal heart monitor.
(3) Serum alpha-fetoprotein (AFP) measurement: This also aids in the diagnosis of multiple pregnancy. In twin pregnancies, 29.3% show significantly elevated serum AFP levels; in triplet pregnancies, 44.8%; and in quadruplet or higher-order pregnancies, the rate reaches 80.0%. Thus, an abnormally elevated serum AFP level in screening suggests the possibility of multiple pregnancy and warrants further examination.
bubble_chart Treatment Measures
Management during Pregnancy
1. Antenatal Care: Upon confirmation of a multiple pregnancy, dietary adjustments should be recommended based on the nutritional status of the pregnant woman, with the principle of increasing calorie, protein, mineral, vitamin, and essential fatty acid intake, along with appropriate iron and folic acid supplementation. After the second trimester, bed rest is advised to enhance uterine blood flow and increase fetal weight, as well as to reduce intrauterine pressure on the cervix and decrease the incidence of premature labor. Strengthen prenatal check-ups to facilitate early detection and timely treatment of complications such as anemia and pregnancy-induced hypertension syndrome. Serial monitoring of fetal growth and placental function is essential. Women with twin pregnancies should be hospitalized at 35–36 weeks of gestation, while those with triplets or higher-order multiple pregnancies should be hospitalized and advised bed rest during the second trimester, with tocolytic agents administered as needed and selective cervical cerclage performed. In the third trimester, corticosteroids should be used to promote fetal lung maturity.
2. Management of Intrauterine Death of One Twin: With the widespread use of ultrasound for perinatal monitoring, diagnosing the intrauterine death of one twin is not difficult when combined with clinical presentation. Whether intervention is required depends on the timing of diagnosis. If one fetus dies in early pregnancy, the dead fetus may be completely absorbed, requiring no intervention. For fetuses dying after the third month of pregnancy, as the trunk is not fully ossified, the water in tissues and organs and amniotic fluid gradually gets absorbed, and the fetus may become mummified and remain on the fetal membrane or be compressed by the surviving twin into a flattened "paper fetus." The key management for the death of one twin after the second trimester lies in monitoring the continued growth of the surviving fetus, amniotic fluid volume, placental function, and maternal coagulation status, including plasma fibrinogen levels, prothrombin time, partial thromboplastin time, platelet count, and fibrin degradation products. Special attention is needed for those complicated by pregnancy-induced hypertension syndrome. Fibrinogen is produced in the liver, and its decline in plasma reflects the degree of consumption when liver function is normal. In chronic disseminated intravascular coagulation, consumption and production may reach a dynamic balance, resulting in minimal fibrinogen decline. If the surviving fetus continues to grow well and maternal plasma fibrinogen levels remain stable, close observation is sufficient. However, if fibrinogen levels drop below 2.0 g/L (200 mg/dL) or the fetus is deemed viable, timely induction of labor to terminate the pregnancy is recommended. Fresh blood and fibrinogen should be prepared postpartum to prevent hemorrhage. For gestational ages <34 weeks, low-dose heparin therapy may be considered to improve fetal survival rates. Heparin inhibits thromboplastin, prevents prothrombin conversion to thrombin, counteracts thrombin, and inhibits platelet aggregation and destruction. Due to its large molecular size, heparin does not cross the placenta and thus does not affect the coagulation function of the surviving fetus. The usual dose is 100 mg/24 h via intravenous infusion, with monitoring of clotting time maintained at around 20 minutes. Typically, after 24–28 hours of heparin therapy, plasma fibrinogen levels recover sufficiently, after which the dose may be tapered, and labor induced as appropriate.
The ideal treatment for inter-fetal blood transfusion is to eliminate placental anastomotic vessels. Experimental success has been achieved using fetoscopy to locate and clamp these vessels or to coagulate blood within them using laser, with clinical application expected soon. Currently, the only option is fetal blood transfusion, performed under ultrasound guidance via maternal abdominal wall puncture into the fetal peritoneal cavity or umbilical vein, or through fetoscopy-directed umbilical vein transfusion. Pregnancy should be terminated at an appropriate time, considering fetal maturity, before the condition becomes severe. In severe twin-to-twin transfusion syndrome with unavoidable adverse outcomes, selective fetal reduction may be considered to improve the survival chances of the remaining fetus.
Postnatal treatment is effective with exchange transfusion. Exchange transfusion can be performed when the donor twin has grade III anemia and the recipient twin has a hematocrit >0.75. The transfusion volume is determined based on the hematocrit. For the recipient twin, exchange transfusion of 10–15 ml/kg is administered, and plasma or 5% glucose solution is infused to reduce blood viscosity and improve microcirculation. For the donor twin, transfusion should be performed if the hemoglobin level is <130 g/L.
4. To avoid high-order multiple pregnancies and improve pregnancy success rates, many scholars abroad advocate for selective fetal reduction in early pregnancy to reduce the number of developing embryos, thereby converting multiple pregnancies into twin pregnancies. This approach achieves reproductive goals while eliminating the high risks and poor prognosis associated with high-order multiple pregnancies. Currently, two operational methods are employed, both guided by ultrasound examination:
(1) Transabdominal approach: Select the gestational sac closest to the abdominal wall and occupying the highest position in the uterine cavity. Perform a transabdominal puncture into the gestational sac, fetal thoracic cavity, or fetal heart, and inject 3ml of 5% NaCl or 2ml of 15% KCl to induce fetal cardiac arrest.
(2) Transvaginal approach: Select the gestational sac closest to the vaginal probe. Perform a puncture through the vaginal fornix into the uterine wall and then into the gestational sac and fetal thoracic cavity, injecting 2ml of 15% KCl. Alternatively, connect the puncture needle to a 20ml syringe via a catheter, insert it into the gestational sac, position the needle tip close to the embryo, and abruptly aspirate to induce fetal cardiac arrest.
However, there is still debate over whether selective fetal reduction is appropriate for high-order multiple pregnancies in early pregnancy. Some scholars argue that it is of little significance and may easily lead to complete late abortion. Instead of passive remedial measures afterward, they advocate for proactive prevention: ① Control the dosage of ovulation-inducing drugs, especially HMG, to avoid excessive ovarian stimulation. ② Reduce the number of gametes or embryos transferred in a single procedure.
Management During Delivery
1. Choice of delivery method: There is considerable debate regarding the delivery method for twins, particularly concerning the gestational age at the onset of labor and the combination of fetal presentations. From the perspective of gestational age, it is currently recommended that twin pregnancies before 34 weeks should undergo vaginal delivery. Regarding fetal presentation combinations, the following consensus exists: ① For vertex-vertex twins, vaginal delivery is preferred, as the likelihood of head collision obstructing delivery is minimal, unless complications such as umbilical cord prolapse, placenta previa, or preeclampsia occur, or if premature rupture of membranes leads to uterine inertia unresponsive to treatment, in which case cesarean section is indicated. ② Transverse lie of the first fetus is an indication for cesarean section. ③ If the first fetus is in breech presentation and vaginal delivery cannot be ensured as safe, cesarean section is advisable. Olofsson et al. (1985) suggested that for pregnancies beyond 36 weeks with the first fetus in breech presentation, management should align with singleton breech deliveries, including pelvic X-ray measurements. A true conjugate diameter of 115mm and an outlet anteroposterior diameter + intertuberous diameter + interspinous diameter = 325mm serve as critical thresholds; values below these warrant cesarean section.
For vertex-breech or vertex-transverse presentations, the delivery method for the non-vertex second fetus after vaginal delivery of the first fetus remains controversial. Some advocate external cephalic version for all non-vertex second fetuses, whether breech or transverse. However, it is generally agreed that breech delivery or internal version followed by breech extraction is preferable. Previously, the criteria for allowing vaginal birth after cesarean (VBAC) included singleton, vertex presentation, and a low transverse uterine incision. Recent studies suggest that favorable maternal and neonatal outcomes can still be achieved even when these criteria are not met, indicating that selected twin pregnancies post-cesarean may attempt vaginal delivery.
For triplet or higher-order multiple pregnancies, most advocate for vaginal delivery. However, due to the increased risk of poor placental perfusion and placental abruption during delivery, rapid delivery is essential, with cesarean section reserved for obstetric complications.
2. Management of the three stages of vaginal delivery: For twin pregnancies planned for vaginal delivery, the management of the first stage of labor is fundamentally the same as for singleton pregnancies. If spontaneous rupture of membranes for the first fetus leads to umbilical cord prolapse, immediate internal examination is required to manually elevate the presenting part and avoid cord compression, followed by emergency cesarean section. If uterine inertia prolongs labor, conventional doses of oxytocin may be administered intravenously to augment contractions. If ineffective, cesarean section should be considered.
The progress of labor is smooth. Before the first fetus is about to be delivered, intravenous infusion is administered to prepare for blood transfusion. The delivery of the first fetus should not be too rapid to prevent placental abruption. After the first fetus is delivered, the umbilical cord is immediately clamped, and the placental end of the cord must be tightly secured to prevent blood loss in the second fetus. An abdominal examination is promptly performed to reposition the second fetus into a longitudinal presentation if possible, preventing it from turning into a transverse position due to the sudden decrease in intrauterine pressure and the still relatively large uterine cavity, which allows excessive movement. A vaginal examination is conducted to confirm the fetal lie and presentation. Once it is confirmed as a cephalic or breech presentation, gentle fundal pressure is applied, fetal heart sounds are closely monitored, and patience is exercised. If no progress is observed after 5 minutes and uterine contractions weaken, artificial rupture of membranes may be performed under fetal heart monitoring, or a routine dose of oxytocin may be administered intravenously. Premature intervention may lead to an overly rapid decrease in intrauterine pressure and increase the risk of fetal injury. Given that uterine contractions after the delivery of the first fetus reduce uteroplacental blood flow, potentially affecting the oxygen supply to the remaining fetus, and the possibility of a constriction ring forming due to cervical retraction hindering delivery, it is advisable to complete childbirth within 20 minutes. If umbilical cord prolapse or suspected placental abruption is detected, forceps-assisted delivery or breech extraction should be performed promptly for the second fetus. If the fetal head is high, internal podalic version and breech extraction may be performed to rescue the fetus. If the second fetus is in a transverse lie, external version may be attempted during the interval between contractions to convert it to a cephalic or breech presentation. If unsuccessful, immediate rupture of membranes followed by internal version and breech extraction should be performed. When the anterior shoulder of the second fetus is delivered, 0.2mg of ergometrine (contraindicated in hypertensive patients) is administered intravenously, and oxytocin infusion is accelerated. After the second fetus is delivered, a sandbag (weighing 1kg) is placed on the upper abdomen or an abdominal binder is tightly applied to prevent shock caused by sudden decreases in abdominal pressure. The height of the uterine fundus and vaginal bleeding are closely monitored, and active management of the third stage of labor is implemented to prevent postpartum hemorrhage. After the placenta is delivered, it should be carefully examined to determine whether the placenta and membranes are complete, and based on their composition, further judgment is made as to whether the twins are monozygotic or dizygotic. Two hours postpartum, once the mother's blood pressure and heart rate stabilize, the weight of the sandbag is reduced; it is removed after 24 hours.
The management of triplets or higher-order pregnancies through vaginal childbirth is similar to that of twin pregnancies.
3. Management of interlocking or collision of twin heads: In twin pregnancies where the first fetus is in breech presentation and the second fetus is in vertex presentation, interlocking of the heads may occur during childbirth. This happens when the head of the second fetus descends into the pelvis ahead of the first fetus, causing the chins of the two fetuses to hook together, resulting in difficult delivery. This rare complication mainly occurs in women with smaller fetuses or an overly large pelvis, especially in monochorionic twins or cases where the amniotic sac of the second fetus ruptures prematurely. If slow descent of the first fetus is observed during labor, the possibility of interlocking should be suspected, and an immediate X-ray can confirm the diagnosis. Once interlocking occurs, manual repositioning is extremely difficult. If the first fetus is alive, an emergency cesarean section is advisable. If detected late and the first fetus has already died, a decapitation may be performed to save the second fetus. If the procedure is too difficult, cesarean section should be performed immediately to rescue the second fetus without delay.
When both fetuses in a twin pregnancy are in vertex presentation, if the fetuses are small and the maternal pelvis is spacious, it is possible for both fetal heads to enter the pelvis simultaneously, colliding and causing obstructive difficult delivery. During childbirth, if the cervix is fully dilated but the first fetus descends slowly, a vaginal examination should be performed promptly. If abdominal examination confirms that the widest part of the second fetal head is below the pubic symphysis, a finger can be inserted vaginally through the cervix to push the second fetal head upward, allowing the first fetal head to descend.
1. General Complications
1. Late abortion: The natural late abortion rate in twin pregnancy is 2–3 times higher than in singleton pregnancy. The risk of late abortion increases with the number of fetuses, which is associated with embryonic malformations, abnormal placental development, placental circulatory disorders, and relative narrowing of the uterine cavity.
2. Fetal malformations: The rate of fetal malformations in twin pregnancy is twice as high as in singleton pregnancy, and the number of malformed fetuses in monozygotic twins is twice that of dizygotic twins. The reason for the increased malformation rate remains unclear. Intrauterine compression may lead to localized fetal deformities such as clubfoot or congenital hip dislocation, but it is unrelated to placental type and lacks evidence of increased chromosomal abnormalities.
3. Intrauterine growth restriction (IUGR): Before 30 weeks of gestation, the growth rate of twins is similar to that of singletons, but slows thereafter. The incidence of IUGR ranges from 12% to 34%, with severity worsening as gestational age advances. IUGR is more pronounced in monozygotic twins than in dizygotic twins.
4. Anemia: Due to increased blood volume, high iron demand, insufficient intake, or poor absorption, iron-deficiency anemia is common in the latter half of pregnancy. The need for folic acid rises during pregnancy, while urinary excretion increases. If dietary intake is inadequate or gastrointestinal absorption is impaired, megaloblastic anemia may occur.
5. Pregnancy-induced hypertension syndrome: The incidence is three times higher than in singleton pregnancy, with symptoms appearing earlier and often being more severe, making it difficult to control. The rate of eclampsia is also higher.
6. Polyhydramnios: Polyhydramnios occurs in 5–10% of twin pregnancies, a rate 10 times higher than in singleton pregnancies. It is particularly common in monozygotic twins and often affects only one of the fetuses.
7. Placenta previa: Due to the larger placental area, it is more likely to extend to the lower uterine segment and cover the internal cervical os, resulting in placenta previa. The incidence is twice as high as in singleton pregnancies.
8. Premature labor: Overdistension of the uterus, especially with multiple fetuses or concurrent polyhydramnios, leads to excessive intrauterine pressure and a high incidence of premature labor. Most cases occur spontaneously or after premature rupture of membranes. On average, twin pregnancies last only 37 weeks.
2. Special Complications
1. Twin-to-twin transfusion syndrome (TTTS): This is a severe complication primarily seen in monochorionic monozygotic twin pregnancies. It occurs when the blood circulation of the two fetuses is interconnected through placental anastomotic vessels, leading to unbalanced blood flow and transfusion.
2. Intrauterine death of one twin: In multiple pregnancies, not only are late abortion and premature labor more common than in singleton pregnancies, but intrauterine fetal death also occurs more frequently. Sometimes, one twin dies in utero while the other continues to grow and develop.
