Multifetal Gestations

Multifetal Gestations

• Multifetal gestations in the U.S. have dramatically increased over several decades.
• Twin birth rates increased 76% between 1980 and 2009, from 18.9 to 33.3 per 1,000 births.
• Twin birth rates experienced a 4% decline between 2014 and 2018, reaching 32.6 twins per 1,000 total births in 2018.
• Triplet and higher-order multifetal gestations increased by 400% in the 1980s and 1990s, peaking at 193.5 per 100,000 births in 1998.
• Triplet and higher-order multiple birth rate was 93.0 per 100,000 births for 2018.
• This is an 8% decrease from 2017 (101.6) and a 52% decline from the 1998 peak (193.5).
• This trend is due to older maternal age at conception as naturally-occurring multifetal gestations are more likely and assisted reproductive technology (ART).
• ART increases the chances of multifetal gestation.
• Perinatal complications are increased with multiple gestations, including fetal anomalies, preeclampsia, and gestational diabetes.
• One concerning issue is preterm birth, which results in high infant morbidity and mortality.

Management approach

• The Practice Bulletin reviews the issues and complications surrounding multiple births.
• It presents an evidence-based approach to management.

Fetal and Infant Morbidity and Mortality

• Multifetal gestations elevate the risk of fetal and infant morbidity, and mortality.
• There is a fivefold increased risk of stillbirth along with a sevenfold increased risk of neonatal death, mostly due to prematurity.
• Women are 6x more likely to give birth preterm.
• They are 13x more likely to give birth before 32 weeks of gestation.
• Increased risks for short-term and long-term neonatal and infant morbidity.
• Twins born preterm are at twice the risk of high-grade intraventricular hemorrhage and periventricular leukomalacia.

Multifetal Gestation Statistics

• Singletons average a birth weight of 3,285 g, twins 2,345 g, triplets 1,680 g, and quadruplets 1,419 g.
• The mean gestational age is 38.5 weeks for singletons, 35.0 weeks for twins, 31.7 weeks for triplets, and 30.3 weeks for quadruplets.
• The percentage of births less than 34 weeks gestation is 2.1% for singletons, 19.5% for twins, 63.1% for triplets, and 82.6% for quadruplets.
• The number of births with gestation less than 37 weeks is 8.2% for singletons, 60.3% for twins, 98.3% for triplets, 97.4% for quadruplets.
• This explains the increased prevalence of cerebral palsy.
• Multifetal gestation is associated with significantly higher costs, due to the costs associated with prematurity
• Average first-year medical costs are up to 10 times greater for preterm infants than for term infants.

Chorionicity

• Ultrasonography determines fetal number, estimated gestational age, chorionicity, and amnionicity.
• Chorionicity is determined due to the increased risk of complications in monochorionic pregnancies.
• Chorionicity assessments are most accurate early in gestation.
• Monochorionic twins have higher rates of fetal and neonatal mortality, fetal/congenital anomalies, prematurity, and fetal growth restriction.
• A triplet gestation that is fully monochorionic, or a monochorionic twin pair has higher risks.
• Need for increased screening and potential interventions highlights the determination of chorionicity.

Maternal Morbidity and Mortality

• Medical complications are more common, which includes hyperemesis, gestational diabetes mellitus, hypertensive disorders of pregnancy, anemia, hemorrhage etc.
• Hypertensive complications scale to the total fetal number.
• Singletons have a 6.5% risk, twins 12.7% risk, and triplets a 20.0% risk
• ART pregnancies have increased risk (RR, 2.1) of preeclampsia.
• Preeclampsia tends to occur earlier in twin pregnancies, resulting in a higher rate of complications including preterm delivery and abruptio placentae.
• Low-dose aspirin (81 mg/day) recommended, initiated between 12 and 28 weeks of gestation and continued daily until delivery.
• Women with higher-order multifetal gestations are more likely to present preeclampsia atypically.
• If hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome develops before term, transfer patient to a tertiary care center.
• The likelihood of multifetal gestation increases with maternal age.
• Multiple birth ratios increase from 16.3 per 1,000 live births for women younger than 20 to 71.1 per 1,000 live births for women 40 and older.
• Older women are more likely to have obstetric complications, including gestational hypertension, gestational diabetes, and abruptio placentae.

Contribution of Assisted Reproductive Technology

• ART has led to a dramatic incline in multifetal births.
• The most effective techniques are IVF and controlled ovarian hyperstimulation with gonadotropins.
• In 2017, 25.5% of pregnancies conceived with ART are twins and 0.9% are higher-order multifetal pregnancies.
• Data from 2017 shows variations in single embryo transfer rates among territories, reflecting variations in embryo-transfer practices among fertility clinics.

Multifetal Reduction and Selective Fetal Termination

• Multifetal reduction lowers the likelihood of preterm delivery and other complications.
• Women who underwent pregnancy reduction from triplets of twins have lower frequencies of pregnancy loss, antenatal complications, preterm birth, low-birth-weight infants, cesarean delivery, and neonatal deaths.
• Multifetal reduction from twins to a singleton before 15 weeks of gestation is associated with a lower risk of preterm birth and a higher birth weight.
• Choices for reduction are based on technical considerations, ex. which is most accessible to intervention and chorionicity.
• Selective fetal termination is the application of the fetal reduction to an abnormal fetus.
• Selective fetal termination has higher risks.
• Pregnancy prolongation has been observed in women who undergo selective fetal termination.

Clinical Considerations and Recommendations

• Fetal risk is dependent on chorionicity.
• Chorionicity should be established as early as possible.
• Optimal timing for chorionicity includes the first trimester and the early second trimester.
• Ultrasound at 14 weeks of gestation or less has sensitivity, specificity, and positive/negative predictive values of 89.8%, 99.5%, 97.8%, and 97.5% for prediction of chorionicity.

Tests To Predict Preterm Birth in Multifetal Gestations

• Don't routinely use transvaginal cervical length, digital examination, fetal fibronectin screening, or home uterine monitoring.
• In symptomatic women who present signs of preterm labor, positive fibronectin test/short cervical length alone should not direct management.

Routine Prophylactic Interventions

• Routine prophylactic interventions including cerclage, hospitalization, bedrest, tocolytics, and pessary, shouldn't be used based solely on the indication of multifetal gestation

Prophylactic Cerclage

• Without history of cervical insufficiency has not been shown to be beneficial.

Routine Hospitalization and Bed Rest

• Not recommended, due to lack of benefit and risks of thrombosis/deconditioning.

Prophylactic Tocolytics

• Prophylactic use is not indicated.
• Risk of side effects such as pulmonary edema may occur.
• No benefit of preterm birth or neonatal outcomes occurred in studies.

Prophylactic Pessary

• No high-quality evidence that prophylactic cervical pessary decreases rates of spontaneous preterm birth of perinatal morbidity.

The Risks of Progesterone Treatment

• Progesterone treatment lowers spontaneous preterm birth risk.

Managing Preterm Labor

• Tocolytic therapy may provide short-term prolongation.
• Calcium channel blockers or nonsteroidal antiinflammatory drugs should be first-line.
• In multifetal gestations a brief course of tocolysis may be considered for 48 hours in acute preterm labor to administer corticosteroids.
• Pulmonary edema maternal risk for tocolytic use.

Corticosteroids

• Administration for singleton gestations has been shown to decrease neonatal death, respiratory distress syndrome, intraventricular hemorrhage and necrotizing enterocolitis.
• Should be administered to all patients at delivery risk between 24 and 34 weeks of gestation unless contraindication exists or it is linked to a family's decision regarding resuscitation.
• Scheduled repeat courses are not recommended.

Magnesium Sulfate

• Used for fetal neuroprotection.
• Large studies have been performed to see if it decreases death and cerebral palsy.
• Perinatal administration of magnesium sulphate reduced cerebral palsy.

Special Considerations

• All women with multifetal gestations are candidates for routine screening for fetal chromosomal abnormalities.
• Monochorionic twins reflect single test results.
• First-trimester, quad, and sequential or integrated screening are options available to screen twin gestations.