Multifetal Gestation

Multifetal gestations are on the rise: twins now represent 33/1000 birth, and triplets or higher order gestations represent 1.53/1000 births. This is likely due to increased maternal age at conception and increased use of assistive reproductive medications and technologies. Certainly a multiple gestation pregnancy is exciting for patients, but convey a multitude of other risks for both maternal and fetal morbidity in pregnancy. Higher rates of almost anything you can imagine, including PIH/preeclampsia (RR 2.6 twins compared to singletons), placental abruption, HELLP, gestational diabetes, hyperemesis, anemia, hemorrhage, CD, PPD, cholestasis, PUPPS are elevated.

Most commonly preterm birth and its associated neonatal morbidity are encountered with these higher order pregnancies. Women with multifetal gestation are 6x more likely to deliver preterm and 13x more likely to deliver before 32 weeks compared to women with singleton gestation. Twins deliver on average around 35-36w and triplets around 32-33w. Furthermore, compared to gestational age matched premature singleton neonates, those in multifetal gestation have worse outcomes, higher rates of stillbirth, neonatal death, intraventricular hemorrhage, periventricular leukomalacia, and cerebral palsy And unfortunately, there are no strategies that exist to reliably mitigate this risk, including progesterone, cerclage, or pessary. However, many ongoing trials seek to answer this question. Multifetal reduction can help to mitigate these risks in higher-order gestations.

Diagnosing Multiple Gestation

The components of chorionicity and amnioniticity are ideally noted in a first or early second trimester sonogram (best at 10-14 weeks).

1. Super important as this dictates antepartum management and delivery recommendations! 

   1. Dating in spontaneously conceived twins: if there is a CRL discordance, most radiologists would date pregnancy with larger CRL in order to not underdiagnose FGR (ART use transfer/IUI dating).

2. Chorionicity (fetal side of uteroplacental interface) and amnionicity (sac with amniotic fluid)

• Fraternal twins: dizygous 70% different sperm and different egg, same genetic relationship as any other set of siblings born at different ages -> dichorionic gestation (which implies diamnionicity as well).

• Monozygous 

  1. Split within 3 days: dichorionic (20% of monozygous)

  2. Split 4-8 days: monochorionic / diamniotic (70%)

  3. Split 9-12 days: monochorionic / monoamniotic (1% of all monochorionic twins) 

  4. Split 13(+): conjoined (unlucky 13)

• Rule of thumb, monochorionic always higher risk than dichorionic.

1. Diagnosis: going back to episode 68 OB ultrasound

   • Dichorionic gestation can be diagnosed by any of the following: two distinct placentas, different fetal sex, or twin peak/lambda sign vs T-sign.

“Lambda” sign for dichorionic gestation. The OBG Project / Nevit Dilmen Creative Commons Attribution-Share Alike 3.0 license https://creativecommons.org/licenses/by-sa/3.0/deed.en

“T” sign for monochorionic, diamniotic gestation. The OBG Project / Nevit Dilmen Creative Commons Attribution-Share Alike 3.0 license https://creativecommons.org/licenses/by-sa/3.0/deed.en

Common Antepartum Considerations for Multiple Gestations

Recommended weight gain

1. CO 548 weight gain in pregnancy 

   1. Normal weight: 37-54

   2. Overweight: 31-50

   3. Obese: 25-42

Aneuploidy screening

1. Inherent increased risk with dizygous gestation - two babies, twice the risk!

2. Serum screening is not as sensitive because analyte levels are estimated by mathematical modeling. In reading serum levels from a multiple gestation, they are essentially “averaged out,” so a genetically normal twin can mask the abnormal level of the twin affected by aneuploidy.

   1. Can add nuchal translucency for increased sensitivity since you can see which twin may have an anomaly.

3. NIPT (cell free DNA, Mat21 esp) in small studies have high sensitivity and specificity similar to singleton gestation, but the reported cases are small and we likely need larger studies to better get at the true sensitivity and specificity.

4. As always, diagnostic testing with CVS or amniocentesis most accurate and should be offered. Loss rate about 1-2% for both procedures and slightly higher than in singleton gestation.

   1. Amnio for dichorionic gestation: can sample one sac, inject indigo carmine, then sample second sac to ensure clear fluid and ensure sampling of two separate sacs.

   2. Amnio for monochorionic gestation - if chorionicity has been confidently established, unlikely to have discordance between the two fetuses so might only sample one; although its possible to have genetic discordance due to fetal mosaicism 

Twin growth

1. Used to have twin growth rates curves, but didn’t pan out in follow up studies. So now we use a singleton growth curve, and note a slow down after 30 weeks.

2. Should obtain anatomy ultrasound 18-22w, and given increased risk of congenital anomalies reasonable to start with L2 or specialized ultrasound.

   1. Monozygous twins have higher rates of anomalies (especially cardiac), so fetal echoes are recommended.

3. Growth ultrasounds every 4 weeks measure % discordance. If discordance > 20% may warrant closer evaluation (EFW lg - EFW sm / EFW lg), could be a sign of developing FGR and associated with poor neonatal outcomes.

   1. Monochorionic every 2-3 weeks after 16w.

   2. Dichorionic every 4-6 weeks after anatomy scan in otherwise uncomplicated pregnancies.

4. Twin gestation with one fetal growth restricted fetus associated with worse perinatal outcomes.

5. Cord anomalies (basically moot, since they’re already getting monitored for growth):

   1. Velamentous cord insertion 

      • 7-12% twin pregnancies compared to 2% in singleton gestation 

   2. Marginal cord insertion 

   3. Placenta previa

      • Higher incidence likely due to more placental mass 

   4. Vasa previa

      • Systematic review of cohort and case control series found that of 438 cases of vasa previa, 11% in twins.

Specific Monochorionic Considerations 

1. Diamniotic (US 16-18 weeks)

   • Twin Twin Transfusion Syndrome

     1. 10-15% of mono/di pregnancies due to arteriovenous connections → unequal vascular sharing; by contrast, in 6% of monochorionic pregnancies  

     2. Diagnosis by Quintero staging 

        1. Stage 1: oligo/poly DVP.

        2. Stage 2: absent bladder in donor twin.

        3. Stage 3: abnormal doppler findings 

           1. UA, DV, UV

        4. Stage 4: hydrops

        5. Stage 5: death of one or both twins  

     3. Stage can remain stable, regress, or progress (sometimes rapidly).

     4. Earlier the diagnosis more severe the disease

     5. Treatment is laser ablation of anastomoses or amnioreduction 

     6. Monitoring:

        1. Weekly AFI 

        2. Every 3-4 weeks growth scan.

        3. After 30 week weekly BPP.

   • TAPS twin anemia polycythemia sequence 

     1. Atypical chronic TTTS where the transfusions happens super slowly, through the smallest vessel connections, manifested in >MCA 1.5 MoM of one twin and < 1.0 MoM of the other twin 

        1. 2-13% due to post-TTTS laser (large anastomosis obliterated, smaller ones persist).

   • To distinguish TTTS vs single IUGR - guide is fluid volume.

   • Twin Reverse Arterial Perfusion (TRAP) Sequence

     • Acardiac twin 

       1. One twin absent head/heart but stays living, other pump twin can develop high output heart failure with 50% mortality rate.

     • Requires ultrasonic laser ablation of acardiac twin vasculature.

2. Monoamniotic

   1. Cord entanglement/accident → IUFD

      • Antenatal management hard to agree upon, some do daily NST beginning in the late second or early third trimester, IP vs OP management, no consensus.

      • Rare, but can have TTTS in mono/mono.

What happens if a twin demises? 

1. Spontaneous reduction or vanishing twin 36% in the first trimester and even higher for higher order multiples 

2. Second trimester: up to 5% twins and 17% triplets undergo death of one of the fetuses 

   1. Monochorionic set higher rate of stillbirth and neurologic deficits in surviving twin than dichorionic set, recommendation to continue with pregnancy until at least 34 weeks. 

   2. Thought to be due to hemodynamic changes where intrauterine demise of one twin becomes a low pressure system, and the other twin can effectively exsanguinate or have hypotension/anemia from perfusion being directed towards the demised twin, subsequently causing death or neurologic injury of surviving twin.

Preterm labor 

1. Asymptomatic

   1. Counseling patients they will be at a higher risk of PTL 

   2. No recommended screening for asymptomatic women, since no interventions have been proven to be helpful for women with multifetal gestation.

   3. One study showed prophylactic cerclage in women with twin gestation and short cervix on US actually increased the rate of sPTB with a RR of 2.2 

2. Managing spontaneous PTL 

   1. Short term of tocolysis for administration of corticosteroids recommended, as those trials included some women with multiple gestation less than 34w.

      • Includes one course of rescue steroids (risk of delivering within the next 7 days, most recent course was at least 7 days ago) and extending to 23w after counseling on expectations and working closely with NICU to go over available resources.

   2. What about ALPS steroids for multiple gestation?

      • They were not included in the original trial, but we extrapolate their benefits and do recommend them at our institution.

      • Currently the ACTWIN trial, a multicenter RCT enrolling based out of Seoul, is attempting to answer this question.

   3. Magnesium sulfate for neuroprotection under 32 weeks regardless of fetal number.

Delivery planning 

1. Dichorionic 

   1. In uncomplicated pregnancies, delivery no later than 38th week.

   2. Candidate for vaginal delivery if presenting twin vertex and someone with experience with internal podalic version and vaginal breech delivery available, including TOLAC candidates (one previous).

2. Monochorionic 

   1. 34 to 37’6, with same principles as above for VD vs CS.

3. mono/mono 

   1. 32-34w scheduled CS.