Selective Intrauterine Growth Restriction in Monochorionic Twins

Abstract

EFW of small fetus less than 10th centile/EFW discordancy >25% pathophysiology-unequal placental sharing role of vascular anastamosis in natural history-larger interfetal blood flow—type 3 better outcome than type 2 classification-based on umbilical artery doppler into three types complications—IUD of snall fetus with acute TTTS-neurological sequelae in normal twin suerviellance and management of types type 1-expectant management, close followup(weekly/biweekly doppler surviellance) and delivery by 34–35 weeks type 2-long latency to deterioration than singleton. Doppler (Ductus venosus) follow up alternate days (if abnormal DV)0r weekly (normal DV) delivery by 30–32 weeks type 3-intermittent doppler changes due to large AA anastamosis. Weekly followup if DV normal or closer follow up if abnormal. Deliver at 32 weeks role of fetal intervention-GA <24 weeks with AREDF/DV PI >95/discordancy >35%.

1. Introduction

Chorionicity decides the surveillance frequency and management in twin pregnancies than zygosity. Chorionicity is best assessed by ultrasound examination of number of placental masses, intertwin membrane thickness, examining the site of intertwin membrane attachment to placenta in cases of single fused placenta in the late first trimester or early second trimester [1].

Monochorionic twins have a higher frequency of fetal and neonatal mortality, as well as morbidities compared to dichorionic twins. Increased perinatal morbidity and mortality in monochorionic pregnancy is due to shared placenta and interplacental vascular anastomosis [2, 3].

Chronic unbalanced vascular transfusion results in twin-twin transfusion syndrome (TTTS) and twin anaemia polycythemia sequence (TAPS). Discordant placental territory results in selective intrauterine growth restriction. Unidirectional acute transfusion happens as a sequelae of single fetal demise.

Selective intrauterine fetal growth restriction (sIUGR) is a common complication in Monochorionic pregnancy. Selective fetal growth restriction is associated with increased risk of intrauterine fetal demise, prematurity and neurological adverse outcomes for one or both twins [4, 5, 6, 7, 8].

2. Definition and prevalence of sIUGR

The term ‘selective intrauterine growth restriction’ is applicable to cases meeting the following criteria.

1. Monochorionic pregnancy.

2. Estimated fetal weight (EFW) of the small fetus falls below the 10th percentile [4, 5].

3. Significant fetal weight discordance is an important element of the clinical picture. This is defined by different authors as discordance between the EFWof two foetuses>25% [9, 10]. Estimated fetal weight discordance is calculated with the following formula: (weight of the larger twin−weight of the smaller twin) × 100/weight of the larger twin.

The clinical significance of cases when both twins’ EFW falls below the 10th percentile without discordance, or cases when discordance exists but the smaller fetus’ EFW is above the 10th percentile, remains to be defined.

The prevalence of sIUGR ranges from 10 to 15% in monochorionic pregnancies [5, 11, 12, 13].

3. Pathophysiology of sIUGR

The principle cause for the development of sIUGR in MC twins is inadequate placental sharing [14, 15, 16, 17] the discordance increases with increase in the discordance of placental territories between twins.

A second factor largely influencing fetal weight discordance and sIUGR in MC twins is the presence of placental vascular anastomoses/shared circulation in the monochorionic placenta [17, 18, 19].

There are basically three types of vascular anastomosis in the placenta: 1) Arterio-venous (AV) anastomoses which is characterised by unidirectional flow where a placental cotyledon is perfused by an artery from one fetus and drained by a vein going to the other fetus. This is a deep anastomosis. 2) Arterio-arterial (AA) and 3) Veno-venous (VV) anastomoses are superficially located in placenta characterised by bidirectional flow of blood; these bidirectional anastomosis have an important role in compensating the volume/pressure imbalances between foetuses.

Because of this unique vascular anastomosis in placenta and feto-fetal blood interchange via the anastamotic channels have a protective effect on the IUGR fetus, which receives blood with a normal oxygen and nutrient content from its co-twin and this is responsible for long latency before deterioration in monochorionic twins as compared to singleton.

Thus inter-twin anastomotic area, net AV transfusion and the diameter of AA anastomoses have been shown to correlate with the degree of inter-twin placental discordance. And this unique vascular anastomosis and inter fetal blood interchange is responsible for the discrepancy observed between the placental discordance and the clinical outcome.

For twins with similar placental area discordance (due to unequal sharing), twins with larger interfetal blood flow interchange (large AA anastomosis) have milder degree of clinical expression of growth restriction and better ioutcome than twins with few or smaller AA anastomosis.

Large AA anastomosis also associated with unpredictable outcomes like Double fetal demise/neurological sequelae in one or both foetuses in the absence of single fetal in type 3 IUGR.

4. Clinical implications of sIUGR

Selective IUGR is a severe complication, particularly if presenting during the second trimester, with potentially significant risks of intrauterine demise or neurological adverse outcome for both the affected IUGR and the normally grown twin [4, 5, 6, 7, 8, 9, 10, 11].

Unique complication in monochorionic twins with sIUGR is single fetal demise/intrauterine death of growth restricted twin. And this event is associated with risk of acute feto fetal transfusion (Acute TTTS) from the normally grown twin to dead fetus due to sudden change in pressure between foetuses subsequent to single fetal demise. Acute feto-fetal transfusion is associated with 20–30% chance of neurological sequelae in surviving twin due to ischemia and hypoxia to the brain and 15–20% chance of death of larger twin due to sudden hypovolemia [20, 21].

In the absence of single fetal demise, sIUGR is associated with risk to normally grown and growth restricted twin due to following reasons:

1. To avoid the complication of single fetal demise of growth restricted twin Iatrogenic prematurity exposes the normally growing twin to face the complication associated with prematurity [22, 23].

2. In cases of type 3 sIUGR there is high risk of acute feto-fetal transfusion accidents in utero due to the large AA anastomosis in the placenta and this event increases the risk of neurological complications in both the foetuses [4, 7, 24].

5. Screening for sIUGR in monochorionic pregnancy

Do not use abdominal palpation or symphysis-fundal height measurements to monitor for fetal growth restriction in women with a monochorionic twin [25].

Ultrasonography is the screening modality of choice. At each ultrasound scan from 16 weeks, assesss fetal biometry and calculate the fetal weight discordance in addition to amniotic fluid level assessment. Surveillance to be conducted every 2 weeks [25].

On surveillance if there is an EFW discordance of 25% or more between twins and the EFW of any of the babies is below the 10th centile for gestational age the women should be referred to a tertiary level fetal medicine centre [25].

6. Classification of sIUGR

In singleton and Dichorionic twin pregnancies, doppler waveform of umbilical artery is commonly used to diagnose, plan surveillance frequency for fetus with growth restriction due to uteroplacental insufficiency [26].

In monochorionic pregnancies the changes in umbilical artery waveform represents combined effect of uteroplacental insufficiency and inter-twin vascular anastamosis [22, 27, 28, 29, 30, 31].

Based on the characteristics of diastolic flow of umbilical artery Doppler waveform selective fetal growth restriction in monochorionic twin pregnancies is categorised into following three types:

1. Type I sIUGR characterised by presence of diastolic flow in umbilical artery waveform.

2. Type II sIUGR characterised by persistent absence/reversal of flow in umbilical artery Doppler waveform.

3. Type III sIUGR characterised by intermittent absence/reversal of flow in umbilical artery Doppler waveform (iAREDF) [22, 27, 28]. These types not only correlate with distinct clinical forms but also with distinct patterns of placental anastomoses

Type 3 also been defined as cyclical pattern because of intermittent changes in Doppler waveform. This intermittent changes happens because of the presence of large interplacental AA anastomosis causing waveforms pattern due to transmission of blood from larger to smaller twin [22, 27].

To diagnose type 3 sIUGR sweep speed of Doppler to be kept low and longer traces has to be observed.

Doppler changes in selective fetal growth restriction are evident early in pregnancy and there is a long latency between onset of Doppler changes and progression because of the presence of shared vascular anastomosis. The clinical outcomes are considered; good in type 1 cases, increased risk of deterioration observed in type 2 cases with poor prognosis. Type 3 sIUGR have comparatively better prognosis than type 2 cases due to large AA anastomosis. Large AA anastomosis also increases the risk of antepartum brain hypoxic and ischemic injury to both the twins with a unpredictable outcome in type 3 cases [4, 24].

7. Differential diagnosis

Monochorionic pregnancies need fortnightly surviellance to rule out evolving complications [21]. during followup ultrasound fetal biometry, estimated fetal weight, single vertical pocket measurement made and weight difference calculated at each visit. Detailed anatomical evaluation with extended cardiac evaluation done around 20–22 weeks in both twins. Doppler assessment of umbilical artery, middle cerebral artery done in each visit.

Detailed evaluation rules out the common differential diagnosis of SIUGR which is TTTS characterised by EFW discordance with a characteristic liquor discordance between twins (SVP <2 cm in donor and SVP >10 cm in recipient) [21].

8. Type I sIUGR

8.1 Definition and placental features

Type I sIUGR is characterised by presence of diastolic flow in umbilical artery of smaller twin (Figure 1). In twin pregnancy with unequal placental sharing there should be a linear relation between shared placental territory and the fetal weight difference between twins. In selective fetal growth restriction this ratio is lower that is the actual fetal weight discordance between twins is lower compared to the placental territory discordance. This is because of the shared vascular anastomosis favours the blood flow from larger to smaller twin in a compensatory manner attenuating the effects of unequal placental territory sharing (placental insufficiency of smaller twin) [7, 16, 17].

Figure 1.

PD of umbilical artery—End diastolic flow noted in smaller twin (type I).

8.2 Clinical evolution and suggested management

Type I cases are generally associated with good outcomes and 90–95% perinatal survival. Intrauterine fetal death rates in type I sIUGR is around 2–4% [7, 24, 30]. and neurological damage was reported in less than 5% of cases [3, 25].

The deterioration or worsening of Doppler parameters in smaller twin is slower than the singleton growth restricted fetus. Most cases of type I sIUGR will remain without progression till delivery.

Smaller twin of sIUGR type I usually will show a linear growth curve without deterioration. Type I sIUGR cases need expectant management with close follow-up to rule out progression to type II. Type I cases need weekly ultrasound and Doppler surveillance.

Elective delivery planned around 34–36 weeks in type I sIUGR cases without deterioration [21].

9. Type II sIUGR

9.1 Definition and placental features

Type II sIUGR pattern is characterised by persistently absent or reversed end-diastolic flow in the umbilical artery (Figure 2). Type II sIUGR cases have more severe placental discordance than type I cases [16]. Despite severe placental territory discordance the fetal weight difference between twins is lower illustrating the attenuating effect of shared vascular anastomosis between twins [16].

Figure 2.

PD of umbilical artery—Absent end diastolic flow in smaller twin (type II sIUGR).

Type II sIUGR have smaller diameter of placental vascular anastomosis and fewer anastomosis than type I sIUGR cases. Hence the protective effect of vascular anastomosis is less efficient in type II sIUGR cases.

Thus, placental insufficiency in type II is far more severe than in type I and cannot be fully compensated by inter-twin transfusion.

Fetal deterioration defined by abnormal progression of Doppler wave forms in ductus venosus happen before 30 weeks of gestation in 70–90% cases of type II sIUGR [4, 7, 22, 24].

9.2 Clinical evolution

Because of the protective effect of shared vascular anastomosis there is a longer latency period between onset of absent or reversed end diastolic flow in umbilical artery to ductus venosus Doppler decompensation (Pulsatality index >95th centile/‘a’ wave absence or reversal) or pathologically abnormal biophysical profile warranting delivery in monochorionic twins (approximately 10 weeks) compared to singleton pregnancy with similar Doppler findings (3–4 weeks) [7, 22].

At the same time the gestational age of onset of abnormal Doppler finding (A/REDF) is much earlier in complicated monochorionic twins (20 weeks) compared to singletons (27 weeks) with clinical deterioration warranting iatrogenic premature delivery around 30 weeks in 90% cases [7, 22].

Elective delivery is indicated in most of these pregnancies earlier than 30 weeks of gestation [7, 22] with only a small minority surviving in utero beyond 32 weeks. Incidence of single fetal demise of smaller twin in type II sIUGR is around 20–30% [3].

9.3 Management

Close fetal surveillance with Doppler evaluation of umbilical and ductus venosus Doppler is practiced although type II sIUGR complicated twins have a longer latency period before clinical deterioration.

Ductus venosus Doppler is useful tool to plan timing of delivery in type II sIUGR cases as DV Doppler abnormality is the predictor of imminent fetal death. Weekly follow up is ideal if ductus venosus Doppler is normal and more frequent follow up scheduled if ductus venosus shows abnormality (pulsatility index >95th centile/absent or reversal of a wave of DV Doppler). Biophysical profile can be included as surveillance tool after fetal viability is reached.

Elective delivery is indicated in most of these pregnancies earlier than 30 weeks of gestation [7, 22] with only a small minority surviving in utero beyond 32 weeks.

9.4 Role of fetal intervention

Fetal therapy is preformed in:

1. severe cases diagnosed before 24 weeks of gestation (cases with severe discordance >35% before viability or ductus venosus Doppler pulsatility index >95th centile before 24 weeks).

2. if smaller fetus shows signs of imminent fetal death (ductus venosus Doppler showing absent or reversal of a wave) before fetal viability (before 24 weeks of gestation).

Fetal intervention methods:

1. Cord occlusion—Bipolar cord coagulation of smaller fetus [32, 33, 34]. Studies showed 90% survival rate in normal fetus after procedure [33]. Cord occlusion is the preferred fetal intervention in indicated cases of sIUGR.

2. fetoscopic laser coagulation of intertwin anastomoses [32, 34] studies found remarkable mortality rates in normally grown fetus (20–30%) with laser coagulation [35]. Fetoscopic laser coagulation of vascular anastomosis associated with increased risk of preterm labour, double fetal demise. Laser coagulation is technically difficult in sIUGR cases than twin to twin transfusion cases due to absence of placental flattening (no polyhydramnios in sIUGR) and presence of amniotic fluid in smaller twin sac hampering the visualisation of vascular equator [32] all yjese are associated with increased complication rates with laser surgery.

10. Type III sIUGR

10.1 Characteristic doppler findings and placental features

Type III sIUGR is defined by the intermittent Absent/Reversed End Diastolic Flow in the Umbilical artery Doppler of the growth restricted twin. This alternation in positive waveform and absent/reversal of diastolic flow in umbilical artery is characteristic of Monochorionic twin due to presence of shared vascular anastomosis in the placenta (Figure 3). This unique wave pattern indicates the presence of a large placental Arterio-Arterial anastomosis [29, 32], facilitating transmission of the systolic waveforms of one twin into the umbilical cord of the other twin.

Figure 3.

PD of umbilical artery—intermittent absent end diastolic flow—Type III SIUGR.

This Doppler pattern of intermittent absent/reversal of flow in end diastolic flow of umbilical artery can also be observed in rare cases of uncomplicated monochorionic pregnancies with very close cord insertions and even in pregnancies complicated with TTTS [31].

10.2 Clinical evolution and pathophysiological basis

The sign is often more pronounced near the placental cord insertion site. Maternal breathing to be withheld during Doppler assessment to avoid artefacts associated with maternal movements. A low sweep speed pulse Doppler setting is ideal to identify the cyclic changes, otherwise it can easily be missed and may lead to under-diagnosis of type III sIUGR cases.

Placental territory discordance is highest in type III sIUGR cases [16]. Large Arterio-arterial anastomosis compensates the imbalance because of the massive transfusion from larger to smaller twin. This large Arterio-arterial anastomosis increases risk of acute feto-fetal transfusion episodes in the event of transient bradycardia of the smaller twin, increasing the risk of unexpected intrauterine death of the growth restricted fetus and ischemic brain injury in the normally grown twin [16].

Normally grown fetus is at risk of hypertrophic cardiomyopathy-like changes (20% cases) as it has to supply blood for smaller twin through large AA anastomosis [36]. So in a way larger twin works as pump twin (in cases of monochorionic pregnancy with acardiac fetus) and experiences cardiac strain. Such cardiac changes are not associated with a immediate poorer neonatal prognosis [37], although the long-term impact on cardiac function has not been evaluated.

IUGR type III pregnancies are characterised by an apparently benign evolution due to the compensating effect of the large Arterio-arterial allowing survival of the severe growth restricted fetus beyond 32 or 34 weeks without any sign of hypoxic deterioration.

Presence of large arterio-arterial anastomosis is associated with risk of fetal demise of smaller twin in 15–20% cases with a risk of hypoxic brain damage in normally grown twin due to acute feto-fetal transfusion in 15–30% cases [4, 26].

However, type III sIUGR is associated with a risk of unpredictable fetal demise of the growth restricted fetus in up to 15–20% of cases. There is also risk of brain damage of the normally grown fetus, even when both foetuses are born alive, affecting as many as 15–30% of cases [4, 24]. These complications are due to acute feto-fetal hemorrhagic accidents through the large Arterio-Arterial anastomosis happening during transient bradycardic episodes of the smaller twin.

10.3 Clinical management of type III sIUGR pregnancies

Management of type III sIUGR represents a challenge.

Prognosis is better than type II cases due to protective effect of smaller twin by the arterio-arterial anastomosis. Same anastomosis is associated with increased risk of unpredictable adverse outcomes like single fetal demise, double fetal demise, hypoxic and ischemic damage to normally grown twin and its sequelae.

Risk associated with type III sIUGR cases are due large Arterio-arterial anastamosis, a high inter fetal weight discordance, and a short distance between the cord insertions.

Weekly ultrasound and Doppler surveillance if ductus venosus doppler is normal and closer followup if ductus venosus flow becomes abnormal.

Elective delivery around 32-34 weeks of gestation [21], to reduce the opportunity for unexpected adverse outcomes.

10.4 Role of fetal intervention

Fetal therapy is considered for very early (before fetal viability)severe cases,cases with extreme estimated fetal weight discordance(>35% discordance).

Cord occlusion is preferred method of fetal intervention. Laser coagulation is also feasible in type III pregnancies, but it is associated with more technical difficulties than in type II [35].

11. Flow chart of management

See Figure 4.

Figure 4.

Flow chart of management of selective fetal growth restriction.