This report illustrated the postnatal neurological consequences in the survivors of monochorionic triplet pregnancy complicating by single intrauterine death in early gestation followed by fetofetal transfusion syndrome. Intrauterine fetal death in triplet pregnancies are not rare event. Dickey et al. [
6] reported incidence of spontaneous reduction of triplet pregnancies was 53% (64/132, 95% CI, 44–61%) before 12 weeks of gestation. After 22 weeks of gestation, Kawaguchi et al. [
5] reported intrauterine fetal death rates were 0.8% (12/1521), 2.8% (12/432) and 2.7% (4/150) for trichorionic triamniotic, dichorionic triamniotic and monochorionic triamniotic triplet pregnancies respectively. Few small case series and case reports are available in the literature describing the pregnancy outcomes [
7,
8]. However, the majority of these studies had undetermined chorionicity and gestational age of fetal demise as well as unknown neurological follow up of the surviving triplets. Compared with triplet pregnancies, the profound adverse outcome of single twin demise in the second and third trimesters on the surviving co-twin has been well described [
9‐
11]. A systematic review by Hillman et al. [
9] found that among the surviving monochorionic twins, 34% had abnormal postnatal cranial imaging and 26% had neurodevelopmental impairment. The postulated mechanism was acute and transient transfusional event from the live fetus to the dead fetus through the placental vascular anastomoses leading to hypoxic-ischeamic injury of central nervous system because of hypoperfusion. Adverse effect on other body systems such as bowel, skin and limbs was also reported [
12]. The anatomical distribution and pattern of cerebral hypoxic-ischaemic lesions would depend on time and duration of insult [
13]. If hypotensive insult occurs before 28 weeks of gestation, multicystic encephalomalacia (MCE) or parenchymal haemorrhage is more likely to develop. MCE is diffuse lesion of the brain in which cerebral parenchyma is replaced by cysts of varying sizes in the perinatal period. It is believed to take around 4–6 months for the insult leading to permanent cortical brain tissue loss [
14]. This type of brain lesion is associated with poor clinical consequences such as severe mental retardation, microcephaly, spastic tetraplegia, epilepsy and spastic hemiplegia [
14‐
17]. On the other hand, the effect of single twin demise at first trimester is unclear. There are case reports about brain damage of surviving co-twins following single fetal death in monochorionic twin pregnancies in the first trimester. One case of fetal ventriculomegaly of MCDA (monochorionic diamniotic) co-twin after single fetal demise at 8–9 weeks [
18]. One case of fetal MCE of MCDA co-twin after single fetal demise at 12 weeks [
19]. Recent case series of 20 MCDA twin pregnancies with single fetal demise at 10–14 weeks, 12 cases had both fetal demise of both fetuses at the same time, 2 cases of twin reversed arterial perfusion sequence resulted in fetal demise of co-twins at second trimester [
20]. The remaining six cases survived with normal neurological outcomes at least 1 year of follow-up [
20]. Overall, the effect of co-twin demise is variable from no sequelae, different degree of multiorgan damages to subsequent demise, which may depend on the type of vascular anastomose in the shared placenta [
21]. For triplet pregnancy, the effect of single demise in first trimester is unknown. The condition is likely under reported due to being missed on ultrasound scan or the dead co-triplet having been already absorbed by the time when dating scan is performed.
Besides, the other possible in-utero cause of multiorgan injury of the survivors in this case is the development of fetofetal transfusion syndrome. Fetofetal transfusion syndrome is a serious complication in monochorionic multiple pregnancies. It occurs in about 15% of monochorionic twin pregnancies [
22], however the prevalence in triplet gestations is not known. The unbalanced blood flow via the placental arteriovenous anastomoses causes hypovolaemia/hypotension in one/two fetus (es) (donor) and hypervolaemia/hypertension in another fetus (es) (recipient) [
23]. This haemodynamic instability can lead to multiple organ damage particularly the brain, and death. The low-flow and high flow injuries can result in vascular disruptive lesions [
2]. In the fetal brain, hypoxic ischaemic injury to the white matter supplied by middle cerebral artery can cause extensive MCE Concurrently, haemorrhagic injury may occur in isolation or with concomitant ischemic lesions. Therefore, severe fetofetal transfusion syndrome exposes the donors and recipients to a higher risk of cerebral damage with wide spectrum of severity. In twin-twin transfusion syndrome, the prevalence of cerebral lesion was reported in 13–35% [
24,
25] and the incidence of long-term neurological morbidity was reported in 10–25% [
24]. However, there is lacking of this information in monochorionic triplet pregnancies.
Finally, the possible postnatal injury to brain and gastrointestinal tract cannot be excluded in this case. The prematurity and low birth weight are potential threats to the integrity of the brain which may worsen the long-term neurological outcomes of the survivors. However, it is difficult to ascribe the causes of final outcomes to solely complication of antenatal related single intrauterine death and/or fetofetal transfusion syndrome since the survivors were also exposed to postnatal sources of brain insults. Normal antenatal fetal brain imaging cannot exclude the in-utero brain insults because brain injuries can take months to evolve and allow cavitation formation, and only become evident on the radiological examination after birth. The first baby’s brain lesion was likely related to a result of prematurity, while the second baby’s MCE was likely due to severe intrauterine hypoxic ischaemic injury leading to cerebral necrosis. Antenatal administration of magnesium sulphate before early preterm delivery can help to alleviate the prematurity related long-term neurological impairment for these babies. However, this was not put into practise in our hospital at that time. Furthermore, the first baby suffered from jejunal atresia which might be related to discordant congenital anomaly. Congenital anomaly is commoner in multiple pregnancies than singleton pregnancies. The second baby suffered from gastric perforation which might be caused by prematurity or iatrogenic problem related to medical intervention after birth.