Twin-to-twin transfusion syndrome (TTTS) may be responsible for complications in fetal organs such as the brain, liver, limbs, and intestinal tract, irrespective of the treatment employed (Morikawa et al., Reference Morikawa, Sago, Yamada, Hayashi, Yamada, Cho, Yamada, Kitagawa and Minakami2008). They have been traditionally attributed to thrombosis secondary to hyperviscosity, and virtually always in the recipient. The best described vascular accidents involve limb defects and limb necrosis (Lopriore et al., Reference Lopriore, Lewi, Oepkes, Debeer, Vandenbussche, Deprest and Walther2008). To date, the pathophysiology of these complications is still unclear but may be related to severe hemodynamic alterations that can occur spontaneously or secondary to interventions such as amniodrainage or laser therapy. We report a case of neonatal meconium peritonitis in both donor and recipient newborns who had undergone antenatal laser surgery for TTTS, diagnosed during the second trimester of gestation. Cases of TTTS treated by selective fetoscopic laser photocoagulation (FLP) in which only the recipient twin was affected with intestinal complications are described in literature. The originality of this case stems from the fact that both twins, not merely the recipient twin, had congenital bowel perforations.
Case
A 41-year-old Caucasian woman was referred to our center for an early TTTS. Her past medical history was remarkable for Rendu–Osler–Weber syndrome and a prior pregnancy that ended in preterm labor at 28 weeks gestation.
Early ultrasound of the current pregnancy revealed a monochorionic diamniotic twin pregnancy. An ultrasound examination at 17 weeks gestation showed signs of early stage 2 TTTS by Quintero staging (Quintero, Reference Quintero2003): oligohydramnios without a detectable bladder in the donor twin and polyhydramnios in the recipient twin. Endoscopic laser surgery with selective FLP was performed at 18 weeks gestation. Karyotyping was normal (46 XY). Ultrasound examinations between 20 and 23 weeks gestation showed no further signs of TTTS. Ultrasound examinations at 25, 26, and 27 weeks gestation showed bowel hyperechogenicity and abdominal ascites in both twins that appeared in the latter two examinations (Figure 1). Fetal growth, amniotic fluid indices, and fetal Doppler examinations were within the normal ranges. Workups for maternal infections and cystic fibrosis were negative. At 25 weeks gestation, the patient was hospitalized for spontaneous preterm labor and corticosteroids therapy for fetal lung maturation was administered. A cesarean section was performed at 276/7 weeks gestation for heart rate decelerations in the donor twin.
Sonographic ascites (arrows) and digestive hyperechogenicity (stars) of donor twin (A) and recipient twin (B).
The donor's weight was 1,025 grams, and the recipient's weight was 925 grams. The infants, both male, received appropriate resuscitative care. At birth, the hemoglobin levels of the donor and the recipient twin were 11.1 g/dL and 13.1 g/dL, respectively. Ascites was diagnosed clinically in both newborns. Peritoneal puncture of the donor, 15 minutes after delivery, yielded 55 mL of a green, meconium-like fluid. Meconium peritonitis secondary to a perforation of the transverse colon was surgically managed with stoma without bowel resection. He left neonatal intensive care at 70 days of life weighing 2,650 grams; neonatal evolution was, in the end, favorable.
The recipient twin had less significant ascites. Surgical management, delayed until 24 hours of life, revealed copious meconial fluid and a distended jejunum upstream of a jejunal perforation, with adhesions severe enough to form a large right lower quadrant conglomeration with necrotic zones. Management consisted of a 29-cm bowel resection and double stoma. Perioperative histologic examination of the resected segment revealed fibrosis of the wall with edematous vessels, amassed pigmented macrophages, and several sub-mucosal capillaries with microthrombi and microemboli. He died of multi-organ failure 24 hours after surgery. On post-mortem examination, there was no bowel atresia. Microscopic examination showed necrotic patches scattered throughout the jejunum, with microemboli or microthrombi in the submucosal capillaries (Figure 2-1). Histological examination of the non-resected jejunum revealed old microthrombi (Figures 2-2A and 2-2B) not found in other organs.
(2-1) Macroscopic view of digestive tract of recipient twin: necrotic patches throughout the jejunum (a), dilated ileum (b), and small caliber colon (c); (2-2A and 2-2B) histological examination of jejunum of recipient twin: microemboli or microthrombi in the submucosal capillaries (arrows).
Discussion
This report is the first example of neonatal meconium peritonitis in both monochorionic twins who had undergone antenatal laser surgery for TTTS. TTTS disrupts fetal peripheral perfusion, leading to organ lesions. These severe hemodynamic alterations can occur spontaneously or secondary to interventions irrespective of the treatment employed such as amniodrainage or laser therapy (Morikawa et al., Reference Morikawa, Sago, Yamada, Hayashi, Yamada, Cho, Yamada, Kitagawa and Minakami2008).
Meconium peritonitis is caused by an in utero fetal bowel perforation and leads to the extrusion of meconium into the peritoneal cavity. Necrosis of the digestive tract could be due to a mechanical accident (Terzibachian et al., Reference Terzibachian, Shu, Levy, Destuynder, Agnani and Daucourt1995) or to a vascular embolus lodging in the intestinal vasculature. In utero exposure to infectious diseases such as parvovirus B19, measles, VZV, or CMV can result in meconium peritonitis; the pathophysiology seems to involve various forms of vasculitis (Staud & Corman, Reference Staud and Corman1996; Zerbini et al., Reference Zerbini, Gentilomi, Gallinella, Morandi, Calvi, Guerra and Musiani1998). In some cases, no etiology for necrosis of the digestive tract can be found.
Ultrasonographic diagnosis of antenatal meconium peritonitis is possible at 20 weeks gestation when fetal intestinal peristalsis is established. Ascites and abdominal calcifications are the main signs (Chan et al., Reference Chan, Tang, Tse, Tang and Tam2005) and are found, respectively, in 100% and 92.9–94% of cases (Shyu et al., Reference Shyu, Shih, Lee, Hwa, Chow and Hsieh2003). Other reported signs are polyhydramnios, pseudocysts, dilated bowel, or fetal anasarca (Shyu et al., Reference Shyu, Shih, Lee, Hwa, Chow and Hsieh2003; Wang et al., Reference Wang, Chang, Chao, Wang, Tseng and Chang2008).
TTTS complicates 10–15% of monochorionic multiple gestations (Duncan et al., Reference Duncan, Denbow and Fisk1997). Inter-twin transfusion is a quasi-constant event due to a balanced flow through permanent vascular placental connections between the twins that exist even in non-pathologic twin pregnancies (Denbow et al., Reference Denbow, Cox, Taylor, Hammal and Fisk2000). TTTS is caused by an imbalance in these connections, creating an excessive unidirectional flow between the twins (El Kateb & Ville, Reference El Kateb and Ville2008). Endoscopic laser surgery with FLP is becoming the first-line treatment for the management of TTTS (Senat et al., Reference Senat, Deprest, Boulvain, Paupe, Winer and Ville2004).
In the presented case, the donor twin survived even though the recipient twin died in multiple-organ failure, despite surgical management. The literature describes five cases of TTTS treated by selective FLP in which the recipient twin suffered intestinal complications. The first case presented ileal atresia with perforation and surgical management was unsuccessful (Morikawa et al., Reference Morikawa, Sago, Yamada, Hayashi, Yamada, Cho, Yamada, Kitagawa and Minakami2008). In the second (Schnater et al., Reference Schnater, van Zalen-Sprock, Schaap, Festen and Aronson2005), third (Arul et al., Reference Arul, Carroll, Kyle, Soothill and Spicer2001), and fourth cases (Saura et al., Reference Saura, Muñoz, Castañón, Eixarch, Corradini, Aguilar and Ma Ribó2010), resection and anastomosis for ileal atresia were curative. In the final case (Arul et al., Reference Arul, Carroll, Kyle, Soothill and Spicer2001), resection of a necrotic ileal mass was also curative. In the latter four cases, the donor twin died in utero after treatment by selective FLP. Two cases of donor twins affected by jejunal atresia and ileocecal ischemia have also been reported, with both recipient survival. They had postnatal surgical treatment and both made an uncomplicated recovery (Saura et al., Reference Saura, Muñoz, Castañón, Eixarch, Corradini, Aguilar and Ma Ribó2010). In TTTS with survival of both fetuses, bowel complications can be caused by different etiologies in the donor and recipient. On one hand, there is polycythemia and hyperviscosity in the recipient. On the other hand, there is low flow and a sort of ‘diving reflex’ in the donor, who exhibits increased systemic vascular resistance secondary to chronic anemia.
Some authors suggest an embolic mechanism for organ damage: a placental vessel coagulated by laser surgical management would be the source of the embolus. Schnater et al. described a case in which intrahepatic thromboembolic calcifications were found upon autopsy of the donor twin, who had undergone antenatal selective FLP. This case strengthens the argument for a thromboembolic mechanism for organ lesions. On the contrary, Morikawa et al. consider that previous intervention is not a prerequisite for ischemic injury in twins suffering from TTTS (Morikawa et al., Reference Morikawa, Sago, Yamada, Hayashi, Yamada, Cho, Yamada, Kitagawa and Minakami2008). Similarly, Philip et al. reported two cases of congenital bowel perforation in non-FLP-treated TTTS: one had undergone amnioreduction and one received no antenatal TTTS treatment (Philip et al., Reference Philip, Ford and Haslam2002).
The uniqueness of our case stems from the fact that both twins had congenital bowel perforations secondary to a defective early vascularization of the mesenteric arterial system. Histologic analysis of the recipient twin's jejunum showed ischemic necrosis with inflammatory granulomatous lesions that support the idea of a defect in vascularization. No other organs showed similar damage, ruling out disseminated intravascular coagulation (DIC) or a coagulopathy. It is impossible to determine if the intestinal lesions were caused by a local thrombotic event or a by placental microemboli. However, as previously argued by Morikawa et al., microemboli from placental veins are unlikely to lodge preferentially in the fetal mesenteric system after having traversed the fetal cardiac circulation.
In conclusion, acute hemodynamic disorders as well as anemia or hyperviscosity can compromise the terminal mesenteric circulation and lead to ischemic and necrotic lesions in both monochorionic twins. Furthermore, the present case highlights the role of end-circulation bowel thrombi as the potential cause of subsequent intestinal perforation.
