Beneath a silent attack: Unraveling lung and brain injuries in a surviving monoamniotic twin

Abstract

Pregnancy with monochorionic monoamniotic twins is highly rare and frequently results in complications. Nevertheless, in monochorionic monoamniotic twin pregnancies, there are no reports of lung injury in the surviving fetus after single intrauterine fetal death. To the best of our knowledge, we present the first report of lung and brain injuries in a surviving fetus after single intrauterine fetal death in a monochorionic monoamniotic twin pregnancy. A male child was born with dyspnea. His healthy 39-year-old mother had a monochorionic monoamniotic twin pregnancy. After the cardiac arrest of one fetus at 17⁺² weeks of gestation, the surviving fetus showed slight bilateral ventricular dilatation from 19 weeks. Delivered full-term alongside the deceased fetus via cesarean section, the surviving fetus exhibited lung and brain injuries and was discharged at 10 days old. His prolonged inflammatory lung injury was considered related to single intrauterine fetal death, after ruling out other neonatal conditions. This case reminds obstetricians and pediatricians that single intrauterine fetal death could cause pulmonary inhalation and cerebral ischemic-hypoxic injury in monochorionic monoamniotic twin surviving fetuses. Antenatal evaluation and postnatal follow-up are essential in this type of high-risk pregnancy.

Introduction

A monochorionic monoamniotic (MCMA) twin pregnancy occurs when several fetuses share a single amniotic cavity and placenta. With an estimated incidence of 8 per 100,000 births, MCMA twins are extremely rare, accounting for 1% of all twin pregnancies and 5% of all monochorionic pregnancies.^1,2 Although assisted reproduction is associated with a higher frequency of reported MCMA twin pregnancies, the exact cause is still unknown. ³ A comparison of MCMA pregnancies with dichorionic or monochorionic diamniotic pregnancies showed that the former is linked to a noticeably higher incidence of complications, including twin–twin transfusion syndrome, twin-reversed arterial perfusion selective fetal growth restriction, structural anomalies, fetal death, birth defects, and conjoined twinning.^4,5

Monochorionic twin pregnancies have an increased risk of twin–twin transfusion syndrome, twin reverse arterial perfusion sequences, and selective intrauterine growth restriction, with higher perinatal mortality and morbidity rates. ⁶ Hemodynamic fluctuations as well as trans chorionic embolization and coagulopathy are the two main causes of the likelihood of mortality and morbidity in identical twins after single intrauterine fetal death (s-IUFD). ⁷ The former, however, is believed to have a greater influence on the cotwin propensity for morbidity and mortality after s-IUFD. ⁷ It is not known whether the occurrence of s-IUFD in the first trimester of pregnancy is harmful to identical twins; however, if s-IUFD occurs in the second or third trimester, it could be harmful to the surviving identical twins. ³ After s-IUFD in the second or third trimester in MCMA twin pregnancies, the surviving fetuses show postnatal manifestations of anemia, bilateral massive cerebral ischemic necrosis, head malformations, renal hypoplasia, hypoglycemia, transient lethargy, and even death.^8–12 However, no cases of lung injury in the surviving fetus after an s-IUFD in MCMA twin pregnancies have been reported. To the best of our knowledge, we report the first case of lung and brain injury in a surviving fetus after s-IUFD in a MCMA twin pregnancy.

Case presentation

In August 2021, a male newborn with dyspnea was admitted to our hospital after birth with Apgar scores of 9 at 1, 5, and 10 min. His 39-year-old healthy mother became pregnant after undergoing assisted reproduction. At 13⁺² weeks of gestation, an ultrasound examination showed MCMA twin pregnancy. At 15 weeks and 2 days of gestation, an ultrasound examination showed no abnormalities in either fetus. However, one fetus experienced a cardiac arrest, and the placenta thickened to 35.4 mm at 17 weeks and 2 days of gestation. From 19 to 33 weeks of gestation, cranial magnetic resonance imaging (MRI) and ultrasound examination revealed slight biventricular dilatation of the surviving fetus, with no abnormal signals in the brain parenchyma (Figure 1(a) to (d)). The peak contraction velocity of the middle cerebral artery was normal in the surviving fetus throughout the pregnancy. Fetal ultrasound at 22 weeks of gestation did not reveal any abnormalities in the lungs of the surviving fetus. Therefore, subsequent routine prenatal ultrasound examinations did not include a detailed lung examination. During pregnancy, the placenta thickened noticeably; however, the size of the dead fetus changed slowly. The maternal D-dimer level gradually increased up to 20.40 mg/L without any other abnormalities. At 38 weeks and 6 days of gestation, two fetuses were delivered via cesarean section with clear amniotic fluid and no intrauterine distress. The paper-like dead fetus was approximately 10 cm in length, and its sex was unknown. The surviving fetus weighed 3720 g. The placenta was approximately 35 × 25 × 2.5 cm in size, weighed 715 g, and was normal. Both umbilical cords had two arteries and a vein; there was a 1-cm distance between the insertion points, and one cord was degenerated.

Figure 1.

Prenatal and postnatal brain images of the surviving fetus. Measurement of the posterior horn of the right (a) and left (b) ventricle of the brain of the surviving fetus at 22 weeks and 4 days of gestation. Axial (c) and sagittal (d) T2-weighed image of the brain at 19 weeks and 2 days of gestation. The brain T1-weighed magnetic resonance imaging scan of the newborn at 12 (e) and 70 (f) days old.

Upon admission, the results of the physical examination of the newborn were as follows: respiratory rate, 62 breaths/min; retraction; no special facial features; no abnormalities of the heart and abdomen; lateral polydactyly of the left thumb (a superfluous digit of approximately 1.5 × 1 cm); increased middle cerebral artery resistance index; mild abnormalities of spontaneous whole-body movement (as revealed by whole-body motor quality assessment); and negative amplitude-integrated electroencephalogram. Routine blood test results showed the following: hemoglobin level, 212 g/L; platelet count, 308 × 10⁹/L; white blood cell count, 35.56 × 10⁹/L; neutrophils, 70%; C-reactive protein level, <0.8 mg/L; serum amyloid level, <4.80 mg/L; and interleukin-6 level, 39 mg/L. Blood gas analysis results showed the following: pH, 7.297; partial pressure of carbon dioxide, 52.1 mmHg; partial pressure of oxygen, 62.2 mmHg; base excess, −2.0 mmol/L; and blood lactic acid level, 1.3 mmol/L. Pathogenetic evaluation showed negative results for sputum culture, sputum pathogenesis, blood culture, mycoplasma, chlamydia, TORCH (toxoplasma, others, rubella virus, cytomegalo virus, herpes virus), and enterovirus. Family history: the 39-year-old mother and the 40-year-old father of the newborn had a nonconsanguineous marriage, and the family had a notable history of multiple familial disorders. The gene panel test result showed no significant abnormalities associated with lung or brain injury.

The infant was born with respiratory distress. A chest X-ray revealed inflamed lungs, mainly in the lower and posterior back (Figure 2(a) and (b)). We treated the newborn with mechanical ventilation (pressure control mode, peak inspiratory pressure: 14.7 mmHg, positive end-expiratory pressure: 5 cmH₂O, Ti: 0.37, respiratory rate: 40, and FiO₂: 30%) and antimicrobials. After 3 days, we switched to high-flow oxygen (flow rate, 5 L/min and FiO₂: 25%), and 8 days later, oxygen administration was discontinued. The newborn also had mildly elevated D-dimer levels and fibrin degradation products. No abnormalities were detected on cardiac ultrasound. At 10 days of age, he was stabilized and discharged. Subsequently, he was followed up in the respiratory and rehabilitation clinic. Cranial MRI revealed biventricular dilatation and widened extracerebral spaces (Figure 1(e) and (f)). Chest X-ray showed reduced inflammation in both lungs (Figure 2(c)), whereas chest computed tomography (CT) showed multiple striated cords and shadows, with scattered cystic translucent shadows of varying sizes in both lungs and part pleural adhesions (Figure 2(d) to (f)). Pulmonary function showed abnormal pulmonary tidal respiratory function and mild obstructive ventilatory dysfunction. At the 3-week follow-up, whole-body motor quality assessment was monotonous; in addition, whole-body movement and long-range video-electroencephalogram showed normal results. He is now in his early third year of life with normal physical, mental, and motor development.

Figure 2.

Postnatal pulmonary images of the surviving fetus. Postnatal chest X-rays of the surviving fetus at 1 day (a), 4 days (b), and 70 days old (c). (d) A transverse plane view of the CT pulmonary scan at 12 days old. Coronal plane view (e) and transverse plane view (f) of the CT pulmonary scan of the newborn at 5 months old. CT: computed tomography.

Discussion

MCMA pregnancies have been linked to fetal loss rates as high as 30%–50%. ⁷ The risk of death and morbidity for the cotwin that survives is significantly increased in case of s-IUFD. ⁷ Among surviving fetuses, s-IUFD has been demonstrated to cause anemia, brain impairment, kidney damage, and mortality.^8–12 Our case illustrated that the surviving fetus had lung and brain injuries as the main clinical features.

Notably, the newborn presented with respiratory distress immediately after birth. Chest X-ray showed patchy exudates in both lungs. After providing respiratory support and anti-infection treatment, his condition gradually improved slightly. Subsequently, chest CT examination revealed multiple patchy and striated exudative shadows in both lungs, with localized cystic translucent shadows and localized thickening of the pleura bilaterally. Five months after birth, lung imaging revealed that lesions were still present in the lungs. The results of the pulmonary function tests at 9 months after birth revealed abnormal pulmonary tidal respiratory function and mild obstructive ventilatory dysfunction. We ruled out possible respiratory-related common and rare diseases. In our case, the amniotic fluid was clear; therefore, meconium aspiration pneumonia was ruled out. A combination of medical history, clinical presentation, pulmonary imaging, and other ancillary findings ruled out infectious pneumonia, pulmonary hemorrhage, malformation of lung development, eosinophilic lung disease, chronic granulomas, and cardiogenic lung disease. In conclusion, we consider that the lung injury in this newborn may be related to the occurrence of s-IUFD in MCMA twin pregnancies. In this case, the size of the dead fetus changed slowly during pregnancy. We suspect that in twin fetuses who are in the same amniotic sac, owing to the warm amniotic fluid environment of the surviving fetus, the dead fetus will not quickly turn into paper-like baby appendages but will continue to release reactive necrotic substances such as inflammatory factors into the amniotic fluid after death, which will be inhaled into the lungs by the surviving fetus, resulting in inhalation inflammation of the lungs, necrosis, and repair, thus manifesting itself in postnatal lung imaging features similar to those in bronchopulmonary dysplasia of the lungs in cases of cystic lungs, fibrosis, and others (Figure 3).

Figure 3.

The hypothesis is that s-IUFD causes lung and brain damage in surviving fetuses in MCMA twin pregnancies. s-IUFD: single intrauterine fetal death; MCMA: monochorionic monoamniotic. Partially created in BioRender. Zhi, L. (2025) https://BioRender.com/y4whfb

Because s-IUFD has not been reported in the literature to cause lung injury, the pathogenesis is unclear. Laboratory testing of the composition of alveolar lavage fluid and amniotic fluid from postnatal infants would better confirm our hypothesized pathogenesis of pulmonary inhalation injury. This case serves as a reminder to obstetricians and pediatricians of the need to consider the impact of specific events in the fetal period when full-term infants present with respiratory distress of unknown etiology.

In the present case, s-IUFD may have occurred at 15–17 weeks of gestation, and the ventricles of the surviving fetus at 14 weeks from 19–33 weeks showed mild dilatation. Cranial MRI of the postnatal surviving infant showed paraventricular white matter injury with white matter parity, enlarged ventricles with widened extracerebral spaces, and reduced brain parenchymal volume. Placental pathology showed that the two umbilical cord insertion points were very close, at a distance of 1 cm. s-IUFD surviving fetus showed pathological changes in the brain both prenatally and postnatally, suggesting that the fetus may have already suffered brain damage in utero, which we believe could be the result of an acute feto-fetal blood transfusion (Figure 3). s-IUFD could result in partial loss of the surviving fetus’s circulating blood volume into the circulation of the dying twin’s circulation, and this process could in turn result in temporary or sustained hypotension and hypoperfusion, leading to organ ischemia or even death. ⁴ At any gestational age (weeks), ventricular dilatation is usually defined as an axial brain scan showing a posterior horn of the lateral ventricle greater than or equal to 10 mm. In our case, the slight prenatal ventricular dilatation may have been because of the early onset of s-IUFD, which did not involve much intravascular blood flow in the traffic vessels and therefore caused less severe ischemic brain damage.

It is generally acknowledged that MCMA pregnancies should be delivered via cesarean section at approximately 33 weeks of gestation.^4,5 Because of the significant risk of intrauterine fetal death, the Royal College of Obstetricians and Gynecologists, the American College of Obstetricians and Gynecologists, and the Society for Maternal–Fetal Medicine recommended in 2016 that MCMA pregnancies be delivered via cesarean section between 32 and 34 weeks.^13,14 In 2019, the National Institute for Health and Care Excellence reaffirmed this advice, supporting cesarean section delivery of MCMA pregnancies between 32 weeks and 33 weeks and 6 days. ⁸ The timing of delivery of the s-IUFD is controversial; however, immediate termination of pregnancy after the detection of a s-IUFD is generally not recommended. ¹⁵ Also, currently there are no clear guidelines for the timing of termination after s-IUFD in MCMA twin pregnancies. After the occurrence of s-IUFD at 17⁺² weeks in this case, we closely monitored brain injury in the surviving fetus and found mild dilatation of the ventricles; however, the change was not significant, and there were no other injuries during pregnancy that have been reported to occur in the surviving fetus after s-IUFD. In view of the mild and unchanged brain injury, we chose to deliver the baby at 38 weeks and 6 days, at term, to avoid the risk of preterm labor. Because of normal lung ultrasound findings at 22 weeks of gestation and the lack of published reports on this type of injury, our late monitoring for lung injury during pregnancy was indeed inadequate. Whether appropriate early termination of the pregnancy can improve the outcome and reduce the degree of lung injury and brain damage needs to be further studied and analyzed by accumulating additional case data.

Conclusion

To the best of our knowledge, we report the first case of lung injury and brain damage in a surviving fetus from a MCMA twin pregnancy, which may be related to inhalation of necrotic material and acute feto-fetal transfusion events by surviving fetuses after s-IUFD. We believe that the description of the fetal condition and details of the diagnostic and therapeutic history in this case will serve as a reference for obstetricians and pediatricians and provide further insight into possible lung and brain damage in MCMA twin pregnancies with s-IUFD.