Fetal proximal and distal limb anomalies following exposure to mycophenolate mofetil during pregnancy: A case report and review of the literature.

BACKGROUND: Mycophenolate mofetil (MMF) is currently used in a wide spectrum of autoimmune diseases and has been rendered very effective in the management of systemic lupus erythematosus and lupus nephritis. MMF is known to be teratogenic (FDA category D) and therefore, women in childbearing period receiving MMF should be counselled to use effective contraceptive methods to avoid an unplanned pregnancy. CASE: A 22-year-old lady accidentally discovered to be pregnant while using MMF as a treatment of lupus nephritis which was replaced later on by azathioprine. After maternal and fetal evaluation, maternal lupus flare was confirmed and multiple fetal skeletal deformities associated with intrauterine growth restriction (IUGR) were diagnosed by 4-dimensional ultrasound. Termination of pregnancy was decided after shared decision making. CONCLUSION: Women in childbearing period should be advised to postpone pregnancy for at least six weeks after stoppage of MMF therapy because of its potential teratogenic effects during pregnancy.

Myelomeningocele sac associated with worse lower-extremity neurological sequelae: evidence for prenatal neural stretch injury?

OBJECTIVE: To determine whether the presence of a myelomeningocele (MMC) sac and sac size correlate with compromised lower-extremity function in fetuses with open spinal dysraphism. METHODS: A radiology database search was performed to identify cases of MMC and myeloschisis (MS) diagnosed prenatally in a single center from 2013 to 2017. All cases were evaluated between 18 and 25 weeks. Ultrasound reports were reviewed for talipes and impaired lower-extremity motion. In MMC cases, sac volume was calculated from ultrasound measurements. Magnetic resonance imaging reports were reviewed for hindbrain herniation. The association of presence of a MMC sac and sac size with talipes and impaired lower-extremity motion was assessed. Post-hoc analysis of data from the multicenter Management of Myelomeningocele Study (MOMS) randomized controlled trial was performed to confirm the study findings. RESULTS: In total, 283 MMC and 121 MS cases were identified. MMC was associated with a lower incidence of hindbrain herniation than was MS (80.9% vs 100%; P < 0.001). Compared with MS cases, MMC cases with hindbrain herniation had a higher rate of talipes (28.4% vs 16.5%, P = 0.02) and of talipes or lower-extremity impairment (34.9% vs 19.0%, P = 0.002). Although there was a higher rate of impaired lower-extremity motion alone in MMC cases with hindbrain herniation than in MS cases, the difference was not statistically significant (6.6% vs 2.5%; P = 0.13). Among MMC cases with hindbrain herniation, mean sac volume was higher in those associated with talipes compared with those without talipes (4.7 ± 4.2 vs 3.0 ± 2.6 mL; P = 0.002). Review of the MOMS data demonstrated similar findings; cases with a sac on baseline imaging had a higher incidence of talipes than did those without a sac (28.2% vs 7.5%; P = 0.007). CONCLUSIONS: In fetuses with open spinal dysraphism, the presence of a MMC sac was associated with fetal talipes, and this effect was correlated with sac size. The presence of a larger sac in fetuses with open spinal dysraphism may result in additional injury through mechanical stretching of the nerves, suggesting another acquired mechanism of injury to the exposed spinal tissue. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Early recognition and management of fetal head trauma with massive subgaleal hemorrhage.

Non-obstetrical fetal head injury is an unusual clinical event. While multiple case reports describe motor vehicle collisions resulting in intrauterine fetal skull fractures, management of these injuries has not been emphasized. We report a case of a depressed fetal skull fracture with massive subgaleal and subperiosteal hemorrhage requiring neurosurgical intervention with good clinical outcomes for both mother and infant dyad.

Fetal gunshot brain injury leading to late postnatal hydrocephalus.

A male fetus was delivered by emergent caesarean section after a term pregnant mother was caught in crossfire and sustained gunshot injury to her abdomen. Examination of the infant was unremarkable except for a small laceration of the scalp at the anterior fontanelle. Skull radiography showed a dense bullet shaped opacity in the brain. He was managed conservatively and was discharged home on full feeds with normal neurological examination. He developed seizures and progressive hydrocephalus, and underwent a ventriculoperitoneal (VP) shunt placement at 5 weeks of age. At 13 months of age the bullet was removed. To our knowledge this is the first report of fetal brain injury with intact bullet in the brain with survival. This case provides the context for a discussion about factors that contribute to survival and favorable prognosis of infants with fetal penetrating gunshot brain injury.

Fetal brain imaging following laser surgery in twin-to-twin surgery.

OBJECTIVE: To describe the incidence and nature of prenatal brain damage following fetoscopic laser selective coagulation (FLSC) of placental vessels for twin-to-twin transfusion syndrome (TTTS). DESIGN: Retrospective observational study. SETTING: Single center cohort. POPULATION: All consecutive cases referred for TTTS treated by FLSC between 2003 and 2015. METHODS: After the FLSC, patients were followed weekly by ultrasound. Fetal magnetic resonance imaging (MRI) scans were systematically planned at 30-32 weeks of gestation. MAIN OUTCOME MEASURES: Brain damage diagnosed prenatally by ultrasound or MRI. RESULTS: In total, 1023 cases were reviewed. Brain damage was diagnosed prenatally in 22/1023 (2.1%) cases. Diagnosis was performed by ultrasound prior to MRI in 18 (82%) cases. All lesions were within the spectrum of ischaemic haemorrhagic lesions. Postoperative twin anaemia polycythaemia sequence and recurrence of TTTS were significantly associated with brain damage. CONCLUSION: The incidence of prenatal brain damage is low following FSLC, and is strongly associated with incomplete surgery. TWEETABLE ABSTRACT: Following FSLC for TTTS, prenatal brain damage occurs in 2% of cases and is associated with incomplete surgery.

MRI Patterns of brain injury and neurodevelopmental outcomes in neonates with severe anaemia at birth.

AIMS: To define patterns of brain injury and associated neurodevelopmental outcomes in infants with severe neonatal anaemia. METHODS: We studied 20 infants with severe anaemia at birth (haemoglobin<7g/dL). Clinical details were analysed for causes of anaemia and co-morbidities. All had early brain magnetic resonance imaging (MRI) scans, which were reviewed for injury pattern. Neurodevelopmental outcomes were assessed at a median age of 24months. RESULTS: The aetiology of the anaemia was feto-maternal haemorrhage in 17 and antepartum haemorrhage in 3 infants. The predominant site of injury was the white matter, which was affected in all infants, with differing grades of severity and with cystic evolution in 45%. Only one infant showed an injury pattern typical of an acute severe hypoxic-ischaemic insult. Outcomes correlated closely to the severity of MRI findings. Cerebral palsy was seen only with the most severe neuroimaging patterns (n=6). Global developmental delay, learning or behavioural problems and seizures were common with moderate injury. Visual impairment occurred, particularly with posterior injury. Microcephaly developed in 45%. INTERPRETATION: Severe neonatal anaemia at birth was associated with a white matter predominant pattern of injury, the severity of which was related to neurodevelopmental outcomes. Early MRI and long-term follow-up are advisable following severe neonatal anaemia.

Blunt prenatal trauma resulting in fetal epidural or subdural hematoma: case report and systematic review of the literature.

Blunt prenatal trauma is known to have consequences to the developing brain, and can result in subdural hematoma (SDH) or epidural hematoma (EDH). The authors present a case of blunt prenatal trauma resulting in a fetal SDH, intraparenchymal hematoma, and intraventricular hemorrhage, and perform a systematic review of the literature. This systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Relevant studies (up to April 2016) that reported on cases of fetal SDH or EDH after blunt prenatal trauma were identified from the PubMed database. The primary outcome was fetal mortality, and the secondary outcome was neurological outcome. Fourteen studies were included in the analysis, comprising a total of 14 patients including the present case. The average gestational age at discovery of hemorrhage was 30.1 weeks. Nine mothers were in a motor vehicle collision and 3 were assaulted; the mechanism of injury for 2 mothers was not defined. Twelve patients had SDH, 1 had EDH, and 1 had conflicting reports. Three patients had intrauterine fetal demise, and 3 died in the neonatal period after birth. Three patients had persistent neurological deficit, and 5 were neurologically intact. Fetal SDH or EDH after blunt trauma to the mother trauma is rare and is associated with mortality. However, a significant number of patients can have good neurological outcomes.

Sequential Amniotic Fluid Thyroid Hormone Changes Correlate with Goiter Shrinkage following in utero Thyroxine Therapy.

Several isolated reports of fetal goiter treatment have shown limited generalizability of approaches and provide no real guidance for optimal timing, dosages, and treatment strategies. Graves' disease accounts for >60% of these cases. Maternal treatments of hyperthyroidism include antithyroid medications such as methimazole and more commonly propylthiouracil (PTU). Here, our management of a patient with a fetal thyroid goiter from maternal exposure to PTU diagnosed at 23.6 weeks' gestation and the management of other cases allow us propose a general strategy for treatment. Intrauterine therapy with 200 and then 400 µg of levothyroxine (3 weeks apart) showed an 85% reduction in fetal thyroid goiter volume. We collected amniotic fluid samples at the time of treatments and assayed thyroid hormones and associated antibodies which closely reflected the changes in thyroid goiter mass volume. Our observations suggest a weekly or biweekly therapeutic intervention schedule. Utilizing both goiter size as well as a novel approach in using amniotic fluid hormone levels to monitor therapy efficacy might improve the quality of treatments. Only with a standardized approach and collection of amniotic fluid thyroid panels do we have the opportunity to develop the database required to determine the number and timing of treatments needed.

Perinatal outcomes of traumatic injuries during pregnancy.

Traumatic injuries although uncommon (affect 6% to 7% of all pregnancies) are associated with poor maternal, fetal, neonatal, and infant outcomes. The magnitude of the problem is most likely largely underestimated secondary to lack of standardized reporting. Newer data are available that stratify maternal risk by type of injury sustained, and may assist in evaluation of the pregnant trauma victim. Long-term adverse events after maternal discharge for a traumatic injury are emerging, and suggest closer monitoring of the patient for preterm labor, growth restriction, and placental abruption during the affected pregnancy.