Fetal and neonatal neuroimaging in twin-twin transfusion syndrome.

OBJECTIVES: To describe the types of brain injury and subsequent neurodevelopmental outcome, to determine risk factors for brain injury and to review the use of neuroimaging modalities in fetuses and neonates with twin-twin transfusion syndrome (TTTS). METHODS: Retrospective cohort study of consecutive TTTS pregnancies treated with laser surgery in a single fetal therapy center between January 2010 and January 2020. Primary outcome was the incidence of brain injury, divided into predefined groups. Secondary outcomes included adverse outcome (perinatal mortality or neurodevelopmental impairment (NDI)), risk factors for brain injury and the numbers of magnetic resonance imaging (MRI) scans. RESULTS: Fetal and neonatal brain ultrasound was performed in all 466 TTTS pregnancies and 685/749 (91%) liveborn neonates. MRI was performed in 3% of pregnancies and 4% of neonates. Brain injury was diagnosed in 16/935 (2%) fetuses and 37/685 (5%) neonates and all predefined injury groups were represented. Four fetal and four neonatal cases of cerebellar hemorrhage were detected. In the group with brain injury, perinatal mortality occurred in 11/16 (69%) fetuses and 8/37 (22%) neonates. Follow-up was available for 29/34 (85%) long-term survivors with brain injury and mean age at follow-up was 46 months. NDI was present in 9/29 (31%) survivors with brain injury. Adverse outcome occurred in 28/53 (53%) TTTS individuals with brain injury. The risk of brain injury was increased after recurrent TTTS/post-laser twin anemia polycythemia sequence (TAPS) (OR 3.095, 95%-CI 1.581 - 6.059, p = .001) and lower gestational age (GA) at birth (OR 1.381 for each week less, 95%-CI 1.238 - 1.541, p < .001). CONCLUSIONS: Based on dedicated neurosonography and limited use of MRI, brain injury was diagnosed in 2% of fetuses and 5% of neonates with TTTS. Adverse outcome was seen in over half of cases with brain injury. Brain injury was related to recurrent TTTS/post-laser TAPS and a lower GA at birth. This article is protected by copyright. All rights reserved.

Changes in structural brain development after selective fetal growth restriction in monochorionic twins.

OBJECTIVES: Fetal growth restriction (FGR) may alter brain development permanently, resulting in lifelong structural and functional changes. However, in studies addressing this research question, FGR singletons have been compared primarily to matched appropriately grown singletons, a design which is inherently biased by differences in genetic and maternal factors. To overcome these limitations, we conducted a within-pair comparison of neonatal structural cerebral ultrasound measurements in monochorionic twin pairs with selective FGR (sFGR). METHODS: Structural cerebral measurements on neonatal cerebral ultrasound were compared between the smaller and larger twins of monochorionic twin pairs with sFGR, defined as a birth-weight discordance (BWD) ≥ 20%, born in our center between 2010 and 2020. Measurements from each twin pair were also compared with those of an appropriately grown singleton, matched according to sex and gestational age at birth. RESULTS: Included were 58 twin pairs with sFGR, with a median gestational age at birth of 31.7 (interquartile range, 29.9-33.8) weeks and a median birth weight of 1155 g for the smaller twin and 1725 g for the larger twin (median BWD, 32%). Compared with both the larger twin and the singleton, the smaller twin had significantly smaller cerebral structures (corpus callosum, vermis, cerebellum), less white/deep gray matter and smaller intracranial surface area and volume. Intracranial-volume discordance and BWD correlated significantly (R2 = 0.228, P < 0.0001). The median intracranial-volume discordance was smaller than the median BWD (19% vs 32%, P < 0.0001). After correction for intracranial volume, only one of the observed differences (biparietal diameter) remained significant for the smaller twin vs both the larger twin and the singleton. CONCLUSIONS: In monochorionic twins with sFGR, neonatal cerebral ultrasound reveals an overall, proportional restriction in brain growth, with smaller cerebral structures, less white/deep gray matter and smaller overall brain-size parameters in the smaller twin. There was a positive linear relationship between BWD and intracranial-volume discordance, with intracranial-volume discordance being smaller than BWD. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Neonatal stroke in premature neonates.

There are many neuro-imaging studies on the presence of brain lesions in the preterm infant, using cranial ultrasound (cUS) and/or term equivalent age MRI (TEA-MRI). These studies however tend to focus on germinal matrix-intraventricular hemorrhage (GMH-IVH) and white matter injury. Data about perinatal arterial ischemic stroke (PAIS) or cerebral sinovenous thrombosis (CSVT) in the preterm infant are very limited. In fact, several large cohort studies on neuro-imaging in preterm infants do not even mention neonatal stroke.1-4 Most studies about PAIS exclude preterm infants.5 The aim of this review was to provide an update on neonatal stroke in the preterm infant, with a focus on neuro-imaging findings.

Cranial Ultrasound Is an Important Tool in the Recognition of Life-Threatening Infratentorial Hemorrhage in Newborns.

Timely detection of severe infratentorial hemorrhage in neonates is crucial, especially in case of life-threatening brain stem compression and/or acute obstructive hydrocephalus, which need lifesaving neurosurgical intervention. Although the detection of infratentorial hemorrhage by ultrasound scanning is often considered as difficult, the use of additional acoustic windows and recognition of characteristic ultrasound features facilitate early diagnosis. In this case series, we report on newborns with severe, symptomatic infratentorial hemorrhage detected primarily by cranial ultrasound. We demonstrate the characteristic ultrasound features present in all cases and discuss how ultrasound diagnosis contributed to early diagnosis and treatment.

Idiopathic SIADH in the premature newborn, a case report.

BACKGROUND: Hyponatremia is a common laboratory finding in premature and ill neonates. When the degree of hyponatremia is more severe, the likelihood of a pathologic entity increases. In this case report we describe a premature neonate with severe hyponatremia due to the idiopathic syndrome of inappropriate antidiuretic hormone secretion (SIADH). CASE DESCRIPTION: The patient is a male neonate, born prematurely. He was admitted to the neonatal intensive care unit and received non-invasive respiratory support. After 48 hours of life serum sodium (Na+) decreased to 115 mmol/l. Hyponatremia progressively worsened despite aggressive Na+ supplementation. The clinical and laboratory data were most consistent with severe SIADH. Fluid restriction was initiated which resulted in a gradual normalization of Na+. A causal factor for development of SIADH could not be identified. CONCLUSION: When a neonate presents with significant hyponatremia that is not responsive to conventional therapy, it is important to perform a diagnostic work-up for SIADH, even in the absence of overt triggering factors.

The CHOPIn Study: a Multicenter Study on Cerebellar Hemorrhage and Outcome in Preterm Infants.

Cerebellar hemorrhage (CBH) is a frequent complication of preterm birth and may play an important and under-recognized role in neurodevelopment outcome. Association between CBH size, location, and neurodevelopment is still unknown. The main objective of this study was to investigate neurodevelopmental outcome at 2 years of age in a large number of infants with different patterns of CBH. Of preterm infants (≤ 34 weeks) with known CBH, perinatal factors, neuro-imaging findings, and follow-up at 2 years of age were retrospectively collected. MRI scans were reassessed to determine the exact size, number, and location of CBH. CBH was divided into three groups: punctate (≤ 4 mm), limited (> 4 mm but < 1/3 of the cerebellar hemisphere), or massive (≥ 1/3 of the cerebellar hemisphere). Associations between pattern of CBH, perinatal factors, and (composite) neurodevelopmental outcome were assessed. Data of 218 preterm infants with CBH were analyzed. Of 177 infants, the composite outcome score could be obtained. Forty-eight out of 119 infants (40%) with punctate CBH, 18 out of 35 infants (51%) with limited CBH, and 18 out of 23 infants (78%) with massive CBH had an abnormal composite outcome score. No significant differences were found for the composite outcome between punctate and limited CBH (P = 0.42). The risk of an abnormal outcome increased with increasing size of CBH. Infants with limited CBH have a more favorable outcome than infants with massive CBH. It is therefore important to distinguish between limited and massive CBH.

Cranial ultrasonography of the immature cerebellum: Role and limitations.

Cranial ultrasonography (CUS) is a reliable and non-invasive tool to detect frequently occurring brain abnormalities and to monitor brain development and maturation in high risk neonates. Standard CUS views are obtained through the anterior fontanel. However, evaluation of the posterior fossa is often suboptimal with this approach. Cerebellar injury occurs frequently in preterm infants and has important prognostic consequences. Early detection is therefore important. This review focuses on techniques that optimize the performance of CUS when studying the preterm cerebellum, including the use of the mastoid fontanel and the adaptation of focus points and scan frequencies. For illustration, CUS images of the normal posterior fossa anatomy as well as examples of abnormalities that may be encountered in preterm infants are included. We also discuss the limitations of CUS and the role of magnetic resonance imaging.

Double fatal outcome after ruptured vasa previa in monochorionic twins: case report and review of the literature.

Vasa previa is a condition in which one or more fetal blood vessels run through the amniotic membranes and cross or run near the external orifice of the uterus. Rupture of membranes can lead to tearing of these vessels and cause acute fetal exsanguination. In monochorionic twin (MC) pregnancies, acute exsanguination in one twin can lead to severe complications in the co-twin due to the presence of inter-twin placental vascular connections. We report a MC pair with severe perinatal asphyxia due to acute exsanguination after prenatally undetected ruptured vasa previa. This resulted in severe hemorrhagic shock in both twins with double fatal outcome. Antenatal detection of vasa previa is of paramount importance to prevent severe morbidity and mortality, especially in MCs. A review of the literature is presented.

Posterior fossa abnormalities in high-risk term infants: comparison of ultrasound and MRI.

OBJECTIVES: We aimed to assess the characteristics of posterior fossa (PF) abnormalities in a cohort of high-risk term neonates, as well as the diagnostic performance of cranial ultrasound (CUS) with additional mastoid fontanelle (MF) views for the detection of these abnormalities, with magnetic resonance imaging (MRI) being the reference standard. METHODS: In this retrospective study, 113 term neonates with CUS and subsequent MRI were included. Sensitivity, specificity, and predictive values of routine CUS and CUS with MF views were calculated. RESULTS: Posterior fossa abnormalities were diagnosed on CUS in 46 of 113 infants. MRI confirmed these findings in 43 and showed additional abnormalities in 32 infants. The sensitivity and specificity of anterior fontanelle views for major PF abnormalities as seen on MRI were 16% and 99%. Adding MF views increased the sensitivity of US to 82%. The sensitivity and specificity of MF views for the detection of any (major or minor) PF abnormality were 57% and 95%. Especially acute hypoxic-ischemic injury and small subdural and punctate cerebellar haemorrhage remained undetected by CUS. CONCLUSIONS: PF abnormalities are frequent in high-risk term infants. MF-CUS enables early diagnosis of major PF abnormalities. We therefore advocate to perform MF-CUS in high-risk term neonates. KEY POINTS: • Posterior fossa abnormalities are a frequent finding in high-risk term infants. • Adding mastoid fontanelle views improves ultrasound detection of clinically relevant abnormalities. • Hypoxic-ischemic injury and small posterior fossa haemorrhages are better detected with MRI. • Cranial ultrasound examination should include mastoid fontanelle views in high-risk term neonates.

Single fetal demise in monochorionic pregnancies: incidence and patterns of cerebral injury.

OBJECTIVE: To evaluate the incidence, type and severity of cerebral injury in the surviving monochorionic (MC) cotwin after single fetal demise in twin pregnancies. METHODS: All MC pregnancies with single fetal demise that were evaluated at the Leiden University Medical Center between 2002 and 2013 were included. Perinatal characteristics, neonatal outcome and the presence of cerebral injury, observed on neuroimaging, were recorded for all cotwin survivors. RESULTS: A total of 49 MC pregnancies with single fetal demise, including one MC triplet, were included in the study (n = 50 cotwins). Median gestational age at occurrence of single fetal demise was 25 weeks and median interval between single fetal demise and live birth was 61 days, with a median gestational age at birth of 36 weeks. Severe cerebral injury was diagnosed in 13 (26%) of the 50 cotwins and was detected antenatally in 4/50 (8%) and postnatally in 9/50 (18%) cases. Cerebral injury was mostly due to hypoxic-ischemic injury resulting in cystic periventricular leukomalacia, middle cerebral artery infarction or injury to basal ganglia, thalamus and/or cortex. Risk factors associated with severe cerebral injury were advanced gestational age at the occurrence of single fetal demise (odds ratio (OR), 1.14 (95% CI, 1.01-1.29) for each week of gestation; P = 0.03), twin-twin transfusion syndrome developing prior to single fetal demise (OR, 5.0 (95% CI, 1.30-19.13); P = 0.02) and a lower gestational age at birth (OR, 0.83 (95% CI, 0.69-0.99) for each week of gestation; P = 0.04). CONCLUSIONS: Single fetal demise in MC pregnancies is associated with severe cerebral injury occurring in 1 in 4 surviving cotwins. Routine antenatal and postnatal neuroimaging, followed by standardized long-term follow-up, is mandatory.

Neonatal thrombocytopenia after perinatal asphyxia treated with hypothermia: a retrospective case control study.

Our objective was to estimate the effect of therapeutic hypothermia on platelet count in neonates after perinatal asphyxia. We performed a retrospective case control study of all (near-) term neonates with perinatal asphyxia admitted between 2004 and 2012 to our neonatal intensive care unit. All neonates treated with therapeutic hypothermia were included in this study (hypothermia group) and compared with a historic control group of neonates with perinatal asphyxia treated before introduction of therapeutic hypothermia (2008). Primary outcome was thrombocytopenia during the first week after birth. Thrombocytopenia was found significantly more often in the hypothermia group than in the control group, 80% (43/54) versus 59% (27/46) (P = .02). The lowest mean platelet count in the hypothermia group and control group was 97 × 10(9)/L and 125 × 10(9)/L (P = .06), respectively, and was reached at a mean age of 4.1 days in the hypothermia group and 2.9 days in the control group (P < .001). The incidence of moderate/severe cerebral hemorrhage was 6% (3/47) in the hypothermia group versus 9% (3/35) in the control group (P = .64). In conclusion, neonates with perinatal asphyxia treated with therapeutic hypothermia are at increased risk of thrombocytopenia, without increased risk of cerebral hemorrhage.

Early-onset thrombocytopenia in near-term and term infants with perinatal asphyxia.

BACKGROUND: Neonates after perinatal asphyxia are at increased risk of thrombocytopenia. The correlation between perinatal asphyxia and the risk and severity of early-onset thrombocytopenia is not well known. OBJECTIVE: To estimate the incidence, severity and risk factors for early-onset thrombocytopenia in neonates after perinatal asphyxia. METHODS: We included all newborns (gestational age ≥ 36 weeks) admitted to our neonatal nursery due to perinatal asphyxia in this retrospective study. We collected platelet counts that were obtained within the first 48 h of life to estimate the incidence and severity of early-onset thrombocytopenia. RESULTS: A total number of 171 neonates with perinatal asphyxia were included in the study. The incidence of early-onset thrombocytopenia (platelet count < 150 × 109/l) was 51% (87/171). Several factors were associated with increased risk of early-onset thrombocytopenia, including prolonged prothrombin time (PT) [odds ratio (OR) 1·18, 95% confidence interval (CI) 1·08­1·30, P < 0·01], prolonged activated partial thromboplastin time (APTT) (OR 1·07, 95% CI 1·03­1·11, P < 0·01), low Apgar score at 10 min (OR 1·25, 95% CI 1·08­1·45, P < 0·01) and high serum lactate (OR 1·12, 95% CI 1·06­1·19, P < 0·01). After multiple logistic regression analysis, we found an independent association between early-onset thrombocytopenia and prolonged PT (OR 1·15, 95% CI 1·00­1·33, P = 0·045) and higher lactate level (OR 1·15, 95% CI 1·03­1·28, P = 0·01). CONCLUSIONS: Early-onset thrombocytopenia occurs frequently in neonates after perinatal asphyxia and is independently associated with PT and lactate level.

Perinatal asphyxia in monochorionic versus dichorionic twins: incidence, risk factors and outcome.

OBJECTIVE: To estimate the incidence, risk factors, severity and outcome after perinatal asphyxia in monochorionic (MC) versus dichorionic (DC) twins. METHODS: We included all consecutive near-term MC and DC twins with perinatal asphyxia admitted to our neonatal ward between 2004 and 2013 and compared the perinatal characteristics and neonatal outcome between both groups. RESULTS: The incidence of perinatal asphyxia in MC and DC twin infants was 4.0 (11/272) and 4.0% (8/200; p = 1.00). In contrast to DC twins, asphyxia in MC twins was strongly associated with acute exsanguination and anemia at birth; 64% (7/11) in MC twins and 0% (0/8) in DC twins (p < 0.01). Median hemoglobin level at birth in the MC and DC groups was 11.5 and 18.6 g/dl, respectively (p < 0.01). CONCLUSIONS: Perinatal asphyxia in MC twins is often associated with severe anemia at birth due to acute hemorrhage through the placental vascular anastomoses.

Renal failure after single fetal demise in monochorionic twins: incidence and description of a case.

Single intrauterine fetal demise in monochorionic (MC) twins may result in acute exsanguination from the surviving twin into the low-pressure circulation of the demised co-twin through the vascular anastomoses. This may lead to severe hypoxic-ischemic injury in the surviving twin due to hypovolemia, hypotension and anemia, resulting in multiorgan damage. Most studies in single fetal demise in MC twin pregnancies have reported on the risk of cerebral injury. The aim of our study was to explore the incidence and severity of renal damage in surviving MC twins after intrauterine co-twin death. We reviewed all cases of MC twins with single fetal demise presented over a 10-year period at our center. One of the 44 (2.3%) surviving co-twins was diagnosed with severe renal damage. We describe this case in detail, as it provides valuable insights into the pathogenesis of renal and other organ failure after MC co-twin death.

Management of twin anemia-polycythemia sequence using intrauterine blood transfusion for the donor and partial exchange transfusion for the recipient.

Twin anemia-polycythemia sequence (TAPS) is a rare condition which may occur either spontaneously in uncomplicated monochorionic twin pregnancies or may develop after laser treatment in twin-twin transfusion syndrome. TAPS is characterized by a large intertwin discordance in hemoglobin levels without discordance in amniotic fluid levels, and may lead to severe complications including fetal hydrops, hematological morbidity and perinatal mortality. Several treatments have been proposed including intrauterine transfusion, laser surgery, elective delivery and expectant management. The optimal treatment remains unclear. In this case series we report 3 TAPS cases managed recently at our center with a combination of intrauterine blood transfusion for the anemic twin and intrauterine partial exchange transfusion for the polycythemic twin. In 1 case, the donor was found to have severe cerebral injury on neuroimaging examination. We propose etiologic mechanisms for cerebral injury in TAPS, discuss the rationale behind this treatment alternative, and evaluate the pros and cons of the various management options.

Routine TORCH screening is not warranted in neonates with subependymal cysts.

BACKGROUND: Congenital infections are associated with a wide variety of clinical symptoms, including subependymal cysts (SEC). OBJECTIVE: To determine the co-occurrence of SEC and congenital infections, as diagnosed by TORCH serologic tests and/or cytomegalovirus (CMV) urine culture. METHODS: We performed a retrospective study of all neonates admitted to our neonatal intensive care unit from 1998 to 2009 in whom SEC were detected on cranial ultrasound and TORCH serologic tests and/or CMV urine cultures were performed. RESULTS: Fifty-nine neonates fulfilled the inclusion criteria. TORCH serologic tests were performed in 69% (41/59) of cases. Urine CMV culture was performed in 68% (40/59) of cases. None of the neonates tested positive for IgM Toxoplasma gondii, Rubella and Herpes simplex virus. Positive CMV IgM titers and/or a positive urine CMV culture were detected in 2% (1/59) of neonates. CONCLUSION: The co-occurrence of TORCH congenital infections in infants with SEC is rare. Routine TORCH screening in neonates with SEC does not seem warranted.

Is routine TORCH screening warranted in neonates with lenticulostriate vasculopathy?

BACKGROUND: Congenital infections are associated with a wide spectrum of clinical symptoms, including lenticulostriate vasculopathy (LSV). OBJECTIVE: To determine the relationship between LSV and congenital infections, as diagnosed by TORCH serology and viral culture for cytomegalovirus (CMV). METHODS: All neonates with LSV admitted to our neonatal intensive-care unit from 2004 to 2008 were included in the study. Results of maternal and neonatal TORCH testing were evaluated. RESULTS: During the study period, cranial ultrasound scans were performed in 2,088 neonates. LSV was detected in 80 (4%) neonates. Maternal and/or neonatal serological TORCH tests were performed in 73% (58/80) of cases. None of the mothers or infants (0 of 58) had positive IgM titres for Toxoplasma, rubella, CMV or herpes simplex virus. Additional urine culture for CMV was performed in 38 neonates. None of the infants (0 of 38) had a positive CMV urine culture test. CONCLUSIONS: Routinely applied efforts to diagnose congenital infections in cases presenting with LSV have a poor yield. Routine TORCH screening in neonates with LSV cases should only be regarded as mandatory once well-designed studies demonstrate a clear diagnostic benefit.

Lenticulostriate vasculopathy in very preterm infants.

OBJECTIVE: To assess for lenticulostriate vasculopathy (LSV) on cranial ultrasound (cUS) scans of very preterm infants: incidence and aetiology, evolution during neonatal period, association with clinical parameters, and MRI equivalent. DESIGN: Prospective study. SETTING: Tertiary neonatal referral centre. PATIENTS: Very preterm infants (<32 weeks) underwent sequential cUS throughout the neonatal period and MRI around term age. cUS were evaluated for LSV and other changes, and MRI for changes in signal and myelination in deep grey matter. LSV was divided into early-onset (7 postnatal days). Perinatal clinical parameters were collected for all infants and compared between groups. RESULTS: In 22/111 (20%) infants LSV was detected: early-onset in 5 and late-onset in 17. LSV mostly presented some weeks after birth and persisted for several months. There were no associations between LSV and other changes on cUS or deep grey matter changes on MRI. Infants with late-onset LSV were younger and smaller at birth than infants with early-onset LSV. Postmenstrual age at first detection was comparable for both LSV groups. There were no associations between LSV and perinatal clinical parameters, but infants with LSV had less episodes of hypotension than infants without LSV. CONCLUSIONS: LSV is a frequent finding on cUS in very preterm infants, but does not show on MRI. The postmenstrual age, rather than gestational and postnatal age, seems important in LSV development. LSV is not associated with clinical parameters. When encountered in otherwise healthy preterm infants, LSV is probably a benign temporary phenomenon.