The distinct placental angioarchitecture in monochorionic (MC) pregnancies increases the risk of complications such as twin–twin transfusion syndrome (TTTS), twin anemia polycythemia sequence (TAPS), and selective fetal growth restriction (sFGR). The aim of this systematic review was to evaluate the incidence, type, and severity of cerebral injury and structural brain development on fetal and/or neonatal cerebral magnetic resonance imaging (MRI) in MC twins with or without complications. Twenty-three studies were included, covering a wide range of complications observed during MC pregnancies, with studies involving sIUFD (n = 12), TTTS (n = 7), mixed complications (n = 2), TAPS (n = 1), and uncomplicated MC pregnancy (n = 1). TAPS and sFGR were largely underrepresented in the current literature. The included studies reported that MC pregnancies with single intrauterine fetal demise (sIUFD) are most at risk for cerebral injury during the fetal period. The overall median incidence of cerebral injury after sIUFD was 28.3% (0–55%). Severe antenatal cerebral injury after sIUFD was detected antenatally in 6.5% (0–36%) of the cases. Three of the included studies described the incidence, type, and severity of cerebral injury on neonatal MRI in MC twins. Structural brain development based on cerebral biometry was only assessed in two studies, revealing significantly smaller biometric measurements of the cerebrum in cases of single sIUFD or smaller twins compared to singleton pregnancies. To enhance our understanding of the potential risks and pathophysiological mechanisms associated with cerebral injury and structural brain development in MC twins, there is a need for future studies and standardized protocols using serial fetal and neonatal MRI imaging in addition to routine ultrasound imaging.

Introduction: There is no consensus regarding the efficacy of add-on therapy with levetiracetam (LEV) in the treatment of seizures in neonates. The aim of this study was to evaluate the efficacy of add-on therapy with LEV for achieving >80% seizure reduction after phenobarbital (PB) treatment. Methods: Retrospective cohort study of near term neonates admitted to the neonatal intensive care unit with EEG-confirmed seizures despite treatment with PB as first-line therapy and using LEV as 2nd-, 3rd- or 4th-line treatment. Antiseizure medication was administered according to national guidelines. All neonates were monitored with 2-channel amplitude-integrated electroencephalography. The total seizure burden in minutes, 2 h before and 4 h after administration of LEV, was calculated using raw EEG. Primary outcome was the efficacy of LEV in achieving >80% seizure reduction. The efficacy of additional midazolam (MDZ) and lidocaine (LDC) was also calculated. Results: A total of 47 full-term neonates were included. The mean total loading dose of LEV was 40 mg/kg (36–44 mg/kg). Seizure etiology consisted of hypoxic-ischemic encephalopathy (n = 11), hemorrhagic or ischemic stroke (n = 16), central nervous system infection (n = 8), genetic (n = 8), metabolic disorders (n = 3), and unknown (n = 1). Following LEV administration, >80% seizure reduction was observed in 17% (8/47) of neonates, whereas it was 23% (6/26) after MDZ and 92% (23/25) after LDC administration. Discussion: Although the cumulative loading dose of LEV was low and the group of infants studied was heterogeneous, the efficacy of LEV as add-on therapy for the treatment of seizures in neonates was limited. The highest seizure reduction rate was seen after LDC administration.

To evaluate the use of a fully automated trend measure of cortical activity, Brain State of the Newborn (BSN), in early stratification of infants for add-on neuroprotective therapies during therapeutic hypothermia (TH). Our retrospective cohort study included 167 infants with moderate-to-severe hypoxic-ischemic encephalopathy who underwent TH and continuous electroencephalography monitoring. The BSN trends were computed using fully automated pipelines, and we used a priori-defined thresholds at 6, 12, 24, and 36 hours after birth to assess prediction of an adverse postrewarming magnetic resonance imaging finding, defined as moderate-to-severe cortical or deep gray matter injury and/or severe white matter injury. Adverse outcome at 2 years of age was defined as death, cerebral palsy, or cognitive/motor scores <85 on the Bayley Scales of Infant Development-III. BSN-based prediction of an adverse outcome on MRI at 12-24 hours after birth showed high sensitivity (81%-87%) and specificity (73%-81%), and the corresponding area under the curve (AUC) ranged from 83% at 6 hours to 93% at 24 hours, stabilizing at 91% by 36 hours. In contrast, the prediction of adverse outcome at 2 years of age at 12-24 hours showed a moderate sensitivity (73%-77%) and specificity (70%-78%, AUC: 70%), whereas mortality prediction achieved high sensitivity (94%-99%) and specificity (69%-75%, AUC: 96%). BSN offers a fully automated and unbiased measure of recovery in spontaneous cortical activity, holding promise as a bedside biomarker in identifying infants who could benefit from early add-on neuroprotective therapies.

Objective: To evaluate the prevalence of acute peripartum twin-to-twin transfusion syndrome (TTTS) in vaginally born monochorionic (MC) twin pregnancies, comparing early cord clamping (ECC) to delayed cord clamping (DCC). Design, setting and patients: Single-centre retrospective cohort study including vaginally born MC twins at our institution between January 2020 and April 2025. Acute peripartum TTTS was defined as intertwin haemoglobin (Hb) difference >8 g/dL within 12 hours after birth, without signs of chronic TTTS or twin anaemia polycythaemia sequence. Twins were categorised to the ECC and DCC group if cord clamping occurred ≤60 s or >60 s after birth of the first twin, respectively. Results: Thirty-five twin pregnancies were included (n=17 in the ECC group; n=18 in the DCC group). Acute peripartum TTTS occurred in 0% (0/17) in the ECC group compared with 17% (3/18) in the DCC group (p<0.01). In the ECC group, no cases of severe brain injury were observed, whereas 8% (3/36) of infants in the DCC group, all with acute peripartum TTTS, showed severe brain injury (p<0.01). DCC time of the first born infant was associated with larger intertwin Hb difference (β=0.01, p=0.04). Potential risk factors for acute TTTS included interval between birth and cord clamping of the first infant (OR 1.02, 95% CI 1.00 to 1.03, p<0.03) and total combined diameter of bidirectional placental anastomoses (OR 1.34, 95% CI 0.97 to 1.84, p=0.07). Conclusion: DCC in MC twin pregnancies may be associated with a higher prevalence of acute peripartum TTTS and severe brain injury and is therefore not recommended.

Background: Monochorionic (MC) twins are at risk of acute exsanguination after single fetal demise (sFD) due to their shared placental circulation, which may result in sequelae for survivors. Objectives: To evaluate the prevalence of ante‐ and postnatal brain injury and long‐term neurodevelopmental impairment (NDI) in co‐twins after sFD. Secondary outcomes were the prevalence of termination of pregnancy (TOP), neonatal death (NND) and potential risk factors for brain injury. Search Strategy: PubMed, Embase, Scopus and Web of Science were searched to identify relevant studies in October 2024. Selection Criteria: Studies reporting MC twin pregnancies with spontaneous sFD. Studies with selective feticide, twin reversed arterial perfusion sequence, twin anaemia–polycythaemia sequence, congenital anomalies, higher‐order multiple pregnancies, fetoscopic laser surgery and double fetal demise were excluded. Data Collection and Analysis: Systematic review and meta‐analysis were performed following the PRISMA and MOOSE guidelines. Main Results: Thirteen studies involving 311 survivors after sFD were included. The prevalence of TOP, NND, brain injury and NDI was 3% (95% CI: 0%–7%), 6% (95% CI: 0%–16%), 27% (95% CI: 18%–37%), 6% (95% CI: 3%–11%), respectively. The median GA at birth in survivors with brain injury was 29 weeks (IQR 27.7–34.1) compared to 36 weeks (IQR: 32.3–37.0) in the overall group of survivors. Conclusions: Brain injury occurs in one in four survivors and is associated with lower GA at birth, suggesting a double‐hit injury due to a combination of exsanguination and (severe) prematurity. NDI occurs in one in 20 survivors, compared to two‐thirds of those with brain injury. Trial Registration: PROSPERO number: CRD42024608912