Comprehensive genetic screening for vascular Ehlers-Danlos syndrome through an amplification-based next-generation sequencing system.

Vascular Ehlers-Danlos syndrome (vEDS) is a hereditary connective tissue disorder (HCTD) characterized by arterial dissection/aneurysm/rupture, sigmoid colon rupture, or uterine rupture. Diagnosis is confirmed by detecting heterozygous variants in COL3A1. This is the largest Asian case series and the first to apply an amplification-based next-generation sequencing through custom panels of causative genes for HCTDs, including a specific method of evaluating copy number variations. Among 429 patients with suspected HCTDs analyzed, 101 were suspected to have vEDS, and 33 of them (32.4%) were found to have COL3A1 variants. Two patients with a clinical diagnosis of Loeys-Dietz syndrome and/or familial thoracic aortic aneurysm and dissection were also found to have COL3A1 variants. Twenty cases (57.1%) had missense variants leading to glycine (Gly) substitutions in the triple helical domain, one (2.9%) had a missense variant leading to non-Gly substitution in this domain, eight (22.9%) had splice site alterations, three (8.6%) had nonsense variants, two (5.7%) had in-frame deletions, and one (2.9%) had a multi-exon deletion, including two deceased patients analyzed with formalin-fixed and paraffin-embedded samples. This is a clinically useful system to detect a wide spectrum of variants from various types of samples.

The perinatal outcomes by gestational weight gain range at 30 weeks of gestation among pre-pregnancy underweight women.

AIMS: To evaluate the perinatal outcomes by gestational weight gain (GWG) range at 30 weeks of gestation among underweight pregnant women (pre-pregnancy body mass index ≤ 18.5 kg/m2 ) in Japan. METHODS: This retrospective study was conducted at a hospital in Japan from 2003 to 2020. The underweight pregnant women (UPW; n = 3643) were divided into quartile groups based on the weight gain at 30 weeks of gestation: group Q1 ≤ 5.7 kg, 5.7 kg < Q2 ≤ 7.2 kg, 7.2 kg < Q3 ≤ 8.8 kg, and 8.8 kg < Q4. Clinical characteristics and outcomes were compared using the t-test, chi-square test, and multivariable logistic regression analysis. RESULTS: The cumulative incidences of preterm births were 7.5% (n = 70), 5.0% (n = 45), 5.4% (n = 50), and 4.9% (n = 44), and the birth rates of small for gestational age (SGA) infants were 15.7% (n = 147), 9.6% (n = 87), 6.9% (n = 64), and 5.9% (n = 53) in Q1, Q2, Q3, and Q4, respectively. Multivariable analysis revealed that Q1 was significantly associated with preterm births (adjusted odds ratio [aOR] = 1.6; 95% confidence interval [CI] = 1.0-2.3), and Q1 and Q2 were significantly associated with SGA (adj. OR = 3.0; 95% CI = 2.2-4.3; adj. OR = 1.7; 95% CI = 1.2-2.5, respectively). None of the quartile groups were significantly associated with the incidence of primary cesarean sections, gestational diabetes mellitus, and macrosomia. CONCLUSIONS: In UPW, GWG at 30 weeks of ≤5.7 kg and ≤7.2 kg are associated with preterm birth and SGA rates, respectively.

Endometritis risk factors after arterial embolisation for postpartum haemorrhage.

Various complications of arterial embolisation (AE) for postpartum haemorrhage (PPH) are reported. Endometritis (EM) frequently causes abscesses, increasing hysterectomy risk. However, risk factors for EM after AE for PPH are unclear. We explored these risk factors. We included patients who underwent AE for PPH in our hospital from 2005 to 2020 and compared those who did (EM group) and did not develop EM after AE (non-EM group) in a case-control study. Twenty patients met the study criteria; eight patients (40%) had EM. There were no differences in risk factors between groups involved in infection, such as premature rupture of membranes. However, the contrast medium extravasation rate on computed tomography scans before the AE procedure was significantly higher in the EM group (p=.019) compared to the non-EM group. The greatest EM risk factor was contrast medium extravasation before AE for PPH, determined by classification and regression tree modelling (relative risk: 4.5).Impact StatementWhat is already known on this subject? Reportedly, the clinical success rate of arterial embolisation (AE) for critical haemorrhage in obstetrics is high, around 90%. However, information regarding AE complications is limited. Endometritis is one of these complications, which not only causes prolonged hospitalisation but may also require further treatment, such as hysterectomy. However, the incidence rate and risk factors for EM remain unknown.What do the results of this study add? In this study, 40.0% of patients developed EM after AE for PPH. Extravasation of contrast medium was the top risk factor (relative risk: 4.5 compared to those without EM, p=.019). The second-leading risk factor was a bleeding volume greater than 2500 mL (relative risk: 4.5 compared to those without EM, p=.019).What are the implications of these findings for future clinical practice and/or future research? We created an EM prediction model using extravasation and a bleeding volume greater than 2500 mL. The model was 87.5% sensitive and 66.7% specific. This prediction model allows for the early detection and treatment of EM by recognising high-risk patients and providing intensive postpartum management.

Acute heart failure associated with toxic shock syndrome due to methicillin-susceptible Staphylococcus aureus during the postpartum period: case report and systematic literature review.

BACKGROUND: Toxic shock syndrome (TSS) caused by Staphylococcus aureus in the postpartum period is a rare but life-threatening disease. We present a case of acute heart failure as the initial presentation of TSS due to methicillin-susceptible Staphylococcus aureus (MSSA) and describe its clinical characteristics with a systematic literature review. CASE PRESENTATION: A 34-year-old woman, 8 days after a normal vaginal delivery presented to our hospital with dyspnea and fever. She had jugular venous distension, bilateral leg edema, and erythema. Laboratory examinations revealed elevated NT-pro-BNP level of 3,233 pg/mL. Transthoracic echocardiography showed elevated tricuspid regurgitation peak gradient, with decreased respiratory variability of the inferior vena cava diameter and bilateral pleural effusions. The patient was hospitalized with suspicion of congestive heart failure. MSSA positive for toxic shock syndrome exotoxin-1 was detected in the culture of the perineal incision wound, and we diagnosed TSS caused by MSSA. Intravenous diuretics were administered, along with eventual cefazolin plus clindamycin. After 2 weeks of antimicrobial therapy, the patient showed improvement and was discharged. No recurrence was observed at the 24-month follow-up. CONCLUSION: This is a rare case report of acute heart failure being the initial manifestation of TSS due to MSSA in the postpartum period. Clinicians should consider TSS as a possibility in postpartum patients with acute heart failure. This systematic review provides insights into its clinical features, treatment regimens, and prognosis of TSS by S. aureus in the postpartum period. TSS requires an appropriate, prompt diagnosis, because delayed treatment can be fatal.

Quantitative Elemental Analysis of a Single Cell by Using Inductively Coupled Plasma-Mass Spectrometry in Fast Time-Resolved Analysis Mode.

The elemental composition of a single yeast, green alga, or red blood cell (RBC) was precisely determined by using inductively coupled plasma-mass spectrometry (ICP-MS) operating in fast time-resolved analysis (TRA) mode. The technique is known as single-cell (SC)-ICP-MS. Phosphorus, sulfur, magnesium, zinc, and iron were detected in the three types of cell. The elemental composition of yeast and green alga obtained by SC-ICP-MS was consistent with results obtained from conventional ICP-MS measurements following acid digestion of the cells. Slight differences were found in the measured values between SC-ICP-MS and the conventional ICP-MS results for RBC. However, the SC-ICP-MS results for S and Fe in RBC were closer to the estimated values for these elements that were calculated from the level of hemoglobin in RBCs. The data suggest that SC-ICP-MS is suitable for the analysis of various cell types, namely, fungus, plant, and animal cells.

Enhanced Universal Quantification of Biomolecules Using Element MS and Generic Standards: Application to Intact Protein and Phosphoprotein Determination.

Tools that provide absolute quantification of biomolecules, particularly of proteins and their post-translational modifications, without needing suitable specific standards, are urgently demanded nowadays. To this end, we have significantly improved the recently introduced strategy based on CH4 addition to the plasma for absolute quantification of biomolecules using HPLC-ICP-MS. Addition of CO2 has been optimized and finally selected as a safer, more efficient quantitative strategy that is able to provide constant (<6% error) signal response factor for the six elements assayed (S, P, As, Se, Br, I) under compromised conditions. In the particular case of absolute protein quantification, accuracy and precision attainable for S-based absolute determination of intact proteins using internal and external S-generic standards were compared. Potential for real sample analysis was demonstrated by the high-sensitivity analysis of toxins present in snake venoms. Finally, multielemental speciation capabilities of the approach have been also demonstrated through P and S simultaneous analysis in phosphoproteomics. Simultaneous accurate determination of both absolute protein amount and corresponding phosphorylation degree for intact ß-casein, and even impurity traces of κ and α-s1 isoforms present, has been successfully achieved using a simple mixture of inorganic P and S standards. The lowest detection limits (<1 fmol protein) ever published for S- and P-based intact protein quantification with ICP-MS are reported.

Risk factors of infant anemia in the perinatal period.

BACKGROUND: Infants are at particular risk of iron-deficiency anemia. We investigated changes in the blood count of the mother and infant as well as the relationship between them and the relationship between infant nutrition method and infant anemia. METHODS: This retrospective cohort study included healthy neonates born between August 2011 and July 2014 at St Luke's International Hospital, Tokyo, Japan. Data from maternal blood samples obtained during late pregnancy and those of infants obtained at birth and at the age of 3, 6, and 9 months were analyzed. Using multivariate logistic regression, we investigated nutrition methods, maternal anemia, and other clinically relevant parameters that were potential risk factors for infant anemia. RESULTS: In total, data for 3472 infants and their mothers were analyzed. Nutrition method was the most significant risk factor for infant anemia, with risk of future anemia decreasing in the following order: exclusive breast-feeding, partial breast-feeding, and formula feeding. Furthermore, low umbilical cord blood hemoglobin led to a tendency toward anemia in the child. CONCLUSION: Infant nutrition method was the most significant factor related to anemia in late infancy. Infants with low umbilical cord blood hemoglobin are more likely to develop anemia in late infancy.

Sudden onset of pheochromocytoma multisystem crisis at 38 weeks of gestation resulted in intrauterine fetal death: A case report.

A 24-year-old woman at 38 weeks of gestation with no past medical history was transferred to our hospital because of acute onset of severe dyspnea. Her conscious level was E4V2M5 on the Glasgow Coma Scale and she displayed stress cardiomyopathy (Takotsubo cardiomyopathy) with multiple organ failure. Intrauterine fetal death was confirmed. After immediate application of intubated ventilation, percutaneous cardiopulmonary support and hemodialysis, she was diagnosed with pheochromocytoma multisystem crisis. After multidisciplinary team discussion, surgical resection of the left pheochromocytoma was performed on the same day. However, the bleeding from retroperitoneal drainage did not decrease, therefore, on the fourth day of hospitalization, embolization of the left renal artery under angiography was performed. A 2774 g female infant was stillborn spontaneously on the seventh day of hospitalization. Percutaneous cardiopulmonary support was discontinued on the fifth day of hospitalization and the tracheal tube was extubated on the 11th day. The patient was discharged after 30 days.

Bent bone dysplasia (BBD)-FGFR2 type: the radiologic manifestations in early gestation.

Bent bone dysplasia-fibroblast growth factor receptor 2 type (BBD-FGFR2) is a recently identified skeletal dysplasia caused by specific FGFR2 mutations, characterized by craniosynostosis and prenatal bowing of the long bones. Only a few cases have been published. We report an affected fetus terminated at 21 weeks of gestation. The clinical and radiologic manifestations mostly recapitulate previous descriptions; however we suggest additional hallmarks of this disorder in early gestation. These hallmarks include distinctive short, thick clavicles and wavy ribs, as well as vertebral bodies that showed striking anteroposterior shortening. Femoral fractures were also present in our case. Although craniosynostosis is a hallmark of the disease, clinicians should be aware that craniosynostosis might not be readily apparent on plain films early in gestation.

Correlation between umbilical cord hemoglobin and rate of jaundice requiring phototherapy in healthy newborns.

BACKGROUND: Delay of umbilical cord clamping by at least 1 min is recommended for newborns not requiring resuscitation in the International Liaison Committee On Resuscitation-Consensus on Science with Treatment Recommendations (ILCOR-CoSTR) 2010 guidelines. The delay in clamping improves iron status through early infancy but may increase the likelihood of jaundice requiring phototherapy. The present study investigated the relationship between umbilical cord hemoglobin and the rate of jaundice requiring phototherapy in healthy Japanese newborns. METHODS: Cord hemoglobin was measured in healthy newborns and the rate of infants receiving phototherapy for jaundice and other data were obtained from medical records. RESULTS: Jaundice requiring phototherapy mostly occurred in association with high cord blood hemoglobin, which is increased by delayed cord clamping. CONCLUSIONS: Higher cord hemoglobin may increase neonatal jaundice in newborns in Japan, therefore the present results support the Japan Resuscitation Council guideline 2010, which does not recommend delay of umbilical cord clamping by at least 1 min, in contrast to the ILCOR guidelines.

Acute pain and analgesic requirement after vaginal childbirth with and without neuraxial labor analgesia-Retrospective cohort study.

BACKGROUND: Few data are available on the intensity of pain that women experience during the first five days after vaginal childbirth. Moreover, it is unknown if the use of neuraxial labor analgesia has any impact on the level of postpartum pain. METHODS: We performed a retrospective cohort study based on chart review of all women who delivered vaginally at an urban teaching hospital between April 2017 and April 2019. The primary outcome was the area under the curve of pain score on numeric rating scale (NRS) documented in electronic medical records for five days postpartum (NRS-AUC5days). Secondary outcomes included peak NRS score, doses of oral and intravenous analgesics consumed during the first five days postpartum, and relevant obstetric outcomes. Logistic regression was used to examine the associations between the use of neuraxial labor analgesia and pain-related outcomes adjusting for potential confounders. RESULTS: During the study period, 778 women (38.6%) underwent vaginal delivery with neuraxial analgesia and 1240 women (61.4%) delivered without neuraxial analgesia. Median (Interquartile range) of NRS-AUC5days was 0.17 (0.12-0.24) among women who received neuraxial analgesia and 0.13 (0.08-0.19) among women who did not (p<0.001). Women who received neuraxial analgesia were more likely to require the first- and second-line analgesics postpartum than women who did not: diclofenac (87.9% vs. 73.0%, p< 0.001, respectively); acetaminophen (40.7% vs. 21.0%, p< 0.001, respectively). The use of neuraxial labor analgesia was independently associated with increased odds of having NRS-AUC5days in the highest 20 percentile (adjusted odds ratio [aOR] 2.03; 95% confidence interval [CI] 1.55-2.65), having peak NRS ≥ 4 (aOR 1.54; 95% CI 1.25-1.91) and developing hemorrhoids during the postpartum hospitalization (aOR 2.13; 95% CI 1.41-3.21) after adjusting for relevant confounders. CONCLUSION: Although women who used neuraxial labor analgesia had slightly higher pain scores and increased analgesic requirement during postpartum hospitalization, pain after vaginal childbirth was overall mild. The small elevation in the pain burden in neuraxial group does not seem to be clinically relevant and should not influence women's choice to receive labor analgesia.

Physical and psychological recovery after vaginal childbirth with and without epidural analgesia: A prospective cohort study.

BACKGROUND: Enhanced recovery is the gold standard in modern perioperative management, including that for cesarean deliveries. However, qualitative and quantitative data on the physical and psychological recovery of women after vaginal childbirth are limited. Whether neuraxial labor analgesia influences postpartum recovery is unknown. METHODS: Primiparous women anticipating a vaginal childbirth between January 2020 and May 2021 were enrolled. Women with major comorbidities or postpartum complications and those who underwent a cesarean delivery were excluded. Daily step count was measured using a wrist-worn activity tracker (FitbitTM Inspire HR) for 120 hours after vaginal childbirth. Subjective fatigue levels and health-related quality of life were assessed using the Multidimensional Fatigue Inventory (MFI) and EuroQol 5 Dimension 5 Level (EQ-5D-5L), respectively, at the 3rd trimester antenatal visit, on postpartum day 1 and 3, and at the one-month postpartum visit. Rest and dynamic pain scores and the location of pain were documented by participants during postpartum hospitalization. RESULTS: Among 300 women who were enrolled antenatally, 95 and 116 had a vaginal delivery without (NCB group) and with (EPL group) epidural analgesia, respectively. The median number of steps per 24 hours increased daily in both groups, and no significant difference was detected between the groups. Postpartum pain was mild overall, with median rest and dynamic pain scores being less than 4 and similar between the groups. MFI and EQ-5D-5L scores were the worst on postpartum day 1 in both groups and gradually improved to antepartum level by the one-month postpartum visit. Higher MFI score on postpartum day 1, but not the use of epidural analgesia, was associated with lower odds of achieving adequate postpartum ambulation (defined as >3500 steps between 48 and 72 hours postpartum). CONCLUSION: The use of epidural analgesia was not associated with worse recovery outcomes during postpartum hospitalization. TRIAL REGISTRATION: UMIN-CTR, #UMIN000039343, registered on January 31, 2020.

Single-cell and bulk ICP-MS investigation of accumulation patterns of Pt-based metallodrugs in cisplatin-sensitive and -resistant cell models.

In research enabling preclinical development and attaining a deeper understanding of the behavior of metallodrugs in cancer cells with acquired resistance, intracellular Pt accumulation could be considered an important biomarker and analytical focus. In this work, Pt accumulation patterns in terms of the number of cells and Pt mass in single cells were precisely defined by using inductively coupled plasma-mass spectrometry (ICP-MS) operating in a fast time-resolved analysis mode. This technique is otherwise known as single-cell (SC)-ICP-MS. By applying the nascent and validated SC-ICP-MS technique, comparisons across three Pt drugs (cisplatin, carboplatin, and oxaliplatin) in the A2780 and A2780cis ovarian cancer cell models could be made. Additional roles of transporters on top of passive diffusion and the drugs' bioactivity could be postulated. The SC-ICP-MS-based observations also served as a cross-validation point to augment preexisting research findings on Pt-resistance mechanisms. Conjectures regarding S and Fe metabolism were also derived based on an additional and direct ICP-MS analysis of endogenous elements. Overall, our work not only confirms the utility of SC-ICP-MS in chemotherapeutic research, but also provided insights into further ICP-MS-based analytical capacities to be developed.

Congenital omphalocele and polyhydramnios: a study of 52 cases.

INTRODUCTION: Unlike gastroschisis, congenital omphalocele is often associated with other anomalies and is frequently complicated by polyhydramnios. We examined the relationships between polyhydramnios, pregnancy outcome and fetal prognosis. PATIENTS AND METHODS: Clinical data from cases diagnosed antenatally with congenital omphalocele from 1993 to 2006 were analyzed retrospectively. RESULTS: Fifty-two cases were diagnosed antenatally with congenital omphalocele, and 38 of these pregnancies resulted in delivered infants. Of these 38 pregnancies, 55.3% were preterm births before 37 weeks of gestation. The mean birth weight was 2,148 g (n = 38). Associated anomalies were recognized in 29 cases (76.3%), including 13 cases (34.2%) of chromosomal aberrations. There were 2 cases of trisomy 13, 10 cases of trisomy 18 and 1 case of trisomy 21. Polyhydramnios was detected in 14 cases (36.8%), and other anomalies were present in all of these cases. DISCUSSION: For antenatal evaluation in cases of congenital omphalocele, it is important to examine the fetus for associated anomalies or underlying disease, especially when polyhydramnios is detected.

Prenatal management of the fetus with lethal malformation: from a study of oligohydramnios sequence.

47 cases of oligohydramnios sequence (OS) diagnosed at Kanagawa Children's Medical Center from 1992 to 2008 were studied retrospectively. Early termination of pregnancy was chosen in 9 cases, observed natural labor was chosen in 23 cases, and 18 cases resulted in natural deliveries. Fetal demise occurred during labor in 44.4% of terminated cases, while it occurred in 5.6% of observed cases. Preterm labors and breech presentations occurred most frequently. Most infants died within 18 hours after their births. There were 3 familial cases. These results provide important information for planning the perinatal care when fetuses are diagnosed with OS.

Prehypertension in early pregnancy is a risk factor for hypertensive disorders during pregnancy: A historical cohort study in Japan.

Objective: We evaluated the association between pre-hypertension (120-139 or 80-89 mmHg) in early pregnancy, hypertensive disorders of pregnancy (HDP), and perinatal adverse outcomes. Methods: We included 14,066 pregnant women, treated between 2003 and 2019 in Japan. Based on a blood pressure chart review recorded before 20 weeks of gestation, we stratified participants into the prehypertension (n = 3,806) and normotensive (n = 10,260) groups. Results: Prehypertension, an independent risk factor for HDP in the multivariate analysis (P< 0.001), was significantly associated with preterm and small-for-gestational age infants. Conclusion: Prehypertension potentially confers a risk for adverse perinatal outcomes in apparently normal pregnancies.

Velamentous cord insertion ruptured during labour leading to acute fetal blood loss.

Umbilical cord rupture (UCR) in utero is a very rare and critical emergency that can cause fetal death within minutes. A 38-year-old nulliparous woman was admitted at 39 weeks in labour. Sudden watery vaginal discharge and bleeding with a rapid drop in the fetal heart rate to 60 beats/min necessitated an emergency caesarean section. A male infant weighing 2632 g was delivered 21 min after the onset of bradycardia; Apgar scores were 0 and 1 at 1 and 5 min, respectively. He was extremely pale; the umbilical arterial blood pH was 6.89 and haemoglobin was 9.0 g/dL. The umbilical cord had a velamentous insertion and was lacerated, with haemorrhage in the outer layer of an umbilical artery close to the placental end. The presentation was typical of UCR: vaginal bleeding following the rupture of membranes. Prompt diagnosis of UCR and termination of pregnancy are essential for fetal survival.

Analysis of birth-related medical malpractice litigation cases in Japan: review and discussion towards implementation of a no-fault compensation system.

AIM: We examined birth-related malpractice civil litigation cases in Japan to clarify the actual status related to the implementation of an obstetrical no-fault compensation system in 2009. MATERIAL & METHODS: In this retrospective review, we analyzed legal and medical information from 64 cases with a delivery date after 1987 and a judgment date between April 1997 and March 2007. RESULTS: The malpractice claim was accepted in 44 cases and rejected in 20 cases. The period from the delivery to the judgment date was lengthy (90.1 months overall). The average amount of damages awarded was yen97 810,000 for cases of cerebral palsy (CP). Preterm births and less than 2500 g infants represented a higher incidence rate in the rejected cases. There were 32 cases (50.0%) with CP, 18 (28.1%) with infant death, 10 (15.6%) with neonatal death, and 4 (6.3%) with fetal death. Twenty-three of 44 accepted cases (52.3%) and 11/20 rejected cases (55.0%) had a gestational age of more than 33 weeks at birth and weighed more than 2000 g. Forced deliveries were performed in 45/64 cases (70.3%), and augmentation/induction of labor was performed in 28/64 cases (43.8%). There were 13/16 (81.3%) accepted cases that underwent vacuum and/or forceps extraction after labor augmentation/induction. CONCLUSIONS: More than half of our cases could be sufficient for a no-fault compensation system in Japan. Though the system is considered to have some problems that need to be solved, this finding suggests that many children and their families may benefit from the new system without having to file.

Simultaneous Analysis of Iodine and Bromine Species in Infant Formula using HPLC-ICP-MS.

Background: A fast and sensitive method for the simultaneous analysis of iodine and bromine species in infant formula was developed using HPLC-inductively coupled plasma-MS (HPLC-ICP-MS). Method: To determine the four halogen species [iodide (I-), iodate (IO3-), bromide (Br-), and bromate (BrO3-)] in a milk-based Standard Reference Material and four commercially available infant formula products. Results: The four halogen species were baseline separated in less than 6.5 min using an anion exchange resin column and 5.0 mM NaH2PO4 / 15.0 mM Na2SO4 / 5.0 mM EDTA (pH 7.0) mobile phase. Following separation, the halogen species were detected by measuring m/z 79 for Br and m/z 127 for I using a triple quadrupole-ICP-MS. The instrument was operated in single quadrupole mode with helium cell gas. Excellent linearity (R = 0.9999 or better) was obtained for all four species with calibration standards ranging from 0 to 100 ppb. The LOD for I-, IO3-, Br-, and BrO3- were all less than 0.67 µg/kg. To test the suitability of the method for the accurate determination of low concentrations of the four species in infant formula samples, a spike recovery test was carried out at 20 and 40 µg/kg into the diluted infant formula samples. Conclusions: Total elemental determinations of iodine and bromine were also performed using the triple quadrupole-ICP-MS without HPLC.

Fetus-in-fetu: parasite or neoplasm? A study of two cases.

INTRODUCTION: Fetus-in-fetu is a rare congenital fetiform mass whose etiology is still controversial. We report two cases of fetus-in-fetu. CASE 1: A fetal retroperitoneal cystic tumor including two masses was detected by ultrasonography at 26 gestational weeks. The masses showed distinctive structures resembling a vertebral axis and were prenatally diagnosed as fetus-in-fetu. A resected specimen revealed two fetiform masses. CASE 2: An intracranial tumor with hydrocephalus was detected by ultrasonography at 19 gestational weeks. The pregnancy was terminated, and a postmortem examination revealed six fetiform masses with immature teratoma. DISCUSSION: The tumors may possibly consist of parasitic monozygotic diamniotic twins or highly differentiated teratomas.