Management of pulmonary hemodynamics prior to delivery in a pregnant woman with development of decompensated pulmonary arterial hypertension.

Prompt termination of pregnancy in patients with decompensated pulmonary arterial hypertension (PAH) is imperative for improvement of maternal hemodynamics, but such termination may also result in maternal death due to further deterioration of PAH immediately after delivery. However, there have been limited reports on whether implementation of PAH therapy with continuation of pregnancy improves the maternal outcome, especially in treatment-naïve patients with PAH. A 24-year-old woman was admitted to our hospital with a chief complaint of dyspnea (WHO functional class IV) at 22 weeks and 3 days of gestation. She was diagnosed with PAH accompanied by right heart failure and low cardiac output. Intensive treatment was initiated with inotropic agents, oxygen therapy, and PAH therapy, resulting in improvement of her hemodynamics. A caesarean section was performed at 23 weeks and 3 days. Although her pulmonary arterial pressure transiently increased with oxygenation deteriorating immediately after delivery, worsening PAH improved without mechanical circulatory support. She continued receiving pulmonary vasodilators without relapse of pulmonary hypertension for three years. The improvement of pulmonary hemodynamics prior to delivery with PAH therapy led to a favorable outcome after delivery. Learning objective: Pulmonary hemodynamics in pregnant patients with pulmonary arterial hypertension (PAH) can deteriorate with the continuation of pregnancy, while termination can also cause PAH surge immediately after delivery. In treatment-naïve patients with PAH, who are most likely to benefit from PAH therapy, implementation of PAH therapy with continuation, even with a decompensated status, may improve the hemodynamics prior to delivery, resulting in a favorable outcome after delivery.

Two-dimensional phase-contrast MRI reveals changes in uterine arterial blood flow in pregnant women administered tadalafil for fetal growth restriction.

INTRODUCTION: We aimed to examine the effect of uterine arterial (UtA) blood flow changes after tadalafil treatment for fetal growth restriction (FGR) using two-dimensional (2D) phase-contrast magnetic resonance imaging (PC-MRI). METHODS: We recruited 14 pregnant women with FGR aged 20-44 years, at ≥20 weeks' gestation, between May 2019 and July 2020. They underwent 2D PC-MRI for UtA blood flow measurement 3 days (interquartile range: 2-4) after diagnosis. This group (FGR group) was compared with 14 gestational age (GA)-matched healthy pregnant women (control group). Six patients in the FGR group received treatment with tadalafil administered at 20 mg twice daily after the first MRI until delivery. They underwent a second MRI a week later. RESULTS: The median total UtA blood/body surface area was 420 mL/min/m2 (290-494) in the FGR group and 547 mL/min/m2 (433-681) in the control group (p = 0.01). Percent increase in blood flow were significantly different between the FGR cases treated with tadalafil and control at 15.8 % (14.3-21.3) and 4.2 % (3.6-8.7), respectively (p = 0.03). DISCUSSION: UtA blood flow in pregnant women with FGR was significantly lower than that in healthy pregnant women. Tadalafil is expected to improve UtA blood flow, thereby improving placental function in pregnant patients with FGR.

Evaluation of fetal acidemia during delivery using the conventional 5-tier classification and Rainbow systems.

The association between prepartum time-series fetal heart rate pattern changes and cord blood gas data at delivery was examined using the conventional 5-tier classification and the Rainbow system for 229 female patients who delivered vaginally. They were classified into three groups based on the results of umbilical cord blood gas analysis at delivery. The fetal heart rate pattern classifications were based on analysis of measurement taken at 10-min intervals, beginning at 120 min pre-delivery. The relationship between fetal heart rate pattern classification and cord blood pH at delivery changed over time. The 5-tier classification at each interval increased before delivery in the Mild and Severe groups compared with the Normal group. No significant differences were observed between acidemia groups. The Rainbow classification showed a significant differences between the acidemia groups at each interval, particularly during the prepartum period. A relationship between classification and outcome was evident before delivery for both the 5-tier classification and Rainbow system.

Efficacy of a portable interface pressure sensor for robotic surgery in preventing compartment syndrome.

BACKGROUND/OBJECTIVE: This study determines whether the use of a portable interface pressure sensor (Palm Q) for robotic surgery could prevent compartment syndrome. METHODS: In the present single center, non-trial observational study, patients diagnosed with gynecological diseases between April 2015 and August 2020 treated with laparoscopic or robotic surgery were enrolled. We assessed 256 cases involving surgery performed in the lithotomy position with an operative time >4 h. The Palm Q device was placed preoperatively on both sides of the patients' lower legs. The pressure was measured every 30 min preoperatively and intraoperatively and adjusted to ≤30 mmHg. If the pressure reached ≥30 mmHg, the operation was stopped, the patient was repositioned, the leg position was released, the pressure was reduced to ≤30 mmHg, and the procedure was resumed. We compared the maximum creatine kinase levels of the Palm Q and non-Palm Q groups. We also analyzed the correlation between the patients' symptoms postoperatively (shoulder and leg pain) and compartment syndrome. RESULTS: Our data showed that immediate postoperative creatine kinase levels predict compartment syndrome. Propensity score matching of the 256 enrolled patients resulted in 92 cases (46 per group), balanced for age, body mass index, and lifestyle disease. Creatine kinase levels differed significantly between the Palm Q and non-Palm Q groups (p = 0.041). None of the patients in the Palm Q group experienced well-leg compartment syndrome complications. CONCLUSION: Palm Q can potentially help to prevent perioperative compartment syndrome.

Transient Decrease in Incidence Rate of Maternal Primary Cytomegalovirus Infection during the COVID-19 Pandemic in Japan.

This study evaluated the impact of the coronavirus disease 2019 (COVID-19) pandemic on the occurrence of maternal primary cytomegalovirus (CMV) infection in Japan. We performed a nested case-control study using data from maternal CMV antibody screening under the Cytomegalovirus in Mother and infant-engaged Virus serology (CMieV) program in Mie, Japan. Pregnant women with negative IgG antibodies at ≤20 weeks of gestation who were retested at ≥28 weeks were enrolled. The study period was divided into 2015-2019 as the pre-pandemic and 2020-2022 as the pandemic period, and the study site included 26 institutions conducting the CMieV program. The incidence rate of maternal IgG seroconversion was compared between the pre-pandemic (7008 women enrolled) and pandemic (2020, 1283 women enrolled; 2021, 1100 women; and 2022, 398 women) periods. Sixty-one women in the pre-pandemic period and five, four, and five women during 2020, 2021, and 2022, respectively, showed IgG seroconversion. The incidence rates in 2020 and 2021 were lower (p < 0.05) than that in the pre-pandemic period. Our data suggest a transient decrease in the incidence of maternal primary CMV infection in Japan during the COVID-19 pandemic, which could be due to prevention and hygiene measures taken at the population level.

Revision of Cytomegalovirus Immunoglobulin M Antibody Titer Cutoff in a Maternal Antibody Screening Program in Japan: A Cohort Comparison Involving a Total of 32,000 Pregnant Women.

Cytomegalovirus (CMV) is associated with congenital infections. We aimed to validate the revised CMV immunoglobulin (Ig) M titer cutoff for IgG avidity measurements as a reflex test in maternal screening to identify women with primary CMV infection and newborn congenital cytomegalovirus (cCMV). We screened maternal CMV antibodies (the Denka assay) in Japan, from 2017 to 2019, using a revised IgM cutoff (≥4.00 index). Participants were tested for IgG and IgM antibodies, and for IgG avidity if IgM levels exceeded the cutoff. We compared these with corresponding results from 2013 to 2017 based on the original cutoff (≥1.21) and recalculated using the revised cutoff. Newborn urine CMV DNA tests were performed for women with low avidity (≤35.0%). Among 12,832 women screened in 2017-2019, 127 (1.0%) had IgM above the revised cutoff. Thirty-five exhibited low avidity, and seven infants developed cCMV. Of 19,435 women screened in 2013-2017, 184 (1.0%) had IgM above the revised cutoff, 67 had low avidity, and 1 had cCMV. The 2017-2019 results were not significantly different from the 2013-2017 results. The revised IgM cutoff improves maternal screening in identifying primary infection and newborn cCMV; however, further study related to other assays than Denka is required.

Measurement of Intermediate Frequency Magnetic Fields Generated by Household Induction Cookers for Epidemiological Studies and Development of an Exposure Estimation Model.

INTRODUCTION: Exposure assessment of intermediate frequency (IF) electromagnetic fields (EMFs) is difficult and epidemiological studies are limited. In the present study, we aimed to estimate the exposure of pregnant women to IF-EMFs generated by induction cookers in the household using a questionnaire and discussed its applicability to epidemiological studies. METHOD: Two main home-visit surveys were conducted: a Phase 1 survey to develop an estimation model and a Phase 2 survey to validate the model. The estimation model included the following variables: wattage, cookware diameter, and distance from the hob center (center of the stove). Four models were constructed to determine the importance of each variable and the general applicability for epidemiological studies. In addition, estimated exposure values were calculated based on the Phase 2 survey questionnaire responses and compared with the actual measured values using the Spearman rank correlation coefficient. RESULT: The average value of the magnetic field measured in the Phase 1 survey was 0.23 µT (variance: 0.13) at a horizontal distance of 30 cm at the height of the cooking table. The highest validity model was inputted distance from the hob center to the body surface that is variable (correlation coefficient = 0.54, 95% confidence interval: 0.22-0.75). No clear differences were identified in the correlation coefficients for each model (z-value: 0.09-0.18, p-value: 0.86-0.93). DISCUSSION AND CONCLUSIONS: No differences were found in the validity of the four models. This could be due to the biased wattage of the validation population, and for versatility it would be preferable to use three variables (distance, wattage, and estimation using the diameter of the cookware) whenever possible. To our knowledge, this is the first systematic measurement of magnetic fields generated by more than 70 induction cookers in a real household environment. This study will contribute to finding dose-response relationships in epidemiological studies of intermediate-frequency exposure without the use of instrumentation. One of the limitations of this study is it estimates instantaneous exposure in place during cooking only.

Adverse Events Associated With Long-term Treatment of Epithelial Ovarian Cancer With Bevacizumab and Chemotherapy.

BACKGROUND/AIM: Adverse events associated with long-term bevacizumab administration for ovarian cancer have been poorly documented in Japan. This study aimed to evaluate the adverse events of bevacizumab combined with chemotherapy for treating primary and recurrent epithelial ovarian cancer in Japan. PATIENTS AND METHODS: In this single-center retrospective study, we analyzed data of patients with advanced and recurrent epithelial ovarian cancer treated with bevacizumab and chemotherapy between January 2013 and November 2019. Statistical analyses were performed using the Fisher's exact test and Kaplan-Meier method. RESULTS: A total of 46 patients were included and the follow-up time was 30 months. The median duration of bevacizumab treatment was 14 months, and the median total dose of bevacizumab was 247.5 mg/kg. The most common adverse events were hypertension (n=30; 65.2%) and proteinuria (n=24; 49%) in all grades. The onset of hypertension and proteinuria occurred at a median of 2 months and 14 months after treatment initiation in all grades, respectively. Gastrointestinal perforation occurred significantly more frequently in patients with a history of radiation therapy. CONCLUSION: This study included cases of primary advanced and recurrent epithelial ovarian cancer, and had a longer observation period and reported more adverse events of bevacizumab with chemotherapy than previous reports. The administration of bevacizumab therapy in patients with a history of radiation should be carefully considered due to increased chances of gastrointestinal perforation.

sFlt-1 value predicts pregnancy prolongation periods from diagnosis in pregnant women diagnosed with early-onset preeclampsia.

PURPOSE: The aim of this study is to analyze whether soluble fms-like tyrosine kinase-1 (sFlt-1) can be correlated with the severity of PE. MATERIALS AND METHODS: This study was conducted in a single hospital and is a prospective, observational study. sFlt-1 was measured at the diagnosis of preeclampsia. The period from diagnosis to pregnancy termination (pregnancy prolongation periods) was defined as the barometer for the severity of PE. The correlations between sFlt-1 level with pregnancy prolongation periods were then analyzed. RESULTS: Eighteen pregnant women diagnosed with early-onset preeclampsia were recruited. sFlit-1 value significantly negatively correlated with the pregnancy prolongation period from diagnosis (p = .003, R = 0.647). CONCLUSION: sFlt-1 was correlated with the pregnancy prolongation periods after onset of PE. sFlt-1 in early-onset PE may reflect the severity of PE in pregnant women.

Characteristics and serology of pregnant women with cytomegalovirus immunoglobulin G seroconversion during pregnancy in Japan.

OBJECTIVE: Investigate the characteristics and serology of pregnant women with cytomegalovirus (CMV) immunoglobulin (Ig)G seroconversion during pregnancy to understand the risk factors associated with primary CMV infection and the occurrence of fetal congenital CMV infection. MATERIALS AND METHODS: We retrospectively studied 3202 pregnant women who were CMV IgG-negative in early pregnancy and were retested for IgG in late pregnancy. Characteristics were compared between participants with and without IgG seroconversion, and serological parameters were compared between participants with and without fetal congenital CMV infection. RESULTS: Twenty-six participants showed CMV IgG seroconversion and fifteen showed fetal congenital CMV infection. Seroconversion rates were significantly higher in teens (5.0%) than in older women (20s: 0.8%; 30s and over: 0.6%) (p < 0.001). Titers of CMV IgM at IgG seroconversion were higher in women without (median 8.66) than with (median 6.54) congenital infection (p = 0.045). The congenital infection rate was high when IgM titers at IgG seroconversion were low (47.1% with 4.00-12.00 titers and 100% with 1.21-3.99 IgM titers) (p = 0.048). CONCLUSIONS: Nulliparous pregnant teenagers have a high risk of CMV IgG seroconversion and the CMV IgM titer at IgG seroconversion may help predict the occurrence of fetal congenital CMV infection.

Primary cytomegalovirus infection during pregnancy and congenital infection: a population-based, mother-child, prospective cohort study.

OBJECTIVE: This study assessed maternal cytomegalovirus antibodies, and the occurrence of primary and congenital cytomegalovirus infections, and risk factors of congenital infection after a maternal primary infection. STUDY DESIGN: We included 19,435 pregnant women in Japan, who were tested for serum cytomegalovirus antibodies before 20 gestational weeks. Immunoglobulin (Ig) G avidity was evaluated in women with both IgG and IgM antibodies; tests were repeated at ≥28 gestational weeks among women without IgG and IgM antibodies. RESULT: Primary and congenital infections were 162 and 23 cases, respectively. The risk ratios for congenital infection were 8.18 (95% confidence interval: 2.44-27.40) in teenage versus older women, and 2.25 (95% confidence interval: 1.28-3.94) in parity ≥ 2 versus parity ≤ 1. Of 22 live birth congenital infection cases, three had abnormal neurological findings. CONCLUSION: We demonstrated teenage and parity ≥ 2 pregnant women as risk factors of post-primary congenital infection.

Carboxylated Poly-l-Lysine as a Macromolecular Cryoprotective Agent Enables the Development of Defined and Xeno-Free Human Sperm Cryopreservation Reagents.

In human sperm cryopreservation, test yolk buffer and human serum albumin have been used as permeating macromolecular-weight cryoprotectants. In clinical reproductive medicine, human serum albumin is frequently used because of low risks of zoonoses and allergic reactions. However, the risk of allogeneic infectious diseases exists, and the supply may be unstable because human serum albumin is derived from human blood. Therefore, the development of xeno-free human sperm cryopreservative reagents that could overcome the aforementioned problems is warranted. We succeeded in developing a new xeno-free and defined sperm cryopreservation reagent containing glycerol, carboxylated poly-l-lysine, and raffinose. The cryopreservation reagent was not significantly different in terms of sperm motility, viability, and DNA fragmentation and was comparable in performance to a commercial cryopreservation reagent containing human serum albumin. Moreover, the addition of saccharides was essential for its long-term storage. These results may help elucidate the unknown function of macromolecular-weight permeating cryoprotective agents.

Maternal tadalafil therapy for fetal growth restriction prevents non-alcoholic fatty liver disease and adipocyte hypertrophy in the offspring.

We aimed to investigate the effects of maternal tadalafil therapy on fetal programming of metabolic function in a mouse model of fetal growth restriction (FGR). Pregnant C57BL6 mice were divided into the control, L-NG-nitroarginine methyl ester (L-NAME), and tadalafil + L-NAME groups. Six weeks after birth, the male pups in each group were given a high-fat diet. A glucose tolerance test (GTT) was performed at 15 weeks and the pups were euthanized at 20 weeks. We then assessed the histological changes in the liver and adipose tissue, and the adipocytokine production. We found that the non-alcoholic fatty liver disease activity score was higher in the L-NAME group than in the control group (p < 0.05). Although the M1 macrophage numbers were significantly higher in the L-NAME/high-fat diet group (p < 0.001), maternal tadalafil administration prevented this change. Moreover, the epididymal adipocyte size was significantly larger in the L-NAME group than in the control group. This was also improved by maternal tadalafil administration (p < 0.05). Further, we found that resistin levels were significantly lower in the L-NAME group compared to the control group (p < 0.05). The combination of exposure to maternal L-NAME and a high-fat diet induced glucose impairment and non-alcoholic fatty liver disease. However, maternal tadalafil administration prevented these complications. Thus, deleterious fetal programming caused by FGR might be modified by in utero intervention with tadalafil.

RETRACTED ARTICLE: Intrapartum cardiotocogram monitoring between obstetricians and computer analysis.

We, the Editors and Publisher of The Journal of Maternal-Fetal & Neonatal Medicine, have retracted the following article:Shoichi Magawa, Hiroaki Tanaka, Fumi Furuhashi, Shintaro Maki, Masafumi Nii, Kuniaki Toriyabe, Eiji Kondo & Tomoaki Ikeda; Intrapartum cardiotocogram monitoring between obstetricians and computer analysis, The Journal of Maternal-Fetal & Neonatal Medicine (Author Accepted Version), 10.1080/14767058.2019.1615876.The incorrect manuscript was provided by the authors resulting in a duplicate publication.We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions.The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as "Retracted".

Intrapartum cardiotocogram monitoring between obstetricians and computer analysis.

Purpose: To investigate the accuracy of computer analysis and its features to be used as a fu fetal heart rate (FHR) interpretation method in clinical settings.Methods: The Trium CTG Online® was used as the computer analysis software. Twenty-six cases of intrapartum FHR tracings (total time, 6900 min) were randomly selected from third-trimester pregnancies. Three obstetricians blinded to the patients' clinical information traced the decelerations, variability, and baseline cardiotocogram (CTG) data. Three obstetrician observer individually interpreted the data and only the waveforms they interpreted were adopted. The agreement between the deceleration and baseline, variability, and level of five-tier system was estimated. Weighted kappa (κ) statistics were used to assess reliability.Results: Based on the observers and Trium's classification, κ was 0.78 and the strength of agreement level was substantial. The obstetricians and Trium mostly agreed on the variability and baseline data. However, κ of each deceleration was approximately 0.65 (0.63-0.66), with substantial strength of agreement.Conclusion: Based on the obstetricians and Trium's interpretation, the latter was found to be excellent for FHR interpretation. However, it was difficult for Trium to interpret specific waveform patterns. Therefore, clinical staff should understand these characteristics to more sensitively evaluate the fetal well-being.

Reference range for C1-esterase inhibitor (C1 INH) in the third trimester of pregnancy.

OBJECTIVES: The objectives of this study were to (i) establish the reference range and mean value for normal levels of C1-esterase inhibitor (C1 INH) during pregnancy, and (ii) investigate the association between C1 INH and uterine atony, as measured by blood loss at delivery. METHODS: We prospectively studied 200 healthy pregnant women who were registered. We studied C1 INH levels in 188 women at 34 and 35 gestational weeks of pregnancy. The reference range for C1 INH during the third trimester of pregnancy was calculated using the value of C1 INH that was determined at registration. RESULTS: The mean value of C1 INH was determined to be 70.3% (95% confidence interval, 68.7-71.9). While the C1 INH levels in four women were determined to be 40% lower than the calculated mean value, amniotic fluid embolism (AFE) did not occur in any of the women studied. CONCLUSIONS: This study successfully demonstrated that a reference value for C1 INH activity can be established using the methods described herein. Further research is needed to determine whether C1 INH is involved in obstetric coagulopathy syndrome such as amniotic fluid embolism.

Tadalafil Treatment Ameliorates Hypoxia and Alters Placental Expression of Proteins Downstream of mTOR Signaling in Fetal Growth Restriction.

Background and Objectives: Fetal growth restriction (FGR) is associated with fetal mortality and is a risk factor for cerebral palsy and future lifestyle-related diseases. Despite extensive research, no effective treatment strategy is available for FGR. Mammalian target of rapamycin (mTOR) signaling is important for the growth of fetal organs and its dysregulation is associated with miscarriage. Here, we focused on mTOR signaling and investigated how the activities of phospho-ribosomal protein S6 (rps6) and phospho-eukaryotic translation initiation factor 4E (eIF-4E), which act downstream of mTOR signaling in the human placenta, change following treatment of FGR with tadalafil and aimed to elucidate the underlying mechanism of action. Placental hypoxia was investigated by immunostaining for hypoxia-inducible factor (HIF)-2α. Materials and Methods: Phosphor-rps6 and phosphor-eIF4E expression were examined by Western blotting and enzyme-linked immunosorbent assay, respectively. Results: HIF-2α expression significantly increased in FGR placenta compared with that in the control placenta but decreased to control levels after tadalafil treatment. Levels of phospho-rps6 and phospho-eIF-4E were significantly higher in FGR placenta than in control placenta but decreased to control levels after tadalafil treatment. Conclusions: Tadalafil restored the levels of HIF-2α, phospho-rps6, and eIF-4E in FGR placenta to those observed in control placenta, suggesting that it could be a promising treatment strategy for FGR.

Cervical schwannoma in the early stage of pregnancy: a case report.

BACKGROUND: Although spinal schwannomas generally grow very slowly, it has been reported that these clinical growths and their associated neurological symptoms accelerate during pregnancy. Because these cases are rare, surgical intervention for this tumor during pregnancy poses a significant challenge. The change of pregnancy-related hormones, such as estrogen and progesterone, is considered to have an effect on the clinical symptoms of spinal tumors. Expressions of the receptors for estrogen and progesterone in orbital and vestibular schwannomas have been reported; however, those expressions in spinal schwannomas have not been examined. CASE PRESENTATION: A 36-year-old woman at 8 weeks' gestation suffered from developing neck pain and neurological symptoms in the right upper extremity. Magnetic resonance imaging (MRI) confirmed the presence of a cervical intradural extramedullary tumor. Under general anesthesia, using intraoperative neurophysiological monitoring of motor-evoked potentials (MEPs), spinal tumor resection following a hemi-laminoplasty was performed in a prone position at 12 weeks gestation. The pathological diagnosis following surgery was spinal schwannoma. Her neurological symptoms were significantly improved after surgery and she delivered a healthy baby in her 40th week of pregnancy. At a 12-month follow-up, no abnormalities were observed during medical examinations of both mother and child. An immunohistochemical study identified the expression of estrogen receptors, but not progesterone receptors, in the spinal schwannoma. CONCLUSIONS: A cervical spinal schwannoma was successfully removed under general anesthesia at 12 weeks gestation by coordination between orthopaedic, obstetric and anesthesia teams. For the first time, an immunohistochemical analysis showed that the expression of estrogen receptors was identified in spinal schwannoma cells, suggesting the possibility that these hormone receptors in spinal schwannoma might contribute to the worsening of neurological symptoms during pregnancy.

Refractory Ileal Perforations in a Cytomegalovirus-Infected Premature Neonate Resolved After Ganciclovir Therapy.

Severe neonatal gastrointestinal diseases such as necrotizing enterocolitis or spontaneous intestinal perforation are potentially lethal conditions which predominantly occur in preterm infants. Cytomegalovirus (CMV), which is known to cause congenital and acquired infections in the newborns, has also been implicated in such severe gastrointestinal diseases in premature infants. However, the pathogenic role of CMV and effect of antiviral therapy in severe gastrointestinal disease in premature neonates is currently unclear. We present an infant, born at 26-weeks' gestation, presented with progressive dyspepsia and abdominal distention after the closure of the symptomatic patent ductus arteriosus at the day of life (DOL) 4, requiring the emergent surgery for ileal perforation at the DOL8. After the surgery, abdominal symptoms persisted and the second emergent surgery was performed for the recurrent ileal perforation at DOL17. Even then the abdominal symptoms prolonged and pathological examination in the affected intestine at the second surgery showed CMV inclusion body. Immunoreactivity for CMV antigen was detected in the specimen at the first surgery on DOL8. Blood and urinary CMV-DNA were detected at DOL28. CMV-DNA was also detected in the dried umbilical cord which was obtained within a week from birth. A 6-week course of intravenous ganciclovir (12 mg/kg/day) was started at DOL34 and then symptoms resolved along with decreasing blood CMV-DNA. Pathological findings characteristic of CMV were not detected in the resection specimen at the ileostomy closure at DOL94. These observations indicate that anti-CMV therapy may be beneficial for some premature infants with severe CMV-associated gastrointestinal diseases and warrants further studies focusing on pathogenic role, diagnosis, treatment and prevention of this underrecognized etiology of severe gastrointestinal diseases particularly in premature neonates.

A literature review of herpes simplex virus hepatitis in pregnancy.

Purpose: Hepatitis due to herpes simplex virus (HSV) during pregnancy is rare, it is often not included in the differential disease. However, hepatitis leads to maternal death; hence, early diagnosis is necessary. Hepatic enzyme elevation in late pregnancy is often associated with obstetric-related diseases, such as acute gestational fatty liver and HELLP syndrome (hemolytic anemia, elevated liver enzymes, low platelet count). These pregnancy-related diseases often improve maternal condition after completion of pregnancy, but in patients with HSV hepatitis, invasive treatment, such as cesarean section, may lead to deterioration of maternal condition after completion of pregnancy. A systematic review was conducted to extract necessary factors to avoid maternal death caused by herpetic hepatitis.Methods: In 24 cases reported since 1991, age, onset gestational weeks, initial symptoms, days from onset of symptoms to consultation, diagnosis method, treatment method, maximum liver escape enzyme value during hospitalization, bilirubin value, international normalized ratio value, and fetal/neonatal prognosis were extracted, and the relationship between maternal death group (n = 6) and maternal alive group (n = 18) was statistically analyzed.Results: Fever as an initial symptom was observed in all cases. Maternal death did not occur in patients administered with acyclovir (ACV) as empiric therapy. No difference was found between the two groups in other factors.Conclusion: Early diagnosis and treatment of herpetic hepatitis during pregnancy are important, as well as administration of empiric ACV concurrently with noninvasive diagnosis when a pregnant woman has elevated liver enzyme accompanied by fever in late pregnancy.