National registry of thoracoamniotic shunting using a double-basket catheter: A post-marketing surveillance registry of 295 patients with fetal hydrothorax.

OBJECTIVE: We report on the 1-year outcomes of fetuses who underwent thoracoamniotic shunting (TAS) with a double-basket catheter for fetal hydrothorax (FHT) using a national post-marketing surveillance registry. METHODS: This surveillance study was conducted for cases enrolled between 2011 and 2019. Preoperative, operative, and postoperative findings and outcomes had to be reported through the national surveillance website. RESULTS: Forty-three institutes enrolled 295 patients. In 60 patients, associated abnormalities were diagnosed after birth. Among the 235 patients with isolated hydrothorax, the survival rate at 1 year of age was 70.5%. Among these patients, 89% did not require oxygen or other respiratory support. The 1-year survival rate in complicated cases was 27%. Trisomy 21 was the most common associated problem (40%). Catheter associated problems, including dislocation (25%), obstruction (24%), and preterm rupture of the membranes (6%) were observed, but there were no severe maternal complications. TAS before 29.5 weeks of gestation (odds ratio [OR] 0.16) and skin edema and ascites (OR 0.06) were risk factors for death at one year, whereas appropriate shunt location for >28 days (OR 4.2) was a protective factor. CONCLUSION: We report a favorable survival rate in fetuses with isolated FHT treated with this double-basket catheter.

Suppression of Sleeping Beauty-induced Gliomagenicity in Ts1Cje Mice, a Model of Down Syndrome.

BACKGROUND/AIM: Individuals with Down syndrome (DS), attributed to triplication of human chromosome 21 (Hsa21), exhibit a reduced incidence of solid tumors. However, the prevalence of glioblastoma among individuals with DS remains a contentious issue in epidemiological studies. Therefore, this study examined the gliomagenicity in Ts1Cje mice, a murine model of DS. MATERIALS AND METHODS: We employed the Sleeping Beauty transposon system for the integration of human oncogenes into cells of the subventricular zone of neonatal mice. RESULTS: Notably, Sleeping Beauty-mediated de novo murine gliomagenesis was significantly suppressed in Ts1Cje mice compared to wild-type mice. In glioblastomas of Ts1je mice, we observed an augmented presence of M1-polarized tumor-associated macrophages and microglia, known for their anti-tumor efficacy in the early stage of tumor development. CONCLUSION: Our findings in a mouse model of DS offer novel perspectives on the diminished gliomagenicity observed in individuals with DS.

Investigation of optimal weight gain during pregnancy: A retrospective analysis of the Japanese perinatal registry database.

AIM: This study aimed to determine the weight gain during pregnancy that minimizes the predicted probability of various perinatal adverse events according to the pre-pregnancy body mass index (BMI) and make recommendations for optimal weight gain in Japan. METHODS: The Japan Society of Obstetrics and Gynecology perinatal database for 2015-2017 was used. From the 719 723 deliveries included in this database, parturients with underlying diseases or missing data were excluded, and 419 114 deliveries were analyzed. A questionnaire survey was also conducted to weigh each perinatal adverse event. For each of the nine outcomes, a restricted cubic spline model was made to estimate the association between the "expected gestational weight gain at 40 weeks" and the outcome risk. RESULTS: Since the classes of medical facilities were generally the same, weights were assigned according to the mean of the questionnaires rather than by the class of the facility. For each pre-pregnancy BMI, the weight gains during pregnancy that minimized the predicted probability of various adverse perinatal events were 12-15, 10-13, 7-10, and upper limit of 5 kg for the underweight, normal-weight, obese 1, and obese ≥2 groups, respectively. CONCLUSIONS: The weight gain during pregnancy that minimizes the predicted probability of various perinatal adverse events according to the pre-pregnancy BMI was established.

Assessment of mediastinal shift angles in congenital pulmonary airway malformation: a new fetal magnetic resonance imaging indicator of congenital lung disease.

BACKGROUND: The mediastinal shift angle is a new fetal magnetic resonance imaging (MRI) index that is reportedly correlated with postnatal survival in fetuses with congenital diaphragmatic hernia. However, its correlation in patients with congenital pulmonary airway malformation (CPAM) has not been assessed. OBJECTIVE: This study aimed to establish a normal range for the right/left mediastinal shift angles, to evaluate the mediastinal shift angle in fetuses with CPAM, to compare the mediastinal shift angle with the CPAM volume ratio, and to evaluate the predictive value of the mediastinal shift angle measurements. MATERIALS AND METHODS: To establish the normal range, we measured the mediastinal shift angle bilaterally in 124 fetuses without any lung abnormality (the control group). Subsequently, the mediastinal shift angle was measured in 32 fetuses pathologically diagnosed with CPAM. Moreover, the mediastinal shift angle and CPAM volume ratio were compared using fetal MRI. RESULTS: The mean values for the right/left mediastinal shift angles were 18.6°/26.3° and 39.2°/35.9° for control fetuses and fetuses with CPAM, respectively. The mediastinal shift angle and the CPAM volume ratio showed a positive statistical correlation. The area under the curve demonstrated high discriminatory accuracy for the mediastinal shift angle (0.76). CONCLUSION: The mediastinal shift angle has potential to replace the CPAM volume ratio for evaluating the severity of CPAM in fetal MRI.

Establishment of a measurement system to evaluate breast milk transfer of biological agents using dry filter paper: A multi-institutional study.

AIMS: Information on breastfeeding and safety of biologics in infants is lacking due to difficulties in case collection. We evaluated methods for determining the concentration of biologics in breast milk using a dry filter method that can simplify the collection, storage and transport of breast milk. METHODS: To generate dried filter paper (DFP) samples, approximately 30 µL of breast milk was placed onto a Whatman 903 card and punched out. After extraction, the supernatant was measured using an enzyme-linked immunosorbent assay. Three concentrations of each drug were prepared in liquid breast milk (LBM) and DFP samples to determine their stability up to 28 days after storage at 2-8°C or -20°C for LBM and 25 ± 5°C for DFP. LBM and DFP samples were also provided by nursing mothers using biologics during lactation, and drug concentrations in both samples were compared. The agreement between the two measurement methods was confirmed by Bland-Altman analysis. RESULTS: Breast milk was provided by 12 mothers who used biologics (tocilizumab, abatacept, etanercept, golimumab, sarilumab and belimumab). The coefficients of variation for within-run and between-run precision for the six drugs were within 15% for both LBM and DFP, and accuracy was within 90%-110% of the quality controls. After 28 days, concentrations remained at more than 90%. The difference between the values obtained by each method was within the acceptable range of error (-12.1 to +16.6 ng/mL). CONCLUSIONS: A method for determining the concentration of biologics using DFP is expected to help improve pharmacotherapy for lactating women.

[ANTIMICROBIAL ALLERGY ASSESSMENT DURING PREGNANCY FOR APPROPRIATE ANTIMICROBIAL USE AT DELIVERY].

BACKGROUND: Avoidance of suspect drugs based solely on a history of drug allergy is detrimental to disease outcomes. Many antimicrobial allergy labels are not usually true allergy. Some studies have demonstrated that antimicrobial allergy assessments can be safely performed on pregnant women. The purpose of this study was to examine the usefulness of antibiotic allergy assessment during pregnancy in Japan. METHODS: We reviewed pregnant women who reported antimicrobial allergies and were referred to the allergy center. Allergists conducted an interview and skin test and selected antibiotics that could be used at delivery. RESULTS: Twenty-four pregnant women were referred to as having antimicrobial allergies. Most of the suspected antimicrobials were cephalosporin (13 cases, 52%) and penicillin (9 cases, 36%). Five women were ruled out only by our interviews. Of the remaining 20 cases, 10 were immediate type, 6 were non-immediate type, and 4 were unknown. All 21 pregnant women who needed antimicrobials were able to use the first-line drugs (ß-lactam antimicrobials) at the time of delivery. No surgical site infections or allergic reactions were observed. CONCLUSION: Pregnant women with antimicrobial allergy labels could be evaluated by antimicrobial allergy assessment during pregnancy, and first-line antimicrobials were safely and properly used at delivery.

Evaluating the association between caesarean delivery and weight status in early childhood in a Japanese birth cohort study.

To examine whether the prevailing hypothesis of an association between caesarean section (CS) delivery method and increased weight status in early childhood is observed in Japanese. A total of 1277 mother-infant pairs from a prospective hospital-based mother-infant birth cohort that recruited women in their first trimester from May 2010 to November 2013 were included. We assessed the relationship between delivery method and weight status of delivered children at 1, 3 and 6 years of age. In total, 366 children (28.7%) were delivered by CS. Delivery by CS was not associated with body mass index (BMI) z-score (≥ 75 percentile) at age 1 year, (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.69-1.36), 3 years (OR 0.98, 95% CI 0.67-1.42), and 6 years (OR 0.71, 95% CI 0.45-1.12), and also showed no association with low weight status (< 25th percentile). Supplemental evaluations addressing the influence of preterm births, pre-pregnancy BMI, emergency CS, and modification by breastfeeding were consistent with the primary analyses. Our findings do not support the hypothesis that children born by CS are at risk of being overweight in childhood among the Japanese population.

Novel therapeutic strategies for injured endometrium: intrauterine transplantation of menstrual blood­derived cells from infertile patients.

BACKGROUND: Menstrual blood-derived cells show regenerative potential as a mesenchymal stem cell and may therefore be a novel stem cell source of treatment for refractory infertility with injured endometrium. However, there have been few pre-clinical studies using cells from infertile patients, which need to be addressed before establishing an autologous transplantation. Herein, we aimed to investigate the therapeutic capacity of menstrual blood-derived cells from infertile patients on endometrial infertility. METHODS: We collected menstrual blood-derived cells from volunteers and infertile patients and confirmed their mesenchymal stem cell phenotype by flow cytometry and induction of tri-lineage differentiation. We compared the proliferative and paracrine capacities of these cells. Furthermore, we also investigated the regenerative potential and safety concerns of the intrauterine transplantation of infertile patient-derived cells using a mouse model with mechanically injured endometrium. RESULTS: Menstrual blood-derived cells from both infertile patients and volunteers showed phenotypic characteristics of mesenchymal stem cells. In vitro proliferative and paracrine capacities for wound healing and angiogenesis were equal for both samples. Furthermore, the transplantation of infertile patient-derived cells into uterine horns of the mouse model ameliorated endometrial thickness, prevented fibrosis, and improved fertility outcomes without any apparent complications. CONCLUSIONS: In our pre-clinical study, intrauterine transplantation of menstrual blood-derived cells may be a novel and attractive stem cell source for the curative and prophylactic therapy for injured endometrium. Further studies will be warranted for future clinical application.

Clinical features of women with thrombotic microangiopathy in pregnancy: A case series from a single Japanese tertiary perinatal care center.

AIM: Although perinatal thrombotic microangiopathy has become increasingly understood, the racial characteristics of patients with this condition remain unclear. Herein, we report the characteristics of patients with perinatal thrombotic microangiopathy at a single institution in Japan. METHODS: We conducted a retrospective study over a 5-year period from January 1, 2017, to December 31, 2021, using the electronic medical records of pregnant women who delivered at the perinatal center of our hospital. We extracted the data of those who developed perinatal thrombotic microangiopathy and evaluated their characteristics at the time of disease onset, final diagnosis, and maternal and fetal outcomes. RESULTS: Of the 10 224 deliveries that occurred during the 5-year period, only seven patients (0.06%) had perinatal thrombotic microangiopathy. The median pre-pregnant body mass index was 18.65 kg/m2 (minimum 17.3 kg/m2 , maximum 20.7 kg/m2 ). More than half of the patients were conceived by in-vitro fertilization, and 42% these had twin deliveries. Four patients had a history of rheumatic disease. The other three patients without underlying diseases developed thrombotic microangiopathy with HELLP syndrome, and one patient transitioned to atypical hemolytic uremic syndrome. CONCLUSIONS: Based on low body mass index and in-vitro fertilization, which are characteristic of Japanese women, medical complications and twin pregnancies may be a risk for thrombotic microangiopathy. Additionally, depending on the cause of thrombotic microangiopathy, its timing and onset differed.

Randomized trial of advice from healthcare professionals to eliminate constriction by maternal clothing on the trunk to prevent preterm birth and improve health status.

AIM: Women's clothing during pregnancy may influence perinatal outcomes. A preliminary study suggested that midwives' advice to avoid wearing tight clothing during pregnancy may reduce the risk of preterm delivery. We examined the effects of such advice to pregnant women on the risk of preterm birth and health status during pregnancy. METHODS: An open-label evaluator-blinded randomized controlled trial was conducted at the National Centre for Child Health and Development in Tokyo, Japan. Normal pregnant women were randomly assigned to receive constrictive clothing elimination care or standard care at 20 weeks gestation. The control group was issued leaflets concerning anemia prevention at entry and skin care at 30 weeks' gestation, along with a brief explanation and answers to questions by midwives as standard care. The intervention group received advice from midwives concerning avoiding constrictive clothing in addition to standard care. The primary outcome was the incidence of preterm birth (<37 weeks). The secondary outcomes were 12 indicators related to preterm delivery or health status. RESULTS: Among 624 randomly assigned women, 599 (intervention group, n = 306; control group, n = 293) completed the study between February 2015 and August 2016. The incidence of preterm birth in the intervention and control groups was 4.2% (13/306) and 5.1% (15/293), respectively (p = 0.614). There were no significant differences regarding any secondary outcomes, including obstetric outcomes and physical/mental indicators, during pregnancy. CONCLUSIONS: Advice from midwives to avoid constrictive clothing during pregnancy did not influence the incidence of preterm birth or maternal health status. TRIAL REGISTRATION: UMIN000016853 (March 30, 2015).

Clinical features of fetal hydrothorax associated with mucopolysaccharidosis-VII.

Mucopolysaccharidosis (MPS)-VII, called Sly disease, is a lysosomal storage disorder that can cause fetal hydrops, including fetal hydrothorax (FHT). We describe two fetal cases that received thoracoamniotic shunting for FHT, which was later found to be associated with MPS-VII by exome sequencing. Bilateral FHT accompanied by skin edema and ascites was found before 20 weeks of gestation in both cases. One fetus died in utero at 35 weeks of gestation, and the other survived with preterm delivery at 30 weeks of gestation. Both cases inherited compound pathogenic variants of GUSB from parents. Comparison with previously reported primary FHT cases revealed distinct clinical features in MPS-VII-associated FHT: early gestational age at diagnosis (<26 weeks), bilateral effusion, skin edema with ascites, and poor survival. A genetic analysis would be considered for FHT cases, with consideration of shunting when they show early-onset bilateral effusions with skin edema and ascites.

The Association Between Eating Quickly and Excessive Gestational Weight Gain.

Objectives: Maintaining an appropriate gestational weight gain (GWG) is essential for a safe pregnancy and delivery. This study aimed to determine the association between the habit of eating quickly and the risk of excessive GWG. Methods: We administered a questionnaire on eating habits to 1246 pregnant Japanese women in their second to third trimesters. We categorized the participants into three groups according to their answers to the question "Do you eat quickly?" Group 1, "always" or "usually"; Group 2, "sometimes"; and Group 3, "rarely" or "never." We assessed GWG according to the "The Optimal Weight Gain Chart" (Ministry of Health, Labor and Welfare, Japan), and those who exceeded the criteria were considered "excessive." Logistic regression analysis was performed with the risk of excess GWG as the dependent variable and quick food intake as the independent variable, to obtain relevant odds ratios (ORs) and 95% confidence intervals (CIs). Model 1 was unadjusted, and Model 2 was adjusted for age, prepregnancy body mass index, energy intake, mother's educational attainment, household income, exercise habits, and childbearing experience. Results: The OR (95% CI) for Groups 2 and 3 in Model 1, compared with Group 1, was 0.80 (0.62-1.05) and 0.61 (0.43-0.88), respectively (p for trend = 0.047). In Model 2, the OR (95% CI) for Groups 2 and 3 were 0.73 (0.55-0.96) and 0.59 (0.40-0.86), respectively (p for trend = 0.003). Conclusion: These results suggest that quick food ingestion increases the risk of excessive GWG.

Ultrasound measurement of umbilical venous flow volume at the intra-abdominal portion in normal fetuses.

PURPOSE: Umbilical venous flow volume (UVFV) measured using ultrasound can be used to assess placental circulation in a fetus. UVFV measured at the intra-abdominal portion using half the maximum flow velocity of the umbilical vein (UV) has good reproducibility with low variance. However, reference values in previous reports were based on a small number of cases with a wide reference range. In the present study, we evaluated UVFV standard values measured at the intra-abdominal portion in normal Japanese fetuses. METHODS: Measurements were performed on normal pregnant women during routine ultrasound screening at around 20 or 30 weeks of gestation. The diameter and flow velocity of the UV were measured at the fetal abdomen point between the insertion of the UV and branches of the portal vein. UVFV (ml/min) was calculated as follows: (UV diameter [cm]/2)2 × maximum velocity [cm/s] × 0.5 × 3.14 × 60). RESULTS: A total of 278 pregnant women were included in the study. UVFV increased with gestational weeks, and UVFV per estimated fetal weight (EFW) slightly decreased with increasing gestational weeks. The 50th (10th-90th) percentiles of UVFV per EFW at 20, 25, and 30 weeks of gestation were 130 (105-165), 123 (94-147), and 104 (80-131) ml/min/kg, respectively. CONCLUSION: New UVFV reference values measured at the intra-abdominal portion of fetuses using large-scale samples were established. Future studies should assess fetuses under pathologic conditions using UVFV reference values.

Association of Isolated Hypothyroxinemia and Subclinical Hypothyroidism With Birthweight: A Cohort Study in Japan.

Context: Isolated hypothyroxinemia (low maternal free thyroxine [FT4] in the absence of thyroid-stimulating hormone [TSH] elevation) and subclinical hypothyroidism (high TSH in the absence of FT4 elevation) during early pregnancy are common. However, there are limited data regarding pregnancy outcomes, particularly their association with birthweight. Objective: We assessed the association between isolated hypothyroxinemia and subclinical hypothyroidism during the first trimester and birthweight. Methods: Analyses were conducted using a database of pregnant women (n = 1105; median age, 35 years) who delivered at the National Center for Child Health and Development, a tertiary hospital in Tokyo. The primary outcomes included the rates of small for gestational age (SGA), large for gestational age (LGA), and low birth weight. Results: Of the 1105 pregnant women, 981 were classified into the euthyroidism group, 25 into the isolated hypothyroxinemia group, and 26 into the subclinical hypothyroidism group during the first trimester. The prevalence of SGA was significantly higher in isolated hypothyroxinemia and subclinical hypothyroidism groups than the euthyroidism group (28.0% and 19.2%, respectively, vs 5.7%; P < .01). The odds ratio with 95% CI for SGA was 12.51 (4.41-35.53) for isolated hypothyroxinemia and 4.44 (1.57-12.56) for subclinical hypothyroidism in a multivariable adjustment model. Isolated hypothyroxinemia and subclinical hypothyroidism were not significantly associated with LGA and low birth weight. Conclusion: Pregnant women with isolated hypothyroxinemia and subclinical hypothyroidism in the first trimester have an increased likelihood of SGA. Screening and careful perinatal checkups for isolated hypothyroxinemia and subclinical hypothyroidism may help identify pregnant women at high risk for SGA.

Comprehensive Analysis of the Expression and Functions of Pattern Recognition Receptors in Differentiated Cytotrophoblasts Derived from Term Human Placentas.

Pregnant women are exposed to various microbes, some of which can harm the mother and/or fetus and can lead to life-long morbidity and even death. The syncytiotrophoblast (STB) covers the placental villi and comes into direct contact with pathogens contained in the maternal blood and plays a key role in placental host defense. However, the precise mechanisms whereby the STB recognizes and responds to pathogenic microbes remain unclear. In this study, we comprehensively analyzed the expression of functional pattern recognition receptors, which are responsible for tissue defense against pathogens, in a primary STB model differentiated from highly purified human term cytotrophoblasts (CTBs). Screening for mRNA expression and multiplex cytokine/chemokine production demonstrated that differentiated CTBs (dCTBs) predominantly expressed dsRNA receptors, including TLR3, MDA5, and RIG-I. We confirmed that term human placentas also expressed TLR3. Transcriptome analysis revealed common and unique responses of dCTBs to a synthetic dsRNA (polyinosinic-polycytidylic acid) compared with human peripheral mononuclear cells. Moreover, polyinosinic-polycytidylic acid induced the release of type I and type III IFNs (IFN-ß, IFN-λ1, IFN-λ2, IFN-λ3), as well as mRNA expression of IFN-stimulated genes (IFIT1, MX1, and OAS1). dCTBs underwent apoptosis via the mitochondrial pathway in response to dsRNA stimulation. These results suggest that dsRNA receptors expressed on the STB are key players in antiviral defense in the placenta. Elucidation of the underpinnings of these defense processes can help us better understand the pathophysiology of viral infections during pregnancy.

A Neonate with Mucopolysaccharidosis Type VII with Intractable Ascites.

We report a case of a patient with severe fetal hydrops and refractory ascites, diagnosed as mucopolysaccharidosis type VII (MPS VII) by whole-exome sequencing, and discharged at 5 months of age after long-term ventilatory management. A male neonate was born by emergency cesarean section due to fetal distress at 30 1/7 weeks' gestation. Physical examination and X-rays revealed pleural effusion, ascites, and generalized edema, indicating severe fetal hydrops. He underwent tracheal intubation because of respiratory distress that was attributed to massive ascites, pulmonary hypoplasia, and pulmonary hypertension. He received mechanical ventilation and inhaled nitric oxide therapy. Prednisone, octreotide, and a factor XIII preparation were used as the treatment for ascites, and the ascites gradually decreased. He was extubated within 2 months of age. At 4 months of age, the results of whole-exome sequencing of the cord blood showed a compound heterozygous mutation in the GUSB gene, the gene responsible for MPS VII. Enzyme replacement therapy was initiated, and the ascites was resolved. Careful systemic management, including lung-protective respiratory management and the early establishment of nutrition, is important for the long-term survival of infants with fetal hydrops, and early aggressive workup, including whole-genome sequencing for the cause, should be performed in the case of refractory ascites.

Predictive factors for successful external cephalic version with regional anesthesia.

AIM: We aimed to investigate predictive factors of successful external cephalic version (ECV) using regional anesthesia. METHODS: In this retrospective study, we included women who underwent ECV at our center from 2010 to 2022. The procedure had been conducted using regional anesthesia and the administration of intravenous ritodrine hydrochloride. The primary outcome was the success of ECV, which was defined as the rotation from a non-cephalic to a cephalic presentation. Primary exposures were maternal demographic factors and ultrasound findings at ECV. To determine predictive factors, we conducted a logistic regression analysis. RESULTS: Of 622 pregnant women who underwent ECV, missing data on any variables (n = 14) were excluded and the remaining 608 were analyzed. The success rate during the study period was 76.3%. Multiparous women had significantly higher success rates than primiparous women (adjusted odds ratio [OR]: 2.06 [95% confidence interval (CI): 1.31-3.25]). Women with a maximum vertical pocket (MVP) of <4 cm had significantly lower success rates than those with 4 cm < MVP ≤6 cm (OR: 0.56 [95% CI: 0.37-0.86]). The non-anterior placental location was associated with higher success rates than the anterior placental location (OR: 1.46 [95% CI: 1.00-2.17]). CONCLUSIONS: Multiparity, MVP >4 cm, and non-anterior placental locations were associated with successful ECV. These three factors could be useful for patient selection for successful ECV.

Predictive factors for vaginal delivery by induction of labor in uncomplicated pregnancies at 40-41 gestational weeks: A Japanese prospective single-center cohort study.

AIM: We investigated cervical parameters predictive of vaginal delivery in elective labor induction among women at 40-41 gestational weeks. METHODS: This Japanese prospective single-center cohort study was conducted between July 2019 and June 2020. We enrolled women with an uncomplicated singleton pregnancy who underwent labor induction at 40-41 gestational weeks. We analyzed background characteristics and cervical parameters, including Bishop score, cervical length, posterior cervical angle, and changes in cervical parameters before and after cervical dilatation. The endpoint was the rate of vaginal delivery. RESULTS: Of 142 eligible participants, all 24 multiparous women underwent vaginal delivery. Among the nulliparous women (n = 118), the following categories showed significantly higher rates of vaginal delivery: Bishop scores of ≥6 before and after dilatation, compared with Bishop score <6 (adjusted prevalence ratio (aPR) [95% confidence interval (CI)]; 1.58 [1.17-2.13] and 1.56 [1.13-2.14], respectively) and cervical length of <10 and 10-20 mm before dilation, compared with cervical length of >30 mm (aPR [95% CI]; 1.47 [1.00-2.15] and 2.13 [1.42-3.18], respectively). The posterior cervical angle and other background characteristics showed no significant associations. Furthermore, women with cervical lengths of ≥20 mm before and <20 mm after dilatation showed a higher rate of vaginal delivery, compared to cervical length of ≥20 mm even after dilatation (aPR [95% CI]; 1.95 [1.19-3.20]). CONCLUSIONS: High Bishop score, short cervical length, and changes in cervical length with dilatation are potential independent predictors of vaginal delivery following elective labor induction in nulliparous women at 40-41 gestational weeks.

Initiation of hydroxychloroquine therapy during pregnancy can cause adverse effects and alter pregnancy outcomes: A case of acute generalised exanthematous pustulosis induced by hydroxychloroquine in a patient with systemic lupus erythematosus.

Hydroxychloroquine (HCQ) is effective for treating a number of autoimmune diseases, including systemic lupus erythematosus. HCQ is generally safe and may be prescribed to pregnant women. Although current guidelines recommend initiating HCQ when considering pregnancy, the drug can cause adverse effects such as acute generalised exanthematous pustulosis (AGEP), which should be carefully evaluated. A 30-year-old pregnant woman with systemic lupus erythematosus at 16 + 5 gestational weeks was referred to National Center for Child Health and Development for persistent proteinuria and alopecia. Tacrolimus was initiated, and the dose of prednisone was increased. At 20 + 3 weeks of gestation, HCQ was administered to allow for a dose reduction of prednisolone. Proteinuria gradually improved as the pregnancy course stabilised. At 27 + 1 weeks of gestation, generalised pustular exanthema developed, presumably due to HCQ. Based on the clinical course and the analysis of the skin lesions, she was diagnosed to have either AGEP or generalised pustular psoriasis. Despite discontinuing HCQ, the skin lesions worsened dramatically, and infliximab therapy was required. After one course of infliximab treatment, exanthema gradually subsided. The final diagnosis was AGEP, based on the clinical course and pathological findings. At 30 weeks, pyothorax developed because of the pyogenic skin lesion and the compromised immune system, and long-term antibiotic therapy was required until 32 + 4 weeks, after which she underwent caesarean section. Although introducing HCQ is occasionally necessary during pregnancy, it is preferable to initiate HCQ in the preconception period and not after pregnancy because of the possible adverse effect, which can alter perinatal prognosis. Rheumatologists should consider the potential risks of HCQ.