Differences Between Cancer Survivors and Healthy Subjects in Factors that Facilitate and Obstruct the Use of the Foster Parent System and Special Adoption System: A Nationwide Cross-Sectional Study in Japan.

Purpose: To investigate factors that obstruct and facilitate the use of the foster parent and special adoption systems (i.e., foster systems) by cancer survivors, and examine how to effectively provide information. Methods: This was a cross-sectional study that compared the results of a questionnaire survey of foster parents and adoptive parents (i.e., foster parents) who were and were not cancer survivors belonging to foster parent associations in 33 locations in Japan. This study was supported by a 2022 Ministry of Health, Labor, and Welfare Grant-in-Aid for Scientific Research (Grant No. 20EA1004). Results: "Lack of information," an obstructive factor and "Sympathetic understanding and cooperation from my partner and family," a facilitative factor were the highest score in both groups. Significant differences between the two groups were found in "Support from government agencies and others for foster parents," a facilitative factor, which was lower in the cancer survivors' group. There were no other significant differences between both the groups. Conclusion: This study found that when considering the use of the foster systems, a lack of information was the biggest obstructive factor and family understanding was the most helpful for both cancer survivors and noncancer groups. It was thought that stronger government support for cancer survivors might encourage cancer survivors to consider becoming foster parents. It would be effective for cancer treatment facilities, reproductive medical facilities, the government, and foster parent associations to work together to provide information carefully to cancer survivors.

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).

COVID-19 mRNA vaccination status and concerns among pregnant women in Japan: a multicenter questionnaire survey.

BACKGROUND: mRNA vaccination is an effective, safe, and widespread strategy for protecting pregnant women against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, information on factors such as perinatal outcomes, safety, and coverage of mRNA vaccinations among pregnant women is limited in Japan. Therefore, this study aimed to investigate the perinatal outcomes, coverage, adverse effects, and short-term safety of mRNA vaccination as well as vaccine hesitancy among pregnant women. METHODS: We conducted a multicenter online survey of postpartum women who delivered their offspring at 15 institutions around Tokyo from October 2021 to March 2022. Postpartum women were divided into vaccinated and unvaccinated groups. Perinatal outcomes, COVID-19 prevalence, and disease severity were compared between the two groups. Adverse reactions in the vaccinated group and the reasons for being unvaccinated were also investigated retrospectively. RESULTS: A total of 1,051 eligible postpartum women were included. Of these, 834 (79.4%) had received an mRNA vaccine, while 217 (20.6%) had not, mainly due to concerns about the effect of vaccination on the fetus. Vaccination did not increase the incidence of adverse perinatal outcomes, including fetal morphological abnormalities. The vaccinated group demonstrated low COVID-19 morbidity and severity. In the vaccinated group, the preterm birth rate, cesarean section rate, and COVID-19 incidence were 7.2%, 33.2%, and 3.3%, respectively, compared with the 13.7%, 42.2%, and 7.8% in the unvaccinated group, respectively. Almost no serious adverse reactions were associated with vaccination. CONCLUSIONS: mRNA vaccines did not demonstrate any adverse effects pertaining to short-term perinatal outcomes and might have prevented SARS-CoV-2 infection or reduced COVID-19 severity. Concerns regarding the safety of the vaccine in relation to the fetus and the mother were the main reasons that prevented pregnant women from being vaccinated. To resolve concerns, it is necessary to conduct further research to confirm not only the short-term safety but also the long-term safety of mRNA vaccines.

The management of women of childbearing age with rheumatoid arthritis: an expert report.

INTRODUCTION: The introduction of biologic therapies and a treat-to-target approach has transformed the management of rheumatoid arthritis (RA), which has led to improved outcomes for women with RA who wish to become pregnant. However, guidelines for the management of reproductive health in female patients with RA are still lacking. AREAS COVERED: A task force (Women of Childbearing Age [WoCBA]-Rheumatoid Arthritis in Japan) comprising 10 experts in the fields of rheumatology, obstetrics and orthopedic surgery developed 10 clinical questions (CQ) related to the management of WoCBA with RA. For each CQ, a systematic literature review was conducted to identify relevant evidence. Based on this evidence, a set of recommendations for each CQ were drafted and evaluated using the modified Delphi method. This article describes the agreed recommendations along with the supporting evidence. EXPERT OPINION: There are many ongoing challenges associated with the provision of reproductive healthcare in WoCBA with RA. It is hoped that the consensus-based recommendations provided here can be implemented in clinical practice in order to increase collaboration between rheumatologists and obstetricians/gynecologists and to improve reproductive health outcomes for WoCBA with RA.

Successful Outcome of Mother and Baby in a Woman With Severe COVID-19 Pneumonia in the Third Trimester of Pregnancy Who Required Extracorporeal Membrane Oxygenation Therapy.

Some studies have reported increased severe coronavirus disease (COVID-19) infection in the third trimester of pregnancy. Therefore, prenatal care in the third trimester requires careful judgment. It has been reported that extracorporeal membrane oxygenation (ECMO) therapy is useful for severe coronavirus disease 2019 (COVID-19) pneumonia; however, the optimal timing for the initiation of ECMO is controversial because the risks and benefits to the mother and fetus require careful consideration. We report a good outcome for mother and baby in a pregnant woman with severe COVID-19 pneumonia at 29 weeks gestation, who underwent urgent delivery and required ECMO therapy. A 34-year-old woman tested positive for COVID-19 at 27 weeks gestation. Despite treatment with remdesivir and prednisolone, her respiratory condition worsened. Consequently, she underwent emergent endotracheal intubation at 28 weeks and 2 days. Although the PaO2/FiO2 (P/F ratio) improved temporarily after endotracheal intubation, her respiratory condition progressively worsened. At 29 weeks gestation, an emergency cesarean section was performed and ECMO was initiated the next day. Although hematoma was observed after ECMO initiation, her respiratory condition improved. She was discharged home 54 days after the cesarean delivery without any complications. The neonate was intubated and transferred to the neonatal intensive care unit and was ultimately discharged home without any complications. Considering the risks and benefits of ECMO for the mother and fetus in the third trimester, ECMO should be initiated after delivery for better outcomes. The P/F ratio may be useful for an appropriate decision regarding delivery and the initiation of ECMO.

The gut microbiota of non-obese Japanese pregnant women with gestational diabetes mellitus.

Recent evidence has shown that gut microbiota dysbiosis is associated with development of gestational diabetes mellitus (GDM). However, the gut microbiota composition of non-obese women with GDM, which accounts for a relatively large percentage of Asian GDM, is unknown. We investigated the characteristics of gut microbiota of Japanese pregnant women with GDM. Fecal samples from Japanese pregnant women with GDM (n=20) and normal glucose tolerance (NGT, n=16) were collected at the time of GDM diagnosis (T1), at 35-37 weeks of gestation (T2), and at 4 weeks postpartum (T3). Gut microbiota composition was characterized from fecal DNA by sequencing of 16S rRNA genes. Serum samples were collected late in the third trimester, and the circulating levels of adiponectin and IL-6 were measured by ELISA. At the genus level, Peptostreptococcaceae Romboutsia was enriched in GDM women at T1 (p=0.008) and T2 (p=0.047). The women with lower serum adiponectin tended to have more Romboutsia. The Shannon index was significantly lower in the GDM women at T3 than in the NGT women (p=0.008), and that of the GDM women decreased significantly from T2 to T3 (p=0.02). No significant difference in bacterial community structure was found in a beta diversity analysis. The non-obese GDM women (body mass index <25.0 kg/m2) showed a lower abundance of Coriobacteriaceae Collinsella at T1 (p=0.03) and higher abundance of Akkermansia at T2 (p=0.04) than the normal control. The non-obese GDM women had the distinctive gut microbiota profiles. Analysis of gut microbiota is potentially useful for risk assessment of GDM in non-obese pregnant women.

Prenatal diagnosis of MAGED2 gene mutation causing transient antenatal Bartter syndrome.

Transient antenatal Bartter syndrome due to melanoma-associated antigen D2 gene mutation is a newly reported type of Bartter syndrome. Its characteristics include an X-linked inheritance pattern, early-onset hydramnios, and spontaneous disappearance of symptoms after childbirth. To date, there have been no reports of prenatally diagnosed cases. We herein present the case of a preterm male born to a mother with early-onset hydramnios and a family history of X-linked idiopathic hydramnios. We suspected melanoma-associated antigen D2 gene mutation and performed direct sequencing. As a result, we were able to prenatally establish a diagnosis of transient Bartter syndrome due to a melanoma-associated antigen D2 gene mutation.

Gene expression shapes the patterns of parallel evolution of herbicide resistance in the agricultural weed Monochoria vaginalis.

The evolution of herbicide resistance in weeds is an example of parallel evolution, through which genes encoding herbicide target proteins are repeatedly represented as evolutionary targets. The number of herbicide target-site genes differs among species, and little is known regarding the effects of duplicate gene copies on the evolution of herbicide resistance. We investigated the evolution of herbicide resistance in Monochoria vaginalis, which carries five copies of sulfonylurea target-site acetolactate synthase (ALS) genes. Suspected resistant populations collected across Japan were investigated for herbicide sensitivity and ALS gene sequences, followed by functional characterization and ALS gene expression analysis. We identified over 60 resistant populations, all of which carried resistance-conferring amino acid substitutions exclusively in MvALS1 or MvALS3. All MvALS4 alleles carried a loss-of-function mutation. Although the enzymatic properties of ALS encoded by these genes were not markedly different, the expression of MvALS1 and MvALS3 was prominently higher among all ALS genes. The higher expression of MvALS1 and MvALS3 is the driving force of the biased representation of genes during the evolution of herbicide resistance in M. vaginalis. Our findings highlight that gene expression is a key factor in creating evolutionary hotspots.

Caesarean Section of Multifetal Pregnancy.

Planned caesarean delivery (CD) did not significantly decrease or increase the risk of fetal or neonatal death or serious neonatal morbidity in twin pregnancy between 32 0/7 and 38 6/7 weeks of gestation, with the first twin in the vertex presentation. As prevalence rises for the second twin, emergency CD is necessary for delivery of the second twin after vaginal delivery of the first twin. Waiting after 38 weeks' gestation essentially requires close fetal and maternal surveillance to identify if those pregnancies may benefit to extend a gestational period. It is important to construct a system in which an emergency CD can be performed anytime. The caesarean section does not change in even multifetal pregnancy. Each step after laparotomy has few tips: (1) because the uterus strongly leans to the right, image the uterine rotation. To avoid thick vessels on the uterine lateral wall, perform long U -shaped incision using a scissor. 2) Ensure not to rupture the membrane of the second twin before delivery of the first twin. (3) Check the presentation of the second twin before rupture of that fetus's membrane. The second twin tends to change the presentation. If the upper uterine segment will clamp down and entrap the second twin, a vertical uterine incision is performed without hesitation. Women with multifetal pregnancy are at increased risk of postpartum hemorrhage (PPH). Mainly PPH is caused by uterine atony. Oxytocin should be prepared before starting the CD. All bleeding may not be recognized in the operation field. Do not lose the timing of blood transfusion.

Mirror syndrome due to anti-Jra alloimmunization.

OBJECTIVE: We report a case of fetal hydrops and mirror syndrome in a pregnancy with anti-Jra alloimmunization. CASE REPORT: A 34-year-old multiparous woman (G3P2) at 29 weeks of gestation had complications which included generalized edema and mild dyspnea. An indirect Coombs test was positive for anti-Jra antibodies. A blood examination showed hemodilution and elevated human chorionic gonadotropin. An ultrasound examination showed fetal hydrops with cardiomegaly and polyhydramnios. The patient delivered a pale and edematous infant by cesarean section and laboratory tests showed that the neonate had severe anemia (Hb 4.4 g/dL). A direct Coombs test was also positive. Microscopic examination of the placenta revealed diffuse villous edema. A genetic test for the ABCG2 gene showed the homozygous point mutation c.376C > T (376TT) in the mother, while her three offsprings all exhibited 376CT heterozygosity. CONCLUSION: The potential risk of severe fetal hydrops and mirror syndrome should be recognized in pregnancies with anti-Jra alloimmunization.

Characterization of the acetolactate synthase gene family in sensitive and resistant biotypes of two tetraploid Monochoria weeds, M. vaginalis and M. korsakowii.

Monochoria vaginalis and M. korsakowii are allotetraploid noxious weeds in rice cultivation. Occurrences of resistance to acetolactate synthase (ALS)-inhibiting herbicides have been reported in these weeds in Japan since the 1990s. The existence of multiple copies of ALS genes in both species has hindered and complicated the detailed study of molecular mechanisms in them. To determine the copy number and full-length of ALS genes in both species, we first amplified partial sequences of ALS genes and separated them by cloning. Five and three distinct sequences were identified in M. vaginalis and M. korsakowii, respectively. RACE and TAIL PCR successfully isolated full-length ALS genes, revealing that one copy of ALS genes in both species is a pseudogene formed by a frameshift mutation. Interestingly, one of the four putative functional ALS genes in M. vaginalis contains an intron in the 3'-untranslated region. Amplification and sequencing of the full-length ALS genes in sensitive and suspected resistant lines revealed a non-synonymous point mutation at codon Pro197, resulting in amino acid substitutions (Leu, Ser, or Ala) well known to endow ALS inhibitor resistance. Importantly, codon Pro197 of the M. korsakowii pseudogene encodes leucine (Leu) both in resistant and sensitive plants, which is also known to confer ALS inhibitor resistance when ALS genes are functional. Dose responses to imazosulfuron of the lines analyzed for ALS genes were in agreement with the existence of the mutations. These results suggest that some caution is needed when diagnosing molecular resistance in M. korsakowii. The information of copy number and full-length sequences will help diagnose ALS resistance and make a basis for the study of the evolution of ALS resistance in Monochoria spp.

Contraction-associated proteins expression by human uterine smooth muscle cells depends on maternal serum and progranulin associated with gestational weight gain.

Pregnant women with obesity are at increased risk of parturition dysfunction; however, the biological mechanism has remained unknown. We hypothesized that molecules circulating in the serum of pregnant women with obesity may induce the aberrant expression of contraction-associated proteins (CAPs), leading to insufficient uterine contractions. This study aimed to investigate the effects of maternal serum on CAPs expression by human uterine smooth muscle cells (UtSMCs) and elucidate the influence of maternal obesity. Blood samples were collected from singleton pregnant women at 36-41 weeks of gestation before the onset of labor. UtSMCs were incubated in the serum, and the mRNA expressions of PTGFR, OXTR, GJA1, and PTGS2 were examined by RT-PCR. Progranulin (PGRN) is a circulating glycoprotein associated with insulin resistance characterized by the accumulation of visceral fat. The serum PGRN levels of the samples were measured by ELISA. After incubated with PGRN (100-1,000 ng/mL), mRNA expression of PTGFR, OXTR, and GJA1 and protein expression of CX43 were examined by RT-PCR and western blotting, respectively. The mRNA expressions of PTGFR, OXTR, and GJA1 showed significantly negative correlations with gestational weight gain (GWG). Serum PGRN levels showed a significantly positive correlation with GWG. High levels of PGRN suppressed the mRNA expression of GJA1 and the protein expression of CX43. The change in maternal serum induced by GWG suppressed the CAPs expression by UtSMCs. PGRN is one of the factors in the serum responsible for inhibiting the expression of CX43.

Plasma estradiol levels and antidepressant effects of omega-3 fatty acids in pregnant women.

BACKGROUND: Omega-3 polyunsaturated fatty acids (PUFAs) reduce depressive symptoms through an anti-inflammatory effect, and injection of both omega-3 PUFAs and estradiol (E2) induces antidepressant-like effects in rats by regulating the expression of inflammatory cytokines. The aims of this study were to examine the association of increased E2 during pregnancy with depressive symptoms and with inflammatory cytokines in women who were and were not supplemented with omega-3 PUFAs. METHODS: Pregnant women with Edinburgh Postnatal Depression Scale scores ≥9 were recruited at 12-24 weeks of gestation. The participants were randomly assigned to receive 1800 mg omega-3 fatty acids (containing 1206 mg eicosapentaenoic acid [EPA]) or placebo for 12 weeks. E2, omega-3 PUFAs, high-sensitivity C-reactive protein, interleukin-6, and adiponectin were measured at baseline and at the 12-week follow-up. Multivariable regression analyses were conducted to examine the association of the changes of E2 and omega-3 PUFAs with the changes in depressive symptoms and with the changes of inflammatory cytokines at follow-up by intervention group. RESULTS: Of the 108 participants in the trial, 100 (92.6%) completed the follow-up assessment including blood sampling. Multivariable regression analyses revealed that the increase of EPA and E2 was significantly associated with a decrease in depressive symptoms among the participants assigned to the omega-3 group, but not among those assigned to the placebo group. Neither E2 nor any PUFAs were associated with a change in inflammatory cytokines. CONCLUSION: Supplementation with EPA and increased levels of E2 during pregnancy might function together to alleviate antenatal depression through a mechanism other than anti-inflammation.

Correction to: Gene expression and DNA methylation changes in BeWo cells dependent on tumor necrosis factor-α and insulin-like growth factor-I.

In the original publication of the article, the author names were abbreviated in the author group. The corrected list of author names is presented above.

Gene expression and DNA methylation changes in BeWo cells dependent on tumor necrosis factor-α and insulin-like growth factor-I.

Pregnant women with increased insulin resistance, characterized by elevated levels of tumor necrosis factor-alpha (TNF-α) and insulin-like growth factor-I (IGF-I), are at high risk of preeclampsia. We hypothesized that TNF-α and IGF-I affect the placentas and cause pathological changes leading to preeclampsia. To understand the genetic and epigenetic effects of TNF-α and IGF-I on trophoblast cells, gene expression microarray and DNA methylation array of BeWo cells stimulated by TNF-α (100 pg/ml, 100 ng/ml) and IGF-I (100 ng/ml) were conducted. Microarray analysis revealed the differential gene expression patterns in BeWo cells co-stimulated by TNF-α and IGF-I. Enrichment analysis identified the terms associated with NF-kappa B signaling pathways and arachidonic acid cascades such as PTGS2 and PTGER2. DNA methylation array revealed the distinct CpG methylation pattern in BeWo cells stimulated by high-TNF-α and IGF-I, while neither of them showed independent effects. Enrichment analysis identified the terms associated with major histocompatibility complex proteins. Integration of transcriptome and DNA methylome analyses identified three differentially expressed genes with significant DNA methylation change: C3, GP1BA, and NFKBIE, which are all possibly associated with pathogenesis of preeclampsia. In conclusion, co-stimulation of TNF-α and IGF-I induced the genetic and epigenetic changes associated with preeclampsia in BeWo cells. The results suggested that BeWo cells stimulated by TNF-α and IGF-I is a good in vitro model of preeclamptic placenta in pregnancy with increased insulin resistance.

National survey of uterine rupture in Japan: Annual report of Perinatology Committee, Japan Society of Obstetrics and Gynecology, 2018.

AIM: To clarify the frequency of occurrence of uterine rupture and its prognosis, a nationwide survey was performed. METHODS: Cases of uterine rupture recorded for a period of 5 years were included. RESULTS: There were 152 cases of uterine rupture with an incidence rate of 0.015%. The scarred uterine rupture cases were found to have a significantly earlier occurrence of uterine ruptures in comparison to the unscarred cases: unscarred 39.0 weeks, cesarean section 37.0 weeks, myomectomy 32 weeks and adenomyomectomy 30-32 weeks. And it became apparent that the frequency of hysterectomy, cerebral palsy and neonatal death were higher in the cases of uterine rupture during labor than before delivery. Among the cases of scarred uterine rupture, neonatal prognosis was poorer in cases of pregnancy after myomectomy or adenomyomectomy in comparison with postcesarean section cases. CONCLUSION: This survey revealed the current incidence of uterine rupture in Japan.

Association between adolescent pregnancy and adverse birth outcomes, a multicenter cross sectional Japanese study.

We aimed to clarify how maternal physical characteristics explains the association between adolescent pregnancy and adverse birth outcomes, focusing on their height. We used a national multicenter-based delivery registry among 30,831 women under age 25 years with a singleton pregnancy between 2005 and 2011. Adolescent pregnancy was defined as younger than 20 years of age, and categorized into "junior adolescent" (aged ≤15 years) and "senior adolescent" (aged 16-19 years). We used multivariate Poisson regression and mediation analysis to assess the extent to which maternal height explained the association between adolescent pregnancy and risk of adverse birth outcomes. Risks for preterm birth [(adjusted risk ratio (aRR) 1.17, 95% confidence interval (95% CI), 1.08-1.27], low birthweight (aRR 1.08, 95% CI, 1.01-1.15), and low Apgar score (aRR 1.41 95%CI, 1.15-1.73) were significantly higher among adolescent women compared to women of 20-24 years of age. The mediation effect of maternal height on these outcomes were moderate for low birthweight (45.5%) and preterm birth (10.5%), and smaller for low Apgar score (6.6%). In all analyses, we did not detect significant differences between junior adolescent and senior adolescent. Adolescent women have higher risk of adverse birth outcomes. This association is partially mediated by shorter maternal height.