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.

Breast milk concentrations of acetaminophen and diclofenac - unexpectedly high mammary transfer of the general-purpose drug acetaminophen.

BACKGROUND: Breastfeeding is considered to be the most effective way of ensuring the health and survival of newborns. However, mammary transfer of drugs administered to mothers to breastfeeding infants remains a pressing concern. Acetaminophen and diclofenac sodium are widely prescribed analgesics for postpartum pain relief, but there have been few recent reports on the mammary transfer of these drugs, despite advances in analytic techniques. METHODS: We conducted a study on 20 postpartum mothers from August 2019-March 2020. Blood and milk samples from participants were analyzed using liquid chromatography-electrospray ionization tandem mass spectrometry within 24 hours after oral administration of acetaminophen and diclofenac sodium. The area under the concentration-time curve (AUC) was calculated from the concentration curve obtained by a naive pooled-data approach. RESULTS: For acetaminophen, AUC was 36,053 ng/mL.h and 37,768 ng/mL.h in plasma and breast milk, respectively, with a milk-to-plasma drug concentration ratio of 1.048. For diclofenac, the AUC was 0.227 ng/mL.h and 0.021 ng/mL.h, in plasma and breast milk, respectively, with a milk-to-plasma drug concentration ratio of 0.093. CONCLUSIONS: While diclofenac sodium showed low mammary transfer, acetaminophen showed a relatively high milk-to-plasma drug concentration ratio. Given recent studies suggesting potential connections between acetaminophen use during pregnancy and risks to developmental prognosis in children, we believe that adequate information regarding the fact that acetaminophen is easily transferred to breast milk should be provided to mothers.

Telemedicine for Pregnant Women on a Japanese Remote Island: A Two-year Report.

Introduction: Remote antenatal checkups were conducted on the northernmost island of Japan to reduce the burden of hospital visits among pregnant women. This study aims to investigate the effectiveness and safety of remote antenatal checkups for pregnant women living on a remote island. Methods: This observational study included singleton pregnancies on Rebun Island between October 2020 and September 2022. General surgeons conducted medical interviews and performed fetal sonography using an obstetrician videoconference system at the main central hospital. The primary outcomes were the degrees of physical, mental, and economic burdens of hospital visits and the levels of anxiety and satisfaction with remote antenatal checkups as assessed using a questionnaire survey. Moreover, we investigated the incidence of adverse perinatal events, including maternal death, fetal death, neonatal death, severe neonatal neurological disorders, and other obstetric complications. Results: This study included 16 out of 22 pregnant women from Rebun Island who visited the central hospital. No adverse perinatal events occurred as a result of the remote antenatal checkups. One pregnant woman had gestational diabetes, whereas the others had no obstetric complications. The participants underwent a median of two remote antenatal checkups. According to a questionnaire survey, 90.0%, 80.0%, and 70.0% of the pregnant women perceived improvements in their physical, mental, and economic burdens, respectively. Although 70.0% of the participants experienced anxiety regarding remote antenatal checkups before the introduction, all were satisfied after delivery. Conclusions: Remote antenatal checkups effectively reduced the burden of hospital visits for pregnant women, who reported high levels of satisfaction. Furthermore, antenatal checkups were safely conducted on remote islands.

Simple and validated method to quantify lacosamide in human breast milk and plasma using UPLC/MS/MS and its application to estimate drug transfer into breast milk.

BACKGROUND: Epilepsy is a common neurological disorder. Lacosamide is a third-generation antiepileptic drug used to treat partial-onset seizures. Limited information is currently available on the transfer of lacosamide to breast milk. To facilitate studies on the safety of lacosamide use during breastfeeding, we aimed to develop a method to quantify lacosamide in human breast milk and plasma using ultra-performance liquid chromatography/tandem mass spectrometry. METHODS: Fifty microliters of breast milk or plasma was used, and samples were prepared by protein precipitation using methanol containing lacosamide-d3 as an internal standard (IS). Chromatography was performed using an ACQUITY HSS T3 column with an isocratic flow of 10 mM ammonium acetate solution/methanol (70:30, v/v). Lacosamide and IS were detected by multiple reaction monitoring in positive ion electrospray mode. The run time was 3.5 min. RESULTS: Calibration curves were linear and in the range of 0.5 to 100 ng/mL both in breast milk and plasma. The validation assessment indicated that precision, accuracy, matrix effects, selectivity, dilution integrity, and stability were acceptable. The developed method was successfully applied to quantify lacosamide in breast milk and plasma obtained from a volunteer who had been orally administered lacosamide twice a day (100 mg × 2). Relative infant dose of lacosamide was estimated to be 14.6% in breast milk at five time points. CONCLUSIONS: We developed a simple and robust method to quantify of lacosamide in human breast milk and plasma. This method could be useful for in future studies investigating the safety of lacosamide use during breastfeeding.

The First Transcriptomic Atlas of the Adult Lacrimal Gland Reveals Epithelial Complexity and Identifies Novel Progenitor Cells in Mice.

The lacrimal gland (LG) secretes aqueous tears. Previous studies have provided insights into the cell lineage relationships during tissue morphogenesis. However, little is known about the cell types composing the adult LG and their progenitors. Using scRNAseq, we established the first comprehensive cell atlas of the adult mouse LG to investigate the cell hierarchy, its secretory repertoire, and the sex differences. Our analysis uncovered the complexity of the stromal landscape. Epithelium subclustering revealed myoepithelial cells, acinar subsets, and two novel acinar subpopulations: Tfrchi and Car6hi cells. The ductal compartment contained Wfdc2+ multilayered ducts and an Ltf+ cluster formed by luminal and intercalated duct cells. Kit+ progenitors were identified as: Krt14+ basal ductal cells, Aldh1a1+ cells of Ltf+ ducts, and Sox10+ cells of the Car6hi acinar and Ltf+ epithelial clusters. Lineage tracing experiments revealed that the Sox10+ adult populations contribute to the myoepithelial, acinar, and ductal lineages. Using scRNAseq data, we found that the postnatally developing LG epithelium harbored key features of putative adult progenitors. Finally, we showed that acinar cells produce most of the sex-biased lipocalins and secretoglobins detected in mouse tears. Our study provides a wealth of new data on LG maintenance and identifies the cellular origin of sex-biased tear components.

Effects of valproic acid on syncytialization in human placental trophoblast cell lines.

The placenta is a critical organ for fetal development and a healthy pregnancy, and has multifaceted functions (e.g., substance exchange and hormone secretion). Syncytialization of trophoblasts is important for maintaining placental functions. Epilepsy is one of the most common neurological conditions worldwide. Therefore, this study aimed to reveal the influence of antiepileptic drugs, including valproic acid (VPA), carbamazepine, lamotrigine, gabapentin, levetiracetam, topiramate, lacosamide, and clobazam, at clinically relevant concentrations on syncytialization using in vitro models of trophoblasts. To induce differentiation into syncytiotrophoblast-like cells, BeWo cells were treated with forskolin. Exposure to VPA was found to dose-dependently influence syncytialization-associated genes (ERVW-1, ERVFRD-1, GJA1, CGB, CSH, SLC1A5, and ABCC4) in differentiated BeWo cells. Herein, the biomarkers between differentiated BeWo cells and the human trophoblast stem model (TSCT) were compared. In particular, MFSD2A levels were low in BeWo cells but abundant in TSCT cells. VPA exposure affected the expression of ERVW-1, ERVFRD-1, GJA1, CSH, MFSD2A, and ABCC4 in differentiated cells (ST-TSCT). Furthermore, VPA exposure attenuated BeWo and TSCT cell fusion. Finally, the relationships between neonatal/placental parameters and the expression of syncytialization markers in human term placentas were analyzed. MFSD2A expression was positively correlated with neonatal body weight, head circumference, chest circumference, and placental weight. Our findings have important implications for better understanding the mechanisms of toxicity of antiepileptic drugs and predicting the risks to placental and fetal development.

A lower ratio of reduced to total albumin in serum is associated with protein nutritional status of pregnant women in Japan.

Protein-energy undernutrition is potentially prevalent among Japanese pregnant women, and biomarkers that objectively indicate the protein nutritional status during pregnancy may help in implementing appropriate protein supplementation to these women. We hypothesized that a serum parameter of pregnant women, the ratio of reduced to total albumin (reduced ALB ratio), would be associated with protein intake during pregnancy. The serum reduced ALB ratio of pregnant women was compared with protein intake and with gestation outcomes (gestation length and infant birth weight) in an observational study of 115 Japanese pregnant women. The serum reduced ALB ratio in the third trimester tended to be positively correlated with gestation length (P = .07). Infant birth weights tended to be different between protein intake tertiles (P = .09); the mean infant birth weight was higher in the third tertile compared with the first and second tertiles. The protein intake of pregnant women was significantly and positively correlated with the serum reduced ALB ratio in the second trimester. The serum reduced ALB ratio reflects protein nutritional status during pregnancy and may contribute to healthier gestation outcomes.

Lacrimal Gland Epithelial Cells Shape Immune Responses through the Modulation of Inflammasomes and Lipid Metabolism.

Lacrimal gland inflammation triggers dry eye disease through impaired tear secretion by the epithelium. As aberrant inflammasome activation occurs in autoimmune disorders including Sjögren's syndrome, we analyzed the inflammasome pathway during acute and chronic inflammation and investigated its potential regulators. Bacterial infection was mimicked by the intraglandular injection of lipopolysaccharide (LPS) and nigericin, known to activate the NLRP3 inflammasome. Acute injury of the lacrimal gland was induced by interleukin (IL)-1α injection. Chronic inflammation was studied using two Sjögren's syndrome models: diseased NOD.H2b compared to healthy BALBc mice and Thrombospondin-1-null (TSP-1-/-) compared to TSP-1WTC57BL/6J mice. Inflammasome activation was investigated by immunostaining using the R26ASC-citrine reporter mouse, by Western blotting, and by RNAseq. LPS/Nigericin, IL-1α and chronic inflammation induced inflammasomes in lacrimal gland epithelial cells. Acute and chronic inflammation of the lacrimal gland upregulated multiple inflammasome sensors, caspases 1/4, and interleukins Il1b and Il18. We also found increased IL-1ß maturation in Sjögren's syndrome models compared with healthy control lacrimal glands. Using RNA-seq data of regenerating lacrimal glands, we found that lipogenic genes were upregulated during the resolution of inflammation following acute injury. In chronically inflamed NOD.H2b lacrimal glands, an altered lipid metabolism was associated with disease progression: genes for cholesterol metabolism were upregulated, while genes involved in mitochondrial metabolism and fatty acid synthesis were downregulated, including peroxisome proliferator-activated receptor alpha (PPARα)/sterol regulatory element-binding 1 (SREBP-1)-dependent signaling. We conclude that epithelial cells can promote immune responses by forming inflammasomes, and that sustained inflammasome activation, together with an altered lipid metabolism, are key players of Sjögren's syndrome-like pathogenesis in the NOD.H2b mouse lacrimal gland by promoting epithelial dysfunction and inflammation.

Association between Edinburgh Postnatal Depression Scale and Serum Levels of Ketone Bodies and Vitamin D, Thyroid Function, and Iron Metabolism.

Suicide due to postpartum depression is the most common perinatal-related death and is a social concern in Japan. Nutritional deficiencies during pregnancy may contribute to postpartum depression; therefore, we investigated the relationship between postpartum depression and nutritional status during pregnancy and postpartum. We focused specifically on ketone bodies because they are known to protect brain cells. The relationship between the Edinburgh Postnatal Depression Scale (EPDS) scores and the serum levels of ketone bodies and vitamin D, thyroid function, and iron metabolism was examined. Overall, 126 pregnant women were identified for the study, and 99 were eventually included in the analysis. We defined an EPDS score of ≥9 as being positive for postpartum depression, and serum ketone levels were found to be higher in the group with an EPDS score of ≥9 during the second trimester; however, there were no other significant findings. We may be able to predict postpartum depression from a pregnant woman's serum ketone levels in the second trimester. There was a positive correlation between the EPDS scores at 3 days and 1 month postpartum (r = 0.534, p < 0.001). EPDS scores assessed in the early postpartum period may be useful for the timely detection of postpartum depression.

Relationship between out-of-facility deliveries and distance and travel time to delivery facilities in Hokkaido, Japan: An ecological study.

AIM: This study aimed to investigate the relationship between the distance and travel time from each municipality to the nearest delivery facilities in the other municipalities and the frequency of out-of-facility deliveries in Hokkaido. METHODS: Vital statistics from 2016 to 2020 were used. For municipalities without delivery facilities, the distance and travel time from the town office of each municipality to the nearest delivery facility was measured using Google maps. Negative binomial regression with an offset term was used to calculate the relative risks (RRs) and 95% confidence intervals (CIs) of out-of-facility delivery for distance (<30, 30-59, ≥60 km), and travel time by car (<30, 30-59, and ≥60 min) from the town office to the nearest delivery facility compared with the presence of delivery facilities. RESULTS: The overall rate of out-of-facility deliveries in Hokkaido was 2.1‰; in municipalities with delivery facilities, 1.8‰, and in municipalities without delivery facilities, 3.1‰. The adjusted RRs (95% CIs) for out-of-facility deliveries were significantly higher in municipalities with less than 30 km and travel time of less than 30 min to delivery facilities, 2.63 (1.34-5.17) and 2.76 (1.36-5.58), respectively, compared to municipalities with delivery facilities. However, the adjusted RR of out-of-facility delivery for municipalities ≥30 km was higher, although the difference was not significant. CONCLUSIONS: Even in municipalities with a distance to delivery facilities of less than 30 km or travel time of less than 30 min, we should keep in mind the occurrence of out-of-facility deliveries.

Spatial transcriptomics of the lacrimal gland features macrophage activity and epithelium metabolism as key alterations during chronic inflammation.

The lacrimal gland (LG) is an exocrine gland that produces the watery part of the tear film that lubricates the ocular surface. Chronic inflammation, such as Sjögren's syndrome (SS), is one of the leading causes of aqueous-deficiency dry eye (ADDE) disease worldwide. In this study we analyzed the chronic inflammation in the LGs of the NOD.B10Sn-H2b/J (NOD.H-2b) mice, a mouse model of SS, utilizing bulk RNAseq and Visium spatial gene expression. With Seurat we performed unsupervised clustering and analyzed the spatial cell distribution and gene expression changes in all cell clusters within the LG sections. Moreover, for the first time, we analyzed and validated specific pathways defined by bulk RNAseq using Visium technology to determine activation of these pathways within the LG sections. This analysis suggests that altered metabolism and the hallmarks of inflammatory responses from both epithelial and immune cells drive inflammation. The most significant pathway enriched in upregulated DEGs was the "TYROBP Causal Network", that has not been described previously in SS. We also noted a significant decrease in lipid metabolism in the LG of the NOD.H-2b mice. Our data suggests that modulation of these pathways can provide a therapeutic strategy to treat ADDE.

[Case Report on a Woman with Epilepsy Who Took Lacosamide during Pregnancy and Gave Birth to a Healthy Infant].

Lacosamide is a novel antiepileptic drug. Although many antiepileptic drugs reportedly pose a risk to fetuses, patients with epilepsy are advised to continue their medications during pregnancy. There have been few reports on lacosamide use during pregnancy, and its effects on the fetus remain unclear. Here, we report a case of lacosamide use during pregnancy. The 33-year-old patient was treated with oral lacosamide (400 mg/d) for symptomatic partial epilepsy. She was concomitantly treated with folic acid (5 mg/d) beginning 4 days before her last menstrual cycle. She was also concomitantly treated with oral perampanel (2 mg/d) at 5-7 weeks' gestation for seizure control but discontinued perampanel after the pregnancy was discovered. She progressed through her pregnancy with only mild seizures. Fetal growth was normal and ultrasonography revealed no external malformations. The patient had an elective cesarean section at 37 weeks and 2 days owing to a previous post-cesarean pregnancy. Her baby boy weighed 3025 g; his Apgar score was 8 and 9, 1 and 5 min, respectively, and his umbilical artery blood pH was 7.348. He had no congenital anomalies and no neonatal drug withdrawal symptoms. This suggests that lacosamide may have a low risk of teratogenicity and fetal toxicity. Thus, this case is valuable for clinicians who are considering the administration of antiepileptic drugs during pregnancy. In the future, more reports on the use of lacosamide during pregnancy should be collected.

Neurodevelopmental delay up to the age of 4 years in infants born to women with gestational diabetes mellitus: The Japan Environment and Children's Study.

AIMS/INTRODUCTION: This study aimed to investigate the neurodevelopment of infants born to women with gestational diabetes mellitus (GDM). MATERIALS AND METHODS: Data from the National Birth Cohort in the Japan Environment and Children's Study from 2011 to 2014 (n = 81,705) were used. Japan uses the GDM guidelines of the International Association of Diabetes and Pregnancy Study Groups. The Japanese translation of the Ages and Stages Questionnaires, third Edition, was used to assess neurodevelopment in the following domains: communication skills, gross motor skills, fine motor skills, problem-solving ability, and personal and social skills. The survey was carried out every 6 months from the age of 6 months to 4 years (total of eight times). Generalized estimating equations were used to evaluate the association between maternal GDM and neurodevelopmental delay based on odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Neurodevelopmental delays, particularly in problem-solving ability, fine motor skills, and personal and social skills, were significantly higher in infants born to women with GDM than in those born to women without GDM (adjusted OR 1.24, 95% CI 1.12-1.36; adjusted OR 1.15, 95% CI 1.03-1.27; and adjusted OR 1.18, 95% CI 1.04-1.33). Furthermore, stratification showed no significant increase in the adjusted ORs (95% CIs) of girls. CONCLUSIONS: Neurodevelopment was significantly delayed up to 4 years-of-age among boys born to women with GDM.

Impact of health literacy on anxiety and depressive symptoms in pregnant women in Japan during the COVID-19 pandemic.

To investigate the relationships between communicative and critical health literacy (CCHL) and anxiety and depressive symptoms (ADs) in pregnant women during the coronavirus disease 2019 (COVID-19) pandemic. A cross-sectional study was conducted and 5466 pregnant women responded in Japan in September 2020. A Kessler 6 scale (K6) score ≥ 10, an Edinburgh Postnatal Depression Scale (EPDS) score ≥ 13, and four CCHL groups were analyzed using a logistic regression model and trend test. The proportions of pregnant women with a K6 score ≥ 10 and EPDS score ≥ 13 were 13.5 and 15.4%, respectively. In comparisons with the low CCHL group, the adjusted odds ratio (95% CI) for anxiety symptoms was 0.770 (0.604-0.982) in the high CCHL group, while those for depressive symptoms were 0.777 (0.639-0.946), 0.665 (0.537-0.824), and 0.666 (0.529-0.838) in the lower, higher, and high CCHL groups (all p < 0.05), respectively, after adjustments for potential confounding factors, such as age, weeks of gestation, complications, history, number of children, marital status, education, employment, and income. Higher CCHL was associated with significantly lower adjusted odds ratios for anxiety (p for trend = 0.019) and depressive symptoms (p for trend < 0.001). These results suggest a relationship between CCHL and ADs in pregnant women during the COVID-19 pandemic.

Changes in Serum Levels of Ketone Bodies and Human Chorionic Gonadotropin during Pregnancy in Relation to the Neonatal Body Shape: A Retrospective Analysis.

Among the physiological changes occurring during pregnancy, the benefits of morning sickness, which is likely mediated by human chorionic gonadotropin (HCG) and induces serum ketone production, are unclear. We investigated the relationship between serum levels of ketone bodies and HCG in the first, second, and third trimesters and neonatal body shape (i.e., birth weight, length, head circumference, and chest circumference) in 245 pregnant women. Serum levels of 3-hydroxybutyric acid peaked in late-stage compared with early stage pregnancy (27.8 [5.0−821] vs. 42.2 [5.0−1420] µmol/L, median [range], p < 0.001). However, serum levels of ketone bodies and HCG did not correlate with neonatal body shape. When weight loss during pregnancy was used as an index of morning sickness, a higher pre-pregnancy body mass index was associated with greater weight loss. This study is the first to show that serum ketone body levels are maximal in the third trimester of pregnancy. As the elevation of serum ketone bodies in the third trimester is a physiological change, high serum levels of ketone bodies may be beneficial for mothers and children. One of the possible biological benefits of morning sickness is the prevention of diseases that have an increased incidence due to weight gain during pregnancy.

The developmental origin and the specification of the adrenal cortex in humans and cynomolgus monkeys.

Development of the adrenal cortex, a vital endocrine organ, originates in the adrenogonadal primordium, a common progenitor for both the adrenocortical and gonadal lineages in rodents. In contrast, we find that in humans and cynomolgus monkeys, the adrenocortical lineage originates in a temporally and spatially distinct fashion from the gonadal lineage, arising earlier and more anteriorly within the coelomic epithelium. The adrenal primordium arises from adrenogenic coelomic epithelium via an epithelial-to-mesenchymal transition, which then progresses into the steroidogenic fetal zone via both direct and indirect routes. Notably, we find that adrenocortical and gonadal lineages exhibit distinct HOX codes, suggesting distinct anterior-posterior regionalization. Together, our assessment of the early divergence of these lineages provides a molecular framework for understanding human adrenal and gonadal disorders.

Challenges facing workstyle reform for Japanese obstetricians and gynecologists revealed from time studies.

AIM: We aimed to grasp the actual working hours of Japanese obstetricians and gynecologists (OB/GYN doctors) as accurately as possible, using the same method of the Ministry of Health, Labour, and Welfare (MHLW). METHODS: The time study targeted OB/GYN doctors working at 10 universities nationwide including Niigata University and 21 institutions which take a role of perinatal care in Niigata prefecture. Working hours per week were calculated based on the following categories: regular and overtime work inside the hospital, work outside the hospital, self-improvement, education, research, and others. Data on weekly working hours were converted to yearly data for analyses. RESULTS: A time study of 10 universities nationwide revealed that 30% of doctors work overtime for more than 1860 h even if they do not include on-call shifts in their working hours. In 21 institutions in Niigata, physicians in Niigata University worked more overtime than other hospitals. It became clear that community health care was supported by dispatching physicians working at university. Furthermore, the results of simulations predicted the pessimistic situation of perinatal medical care in Niigata. CONCLUSIONS: Our study showed the possibility to exist much more OB/GYN doctors who work more than 1860 h of overtime work per year than the data presented by the MHLW based on nation-wide survey in 2019. The fact that the working hours at the side jobs had a great influence on the increase in overtime work of physicians in University was the same result as the report of MHLW published in 2021.

A mesenchymal to epithelial switch in Fgf10 expression specifies an evolutionary-conserved population of ionocytes in salivary glands.

Fibroblast growth factor 10 (FGF10) is well established as a mesenchyme-derived growth factor and a critical regulator of fetal organ development in mice and humans. Using a single-cell RNA sequencing (RNA-seq) atlas of salivary gland (SG) and a tamoxifen inducible Fgf10CreERT2:R26-tdTomato mouse, we show that FGF10pos cells are exclusively mesenchymal until postnatal day 5 (P5) but, after P7, there is a switch in expression and only epithelial FGF10pos cells are observed after P15. Further RNA-seq analysis of sorted mesenchymal and epithelial FGF10pos cells shows that the epithelial FGF10pos population express the hallmarks of ancient ionocyte signature Forkhead box i1 and 2 (Foxi1, Foxi2), Achaete-scute homolog 3 (Ascl3), and the cystic fibrosis transmembrane conductance regulator (Cftr). We propose that epithelial FGF10pos cells are specialized SG ionocytes located in ducts and important for the ionic modification of saliva. In addition, they maintain FGF10-dependent gland homeostasis via communication with FGFR2bpos ductal and myoepithelial cells.

Prevention of venous thromboembolism in pregnant women with congenital antithrombin deficiency: a retrospective study of a candidate protocol.

BACKGROUND: The best thromboprophylaxis for pregnant women with congenital antithrombin deficiency (CAD) is controversial. OBJECTIVE: To clarify the effectiveness of a protocol for venous thromboembolism (VTE) prevention in pregnant women with CAD. METHODS: Women at high risk of VTE were administered antithrombin concentrate and heparin after conception, whereas those at low risk of VTE were administered heparin alone until delivery. All women received antithrombin concentrate at delivery except for one who was diagnosed with CAD. RESULTS: Ten women had CAD, including one in the high-risk group and nine in the low-risk group. No women had VTE at delivery as per the protocol for VTE prevention. Almost all women had increased antithrombin activity before delivery followed by maintenance at ≥ 70% due to antithrombin concentrate administration. VTE prophylaxis during and after delivery was successful in all women with CAD. However, one woman in the low-risk group did not receive heparin and developed VTE induced by severe hyperemesis at 9 gestational weeks, before the diagnosis of CAD. Women in the high-risk group received antithrombin concentrate after delivery but had increased D-dimer levels at postpartum. CONCLUSIONS: Our protocol to prevent VTE in pregnant women with CAD is safe and effective.