Virological outcomes of various first-line ART regimens in patients harbouring HIV-1 E157Q integrase polymorphism: a multicentre retrospective study.

BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are recommended as first-line ART for people living with HIV (PLWH) in most guidelines. The INSTI-resistance-associated mutation E157Q, a highly prevalent (2%-5%) polymorphism of the HIV-1 (human immunodeficiency virus type 1) integrase gene, has limited data on optimal first-line ART regimens. We assessed the virological outcomes of various first-line ART regimens in PLWH with E157Q in real-world settings. METHODS: A multicentre retrospective observational study was conducted on PLWH who underwent integrase genotypic drug-resistance testing before ART initiation between 2008 and 2019 and were found to have E157Q. Viral suppression (<50 copies/mL) rate at 24 and 48 weeks, time to viral suppression and time to viral rebound (≥100 copies/mL) were compared among the first-line ART regimens. RESULTS: E157Q was detected in 167 (4.1%) of 4043 ART-naïve PLWH. Among them, 144 had available clinical data after ART initiation with a median follow-up of 1888 days. Forty-five started protease inhibitors + 2 NRTIs (PI group), 33 started first-generation INSTI (raltegravir or elvitegravir/cobicistat) + 2 NRTIs (INSTI-1 group), 58 started once-daily second-generation INSTI (dolutegravir or bictegravir) + 2 NRTIs (INSTI-2 group) and eight started other regimens. In the multivariate analysis, the INSTI-2 group showed similar or favourable outcomes compared with the PI group for viral suppression rates, time to viral suppression and time to viral rebound. Two cases in the INSTI-1 group experienced virological failure. CONCLUSIONS: The general guideline recommendation of second-generation INSTI-based first-line ART for most PLWH is also applicable to PLWH harbouring E157Q.

Sex-specific differences in head circumference of term singletons after assisted reproductive technology: a multicentre study in Japan.

RESEARCH QUESTION: Does fertility treatment, specifically assisted reproductive technology (ART), affect head circumference in term singletons? DESIGN: A total of 32,651 women who delivered at term at 12 maternity hospitals in Japan between 2010 and 2018 were included in the analysis; of these, 1941 (5.9%) and 2984 (9.1%) women conceived through ART and non-ART fertility treatments (timed intercourse, ovulation induction or artificial insemination), respectively. The study evaluated the adjusted odds ratios of head circumference ≥90th percentile stratified by infant sex and type of ART procedure after adjusting for covariates, with natural conception as the reference group. RESULTS: ART significantly increased the risk of head circumference ≥90th percentile (adjusted odds ratio 1.56 [95% confidence interval 1.25-1.96]), whereas non-ART fertility treatment did not increase the risk (1.14 [0.92-1.42]). This increased risk of head circumference ≥90th percentile was observed exclusively in male neonates (1.73 [1.33-2.26]) and not in female neonates (1.18 [0.76-1.85]) in the ART group. Frozen embryo transfer (FET), FET in a hormone replacement cycle (HRC-FET) and blastocyst-stage embryo transfer were significantly associated with head circumference ≥90th percentile (1.60 [1.26-2.02], 1.70 [1.30-2.22] and 1.72 [1.33-2.24], respectively). CONCLUSIONS: The use of ART, particularly FET, HRC-FET or blastocyst-stage embryo transfer, was linked with a heightened risk of head circumference ≥90th percentile compared with non-ART fertility treatment or natural conception. The increased risk was observed only in male neonates.

New-onset postpartum hypertension in women without a history of hypertensive disorders of pregnancy: a multicenter study in Japan.

The aim of this study was to investigate the prevalence and risk factors of new-onset postpartum hypertension (PPHTN), defined as new-onset hypertension during the postpartum period, among women without a history of hypertension during pregnancy and labor. A multicenter retrospective study was conducted using clinical data of women who delivered at term between 2011 and 2018 at 12 maternity hospitals. A total of 18,295 normotensive women were eligible, after excluding those with hypertensive disorders of pregnancy or hypertension during labor. New-onset PPHTN was defined as multiple blood pressure readings of ≥ 140/90 mmHg between 1 d and 4 weeks postpartum among normotensive women throughout pregnancy. Multivariate regression analyses were performed to evaluate the risk factors for new-onset PPHTN. Among the 18,295 normotensive women, 227 (1.2%) presented with new-onset PPHTN. The prevalence was higher in women who delivered via cesarean section than in those who delivered vaginally (7.0% and 1.0%, respectively). The independent risk factors were maternal age ≥ 35 years (adjusted odds ratio 1.67, 95% confidence interval [1.10-2.53]), nulliparity (1.83 [1.24-2.71]), high normal blood pressure (systolic blood pressure [SBP] 120-129 and diastolic blood pressure [DBP] < 80) at the last prenatal check-up (1.96 [1.23-3.13]), elevated blood pressure (SBP 130-139 and/or DBP 80-89) (6.42 [4.15-9.95]), urinary protein 1+ (1.99 [1.27-3.11]), scheduled cesarean section (4.05 [1.69-9.69]), and emergency cesarean section (10.02 [5.10-19.70]). New-onset PPHTN was observed in 1.2% of the normotensive women, with women who delivered via cesarean section having the highest risk. Close postpartum blood pressure monitoring may be required for women with multiple risk factors to identify new-onset PPHTN in a timely manner and reduce adverse maternal consequences.

Evaluating glucose variability through OGTT in early pregnancy and its association with hypertensive disorders of pregnancy in non-diabetic pregnancies: a large-scale multi-center retrospective study.

BACKGROUND: Recent evidence suggests increased glucose variability (GV) causes endothelial dysfunction, a central pathology of hypertensive disorders of pregnancy (HDP). We aimed to investigate the association between GV in early pregnancy and subsequent HDP development among non-diabetes mellitus (DM) pregnancies. METHODS: This multicenter retrospective study used data from singleton pregnancies between 2009 and 2019. Among individuals who had 75 g-OGTT before 20 weeks of gestation, we evaluated GV by 75 g-OGTT parameters and examined its relationship with HDP development, defining an initial-increase from fasting-plasma glucose (PG) to 1-h-PG and subsequent-decrease from 1-h-PG to 2-h-PG. RESULTS: Approximately 3.0% pregnancies (802/26,995) had 75 g-OGTT before 20 weeks of gestation, and they had a higher prevalence of HDP (14.3% vs. 7.5%). The initial-increase was significantly associated with overall HDP (aOR 1.20, 95% CI 1.02-1.42), and the subsequent-decrease was associated with decreased and increased development of early-onset (EoHDP: aOR 0.56, 95% CI 0.38-0.82) and late-onset HDP (LoHDP: aOR 1.38, 95% CI 1.11-1.73), respectively. CONCLUSIONS: A pattern of marked initial-increase and minor subsequent-decrease (i.e., sustained hyperglycemia) was associated with EoHDP. Contrarily, the pattern of marked initial-increase and subsequent-decrease (i.e., increased GV) was associated with LoHDP. This provides a new perspective for future study strategies.

Association of demographics, HCV co-infection, HIV-1 subtypes and genetic clustering with late HIV diagnosis: a retrospective analysis from the Japanese Drug Resistance HIV-1 Surveillance Network.

INTRODUCTION: Late diagnosis of the human immunodeficiency virus (HIV) is a major concern epidemiologically, socially and for national healthcare systems. Although the association of certain demographics with late HIV diagnosis has been reported in several studies, the association of other factors, including clinical and phylogenetic factors, remains unclear. In the present study, we conducted a nationwide analysis to explore the association of demographics, clinical factors, HIV-1 subtypes/circulating recombinant form (CRFs) and genetic clustering with late HIV diagnosis in Japan, where new infections mainly occur among young men who have sex with men (MSM) in urban areas. METHODS: Anonymized data on demographics, clinical factors and HIV genetic sequences from 39.8% of people newly diagnosed with HIV in Japan were collected by the Japanese Drug Resistance HIV-1 Surveillance Network from 2003 to 2019. Factors associated with late HIV diagnosis (defined as HIV diagnosis with a CD4 count <350 cells/µl) were identified using logistic regression. Clusters were identified by HIV-TRACE with a genetic distance threshold of 1.5%. RESULTS: Of the 9422 people newly diagnosed with HIV enrolled in the surveillance network between 2003 and 2019, 7752 individuals with available CD4 count at diagnosis were included. Late HIV diagnosis was observed in 5522 (71.2%) participants. The overall median CD4 count at diagnosis was 221 (IQR: 62-373) cells/µl. Variables independently associated with late HIV diagnosis included age (adjusted odds ratio [aOR] 2.21, 95% CI 1.88-2.59, ≥45 vs. ≤29 years), heterosexual transmission (aOR 1.34, 95% CI 1.11-1.62, vs. MSM), living outside of Tokyo (aOR 1.18, 95% CI 1.05-1.32), hepatitis C virus (HCV) co-infection (aOR 1.42, 95% CI 1.01-1.98) and not belonging to a cluster (aOR 1.30, 95% CI 1.12-1.51). CRF07_BC (aOR 0.34, 95% CI 0.18-0.65, vs. subtype B) was negatively associated with late HIV diagnosis. CONCLUSIONS: In addition to demographic factors, HCV co-infection, HIV-1 subtypes/CRFs and not belonging to a cluster were independently associated with late HIV diagnosis in Japan. These results imply the need for public health programmes aimed at the general population, including but not limited to key populations, to encourage HIV testing.

Opioid modulation of T-type Ca2+ channel-dependent neuritogenesis/neurite outgrowth through the prostaglandin E2/EP4 receptor/protein kinase A pathway in mouse dorsal root ganglion neurons.

Irregular regeneration or inappropriate remodeling of the axons of the primary afferent neurons after peripheral nerve trauma could be associated with the development of neuropathic pain. We analyzed the molecular mechanisms for the neuritogenesis and neurite outgrowth caused by prostaglandin E2 (PGE2) in mouse dorsal root ganglion (DRG) neurons, and evaluated their opioid modulation. PGE2 in combination with IBMX, a phosphodiesterase inhibitor, caused neuritogenesis/neurite outgrowth in DRG cells, an effect abolished by a prostanoid EP4, but not EP2, receptor antagonist, and inhibitors of adenylyl cyclase or protein kinase A (PKA). Blockers of T-type Ca2+ channels (T-channels), that are responsible for window currents involving the sustained low-level Ca2+ entry at voltages near the resting membrane potentials and can be functionally upregulated by PKA, inhibited the neuritogenesis/neurite outgrowth caused by PGE2/IBMX or dibutylyl cyclic AMP, a PKA activator, in DRG neurons, an inhibitory effect mimicked by ZnCl2 and ascorbic acid that block Cav3.2, but not Cav3.1 or Cav3.3, T-channels. Morphine and DAMGO, µ-opioid receptor (MOR) agonists, suppressed the neuritogenesis and/or neurite outgrowth induced by PGE2/IBMX in DRG neurons and also DRG neuron-like ND7/23 cells, an effect reversed by naloxone or ß-funaltrexamine, a selective MOR antagonist. Our data suggest that the EP4 receptor/PKA/Cav3.2 pathway is involved in the PGE2-induced neuritogenesis/neurite outgrowth in DRG neurons, which can be suppressed by MOR stimulation. We propose that MOR agonists including morphine in the early phase after peripheral nerve trauma might delay the axonal regeneration of the primary afferent neurons but prevent the development of neuropathic pain.

A hydrolysate of poly-trans-[(2-carboxyethyl)germasesquioxane] (Ge-132) suppresses Cav3.2-dependent pain by sequestering exogenous and endogenous sulfide.

Poly-trans-[(2-carboxyethyl)germasesquioxane] (Ge-132), an organogermanium, is hydrolyzed to 3-(trihydroxygermyl)propanoic acid (THGP) in aqueous solutions, and reduces inflammation, pain and cancer, whereas the underlying mechanisms remain unknown. Sulfides including H2S, a gasotransmitter, generated from l-cysteine by some enzymes including cystathionine-γ-lyase (CSE), are pro-nociceptive, since they enhance Cav3.2 T-type Ca2+ channel activity expressed in the primary afferents, most probably by canceling the channel inhibition by Zn2+ linked via coordinate bonding to His191 of Cav3.2. Given that germanium is reactive to sulfur, we tested whether THGP would directly trap sulfide, and inhibit sulfide-induced enhancement of Cav3.2 activity and sulfide-dependent pain in mice. Using mass spectrometry and 1H NMR techniques, we demonstrated that THGP directly reacted with sulfides including Na2S and NaSH, and formed a sulfur-containing reaction product, which decreased in the presence of ZnCl2. In Cav3.2-transfected HEK293 cells, THGP inhibited the sulfide-induced enhancement of T-type Ca2+ channel-dependent membrane currents. In mice, THGP, administered systemically or locally, inhibited the mechanical allodynia caused by intraplantar Na2S. In the mice with cyclophosphamide-induced cystitis and cerulein-induced pancreatitis, which exhibited upregulation of CSE in the bladder and pancreas, respectively, systemic administration of THGP as well as a selective T-type Ca2+ channel inhibitor suppressed the cystitis-related and pancreatitis-related visceral pain. These data suggest that THGP traps sulfide and inhibits sulfide-induced enhancement of Cav3.2 activity, leading to suppression of Cav3.2-dependent pain caused by sulfide applied exogenously and generated endogenously.

Optimal annual body mass index change for preventing spontaneous preterm birth in a subsequent pregnancy.

Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality. Although PTB is known to recur, interpregnancy preventive strategies for PTB have not been established to date. Annual BMI change can serve as a specific target value for preventing obstetric complications during interpregnancy care/counseling. This value can also account for age-related weight gain (0.2 kg/m2/year). In a multicenter retrospective study, we investigated the optimal annual BMI change for preventing PTB recurrence using the data of individuals who had two singleton births from 2009 to 2019. The association between annual BMI change and spontaneous PTB (sPTB) was analyzed by separating cases of medically indicated PTB (mPTB) from those of sPTB. Previous history of sPTB was strongly associated with sPTB in the subsequent pregnancy (adjusted odds ratio [aOR], 12.7; 95% confidence interval [CI], 6.5-24.8). Increase in annual BMI was negatively associated with sPTB (aOR, 0.6; 95% CI 0.5-0.9). The sPTB recurrence rate was significantly lower in patients with an annual BMI change of ≥ 0.25 kg/m2/year than in those with an annual BMI change of < 0.25 kg/m2/year (7.7% vs. 35.0%, p = 0.011). Our findings suggest that age-related annual BMI gain between pregnancies may help prevent sPTB recurrence.

Discovery of pimozide derivatives as novel T-type calcium channel inhibitors with little binding affinity to dopamine D2 receptors for treatment of somatic and visceral pain.

T-type Ca2+ channels (T-channels), particularly Cav3.2 and Cav3.1 isoforms, are promising targets for treating various diseases including intractable pain. Given the potent inhibitory activity of pimozide, an antipsychotic, against T-channels, we conducted structure-activity relationship studies of pimozide derivatives, and identified several compounds including 3a, 3s, and 4 that had potency comparable to that of pimozide in inhibiting T-channels, but little binding affinity to dopamine D2 receptors. The introduction of a phenylbutyl group on the benzoimidazole nuclei of pimozide was considered a key structural modification to reduce the binding affinity to D2 receptors. Those pimozide derivatives potently suppressed T-channel-dependent somatic and visceral pain in mice, without causing any motor dysfunctions attributable to D2 receptor blockade, including catalepsy. The present study thus provides an avenue to develop novel selective T-channel inhibitors available for pain management via the structural modification of existing medicines.

Reassessing the duration of each stage of labor and their relation to postpartum hemorrhage in the current Japanese population.

AIM: To reassess the normal duration of each stage of labor in a contemporary Japanese cohort, and to determine whether prolongation of each stage of labor increases the rate of postpartum hemorrhage (PPH) in vaginal deliveries. METHODS: Clinical data of women who delivered at term at 12 facilities between 2012 and 2018 were retrospectively collected. A total of 31 758 women were subdivided into three or four subgroups according to the duration of each stage of labor and parity. Univariate and multivariate logistic regression analyses were performed to estimate crude and adjusted odds ratios (ORs) of PPH (blood loss ≥ 1000 mL) in each subgroup, with women with the shortest durations in each subgroup used as the reference group. RESULTS: The reference range of each stage of labor was found to be shorter than that previously reported. Women with prolonged second (primiparity, adjusted OR: 1.15-1.78; multiparity, adjusted OR: 1.14-1.74) and third (primiparity, adjusted OR: 1.39-4.95; multiparity, adjusted OR: 1.46-3.80) stages of labor showed an increased risk of PPH, whereas those with prolonged first stage did not. A significantly increased risk of PPH was found both in primiparous and multiparous women with third stages of labor ≥ 5 min. CONCLUSIONS: The normal duration of each stage of labor in the Japanese population needs to be revised and well-recognized by obstetric care providers. A prolonged third stage of labor was a more important contributing factor to PPH than prolonged first or second stages.

Annual Body Mass Index Gain and Risk of Gestational Diabetes Mellitus in a Subsequent Pregnancy.

Introduction: Weight change during the interpregnancy is related to gestational diabetes mellitus (GDM) in the subsequent pregnancy. In interpregnancy care/counseling, the timeframe for goal setting is important, while the timing of the next conception is unpredictable and preventing age-related body weight gain is difficult. This study aimed to investigate the association between annual weight gain during the interpregnancy, which provide clearer timeframe, and GDM in subsequent pregnancies. Methods: This multicenter retrospective study was conducted by collecting data on two pregnancies of the same women in 2009-2019. The association between annual BMI gain and GDM during the subsequent pregnancy was examined. Results: This study included 1,640 pregnant women. A history of GDM [adjusted odds ratio (aOR), 26.22; 95% confidence interval (CI), 14.93-46.07] and annual BMI gain (aOR, 1.48; 95% CI, 1.22-1.81) were related to GDM during the subsequent pregnancy. In the women with a pre-pregnant BMI of <25.0 kg/m2 and without GDM during the index pregnancy, an annual BMI gain of ≥0.6 kg/m2/year during the interpregnancy were associated with GDM in subsequent pregnancies; however, in the other subgroups, it was not associated with GDM in subsequent pregnancies. Conclusions: For women with a pre-pregnant BMI of <25.0 kg/m2 and without GDM during the index pregnancy, maintaining an annual BMI gain of <0.6 kg/m2/year may prevent GDM during the subsequent pregnancy.

Machine learning prediction models for postpartum depression: A multicenter study in Japan.

AIM: Postpartum depression (PPD) and perinatal mental health care are of growing importance worldwide. Here we aimed to develop and validate machine learning models for the prediction of PPD, and to evaluate the usefulness of the recently adopted 2-week postpartum checkup in some parts of Japan for the identification of women at high risk of PPD. METHODS: A multicenter retrospective study was conducted using the clinical data of 10 013 women who delivered at ≥35 weeks of gestation at 12 maternity care hospitals in Japan. PPD was defined as an Edinburgh Postnatal Depression Scale score of ≥9 points at 4 weeks postpartum. We developed prediction models using conventional logistic regression and four machine learning algorithms based on the information that can be routinely collected in daily clinical practice. The model performance was evaluated using the area under the receiver operating characteristic curve (AUROC). RESULTS: In the machine learning models developed using clinical data before discharge, the AUROCs were similar to those in the conventional logistic regression models (AUROC, 0.569-0.630 vs. 0.626). The incorporation of additional 2-week postpartum checkup data into the model significantly improved the predictive performance for PPD compared to that without in the Ridge regression and Elastic net (AUROC, 0.702 vs. 0.630 [p < 0.01] and 0.701 vs. 0.628 [p < 0.01], respectively). CONCLUSIONS: Our machine learning models did not achieve better predictive performance for PPD than conventional logistic regression models. However, we demonstrated the usefulness of the 2-week postpartum checkup for the identification of women at high risk of PPD.

Liver transaminase levels during pregnancy: a Japanese multicenter study.

INTRODUCTION: There are conflicting reports on the effect of pregnancy on liver transaminase (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) levels. In this study, we sought to investigate the trajectories of AST and ALT levels during normal pregnancy and to compare them with AST and ALT levels of matched nonpregnant controls. MATERIALS AND METHODS: Our multicenter retrospective study included 34,396 women who delivered at term at 12 primary maternity care units between January 2011 and December 2018 and 57,152 nonpregnant women younger than 45 years who received a medical checkup between 2016 and 2019. After matching at a ratio of 1:1 for adjustment of several factors (age, weight, and height), a total of 30,460 normal pregnant women and 30,460 nonpregnant women were selected for this study. We measured serum AST and ALT levels during each trimester and the postpartum period to compare with those of the nonpregnant women. RESULTS: The ALT level began to decrease in the first half of the third trimester and was lowest in the second half of third trimester and at postpartum day 1 (median [interquartile range]: 8 [6-11] U/L, 8 [6-10] U/L, respectively). The decline reversed and returned to the level of a nonpregnant state by postpartum days 2-7. The AST level remained unchanged regardless of pregnancy. The prevalence of abnormal liver transaminases (AST >40 U/L and ALT >40 U/L) was <1% at third trimester; however, it increased to 3-5% on postpartum days 2-7. CONCLUSIONS: The ALT level was lower during pregnancy compared with nonpregnant women matched for several factors, whereas the AST level remained unchanged during pregnancy. Understanding the trajectories of AST and ALT levels during pregnancy may facilitate early recognition and diagnosis of impaired liver function, including liver disease and pregnancy complications that affect liver transaminases, such as pre-eclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome.

Pre-pregnancy sleep duration and postpartum depression: a multicenter study in Japan.

Postpartum depression (PPD) is as a major public health issue and clinical priority worldwide. This study aimed to investigate the association between pre-pregnancy sleep duration and PPD. A multicenter retrospective study was conducted using clinical data of women who delivered at term between 2014 and 2018 at 12 maternity care hospitals in Japan. A total of 15,314 women were stratified into five groups according to their pre-pregnancy sleep duration: < 6, 6-7, 7-8, 8-9, and ≥ 9 h. Univariate and multivariate regression analyses were conducted to determine whether pre-pregnancy sleep duration affects the Edinburgh Postnatal Depression Scale (EPDS) scores at 1 month postpartum. We also evaluated whether the risk for PPD differs between primipara and multipara women classified according to pre-pregnancy sleep duration. The adjusted odds ratio for high EPDS scores (≥ 9) among women who slept for < 6 h and 6-7 h was 2.08 (95% confidence interval [CI]: 1.60-2.70) and 1.41 (95% CI: 1.18-1.68), respectively, relative to that in women with 7-8 h of sleep as the reference group. A 1-h increase in sleep duration was associated with an approximately 14% reduction in the risk for high EPDS scores. The association between short sleep duration and high EPDS scores was more remarkable in multipara women than in primipara women. Short pre-pregnancy sleep duration is associated with high EPDS scores, and this association is more significant in multipara women than in primipara women. Our findings emphasize the importance of collecting information on pre-pregnancy sleep duration to identify women at a high risk for PPD.

Annual body mass index gain and risk of hypertensive disorders of pregnancy in a subsequent pregnancy.

Weight gain during interpregnancy period is related to hypertensive disorders of pregnancy (HDP). However, in interpregnancy care/counseling, the unpredictability of the timing of the next conception and the difficulties in preventing age-related body weight gain must be considered while setting weight management goals. Therefore, we suggest considering the annual change in the body mass index (BMI). This study aimed to clarify the association between annual BMI changes during the interpregnancy period and HDP risk in subsequent pregnancies. A multicenter retrospective study of data from 2009 to 2019 examined the adjusted odds ratio (aOR) of HDP in subsequent pregnancies. The aORs in several annual BMI change categories were also calculated in the subgroups classified by HDP occurrence in the index pregnancy. This study included 1,746 pregnant women. A history of HDP (aOR, 16.76; 95% confidence interval [CI], 9.62 - 29.22), and annual BMI gain (aOR, 2.30; 95% CI, 1.76 - 3.01) were independent risk factors for HDP in subsequent pregnancies. An annual BMI increase of ≥ 1.0 kg/m2/year was related to HDP development in subsequent pregnancies for women without a history of HDP. This study provides data as a basis for interpregnancy care/counseling, but further research is necessary to validate our findings and confirm this relationship.

Prevalence and risk factors of labor-onset hypertension: A multicenter study in Japan.

OBJECTIVES: To investigate the prevalence and risk factors of labor-onset hypertension (LOH), defined as hypertension first detected during labor among women without hypertension prior to admission for labor. STUDY DESIGN: In this multicenter retrospective study, clinical data of women who delivered vaginally at term between 2012 and 2018 were collected from 12 primary maternity care units. Blood pressure was measured at five time points from admission to 2 h postpartum in a total of 30,129 normotensive women at the last prenatal check-up. LOH was defined as systolic blood pressure (SBP) of ≥ 140 mmHg or diastolic blood pressure (DBP) of ≥ 90 mmHg during the first to fourth stages of labor. MAIN OUTCOME MEASURES: Multivariate regression analyses were conducted to evaluate the risk factors of LOH and severe LOH (SBP of ≥ 160 mmHg or DBP of ≥ 110 mmHg). RESULTS: Among the 30,129 women, 8,565 (28.4%) presented with LOH and 734 (2.4%) with severe LOH. The prevalence of LOH was the highest at the second stage of labor (21.7%) and decreased rapidly after delivery. The independent risk factors of LOH were maternal age of ≥ 35 years, pre-pregnancy body mass index of ≥ 25 kg/m2, and pregnancy weight gain of ≥ 15 kg. CONCLUSION: LOH is common, with approximately one in four women experiencing LOH during labor and early postpartum. Meanwhile, severe LOH occurred in 2.4% of the pregnancies. Closer blood pressure monitoring during labor may enable obstetric caregivers to recognize LOH in a timely manner and reduce maternal adverse outcomes, such as eclampsia and stroke.

Manual removal of the placenta and postpartum hemorrhage: A multicenter retrospective study.

AIM: In postpartum women, retained placenta is diagnosed in the absence of signs of placental separation and expulsion, and requires manual removal of the placenta (MROP). MROP may lead to massive hemorrhage, hemodynamic instability, and the need for emergency interventions including blood transfusion, interventional radiology, and hysterectomy. In this study, we aimed to identify the risk factors for retained placenta requiring MROP after vaginal delivery and postpartum hemorrhage (PPH) following MROP. METHODS: A multicenter retrospective study was performed using data from women who delivered at term between 2010 and 2018 at 13 facilities in Japan. Of 36 454 eligible women, 112 women who required MROP were identified. Multivariate logistic regression analyses were conducted to evaluate the risk factors for retained placenta and PPH following MROP. RESULTS: A history of abortion, assisted reproductive technology (ART), instrumental delivery, and delivery of small-for-gestational-age infant were independent risk factors for MROP (adjusted odds ratios [95% confidence intervals]: 1.93 [1.28-2.92], 8.41 [5.43-13.05], 1.80 [1.14-2.82], and 4.32 [1.97-9.48], respectively). ART was identified as an independent risk factor for PPH (adjusted odds ratio [95% confidence interval]: 6.67 [2.42-18.36]) in patients who underwent MROP. CONCLUSION: ART pregnancies significantly increased the risk of retained placenta requiring MROP and PPH. Our results suggest that clinicians need consider patient transfer to a higher-level facility and preparation of sufficient blood products before initiating MROP in cases of ART pregnancies. Our study may assist in identifying high-risk women for PPH before MROP and in guiding treatment decisions, especially in facilities without a blood bank.

Platelet counts during normal pregnancies and pregnancies complicated with hypertensive disorders.

OBJECTIVES: To determine the trajectories of platelet counts and the prevalence of gestational thrombocytopenia (<150 × 109/L) during normal pregnancies and pregnancies with complications, such as hypertensive disorders of pregnancy (HDP), preeclampsia, and fetal growth restriction (FGR). STUDY DESIGN: A multicenter retrospective study was conducted using laboratory data on women who delivered term singletons at 11 primary maternity care units between 2011 and 2018 (n = 35,045), and non-pregnant women who underwent a medical check-up between 2016 and 2019 (n = 61,189). After 1:1 matching, 28,073 pregnant women and 28,073 non-pregnant women were selected for analysis. MAIN OUTCOMES MEASURES: The trajectories of platelet counts and prevalence of gestational thrombocytopenia were evaluated in normal pregnant women, pregnant women with complications, and non-pregnant women. RESULTS: The platelet counts declined throughout pregnancy, with the nadir occurring on postpartum day 1. The platelet counts recovered to the level of the non-pregnant state at postpartum 2-7 days. The mean platelet counts at postpartum day 1 decreased by an estimated 19.8% and 9.7% compared to those in the non-pregnant state and first trimester, respectively. The prevalence of gestational thrombocytopenia in normal pregnant women at 37-41 gestational weeks and in pregnant women with complications of HDP, preeclampsia, and FGR were 6.1%, 7.3%, 17.5%, and 7.7%, respectively. CONCLUSION: Platelet counts declined throughout pregnancy and recovered to the level of the non-pregnant state in the early postpartum period. Gestational thrombocytopenia is common during normal pregnancy, and its prevalence is significantly higher in women with preeclampsia.

Maternal low birth weight and hypertensive disorders of pregnancy.

OBJECTIVES: To investigate the association between maternal own low birth weight (<2500 g) and subsequent risks for hypertensive disorders of pregnancy (HDP) and preeclampsia. STUDY DESIGN: A multicenter retrospective study was conducted using clinical data from 12 primary maternity care units from 2012 to 2018. A total of 17,119 women with information about their own birth weight, who delivered at term, were subdivided into four groups according to maternal birth weights [(<2500, 2500-3499, 3500-3999, and ≥4000) g]. MAIN OUTCOME MEASURES: Multivariate regression analyses were conducted to evaluate the risks for HDP and preeclampsia among women born with low birth weight compared with women born with a birth weight of 2500-3499 g. We evaluated these risks, stratified by pre-pregnancy BMI or their infants' birth weight categories. RESULTS: Maternal low birth weight was an independent risk factor for HDP after adjustment for several covariates, but not for preeclampsia. A 100-g increase in maternal birth weight was associated with a 3% risk reduction for HDP. Additionally, women born with low birth weight had the highest risk for HDP among those with a pre-pregnancy BMI of ≥25 kg/m2. Conversely, women born with high birth weight (≥4000 g) had the highest risk for preeclampsia if they complicate with fetal growth restrictions. CONCLUSION: Women born with low birth weight had an increased risk for HDP. Collection of information on maternal birth weight may facilitate the prediction of HDP and patients' self-awareness of such risk, allowing the modification of lifestyle factors associated with HDP.

Shock Index and Postpartum Hemorrhage in Vaginal Deliveries: A Multicenter Retrospective Study.

INTRODUCTION: Shock index (SI), calculated by dividing heart rate by systolic blood pressure, is used to detect hemodynamic instability and hypovolemia. In obstetric practice, limited evidence is available regarding its usefulness in detecting postpartum hemorrhage (PPH). We aimed to evaluate the usefulness of SI in detecting PPH in vaginal deliveries using clinical data from 12 primary maternity care units in Japan. MATERIAL AND METHODS: In this multicenter retrospective study, a total of 30,820 women who delivered vaginally at term at 12 primary maternity care units from January 2012 to December 2018 were included. Systolic and diastolic blood pressures and heart rate were measured at five different time points from admission to postpartum 2 h, and postpartum blood loss was measured. We evaluated the trend of average SI and the performance of each vital sign for detection of PPH. RESULTS: The trend of average SI during labor and the immediate postpartum period was approximately 0.7 in women with blood loss of <500 mL. SI from the time of delivery of the placenta increased with an increase in blood loss. SI had the highest area under the receiver operating characteristic curve of 0.699 [95% confidence interval (CI), 0.682-0.716] and 0.758 (95% CI, 0.729-0.788) for PPH of ≥1,000 and ≥1,500 mL, respectively. However, both sensitivity of SI (1.0) for PPH (≥1,000 mL; 29.9%, and ≥1,500 mL; 40.5%, respectively) and correlation between maximum SI and blood loss (coefficient of correlation, 0.263) were low. CONCLUSIONS: SI is a better parameter for PPH detection in vaginal deliveries than other vital signs. However, clinical judgment must incorporate other vital signs and symptoms associated with hypovolemic shock due to the low sensitivity of SI.