Uterine cervical conisation and chorioamnionitis: A nationwide observational study.

OBJECTIVE: To investigate whether conisation increases chorioamnionitis (CAM) and assess whether this risk differs between preterm and term periods. Furthermore, we estimated mediation effects of CAM between conisation and preterm birth (PTB). DESIGN: A nationwide observational study. SETTING: Japan. POPULATION: Singleton pregnant women derived from the perinatal registry database of the Japan Society of Obstetrics and Gynaecology between 2013 and 2019. METHODS: The association between a history of conisation and clinical CAM was examined using a multivariable logistic regression model with multiple imputation. We conducted mediation analysis to estimate effects of CAM on PTB following conisation. MAIN OUTCOME MEASURES: Clinical CAM. RESULTS: Of 1 500 206 singleton pregnant women, 6961 (0.46%) underwent conisation and 1 493 245 (99.5%) did not. Clinical CAM occurred in 150 (2.2%) and 11 484 (0.8%) women with and without conisation, respectively. Conisation was associated with clinical CAM (odds ratio [OR] 3.09; 95% confidence interval (CI) 2.63-3.64; p < 0.001) (risk difference 1.57%; 95% CI 1.20-1.94). The association was detected among 171 440 women with PTB (OR 3.09; 95% CI 2.57-3.71), whereas it was not significant among 1 328 284 with term birth (OR 0.88; 95% CI 0.58-1.34). OR of total effect of conisation on PTB was 2.71, OR of natural indirect effect (effect explained by clinical CAM) was 1.04, and OR of natural direct effect (effect unexplained by clinical CAM) was 2.61. The proportion mediated was 5.9%. CONCLUSIONS: Conisation increased CAM occurrence. Obstetricians should be careful regarding CAM in women with conisation, especially in preterm period. Bacterial infections may be an important cause of PTB after conisation.

Maternal outcomes of placental abruption with intrauterine fetal death and delivery routes: A nationwide observational study.

INTRODUCTION: Placental abruption is a serious complication, especially when accompanied by intrauterine fetal death. The optimal delivery route for placental abruption with intrauterine fetal death for reducing maternal complications is still unclear. In this study we aimed to compare the maternal outcomes between cesarean delivery and vaginal delivery in women with placental abruption with intrauterine fetal death. MATERIAL AND METHODS: Using the Japan Society of Obstetrics and Gynecology nationwide perinatal registry database, we identified pregnant women with placental abruption with intrauterine fetal death between 2013 and 2019. The following women were excluded: those with multiple pregnancies, placenta previa, placenta accreta spectrum, amniotic fluid embolism, or whose delivery route was missing data. The association between delivery routes (cesarean delivery and vaginal delivery) and the maternal outcome was examined using a linear regression model with inverse probability weighting. The primary outcome was the amount of bleeding during delivery. Missing data were imputed using multiple imputation. RESULTS: The number of women with placental abruption with intrauterine fetal death was 1218/1601932 (0.076%). Of 1134 women analyzed, 608 (53.6%) underwent cesarean delivery. Bleeding during delivery (median [interquartile range]) was 1650.00 (950.00-2450.00) (mL) and 1171.00 (500.00-2196.50) (mL) in cesarean and vaginal delivery, respectively. Bleeding during delivery (mL) was significantly greater in cesarean delivery than in vaginal delivery (regression coefficient, 1086.39; 95% confidence interval, 130.96-2041.81; p = 0.026). Maternal death and uterine rupture occurred in four (0.4%) and five (0.4%) women, respectively. The four maternal deaths were noted in the vaginal delivery group. CONCLUSIONS: Bleeding during delivery was significantly greater in cesarean delivery than that in vaginal delivery in women with placental abruption with intrauterine fetal death. However, severe complications, including maternal death and uterine rupture, occurred in vaginal delivery-related cases. The management of women with placental abruption with intrauterine fetal death should be cautious regardless of the delivery route.

Usefulness of dynamic computed tomography for diagnosing and evaluating uterine artery pseudoaneurysms in women with late post-partum hemorrhage not complicated by retained products of conception.

AIM: We examined whether critical conditions, which were defined as having hemoglobin (Hb) less than 7.0 g/dL, shock index ≥1.0, or need for transfusion, were associated with the presence of extravasation (EV) on dynamic computed tomography (CT) in women with late post-partum hemorrhage (PPH). METHODS: Forty post-partum women with late PPH without evident retained products of conception performed dynamic CT. Two radiologists retrospectively evaluated dynamic CT, and determined the presence or absence of EV and a sac-like structure within the uterine cavity with enhancement. RESULTS: Ultrasound images were available in 34/40 patients. Color Doppler flow in uterine cavity was evaluated in 33/34 (97%), and all women showed abnormal flow. Of 40 patients, dynamic CT revealed EV in 8 (20%), and a sac-like structure in 30 (75%). Thus, we diagnosed these 38 (95%) as having uterine artery pseudoaneurysm (UAP). Uterine artery embolization was performed in 36/38 diagnosed as having UAP, and in 2/2 patients with an unknown cause of hemorrhage. The incidence rates of critical conditions were significantly increased in PPH women with than without EV on dynamic CT: Hb <7.0 g/dL (62.5 vs 0%, [P < 0.001]), shock index ≥1.0 (50 vs 9.4% [P = 0.020]), and need for transfusion (37.5 vs 0% [P = 0.006]). Abnormal color Doppler flows were observed in all patients with either EV and sac on dynamic CT. CONCLUSION: Dynamic CT was useful for diagnosing UAP, and for evaluating critical conditions, in women with late PPH not complicated by retained products of conception.

Matsubara-Yano suture: a simple uterine compression suture for postpartum hemorrhage during cesarean section.

AIMS: The aims of this study were to clarify: (i) the effectiveness of Matsubara-Yano uterine compression suture (MY) to achieve hemostasis in the presence of postpartum hemorrhage (PPH) during cesarean section, (ii) the type of PPH for which MY is effective, (iii) post-operative complications of MY, and (iv) outcomes of pregnancy after MY. METHODS: This retrospective observational study was performed using medical records of patients for whom MY had been performed between January 1, 2009 and December 31, 2017. RESULTS: MY was performed for 50 patients, with hemostasis achieved in 46 (92%). The other four (8%: 4/50) patients required transarterial embolization or hysterectomy. Of these four, three patients had placenta accreta spectrum (PAS) disorder-related bleeding. Post-operative complications were observed in three (6%: 3/50) patients, with all showing intrauterine infection. All three patients recovered solely with antibiotics. Eight pregnancies were confirmed (five livebirths, two spontaneous abortions in the first trimester, and one case of ongoing pregnancy). Of the five livebirths, one resulted in cesarean hysterectomy due to placenta previa with PAS disorders. CONCLUSIONS: MY had a hemostatic effect on PPH. All cases except one with hemostatic failure were associated with PAS disorders, indicating that the hemostatic rate was lower in those with PAS than non-PAS disorders.

Vaginal Ureaplasma species increase chorioamnionitis in very preterm infants with preterm premature rupture of the membranes at < 28 weeks of gestation.

Our aim was to investigate the association between vaginal Ureaplasma species (spp.) and the subsequent occurrence of chorioamnionitis (CAM), perinatal death, neonatal morbidity, and long-term neurodevelopmental impairments (NDIs) at 3 years of age. We analyzed 55 pregnant women with singleton pregnancy who had preterm premature rupture of the membranes (pPROM) at < 28+0 weeks of gestation, and delivered between 22+0 and 31+6 weeks at our tertiary hospital in 2007-2016. NDIs were defined as either cerebral palsy or developmental delay evaluated at 1.5 and/or 3 years old. The presence of Ureaplasma spp. and Mycoplasma hominis were evaluated using urea-arginine broth and Mycoplasma PPLO Agar. The presence of Ureaplasma spp. in the vagina was positive in 41%. Vaginal Ureaplasma spp. was a significant risk factor for CAM; however, it was not significantly associated with the occurrence of perinatal death, pulmonary hypoplasia, respiratory distress syndrome, transient tachypnea of the newborn, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia defined as oxygen required and occasional ventilatory assistance required at week 36 as modified (BPD36), or NDIs. The crude odds ratio (95% confidence interval) of Ureaplasma spp. for the occurrence of CAM was 9.5 (1.10-82) (p = 0.041). In very preterm birth infants with pPROM, CAM, BPD36, and NDIs occurred in 78, 60, and 36%, respectively. Vaginal Ureaplasma spp. was a significant risk factor for CAM in very preterm birth infants with pPROM. The incidences of BPD36 and NDIs in such infants were very high, nearing 3/5 and 1/3, respectively.

Magnetic resonance imaging of degeneration of uterine adenomyosis during pregnancy and post-partum period.

Degeneration of adenomyosis during pregnancy and the post-partum period is very rare. A 42-year-old Japanese parous woman with four normal-term deliveries, who presented with abdominal pain and fever at 22 weeks of gestation with transient increases of the white blood cell count and C-reactive protein, demonstrated sustained inflammation after cesarean section at 29 weeks of gestation due to the occurrence of gestational hypertension with late deceleration. The noncontrast-enhanced magnetic resonance imaging (MRI) at 22 weeks demonstrated a poorly demarcated hypointense area at the posterior uterine wall on T1- and T2-weighted imaging. The 2nd MRI 2 weeks after the cesarean section showed hypointensity on a T1-weighted image and hyperintensity on a T2-weighted image, allowing confirmation of the diagnosis of degeneration of adenomyosis. Repeated MRIs were clinically useful to diagnose the degeneration of adenomyosis.

Ritodrine-induced rhabdomyolysis, infantile myotonic dystrophy, and maternal myotonic dystrophy unveiled.

A primiparous pregnant woman in remission of myositis suffered very acute-onset ritodrine-induced rhabdomyolysis. At 29 gestational weeks, ritodrine was administered for threatened preterm labor. Just 3 h later, she complained of severe limb muscle pain, with serum creatinine phosphokinase elevated to 32 019 U/L and myoglobinuria. The muscle pain disappeared immediately after ceasing administration of ritodrine. At 31 weeks, premature rupture of the membranes occurred, necessitating cesarean section, yielding a baby with weak tonus, and the presence of infantile muscle diseases was suspected. Genetic analysis of the infant confirmed myotonic dystrophy (dystrophia myotonica, DM), which prompted us to perform maternal genetic analysis, confirming maternal DM. Ritodrine can induce rhabdomyolysis even in the prodromal phase with a mild phenotype of DM. A literature review suggested that ritodrine-induced rhabdomyolysis may be likely to occur more acutely after ritodrine administration in DM compared with non-DM mothers.

Urinary protein-to-creatinine ratio indicative of significant proteinuria in normotensive pregnant women.

AIM: In hypertensive pregnant women, the protein-to-creatinine (P/C) ratio is well correlated with 24-h proteinuria and a P/C ratio of 0.27 (g/gCr) is used to reflect significant proteinuria (>0.3 g/day). The aim of this study was to obtain data on normotensive pregnant women, which have so far been lacking. METHODS: The study population consisted of 74 pregnant women who met the following criteria: (i) ≥22 gestational weeks; (ii) a positive result (≥1+) on dipstick test; (iii) a positive result (>0.27) for P/C ratio; and (iv) 24-h urine test performed within 2 days of the P/C ratio. The correlation between the P/C ratio and 24-h proteinuria, the incidence rates of significant proteinuria according to P/C ratios, and appropriate threshold of the P/C ratio to rule in significant proteinuria were determined using the appropriate statistical methods. RESULTS: The P/C ratio was moderately correlated with the 24-h proteinuria, with a correlation coefficient of 0.64 (95% confidence interval, 0.487-0.76). The area under the receiver-operator curve was 0.76 (95% confidence interval, 0.66-0.87); however, no clear shoulder was identifiable. The incidence rates of significant proteinuria according to P/C ratios of 0.27-0.49, 0.50-0.74, 0.75-0.99, and >1 were 41, 66, 100, and 100%, respectively, indicating that all normotensive pregnant women with a P/C ratio > 0.75 had significant proteinuria. CONCLUSION: Normotensive pregnant women showed a significant correlation between the P/C ratio and 24-h urine protein level. All normotensive pregnant women with a P/C ratio > 0.75 had significant proteinuria, suggesting that a P/C ratio > 0.75 may be the 'rule-in' threshold of significant proteinuria in this population.

Which type of placenta previa requires blood transfusion more frequently? A new concept of indiscernible edge total previa.

AIM: During cesarean section (CS) for placenta previa (PP), the size/area/portion of the lower uterine segment occupied by the placenta may affect the bleeding amount and the subsequent need for a blood transfusion (BT). We propose a new concept, indiscernible edge total PP (IEPP), when vaginal ultrasound does not discern the lower placental edge because the placenta covers the visible lower segment. We characterized IEPP, focusing on its allogeneic BT requirement. METHODS: We classified PP (n = 307) into four types: marginal, partial, discernible edge total PP (DEPP) and IEPP: internal ostium (os)-placental edge distance measurable or unmeasurable on vaginal ultrasound in DEPP or IEPP, respectively. We determined the clinical characteristics according to the four types; the relationship between the intraoperative blood loss and os-edge distance in DEPP; and risk factors for allogeneic BT. RESULTS: The following were significantly higher/larger in cases of IEPP: previous CS; anterior placentation; lacunae; elective cesarean hysterectomy; intraoperative blood loss; autologous BT; allogeneic BT; intensive care unit admission; and an abnormally invasive placenta (AIP). In DEPP, the os-edge distance was weakly correlated with the bleeding amount (r = 0.214). Multivariate logistic regression analysis showed that previous CS, lacunae, AIP and IEPP were independent risk factors for allogeneic BT (odds ratios 3.8, 3.1, 13.8 and 4.6, respectively). After excluding patients undergoing hemostatic procedures during CS, IEPP remained the only independent risk factor for allogeneic BT (odds ratio 5.2). CONCLUSIONS: The new concept of IEPP may be useful for predicting BT in CS for patients with PP.

Spontaneous resolution of post-delivery or post-abortion uterine artery pseudoaneurysm: A report of three cases.

Post-delivery/-abortion uterine artery pseudoaneurysm (UAP) sometimes causes life-threatening bleeding, requiring transarterial embolization (TAE). It is unclear whether some UAP resolve spontaneously. In three patients, UAP resolved spontaneously without TAE. Case 1 was after vacuum delivery with slight bleeding: at day 5 post-partum, a yin-yang sign on Color Doppler and an enhanced intrauterine sac-like structure were observed, leading to the diagnosis of UAP, which disappeared at 4 weeks post-partum. Case 2 was after vacuum delivery with manual placental removal and was asymptomatic: a hypoechoic intrauterine mass with a yin-yang sign were observed during a post-partum routine check-up and the intrauterine flow disappeared at 4 weeks post-partum. Case 3 was after dilatation and curettage in the first trimester with slight bleeding: UAP was detected at 4 weeks post-abortion, which disappeared at 6 weeks post-abortion. All three cases had a small UAP (diameter: 10-15 mm) and low-level or no symptoms. Some UAP may resolve spontaneously and, thus, may not require TAE.

Routine blood cultures in the management of pyelonephritis in pregnancy for improving outcomes.

BACKGROUND: Pyelonephritis is a type of urinary tract infection (UTI) that affects the upper urinary tract and kidneys, and is one of the most common conditions for hospitalisation among pregnant women, aside from delivery. Samples of urine and blood are obtained and used for cultures as part of the diagnosis and management of the condition. Acute pyelonephritis requires hospitalisation with intravenous administration of antimicrobial agents. Several studies have questioned the necessity of obtaining blood cultures in addition to urine cultures, citing cost and questioning whether blood testing is superfluous. Pregnant women with bacteraemia require a change in the initial empirical treatment based on the blood culture. However, these cases are not common, and represent approximately 15% to 20% of cases. It is unclear whether blood cultures are essential for the effective management of the condition. OBJECTIVES: To assess the effectiveness of routine blood cultures to improve health outcomes in the management of pyelonephritis in pregnant women. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register without language or date restrictions (31 December 2014). SELECTION CRITERIA: Randomised controlled trials and quasi-randomised trials comparing outcomes among pregnant women with pyelonephritis who received initial management with or without blood cultures. Cluster-randomised trials were eligible for inclusion in this review but none were identified. Clinical trials using a cross-over design were not eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed one trial report for inclusion. MAIN RESULTS: We identified one trial report but this was excluded. No clinical trials met the inclusion criteria for this review. AUTHORS' CONCLUSIONS: There are no large-scale randomised controlled trials to assess outcomes in the management of pyelonephritis in pregnancy with or without blood cultures. Randomised controlled trials are needed to evaluate the effectiveness of managing pyelonephritis in pregnant women with or without blood cultures, and to assess any adverse outcomes as well as the cost-effectiveness of excluding blood cultures from treatment.

Calculating probability of requiring allogeneic blood transfusion using three preoperative risk factors on cesarean section for placenta previa.

PURPOSE: To construct a model to calculating probability of requiring allogeneic blood transfusion on cesarean section (CS) for placenta previa (PP). METHODS: A retrospective cohort study involving all 205 patients with PP who underwent CS in our institute. We determined the relationship between allogeneic blood transfusion and nine preoperative factors: (1) maternal age, (2) parity, (3) uterine myoma, (4) previous CS, (5) the placenta covering the previous CS scar (referred to as "scar covering"), (6) degree of previa, (7) ultrasound finding of lacunae, (8) preoperative anemia, and (9) preparation of autologous blood. Independent risk factors of allogeneic blood transfusion were identified by multivariate logistic regression analysis. These significant factors were included in the final model, and, the probability of allogeneic blood transfusion was calculated. RESULTS: Independent risk factors of allogeneic blood transfusion were scar covering, previous CS without scar covering, and lacunae. These three factors were used to create a predictive model. The model revealed that patients with scar covering and lacunae had the highest probability (0.73), while those with no risk factors had the lowest probability (0.02). CONCLUSION: This simple model may be useful to calculate probability of requiring allogeneic blood transfusion on CS for placenta previa.

Two nursing mothers treated with zonisamide: Should breast-feeding be avoided?

Zonisamide, an antiepileptic drug, is excreted into breast milk, but information regarding the safety of breast-feeding while using this drug is limited. We present the cases of two nursing mothers, taking 300 and 100 mg/day zonisamide. At 5 days after delivery, the milk concentrations and relative infant doses of the drug were 18.0 and 5.1 µg/mL, and 44 and 36%, respectively. In the first case, the mother fed colostrum and continued partial breast-feeding thus reducing the relative infant dose to 8%. The neonatal serum concentration of zonisamide declined to below the limit of detection at day 34 after birth. In the second case, the mother breast-fed partially until 2 weeks postpartum. No adverse effect was observed in the infants. These findings suggest that mothers taking zonisamide should not breast-feed exclusively, but may not have to avoid partial breast-feeding, with significant caution regarding adverse effects in infants.

Anterior placentation as a risk factor for massive hemorrhage during cesarean section in patients with placenta previa.

AIM: In placenta previa (PP), anterior placentation, compared with posterior placentation, is reported to more frequently cause massive hemorrhage during cesarean section (CS). Whether this is due to the high incidence of placenta accreta, previous CS, or a transplacental approach in anterior placenta is unclear. We attempted to clarify this issue. MATERIAL AND METHODS: We retrospectively analyzed the relation between the bleeding amount during CS for PP and various factors that may cause massive hemorrhage (>2400 mL) (n = 205) in a tertiary center. If the preoperatively ultrasound-measured distance from the internal cervical ostium to the placental edge was longer in the uterine anterior wall than in the posterior wall, we defined it as anterior previa, and vice versa. RESULTS: Patients with accreta, previous CS, total previa, and anterior placentation bled significantly more than their counterparts. Multivariate logistic regression analysis showed that accreta (odds ratio [OR] 12.6), previous CS (OR 4.7), total previa (OR 4.1), and anterior placentation (OR 3.5) were independent risk factors of massive hemorrhage. CONCLUSIONS: Anterior placentation, namely, the placenta with a longer os-placental edge distance in the anterior wall than in the posterior wall, was a risk of massive hemorrhage during CS for PP.

Maternal manifestation of Ballantyne's syndrome occurring concomitantly with the development of fetal congenital mesoblastic nephroma.

Various fetal or placental disorders cause Ballantyne's (mirror) syndrome. For the first time, we report a maternal manifestation of Ballantyne's syndrome occurring concomitantly with the development of fetal congenital mesoblastic nephroma (CMN). In a pregnant woman with a CMN fetus, lung edema, hypertension, hyperthyroidism, and high serum human chorionic gonadotrophin level occurred, all of which characterize maternal manifestation of Ballantyne's syndrome. The fetus and placenta were devoid of 'edema', lacking 'triple edema', and thus this condition was not diagnosed as Ballantyne's syndrome; however, we considered this condition as the maternal manifestation of Ballantyne's syndrome. We performed emergent cesarean section at 28 weeks. Delivery acutely ameliorated maternal symptoms. Tumor was resected and was confirmed as CMN. Maternal manifestations of Ballantyne's syndrome, such as lung edema and hypertension, can occur in a mother with fetal CMN even without fetal and/or placental edema. The clinical course of this patient may suggest an etiology of Ballantyne's syndrome.

Changes in expression of vascular endothelial growth factor D-related genes in placental mesenchymal dysplasia.

A recent report indicated that vascular endothelial growth factor (VEGF)-D, regulating cell proliferation and/or differentiation, may be associated with the development of placental mesenchymal dysplasia (PMD), a disorder characterized by cell proliferation/differentiation. In PMD placenta, we examined the expression of five cell-proliferation/differentiation-associated genes, namely, Wnt3a, Wnt5a, ß-catenin, VEGF-D and Dickkopf-1 (DKK-1). In PMD, expressions of Wnt3a, Wnt5a and ß-catenin were decreased, whereas those of VEGF-D and DKK-1 were increased. These abnormal expressions suggest a relationship between these genes and PMD pathogenesis/pathophysiology.

Uterine artery pseudoaneurysm: not a rare condition occurring after non-traumatic delivery or non-traumatic abortion.

PURPOSE: Uterine artery pseudoaneurysm (UAP) is considered a rare disorder after traumatic delivery or traumatic pregnancy termination such as cesarean section or dilatation and curettage, initially manifesting as genital hemorrhage. Our clinical impression contradicts these three assumptions; after traumatic delivery/termination, hemorrhage, and its rarity. Thus, we attempted to clarify these three issues. METHODS: We retrospectively analyzed 22 UAP cases treated at our institute over a 6-year period. RESULTS: Uterine artery pseudoaneurysm occurred in 2-3/1,000 deliveries. Of 22 cases, half occurred after non-traumatic deliveries or non-traumatic pregnancy termination. Fifty-five percent (12/22) showed no hemorrhage; ultrasound or color Doppler revealed UAP. Thus, half of UAP occurred after non-traumatic deliveries or non-traumatic pregnancy termination and showed no hemorrhage at the time of their diagnoses. All patients received transarterial embolization, which stopped blood flow into UAP or achieved hemostasis. CONCLUSION: We must be aware that UAP may not be so rare and it may be present in patients after non-traumatic deliveries/pregnancy termination and without postpartum or postabortal hemorrhage.

A novel 'uterine sandwich' for haemorrhage at caesarean section for placenta praevia.

Although massive haemorrhage at caesarean section (CS) for placenta praevia is a serious concern, effective treatment is not yet determined. We performed a new uterine sandwich to achieve haemostasis at CS for total placenta praevia in five consecutive cases in whom the placenta reached up to >5 cm from the internal cervical os in all directions of an uterine wall. A Matsubara-Yano (MY) uterine compression suture was placed, followed by placement of an intrauterine balloon. Haemostasis was achieved in all five cases with median blood loss of 1618 mL. No short-term adverse events were observed. The MY sandwich can be used to achieve haemostasis at CS for placenta praevia.