A Novel Method for Determining Fibrin/Fibrinogen Degradation Products and Fibrinogen Threshold Criteria via Artificial Intelligence in Massive Hemorrhage during Delivery with Hematuria.

(1) Background: Although the diagnostic criteria for massive hemorrhage with organ dysfunction, such as disseminated intravascular coagulation associated with delivery, have been empirically established based on clinical findings, strict logic has yet to be used to establish numerical criteria. (2) Methods: A dataset of 107 deliveries with >2000 mL of blood loss, among 13,368 deliveries, was obtained from nine national perinatal centers in Japan between 2020 and 2023. Twenty-three patients had fibrinogen levels <170 mg/dL, which is the initiation of coagulation system failure, according to our previous reports. Three of these patients had hematuria. We used six machine learning methods to identify the borderline criteria dividing the fibrinogen/fibrin/fibrinogen degradation product (FDP) planes, using 15 coagulation fibrinolytic factors. (3) Results: The boundaries of hematuria development on a two-dimensional plane of fibrinogen and FDP were obtained. A positive FDP-fibrinogen/3-60 (mg/dL) value indicates hematuria; otherwise, the case is nonhematuria, as demonstrated by the support vector machine method that seemed the most appropriate. (4) Conclusions: Using artificial intelligence, the borderline criterion was obtained, which divides the fibrinogen/FDP plane for patients with hematuria that could be considered organ dysfunction in massive hemorrhage during delivery; this method appears to be useful.

Achievement of Target Glycemic Goal with Simple Basal Insulin Regimen in Women with Gestational Diabetes: A Prospective Cohort Study.

There is little evidence concerning the need to treat gestational diabetes (GDM) in the same way as pregestational diabetes. We evaluated the efficacy of the simple insulin injection (SII) regimen for achieving the target glucose goal without increasing adverse perinatal outcomes in singleton pregnant women with GDM. All subjects underwent self-monitoring of blood glucose (SMBG), and insulin therapy was indicated according to the SMBG profile. Insulin was initially started with the SII regimen, in which one daily injection of NPH insulin before breakfast was used, and another NPH injection was added at bedtime, if necessary. We used the target glucose as <95 mg/dL at fasting and <120 mg/dL postprandial and accepted <130 mg/dL for the latter. If the target glucose did not reach with the regimen, we switched to the multiple daily injection (MDI) with additional prandial insulin aspart. We compared the SMBG profile before delivery as well as the perinatal outcomes between the SII and MDI groups. Among 361 women (age 33.7 years, nullipara 41%, prepregnancy body mass index 23.2 kg/m2) with GDM, 59%, 18%, and 23% were in the diet-alone, SII, and MDI groups, respectively. Consequently, regarding women requiring insulin therapy, 43% were treated with the SII regimen throughout pregnancy. The severity of baseline hyperglycemia according to the SMBG data at baseline was the MDI>the SII>the diet group. The rate of achieving target glucose levels before delivery in the SII group at fasting, postprandial < 120 mg/dL and <130 mg/dL were 93%, 54% and 87%, respectively, which were similar to that in the MDI group (93%, 57%, and 93%, respectively), with no significant differences in perinatal outcomes. In conclusion, more than 40% of women with GDM requiring insulin therapy achieved the target glucose goal with this simple insulin regimen without any increase in adverse effects.

Risk of fetal undergrowth in the management of gestational diabetes mellitus in Japan.

AIMS/INTRODUCTION: In Japan, the increasing frequency of underweight among women of reproductive age and the accompanying increase in the rate of low birth weight (LBW) are social issues. The study aimed to establish a prospective registry system for gestational diabetes mellitus (GDM) in Japan and to clarify the actual status of GDM according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. MATERIALS AND METHODS: Pregnant women with gestational diabetes mellitus and those in the normal glucose tolerance (NGT) group were enrolled in the Diabetes and Pregnancy Outcome for Mother and Baby study from October 2015. Pregnant women with positive glucose screening in early and mid-to-late pregnancy underwent a 75 g oral glucose tolerance test by gestational week 32. Gestational diabetes mellitus was diagnosed according to IADPSG criteria. Women with a positive glucose screening test at mid-to-late pregnancy but NGT were enrolled as references (NGT group). Treatment for gestational diabetes mellitus and maternal and neonatal pregnancy data were prospectively collected on outcomes. RESULTS: In total 1,795 singleton pregnancies (878 women with GDM and 824 NGT women) were analyzed. The risk of LBW and small-for-gestational age in the GDM group was significantly higher than in the NGT group. A similar relationship was found for LBW risk in the non-overweight/obese group but not in the overweight/obese group. CONCLUSIONS: We established a prospective GDM registry system in Japan. In the management of GDM in Japan, suppression of maternal weight gain may be associated with reduced fetal growth, especially in non-overweight/obese women with GDM; however, further investigation is required.

Exponential increase of the gestational-age-specific incidence of preeclampsia onset (COPE study): a multicenter retrospective cohort study in women with maternal check-ups at <20 weeks of gestation in Japan.

According to the 2004 Japanese definition, early-onset (EO) preeclampsia (PE) is defined as PE occurring at <32 weeks of gestation. This was based on the presence of "dual peaks" (30-31 and 34-35 weeks) in the prevalence of severe forms of hypertension. In contrast, the international definition adopted a cutoff of 34 weeks based on the consensus. Our aim was to investigate whether there were "dual peaks" in the gestational-age-specific incidence or prevalence of PE onset in pregnant women who underwent maternal check-ups at <20 weeks of gestation in a multicenter retrospective cohort study. Diagnoses of PE and superimposed preeclampsia (SPE) were based on the new Japanese definition. A total of 26,567 pregnant women with singleton pregnancy were investigated. The best fitting equations for the distribution of the onset of gestational-age-specific incidence (hazard) rates of PE/SPE, PE, and PE with severe hypertension (a systolic blood pressure ≥160 and/or a diastolic blood pressure ≥110 mmHg) were investigated using the curve estimation function in SPSS. PE/SPE occurred in 1.83% of the patients. EO-PE/SPE with onset at <32 and <34 weeks of gestation and preterm PE/SPE occurred in 0.38, 0.56, and 1.07% of the patients, respectively. Gestational-age-specific incidence rates of PE/SPE, PE, and PE with severe hypertension showed exponential increases, with very high R2 values (0.975, 0.976, and 0.964, respectively). There were no "dual peaks" in the prevalence rates of women with SPE/PE, PE, and PE with severe hypertension. In conclusion, the absence of "dual peaks" refutes the previous rationale of EO-PE being defined as PE at <32 weeks of gestation. Further studies to determine an appropriate definition of EO-PE/SPE are needed.

Tadalafil treatment for fetuses with early-onset growth restriction: a protocol for a multicentre, randomised, placebo-controlled, double-blind phase II trial (TADAFER IIb).

INTRODUCTION: TheTADAlafil treatment for Fetuses with early-onset growth Restriction: multicentrer, randomizsed, phase II trial (TADAFER II) study showed the possibility of prolonging the pregnancy period in cases of early-onset fetal growth restriction; however, it was an open-label study. To establish further evidence for the efficacy of tadalafil in this setting, we planned a multicentre, randomised, placebo-controlled, double-blind trial. METHODS AND ANALYSIS: This trial will be conducted in 180 fetuses with fetal growth restriction enrolled from medical centres in Japan; their mothers will be randomised into three groups: arm A, receiving two times per day placebo; arm B, receiving one time per day 20 mg tadalafil and one time per day placebo and arm C, receiving 20 mg two times per day tadalafil. The primary endpoint is the prolongation of gestational age at birth, defined as days from the first day of the protocol-defined treatment to birth. To minimise bias in terms of fetal baseline conditions and timing of delivery, a fetal indication for delivery as in TADAFER II will be established in this trial. The investigator will evaluate fetal baseline conditions at enrolment and decide the timing of delivery based on this indication. ETHICS AND DISSEMINATION: This study has been approved by Mie University Hospital Clinical Research Review Board on 22 July 2019 (S2018-007). Written informed consent will be obtained from all mothers before recruitment. Our findings will be widely disseminated through peer-reviewed publications. TRIAL REGISTRATION: jRCTs041190065.

Vaginal Ureaplasma urealyticum or Mycoplasma hominis and preterm delivery in women with threatened preterm labor.

BACKGROUND: Amniotic fluid infection with Ureaplasma urealyticum or Mycoplasma hominis can cause chorioamnionitis and preterm birth. The aim of this study was to examine whether vaginal Ureaplasma urealyticum/Mycoplasma hominis colonization is predictive of preterm delivery in patients exhibiting signs of threatened preterm birth or those with asymptomatic short cervix. METHODS: The present retrospective study, which was performed in a perinatal tertiary center, included patients carrying a singleton pregnancy who were referred to the emergency Ob/Gyn unit because of regular preterm uterine contractions and/or short cervical length (<20 mm) at 22-33 weeks of gestation, and in whom a vaginal U. urealyticum/M. hominis examination (Urea-arginine LYO-2, BioMerieux®) was performed. Univariate and multivariate analyses were performed to assess the association between vaginal U. urealyticum or M. hominis and chorioamnionitis or preterm delivery. RESULTS: The median gestational age of the 94 enrolled patients was 29.9 weeks, and 54 (57%) of the patients were vaginal U. urealyticum/M. hominis-positive. The preterm delivery rate in the positive group was higher than in the negative group (53 versus 25%; p = .007). Vaginal U. urealyticum/M. hominis positivity was found to be an independent risk factor for preterm birth at <37 weeks of gestation (adjusted odds ratio = 4.0, 95% confidence interval, 1.1-15.3) in a multivariate analysis adjusted for age, history of preterm delivery and conization, gestational age, cervical length, presence of vaginal bleeding, vaginal fetal fibronectin and serum C-reactive protein at test. U. urealyticum/M. hominis positivity was not associated with delivery at <34 weeks or chorioamnionitis. CONCLUSION: A positive vaginal U. urealyticum/M. hominis culture is an independent predictive factor for preterm birth in patients with symptomatic threatened preterm labor and/or short cervix.

Comparison of the benefits and hemodynamic side effects of oxytocin between intravenous infusion with and without bolus injection during caesarean section.

The aim of this study was to compare the benefits and hemodynamic side effects of oxytocin between intravenous infusion with and without a bolus injection during a caesarean section. Women with singleton pregnancies who underwent caesarean sections under spinal anaesthesia were included. Oxytocin was administered by an iv bolus injection (5 U) followed by an intravenous infusion (10 U of oxytocin in 500 mL normal saline); this was switched to just an intravenous infusion. The amount of blood loss did not differ between the groups. In a multivariate analysis, the adjusted odds ratios for the risk of hypotension (≥20% reduction of systolic BP) and tachycardia (heart rate ≥100 bpm) were 4.5 (95% confidence interval [CI], 1.6-12.5) and 3.7 (95%CI 1.9-7.2) in the iv bolus group, respectively, compared with the just the infusion group. The oxytocin administration by iv bolus injection did not decrease blood loss and increased the rate of hemodynamic side effects.Impact statementWhat is already known on this subject? Oxytocin is used as the first-line uterotonic treatment to prevent a postpartum haemorrhage in women undergoing Caesarean Sections. Oxytocin is known to relax vascular smooth muscle, which can cause hypotension and tachycardia. The protocols for administering oxytocin during CS vary by institution.What do the results of this study add? Combined treatment with oxytocin by iv bolus injection (5 U) followed by iv infusion (10 U of oxytocin in 500 mL normal saline) during CS increased the risk of developing adverse hemodynamic side effects, including hypotension, tachycardia, and the need for vasopressors, without any benefit in the control of intraoperative blood loss in comparison to iv infusion alone.What are the implications of these findings for clinical practice and/or further research? We should abandon the iv bolus injection of oxytocin during CS, especially for women undergoing an elective CS who are not in labour.

Fetal sex and maternal insulin resistance during mid-pregnancy: a retrospective cohort study.

BACKGROUND: Recent studies have suggested that fetal sex influences maternal glucose and insulin metabolism during pregnancy. We examined whether fetal sex is associated with maternal insulin resistance and the ß-cell function during mid-pregnancy. METHODS: This retrospective study included singleton pregnant women who underwent a 75-g oral glucose tolerance test (OGTT) at 24-34 weeks of gestation due to positive diabetic screening. In addition to plasma glucose (PG), we measured plasma insulin during the OGTT to obtain surrogate indices associated with insulin resistance (IR), including homeostasis assessment model (HOMA) -IR and insulin sensitivity index (IsOGTT), and ß-cell function, including insulinogenic index (II), HOMA-ß, and area under the curve of insulin response. We compared these indices between women carrying male fetuses to those carrying female fetuses. RESULTS: The study population included 617 women (mean age, 32.4 ± 4.9 years) with a mean pre-pregnancy body mass index (BMI) of 22.6±4.5. They underwent the 75g-OGTT at 29.0 ± 2.5 weeks. Two hundred fifty-eight (42%) women were diagnosed with gestational diabetes (GDM). There was no significant difference in maternal age, pre-pregnancy BMI, gestational age at OGTT, PG at OGTT, or the prevalence of GDM between women with a male fetus (n=338) (male group) and those with a female fetus (n=279) (female group). Regarding the indices of IR, IR was significantly higher and insulin sensitivity was lower in the female group than in the male group (HOMA-IR: 7.0 [5-9.6] vs. 6.2 [4.6-8.8], p< 0.05; IsOGTT: 5.86 [4.29-7.83] vs. 6.29 [4.59-8.84], p< 0.01) (median [quartile range]). These differences remained significant after adjustment for maternal age, pre-pregnancy BMI, gestational age and fasting PG at OGTT, and the diagnosis of GDM. In contrast, the ß-cell function did not differ between the two groups. CONCLUSION: Maternal IR during mid-pregnancy was significantly higher in women carrying a female fetus than in those with a male fetus. The sex of the fetus may affect maternal insulin sensitivity during mid-pregnancy.

Impact of tocolysis-intent magnesium sulfate and beta-adrenergic agonists on perinatal brain damage in infants born between 28-36 weeks' gestation.

AIMS: Magnesium sulfate has neuroprotective effects in preterm infants. Whether other antepartum treatments interfere with the neuroprotective actions is not well known. This study aims to explore the impacts of antenatal administration of Magnesium sulfate or beta-2 adrenergic agonists as tocolytic agents on the developing brain in premature infants. METHODS: This is a retrospective cohort study in four tertiary perinatal centers in Japan. We collected data of pregnant women and infants born between 28 and 36 weeks for tocolytic agents, gestational age, sex, antenatal corticosteroid, fetal growth restriction, pathological chorioamnionitis, low umbilical arterial pH values (<7.1), multiple pregnancy, mode of delivery and institutions after excluding clinical chorioamnionitis, non-reassuring fetal status or major anomalies. Tocolytic agents were categorized into four groups: no-tocolysis, magnesium sulfate, beta-2 adrenergic agonists and the combination of them. We conducted multiple comparisons with multivariate analyses using generalized linear regression models to compare the prevalence of a poor perinatal outcome defined as infant's death, brain damage, particularly cerebral palsy and developmental delay. RESULTS: Among 1083 infants, 39% were no-tocolysis, 47% were magnesium sulfate, 41% were beta-2 adrenergic agonists and 27% were combination group, including the duplication. The incidence of poor perinatal outcome was decreased by magnesium sulfate (OR 0.27, 95% CI 0.10-0.72), but not changed significantly by beta-2 adrenergic agonists (OR 1.28, 95% CI 0.63-2.59) or the combination group (OR 2.24, 95% CI 0.67-7.54), compared with the no-tocolysis. CONCLUSION: The combination therapy for tocolysis with beta-2 adrenergic agonists diminished the magnesium sulfate neuroprotective action after adjusting for covariables.

Risk factors during the early postpartum period for type 2 diabetes mellitus in women with gestational diabetes.

For women with gestational diabetes mellitus (GDM), the evaluation of glucose tolerance (GT) in the early postpartum period is universally recommended. Nevertheless, few studies have evaluated the risk factors for T2DM on the basis of GT data obtained during the early postpartum period. We aimed to identify the risk factors for type 2 diabetes mellitus (T2DM) by evaluating GT in the first 12 weeks postpartum (12wPP) in women with GDM and to categorize the risk using a combination of the principal risk factors. This retrospective multicenter observational study included 399 East Asian women with GDM who underwent a 75-g oral glucose tolerance test (OGTT) within 12wPP, which was repeated annually or biennially and used to identify the postpartum development of T2DM. Forty-three women (10.8%) developed T2DM during a median follow-up period of 789 ± 477 days. The independent risk factors for T2DM were pre-pregnancy obesity (BMI ≥25 kg/m2), early postpartum impairment in glucose tolerance (IGT), and an early postpartum glycated hemoglobin (HbA1c) ≥5.7%. The odds ratios (95% confidence intervals) for T2DM were 3.2 (1.3-7.8) in women with either early postpartum IGT or pre-pregnancy obesity, 9.2 (3.0-28.3) in those with early postpartum IGT, pre-pregnancy obesity, and HbA1c <5.7%, and 51.4 (16.1-163.9) in those with early postpartum IGT, pre-pregnancy obesity, and HbA1c ≥5.7%, compared with those without obesity or IGT. T2DM risk in East Asian women with GDM should be stratified according to pre-pregnancy obesity and early postpartum IGT, and these patients should be followed up and receive appropriate care for their risk category.

New method for determining fibrinogen and FDP threshold criteria by artificial intelligence in cases of massive hemorrhage during delivery.

AIM: To investigate the feasibility of a novel method using artificial intelligence (AI), in which the fibrinogen criterion was determined by the quantitative relation between the distributions of fibrin/fibrinogen degradation products (FDPs) and fibrinogen. METHODS: A dataset of 154 deliveries comprising more than 2000 g of blood lost due to hemorrhage, excluding disseminated intravascular coagulation (DIC), among patients from eight national perinatal centers in Japan from 2011 to 2015 were obtained. The fibrinogen threshold criterion was identified by using the function that best fit the distributions of FDP as determined by AI. FDP production was described by differential equations using a dataset containing fibrinogen levels less than the fibrinogen criterion and solved numerically. RESULTS: A fibrinogen level of 237 mg/dL as the threshold criterion was obtained. The FDP threshold criteria were 2.0 and 8.5 mg/dL for no coagulopathy and a failed coagulation system, respectively. CONCLUSION: The fibrinogen threshold criterion for patients with massive hemorrhage excluding DIC at delivery were obtained by selecting the functions that best fit the distributions of FDP data by using AI.

High-intensity breastfeeding improves insulin sensitivity during early post-partum period in obese women with gestational diabetes.

AIM: To investigate whether high-intensity breastfeeding (HIB) reduces insulin resistance during early post-partum period in women with gestational diabetes (GDM), independent of post-partum weight change (PWC). MATERIALS AND METHODS: In this multicentre prospective study, we included Japanese women with GDM who underwent a 75-g oral glucose tolerance test (OGTT) during early post-partum. We measured plasma insulin during OGTT to obtain a homeostasis model of assessment of insulin resistance (HOMA-IR). We defined the condition in which infants were fed by breastfeeding alone or greater than or equal to 80% of the volume as HIB, and other statuses, including partial and nonbreastfeeding, as non-HIB. We investigated the association between post-partum HOMA-IR and the breastfeeding status after adjusting for confounders including PWC. RESULTS: Among 222 women with GDM who underwent the OGTT at 7.9 ± 2.3 weeks post-partum with a PWC of -7.8 ± 3.4 kg, although the rate of abnormal glucose tolerance (prediabetes and diabetes) did not differ between the groups (33% vs 32%), the HOMA-IR in the HIB women (n = 166) was significantly lower than that in the non-HIB women (n = 56) (1.12 ± 0.85 vs 1.72 ± 1.43, P = 0.0002). The effect of the HIB was independently associated with lower HOMA-IR after adjusting for confounders including PMC. However, the subgroup analysis according to their pre-pregnancy obesity states showed that the effect was seen only in the obese subjects (BMI ≥ 25). CONCLUSIONS: In obese Japanese women with GDM, HIB has a significant effect in reducing insulin resistance during early post-partum, independent of the post-partum weight loss.

Type 1 Diabetes Mellitus Diagnosed during Follow-up of Gestational Diabetes Mellitus in the Early Postpartum Period.

A 27-year-old woman with a history of gestational diabetes mellitus (GDM) developed type 1 diabetes mellitus (T1D) in the early postpartum period. Women with a history of GDM are at an increased risk of developing T1D, which is rarer than type 2 diabetes mellitus. A postpartum follow-up 75-g oral glucose tolerance test and the measurement of glutamic acid decarboxylase autoantibodies aided in the early detection of T1D in this patient. Careful attention should be paid to women with a history of GDM who exhibit clinical features suggestive of future development of T1D.

Risk factors associated with the development of postpartum diabetes in Japanese women with gestational diabetes.

BACKGROUND: Although the onset of gestational diabetes (GDM) is known to be a significant risk factor for the future development of type 2 diabetes, this risk specifically in women with GDM diagnosed by the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria has not yet been thoroughly investigated. This study was performed to investigate the risk factors associated with the development of postpartum diabetes in Japanese women with a history of GDM, and the effects of the differences in the previous Japanese criteria and the IADPSG criteria. METHODS: This retrospective cohort study included Japanese women with GDM who underwent at least one postpartum oral glucose tolerance test (OGTT) between 2003 and 2014. Cases with overt diabetes in pregnancy were excluded. We investigated the risk factors including maternal baseline and pregnancy characteristics associated with the development of postpartum diabetes. RESULTS: Among 354 women diagnosed with GDM during the study period, 306 (86%) (116/136 [85.3%] and 190/218 [87.2%] under the previous criteria and the IADPSG criteria, respectively) who underwent at least 1 follow-up OGTT were included in the study. Thirty-two women (10.1%) developed diabetes within a median follow-up period of 57 weeks (range, 6-292 weeks). Eleven (9.5%) and 21 (11.1%) were diagnosed as GDM during pregnancy based on the previous Japanese criteria and the IADPSG criteria, respectively, which did not significantly differ between those criteria. A multivariate logistic regression analysis revealed that HbA1c and 2-h plasma glucose (PG) at the time of the diagnostic OGTT during pregnancy were independent predictors of the development of diabetes after adjusting for confounders. The adjusted relative risk of HbA1c ≥5.6% for the development of diabetes was 4.67 (95% confidence interval, 1.53-16.73), while that of 2-h PG ≥183 mg/dl was 7.02 (2.51-20.72). CONCLUSIONS: A modest elevation of the HbA1c and 2-h PG values at the time of the diagnosis of GDM during pregnancy are independent predictors of the development of diabetes during the postpartum period in Japanese women with a history of GDM. The diagnostic criteria did not affect the incidence of postpartum diabetes.

Factors associated with patients with gestational diabetes in Japan being at increased risk of requiring intensive care.

OBJECTIVE: To investigate factors associated with high-risk gestational diabetes (GDM) among patients with GDM. METHODS: The present retrospective study included women with singleton pregnancies diagnosed with GDM using International Association of Diabetes and Pregnancy Study Group criteria at a single tertiary perinatal care center in Japan between July 1, 2010, and October 31, 2014. High-risk GDM was defined as patients who required at least 20 units of insulin therapy a day, delivering a large-for-gestational age neonate regardless of insulin therapy, or both. Maternal characteristics and diagnostic test results were investigated to identify associations with the high-risk criteria, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS: Among 217 patients, 95 (43.8%) were categorized as high risk. After adjusting for confounders, a fasting plasma glucose level at diagnosis of at least 4.66 mmol/L (adjusted OR 2.88, 95% CI 1.51-5.58) and pre-pregnancy body mass index (calculated as weight in kilograms divided by the square of height in meters) of at least 24 (adjusted OR 3.27, 95% CI 1.60-6.90) were independently associated with meeting the high-risk criteria. CONCLUSION: Among Japanese patients with GDM, pre-pregnancy body mass index and fasting plasma glucose levels could be used to identify high-risk patients requiring intensive care during pregnancy.

The Routine Use of Prophylactic Oxytocin in the Third Stage of Labor to Reduce Maternal Blood Loss.

OBJECTIVE: To demonstrate whether or not the routine use of prophylactic oxytocin (RUPO) reduces the blood loss and incidence of postpartum hemorrhaging (PPH). METHODS: We used a prospective cohort and a historical control in a tertiary perinatal care center in Japan. In the prospective cohort, we introduced RUPO in April 2012 by infusing 10 units of oxytocin per 500 mL of normal saline into a venous line after anterior shoulder delivery (RUPO group). In the historical control, oxytocin was administered via a case-selective approach (historical control group). We included completed singleton vaginal deliveries and compared the volume of blood loss and the incidence of PPH between the groups. RESULTS: We found a significantly lower volume of blood loss (520 ± 327 versus 641 ± 375 mL, p < 0.001) and a lower incidence of PPH (6.1% versus 14.0%, p < 0.001) in the RUPO group (n = 392) than in the control group (n = 407). Although the oxytocin dose was significantly higher in the RUPO group (12.8 ± 6.7 versus 10.1 ± 8.0 IU, p < 0.001), no adverse outcomes were observed to be associated with RUPO. CONCLUSIONS: The introduction of RUPO significantly reduced blood loss and the incidence of PPH during completed singleton vaginal deliveries without an increase in adverse effects.

The effect of high-intensity breastfeeding on postpartum glucose tolerance in women with recent gestational diabetes.

BACKGROUND: Although breastfeeding is expected to reduce the incidence of diabetes in women with gestational diabetes, the effect has not been clearly confirmed. We examined whether or not high-intensity breastfeeding reduces the incidence of abnormal glucose tolerance and investigated the effect of high-intensity breastfeeding on insulin resistance during the first year postpartum in Japanese women with current gestational diabetes. METHODS: In this retrospective study, we included women with gestational diabetes who underwent postpartum 75 g oral glucose tolerance test during the first year (12-14 months) postpartum from 2009 to 2011 at a single tertiary perinatal care center in Japan. High-intensity breastfeeding was defined as the condition in which infants were fed by breastfeeding alone or 80% or more of the volume. We investigated the effect of high-intensity breastfeeding on the prevalence of postpartum abnormal glucose tolerance and the postpartum homeostasis model of assessment of insulin resistance (HOMA-IR), after controlling for confounders, including prepregnancy obesity and weight changes during pregnancy and postpartum. RESULTS: Among 88 women with gestational diabetes, 46 (52%) had abnormal glucose tolerance during the postpartum period. High-intensity breastfeeding women (n = 70) were significantly less likely to have abnormal glucose tolerance than non-high-intensity breastfeeding women (n = 18) (46% vs. 78%, p = 0.015). High-intensity breastfeeding was also associated with a lower HOMA-IR at 12-14 months postpartum than non-high-intensity breastfeeding (1.41 ± 1.02 vs. 2.28 ± 1.05, p = 0.035). Those associations remained significant after controlling for confounders. At least six months of high-intensity breastfeeding had a significant effect on lowering both the abnormal glucose tolerance prevalence and HOMA-IR compared with non-high-intensity breastfeeding. CONCLUSIONS: In Japanese women with gestational diabetes, high-intensity breastfeeding ≥6 months had a protective effect against the development of abnormal glucose tolerance during the first year postpartum through improving insulin resistance, independent of obesity and postpartum weight change.

Potential protective effect of lactation against incidence of type 2 diabetes mellitus in women with previous gestational diabetes mellitus: A systematic review and meta-analysis.

Lactation may protect women with previous gestational diabetes mellitus (GDM) from developing type 2 diabetes mellitus, but the results of existing studies are inconsistent, ranging from null to beneficial. We aimed to conduct a systematic review to gather available evidence. Databases MEDLINE, CINAHL, PubMed, and EMBASE were searched on December 15, 2015, without restriction of language or publication year. A manual search was also conducted. We included observational studies (cross-sectional, case-control, and cohort study) with information on lactation and type 2 diabetes mellitus incidence among women with previous GDM. We excluded case studies without control data. Data synthesis was conducted by random-effect meta-analysis. Fourteen reports of 9 studies were included. Overall risk of bias using RoBANS ranged from low to unclear. Longer lactation for more than 4 to 12 weeks postpartum had risk reduction of type 2 diabetes mellitus compared with shorter lactation (OR 0.77, 95% CI 0.01-55.86; OR 0.56, 95% CI 0.35-0.89; OR 0.22, 95% CI 0.13-0.36; type 2 diabetes mellitus evaluation time < 2 y, 2-5 y, and >5 y, respectively). Exclusive lactation for more than 6 to 9 weeks postpartum also had lower risk of type 2 diabetes mellitus compared with exclusive formula (OR 0.42, 95% CI 0.22-0.81). The findings support the evidence that longer and exclusive lactation may be beneficial for type 2 diabetes mellitus prevention in women with previous GDM. However, the evidence relies only on observational studies. Therefore, further studies are required to address the true causal effect.

Influence of the interval between antenatal corticosteroid therapy and delivery on respiratory distress syndrome.

AIM: In spite of the recommendation for rescue antenatal corticosteroids (ACS), the optimal time interval between primary and rescue courses has not been clearly demonstrated. The aim of this study was to determine the effects of the interval between a single ACS course and delivery on the incidence of respiratory distress syndrome (RDS). METHODS: In this retrospective study, we included singleton pregnant women who received a single course of ACS and delivered beyond 48 h after ACS administration between 24 and 33 weeks' gestation. The risk of RDS was compared between patients who delivered within seven days (Group I), 7-14 days (Group II) and beyond 14 days (Group III) after ACS administration. RESULTS: We included 83, 14 and 20 patients in Groups I, II and III, respectively. After adjusting for confounders, the ACS delivery interval was significantly associated with RDS in Group II (adjusted odds ratio 12.8, 95% confidence interval 1.31-164.7) and Group III (adjusted odds ratio 64.0, 95% confidence interval 1.32-5808.6). CONCLUSION: A longer ACS delivery interval is associated with a higher risk of RDS. Thus, the use of a rescue course could be expected to reduce the incidence of RDS in patients beyond seven days after ACS administration who remain at risk for preterm delivery within seven days, especially in cases of placenta previa and/or women bearing a male fetus.

Risk factors associated with respiratory disorders in late preterm infants.

OBJECTIVE: Late preterm infants are still high risk for respiratory problems. The aim of this study was to identify risk factors associated with respiratory problems in Japanese late preterm infants. METHODS: In this retrospective multicenter study, we included singleton late preterm deliveries at 34+(0/7)-36+(6/7) weeks of gestation. We excluded cases with congenital anomalies. We defined neonatal respiratory disorders (NRD) as the combination of the need for mechanical ventilation or the use of nasal continuous positive airway pressure. We examined the perinatal risk factors associated with NRD. RESULTS: We included 683 late preterm infants. We found that 13.7%, 6.8% and 2.6% of the infants with NRD were born at 34, 35 and 36 weeks of gestation, respectively. In a multivariate logistic regression analysis adjusting for confounders, the gestational age (GA) at birth (adjusted odds ratio 0.40 per week [95% confidence interval, 0.25-0.61]), cesarean birth (4.18 [2.11-8.84]), and a low Apgar score (33.3 [9.93-121.3]) were independent risk factors associated with NRD. CONCLUSIONS: An earlier GA, cesarean delivery, and a low Apgar score are independent risk factors associated with NRD in singleton late preterm infants. Patients with late preterm deliveries exhibiting these risk factors should be managed in the intensive delivery setting.