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Introduction: In extremely and very preterm infants, predicting individual risks for adverse outcomes antenatally is challenging but necessary for risk-stratified perinatal management and parents’ participation in decision-making about treatment. Our aim was to develop and validate prediction models for short-term (neonatal period) and medium-term (3 years of age) outcomes based on antenatal maternal and fetal factors alone. Material and methods: A population-based study was conducted on 31 157 neonates weighing ≤1500 g and born between 22 and 31 weeks of gestation registered in the Neonatal Research Network of Japan during 2006–2015. Short-term outcomes were assessed in 31 157 infants and medium-term outcomes were assessed in 13 751 infants among the 31 157 infants. The clinical data were randomly divided into training and validation data sets in a ratio of 2:1. The prediction models were developed by factors selected using stepwise logistic regression from 12 antenatal maternal and fetal factors with the training data set. The number of factors incorporated into the model varied from 3 to 10, on the basis of each outcome. To evaluate predictive performance, the area under the receiver operating characteristics curve (AUROC) was calculated for each outcome with the validation data set. Results: Among short-term outcomes, AUROCs for in-hospital death, chronic lung disease, intraventricular hemorrhage (grade III or IV) and periventricular leukomalacia were 0.85 (95% CI 0.83–0.86), 0.80 (95% CI 0.79–0.81), 0.78 (95% CI 0.75–0.80), and 0.58 (95% CI 0.55–0.61), respectively. Among medium-term outcomes, AUROCs for cerebral palsy and developmental quotient of <70 at 3 years of age were 0.66 (95% CI 0.63–0.69) and 0.72 (95% CI 0.70–0.74), respectively. Conclusions: Although the predictive performance of these models varied for each outcome, their discriminative ability for in-hospital death, chronic lung disease, and intraventricular hemorrhage (grade III or IV) was relati

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.

Objectives: To determine the trajectories of platelet counts and the prevalence of gestational thrombocytopenia (<150 × 10^9/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.

Objectives: Infants born to mothers with hypertensive disorders of pregnancy (HDP) reportedly have negative behavioral and neurodevelopmental outcomes. However, the effects of maternal HDP on infant brain growth have not been fully evaluated. We aimed to evaluate brain volumes and brain injury in preterm infants born to mothers with HDP using magnetic resonance (MR) imaging at term-equivalent age. Study design: In this cohort study, MR imaging was performed for 94 preterm infants born before 34 weeks of gestation at Nagoya University Hospital between 2010 and 2018. Twenty infants were born to mothers with HDP and 74 to mothers without HDP. Main outcome measures: Total brain volumes and regional volumetric alterations were assessed by voxel-based morphometry, and brain injury was evaluated using the Kidokoro global brain abnormality score. Developmental quotient was assessed at a corrected age of 1.5 years in 59 infants (HDP, n = 11; non-HDP, n = 48). Results: No significant differences were observed in the gray and white matter volumes of the two groups (HDP: 175 ± 24 mL, 137 ± 13 mL, respectively; non-HDP: 172 ± 24 mL, 142 ± 13 mL, respectively). Additionally, no regional volumetric alterations were observed between the two groups after covariate adjustment (gestational age and infant sex). The total Kidokoro score and developmental quotient were similar in both groups. Conclusions: No significant differences in the global and regional brain volumes were observed. Further research is needed to confirm our findings at different time points of MR imaging and in different populations.

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.

Background: Infants born to mothers with hypertensive disorders of pregnancy (HDP) have adverse neurodevelopmental consequences in later life. Magnetic resonance spectroscopy (MRS) is used to predict subsequent neurodevelopment in the field of perinatology. Aim: We aimed to determine whether exposure to HDP in utero leads to alterations in brain metabolites in preterm infants using multi-voxel proton MRS at term-equivalent age. Study design: Retrospective cohort study. Subjects: A total of 103 preterm infants born before 34 weeks of gestation at Nagoya University Hospital between 2010 and 2018 were eligible. Twenty-seven infants were born to mothers with HDP (HDP group), and 76 were born to mothers without HDP (non-HDP group). Outcome measures: The peak area ratios of N-acetylaspartate (NAA)/choline (Cho), NAA/creatine (Cr), and Cho/Cr were evaluated at 10 designated regions of interest (bilateral frontal lobes, basal ganglia, thalami, temporal lobes, and occipital lobes). Results: The peak area ratios of NAA/Cho and NAA/Cr in the bilateral thalami were significantly higher in the HDP group than in the non-HDP group after adjustment for covariates (postmenstrual age at MRS assessment and infant sex). No significant differences were observed in other regions. Preeclampsia, abnormal umbilical artery blood flow, and fetal growth restrictions were significantly associated with increased NAA/Cho and NAA/Cr ratios in the thalami. Conclusions: Based on the evidence that NAA/Cho and NAA/Cr ratios constantly increase with postmenstrual age in normal brain development, exposure to maternal HDP in utero may accelerate brain maturation and increase neuronal activity in preterm infants.

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.

Background: Shellfish allergy is one of the most common food allergies. Recent studies have shown that sensitization to allergens via the skin is involved in the development of food allergies. In this study, a mouse model of shrimp allergy was generated by epicutaneous sensitization and used to identify skin conditions associated with susceptibility to sensitization. Methods: Four-week-old female BALB/c mice were sensitized by repeated application of 0.1 mg of tropomyosin to tape-stripped skin on days 0, 7, and 15, followed by a challenge on days 28 and 35. Results: Epicutaneously sensitized mice exhibited higher serum levels of tropomyosin-specific IgE on day 15 than control mice. After the oral challenge, model mice had higher anaphylaxis scores and lower rectal temperature. After three tape-strip treatments for sensitization, the skin was analyzed by Raman microscopy. The sensitized mice exhibited lower relative intensities of Raman bands at 399, 915, and 1073 cm−1 than control mice, which could be helpful noninvasive markers in screening for potential sensitization via the skin. Conclusions: An epicutaneous sensitization shellfish allergy model was generated. This model will be useful in studies to elucidate the pathogenesis of skin sensitization. Raman microscopy may also be valuable for capturing subtle skin changes leading to sensitization.

Intravesical immunotherapy using bacillus Calmette‑Guérin (BCG) is recommended for patients with intermediate‑ to high‑risk non‑muscle invasive bladder cancer. Bladder tuberculosis (TB) is a rare complication of BCG therapy. The present study describes the case of a 73‑year‑old man who underwent intravesical BCG therapy for urothelial carcinoma in situ of the bladder. Red patches around the resection scar were first detected 1 year and 5 months after BCG treatment; these findings gradually spread to encompass more of the bladder wall. Transurethral biopsy revealed a benign lesion, but the patient developed bilateral hydronephrosis and mild voiding dysfunction. The patient was eventually diagnosed with bladder TB by mycobacterial urine culture and TB‑specific polymerase chain reaction (PCR). The patient was given multidrug therapy (isoniazid, rifampicin and ethambutol) and their bladder TB was completely cured; however, their voiding dysfunction and bilateral hydronephrosis did not fully improve. Bladder TB can occur long after intravesical BCG administration and cystoscopy findings consistent with inflammation can be the key to suspecting this condition. Acid‑fast examination and PCR testing of a urine sample are necessary for early diagnosis.