Antenatal prediction models for outcomes of extremely and very preterm infants based on machine learning.

PURPOSE: Predicting individual risks for adverse outcomes in preterm infants is necessary for perinatal management and antenatal counseling for their parents. To evaluate whether a machine learning approach can improve the prediction of severe infant outcomes beyond the performance of conventional logistic models, and to identify maternal and fetal factors that largely contribute to these outcomes. METHODS: A population-based retrospective study was performed using clinical data of 31,157 infants born at < 32 weeks of gestation and weighing ≤ 1500 g, registered in the Neonatal Research Network of Japan between 2006 and 2015. We developed a conventional logistic model and 6 types of machine learning models based on 12 maternal and fetal factors. Discriminative ability was evaluated using the area under the receiver operating characteristic curves (AUROCs), and the importance of each factor in terms of its contribution to outcomes was evaluated using the SHAP (SHapley Additive exPlanations) value. RESULTS: The AUROCs of the most discriminative machine learning models were better than those of the conventional models for all outcomes. The AUROCs for in-hospital death and short-term adverse outcomes in the gradient boosting decision tree were significantly higher than those in the conventional model (p = 0.015 and p = 0.002, respectively). The SHAP value analyses showed that gestational age, birth weight, and antenatal corticosteroid treatment were the three most important factors associated with severe infant outcomes. CONCLUSION: Machine learning models improve the prediction of severe infant outcomes. Moreover, the machine learning approach provides insight into the potential risk factors for severe infant outcomes.

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.

Impact of hypertensive disorders of pregnancy on respiratory outcomes in extremely and very preterm infants: A population-based study in Japan.

OBJECTIVES: We aimed to evaluate the impact of hypertensive disorders of pregnancy (HDP) on short- and medium-term respiratory outcomes in extremely and very preterm infants using the Neonatal Research Network of Japan database. STUDY DESIGN: This was a population-based retrospective study of preterm infants weighing ≤ 1500 g born between 22 and 31 weeks of gestation between 2003 and 2017. After 1:1 stratification matching by four factors (maternal age, gestational age, parity, and year of delivery), a total of 5137 infants in each group (HDP and non-HDP groups) were selected. MAIN OUTCOME MEASURES: The association between HDP and various respiratory outcomes was evaluated using univariate and multivariate logistic regression analyses. RESULTS: In the multivariate analyses, HDP was associated with higher odds for respiratory distress syndrome (RDS) (odds ratio 1.83, 95% confidence interval [1.65-2.03]), but reduced odds of persistent pulmonary hypertension of the newborn (PPHN) (0.34 [0.26-0.46]) and inhaled nitric oxide use (0.43 [0.33-0.55]). Although HDP was associated with an increased risk of chronic lung disease (CLD) in the univariate analysis, this association was not significant after adjustment for covariates (0.94 [0.83-1.07]). No significant association was found between HDP and home oxygen therapy (HOT) and medium-term oxygen use. CONCLUSION: The impact of maternal HDP largely differed depending on respiratory disorders and respiratory support. HDP was associated with higher odds of RDS but reduced odds of PPHN. The risks for CLD, HOT, and medium-term respiratory outcomes in the HDP group were comparable to those in the non-HDP group.

Pregnancy Outcomes in Women with Thyroid Diseases.

Introduction: Overt hyperthyroidism and hypothyroidism are associated with pregnancy complications; however, most women with these conditions are diagnosed before conception and are under treatment during pregnancy, especially in high-income countries. The purpose of this study was to investigate pregnancy complications among these women. Methods: A retrospective cohort study was conducted, and data on pregnant women who gave birth to a singleton at Nagoya University Hospital in Japan in 2005-2014 was collected. The pregnancy outcomes were divided and compared among three groups: the control group (n = 3531), the hyperthyroidism group (n = 48), and the hypothyroidism group (n = 61). Additionally, risk factors for placental abruption were evaluated by multivariable logistic regression analysis. Moreover, in hyperthyroidism, thyroid function at the placentation period was compared between placental-related diseases and nonplacental-related disease groups, and the latter group included placental abruption and preeclampsia. Results: The incidence of placental abruption was higher in hyperthyroidism than in control and hypothyroidism groups. Hyperthyroidism was independently associated with an increased risk of placental abruption (adjusted odds ratio, aOR = 8.21, 95% confidence interval, CI: 1.76-38.34), as well as preeclampsia (aOR = 4.10, 95% CI: 1.13-14.76) and preterm labor (aOR = 3.38, 95% CI: 1.19-9.64). Additionally, thyroid-stimulating hormone (TSH) at the placentation period was significantly lower in the placental-related disease group than in the nonplacental-related disease group (p < 0.05). Conclusions: Pregnancy outcomes in women with hyperthyroidism and hypothyroidism would be comparable with those without thyroid disease. Hyperthyroidism was an independent risk factor for placental abruption as well as preterm labor and preeclampsia. However, its frequency was extremely low, and further research is required to validate our findings.

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.

Intrauterine exposure to hypertensive disorders of pregnancy and postnatal growth in extremely and very preterm infants.

OBJECTIVES: There is growing evidence regarding the association between rapid growth during infancy and metabolic and cardiovascular diseases later in life. We aimed to evaluate postnatal growth trajectories in extremely and very preterm infants exposed to hypertensive disorders of pregnancy (HDP) in utero. STUDY DESIGN: This multicenter retrospective study used a nationwide database of preterm infants weighing ≤1,500 g born between 22 and 31 weeks of gestation between 2003 and 2015. MAIN OUTCOME MEASURES: The Z-scores for height and weight were evaluated at three time points (at birth, corrected age of 1.5 years, and chronological age of 3 years) in 5,144 infants (HDP, n = 1,188; non-HDP, n = 3,956). Univariate and multivariate regression analyses were performed to investigate the associations between HDP exposure and accelerated postnatal growth. RESULTS: Male and female infants in the HDP group showed increased mean Z-scores for height and weight, whereas those in the non-HDP group showed decreased mean Z-scores. Multivariate analyses showed that HDP were associated with accelerated postnatal growth (Δ Z-scores) in weight in both male and female infants (ß coefficient [95% CI]; male 0.17 [0.05-0.30], female 0.27 [0.14-0.39]), but not in height (male 0.02 [-0.09 to 0.13], female 0.04 [-0.06 to 0.15]). An interaction analysis revealed no significant differences in the effects of HDP on postnatal growth between male and female infants. CONCLUSIONS: Intrauterine exposure to HDP contributes to accelerated postnatal weight growth in extremely and very preterm infants during early childhood. In addition, no sex differences were observed in postnatal growth.

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.

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.

Assessment of placental abruption with diffusion-weighted imaging.

AIM: To investigate whether placental abruption without fetal distress could be assessed by apparent diffusion coefficient (ADC) values in magnetic resonance imaging (MRI). METHODS: We conducted a retrospective case-control study at a single center. ADC values at the lesions of placental abruption in the abruption group (n = 8) were compared to those in the control group (n = 32). In the abruption group, ADC values at the sites of abruption were also compared to those at the nonabruption sites within the same placenta. RESULTS: The ADC values in the placental area above the abruption site in the abruption group showed lower values than those in the control group when the slice containing the umbilical cord insertion site was set as the reference, and those values were compared in each corresponding slice. Compared with average ADC values, those above the abruption site in the abruption group were also significantly lower than those in the control group (p < 0.001). Furthermore, ADC values at the area above abruption were lower than those at the nonabruption area of all planes in the abruption group. CONCLUSIONS: ADC values at the lesions above the placental abruption site were reduced compared to those in the normal placenta and those in the nonabruption area. Thus, it would be helpful to understand the pathophysiology of placental abruption in expectant management, although further investigations would be needed.

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.

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.

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.

Hypertensive disorders of pregnancy and alterations in brain metabolites in preterm infants: A multi-voxel proton MR spectroscopy study.

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.

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.

Prenatal Molecular Hydrogen Administration Ameliorates Several Findings in Nitrofen-Induced Congenital Diaphragmatic Hernia.

Oxidative stress plays a pathological role in pulmonary hypoplasia and pulmonary hypertension in congenital diaphragmatic hernia (CDH). This study investigated the effect of molecular hydrogen (H2), an antioxidant, on CDH pathology induced by nitrofen. Sprague-Dawley rats were divided into three groups: control, CDH, and CDH + hydrogen-rich water (HW). Pregnant dams of CDH + HW pups were orally administered HW from embryonic day 10 until parturition. Gasometric evaluation and histological, immunohistochemical, and real-time polymerase chain reaction analyses were performed. Gasometric results (pH, pO2, and pCO2 levels) were better in the CDH + HW group than in the CDH group. The CDH + HW group showed amelioration of alveolarization and pulmonary artery remodeling compared with the CDH group. Oxidative stress (8-hydroxy-2'-deoxyguanosine-positive-cell score) in the pulmonary arteries and mRNA levels of protein-containing pulmonary surfactant that protects against pulmonary collapse (surfactant protein A) were significantly attenuated in the CDH + HW group compared with the CDH group. Overall, prenatal H2 administration improved respiratory function by attenuating lung morphology and pulmonary artery thickening in CDH rat models. Thus, H2 administration in pregnant women with diagnosed fetal CDH might be a novel antenatal intervention strategy to reduce newborn mortality due to CDH.

Impact of maternal hypertensive disorders of pregnancy on brain volumes at term-equivalent age in preterm infants: A voxel-based morphometry study.

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.

Postpartum alterations following inflammation in rat pregnancy: a discovery proteomic analysis.

Women with a history of preeclampsia have an increased risk of subsequent cardiovascular and metabolic disease. While aberrant inflammation during pregnancy is associated with the development of preeclampsia, whether maternal inflammation increases the risk of disease later in life is unclear. Using a rat model we determined whether aberrant inflammation in pregnancy alters the levels of plasma proteins associated with cardiovascular and metabolic disease risk in the postpartum period. Pregnant rats were administered lipopolysaccharide (LPS) or saline on gestational days 13.5-16.5 to induce inflammation. Non-pregnant controls consisted of age-matched female rats subjected to similar administration of LPS or saline. Examination of the proteomic profile of plasma collected 16 weeks after delivery or from non-pregnant controls using liquid chromatography-tandem mass spectrometry revealed 100 differentially expressed proteins. Moreover, we identified 188 proteins in pregnant rats, of which 49 were differentially expressed in saline- vs LPS-treated dams. Of the 49 proteins regulated by LPS, 28 were pregnancy specific. PANTHER classification software, DAVID database and Ingenuity Pathways analysis revealed that the differentially expressed proteins in pregnant saline vs LPS-treated rats are associated with alterations in lipid and glucose metabolism and atherosclerosis, all of which may contribute to cardiovascular and metabolic disease risk. Results from proteomic and pathway analyses were validated by immunoassay of three serum proteins selected a priori and by assessment of serum metabolites. This discovery study demonstrates that aberrant inflammation during pregnancy results in long-lasting postpartum physiological alterations known to be associated with metabolic and cardiovascular disease.

Trisomy 5p with bilateral congenital diaphragmatic hernia: a case report.

BACKGROUND: Bilateral congenital diaphragmatic hernia (CDH) is very rare. A few studies have reported the pathogenic role of 5p in CDH. CASE PRESENTATION: A 23-year-old primigravida Japanese woman was referred for the following abnormal findings at 33 weeks of gestation: polyhydramnios, macroglossia, talipes equinovarus, and levocardia. A marker chromosome was detected by amniocentesis. Fluorescence in situ hybridization with whole chromosome paint 5 and nucleolus organizer region probes confirmed its origin from chromosome 5 and an acrocentric chromosome. The karyotype of the fetus was diagnosed as 47, XY, +mar. ish +mar(WCP5+). At 39 + 5 weeks, a 2462 g male infant was delivered, with a specific facial configuration. Bilateral CDH, hypoplasia of the corpus callosum, atrial septal defect, and hypothyroidism were also detected in the baby. The karyotype of the peripheral blood was consistent with that of the amniocentesis. CONCLUSION: Genes coded on 5p might be associated with the pathogenesis of CDH; however, further investigation is required.

Antenatal prediction models for short- and medium-term outcomes in preterm infants.

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 relatively good. We provided a bedside prediction tool for calculating the likelihood of various infant complications for clinical use. To develop these prediction models would be valuable in each country, and these risk assessment tools could facilitate risk-stratified perinatal management and parents' shared understanding of their infants' subsequent risks.