Maternal insulin resistance in pregnancy is associated with fetal fat deposition: findings from a longitudinal study.

BACKGROUND: Newborns exhibit substantial variation in fat mass accretion over gestation. These individual differences in newborn adiposity extend into infancy and childhood and relate to subsequent risk of obesity and metabolic dysregulation. Maternal glucose homeostasis in pregnancy has been proposed as an underlying mechanism; however, the timing in gestation when maternal glucose regulation influences the progression of fetal fat deposition remain unclear. OBJECTIVE: This study aimed to investigate the cross-sectional and longitudinal association of maternal insulin resistance in early, mid, and late pregnancy with fetal fat deposition in uncomplicated pregnancies. We hypothesized that maternal insulin resistance at early, mid, and late gestation is positively associated with fetal fat deposition, and that the magnitude of the association is greater for the mid and late gestation measures than for the early gestation measure. STUDY DESIGN: In a longitudinal study of 137 low-risk pregnancies, a fasting maternal blood sample was obtained and fetal ultrasonography was performed at ≈ 12, 20, and 30 weeks' gestation. Maternal insulin resistance was quantified using the homeostasis model assessment of insulin resistance (fasting insulin×fasting glucose/405). Estimated fetal adiposity was calculated by integrating measurements of cross-sectional arm and thigh percentage fat area and anterior abdominal wall thickness. The associations between maternal homeostasis model assessment of insulin resistance and estimated fetal adiposity and estimated fetal weight were determined by multiple linear regression adjusted for potential confounding factors including maternal age, parity, race and ethnicity, prepregnancy body mass index, gestational weight gain per week, fetal sex, and gestational age at assessments. RESULTS: Maternal homeostasis model assessment of insulin resistance at ≈ 12, 20, and 30 weeks was 2.79±1.79 (±standard deviation), 2.78±1.54, and 3.76±2.30, respectively. Homeostasis model assessment of insulin resistance at 20 weeks was positively associated with estimated fetal adiposity at 20 weeks (r=0.261; P=.005). Homeostasis model assessment of insulin resistance at 20 weeks (r=0.215; P=.011) and 30 weeks (r=0.285; P=.001) were also positively associated with estimated fetal adiposity at 30 weeks. These relationships remained significant after adjustment for confounding factors. There was no significant correlation between homeostasis model assessment of insulin resistance and estimated fetal weight at 20 and 30 weeks' gestation. CONCLUSION: In low-risk pregnancies, maternal insulin resistance at mid and late but not early pregnancy is significantly associated with fetal adiposity but not with fetal weight. Maternal insulin resistance in mid-gestation could provide a basis for risk identification and interventions that target child adiposity.

Fetal heart rate patterns complicated by chorioamnionitis and subsequent cerebral palsy in Japan.

AIM: This retrospective study was performed to investigate whether certain fetal heart rate patterns were associated with subsequent cerebral palsy (CP) in infants with chorioamnionitis at or near term. METHODS: We used cases registered by the Japan Obstetric Compensation System for CP, which is a nationwide population-based database. Among them, 133 infants with chorioamnionitis who were born at ≥34 weeks of gestation were enrolled. All infants underwent magnetic resonance imaging (MRI), and all fetal heart rate charts had been interpreted according to the National Institute of Child Health and Human Development criteria, focusing on antepartum and immediately before delivery. RESULTS: The incidence of CP after chorioamnionitis at ≥34 weeks of gestation was 0.3 per 10 000 in Japan. Between the clinical (24%) and subclinical groups (76%), the incidence of abnormal fetal heart rate patterns did not differ. According to the MRI classification, 88% of the infants with CP showed hypoxic-ischemic encephalopathy. Half of the infants with CP experienced terminal bradycardia, leading to severe acidosis and exclusively to hypoxic-ischemic encephalopathy. In another half, who did not experience bradycardia, 80% had moderate acidosis (pH 7.00-7.20) resulting in hypoxic-ischemic encephalopathy, and the remaining 20% showed non-acidosis resulting in brain damage other than hypoxic-ischemic encephalopathy. The fetal heart rate patterns before the terminal bradycardia showed that the incidence rates of late deceleration or decreased variability were high (>60%). CONCLUSION: Fifty percent of pregnant women with chorioamnionitis-related CP had terminal bradycardia that exclusively resulted in hypoxic-ischemic encephalopathy.

Establishment of a new practical telesurgical platform using the hinotori™ Surgical Robot System: a preclinical study.

AIM: The recent development of new surgical robots and network telecommunication technology has opened new avenues for robotic telesurgery. Although a few gastroenterological surgeries have been performed in the telesurgery setting, more technically demanding procedures including gastrectomy with D2 lymphadenectomy and intracorporeal anastomosis have never been reported. We examined the feasibility of telesurgical robotic gastrectomy using the hinotori™ Surgical Robot System in a preclinical setting. METHODS: First, the suturing time in the dry model was measured in the virtual telesurgery setting to determine the latency time threshold. Second, a surgeon cockpit and a patient unit were installed at Okazaki Medical Center and Fujita Health University, respectively (approximately 30 km apart), and connected using a 10-Gbps leased optic-fiber network. After evaluating the feasibility in the dry gastrectomy model, robotic distal gastrectomies with D2 lymphadenectomy and intracorporeal B-I anastomosis were performed in two porcine models. RESULTS: The virtual telesurgery study identified a latency time threshold of 125 ms. In the actual telesurgery setting, the latency time was 27 ms, including a 2-ms telecommunication network delay and a 25-ms local information process delay. After verifying the feasibility of the operative procedures using a gastrectomy model, two telesurgical gastrectomies were successfully completed without any unexpected events. No fluctuation was observed across the actual telesurgeries. CONCLUSION: Short-distance telesurgical robotic surgery for technically more demanding procedure may be safely conducted using the hinotori Surgical Robot System connected by high-speed optic-fiber communication.

Potential Usefulness of Tracking Head Movement via a Wearable Device for Equilibrium Function Testing at Home.

Many studies have reported the use of wearable devices to acquire biological data for the diagnosis and treatment of various diseases. Balance dysfunction, however, is difficult to evaluate in real time because the equilibrium function is conventionally examined using a stabilometer installed on the ground. Here, we used a wearable accelerometer that measures head motion to evaluate balance and examined whether it performs comparably to a conventional stabilometer. We constructed a simplified physical head-feet model that simultaneously records "head" motion measured using an attached wearable accelerometer and center-of-gravity motion at the "feet", which is measured using an attached stabilometer. Total trajectory length (r = 0.818, p -false discovery rate [FDR] = 0.004) and outer peripheral area (r = 0.691, p -FDR = 0.026) values measured using the wearable device and stabilometer were significantly positively correlated. Root mean square area values were not significantly correlated with wearable device stabilometry but were comparable. These results indicate that wearable, widely available, non-medical devices may be used to assess balance outside the hospital setting, and new approaches for testing balance function should be considered.

Cerclage in surgically shortened uterine cervix and pregnancy outcome: A retrospective comparison between the abdominal and vaginal procedures.

BACKGROUND: Cerclage for uterine cervical incompetence can be performed by the transabdominal or transvaginal approach. Transabdominal cerclage (TAC) is indicated for women with a short cervix or a cervical laceration who are inapplicable to transvaginal cerclage (TVC). The larger the volume of tissue removed in cervical conization, the greater the rate of miscarriage or preterm delivery in the subsequent pregnancy. AIMS: The aim of this study was to compare TAC and TVC in post-cervical conization pregnancies. METHODS: A retrospective, two-group, comparative study was conducted involving subjects who underwent cervical cerclage (TAC, n = 14; TVC, n = 18) following cervical conization and who were cared for at the University of Miyazaki Hospital between 2008 and 2020. We compared study subject characteristics and outcomes between the two groups. Primary outcome was incidence of preterm labor <37 weeks of gestation between the two groups. RESULTS: The preoperative median cervical length was significantly shorter in the TAC group (20.0 mm) than in the TVC group (31.0 mm; p < 0.01). Preoperative vaginal discharge cultures positive for Gardnerella showed a tendency to be greater in the TAC group (p = 0.073). There was no significant difference in the preterm delivery rate < 37 weeks of gestation between TAC (1/14, 7.1%) and TVC (6/18, 33.3%) groups, p = 0.10. Noninferiority test using multiple regression analysis showed that TAC is not inferior to TVC regarding gestational age at delivery, even though cervical length of TAC was significantly shorter. CONCLUSION: Women who were inapplicable to TVC due to a short cervix still achieved an equivalent outcome with TAC.

Intrapartum fetal heart rate patterns and perinatal outcome in chorioamnionitis at or beyond 34 weeks of gestation.

AIM: To investigate intrapartum fetal heart rate (FHR) patterns in women with chorioamnionitis at or beyond 34 weeks of gestation in relation to neonatal outcome and to compare clinical and subclinical chorioamnionitis. METHODS: A retrospective questionnaire survey on deliveries during 2015 was conducted by the Perinatology Committee of the Japan Society of Obstetrics and Gynecology from 2016 to 2018. A total of 498 singleton births complicated by chorioamnionitis delivered at ≥34 weeks of gestation without major congenital malformations were included. The subjects were divided into clinical and subclinical chorioamnionitis groups based on Lencki's criteria. Poor perinatal outcome was defined as death or brain damage. We analyzed clinical features, FHR patterns in the last 2 h before delivery, gestational age, birthweight, Apgar score, umbilical arterial blood gas analysis, and infant's outcome. RESULTS: Incidence of chorioamnionitis at ≥34 weeks of gestation was 0.59% (522/87827). Clinical and subclinical chorioamnionitis comprised 240 and 258 cases, respectively. Abnormal FHR patterns (late deceleration or decreased baseline variability) were significantly associated with poor perinatal outcome. Combined late deceleration and decreased variability showed low positive predictive value (12.8%) and high negative predictive value (99.5%), and was significantly associated with long-term poor outcome in clinical chorioamnionitis only (odds ratio: 29.4, p < 0.01). Poor perinatal outcome showed no significant difference between the clinical and subclinical chorioamnionitis groups. CONCLUSIONS: Combined late deceleration and decreased variability could predict poor perinatal outcome in clinical chorioamnionitis. Poor perinatal outcome occurred in infants born to mothers with clinical and subclinical chorioamnionitis.

Placental Corticotrophin-Releasing Hormone is a Modulator of Fetal Liver Blood Perfusion.

CONTEXT: Variation in fetal liver blood flow influences fetal growth and postnatal body composition. Placental corticotrophin-releasing hormone has been implicated as a key mediator of placental-fetal perfusion. OBJECTIVE: To determine whether circulating levels of placental corticotrophin-releasing hormone across gestation are associated with variations in fetal liver blood flow. DESIGN: Prospective cohort study. METHODS: Fetal ultrasonography was performed at 30 weeks' gestation to characterize fetal liver blood flow (quantified by subtracting ductus venosus flow from umbilical vein flow). Placental corticotrophin-releasing hormone was measured in maternal circulation at approximately 12, 20, and 30 weeks' gestation. Multiple regression analysis was used to determine the proportion of variation in fetal liver blood flow explained by placental corticotrophin-releasing hormone. Covariates included maternal age, parity, pre-pregnancy body mass index, gestational weight gain, and fetal sex. RESULTS: A total of 79 uncomplicated singleton pregnancies were analyzed. Fetal liver blood flow was 68.4 ± 36.0 mL/min (mean ± SD). Placental corticotrophin-releasing hormone concentrations at 12, 20, and 30 weeks were 12.5 ± 8.1, 35.7 ± 24.5, and 247.9 ± 167.8 pg/mL, respectively. Placental corticotrophin-releasing hormone at 30 weeks, but not at 12 and 20 weeks, was significantly and positively associated with fetal liver blood flow at 30 weeks (r = 0.319; P = 0.004) and explained 10.4% of the variance in fetal liver blood flow. CONCLUSIONS: Placental corticotrophin-releasing hormone in late gestation is a possible modulator of fetal liver blood flow and may constitute a biochemical marker in clinical investigations of fetal growth and body composition.

Prenatal diagnosis of premature chromatid separation/mosaic variegated aneuploidy (PCS/MVA) syndrome.

Premature chromatid separation/mosaic variegated aneuploidy (PCS/MVA) syndrome is a rare genetic disorder. In this case report, we describe the prenatal diagnosis of PCS/MVA syndrome in a 24-year-old, gravida 1, para 1, woman who was referred to us in her second trimester due to fetal growth restriction and extreme microcephaly (-5.0 standard deviations). Amniocentesis and chromosomal analysis confirmed PCS in 80% of cultured fetal cells. PCS findings were positive in 9% of paternal cells and 11% of maternal cells, indicative that both were PCS carriers. Genetic analysis confirmed that the fetus carried a combined heterozygote of maternal G > A point mutation of the promoter area of the BUB1B gene and a paternal Alu sequence insertion between intron 8 and exon 9 of the BUB1B gene. As PCS/MVA syndrome is associated with the development of various malignancies in early life, prenatal diagnosis is important for effective planning of post-natal care.

Annual Report of the Perinatology Committee, Japan Society of Obstetrics and Gynecology, 2016: Overall report on a comprehensive retrospective study of obstetric management of preterm labor and preterm premature rupture of the membranes.

We conducted a questionnaire survey on the current obstetric management of preterm labor (PL) and preterm premature rupture of the membranes (pPROM). The questionnaire covered approximately a third of all preterm deliveries and nearly half of the preterm deliveries before 32 gestational weeks. The diagnostic criterion for PL was either painful uterine contractions or cervical dilatation. Tocolytic agents were primarily used as long-term maintenance therapy. Intrauterine infection was clinically diagnosed at most responding institutions. Amniocentesis was performed for PL or pPROM at only a small number (10%) of institutions. Prenatal steroids were administered for PL or pPROM, if indicated, at approximately 40-60% of responding institutions. Prophylactic antibiotics to maintain pregnancy were administered for pPROM at approximately 90% and for PL at approximately 20% of institutions. Maintenance therapy with a tocolytic agent was used for pPROM at approximately 90% of institutions.

PCS/MVA syndrome caused by an Alu insertion in the BUB1B gene.

We report a case of premature chromatid separation/mosaic variegated aneuploidy syndrome identified by microcephaly on fetal ultrasound and confirmed by cytogenetic analysis of amniotic fluid. Initial mutational analysis of the entire coding region of the BUB1B gene failed to identify any causative mutations. However, further analysis revealed a known compound heterozygous mutation in the upstream region of this gene and a novel Alu insertion mutation in the intron.

Prospective association of fetal liver blood flow at 30 weeks gestation with newborn adiposity.

BACKGROUND: The production of variation in adipose tissue accretion represents a key fetal adaptation to energy substrate availability during gestation. Because umbilical venous blood transports nutrient substrate from the maternal to the fetal compartment and because the fetal liver is the primary organ in which nutrient interconversion occurs, it has been proposed that variations in the relative distribution of umbilical venous blood flow shunting either through ductus venosus or perfusing the fetal liver represents a mechanism underlying this adaptation. OBJECTIVE: The objective of the present study was to determine whether fetal liver blood flow assessed before the period of maximal fetal fat deposition (ie, the third trimester of gestation) is prospectively associated with newborn adiposity. STUDY DESIGN: A prospective study was conducted in a cohort of 62 uncomplicated singleton pregnancies. Fetal ultrasonography was performed at 30 weeks gestation for conventional fetal biometry and characterization of fetal liver blood flow (quantified by subtracting ductus venosus flow from umbilical vein flow). Newborn body fat percentage was quantified by dual energy X-ray absorptiometry imaging at 25.8 ± 3.3 (mean ± standard error of the mean) postnatal days. Multiple regression analysis was used to determine the proportion of variation in newborn body fat percentage explained by fetal liver blood flow. Potential confounding factors included maternal age, parity, prepregnancy body mass index, gestational weight gain, gestational age at birth, infant sex, postnatal age at dual energy X-ray absorptiometry scan, and mode of infant feeding. RESULTS: Newborn body fat percentage was 13.5% ± 2.4% (mean ± standard error of the mean). Fetal liver blood flow at 30 weeks gestation was significantly and positively associated with newborn total fat mass (r=0.397; P<.001) and body fat percentage (r=0.369; P=.004), but not with lean mass (r=0.100; P=.441). After accounting for the effects of covariates, fetal liver blood flow explained 13.5% of the variance in newborn fat mass. The magnitude of this association was pronounced particularly in nonoverweight/nonobese mothers (prepregnancy body mass index, <25 kg/m2; n=36) in whom fetal liver blood flow explained 24.4% of the variation in newborn body fat percentage. CONCLUSION: Fetal liver blood flow at the beginning of the third trimester of gestation is associated positively with newborn adiposity, particularly among nonoverweight/nonobese mothers. This finding supports the role of fetal liver blood flow as a putative fetal adaptation underlying variation in adipose tissue accretion.

Impact of new gestational diabetes mellitus criteria on stillbirth: a regional population-based study in Japan.

AIM: The aim of this study was to determine whether the new gestational diabetes mellitus (GDM) criteria increase the prevalence of diabetes-mellitus-related stillbirths by using a regional population-based approach. MATERIAL AND METHODS: A retrospective, population-based study was conducted to assess 114 036 deliveries from 2000 to 2010 in Miyazaki, Japan. During this period 318 stillbirths occurred after 22 weeks of gestation. Of these cases, 236 were examined to determine the cause of death. The remaining 82 cases were not fully investigated. In particular, we investigated the prevalence of pregestational diabetes mellitus and GDM among the stillbirths. We also applied new GDM criteria to evaluate the impact of these factors on stillbirth. RESULTS: Of the 236 stillbirths, 47% were due to an explainable cause. Application of previous criteria indicated two cases of pregestational diabetes mellitus and three GDM cases in the remaining unexplained stillbirths. By applying new GDM criteria, the GDM count increased to 17. CONCLUSIONS: In an unselected population in southern Japan, the application of new GDM criteria resulted in a 5.7-fold increase (from 2.4% [3/126] to 13.5% [17/126]) in the number of GDM cases in unexplained stillbirths. Even in women with a mild degree of GDM, proper management of both mother and fetus could reduce the number of unexplained stillbirths.

Risk-based screening for thyroid dysfunction during pregnancy.

OBJECTIVE: We conducted the study to see the incidence of thyroid dysfunction in women with obstetrical high-risk factors. METHODS: We retrospectively reviewed medical charts of high-risk pregnant women who had examination for thyroid function during pregnancy. Women were divided according to clinical presentation, symptoms of thyroid disease and those with a personal history of thyroid disease (thyroid disease, n = 32), intrauterine growth restriction (IUGR, n = 115), diabetes mellitus (diabetes, n = 115), hypertension (n = 63), intrauterine fetal death (IUFD, n = 52), and placental abruption (abruption, n = 15). The incidence of thyroid dysfunctions including hyperthyroidism or hypothyroidism was compared. RESULTS: The overall prevalence of thyroid dysfunction was 24.7%. The incidence of thyroid dysfunction in each group was as follows: 31% in thyroid disease, 25% in IUGR, 30% in diabetes, 27% in hypertension, 12% in IUFD, and 7% in abruption. Except IUFD, the incidence was not statistically significant from the group of thyroid disease (thyroid disease versus IUFD, P = 0.03 by χ (2) test). Thyroid disease represented for only 10% of all thyroid dysfunctions. CONCLUSION: Testing of women with a personal history or current symptoms of thyroid disease during pregnancy may be insufficient to detect women with thyroid dysfunction, who will become at high-risk pregnancy.

Fetal heart rate patterns related to neonatal brain damage and neonatal death in placental abruption.

AIM: The aim of this study was to determine the correlation between non-reassuring fetal heart rate (NRFHR) patterns and poor neonatal outcome in placental abruption. MATERIAL AND METHODS: A retrospective study was performed involving 83 placental abruptions with a live fetus at one tertiary and one secondary hospital in Miyazaki prefecture, Japan. We examined the correlation among NRFHR, umbilical arterial blood gas status, and neonatal poor outcomes, including neonatal death (ND) and cerebral palsy (CP). RESULTS: A total of 83 cases were divided into bradycardia (n=27), recurrent late deceleration (rLD, n=29), severe variable deceleration or prolonged deceleration (sVD/PD, n=8), and other cases (n=19). In the bradycardia group, the incidence of low umbilical artery (UA) pH (<7.0) was 59% and the average UA pH was 6.96±0.22. Among these cases, 10 showed severe bradycardia (less than 80 b.p.m.) and an average UA pH of 6.85±0.24, and four cases resulted in poor outcome (three CP and one ND). In the rLD group, the incidence of low UA pH (<7.0) was 7% and the average UA pH was 7.24±0.12. In this group, a 40-week-old fetus with umbilical phlebitis had a lower UA pH (6.92) and developed CP. In the sVD/PD group, there were no cases of a low UA pH (<7.0) and the average UA pH was 7.30±0.04. In this group, a 31-week-old boy with a UA pH of 7.36 developed CP (PVL). The remaining 19 cases had no CP. CONCLUSION: Poor neonatal outcome of placental abruption is closely related to NRFHR, especially the degree of bradycardia. In the rLD and sVD/PD groups, risk factors, such as prematurity and fetal inflammation, co-existed.

Is the perinatal outcome of placental abruption modified by clinical presentation?

OBJECTIVE: The purpose of this study was to elucidate the impact of the clinical presentation on perinatal outcome in placental abruption. STUDY DESIGN: A retrospective study was performed in 97 placental abruptions. Placental abruptions were classified according to clinical presentation: pregnancy-induced hypertension (HT, n = 22), threatened premature labor and/or premature rupture of membranes (TPL/ROM, n = 35), clinically low risk (LR, n = 27), and others (n = 13). Perinatal outcomes were compared among the HT, TPL/ROM, and LR groups. RESULTS: The HT had significantly higher incidence of IUGR, IFUD, and low fibrinogen. The TPL/ROM had less severe disease. However, the LR had significantly higher incidence of IUFD, low UA pH < 7.1, low Apgar score of <7 at 5 min, and low fibrinogen. CONCLUSION: Disease severity in placental abruption is likely to depend on the clinical presentation.