Takashi Kaji

Differences in insulin sensitivity in pregnant women with overweight and gestational diabetes mellitus

Aim. The purpose of the present study was to investigate changes in insulin sensitivity using homeostasis model assessment (HOMA) and the quantitative insulin sensitivity check index (QUICKI) in normal-weight and overweight women with normal glucose tolerance (NGT) and gestational diabetes mellitus (GDM) during pregnancy. Methods. Ninety-two pregnant women in the first trimester, 202 in the second trimester and 154 in the third trimester were enrolled in this study. Fasting plasma glucose and insulin concentrations were measured in all women in the first, second and third trimesters. HOMA indices (insulin resistance, HOMA-IR and β-cell function, HOMA-β) and QUICKI were calculated from fasting glucose and insulin concentrations. Results. HOMA-IR values in overweight women with NGT and in women with GDM were significantly (p < 0.01) higher than those in normal-weight women with NGT. HOMA-IR in women with GDM increased significantly (p < 0.05) during pregnancy, but HOMA-IR values in normal-weight and overweight women with NGT did not change significantly with advance of gestation. QUICKI values in overweight women with NGT and in women with GDM were also significantly (p < 0.01) lower than those in normal-weight women with NGT, and QUICKI in women with GDM decreased significantly (p < 0.05) during pregnancy. HOMA-β in normal-weight women with NGT increased significantly (p < 0.01) during pregnancy. Conclusion. We showed that insulin sensitivities determined by using HOMA-IR and QUICKI in overweight women with NGT and women with GDM were lower than those in normal-weight women with NGT, and that insulin sensitivity in women with GDM declined with advance of gestation.

Fetal cell-free DNA fraction in maternal plasma is affected by fetal trisomy.

The purpose of this noninvasive prenatal testing (NIPT) study was to compare the fetal fraction of singleton gestations by gestational age, maternal characteristics and chromosome-specific aneuploidies as indicated by z-scores. This study was a multicenter prospective cohort study. Test data were collected from women who underwent NIPT by the massively parallel sequencing method. We used sequencing-based fetal fraction calculations in which we estimated fetal DNA fraction by simply counting the number of reads aligned within specific autosomal regions and applying a weighting scheme derived from a multivariate model. Relationships between fetal fractions and gestational age, maternal weight and height, and z-scores for chromosomes 21, 18 and 13 were assessed. A total of 7740 pregnant women enrolled in the study, of which 6993 met the study criteria. As expected, fetal fraction was inversely correlated with maternal weight (P<0.001). The median fetal fraction of samples with euploid result (n=6850) and trisomy 21 (n=70) were 13.7% and 13.6%, respectively. In contrast, the median fetal fraction values for samples with trisomies 18 (n=35) and 13 (n=9) were 11.0% and 8.0%, respectively. The fetal fraction of samples with trisomy 21 NIPT result is comparable to that of samples with euploid result. However, the fetal fractions of samples with trisomies 13 and 18 are significantly lower compared with that of euploid result. We conclude that it may make detecting these two trisomies more challenging.

Differences in bone metabolism between singleton pregnancy and twin pregnancy

OBJECTIVE The objective of this study was to examine the influence of twin pregnancy on calcium metabolism, including bone turnover markers and calcium-regulating factors, by comparison between singleton pregnancy and twin pregnancy in women during pregnancy and puerperium in cross-sectional and longitudinal studies. METHODS Women with singleton and twin pregnancies were recruited from the outpatient clinic of Tokushima University Hospital. In both cross-sectional and longitudinal studies, bone formation and resorption markers, mineral metabolism and calcium-regulating factors were measured at 10, 25, 30 and 36 weeks of pregnancy and at 4 days and 1 month postpartum in women with singleton and twin pregnancies. RESULTS Urinary levels of cross-linked type I collagen N-telopeptides and C-terminal telopeptides of type I collagen in women with twin pregnancy were significantly higher than those in women with singleton pregnancy and those high levels were observed earlier than those in women with singleton pregnancy. In the cross-sectional study, serum levels of bone-specific alkaline phosphatase, calcium and phosphate in women with twin pregnancy were higher and the levels of 1,25-(OH)2 vitamin D and 25-(OH) vitamin D in women with twin pregnancy were lower than those in women with singleton pregnancy. CONCLUSION Changes in bone metabolism in women with twin pregnancy are different from those in women with singleton pregnancy. Early and large increases in bone turnover markers allow women with twin pregnancy to meet high fetal demand for calcium during pregnancy.

Intraoperative red cell salvage during obstetric surgery in 50 Japanese women

To determine the clinical usefulness of intraoperative cell salvage (ICS) in obstetrics.

Diagnosis of truncus arteriosus in first trimester of pregnancy using transvaginal four‐dimensional color Doppler ultrasound

We present our experience of using transvaginal three/four-dimensional (3D/4D) color Doppler with glass-body rendering mode and spatiotemporal image correlation (STIC) software to construct an image of persistent truncus arteriosus in the first trimester of pregnancy. There have been numerous reports on the antenatal diagnosis of truncus arteriosus using two-dimensional (2D) grayscale echocardiography, color Doppler and multiplanar display in 3D/4D ultrasound1–3; however, to the best of our knowledge, this is the first report on the antenatal diagnosis of truncus arteriosus using transvaginal

Association of N-terminal pro B-type natriuretic peptide and sex hormone-binding globulin in non-obese peri- and postmenopausal women

BACKGROUND The relationships between N-terminal fragment proBNP (B-type natriuretic peptide) (NT-proBNP) and sex steroid hormones have not been fully elucidated. We examined these associations in pre-, peri- and postmenopausal women without known cardiovascular disease. We also examined the change in circulating NT-proBNP caused by a gonadotrophin-releasing hormone (GnRH) agonist in order to clarify the effect of acute hormone deficiency on NT-proBNP. METHODS Forty-nine premenopausal women, 101 perimenopausal women and 108 postmenopausal women were enrolled in one study. Forty-four premenopausal women with leiomyoma were recruited for another study, and 22 of those women were treated with a GnRH agonist. Serum levels of NT-proBNP, estradiol, testosterone and sex hormone-binding globulin (SHBG) were measured. RESULTS NT-proBNP concentrations showed significant inverse correlations with body mass index (BMI) in peri- and postmenopausal women. Serum NTproBNP concentrations showed significant positive correlations with SHBG in peri- and postmenopausal women. These significant correlations remained after adjustment for age and BMI. Serum NT-proBNP concentration was significantly decreased after GnRH agonist administration, while NT-proBNP concentration in the control group did not change significantly. Serum SHBG level was also significantly decreased after GnRH agonist administration. CONCLUSION Circulating NT-proBNP levels are positively associated with SHBG levels in non-obese peri- and postmenopausal women, and this relationship was found under the condition of acute hormone deficiency induced by GnRH agonist treatment.

Current status of non‐invasive prenatal testing in Japan

The purpose of this study was to report the 3‐year experience of a nationwide demonstration project to introduce non‐invasive prenatal testing (NIPT) of maternal plasma for aneuploidy, and review the current status of NIPT in Japan.

Simultaneous recordings of pulsed wave Doppler signals in hepatic vein and descending aorta using dual Doppler: a novel method for evaluating fetal arrhythmias

Fetal arrhythmias, which affect 1–2% of pregnancies, are common1. Cardiac-rhythm analysis involves recording atrial and ventricular contractions simultaneously. Fouron and Reed introduced simultaneous pulsed Doppler interrogation of flow in the superior vena cava (SVC) and the ascending aorta (AAo) to assess fetal cardiac rhythms2,3. The SVC-AAo method is widely used to analyze fetal arrhythmias. A-wave reversal in the SVC during atrial systole, and forward flow in the AAo, indirectly define the mechanical relationship between atria and ventricles. However, numerous factors can influence success with this method. Doppler interrogation of low-velocity SVC atrial systolic flow depends on an optimal angle of insonation and a low set wall-motion filter, rendering the signal susceptible to contamination. Furthermore, the A-wave in the SVC might be hidden within the arterial systolic flow spectrum in the AAo and thus be difficult to interpret. When atrial systole coincides with ventricular systole in arrhythmias, the Awave may not be distinguished from the arterial systolic flow spectrum, or vice versa. The Doppler gate can be placed simultaneously over other arteries and veins (e.g. pulmonary and renal arteries and veins)4–6. These techniques are less limited by the fetal position than is the SVC-AAo method. However, as with the SVC-AAo method, the venous A-wave might be hidden within the arterial systolic flow spectrum when atrial systole coincides with ventricular systole. To evaluate fetal arrhythmias, we simultaneously recorded pulsed wave Doppler signals in the hepatic vein and the descending aorta (DAo) using dual Doppler. Dual Doppler has two separate sample gates, thus allowing simultaneous recording of signals from two locations. We obtained dual Doppler recordings using a Preirus or a EUB-7500 (Hitachi Aloka Medical, Ltd., Tokyo, Japan) ultrasound device. Hepatic veins were visualized in color flow mode in a transverse section of the fetal abdomen, spreading out from the inferior vena cava (IVC) between

A survey on awareness of genetic counseling for non-invasive prenatal testing: The first year experience in Japan

The purpose of this study is to summarize the results from a survey on awareness of genetic counseling for pregnant women who wish to receive non-invasive prenatal testing (NIPT) in Japan. As a component of a clinical study by the Japan NIPT Consortium, genetic counseling was conducted for women who wished to receive NIPT, and a questionnaire concerning both NIPT and genetic counseling was given twice: once after pre-test counseling and again when test results were reported. The responses of 7292 women were analyzed. They expressed high satisfaction with the genetic counseling system of the NIPT Consortium (94%). The number of respondents who indicated that genetic counseling is necessary for NIPT increased over time. Furthermore, they highly valued genetic counseling provided by skilled clinicians, such as clinical geneticists or genetic counselors. The vast majority (90%) responded that there was sufficient opportunity to consider the test ahead of time. Meanwhile, women who received positive test results had a poor opinion and expressed a low-degree satisfaction. We confirmed that the pre-test genetic counseling that we conducted creates an opportunity for pregnant women to sufficiently consider prenatal testing, promotes its understanding and has possibilities to effectively facilitate informed decision making after adequate consideration. A more careful and thorough approach is considered to be necessary for women who received positive test results.

Fetal cell-free DNA fraction in maternal plasma for the prediction of hypertensive disorders of pregnancy

OBJECTIVE The purpose of this study is to compare the fetal fractions during non-invasive prenatal testing (NIPT) in singleton pregnancies according to gestational age and maternal characteristics to evaluate the utility of this parameter for the prediction of pregnancy complications including gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP). STUDY DESIGN This study was a multicenter prospective cohort study. The present data were collected from women whose NIPT results were negative. The relationships between the fetal fractions and the gestational age, maternal weight and height, and incidences of miscarriage, preterm delivery, and pregnancy complications including GDM, HDP and placental abruption were assessed. RESULTS A total of 5582 pregnant women with verified NIPT negative results were registered in the study. The demographic characteristics of the study populations were statistically analyzed, and the women with HDP tended to have a low fetal fraction in samples taken during early gestation. The area under the curve (AUC) in a receiver operating characteristic curve (ROC) analysis was 0.608 for women with HDP. CONCLUSION A low fetal fraction on NIPT might be correlated with future HDP. However, predicting HDP during early pregnancy in women with a low fetal fraction might be difficult.