Maternal vascular-placental axis in the third trimester in women with gestational diabetes mellitus, hypertensive disorders, and unaffected pregnancies.

BACKGROUND: Hypertensive disorders of pregnancy and gestational diabetes mellitus are characterized by vascular dysfunction and are associated with long term cardiovascular risks. OBJECTIVE: This study aimed to compare different markers of maternal vascular function in women with gestational diabetes mellitus, preeclampsia, or gestational hypertension and in women whose pregnancies were unaffected by these complications and to assess the association between maternal vascular function and markers of placental perfusion and maternal vascular-placental axis in 4 groups of women. STUDY DESIGN: This was a prospective observational study of women who had routine hospital visits at 35 0/7 to 36 6/7 weeks of gestation at King's College Hospital, London, United Kingdom. The routine hospital visit included recording of maternal demographic characteristics and medical history, ultrasound examination for fetal anatomy and growth, Doppler studies of the uterine arteries and ophthalmic arteries, carotid-femoral pulse wave velocity measurements, estimation of the augmentation index and total peripheral resistance, and measurements of serum placental growth factor and soluble fms-like tyrosine kinase 1. Linear regression analysis was performed for the outcomes of uterine artery pulsatility index multiple of the median, placental growth factor multiple of the median, and soluble fms-like tyrosine kinase 1 multiple of the median. The ophthalmic artery peak systolic velocity ratio, pulse wave velocity, augmentation index, and total peripheral vascular resistance were assessed as potential predictors. This analysis was performed on all women and separately in the different groups. RESULTS: The study population of 6502 women included 614 (9.4%) with gestational diabetes mellitus, 140 (2.1%) who subsequently developed preeclampsia, and 129 (2.0%) who developed gestational hypertension. Women with gestational diabetes mellitus had increased pulse wave velocity compared with those with pregnancies unaffected by gestational diabetes mellitus, preeclampsia, or gestational hypertension. Women with preeclampsia or gestational hypertension had lower placental growth factor multiple of the median and higher uterine artery pulsatility index multiple of the median, soluble fms-like tyrosine kinase 1 multiple of the median, augmentation index, pulse wave velocity, total peripheral resistance, and ophthalmic artery peak systolic velocity ratio than those with unaffected pregnancies. In women with unaffected pregnancies, the ophthalmic artery peak systolic velocity ratio was predictive of the uterine artery pulsatility index multiple of the median, and ophthalmic artery peak systolic velocity ratio, augmentation index, total peripheral resistance, and pulse wave velocity were predictive of the placental growth factor multiple of the median and the soluble fms-like tyrosine kinase 1 multiple of the median. In women with gestational diabetes mellitus, the ophthalmic artery peak systolic velocity ratio was predictive of the uterine artery pulsatility index multiple of the median; the ophthalmic artery peak systolic velocity ratio, total peripheral resistance, and pulse wave velocity were predictive of the placental growth factor multiple of the median; and total peripheral resistance was predictive of the soluble fms-like tyrosine kinase 1 multiple of the median. In women with preeclampsia, the ophthalmic artery peak systolic velocity ratio was predictive of the uterine artery pulsatility index multiple of the median, placental growth factor multiple of the median, and soluble fms-like tyrosine kinase 1 multiple of the median. In women unaffected by gestational diabetes mellitus, preeclampsia, or gestational hypertension, the ophthalmic artery peak systolic velocity ratio was predictive of the uterine artery pulsatility index multiple of the median, and the augmentation index, total peripheral resistance, pulse wave velocity, and the ophthalmic artery peak systolic velocity ratio were predictive of the placental growth factor multiple of the median and the soluble fms-like tyrosine kinase 1 multiple of the median. CONCLUSION: In the third trimester of pregnancy, women with preeclampsia, gestational hypertension, and gestational diabetes mellitus present with increased arterial stiffness. In addition, women diagnosed with hypertensive complications showed increased peripheral vascular resistance. The ophthalmic artery peak systolic velocity ratio provided predictive information for placental perfusion and function in all pregnant women, whereas vascular indices were more informative for placental function in women with unaffected pregnancies and those with gestational diabetes mellitus than in those with preeclampsia or gestational hypertension. Our data suggest that vascular assessment in women during pregnancy not only may provide information about maternal vascular health but also can be used to provide information about individual risk factors for placental insufficiency. The selection of the vascular index will have to be tailored according to the maternal profile and pregnancy complication.

Maternal vascular indices at 36 weeks' gestation in the prediction of preeclampsia.

BACKGROUND: Epidemiological studies have shown that women with preeclampsia (PE) are at increased long term cardiovascular risk. This risk might be associated with accelerated vascular ageing process but data on vascular abnormalities in women with PE are scarce. OBJECTIVE: This study aimed to identify the most discriminatory maternal vascular index in the prediction of PE at 35 to 37 weeks' gestation and to examine the performance of screening for PE by combinations of maternal risk factors and biophysical and biochemical markers at 35 to 37 weeks' gestation. STUDY DESIGN: This was a prospective observational nonintervention study in women attending a routine hospital visit at 35 0/7 to 36 6/7 weeks' gestation. The visit included recording of maternal demographic characteristics and medical history, vascular indices, and hemodynamic parameters obtained by a noninvasive operator-independent device (pulse wave velocity, augmentation index, cardiac output, stroke volume, central systolic and diastolic blood pressures, total peripheral resistance, and fetal heart rate), mean arterial pressure, uterine artery pulsatility index, and serum concentration of placental growth factor and soluble fms-like tyrosine kinase-1. The performance of screening for delivery with PE at any time and at <3 weeks from assessment using a combination of maternal risk factors and various combinations of biomarkers was determined. RESULTS: The study population consisted of 6746 women with singleton pregnancies, including 176 women (2.6%) who subsequently developed PE. There were 3 main findings. First, in women who developed PE, compared with those who did not, there were higher central systolic and diastolic blood pressures, pulse wave velocity, peripheral vascular resistance, and augmentation index. Second, the most discriminatory indices were systolic and diastolic blood pressures and pulse wave velocity, with poor prediction from the other indices. However, the performance of screening by a combination of maternal risk factors plus mean arterial pressure was at least as high as that of a combination of maternal risk factors plus central systolic and diastolic blood pressures; consequently, in screening for PE, pulse wave velocity, mean arterial pressure, uterine artery pulsatility index, placental growth factor, and soluble fms-like tyrosine kinase-1 were used. Third, in screening for both PE within 3 weeks and PE at any time from assessment, the detection rate at a false-positive rate of 10% of a biophysical test consisting of maternal risk factors plus mean arterial pressure, uterine artery pulsatility index, and pulse wave velocity (PE within 3 weeks: 85.2%; 95% confidence interval, 75.6%-92.1%; PE at any time: 69.9%; 95% confidence interval, 62.5%-76.6%) was not significantly different from a biochemical test using the competing risks model to combine maternal risk factors with placental growth factor and soluble fms-like tyrosine kinase-1 (PE within 3 weeks: 80.2%; 95% confidence interval, 69.9%-88.3%; PE at any time: 64.2%; 95% confidence interval, 56.6%-71.3%), and they were both superior to screening by low placental growth factor concentration (PE within 3 weeks: 53.1%; 95% confidence interval, 41.7%-64.3%; PE at any time: 44.3; 95% confidence interval, 36.8%-52.0%) or high soluble fms-like tyrosine kinase-1-to-placental growth factor concentration ratio (PE within 3 weeks: 65.4%; 95% confidence interval, 54.0%-75.7%; PE at any time: 53.4%; 95% confidence interval, 45.8%-60.9%). CONCLUSION: First, increased maternal arterial stiffness preceded the clinical onset of PE. Second, maternal pulse wave velocity at 35 to 37 weeks' gestation in combination with mean arterial pressure and uterine artery pulsatility index provided effective prediction of subsequent development of preeclampsia.

Competing risks model for prediction of small-for-gestational-age neonates from biophysical markers at 19 to 24 weeks' gestation.

BACKGROUND: Antenatal identification of women at high risk to deliver small-for-gestational-age neonates may improve the management of the condition. The traditional but ineffective methods for small-for-gestational-age screening are the use of risk scoring systems based on maternal demographic characteristics and medical history and the measurement of the symphysial-fundal height. Another approach is to use logistic regression models that have higher performance and provide patient-specific risks for different prespecified cutoffs of birthweight percentile and gestational age at delivery. However, such models have led to an arbitrary dichotomization of the condition; different models for different small-for-gestational-age definitions are required and adding new biomarkers or examining other cutoffs requires refitting of the whole model. An alternative approach for the prediction of small-for-gestational-age neonates is to consider small for gestational age as a spectrum disorder whose severity is continuously reflected in both the gestational age at delivery and z score in birthweight for gestational age. OBJECTIVE: This study aimed to develop a new competing risks model for the prediction of small-for-gestational-age neonates based on a combination of maternal demographic characteristics and medical history with sonographic estimated fetal weight, uterine artery pulsatility index, and mean arterial pressure at 19 to 24 weeks' gestation. STUDY DESIGN: This was a prospective observational study of 96,678 women with singleton pregnancies undergoing routine ultrasound examination at 19 to 24 weeks' gestation, which included recording of estimated fetal weight, uterine artery pulsatility index, and mean arterial pressure. The competing risks model for small for gestational age is based on a previous joint distribution of gestational age at delivery and birthweight z score, according to maternal demographic characteristics and medical history. The likelihoods of the estimated fetal weight, uterine artery pulsatility index, and mean arterial pressure were fitted conditionally to both gestational age at delivery and birthweight z score and modified the previous distribution, according to the Bayes theorem, to obtain an individualized posterior distribution for gestational age at delivery and birthweight z score and therefore patient-specific risks for any desired cutoffs for birthweight z score and gestational age at delivery. The model was internally validated by randomly dividing the data into a training data set, to obtain the parameters of the model, and a test data set, to evaluate the model. The discrimination and calibration of the model were also examined. RESULTS: The estimated fetal weight was described using a regression model with an interaction term between gestational age at delivery and birthweight z score. Folded plane regression models were fitted for uterine artery pulsatility index and mean arterial pressure. The prediction of small for gestational age by maternal factors was improved by adding biomarkers for increasing degree of prematurity, higher severity of smallness, and coexistence of preeclampsia. Screening by maternal factors with estimated fetal weight, uterine artery pulsatility index, and mean arterial pressure, predicted 41%, 56%, and 70% of small-for-gestational-age neonates with birthweights of <10th percentile delivered at ≥37, <37, and <32 weeks' gestation, at a 10% false-positive rate. The respective rates for a birthweight of <3rd percentile were 47%, 65%, and 77%. The rates in the presence of preeclampsia were 41%, 72%, and 91% for small-for-gestational-age neonates with birthweights of <10th percentile and 50%, 75%, and 92% for small-for-gestational-age neonates with birthweights of <3rd percentile. Overall, the model was well calibrated. The detection rates and calibration indices were similar in the training and test data sets, demonstrating the internal validity of the model. CONCLUSION: The performance of screening for small-for-gestational-age neonates by a competing risks model that combines maternal factors with estimated fetal weight, uterine artery pulsatility index, and mean arterial pressure was superior to that of screening by maternal characteristics and medical history alone.

Robot-assisted laparoscopic myomectomy for deep intramural myomas.

BACKGROUND: To evaluate the efficacy of robot-assisted laparoscopic myomectomy for deep intramural myomas. METHODS: We have conducted a retrospective study for 170 patients who underwent robot-assisted laparoscopic myomectomy by a single operator of tertiary university hospital. RESULTS: There were 100 cases of robot-assisted laparoscopic myomectomy for deep intramural myomas. The patients had 3.8±3.5 myomas on average, and the mean size of the largest myoma of each patient was 7.5±2.1 centimeters in diameter. Mean operative time was 276.4±97.1 minutes, and mean console time was 146.0±62.7 minutes. Thirty two patients had surgeries for other gynecologic conditions such as pelvic endometriosis or endometrial polyps along with myomectomy at the same time. All the patients recovered without any major complication. After the surgery, nine(75.0 %) of the 12 women pursuing a pregnancy became pregnant. CONCLUSION: Robot-assisted laparoscopic myomectomy for deep intramural myomas could be a minimal invasive surgical option for women who wish preserve fertility. Copyright © 2016 John Wiley & Sons, Ltd.