Effects of sildenafil on Doppler parameters, maternal and neonatal outcomes in the active labor phase of low-risk pregnancies: a randomized clinical trial.

OBJECTIVES: The benefits of sildenafil by increasing blood flow in the improvement of Doppler parameters of umbilical (UA), uterine (UtA), and fetal middle cerebral arteries (MCA) remain uncertain. On the other hand, insufficient blood flow during uterine contractions in labor can lead to decrease blood supply and fetal distress. Therefore, we aimed to assess the changes in fetal Doppler indices and maternal and neonatal outcomes following the use of sildenafil in the active phase of labor in low-risk pregnancies with healthy fetuses. METHODS: This randomized double-blinded controlled trial was conducted on 70 pregnant single low-risk, pregnant women. The patients were randomly assigned into two groups receiving sildenafil (n=35) or placebo (n=35) when the active phase of labor was initiated. Doppler parameters were assessed at baseline as well as 3 h after that. Indeed, the maternal and neonatal outcomes were compared between groups. RESULTS: The Doppler parameters including the pulsatility index of MCA, UA, and left and right UtA remained unchanged after the administration of sildenafil. Neonatal outcomes including birth weight, PH of the umbilical artery, Apgar score, respiratory distress syndrome, and neonatal intensive care unit admission as well as maternal outcomes such as cesarean section rate and the occurrence of intrapartum/postpartum hemorrhage had no difference between groups. CONCLUSIONS: The use of sildenafil in the active phase of labor in low-risk pregnancies may not be beneficial in improving Doppler parameters in MCA, umbilical, and uterine arteries and thus may not improve pregnancy outcomes.

Third trimester cortisol is positively associated with gestational weight gain in pregnant women with class one obesity.

BACKGROUND/OBJECTIVE: Prevalence of pre-pregnancy obesity and excessive gestational weight gain (GWG) are higher among women of color with low SES. Dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis and its end-product, cortisol, during pregnancy is hypothesized to be associated with excessive GWG. However, past studies have produced inconsistent findings and often did not include health disparities populations. This study examined the association between pre-pregnancy body mass index (BMI), third trimester diurnal cortisol, and GWG in low-income, predominantly Hispanic women. SUBJECTS/METHODS: The MADRES study is an ongoing prospective cohort study of primarily Hispanic, low-income pregnant women and their children in Los Angeles, California. Data from 176 participants were included in this study. Total cortisol secretion (area under the curve, AUC) was quantified using four salivary cortisol samples (awakening, 30 min after awakening, afternoon, and bedtime) that were collected at home on one day during the third trimester of pregnancy. Moderation of the association between total cortisol and GWG by pre-pregnancy BMI was tested using multiple linear regression with a multiplicative interaction term. RESULTS: There was no association between total cortisol secretion and GWG overall (p = 0.82), but the association between total cortisol and GWG was stronger for women with class 1 pre-pregnancy obesity compared to women with normal pre-pregnancy BMI (interaction term p = 0.04). CONCLUSIONS: Results suggest that obesity status before pregnancy may be exacerbating the physiological impact of cortisol on GWG.

Conus medullaris migration during the third trimester: A retrospective study.

OBJECTIVE: To explore the migration process of the conus medullaris (CM) and propose a normal range of CM levels during the third trimester. METHOD: We retrospectively collected the ultrasonographic and clinical data of 588 fetuses during the third trimester. We located the CM and assigned scores. One-way analysis of variance and linear regression analyses were used to statistically analyze CM migration. Statistical significance was set at p < 0.05. RESULTS: The CM levels were statistically different among the different gestational weeks of the third trimester. The CM level showed a linear regression correlation with the gestational weeks. On an average, the CM migrated from the top third of the L2 vertebra to the L1/2 intervertebral disc level. CONCLUSION: The CM continues to migrate, from the top third of the L2 vertebra to the L1/2 intervertebral disc level, during the third trimester. The term infant could have the CM at the normal adult level at birth. At the beginning of the third trimester, a CM located above the L2/3 intervertebral disc level could be normal; the CM location at the L3 vertebra level could be physiological and needs follow-up; and a CM presenting below the L3 vertebra level might indicate tethered cord syndrome. The fetus with a CM significantly above the L1/2 intervertebral disc level may have caudal regression syndrome.

Antenatal screening of small for gestational age: Impact on obstetrical management and neonatal outcomes in case of trial of labor after 37 weeks.

OBJECTIVE: Antenatal screening of small fetuses for gestational age (SGA) is a public health challenge. The aim of this study is to assess the obstetrical management and the immediate neonatal outcomes, according to the antenatal screening of the SGA fetuses. METHODS: We performed a retrospective study in a French tertiary care hospital between January 1, 2016 and December 31, 2018. Women were eligible if they had a monofetal pregnancy with a fetus in head presentation and a trial of labor after 37 weeks. A fetus was considered SGA when the estimated fetal weight was less than the 10th percentile at the third trimester ultrasound. A newborn was considered hypotrophic when the birthweight was less than the 10th percentile. RESULTS: 8 153 newborns were included and 948 of the newborns were hypotrophic (308 were suspected for SGA, 640 were not suspected for SGA) and 7205 were eutrophic. Among the hypotrophic neonates, we observed no significant difference regarding the immediate neonatal outcomes between the two groups of fetuses suspected and not suspected for SGA. Among the fetuses not suspected for SGA, the rate of arterial umbilical cord pH below 7.10 was significantly higher in the hypotrophic newborns compared to the non hypotrophic newborns (4.7% vs 3.1%, p = 0.041). CONCLUSION: In our population, unsuspected fetal hypotrophy may be associated with an increased risk of neonatal acidosis. These results emphasize the benefit of improving prenatal screening to identify the SGA fetuses.

Acute fetal response to high-intensity interval training in the second and third trimesters of pregnancy.

The majority of women do not meet the recommended levels of exercise during their pregnancies, frequently due to a lack of time. High-intensity interval training offers a potential solution, providing an effective, time-efficient exercise modality. This exercise modality has not been studied in pregnancy therefore, the objective of this study was to evaluate fetal response to a high-intensity interval training resistance circuit in the late second and early third trimesters of pregnancy. Fourteen active, healthy women with uncomplicated, singleton pregnancies participated in a high-intensity interval training resistance circuit between 28 + 0/7 and 32 + 0/7 weeks. A Borg rating of perceived exertion of 15-17/20 and an estimated heart rate of 80%-90% of maternal heart-rate maximum was targeted. Fetal well-being was evaluated continuously with fetal heart-rate tracings and umbilical artery Doppler velocimetry conducted pre-and post-exercise. Fetal heart rate tracings were normal throughout the exercise circuit. Post-exercise, umbilical artery end-diastolic flow was normal and significant decreases were observed in the mean systolic/diastolic ratios, pulsatility indexes and resistance indexes. Therefore, in a small cohort of active pregnant women, a high-intensity interval training resistance circuit in the late second and early third trimesters of pregnancy appears to be a safe exercise modality with no acute, adverse fetal effects but further study is required. Novelty: High-intensity interval training, at an intensity in excess of current recommendations, does not appear to be associated with any adverse fetal effects in previously active pregnant women. High-intensity interval training is an enjoyable and effective exercise modality in previously active pregnant women.

Sleep, evening light exposure and perceived stress in healthy nulliparous women in the third trimester of pregnancy.

OBJECTIVE: Sleep disturbances are common in pregnancy, and the prevalence increases during the third trimester. The aim of the present study was to assess sleep patterns, sleep behavior and prevalence of insomnia in pregnant women in the third trimester, by comparing them to a group of non-pregnant women. Further, how perceived stress and evening light exposure were linked to sleep characteristics among the pregnant women were examined. METHODS: A total of 61 healthy nulliparous pregnant women in beginning of the third trimester (recruited from 2017 to 2019), and 69 non-pregnant women (recruited in 2018) were included. Sleep was monitored by actigraphy, sleep diaries and the Bergen Insomnia Scale. The stress scales used were the Relationship Satisfaction Scale, the Perceived Stress Scale and the Pre-Sleep Arousal Scale. Total white light exposure three hours prior to bedtime were also assessed. RESULTS: The prevalence of insomnia among the pregnant women was 38%, with a mean score on the Bergen Insomnia Scale of 11.2 (SD = 7.5). The corresponding figures in the comparing group was 51% and 12.3 (SD = 7.7). The pregnant women reported lower sleep efficiency (mean difference 3.8; 95% CI = 0.3, 7.3), longer total sleep time derived from actigraphy (mean difference 59.0 minutes; 95% CI = 23.8, 94.2) and higher exposure to evening light (mean difference 0.7; 95% CI = 0.3, 1.2), compared to the non-pregnant group. The evening light exposure was inversely associated with total sleep time derived from actigraphy (B = -8.1; 95% CI = -14.7, -1.5), and an earlier midpoint of sleep (B = -10.3, 95% CI = -14.7, -5.9). Perceived stressors were unrelated to self-reported and actigraphy assessed sleep. CONCLUSION: In healthy pregnant participants sleep in the third trimester was preserved quite well. Even so, the data suggest that evening light exposure was related to shorter sleep duration among pregnant women.

Longitudinal changes in HRV across pregnancy and postpartum: Effect of negative partner relationship qualities.

During pregnancy, there are significant physiological changes to support a healthy fetus. Parasympathetic activity normatively decreases across pregnancy, and psychological stress can promote even further decreased heart rate variability (HRV). This study evaluated (1) changes in vagally-mediated HRV from pregnancy to postpartum, (2) changes in vagally-mediated HRV from pregnancy to postpartum based on negative partner relationship qualities, and (3) changes in depressive symptoms from pregnancy to postpartum based on negative partner relationship qualities. 78 participants in their 3rd trimester self-reported their relationship quality with their partner at the first visit. Depressive symptoms and vagally-mediated HRV were evaluated at rest at five time points from 3rd trimester to 12 months postpartum. On average, the only significant increase in vagally-mediated HRV occurred between the 3rd trimester and 4-6 weeks postpartum. However, those who reported more negative partner relationship qualities during their 3rd trimester of pregnancy maintained lower vagally-mediated HRV levels across all of the first year postpartum and significantly lower vagally-mediated HRV at both 4 and 8 months postpartum as compared to people who reported fewer negative partner relationship qualities. Across the first year postpartum, people reporting more negative partner relationship qualities experienced more severe depressive symptoms than their counterparts with fewer negative partner relationship qualities; however, there was no difference in the rate of change of depressive symptoms across the first year postpartum based on negative partner relationship qualities. Because lower vagally-mediated HRV is associated with depressive symptoms, future work should explore the temporal relationship between vagally-mediated HRV and depressive symptoms in the postpartum period.

Maternal food consumption during late pregnancy and offspring risk of islet autoimmunity and type 1 diabetes.

AIMS/HYPOTHESIS: We aimed to investigate the association between maternal consumption of gluten-containing foods and other selected foods during late pregnancy and offspring risk of islet autoimmunity (IA) and type 1 diabetes in The Environmental Determinants of Diabetes in the Young (TEDDY) study. METHODS: The TEDDY study recruited children at high genetic risk for type 1 diabetes at birth, and prospectively follows them for the development of IA and type 1 diabetes (n = 8556). A questionnaire on the mother's diet in late pregnancy was completed by 3-4 months postpartum. The maternal daily intake was estimated from a food frequency questionnaire for eight food groups: gluten-containing foods, non-gluten cereals, fresh milk, sour milk, cheese products, soy products, lean/medium-fat fish and fatty fish. For each food, we described the distribution of maternal intake among the four participating countries in the TEDDY study and tested the association of tertile of maternal food consumption with risk of IA and type 1 diabetes using forward selection time-to-event Cox regression. RESULTS: By 28 February 2019, 791 cases of IA and 328 cases of type 1 diabetes developed in TEDDY. There was no association between maternal late-pregnancy consumption of gluten-containing foods or any of the other selected foods and risk of IA, type 1 diabetes, insulin autoantibody-first IA or GAD autoantibody-first IA (all p ≥ 0.01). Maternal gluten-containing food consumption in late pregnancy was higher in Sweden (242 g/day), Germany (247 g/day) and Finland (221 g/day) than in the USA (199 g/day) (pairwise p < 0.05). CONCLUSIONS/INTERPRETATION: Maternal food consumption during late pregnancy was not associated with offspring risk for IA or type 1 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00279318.

Deoxyribonuclease activity negative correlates with extracellular DNA in uncomplicated singleton pregnancies in the third trimester.

OBJECTIVES: It is not clear, which factors affect extracellular DNA (ecDNA) concentrations in healthy women with singleton uncomplicated pregnancies, although deoxyribonucleases (DNases) are hypothesized to be responsible for the cleavage of plasma ecDNA. The aim of this study was to analyze potential determinants of total ecDNA including plasma DNase activity. METHODS: Plasma samples were collected from 48 healthy women with singleton uncomplicated pregnancies in the third trimester (gestation week 37). DNA was isolated and quantified using fluorometry and real time PCR. DNase activity was assessed using the single radial enzyme-diffusion method. RESULTS: Neither ecDNA, nor DNase activity were affected by maternal age or BMI. DNase activity negatively correlated with total plasma ecDNA (r=-0.40, p=0.007). Similar associations were found for ecDNA of nuclear and mitochondrial origin, but not with fetal DNA quantified using Y-targeted PCR in male fetus-bearing pregnancies. CONCLUSIONS: The role of plasma ecDNA of fetal and maternal origin is studied in the pathogenesis of pregnancy-complications. The results indicate that plasma DNase activity could negatively regulate ecDNA concentrations and should, thus, be analyzed in preeclampsia, preterm birth and other ecDNA-related pregnancy complications.

Comparison of maternal third trimester hemodynamics between singleton pregnancy and twin pregnancy.

OBJECTIVES: The impedance cardiography (ICG) technique measures the variation of impedance in the thorax due to the physical contractile activity of the heart. Twin pregnancy is characterized by greater maternal hemodynamic changes than a singleton pregnancy. METHODS: In a study on 121 pregnant women in the last trimester we performed ICG, evaluating the following hemodynamic parameters: stroke volume, heart rate, cardiac output, ventricular ejection time, left ventricular ejection time, thoracic impedance, and systemic vascular resistance. RESULTS: The study included singleton and twin pregnancies. Heart rate values in women with single fetus was lower than in those carrying twins (85 vs. 100 beats/min, p=0.021) as were the stroke volume values (64 vs. 83 mL, p=0.010) and the cardiac output (p<0.0001). Systemic vascular resistance decreased in twin pregnancies compared to singleton pregnancy (p=0.023). CONCLUSIONS: ICG studies are rare, and the validation of their results is an ongoing process. However, the ICG technique is applicable in the third trimester of pregnancy and can yield important information regarding the hemodynamic profile of singleton and twin pregnancies, revealing maternal heart changes specific to twin pregnancies.

Uterine electromyography (EMG) measurements to predict preterm caesarean section in patients with complete placenta previa.

The objective of the study was to evaluate uterine electrical activity (EA) with EMG methods in pregnant women with complete placenta previa with preterm caesarean section (CS). This prospective study included 78 patients with complete placenta previa who were recorded for uterine EA activity from 32 to 34 weeks of gestation. The clinical and the uterine EMG burst characteristics, that are responsible for contractions, were compared between a preterm CS group (case group, n = 33) and an elective control group (control group, n = 45). The uterine EA burst duration was longer in the case group compared with the control group (28.79 ± 3.75 vs 19.35 ± 2.56 s; p < .001). Also, the number of burst per 30 min was also higher in the case group compared with the control group (3.28 ± 0.18 vs 1.72 ± 0.22; p < .001), Similarly, the RMS was higher in the case group compared with the control group (0.07 ± 0.01 vs 0.04 ± 0.01 mV; p = .041). In addition, the PDS was higher in the case group compared with the control group (0.47 ± 0.03 vs 0.39 ± 0.02 Hz; p = .023). This study demonstrates that women with complete placenta previa have higher uterine EA at 32-34 weeks of gestation and this is associated with a higher risk of preterm CS due to massive vaginal bleeding.IMPACT STATEMENTWhat is already known on this subject? Antepartum massive bleeding in complete placenta previa causes maternal and foetal mortality and morbidity, currently there is no effective method to predict it.What do the results of this study add? This study showed in patients with complete placenta previa who were delivered preterm via emergent caesarean section, the uterine electrical activity measured by uterine electromyography (EMG) at 32-34 weeks of gestation had an active patternWhat are the implications of these findings for clinical practice and/or further research? Uterine EMG is a potential tool to measure uterine electrical activity and can guide clinical management of patients with complete placenta previa, further study are needed to confirm its effectiveness in a large sample size.

Can Pregnancy Lead to Changes in Hearing Threshold?

PURPOSE: This study explores the changes in hearing thresholds in pregnancy. MATERIALS AND METHODS: A prospective hospital-based observational study was performed with a total of 69 patients in the age-group of 18 to 40 years. Patients underwent hearing assessment twice during the study period. Conventional pure tone audiometry and impedance audiometry were performed, first during the antepartum period (28-32 weeks of gestational age) and second time during the postpartum period (6 weeks postpartum). RESULTS: Significant difference was seen between the average of air conduction threshold values at speech frequencies when antepartum values were compared with postpartum values. CONCLUSION: The alterations in hearing sensitivity in pregnant females which improved during the postpartum period can be attributed to pregnancy.

Cross-modality and in-vivo validation of 4D flow MRI evaluation of uterine artery blood flow in human pregnancy.

OBJECTIVES: Clinical assessment of uterine artery (UtA) hemodynamics is currently limited to Doppler ultrasound (US) velocimetry. We have demonstrated previously the feasibility of applying four-dimensional (4D) flow magnetic resonance imaging (MRI) to evaluate UtA hemodynamics during pregnancy, allowing flow quantification of the entire course of the vessel. In this study, we sought to further validate the physiological relevance of 4D flow MRI measurement of UtA blood flow by exploring its association with pregnancy outcome relative to US-based metrics. METHODS: Recruited into this prospective, cross-sectional study were 87 women with a singleton pregnancy who underwent 4D flow MRI between May 2016 and April 2019 to measure the UtA pulsatility index (MRI-PI) and blood flow rate (MRI-flow, in mL/min). UtA-PI was also measured using US (US-PI). The primary outcome was a composite (COMP) of pre-eclampsia (PE) and/or small-for-gestational-age (SGA) neonate, and secondary outcomes were PE and SGA neonate individually. We assessed the ability of MRI-flow, MRI-PI and US-PI to distinguish between outcomes, and evaluated whether MRI-flow changed as gestation progressed. RESULTS: Following 4D flow postprocessing and exclusions from the analysis, 74 women had 4D flow MRI data analyzed for both UtAs. Of these, 18 developed a COMP outcome: three developed PE only, 11 had a SGA neonate only and four had both. A comparison of the COMP group vs the no-COMP group found no differences in maternal age, body mass index, nulliparity, gravidity or race. For 66 of the 74 subjects, US data were also available. In these subjects, both median MRI-PI (0.95 vs 0.70; P < 0.01) and median US-PI (0.95 vs 0.73; P < 0.01) were significantly increased in subjects in the COMP group compared with those in the no-COMP group. The UtA blood-flow rate, as measured by MRI, did not increase significantly from the second to the third trimester (median flow (interquartile range (IQR)), 543 (419-698) vs 575 (440-746) mL/min; P = 0.77), but it was significantly lower overall in the COMP compared with the no-COMP group (median flow (IQR), 486 (366-598) vs 624 (457-749) mL/min; P = 0.04). The areas under the receiver-operating-characteristics curves for MRI-flow, MRI-PI and US-PI in predicting COMP were not significantly different (0.694, 0.737 and 0.731, respectively; P = 0.87). CONCLUSIONS: 4D flow MRI can yield physiological measures of UtA blood-flow rate and PI that are associated with adverse pregnancy outcome. This may open up new avenues in the future to expand the potential of this technique as a robust tool with which to evaluate UtA hemodynamics in pregnancy. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Hemodynamic findings in normotensive women with small-for-gestational-age and growth-restricted fetuses.

INTRODUCTION: Fetal growth restriction (FGR) in most instances is a consequence of primary placental dysfunction due to inadequate trophoblastic invasion. Maternal cardiac maladaptation to pregnancy has been proposed as a possible determinant of placental insufficiency and impaired fetal growth. This study aimed to compare the maternal hemodynamic parameters between normotensive women with small-for-gestational-age (SGA) and FGR fetuses and to evaluate their correlation with neonatal outcome. MATERIAL AND METHODS: An observational cohort study including singleton pregnancies referred to our tertiary care center due to fetal smallness. At the time of diagnosis, fetuses were classified as SGA or FGR according to the Delphi consensus criteria, and pregnant women underwent hemodynamic assessment using a cardiac output monitor. A group of women with singleton uncomplicated pregnancies ar ≥35 weeks of gestation were recruited as controls. Cardiac output, systemic vascular resistance, stroke volume, and heart rate were measured and compared among the three groups (controls vs FGR vs SGA). The correlation between antenatal findings and neonatal outcome was also evaluated by multivariate logistic regression analysis. RESULTS: A total of 51 women with fetal smallness were assessed at 34.8 ± 2.6 weeks. SGA and FGR were diagnosed in 22 and 29 cases, respectively. The control group included 61 women assessed at 36.5 ± 0.8 weeks of gestation. Women with FGR had a lower cardiac output Z-score (respectively, -1.3 ± 1.2 vs -0.4 ± 0.8 vs -0.2 ± 1.0; P < .001) and a higher systemic vascular resistance Z-score (respectively, 1.2 ± 1.2 vs 0.2 ± 1.1 vs -0.02 ± 1.2; P < .001) compared with both SGA and controls, whereas no difference in the hemodynamic parameters was found between women with SGA and controls. The incidence of neonatal intensive care unit admission did not differ between SGA and FGR fetuses (18.2% vs 41.4%; P = .13), but FGR fetuses had a longer hospitalization compared with SGA fetuses (14.2 ± 17.7 vs 4.5 ± 1.6 days; P = .02). Multivariate analysis showed that the cardiac output Z-score at diagnosis (P = .012) and the birthweight Z-score (P = .007) were independent predictors of the length of neonatal hospitalization. CONCLUSIONS: Different maternal hemodynamic profiles characterize women with SGA or FGR fetuses. Furthermore, a negative correlation was found between the maternal cardiac output and the length of neonatal hospitalization.

Ultrasound Image Characteristic Analysis of Sciatic Nerve and Main Branches in Third Trimester.

BACKGROUND: The pathogenesis and clinical characteristics of sciatica caused by pregnancy were summarized to reduce the incidence of misdiagnoses and missed diagnoses. The sciatic nerve, tibial nerve, common peroneal nerve, sural nerve, superficial peroneal nerve, saphenous nerve, and lateral femoral cutaneous nerve were examined using ultrasonography for 7 imaging features, including the shape and internal structure of the peripheral nerves of the lower extremities. METHODS: Randomly selected healthy pregnant women and pregnant women without peripheral nerve damage in the third trimester were examined using a Philips iU22 color Doppler ultrasound scanner with a L12-5 high-frequency probe. The probe was moved anatomically along the peripheral nerves of the lower extremities, including the sciatic nerve, tibial nerve, superficial peroneal nerve, saphenous nerve, and lateral femoral cutaneous nerve. The nerve morphology, structural characteristics, and accompanying blood vessels, tendons, muscles, bones, and other tissues and structures were examined. To determine the site at which to measure the cross-sectional area of the target nerve, we selected places with obvious body surface signs (e.g., popliteal fossa, medial malleolus), less nerve position variation (e.g., neurology start, nerve bifurcation), ultrasound-visible features (e.g., popliteal arteriovenous, fibula head). RESULTS: Ultrasound examination showed that the cross-sections of the peripheral nerves of the lower limbs were triangular, circular, quasicircular, quasitriangular, oval, broad bean-shaped, and drop-shaped. When viewing the same measurement site, the nerve shape was similar and the shape variation was small. However, at different measurement sites, large differences were seen in the shape of the nerves. Hyperechoic shadows are present around the nerves, which make the nerves and adjacent tissues clearly visible. Inside the nerves, at the proximal end of the limbs and in the nerves with larger cross-sections, echo images of varying heights were seen. The arrangement was uniform and regular, and the high echo images were arranged in dots or lines, interlayered with the low echo images to form a honeycomb-like structure. The high and low echo images were arranged uniformly and densely in the distal limbs or inside the small nerves with a small cross section. Arranged in a dot pattern, the structure of nerve walking and accompanying tissues is consistent with the anatomy and is characteristic. CONCLUSION: We found no significant differences in the peripheral nerve cross-sectional area between the left and right legs but did find a positive correlation with body mass index and age.

Impact of gestational diabetes mellitus on fetal cardiac morphology and function: cohort comparison of second- and third-trimester fetuses.

OBJECTIVES: To assess differences in cardiac morphology and function in fetuses of mothers with gestational diabetes mellitus (GDM) compared to controls, and to assess whether, in women with GDM, fetal cardiac changes are accentuated with advancing gestational age. METHODS: We studied 112 women with GDM and 224 women with uncomplicated pregnancy at 24-40 weeks' gestation. In all fetuses, a standard four-chamber oblique view was obtained and offline speckle-tracking analysis was performed to measure right and left endocardial global longitudinal strain (GLS) and tricuspid and mitral annular plane systolic excursion. Global sphericity index was also calculated. Echocardiographic parameters were compared between GDM fetuses and controls at two gestational time periods of 24 + 0 to 32 + 0 weeks and 32 + 1 to 40 + 1 weeks. RESULTS: At 24 + 0 to 32 + 0 weeks, we phenotyped 43 fetuses from mothers with GDM and 71 from uncomplicated pregnancies, and, at 32 + 1 to 40 + 1 weeks, we phenotyped 69 fetuses from mothers with GDM and 153 from women with uncomplicated pregnancy. In fetuses of mothers with GDM, compared to controls, right ventricular functional indices were consistently lower both at 24 + 0 to 32 + 0 weeks and at 32 + 1 to 40 + 1 weeks. Right ventricular GLS was reduced in the GDM group at 24 + 0 to 32 + 0 weeks (adjusted mean difference, 0.7%; 95% CI, 0.3-1.1%) and at 32 + 1 to 40 + 1 weeks (adjusted mean difference, 0.9%; 95% CI, 0.6-1.1%). Fetal left ventricular global longitudinal function was similar in GDM pregnancies compared with controls, with the exception of the contractility of the left ventricular basal segment, which was reduced. Global sphericity index was reduced in GDM pregnancies only at 32 + 1 to 40 + 1 weeks (adjusted mean difference, -0.4; 95% CI, -0.7 to 0.1). CONCLUSIONS: The offspring of women with GDM are at high risk for development of cardiovascular disease in childhood and early adulthood. Our study demonstrates that GDM is associated with a reduction mainly in fetal right ventricular function, compared to controls, and this response is not exaggerated with increasing gestational age. Further studies are needed to determine whether fetuses with the observed alterations in cardiac function are those at highest risk for subsequent development of cardiovascular disease. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Sight-Threatening Graves' Ophthalmopathy during the Third Trimester of Pregnancy: A Case Report.

Dysthyroid optic neuropathy is a severe manifestation of Graves' ophthalmopathy that can result in permanent vision loss. We report a 37-year-old pregnant woman with Graves' ophthalmopathy which was deteriorated to dysthyroid optic neuropathy in the third trimester of pregnancy. Diplopia, bilateral eye lid retraction, lid edema and proptosis were observed in the 29th week of gestation. Thyroid-stimulating hormone (TSH) level was decreased with a normal level of free triiodothyronine (FT3) and an upper normal level of free thyroxine (FT4). Anti-TSH receptor antibodies (16.2 IU/L, reference range < 2.0 IU/L) and thyroid stimulating antibody (4,443%, reference range < 120%) were positive. Magnetic resonance imaging (MRI) demonstrated a significant enlargement of the extraocular muscles with a high signal intensity on T2-weighted image. She was diagnosed as Graves' ophthalmopathy and subclinical hyperthyroidism, and followed without treatment. In the 34th week of gestation, the symptom of color vision abnormality appeared, suggesting dysthyroid optic neuropathy. She delivered a female infant during the 36th week of gestation. Four days after delivery, she had a spontaneous orbital pain. MRI showed that the extraocular muscles were more enlarged than the findings in the 29th week of gestation. FT3 and FT4 levels were mildly elevated. Dysthyroid optic neuropathy was diagnosed. She was treated with methylprednisolone pulse therapy and retrobulbar injections of betamethasone valerate, and the ocular symptoms improved. The present case shows that the glucocorticoid therapy performed one week after delivery is effective against Graves' ophthalmopathy which was deteriorated to dysthyroid optic neuropathy during the third trimester of pregnancy.

Weight Gain Before the Third Trimester and Risk of Hypertensive Disorders of Pregnancy: A Prospective Cohort Study.

BACKGROUND The association between excessive gestational weight gain (GWG) and the risk of hypertensive disorders of pregnancy (HDP) remains uncertain in women with increased water retention in late gestation associated with the pathophysiology of HDP. This study aimed to investigate the association between GWG before the third trimester and the risk of HDP. MATERIAL AND METHODS This was a prospective cohort study in singleton-pregnant women in Tianjin, China, from 2016. Generalized linear models were used to analyze the relationship between weight gain and the risk of HDP. RESULTS A total of 5295 singleton-pregnant women were included. Even after adjusting for relevant confounders, weight gain at approximately 28 weeks remained an independent risk factor for HDP in the normal-weight group. Compared to the reference of low weight gain (+1 SD was associated with an approximately 2.0 times greater likelihood of HDP (RR: 2.08, 95% CI: 1.06-4.08). Moreover, there was a positive relationship between weight gain in the short interval of early pregnancy and risk of HDP in overweight women. CONCLUSIONS Excessive weight gain before the third trimester was associated with a greater risk of developing HDP among women with early-pregnancy normal weight, which may provide a chance to identify subsequent hypertensive disorders. Additional research is needed to determine whether early-pregnancy weight gain is associated with HDP risk.

Trophoblast invasion: Lessons from abnormally invasive placenta (placenta accreta).

The invasion of the uterine wall by extravillous trophoblast is acknowledged as a crucial component of the establishment of pregnancy however, the only part of this process that has been clearly identified is the differentiation of cytotrophoblast (CTB) into the invasive extravillous trophoblast (EVT). The control of invasion, both initiation and termination, have yet to be elucidated and even the mechanism of differentiation is unclear. This review describes our studies which are designed to characterize the intracellular mechanisms that drive differentiation. We have used the over-invasion observed in abnormally invasive placenta (AIP; placenta accreta) to further interrogate this mechanism. Our results show that first trimester CTB to EVT differentiation is accomplished via an epithelial-mesenchymal transition (EMT), with EVT displaying a metastable, mesenchymal phenotype. In the third trimester, while the invasiveness of the EVT is lost, these cells still demonstrate signs of the EMT, albeit diminished. EVT isolated from AIP pregnancies do not however, show the same degree of reduction in EMT shown by normal third trimester cells. They exhibit a more mesenchymal phenotype, consistent with a legacy of greater invasiveness. The master regulatory transcription factor controlling the EMT appears, from the observational data, to be ZEB2 (zinc finger E-box binding protein 2). We verified this by overexpressing ZEB2 in the BeWo and JEG3 trophoblast cell lines and showing that they became more stellate in shape, up-regulated the expression of EMT-associated genes and demonstrated a substantially increased degree of invasiveness. The identification of the differentiation mechanism will enable us to identify the factors controlling invasion and those aberrant processes which generate the abnormal invasion seen in pathologies such as AIP and preeclampsia.

Beat-to-Beat Blood Pressure Variability in the First Trimester Is Associated With the Development of Preeclampsia in a Prospective Cohort: Relation With Aortic Stiffness.

Women with preeclampsia, a hypertensive disorder of pregnancy, exhibit greater beat-to-beat blood pressure variability (BPV) in the third trimester after clinical onset of the disorder. However, it remains unknown whether elevated BPV precedes the development of preeclampsia. A prospective study cohort of 139 women (age 30.2±4.0 years) were enrolled in early pregnancy (<14 weeks gestation). BPV was quantified by time domain analyses of 10-minute continuous beat-to-beat blood pressure recordings via finger photoplethysmography in the first, second, and third trimesters. Aortic stiffness (carotid-femoral pulse wave velocity) and spontaneous cardiovagal baroreflex sensitivity were also measured each trimester. Eighteen women (13%) developed preeclampsia. Systolic BPV was higher in all trimesters among women who developed versus did not develop preeclampsia (first: 4.8±1.3 versus 3.7±1.2, P=0.001; second: 5.1±1.8 versus 3.8±1.1, P=0.02; third: 5.2±0.8 versus 4.0±1.1 mm Hg, P=0.002). Elevated first trimester systolic BPV was associated with preeclampsia (odds ratio, 1.94 [95% CI, 1.27-2.99]), even after adjusting for risk factors (age, body mass index, systolic blood pressure, history of preeclampsia, and diabetes mellitus) and was a significant predictor of preeclampsia (area under the receiver operator characteristic curve=0.75±0.07; P=0.002). Carotid-femoral pulse wave velocity was elevated in the first trimester among women who developed preeclampsia (5.9±0.8 versus 5.2±0.8 m/s; P=0.002) and was associated with BPV after adjustment for mean blood pressure (r=0.26; P=0.005). First trimester baroreflex sensitivity did not differ between groups (P=0.23) and was not related to BPV (P=0.36). Elevated systolic BPV is independently associated with the development of preeclampsia as early as the first trimester, possibly mediated in part by higher aortic stiffness.