Fetal cerebrovascular response to maternal hyperoxygenation in congenital heart disease: effect of cardiac physiology.

OBJECTIVE: Fetal cerebrovascular resistance is influenced by several factors in the setting of intact autoregulation to allow for normal cerebral blood flow and oxygenation. Maternal hyperoxygenation (MH) allows for acute alterations in fetal physiology and can be a tool to test cerebrovascular reactivity in late-gestation fetuses. In this study, we utilized MH to evaluate cerebrovascular reactivity in fetuses with specific congenital heart disease (CHD). METHODS: This was a cross-sectional study of fetuses with complex CHD compared to controls without CHD. CHD cases were grouped according to physiology into: left-sided obstructive lesion (LSOL), right-sided obstructive lesion (RSOL) or dextro-transposition of the great arteries (d-TGA). Subjects underwent MH testing during the third-trimester fetal echocardiogram. The pulsatility index (PI) was calculated for the fetal middle cerebral artery (MCA), umbilical artery (UA) and branch pulmonary artery (PA). The change in PI from baseline to during MH was compared between each CHD group and controls. RESULTS: Sixty pregnant women were enrolled (CHD, n = 43; control, n = 17). In the CHD group, there were 27 fetuses with LSOL, seven with RSOL and nine with d-TGA. Mean gestational age was 33.9 (95% CI, 33.6-34.2) weeks. At baseline, MCA-PI Z-score was lowest in the LSOL group (-1.8 (95% CI, -2.4 to -1.2)) compared with the control group (-0.8 (95% CI, -1.3 to -0.3)) (P = 0.01). In response to MH, MCA-PI Z-score increased significantly in the control and d-TGA groups but did not change significantly in the LSOL and RSOL groups. The change in MCA-PI Z-score was significantly higher in the control group than in the LSOL group (0.9 (95% CI, 0.42-1.4) vs 0.12 (95% CI, -0.21 to 0.45); P = 0.03). This difference was more pronounced in the LSOL subgroup with retrograde aortic arch flow. Branch PA-PI decreased significantly in response to MH in all groups, with no difference in the change from baseline to MH between the groups, while UA-PI was unchanged during MH compared with at baseline. CONCLUSIONS: The fetal cerebrovascular response to MH varies based on the underlying CHD diagnosis, suggesting that cardiovascular physiology may influence the autoregulatory capacity of the fetal brain. Further studies are needed to determine the clinical implications of these findings on long-term neurodevelopment in these at-risk children. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Fetal cerebrovascular impedance is reduced in left congenital diaphragmatic hernia.

OBJECTIVES: Congenital diaphragmatic hernia (CDH) can cause a significant mass effect in the fetal thorax, displacing the heart into the opposite hemithorax. In left-sided CDH (L-CDH), this is associated with smaller left-sided cardiac structures and reduced left-ventricular cardiac output (LVCO). The effect of these physiologic changes on cerebral blood flow is not well understood. We sought to describe the middle cerebral artery (MCA) pulsatility index (PI), a measure of cerebrovascular impedance, in fetuses with L-CDH and those with right-sided CDH (R-CDH) compared with unaffected fetuses, and the relationship between MCA-PI and LVCO. We hypothesized that MCA-PI would be lower in fetuses with L-CDH and similar in those with R-CDH compared to controls, and that MCA-PI would be correlated with LVCO. METHODS: We identified all fetuses with CDH evaluated at The University of California San Francisco, San Francisco, CA, USA from 2011 to 2018. Fetal echocardiograms and ultrasound scans were reviewed. Umbilical artery and MCA Doppler examinations were assessed to calculate pulsatility indices. Ventricular outputs were calculated using Doppler-derived stroke volume and fetal heart rate. Lung-to-head ratio (LHR), estimated fetal weight, biparietal diameter (BPD) and head circumference (HC) were obtained from fetal sonograms. Measurements in fetuses with CDH, according to the side of the defect, were compared with those in unaffected, gestational age-matched controls. A subset of CDH survivors had available data on neurodevelopmental outcome, as assessed using the Bayley Scales of Infant Development, 3rd edition. RESULTS: A total of 64 fetuses with CDH (L-CDH, n = 53; R-CDH, n = 11) comprised the study groups, with 27 unaffected fetuses serving as controls. Mean gestational age at evaluation was similar between the three groups. Compared to controls, fetuses with L-CDH had significantly lower LVCO expressed as a percentage of combined cardiac output (CCO) (32%; 95% CI, 29-35% vs 38%; 95% CI, 33-42%; P = 0.04) and lower MCA-PI Z-score (-1.3; 95% CI, -1.7 to -1.0 vs 0.08; 95% CI, -0.5 to 0.6; P < 0.001), while they did not differ between the R-CDH group and controls. There was a strong positive association between LVCO as a percentage of CCO and MCA-PI Z-score in the overall cohort of CDH and control fetuses (P = 0.01). BPD and HC were similar between the three groups. At neurodevelopmental follow-up, mean cognitive, motor and language scores in the CDH group were within 1 SD of those in the general population. CONCLUSION: MCA-PI values are significantly lower in fetuses with L-CDH as compared to controls, and lower LVCO was correlated with lower MCA vascular impedance. The neurodevelopmental effect of changes in MCA-PI in response to decreased LVCO is unknown, although, on average, CDH survivors had neurodevelopmental scores in the normal range. This may reflect a fetal compensatory mechanism in response to diminished antegrade cerebral blood flow. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Twin-reversed arterial perfusion sequence associated with decreased fetal cerebral vascular impedance.

OBJECTIVES: Twin-reversed arterial perfusion (TRAP) sequence affects 1% of monochorionic twin pregnancies and is caused by abnormal vascular connections between a pump twin and an acardiac mass. The effects of abnormal vascular connections on cerebral vasculature in the pump twin are unknown. We hypothesize that abnormal cerebral vascular impedance, as assessed by the pulsatility index (PI), is present in pump twins and that fetal intervention alters cerebral impedance. METHODS: Fetal echocardiograms performed between 2010 and 2013 in pregnancies diagnosed with TRAP (n = 19), recorded at presentation, and uncomplicated monochorionic twin pregnancies (controls, n = 18; 36 fetuses) were analyzed. In all subjects, the middle cerebral artery (MCA)-PI, combined cardiac output (CCO) and cardiothoracic ratio were calculated, and the values for cases and controls were compared. RESULTS: The mean gestational age at the time of echocardiography was 20 weeks in both groups. MCA-PI was lower in TRAP cases than in controls (1.55 (95% CI, 1.47-1.64) vs 1.74 (95% CI, 1.65-1.82), respectively; P = 0.004). CCO in TRAP cases was mildly elevated for gestational age (199.7 (95% CI, 138.4-261.1) mL/min) compared with that of controls (131.4 (95% CI, 102.2-160.7) mL/min). In six TRAP cases with a second echocardiogram available, the mean MCA-PI increased after intervention, from 1.5 (95% CI, 1.3-1.7) to 1.8 (95% CI, 1.4-2.2). CONCLUSIONS: TRAP pump twins have lower cerebral vascular impedance than do controls, suggestive of a brain-sparing effect. MCA-PI appeared to increase in a small group of pump twins after intervention. These findings suggest a fetal cerebral autoregulatory response to a high cardiac output state that begins to change after fetal intervention. The long-term implications for neurodevelopmental outcome warrant further study.

Pulmonary artery blood flow patterns in fetuses with pulmonary outflow tract obstruction.

OBJECTIVES: Fetuses with pulmonary outflow tract obstruction (POTO) have altered blood flow to the pulmonary vasculature. We sought to determine whether pulmonary vascular impedance, as assessed by the pulsatility index (PI), is different in fetuses with POTO compared with normal controls. METHODS: Branch pulmonary artery PI was evaluated in age-matched normal control fetuses (n=22) and 20 POTO fetuses (pulmonary stenosis n=15, pulmonary atresia n=5). Pulsed-wave Doppler was performed in the proximal (PA1), mid (PA2) and distal (PA3) branch pulmonary artery. The direction of flow in the ductus arteriosus was noted. The study and control groups were compared with Student's t-test and ANOVA. A linear mixed model evaluated the relationship between PI and ductus arteriosus flow patterns. RESULTS: There was no difference in PI between control, pulmonary stenosis and pulmonary atresia subjects at PA1 and PA2; however, there was a significant difference at PA3. Subjects with pulmonary atresia had a lower PI at PA3 than did controls (P=0.003) and pulmonary stenosis subjects (P=0.003). Subjects with retrograde flow in the ductus arteriosus had lower PIs in PA2 and PA3 than did those with antegrade flow (P=0.01 and 0.005, respectively). The PI in PA3 was lower in fetuses that required prostaglandin postnatally than in those that did not (P=0.008). CONCLUSIONS: Fetuses with pulmonary atresia or severe pulmonary stenosis with retrograde flow in the ductus arteriosus have decreased PI in the distal pulmonary vasculature. Our findings indicate the capacity of the fetal pulmonary vasculature to vasodilate in response to anatomical obstruction of flow.

Comparison of pregnancy and implantation rates in zygote intrafallopian transfer and uterine embryo transfer for nontubal infertility.

We carried out a prospective randomized trial on 220 couples with nontubal factor infertility to compare pregnancy rates and implantation rates after zygote intrafallopian transfer (ZIFT) and uterine embryo transfer (UET). The zygote was transferred by laparoscopy into the fallopian tube 24 hours after oocyst retrieval. UET was performed 72 hours after retrieval with abdominal sonography guide. Transfer was performed in 102 cycles in the ZIFT and 100 cycles in the U ET group. The pregnancy and implantation rates were significantly higher in the ZIFT group (42.1% and 11.7%) than in the UET group (21.0% and 7.8%) (P < 0.05). ZiFT could be considered for couples who have limited time and adequate financial support.

Comparison of pregnancy and implantation rates in zygote intrafallopian transfer and uterine embryo transfer for nontubal infertility

We carried out a prospective randomized trial on 220 couples with nontubal factor infertility to compare pregnancy rates and implantation rates after zygote intrafallopian transfer [ZIFT] and uterine embryo transfer [UET]. The zygote was transferred by laparoscopy into the fallopian tube 24 hours after oocyst retrieval. UET was performed 72 hours after retrieval with abdominal sonography guide. Transfer was performed in 102 cycles in the ZIFT and 100 cycles in the UET group. The pregnancy and implantation rates were significantly higher in the ZIFT group [42.1% and 11.7%] than in the UET group [21.0% and 7.8%] [P < 0.05]. ZIFT could be considered for couples who have limited time and adequate financial support

Evaluation of vaginal misoprostol effect on pregnancy rate after intrauterine insemination.

The goal of this study was to evaluate the effect ofmisoprostol on pregnancy rate after intrauterine insemination. This randomized double blind clinical trial study was performed on 66 (33 cases and 33 controls) infertile women who referred to infertility center of Imam Khomeini Hospital Sari, Iran for intrauterine insemination during 2006-2007. The two groups were matched for age, infertility causes and BMI. After intrauterine insemination, 200 mcg misoprostol was placed in posterior fornix of case group and a similar placebo tablet in control group. Chemical and clinical pregnancies and complications were recorded. Results were analyzed by means of SPSS 11 software, paired t-test and student t-test. The p-values of less than 0.05 were considered to be statistically significant. Chemical pregnancy (positive BHCG) occurred in 6 patients (18.2%) in each group. Clinical pregnancy occurred in 5 patients (15.15%) in case and 6 patients (18.2%) in controls. There were no significant statistical differences in complications between the two groups. Vaginal misoprostol after intrauterine insemination does not improve pregnancy rate.

Urinary protein assessment in preeclampsia: which sample is more suitable?

Mild or severe preeclampsia is responsible for about 70% of hypertensive disorders observed during pregnancy and 24 h urine collection is a gold standard for diagnosis ofpreeclampsia. This study was performed to determine whether the gold standard of 24 h urine protein value in pre-eclampsia can be substituted with 8 or 12 h urine protein values and to evaluate the effect of ambulation and immobilization on amount of protein excretion. A cross sectional study was conducted on 40 women with pre-eclampsia (BP > or = 140/90 mmHg), who referred to the Department of Obstetric and Gynecology, Imam Khomeiny hospital in Sari, Iran from April 2005 to September 2005. Positive urinary strip for protein of at least 1+ samples were collected over 24 h in subsequent periods: the first 8 h and the next 4 h and remaining 12 h urine, in separate containers. The correlation between groups was determined by Pearson's correlation. A total of 40 women were recurited in this study of which 36 had completed urine collection. A total of 21 had mild proteinuria, 5 had severe proteinuria and 10 had no proteinuria. There was significant correlation between the 8 or 12 h (day) and 12 h (night) with 24 h urine protein. Total protein values of 8 and 12 h (day) and 12 h (night) samples, positively correlated with values of 24 h samples in pre-eclampsia and could be substituted for assessment of proteinuria instead of 24 h urine collection in women with pre-eclampsia, as a simpler, faster and cheaper method for diagnosis of pre-eclampsia. And ambulation and immobilization in preeclamptic patients has not any effect on protein excretion.