Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology, 2015
Corin, an atrial natriuretic peptide-converting enzyme, has been found to promote trophoblast inv... more Corin, an atrial natriuretic peptide-converting enzyme, has been found to promote trophoblast invasion and spiral artery remodeling. Yet, elevated maternal plasma atrial natriuretic peptide (ANP) and corin levels have been reported in pregnancies complicated by pre-eclampsia (PE). The aim of this study was to investigate longitudinal changes in maternal plasma levels of corin and mid-regional proatrial natriuretic peptide (MR-PANP) in pregnancies that develop PE and gestational hypertension (GH). This was a nested case-control study drawn from a larger prospective longitudinal study in singleton pregnancies identified as being at high risk for PE by screening at 11 + 0 to 13 + 6 weeks' gestation. Blood samples were taken every 4 weeks until delivery. Values were compared in pregnancies that developed preterm PE (requiring delivery before 37 weeks' gestation), term PE, GH and those that remained normotensive. A total of 471 samples were analyzed from 122 women, including 85 t...
To investigate the possible association between a particular pulsed Doppler waveform pattern, mit... more To investigate the possible association between a particular pulsed Doppler waveform pattern, mitral gap, and trisomy 21 at 11 + 0 to 13 + 6 weeks. We performed two studies. The first was a retrospective analysis of pulsed Doppler velocity waveforms of the mitral valve inflow, recorded during specialist fetal echocardiography in 291 chromosomally normal and 144 trisomy 21 fetuses with a nuchal translucency (NT) thickness of 3.5 mm or more. We examined each waveform in each trace to determine whether there was a gap between the E-wave (early diastolic filling) and A-wave (atrial contraction) in the waveform across the mitral valve. We also examined each trace that contained at least one waveform with a mitral gap and, first, noted the order of waveforms with a mitral gap relative to those without and, second, measured the A-wave peak velocity in a representative waveform with a mitral gap and in one without. The second study was a prospective investigation in which Doppler velocity waveforms of the mitral valve inflow were assessed in 227 singleton pregnancies immediately before chorionic villus sampling. A mitral gap was observed in 16 (5.5%) of the chromosomally normal and in 25 (17.4%) of the trisomy 21 fetuses. The incidence of mitral gap was significantly associated with the presence of cardiac defects but not with thickness of NT. The median number of waveforms per recorded image was 6 (range, 3-7) and in 32 (78%) of the 41 traces with a mitral gap only one or two of the waveforms was abnormal. The abnormal waveforms were in the middle or at the end of the trace in 95% of cases and had a lower mean A-wave peak velocity than did the normal waveforms (mean difference 3.7 cm/s; 95% CI, 0.3-7.0 cm/s; P = 0.03). In a prospective study of 10 normal fetuses we could produce a mitral gap deliberately by moving the sample volume out of the center of flow in the atrioventricular valve. In the prospective study of 227 pregnancies undergoing chorionic villus sampling a mitral gap was observed in 26/197 (13.2%) in which the fetal karyotype was subsequently found to be normal, 4/20 (20%) with trisomy 21 and 1/10 with other chromosomal defects. At 11 + 0 to 13 + 6 weeks, a mitral gap may be more common in fetuses with trisomy 21 than in fetuses with a normal karyotype. However, it is possible that a mitral gap does not reflect an underlying hemodynamic abnormality, but is rather the result of suboptimal positioning of the Doppler sample volume as the fetus moves during acquisition.
To examine the relationship between low maternal serum pregnancy-associated plasma protein-A (PAP... more To examine the relationship between low maternal serum pregnancy-associated plasma protein-A (PAPP-A) and uterine artery pulsatility index (UtA-PI) at 11+0 to 13+6 weeks with subsequent development of pre-eclampsia (PE). UtA-PI and serum PAPP-A were measured in women attending for routine care at 11+0 to 13+6 weeks of gestation. In the population, 156 (1.9%) women developed PE, including 32 (0.4%) in whom delivery was before 34 weeks (early PE) and 124 (1.5%) with delivery at 34 weeks or more (late PE); 7895 (98.1%) women had no PE. Regression analysis was used to examine which of the factors amongst maternal characteristics, log PAPP-A multiples of the median (MoM) and log UtA-PI MoM contributed to the prediction of PE. The median PAPP-A MoM was 1.002 (interquartile range (IQR), 0.685-1.411) in the unaffected group, 0.555 (IQR, 0.463-0.922) in early PE and 0.911 (IQR, 0.580-1.247) in late PE. Serum PAPP-A was below the 5th centile in 21.9% of early PE and 6.5% of late PE cases. The PAPP-A-related patient-specific risk for PE was strongly influenced by maternal characteristics. There was a significant association between log UtA-PI MoM and log PAPP-A MoM (P=0.001), and the detection rate of screening for PE by maternal variables and UtA-PI was not improved by inclusion of PAPP-A. Regression analysis was used to establish tables that allow modification of the maternal history and PAPP-A-related patient-specific risk for PE by the measurement of UtA-PI. Low PAPP-A is a marker for subsequent development of PE. The PAPP-A-related patient-specific risk for PE can be modified by the measurement of UtA-PI.
To examine the independent contribution of abnormal flow in the ductus venosus at 11 to 13 weeks ... more To examine the independent contribution of abnormal flow in the ductus venosus at 11 to 13 weeks of gestation in the prediction of adverse pregnancy outcome in relation to chorionicity. This was a prospective study in 516 dichorionic and 179 monochorionic twin pregnancies in which the fetal ductus venosus flow was assessed at 11 0/7 to 13 6/7 weeks of gestation. The prevalence of reversed a-wave in the fetal ductus venosus was compared between monochorionic and dichorionic pregnancies and between those with and without pregnancy complications. Comparisons between each of the pregnancy outcomes and the normal outcome group and between monochorionic and dichorionic pregnancies were made using the Mann-Whitney U-test for continuous variables and the chi2 test and Fisher exact test for categorical variables. The prevalence of reversed a-wave in at least one of the fetuses was significantly higher in monochorionic than in dichorionic pregnancies (18.4% compared with 8.3%, P<.001) and in pregnancies complicated by miscarriage (28.6%, P=.005), fetal aneuploidy (70.0%, P<.001), and twin-twin transfusion syndrome (38.5%, P<.001) compared with the pregnancies with two healthy live births (7.7%). Pregnancy outcome was normal in 33 of the 43 (76.7%) dichorionic and in 14 of the 33 (42.4%) monochorionic twins with reversed a-wave in at least one of the fetuses. In twins, reversed a-wave in the ductus venosus at 11 to 13 weeks of gestation is associated with increased risk for aneuploidies, miscarriage, and development of severe twin-twin transfusion syndrome. However, in about 75% of dichorionic twins and 40% of monochorionic twins with reversed a-wave, the pregnancy outcome is normal. II.
To examine the performance of screening for hypertensive disorders in pregnancy and to compare sy... more To examine the performance of screening for hypertensive disorders in pregnancy and to compare systolic blood pressure (BP), diastolic BP, and mean arterial pressure (MAP) measured by validated automated devices in a large population of pregnant women at 11-13 weeks. We recorded maternal variables and measured BP by automated devices in 9149 women with singleton pregnancies. The performance of screening for preeclampsia (PE) and gestational hypertension (GH) by combinations of disease-specific maternal factor-derived a priori risk with systolic BP, diastolic BP, and MAP was determined. There were 8061 cases that were unaffected by PE or GH, 37 that developed PE requiring delivery before 34 weeks (early-PE), 128 with late-PE, and 140 with GH. The systolic BP, diastolic BP, and MAP were significantly higher in early-PE, late-PE, and GH than in the controls (p < 0.0001). The systolic BP was significantly higher in early-PE than in late-PE (p = 0.008) and both systolic BP and MAP were significantly higher in early-PE than in GH (p < 0.01). The best performance in screening was provided by MAP. The detection rate of early-PE at a 10% false-positive rate increased from 47% in screening by maternal factor-derived a priori risk alone to 76% in screening by its combination with MAP. The respective detection rates for late-PE increased from 41 to 52% and for GH increased from 31 to 48%. The measurement of BP can be combined with the maternal factor-derived a priori risk to provide effective first-trimester screening for PE and GH.
Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology, 2015
Corin, an atrial natriuretic peptide-converting enzyme, has been found to promote trophoblast inv... more Corin, an atrial natriuretic peptide-converting enzyme, has been found to promote trophoblast invasion and spiral artery remodeling. Yet, elevated maternal plasma atrial natriuretic peptide (ANP) and corin levels have been reported in pregnancies complicated by pre-eclampsia (PE). The aim of this study was to investigate longitudinal changes in maternal plasma levels of corin and mid-regional proatrial natriuretic peptide (MR-PANP) in pregnancies that develop PE and gestational hypertension (GH). This was a nested case-control study drawn from a larger prospective longitudinal study in singleton pregnancies identified as being at high risk for PE by screening at 11 + 0 to 13 + 6 weeks' gestation. Blood samples were taken every 4 weeks until delivery. Values were compared in pregnancies that developed preterm PE (requiring delivery before 37 weeks' gestation), term PE, GH and those that remained normotensive. A total of 471 samples were analyzed from 122 women, including 85 t...
To investigate the possible association between a particular pulsed Doppler waveform pattern, mit... more To investigate the possible association between a particular pulsed Doppler waveform pattern, mitral gap, and trisomy 21 at 11 + 0 to 13 + 6 weeks. We performed two studies. The first was a retrospective analysis of pulsed Doppler velocity waveforms of the mitral valve inflow, recorded during specialist fetal echocardiography in 291 chromosomally normal and 144 trisomy 21 fetuses with a nuchal translucency (NT) thickness of 3.5 mm or more. We examined each waveform in each trace to determine whether there was a gap between the E-wave (early diastolic filling) and A-wave (atrial contraction) in the waveform across the mitral valve. We also examined each trace that contained at least one waveform with a mitral gap and, first, noted the order of waveforms with a mitral gap relative to those without and, second, measured the A-wave peak velocity in a representative waveform with a mitral gap and in one without. The second study was a prospective investigation in which Doppler velocity waveforms of the mitral valve inflow were assessed in 227 singleton pregnancies immediately before chorionic villus sampling. A mitral gap was observed in 16 (5.5%) of the chromosomally normal and in 25 (17.4%) of the trisomy 21 fetuses. The incidence of mitral gap was significantly associated with the presence of cardiac defects but not with thickness of NT. The median number of waveforms per recorded image was 6 (range, 3-7) and in 32 (78%) of the 41 traces with a mitral gap only one or two of the waveforms was abnormal. The abnormal waveforms were in the middle or at the end of the trace in 95% of cases and had a lower mean A-wave peak velocity than did the normal waveforms (mean difference 3.7 cm/s; 95% CI, 0.3-7.0 cm/s; P = 0.03). In a prospective study of 10 normal fetuses we could produce a mitral gap deliberately by moving the sample volume out of the center of flow in the atrioventricular valve. In the prospective study of 227 pregnancies undergoing chorionic villus sampling a mitral gap was observed in 26/197 (13.2%) in which the fetal karyotype was subsequently found to be normal, 4/20 (20%) with trisomy 21 and 1/10 with other chromosomal defects. At 11 + 0 to 13 + 6 weeks, a mitral gap may be more common in fetuses with trisomy 21 than in fetuses with a normal karyotype. However, it is possible that a mitral gap does not reflect an underlying hemodynamic abnormality, but is rather the result of suboptimal positioning of the Doppler sample volume as the fetus moves during acquisition.
To examine the relationship between low maternal serum pregnancy-associated plasma protein-A (PAP... more To examine the relationship between low maternal serum pregnancy-associated plasma protein-A (PAPP-A) and uterine artery pulsatility index (UtA-PI) at 11+0 to 13+6 weeks with subsequent development of pre-eclampsia (PE). UtA-PI and serum PAPP-A were measured in women attending for routine care at 11+0 to 13+6 weeks of gestation. In the population, 156 (1.9%) women developed PE, including 32 (0.4%) in whom delivery was before 34 weeks (early PE) and 124 (1.5%) with delivery at 34 weeks or more (late PE); 7895 (98.1%) women had no PE. Regression analysis was used to examine which of the factors amongst maternal characteristics, log PAPP-A multiples of the median (MoM) and log UtA-PI MoM contributed to the prediction of PE. The median PAPP-A MoM was 1.002 (interquartile range (IQR), 0.685-1.411) in the unaffected group, 0.555 (IQR, 0.463-0.922) in early PE and 0.911 (IQR, 0.580-1.247) in late PE. Serum PAPP-A was below the 5th centile in 21.9% of early PE and 6.5% of late PE cases. The PAPP-A-related patient-specific risk for PE was strongly influenced by maternal characteristics. There was a significant association between log UtA-PI MoM and log PAPP-A MoM (P=0.001), and the detection rate of screening for PE by maternal variables and UtA-PI was not improved by inclusion of PAPP-A. Regression analysis was used to establish tables that allow modification of the maternal history and PAPP-A-related patient-specific risk for PE by the measurement of UtA-PI. Low PAPP-A is a marker for subsequent development of PE. The PAPP-A-related patient-specific risk for PE can be modified by the measurement of UtA-PI.
To examine the independent contribution of abnormal flow in the ductus venosus at 11 to 13 weeks ... more To examine the independent contribution of abnormal flow in the ductus venosus at 11 to 13 weeks of gestation in the prediction of adverse pregnancy outcome in relation to chorionicity. This was a prospective study in 516 dichorionic and 179 monochorionic twin pregnancies in which the fetal ductus venosus flow was assessed at 11 0/7 to 13 6/7 weeks of gestation. The prevalence of reversed a-wave in the fetal ductus venosus was compared between monochorionic and dichorionic pregnancies and between those with and without pregnancy complications. Comparisons between each of the pregnancy outcomes and the normal outcome group and between monochorionic and dichorionic pregnancies were made using the Mann-Whitney U-test for continuous variables and the chi2 test and Fisher exact test for categorical variables. The prevalence of reversed a-wave in at least one of the fetuses was significantly higher in monochorionic than in dichorionic pregnancies (18.4% compared with 8.3%, P<.001) and in pregnancies complicated by miscarriage (28.6%, P=.005), fetal aneuploidy (70.0%, P<.001), and twin-twin transfusion syndrome (38.5%, P<.001) compared with the pregnancies with two healthy live births (7.7%). Pregnancy outcome was normal in 33 of the 43 (76.7%) dichorionic and in 14 of the 33 (42.4%) monochorionic twins with reversed a-wave in at least one of the fetuses. In twins, reversed a-wave in the ductus venosus at 11 to 13 weeks of gestation is associated with increased risk for aneuploidies, miscarriage, and development of severe twin-twin transfusion syndrome. However, in about 75% of dichorionic twins and 40% of monochorionic twins with reversed a-wave, the pregnancy outcome is normal. II.
To examine the performance of screening for hypertensive disorders in pregnancy and to compare sy... more To examine the performance of screening for hypertensive disorders in pregnancy and to compare systolic blood pressure (BP), diastolic BP, and mean arterial pressure (MAP) measured by validated automated devices in a large population of pregnant women at 11-13 weeks. We recorded maternal variables and measured BP by automated devices in 9149 women with singleton pregnancies. The performance of screening for preeclampsia (PE) and gestational hypertension (GH) by combinations of disease-specific maternal factor-derived a priori risk with systolic BP, diastolic BP, and MAP was determined. There were 8061 cases that were unaffected by PE or GH, 37 that developed PE requiring delivery before 34 weeks (early-PE), 128 with late-PE, and 140 with GH. The systolic BP, diastolic BP, and MAP were significantly higher in early-PE, late-PE, and GH than in the controls (p < 0.0001). The systolic BP was significantly higher in early-PE than in late-PE (p = 0.008) and both systolic BP and MAP were significantly higher in early-PE than in GH (p < 0.01). The best performance in screening was provided by MAP. The detection rate of early-PE at a 10% false-positive rate increased from 47% in screening by maternal factor-derived a priori risk alone to 76% in screening by its combination with MAP. The respective detection rates for late-PE increased from 41 to 52% and for GH increased from 31 to 48%. The measurement of BP can be combined with the maternal factor-derived a priori risk to provide effective first-trimester screening for PE and GH.
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Papers by N. Maiz