Uterine artery resistance and anxiety in the second trimester of pregnancy.

OBJECTIVE: To investigate the association between maternal anxiety and uterine artery resistance index (RI) at 20 weeks of gestation. METHODS: Uterine artery blood flow was assessed using color Doppler ultrasound and maternal anxiety was measured using the Hospital Anxiety and Depression (HAD) scale in 96 healthy primigravid women attending consecutively for their routine 20-week anomaly scan. RESULTS: The mean uterine artery RI was 0.54 (95% confidence interval, 0.52-0.56) and the median HAD anxiety score was 6 (range, 0-20). There was no association between RI and anxiety scores (r = 0.09, P = 0.36). Women scoring as definite cases of anxiety did not have a significantly elevated uterine artery RI or increased frequency of waveform notching compared to women with doubtful or no anxiety. CONCLUSIONS: The data of this study do not suggest a significant association between maternal anxiety and uterine artery RI at 20 weeks of gestation in healthy primigravid women with normally developing pregnancies. A prospective cohort study would be useful to determine the nature of the relationship between maternal anxiety, alteration in uterine artery blood flow and abnormal pregnancy outcome.     

Screening for Down syndrome based on maternal age or fetal nuchal translucency: a randomized controlled trial in 39,572 pregnancies.

OBJECTIVES: Nuchal translucency (NT) screening increases antenatal detection of Down syndrome (DS) compared to maternal age-based screening. We wanted to determine if a change in policy for prenatal diagnosis would result in fewer babies born with DS. METHODS: A total of 39,572 pregnant women were randomized to a scan at 12-14 gestational weeks including NT screening for DS (12-week group) or to a scan at 15-20 weeks with screening for DS based on maternal age (18-week group). Fetal karyotyping was offered if risk according to NT was > or = 1:250 in the 12-week group and if maternal age was > or = 35 years in the 18-week group. Both policies included the offer of karyotyping in cases of fetal anomaly detected at any scan during pregnancy or when there was a history of fetal chromosomal anomaly. The number of babies born with DS and the number of invasive tests for fetal karyotyping were compared. RESULTS: Ten babies with DS were born alive with the 12-week policy vs. 16 with the 18-week policy (P = 0.25). More fetuses with DS were spontaneously lost or terminated in the 12-week group (45/19,796) than in the 18-week group (27/19 776; P = 0.04). All women except one with an antenatal diagnosis of DS at < 22 weeks terminated the pregnancy. For each case of DS detected at < 22 weeks in a living fetus there were 16 invasive tests in the 12-week group vs. 89 in the 18-week group. NT screening detected 71% of cases of DS for a 3.5% test-positive rate whereas maternal age had the potential of detecting 58% for a test-positive rate of 18%. CONCLUSIONS: The number of newborns with DS differed less than expected between pregnancies that had been screened at 12-14 weeks' gestation by NT compared with those screened at 15-20 weeks by maternal age. One explanation could be that NT screening--because it is performed early in pregnancy--results in the detection and termination of many pregnancies with a fetus with DS that would have resulted in miscarriage without intervention, and also by many cases of DS being detected because of a fetal anomaly seen on an 18-week scan. The major advantage of the 12-week scan policy is that many fewer invasive tests for fetal karyotyping are needed per antenatally detected case of DS.     

The influence of maternal hematocrit on placental development from the first to the second trimesters of pregnancy.

OBJECTIVES: To study the influence of maternal hematocrit (Ht) and hemoglobin (Hb) levels on placental size and growth in the first and mid-second trimesters of pregnancy. SUBJECTS/METHODS: This was a prospective study performed at the fetal medicine unit of a university hospital. One hundred and eighty-one women with a singleton pregnancy were recruited at 11-14 weeks' gestation. For each case three scans of the placenta were performed, the first at recruitment and the following two at 3-week intervals. The volume of the placenta was measured at each visit using a three-dimensional ultrasound scanner. The maternal Hb and Ht were measured within 2 weeks of the first scan. RESULTS: The placental growth during the second trimester was inversely related to the Ht levels (r = -0.29, P = 0.001). It was also related to the Hb level (r = -0.20, P = 0.021). An increase of 0.1 units of Ht was associated with 38% less growth of the placenta (95% confidence interval: 18-54% less growth). DISCUSSION: This study demonstrates the effects of maternal environment on placental growth. Our data suggest that the levels of Ht appear to affect the placental growth during the second trimester. Further studies on the factors that regulate placental growth are needed to elucidate the pathophysiology of these interactions and their effect on pregnancy outcome.     

The preferred timing of second-trimester obstetric sonography based on maternal body mass index.

OBJECTIVE: To determine the preferred timing of sonographic screening of fetal anatomy based on the maternal body mass index (BMI). METHODS: We abstracted the sonographic reports of 2,303 gravidas undergoing routine fetal anatomic screening between 15 and 24 weeks' gestation to determine the completeness of the study. Height and weight information was available on 1444 patients. The maternal BMI (weight [kilograms]/height [square meters]) was categorized as underweight (<19.8), normal weight (19.8-26.0), overweight (26.1-29.0), and obese (>29.0). Completion rates were compared by chi(2) analysis. Multiple logistic regression was used to evaluate for independent predictors of a completed study. RESULTS: Except for underweight women, completion rates for all BMI categories were significantly higher when the sonographic examinations were performed between 18 weeks and 19 weeks 6 days compared with those performed between 15 weeks and 17 weeks 6 days. Body mass index, estimated gestational age, and black race were independent predictors of a completed study. CONCLUSIONS: Except in underweight women, the 18- to 20-week interval appears to be superior to the 15- to 18-week interval when performing sonographic screening of the fetal anatomy.     

Placental and spiral artery volume and gray-scale value assessment via 3-dimensional sonography in the second trimester

PURPOSE: Extreme placental size has been associated with abnormal pregnancy outcomes. The purpose of this study was to establish normal values for placental and spiral artery volume and gray-scale value as assessed via 3-dimensional (3D) sonography in the second trimester. METHODS: The entry criterion was a documented singleton pregnancy at 14-25 weeks' gestation. Patients with normal pregnancy outcome were stratified into 6 subgroups representing 2-week intervals. Automatic 3D sonographic acquisition of the placental and spiral artery volume and gray-scale value, expressed as a percentage, was obtained. RESULTS: Out of 199 patients with normal pregnancy outcome, the placental volume was between 77.7 and 213.9 cm(3) and the gray-scale value was between 28.6 and 29.2 cm(3) (depending on gestational age). The spiral artery volume adjacent to placenta was between 47.9 and 108.7 cm(3), and the gray-scale value was between 27.5 and 29.5 cm(3). Statistical analysis in each subgroup of patients revealed a significant difference between placental and spiral artery volumes but no difference when the gray-scale value was compared. CONCLUSIONS: We defined normal placental and spiral artery volume and gray-scale value in the second trimester of normal pregnancy using 3D sonography.     

Absolute and relative quantification of placenta-specific micrornas in maternal circulation with placental insufficiency-related complications

Placental insufficiency-related complications are one of the leading causes of maternal and perinatal morbidity and mortality. This study investigated the quantification of placenta-specific microRNAs (miRNAs) in the maternal circulation during gestation in a cohort of women with normally progressing pregnancies, the differentiation between placental insufficiency-related complications and normally progressing pregnancies, and the differentiation between placental insufficiency and normally progressing pregnancies during the early stages of gestation. Both absolute and relative quantification of placenta-specific miRNAs (ie, miR-516-5p, miR-517*, miR-518b, miR-520a*, miR-520h, miR-525, and miR-526a) was determined in 50 women with normally progressing pregnancies, 32 with complicated pregnancies [21 with preeclampsia with or without intrauterine growth retardation (IUGR) and 11 with IUGR], and 7 women with pregnancies at various gestational stages who later developed preeclampsia and/or IUGR using real-time PCR and a comparative C(T) method relative to normalization factor (ie, geometric mean of ubiquitous miR-16 and let-7d). Both quantification approaches revealed significant increases in extracellular placenta-specific miRNA levels over time in women with normally progressing pregnancies; however, they were not able to differentiate between normally progressing and complicated pregnancies at the time of preeclampsia and/or IUGR onset. Nevertheless, significant elevation of extracellular miRNA levels was observed during early gestation (ie, within the 12th to 16th weeks) in pregnancies with later onset of preeclampsia and/or IUGR. Early gestation extracellular miRNA screening can differentiate between women with normally progressing pregnancies and those who may later develop placental insufficiency-related complications.     

Ultrasonic tissue characterization of the placenta: is it of clinical value?

Placentas of 84 antenatal patients have been examined throughout pregnancy (14-40 weeks of gestation). The coefficient of variation (the standard deviation divided by the mean) of echo-peak amplitude distributions obtained from placental images was used to characterize the placentas in different groups. Placentas of smokers yielded higher coefficient of variation values throughout pregnancy (P less than 0.05). This placental texture index was significantly lower for nonsmoking mothers of low-birth-weight babies after 30 weeks of gestation (P less than 0.001). Quantitative analysis of placental appearance may be of clinical value in selecting nonsmoking women at risk for low-birth-weight babies during the third trimester.     

肝细胞癌的灰阶超声、彩色多普勒超声和超声造影的对比研究

目的通过肝细胞癌(HCC)的灰阶超声、彩色多普勒超声(CDFI)和超声造影(CEUS)诊断的对比研究,探讨超声造影在肝细胞癌诊断中的优势。方法肝细胞癌患者20例,共26个病灶,均经手术或穿刺活检病理证实为肝细胞癌;分别用灰阶超声、彩色多普勒超声和超声造影检查,观察肿瘤的大小、回声强度、肿瘤内的血管和肿瘤实质的血流灌注。结果在肿瘤结节的形态上,超声造影与灰阶超声基本相似,但在肿瘤直径和面积的测值上,超声造影大于灰阶超声,存在显著差异(P<0.01),而且可以发现灰阶超声所不能显现的病灶。超声造影与彩色多普勒均显示肿瘤的血管和血供,但在显示肿瘤的微血管和血流灌注时,超声造影明显优于彩色多普勒(P<0.01)。肝细胞癌超声造影血管相的增强方式与细胞分化程度有一定的相关性。结论超声造影是实时、有效显示肝细胞癌肿瘤血管和血流灌注的方法。在HCC探测和定性方面明显优于灰阶超声和彩色多普勒超声,而且对肝细胞癌的恶性程度可做出一定的判断。     

Feasibility of the second-trimester fetal ultrasound examination in an unselected population at 18, 20 or 22 weeks of pregnancy: a randomized trial.

OBJECTIVE: To date, there have been no studies on the optimal timing of second-trimester ultrasound screening for fetal abnormalities. The purpose of this study was to investigate whether, of three gestational ages (18, 20 and 22 weeks), any one was associated with a significant advantage in terms of identification of abnormalities or need for further ultrasound assessment. DESIGN: Prospective, randomized study of second-trimester unselected pregnant women, who had had an ultrasound examination with normal results at 10-14 weeks. SUBJECTS AND METHODS: A total of 1206 women were randomized into three mutually exclusive groups relating to their second-trimester appointment for a screening ultrasound examination for fetal abnormalities in the second trimester of pregnancy: Group 1 at 18-18 + 6 weeks, Group 2 at 20-20 + 6 weeks and Group 3 at 22-22 + 6 weeks. The anomaly scans were carried out according to a standardized protocol. The fetuses were examined for structural and developmental abnormalities. Uterine artery Doppler measurements, including waveform recordings, were performed in all cases. The main end-points were the need for rescanning of all or part of the fetal anatomy, fetal outcome, placental localization, and incidence of notches in the uterine artery waveform. RESULTS: The baseline demographic characteristics and risk factors in the three groups were similar and gestational age-related fetal measurements were comparable. There were significantly higher percentages of completed scans in Group 2 (90%) and Group 3 (88%) than in Group 1 (76%; p < 0.001), but no significant difference between those scanned at 20 and at 22 weeks. This was associated with a higher incidence of non-cephalic presentation in Group 1 (46%) than in the other two groups (36%, p < 0.001). Significant differences in completing the assessment of the thorax, heart, spine and skeleton were also observed. There was no significant difference in maternal body habitus, fetal movements or the occurrence of uterine fibroids between the study groups. The incidences of low-lying placenta and of abnormal uterine artery Doppler screening were also higher at 18 weeks than at 20 and 22 weeks (p < 0.001 for both variables), with no difference seen between Groups 2 and 3. The numbers of fetal anomalies detected in the three groups were three, two and two, respectively; these did not differ significantly between the groups. CONCLUSIONS: This study suggests that, in an unselected pregnant population, second-trimester ultrasound screening is easier to perform and less likely to require an additional scan at 20-22 weeks than at 18 weeks.     

Impaired uteroplacental blood flow in pregnancies complicated by falciparum malaria.

OBJECTIVE: In endemic areas, maternal malaria infection is usually asymptomatic. However, it is known that infected maternal erythrocytes sequester in the intervillous space of the placenta. There is a strong association between placental malaria infection and both low birth weight (LBW) and severe maternal anemia. We aimed to determine whether impaired uteroplacental blood flow might account for the low infant birth weight associated with maternal falciparum malaria infection. METHODS: This observational study was carried out during a large double-blind, randomized, controlled trial of an antimalarial drug intervention for primigravidae. Nine hundred and ninety-five women were recruited from the antenatal clinic at a district hospital on the Kenya coast and had at least one Doppler ultrasound scan. Uterine artery resistance index and the presence or absence of a diastolic notch were recorded. In the third trimester, blood was taken for hemoglobin and malaria film. RESULTS: Malaria infection at 32-35 weeks of gestation was associated with abnormal uterine artery flow velocity waveforms on the day of blood testing (relative risk (RR) 2.11, 95% confidence interval (CI) 1.24-3.59, P = 0.006). This association persisted after controlling for pre-eclampsia. Impaired uteroplacental blood flow in the women studied was also predictive of poor perinatal outcome, including low birth weight, preterm delivery and perinatal death. The risk of preterm delivery in women with histological evidence of past placental malaria infection was more than twice that of women without infection (RR 2.33, 95% CI 1.31-4.13, P = 0.004). CONCLUSIONS: Uteroplacental hemodynamics are altered in the presence of maternal falciparum malaria infection. This may account for some of the excess of LBW babies observed in malaria endemic areas. Strategies that prevent or clear placental malaria may confer perinatal benefit through preservation of placental function.     

Power spectrum analysis of heart rate and blood flow velocity variability measured in the umbilical and uterine arteries in early pregnancy: a comparative study.

OBJECTIVE: To compare power spectral derived variability parameters from the fetal side of the placental circulation with those from the maternal side of the placental circulation, during early pregnancy. METHODS: Doppler velocity waveforms were obtained from both the umbilical and the uterine arteries in a study group of 40 pregnant women between 10 and 14 (n = 25) and 15 and 20 (n = 15) weeks of gestation. The coefficient of variation of both the beat-to-beat heart rate variability and the blood flow velocity variability was determined. The ratio of the integrated low-frequency components (< 0.2 Hz) and the integrated high-frequency components (> 0.2 Hz) from normalized power spectrum analysis (LH-ratio) was established, to reflect sympathovagal balance. RESULTS: The coefficient of variation and LH-ratio of fetal heart rate variability constitute only a fraction of the same maternal heart rate variability parameters. Nevertheless a highly significant increase (P < 0.001) in LH-ratio was demonstrated with advancing gestational age. The coefficient of variation and LH-ratio of blood flow velocity variability were significantly lower in the fetal umbilical artery only in the 10-14-weeks' gestation group. Due to a decrease of the maternal uterine blood flow velocity variability parameters with advancing gestational age, statistically equal fetal and maternal values for coefficient of variation and LH-ratio were found in the 15-20 weeks' gestation group. CONCLUSIONS: The increase in LH-ratio of fetal heart rate variability indicates functional development of the fetal autonomic nervous system at 15-20 weeks' gestation. The umbilical blood flow velocity variability may be secondary to maternal uterine arterial flow variability rather than due to primary changes in fetal cardiovascular function.     

The effect of gestational age and placental location on the prediction of pre-eclampsia by uterine artery Doppler velocimetry in low-risk nulliparous women.

OBJECTIVE: To assess how placental position and gestational age can influence the value of a diastolic notch of the uterine arteries as a screening test for pre-eclampsia, in a low-risk population of healthy nulliparous women. METHODS: Color Doppler ultrasound was used to examine both uterine arteries in 654 healthy nulliparas at 4-week intervals between 20 and 32 weeks. The only criterion for an abnormal result was the presence of an early diastolic notch. In each subject the placental position was also recorded. The major end points were pre-eclampsia and pre-eclampsia requiring delivery before the 34th week. RESULTS: Ninety-eight women (15%) had abnormal flow velocity waveforms at their first visit. Twenty-one out of 654 women developed pre-eclampsia (3.2%). The sensitivity of the test became lower as gestational age advanced and ranged from 81% at 20 weeks, to 71.4% at 32 weeks. In contrast, the specificity and positive predictive value increased significantly. Eleven out of 12 women who delivered before 34 weeks had abnormal waveforms at the 24th week. In women with a full lateral placenta, the predictive value of the test was extremely low, especially in cases with unilateral notches. CONCLUSION: Pre-eclampsia can be more accurately predicted if, along with the presence of a notch, both gestational age and placental position are taken into account. At week 24 the test maintains a high sensitivity (76.1%), but also has an improved specificity (95.1%) and positive predictive value (34%), which allow the clinician to intervene with a potential preventive treatment.     

Low‐molecular‐weight heparin added to aspirin in the prevention of recurrent early‐onset pre‐eclampsia in women with inheritable thrombophilia: the FRUIT‐RCT

Summary. Background: Early‐onset hypertensive disorders (HD) of pregnancy and small‐for‐gestational age infants (SGA) are associated with placental vascular thrombosis, these often recur and are also associated with inheritable thrombophilia. Aspirin reduces the recurrence risk. Objectives: Adding low‐molecular‐weight heparin (LMWH) to aspirin at < 12 weeks gestation reduces the recurrence of HD in women with previous early‐onset HD (pre‐eclampsia, hemolysis, elevated liver enzymes and low platelets [HELLP] syndrome and eclampsia) and/or SGA, in the context of inheritable thrombophilia without antiphospholipid antibodies. Patients/methods: In a multicenter randomized control trial (RCT), 139 women included were < 12 weeks gestation. Inclusion criteria: previous delivery < 34 weeks gestation with HD and/or SGA; inheritable thrombophilia (protein C deficiency, protein S deficiency, activated protein C resistance, factor V Leiden heterozygosity and prothrombin gene G20210A mutation heterozygosity); and no antiphospholipid antibodies detected. Intervention: either daily LMWH (dalteparin, 5000 IU weight‐adjusted dosage) with aspirin 80 mg or aspirin 80 mg alone. Main outcome measures: Primary outcomes: recurrent HD onset (i) < 34 weeks gestation and (ii) irrespective of gestational age. Secondary outcomes: recurrent SGA, preterm birth, maternal/neonatal hospitalization, spontaneous abortion and individual HD. Analysis by intention‐to‐treat. Results: Low‐molecular‐weight heparin with aspirin reduced recurrent HD onset < 34 weeks gestation (risk difference [RD] 8.7%: confidence interval [CI] of RD 1.9–15.5%; P = 0.012; number needed to treat [NNT] 12). Recurrent HD irrespective of gestational age was not different between the arms. No women withdrew as a result of adverse effects. Trial Registration: http://www.isrctn.org ) (isrctn87325378). Conclusions: Adding LMWH to aspirin at < 12 weeks gestation reduces recurrent HD onset < 34 weeks gestation in women with inheritable thrombophilia and prior delivery for HD/SGA <34 weeks. However, close monitoring of the mother and fetus remains important throughout pregnancy.     

在妊娠期高血压中使用低分子肝素可以提高子宫动脉阻力指数预测子痫前期和胎儿生长受限

目的探讨在高危孕妇中短疗程的皮下注射低分子肝素是否能提高子宫动脉阻力指数预测子痫前期和胎儿生长受限。方法挑选24至26周妊娠期高血压患者96名和正常孕妇30名,治疗前和治疗2周后超声多普勒测量子宫动脉阻力指数,58例妊娠期高血压为治疗组,38例妊娠期高血压和30正常孕妇为对照组。结果低分子肝素治疗组子宫动脉阻力指数明显下降,而对照组无明显改变。然而低分子肝素引起的子宫动脉阻力指数减少只局限有正常妊娠结局的产妇,从0.64±0.01降至0.52±0.01（P〈0.05）。结论低分子肝素可以提高子宫动脉阻力指数预测子痫前期和胎儿生长受限。     

Fetal subcutaneous tissue thickness (SCTT) in healthy and gestational diabetic pregnancies.

OBJECTIVE: To determine reference values of fetal subcutaneous tissue thickness (SCTT) throughout gestation in a healthy population and to compare them with those from a population of pregnant women with gestational diabetes under standard therapy. METHODS: Three hundred and three women recruited from a high-risk pregnancy clinic were classified as being healthy (n = 218) or as having gestational diabetes (n = 85) on the basis of a negative or positive oral glucose tolerance test, respectively. They were enrolled into the cross-sectional study at 20 weeks' gestation. Ultrasound examinations were performed approximately every 3 weeks until delivery at term. The mid-arm fat mass and lean mass (MAFM, MALM), the mid-thigh fat mass and lean mass (MTFM, MTLM), the abdominal fat mass (AFM) and the subscapular fat mass (SSFM) were evaluated. Time-specific reference ranges were constructed from the 218 healthy women and a conventional Student's t-test was performed to compare SCTT values between the two study groups throughout gestation. RESULTS: Normal ranges, including 5th, 50th and 95th centiles of the distribution, were generated for each SCTT parameter obtained in each of the two groups of women. Significant differences were found between the two study groups at 37-40 weeks' gestation for MTFM, at 20-22 and 26-28 weeks for MTLM, at 31-34 and 35-37 weeks for MAFM, at 26-28 and 38-40 weeks for SSFM, and at 39-40 weeks for AFM, the mean residual values always being greater in gestational diabetic women than they were in the group of healthy pregnant women. CONCLUSIONS: We provide gestational age-specific reference values for fetal SCTT. Fetal fat mass values, particularly in late gestation, are greater in women with gestational diabetes compared with healthy women. The reference values may have a role in assessing the influence of maternal metabolic control on fetal state.     

A new strategy for prenatal diagnosis of homozygous alpha(0)-thalassemia.

OBJECTIVES: We have shown previously that ultrasound examination performed by one experienced operator can be useful to exclude homozygous alpha(0)-thalassemia in a tertiary referral center. This study aimed to determine whether the technique was still applicable when performed by several operators and in different centers. METHODS: At the Maternal and Neonatal Hospital of Guangzhou (MNH) and Tsan Yuk Hospital of Hong Kong (TYH), women at risk of homozygous alpha(0)-thalassemia were given the option of a non-invasive approach (using serial ultrasound examinations at 12-15, 16-20 and 25-30 weeks' gestation) to exclude an affected pregnancy. The fetal cardiothoracic ratio (CTR) was measured at each of these examinations and the placental thickness was measured at 12-15 weeks' gestation. The operators of MNH received training on the ultrasound examination techniques at TYH and the quality of the subsequent ultrasound examinations was checked regularly. The final diagnosis of homozygous alpha(0)-thalassemia was confirmed using an invasive test. RESULTS: Of 832 at-risk pregnancies studied in the two hospitals, 168 (20.2%) were affected. The overall sensitivity and specificity of the non-invasive approach was 100% and 95.6%, respectively. At MNH, the need for an invasive test was reduced by 80.8%, and all the affected pregnancies were diagnosed before 24 weeks' gestation. The results achieved at MNH were comparable with those at TYH. The at-risk pregnancies including the affected ones presented at a more advanced gestational age at MNH. At each hospital, one affected pregnancy was missed at the 12-week scan but this was subsequently detected at the 15-18-week scan. CONCLUSIONS: This non-invasive approach to exclude homozygous alpha(0)-thalassemia can be applicable when it is performed by several operators and in different centers.     

Primary glomerulonephritis and pregnancy

Three hundred and ninety-five pregnancies undertaken by 238 women with primary glomerulonephritis between 1962 and 1987 were analysed to record fetal and maternal outcome and identify risk factors for a poor outcome. Of 398 fetuses, 26 per cent were lost (including therapeutic abortions), 24 per cent surviving infants were premature (less than or equal to 36 weeks gestation) and 51 per cent were term. Excluding therapeutic abortions, 20 per cent of fetuses were lost, 15 per cent after 20 weeks gestation. Fifteen per cent of 237 fetuses whose birth weight was recorded were small for gestational age: Deterioration in maternal renal function was seen in 15 per cent of pregnancies and in 5 per cent of women failed to resolve post partum. Only four women had impaired renal function recorded in the first-trimester and two of these were known to have renal impairment before pregnancy. Hypertension was recorded in 52 per cent of pregnancies, developed early (less than or equal to 32 weeks gestation) in 26 per cent and was severe in 18 per cent. Treated hypertension pre-dated 12 per cent of pregnancies and in 7 per cent (included in the overall incidence of hypertension) exacerbation occurred during pregnancy despite continued antihypertensive medication. Forty-four women (18 per cent) who developed de novo hypertension in pregnancy had permanent hypertension postpartum. Increased proteinuria was recorded in 59 per cent of pregnancies and was irreversible in 15 per cent of women. Comparison of pregnancies which occurred before or after renal biopsy revealed a significantly higher fetal loss rate after 20 weeks gestation in those pregnancies undertaken before the diagnosis of renal disease, and a significantly higher incidence of hypertension and increased proteinuria. Impaired renal function, early or severe hypertension or nephrotic range proteinuria was significantly associated with increased fetal loss, prematurity and fewer full-term infants. There was no significant difference in fetal outcome or maternal complications in pregnancy in patients with treated hypertension before pregnancy and those who were normotensive in the first-trimester. The highest incidence of fetal and maternal complications occurred in patients with primary focal and segmental hyalinosis and sclerosis and the lowest in non-IgA diffuse mesangial proliferative glomerulonephritis. The presence of severe vessel lesions on renal biopsy was associated with a significantly higher total fetal loss and fetal loss after 20 weeks gestation.     

The radioimmunoassay of human placental protein 14 (PP14)

The development and validation of a radioimmunoassay for the measurement of human placental protein 14 in maternal serum is described. The mean concentration of this protein in serum from 22 normal pregnant women showed a decline during the third trimester from 120 micrograms/l at 27 weeks gestation to 65 micrograms/l at term. Serum samples from 16 patients with intra-uterine growth retardation tended to contain lower concentrations of placental protein 14, these results reaching significance at weeks 36-38 of gestation. Of seven patients with pre-eclampsia from whom two or more blood samples were taken, four showed increases in concentration of this protein as pregnancy proceeded, compared with the normal pattern of decreasing values.     

An open-label randomized-controlled trial of low dose aspirin with an early screening test for pre-eclampsia and growth restriction (TEST): Trial protocol

ObjectivePre-eclampsia remains a worldwide cause of maternal and perinatal morbidity and mortality. Low dose aspirin (LDA) can reduce the occurrence of pre-eclampsia in women with identifiable risk factors. Emerging screening tests can determine the maternal risk of developing placental disease, such as pre-eclampsia from the first trimester of pregnancy. The aim of this study is to determine if it is more beneficial in terms of efficacy and acceptability to routinely prescribe LDA to nulliparous low-risk women compared to test indicated LDA on the basis of a positive screening test for placental disease.MethodsWe propose a three armed multi-center open-labeled randomized control trial of; (i) routine LDA, (ii) no aspirin, and (iii) LDA on the basis of a positive first trimester pre-eclampsia screening test. LDA (75 mg once daily) shall be given from the first trimester until 36-week gestation. The primary outcome measures include; (i) the proportion of eligible women that agree to participate (acceptability), (ii) compliance with study protocol (acceptability and feasibility), (iii) the proportion of women in whom it is possible to obtain first trimester trans-abdominal uterine artery Doppler examination (feasibility) and (iv) the proportion of women with a completed screening test that are issued the screening result within one week of having the test performed (feasibility).ConclusionThis will be the first clinical trial to determine the efficacy and acceptability in low-risk women of taking routine LDA versus no aspirin versus LDA based on a positive first trimester screening test for the prevention of placental disease.