The association between hypertensive disorders of pregnancy and abnormal second-trimester maternal serum levels of hCG and alpha-fetoprotein.

OBJECTIVE: To examine the association between hypertensive disorders of pregnancy and second-trimester maternal serum alpha-fetoprotein (MSAFP) and hCG levels. METHODS: The proportions of abnormal second-trimester MSAFP and hCG levels in the serum samples from 65 women with true pregnancy-induced hypertension or preeclampsia (cases) were compared to the proportions of abnormal levels in all 1943 women without this disorder in the same cohort in a hospital setting. Maternal serum alpha-fetoprotein and hCG levels of the 65 cases also were compared to those of 325 completely uncomplicated matched control pregnancies, selected from the same cohort. Fisher exact test and Student t test were used for statistical analysis and P < .05 was considered statistically significant. RESULTS: An MSAFP level at least 2.5 multiples of the median (MoM) was found in two of 65 cases (3.1%) and in 27 of 1943 women (1.4%) in the rest of the cohort, a nonsignificant difference (relative risk [RR] = 2.2; P = .24). The statistical power to identify a significant difference for this RR was .27. An hCG level of at least 2.5 MoM was found in six cases (9.2%) and in 89 (4.6%) of women in the rest of the cohort, also a nonsignificant difference (RR = 2.0; P = .12). The statistical power to identify a significant difference for this RR was .38. The mean (+/-standard deviation) logarithms of the MSAFP and hCG MoMs in the 65 cases (0.039 +/- 0.191 and 0.048 +/- 0.265, respectively) were not significantly different from those in the 325 matched controls (0.006 +/- 0.148 and -0.010 +/- 0.244, respectively; P = .12 and .08, respectively). CONCLUSION: Although a weak association cannot be excluded, this study found no clinically important increase in risk of developing subsequent hypertensive disorders of pregnancy among women with abnormal second-trimester levels of MSAFP or hCG.

Variation in semen parameters derived from computer-aided semen analysis, within donors and between donors.

The development of computer-aided semen analysis (CASA) has made it possible to study sperm motility characteristics objectively and longitudinally. In this 2-year study of 8 sperm donors, we used CASA to measure 7 semen parameters (concentration, percentage of motile spermatozoa, curvilinear velocity, average path velocity, straight-line velocity, amplitude of lateral head displacement, and beat/cross frequency). The frequency distributions of the 7 parameters in the semen samples of each donor were investigated. All parameters but one were normally distributed; concentration was distributed log-normally. Variation within individual donors and between donors was studied. Analysis of variance demonstrated that variation between donors was not explained by the longitudinal variation within individual donors. Variations in motility characteristics between donors were substantial, which may make motility characteristics of limited value as a tool for establishing fertility. Strong correlations were found between the 7 parameters, partly because by definition, motility characteristics are interdependent. Fisher's discriminant analysis demonstrated that each donor appeared to have his own set of semen characteristics and, more specifically, his own motility signature. From this data set it can be predicted that in order to find population means among sperm, it may be more efficient to measure more subjects than to increase the number of samples per subject.

Doppler ultrasound screening predicts recurrence of poor pregnancy outcome in subsequent pregnancies, but not the recurrence of PIH or preeclampsia.

OBJECTIVE: To assess the role of Doppler uterine artery screening in the prediction of recurring hypertensive disorders in a high-risk population. METHODS: Ninety-four women with a history of hypertensive disorders in previous pregnancies underwent ultrasound color Doppler to analyze blood flow in the uterine arteries at 21-22 weeks of gestation. We evaluated the performance of the Pulsatility Index (PI) as well as the diastolic notch to predict recurring hypertensive disorders. Outcome measures were the recurrence of hypertensive disorders, and poor pregnancy outcome due to intrauterine death growth retardation, intrauterine death, placental abruption, hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, eclampsia, or premature birth. Onset of symptoms was before 35 weeks in all cases of poor pregnancy outcome. RESULTS: Doppler flow recordings were obtained from a well-defined location in both uterine arteries. The predictive value of the uterine artery PI for recurring hypertensive disease was poor and not significant; interestingly, however, the predictive values for poor pregnancy outcome were good (sensitivity 83%, specificity 71%, p < 0.001). The PI also provides a good test for intrauterine growth retardation (sensitivity 80%, specificity 69%, p < 0.01). The "diastolic notch" did not perform as well as the PI. CONCLUSIONS: Uterine artery screening did significantly predict the recurrence of poor pregnancy outcome due to hypertensive complications in this high-risk group. In contrast, gestational hypertension and preeclampsia with normal pregnancy outcome were not significantly predicted by uterine artery screening.

[Predicting the day of ovulation with a do-it-yourself test]. / Het voorspellen van de ovulatiedag met een 'doe-het-zelf'-test.

PIP: This study reviews biological and immunochemical methods for prediction of the day of ovulation. Biological methods include the calendar, the temperature, the ovulation pain and the cervix mucus methods. Because none of these is very reliable, immunochemical tests for the presence of luteinizing hormone (LH) in the urine have been placed on the market during the past few years. These tests are designed to show a color change in the test sample when urine LH is 40-50 IU/1. This value represents the peak of the preovulatory LH wave which lasts an average of 14 hours. According to information provided by manufactures of 5 tests available in the Netherlands, the chance of a positive test result with 1 test/day varies from 77% for LH-color, 80% for Discretest, 91% for Clearplan, 92% for Ovuquick, and 93% for Ovustick. In independent tests of Clearplan and Discretest, the brands most used in the Netherlands, laboratory technicians encountered persistent problems in interpreting the color indications of the test in terms of the LH concentration. Discretest sometimes gave false positives and Clearplan false negatives. The newer Ovuquick test, which works in 6-8 minutes compared to the 30 minutes required for LH-color, Discretest and Clearplan and 60 minutes for Ovustick, proved to be easier to read but gave false positives with LH concentrations as low as 20-30 IU/1. The authors conclude that do-it-yourself LH tests should be sold only by prescription.^ieng

[Serum screening of pregnant women for fetal neural tube defects and Down syndrome; initial experiences in The Netherlands]. / Serumscreening van zwangeren op foetale neurale-buisdefecten èn Down-syndroom; eerste ervaringen in Nederland.

OBJECTIVE: To examine if, and if so, in what way, the maternal serum screening for fetal neural tube defects (NTD) and Down's syndrome (DS) in the Dutch decentralized obstetrical organization would be feasible and effective. DESIGN: Prospective. SETTING: University Hospital Groningen. METHOD: Between October 1st 1990 and December 1st 1991 we determined the likelihood of a baby with a NTD and/or DS in 2580 pregnant women, at 15 to 20 weeks gestation, by serum screening. RESULTS: Five foetuses with DS were detected, as well as two with a NTD, one foetus with an omphalocele, and one with Turner's syndrome. One infant with a NTD and one with DS were not found prenatally. Of all 98 women of 36 years or older, 68 declined amniocentesis because their risk was lower than the age related risk. CONCLUSIONS: Maternal serum screening for NTD and DS is feasible and effective in principle. In a decentralized prenatal care system, special attention has to be paid to the time needed to report the results and to the completion of the follow-up. The detection rate of DS in pregnant women of 36 years or older remains almost the same, but a significant number of them decline prenatal diagnosis. An increased risk of foetal DS, determined by serum screening, should be added to the official list of indications for prenatal diagnosis in the Netherlands.

Evaluation of a computer-aided semen analysis system with sperm tail detection.

The aim of this study was to evaluate the Stroemberg-Mika cell motion analyser (SM-CMA) which uses tail detection in order to discriminate between immotile spermatozoa and other particles. Analysis of the spermatozoa by the SM-CMA can easily be checked on a video monitor. The semen samples were from donors and patients visiting the fertility unit of the University Hospital, Hanzeplein, The Netherlands. Both fresh semen samples and purified sperm suspensions were used to estimate sperm counts and motility characteristics. We tested the use of the x10 objective instead of the x20 and we assessed the ways in which motility characteristics were influenced by temperature. We found a considerable discrepancy between sperm concentrations measured manually and by computerized analysis, both in semen samples and in purified sperm suspensions. The SM-CMA correctly recognizes motile spermatozoa, but underestimates immotile ones. Although temperature affects motility characteristics, in routine measurements the influence of short cooling periods, which are unavoidable, was nil. We found that using the x10 objective can be useful, especially at low sperm concentrations. In our opinion, the SM-CMA system is, despite some shortcomings in its user-interface, a useful and versatile instrument for examination of human semen samples, with desirable features.

Raised maternal serum-alpha-fetoprotein levels and spontaneous fetomaternal transfusion.

Study of blood smears showed that spontaneous fetomaternal transfusions were significantly more common among 42 pregnant women with raised serum-alpha-fetoprotein (AFP) levels than among 45 pregnant women with normal serum-AFP levels. Raised serum-AFP was associated with a spontaneous fetomaternal transfusion of greater than or equal to 0.1 ml in at least 21 of the 42 women in the study group.

Nuchal muscle activity at different levels of hypoxemia in fetal sheep.

The effects of hypoxemia on nuchal muscle activity, a parameter of gross body movements, were studied during 12 experiments in five chronically instrumented fetal lambs. Hypoxemia was accomplished by tracheal infusion of nitrogen and did not result in significant changes in fetal arterial pH and PCO2. Fetal arterial blood gases and pH were continuously measured with an extracorporeal flow-through cuvette. Nuchal muscle activity was measured by electromyography and was expressed as the percentage of time spent moving. A decrease in fetal arterial oxygen saturation to three fourths of the initial value for 2 hours was not associated with significant changes in nuchal muscle activity. When fetal arterial oxygen saturation was further reduced for 2 hours to one half, fetal nuchal muscle activity fell significantly from 34.6% +/- 10.5% during normoxemia to 20.9% +/- 13.9% during hypoxemia. However, the most pronounced changes in fetal nuchal muscle activity occurred in the first 15 minutes after the changes in arterial oxygen saturation. A considerable transient increase in nuchal muscle activity was observed during the first 15 minutes after recovery from hypoxemia. During hypoxemia there was a relative predominance of short-lasting (less than 3 minute) movements.

The influence of serum screening on the amniocentesis rate in women of advanced maternal age.

We investigated the effect of maternal serum screening on the amniocentesis (AC) rate in women of advanced maternal age. The AC rate after maternal serum screening was compared in two groups of women with a singleton pregnancy, 855 women of 30-35 years and 98 of 36 years and older. In our population, 34.1 per cent of the women of 36 years or older were 'screen-positive' for Down syndrome. Only 41.2 per cent of these women chose to undergo AC as opposed to 88.2 per cent in the younger age group. Within the older age group, the tendency to avoid AC increased with increasing age. Maternal serum screening led to a significant decrease in the AC rate in the older women. In this group, a comparison between the 'a priori' and the calculated risk might have had more influence on the decision to undergo AC than being screen-positive or screen-negative as such. We conclude that maternal serum screening had a major effect on the AC rate in women of advanced maternal age. This is of importance in a society in which the average maternal age is steadily increasing.

Increased maternal serum alpha-fetoprotein and human chorionic gonadotropin in compromised pregnancies other than for neural tube defects or Down syndrome.

Intrauterine fetal death occurred in four women who were 'screen-positive' in a screening programme for neural tube defects (NTDs) and Down syndrome (DS). These women had very high levels of maternal serum alpha-fetoprotein (MSAFP) and maternal serum human chorionic gonadotropin (MShCG). Therefore, we evaluated all 'screen-positive' women in whom both of these markers were greater than or equal to 2.0 multiples of the median. The cases fulfilling these criteria totalled 11, and only one of them had no complications. High concentrations of both MSAFP and MShCG in a number of these cases might have been caused by an increased placental volume, which, in turn, might have been induced by decreased perfusion of the placenta. We conclude that screening programmes wrongly determine a high risk of fetal NTD or DS if the concentrations of both these parameters are very high. Invasive diagnostic procedures should be avoided in these cases, particularly in view of the increased risk of an adverse pregnancy outcome.

First-trimester maternal serum human thyroid-stimulating hormone in chromosomally normal and Down syndrome pregnancies.

Maternal serum human thyroid-stimulating hormone (TSH) levels were investigated in chromosomally normal and Down syndrome pregnancies to determine whether TSH can be used as a marker for Down syndrome in the first trimester. Measurements were conducted on stored serum samples collected from 23 Down syndrome pregnancies and 115 unaffected pregnancies before chorionic villus sampling (CVS), between 9 and 11 completed weeks of pregnancy. The samples were matched for gestational age, maternal age, maternal weight and duration of storage of the serum sample. Maternal TSH concentration was slightly decreased in Down syndrome pregnancies, with a median of 0.84 multiples of the median (MoM). Maternal serum human chorionic gonadotropin (hCG) concentration was slightly elevated in Down syndrome pregnancies, with a median of 1.03 MoM. Both differences were not significant applying matched rank analysis (p=0.50 for TSH and p=0.43 for hCG). The association between TSH and hCG in unaffected pregnancies was also measured. The Spearman correlation coefficient between TSH and hCG was -0.21 which was statistically significant (p=0.02, 95% confidence interval -0.38 to -0.03). However, it was concluded that TSH is not a useful marker for distinguishing Down syndrome-affected pregnancies from normal pregnancies in the first trimester.

Quantification of the diastolic notch in Doppler ultrasound screening of uterine arteries.

OBJECTIVE: To investigate a new method of quantification of the diastolic notch of the flow velocity waveforms of uterine arteries in the prediction of hypertensive disorders of pregnancy. METHODS: Pulsed-wave Doppler was used to obtain flow velocity waveforms (FVWs) from the uterine arteries at 21-22 weeks of gestation from 531 nulliparous women and 94 multiparous women at high risk. From the FVWs, both the pulsatility index (PI) and the notch index (NI) were calculated and the predictive values for both indices were compared using logistic regression analysis for mild and severe early onset hypertensive pregnancy complications. RESULTS: Both the PI and the NI were poor predictors for mild gestational hypertension and pre-eclampsia; predictive values for severe early onset disease, however, were much better. Logistic regression analysis showed the NI has no additional value compared with the PI in the prediction of either mild or severe disease. CONCLUSIONS: The NI offers the possibility to quantify the diastolic notch in uterine artery analysis. Compared to the PI, this does not lead to better predictive values for hypertensive disorders of pregnancy.

Nuchal translucency cannot be used as a screening test for chromosomal abnormalities in the first trimester of pregnancy in a routine ultrasound practice.

We decided to assess the practicability of introducing nuchal translucency (NT) measurements as a screening programme for fetal Down's syndrome in the first trimester of pregnancy, within the population of women who receive ultrasound examinations in our department. Over a 1-year period, measurements were made in 923 fetuses at < or = 13 weeks' gestation. Fifty-two per cent of the mothers were 36 years or older or had a past history of a chromosomally abnormal fetus or child. Measurements were only successful 58 per cent of the time; this improved to 74 per cent if the fetus was > or = 10 weeks' gestation. Inter-observer variability did not cause a major problem. There were 36 fetuses with an NT > or = 3 mm. Two of these fetuses had a chromosomal abnormality (both trisomy 21). The translucency in these two cases was so large that they would have been detected and offered prenatal diagnosis even prior to this study. There was a total of ten aneuploidies in the study group. Only two of these fetuses were detected by this screening method; five had an NT measurement < 3 mm and in three fetuses (all trisomy 21), measurements were not successful. We outline the practical problems that could be expected by introducing ultrasound screening in a routine setting. Although the efficacy of the test in a research setting may seem good, the effectiveness in everyday usage appears much less impressive, making its uptake as a screening technique in a general ultrasound practice at this stage imprudent.

Placental mosaicism is associated with unexplained second-trimester elevation of MShCG levels, but not with elevation of MSAFP levels.

In this patient-control study, we examined the impact of placental mosaicism on the concentrations of maternal serum human chorionic gonadotropin (MShCG) and maternal serum alpha-fetoprotein (MSAFP) in the second trimester of pregnancy. Patient and control groups were selected from 2347 women with a singleton pregnancy, who underwent chorionic villous sampling in the first trimester and from whom second-trimester serum samples had been collected. The concentrations of both serum markers, expressed in multiples of the median (MOM), in 35 women with confined placental mosaicism (CPM) were compared with those in 70 controls with uncomplicated pregnancies. Elevated MSAFP or MShCG was defined as a concentration of > or = 2.0 MOM. Of the 35 pregnancies with CPM, none had an elevated MSAFP level, as opposed to two out of the 70 women (2.9 per cent) in the control group (P = NS). Nine women in the placental mosaicism group (26 per cent) had an MShCG level of > or = 2.0 MOM, compared with five in the control group (7.1 per cent; P = 0.0135). Nineteen women in the placental mosaicism group (54 per cent) were screen-positive for Down's syndrome (cut-off 1:250), compared with 17 women (24 per cent) in the control group (P = 0.0042; relative risk = 2.3). The three highest MShCG levels were found in pregnancies with CPM that involved trisomy 16; all these women delivered a small-for-gestational age (SGA) infant. CPM, especially with trisomy 16, is associated with elevated levels of MShCG, but not with elevated levels of MSAFP. It is an important cause of false-positive results in serum screening programmes for fetal Down's syndrome. It is possible that abnormal MShCG levels in pregnancies with CPM result from dysfunctional placenta, caused by chromosomally abnormal areas. We therefore recommend increased surveillance of pregnancies with unexplained elevated MShCG levels.

The HELLP syndrome: its association with unexplained elevation of MSAFP and MShCG in the second trimester.

In this study, we examined the relationship between concentrations of maternal serum alpha-fetoprotein (MSAFP) and maternal serum human chorionic gonadotropin (MShCG) in the second trimester and the haemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome. The concentrations of both serum markers, expressed in multiples of the median (MOM), in 16 women with the HELLP syndrome were compared with those in 10443 women without this syndrome who were screened for Down's syndrome and neural tube defects. All the women with a singleton pregnancy and a known pregnancy outcome were included in this study. At a cut-off level of 2.5 MOM, 37.5 per cent of the pregnancies with the HELLP syndrome had an elevated MShCG level, compared with 4.8 per cent in the whole population (P < 0.0001). 12.5 per cent of the women with the HELLP syndrome had an elevated MSAFP level, compared with 1.3 per cent in the whole population (P < 0.025). Women with a combined elevation of MSAFP and MShCG levels (0.3 per cent of the screened population) had a 47 time greater risk of developing the HELLP syndrome than the others (P < 0.01). The HELLP syndrome should be taken into account in the case of unexplained elevated levels of MShCG and MSAFP, especially in the rare event of combined elevation of both markers.

Abnormal levels of maternal serum human chorionic gonadotropin and alpha-fetoprotein in the second trimester: relation to fetal weight and preterm delivery.

The aim of this prospective descriptive cross-sectional study was to examine the clinical significance of abnormal maternal serum human chorionic gonadotropin (MShCG) and alpha-fetoprotein (MSAFP) in the second trimester of pregnancy. The study group comprised 8892 women with a singleton pregnancy, who were screened for a neural tube defect and Down's syndrome. Exclusion criteria were unknown pregnancy outcome, a congenital anomaly, delivery before 25 weeks of amenorrhoea, or known insulin-dependent diabetes. MSAFP and MShCG were determined between 15 and 20 weeks' amenorrhoea. An abnormal result was defined as (a) MSAFP or MShCG > or = 2.5 MOM, (b) MSAFP or MShCG < or = 0.5 MOM, and (c) MSAFP and MShCG > or = 2.5 MOM. Birth weight percentiles and the duration of amenorrhoea at the time of delivery were employed as outcome parameters. Of the women with an abnormally elevated MSAFP, 9.4 per cent had an extremely small-for-gestational age (SGA) infant (< 2.3rd percentile; P < 0.01, relative risk 4.5), 27.1 per cent had an SGA infant (< tenth percentile; P < 0.01, relative risk 2.7), and 14.3 per cent had an appropriate-for-gestational age (AGA) infant that was delivered preterm (< 259 days; P < 0.01, relative risk 2.4). In the cases where the MShCG level was elevated, 4.4 per cent had an extremely SGA infant (P < 0.01, relative risk 2.1) and 15.5 per cent had an SGA infant (P < 0.01, relative risk 1.5). No significant association was found between an elevated MShCG level and preterm delivery. Low MShCG was significantly associated with SGA infants (P < 0.01, relative risk 1.2) but not with extremely SGA or preterm deliveries. In the group whose MSAFP and MShCG levels were both elevated, 23.8 per cent delivered an extremely SGA infant (P < 0.01, relative risk 10.9), 38.1 per cent an SGA infant (P < 0.01, relative risk 3.7) and 47.6 per cent had a preterm delivery or an SGA infant (P < 0.01, relative risk 3.0). Isolated or combined elevation of the MSAFP and MShCG levels in the second trimester of pregnancy is an indication for extra vigilance during further prenatal care. This applies to a lesser extent to a low MShCG level.

Anatomical and functional changes in the lower urinary tract during pregnancy.

OBJECTIVE: To assess the prevalence and the development of urinary incontinence in nulliparous pregnant women, both subjectively and objectively, and to investigate the relation of incontinence with the mobility of the urethro-vesical junction measured by perineal ultrasound. DESIGN: A prospective longitudinal study. SETTING: University Hospital and Martini Hospital Groningen, the Netherlands. POPULATION: A cohort of 117 nulliparous pregnant women and 27 nulliparous non-pregnant controls. METHODS: Urinary incontinence was measured by a questionnaire and by a 24-hour pad test. The position of the urethro-vesical junction and its mobility were measured by perineal ultrasound. MAIN OUTCOME MEASURE: Prevalence of urinary incontinence; mobility of the urethro-vesical junction, indicated by the displacement/pressure coefficient. RESULTS: Up to 35% of the women reported urinary incontinence in pregnancy, and 20% of the women had a positive pad test. The angle of the urethro-vesical junction angle at rest and the displacement/pressure coefficient during coughing showed a significant increasing trend during pregnancy, but no changes were seen during the Valsalva manoeuvre. No relationship was found between subjective and objective incontinence data and the position and mobility of the urethro-vesical junction. CONCLUSION: The prevalence of incontinence in nulliparous women as found by the pad test was significantly higher in pregnancy (20%) than in the non-pregnant control group (4%). Perineal ultrasound of the urethrovesical junction showed lowering of the pelvic floor occurring as early as 12-16 weeks of pregnancy. Serial measurements of the displacement/pressure coefficient suggest that the dynamic characteristics of the connective tissues of the pelvic floor remain unaltered,whereas a significant decrease in pelvic floor muscle contraction occurs. Since no relation was found between measurements of the urethro-vesical junction and incontinence, urinary incontinence in pregnancy is most likely explained by other factors.