The effect of low-dose aspirin on serum placental growth factor levels in a high-risk PREDO cohort.

OBJECTIVES: Our first aim was to study the longitudinal changes of serum placental growth factor (PlGF) concentration between 12+0 and 28+0 weeks of gestation in the prospective PREDO cohort. Our second aim was to study the effect of low-dose acetylsalicylic acid (LDA; 100 mg/day), started before the 14th week of gestation, on PlGF concentration. STUDY DESIGN: Blood samples were collected at 12+0-14+0, 18+0-20+0 and 26+0-28+0 weeks of gestation in 101 women without and 309 with clinical risk factors for pre-eclampsia. Risk-women were divided into two groups: to those who had medium risk for pre-eclampsia and to those who had high risk for pre-eclampsia. Finally there were seven groups according to risk, treatment (no prevention/placebo/LDA) and outcome measure pre-eclampsia. Longitudinal changes in the PlGF concentration between groups were compared. To investigate the effect of LDA on serum PlGF concentration, placebo (N = 62) and LDA (N = 61) groups were compared. A repeated measures ANOVA was used to analyze differences in PlGF levels between the groups. RESULTS: The increase in serum PlGF concentration was higher in LDA than in placebo group (time × group effect, p = 0.046). The increase in serum PlGF concentration during pregnancy was lower in high-risk women who had placebo and developed pre-eclampsia and in medium-risk women who developed pre-eclampsia compared to the other women (time × group effect, p < 0.001). There were no differences in PlGF change between low-risk women, medium-risk women who did not develop pre-eclampsia, high-risk women in the placebo group without pre-eclampsia and high-risk women in the LDA group with and without pre-eclampsia (p = 0.15). CONCLUSIONS: Our finding suggests an association between LDA started before 14 weeks of gestation and higher increase in serum PlGF concentration.

The diagnostic accuracy of pelvic measurements: threshold values and fetal size.

PURPOSE: This study aimed to correlate pelvic dimensions and fetal size to the risk for cesarean section caused by protracted labor. METHODS: This is an observational, retrospective cohort study on pregnant women with an increased risk of labor dystocia. After pelvimetry, pelvic adequacy was clinically tested in a trial of labor. A multivariable regression analysis was made to identify the risk factors for cesarean section. Two subgroups were established according to the size of the estimated fetal head circumference (HC) (arbitrary cutoffs of ≤340 and >340 mm), and the pelvic measurements were compared by the mode of delivery. Receiver operating characteristic (ROC) curves were evaluated. RESULTS: Altogether, 274 patients were ultimately included. The mean size of the maternal inlet was 1.0 cm larger in fetal HC >340 mm group compared with ≤340 mm. In the vaginal delivery group, the difference was 1.3 cm. In the multivariable modeling, maternal age (odds ratio [OR] 1.09, 95 % confidence interval [CI] 1.02-1.17), fetal HC (OR 1.05, 95 % CI 1.02-1.09), and maternal inlet circumference (OR 0.95, 95 % CI 0.92-0.97) had significance for the risk of cesarean section. In the ROC analysis, the area under the curve (AUC) value for the pelvic inlet was 0.736 (p < 0.001, 95 % CI 0.656-0.816), and in the subgroups with fetal HC ≤340 and >340 mm, AUCs were 0.634 (p < 0.11, 95 % CI 0.493-0.775) and 0.836 (p < 0.001, 95 % CI 0.751-0921), respectively. CONCLUSIONS: Labor arrest was associated with the linear relationship between the maternal pelvic dimensions and the fetal size. Therefore, the approach should be changed from standardized pelvimetric threshold values to passenger-passageway ratio analyzed by multivariable modeling to find more accurate methods to predict cephalopelvic disproportion.

Aspirin in the prevention of pre-eclampsia in high-risk women: a randomised placebo-controlled PREDO Trial and a meta-analysis of randomised trials.

OBJECTIVE: To study the effect of aspirin in the prevention of pre-eclampsia in high-risk women. DESIGN: Randomised, double-blinded, placebo-controlled trial. SETTING: Maternity clinics in ten Finnish hospitals participating in the PREDO Project. SAMPLE: A total of 152 women with risk factors for pre-eclampsia and abnormal uterine artery Doppler velocimetry. METHODS: Participants were randomised to start either aspirin 100 mg/day or placebo at 12 + 0 to 13 + 6 weeks + days of gestation. Because of the limited power of this trial, we also conducted a meta-analysis of randomised controlled trials that included data on 346 women with abnormal uterine artery Doppler flow velocimetry, and aspirin 50-150 mg/day started at or before 16( ) weeks of gestation. MAIN OUTCOME MEASURE: Pre-eclampsia, gestational hypertension and birthweight standard deviation (SD) score. Outcome measures for the meta-analysis were pre-eclampsia, severe pre-eclampsia, preterm (diagnosed <37 + 0 weeks of gestation) and term pre-eclampsia. RESULTS: From the 152 randomised women, 121 were included in the final analysis. Low-dose aspirin did not reduce the rate of pre-eclampsia (relative risk [RR] 0.7, 95% CI 0.3-1.7); gestational hypertension (RR 1.6, 95% CI 0.6-4.2); early-onset pre-eclampsia (diagnosed <34 + 0 weeks of gestation) (RR 0.2, 95% CI 0.03-2.1); or severe pre-eclampsia (RR 0.4, 95% CI 0.1-1.3); and the results were not statistically significant in an intention-to-treat analysis. However, our meta-analysis, including the current data, suggested that low-dose aspirin initiated before 16 weeks of gestation reduces the risk of pre-eclampsia (RR 0.6, 95% CI 0.4-0.8) and severe pre-eclampsia (RR 0.3, 95% CI 0.1-0.7). CONCLUSIONS: Our trial showed no statistically significant effect of aspirin in preventing pre-eclampsia in high-risk women. However, our meta-analysis suggested that aspirin may reduce the incidence of pre-eclampsia.

MR pelvimetry measurements, analysis of inter- and intra-observer variation.

OBJECTIVE: To set reference standards and then to evaluate the measurement variation in magnetic resonance (MR) pelvimetry between observations and observers. METHODS: The study was carried out retrospectively using 100 MR pelvimetry examinations performed in North Carelian Central Hospital between September 2006 and January 2008. Pelvimetric parameters of pelvic inlet and outlet were measured four times to determine the standard reference for each measurement and then intra- and inter-observer variations were compared. RESULTS: The accuracy of MR pelvimetry, defined as a deviation of <5mm from the reference standard, was better in pelvic inlet measurements than in the corresponding outlet measurements (95-99% vs. 86-89%). Intra-observer variation was acceptable in all of the measurements with intraclass correlation coefficient (ICC) in the range 0.956-0.981 in all parameters. Inter-observer variation was higher than intra-observer variation. The largest variation of measurements was in pelvic outlet parameters between observers with the ICC in the range of 0.710-0.813. CONCLUSION: MR pelvimetry measurement should be conducted in a centralized location to decrease observer-related variation. Clinicians should be aware that millimeter differences are not reliable in MR pelvimetry and therefore the use of millimeter accurate limits are not recommended in obstetric decision making.

Three-dimensional ultrasound volume calculations of human embryos and young fetuses: a study on the volumetry of compound structures and its reproducibility.

OBJECTIVE: To evaluate volumetry with three-dimensional (3D) ultrasonography in the assessment of the size of human embryos and fetuses. METHODS: Forty-four healthy embryos/fetuses with crown-rump length (CRL) ranging from 9 mm to 58 mm were studied using a 7.5-MHz annular array transvaginal 3D probe. EchoPAC 3D software was used to calculate the volumes of the head, body and limbs in the same data set by two observers working independently of each other. Regression analysis was used to assess the relationship between estimated volumes and CRL. RESULTS: The embryonic and fetal volume estimates of both observers ranged from a mean of 93 mm3 at 10 mm CRL to a mean of 11 169 mm3 at 55 mm CRL. The volume of the limbs as a proportion of the mean whole-body volume increased from 4.7% at a CRL of 15 mm to 9.3% at a CRL of 55 mm. Limits of agreement between the observers were calculated to be -0.12 +/- 9.2%. CONCLUSION: It is possible to reconstruct complex small anatomic structures and calculate the volumes of human embryos and fetuses in vivo by using dedicated 3D ultrasound equipment. The reproducibility of whole-body volume estimates seems to be high. The limbs represent a significant proportion of the size of the embryonic/fetal body.

First-trimester diagnosis of imperforate anus.

Imperforate anus or anorectal atresia is often associated with major fetal structural defects but it may also be an isolated abnormality. Prenatal diagnosis is difficult but may be assisted by ultrasound detection of a dilated distal bowel or rectum. We report on a fetus at 12 weeks of gestation in which a dilated colon was detected at ultrasound examination. Dilatation of the colon was clearly seen in the first and third trimesters of pregnancy, but was difficult to detect in the second trimester. At birth, the newborn was diagnosed with a low type of imperforate anus.

Fetal nuchal translucency and normal chromosomes: a long-term follow-up study.

OBJECTIVE: To assess the impact of increased nuchal translucency observed during early pregnancy on the subsequent health of children with normal chromosomes, with special attention to cardiac anatomy and function. METHODS: Clinical examination and detailed cardiac evaluation were carried out in 50 chromosomally normal children at the age of 2.4-7.1 years who had had a nuchal translucency measurement of > or = 3 mm at 13-15 weeks' gestation. The data of two babies who died of heart defects were also included. RESULTS: Major cardiac defects were identified in four (8%) of the children. The growth of all children was within normal limits. One child had Noonan syndrome, one had a cleidocranial dysplasia and a third had a developmental delay together with an unrecognized syndrome. Webs in the neck region were noticed in two children, with no associated pathology. CONCLUSIONS: In chromosomally normal fetuses with increased nuchal translucency, fetal echocardiography is necessary to identify major cardiac defects. In general, the parents can be reassured that, in the great majority, postnatal development is normal.

Weights of placentae from small-for-gestational age infants revisited.

The objective of the study was to investigate the association between placental weight and birthweight in appropriate (AGA) and small for gestational age (SGA) infants. Placental weight, birthweight and their ratio in chromosomally normal singleton pregnancies with SGA (n=1569) and AGA (n=15 047) infants were compared, and their determinants were studied by logistic regression. SGA infants had 24 per cent smaller placentae than AGA infants when gestational age was used as a covariate. Placental actual weight was also lower in SGA infants than in AGA infants of the same birthweight (P< 0.001). SGA infants had smaller placentae than the controls, suggesting that fetal growth depends on the actual weight of the placenta. Future studies should evaluate whether growth restriction could be reversed by therapeutic approaches increasing placental weight.

Predicting delivery date by ultrasound and last menstrual period in early gestation.

OBJECTIVE: To compare last menstrual period and ultrasonography in predicting delivery date. METHODS: We used ultrasound to scan 17,221 nonselected singleton pregnancies at 8-16 completed weeks. The last menstrual period (LMP) was considered certain in 13,541 and uncertain in 3680 cases. The duration of pregnancy from the scan to the day of spontaneous delivery was predicted by crown-rump length, biparietal diameter (BPD), and femur length (FL) using linear regression models, and the results were compared with estimates based on LMP. RESULTS: At all gestational ages, ultrasound was superior to certain LMP in predicting the day of delivery by at least 1.7 days. When deliveries before 37 weeks were excluded, crown-rump length measurement of 15-60 mm (corresponding to 8-12.5 weeks) had the lowest prediction error of 7.3 days. After that time, BPD (at least 21 mm) showed a similar error (7.3 days) and was more precise than crown-rump length. Femur length was slightly less accurate than crown-rump length or BPD. Regression models using a combination of any two or three ultrasonic variables did not improve accuracy of prediction. When ultrasound was used instead of certain LMP, the number of postterm pregnancies decreased from 10.3% to 2.7% (P <.001). CONCLUSION: Ultrasound was more accurate than LMP in dating, and when it was used the number of postterm pregnancies decreased. Crown-rump length of 15-60 mm was superior to BPD, but then BPD (at least 21 mm) was more precise. Combining more than one ultrasonic measurements did not improve dating accuracy.

Heritability and risk factors of uterine fibroids--the Finnish Twin Cohort study.

OBJECTIVES: Our aim was to study heritability, risk factors and hospitalization for uterine fibroids. METHODS: A random sample of 80 MZ and 80 DZ twins from the Finnish Twin Cohort were invited and 51% of the eligible women (n=82, 17 MZ and 16 DZ pairs, 40-47 years, mean age 43.0), underwent a transvaginal ultrasound. The entire cohort of 13872 women was linked to the national hospital discharge registry 1972-1990. RESULTS: Prevalence of fibroids was 66% and the average number of fibroids 1.7. The casewise concordance for being hospitalized for uterine fibroids was higher in MZ (0.31, 95% CI 0.24-0.37) than in DZ pairs (0.18, 95% CI 0.14-0.22). The proportion of variance in liability to fibroid hospitalization accounted for by genetic factors was 54.8% (95% CI 46.2-62.7%). Women with fibroids had higher body mass index (23.7 vs 21.7, P=0.0086), lower age at first birth (25.7 vs 29.3, P=0.012) and higher parity (3+ children 48.2 vs 29.6%, P=0.009) than women without fibroids. Risk ratio (RR) for fibroids in a MZ twin whose sister had been diagnosed with fibroids was 1.1 (95% CI 0.08;15), for a DZ twin 1.1 (95% CI 0.16;8.8) and for all twins 1.3 (95% CI 0.3; 6.1). Intraclass correlation for the number of fibroids was 0.24 for MZ and 0.11 for DZ twins, yielding an heritability estimate of 0.26. CONCLUSION: Reproductive and anthropometric factors may have at least as large role in pathogenesis of fibroids than genetic factors.

Monoclonal gammopathy may disturb oestradiol measurement in the treatment and monitoring of in-vitro fertilization: case report.

A 31 year old woman had her treatment for infertility by in-vitro fertilization (IVF) cancelled because a highly elevated serum concentration of oestradiol was detected, contrary to the clinical picture and that observed by vaginal ultrasound. The immunoassay for measuring oestradiol had been affected by circulating heterophilic antibodies in the form of an elevated immunoglobulin (Ig) G-kappa M component. This may often be associated with a haematological malignancy of lymphoid origin, but this patient had a benign monoclonal gammopathy. Monoclonal gammopathy has not been described in IVF patients previously, nor has monoclonal gammopathy been reported as a cause of erroneously elevated oestradiol concentration. This sort of interference in oestradiol analysis is probably very rare, but may lead to unnecessary cancellation of the treatment. A highly elevated oestradiol that is not in accordance with the clinical course may indicate heterophilic antibody interference, and the cause should always be investigated.

Sonographic measurement of uterine cervix at 18-22 weeks' gestation and the risk of preterm delivery.

OBJECTIVE: Premature delivery is difficult to predict and causes considerable neonatal morbidity and mortality. Despite much research, little progress has been made in timely identification of the mothers at risk. We examined the uterine cervix with ultrasonography to discover whether such a procedure would be helpful in determining which women will deliver prematurely. METHODS: We performed transvaginal ultrasound examinations in addition to routine transabdominal ultrasonography at 18 to 22 weeks' gestation in 3694 consecutive pregnant women with live singleton fetuses. We measured the length of the uterine cervix and evaluated the dilatation, if any, of the internal os. The results of cervical ultrasonography were not available to the clinicians. RESULTS: Spontaneous delivery occurred before 37 completed weeks in 88 women (2.4%) and before 35 weeks in 31 (0.8%). The relative risk of delivery before 35 weeks was 8 (95% confidence interval 3, 19) when the cervical length was 29 mm or shorter. When dilatation of the internal cervical os of 5 mm or greater was present, the relative risk of delivery before 35 weeks was 28 (95% confidence interval 12, 67). Either short cervix (29 mm or less) or dilatation of internal cervical os (5 mm or greater) was present in 3.6% of the population; this combination had a sensitivity of 29% in predicting delivery at earlier than 35 weeks. After adjusting for cervical dilatation and length by using multiple logistic regression, nulliparity also remained a risk factor for delivery before 35 weeks (odds ratio 3.6, 95% confidence interval 1.7, 7.5). CONCLUSION: Transvaginal ultrasonography performed as an addition to routine transabdominal ultrasonography at 18 to 22 weeks helps to identify many patients at significant risk for prematurity; however, low sensitivity and low positive predictive value limit its usefulness in screening low-risk obstetric populations.

Transvaginal ultrasonography at 18-23 weeks in predicting placenta previa at delivery.

OBJECTIVE: To evaluate whether transvaginal ultrasonography at 18-23 weeks' gestation is useful in predicting placenta previa at delivery. DESIGN: We performed transvaginal ultrasonography in addition to routine transabdominal ultrasonography in 3696 consecutive non-selected pregnant women with singleton fetuses and measured the distance from the placental edge to the internal cervical os. RESULTS: In 57 of 3696 patients (1.5%), the placental edge extended to or over the internal cervical os. In 27 patients (0.7%), the placenta extended > or = 15 mm over the internal cervical os; in these cases the positive predictive value of placenta previa at delivery was 19% (95% CI, 6-38%) with 100% (95% CI, 48-100%) sensitivity. With > or = 25 mm used as the cut-off point, ten cases (0.3%) were screen-positive and the positive predictive value for previa at delivery was 40% (95% CI, 12-74%) and sensitivity was 80% (95% CI, 28-100%). The frequency of placenta previa at delivery in this population was five of 3696 (0.14%, 95% CI, 0.04-0.31%). CONCLUSIONS: We recommend confirmatory transvaginal ultrasonography if placenta previa is suspected at transabdominal ultrasonography in mid-pregnancy, and reexamination at 26-30 weeks if the placental edge covers the internal cervical os by 15 mm or more.