Adverse fetal outcome: is first trimester ultrasound and Doppler better predictor than biomarkers?

Aims and objectives: To evaluate the predictive value of first trimester biomarkers and ultrasound in determining adverse fetal outcomes in a low risk Asian population.

Material and method: All low risk, singleton pregnancies between 11 and 14 weeks gestation underwent ultrasound with uterine artery Doppler along with PAPP-A and free β-hCG estimation, and were followed till delivery to observe the outcome. The adverse fetal outcomes detected were structural anomaly, aneuploidy, intrauterine growth restriction, preterm birth and stillbirth (SB).

Results: Out of 3500 women screened, 417 cases had adverse fetal outcome in the absence of maternal complication, 2151 had normal outcome. Major structural anomaly was detected in first trimester in 17/28 (60.7%) cases. The most important markers for adverse fetal outcome were increased uterine artery pulsatility index (UPI) (p?=?0.028, OR 1.5, 95% CI: 1.05–2.38, AUC 0.56) for IUGR, nuchal translucency (p?=?0.001, OR 1.7, 95% CI: 1.11–2.77, AUC 0.60) for major anomaly and low PAPP-A (p?=?0.017, OR ?0.075, 95% CI: 0.87–0.98, AUC 0.621) for SB.

Conclusion: UPI, NT and PAPP-A in the first trimester are significant markers of adverse fetal outcome, although the sensitivity and specificity are not high they have a high negative predictive value.     

Lower placental growth factor and higher free β-hCG and PAPP-A levels in the fetal circulation of near-term pregnancies complicated with severe preeclampsia

Background: An imbalance between anti- and angiogenic factors during early placentation is key for the development of preeclampsia. Nevertheless, the majority of studies addressing this issue relate to maternal blood and not the fetal circulation.

Objective: To measure placental growth factor (PlGF), free beta human chorionic gonadotropin (β-hCG), and pregnancy-associated plasma protein-A (PAPP-A) levels in the fetal circulation of near-term pregnancies complicated with severe preeclampsia (n?=?20), and their controls matched for parity, and maternal and gestational age.

Method: Upon delivery, a blood sample was withdrawn from the umbilical artery and vein of each case and its control in order to measure the proposed analytes using direct fluoroimmunoassay.

Results: Preeclampsia cases showed significantly lower median PlGF levels in fetal circulation as compared to controls (25.2 versus 36.9 and 23.6 versus 33.9?pg/mL, artery and vein, respectively, p?0.05). Contrarily, cases displayed higher concentrations of PAPP-A (1024.0 versus 720.9 [median] and 1027.0?±?298.4 versus 690.3?±?401.9 mIU/L, artery and vein, respectively, p?<?0.05), and free β-hCG (mean: 33.9?±?4.3 versus 17.2?±?4.0 and 30.1?±?5.2 versus 13.7?±?3.3?ng/mL, artery, and vein respectively, p?<?0.05).

Conclusion: Lower PlGF and higher PAPP-A and free β-hCG levels were found in the fetal circulation of near-term severe preeclamptic pregnancies. There is a need for more research in this regard.     

Analysis of the impact of PAPP-A, free β-hCG and nuchal translucency thickness on the advanced first trimester screening

Objectives

The intention of this study is to analyze the impact of the single parameters NT, PAPP-A and free β-hCG used in combined first trimester screening and to determine their contribution in the risk assessment.

Methods

A retrospective risk assessment on the advanced first trimester screening (AFS) algorithm was made to determine the effect of a particular parameter while the remaining ones were fixed for calculation. Afterward data were recalculated by the AFS module. Test performance was measured by receiver operating characteristics (ROC) curves and their area under curve (AUC).

Results

Among the 14,862 cases are 14,748 healthy fetuses, 86 with trisomy 21, 22 with trisomy 18 and 6 with trisomy 13. Some settings obtain at default cut-off a very high sensitivity. However, a lack of specificity, as a high false-positive rate, too. The ROC analysis was best for NT, followed by PAPP-A. Free β-hCG showed the lowest AUC. Combining PAPP-A and free β-hCG offered a better AUC than each parameter alone. Best test performance was obtained by including all three parameters.

Discussion

A detection rate of 69 % for testing NT discretely is in order with present study data. PAPP-A is following and free β-hCG is not useful with a test positive rate of about a third. The detection rate of the biochemical parameters combined is higher than for NT alone, but results in a five times higher punctuation rate. All parameters together in the AFS provide the best test performance. The impact of each parameter NT, PAPP-A and free-β-hCG in a combined test strategy is nearly a third. Thus, every single parameter is needed to provide a high detection rate for all of the trisomies and minimize the number of unnecessary invasive diagnostics.     

Semilobar holoprosencephaly with associated cyclopia and radial aplasia: first trimester diagnosis by means of integrating 2D–3D ultrasound

Introduction  Holoprosencephaly (HPE) is commonly associated with facial malformations. We present a case of semilobar HPE associated with distal limb defect which was detected at 12 weeks of gestation. Case  The fetus had a crown-rump length of 60 mm (12 weeks–4 days), had nuchal translucency thickness of 1.5 mm. Initial two-dimensional (2D) ultrasound revealed the absence of nasal bone, decreased BPD and abnormal profile. Transvaginal 2D ultrasound was effective in the detection of HPE (partially absence of the interhemispheric fissure, fused thalami, the choroid plexuses were not visualized bilateraly: absent ‘butterfly’ sign), cylopia, absence of the nose and unilateral radial aplasia. Three dimensional (3D) ultrasound provided a better visualization of the associated anomalies. The necropsy result confirmed the sonographic findings: the diagnosis was semilobar HPE, cyclopia, absence of the nose, and the absence of the radius and the thumb in the left arm. Discussion  Transvaginal 2D sonographic examination is effective in detection of the cases with HPE at first trimester. Fetal morphological study through 3D ultrasound may facilitate the diagnosis of associated anomalies.     

Is an isolated ventricular septal defect detected before 24 weeks on ultrasound associated with fetal aneuploidy?

Objective: Whether the isolated VSD (i-VSD) is associated with aneuploidy to the same degree as a more severe heart anomaly is unclear. Our objective was to determine the likelihood of aneuploidy in pregnancies at a tertiary referral center when an i-VSD is detected before 24 weeks.

Methods: A retrospective chart review of all detailed anatomy ultrasounds before 24 weeks performed at the University of Kansas Medical Center from 08/23/2006 to 06/07/2012 was conducted. A complete evaluation of the fetal heart was accomplished using gray scale and spectral/color Doppler examinations. The outcomes of each pregnancy were reviewed for any diagnoses of aneuploidy. Odds ratios were calculated.

Results: A total of 4078 pregnancies with complete obstetric and neonatal data were reviewed. The prevalence of an i-VSD was 2.7% (112/4078). The odds ratio of aneuploidy when an i-VSD was present was (OR: 36.0, 95% CI: 5.0, 258.1). This odds ratio remained large when either an abnormal or unknown serum screen was present.

Conclusion: The presence of an i-VSD present before 24 weeks does increase the risk of fetal aneuploidy. Whether a normal serum screen or first trimester screen for aneuploidy negates the association of an i-VSD with aneuploidy still remains undetermined.     

Does diurnal variation affect the first trimester fetal aneuploidy screening test biochemical parameters of fetuses with normal nuchal translucency?

Objective: The purpose of this study was to investigate the effect of diurnal variation on biochemical results of first trimester aneuploidy screening test.

Methods: A total of 2725 singleton pregnant female, who had normal fetal nuchal translucency (NT) thickness, were included in the study during this period. Individuals were divided into two groups according to the sampling time (morning group: 09:00–11:00 am and afternoon group: 02:00–04:00?pm). Hormonal parameters (free-beta human chorionic gonadotropin [free β-hCG] and pregnancy-associated plasma protein-A [PAPP-A] multiples of median [MoM] levels) of first trimester (11⁺⁰–13⁺⁶ weeks) combined aneuploidy screening test were compared between morning and afternoon groups.

Results: PAPP-A MoM levels were significantly lower in the afternoon group when compared to the morning group (p?=?0.001), whereas free β-hCG MoM levels were similar in the both groups (p?=?0.392). Rate of high risk for Down syndrome (Combine risk >1/300) and amniocentesis ratio were found higher in the afternoon group than morning group, but there were no difference between groups for the number of fetuses with Down syndrome.

Conclusion: Receiving the venous blood sample for first trimester aneuploidy screening test in the afternoon causes low PAPP-A MoM levels.     

Is preeclampsia associated with fetal malformation? A review and report of original research

Objective: To examine fetal malformations in mother–infant pairs with and without pregnancy-related hypertension.

Methods: This was an observational, population-based study of women delivering a singleton at our hospital. Specific fetal malformations identified in women with gestational hypertension or preeclampsia were compared to those without pregnancy-related hypertension. Women with chronic hypertension, superimposed preeclampsia on chronic hypertension and pregestational diabetes were excluded.

Results: Between March 2002 and December 2012, a total of 151 997 women delivered, and 10?492 (7%) had preeclampsia, 4282 (3%) had gestational hypertension and 137?223 (90%) were referent normotensive controls. Women with preeclampsia were significantly more likely to deliver infants with malformations when compared to normotensive controls (2.5% versus 1.6%, p?<?0.001), whereas women with gestational hypertension were not (1.9% versus 1.6%, p?=?0.16). The overall risk for fetal malformation associated with preeclampsia remained significant following logistic regression for age, race, parity and maternal body-habitus (adjusted OR 1.5; 95% CI: 1.3–1.7). Only single-organ system malformations – microcephaly and hypospadias – remained associated with preeclampsia (p?<?0.001), and fetal growth restriction was a co-factor for both.

Conclusions: Preeclampsia was associated with increased rates of fetal malformations when compared to normotensive women – specifically microcephaly and hypospadias. These associations appear predominantly as a consequence of impaired fetal growth.     

孕早期性染色体缺陷胎儿母血清Fβ-hCG和PAPP-A水平的研究

胎儿性染色体畸形(47,XXX;47,XXY;47,XYY,45,X)是活婴中最常见一类染色体异常。在妊娠10～14周行产前筛查时其检出率为2‰～3‰。孕中期筛查显示:特纳氏综合征(45,X)母血清中游离绒毛膜促性腺激素β-亚单位(Fβ-hCG),抑制素-A及孕酮水平增高。通过对常染色体畸形孕妇血清Fβ-hCG和妊娠相关血浆蛋白-A(PAPP-A)以及超声波胎儿颈项部皮肤厚度(NT)的联合检测可筛查出90％唐氏     

Age related detection and false positive rates when screening for Down's Syndrome in the first trimester using fetal nuchal translucency and maternal serum free βhCG and PAPP-A

Objective To determine how first trimester detection rates for Down's Syndrome vary with maternal age and to calculate the predictive value of an increased risk report at various maternal ages.Design Mathematical modelling of first trimester screening performance using fetal nuchal translucency and maternal serum free βhCG and pregnancy associated plasma protein-A (PAPP-A).Methods From within the Gaussian distributions of each marker in normal pregnancies and those affected by Down's Syndrome a series of 15,000 marker multiple of the medians were obtained for each group. These markers were then used to calculate the risks of Down's Syndrome using maternal ages ranging from 15 to 49 and the background risk of Down's Syndrome at each age. Using a 1 in 300 risk cutoff (at time of sampling) the false positive rate and detection rate was assessed at each year of maternal age. The predictive value of a positive result was calculated using Baye's theorem.Outcome measures False positive rates and detection rates at each year of maternal age between 15 and 49; the predictive value of a positive result for each maternal age between 15 and 49.Results At 15 years of age the detection rate was 77% at a 1.9% false positive rate, 84% at a 4% false positive rate at age 30, rising to 100% at a 67% false positive rate at age 49. The probability of Down's Syndrome once identified with an increased risk was 1:34 at 15 years, 1:29 at 30 years and 1:6 at 49 years.Conclusions As with second trimester biochemical screening, the detection rate and false positive rate vary considerably with age. However, detection rates across all ages are significantly higher than with second trimester screening. The risk of a positive screening result being a Down's pregnancy is considerably greater than with second trimester screening with an average probability of 1:29, compared with 1:55 in the second trimester. This information may be useful in counselling women with an increased risk result in first trimester screening.     

Are there differences in ultrasound parameters between Chinese women with polycystic ovaries only and with polycystic ovary syndrome?

OBJECTIVE: We aimed to compare antral follicle count (AFC), ovarian volume, ovarian stromal blood flow between Chinese women with polycystic ovary (PCO) only and polycystic ovary syndrome (PCOS) and to evaluate the effect of age on these ultrasound parameters in these women. STUDY DESIGN: In the second to fourth day of the period, they underwent a transvaginal three-dimensional scanning with power Doppler to determine total AFC, total ovarian volume, total ovarian vascularization index (VI), flow index (FI) and vascularization flow index (VFI). Hormonal profile was also measured. RESULTS: A total of 71 Chinese women were recruited in the study: 39 women with PCO only and 32 women with PCOS. Women with PCO only had significantly lower AFC, ovarian volume, ovarian VI, serum LH, testosterone and DHEAS concentrations but higher serum SHBG concentration when compared with PCOS women. When women with PCO only and PCOS were considered together, the rate of decline of AFC over age was 0.905 follicle per year (95% CI=0.008-1.803, p=0.048) and there was no significant decline of ovarian volume and total ovarian VI, FI and VFI over age. CONCLUSION: PCO only represents a milder end of the PCOS spectrum.     

Two- versus three-dimensional ultrasound in the second and third trimester of pregnancy: impact on recognition and maternal–fetal bonding. A prospective pilot study

Objective To assess the impact of three-dimensional (3D) versus two-dimensional (2D) ultrasound (US) on maternal–fetal bonding. Study design Prospective randomized pilot study among low risk women with singleton fetuses in the second and third trimester. Dependent on the randomization pattern, US was commenced either with 2D US or 3D US and the effects were recorded with standardized questionnaires. Results Sixty patients were included. Although the quality of 2D US, assessed by the examinator, was superior to 3D US, maternal recognition was higher with 3-D US (P = 0.004). With 2D US, nulliparous patients had significantly more difficulties visualizing the fetus, than multiparous (P = 0.03). However, the maternal preference of 3D US had no significant impact on maternal–fetal bonding. Conclusion Ultrasound had no significant effect on maternal–fetal bonding. Three-dimensional images may facilitate recognition of the fetus, but 3D US did not have higher impact on maternal–fetal bonding. This finding may be a reason not to consider 3D ultrasound for routine scanning.