Melanie Engels

Normal fetal lung volume measured with three-dimensional ultrasound.

To construct reference intervals for fetal lung volumes measured longitudinally using three‐dimensional (3D) ultrasound, and to evaluate the effect of gender on lung size.

First-trimester serum marker distribution in singleton pregnancies conceived with assisted reproduction

To evaluate marker distribution of free β‐human chorionic gonadotrophin (fβ‐hCG) and pregnancy‐associated plasma protein‐A (PAPP‐A) in singleton pregnancies conceived by assisted reproduction techniques (ART).

The effectiveness of multifetal pregnancy reduction in trichorionic triplet gestation

OBJECTIVE The objective of the study was to assess in trichorionic triplet pregnancies the effectiveness of elective reduction to twins. STUDY DESIGN This was a nationwide retrospective cohort study. We compared the time to delivery and perinatal mortality in trichorionic triplet pregnancies electively reduced to twins with ongoing trichorionic triplets and primary dichorionic twins. RESULTS We identified 86 women with reduced trichorionic triplet pregnancies, 44 with ongoing trichorionic triplets, and 824 with primary twins. Reduced triplets had a median gestational age at delivery of 36.1 weeks (interquartile range [IQR], 33.3-37.5 weeks) vs 33.3 (IQR, 28.1-35.2) weeks for ongoing triplets and 37.1 (IQR, 35.3-38.1) weeks for primary twins (P < .001). The total number of surviving children in the reduced group was 155 (90%) vs 114 (86%) in the ongoing triplet group. After reduction, 75 of women (87%) had all their fetuses surviving, compared with 36 (82%) (relative risk [RR], 1.3; 95% confidence interval [CI], 0.72-2.3) for ongoing triplets and 770 (93%) (RR, 0.91; 95% CI, 0.82-1) for primary twins. There were 6 women without any surviving children (7%) after reduction vs 5 (11.4%) (RR, 0.81; 95% CI, 0.47-1.4) among women with ongoing triplets and 32 (3.9%) (RR, 1.7; 95% CI, 0.8-3.7) in women with primary twins. CONCLUSION In women with a triplet pregnancy, fetal reduction increases gestational age at birth with 3 weeks as compared with ongoing triplets. However, there the impact on neonatal survival is limited.

Performance of first‐trimester combined test for Down syndrome in different maternal age groups: reason for adjustments in screening policy?

To evaluate the performance of the first‐trimester combined test (FCT) in different maternal age groups and to discuss whether adjustments in screening policies should be made.

Prenatal diagnosis of aneurysms of the vein of Galen (vena magna cerebri) with conventional sonography, three-dimensional sonography, and magnetic resonance imaging: report of 2 cases.

Objective. To describe the cases of 2 fetuses with aneurysms of the vein of Galen diagnosed prenatally. Methods. The techniques used were conventional sonography, three‐dimensional sonography, and ultrafast magnetic resonance imaging. On the basis of these imaging modalities, prognostic factors, such as drainage and secondary damage, were assessed. Results. The first fetus had good prognostic indices, and embolization after birth was successful. According to the prognostic factors, a poor neonatal outcome was predicted for the second fetus. The neonate died soon after birth. Conclusions. Conventional sonography, color Doppler imaging, and magnetic resonance imaging appeared to be useful diagnostic tools. The prognostic factors can be useful in counseling patients and providing the best possible care after birth.

Evaluation of the introduction of the national Down syndrome screening program in the Netherlands: age-related uptake of prenatal screening and invasive diagnostic testing

OBJECTIVE To study the effect of different government prenatal screening (PNS) policies on the uptake of PNS and prenatal diagnostic testing (PND) over the periods 2001-2003 (PNS on request), 2004-2006 (permission to offer the first-trimester combined test (FCT) to women of advanced maternal age (AMA), with women aged <36 years informed on explicit request) and 2007-2010 (introduction of population screening) and to evaluate whether trends in uptake are related to maternal age. The indication AMA for PND is still warranted, and the costs for FCT are only reimbursed for AMA women. STUDY DESIGN Analysis of data on the first- and second-trimester screening program (n=41,600) for Down syndrome (DS) and on PND (n=10,795) performed from 2001 to 2010 in the region North-Holland of the Netherlands. To evaluate the actual participation in PNS and PND in different maternal age groups, estimation of the age distribution of women who underwent a fetal anomaly scan in 2009 (n=14,481) was used as a reference population (participation of 85.2%). RESULTS The overall uptake of FCT was 35.2% in 2010. Over the years the number of FCT in all age groups increased significantly (P<0.001). Overall the number of PND decreased significantly; the number of PND for AMA decreased and the number of PND for increased risk at FCT (in women <36 and ≥36 years) increased (P<0.05). Since 2004 significantly more DS cases were detected with FCT in AMA women and fewer with PND for AMA, and since 2007 more DS cases were detected with FCT in women <36 years (P<0.001). CONCLUSION The effect of the national screening program is limited. Significantly more women opt for PNS but the overall uptake remains low, especially in younger women. A significant number of AMA women still opt for PND for AMA. The choice for FCT and PND for AMA seems dependent on background risk. To accomplish a more effective screening policy, reimbursement of the cost of the test should apply to all women and the indication for PND for AMA should be abolished.

Validation of Correction Factors for Serum Markers for First-Trimester Down Syndrome Screening in Singleton Pregnancies Conceived with Assisted Reproduction

Objective: To validate previously computed correction factors for free β-human chorionic gonadotrophin (fβ-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) pregnancies with hormone treatment and to determine the effect on false-positive rate (FPR). Methods: Retrospective study on 249 IVF and 250 ICSI cases and 20,190 controls. Correction factors 1.42 (PAPP-A), 1.17 (fβ-hCG) in IVF; 1.56 (PAPP-A) in ICSI were applied on the absolute serum concentrations. Analysis was done on log10-transformed multiples of medians (MoMs). Results: In the controls, mean PAPP-A and fβ-hCG MoM were 1.004 and 1.062. Before correction, mean PAPP-A MoM was significantly lower in IVF (0.757; p < 0.001) and in ICSI (0.671; p < 0.001) and after correction comparable (1.071; p = 0.053 in IVF; 1.048; p = 0.178 in ICSI). Before correction, mean fβ-hCG MoM was comparable (1.054; p = 0.59 in IVF and 1.051; p = 0.56 in ICSI) and after correction significantly higher in IVF (1.241; p < 0.001). After correction the likelihood for receiving a false-positive result was 1.03 in IVF pregnancies (95% CI 0.98-1.09; p = 0.248) and 1.02 in ICSI pregnancies (95% CI 0.97-1.07; p = 0.448). Conclusions: After correction the FPR in IVF and ICSI pregnancies with hormone treatment reduces to the observed FPR in the controls.

Age independent first trimester screening for Down syndrome: improvement in test performance

The aim of this study was to compare screening performance for Down syndrome of the absolute risk (AR) method to the first trimester combined test (FCT) at different maternal ages.

First-Trimester Screening for Down Syndrome with Serum Sampling at Different Gestational Ages: The Effect on Screening Performance

Introduction: The objective of this study was to evaluate the performance of first-trimester Down syndrome (DS) screening with serum sampling at different weeks of gestation. Material and Methods: We studied 35,431 singleton pregnancies (2005-2011), including 145 DS cases. Screening performance was determined in different maternal age groups with serum sampling between weeks 9 + 0 and 13 + 6. Results: No significant differences were found between the detection rates at different gestational weeks. The false-positive rate (FPR) in week 9 (6%) was comparable to the FPR in week 10 (6.5%; p = 0.214), whereas it was significantly lower compared to weeks 11 (7.2%; p = 0.007), 12 (7.4%; p = 0.003) and 13 (8.5%; p < 0.001). The odds of receiving a false-positive result was significantly increased with serum sampling in week 11 (OR 1.32, 95% CI 1.08-1.63; p = 0.008) for women ≥36 years and from week 12 onwards (OR 1.28, 95% CI 1.01-1.61; p = 0.04) for women <36 years. There were no differences in mean log10 multiple of the median values of pregnancy-associated plasma protein-A, free β-human chorionic gonadotrophin or nuchal translucency between both age groups, nor in mean maternal age between the different gestational weeks in either age group. Discussion: Early serum sampling (<11 weeks) resulted in higher screening performance. The impact of the increase in the FPR was highest in women ≥36 years.

A trend toward increased first trimester free β‐hCG and PAPP‐A in monochorionic twins complicated by Twin‐to‐Twin Transfusion syndrome

First trimester combined screening calculates the individual risk for a woman carrying a pregnancy affected by Down syndrome from the ultrasound measurement of the nuchal translucency (NT), maternal serum free β human chorionic gonadotrophin (free β-hCG) combined with pregnancy associated plasma protein-A (PAPP-A) and background risk based on maternal age. First trimester biochemical Down syndrome screening markers have been described in relation to adverse pregnancy outcome such as preeclampsia, fetal growth restriction, stillbirth and preterm birth (Dugoff et al., 2004). Approximately 9% to more than 15% of all monochorionic (MC) twin pregnancies have been described to be complicated by Twin-to-Twin Transfusion syndrome (TTTS) (Quintero et al., 1999; Lewi et al., 2008). TTTS with out intervention leads to either severe morbidity mostly associated with preterm birth or demise of one or both fetuses (Quintero et al., 1999; Berghella and Kaufmann 2001). The association between NT discordance ≥20% between fetuses in MC twins and subsequent development of TTTS was described earlier (Kagan et al., 2007; Linskens et al., 2009). Biochemical markers for the identification of MC pregnancies at risk for TTTS would be highly useful in clinical practice for early and timely diagnosis and subsequent therapy of TTTS, besides the use of NT discordance. Second trimester Down syndrome markers were recently suggested to be increased in MC twin pregnancies complicated by TTTS (Fox et al., 2009; Sermondade et al., 2009). In sixty TTTS cases, the median multiple of the median (MoM) free β-hCG (corrected for twin chorionicity) was significantly increased (1.39 vs 0.98) in the second trimester compared to MC twins with uncomplicated outcome. For alpha-fetoprotein (AFP) there was a small increase of 1.15 versus 0.99 in TTTS compared with uncomplicated MC twin pregnancies (Muller et al., 2003; Sermondade et al., 2009). In the