G. Daskalakis

Screening for pre‐eclampsia and fetal growth restriction by uterine artery Doppler and PAPP‐A at 11–14 weeks' gestation

To assess the role of maternal demographic characteristics, uterine artery Doppler velocimetry, maternal serum pregnancy‐associated plasma protein‐A (PAPP‐A) and their combination in screening for pre‐eclampsia and small‐for‐gestational age (SGA) fetuses at 11–14 weeks.

Embryo reduction versus expectant management in triplet pregnancies

OBJECTIVE In triplet pregnancies, to compare pregnancy outcome of expectant management with that after embryo reduction to twins. METHODS Retrospective study of 255 trichorionic triplet pregnancies, of which 185 had embryo reduction to twins (reduced group) and 70 were managed expectantly (non-reduced group). RESULTS Median birth weight was higher by about 500 g and gestation prolonged by about 3 weeks in the reduced pregnancies compared with the expectantly managed pregnancies (2300 vs. 1760 g; 36 vs. 33 weeks). The rates of preterm delivery were significantly lower in the reduced group (11.17 vs. 36.76% for delivery at < or = 32 weeks and 40.58 vs. 83.82% for delivery at < or = 35 weeks, reduced vs. non-reduced group). The percentage of infants born with low birth weight was significantly higher in the expectantly managed triplets (10.98 vs. 28.44% for birth weight < or = 1500 g and 68.55 vs. 92.89% for birth weight < or = 2500 g, reduced vs. non-reduced group). Total fetal loss was significantly higher in the reduced group than in the non-reduced group (15.41 and 4.76%, respectively) and the difference was mainly due to the higher miscarriage rate in the reduced group (8.11 vs. 2.86% in the non-reduced group). With the expected rates of handicap in preterm infants, we would anticipate 0.63% of severely handicapped children due to extreme prematurity in the reduced group and 1.64% in the non-reduced group. CONCLUSION In triplet pregnancies, embryo reduction to twins significantly reduces the risk of severe preterm delivery and very low birth weight by about one-third, at the expense of a significant increase in total fetal loss, by about one-quarter. The procedure is likely to reduce the risk of having a severely handicapped child due to extreme prematurity.

Screening for pre-eclampsia by oxidative stress markers and uteroplacental blood flow

Summary Recent evidence suggests that the oxidative stress is an important factor in the pathophysiology of pre-eclampsia. The purpose of this study was to evaluate the possible relationship between increased resistance at the Doppler assessment of the uterine arteries between 20–23 gestational weeks and biochemical markers of oxidative stress, with the development of pre-eclampsia and/or growth restricted infants. This was a prospective study of 34 pregnant women with normal uteroplacental flow and 30 women with abnormal uterine arteries Doppler analysis (mean PI ≥ 1.60) during the transvaginal assessment of the uterine arteries at the routine anomaly scan. Blood samples were obtained in order to assess the plasma oxidative stress, namely malondialdehyde (MDA) and uric acid levels. The MDA was significantly higher in the group of women with abnormal uterine arteries Dopplers. This group is at increased risk for the development of pre-eclampsia. The uric acid levels did not differ significantly between the two groups of women. There was no significant difference regarding the sensitivity or the specificity of the uterine arteries Doppler examination in detecting pre-eclampsia in comparison to the combination of oxidative stress and Dopplers. Our study provides additional evidence regarding the role of oxidative stress in the pathophysiology of pre-eclampsia. Whether antioxidant supplementation in the group of women with abnormal uterine Dopplers is effective in reducing the incidence of the disease remains to be established.

Prenatal diagnosis of fetal left ventricular non-compaction cardiomyopathy

Isolated left ventricular non‐compaction (LVNC) is a rare disorder, classified as a primary genetic cardiomyopathy by the American Heart Association or as an unclassified cardiomyopathy by the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. The key features are the prominent trabeculae and deep intratrabecular recesses resulting in thickened myocardium with the two layers consisting of compacted and non‐compacted myocardium. These recesses are in continuity with the left ventricular cavity and are filled with blood without evidence of communication to the epicardial coronary artery system. We present a case of LVNC detected prenatally at 25 + 4 weeks of gestation. Copyright

Prenatal detection of congenital cataract in a fetus with Lowe syndrome

The oculocerebrorenal syndrome of Lowe (OCRL) is a rare Xlinked recessive genetic disorder (Lowe et al. 1952). A hallmark of the syndrome is the prenatal development of congenital cataract. Additional characteristics include Fanconi syndrome with tubular acidosis, bicarbonaturia, phosphaturia, hypercalciuria, proteinuria, generalised aminoaciduria, polyuria, carnitine wasting and vitaminD-resistant rickets and scoliosis. The syndrome affects the central and peripheral nervous system, resulting in neonatal muscular hypotonia and areflexia by the first year of life. Maladaptive behaviour with mental retardation is also a key feature of the disease. The responsible gene, OCRL1, was studied and cloned in 1992. It is located on chromosome Xq25–q26 and contains 24 exons. Prenatal diagnosis is only practical for informative families with a known disease history (Lin et al. 1997).

Prenatal diagnosis of prune-belly syndrome at 13 weeks of gestation: case report and review of literature.

We present a case report of a foetus with Prune-Belly syndrome (PBS) which was diagnosed sonographically during the 13th week of gestation and review of the literature. Sonographic diagnosis was based on abnormally distended urinary bladder and abdomen and absence of ‘keyhole sign’. Termination was performed on parental request and post-mortem examination revealed absence of abdominal wall musculature and the distended urinary bladder in a male foetus. Prenatal diagnosis of PBS is based on ultrasound and is usually diagnosed in the second trimester. In the first trimester there are very few reports to date. Prognosis and possible treatment options are herein discussed as well as the underlying mechanisms that may explain the clinical presentation of the syndrome.

Cesarean vs. vaginal birth for term breech presentation in 2 different study periods

Objective: To compare outcomes for fetuses at term in breech presentation during 2 periods when different delivery policies were in effect. Methods: Outcomes of the 392 planned vaginal deliveries and 1160 elective cesarean sections (CSs) performed from January 1, 1988, through December 31, 2000, were compared with those of the 24 emergency vaginal deliveries, the 403 planned CSs, and 75 emergency CSs performed from January 1, 2001 through December 31, 2004 at Alexandra Hospital, Athens, Greece. Results: A significant difference was found in rates of low 5‐minute Apgar score, birth trauma, serious neonatal morbidity, and admission to the neonatal intensive care unit (0% vs. 1.02% [P = 0.004], 1.02% vs. 0% [P = 0.004], 3.06% vs. 0.43% [P < 0.001], and 2.8% vs. 0.43% [P < 0.001], respectively) between neonates born by planned vaginal delivery and those born by elective CS during the first period. Only a reduction in rates of admission to the neonatal intermediate care unit was found between the first and second periods. Conclusions: Planned CS was found to be safer than planned vaginal delivery for fetuses at term in breech presentation. However, the study did not demonstrate that the change in policy improved neonatal outcome.

Pregnancy outcome after multifetal pregnancy reduction

Objective: To study the effects of multifetal pregnancy reduction (MFPR) as a means to reduce the adverse outcome of multiple gestations. Methods: This was a retrospective study evaluating the outcome of 334 multiple pregnancies after embryo reduction. Results: In 313 multiple pregnancies in which MFPR was performed before 15 weeks, the rates of miscarriage, preterm delivery < 33 weeks, preterm delivery < 36 weeks and total fetal loss were 9.12%, 13.33%, 38.60% and 16.25%, respectively, and median gestational age at delivery was 35 weeks. There was a significant correlation between miscarriage and the finishing number of fetuses. In 185 triplets reduced to twins, miscarriage, preterm delivery < 33 weeks, preterm delivery < 36 weeks and total fetal loss occurred in 8.25%, 11.18%, 40.59% and 15.41% of cases, respectively, and median gestational age at delivery was 36 weeks. In the subgroup of 32 reduced triplet pregnancies that also had second-trimester amniocentesis, the risk of miscarriage (3.13%) was not significantly different from that in the rest of the group. Among 21 twin pregnancies that had selective termination at or after 15 weeks, the risk of preterm delivery < 33 weeks was three times higher than in the group of 22 twin pregnancies with first-trimester procedures. Conclusion: MFPR resulted in at least one live neonate in 83.75% of cases and was effective in reducing the risks of pregnancy loss and severe prematurity in quadruplets and higher-order pregnancies. The risk of miscarriage increased with increasing finishing number of fetuses. In reduced triplets gestation was prolonged in comparison with average figures reported in the literature. In twin pregnancies selective termination in the first trimester carries a lower risk of severe preterm delivery and this emphasizes the need for first-trimester diagnosis.

The role of cervical length measurement at 11–14 weeks for the prediction of preterm delivery

Objective. To determine whether cervical length (CL) measurement at 11–14 weeks is predictive of preterm delivery (PTD). Methods. This was a prospective study of a low-risk population of 1113 women, who underwent CL measurement at 11–14 weeks. Mean CL was calculated for deliveries at >37, <37 and <34 weeks. Cut-off limits of 27 mm and 30 mm were used to examine the predictive value of CL. Results. Mean ± SD CL for the entire study population was 40.6 ± 5.5 mm. CL was analyzed for term and PTD (<37 weeks) and further analyzed for deliveries at 34–37 and <34 weeks. Mean CL was 38.9 ± 5.5 mm for PTD and 40.8 ± 5.5 mm for deliveries >37 weeks (p = 0.001). Receiver operating characteristic analysis showed small predictive value of CL for PTD <37 weeks (sensitivity = 63.3% and specificity = 51.1%, area under the curve (AUC) = 0.60, 95% CI: 0.54–0.66) (p = 0.001) and did not show any predictive value for PTD <35 weeks (AUC = 0.55, 95% CI: 0.43–0.67, p = 0.355) or PTD <32 weeks (AUC = 0.51, 95% CI: 0.30–0.74, p = 0.851). Conclusion. CL at 11–14 weeks does not appear to be predictive of PTD. Statistical analysis of CL did not show any predictive value for PTD <35 weeks, or <32 weeks and although it showed a predictive value for PTD at <37 weeks, the sensitivity was very low.

Prenatal diagnosis of Wolf–Hirschhorn syndrome: ultrasonography and genetics

A 36-year-old primigravida attended our Fetal Medicine Unit for the routine second trimester anomaly scan at 19 weeks of her pregnancy. Her first trimester screening for chromosomal abnormalities (nuchal translucency, nasal bone, ductus venosus combined with b-hCG and PAPP-A) had given a low risk of 1/2320 for trisomy 21. The ultrasound examination of the fetus revealed increased nuchal fold (NF) thickness, with an abnormal flat facial profile with hypoplastic nasal bone, hypertelorism and possible hypospadias (Figure 1a–d). The rest of the fetal anatomy including fetal echocardiography was unremarkable. After genetic counseling the patient was advised to undergo invasive testing to check the fetal karyotype. An amniocentesis was performed and the karyotype showed that the short arm of chromosome 4 was missing some genetic material. In particular R-banded chromosome analysis was performed at the 550 band level using standard procedures [1]. The karyotype was 46, XY, del (4) (p16.3) de novo. Multiplex ligation-dependent probe amplification specific molecular probe detected a 19-Mb deletion of the gene LETM1 1.81 Mb from the telomere. A further molecular cytogenetic analysis with fluorescent in situ hybridization (FISH) using specific probe locus-specific identification (LSI) Wolf–Hirschhorn/CEP4 (4p16.3) was performed and confirmed the initial karyotype diagnosis compatible with Wolf–Hirschhorn syndrome (WHS; Figure 2). Totally 100 nuclei were studied, one copy of the region 4p16.3 was observed which defines deletion in this region. Both parental karyotypes were normal. The parents after genetic and pediatric counseling about the prognosis of WHS elected to terminate the pregnancy. Post-mortem examination of a 350 g fetus confirmed the ultrasound findings.