R. Bindra

A novel approach to first‐trimester screening for early pre‐eclampsia combining serum PP‐13 and Doppler ultrasound

To investigate the value of maternal serum placental protein 13 (PP‐13) measurement and uterine artery Doppler during first‐trimester screening in the prediction of early pre‐eclampsia.

Delta-NT or NT MoM: which is the most appropriate method for calculating accurate patient-specific risks for trisomy 21 in the first trimester?

To assess whether in screening for trisomy 21 by nuchal translucency (NT) the delta or the multiples of the median (MoM) approach is the most appropriate method for calculating accurate individual patient‐specific risks.

Fetal nasal bone length in chromosomally normal and abnormal fetuses at 11- 14 weeks of gestation

Objective: To determine the value of measuring fetal nasal bone length at 11-14 weeks of gestation in screening for chromosomal defects. Methods: The fetal profile was examined and the nasal bone length was measured in 1092 fetuses immediately before chorionic villous sampling for karyotyping at 11-14 weeks of gestation. Results: The median gestation was 12 (11-14) weeks. The fetal profile was successfully examined in all cases. The fetal karyotype was normal in 955 pregnancies and abnormal in 137, including 79 cases of trisomy 21. In the chromosomally normal group, the fetal nasal bone length increased significantly with crown-rump length (CRL) from a mean of 1.3 mm at a CRL of 45 mm to 2.1 mm at a CRL of 84 mm. In 54 of the 79 (68.4%) cases of trisomy 21, the nasal bone was absent. In the 25 cases with present nasal bone, the nasal bone length for the CRL was not significantly different from normal. Similarly, there were no significant differences from normal in the nasal bone length of fetuses with other chromosomal defects. Conclusions: At 11-14 weeks of gestation, the nasal bone length of chromosomally abnormal fetuses is not significantly different from normal.

First trimester sex hormone-binding globulin and subsequent development of preeclampsia or other adverse pregnancy outcomes.

Objective. To investigate whether first trimester maternal serum sex hormone-binding globulin (SHBG) concentrations are altered in women who subsequently develop preeclampsia or other pregnancy complications. Population. Women undergoing first trimester combined ultrasound and biochemical screening for chromosomal anomalies. We searched the database and identified 32 pregnancies resulting in miscarriage, 64 pregnancies with preexisting or gestational diabetes mellitus, 107 with fetal growth restriction, 103 with preeclampsia, 64 with pregnancy-induced hypertension, and 26 with spontaneous preterm delivery. We also selected 400 controls from among the population of pregnancies that had a delivery of a normal baby with no pregnancy complications. Methods. Maternal serum SHBG concentrations were measured retrospectively using a competitive chemiluminescent immunoassay. The levels between those with normal outcome and those resulting in adverse outcome were compared. Results. The median maternal serum SHBG concentration was not significantly different from controls, in those that subsequently developed preeclampsia (median MoM 1.05), nonproteinuric hypertension (median MoM 0.94) or preterm delivery (median MoM 1.15). The levels were significantly lower in those with diabetes (median MoM, 0.81 p = 0.0005) and those pregnancies resulting in miscarriage (median MoM 0.80, p = 0.008). Conclusion. First trimester maternal serum SHBG concentrations are no different from controls in women who subsequently develop preeclampsia, pregnancy-induced hypertension, fetal growth restriction, or preterm delivery. Levels are reduced in those who subsequently miscarry or in those presenting with diabetes.

Screening for Chromosomal Defects by Fetal Nuchal Translucency at 11 to 14 Weeks

The first method of screening for trisomy 21, introduced in the early 1970s, was based on maternal age. Amniocentesis was offered to women aged 35 years or more; this “highrisk” group constituted 5% of the pregnant population and contained 30% of trisomic pregnancies. In the late 1980s, a new method of screening was introduced that takes into account not only maternal age but also the concentration of various fetoplacental products (alpha-fetoprotein, estriol, and human chorionic gonadotropin [hCG]) in the maternal circulation at 16 weeks of gestation. This method of screening is more effective than maternal age alone and, for the same rate of invasive testing (5%), it can identify about 65% of the fetuses with trisomy 21. In the 1990s, screening by a combination of maternal age and fetal nuchal translucency thickness (NT) at 11 to 14 weeks of gestation was introduced. This method has now been shown to identify about 75% of affected fetuses, for a screen-positive rate of 5%. When maternal serum free beta-hCG and pregnancy-associated plasma protein-A (PAPPA) at 11 to 14 weeks are also taken into account, the detection rate of trisomy 21 and all major chromosomal defects is about 90%. Furthermore, the development of new methods of biochemical testing, within 30 minutes of taking a blood sample, has now made it possible to combine ultrasound and biochemistry in “One-Stop Clinics for Assessment of Risk” (OSCAR). Recent evidence suggests that examination of the fetal profile for the presence or absence of the nasal bone at the 11-to-14-week scan can potentially improve the sensitivity of screening to >95%. In addition to its value in screening for Correspondence: K. H. Nicolaides, Harris Birthright Research Centre for Fetal Medicine, King’s College Hospital, King’s College, Denmark Hill, London SE5 8RX. E-mail: kypros@fetalmedicine.com. PROD. # GRF20335

Second-trimester sex hormone-binding globulin and subsequent development of pre-eclampsia.

OBJECTIVE To investigate whether maternal plasma sex hormone-binding globulin (SHBG) concentrations are reduced in women who subsequently develop pre-eclampsia. METHODS This was a cross-sectional study, carried out at antenatal clinics in seven hospitals in and around London. Healthy women underwent uterine artery Doppler velocimetry as a screening method for pre-eclampsia at 22-24 weeks of gestation. The first group (408 women) had normal uterine artery Doppler waveforms (mean uterine artery pulsatility index (PI) below 1.6). The second group (274 women) had increased impedance to flow in the uterine arteries (mean PI above the 95th centile, 1.6). Maternal plasma SHBG concentrations were measured retrospectively using a competitive chemiluminescent immunoassay. Pre-eclampsia was as defined by the International Society for the Study of Hypertension in Pregnancy. RESULTS Plasma SHBG concentrations in the 80 (11.7%) women who subsequently developed pre-eclampsia were significantly lower than in the 585 (85.8%) women with normal pregnancy outcomes (median 336, range 142-674 nmol/l vs. median 336, range 142-674 nmol/l, p = 0.001). There was a strong correlation between SHBG concentrations and body mass index (r =-0.232246, p < 0.0001). There were no significant differences in maternal plasma SHBG concentrations in women with abnormal uterine artery Doppler (n = 274) compared with controls (n = 408) (median 324, range 101-635 nmol/l vs. median 336, range 142-674 nmol/l, p = 0.09). CONCLUSION Maternal plasma SHBG concentrations are reduced in women who subsequently develop pre-eclampsia.

OC38.03: One stop clinic for assessment of risk (OSCAR) for trisomy 21 in singleton pregnancies at 11 to 13 + 6 weeks of gestation

Objective: To evaluate the performance of first-trimester screening for trisomy 21 using maternal age, fetal nuchal translucency (NT) and maternal serum free s-hCG and PAPP-A at 11 to 13 + 6 weeks. Methods: All women attending between 11 to 13 + 6 weeks of gestation were offered screening for trisomy 21. Assessment of NT was performed by appropriately trained sonographers (Fetal Medicine Foundation Certificate of competence), and maternal serum s-hCG and PAPP-A was measured using the Kryptor analyser. Patients were counselled with regards to their combined estimated risk and the available options for the management of the pregnancy. Data on pregnancy outcome were obtained from the cytogenetics laboratory, and by letters and telephone calls to the patients, their general practitioners or the maternity units in which they delivered. Detection rates and false positive rates were calculated for use of maternal age, maternal age and NT, and maternal age, fetal NT and maternal biochemistry. Results: Screening for trisomy 21 was carried out in 31 904 singleton pregnancies and pregnancy outcome was obtained in 30 564 (95.8%) cases. There were 330 pregnancies affected with a chromosomal abnormality, including 196 cases of trisomy 21. Of these, in 185 cases the diagnosis was made prenatally (178 in the screen positive and seven in the screen negative pregnancies) and 11 where the diagnosis was made postnatally in live births (five in the screen positive pregnancies, in which the parents chose to avoid invasive testing, and six in the screen negative pregnancies). The estimated risk for trisomy 21 was 1 in 300 or greater in 7.5% of the normal pregnancies, in 93.4% of those with trisomy 21 and in 88.8% of those with other chromosomal defects. Conclusion: Currently, the most effective method of screening for trisomy 21 is by a combination of maternal age, fetal NT and maternal serum free s-hCG and PAPP-A at 11 to 13 + 6 weeks.

OC042: Five years experience of screening for chromosomal anomalies in a 1st trimester OSCAR clinic

abortion and an extra 3% in a IUD. Twenty-eight structural defects (8%) were detected at subsequent scans or after birth, 15 of which consisted of heart anomalies. Genetic and monogenetic syndromes were detected in 4% of the fetuses. The incidence of an unfavorable outcome, divided per degree of NT enlargement was 10% for NT between the 95th centileand 4 mm, 21% for NT between 3.5 and 4.4 mm, 22% for NT between 4.5–5.4 and 52% for an enlargement of more than 5.5 mm. Results: There is a tendency for the risk to increase according to the degree of enlargement. In the group of fetuses where at 20 weeks subtle dysmorphic feature are present a genetic syndrome may be suspected. In contrast, absence of evident anomalies sharply reduces the residual risk of adverse outcome in these fetuses.