High macrosomia rate in healthy fetuses after enlarged nuchal translucency.

OBJECTIVE: The aim of this study was to investigate the association of the first trimester screening variables nuchal translucency (NT), pregnancy associated plasma protein (PAPP-A), and free beta-human chorionic gonadotrophin (ßhCG) and birth weight, with a focus on the prediction of macrosomia. METHODS: The database of our Fetal Medicine Unit was searched for all singleton pregnancies, who underwent first trimester Down syndrome screening. Live born infants born at term without chromosomal or structural defects from non-diabetic mothers constituted the study population. Birth weight percentiles were corrected for gestational age at delivery, parity, and gender. Macrosomia was defined as birth weight ≥95th centile. RESULTS: We included 6503 fetuses. Multivariate analysis demonstrated that birth weight centile was positively correlated with NT multiples of the median (MoM), PAPP-A MoM, and maternal body mass index, and it was negatively correlated with smoking. An NT ≥95th centile was present in 315 fetuses (4.8%). Although median birth weight centile was not significantly different between cases with NT ≥95th centile and those <95th (P54 vs P52), a birth weight >95th centile was more common (11% vs 7%) in the presence of NT ≥95th centile. Pregnancy associated plasma protein was elevated (≥95th centile) in 303 cases (7.9%). Median birth weight was higher (P56 vs P51, P = 0.03) in case of elevated PAPP-A compared with PAPP-A <95th centile. There was a trend toward higher macrosomia rate in case of PAPP-A ≥95th centile (7.4% vs 6.3%, P = 0.07). Area under the receiver operating characteristics (ROC) curve for the prediction of macrosomia (birth weight ≥95th centile) by NT MoM, PAPP-A MoM, maternal body mass index, and maternal smoking was 0.64 (P < 0.001). CONCLUSIONS: First trimester PAPP-A MoM and NT MoM are significantly related to birth weight centiles. Enlarged NT is associated with macrosomia.

Low-resistance hepatic artery flow in first-trimester fetuses: an ominous sign.

OBJECTIVE: Low-resistance hepatic artery (HA) flow has been reported in severely growth-restricted fetuses. The same finding has been incidentally observed in first-trimester fetuses with enlarged nuchal translucency (NT). The aim of this study was to investigate HA flow in first-trimester fetuses. METHODS: Crown-rump length (CRL), NT, ductus venosus (DV) pulsatility index for veins (PIV) and HA pulsatility index (PI) were measured prospectively in fetuses at increased risk on first-trimester assessment for aneuploidy and in a control group of low-risk fetuses. Outcome of pregnancy was known in all cases. Independent sample t-test was used for intergroup comparison. RESULTS: NT, DV-PIV and HA-PI were measured prospectively in 59 fetuses. Thirty-four had an enlarged NT and underwent karyotyping, which was abnormal in 16 cases (trisomy 21, n = 12; trisomy 18, n = 3; 47,XXY, n = 1). Two pregnancies were terminated in view of fetal anomalies. In three other infants an abnormality was confirmed after birth (Noonan syndrome, unspecified genetic syndrome and cardiac defect). The remaining 13 fetuses with enlarged NT and the 25 with normal NT had an uneventful pregnancy outcome. HA-PI was significantly and inversely correlated with NT and DV-PIV. Mean HA-PI was significantly lower in fetuses with adverse outcome (chromosomal anomalies 1.60; chromosomally normal fetuses with adverse outcome 1.66) than in controls (2.03). CONCLUSIONS: Low-resistance HA flow can be observed in first-trimester fetuses and, based on its association with adverse outcome, it can be regarded as an ominous sign.

Enlarged nuchal translucency in chromosomally normal fetuses: strong association with orofacial clefts.

OBJECTIVES: The aim of this study was to investigate whether there is an association between enlarged nuchal translucency (NT) and orofacial clefts. METHODS: The pregnancy outcome of women who underwent an NT measurement between January 2000 and November 2008 was reviewed. All orofacial clefts detected prenatally and postnatally in karyotypically normal fetuses/infants were reviewed and a distinction was made between isolated defects and clefts as part of multiple congenital anomalies (associated). RESULTS: The cohort included 8638 fetuses. The NT was enlarged in 746 (8.6%). The karyotype was normal in 8347 fetuses, including 513 of the fetuses with an enlarged NT. Isolated or associated cleft lip, with or without cleft palate (CL/P), or cleft palate (CP) were diagnosed in 18 chromosomally normal fetuses (an incidence of 2.2 per 1000). In eight of these cases the NT was normal (8/7834; an incidence of 1.0 per 1000) and in the remaining 10 it was enlarged (10/513; an incidence of 19.5 per 1000). CL/P and CP were isolated or associated in three and seven of the chromosomally normal fetuses with an enlarged NT, respectively. Euploid fetuses with an enlarged NT had a relative risk for any clefts of 19 and a relative risk for isolated or associated clefts of 8 and 53, respectively (P < 0.001). CONCLUSIONS: Chromosomally normal fetuses with an enlarged NT have an increased risk of orofacial clefts. CL/P and CP are, in these fetuses, mostly associated findings, frequently part of a genetic syndrome. A detailed ultrasound examination with special attention given to the orofacial area is indicated in these fetuses.

First-trimester measurement of the ductus venosus pulsatility index and the prediction of congenital heart defects.

OBJECTIVE: This study was carried out to evaluate the additional predictive value of ductus venosus pulsatility index for veins (DV-PIV) in the identification of congenital heart defects (CHDs) in fetuses with an enlarged nuchal translucency (NT) and a normal karyotype. METHODS: All chromosomally normal fetuses referred to our Fetal Medicine Unit between September 1996 and December 2008 with known NT, DV-PIV and ductus venosus (DV) a-wave measurements were included. Intrafetus variation in DV-PIV was overcome by averaging three recordings. Follow-up included special focus on CHD. The odds of CHD at any NT and DV-PIV value were evaluated using logistic regression analysis. RESULTS: Of 792 fetuses included, the NT was enlarged (equal to or above the 95(th) percentile (P95)) in 318 (40.2%). The DV-PIV was abnormal (≥ P95) in 41.8% of the fetuses with an enlarged NT and the a-wave was abnormal (negative or reversed) in 29.9%. CHD was diagnosed in 35 fetuses, 33 of which had an enlarged NT. Amongst the fetuses with an enlarged NT, the sensitivities for CHD of abnormal DV-PIV and DV a-wave were 73% and 55%, with specificities of 62% and 73%, respectively. Logistic regression analysis showed that in this risk group the DV-PIV multiple of the median (MoM) (as a continuous variable) was significantly associated with the risk of CHD (odds ratio = 2.4), independent of the degree of NT enlargement, whereas the DV a-wave did not significantly add to the prediction of CHD. CONCLUSION: Two-thirds of fetuses with an enlarged NT, a normal karyotype and CHD have an increased DV-PIV. DV-PIV can be used as continuous variable in combination with NT to increase specificity in the identification of CHD and to refine the individual risk assessment.

Ductus venosus pulsatility index measurement reduces the false-positive rate in first-trimester screening.

OBJECTIVE: To investigate if ductus venosus (DV) pulsatility index for veins (PIV) and a-wave measurements can increase the accuracy of first-trimester Down syndrome screening in a high-risk population. METHODS: The database of our fetal medicine unit was searched for all cases at increased first-trimester Down syndrome risk. Multivariable logistic regression was used to construct a prediction rule for chromosomal anomalies at any given maternal age, nuchal translucency multiples of the median (NT-MoM) and DV-PIV MoM. The discriminative ability of the model was assessed by using receiver-operating characteristics (ROC) analysis. RESULTS: The study population included 445 fetuses. DV-PIV was increased (≥ 95(th) percentile) in 239 (54%) and DV a-wave was abnormal in 187 fetuses (42%). In this cohort, 80% of all chromosomal anomalies were identified by an increased DV-PIV and 68% by an abnormal a-wave. The odds of chromosomal anomalies increased by a factor of 4.2 per MoM increase in DV-PIV, adjusted for NT and maternal age. The area under the ROC curve for the prediction of chromosomal anomalies was 0.79. After correction for DV-PIV, DV a-wave did not significantly add to the prediction of chromosomal anomalies. CONCLUSION: In a population of fetuses at increased first-trimester risk for Down syndrome, the combination in a logistic regression model of NT, DV-PIV and maternal age can improve the accuracy of screening for trisomy 21 and other chromosomal anomalies. This is the first study that models the additional value of DV-PIV as a continuous variable to NT measurement alone in a high-risk first-trimester population.

Increased nuchal translucency in euploid fetuses--what should we be telling the parents?

Nuchal translucency (NT) measurement between 11 and 14 weeks' gestation is an undisputed marker for aneuploidies. When conventional karyotyping is normal, enlarged NT is a strong marker for adverse pregnancy outcome, associated with miscarriage, intrauterine death, congenital heart defects, and numerous other structural defects and genetic syndromes. The risk of adverse outcome is proportional to the degree of NT enlargement. Although the majority of structural anomalies are amenable to ultrasound detection, unspecified genetic syndromes involving developmental delay may only emerge after birth. Concern over these prenatally undetectable conditions is a heavy burden for parents. However, following detection of enlarged NT the majority of babies with normal detailed ultrasound examination and echocardiography will have an uneventful outcome with no increased risk for developmental delay when compared to the general population. Counseling should emphasize this to help parents restore hope in normal pregnancy outcome and infant development.

Male gender as a favorable prognostic factor in pregnancies with enlarged nuchal translucency.

OBJECTIVE: The aim of this study was to investigate the influence of fetal gender on pregnancy outcome in fetuses with enlarged nuchal translucency (NT). METHODS: Pregnancy outcomes of all women who underwent an NT measurement at our institution between January 2000 and November 2007 were retrospectively reviewed. Separate analyses were performed for fetuses with normal and with enlarged (>or= 95(th) percentile) NT. RESULTS: A normal NT was measured in 3637 males (51.4%) and 3435 females (48.6%). Of the fetuses with enlarged NT 365 were males (57.4%) and 271 females (42.6%) (P = 0.001). In this group a normal pregnancy outcome-of those pregnancies for which the outcome was known-was registered for 187/332 (56.3%) of the male fetuses and 98/249 (39.4%) of the female fetuses (P < 0.001; relative risk (RR) for adverse outcome for male gender, 0.72). Eighty percent of the chromosomally normal male fetuses with an enlarged NT had an uneventful pregnancy outcome; this increased to 90% when only the male fetuses with NT measurements >or= 95(th) percentile and < 99(th) percentile and normal karyotype were considered (RR for adverse outcome for male gender, 0.47). CONCLUSION: In a population of fetuses with enlarged NT there are significantly more males. Male fetuses with enlarged NT and normal chromosomes have an almost two-fold greater chance of a favorable outcome than females. We believe that a minimal degree of NT enlargement in male fetuses without genetic or structural anomalies may be interpreted as a feature of accelerated growth or, alternatively, as a maturational delay of the cardiovascular system more common in males, leading to moderately increased nuchal fluid accumulation.

[Interstitial pregnancy: a rare type of ectopic pregnancy]. / De interstitiële graviditeit: niet zomaar een extra-uteriene.

Three women, aged 21, 28 and 37 years, respectively, were diagnosed with interstitial pregnancies. The first patient presented with lateral abdominal pain, the second patient was asymptomatic and consulted the physician for a routine first trimester scan and the third patient had painless vaginal bleeding in the first trimester. Each was treated with systemic methotrexate in a multiple dose regimen, which was successful in the latter two patients. The first patient was discharged in good condition after her last methotrexate injection, but developed severe abdominal pain and collapsed at home after the interstitial pregnancy had ruptured. She underwent surgery and recovered. Today, the incidence of ectopic pregnancy in the Netherlands is around 8 per 1000 live births. Interstitial pregnancies, which nidate in the portion of the fallopian tube embedded in the uterine wall, account for 2-3% of all ectopic pregnancies. A urinary pregnancy test should be performed for any fertile woman with abdominal pain or abnormal vaginal bleeding. If the result is positive, the patient should be referred to a gynaecologist for transvaginal ultrasound to exclude ectopic pregnancy. In case of a pregnancy of unknown location, one should search for specific ultrasound markers of non-tubal ectopic pregnancy and assess serum human chorionic gonadotropin (HCG). Interstitial ectopic pregnancy should be considered if the serum HCG level is above 2000 U/l.

Vaccination against Ostertagia ostertagi with subfractions of the protective ES-thiol fraction.

Previous vaccination trials against Ostertagia ostertagi in cattle have demonstrated the protective capacity of a protein fraction termed ES-thiol, which is enriched for activation-associated secreted proteins (ASPs) and cysteine proteases. In this study, ES-thiol was subfractionated through Q-Sepharose anion exchange chromatography to determine whether the ASPs and/or the cysteine proteases are responsible for the induced protection. Calves (seven/group) were immunized three times intramuscularly with 100 microg of ES-thiol or equivalent amounts of an ASP-enriched fraction, a cysteine protease-enriched fraction or a rest fraction, with QuilA adjuvant. A negative control group only received QuilA. After the final immunization the animals were challenged with a trickle infection of 25,000 infectious L3 larvae (1000 L3/day; 5 days/week). During a 2-month period the geometric mean cumulative faecal egg count (FEC) of the ES-thiol group was reduced by 62% compared to the QuilA control group (P<0.05). Groups injected with the ASP-enriched, the cysteine protease-enriched and the rest fraction demonstrated a reduction in cumulative FEC of 74, 80 and 70%, respectively (P<0.01). Although no significant reductions in worm burdens were observed, adult male and female worms were significantly smaller in all vaccinated groups (P<0.05), except for male worms from the ES-thiol group. These results suggest the protective capacity of ASPs and the presence of other protective antigens in the ES-thiol fraction.

Structural comparison of a translated dental attitude questionnaire: a factor analytic study.

In 1984 the Dental Attitude Questionnaire (DAQ), an instrument for assessing various aspects of a person's attitude toward oral health care, was presented by STOCKWELL & BANTING. The DAQ consists of six content scales, Cynicism, Health Concern, Motivation, Oral Function, Social Aesthetic and Susceptibility, and two validity scales, Halo and Infrequency. A Dutch translation was presented in 1986 by HOOGSTRATEN & BROERS. In order to replicate the factor analysis on the original DAQ as reported by STOCKWELL & BANTING, the present study was undertaken. The results show a change in factor structure from a three factor solution to a two factor solution. A confirmatory factor analysis shows that the original three factor structure of the DAQ is not present in the data collected with the translated version. To account for this change, some possible reasons are discussed.

On the assessment of dental health care attitudes in 1986 and 1995, using the dental attitude questionnaire.

OBJECTIVE: To re-establish and update the empirical data obtained in 1986 with the Dental Attitude Questionnaire. DESIGN: In 1995 this questionnaire, presented earlier by Hoogstraten and Broers (1986), was completed in a similar setting using similar subjects as in 1985, to make a comparison between 1986 and 1995 possible. SUBJECTS: 375 persons, all first grade psychology students who participated for additional course credit. Mean age was 21.7 years, 65 per cent were female. RESULTS: Data show a change in oral health care attitudes and a change in the internal consistency of the DAQ subscales, making the present version of the questionnaire inadequate for measuring present oral health care attitudes. CONCLUSION: This study has shown once more the importance of conducting replication studies after relatively long periods of time in order to update the psychometric characteristics of questionnaires.

Nuchal translucency measurement and congenital heart defects: modest association in low-risk pregnancies.

OBJECTIVE: To assess the performance of nuchal translucency (NT) measurement in the first trimester of pregnancy as a marker for congenital heart defects (CHD) in the fetus in a low-risk obstetric population. METHODS: Nuchal translucency screening was offered over a 3-year period to consecutive pregnant women without known a priori risk factors and attending midwife practices in three different areas in the Netherlands. In chromosomally normal fetuses and infants from the study population the NT measurements were matched with CHD detected either prenatally or postnatally. RESULTS: NT screening was offered to 6132 women with an uptake of 83%. A total of 4876 NT measurements was performed. Pregnancy outcome data were available in 4181 cases (86%). Defects of the heart and great arteries (CHD) were diagnosed in 24 cases (prevalence 5.8/1000). Thirteen of these were classified as major (prevalence 3.1/1000). Two major CHD occurred in fetuses showing an increased NT at the first-trimester scan. The sensitivity of NT measurement > 95th and > 99th percentile for all CHD and for major CHD, was 8% and 15%, respectively. The positive likelihood ratios of NT > 95(th) and > 99th percentile for major CHD were 6, 5 and 33, respectively. CONCLUSION: In pregnancies without known risk factors also, an increased NT is associated with major cardiac defects in the fetus and therefore represents an indication for specialized fetal echocardiography. However, this association is too weak to envisage a role for NT measurement as single screening strategy for the prenatal detection of cardiac defects.

Axial length as a risk factor to branch retinal vein occlusion.

PURPOSE: To determine whether axial length is a factor in branch retinal vein occlusion. METHODS: Axial length measurements in a group of 24 patients with a unilateral branch retinal vein occlusion were compared with the axial length measurements in a control group. Axial length measurements were taken with an A-scan; affected and unaffected eyes were measured. The control group consisted of 24 individuals who matched the patients in the branch retinal vein occlusion group in age, systemic hypertension status, and diabetes mellitus status. RESULTS: The affected and fellow eye in patients in the branch retinal vein occlusion group did not differ statistically in axial length (P = 0.26). The mean axial length of affected eyes in the branch retinal vein occlusion group was 22.76 +/- 0.92 mm, and the mean axial length of control eyes was 23.36 +/- 1.08 mm. The difference in axial length between the eyes with a branch retinal vein occlusion and the eyes in the control group was statistically significant (P = 0.023). CONCLUSION: The axial length of affected eyes of patients with branch retinal vein occlusion was on average 0.60 mm shorter than that of eyes of matched controls (95% confidence interval, 0.30-0.90 mm). The shorter axial length could be a local risk factor in the pathogenesis of a branch retinal vein occlusion.