[The translation of genetic risk variants to molecular disease mechanisms]. / De vertaling van genetische risicovarianten naar moleculaire ziektemechanismen.

BACKGROUND: Genetic studies have found large numbers of genetic risk variants that increase the risk to develop neuropsychiatric disorders. AIM: We aim to explain how to investigate the effects of these genetic risk variants on the expression of genes and whether this plays a potential role in neuropsychiatric disorders. METHOD: We describe the main findings of a study that we recently performed to study the association between genetic risk factors for neuropsychiatric disorders and gene expression in microglia, the immune cells of the brain. RESULTS: Part of the risk variants for neuropsychiatric disorders could be related to gene expression in microglia. These
associations were particularly strong for neurodegenerative disorders. CONCLUSION: Our study provided more insight into how genetic risk to neuropsychiatric disorders is related to gene expression in microglia. These findings show suggestions for potential new treatment options.

[Solitary angiokeratoma of the tongue]. / Solitair angiokeratoom van de tong.

A 41-year-old woman, who was referred with a reddish purple like lesion on the left side of the tongue, appeared to have an angiokeratoma after histopathological examination. Because of the benign character of this lesion and the absence of any complaints, no adjuvant treatment after excisional biopsy was indicated. Angiokeratomas rarely appear as solitary oral lesions. More often they are seen as part of an underlying systemic disease, mostly Fabry disease. Due to widespread skin involvement of angiokeratomas with Fabry disease, referral to a dermatologist is indicated when oral lesions are encountered. Esthetically unpleasing or painful angiokeratomas can be locally excised or treated by laser- or cryotherapy.

Validation of Reference Charts for Mid-Trimester Fetal Biometry.

OBJECTIVE: The aim of our study was to assess charts proposed for international use in the Intergrowth-21st Project. METHODS: Ultrasound data were collected from 43,923 healthy singleton pregnancies examined at 18-23 weeks of gestation in the Netherlands. Fetal measurements were converted into Z-scores using previous and current Dutch reference charts and Intergrowth charts. The distributions of the Z-scores were compared with the expected standard normal distribution. RESULTS: In the Dutch population, Intergrowth curves perform well for head circumference and biparietal diameter, but not for abdominal circumference (AC, Z- score = 0.43) and femur length (FL, Z-score = 0.26). Similar findings have been reported in other European countries. Compared with the population in the Intergrowth study, Dutch women are relatively tall (170 vs. 162 cm) and sturdy (67 vs. 61 kg) with a moderately high BMI. Maternal size, in particular maternal height, is positively correlated with birthweight. CONCLUSIONS: Whilst the establishment of the Intergrowth charts is an important step towards worldwide uniformity, for now locally derived charts still perform better, especially for AC and FL. Results from our validation study indicate that distinction between normal and pathologically small babies may be improved by taking maternal size into account.

Prevalence, diagnosis and outcome of cleft lip with or without cleft palate in The Netherlands.

OBJECTIVE: To examine the accuracy and timing of diagnosis of fetal cleft lip with or without cleft palate (CL ± P) in the years following the introduction of a national screening program, and to assess the completeness and accuracy of information in The Netherlands Perinatal Registry. METHODS: A list was obtained of cases with a prenatal or postnatal diagnosis of CL ± P from two fetal medicine units between 2008 and 2012. All cases of CL ± P were included irrespective of the presence or absence of additional anomalies. Cases were included if the estimated date of delivery was between 1 January 2008 and 31 December 2012. RESULTS: During the study period, 330 cases of CL ± P were identified, with a prevalence of 15 per 10 000 pregnancies. The number of cases that were detected before 24 weeks' gestation increased during the study period, while the rate of termination of pregnancy did not change significantly (P = 0.511). CL ± P was isolated in 217 (66%) cases and karyotype was abnormal in 69 (21%) cases. In 5% of the cases in which CL ± P seemed to be isolated during the 18-23-week anomaly scan, postnatal array comparative genomic hybridization (array-CGH) revealed an abnormal karyotype and 50% of these cases had major additional anomalies. Examination of data from The Netherlands Perinatal Registry demonstrated that in 37% of cases CL±P was not recorded in the pregnancy records. CONCLUSION: CL ± P is increasingly being diagnosed prenatally, without a significant effect on the rate of pregnancy termination. Further improvement in the diagnostic accuracy may be achieved by advocating prenatal array-CGH to reduce the frequency of unexpected anomalies being diagnosed after birth. It is important that healthcare providers register accurately the presence or absence of anomalies in the birth records to ensure that, in the future, data from The Netherlands Perinatal Registry can be relied upon to monitor prevalence. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Timing of detection of anencephaly in The Netherlands.

OBJECTIVE: The objective of this study is to assess the gestational age at detection and prevalence of anencephaly in the North of The Netherlands over a 5-year period. METHODS: A case list of all cases of anencephaly from two fetal medicine units was compiled. Cases were included if the estimated due date was between 1 August 2008 and 31 July 2013. RESULTS: Overall prevalence of anencephaly was 5.4 per 10.000 pregnancies (n = 110). The majority of cases (69%) was detected before 18 weeks' gestation. Factors determining successful early diagnosis were competence level of the sonographers, with a significantly higher detection rate when scans were performed by a sonographer licensed by the Fetal Medicine Foundation (FMF) for nuchal translucency measurement (p = 0.001), and gestational age at or beyond 11 weeks of gestation (p = 0.024). CONCLUSION: Improving detection of anencephaly in the first trimester requires ultrasound screening at or after 11 weeks of gestation, performed by experienced sonographers trained in recognizing fetal anomalies. Sonographers should be instructed that the goal of the first trimester scan is not only to measure nuchal translucency thickness but also to exclude major anomalies.

Impact of introduction of mid-trimester scan on pregnancy outcome of open spina bifida in The Netherlands.

OBJECTIVE: To examine the impact of introduction of the mid-trimester scan on pregnancy outcome in cases of open spina bifida in two regions of The Netherlands. METHODS: This was a retrospective cohort study of 190 cases of open spina bifida diagnosed pre- or postnatally, with an estimated date of delivery between 2003 and 2011. RESULTS: With implementation of the mid-trimester scan the percentage of cases of open spina bifida detected before the 24(th) week of pregnancy increased from 43% to 88%. The rise in prenatal detection rate was associated with a significant increase in the number of terminated pregnancies and a decrease in the rate of perinatal loss; the percentage of children born alive did not change significantly. In the subgroup that underwent a scan between 18 and 24 weeks of pregnancy, cranial signs were present in 94.4% of cases. CONCLUSION: Introduction of the mid-trimester scan has led to an increase in early identification of pregnancies complicated by open spina bifida. Pregnancies previously destined to end in perinatal loss are now terminated whilst pregnancies with a relatively good prognosis are frequently continued; the number of children with open spina bifida who are born alive has not changed significantly. Our study confirms that prenatal diagnosis is usually triggered by visualization of a lemon-shaped skull or a banana-shaped cerebellum.

Impact of introduction of 20-week ultrasound scan on prevalence and fetal and neonatal outcomes in cases of selected severe congenital heart defects in The Netherlands.

OBJECTIVES: To evaluate in a population-based cohort the effect of the introduction of the 20-week ultrasound scan in 2007 on the time of diagnosis, pregnancy outcome and total prevalence and liveborn prevalence of cases with selected congenital heart defects (CHDs) in The Netherlands. METHODS: We included children and fetuses diagnosed with selected severe CHD, born in the 11-year period from 2001 to 2011. Two groups of CHD were defined: those associated with an abnormal four-chamber view at ultrasound (Group 1), and those associated with a normal four-chamber view at ultrasound (Group 2). The time of diagnosis, pregnancy outcome and total liveborn prevalence were compared for both groups over two 5-year periods, before and after the introduction of the 20-week ultrasound scan. Trends in total and liveborn prevalence were examined over 2001 to 2011. RESULTS: Information was collected on 269 children and fetuses. After the introduction of the 20-week ultrasound scan, the prenatal detection rate of CHDs increased in both groups (Group 1, 34.6% in 2001-2005 vs 84.8% in 2007-2011 (P < 0.001); Group 2, 14.3% in 2001-2005 vs 29.6% in 2007-2011 (P = 0.037)). The rate of termination of pregnancy (TOP) increased significantly only for Group 1 (15.4% vs 51.5% (P < 0.001)). The total prevalence of CHD in Group 1 increased over time from 2.9 per 10 000 births in 2001 to 6.4 per 10 000 births in 2011 (P = 0.016). The liveborn prevalence did not show a trend over time. For Group 2, no trends in total or liveborn prevalence could be detected over time. CONCLUSIONS: Since the implementation of the routine 20-week ultrasound scan in The Netherlands, prenatal detection rate of selected severe CHDs increased significantly. Improved prenatal detection was accompanied by a more than three-fold increase in TOP, although only in those CHDs with an abnormal four-chamber view at prenatal ultrasound.

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.

Relationship of isolated single umbilical artery to fetal growth, aneuploidy and perinatal mortality: systematic review and meta-analysis.

OBJECTIVE: To review the available literature on outcome of pregnancy when an isolated single umbilical artery (iSUA) is diagnosed at the time of the mid-trimester anomaly scan. METHODS: We searched MEDLINE (1948-2012), EMBASE (1980-2012) and the Cochrane Library (until 2012) for relevant citations reporting on outcome of pregnancy with iSUA seen on ultrasound. Data were extracted by two reviewers. Where appropriate, we pooled odds ratios (ORs) for the dichotomous outcome measures: small for gestational age (SGA), perinatal mortality and aneuploidy. For birth weight we determined the mean difference with 95% CI. RESULTS: We identified three cohort studies and four case-control studies reporting on 928 pregnancies with iSUA. There was significant heterogeneity between cohort and case-control studies. Compared to fetuses with a three-vessel cord, fetuses with an iSUA were more likely to be SGA (OR 1.6 (95% CI, 0.97-2.6); n = 489) or suffer perinatal mortality (OR 2.0 (95% CI, 0.9-4.2); n = 686), although for neither of the outcomes was statistical significance reached. The difference in mean birth weight was 51 g (95% CI, -154.7 to 52.6 g): n = 407), but again this difference was not statistically significant. We found no evidence that fetuses with iSUA have an increased risk for aneuploidy. CONCLUSION: In view of the non-significant association between iSUA and fetal growth and perinatal mortality, and in view of the heterogeneity in studies on aneuploidy, we feel that large-scale, prospective cohort studies are needed to reach definitive conclusions on the appropriate work-up in iSUA pregnancies. At present, targeted growth assessment after diagnosis of iSUA should not be routine practice.

A comparative study of the Osstell™ versus the Osstell Mentor™ to evaluate implant stability in human cadaver mandibles.

The aim of this study was to assess the primary stability of dental implants by resonance frequency analysis (RFA) using the Osstell™ and Osstell Mentor™ devices and to investigate the reproducibility and comparability of the results obtained with these devices. Twenty-four Straumann implants (Straumann AG, Basel, Switzerland) were placed in the anterior mandible of 12 fresh edentulous human cadaver mandibles. The implant stability quotients (ISQs) were measured with the Osstell™ and Osstell Mentor™ when implants were inserted at 50% of their length and following their complete insertion. The Osstell™ device measured lower scores compared with the Osstell Mentor™. This was significant for the full position (mean difference = 9·9), t (11) = 7·4, P < 0·001 and for the halfway position (mean difference = 5·9), t (11) = 2·41, P = 0·03. In conclusion, the Osstell™ produced relatively lower ISQ scores than the Osstell Mentor™.

New charts for ultrasound dating of pregnancy and assessment of fetal growth: longitudinal data from a population-based cohort study.

OBJECTIVES: Correct assessment of gestational age and fetal growth is essential for optimal obstetric management. The objectives of this study were, first, to develop charts for ultrasound dating of pregnancy based on crown-rump length and biparietal diameter and, second, to derive reference curves for normal fetal growth based on biparietal diameter, head circumference, transverse cerebellar diameter, abdominal circumference and femur length from 10 weeks of gestational age onwards. METHODS: A total of 8313 pregnant women were included for analysis in this population-based prospective cohort study. All women had repeated ultrasound assessments to examine fetal growth. RESULTS: Charts for ultrasound dating of pregnancy, based on crown-rump length and biparietal diameter, were derived. Internal validation with the actual date of delivery showed that ultrasound imaging provided reliable gestational age estimates. Up to 92% of deliveries took place within 37-42 weeks of gestation if gestational age was derived from ultrasound data, compared with 87% based on a reliable last menstrual period. The earlier the ultrasound assessment the more accurate the prediction of date of delivery. After 24 weeks of gestation a reliable last menstrual period provided better estimates of gestational age. Reference curves for normal fetal growth from 10 weeks of gestational age onwards were derived. CONCLUSIONS: Charts for ultrasound dating of pregnancy and reference curves for fetal biometry are presented. The results indicate that, up to 24 weeks of pregnancy, dating by ultrasound examination provides a better prediction of the date of delivery than does last menstrual period. The earlier the ultrasound assessment in pregnancy, preferably between 10 and 12 weeks, the better the estimate of gestational age.

Accuracy in identifying the elbow rotation axis on simulated fluoroscopic images using a new anatomical landmark.

External fixation of the elbow requires identification of the elbow rotation axis, but the accuracy of traditional landmarks (capitellum and trochlea) on fluoroscopy is limited. The relative distance (RD) of the humerus may be helpful as additional landmark. The first aim of this study was to determine the optimal RD that corresponds to an on-axis lateral image of the elbow. The second aim was to assess whether the use of the optimal RD improves the surgical accuracy to identify the elbow rotation axis on fluoroscopy. CT scans of elbows from five volunteers were used to simulate fluoroscopy; the actual rotation axis was calculated with CT-based flexion-extension analysis. First, three observers measured the optimal RD on simulated fluoroscopy. The RD is defined as the distance between the dorsal part of the humerus and the projection of the posteromedial cortex of the distal humerus, divided by the anteroposterior diameter of the humerus. Second, eight trauma surgeons assessed the elbow rotation axis on simulated fluoroscopy. In a preteaching session, surgeons used traditional landmarks. The surgeons were then instructed how to use the optimal RD as additional landmark in a postteaching session. The deviation from the actual rotation axis was expressed as rotational and translational error (±SD). Measurement of the RD was robust and easily reproducible; the optimal RD was 45%. The surgeons identified the elbow rotation axis with a mean rotational error decreasing from 7.6° ± 3.4° to 6.7° ± 3.3° after teaching how to use the RD. The mean translational error decreased from 4.2 ± 2.0 to 3.7 ± 2.0 mm after teaching. The humeral RD as additional landmark yielded small but relevant improvements. Although fluoroscopy-based external fixator alignment to the elbow remains prone to error, it is recommended to use the RD as additional landmark.

Neurotensin induces catalepsy in mice.

Intracerebroventricular (i.c.v.) injection of neurotensin (NT) induced catalepsy in mice at doses greater than or equal to 0.02 microgram. The cataleptic effect progressively increased, reaching a maximum at approx. 2 hr after injection. In contrast, the hypothermic effect of neurotensin reached a maximum 1 hr after the injection, and was declining at 2 hr. Not all mice that showed hypothermia also showed catalepsy, and some mice showed catalepsy without hypothermia. Catalepsy induced by intracerebroventricular injection of neurotensin was not significantly correlated with the hypothermia. Furthermore, oxotremorine induced hypothermia without catalepsy. Thus, several lines of evidence indicate that the catalepsy induced by neurotensin is not the consequence of the neurotensin induced hypothermia. Thyrotropin releasing hormone (TRH), injected either intracerebroventricularly with neurotensin, or intraperitoneally before neurotensin abolished the hypothermia but only diminished the catalepsy scores. The cataleptic effect of neurotensin is consistent with its other neuroleptic-like activities.

Increased nuchal translucency in trisomy 13 fetuses at 10-14 weeks of gestation.

In a multicenter screening study for trisomy 21 involving ultrasonographic measurement of fetal nuchal translucency thickness (NT) at 10-14 weeks of gestation, 100,311 singleton pregnancies with a live fetus were examined. There were 46 cases of trisomy 13, and in 33 (72%) of these, the NT was above the 95th centile. The estimated risk for trisomy 21, based on maternal age-related risk for this chromosomal abnormality and fetal NT, was above 1 in 300 in 37 (80.1%) of the trisomy 13 fetuses. The fetal crown-rump length was significantly reduced, but the fetal heart rate was increased, being above the 95th centile in 64% of cases. Additionally, 24% of trisomy 13 fetuses had holoprosencephaly and 10% had exomphalos. This study has demonstrated that at 10-14 weeks of gestation, about 80% of fetuses with trisomy 13 can be identified in a screening program for trisomy 21, based on a combination of maternal age and fetal NT.

Fetal venous, arterial, and intracardiac blood flows in red blood cell isoimmunization.

OBJECTIVE: To investigate the effect of anemia on fetal venous, arterial, and intracardiac blood flows. METHODS: Color flow Doppler was used to record flow-velocity waveforms from the atrioventricular valves, ductus venosus, right hepatic vein, inferior vena cava, middle cerebral artery, and descending thoracic aorta from 38 cases of red blood cell isoimmunized pregnancies. Immediately after the Doppler studies, funipuncture was performed and the fetal hemoglobin concentration was measured. RESULTS: Blood flow velocities in the thoracic aorta, middle cerebral artery, and the ductus venosus were increased compared to reference ranges established previously; however, a significant association with the degree of anemia was found only for the velocity in the thoracic aorta. Pulsatility indices in arteries and veins and the ratio of early to late atrioventricular inflow velocities were not significantly different from normal. CONCLUSIONS: Fetal anemia is associated with a hyperdynamic circulation in both arterial and venous vessels. Even in severe anemia, there is no evidence of congestive heart failure. Venous and intracardiac Doppler studies do not provide a clinically useful contribution in the management of red blood cell isoimmunization.

First-trimester fetal nuchal translucency thickness and risk for trisomies.

OBJECTIVE: To define the relation between fetal nuchal translucency thickness at 10-13 weeks' gestation and the risk for fetal trisomies and pregnancy outcome. METHODS: Five hundred sixty fetuses with nuchal translucency thickness of 3-9 mm at 10-13 weeks' gestation were karyotyped. The ratio of the observed number of fetal trisomies to that expected on the basis of maternal age was calculated. RESULTS: The incidence of trisomies 21, 18, or 13 was 18% (102 of 560 cases) and was significantly associated with both maternal age (r = 0.97) and fetal nuchal translucency thickness (r = 0.75). In 383 fetuses with nuchal translucency of 3 mm, the observed number of fetal trisomies was 23, in contrast to the frequency of 6.0 expected on the basis of maternal age. In 177 fetuses with nuchal translucency of 4 mm or more, 79 cases were observed, compared with 2.7 expected on the basis of maternal age. In fetuses with nuchal translucency of 4 mm or more and normal karyotype, there was a high association with other defects and the prognosis was often poor, whereas the translucency resolved for those with 3 mm and the pregnancy outcome was usually normal. CONCLUSION: At 10-13 weeks' gestation, fetal nuchal translucency of 3 mm is associated with a fourfold increase, and translucency of greater than 3 mm with a 29-fold increase, in the maternal age-related risk for trisomies 21, 18, and 13. Fetal nuchal translucency of 4 mm or more is associated with poor pregnancy outcome even when the fetal karyotype is normal.

Thyroid function in small for gestational age fetuses.

Thyroid function was studied in fetal blood samples obtained by funipuncture from 49 small for gestational age (SGA) fetuses at 21-38 weeks' gestation. Levels of TSH, thyroxine-binding globulin, thyroxine (T4), free T4, triiodothyronine (T3), and free T3 were compared with those from 62 appropriate for gestational age (AGA) fetuses. Levels of TSH were significantly higher and T4 and free T4 significantly lower in the SGA than in AGA fetuses. Furthermore, there were significant associations between the increase in TSH and decrease in free T4 and the degrees of fetal hypoxemia and acidemia, respectively.

Maternal serum pregnancy-associated plasma protein A and fetal nuchal translucency thickness for the prediction of fetal trisomies in early pregnancy.

OBJECTIVE: To determine if the risk for fetal trisomies during the first trimester of pregnancy can be derived by combining data from maternal serum pregnancy-associated plasma protein A (PAPP-A) and fetal nuchal translucency thickness. METHODS: Pregnancy-associated plasma protein A was measured in samples from 87 singleton pregnancies with fetal chromosomal abnormalities (45 trisomy 21, 19 trisomy 18, eight trisomy 13, 11 sex chromosome aneuploidies, four triploidies) and 348 chromosomally normal controls at 10-13 weeks' gestation. Likelihood ratios for trisomies 21, 18, and 13 in relation to PAPP-A, in multiples of the normal median (MoM) for crown-rump length, were derived from the overlapping gaussian frequency distribution curves for normal and abnormal pregnancies. RESULTS: In the chromosomally normal group, maternal serum PAPP-A correlated significantly with fetal crown-rump length (r = 0.421, P < .0001). In the chromosomally abnormal group, the median PAPP-A was significantly lower than in the normal controls. The respective median values expressed in MoM for trisomies 21, 18, and 13 and other aneuploidies were 0.5 MoM (90% confidence interval [CI] 0.09-1.67, z = 6.0, P < .001), 0.17 MoM (90% CI 0.06-1.45, z = 6.6, P < .001), 0.25 MoM (90% CI 0.10-0.62, z = 4.5, P < .001), and 0.72 MoM (90% CI 0.09-2.48, z = 2.2, P < .05), respectively. There was no significant linear association between PAPP-A and fetal nuchal translucency thickness in either the chromosomally normal (r = -0.01, P = .89) or abnormal groups (r = -0.19, P = .08). CONCLUSION: The risks for fetal trisomies at 10-13 weeks' gestation can be derived by combining data on maternal age, maternal serum PAPP-A, and fetal nuchal translucency thickness.

Fetal nuchal translucency thickness at 10-14 weeks' gestation and congenital diaphragmatic hernia.

OBJECTIVE: To examine the possible association between increased fetal nuchal translucency thickness at 10-14 weeks and congenital diaphragmatic hernia. METHODS: This was a multicenter ultrasound screening study for chromosomal defects in singleton pregnancies by a combination of maternal age and fetal nuchal translucency at 10-14 weeks' gestation. The prevalence of diaphragmatic hernia diagnosed prenatally or postnatally was calculated in the chromosomally normal group and in those pregnancies resulting in live births with no dysmorphic features suggestive of a chromosomal abnormality. We calculated the sensitivity of nuchal translucency above the 95th centile of the normal range in the detection of diaphragmatic hernia and the possible prognostic value of increased nuchal translucency in the prediction of outcome. RESULTS: There were 78,639 pregnancies presumed to be normal chromosomally, including 19 with diaphragmatic hernia. In four cases, the parents opted for termination of the pregnancy. The other 15 pregnancies resulted in live births; nine infants survived after successful surgical repair of the hernia, but six neonates died because of pulmonary hypoplasia. At the 10- to 14-week scan, the fetal nuchal translucency was above the 95th centile for crown-rump length in seven (37%) cases of diaphragmatic hernia. The translucency was increased in five of the six cases that resulted in neonatal death, compared with two of the nine survivors (Z = 2.32, P < .05). CONCLUSION: The prevalence of diaphragmatic hernia in chromosomally normal fetuses is about one in 4000, and nearly 40% of affected fetuses have increased nuchal translucency at 10-14 weeks' gestation. Increased nuchal translucency may be a marker of intrathoracic compression-related pulmonary hypoplasia.

Maternal serum Schwangerschafts protein-1 (SP1) and fetal chromosomal abnormalities at 10-13 weeks' gestation.

Maternal serum SP1 concentration was measured at 10-13 weeks' gestation in samples from 87 pregnancies with fetal chromosomal abnormalities (trisomy 21 n = 45; trisomy 18 n = 19; trisomy 13 n = 8; Turner syndrome n = 7; 47,XXX or 47,XXY n = 4; triploidy n = 4), and in samples from 348 matched controls. In the control group, SP1 increased significantly with fetal crown-rump length (r = 0.20, P < 0.0001) and there was no significant association with fetal nuchal translucency thickness (r = 0.03). Similarly, in the group with fetal chromosomal abnormalities, SP1 increased significantly with crown-rump length (r = 0.31, P < 0.01) and there was no significant association with nuchal translucency thickness (r = -0.08). In the groups with fetal trisomy 18 and trisomy 13, the median SP1 (0.76 MoM and 0.57 MoM, respectively) was significantly lower than in the controls (z = 2.64 and z = 3.27, respectively); in 21% and 25% of the cases, values were below the 5th centile. In the group with trisomy 21 and other chromosomal abnormalities the median SP1 (0.96 MoM and 0.93 MoM, respectively) was not significantly different from controls (z = 1.17 and z = 0.67, respectively). Measurement of SP1 concentration at 10-13 weeks' gestation is not likely to be useful in the prediction of fetal chromosomal abnormalities.