Evaluation and evolution during time of prenatal diagnosis of congenital heart diseases by routine fetal ultrasonographic examination

The objectives of this study were to evaluate routine prenatal diagnosis of congenital heart diseases (CHD) by fetal ultrasound examination in a well-defined population during the period 1994-1999 and to compare these results with the results from 1979 to 1993. This study included 80,076 consecutive pregnancies of known outcome from 1994 to 1999. CHD were classified as isolated or associated when at least one other major extra-cardiac malformation was present. Only 137 out of 688 malformed fetuses with CHD without chromosomal anomalies were detected (19.9%). The sensitivity of detection varied from 61.9% for malformations such as isolated hypoplastic left heart and single ventricle, to around 7-19% for atrial and ventricular septal defects. Prenatal detection rate of CHD was 11.4% for isolated cases, and 40.2% for multiple malformed with CHD. The gestational age at discovery varied from 16 to 36 weeks. There is no upper limit for termination of pregnancies in our country; 12.3% of all pregnancies were terminated after prenatal diagnosis. However, 62% of the pregnancies with a CHD detected prenatally were terminated. The detection rate of CHD increased during time from 9.2% during the period 1979-1988 to 13.7% during the period 1990-1993 and to 19.1% during the period 1994-1999. Our study shows large variation in the prenatal detection rate of CHD. Prenatal diagnosis of CHD is significantly higher when associated malformations are present. Cardiac defects affecting the size of the ventricles have the highest detection rate. Gestational age at discovery was 20-24 weeks for the majority of associated cardiac defects. The prenatal detection rate of CHD increased during time from 1979 to 1999.     

Impact of prenatal diagnosis on livebirth prevalence of children with congenital anomalies

The objectives of this study were to describe the impact of prenatal diagnosis on the birth prevalence of congenital anomalies over 21 years (1979-1999) in a well defined population in northeastern France (13,500 births per year). The material for this study came from the analysis of data from multiple sources on births and terminations of pregnancy after prenatal diagnosis of congenital anomalies in 279,642 consecutive pregnancies of known outcome. The study period was divided into three subgroups 1979-1988, 1989-1993 and 1994-1999. Between 1979-1988, 1989-1993 and 1994-1999, prenatal detection of congenital anomalies increased, respectively, from 12.0% to 25.5% and to 31.7%. Termination of pregnancy (TOP) increased in the same proportions during the three time periods. However, the increase of TOP was much higher for chromosomal anomalies than for nonchromosomal congenital anomalies. The birth prevalence of Down's syndrome fell by 80% from 1979-1988 to 1994-1999. Sensitivity of prenatal detection of congenital anomalies and TOPs were lower for isolated cases (only one malformation present in the fetus) than for multiple malformations in the same fetus. Sensitivity varied with the type of malformations: it was high for neural tube defect (79.7%) and urinary anomalies (50.7%) and low for congenital heart defects (16.4%). In conclusion, the introduction of routine prenatal diagnosis has resulted in a significant fall in the birth prevalence of children with congenital anomalies. However, this fall varied with the types of congenital anomalies.     

Evaluation of routine prenatal ultrasound examination in detecting fetal chromosomal abnormalities in a low risk population

Prenatal diagnosis performed by fetal ultrasound scan is now a routine part of antenatal care in many countries. We have used our registry of congenital malformations to determine how many fetal anomalies and consequently how many chromosomal abnormalities are detected by this procedure. In our region, evaluation of prenatal diagnosis of chromosomal abnormalities in women of 38 years and younger (chromosomal prenatal diagnosis is offered to women 38 years) with no personal or familial history of chromosomal anomaly was performed in 119 099 consecutive pregnancies of known outcome from 1980 to 1987. At least one ultrasonographic examination seeking congenital malformations was performed in more than 95% of the pregnant women studied. The total number of chromosomal anomalies during the study period was 199, 123 of these being Down syndrome. Only 41 (34.5%) of the 119 fetuses with chromosomal abnormalities and congenital malformation examined had been found to have a malformation at ultrasound examination. This low sensitivity was different for the diverse chromosomal abnormalities. Only 10 out of the 54 fetuses with Down syndrome and malformations (18.5%) were detected and only 3 out of 24 (12.5%) atrioventricular canal defects in those trisomie 21 patients were detected. Only 5 out of 11 (45.4%) fetuses with trisomy 13, 13 out of 26 (50.0%) fetuses with trisomy 18, 7 out of 12 patients with monosomy X (58.3%) and 6 out of 27 (22.2%) fetuses with other chromosomal abnormalities were diagnosed. Moreover, the time of detection of these anomalies was early enough to allow amniocentesis and termination of pregnancy in the case of a chromosomal abnormality in only 15 out of these 41 patients, including 7 cases of cystic hygroma in fetuses with monosomy X. This low sensitivity is not the result of the quality of the ultrasound equipment. It may be explained by the inadequate qualification of some operators and by the insufficient duration of the routine examination. In conclusion, our study has shown that the sensitivity of the detection of chromosomal abnormalities by routine prenatal ultrasound screening is low. Other screening methods are needed.     

Associated malformations in cases with neural tube defects

Infants with neural tube defects (NTDs) may have other associated congenital defects. The reported incidence and the types of associated malformations vary between different studies. The purpose of this investigation was to assess the prevalence of associated malformations in a geographically defined population. The prevalences at birth of associated malformations in infants with NTDs were collected between 1979 and 2003 on all infants born in the area covered by the registry of congenital anomalies of Northeastern France in 334,262 consecutive births. Of the 360 infants with NTDs born during this period, 20.5 % had associated malformations. Associated malformations were more frequent in infants who had encephalocele (37.5 %) than in infants with anencephaly (11.8 %) or infants with spina bifida (23.7 %). Malformations in the face (oral clefts), in the musculoskeletal system, in the renal system, and in the cardiovascular system were the most common other anomalies. In conclusion the overall prevalence of malformations, which was one in five infants, emphasizes the need for a thorough investigation of infants with NTDs. A routine screening for other malformations especially facial clefts, musculoskeletal, renal and cardiac anomalies may need to be considered in infants with NTDs, and genetic counseling seems warranted in most of these complicated cases.     

Contribution of ultrasonographic examination to the prenatal detection of chromosomal abnormalities in 19 centres across Europe.

The objective of this study was to evaluate the prenatal detection of chromosomal abnormalities by fetal ultrasonographic examination in a large database provided by 19 Registries of Congenital Anomalies from 11 European countries. This study included 1738 cases of chromosomal abnormalities, liveborn, stillborn or termination of pregnancy regardless of maternal age from a population of 664,340 births during the period 1996 - 1998. The most frequent chromosomal anomalies were Down syndrome (n=1050), trisomy 18 (n=191), Turner syndrome (n=125), trisomy 13 (n=86), and triploidy (n=56). Fetal ultrasonographic examination resulted in the prenatal detection of 37.7% of the chromosomal abnormalities, thereby resulting in a reduction of 28.6% in their prevalence at birth due to terminations of pregnancy. The detection rate by ultrasound examination varied according to local policies of prenatal diagnosis : it was lower in countries where routine scan were not performed and higher in countries in which at least one routine anomaly scan during the second trimester of pregnancy was performed. The ultrasound detection varied according to the specific chromosomal anomaly and was lowest for Klinefelter syndrome (5.7%) and highest for triploidy (78.6%). For Down syndrome it was 26.4%. Termination of pregnancy was performed in 75.9% of the cases. Among the 655 cases detected by ultrasound, the most frequent ultrasound signs by category of chromosomal abnormalities were analysed. This study shows that ultrasound screening is an important tool in the prenatal detection of chromosomal abnormalities in Europe, leading to a significant reduction in the prevalence of livebirth children with chromosomal anomalies.     

Epidemiology of diaphragmatic hernia in Languedoc-Roussillon.

The frequency of diaphragmatic hernia (DH) varies, according to the studies, between 1/2000 and 1/7000. In the Languedoc-Roussillon (South of France), due to the presence of a Regional Foeto-Pathology Department and Medico Surgical Paediatric Department, it was possible to itemize all of the DH over a 24 month period (June 1989----May 1991). 20 children presenting DH (10 foetuses and 10 liveborns) were examined for a total population of 49.350 foetuses and liveborns (frequency of DH: 0.40/1000). 10 DH were associated with extra-pulmonary malformations (50%). 4 chromosome abnormalities were found (20%). Prenatal chromosome analysis in cases of ultrasound malformation detection has increased the number of karyotype abnormalities diagnosed.     

Chromosomal mosaicism detected by karyotyping and chromosomal microarray analysis in prenatal diagnosis

To investigate the incidence and clinical significance of chromosomal mosaicism (CM) in prenatal diagnosis by G-banding karyotyping and chromosomal microarray analysis (CMA). This is a single-centre retrospective study of invasive prenatal diagnosis for CM. From 5758 karyotyping results and 6066 CMA results, 104 foetal cases with CM were selected and analysed further. In total, 50% (52/104) of foetal cases with CM were affected by ultrasound-detectable phenotypes. Regardless of whether they were singleton or twin pregnancies, isolated structural defects in one system (51.35%, 19/37 in singletons; 86.67%, 13/15 in twins) and a single soft marker (18.92%, 7/37 in singletons; 13.33%, 2/15 in twins) were the most common ultrasound anomalies. Mosaic autosomal trisomy (19.23%, 20/104) was the most frequent type, and its rate was higher in phenotypic foetuses (28.85%, 15/52) than in non-phenotypic foetuses (9.62%, 5/52). There was no difference in mosaic fractions between phenotypic and non-phenotypic foetuses based on specimen sources or overall classification. Discordant mosaic results were observed in 16 cases (15.38%, 16/104) from different specimens or different testing methods. Genetic counselling and clinical management regarding CM in prenatal diagnosis remain challenging due to the variable phenotypes and unclear significance. Greater caution should be used in prenatal counselling, and more comprehensive assays involving serial ultrasound examinations, different specimens or testing methods verifications and follow-up should be applied.     

Neural tube defects and associated anomalies in South Carolina

BACKGROUND: Neural tube defects (NTDs) occur as isolated malformations and in the company of other birth defects. This study was conducted to determine the frequency of coexisting anomalies and the relationship between them. METHODS: Since 1992, NTDs have been identified through prenatal and postnatal surveillance activities in South Carolina. The type of NTD and presence of associated anomalies were determined by prenatal ultrasound, postnatal and/or postmortem examination. RESULTS: During the ten-year period from 1992 to 2002, 564 NTDs were identified by the surveillance system. Seventeen percent of NTDs (98/564) had associated malformations. In approximately half (n = 51) of these cases, the NTDs and associated anomalies were components of a recognizable syndrome. In the remaining cases (n = 47), no syndrome was identified or suspected, but the associated anomalies were believed in most instances to be secondary to space limitation or neural crest abnormalities imposed by the NTD. CONCLUSION: Seventeen percent of NTDs in South Carolina have associated malformations. In most cases, the associated anomalies are considered either components of a multiple malformation syndrome or secondary to the NTD.     

Strain differences in response of Sprague-Dawley and Long Evans Hooded rats to the teratogen nitrofen

Administration of nitrofen (2,4-dichloro-4'-nitrodiphenyl ether) during organogenesis in rodents produces neonatal lethality accompanied by lung hypoplasia, diaphragmatic hernias, heart anomalies, and hydronephrosis. Different strains of rats, Long Evans Hooded (LEH) and Sprague-Dawley (SD), are reported to have different malformation responses to prenatal exposure, which could be due to true strain differences, to different levels and times of exposure, or to the use of different methods for detecting visceral malformations. In the present study, LEH, SD, and "virus-antibody-negative" SD (VAN-SD) rats were identically exposed to 0, 6.25, 12.5, or 25 mg/kg/day of nitrofen by gavage in corn oil on days 6 15 of gestation. At term, half of the litter was examined by the Wilson method of razorblade sectioning and the remainder by a modified Staples method of fresh visceral examination. The two methods were equally sensitive for detecting diaphragm, kidney, and lung anomalies, whereas heart malformations were more frequently identified with fresh visceral examination. The frequency of total malformations did not vary across strains at any dose, but there were substantial differences in the pattern of malformations in each strain. SD and VAN-SD rats responded similarly for all malformations, but had significantly higher incidences of diaphragm and lung anomalies than LEH rats. Conversely, LEH rats had significantly elevated levels of kidney anomalies compared to SD and VAN-SD rats, whereas frequency of heart malformations was low and comparable across strains. These results suggest that true strain differences exist in the pattern of malformation produced by prenatal exposure to nitrofen that may be based on genetic differences in embryonic susceptibility.     

Periconceptional health and lifestyle factors of both parents affect the risk of live-born children with orofacial clefts

BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (CL/P) or cleft palate only (CPO) are orofacial clefts and have a multifactorial etiology. The identification of amendable parental risk factors may contribute to a reduced occurrence of these malformations in the future. METHODS: Standardized demographic and periconceptional exposure data from 284 parents of a child with CL/P, 66 parents of a child with a CPO and 222 parents of a child without congenital malformations were collected at approximately 24 months after the periconceptional period of the index child. Univariate and multivariate logistic regression analyses were used to estimate relative risks by odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Univariate results suggest that low parental education, periconceptional maternal medication use and illnesses, paternal smoking, and first-trimester maternal common cold increased CL/P risk. Pregnancy planning and periconceptional folic acid supplementation, however, reduced CL/P risk by approximately 50% (OR, 0.5; 95% CI, 0.3-0.8) and 40% (OR, 0.6; 95% CI, 0.4-0.9), respectively. Mostly comparable results were obtained for CPO. Being a boy (OR, 2.0; 95% CI, 1.4-3.0), folic acid supplementation (OR, 0.6; 95% CI, 0.4-0.9), and low paternal education (OR, 1.6; 95% CI, 1.0-2.3) mainly determined CL/P in the multivariate analyses, compared to low paternal (OR, 4.5; 95% CI, 2.1-9.4) and maternal medication use (OR, 2.0; 95% CI, 1.0-4.0) for CPO. CONCLUSIONS: Preconceptional counseling for orofacial cleft risk assessment should pay attention to maternal medication use, periconceptional folic acid supplementation, and exposures of the father. These determinants can be amended, thereby modifying orofacial cleft risk.     

A study of the relationship between chromosome anomalies and reproductive wastage in domestic animals

A cytogenetic survey was carried out on a partially unselected group of aborted foetuses, stillbirths/neonatal deaths and congenital defects originating from various domestic animals such as the feline, porcine, ovine, canine and bovine species. Chromosomes were analysed largely from fibroblast cultures of somatic tissue specimens received from different sources. Both fibroblast and lymphocyte cultures were simultaneously initiated whenever possible (e.g. from liveborns that had to be subjected to suthanasia as a result of debilitating phenotypic malformations).Forty-three and eight-tenths percent of the specimens cultured (i.e., 46 out of 105 specimens) could be adequately karyotyped. The overall incidence of chromosome anomalies was 8.7%, with mosaicism being the predominant observation. Because no gross chromosome abnormalities such as trisomy or polyploidy were found, it was concluded that any grossly abnormal foetuses might have already been selectively eliminated before the gestational stage at which this investigation was undertaken. The relatively low incidence of chromosome anomalies observed so far in various studies of domestic animals is discussed and compared to corresponding studies in humans.     

Maternal exposure to magnetic fields from high-voltage power lines and the risk of birth defects

The issue of adverse human health effects due to exposure to electromagnetic fields is still unclear, and congenital anomalies are among the outcomes that have been inconsistently associated with such exposure. We conducted a population-based, case-control study to examine the risk of congenital anomalies associated with maternal exposure to magnetic fields (MF) from high-voltage power lines during pregnancy in a community in northern Italy. We identified 228 cases of congenital malformations diagnosed in live births, stillbirths, and induced abortions among women living in the municipality of Reggio Emilia during the period 1998-2006, and a reference group of healthy newborns was matched for year of birth, maternal age, and hospital of birth. We identified maternal residence during early pregnancy and used Geographic Information System to determine whether the residences were within geocoded corridors with MF ≥0.1 μT near high-voltage power lines, then calculated the relative risk (RR) of congenital anomalies associated with maternal exposure. One case and 5 control mothers were classified as exposed, and the RR associated with MF ≥0.1 μT was 0.2 (95% CI: 0.0-2.0) after adjusting for maternal education. While small or moderate effects may have gone undetected due to low statistical power, the results of this study overall do not provide support for major effects of a teratogenic risk due to exposure to MF during early pregnancy.     

An epidemiologic study of congenital malformations of the anterior abdominal wall in more than half a million consecutive live births.

The records of an ongoing health surveillance registry that utilizes multiple sources of ascertainment were used to study the incidence rate of congenital malformations of the anterior abdominal wall in live-born children in British Columbia during the period 1964--1978 inclusive. No overall increase in incidence rate of these anomalies was detected during the study period. The estimated live-born incidence rates were: one in 4,175 live births for omphalocoele, one in 12,328 live births for gastroschisis, and one in 29,231 live births for prune belly. The data were analyzed with regard to sex and associated anomalies. Some practical implications regarding assessment of these infants are discussed.     

Genetic heterogeneity in neural tube defects.

In 1985-1987, the authors attempted to ascertain all cases of confirmed neural tube defects (NTD) in California and Illinois, not only among live-born infants (postnatal) but also cases ascertained during pregnancy (prenatal). Mothers of both prenatal and postnatal NTD cases were interviewed within 5 months. Among postnatal NTD cases, 14.9% (45/303) had anomalies not ordinarily associated with NTD. The frequency of non-NTD related anomalies was 9.4% (5/53) in anencephaly, 0/3 in craniorachischisis, 22.9% (8/35) in encephalocele, 14.5% (27/186) in spina bifida, 20% (1/5) in multiple NTD cases and 19% (4/21) in other NTDs. However, relatively few postnatal NTD cases had known multiple malformation patterns; Meckel-Gruber syndrome was the most common, with 2 postnatal cases, and 3 additional prenatal cases. Maternal age, paternal age and birth order in postnatal cases were 26.7 +/- 5.4 SD, 28.9 +/- 5.8 and 2.8 +/- 1.8, respectively. These characteristics were similar in prenatal NTD cases (27.9 +/- 6.0, 30.1 +/- 6.3, 2.5 +/- 1.5, respectively). We also found no differences in parental ages among different types of NTD. Frequency of prior spontaneous abortion differed neither between postnatal NTD (9.3%) and postnatal controls (8.1%), nor between prenatal NTD (10.7%) and prenatal control (8.7%). Loss rates in the pregnancy immediately prior to the index NTD cases were not significantly higher than in control subjects. The high frequency of non-NTD associated malformations (14.9%) indicates the caution must be exercised before assuming that a given NTD case is polygenic-multifactorial in etiology, especially cases of encephalocele.     

Molecular evaluation of foetuses with holoprosencephaly shows high incidence of microdeletions in the HPE genes

Holoprosencephaly (HPE), the most common structural malformation of the forebrain in humans, can be detected early during pregnancy using prenatal ultrasonography . Among foetuses with a normal karyotype, 14% have mutations in the four main HPE genes (SHH, ZIC2, SIX3 and TGIF). Genomic rearrangements have now been implicated in many genetic diseases, so we hypothesized that microdeletions in the major HPE genes may also be common in HPE foetuses with severe phenotype or other associated malformations. We screened the DNA obtained from 94 HPE foetuses with a normal karyotype for the presence of microdeletions involving the four major HPE genes (SHH, ZIC2, SIX3 and TGIF). Thirteen of the foetuses had a point mutation in one of the 4 genes and 81 had no known mutations. Quantitative multiplex PCR of short fluorescent fragments (QMPSF) analysis was used for rapid determination of HPE genes copy numbers and the identified microdeletions were confirmed by real time quantitative PCR, or fluorescent in situ hybridization (FISH) (if a cell line was available). Microdeletions were detected in 8 of 94 foetuses (8.5%) (2 in SHH, 2 in SIX3, 3 in ZIC2 and 1 in TGIF genes), and only among the 81 foetuses with a normal karyotype and no point mutations. These data suggest that microdeletions in the four main HPE genes are a common cause of prenatal HPE, as well as point mutations, and increase the total diagnosis rate close to ≈22.3% of foetuses with normal karyotype. Detection can be achieved by the QMPSF testing method that proved to be efficient for testing several genes in a single assay. Databases: SHH - OMIM: 600725; GenBank: NM_000193.2, ZIC2 - OMIM: 603073; GenBank: AF104902.1, SIX3 - OMIM: 603714; GenBank: NM_005413.1, TGIF - OMIM: 602630; GenBank: NM_003244.2, On-line Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/omim/, UCSC (http://www.genome.ucsc.edu/), Ensembl (http://www.ensembl.org/), Database of genomic variants (http://projects.tcag.ca/variation/genomeView.html)     

Development of hypothalamic control over thyrotropin secretion during human prenatal life]

It was shown in the tissue culture experiments that the human hypophysis secreted autonomously the thyrotrophin during the last three fourths of the prenatal life. The intensity of secretion is the highest in the end of the first third of this period, then it decreases, but during the last third it increases reliably again. During the second half of development the level of thyrotrophin in female foetuses in reliably higher than in the male ones. In the beginning of the second third of prenatal life, the hypothalamic factors decrease the autonomous thyrotrophin secretion twice in foetuses of both the sexes. In the end of the second third, sexual differences appear in their effect; they decrease reliably the autonomous thyrotrophin secretion in the male foetuses, whereas no such effect is observed in the female ones. The stimulating effect of the hypothalamic thyrotrophin releasing hormone manifests itself during the last third of prenatal life in foetuses of both the sexes. During the second half of prenatal life, the thyrotrophin concentration in blood of female foetuses is also reliably higher than in male foetuses. There is a positive correlation in female foetuses between the thyrotrophin concentration in blood and the level of hypophysial secretion under the effect of hypothalamic factors. Thyrotrophin is found in the cranial fluid of foetuses. In some cases its concentration in the cranial fluid is higher than in the blood. No correlation was found between the levels of the hormone in fluid and blood in female foetuses; a positive correlation was found in male foteuses.     

Inhibiting effects of nicotinamide on urethane-induced malformations and tumors in mice

The antipellagratic vitamin, nicotinamide, significantly suppressed urethane-induced malformations, when it was given intraperitoneally to pregnant JCL:ICR mice immediately after a single subcutaneous injection of urethane (1.0 mg/g) on the 9th day of gestation. The level of inhibition increased with the doses of nicotinamide: 33.0, 55.8, and 70.0% at doses of 0.1, 0.3, and 0.5 mg/g, respectively. Polydactyly and tail anomalies were markedly suppressed by the post-treatment with nicotinamide, while cleft palates were less effectively suppressed. Nicotinamide was still effective, when it was given during the period of 24-48 h after urethane treatment. Furthermore, dietary administration of nicotinamide also reduced urethane-induced malformations. The level of inhibition was 39.4 and 61.1% at 0.5 and 1.0% of nicotinamide in the diet, respectively. Higher doses of nicotinamide (3 and 5% in diet) also inhibited urethane-induced malformations, but not so effectively as lower doses. The inhibiting effects of nicotinamide on the spontaneous incidence of cleft lips and palates in CL/Fr mice were significant at a low dose (0.5% in diet), but not at a higher dose (1.0%). When [carbonyl-14C]nicotinamide was given to pregnant mice, nicotinamide and small amounts of nicotinamide adenine dinucleotide (NAD+), but not nicotinic acid, were detected chromatographically in the fetus and placenta, indicating that nicotinamide or NAD+ acts directly on the fetus to suppress urethane-induced malformations. A preliminary study revealed that urethane-induced lung tumorigenesis in JCL:ICR mice was also inhibited by post-treatment with nicotinamide in the diet. The level of inhibition was proportional to the dose of nicotinamide, that is, 35.0 and 62.8% at 1.0 and 2.5% of nicotinamide in the diet, respectively.     

Influence of the stage of pregnancy on Neospora caninum distribution, parasite loads and lesions in aborted bovine foetuses

In the present work we have studied in Neospra caninum aborted bovine foetuses the influence of foetal age (first, second and third gestational periods) on parasite distribution by nested PCR, parasite loads by real-time PCR and N. caninum associated lesions. For this purpose, a total of 220 aborted foetuses were analysed and detection of N. caninum infection was accomplished by nested-PCR in brain, heart and liver, detecting the presence of the parasite in 72 (32.7%) bovine foetuses. When the different age classes were compared, parasite DNA-detectability in heart and liver was reduced over time of gestation (P < 0.05, Fisher F-test). N. caninum distribution, parasite loads and lesions were studied on 34 out of 72 N. caninum-infected foetuses selected according to the stage of pregnancy and organs recovered. A higher number of positive-PCR tissue samples were observed in the foetuses corresponding to the first and second pregnancy periods. In the last trimester, the parasite could only be detected in the brain and, sporadically, in the diaphragm, heart and lymph nodes. The parasite loads decreased during pregnancy and the foetuses from the first period had higher parasite burdens in brain, heart, kidney and lung (P < 0.05, Kruskal-Wallis H-test) than in those corresponding to the other two trimesters of pregnancy. In addition, the observed lesions were more severe in foetuses from the first and second pregnancy periods than those from the third period (P > 0.05, Kruskal-Wallis H-test). Our results confirm the influence of N. caninum foetal age on pathogenesis in natural N. caninum infections.     

Risk factors in congenital abdominal wall defects (omphalocele and gastroschisi): a study in a series of 265,858 consecutive births.

The aim of this study was to describe the prevalence at birth of two abdominal wall defects (AWD), omphalocela and gastroschisis and to identify possible etiologic factors. The AWD came from 265,858 consecutive births of known ouome registered in the registry of congenital malformations of Strasbourg for the period 1979 to 1998. Request information on the child, the pregnancy, the parents and the family was obtained for cases and for controls. Hundred five cases with AWD were analysed, 55.2 % were omphalocele and 44.8 % were gastroschisis. The mean prevalence rate for omphalocele was 2.18 per 10,000 and for gastroschisis 1.76 per 10,000. Associated malformations were found in 74.1 % of omphalocele compared with 53.2 % of gastroschisis; 29.3 % of fetuses with omphalocele had an abnormal karyotype, 44,8 % had a recognizable syndrome, association or an unspecified malformation pattern; 51.0 % of fetuses with gastroschisis had additional malformations that were not of chromosomal origin, but 1 case. Antenatal ultrasound examination was able to detect 39 (67.2 %) cases of omphaloceles and 27 (57.4 %) cases of gastroschisis. In 30 (51.7 %) cases of omphalocele and in 7 (14.9 %) cases of gastroschisis parents opted for termination of pregnancy. The overall survival rate was 14 (24.1 %) for omphalocele and 30 (63.8 %) for gastroschisis. Weight, length and head circumference at birth of infants with AWD were less than those of controls. The weight of placenta of infants with AWD was not different from the weight of placenta of controls. Gastroschisis was associated with significantly younger maternal age than omphalocele. Pregnancies with AWD were more often complicated by threatened abortion, oligohydramnios and polyhydramnios. Mothers of children with AWD took more often medication during pregnancy than mothers of controls.     

From karyotyping to array-CGH in prenatal diagnosis

Conventional karyotyping detects chromosomal anomalies in up to 35% of pregnancies with fetal ultrasound anomalies, depending on the number and type of these anomalies. Extensive experience gained in the past decades has shown that prenatal karyotyping is a robust technique which can detect the majority of germline chromosomal anomalies. For most of these anomalies the phenotype is known. In postnatal diagnosis of patients with congenital anomalies and intellectual disability, array-CGH/SNP array has become the first-tier investigation. The higher abnormality detection yield and its amenability to automation renders array-CGH also suitable for prenatal diagnosis. As both findings of unclear significance and unexpected findings may be detected, studies on the outcome of array-CGH in prenatal diagnosis were initially performed retrospectively. Recently, prospective application of array-CGH in pregnancies with ultrasound anomalies, and to a lesser extent in pregnancies referred for other reasons, was studied. Array-CGH showed an increased diagnostic yield compared to karyotyping, varying from 1-5%, depending on the reason for referral. Knowledge of the spectrum of array-CGH anomalies detected in the prenatal setting will increase rapidly in the years to come, thus facilitating pre- and posttest counseling. Meanwhile, new techniques like non-invasive prenatal diagnosis are emerging and will claim their place. In this review, we summarize the outcome of studies on prenatal array-CGH, the clinical relevance of differences in detection rate and range as compared to standard karyotyping, and reflect on the future integration of new molecular techniques in the workflow of prenatal diagnosis.