Chemical and biochemical studies in fetuses affected with Nieman-Pick disease type A

Chemical and biochemical studies were performed on two unrelated fetuses affected with Niemann-Pick disease type A, following abortion at about the 19th week of gestation. Abortion was performed as a consequence of previous findings, in amniotic fluid cell cultures, that sphingomyelinase activity was completely absent. Phospholipid analyses of various organs of the fetuses, spleen and liver were the organs mostly affected. Interestingly enough considerable accumulation of sphingomyelin was found in the placenta. The brain was the only organ in which sphingomyelin storage could not be proved. In addition to sphingomyelin a slight accumulation of cholesterol was noticed. Deficiency of sphingomyelinase activity measured at pH 5.0 was the general characteristic of the affected tissues. It is concluded that the accumulation of sphingomyelin in various organs throughout the body of fetuses affected with Niemann-Pick disease is suggestive of the essential role of the enzyme sphingomyelinase and its biochemical maturation, even during the early stages of gestation.     

First-trimester transvaginal ultrasonographic diagnosis of Dandy-Walker malformation.

We present transvaginal ultrasonographic findings of a fetus with Dandy-Walker malformation and associated massive obstructive hydrocephalus at 13 weeks' gestation. First-trimester ultrasonographic diagnosis of Dandy-Walker malformation is uncommon with only two such occurrences having been reported previously. These cases and recent reports of single gene transmission of this condition in some families emphasize the importance of first-trimester transvaginal ultrasound assessment especially in women with previously affected fetuses.     

Hydatidiform mole in a triplet pregnancy following gonadotropin therapy

A first case is reported of complete hydatidiform mole with two coexistent fetuses in a triple pregnancy following human menopausal gonadotropin human chorionic gonadotropin (hMG-hCG) therapy. The molar mass and two fetuses were delivered separately at 17 weeks of gestation. The fetuses were female (155 g) and male (160 g) with individual placentae (85 g, 90 g). The hydatidiform mole (650 g) had a normal 46,XX karyotype. The sexes of the two fetuses and the karyotype of the mole are consistent with previous reports that the chromosomes of fetuses and moles are derived from both parents and the father, respectively.     

Protection of murine gestational tissues from picornavirus infection in the preimplantation period

Mice were inoculated with Theiler's murine encephalomyelitis virus (TMEV) on gestational days 1-3 (pre-implantation) or days 4-5 (peri- or post-implantation) or with control cell lysate (days 1-5). Dams were subsequently sacrificed between days 11-14 of gestation, and placentae and fetuses were harvested. Few placentae from dams inoculated with virus on days 1-3 were positive by virus culture (2 per cent) or in situ hybridization (6 per cent), and no fetuses were positive by either technique. In contrast, most placentae from dams inoculated with virus on days 4-5 were virus-positive by culture (96 per cent) or in situ hybridization (100 per cent), and a moderate number of fetuses were also positive (30 per cent by culture, 19 per cent by in situ hybridization). Necrosis was present more frequently in placentae from mice inoculated with virus on days 4-5 (55 per cent) than in placentae from dams inoculated with virus on days 1-3 (19 per cent) or with control cell lysate (18 per cent). Viral infection, mononuclear inflammation and cell necrosis were identified in the heart and great vessels of TMEV-infected fetuses. These results indicate that gestational tissues are largely protected from viral infection before implantation. After implantation, gestational tissues are more readily infected and damaged by maternal picornavirus infection.     

The effect of a reversible period of adverse intrauterine conditions during late gestation on fetal and placental weight and placentome distribution in sheep

Adverse intrauterine conditions occurring during early to mid-gestation or throughout the whole of gestation influence placental weight and the distribution of placentome types in sheep. However, no study to date has investigated the effect of a reversible period of adverse intrauterine conditions during late gestation upon fetal and placental weight and placentome distribution in sheep. Twenty-two sheep fetuses were chronically instrumented with an inflatable cord occluder, amniotic and vascular catheters and with a Transonic flow probe around an umbilical artery. At 125 days (term isca.145 days) the occluder was inflated to reduce umbilical blood flow by ca.30 per cent for 3d in 12 fetuses (umbilical cord compressed, UCC). The occluder was then deflated and umbilical blood flow allowed to return to baseline. The remaining 10 fetuses acted as sham-operated controls in which the occluder remained deflated at all times. At 135-137dGA ewes were humanely killed and tissues collected, weighed and placentomes classified. A reduction in umbilical blood flow by approximately 30 per cent from baseline for 3 days in UCC fetuses led to mild fetal asphyxia throughout the period of cord-compression. After deflation of the occluder cuff, umbilical blood flow returned to a level that was significantly greater than that measured during baseline. Umbilical cord compression had no effect on fetal body weight but significantly increased fetal adrenal weight relative to body weight. While the total number of placentomes was not altered by cord-compression, total placentome weight and the total weight of C/D-type placentomes were both reduced in UCC relative to control placentae. In addition, the mean weight of placentomes, and of C/D-type placentomes specifically, was significantly lower in UCC relative to control placentae. When expressed as a percentage of the total number of placentomes in the placenta, there was a significantly lower percentage of C/D-type placentomes in UCC relative to control placentae. In addition, there was a significant relationship between the total number of placentomes and the percentage C/D-type placentomes in control, but not UCC, placentae. The data suggest that a temporary, reversible period of adverse intrauterine conditions occurring late in gestation in sheep has persisting effects upon the placenta, mean placentome weight and placentome distribution.     

Ultrasonographic measurement of the abdominal circumference in fetuses with congenital diaphragmatic hernia

OBJECTIVE: To determine whether ultrasonographic measurements of the abdominal circumference are smaller in fetuses with congenital diaphragmatic hernia and whether this is reflected as an underestimation of the estimated fetal weight. STUDY DESIGN: A retrospective review of 225 abdominal circumference measurements made between 24 and 41 weeks of gestation in 85 fetuses with congenital diaphragmatic hernia was performed. The individual and mean abdominal circumference value at each week of gestation versus gestational age was plotted and compared with normative data. Comparisons between abdominal circumference measurements and hernia variables were made with the chi(2) test. The Pearson correlation was used to examine the accuracy of ultrasonographic determination of the estimated fetal weight. RESULTS: The mean measurements of abdominal circumference were not found to differ significantly from normative data until term, although fetuses with liver herniation were less likely to have measurements more than 2 standard deviations below the mean. Calculation of estimated fetal weight was similar in accuracy to that in normal fetuses. CONCLUSION: Small abdominal circumference measurements should not be expected in fetuses with congenital diaphragmatic hernia. Abnormalities of the abdominal circumference or an abdominal circumference-dependent estimated fetal weight should not be attributed to the anatomic defect without considering other etiologies.     

Immunohistochemical localization of pregnancy-associated plasma protein A (PAPP-A) in placentae from normal and pre-eclamptic pregnancies

An immunohistochemical method was used to locate pregnancy-associated plasma protein A (PAPP-A) in the placenta and uterus. In addition to 10 placentae and basal plates from normal pregnancies, ranging in gestational age from 37 to 40 weeks, the following specimens were studied: three uteri obtained by hysterectomy during early pregnancy; and three placentae from patients with severe hypertensive pre-eclampsia. In early gestation, PAPP-A was localized in the villous cytotrophoblastic cell layer and the endometrial glands but was not found in the villous syncytiotrophoblast, the cytotrophoblastic cell columns or the decidual cells. On histochemical examination of placentae from cases of pre-eclampsia with hypertension, an increased number of villous cytotrophoblastic cells and so-called X-cells was observed. The monospecific antiserum to PAPP-A reacted strongly and evenly with the cytoplasm of these cells. The present study strongly suggests that the active production sites of PAPP-A are the villous cytotrophoblastic cells and the X-cells.     

Distribution of Placental Grading by Gestational Age

Objective: to describe the ultrasonography-based gestation-specific placental grading distribution in a Chinese population.Methods: ultrasonographic examination of placentae was performed in 5,476 normal pregnancies (more than 95% first births) in five obstetric ultrasound laboratories in Central-South China between January 1, 1992 and December 31, 1993. A gestation-specific placental grading distribution was presented and compared with previous studies.Results: the gestational ages of the patients included in this study ranged from 16 to 40 weeks. The gestation-specific distribution of placental grading showed patterns similar to those observed previously, with grade III placentae starting to occur at 32 weeks and increasing to 32.3 percent at 40 weeks of gestation.Conclusions: the occurrence of grade III placentae is too high in preterm and too low in term pregnancies. Ultrasonographic placental grading alone is not a reliable measure of fetal pulmonary maturity.     

Effect of dexamethasone on amniotic fluid absorbance in Rh-sensitized pregnancy

Five Rh-sensitized pregnant women between 23 and 30 weeks gestation, with a poor obstetric history and initially high delta A450 values, were treated with weekly doses of 24 mg of dexamethasone over a period of 2-7 weeks to enhance fetal lung maturation. Four women showed a gradual decline in delta A450 during the treatment. All five deliveries were delayed until fetal lung maturity was confirmed by amniotic fluid lecithin/sphingomyelin (L/S) ratio and all five fetuses survived. It is possible that high doses of dexamethasone delayed the anticipated intrauterine deterioration of the fetuses and may have prevented the need for intrauterine transfusions.     

Utility of minor ultrasonographic markers in the prediction of abnormal fetal karyotype at a prenatal diagnostic center.

OBJECTIVE: This study was undertaken to assess the value of minor ultrasonographic markers in predicting significant karyotypic abnormalities. STUDY DESIGN: A total of 2743 fetuses (14-24 weeks' gestation) prospectively underwent a detailed ultrasonographic survey before genetic amniocentesis. Criteria for 8 minor ultrasonographic markers were established. Odds ratios for significant karyotypic abnormalities in the presence of minor ultrasonographic markers were calculated with the chi(2) and Fisher exact tests. RESULTS: Of the fetuses, 14.6% had a single minor ultrasonographic marker, 2.1% had >/=2 minor ultrasonographic markers, and 2.7% had >/=1 major ultrasonographic abnormality. One hundred four fetuses (3.8%) had an abnormal karyotype. Compared with a normal ultrasonographic examination result a single minor ultrasonographic marker increased the risk of karyotypic abnormality 5.7-fold (95% confidence interval, 3.5-9.3), whereas multiple minor markers increased the risk of an abnormal karyotype 12-fold (95% confidence interval, 5.5-26.5). When they were identified ultrasonographically in isolation, echogenic bowel, 2-vessel umbilical cord, echogenic intracardiac foci, choroidal separation, and choroid plexus cysts were statistically associated with an abnormal karyotype. When minor markers were identified in clusters of >/=2, echogenic bowel, short femur, 2-vessel umbilical cord, echogenic intracardiac foci, and mild ventriculomegaly were significantly predictive of karyotypic abnormality. With respect to the a priori aneuploidy risk of 1:26 and the a priori Down syndrome risk of 1:50, a normal ultrasonographic examination result reduced the risks to 1:67 and 1:120, respectively. The use of minor ultrasonographic markers in addition to major ultrasonographic abnormalities increased the detection of karyotypic abnormality from 27.9% to 68.3%. For trisomy 21 the sensitivity rose from 16.4% to 67. 3%. CONCLUSIONS: Significant karyotypic abnormality risk assessment by ultrasonography was greatly enhanced by the addition of minor ultrasonographic markers. Further, clusters of minor ultrasonographic markers greatly increased the likelihood of karyotypic abnormality compared with a single minor marker. A completely normal ultrasonographic examination result reduced the risk of an abnormal karyotype by 62%. Inclusion of minor ultrasonographic markers in the genetic sonogram in a high-risk population will allow the detection of 68% of fetuses with karyotypic abnormalities with a false-positive rate of 17%.     

Transvaginal fetal echocardiography in early pregnancy: normative data

Fifty-two transvaginal ultrasonographic examinations were performed between 10.0 and 14.9 weeks' gestation for the purpose of documenting normal fetal cardiac anatomy. All standard cardiac projections could be obtained by gestational week 12, and many were imaged by week 11. The four-chamber view was visualized in 90% of fetuses at 12 weeks' gestation and in 100% of fetuses examined at 13 weeks. The aortic root in short axis projection and the left ventricle in long axis view could be imaged in 70% and 40% of fetuses, respectively, by 12 weeks' gestation. Aortic and pulmonary valves were first visualized at 12 weeks, as were five-chamber, ductus arteriosus, and aortic arch views. The mitral and tricuspid valves were resolved in 60% of fetuses by 11 weeks' gestation. This study of normal cardiac anatomy suggests that there may be significant potential for the diagnosis of many fetal cardiac anomalies during the late first and early second trimesters of pregnancy.     

Incidence of Chromosomopathies and Cystic Fibrosis Mutations in Second Trimester Fetuses with Isolated Hyperechoic Bowel

Objective: Fetal echoic bowel can be a normal second trimester ultrasonographic finding which usually disappears by 20 weeks on serial sonograms. Recent studies have suggested a possible association of hyperechoic fetal bowel with chromosomopathies and cystic fibrosis. The aim of our study is to determine the incidence of chromosomopathies and cystic fibrosis mutations among the fetuses with isolated hyperechoic bowel.

Methods: Sixteen fetuses with isolated echoic bowel were detected: 13 fetuses S20 weeks gestation (group I) and 3 fetuses at 20-26 weeks gestation (group II). Cytogenetic studies were performed in all 16 cases and 11 families had deoxyribonucleic acid-based risk assessment for cystic fibrosis. The echogenity of bowel was that of surrounding bone.

Results: Two cases of trisomy 21 and 1 case of trisomy 13 were detected (18.7%). The other ultrasonographic markers begin to appear after 21 weeks gestation in fetuses with trisomy 13. Two of 3 pregnant women with pathological karyotype were younger than 35 years. One of 11 cases (9%) was found to be a heterozygote carrier for ΔF508 mutation.

Conclusions: Isolated hyperechoic bowel in the second trimester was found to be associated with a significantly higher risk of fetal aneuploidy.     

Periplacental hemorrhage and renal necrosis in protein and choline deficient pregnant rats following progesterone administration: A preliminary report

When pregnant rats are given parenteral progesterone late in gestation, about one fourth suffer intrauterine death of their fetuses and/or periplacental hemorrhage, and about one sixth have renal or liver necrosis. All the animals with uterine lesions were fed a diet deficient in choline or qualitatively deficient in protein. Nevertheless, until the effect of progesterone at different and precise times of gestation is known, the effect of defective diets must remain problematical.The similarity of these experimental findings with the condition of human abruptio placentae is pointed out.     

Non-invasive first trimester fetal gender assignment in pregnancies at risk for X-linked recessive diseases

OBJECTIVES: Prenatal diagnosis in families affected by X-linked recessive disorders should ideally be limited to the subjects at increased risk, i.e. male fetuses, in order to avoid the risk of fetal loss due to the invasive procedure in healthy female fetuses. The aim of the study was to assess the fetal sex within the first trimester of gestation by two non-invasive approaches, using ultrasonography and a molecular analysis of fetal DNA extracted from whole maternal blood with specific markers, in order to avoid invasive sampling in female fetuses. METHODS: A total number of 18 fetuses at risk for an X-linked recessive disease were included in the present investigation. Maternal peripheral blood was analysed between 7 and 12 weeks of gestation by nested PCR for the detection of fetal DNA and the prediction of fetal gender. In addition, when the biparietal diameter (BPD) was between 21 and 23 mm, an ultrasonographic examination was carried out to assess the fetal gender. CVS was then performed in male fetuses only. RESULTS: Fetal gender was correctly assigned by ultrasonography between 21 and 23 mm of BPD in all the cases studied, whereas DNA extracted from whole maternal blood accurately predicted the gender in all the female cases (10), but failed in 4 out of 8 male fetuses, erroneously assigned as females. CONCLUSION: The present study shows that sonography is able to accurately predict the fetal gender within the first trimester of pregnancy, whereas the molecular analysis of DNA extracted from whole maternal blood is biased by false-Y-negative results in 50% of the cases.     

Evaluation of the lemon and banana signs in one hundred thirty fetuses with open spina bifida

The incidence and diagnostic accuracy of the lemon and cerebellar ultrasonographic markers, as well as head size and ventriculomegaly, were evaluated in a study of 1561 patients at high risk for fetal neural tube defects. In the 130 fetuses with open spina bifida there was a relationship between gestational age and the presence of each of these markers. The lemon sign was present in 98% of fetuses at less than or equal to 24 weeks' gestation but in only 13% of those at greater than 24 weeks' gestation. Cerebellar abnormalities were present in 95% of fetuses irrespective of gestation; however, the cerebellar abnormality at less than or equal to 24 weeks' gestation was predominantly the banana sign (72%) whereas at gestations greater than 24 weeks it was cerebellar "absence" (81%). Both growth retardation and cerebral ventriculomegaly significantly worsened with gestation while the head circumference remained disproportionately small throughout gestation. On the basis of these data, a new approach is proposed for the investigation of patients at high risk for fetal open spina bifida.     

Effect of a failure of energy supply on adenine nucleotide breakdown in placentae and other fetal tissues from rat and guinea pig

The effects of ischaemia on adenylate energy charge of tissues from fetal rats and fetal guinea pigs were measured. Adult rat and guinea-pig tissues, as well as human placentae, were also studied. The largest differences observed were between the fetuses from different pregnant animals (P = 4.74 X 10(-15). Reductions in energy charge in placentae were slower than in other defined fetal tissues, especially brain. In the rat, an immature species at birth, greater 'stability' was observed in placentae of 14 days of gestation than near term at 20 days of gestation. As contrast, in the guinea pig, a mature species at birth, there was no difference in 'stability' in placenta or other fetal tissues between about 40 days of gestation and near term, about 60 days of gestation. In addition to these tissue and maturity effects in the fetus, it has been confirmed that fetal tissues are more 'resistant' than adult tissues to failures of energy supply. Concentrations of adenosine, uridine, guanosine and cytidine nucleotides in placenta show similar patterns in rats and guinea pigs. Fetal liver contains more uridine nucleotides and brain more cytidine nucleotides. It is suggested that the placenta retains an early fetal ability to maintain itself during ischaemia; this might be advantageous during parturition. Possible endocrine and other mechanisms 'damping' fetoplacental metabolism are linked with a discussion of the large maternal effect.     

Expression of apoptosis in placentae from mice lacking the prostaglandin F receptor

This study aimed to investigate the changes in apoptosis in the placenta and decidua of pregnant mice lacking the prostaglandin F receptor. Mouse placentae were removed from fetuses on days 10-23 of pregnancy. Apoptotic cells were examined by a DNA fragmentation assay and the terminal deoxynucleotidyl transferase-mediated dUDP nick end-labelling (TUNEL) technique. The placenta and decidual weight increased before day 18 and 14 of pregnancy, and then decreased with gestational day. After day 19, the fetuses gradually died in the uterus. All fetuses died in the uterus on day 23 of pregnancy. The number of apoptosis was not significantly different between wild type and FP-deficient mice before day 18 of pregnancy by DNA fragmentation and TUNEL staining. The DNA fragmentation was always more pronounced in decidual tissue on each day of pregnancy. DNA laddering on placentae was more extensive on day 22 than day 18. In placenta, most TUNEL-positive cells were detected in trophoblast and stromal cells. A higher intensity of apoptotic cells was in the decidual basalis. The main area was the centre of the decidual basalis, and was in decrease toward to margin of placenta. The index of TUNEL positive cells increased as gestation progressed toward termination. Especially, it was prominent in the placentae on day 22 compared with that day 18 of pregnancy. The increased TUNEL-positive staining in syncytiotrophoblast surface was found in placenta at post-term, compared with those at term. Apoptosis may provide insights into both normal placental development and placental dysfunction during an abnormal pregnancy from post-term pregnancy.     

Amnion-chorion separation after 17 weeks' gestation

OBJECTIVE: To evaluate the cause of and perinatal outcomes of amnion-chorion separation that is apparent sonographically after 17 weeks' gestation. METHODS: We searched our ultrasound database over 7 years for information on pregnant women who had live fetuses and complete separation between amnion and chorion that persisted beyond 17 weeks' gestation. For inclusion in the study, the women had to have amnion separated from chorion on at least three sides of the gestational sac. Medical records were reviewed for whether women had amniocenteses, results of the amniocenteses, and outcomes of the pregnancies. RESULTS: Of 15 pregnant women with live fetuses, ten had amniocenteses before identification of amnion-chorion separation and five did not. Three had fetuses with Down syndrome, two of whom had amnion-chorion separation evident before amniocentesis, and all three had other sonographic findings suggestive of aneuploidy. Three fetuses died. The other pregnancies were complicated by one or more adverse events, including two fetuses with growth restriction, five preterm deliveries, two with oligohydramnios, and one with abruptio placentae. Five infants were delivered at term and are alive and well. Overall, ten of 15 pregnancies resulted in live newborns, one of whom had Down syndrome. CONCLUSION: Complete amnion-chorion separation that persisted after 17 weeks' gestation is associated with a variety of adverse perinatal outcomes, including aneuploidy.     

Picornavirus infection in early murine gestation: significance of maternal illness

To evaluate whether maternal illness following picornavirus infection during pregnancy adversely affects placental and fetal health, mice were inoculated with the GDVII strain of Theiler's murine encephalomyelitis virus or control cell lysate during days 4-7 of gestation. Gross appearance, histopathology and viral culture, and in situ hybridization positivity of placentae and fetuses from ill GDVII-infected, healthy GDVII-infected and control mice were compared. Twenty of 34 (59 per cent) GDVII-infected dams became clinically ill. More placenta-fetus pairs from ill mice were grossly abnormal (68 per cent) than from well GDVII-infected (51 per cent;P< 0.01) or control mice (9 per cent;P< 0.001). Virus was detected by in situ hybridization in 73 per cent of placentae and 29 per cent of fetuses from sick GDVII-infected dams, and in 85 per cent of placentae and 19 per cent of fetuses from healthy GDVII-infected mice (differences not significant). Histological abnormalities consisting of necrosis or an increase in hyaline tissue in the vascular labyrinth layer were similarly frequent in placentae from ill and well GDVII-infected mice (58 per cent versus 67 per cent, P=0.5). Viral RNA, inflammation and necrosis were evident in the heart, great vessels, brain and spinal cord of GDVII-infected fetuses. Infection with GDVII in early pregnancy produces a high rate of gross placental and fetal abnormalities. The rate of gross abnormalities exceeds the incidence of fetal infection and more closely parallels the rates of infection and histopathology in the placenta, suggesting that much of the damage to placenta-fetus pairs is a consequence of placental infection. In addition, the occurrence of viral-induced maternal illness is associated with additive risk to placental and fetal health not explained by an increased rate of placental or fetal infection.     

Morphometry of the microvillous membrane of the human placenta in maternal diabetes mellitus

The syncytiotrophoblast microvillous membrane of the human placenta has been investigated with quantitative analyses in a group of placentae from diabetic mothers, these placentae being compared to a group of normal placentae. This study has shown that, in the placentae of the diabetic mothers, there was a significant increase in the surface density of the microvilli and in the microvillous surface enlargement factor as compared to those of the controls. Consequently, it has demonstrated that the already large villous surface area found in the placentae of diabetic mothers can be enlarged very significantly by the microvilli, in terms of the total trophoblastic surface area which is in contact with the maternal blood. On a functional basis, these findings support the theory that placental function is probably not adversely affected in these placentae, and that these placentae can efficiently support the growth of large fetuses.