Clinical course and outcome of antenatally detected atrioventricular block: experience of a single tertiary centre and review of the literature.

OBJECTIVE: The objective is to study the course and outcome of fetuses with congenital atrioventricular block (AVB) in a single centre. METHODS: Retrospective analysis of cases diagnosed prenatally with second and third degree AVB. The clinical characteristics and outcome of fetal AVB were evaluated including in utero treatment. RESULTS: Sixty-two cases were studied. AVB was associated with a congenital heart defect (CHD-AVB) in 17 cases (27%), whereas it was isolated (i-AVB) in 45 (73%), 42 of which were associated with maternal antibodies. There were nine (52.9%) live births in the CHD-AVB group, five of which (55%) resulted in infant deaths. In the i-AVB group, there were 40/45 (88.9%) live births and 1/40 (2.5%) infant death; 36 (90%) babies required a permanent pacemaker. The only factor predictive of postnatal death was the presence of CHD (5/9 vs 1/39 or 48.7 [3.6; 1457.7], p < 0.001). Nineteen fetuses (40.5%) with i-AVB received steroids in utero. No difference in outcome was found between the AVB treated in utero versus the no-treatment group in terms of permanent pacemaker placement, postnatal death or development of dilated cardiomyopathy. CONCLUSION: The most important prognostic factor for congenital AVB is the association with CHD. In utero treatment remains questionable.

Three-dimensional helical computed tomography in prenatal diagnosis of fetal skeletal dysplasia.

OBJECTIVES: (1) To study the use and diagnostic value, as a complement to ultrasound, of helical computed tomography (helical CT) to differentiate normal fetuses from cases of skeletal dysplasia; (2) to define the most relevant indications for helical CT; and (3) to evaluate its diagnostic performance with respect to radiological criteria considered discriminatory. METHODS: This was a retrospective study from 2005 to 2008 in 67 pregnant women who underwent helical CT after 26 weeks of gestation for suspected fetal skeletal dysplasia due to fetal shortened long bones on ultrasound (≤ 10(th) percentile), either alone or associated with other bone abnormalities. The results were compared with pediatric examinations in 41 cases and with fetal autopsy findings after elective termination of pregnancy in the others. RESULTS: Helical CT had a sensitivity of 82%, specificity of 91% and positive and negative predictive values of 90% and 83%, respectively, for diagnosis of fetal skeletal dysplasia. An etiological diagnosis that had not been suspected at ultrasound was specified in 15% of cases and diagnoses suspected at ultrasound were confirmed in 24% and discounted in 43% of cases. The prevalence of skeletal dysplasia was increased in cases of micromelia < 3(rd) percentile or if there was a combination of bone signs. Helical CT showed 69% sensitivity in identifying individual predefined pathological bone signs which were confirmed on fetal autopsy findings. CONCLUSION: Helical CT is a key examination, in combination with ultrasound, in the diagnosis of fetal skeletal dysplasia from 26 weeks of gestation. It should be reserved for cases with severe micromelia below the 3(rd) percentile and for those with micromelia ≤ 10(th) percentile associated with another bone sign. A checklist of discriminatory signs is proposed.

Is complex gastroschisis predictable by prenatal ultrasound?

OBJECTIVE: To establish a correlation between prenatal ultrasound findings and postnatal outcome in neonates with gastroschisis (GS). DESIGN: Retrospective case-control study. SETTING: Prenatal ultrasound reports, labour and neonatal intensive care unit notes, and paediatric surgical clinic records were reviewed. POPULATION: Neonates with an antenatal diagnosis of isolated GS. METHODS: The neonates were divided into two groups: one with associated bowel complications including intestinal atresia, perforation, necrosis or volvulus ('complex' GS), and the second without bowel complication ('simple' GS). Prenatal ultrasound markers: small-for-gestational-age, intra-abdominal and extra-abdominal bowel dilatation (>6 mm), thickened intestinal wall and stomach dilatation were correlated with outcome. MAIN OUTCOME MEASURES: Fetal or neonatal death in complex versus simple GS. Time on parenteral nutrition and duration of hospital stay were also noted. RESULTS: In all, 105 cases were eligible for analysis. Survival rate was 101/105 (96.2%). None of the ultrasound markers was predictive of fetal or neonatal death. Fourteen of 103 live-born babies (14.6%) had complex GS, which was associated with longer time on parenteral nutrition [8.0 (51.5-390) versus 33.5 (25.3-53.3) days, P<0.001] and longer duration of hospital stay [85.3 (55.5-210) versus 41.5 (33.0-64.8) days, P<0.001]. Infants with complex GS were more likely to require bowel resection and stoma placement (P<0.05). Intra-abdominal bowel dilatation was the only predictive ultrasound marker of complex GS (odds ratio 4.13, 95% CI 1.32-12.90; P=0.018). Receiver operating characteristic curve for observed/expected bowel diameter yielded 6 as the cutoff value for predicting complex GS (odds ratio 7.9, 95% CI 2.3-27.3; P=0.001) with 54% and 88% for sensibility and specificity, respectively. CONCLUSIONS: Intra-abdominal bowel dilatation is the only ultrasound marker predictive of complex GS but it is a strong marker.

Hidden mortality of prenatally diagnosed vein of Galen aneurysmal malformation: retrospective study and review of the literature.

OBJECTIVE: To evaluate the prognosis of prenatally diagnosed vein of Galen aneurysmal malformation (VGAM) in a large cohort with this condition and to review the literature on prenatally diagnosed VGAM. METHODS: This was a retrospective study of all cases of prenatally diagnosed VGAM managed in our referral center during a 12-year period. VGAM was categorized as being either isolated or associated with any other abnormality, based on fetal ultrasound and magnetic resonance imaging findings. Poor outcomes comprised termination of pregnancy with confirmation of antenatal findings, perinatal death and severe cardiac and/or neurological impairment in survivors. The literature was also reviewed for similar cases. RESULTS: Twenty-one cases of prenatally diagnosed VGAM were managed in our center. Four (19.0%) cases were isolated and 17 (81.0%) were associated with other anomalies. There were nine terminations (42.9%) and six neonatal deaths (28.6%). Six children (28.6%) were still alive at last follow-up, of whom three had abnormal neurological development. VGAM associated with other anomalies was strongly associated with a poor outcome compared with isolated forms (P < 0.0001). One hundred and nine cases from the literature were also reviewed. CONCLUSION: Fetuses with prenatally diagnosed VGAM have unexpectedly poor outcomes in the presence of cardiac or cerebral anomalies, while those with strictly isolated VGAM tend to have more favorable outcomes. Our literature review corroborates these findings.

The value of daily fetal heart rate home monitoring in addition to serial ultrasound examinations in pregnancies complicated by fetal gastroschisis.

OBJECTIVES: To audit the practice of daily fetal heart rate home monitoring (FHM) in pregnancies complicated by fetal gastroschisis (GS). METHODS: Prenatal records and pregnancy outcome were reviewed of all cases with fetal GS between 1999 and 2010, managed with a consistent protocol, which included weekly fetal cardiotocography and ultrasound examinations after 30 weeks, and option of daily FHM. Data were collected including gestational age (GA) at FHM and the presence of fetal heart rate anomaly. Follow-up included fetal growth, amniotic fluid volume, gastrointestinal appearance and cardiotocography findings. RESULTS: One hundred five cases of GS were identified. Stillbirth rate was 1.9% (2/105). FHM was performed in 97/105 (92.4%) cases. Abnormal FHM was recorded in 24 cases. Fetuses with abnormal versus normal FHM were more likely to have C-section for fetal heart rate anomaly (50% vs 24%, p=0.025) at an earlier gestational age (34.9 ± 1.7 vs 35.8 ± 1.4 weeks, p=0.016). There was no difference in Apgar score or umbilical artery pH at birth. CONCLUSION: Fetal heart rate abnormalities are frequent in fetuses with GS. FHM appears useful in detecting fetal distress necessitating expedited delivery. However, the impact of a daily FHM policy on neonatal outcome should be evaluated in a randomized study.

Factors associated with partial and complete regression of fetal lung lesions.

OBJECTIVE: A decrease in the volume of congenital pulmonary malformations (CPM) can be observed on prenatal ultrasonography, but the underlying mechanism for this phenomenon is unknown. Our objective was to identify factors associated with the prenatal reduction in size of cystic and/or hyperechoic lung lesions. METHODS: This was a retrospective study of cases with a prenatal diagnosis of hyperechoic and/or cystic lung lesion. The extent of reduction in lesion size was calculated from ultrasound measurements. Clinical, ultrasound, radiological and histological data were tested for their relationship with prenatal CPM reduction. RESULTS: In a 4-year period, 36 patients were referred with a cystic and/or hyperechoic fetal lung lesion diagnosed at a mean gestational age of 23.4 weeks. The lesions were cystic in 16 cases (44%), hyperechoic in 12 (33%) and both in eight (22%). The malformation was no longer visible before birth (apparent disappearance) in nine cases (25%), shrank by 18-90% in 15 (42%) and did not reduce in 12 (33%). Findings on postnatal computed tomography were always abnormal. Isolated hyperechoic lesions were significantly more likely to shrink in utero. The mean reductions were 79%, 35% and 19%, for isolated hyperechoic, cystic and mixed lesions, respectively (P=0.001). Only 8% of hyperechoic lesions demonstrated no volume reduction, as compared to 50% and 42% of cystic and mixed lesions, respectively (P=0.03). Greater gestational age at birth was also associated with a decrease in the incidence of malformations (P=0.02). In cases that underwent surgery, hyperechoic lesions were linked to a variety of pathological diagnoses, whereas cystic lesions were all described histologically as congenital cystic adenomatoid malformations. CONCLUSIONS: Prenatal size reduction of fetal lung malformations is associated with isolated hyperechogenicity and greater gestational age at birth. This might result from the resumption of normal lung development after local disruption of lung growth.

Keyhole sign: how specific is it for the diagnosis of posterior urethral valves?

OBJECTIVES: Posterior urethral valves (PUV) are the most common cause of renal impairment in boys during early childhood. Although antenatal suspicion of this pathology has become quite common in recent years, prenatal diagnosis remains challenging. The aim of this study was to evaluate the predictive value of different ultrasound criteria currently used to diagnose PUV. METHODS: We reviewed the antenatal and postnatal files of 54 male patients referred to our center from 2000 to 2006 after detection of fetal bilateral hydronephrosis. The following ultrasound criteria were evaluated in relation to the postnatal diagnosis of PUV: amniotic fluid volume, bladder wall thickness, bladder dilatation and the presence of the 'keyhole sign'. RESULTS: Forty-two fetuses (77.8%) were suspected to have PUV on prenatal examination. Out of these, 29 (69.0%) had PUV confirmed postnatally. The sensitivity and specificity of the antenatal diagnosis of PUV were 94% and 43%, respectively. Increased bladder wall thickness and bladder dilatation were highly associated with the diagnosis of PUV (P < 0.001). However, a thick-walled bladder was observed in 39.1% and a dilated bladder in 47.8% of the infants with a postnatal diagnosis other than PUV. The presence of the keyhole sign was not found to predict a diagnosis of PUV (P = 0.27). CONCLUSION: In this series the use of classical prenatal ultrasound signs to diagnose PUV showed high sensitivity but low specificity. The best diagnostic indicators were increased bladder wall thickness and dilatation of the bladder. The keyhole sign was not found to be a reliable predictor of PUV.

Prenatal diagnosis of cardiac rhabdomyomas: incidence of associated cerebral lesions of tuberous sclerosis complex.

OBJECTIVES: To determine the prevalence of specific cerebral lesions of tuberous sclerosis complex (TSC) and neurological outcome in cases diagnosed prenatally with cardiac rhabdomyomas. METHODS: We reviewed all fetuses diagnosed prenatally with cardiac rhabdomyomas which had undergone detailed ultrasound evaluation and cerebral magnetic resonance imaging (MRI) and which were recorded in the database of a single institution covering the period January 1992 to December 2005. RESULTS: Fifty-one fetuses were included in the study. MRI was performed at a mean +/- SD gestational age of 30 +/- 3 gestational weeks and showed specific lesions of TSC in 49% of cases. Termination of pregnancy was chosen by the parents in 26 cases. Neurological development was studied in 20 cases, follow-up lasting 4.8 +/- 2.9 years. Neurodevelopmental events occurred during the follow-up period in 45% of cases. Neurological complications occurred in 67% of patients who had cerebral lesions at MRI and in 33% of patients with normal MRI results. There was no significant difference between the two groups of patients (P = 0.2). CONCLUSION: In fetuses with cardiac rhabdomyomas detailed ultrasound examination and third-trimester cerebral MRI are able to diagnose most TSC cerebral lesions, but fail to determine neurological outcome.

Stability of the m.8993T->G mtDNA mutation load during human embryofetal development has implications for the feasibility of prenatal diagnosis in NARP syndrome.

BACKGROUND: Mitochondrial DNA (mtDNA) mutations cause a wide range of serious genetic diseases with maternal inheritance. Because of the high transmission risk and the absence of therapy in these disorders, at-risk couples often ask for prenatal diagnosis (PND). However, because heteroplasmy load (coexistence of mutant and wild-type mtDNA) may vary among tissues and with time, the possibility that a single fetal sample may not reflect the whole neonate impedes prenatal diagnosis of mtDNA diseases. METHODS: We performed 13 prenatal diagnoses for the NARP (neurogenic weakness, ataxia, retinitis pigmentosa) m.8993T-->G mtDNA mutation (p.Leu156Arg) in the ATP synthase subunit 6 gene. Analyses were performed on chorionic villous (CVS) and/or amniocyte samples carried out at various stages of pregnancy, using a method enabling quantification of low DNA amounts. RESULTS: Maternal mutant loads ranged from 0 to 75% in blood and had no predictive value for the fetus status, except for women with no detectable mutant DNA, whose fetuses were consistently mutation-free. In 8/13 PND, mutant load was <30%. These children are healthy at 2-7 years of age. In 5/13 PND, mutant load ranged from 65 to 100%, and parents preferred to terminate the pregnancies (15-22 weeks of gestation). Single-cell analysis of 20 trophoblastic cells and 21 amniocytes isolated from two affected fetuses found an average mutant load close to the overall CVS and amniocyte mutant load, despite striking intercellular variation. The m.8993T-->G mutant loads, assessed in 7, 17, 11, and 5 different tissues from 4 terminations, respectively, were identical in all tissues from a given individual (mean (SD) 78 (1.2)%, 91 (0.7)%, 74 (2)%, and 63 (1.6)% for the 4 fetuses, respectively). CONCLUSIONS: Our results indicate that the placental/amniotic mutant loads do reflect the NARP mutant mtDNA load in the whole fetus, even when the sample amount is small, and suggest that heteroplasmy level remains stable during pregnancy, at least after 10 weeks of gestation. Although these data establish the feasibility of PND for this mutation, assessing more precisely the correlation between mutant load and disease severity should further help in interpreting PND results.

Prenatal diagnosis of myopathy, encephalopathy, lactic acidosis, and stroke-like syndrome: contribution to understanding mitochondrial DNA segregation during human embryofetal development.

INTRODUCTION: Myopathy, encephalopathy, lactic acidosis, and stroke-like (MELAS) syndrome, a maternally inherited disorder that is among the most common mitochondrial DNA (mtDNA) diseases, is usually associated with the m.3242A>G mutation of the mitochondrial tRNA(leu) gene. Very few data are available with respect to prenatal diagnosis of this serious disease. The rate of mutant versus wild-type mtDNA (heteroplasmy) in fetal DNA is indeed considered to be a poor indicator of postnatal outcome. MATERIALS AND METHODS: Taking advantage of a novel semi-quantitative polymerase chain reaction test for m.3243A>G mutant load assessment, we carried out nine prenatal diagnoses in five unrelated women, using two different fetal tissues (chorionic villi v amniocytes) sampled at two or three different stages of pregnancy. RESULTS: Two of the five women, although not carrying m.3243A>G in blood or extra-blood tissues, were, however, considered at risk for transmission of the mutation, as they were closely related to MELAS-affected individuals. The absence of 3243A>G in the blood of first degree relatives was associated with no mutated mtDNA in the cardiovascular system (CVS) or amniocytes, and their three children are healthy, with a follow-up of 3 months-3 years. Among the six fetuses from the three carrier women, three were shown to be homoplasmic (0% mutant load), the remaining three being heteroplasmic, with a mutant load ranging from 23% to 63%. The fetal mutant load was fairly stable at two or three different stages of pregnancy in CVS and amniocytes. Although pregnancy was terminated in the case of the fetus with a 63% mutant load, all other children are healthy with a follow-up of 3 months-6 years. CONCLUSION: These data suggest that a prenatal diagnosis for MELAS syndrome might be helpful for at-risk families.

Phenotypic spectrum of CHARGE syndrome in fetuses with CHD7 truncating mutations correlates with expression during human development.

BACKGROUND: The acronym CHARGE refers to a non-random cluster of malformations including coloboma, heart malformation, choanal atresia, retardation of growth and/or development, genital anomalies, and ear anomalies. This set of multiple congenital anomalies is frequent, despite rare patients with normal intelligence, and prognosis remains poor. Recently, CHD7 gene mutations have been identified in CHARGE patients; however, the function of CHD7 during development remains unknown. METHODS: We studied a series of 10 antenatal cases in whom the diagnosis of CHARGE syndrome was suspected, considering that a careful pathological description would shed light on the CHD7 function during development. CHD7 sequence analysis and in situ hybridisation were employed. RESULTS: The diagnosis of CHARGE syndrome was confirmed in all 10 fetuses by the identification of a CHD7 heterozygous truncating mutation. Interestingly, arhinencephaly and semi-circular canal agenesis were two constant features which are not included in formal diagnostic criteria so far. In situ hybridisation analysis of the CHD7 gene during early human development emphasised the role of CHD7 in the development of the central nervous system, internal ear, and neural crest of pharyngeal arches, and more generally showed a good correlation between specific CHD7 expression pattern and the developmental anomalies observed in CHARGE syndrome. CONCLUSIONS: These results allowed us to further refine the phenotypic spectrum of developmental anomalies resulting from CHD7 dysfunction.

[Emergency thoraco amniotic shunting in cases with compressive pleural effusion with hydrops: A retrospective study of 60 cases]. / Drainage thoraco-amniotique en urgence en cas d'épanchement pleural compressif responsable d'anasarque foetale: une série rétrospective de 60 cas.

OBJECTIVES: To study perinatal outcome following thoraco-amniotic shunting for fetal pleural effusions with hydrops. MATERIALS AND METHODS: Retrospective study (1984-2004) to evaluate a policy of emergency thracoamniotic shunting in hydropic fetuses with suspected chylothorax, on the basis of the rationale that mediastinal compression could lead to acute fetal distress. RESULTS: Shunting was performed immediately following diagnosis, and was successful in all 60 cases attempted. There were 7 pregnancy terminations, 10 in utero deaths, and 43 live births, of which 7 children died in the neonatal period and 36 survived (33 without sequels). Among the liveborn, 26 were delivered preterm (72%), of which 7 (19%) had preterm premature rupture of membranes and 4 (11%) had chorioamnionitis. Perinatal death (24/60, 40%) was related to underlying anomalies (7 cases), pulmonary hypoplasia (5 cases), chorioamnionitis (2 cases), or treatment failure for unknown reasons (10 cases). All 36 survivors had chylothorax, 33 of which were primary, and 3 were secondary to right congenital diaphragmatic hernia, pulmonary sequestration, or Noonan syndrome. CONCLUSION: Following shunting, pleural effusion with hydrops has survival rate >50%, but still have a high rate of morbidity and mortality.

Maternal uniparental heterodisomy of chromosome 14: chromosomal mechanism and clinical follow up.

To our knowledge, 22 cases of chromosome 14 maternal uniparental disomy (UPD(14)mat) have been reported so far. The majority of cases were ascertained because of an abnormal phenotype associated with a Robertsonian translocation involving chromosome 14. We report here on a child with UPD(14)mat detected prenatally and resulting from trisomy rescue in a maternal meiosis I non-disjunction trisomic zygote. After four years of clinical follow up, in addition to intrauterine growth retardation (IUGR), only short stature and small hands and feet were observed. These clinical data as well as the ascertainment and mechanism of origin of UPD(14)mat were compared with those observed in previously reported cases. It appears that the clinical spectrum of UPD(14)mat is milder in our patient than in patients with UPD(14)mat resulting from other chromosomal mechanisms. In addition, a hypothesis based on abnormal imprinting is proposed to explain the variability of the UPD(14)mat.

Hematopoiesis in the human yolk sac: quantitation of erythroid and granulopoietic progenitors between 3.5 and 8 weeks of development.

In a first attempt to investigate the regulation of the early steps of human embryonic hematopoiesis, we measured the number of erythroid and granulopoietic progenitors in 38 human yolk sacs and 15 embryonic livers between 27 and 62 days of development. Both erythroid and granulopoietic progenitors were identified in the yolk sac as soon as 27 days, while in the embryonic liver significant numbers were not observed before 40 days. In the yolk sac, the number of granulopoietic and/or macrophagic progenitors was significantly negatively correlated with gestational age. Such a correlation was not observed for CFU-E and BFU-E, even though in the youngest (less than 30 days) and the oldest embryos studied (greater than 40 days), the number of BFU-E was clearly lower.

Fetal urinary biochemistry predicts postnatal renal function in children with bilateral obstructive uropathies.

OBJECTIVE: To investigate the ability of fetal urinalysis to predict in utero the renal function of children with bilateral uropathy who survive to the second year of life. METHODS: This was a prospective cohort study of 100 consecutive patients with prenatal diagnosis of bilateral uropathy who underwent fetal urine sampling. Fetal urinary concentrations of sodium, chloride, calcium, phosphorus, ammonium, urea, creatinine, glucose, proteins, and beta 2 microglobulin were measured. Prenatal findings were matched with renal function of survivors at 1-2 years. The single end point was serum creatinine, which was considered abnormal when greater than 50 mumol/L (0.56 mg/dL) during the second year of life. RESULTS: Elevated serum creatinine was found in 17 of 42 children with isolated uropathy who survived more than 1 year. For prediction of elevated serum creatinine during the second year of life, the fetal urinary concentration of beta 2 microglobulin was both specific (0.83) and sensitive (0.80); sodium, chloride, and urea levels were sensitive (0.70 or greater) but lacked specificity (less than 0.65); and fetal urinary glucose, phosphorus, calcium, ammonium, and total proteins were specific (0.70 or greater) but lacked sensitivity (0.65 or less). CONCLUSIONS: Our results provide a new approach to prenatal management of congenital obstructive uropathies by identifying those fetuses at risk for survival with suboptimal renal function. These fetuses might benefit from intrauterine therapy. In contrast, no attempt at prenatal uro-amniotic shunting should be made when a spontaneously good outcome is predicted by fetal urinalysis.

Efficacy of transabdominal multifetal pregnancy reduction: collaborative experience among the world's largest centers.

OBJECTIVE: To evaluate the safety and efficacy of transabdominal multifetal pregnancy reduction (MFPR) in the management of iatrogenic and spontaneous multifetal pregnancies. METHODS: Data were combined from 463 completed pregnancies that underwent MFPR at major worldwide centers. RESULTS: Multifetal pregnancy reduction was performed with a 100% technical success rate (there were no failed procedures); 83.8% had delivery of potentially viable fetuses (defined as 24 weeks' gestation or later), and 83.5% of these viable pregnancies delivered at 33 weeks or later. The risk of fetal loss was 3.9% at 2 weeks or less post-procedure, 4.6% at 4 weeks or less, and 16.2% at less than 24 weeks of gestation. Gestational age at delivery varied principally with the number of fetuses remaining, with 7.1% delivering prematurely at less than 28 weeks, and 9.4% at 29-32 weeks. The incidence of obstetric and medical complications appeared to be unaffected, and there was no increase in congenital malformations. CONCLUSIONS: Multifetal pregnancy reduction is an efficient and safe way of improving outcome in multifetal pregnancies, unambiguously for quadruplets or more, and arguably for triplets. However, particularly at higher starting numbers, there are still suboptimal outcomes. We cannot answer the question of whether MFPR should be offered to women with triplets or twins. The only major risk appears to be fetal loss per se, and because the procedure itself does not damage the survivors, parental autonomy should be given a higher priority in the decision process than previously. However, to obviate the need for this procedure, infertility specialists must continue to be vigilant in the use of fertility drugs.

Molecular forms and solubility of acetylcholinesterase during the embryonic development of rat and human brain.

Acetylcholinesterase (EC 3.1.1.7) and butyrylcholinesterase (EC 3.1.1.8) form homologous sets of multiple molecular forms. The central nervous system of mammals contains mostly tetramers (G4) and monomers (G1). Their proportions have been shown to vary during maturation in rat brain. In order to examine whether a similar evolution occurs in the human, we performed parallel studies of the activity, solubility and molecular forms of acetylcholinesterase in rat and human brains at various stages. We find both similarities and differences: in rat brain, the enzyme increases mostly postnatally but in human brain acetylcholinesterase reaches a maximum at birth. There is an increase in the proportion of G4 and a decrease in the solubility of this from in the absence of detergent in human as well as in rat brain. These changes occur around birth in rat, but during early pregnancy, before 11 weeks in human brain. In both species, the solubility of the enzyme in detergent-free buffers decreases progressively from more than 50% before birth to about 10-20% in the adult. In addition we analyzed butyrylcholinesterase as well as the levels of the neuron-specific enolase and of the glial S-100 protein. In human, gamma gamma-enolase rises to its adult level after birth, but before the S-100 protein.

Embryo reduction in multifetal pregnancies after infertility therapy: obstetrical risks and perinatal benefits are related to operative strategy.

To assess the benefits that can be expected from embryo reduction of multiple pregnancies after infertility therapy, we report 58 consecutive cases of selective termination using either a transcervical or a transabdominal approach. The initial number of embryos was five or more in 13 patients, four in 29 patients, and three in 15 patients. The miscarriage rate after transabdominal procedures (23%) was one half of that after transcervical aspiration. Forty pregnancies resulted in the live birth of one child or more. The rate of prematurity was strongly related to the number of embryos left. Mean gestational age at birth was 35.5 weeks but reached 37.7 weeks when only one embryo was left. A reduction in premature birth after selective termination appeared clear for pregnancies with four or more embryos but was less significant for triplets.

International, collaborative experience of 1789 patients having multifetal pregnancy reduction: a plateauing of risks and outcomes.

OBJECTIVE: To develop the most up-to-date, complete data base of multifetal pregnancy reduction (MFPR) from cases, and to provide the best counseling for couples with multifetal pregnancies. METHODS: From nine centers in five countries, 1789 completed MFPR cases were collected and outcomes evaluated. Pregnancy losses were defined as through 24 weeks and deliveries categorized in groups of 25-28, 29-32, 33-36, and 37 or more weeks. RESULTS: Overall, the pregnancy loss rate was 11.7% but varied from a low of 7.6% for triplets to twins and increased with each additional starting number to 22.9% for sextuplets or higher. Early premature deliveries (25-28 weeks) were 4.5% and varied with starting number. Loss rates by finishing number were highest for triplets and lowest for twins, but gestational age at delivery was highest for singletons. CONCLUSIONS: Multifetal pregnancy reduction has been shown to be a safe and effective method to improve outcome in multifetal pregnancies. Outcomes are worse with higher-order gestations and support the need for continued vigilance of fertility therapy.

Extrathoracic heart (ectopia cordis). Report of two cases and review of the literature.

We report 2 cases of extrathoracic heart (ectopia cordis) operated on a few hours after birth at Laennec Hospital, Paris. The first patient had an associated diastasis of the rectus muscles. The second one, in whom diagnosis was made by ultrasound during fetal life, had a normal abdominal wall. In both cases it was possible to accommodate the heart in the left pleural cavity after a wide dissection of the posterior mediastinum. Both babies, however, died soon after the operation. Double outlet right ventricle was found in both. We have reviewed those cases previously described and discuss the importance of prenatal echocardiographic diagnosis in this rare condition.