Inexperienced sonographers can successfully visualize and assess a three-dimensional image of the fetal face using a standardized ultrasound protocol

Introduction: A standardized three-dimensional ultrasonographic (3DUS) protocol is described that allows fetal face reconstruction. Ability to identify cleft lip with 3DUS using this protocol was assessed by operators with minimal 3DUS experience. Material and Methods: 260 stored volumes of fetal face were analyzed using a standardized protocol by operators with different levels of competence in 3DUS. The outcomes studied were: (1) the performance of post-processing 3D face volumes for the detection of facial clefts; (2) the ability of a resident with minimal 3DUS experience to reconstruct the acquired facial volumes, and (3) the time needed to reconstruct each plane to allow proper diagnosis of a cleft. Results: The three orthogonal planes of the fetal face (axial, sagittal and coronal) were adequately reconstructed with similar performance when acquired by a maternal-fetal medicine specialist or by residents with minimal experience (72 vs. 76%, p = 0.629). The learning curve for manipulation of 3DUS volumes of the fetal face corresponds to 30 cases and is independent of the operator's level of experience. Discussion: The learning curve for the standardized protocol we describe is short, even for inexperienced sonographers. This technique might decrease the length of anatomy ultrasounds and improve the ability to visualize fetal face anomalies.

Prenatally engineered autologous amniotic fluid stem cell-based heart valves in the fetal circulation.

Prenatal heart valve interventions aiming at the early and systematic correction of congenital cardiac malformations represent a promising treatment option in maternal-fetal care. However, definite fetal valve replacements require growing implants adaptive to fetal and postnatal development. The presented study investigates the fetal implantation of prenatally engineered living autologous cell-based heart valves. Autologous amniotic fluid cells (AFCs) were isolated from pregnant sheep between 122 and 128 days of gestation via transuterine sonographic sampling. Stented trileaflet heart valves were fabricated from biodegradable PGA-P4HB composite matrices (n = 9) and seeded with AFCs in vitro. Within the same intervention, tissue engineered heart valves (TEHVs) and unseeded controls were implanted orthotopically into the pulmonary position using an in-utero closed-heart hybrid approach. The transapical valve deployments were successful in all animals with acute survival of 77.8% of fetuses. TEHV in-vivo functionality was assessed using echocardiography as well as angiography. Fetuses were harvested up to 1 week after implantation representing a birth-relevant gestational age. TEHVs showed in vivo functionality with intact valvular integrity and absence of thrombus formation. The presented approach may serve as an experimental basis for future human prenatal cardiac interventions using fully biodegradable autologous cell-based living materials.

Inexperienced sonographers can successfully visualize and assess a three-dimensional image of the fetal face using a standardized ultrasound protocol.

Introduction: A standardized three-dimensional ultrasonographic (3DUS) protocol is described that allows fetal face reconstruction. Ability to identify cleft lip with 3DUS using this protocol was assessed by operators with minimal 3DUS experience. Material and Methods: 260 stored volumes of fetal face were analyzed using a standardized protocol by operators with different levels of competence in 3DUS. The outcomes studied were: (1) the performance of post-processing 3D face volumes for the detection of facial clefts; (2) the ability of a resident with minimal 3DUS experience to reconstruct the acquired facial volumes, and (3) the time needed to reconstruct each plane to allow proper diagnosis of a cleft. Results: The three orthogonal planes of the fetal face (axial, sagittal and coronal) were adequately reconstructed with similar performance when acquired by a maternal-fetal medicine specialist or by residents with minimal experience (72 vs. 76%, p = 0.629). The learning curve for manipulation of 3DUS volumes of the fetal face corresponds to 30 cases and is independent of the operator's level of experience. Discussion: The learning curve for the standardized protocol we describe is short, even for inexperienced sonographers. This technique might decrease the length of anatomy ultrasounds and improve the ability to visualize fetal face anomalies.

The current molecular phylogeny of Eutherian mammals challenges previous interpretations of placental evolution.

Based on histology, the placentae of eutherians are currently grouped in epitheliochorial, endotheliochorial and haemochorial placentae. In a haeckelian sense, the epitheliochorial contact with marked histiotrophic feeding by uterine milk is generally considered as primitive, especially since similar contacts exist in Marsupials. In contrast, the more intimate endotheliochorial and haemochorial contact, facilitating haemotrophic nutrition, is interpreted as a derived state. A cladistic analysis based on the phylogenetic relationships established by molecular analyses reveals that the basic clades are all characterized by an endotheliochorial or haemochorial placenta, and that the epitheliochorial placenta evolved at least three times in a convergent manner. This evolution may be explained by the fact that the epitheliochorial placenta in eutherians is more efficient in nutritional transfer (flow rate by exchange surface). Moreover, this arrangement may confer an advantage to the mother who can probably reduce the degree of manipulation by a genetically imprinted embryo.

In utero exposure to immunosuppressive drugs.

The number of pregnant women receiving immunosuppressants for anti-rejection therapy or autoimmune diseases is increasing. All immunosuppressive drugs cross the placenta, raising questions about the long-term outcome of the children exposed in utero. There is no higher risk of congenital anomalies. However, an increased incidence of prematurity, intrauterine growth retardation (IUGR) and generally low birth weight has been reported, as well as maternal hypertension and preeclampsia. The most frequent neonatal complications are those associated with prematurity and IUGR, as well as adrenal insufficiency with corticosteroids, immunological disturbances with azathioprine and cyclosporine, and hyperkalemia with tacrolimus. The long-term follow-up of infants exposed to immunosuppressants in utero is still limited and experimental studies raise the question whether there could be an increased incidence at adult age of some pathologies including renal insufficiency, hypertension and diabetes.

Plutonium from above-ground nuclear tests in milk teeth: investigation of placental transfer in children born between 1951 and 1995 in Switzerland.

BACKGROUND: Occupational risks, the present nuclear threat, and the potential danger associated with nuclear power have raised concerns regarding the metabolism of plutonium in pregnant women. OBJECTIVE: We measured plutonium levels in the milk teeth of children born between 1951 and 1995 to assess the potential risk that plutonium incorporated by pregnant women might pose to the radiosensitive tissues of the fetus through placenta transfer. METHODS: We used milk teeth, whose enamel is formed during pregnancy, to investigate the transfer of plutonium from the mother's blood plasma to the fetus. We measured plutonium using sensitive sector field inductively coupled plasma mass spectrometry techniques. We compared our results with those of a previous study on strontium-90 ((90)Sr) released into the atmosphere after nuclear bomb tests. RESULTS: Results show that plutonium activity peaks in the milk teeth of children born about 10 years before the highest recorded levels of plutonium fallout. By contrast, (90)Sr, which is known to cross the placenta barrier, manifests differently in milk teeth, in accordance with (90)Sr fallout deposition as a function of time. CONCLUSIONS: These findings demonstrate that plutonium found in milk teeth is caused by fallout that was inhaled around the time the milk teeth were shed and not from any accumulation during pregnancy through placenta transfer. Thus, plutonium may not represent a radiologic risk for the radiosensitive tissues of the fetus.

Isolated congenital atrioventricular block diagnosed in utero: natural history and outcome.

BACKGROUND: Isolated congenital atrioventricular block (CAVB) diagnosed in utero is associated with a high morbidity and mortality. Prognosis is especially poor when heart rate drops below 55 beats per minute (bpm) and when fetal hydrops develops. We describe the natural history and outcome of 24 infants with isolated CAVB diagnosed in utero, review the literature, and assess the risk factors that could predict outcome. METHODS: This was a retrospective multicenter study of 24 patients with isolated CAVB diagnosed in utero. RESULTS: CAVB was detected at a mean gestational age (GA) of 24.7 +/- 5.1 weeks. Ten fetuses initially presented with complete heart block. Low heart rate or incomplete heart block was the first documentation of bradyarrhythmia in the other 14 fetuses. In 11 of them, CAVB developed during pregnancy after a median time of 3 (range 1-16) weeks. Fetal hydrops developed in 10 of 24 (42%) fetuses at a mean GA of 27.6 +/- 5.1 weeks. Hydropic fetuses showed lower heart rates during pregnancy (47 +/- 10 bpm) than non-hydropic fetuses (57 +/- 10 bpm). There were three intrauterine deaths; all were hydropic and female. Nine viable females and 12 males were born at a mean GA of 37.1 +/- 6.1 weeks with an average birth weight of 3097 +/- 852 g. Fifteen CAVB patients required pacemaker (PM) intervention, 10 of them immediately after birth. Dilated cardiomyopathy (DCM) developed in three infants of whom two died of congestive heart failure, shortly after the diagnosis was made; one is still alive. Mortality before or after birth was 21%, and was associated with heart rates below 50 bpm and development of fetal hydrops. Poor outcome, defined as death, PM implantation, or development of DCM, occurred in 83% of cases and was associated with heart rates below 60 bpm during pregnancy. CONCLUSIONS: Isolated CAVB diagnosed in utero is associated with high morbidity and mortality. Patients who develop fetal hydrops show lower heart rates during pregnancy than patients who do not. A fetal heart rate below 50 bpm and development of fetal hydrops is associated with increased mortality. Rates below 60 bpm are associated with PM requirement and/or DCM.

Placental transfer of pyrimethamine studied in an ex vivo placental perfusion model.

Pyrimethamine is used as and anti-infectious agent because of its antifolate properties. Its action is synergistic with that of dapsone and sulfamides on Toxoplasma gondii. The goal of the present study was to evaluate the placental transfer of pyrimethamine in an ex vivo model of perfused human placental cotyledon at term. Human placentas were perfused according to the slightly modified method of Schneider. The pyrimethamine fetal transfer rate was approximately 30%, while cotyledon clearance was about 1.8 ml/min. The placental transfer of pyrimethamine seems to be independent of the maternal concentrations of pyrimethamine, suggesting passive diffusion mechanisms or a nonsaturable active transport at the tested concentrations.

Adverse obstetrical and neonatal outcomes in elective and medically indicated inductions of labor at term.

OBJECTIVE: To compare the adverse neonatal and maternal outcomes after medically indicated and elective labor induction. Both induction groups were also compared to women with spontaneous onset of labor. METHOD: Retrospective cohort study of 13 971 women with live, cephalic singleton pregnancies who delivered at term (from 1997 to 2007). Adverse maternal and neonatal outcomes were compared between women who underwent an induction of labor in the presence and absence of standard medical indications. RESULTS: Among 5090 patients with induced labor, 2059 (40.5%) underwent elective labor inductions, defined as inductions without any medical or obstetrical indication. Risks of cesarean or instrumental delivery, postpartum hemorrhage >500 ml, prolonged maternal hospitalization >6 days, Apgar<7 at 5 min of life, arterial umbilical cord pH<7.1, admission in neonatal intensive care unit (NICU) and prolonged NICU hospitalization >7 days were similar between nulliparous who underwent elective and medical labor induction. Similar results were obtained for multiparous. All the above mentioned risks, but the Apgar<7 at 5 min of life, were significantly increased after induction in comparison to spontaneous labor. CONCLUSION: Elective induction of labor carries similar obstetrical and neonatal risks as a medically indicated labor induction. Thus, elective induction of labor should be strongly discouraged.

Intrauterine growth restriction is associated with structural alterations in human umbilical cord and decreased nitric oxide-induced relaxation of umbilical vein.

INTRODUCTION: Intrauterine growth restriction (IUGR) affects ∼8% of all pregnancies and is associated with major perinatal mortality and morbidity, and with an increased risk to develop cardiovascular diseases in adulthood. Despite identification of several risk factors, the mechanisms implicated in the development of IUGR remain poorly understood. In case of placental insufficiency, reduced delivery of oxygen and/or nutrients to the fetus could be associated with alterations in the umbilical circulation, contributing further to the impairment of maternal-fetal exchanges. We compared the structural and functional properties of umbilical cords from growth-restricted and appropriate for gestational age (AGA) term newborns, with particular attention to the umbilical vein (UV). METHODS: Human umbilical cords were collected at delivery. Morphological changes were investigated by histomorphometry, and UV's reactivity by pharmacological studies. RESULTS: Growth-restricted newborns displayed significantly lower growth parameters, placental weight and umbilical cord diameter than AGA controls. Total cross-section and smooth muscle areas were significantly smaller in UV of growth-restricted neonates than in controls. Maximal vasoconstriction achieved in isolated UV was lower in growth-restricted boys than in controls, whereas nitric oxide-induced relaxation was significantly reduced in UV of growth-restricted girls compared to controls. CONCLUSION: IUGR is associated with structural alterations of the UV in both genders, and with a decreased nitric oxide-induced relaxation in UV of newborn girls, whereas boys display impaired vasoconstriction. Further investigations will allow to better understand the regulation of umbilical circulation in growth-restricted neonates, which could contribute to devise potential novel therapeutic strategies to prevent or limit the development of IUGR.

Exposition aux immunosuppresseurs in utero [Exposure in utero to immunosuppressives]

The number of pregnant women receiving immunosuppressive therapy is increasing. Use of immunosuppressants during pregnancy is indicated for anti-rejection therapy in transplantation patients and treatment of autoimmune diseases. Despite the maternal and fetal risks of these pregnancies, the proportion of surviving infants is improving and the possibility that a pregnancy could occur in these women during their childbearing years should be considered. All immunosuppressant drugs and their metabolites cross the placenta, raising questions about the long-term outcome of the children exposed to these agents in utera. There is no increased risk of congenital anomalies. However, there is an elevated incidence of prematurity, intrauterine growth retardation (IUGR) and therefore low birthweight, as well as maternal hypertension and preeclampsia. The most frequent neonatal complications are those associated with prematurity and IUGR, as well as adrenal insufficiency with corticosteroids, immunological disturbances with azathioprine and cyclosporin, and hyperkalemia with tacrolimus. The long-term follow-up of infants exposed to immunosuppressants in utero is still limited and experimental studies raise the question whether there could be an increased incidence at adult age of some pathologies including renal insufficiency, hypertension and diabetes. The follow-up of these infants should be carefully organized and multidisciplinary, taking the perinatal context into account.

Enzyme polymorphism and clinical variability of diseases: a study of diabetes mellitus.

We investigated possible relations among four common neonatal manifestations of diabetic pregnancy (macrosomia, hypoglycemia, hypocalcemia, jaundice) and four enzyme polymorphisms (PGM1, ADA, AK1, ACP1 in a sample of infants born of diabetic mothers. The pattern of associations observed between the two sets of variables is consistent with known differences in enzymatic activity within phenotypes of each system, suggesting that low enzymatic activity may have unfavorable effects on fetal development and on adaptability of the neonate to the extrauterine environment, Some of the polymorphic enzymes studied influence fetal growth in normal pregnancy as well. Analysis of relations between genetic polymorphisms and the clinical pattern of common diseases may provide a better understanding of the genetic basis of the clinical variability of diseases within and between human populations.

When the spleen meets the fetus.

Patient's first pregnancy was complicated by mild thrombocytopenia caused by a 13-cm splenic cyst, who delivered vaginally without complication. Risks and management of maternal splenic cysts in pregnancy and delivery are reviewed here.

Maternal coping, appraisals and adjustment following diagnosis of fetal anomaly.

OBJECTIVE: So far, associations between appraisals, maternal adjustment and coping following diagnosis of fetal anomaly have not been investigated in women who continue with their pregnancy. METHOD: This study measured maternal coping and adjustment after and appraisal of a diagnosis of fetal anomaly in 40 mothers who had continued with their pregnancy using a cross-sectional questionnaire design. RESULTS: Based on retrospective reporting, 35% of participants met full diagnostic criteria for post-traumatic stress disorder after having received the diagnosis. Women were significantly more depressed (p < 0.001) and anxious (p < 0.001) and reported significantly less positive affect (p < 0.05) after having received the diagnosis in comparison to the time after childbirth. There were no significant differences between emotion-focused and problem-focused coping. Stressful life events, women's age, number of people providing support and problem-focused coping explained 57.6% of variance in anxiety and depression after childbirth. Satisfaction with social support, emotion-focused coping and problem-focused coping significantly explained 40.6% of variance in positive affect after childbirth. CONCLUSION: Following a prenatal diagnosis and for the remainder of their pregnancy, particular attention should be paid to older mothers, those experiencing additional stressful life events and those who are socially isolated, as these women may experience greater distress after childbirth.