Prenatal management of fetal anemia due to pyruvate kinase deficiency: A case report.

BACKGROUND: Pyruvate Kinase (PK) deficiency is the most common enzyme defect of glycolysis, leading to congenital hemolytic anemia, which can occur during the neonatal period. STUDY DESIGN AND METHODS: We report the prenatal management of fetal anemia related to PK deficiency in a family with a severe proband. RESULTS: The couple had a first child born with hydrops, whose PK deficiency was diagnosed at 18 months of life. He was treated with allogeneic bone marrow transplantation. The second child was free from disease. For the third pregnancy, the amniocentesis revealed a PK deficiency. Weekly ultrasound monitoring of the middle cerebral artery velocity allowed the detection of severe fetal anemia. Two intrauterine red blood cell transfusions (IUTs) were performed, raising the fetal hemoglobin from 6.6 to 14.5 g/dl at 28 weeks' gestation and from 8.9 to 15.3 g/dl at 31 weeks. A hematopoietic stem cell allograft was discussed prenatally but not chosen, as it would not have significantly changed the perinatal prognosis. The patient delivered a 2730 g girl at 37 weeks, with hemoglobin of 13.6 g/dl. The child presented with neonatal jaundice treated with phototherapy and received postnatal transfusions. DISCUSSION: When a proband is identified in a family, fetal investigation is warranted, to set up third-trimester ultrasound surveillance and perinatal management. In case of fetal severe anemia of unknown etiology, the workup on fetal blood sampling before IUT should comprise the search for erythrocytes enzymopathies, such as PK deficiency. IUTs allow safer full-term delivery in cases with PK deficiency.

Can Children With Perinatal Stroke Use a Simple Brain Computer Interface?

Background and Purpose: Perinatal stroke is the leading cause of hemiparetic cerebral palsy resulting in lifelong disability for millions of people worldwide. Options for motor rehabilitation are limited, especially for the most severely affected children. Brain computer interfaces (BCIs) sample brain activity to allow users to control external devices. Functional electrical stimulation enhances motor recovery after stroke, and BCI-activated functional electrical stimulation was recently shown to improve upper extremity function in adult stroke. We aimed to determine the ability of children with perinatal stroke to operate a simple BCI. Methods: Twenty-one children with magnetic resonance imaging­confirmed perinatal stroke (57% male, mean [SD] 13.5 [2.6] years, range 9­18) were compared with 24 typically developing controls (71% male, mean age [SD] 13.7 [3.7] years, range 6­18). Participants trained on a simple EEG-based BCI over 2 sessions (10 trials each) utilizing 2 different mental imagery strategies: (1) motor imagery (imagine opening and closing of hands) and (2) goal oriented (imagine effector object moving toward target) to complete 2 tasks: (1) drive a remote controlled car to a target and (2) move a computer cursor to a target. Primary outcome was Cohen Kappa with a score >0.40 suggesting BCI competence. Results: BCI performance was comparable between stroke and control participants. Mean scores were 0.39 (0.18) for stroke versus 0.42 (0.18) for controls (t[42]=0.478, P=0.94). No difference in performance between venous (M=0.45, SD=0.29) and arterial (M=0.34, SD=0.22) stroke (t[82]=1.89, P=0.090) was observed. No effect of task or strategy was observed in the stroke participants. Over 90% of stroke participants demonstrated competency on at least one of the 4 task-strategy combinations. Conclusions: Children with perinatal stroke can achieve proficiency in basic tasks using simple BCI systems. Future directions include exploration of BCI-functional electrical stimulation systems for rehabilitation for children with hemiparesis and other forms of cerebral palsy.

Excessive Prenatal Supplementation of Iodine and Fetal Goiter: Report of Two Cases Using Three-dimensional Ultrasound and Magnetic Resonance Imaging.

Fetal thyroid complications in pregnancy are uncommon, and are commonly related to the passage of substances through the placenta. The excessive iodine intake during the pregnancy is a well-known mechanism of fetal thyroid enlargement or goiter, and invasive procedures have been proposed for the treatment of fetal thyroid pathologies. In the present report, we demonstrate two cases from different centers of prenatal diagnosis of fetal thyroid enlargement and/or goiter in three fetuses (one pair of twins, wherein both fetuses were affected, and one singleton pregnancy). The anamnesis revealed the ingestion of iodine by the patients, prescribed from inadequate vitamin supplementation. In both cases, the cessation of iodine supplement intake resulted in a marked reduction of the volume of the fetal thyroid glands, demonstrating that conservative treatment may be an option in those cases. Also, clinicians must be aware that patients may be exposed to harmful dosages or substances during pregnancy.

As complicações fetais da tireoide na gravidez são incomuns e são comumente relacionadas à passagem de substâncias pela placenta. A ingestão excessiva de iodo durante a gravidez é um mecanismo bem conhecido de aumento da tireoide ou bócio fetal, e procedimentos invasivos foram propostos para o tratamento de patologias da tireoide fetal. No presente relato de caso, demonstramos dois casos de diferentes centros de diagnóstico pré-natal de aumento da tireoide fetal e/ou bócio em três fetos (um par de gêmeos, em que ambos os fetos foram afetados, e uma gravidez única). A anamnese revelou a ingestão de iodo pelos pacientes prescrita por suplementação inadequada de vitaminas. Nos dois casos, a interrupção da ingestão de suplemento de iodo resultou em uma redução acentuada do volume das glândulas tireoides fetais, demonstrando que o tratamento conservador pode ser uma opção nestes casos. Além disso, os médicos devem estar cientes de que as pacientes podem ser expostas a doses ou substâncias nocivas durante a gravidez.

Excessive prenatal supplementation of iodine and fetal goiter: report of two cases using three-dimensional ultrasound and magnetic resonance imaging / Suplementação pré-natal excessiva de iodo e bócio fetal: Relato de dois casos utilizando ultrassonografia tridimensional e ressonância magnética

Abstract Fetal thyroid complications in pregnancy are uncommon, and are commonly related to the passage of substances through the placenta. The excessive iodine intake during the pregnancy is a well-known mechanism of fetal thyroid enlargement or goiter, and invasive procedures have been proposed for the treatment of fetal thyroid pathologies. In the present report, we demonstrate two cases from different centers of prenatal diagnosis of fetal thyroid enlargement and/or goiter in three fetuses (one pair of twins, wherein both fetuses were affected, and one singleton pregnancy). The anamnesis revealed the ingestion of iodine by the patients, prescribed from inadequate vitamin supplementation. In both cases, the cessation of iodine supplement intake resulted in a marked reduction of the volume of the fetal thyroid glands, demonstrating that conservative treatmentmay be an option in those cases. Also, clinicians must be aware that patients may be exposed to harmful dosages or substances during pregnancy.

Resumo As complicações fetais da tireoide na gravidez são incomuns e são comumente relacionadas à passagem de substâncias pela placenta. A ingestão excessiva de iodo durante a gravidez é um mecanismo bem conhecido de aumento da tireoide ou bócio fetal, e procedimentos invasivos foram propostos para o tratamento de patologias da tireoide fetal. No presente relato de caso, demonstramos dois casos de diferentes centros de diagnóstico pré-natal de aumento da tireoide fetal e/ou bócio em três fetos (um par de gêmeos, em que ambos os fetos foram afetados, e uma gravidez única). A anamnese revelou a ingestão de iodo pelos pacientes prescrita por suplementação inadequada de vitaminas. Nos dois casos, a interrupção da ingestão de suplemento de iodo resultou em uma redução acentuada do volume das glândulas tireoides fetais, demonstrando que o tratamento conservador pode ser uma opção nestes casos. Além disso, os médicos devem estar cientes de que as pacientes podem ser expostas a doses ou substâncias nocivas durante a gravidez.

Fully automatic 3D reconstruction of the placenta and its peripheral vasculature in intrauterine fetal MRI.

Recent advances in fetal magnetic resonance imaging (MRI) open the door to improved detection and characterization of fetal and placental abnormalities. Since interpreting MRI data can be complex and ambiguous, there is a need for robust computational methods able to quantify placental anatomy (including its vasculature) and function. In this work, we propose a novel fully-automated method to segment the placenta and its peripheral blood vessels from fetal MRI. First, a super-resolution reconstruction of the uterus is generated by combining axial, sagittal and coronal views. The placenta is then segmented using 3D Gabor filters, texture features and Support Vector Machines. A uterus edge-based instance selection is proposed to identify the support vectors defining the placenta boundary. Subsequently, peripheral blood vessels are extracted through a curvature-based corner detector. Our approach is validated on a rich set of 44 control and pathological cases: singleton and (normal / monochorionic) twin pregnancies between 25-37 weeks of gestation. Dice coefficients of 0.82 â€¯±â€¯ 0.02 and 0.81 â€¯±â€¯ 0.08 are achieved for placenta and its vasculature segmentation, respectively. A comparative analysis with state of the art convolutional neural networks (CNN), namely, 3D U-Net, V-Net, DeepMedic, Holistic3D Net, HighRes3D Net and Dense V-Net is also conducted for placenta localization, with our method outperforming all CNN approaches. Results suggest that our methodology can aid the diagnosis and surgical planning of severe fetal disorders.

Fetal intracranial hemorrhage due to maternal subclinical vitamin K deficiency associated with long-term eating disorder.

Vitamin K deficiency in pregnant women causes intracranial hemorrhage (ICH) in fetuses. Fetal ICH frequently causes life-threatening and persistent neurological damage. However, indicators for preventing fetal ICH are not established. Two pregnant women developed long-term eating disorders caused by psychosis. They were administered intravenous fluid and vitamin supplementation, excluding vitamin K. The intracranial low-hypoechoic area on fetal ultrasound was suggestive of fetal ICH due to vitamin K deficiency. Their neonates showed severe developmental delay. Laboratory analysis revealed a normal prothrombin time, but elevated protein induced by vitamin K absence II. Pregnant women who have eating disorders more than 3 weeks could develop fetal ICH due to maternal subclinical vitamin K deficiency. Illness duration and protein induced by vitamin K absence II of pregnant woman may be indicators for vitamin K administration to prevent fetal intracranial hemorrhage.

Maternal Iodine Exposure: A Case of Fetal Goiter and Neonatal Hearing Loss.

A 27-year-old gravid 1 at 27 weeks 6 days with a history of hypothyroidism had an ultrasound that demonstrated a 3.9 × 3.2 × 3.3-cm well-circumscribed anterior neck mass, an extended fetal head, and polyhydramnios. Further characterization by magnetic resonance imaging (MRI) showed a fetal goiter. During her evaluation for the underlying cause of the fetal goiter, the patient revealed she was taking nutritional iodine supplements for treatment of her hypothyroidism. She was ingesting 62.5 times the recommended amount of daily iodine in pregnancy. The excessive iodine consumption caused suppression of the fetal thyroid hormone production, resulting in hypothyroidism and goiter formation. After the iodine supplement was discontinued, the fetal goiter decreased in size. At delivery, the airway was not compromised. The infant was found to have reversible hypothyroidism and bilateral hearing loss postnatally. This case illustrates the importance of examining for iatrogenic causes for fetal anomalies, especially in unregulated nutritional supplements.

[THE FETAL MIDDLE CEREBRAL ARTERY PEAK SYSTOLIC VELOCITY AS A PEDICTOR OF FETAL ANEMIA IN RH-ALLOIMMUNIZED PREGNANCY].

UNLABELLED: Rh-isoimmunization is a pathological condition in which the fetal red blood cells of a Rh (+) fetus are destroyed by the isoantibodies of a Rh (-) woman sensitized in a previous event. Despite of the wide spread implementation of anti D-gammaglobolin prophylaxis this is still the most common cause for fetal anemia. Recently, sonographic measurement of the fetal middle cerebral artery peak systolic velocity (MCA-PSV) has been shown to be an accurate non-invasive test to predict low fetal hemoglobin levels. We present a case report of Rh-alloimmunized pregnancy with moderate fetal anemia, followed-up by weekly MCA-PSV measurements. CASE REPORT: A 37-year-old Rh (-) negative gravida 3, para 1, without anti-D gammaglobolin prophylaxis in her previous pregnancies, presented at 27+0 weeks of gestation (w.g.) for a routine third trimester scan. Subsequent ultrasound measurements of MCA-PSV confirmed a progressive increase of the peak systolic velocities from 40 to 80 cm/sec, as well as a gradual rise in the anti-D titers. The evidence of developing fetal anemia necessitated elective Caesarean section performed at 35 wg. The neonate was admitted in the intensive care unit and required resuscitation, one exchange blood transfusion and several courses of phototherapy. The patient was discharged two weeks post partum. CONCLUSIONS: There is a strong correlation between the high peak systolic velocities in the middle cerebral artery (MCA-PSV) and the low levels of fetal hemoglobin. The high sensitivity and positive predictive value concerning the development of fetal anemia, as well as its good repeatability, makes this non-invasive test a valuable asset in the management of all pregnancies complicated by severe Rh-alloimmunization.

[PREVFNAIT prevention of foetal/neonatal alloimmune thrombocytopenia (FNAIT) in Polish foetuses and newborns--the PREVFNAIT program]. / Zapobieganie alloimmunologicznej maloplytkowosci plodów i noworodków (AIMPN) w Polsce--program PREVFNAIT.

The scientific goals related to the grant include 1) estimation of FNAIT prevalence in Poland and 2) search for biomarkers to predict the risk of the antibody production and severity of fetal thrombocytopenia. Fetal/Neonatal Alloimmune Thrombocytopenia (FNAIT) is caused by destruction of fetal blood platelets due to maternal antibodies. This condition, which most commonly results from incompatibility between the mother and the fetus for the Human Platelet Antigen-1a (HPA-1a), may lead to intracranial hemorrhage, damage of the central nervous system (CNS) and even death of the fetus or the newborn. It can be the cause of strokes in term newborns. FNAIT is usually attributed to the presence of anti-HPA-1a antibodies. Its incidence rate is estimated at approximately 1/1000-2000 live births. In the absence of a screening program, it is usually diagnosed after birth of a child with symptoms of thrombocytopenia or CNS hemorrhage. Monitoring of antibody production and thrombocytopenia treatment to effectively minimize the risk of stroke are therefore launched only at the next pregnancy. Testing indications are broader to include fetal ultrasound for symptoms of stroke to the CNS, ventricular enlargement or hydrocephalus, and obstetric failure. Diagnostic process is also recommended prior to the planned cordocentesis, in vitro fertilization and in sisters of mothers with children with FNAIT history. HPA-1a testing remains the best method for diagnosing pregnancies at risk. The detection frequency for FNAIT in Poland remains low. Therefore, the Institute of Hematology and Transfusion Medicine (IHTM) will have performed such HPA-1a antigen testing in 30 000 Polish women within the framework of the PREVFNAIT program by March 2016. HPA-1a negative women (2% of the population) are a risk group for production of anti- HPA-1a antibodies responsible for FNAIT therefore all of them will be monitored for the presence and activity of anti-HPA-1a antibodies. Such testing will be performed free of charge for the women.

Evaluation of oxidative stress in placenta of fetal cardiac dysfunction rat model and antioxidant defenses of maternal vitamin C supplementation with the impacts on P-glycoprotein.

AIM: The oxidative stress of placenta during fetal heart dysfunction (FHD) is lack of evaluation. So, we carried out an experiment to explore whether vitamin C (VitC) can be supplied for placental protection under FHD and its impacts on P-glycoprotein expression. METHODS: Fetal heart dysfunction was induced by two intra-amniotic injections of isoproterenol, then (VitC) was supplied. Hematoxylin-eosin (HE) staining was used to evaluate placental histology, and oxidative stress was measured by total antioxidant capacity, total superoxide dismutase and level of advanced oxidation protein products (AOPP), as well as apoptosis rate. Real-time polymerase chain reaction was adopted to measure the expressions of superoxide dismutase-1 (Sod-1), glutathione peroxidase-1 (Gpx-1) and endothelial nitric oxide synthase (eNOS) in placenta. Finally, western blot was performed to detect P-glycoprotein expression. RESULTS: All isoproterenol twice-treated fetuses exhibited significant (P < 0.05) contractile dysfunction by fetal echocardiography compared to others. The HE staining showed severe placental hydrops in the FHD group, and that hydrops could be reduced by VitC treatment. Total antioxidant capacity and total Sod-1 decreased in FHD and elevated after VitC supplementation. Also, level of AOPP increased in FHD and dropped after VitC supplementation. Analysis of apoptosis demonstrated that there was a mild increase in apoptosis rate of FHD. Reductions of Sod-1 and eNOS mRNA expression were confirmed in FHD, but these could recovered after VitC supplementation, with the same tendency of the P-glycoprotein. CONCLUSION: Severe oxidative injuries were identified in placentas of FHD with P-glycoprotein repression. VitC administration can reduce the oxidative stress and rebuild the protective mechanism of placenta.

Conservatively managed fetal goiter: an alternative to in utero therapy.

Fetal goiter may arise from a variety of etiologies including iodine deficiency, overtreatment of maternal Graves' disease, inappropriate maternal thyroid replacement and, rarely, congenital hypothyroidism. Fetal goiter is often associated with a retroflexed neck and polyhydramnios, raising concerns regarding airway obstruction in such cases. Prior reports have advocated for cordocentesis and intra-amniotic thyroid hormone therapy in order to confirm the diagnosis of fetal thyroid dysfunction, reduce the size of the fetal goiter, reduce polyhydramnios, aid with the assistance of maternal thyroid hormone therapy and reduce fetal malpresentation. We report two cases of conservatively managed fetal goiter, one resulting in a vaginal delivery, and no evidence of postnatal respiratory distress despite the presence of polyhydramnios and a retroflexed neck on prenatal ultrasound.

Isolated congenital megacystis without intestinal obstruction: a mild variant of chronic intestinal pseudoobstruction syndrome?

Megacystis is frequently involved with chronic intestinal pseudoobstruction syndrome; however, isolated megacystis without intestinal obstruction is extremely rare. We present the case of a female patient with isolated congenital megacystis without severe intestinal obstruction. In this case, barium enema did not reveal any significant findings; however, histologic evaluation of her rectum showed hypoganglionosis of the submucous and myenteric plexuses. These findings indicate that this case may be a mild variant of chronic intestinal pseudoobstruction syndrome. The presence of megacystis should alert the physician to the possibility of chronic intestinal pseudoobstruction syndrome.

Middle cerebral artery-peak systolic velocity in dizygotic twins with anti-E alloimmunization.

Middle cerebral artery-peak systolic velocity (MCA-PSV) has been reported to predict fetal anemia with similar accuracy as amniotic ΔOD450 assay. Alloimmunized dizygotic twin pregnancy allows us to compare anemic and non-anemic twins in the same intrauterine environment. We herein present a case of Rh (E)-incompatible dizygotic twin pregnancy, where MCA-PSV could precisely detect the anemia in one of the twins. A 36-year-old woman, whose previous child required exchange transfusion due to hemolytic anemia of newborn (HFDN), conceived twins after in vitro fertilization-embryo transfer. At 24 weeks' gestation, MCA-PSV of twin A and twin B were 23.9 cm/s (0.8 multiples of median; MoM) and 30.7 cm/s (1.0 MoM), respectively. At 31 weeks' gestation, MCA-PSV values of both twins were sharply elevated to nearly 1.4 MoM. Thereafter, MCA-PSV of twin A fell to 1.0 MoM, whereas MCA-PSV of twin B exceeded 1.5 MoM at 34 weeks' gestation. Development of fetal anemia was suspected and emergency cesarean section was performed. Twin B showed moderate anemia with positive direct Coombs' test and was diagnosed as HFDN due to anti-E alloimmunization. Twin B required phototherapy and red cell transfusion, but exchange transfusion was safely obviated.

Management of red cell alloimmunized pregnancies using conventional methods compared with that of middle cerebral artery peak systolic velocity.

The aim of this retrospective study was to find out the effect of change in the management of red cell alloimmunized pregnancies from conventional method of amniocentesis to the Doppler assessment of middle cerebral artery peak systolic velocity (MCA-PSV). There were 29 alloimmunized pregnancies affected by red cell antibodies. Ten cases were managed by amniocentesis and another 19 were managed by MCA-PSV measurements. The antenatal management and perinatal outcome of both groups are presented. This study suggests that the non-invasive monitoring should be the method of choice to monitor alloimmunized pregnancies.

Foetal chondrodysplasia: intrauterine diagnosis.

Chondrodysplasias are rare occurrence. We present a case of short-limbed chondrodyplasia diagnosed in a 22 week fetus of a 28 year old. She was para 4(+0) with two children alive. She had similar occurrences in her last two pregnancies. The index pregnancy and the last two eventful pregnancies were preceded with ingestion of trado-herbal drug to treat subfertility.

Reassuring fetal middle cerebral artery doppler velocimetry in alloimmunised pregnancies: neonatal outcomes without invasive procedures.

OBJECTIVE: To assess the neonatal outcome in red blood cell alloimmunised pregnancies at increased risk of fetal anaemia where invasive testing was avoided based on reassuring middle cerebral artery (MCA) Doppler velocity results. METHODS: We included 28 alloimmunised pregnant women at significant risk of fetal or neonatal anaemia who did not have invasive testing because of reassuring MCA Doppler velocimetry. Women requiring invasive testing or intrauterine transfusion were excluded. Outcome measures were admission to neonatal intensive care unit, cord haemoglobin and bilirubin levels and neonatal therapy. RESULTS: Ten neonates (36%) were anaemic at birth while 18 (64%) had normal haemoglobin. Seven neonates (25%) did not require any form of neonatal therapy, 10 (36%) had phototherapy only, 7 (25%) required exchange transfusions and 4 (14%) top-up transfusions. There were no treatment-related complications. Mean cord haemoglobin was 13.9 g/dl (range 7-18.9) and mean bilirubin was 84.1 micromol/l (range 29-192). CONCLUSION: Avoiding invasive procedures in pregnancies at risk of fetal anaemia by relying on reassuring MCA Doppler velocimetry did not result in life-threatening fetal or neonatal morbidities. The extent of neonatal therapy was acceptable. The routine use of this test can lead to less unnecessary invasive procedures in at-risk fetuses.

Nitroglycerin for relaxation to establish a fetal airway (EXIT procedure).

BACKGROUND: The ex utero intrapartum treatment (EXIT) procedure is a technique designed to establish an airway at the time of delivery in fetuses at risk of airway obstruction and requires maintenance of uterine relaxation to continue placental perfusion and prevent placental separation. We describe the use of intravenous nitroglycerin to maintain uterine relaxation during the EXIT procedure. CASE: A 17-year-old primigravida with a fetus known to have an anterior neck mass was admitted for a scheduled operative delivery at 38 weeks of gestation using a modified EXIT procedure. Anesthesia was administered with a combined spinal-epidural technique. Intravenous nitroglycerin was administered as a bolus and then as a continuous infusion to maintain uterine relaxation until evaluation of the neonatal airway was completed. CONCLUSION: Intravenous nitroglycerin is an effective agent for maintenance of uterine relaxation and placental perfusion during the EXIT procedure.

Presenting and discussing nuchal translucency screening for fetal abnormality in the UK.

OBJECTIVE: to investigate the relationship between information giving by midwives and decision-making by women offered nuchal translucency (NT) screening. To establish how risk figures are discussed in practice, with the intention of relating this to the existing, and often critical, literature on women's accounts of antenatal screening. DESIGN: a qualitative study following women through the process of being offered and deciding to undergo NT screening. Tape recording of consultations, analysed in their entirety, was combined with post-screening interviews. SETTING: a large teaching hospital in the UK. PARTICIPANTS: fourteen pregnant women eligible for NT screening at the time of recruitment. DATA COLLECTION: (i) tape recordings of consultations between community midwives and pregnant women where nuchal translucency screening was offered; (ii) tape recordings of consultations between hospital midwives and pregnant women immediately post-screening; (iii) individual face-to-face interviews with pregnant women between two and six weeks after the screening, carried out by the first author. FINDINGS: NT screening was in general well received, particularly by those women who had undergone serum screening with previous pregnancies. However, communicating the nature of a risk figure is an interactionally complex process. A large amount of interactional work is required by midwives both before and after screening to ensure that women comprehend this information. Despite the emphasis placed in these consultations on understanding the purpose of NT screening and the status of the results, women often framed their decision to undergo NT screening in terms of it being a formality, or of presuming that all was well. This sometimes created practical and personal difficulties in terms of decision-making. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: previous sociological and psychological research has tended to be critical of midwives in terms of ensuring informed choice in screening, but this research is often based on post hoc accounts. Examining actual consultations with these accounts helps to illustrate the other factors that affect women's perceptions of testing, and the way in which risk, choice and decision-making are introduced and discussed in practice. Encouraging women to consider what action they might take on the basis of a personally unfavourable NT result in advance of undergoing the scan may help them to decide whether the information gained will be useful to them. Recognising the complex interactional work required in making sure that women understand the nature of the results that will be obtained is an important issue for the education and training of midwives.