Avoiding the Use of Halogenated Anesthetic Agents for Uterine Relaxation in Open Mid-Gestation Fetal Surgery: A Case Report.

INTRODUCTION: Profound uterine relaxation is required for open fetal surgery. This is typically achieved by the administration of high-dose halogenated anesthetic agents. However, this anesthetic technique is associated with adverse cardiovascular effects in the fetus and may have long-term neurocognitive effects as well. CASE PRESENTATION: We pre-sent reports for 2 patients in whom uterine relaxation was maintained with nitroglycerin and magnesium infusions without any exposure to halogenated anesthetic agents. There were no adverse fetal or maternal effects from this technique. DISCUSSION/CONCLUSION: To the best of our knowledge, these are the first reports of open fetal surgery being performed without the use of halogenated anesthetic agents. This has potential short- and long-term benefits for the fetus, particularly as more complex and longer duration minimally invasive procedures are developed.

Spina bifida occulta and aperta: a review of current treatment paradigms.

Spina bifida remains a challenging neurosurgical entity to manage despite both an increased awareness of the disease as well as a decreased incidence due to folic acid supplementation. We review the spectrum of neural tube defects, which are the second most common serious congenital defect and the most common of the central nervous system, and discuss the latest management paradigms. The challenges of timely diagnosis and treatment of spina bifida occulta and the latest advances in fetal repair of spina bifida aperta (myelomeningocele) will be discussed. The authors review the literature and share their experience with managing neural tube defects.

What parents say about disclosing the end of their pregnancy due to fetal abnormality.

OBJECTIVE: to describe men's and women's experiences of deciding whether to tell people in their social network, including their children, about their pregnancy loss following a termination for fetal abnormality. DESIGN: secondary analysis of qualitative narrative interview data informed by a critical realist approach. SETTING: respondents were recruited throughout the United Kingdom and interviewed at home between 2004 and 2005. PARTICIPANTS: twenty-eight women and nine men who had ended a pregnancy diagnosed with a fetal abnormality and who talked about disclosing or not disclosing the termination to others. FINDINGS: few respondents reported having any advice or information about whether or how to disclose their termination. None said they completely concealed their decision from adults in their social network; most said they disclosed selectively, telling close friends and family they had terminated and acquaintances they had miscarried. Most respondents reported telling their young children that the baby had died but did not reveal that they had chosen to end the pregnancy. A minority had not told their existing offspring about the pregnancy loss. Common reasons given for (partially) concealing a termination were: guilt over the decision; to avoid being judged; and to protect other people's feelings. Common reasons for disclosure were: others knew of the pregnancy; needing time off work; needing practical help and/or emotional support during diagnosis and termination; and wanting recognition of their loss. Positive consequences of disclosure were said to be getting more support and less criticism than expected; negative consequences included not getting the anticipated support and empathy; and encountering disapproval. Some respondents felt that concealing their pregnancy loss from their children had resulted in their confusion over the cause of their parents' distress. Some men said they found it hard to access emotional support from their social networks because of expectations about how men 'should' deal with emotions. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: midwives have to make difficult judgements about what, how and when to provide information when trying to support and advise parents who have ended a pregnancy due to fetal abnormality. Further education and training in this area could be of benefit. Midwives could signpost parents to existing sources of advice around disclosure, taking into account parents' individual preferences, help parents to consider the potential implications of disclosure and concealment and different ways of disclosing. They could also recommend alternative sources of emotional support, bearing in mind that men in particular may find it harder to access support from their social networks.

Neural tube defects: review of experimental evidence on stem cell therapy and newer treatment options.

The failure of closure of the neural tube during development leads to malformations called neural tube defects (NTDs). The most common neural malformations in humans include anencephaly, encephalocele, exencephaly, craniorachischisis spina bifida with or without myelomeningocele, lipomyeloschisis, lipomyelomeningocele, meningocele and myelocystocele. Current preventive strategies are mainly based on pharmacologic/folic acid supplementation. However, stem cell-based and other combination approaches may emerge as potential treatment options for NTDs. This review provides an account of experimental evidence on stem cell therapy and newer treatment options for NTDs which have become available in recent years.

A method to reduce the invasiveness of fetal catheterization in the cow.

Surgical intervention in general anesthesia (GA) of the cow in late gestation is a stressful condition for both mother and fetus, potentially leading to premature delivery or fetal death. The present study hypothesized that fetal catheterization at days 246-253 (90% of gestation) is done with less physical and metabolic stress for the mother and fetus, when the surgery is performed on a standing cow and local anesthesia (LA) rather than on a recumbent cow in general anesthesia. Fetal and uterine maternal intra-vascular catheters were implanted during general anesthesia (GA, n=24) or local analgesia (LA, n=7). Blood gases and metabolite levels in the fetal calves and their mothers were measured during surgery and for 5 days post-operatively. During surgery, venous blood pH was higher (7.44 +/- 0.01 versus 7.39 +/- 0.01, P<0.05) and hemoglobin and oxygen contents lower in LA cows compared with GA cows (9.3 +/- 0.3 mg/dl versus 11.8 +/- 0.2 mg/dl, P<0.001 and 10.0 +/- 0.3 ml/dl versus 12.6 +/- 0.6 ml/dl, P<0.05). The differences between the two groups of fetuses reflected those of their dams in that LA fetuses showed lower arterial oxygen pressure (18.3 +/- 1.4 mmHg versus 24.8 +/- 1.4 mmHg, P<0.05) and hemoglobin (7.81 +/- 0.30 mg/dl versus 9.22 +/- 0.21 mg/dl P<0.01) and furthermore, they also showed higher blood glucose (2.4 +/- 0.2 mM versus 1.4 +/- 0.1 mM, P<0.01). During the 5 days post-surgery, 10 GA fetuses (42%) and 1 LA fetus (14%) died in utero. Bacterial contamination was implicated in six of the GA deaths and in the one LA death. In the dams with surviving calves, differences in hemoglobin (9.49 +/- 0.21 mg/dl versus 11.17 +/- 0.23 mg/dl P<0.001) and O2ct (10.9 +/- 0.3 ml/dl versus 12.5 +/- 0.5 ml/dl, P<0.05) were still present, and in addition, blood glucose was higher in LA versus GA cows (4.3 +/- 0.2 mM versus 3.8 +/- 0.1 mM, P<0.05). The choice of surgical method did not affect post-surgery blood chemistry in the surviving fetuses, except that the higher blood glucose in the LA fetuses at surgery tended to be maintained also post-operatively (2.0 +/- 0.2 mM versus 1.5 +/- 0.1 mM, P=0.07). The observed differences in blood chemistry parameters between the two methods of surgery and possibly in the fetal death may be explained by differences in catheterization method and the associated differences in physical and metabolic stress during and after surgery. Thus, surgery upon a standing cow in local anesthesia should be considered as an alternative to surgery in universal anesthesia for fetal catheterization in the cow in late gestation.

Clostridium botulinum toxin inhibits myometrial activity in vitro: possible application on the prevention of preterm labor after fetal surgery.

BACKGROUND/PURPOSE: The current study aimed to analyze the effects of Clostridium botulinum toxin (Botox) on pregnant myometrium activity in vitro. METHODS: Strips of myometrium were obtained from pregnant Wistar rats on gestational day 13 through 15 and placed under controlled conditions within tissue baths containing DeJalon solution. Muscular activity, including amplitude and frequency of contractions, was recorded by a force transducer connected to a polygraph. After stable baseline values were recorded, different concentrations of Botox were added to the tissue baths. Myometrial activity data points for each drug concentration were entered as mean percentual variations of the baseline. A total of 26 uterine samples from 13 animals were studied. Statistical analysis was by single-factor analysis of variance (ANOVA) with P <.05 considered significant. RESULTS: Except for a narrow concentration range, when the effects were nonmonotonic, both amplitude and frequency of myometrial contractions were significantly depressed (P <.05) and eventually totally abolished at most concentrations studied, albeit in a potentially biphasic pattern. Those effects could be reversed by a complete washout of the tissue bath. CONCLUSIONS: Within appropriate concentrations, Botox consistently inhibits or completely arrests myometrial activity in potentially reversible fashion. This agent may prove valuable in premature labor prevention after fetal surgery.

The development of fetal surgery.

The history of fetal surgery features an absolute dependency upon the possibility of diagnosis before birth. Powerful new imaging methods, the techniques of sampling amniotic fluid and fetal tissue, and modern molecular genetics for the prenatal diagnosis of various congenital diseases have removed the veil of secrecy from the fetus. Even though most prenatally detected congenital malformations can be managed after maternal transport, a few simple anatomic defects require fetal surgery, albeit with predictably poor results. The understanding of intrauterine physiology and pathophysiology in several congenital malformations has been worked out in animal model study, and the natural history of congenital defects revealed by prenatal observations on human fetuses. Selection criteria for intrauterine intervention have been developed. Over the last two decades, surgical techniques for open and endoscopic fetal surgery have been defined and anesthesia and tocolysis for fetal surgery improved. As we enter the 21st century, this field of surgery will surely expand.

The development of fetal surgery

The history of fetal surgery features an absolute dependency upon the possibility of diagnosis before birth. Powerful new imaging methods, the techniques of sampling amniotic fluid and fetal tissue, and modern molecular genetics for the prenatal diagnosis of various congenital diseases have removed the veil of secrecy from the fetus. Even though most prenatally detected congenital malformations can be managed after maternal transport, a few simple anatomic defects require fetal surgery, albeit with predictably poor results. The understanding of intrauterine physiology and pathophysiology in several congenital malformations has been worked out in animal model study, and the natural history of congenital defects revealed by prenatal observations on human fetuses. Selection criteria for intrauterine intervention have been developed. Over the last two decades, surgical techniques for open and endoscopic fetal surgery have been defined and anesthesia and tocolysis for fetal surgery improved. As we enter the 21st century, this field of surgery will surely expand.

Prolonged local myometrial blockade prevents preterm labor after fetal surgery in a leporine model.

BACKGROUND/PURPOSE: Postoperative premature labor remains the foremost limiting factor to the development of fetal surgery. Most attempts at controlling this complication have involved the use of drugs delivered systemically to the mother. This study assessed the effects of prolonged local anesthetic blockade of the myometrium on preterm delivery after open fetal surgery. METHODS: Eighteen New Zealand rabbits at 23 days' gestation (term, 31 to 33 days) were divided in three groups. In group I (n = 6), the most proximal fetuses of both uterine horns were submitted to open amputation of a forelimb; in a few animals, one of the uterine horns was empty, hence, only one fetus was manipulated. In groups II (n = 5) and III (n = 7), an identical surgical procedure was performed. In group II, immediately before hysterotomy, the myometrium was injected with 0.5 mL of 0.5% bupivacaine along the incision line. In group III, only saline was injected. In group II, before uterine closure, the incised area of the myometrium was injected with 1.5 mL of a novel suspension of biodegradable polylactic-co-glycolic acid microspheres loaded with 75% w/w bupivacaine and 0.05% w/w dexamethasone. This suspension previously has been shown to provide peripheral nerve blockade for approximately 5 days. In group III, microspheres without any drug were injected. RESULTS: Abortion rates were significantly different among the groups: 83.3% (five of six) for the does in group I, zero in group II, and 71.4% (five of seven) in group III (P < .05). The absence of abortions observed in group II occurred despite the fact that the fetal mortality rate was significantly higher in this group (87.5%, seven of eight fetuses) than in groups I (0) and III (33.3%, 4 of 12 fetuses, P < .05). CONCLUSIONS: Prolonged local blockade of the myometrium with bupivacaine inhibits preterm labor after fetal surgery in rabbits. The high fetal mortality rate observed in this study may be caused by "transplacental" transfer of the local anesthetic to the fetus. Notably, the abortifacient effect of a dead fetus was completely suppressed by the local blockade. Studies using microspheres with local anesthetics that do not cross the placenta, in animal models with longer gestational periods, are warranted.

Management of fetal hemolytic disease by cordocentesis. II. Outcome of treatment.

Forty-eight of 128 pregnancies complicated by maternal red blood cell alloimmunization (49%) received a total of 142 intravascular transfusions (range, 1 to 7) for treatment of severe anemia (hematocrit, less than or equal to 30%). Thirteen fetuses (27%) had hydrops when therapy was initiated. The overall survival rate was 96%. Eighty-five percent of survivors received two or more transfusions before delivery. The mean gestational age at initiation of therapy was 28 weeks (range, 18 to 36 weeks). Bleeding from uterine and umbilical cord puncture sites was not of clinical significance. The most common complication was fetal bradycardia (8%). Simple intravascular transfusion resulted in the replacement of fetal red blood cells with adult red blood cells and suppression of fetal erythropoiesis. By the completion of the second transfusion, on average, less than 1% of circulating red blood cells were fetal. Within 3 weeks of the second transfusion, the mean reticulocyte count was less than 1%. The rate at which the fetal hematocrit declined after a transfusion (exclusive of the first) was inversely related to gestational age (r = -0.84, p less than 0.0001), permitting a 4- to 5-week interval between transfusions after 32 weeks' gestation. A total of 78% of surviving neonates were delivered at term. Neonates transfused more than once antenatally required less phototherapy (75.8 +/- 54 vs 165 +/- 101 hours, p less than 0.003) and, when delivered at term, fewer hospital days (4.8 +/- 2 vs 8.6 +/- 6 days, p = 0.01) compared with those transfused once. We conclude that the treatment of fetal anemia by intrauterine simple intravascular transfusion permits a term delivery in the majority of cases and is associated with high perinatal survival and low perinatal morbidity.

Fetal hypothalamic transplants: neuronal and neurovascular interrelationships.

This investigation is one of a series aimed at developing an understanding of the neuroanatomical correlates of neuronal and vascular interactions that occur between heterografts of normal fetal hypothalamic tissue transplanted into the third cerebral ventricle of adult Brattleboro rats with homozygous autosomal diabetes insipidus (DI). Rapid vascular invasion of fetal neurografts occurred within 3 days and arose from the mantle plexus of portal capillaries in the underlying host median eminence. Host vessels also invaded from the periventricular stratum and preoptic area. In the ventral regions of heterografts neurites were observed to terminate upon perivascular spaces that surrounded local capillaries. Despite the development of apparently normal neurovascular zones, none of the DI host recipients demonstrated an amelioration of polydipsia or polyuria characteristic of diabeties insipidus.

Anaesthesia for fetal surgery.

Anaesthesia for fetal surgery is described as used for thirteen procedures in seven patients. Analgesia was accomplished by local infiltration of lignocaine 1% by the surgeons and small incremental doses of intravenous medication by the anaesthetist as needed to make the mother comfortable and reduce fetal movement. There were no maternal or fetal complications. Ethical issues of this therapy are described.