Previable Fetuses Research Articles

An Imperative Role of Fetal Autopsy in Previable Fetuses - ADAM Complex Revisited

Abstract Objective To identify the occurrence of the amniotic deformity adhesions, mutilation (ADAM) complex and imperative role of fetal autopsy in diagnosing this condition. Methods A retrospective descriptive study spanning nine years, from January 2014 to January 2022, was conducted at the Department of Pathology within a tertiary care hospital in South India. The study focused on analyzing the clinical presentation, prenatal ultrasonogram, and morphological features of fetuses with the ADAM complex, limb body wall complex, or amniotic bands. Results Among the 438 fetuses assessed during the study period, five fetuses showed features of the ADAM complex (0.01%). The most frequent gestational age observed was 12–18 weeks and most fetuses were female. The common anomaly encountered was limb defects, followed by abdominal and cranial anomalies. Conclusion The diagnosis of the ADAM complex relies primarily on fetal autopsy to differentiate it from similar conditions like anencephaly or body-stalk anomalies. The pathologist plays a crucial role in understanding the complexities of the ADAM complex. Advanced antenatal imaging and therapies offer potential for prevention through improved counseling.

The outcome of cervical stitch in the prevention of pre-viable and preterm deliveries in Nigerian Tertiary Hospital

Background: Cervical incompetence, defined as the inability to sustain a pregnancy to term due to functional and anatomical defects of the cervix is a distressing cause of childlessness in Nigeria. Cervical cerclage, introduced into clinical practice by Shirodkar and McDonald in the 1950s still a time-tested intervention in the prevention of pregnancy wastages from cervical incompetence. Aim: The purpose of this study was to audit the outcome of the applications of cervical cerclages in the prevention of pregnancy wastages at the Maternity Complex of the Ekiti State University Teaching Hospital and Maternal and Child Specialists’ Clinic in Ekiti State, Southwest Nigeria. Methods: In this prospective observational cohort study, we included all pregnant women who had cervical stitches applied over ten years, (2010-2019). Information on sociodemographic biodata, risk factors, indications, and outcomes were collated. Statistical analysis was performed using the SPSS package, version 22 (SPSS Inc, Chicago, IL). Statistical significance of the categorical variables was tested using the chi-square or Fisher’s exact test, confidence level of 95%and P-value of 0.05. Results: The 134 pregnant women diagnosed with cervical incompetence had cervical stitches applied over the ten years. 15,037 deliveries giving a prevalence rate of 0.89% of cervical incompetence. 75% were multigravida, while 92.5% were of low parity. Risk factors found included recurrent mid-trimester abortions (55%), and prior cervical dilatation (20%). The cervical cerclages were history and physical examination indicated in 22.5% and 75% had ultrasound scanning confirmation. In the majority (82.5%), cervical cerclage was placed at 14-16 weeks using Mersilene tape in 92.5%. Spinal anesthesia and conscious sedation were administered in equal proportion. Majority had McDonald’s procedure (96.27%) whereas only 3.73% had Shirodkar’s. Placement to removal interval ranged from 10-20 weeks in 53%, while in 12.5% it lasted 4 weeks. The indications for removal included pregnancy carried to term at 72.5%, preterm labor at 7.5%, and vagina bleeding occurred in 7.5% of cases. Vaginal deliveries were achieved in 62.5% while 25% had cesarean delivery. 7.5% expelled pre-viable fetuses. Cervical cerclage placement was successful in 75%, while 25% had failed cerclage. 10% of those who had failed cerclage had live births. We achieved 85% of babies take home. There was no significant association between the overall outcomes of cervical cerclage (inevitable abortion, preterm delivery, term delivery) and certain defined co-variables (age, gravidity, and parity). On multivariate linear regression. Conclusion: We recommend that timely application of cervical stitches will rescue women from pregnancy wastages associated with cervical incompetence in Ekiti State.

Intussusceptive-like angiogenesis in human fetal lung xenografts: Link with bronchopulmonary dysplasia-associated microvascular dysangiogenesis?

ABSTRACTBackground: Human fetal lung xenografts display an unusual pattern of non-sprouting, plexus-forming angiogenesis that is reminiscent of the dysmorphic angioarchitecture described in bronchopulmonary dysplasia (BPD). The aim of this study was to determine the clinicopathological correlates, growth characteristics and molecular regulation of this aberrant form of graft angiogenesis. Methods: Fetal lung xenografts, derived from 12 previable fetuses (15 to 22 weeks’ gestation) and engrafted in the renal subcapsular space of SCID-beige mice, were analyzed 4 weeks posttransplantation for morphology, vascularization, proliferative activity and gene expression. Results: Focal plexus-forming angiogenesis (PFA) was observed in 60/230 (26%) of xenografts. PFA was characterized by a complex network of tortuous nonsprouting vascular structures with low endothelial proliferative activity, suggestive of intussusceptive-type angiogenesis. There was no correlation between the occurrence of PFA and gestational age or time interval between delivery and engraftment. PFA was preferentially localized in the relatively hypoxic central subcapsular area. Microarray analysis suggested altered expression of 15 genes in graft regions with PFA, of which 7 are known angiogenic/lymphangiogenic regulators and 5 are known hypoxia-inducible genes. qRT-PCR analysis confirmed significant upregulation of SULF2, IGF2, and HMOX1 in graft regions with PFA. Conclusion: These observations in human fetal lungs ex vivo suggest that postcanalicular lungs can switch from sprouting angiogenesis to an aberrant intussusceptive-type of angiogenesis that is highly reminiscent of BPD-associated dysangiogenesis. While circumstantial evidence suggests hypoxia may be implicated, the exact triggering mechanisms, molecular regulation and clinical implications of this angiogenic switch in preterm lungs in vivo remain to be determined.

Ethical and legal dilemmas around termination of pregnancy for severe fetal anomalies: A review of two African neonates presenting with ventriculomegaly and holoprosencephaly.

Termination of pregnancy (TOP) or feticide for severe fetal anomalies is ethically and morally challenging and maybe considered illegal in countries with restrictive abortion laws. While diagnostic modalities such as fetal ultrasound, magnetic resonance imaging, and genetic screening have improved prenatal diagnosis, these technologies remain scarce in many African countries making diagnosis and counseling regarding TOP difficult. Ethical dilemmas such as women's autonomy rights may conflict with fetus' right to personhood, and doctor's moral obligations to society. In liberal jurisdictions, previable fetuses may not have legal rights of personhood; therefore, appropriate action would be to respect pregnant women's decisions regarding TOP. However, in countries with restrictive abortion laws the fetus maybe imbued with the right of personhood at conception, making TOP illegal and exposing doctors and patients to potential criminal prosecution. Birth of a severely disabled baby with independent legal rights creates further conflicts between parents and clinicians complicating healthcare decision-making. Irrespective of the maternal decision to accept or refuse TOP, the psychological and emotional impact of an impaired fetus or neonate, often lead to moral distress and posttraumatic stress reactions in parents. Doctors have legal and ethical obligations to provide an accurate antenatal diagnosis with full disclosure to enable informed decision making. Failure to provide timely or accurate diagnosis may lead to allegations of negligence with potential liability for "wrongful birth" or "wrongful life" following birth of severely disabled babies. Mismanagement of such cases also causes misuse of scarce healthcare resources in resource-poor countries. This paper describes ethical challenges in clinical management of two neonates born following declined and failed feticide for severe central nervous system anomalies with a critical appraisal of the relevant literature.

Syntopical peculiarities of internal female genital organs and the rectum in the second trimester of pregnancy

The research is devoted to topical issues of modern medicine – the laws of perinatal morphogenesis and the establishment of anatomical standards of the perinatal period. By means of classical methods of anatomical study the structural features and correlative interrelations of internal female genital organs and the rectum on 17 specimens of fetuses aged 4-6 months. It has been found that the rectum touches with its front surface the bladder, the urinary ducts, intestinal surface of the uterus, the rear surface of the vagina. In most cases at the beginning the fetal period the uterus is in a vertical position. The slope of the uterus to the sides may be determined by the length of the round ligaments of the uterus. Previable fetuses are characterized by the rising position of the ovaries and fallopian tubes and their location along the straight and sigmoid colon.

Blood flow measurement system for fetoscopic laser photocoagulation of chorionic plate anastomosing vessels (FLPC)

Fetoscopic laser photocoagulation of chorionic plate anastomosing vessels (FLPC) applies to the treatment of previable fetuses with severe twin-twin transfusion syndrome (TTTS). The ultimate goal of FLPC is selective blood flow interruption of anastomotic communicating vessels on the placenta fetoscopically. However, there has not been an established method to confirm that the blood flow is blocked, thus, it depends on the operator's experience or intuition to evaluate whether the FLPC was performed successfully or not. For this issue, we have developed a composite-type optical fiberscope (2.2 mm in diameter), which has centrally-located cautery laser fiber and surrounding located fiberglasses for viewing. This fiberscope enables transmission of 50 W Yb fiber laser which can be focused to 10 mm focal length using two lenses on the fiberscope tip. In this study, we combined the fiberscope and a laser blood-flow meter, and irradiated cautery laser to porcine mesenteric vein with measuring blood flow at the same time. From the experimental results, we could quantitatively measure the blood flow before and after laser irradiation, and confirm the blood flow blocking with our system.

Amniotic Band Sequence

After completing this article, readers should be able to: 1. Identify the clinical spectrum of defects seen in amniotic band sequence. 2. Describe possible mechanisms involved in the formation of defects. 3. Formulate a differential diagnosis for amniotic band sequence. Amniotic band sequence (OMIM #217100) comprises a broad clinical spectrum of defects that includes disruptions, deformations, and malformations. Disruptions may be caused by adhesions or constrictions by amniotic bands of structures programmed to develop normally. Deformations may result from distortion of embryologically normal structures. Amnion rupture may lead to oligohydramnios, which results in fetal constraint and tethering of fetal parts that may cause vascular engorgement, hemorrhage, edema, and tissue necrosis. Malformations may result from the presence of amniotic bands in the early embryonic period that interfere with normal embryogenesis. Amniotic band sequence is also known as amnion rupture sequence, ADAM complex (amniotic deformities/adhesions/mutilations), amniotic band disruption complex, congenital constricting bands, terminal transverse defects, and Streeter anomaly. Amnion rupture sequence has been described clinically as rupture of the amnion followed by encircling of developing structures by strands of amnion. These may vary from constricting bands to limb reduction defects. In addition, deformational defects such as scoliosis or talipes equinovarus may seen. Thoracoabdominoschisis, facial clefts, and encephaloceles also may be associated with amniotic adhesions, ruptured amnion, and amputation defects, and this has been referred to as the Limb Body Wall Complex (LBWC). Several reports regarding the incidence of amniotic band sequence have been cited in the literature. A frequency of 1 in 1,000 for congenital ring constrictions and amputations was reported by Baker and Rudolf. (1) The frequency of amniotic bands has been estimated to range from 1 in 1,234 to 15,000 live births, (2) but may be up to 1 in 56 in previable fetuses. (3) The incidence …

Survival of “pre-viable” infants in the United States

We investigated temporal trend in survival of pre-viable (200-499 g) fetuses over the previous decade, and estimated future survival rates based on previous and current survival thresholds. This was a retrospective cohort study on live-born pre-viable fetuses (200-499 g) in the United States comparing two period cohorts; 1985-1988 versus 1995-1999. We computed survival of pre-viable babies (who were still alive at 24 hours) during the two periods and based on these results, we estimated future survival rates for the coming decades. Survival beyond the neonatal period. About 35 million live births were analyzed for the two periods. In the first period (1985-1988), 927 live births among pre-viable fetuses were recorded while in the second period (1995-1999) 2585 were counted, equivalent to a birth rate of 60.6 and 131.9 per million live births respectively. This corresponds to an increase of more than 100% across the decade (p for trend < 0.0001). Survival improved by about 50% across the period, from 12.0% to 17.4% (p < 0.0001). Based on these results, the survival rate among pre-viable fetuses will be expected to rise to about 24.0% within the next 6 years (2010). Survival among pre-viable fetuses is increasing in the United States. This raises ethical, legal and medical issues concerning the defined viability status of these babies, which is currently described as "non-viable".

Bilateral brachial amelia, facial clefts, encephalocele, orbital cyst and omphalocele: a recurrent fetal malformation pattern coming into focus

Ultrasonographic and pathoanatomical features of a fetus displaying bilateral brachial amelia, complex facial clefting, encephalocele and omphalocele are described. The findings are compared with the few previously published cases. Bilateral brachial amelia with complex other organ malformations in previable fetuses may be more frequently diagnosed with improving prenatal ultrasonography.

MUCIN HISTOCHEMISTRY OF THE DEVELOPING GASTROESOPHAGEAL JUNCTION

Mucin histochemistry was performed on the squamocolumnar junction (Z-line) of the gastroesophageal region of 49 autopsied previable fetuses, stillbirths, infants, and young children, using alcian blue pH 2.5/periodic acid-Schiff (PAS) and alcian blue pH 1.0/PAS stains. Sialylated and neutral mucins were present in most and sulfated mucin in many cases. In only one fetus was a heterotopic focus of goblet cells found in the distal esophagus. This study confirms that the presence of acidic mucins in columnar epithelium, without goblet cells, at the Z-line and adjacent cardia is common in this age group. Undue reliance on mucin stains to identify metaplastic columnar epithelium, in the absence of goblet cells, may result in overdiagnosis of Barrett's esophagus in children.

Limb defects and chorionic villus sampling: results from an international registry, 1992-94

Summary Background Several reports of limb defects occurring among infants exposed to chorionic villus sampling (CVS) during pregnancy resulted in concern about the safety of this procedure for prenatal diagnosis. To avoid publication bias and evaluate the true risk of limb defects in a CVS cohort, the World Health Organization initiated international registration of post-CVS limb defects in 1992. Methods From May, 1992, to May, 1994, 77 infants or fetuses with limb defects from 138 996 pregnancies having CVS were reported to the WHO CVS Registry. These cases were analysed by standardised methods-ie, exclusion of syndromes, inherited disorders, and defects occurring in previable fetuses. The included limb deficiencies were studied by pattern analysis. Findings Defects of the upper limbs were reported in 64·6%, of the lower limbs in 12·5%, and of both upper and lower limbs in 20·8% of cases. These figures are in agreement with the distribution of limb defects in several large population-based studies. Transverse limb defects occurred in 40·8% and longitudinal defects in 59·2%, compared with 42·7% and 57·3% in an unexposed population. Interpretation The analysis of this cohort did not show any differences from the background population in the overall frequency or pattern distribution of limb deficiencies. There was also no correlation between gestational age at CVS and severity of defects. Therefore these results do not indicate any increased risk of limb defects after CVS.

Mucin Histochemistry of the Developing Gastroesophageal Junction

Mucin histochemistry was performed on the squamocolumnar junction (Z-line) of the gastroesophageal region of 49 autopsied previable fetuses, stillbirths, infants, and young children, using alcian blue pH 2.5/periodic acid-Schiff (PAS) and alcian blue pH 1.0/PAS stains. Sialylated and neutral mucins were present in most and sulfated mucin in many cases. In only one fetus was a heterotopic focus of goblet cells found in the distal esophagus. This study confirms that the presence of acidic mucins in columnar epithelium, without goblet cells, at the Z-line and adjacent cardia is common in this age group. Undue reliance on mucin stains to identify metaplastic columnar epithelium, in the absence of goblet cells, may result in overdiagnosis of Barrett's esophagus in children.

Fetoscopic laser ablation of placental vessels in severe previable twin-twin transfusion syndrome

OBJECTIVE: We undertook a pilot study to determine the feasibility and efficacy of fetoscopic laser occlusion of chorioangiopagous vessels in severe previable twin-twin transfusion syndrome. STUDY DESIGN: A total of 35 patients were referred to the investigators with ultrasonographic findings consistent with twin-twin transfusion syndrome, posterior placental implantation, gestational age < 25 weeks, and clinical hydramnios. Placental vessel occlusion was performed with a rigid 2.9 × 3.85 mm dual-channel fetoscope and neodymium:yttrium-aluminum-garnet laser light. RESULTS: Of the original 35 patients, 5 were eliminated preoperatively and 4 intraoperatively for various factors. The 26 treated patients had a mean gestational age of 20.8 weeks (range 18 to 24) and a mean fundal height of 36.1 cm (range 29 to 44). One patient has surviving triplets, 8 have surviving twins, 9 have a single survivor (2 neonatal and 7 fetal deaths occurred in this group), and 8 have no survivors (all had pregnancy loss within 3 weeks of treatment). The cases with survivors were delivered for obstetric indications at a mean of 32.2 weeks (range 26 to 37), having gained a mean of 11.7 weeks (range 6 to 17) in utero. Fifty-three percent ( 28 53 ) of the fetuses survived with 96% ( 27 28 ) developing normally at a mean age of 35.8 months (range 1 to 68). Thirty-three of 35 placentas were monochorionic with chorioangiopagous vessels on gross and microscopic evaluation. CONCLUSIONS: Fetoscopic laser occlusion of chorioangiopagous vessels is technically feasible and improves the course and outcome of severe twin-twin transfusion syndrome in previable fetuses.

Antepartum corticosteroids: Disease stabilization in patients with the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP)

Our purpose was to evaluate the impact of antepartum administration of corticosteroids on the course of the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP) in pregnancies at 24 to 37 weeks' gestation. This prospective, randomized study was undertaken in 25 antepartum patients with atypical severe preeclampsia expressed as HELLP syndrome. Twelve pregnant women were randomized to receive double-dose dexamethasone (10 mg intravenously every 12 hours) until delivery, and 13 women were randomized to the control arm. Management and delivery decisions for all patients were based on a common protocol, with delivery undertaken for a deteriorating maternal or fetal condition. In the corticosteroid-treated group the maternal platelet count significantly increased (p = 0.006), whereas lactic dehydrogenase and alanine aminotransferase significantly decreased over time (p = 0.03 and p = 0.005) in comparison to the 13 women who did not receive corticosteroids. Maternal urinary output after entry into the study was significantly increased within hours after steroid administration versus the control group (p = 0.0006). The study entry-to-delivery interval (41 +/- 15 hours) was significantly longer in the group of steroid-treated women (p = 0.0068). Stabilization and significant improvement in the laboratory and clinical parameters associated with HELLP syndrome occurred in women who received high-dose antenatal corticosteroids, as measured by maternal platelet count, urinary output, lactic dehydrogenase, alanine aminotransferase, and postponement of delivery. We believe the findings of this investigation permit us to speculate that this therapeutic approach could enhance maternal-fetal care by postponing delivery of some previable fetuses, reduce the need for maternal transfusion of blood products, reduce neonatal morbidity or mortality from multiple systemic effects, and facilitate a safer transfer of the ill mother to a tertiary care site for optimal peripartal care.

The pathological diagnosis of pulmonary atresia with abnormal ventriculoarterial connections in the fetus

AbstractPulmonary atresia with abnormal ventriculoarterial connections in the presence of an intact ventricular septum is rare even in postnatal life. Two cases are described in which this combination of lesions was diagnosed in previable fetuses at autopsy. Both pregnancies were terminated for gross structural abnormalities discovered on antenatal ultrasound scans. In the first case, the pulmonary atresia was associated with intact ventricular septum, a double outlet left ventricle and hypoplasia of the tricuspid valve, right ventricle and arterial duct, a combination of lesions that would appear to be unique. In the second case, there was complete transposition and a hypoplastic left ventricle. The severity of the cardiac lesions in both fetuses was such that it is unlikely that either would have survived to term. In the first case no other malformation was present, but in the second there was also a large encephalocoele secondary to early amnion rupture, and a single umbilical artery. The association of the cardiac lesion with early amnion rupture in this second fetus would appear to be a chance event.

Disposal of previable fetuses

Disposal of previable fetuses

Does obstetric ethics have any role in the obstetrician's response to the abortion controversy?

We defend the view that the obstetrician's response to the abortion controversy cannot be based on accounts of the independent moral status of the fetus, because all such accounts are irresolvably disputable. That response, however, can be based on an account of the dependent moral status of the fetus. For such an account the central question is, When is the fetus a patient? Viable fetuses are patients. Nonviable third-trimester fetuses are not patients. Previable fetuses are patients solely as a function of the woman's autonomous decision to confer such status. The abortion of a viable fetus is, with few exceptions, never ethically justified, because it is a patient. The abortion of nonviable third-trimester fetuses (i.e., premature termination of pregnancy) is justified when the pregnant women consents to it. Abortion of the previable fetus is justifiable when the pregnant women consents to it. We distinguish between professional and private conscience. We identify the limits of the former and the legitimate role of the latter, especially in the area of religious beliefs. Finally, we address the implications of our view for residency training programs. The most important of these implications is that requiring all residents to perform abortions is ethically unjustifiable.

Does obstetric ethics have any role in the obstetrician's response to the abortion controversy?

We defend the view that the obstetrician's response to the abortion controversy cannot be based on accounts of the independent moral status of the fetus, because all such accounts are irresolvably disputable. That response, however, can be based on an account of the dependent moral status of the fetus. For such an account the central question is, "When is the fetus a patient?" Viable fetuses are patients. Nonviable third-trimester fetuses are not patients. Previable fetuses are patients solely as a function of the woman's autonomous decision to confer such status. The abortion of a viable fetus is, with few exceptions, never ethically justified, because it is a patient. The abortion of nonviable third-trimester fetuses (i.e., premature termination of pregnancy) is justified when the pregnant woman consents to it. Abortion of the previable fetus is justifiable when the pregnant woman consents to it. We distinguish between professional and private conscience. We identify the limits of the former and the legitimate role of the latter, especially in the area of religious beliefs. Finally, we address the implications of our view for residency training programs. The most important of these implications is that requiring all residents to perform abortions is ethically unjustifiable.

Amnlon Rupture Sequence in Previable Fetuses

Amnlon Rupture Sequence in Previable Fetuses

Amnion rupture sequence in previable fetuses.

Amnion rupture sequence is considered an uncommon, sporadic condition among liveborn infants. We have examined 1,010 previable fetuses (9-20 weeks developmental age) to determine the incidence and nature of amnion rupture sequence at this stage of development. We found 18 affected fetuses (15 spontaneous and 3 induced abortions) with the incidence of 1:56. Eleven fetuses had limb constrictions and amputations only; 7 fetuses also had nonlimb involvement, including disruptions of the craniofacial region mimicking encephalocele, unusual facial clefts, and abdominal defects. In 6 pregnancies, constrictions of the umbilical cord by amniotic bands were the cause of fetal intrauterine death.