Fetal Arrest Research Articles

Clinical application of single nucleotide polymorphism microarray analysis in pregnancy loss in Northwest China.

Background: Spontaneous abortion is the most common complication of early pregnancy. In this study, we aim to investigate the clinical application value of genetic diagnosis using single nucleotide polymorphism (SNP) microarray analysis on the products of conception and to characterize the types of genetic abnormalities and their prevalence in pregnancy loss in Northwest China. Methods: Over 48months, we selected 652 products of conception, which included chorionic villi, fetal tissues, germ cell samples, amniotic fluid samples, cord blood samples, and a cardiac blood sample. We analyzed the distribution of chromosomal abnormalities leading to fetal arrest or abortion using SNP array. The patients were then categorized divided into groups based on maternal age, gestational age, number of miscarriages, and maternal ethnic background. The incidences of various chromosomal abnormalities in each group were compared. Results: Of the 652 cases, 314 (48.16%) exhibited chromosomal abnormalities. These included 286 cases with numerical chromosomal abnormalities, 24 cases with copy number variation, and four cases with loss of heterozygosity. Among them, there were 203 trisomy cases, 55 monosomy cases, and 28 polyploidy cases. In the subgroup analysis, significant differences were found in the frequency of numerical chromosomal abnormalities and copy number variation between the advanced and younger maternal age group as well as between the early and late abortion groups. Furthermore, we identified significant differences in the frequency of numerical chromosomal abnormalities between the first spontaneous abortion and recurrent miscarriage groups. However, there were no significant differences in the frequency of numerical chromosomal abnormalities between the Han and Uighur groups. Conclusion: Our research highlights chromosomal abnormalities as the primary cause of spontaneous abortion, with a higher incidence in early pregnancy and among women of advanced age. The use of SNP array analysis emerges as an effective and reliable technique for chromosome analysis in aborted fetuses. This method offers a comprehensive and dependable genetic investigation into the etiology of miscarriage, establishing itself as a valuable routine selection for genetic analysis in cases of natural abortions.

Prenatal diagnosis of paternal uniparental disomy for chromosome 2 in two fetuses with intrauterine growth restriction

Uniparental disomy (UPD) is when all or part of the homologous chromosomes are inherited from only one of the two parents. Currently, UPD has been reported to occur for almost all chromosomes. In this study, we report two cases of UPD for chromosome 2 (UPD2) encountered during prenatal diagnosis. The ultrasound findings of the fetuses from two unrelated families showed intrauterine growth restriction. The karyotype analyses were normal. The two fetuses both had complete paternal chromosome 2 uniparental disomy detected by whole-exome sequencing, but their clinical outcomes were significantly different, with fetal arrest in case 1 and birth in case 2. In this report, we analyzed and discussed the phenotypes of the fetuses in these two cases and reviewed the literature on UPD2.

The Role and Application of Exosomes and Their Cargos in Reproductive Diseases: A Systematic Review.

In recent years, the incidence of the reproductive diseases is increasing year-by-year, leading to abortion or fetal arrest, which seriously affects the reproductive health of human beings and the reproductive efficiency of animals. Exosomes are phospholipid bilayer vesicles that are widely distributed in living organisms and released by the cells of various organs and tissues. Exosomes contain proteins, RNA, lipids, and other components and are important carriers of information transfer between cells, which play a variety of physiological and pathological regulatory functions. More and more studies have found that exosomes and their connotations play an important role in the diagnosis, prognosis and treatment of diseases. A systematic review was conducted in this manuscript and then highlights our knowledge about the diagnostic and therapeutic applications of exosomes to reproductive diseases, such as polycystic ovary syndrome (PCOS), endometriosis, premature ovarian failure (POF), preeclampsia, polycystic, endometrial cancer, cervical cancer, ovarian cancer, and prostate gland cancer.

Parental genomes segregate into distinct blastomeres during multipolar zygotic divisions leading to mixoploid and chimeric blastocysts

BackgroundDuring normal zygotic division, two haploid parental genomes replicate, unite and segregate into two biparental diploid blastomeres.ResultsContrary to this fundamental biological tenet, we demonstrate here that parental genomes can segregate to distinct blastomeres during the zygotic division resulting in haploid or uniparental diploid and polyploid cells, a phenomenon coined heterogoneic division. By mapping the genomic landscape of 82 blastomeres from 25 bovine zygotes, we show that multipolar zygotic division is a tell-tale of whole-genome segregation errors. Based on the haplotypes and live-imaging of zygotic divisions, we demonstrate that various combinations of androgenetic, gynogenetic, diploid, and polyploid blastomeres arise via distinct parental genome segregation errors including the formation of additional paternal, private parental, or tripolar spindles, or by extrusion of paternal genomes. Hence, we provide evidence that private parental spindles, if failing to congress before anaphase, can lead to whole-genome segregation errors. In addition, anuclear blastomeres are common, indicating that cytokinesis can be uncoupled from karyokinesis. Dissociation of blastocyst-stage embryos further demonstrates that whole-genome segregation errors might lead to mixoploid or chimeric development in both human and cow. Yet, following multipolar zygotic division, fewer embryos reach the blastocyst stage and diploidization occurs frequently indicating that alternatively, blastomeres with genome-wide errors resulting from whole-genome segregation errors can be selected against or contribute to embryonic arrest.ConclusionsHeterogoneic zygotic division provides an overarching paradigm for the development of mixoploid and chimeric individuals and moles and can be an important cause of embryonic and fetal arrest following natural conception or IVF.

Progesterone-induced blocking factor-mediated Th1/Th2 balance correlates with fetal arrest in women who underwent in vitro fertilization and embryo transfer

The role of progesterone-induced blocking factor (PIBF)-mediated Th1/Th2 balance in delivery outcomes of in vitro fertilization and embryo transfer (IVF-ET) has not been fully elucidated. In this study, 73 infertile women with successful IVF-ET were enrolled (16 fetal arrests and 57 live births). PIBF and IL-4 levels were significantly lower in the fetal arrest group than in the live birth group (p < 0.05). TNF-α level and Th1/Th2 ratios were significantly higher in the fetal arrest group than in the live birth group (p < 0.05). High TNF-α level and Th1/Th2 ratios were risk factors for fetal arrest, whereas increased PIBF and IL-4 levels were protective factors (P < 0.05). Increased TNF-α/IL-4 exhibited relatively strong predictive value for fetal arrest (AUC, 0.855; sensitivity, 93.8%; specificity, 71.9%). In summary, the PIBF-mediated Th1/Th2 balance is closely correlated with delivery outcomes of IVF-ET. TNF-α/IL-4 may be a predictive marker of fetal arrest.

Fetal brain arrest broadens the spectrum of WDR81-related developmental brain malformations.

Fetal brain arrest is an extremely rare genetic disorder that was described in few patients and encompasses very unique findings of underdeveloped cerebral hemispheres in association with collapsed skull bones. Based on the recurrence among sibs, an autosomal recessive mode of inheritance was proposed; however, no causative gene was identified so far. Here, we report the identification of biallelic variants in the WDR81 gene in two unrelated families (4 patients) with fetal brain arrest including the originally described family and an additional new family. Two homozygous variants were identified: a new missense (c.1157T > C, p.Val386Ala) and a previously described frameshift variant, c.4668_4669delAG (p.Gly1557AspfsTer16). We assessed the expression of WDR81 at the protein level by western blot analysis using primary skin fibroblast cultures established from the patient with the missense variant and noticed that WDR81 expression was significantly reduced in comparison to normal control confirming the pathogenicity of this variant. Our findings confirm the involvement of WDR81 in the pathogenesis of fetal brain arrest syndrome and suggest that fetal brain arrest represents the severe end of the spectrum phenotypes caused by pathogenic variants in WDR81. In addition, we reviewed the clinical and molecular data on WDR81-related disorders and phenotype/genotype correlations.

Partial trisomy 4q and monosomy 5p inherited from a maternal translocationt(4;5)(q33; p15) in three adverse pregnancies

BackgroundCarriers of balanced reciprocal chromosomal translocations are at known reproductive risk for offspring with unbalanced genotypes and resultantly abnormal phenotypes. Once fertilization of a balanced translocation gamete with a normal gamete, the partial monosomy or partial trisomy embryo will undergo abortion, fetal arrest or fetal malformations. We reported a woman with chromosomal balanced translocation who had two adverse pregnancies. Prenatal diagnosis was made for her third pregnancy to provide genetic counseling and guide her fertility.Case presentationWe presented a woman with chromosomal balanced translocation who had three adverse pregnancies. Routine G banding and CNV-seq were used to analyze the chromosome karyotypes and copy number variants of amniotic fluid cells and peripheral blood. The karyotype of the woman was 46,XX,t(4;5)(q33;p15). During her first pregnancy, odinopoeia was performed due to fetal edema and abdominal fluid. The umbilical cord tissue of the fetus was examined by CNV-seq. The results showed a genomic gain of 24.18 Mb at 4q32.3-q35.2 and a genomic deletion of 10.84 Mb at 5p15.2-p15.33 and 2.36 Mb at 15q11.1-q11.2. During her second pregnancy, she did not receive a prenatal diagnosis because a routine prenatal ultrasound examination found no abnormalities. In 2016, she gave birth to a boy. The karyotype the of the boy was 46,XY,der(5)t(4;5)(q33;p15)mat. The results of CNV-seq showed a deletion of short arm of chromosome 5 capturing regions 5p15.2-p15.33, a copy gain of the distal region of chromosome 4 at segment 4q32.3q35.2, a duplication of chromosome 1 at segment 1q41q42.11 and a duplication of chromosome 17 at segment 17p12. During her third pregnancy, she underwent amniocentesis at 17 weeks of gestation. Chromosome karyotype hinted 46,XY,der(5)t(4;5)(q33;p15)mat. Results of CNV-seq showed a deletion of short arm (p) of chromosome 5 at the segment 5p15.2p15.33 and a duplication of the distal region of chromosome 4 at segment 4q32.3q35.2.ConclusionsChromosomal abnormalities in three pregnancies were inherited from the mother. Preimplantation genetic diagnosis is recommended to prevent the birth of children with chromosomal abnormalities.

Management of Fetal Growth Arrest in One of Dichorionic Twins: Three Cases and a Literature Review.

Progressive fetal growth restriction (FGR) is often an indication for delivery. In dichorionic diamniotic (DD) twin pregnancy with growth restriction only affecting one fetus (selective fetal growth restriction: sFGR), the normal twin is also delivered prematurely. There is still not enough evidence about the optimal timing of delivery for DD twins with sFGR in relation to discordance and gestational age. We report three sets of DD twins with sFGR (almost complete growth arrest affecting one fetus for ≥2 weeks) before 30 weeks of gestation. The interval from growth arrest to delivery was 21–24 days and the discordance was 33.7–49.8%. A large-scale study showed no difference of overall mortality or the long-term outcome between immediate and delayed delivery for FGR, while many studies have identified a risk of developmental delay following delivery of the normal growth fetus before 32 weeks. Therefore, delivery of DD twins with sFGR should be delayed if the condition of the sFGR fetus permits in order to increase the gestational age of the normal growth fetus.

The CAG repeat polymorphism in the Androgen receptor gene modifies the risk for hypospadias in Caucasians

BackgroundHypospadias is a birth defect of the urethra in males, and a milder form of 46,XY disorder of sexual development (DSD). The disease is characterized by a ventrally placed urinary opening due to a premature fetal arrest of the urethra development. Moreover, the Androgen receptor (AR) gene has an essential role in the hormone-dependent stage of sexual development. In addition, longer AR polyglutamine repeat lengths encoded by CAG repeats are associated with lower transcriptional activity in vitro. In the present study, we aimed at investigating the role of the CAG repeat length in the AR gene in hypospadias cases as compared to the controls. Our study included 211 hypospadias and 208 controls of Caucasian origin.MethodsWe amplified the CAG repeat region with PCR, and calculated the difference in the mean CAG repeat length between the hypospadias and control group using the T-test for independent groups.ResultsWe detected a significant increase of the CAG repeat length in the hypospadias cases when compared to the controls (contrast estimate: 2.29, 95% Confidence Interval (1.73-2.84); p-value: 0.001). In addition, the odds ratios between the hypospadias and controls revealed that the hypospadias cases are two to 3 times as likely to have longer CAG repeats than a shorter length for each repeat length investigated.ConclusionsWe have investigated the largest number of hypospadias cases with regards to the CAG repeat length, and we provide evidence that a higher number of the CAG repeat sequence in the AR gene have a clear effect on the risk of hypospadias in Caucasians.

Sudden Death of a Pregnant Woman in Third Trimester with No Risk Factor

Acute myocardial infarction in pregnancy is rare and life-threatening for both the mother and the fetus. We present the case of a 31-year-old previously healthy woman with no risk factors at 32 weeks of gestation who applied with vomiting, dyspnea and orthopnea. A respiratory arrest developed followed by loss of the fetal viability, cardiac arrest, and failure of resuscitation. We aim to raise awareness about the clinical approach to pregnant patients who are to be considered with a broad spectrum of differential diagnosis.

Expression of angiogenic basic fibroblast growth factor, platelet derived growth factor, thrombospondin-1 and their receptors at the porcine maternal-fetal interface

BackgroundCommercial swine breeds in North America undergo two waves of spontaneous fetal loss; one during peri-attachment and another during mid-gestation. Although an exact mechanism for this loss is not known, deficits in vasculature at the attachment sites appear to be a major cause. We hypothesized that a balance between pro-angiogenic and anti-angiogenic factors is needed at the maternal-fetal interface for successful conceptus development. Six selected members of the pro-angiogenic fibroblast growth factor (FGF) and platelet derived growth factor (PDGF) families and anti-angiogenic factor thrombospondin-1 (TSP-1) and its receptor CD36 were quantified and localized at the porcine maternal-fetal interface at early and midgestation time points.MethodsMesometrial endometrium was collected from non-pregnant gilts (n = 8). Endometrial and chorioallantoic membrane samples were collected from healthy and arresting conceptus attachment sites at gestation day (gd) 20 (n = 8) and gd 50 (n = 8). At gd20 arresting conceptus attachment sites were distinguished by decreased vasculature of the placental membranes and decreased conceptus size. At gd50 arresting conceptuses attachment sites were identified by smaller conceptus length and weight measurements. Quantitative real time PCR was used to determine relative transcript levels of genes of interest, and cellular localization was determined by immunohistochemistry in paraffin embedded endometrial sections.ResultsAt gd20, endometrial samples from arresting conceptuses had elevated transcripts for bFGF, and PDGF-bb than healthy sites (p < 0.05). At gd50, bFGF, FGFR2, and CD36 were more abundant at arresting than at healthy conceptus attachment sites (p < 0.05). Chorioallantoic membrane from arresting conceptus attachment sites at gd20 had elevated transcripts for bFGF, FGFR1, FGFR2 and CD36 compared with healthy sites (p < 0.05). FGFR2 transcripts were more abundant in chorioallantoic membrane from arresting conceptuses at gd 50 (p < 0.05). Immunohistochemical localization of selected pro- and anti-angiogenic factors and receptors revealed their abundance in the luminal epithelium, uterine glands and perivascular areas of endometrium at gd20 and gd50.ConclusionsWe provide comprehensive analysis of pro and anti-angiogenic factors at the porcine maternal fetal interface during early and mid-pregnancy. At mRNA levels, the majority of pro-angiogenic factors investigated were elevated at the sites of fetal arrest. These observations contrast with our previous findings of decreased Vascular Endothelial Growth Factor (VEGF) family members at arresting sites, and suggest that the bFGF family functions as a compensatory survival mechanism when major angiogenic proteins are decreasing at the sites of fetal arrest.

In utero development of symmetric thalamic and brainstem necrosis in a preterm hydropic stillborn

Focal and symmetric necrotic lesions of the brainstem are thought to result from fetal hypotension or cardiac arrest in the perinatal period and thus occur in the course of postnatal intensive care rather than in utero. Here, we report for the first time on brainstem necrosis in a preterm stillborn demonstrating that brainstem necrosis occurs already in utero. The preterm stillborn of 28 weeks gestation of a mother that suffered from HELLP-syndrome was severely affected by a fetal hydrops with bilateral pleural effusions and lung hypoplasia. Bilateral tegmental brainstem necrosis and thalamic lesions were detected.

Expression of chemokine decoy receptors and their ligands at the porcine maternal–fetal interface

Successful pregnancy requires coordinated maternal-fetal cross-talk to establish vascular connections that support conceptus growth. In pigs, two waves of spontaneous fetal loss occur and 30-40% of conceptuses are lost before parturition. Previous studies associated these losses with decreased angiogenic and increased inflammatory cytokines. Chemokines, a sub-category of cytokines, and decoy receptors control leukocyte trafficking, angiogenesis and development. The availability of chemokines is regulated by three non-signalling decoy receptors: chemokine decoy receptor (D6), Duffy antigen receptor for chemokines (DARC) and Chemocentryx decoy receptor (CCX CKR). We hypothesized that the expression of these receptors and their chemokine ligands regulate the porcine pregnancy success or failure. Here, we describe for the first time the transcription and translation of all three decoy receptors and several chemokine ligands in endometrium and trophoblast associated with healthy and arresting conceptuses at gestation day (gd) 20 and gd50. Among decoy receptors, transcripts for DARC were significantly reduced in endometrium, whereas that for CCX CKR were significantly increased in endometrium and trophoblast at gd50 arresting compared with healthy sites. However, western blot analysis revealed no differences in decoy receptor expression between healthy and arresting tissues. Transcripts for decoy receptor ligands CCL2, CCL3, CCL4, CCL5, CCL11, CCL19, CCL21, CXCL2 and CXCL8 were stable between healthy and arresting littermates. Quantification by SearchLight chemiluminescent protein array confirmed ligand expression at the protein level. These data indicate that decoy receptors and ligands are expressed at the porcine maternal-fetal interface and dysregulation of decoy receptor (DARC and CCX CKR) transcripts occurs at sites of fetal arrest.

Purkinje Fiber Dysplasia (Histiocytoid Cardiomyopathy) with Ventricular Noncompaction in a Savannah Kitten

In a 2-month-old female savannah kitten that died unexpectedly, the pathologic findings of significance were restricted to the heart and included abnormal Purkinje fibers and biventricular myocardial trabeculation or noncompaction. The Purkinje fibers were large, angular, and tightly packed. They contained few disorganized myofibrils among a rarified cytoplasm. The fibers were distinct from adjacent myocytes and were immunohistochemically positive for desmin, muscle actin, myoglobin, sarcomeric actin, and chromogranin A. These findings are identical to those that occur in children with histiocytoid cardiomyopathy, a fatal genetic mitochondrial disorder of Purkinje fibers. Ventricular noncompaction likely has a multifactoral cause that results from fetal arrest of ventricular organizational development that might occur in conjunction with, or independent of, histiocytoid cardiomyopathy.

Transcriptional coactivators PGC-1α and PGC-lβ control overlapping programs required for perinatal maturation of the heart

Oxidative tissues such as heart undergo a dramatic perinatal mitochondrial biogenesis to meet the high-energy demands after birth. PPARgamma coactivator-1 (PGC-1) alpha and beta have been implicated in the transcriptional control of cellular energy metabolism. Mice with combined deficiency of PGC-1alpha and PGC-1beta (PGC-1alphabeta(-/-) mice) were generated to investigate the convergence of their functions in vivo. The phenotype of PGC-1beta(-/-) mice was minimal under nonstressed conditions, including normal heart function, similar to that of PGC-1alpha(-/-) mice generated previously. In striking contrast to the singly deficient PGC-1 lines, PGC-1alphabeta(-/-) mice died shortly after birth with small hearts, bradycardia, intermittent heart block, and a markedly reduced cardiac output. Cardiac-specific ablation of the PGC-1beta gene on a PGC-1alpha-deficient background phenocopied the generalized PGC-1alphabeta(-/-) mice. The hearts of the PGC-1alphabeta(-/-) mice exhibited signatures of a maturational defect including reduced growth, a late fetal arrest in mitochondrial biogenesis, and persistence of a fetal pattern of gene expression. Brown adipose tissue (BAT) of PGC-1alphabeta(-/-) mice also exhibited a severe abnormality in function and mitochondrial density. We conclude that PGC-1alpha and PGC-1beta share roles that collectively are necessary for the postnatal metabolic and functional maturation of heart and BAT.

A Review of Molecular Contrasts Between Arresting and Viable Porcine Attachment Sites

Significant spontaneous fetal loss of unknown cause occurs in North American commercial swine. About 30% of conceptuses, thought to be genetically normal, are lost during the peri-attachment period. An additional 20% are lost at mid-pregnancy. Littermate endometrial and trophoblast biopsies were studied by quantitative real-time PCR for gene expression, and immunohistochemistry for protein expression at gestation day (gd)15-23 and 50. RNA analyses were also conducted on endometrial lymphocytes and arterial endothelial cells removed from biopsies by laser capture microdissection. Genes were selected for study from human literature and cloned as required. As in humans, angiogenic, cytokine, chemokine and chemokine decoy receptor gene expression occurs at the porcine maternal-fetal interface. In each tissue studied, distinct patterns of expression are found between early and mid-pregnancy, as well as between viable and arresting conceptus attachment sites. These changes involve both endometrial lymphocytes and dendritic cells. Restriction in endometrial angiogenesis, reduction in expression of the chemokine decoy receptor D6, and reduction in dendritic cell numbers contribute to fetal arrest. In peri-attachment loss, interferon-gamma is more abundantly transcribed than tumor necrosis factor-alpha, but this ratio is reversed during midgestation failure. Further characterization of spontaneous fetal loss in pigs will identify targets for modification by hog producers and may provide a model for identification of antecedents to fetal loss in humans.

Lymphocyte contributions to altered endometrial angiogenesis during early and midgestation fetal loss

Peri-implantation and midgestational fetal losses reduce potential litter sizes up to 40% in commercial swine. Peri-implantation studies [gestation days (gd)15-23] of porcine RNA from laser capture microdissected uterine lymphocytes and biopsies of mesometrial endometrium and trophoblast previously linked gd21-23 fetal arrest with transcriptional deficits in vascular endothelial growth factor (VEGF) and its regulatory factor, hypoxia inducible factor (HIF)-1alpha, and with elevations in IFN-gamma and TNF-alpha and suggested endometrial lymphocytes played a pivotal, proangiogenic role in fetal survival. Here, we address more comprehensively porcine endometrial angiogenesis by comparing transcription between endometrial endothelium and lymphocytes during early (gd20) and midgestation (gd50) losses and by incorporation of histopathology and protein immunolocalization of VEGF, placenta growth factor (PlGF), VEGF receptor I (VEGFRI), and VEGFRII. In healthy sites, endometrial lymphocytes transcribed more VEGF at gd50 than gd20, and transcripts were more abundant in lymphocytes than in endothelium or trophoblast. Arterial endothelial cells showed the most abundant transcription of PlGF. With fetal arrest, maternal transcripts for VEGF but not PlGF dropped, and fetal transcripts remained relatively stable. Maternal and fetal HIF-1alpha transcription declined. Lymphocytes preferentially transcribed VEGFRI over VEGFRII, and endometrial arterial endothelium and trophoblast preferentially transcribed VEGFRII. IFN-gamma and TNF-alpha transcripts were present in gd20 and gd50 healthy- and arresting-implantation sites. gd20 arrest was associated with greater transcription of IFN-gamma than TNF-alpha in maternal and fetal tissues. At gd50, this was reversed. Endometrial, vascular pathology was evident only at gd50. These data suggest the critical importance for lymphocyte-driven endometrial angiogenesis, which extends to midgestation.

A Review of Gene Expression in Porcine Endometrial Lymphocytes, Endothelium and Trophoblast During Pregnancy Success and Failure

Meat pig breeds used commercially in North America lose significant numbers of genetically-normal fetuses in the peri-implantation (attachment) period and at mid-gestation (day 50 of the 114 day gestation interval). Fetal demand that is in excess to the placental blood supply is thought to underlie these waves of fetal loss. In many species, the endometrium of early normal pregnancy is enriched in innate immune cells, particularly uterine natural killer (uNK) cells. In pigs, a species with epitheliochorial placentation, conceptuses mediate about a three-fold enrichment in uNK cells at attachment sites but the functions of these cells are unknown. In species with hemochorial placentation, uNK cells are highly enriched during the process of decidualization and promote endometrial angiogenesis. We have conducted molecular analyses using pure samples of endometrial lymphocytes or endothelium and trophoblast from healthy and arresting conceptus attachment sites in Yorkshire gilts immediately post-attachment [gestation day (GD) 20] and at mid pregnancy (GD50). In healthy sites, angiogenesis was more robustly promoted by lymphocytes than by trophoblasts. An early sign of impending fetal arrest was loss of vascular endothelial growth factor (VEGF) transcription from the lymphocytes and elevation in transcription of the pro-inflammatory gene Interferon (IFN)-gamma. We have postulated that newly differentiated endometrial endothelial cells, not fetal trophoblasts, are damaged by the maternal withdrawal of vascular support and onset of inflammation and that this endometrial damage contributes significantly to peri-implantation fetal death.

Sacrococcygeal teratoma: prenatal assessment, fetal intervention, and outcome

Purpose To understand the natural history and define indications for fetal intervention in sacrococcygeal teratoma (SCT), the authors reviewed all cases of fetal SCT presenting for evaluation. Methods Prenatal diagnostic studies including ultrasound scan, magnetic resonance imaging (MRI), echocardiography and pre- and postnatal outcomes were reviewed in 30 cases of SCT that presented between September 1995 and January 2003. Results The mean gestational age (GA) at presentation was 23.9 weeks (range, 19 to 38.5) with 3 sets of twins (10%). Overall outcomes included 4 terminations, 5 fetal demises, 7 neonatal deaths, and 14 survivors. Significant obstetric complications occurred in 81% of the 26 continuing pregnancies: polyhydramnios (n = 7), oligohydramnios (n = 4), preterm labor (n = 13), preeclampsia (n = 4), gestational diabetes (n = 1), HELLP syndrome (n = 1), and hyperemesis (n = 1). Fetal intervention included cyst aspiration (n = 6), amnioreduction (n = 3), amnioinfusion (n = 1), and open fetal surgical resection (n = 4). Indications for cyst aspiration and amnioreduction were maternal discomfort, preterm labor, and prevention of tumor rupture at delivery. Although 15 SCTs were solid causing risk for cardiac failure, only 4 fetuses met criteria for fetal debulking based on ultrasonographic and echocardiographic evidence of impending high output failure and favorable anatomy at 21, 23.6, 25, and 26 weeks’ gestation. Intraoperative events included maternal blood transfusion (n = 1), fetal blood transfusion (n = 2), chorioamniotic membrane separation (n = 2), and fetal arrest requiring successful cardiopulmonary resuscitation (CPR) (n = 1). In the fetal resection group, 3 of 4 survived with mean GA at delivery of 29 weeks (range, 27.6 to 31.7 weeks), mean birth weight of 1.3 kg, hospital stay ranging from 16 to 34 weeks, and follow-up ranging from 20 months to 6 years. Postnatal complications in the fetal surgery group included neonatal death (n = 1, secondary to premature closure of ductus arteriosus with cardiac failure), embolic event (n = 1, resulting in unilateral renal agenesis, jejunal atresia), chronic lung disease (n = 1), and tumor recurrence (n = 1). Conclusions For fetal SCT, the rapidity at which cardiac compromise can develop and the high incidence of obstetric complications warrant close prenatal surveillance. Amnioreduction, cyst aspiration, and surgical debulking are potentially life-saving interventions.

Neonatal Acidosis and Method of Delivery

Seven hundred and four women who had a forceps termination (177 elective, 293 indicated low, and 234 indicated midforceps) of labor over 24 months were compared with 303 spontaneous and 111 cesarean deliveries over the same time period. There was no significant difference between indicated low or midforceps either for fetal distress or arrest of descent with regard to fetal acidosis (pH less than 7.20), one- or five-minute Apgar scores less than 7, fetal trauma, or neurologic deficit at discharge. Fourteen percent of indicated forceps for arrest of descent had neonatal acidosis, versus 8% of cesarean sections for cephalopelvic disproportion (P = NS), and 23% of indicated forceps for fetal distress had acidosis, versus 33% of cesarean sections (P = not significant). There was no significant difference either in the incidence of acidosis or in low Apgar scores in neonates delivered by elective low forceps compared with those born by spontaneous vaginal delivery. The only significant differences in midforceps versus low forceps were between maternal pre- and postdelivery hematocrits (P less than .0001) and vaginal lacerations (P less than .0001). The authors' data support the continued usage of indicated low and selected midforceps operations.