Cause Of Intrauterine Fetal Death Research Articles

Umbilical Cord Hypercoiling and Thinning: A Rare Cause of Intrauterine Death in the Second Trimester of Pregnancy

Little attention has been paid to the pathologic features of the umbilical cord, which might fatally damage the fetus. We determined the association of hypercoiling (more than 1 coil per 5 cm) and thinning with consecutive constriction of the umbilical vessels (thin cord syndrome; TCS) and intrauterine fetal death (IUFD). Three hundred and three cases of consecutive fetal autopsies over a 5-year period, including spontaneous and induced abortions of the 2nd trimester of pregnancy, were examined using a standardized protocol. The mean maternal age was 28.5 years and the mean gestational age was 19.1 weeks (range: 12.6 to 24.5 weeks). Thirty-six percent of all cases were induced abortions because of congenital malformations, and 8.9% resulted from legal abortions, as regulated by German law. One hundred sixty-seven cases (55.1%) were spontaneous abortion specimens. The leading cause for IUFD in the spontaneous abortion group was an amnion infection (34.7%), followed by abruptio placentae (15.6%). In 25.1% of cases, placental dysmaturity with consecutive placental insufficiency was responsible for IUFD. Pathologies of the umbilical cord as the cause of IUFD were seen in 10.2% of the cases. Most of these cases (15/17) involved TCS. In 14.4% of all spontaneous abortion specimens the cause of IUFD could not be determined by autopsy. There was an apparent difference in the frequency of TCS in the spontaneous abortion group (15/167 = 9%) compared to the nonspontaneous group (2/136 = 1.5%). A remarkably high percentage (17/303 = 5.6%) of all cases showed TCS. In cases of spontaneous abortions, TCS was causative for intrauterine death in 9% of cases (15/167). Careful pathologic examination of the umbilical cord is recommended to detect TCS and to reduce the cases with unexplained intrauterine death.

Detection of Parvovirus B19, Cytomegalovirus, and Enterovirus Infections in Cases of Intrauterine Fetal Death

In Sweden, between 6% and 20% of fetal deaths are ascribed to infectious diseases, and a substantial number of these are associated with maternal viral infections. In this prospective study, extending over 38 months, placental biopsies, fetal blood, and amniotic fluid were collected in 52 cases of intrauterine fetal death (IUFD). Biopsies from 53 normal pregnancies at term made up a control group. Tissues were examined by the polymerase chain reaction (PCR) technique for parvovirus B19 DNA, cytomegalovirus (CMV) DNA, and enterovirus RNA. Serologic studies for viral infection were done in 46 cases and, in 31, maternal stool samples were examined for enterovirus. The incidence of IUFD during the study period was 0.52%. Viral DNA was identified in 1 or more tissue samples in 6 cases. Parvovirus B19 DNA was found in the placenta in 2 cases, and also in fetal blood and amniotic fluid that were available in 1 of these cases. In the other, immunohistochemical analysis confirmed the diagnosis. CMV-DNA was present in the placenta but not in fetal blood in 1 case and in fetal blood but not the placenta in 2 cases. In 1 case, enterovirus RNA was present in amniotic fluid. All 31 attempts to isolate enterovirus from maternal stool samples were negative. Seroconversion for parvovirus B19 was documented only in the 2 DNA-positive cases. In no mother were there signs of primary infection by herpes simplex, rubella or Toxoplasma gondii. Maternal immunoglobulin G but no IgM or increase in IgG activity was found in the 3 CMV-DNA-positive cases. None of the women having an IUFD associated with viral infection had clinical signs of infection during pregnancy. No other obvious cause of IUFD was found in the women with documented infection. All 53 placental biopsies from normal term pregnancies were PCR-negative for parvovirus B19, CMV, and enterovirus. The investigators recommend that PCR studies of placental and/or fetal tissue for parvovirus B19, CMV, and enterovirus be included in the routine analysis of fetal deaths.

A comparison of prenatal versus postnatal karyotyping for the investigation of intrauterine fetal death after the first trimester of pregnancy

Aneuploidy is an important cause of intrauterine fetal death (IUFD) after the first trimester. Determination of the fetal karyotype of these pregnancies is commonly done in most units from solid tissues. Results from such techniques are disappointing. The aim of this audit was to compare the results of karyotyping IUFD by invasive testing (amniocentesis or chorionic villus sampling) and solid tissues (skin biopsy). Women with IUFD managed in our unit between 1 January 1998 and 31 December 2002 (inclusive) were offered either invasive testing before medical induction of labour or solid tissue biopsy after delivery. The amniotic fluid, chorionic villi and biopsies were processed following standard laboratory procedures. During the 60 months, 230 samples from cases of IUFD were received by the laboratory in our unit; 126 had skin biopsies and 104 underwent invasive testing (81 amniocenteses and 23 chorionic villus sampling). Successful karyotyping was possible in 90% of those who underwent amniocentesis, 100% of those who had chorionic villus sampling and 13.5% of those who had skin biopsies. 50% of skin biopsies were unsuitable for analysis compared to none in the CVS and amniocentesis group. The difference in successful karyotyping between invasive testing and solid tissue testing was statistically significant (P < 0.0001). There were 12 (10.6%) abnormal karyotypes from the 113 successful samples (11/96 in the invasive group versus 1/17 in the solid tissue group). Invasive testing has a much higher success rate of karyotyping in cases of IUFD and should, therefore, be offered to women presenting with this complication irrespective of gestational age.

Unexplained intrauterine fetal death is accompanied by activation of complement

The complement system has recently been implicated in the mechanisms of fetal loss in the anti-phospholipid antibody syndrome (JCI 2003; 112:1644). We propose that complement activation may also be involved in other causes of intrauterine fetal death (IUFD) in the second and third trimesters of pregnancy. This study was conducted to determine if IUFD is associated with changes in maternal plasma C5a concentration, the most biologically relevant product generated during complement activation.

Participation of the 27kDa heat shock protein (hsp27) in mid-trimester amniotic fluid: Ethnic variability and association with anti-inflammatory immunity

AMNIOTIC FLUID: ETHNIC VARIABILITY AND ASSOCIATION WITH ANTIINFLAMMATORY IMMUNITY SRIRAM C. PERNI, EMRE KARASAHIN, ROBIN B. KALISH, STEPHEN T. CHASEN, STEVEN S. WITKIN, Weill Medical College of Cornell University, Obstetrics and Gynecology, New York, New York OBJECTIVE: Modulation of pro-inflammatory immune responses during gestation is essential for pregnancy prolongation. The extracellular release of the 27 kDa heat shock protein (hsp27) induces anti-inflammatory immunity. However, the possible presence of hsp27 in amniotic fluid (AF) and its interaction with other AF components has not been determined. We investigated whether hsp27 was present in mid-trimester amniotic fluid and determined its relationship with other AF immuno-modulating components and with maternal ethnicity. STUDY DESIGN: 278 pregnant women with singleton gestations who presented for genetic amniocentesis were enrolled. Clara cell protein 16 (CCP16) and cortisol, two anti-inflammatory components of AF, as well as the cytokines interleukin (IL)-1b, IL-1 receptor antagonist (IL-1ra), IL-6, IL-13, and hsp27 were measured by ELISA. Mann-Whitney U tests and linear regression analysis were used for statistical analysis. RESULTS: Hsp27 was detected in all samples with a median (range) of 5.8 ng/ mL (0.2-43.3). Median AF hsp27 concentrations were higher in blacks (6.3 ng/ mL) than in whites (4.5 ng/mL) (P = .04). IL-1b was identified in 67.8% of the AFs with a median concentration of 13.8 pg/mL (1.0-92.8). AF concentrations of hsp27 were strongly negatively correlated with AF IL-1b concentrations (r = .4360, P ! .0001) and positively correlated with CCP16 (r = .2199, P = .0012) and cortisol (r = 0.1396, P = .04) levels. CCP16 concentrations were also negatively associated with IL-1b (r = .1753, P = .006), but not as strongly as hsp27. There was no relationship between cortisol and IL-1 b levels. There was no relationship between hsp27 levels and IL-1ra, IL-6, IL-13 concentrations or neonatal gender. CONCLUSION: Hsp27 is present in AF and contributes to the down-regulation of IL-1b-induced pro-inflammatory immunity during the mid-trimester. Whether differences in baseline hsp27 levels between blacks and whites contribute to observed ethnic variations in rates of preterm birth and neonatal morbidities remains to be determined. Supported by NIH HD41676. 568 UNEXPLAINED INTRAUTERINE FETAL DEATH IS ACCOMPANIED BY ACTIVATION OF COMPLEMENT KARINA RICHANI, ELEAZAR SOTO, JIMMY ESPINOZA, JYH KAE NIEN, TINNAKORN CHAIWORAPONGSA, JERRIE REFUERZO, SEAN BLACKWELL, SAMUEL EDWIN, MOSHE MAZOR, ROBERTO ROMERO, Wayne State University School of Medicine, Detroit, Michigan, Perinatology Research Branch, NICHD, NIH, DHHS, Bethesda, Maryland, Wayne State University School of Medicine, Department of Obstetrics and Gynecology, Detroit, Michigan, Soroka University Medical Center, Beer Sheva, Israel, Israel OBJECTIVE: The complement system has recently been implicated in the mechanisms of fetal loss in the anti-phospholipid antibody syndrome (JCI 2003; 112:1644). We propose that complement activation may also be involved in other causes of intrauterine fetal death (IUFD) in the second and third trimesters of pregnancy. This study was conducted to determine if IUFD is associated with changes in maternal plasma C5a concentration, the most biologically relevant product generated during complement activation. STUDY DESIGN: A cross-sectional study was designed to include normal pregnant women (n = 60) and patients with IUFD (n = 60). The IUFD group was classified according to the cause of fetal death into: (a) unexplained (n = 44); (b) associated with preeclampsia (n = 8); and (c) chromosomal abnormality or major malformation (n = 8). The plasma concentration of C5a was measured by ELISA. Non-parametric statistics were used for analysis. RESULTS: (1) The median plasma concentration of C5a in patients with IUFD was significantly higher than that of normal pregnant women (median 16.05 ng/mL, range 4.59–402.52 ng/mL vs. median 11.64 ng/mL, range 1.22– 87.13 ng/mL, respectively; P! .001); (2) Among patients with IUFD, those with unexplained fetal death and fetal death with preeclampsia had a median plasma C5a concentration higher than that of normal pregnant women (P = .002 and P ! .001, respectively); (3) There was no significant difference in median plasma concentration of C5a between IUFD with congenital anomalies and normal pregnancy. CONCLUSION: Unexplained IUFD is accompanied by complement activation.

Pathological evidence of prolonged umbilical cord encirclement as a cause of fetal death.

A case is presented in which autopsy findings (deep groove around the fetal waist and buttock), and gross and microscopic umbilical cord and placental examination (linear ulcer of umbilical cord histologically rimmed by fetal epidermal implants with evidence of remote bleeding) established the diagnosis of umbilical cord encirclement as a cause of intrauterine fetal death despite the lack of prenatal or postnatal obstetrical evidence.

Umbilical cord torsion; a rare cause of intra-uterine fetal death

Umbilical cord torsion; a rare cause of intra-uterine fetal death

Coarctation of the umbilical cord: a cause of intrauterine fetal death.

This article presents 16 cases of coarctation of the umbilical cord, resulting in fetal death in utero in pregnant women of more than 6 months' gestation. Coarctation of the umbilical cord can occur in any phase of the gestational period and is not related to parity. The stricture of the cord is usually accompanied by torsion and characterized by a fibrosis of the Wharton's jelly and a thickening of the vascular walls which obstructs the fetoplacental circulation, leading to anoxia and fetal death. Although this entity must occur frequently, it is not often reported by obstetricians because the umbilical cord is not carefully examined in all cases of stillbirth.

NATURAL INJURY OF NEWBORNS AND MEASURES TO COMBAT IT

One of the main causes of intrauterine fetal death and death of children during the neonatal period is birth trauma, in the form of intracranial hemorrhages, caused mainly by fetal asphyxia and mechanical obstacles. We studied 63 cases of death of newborns (34 full-term and 29 premature), observed in the clinic in recent years. Birth trauma in the form of intracranial hemorrhages was observed in 33 children (14 full-term and 19 premature), which is 52.3%. The birth trauma in all cases was confirmed by autopsy and was expressed in a typical pattern for this trauma.

Amniotic bands as a cause of intrauterine fetal death: A case report

A MNIOTIC bands are not rare in pregnancies ending in ahnrticm in thtl early months. Small threadlike strands have been described connecting the aborted fetus to an otherwise normal-appearing amnion. Instead of t,hreadlike, they may be tent shaped, with the apex attached to the body, head, or ends of the fingers or toes. In early intrauterine esistencc, due to a more right-angular attachment of the appendages to the body, contact with thcx amnion might be expected to occur readily t,o the head and digits.’ Wha.t causes these adhesions can only be conjectured. Amniotic aclhesions and resulting fetal deformities a,re known to occur in ectopic gestations wit.h more frequency than in normal gestations. In the term or near-term, otherwise normal intrauterine gestation, these amniotic bands are extremely rare. When they do occur. such bands, arising from the amnion, may be free at the other end, or attached to t,he fetns or to another area of the amnion. Loops may form around portions of the fetus, including digits or portions of extremities, causing corresponding deformities. These strands may entangle the umbilical cord, causing strangulation of t,he cord and intrauterine death. Fetal death may occur ante partum, intrapartum, or post partum. One reported cast was that of a child born alive at term who died shortly thereafter.2 Duncan2 compiled from the world literature 8 cases of fetal dea.th causccl by amniotic strings and added 2 others, one of his own and one of C(ra~cn ant1 &ddes4 in the addendum to his article. The case herewith report,4 brings the total from the world literature to 11.

New viewpoints on the cause of intrauterine fetal death

New viewpoints on the cause of intrauterine fetal death

Fetal capillary injuries as a cause of intrauterine fetal death

Fetal capillary injuries as a cause of intrauterine fetal death

ETIOLOGY AND DIAGNOSIS OF INTRA-UTERINE FETAL DEATH

Fetal syphilis, fetal anomalies, toxemias of pregnancy and maternal acute infections have long been recognized as causes of intra-uterine fetal death at any time during pregnancy. When no cause could be demonstrated for the death of the fetus, cases were classified as idiopathic. In the last decade certain observers, namely, De Lee 1 and Curtis, 2 have assumed and have more or less completely verified infectious organisms as the cause for intra-uterine fetal death. Of necessity, the verification beyond a reasonable doubt of such organisms being the cause of the death of the fetus in utero presents numerous obstacles, and in many instances only probable or presumable data can be obtained in support of such a view. It would seem important, in view of the limited number of cases on record, to study as completely as possible cases that give indication of falling into this class, and to place them