ASSOCIATION BETWEEN BREUS' MOLE AND PARTIAL HYDATIDIFORM MOLE: CHANCE OR CAN HYDROPIC VILLI PRECIPITATE PLACENTAL MASSIVE SUBCHORIONIC THROMBOSIS?

Breus' mole (massive subchorionic hematoma) is a rare entity most often found in the placentae of macerated stillborn fetuses. Previously considered to represent a postmortem event, recent evidence suggests that it occurs prior to fetal demise. A 23-week gestation male neonate was delivered of a 23-year-old gravida 3, para 2 woman and survived for 49 min. An autopsy with chromosomal studies resulted in a diagnosis of triploidy. Placental examination showed the presence of both Breus' mole and also partial hydatidiform mole. DNA samples extracted from portions of the fresh hematoma and from the fetal spleen were compared using molecular techniques. PCR analysis showed the presence of Y chromosome specific DNA in the placental clot, but a semiquantitative Southern blot demonstrated that roughly 85% of the clot DNA was of maternal origin. These findings suggest that Breus' mole represents primarily maternal thrombosis rather than fetal hemorrhage. We hypothesize that the partial mole could have contributed to the formation of the Breus' mole as some of the hydropic villi may have focally obstructed the maternal venous return from the intervillus space causing sluggish flow and promoting thrombosis. A review of the literature on Breus' mole shows that the majority of reported cased have not included cytogenetic findings. However, several authors have reported an association with triploidy and other chromosomal anomalies characterized by scattered placental hydropic villi. Thus, we suggest that obstruction of maternal venous return by hydropic villi may have played a contributory role in some of these other reported cases.     

Association between Breus' mole and partial hydatidiform mole: chance or can hydropic villi precipitate placental massive subchorionic thrombosis?

Breus' mole (massive subchorionic hematoma) is a rare entity most often found in the placentae of macerated stillborn fetuses. Previously considered to represent a postmortem event, recent evidence suggests that it occurs prior to fetal demise. A 23-week gestation male neonate was delivered of a 23-year-old gravida 3, para 2 woman and survived for 49 min. An autopsy with chromosomal studies resulted in a diagnosis of triploidy. Placental examination showed the presence of both Breus' mole and also partial hydatidiform mole. DNA samples extracted from portions of the fresh hematoma and from the fetal spleen were compared using molecular techniques. PCR analysis showed the presence of Y chromosome specific DNA in the placental clot, but a semiquantitative Southern blot demonstrated that roughly 85% of the clot DNA was of maternal origin. These findings suggest that Breus' mole represents primarily maternal thrombosis rather than fetal hemorrhage. We hypothesize that the partial mole could have contributed to the formation of the Breus' mole as some of the hydropic villi may have focally obstructed the maternal venous return from the intervillus space causing sluggish flow and promoting thrombosis. A review of the literature on Breus' mole shows that the majority of reported cases have not included cytogenetic findings. However, several authors have reported an association with triploidy and other chromosomal anomalies characterized by scattered placental hydropic villi. Thus, we suggest that obstruction of maternal venous return by hydropic villi may have played a contributory role in some of these other reported cases.     

Maternal endocrine adaptations to placental hormones in houmans

Evain-Brion D. Maternal endocrine adaptations to placental hormones in humans. Acta Pzdiatr 1999; Suppl 428: 12-16. Stockholm. ISSN 0803-5326
The remarkable endocrine alterations that are characteristic of human pregnancy are attributable to the placenta. In this tissue, steroid and peptide hormones are produced in extraordinary amounts. In addition, the haemomonochorioendothelial placentation of human pregnancy contributes to the unique distribution of products formed in trophoblasts into maternal and fetal compartments. In this review, the partial control exerted by the trophoblast on maternal metabolism is illustrated by the replacement in the maternal compartment of pituitary growth hormone (GH) with the trophoblast's own product, human placental GH. Placental GH differs from pituitary GH by 13 amino acids, has high somatogenic and low lactogenic activities and is secreted by the syncytiotrophoblast in a non-pulsatile manner. This continuous secretion appears to have important implications for the control of maternal levels of insulin-like growth factor I. Placental GH secretion is inhibited by glucose in vitro and in vivo, and is significantly decreased in the maternal circulation in cases of pregnancies with intrauterine growth retardation. U Fetal growth, growth hormone, human placenta, intrauterine growth retardation     

Intrauterine infection with Klebsiella pneumoniae: report of a case and literature review.

We report a case of intrauterine Klebsiella pneumoniae infection that resulted in premature rupture of membranes and fetal demise at 20 weeks' gestation in a pregnancy achieved by in vitro fertilization. Postmortem findings included massive panlobar pneumonia, the presence of abundant gram-negative, rod-shaped bacteria within the pulmonary air spaces and the lumen of the gastrointestinal tract, and fetal lung and blood cultures positive for Klebsiella pneumoniae. The placenta showed severe acute chorioamnionitis associated with a brisk fetal inflammatory response (umbilical cord and chorionic plate vasculitis). Marked pancreatic fibrosis was noted, indicative of a preceding necrotizing pancreatitis. In spite of this fulminant histopathologic evidence of intrauterine infection, the infection was clinically silent. This represents, to our knowledge, the 1st reported case of fatal intrauterine Klebsiella pneumoniae infection fully supported by conclusive fetal and placental histopathological evidence.     

Relationship between placental perfusion and endocrine parameters of pregnants in cases of intrauterine growth retardation

The placental perfusion index (PPI) measured I-27 days before delivery was compared with maternal urinary and serum oestriol (OT) and serum human chorial somatomammotropine (HCS) levels in the mothers of 24 newborns born with intrauterine growth retardation. No significant correlation between placental perfusion and the above endocrine parameters was found. Placental perfusion was not reduced in every case of intrauterine growth retardation. Mathematical analysis has shown that hit accuracy can be increased by the use of more endocrine parameters in pathological pregnancy.     

Third trimester intrauterine fetal death caused by arterial aneurysm of the umbilical cord.

Umbilical artery aneurysm (UAA) of the umbilical cord is an extremely rare lesion, with only 8 reported cases in the English-language literature; 7 of these were associated with significant fetal morbidity or mortality and 4 were associated with fetal trisomy 18. We report an additional case of UAA with normal karyotype that resulted in intrauterine growth restriction and fetal demise. It has been suggested that these aneurysms cause fetal hypoxia and intrauterine fetal death, either by compression of the umbilical vein or by acute kinking of the umbilical cord. Cytogenetic analysis should be performed in all cases diagnosed with this unusual lesion, and placental mosaicism for trisomy 18 should be excluded.     

Prostaglandin production and zinc depletion in human pregnancy

An association between zinc depletion and intrauterine growth retardation might occur through disturbed prostaglandin (PG) synthesis. The zinc content and PG metabolism of leucocytes from control, nonpregnant women and mothers 24-48 h after delivery, were measured and related to fetal growth and maternal smoking. Mothers of small for gestational age babies had lower polymorphonuclear and mononuclear cell zinc contents than mothers of appropriate for gestational age babies or nonpregnant controls. Monocytes were the major leucocytes producing PGs. Mothers of small for gestational age babies had higher PGE2:F2 alpha ratios than mothers of appropriate for gestational age babies. PGF2 alpha production and PGE2:F2 alpha ratio were correlated with tissue zinc status. Monocytes from nonsmokers tended to produce more PGs than those from smokers but the differences were not significant. Mild maternal zinc depletion is not significantly sufficient to alter absolute PG production, but is associated with altered differential production of PGs in human leucocytes. Zinc depletion or malnutrition may contribute to intrauterine growth retardation by affecting placental and/or umbilical PG production.     

Association of Fetal Heart Block and Massive Placental Infarction Due to Maternal Autoantibodies

Two different effects of maternal autoantibodies presented in a third-trimester pregnancy. The first was complete fetal heart block, demonstrated ultrasonographically, which correlated with the presence of anti-Ro and anti-La antibodies in the maternal serum. The second effect was decidual vasculopathy and thrombosis, a morphologic finding in the placenta that caused massive placental infarction and intrauterine death. The placental pathology correlated with the presence of anticardiolipin antibodies in the maternal serum at the time of stillbirth.     

Outcome in infants born to mothers with unexplained elevations of maternal serum alpha-fetoprotein

The outcome in infants without fetal neural tube defect born to mothers with elevated maternal serum alpha-fetoprotein was studied. Elevated maternal serum alpha-fetoprotein with normal amniotic fluid alpha-fetoprotein was found to be associated with an increased incidence of intrauterine growth retardation and nonneural tube congenital anomalies. There was no increased incidence of developmental disabilities in infants born to mothers with elevated maternal serum alpha-fetoprotein. It is speculated that adverse events occurring early in gestation may simultaneously result in congenital anomalies and subsequently elevated maternal serum alpha-fetoprotein, perhaps through disruption of the normal placental barrier between the fetal and maternal circulations.     

Abnormal Umbilical Cord Coiling Is Associated with Adverse Perinatal Outcomes

The normal umbilical cord coil index is one coil/5 cm, i.e., 0.2 ± 0.1 coils completed per cm. We report the frequency and clinical correlations of abnormally coiled cords among 1329 cases referred to our placental pathology services. Twenty-one percent of cords were overcoiled and 13% were undercoiled. Abnormal cord coiling was seen at all gestational ages. Principal clinical correlations found in overcoiled cords were fetal demise (37%), fetal intolerance to labor (14%), intrauterine growth retardation (10%), and chorioamnionitis (10%). For undercoiled cords, the frequencies of these adverse outcomes were 29%, 21%, 15%, and 29%, respectively. Abnormal cord coiling was associated with thrombosis of chorionic plate vessels, umbilical venous thrombosis, and cord stenosis. Thus, abnormal cord coiling is a chronic state, established in early gestation, that may have chronic (growth retardation) and acute (fetal intolerance to labor and fetal demise) effects on fetal well-being. The cause of abnormal cord coiling is not known. Its effects on neurological status of survivors are also unknown. Antenatal detection of abnormal cord coil index by ultrasound could lead to elective delivery of fetuses at risk, thereby reducing the fetal death rate by about one-half. We recommend that the cord coil index become part of the routine placental pathology examination. Received December 1, 1999; accepted February 15, 2000.     

Co-occurrence of massive perivillous fibrin deposition and chronic intervillositis: case report.

Chronic intervillositis (CI) and massive perivillous fibrin deposition (MFD), together with its related entity, maternal floor infarction (MFI), are rare and poorly understood placental lesions. Both MFD/MFI and CI are associated with poor fetal outcome and high risk of recurrence. We report a patient who was found to have both MFD and CI in the same placenta, resulting in severe intrauterine fetal growth restriction and intrauterine fetal death at 37 weeks of gestation. Characteristic histological findings included both very extensive perivillous deposition of fibrinoid material and a heavy infiltrate of CD68-positive macrophages/monocytes in the maternal intervillous space. To our knowledge, this is the first time the co-occurrence of MFD and CI is reported in the literature.     

Maternal endocrine adaptations to placental hormones in humans

The remarkable endocrine alterations that are characteristic of human pregnancy are attributable to the placenta. In this tissue, steroid and peptide hormones are produced in extraordinary amounts. In addition, the haemomonochorioendothelial placentation of human pregnancy contributes to the unique distribution of products formed in trophoblasts into maternal and fetal compartments. In this review, the partial control exerted by the trophoblast on maternal metabolism is illustrated by the replacement in the maternal compartment of pituitary growth hormone (GH) with the trophoblast's own product, human placental GH. Placental GH differs from pituitary GH by 13 amino acids, has high somatogenic and low lactogenic activities and is secreted by the syncytiotrophoblast in a non-pulsatile manner. This continuous secretion appears to have important implications for the control of maternal levels of insulin-like growth factor I. Placental GH secretion is inhibited by glucose in vitro and in vivo, and is significantly decreased in the maternal circulation in cases of pregnancies with intrauterine growth retardation.     

Fetal origins of cardiovascular disease

Several epidemiologic studies have shown that intrauterine growth retardation is a risk factor for the development of cardiovascular disease in later life. In this review, we discuss these epidemiologic studies and animal models that have been developed to investigate the pathophysiology of this phenomenon. We discuss data suggesting that intrauterine growth retardation leads to fetal exposure to maternal glucocorticoids. In addition, we present other data showing that fetal exposure of glucocorticoids during specific times of fetal development results in focal and segmental glomerulosclerosis, a reduced number of nephrons, hypertension, and diabetes. These studies suggest that at critical times during fetal development fetal injury programs the development of cardiovascular disease and diabetes in later life.     

基于胎盘病理性炎症的<34孕周早产危险因素分析

目的 基于胎盘病理性炎症,探讨<34孕周早产的危险因素。方法 以2008年1月至2010年10月在上海交通大学附属国际和平妇幼保健院孕27+0～33+6周住院并分娩的孕产妇为研究对象。将研究对象分为孕27+0～31+6周和孕32+0～33+6周组,探讨<34孕周早产的危险因素。结果 ①孕27+0～31+6周组和孕32+0～33+6周组分别纳入106和110例,两组在母亲年龄、剖宫产和产前使用激素方面差异均无统计学意义。48.1%（104/216）胎盘病理性炎症反应阳性（MIR+）,其中51.0%（53/104）为仅母体炎症反应阳性（MIR+FIR-）,49.0%（51/104）母体-胎儿炎症反应均阳性（MIR+FIR+）;51.9％（112/216）母体-胎儿炎症反应均阴性(MIR-FIR-),未见母体炎症阴性-胎儿炎症阳性（MIR-FIR+）的病理结果。②早产主要危险因素包括早产胎膜早破（n=105）、临产(n=115)、妊娠高血压(n=52)、胎儿宫内窘迫(n=51)、产前出血(n=47)、前置胎盘(n=21)、流产史(n=108)、非正规产检(n=46)、妊娠合并内科疾病(n=23)和宫内生长迟缓(n=10)等。③在孕27+0～31+6周组中,MIR+FIR-亚组和MIR+FIR+亚组早产胎膜早破以及临产发生率显著高于MIR-FIR-亚组（64.3% 、83.9% vs 21.3%,P=0.000;78.6%、67.7% vs 46.8%,P=0.016）;母亲妊娠高血压发生率显著低于MIR-FIR-亚组(0、6.5% vs 40.4%,P=0.000);MIR+FIR+亚组产前出血的发生率显著低于MIR-FIR-和MIR+FIR-亚组（6.5% vs 29.8%,32.1％,P=0.027）。在孕32+0～33+6周组中,MIR+FIR-亚组和MIR+FIR+亚组早产胎膜早破、临产发生率显著高于MIR-FIR-亚组(52.0%、90.0% vs 30.8%,P=0.000)。④当MIR-FIR-时,孕27+0～31+6周组临产发生率显著高于孕32+0～33+6周组（46.8%和20.0%,P=0.003）。当MIR+FIR-和MIR+FIR+时,各胎龄组间危险因素差异均无统计学意义。结论 宫内炎症阳性时多为自发性早产,合并早产的其他危险因素较少;宫内炎症阴性时多存在多样的医源性早产因素。宫内炎症存在时并不增加胎儿宫内窘迫、胎盘早剥发生率。     

Maternal smoking and feto-infant mortality: biological pathways and public health significance

Smoking during pregnancy has in many countries replaced poverty as the most important preventable risk factor for an unsuccessful pregnancy outcome. Maternal smoking induces fetal hypoxia and morphological changes of the placenta, which increase the risks of intrauterine growth retardation and placental abruption, which may cause late fetal death and possibly also neonatal mortality. Smoking influences post-neonatal mortality through increased risk of sudden infant death syndrome (SIDS), but why maternal smoking increases the risk of SIDS is essentially unknown. In reducing the overall smoking prevalence in society, general preventive measures have been successful. Such measures. which aim at preventing young girls from starting to smoke are in the long run the most effective way to reduce smoking during pregnancy.     

Insulin-like growth factor I in substrate-deprived, growth-retarded fetal rats

Plasma, amniotic fluid, and tissue concentrations of IGF-I were examined in nutritionally deprived, growth-retarded fetal rats to determine whether IGF-I concentration serves as a marker for nutritional status. Growth retardation was induced by 72 h of maternal fasting. Twenty-three control and 17 growth-retarded fetuses were individually analyzed and compared. Plasma IGF-I concentrations were significantly lower in test compared with control animals (test 56.8 +/- 14.9, control 87.4 +/- 17.5 ng/mL, p less than 0.01). Amniotic fluid IGF-I concentrations were not different (test 14.0 +/- 8.7, control 12.2 +/- 2.6 ng/mL). IGF-I concentrations obtained from both placental and hepatic tissues were lower in test compared with control animals [placenta: test 293 +/- 25 versus control 655 +/- 114 ng/g (p less than 0.001); hepatic: test 173 +/- 38 versus control 230 +/- 51 ng/g (p less than 0.01)]. Reductions in fetal, placental, and hepatic weights in test animals were more closely related to changes in placental IGF-I concentration than to either plasma or hepatic IGF-I concentrations. We conclude that fetal plasma IGF-I is a valuable marker for intrauterine substrate deprivation and that the growth-retarded rat fetus is accurately identified and specifically characterized by a low placental concentration of extractable IGF-I.     

Intrauterine fetal death of a monochorionic twin with peripheral pulmonary infarcts: potential thromboembolic events following death of co-twin

In utero fetal lung infarction has rarely been reported. We present a case of intrauterine lung infarction in a 28-3/7 weeks' gestation monochorionic twin following intrauterine fetal demise of the co-twin at 20 weeks. This case highlights the potential for thromboembolic events (TBEs) associated with monochorionic gestations to include pulmonary TBE and infarction among the risks for fetal morbidity and mortality.     

Determinants of fetal growth and body proportionality

Previous studies of fetal growth and body proportionality have been based on error-prone gestational age estimates and on inappropriate comparisons of infants with dissimilar birth weights. Based on a cohort of 8719 infants with validated (by early ultrasonography) gestational ages and indexes of body proportionality standardized for birth weight, potential maternal and fetal determinants of fetal growth and proportionality were assessed. Maternal history of previous low birth weight infants, pregnancy-related hypertension (particularly if severe), diabetes, prepregnancy weight, net gestational weight gain, cigarette smoking, height, parity, and fetal sex were all significantly associated with fetal growth in the expected directions. Consistent with previous reports, maternal age, marital status, and onset or total amount of prenatal care had no significant independent effects. Fetal growth ratio (relative weight for gestational age), pregnancy-related hypertension, fetal sex, and maternal height were the only significant determinants of proportionality. Infants who were growth-retarded, those with taller mothers, those whose mothers had severe pregnancy-related hypertension, and males tended to be longer and thinner and had larger heads for their weight, although these variables explained only a small fraction of the variance in the proportionality measures. Among infants with intrauterine growth retardation, gestational age was not independently associated with proportionality (in particular, late term and post-term infants did not tend to be more disproportional), a finding that does not support the hypothesis that earlier onset of growth retardation leads to more proportional growth retardation. The results raise serious questions about previous studies of proportionality, particularly those suggesting a nutritional etiology for proportional intrauterine growth retardation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Luteinized cystic ovarian hyperplasia associated with placentomegaly due to chorangiomatosis

Luteinized cystic ovarian hyperplasia (LCOH) is a rare benign condition characterized by bilateral ovarian enlargement during pregnancy secondary to high maternal human chorionic gonadotropin serum levels referred to occur under several conditions. We report the case of a 29-year-old obese woman with LCOH incidentally discovered during cesarean section of a single pregnancy at 35 weeks of gestation for fetal intrauterine demise. The fetus showed external ambiguous genitalia, imperforate anus, bilateral dysplastic kidneys, and hydrometrocolpos secondary to atresia of the vagina. The placental weight was 1,450 g (normal for gestational age: 415 g). The placenta showed diffuse chorangiomatosis (CM) characterized by multifocal stem villi enlargement containing increased number of small vessels with alpha-smooth muscle actin positive cells in the walls in a dense reticulin fibers-rich stroma. The combination of LCOH and placentomegaly due to CM appears to be unique.     

Intrauterine feeding of the growth retarded fetus: can we help?

Intrauterine feeding of the growth retarded fetus appears an attractive therapeutic possibility. However the factors which determine the reversibility of intrauterine growth retardation are poorly understood. While fetal substrate supply is the final common pathway by which many factors restrict fetal growth, improving fetal substrate supply does not always lead to improved fetal growth. Similarly, fetal substrate supply is an important regulator of fetal endocrine status, such as circulating IGF-1 levels, but again, improving fetal substrate supply does not always alter fetal endocrine status or fetal growth. The relationship between substrate supply, endocrine status and growth is regulated in a complex way by placental function. Understanding the role of the placenta in this regulation is essential if in the future we are to help the growth retarded fetus.