A piece in the puzzle of intrauterine fetal death: Pathological findings in placentas from term and preterm intrauterine fetal death pregnancies

Objective.?To compare pathological findings of placentas from term and preterm pregnancies complicated by intrauterine fetal death (IUFD).

Study design.?A retrospective cohort study was conducted including deliveries complicated by IUFD. A comparison was made between placentas from term and preterm (<37 weeks' gestation) pregnancies complicated by IUFD. A second analysis was undertaken comparing IUFD placentas delivered before and after 34 weeks' gestation. Uteroplacental insufficiency was defined when one or more of the following pathological features were found: placental infarct, poor vascularity of the chorionic villi, intravascular thrombi and vascular occlusion.

Results.?During the study period, 849 placentas of IUFD were examined. Gross and microscopic pathological finding were noted. When comparing gross and microscopic findings in term and preterm (<37 weeks) IUFD placentas, higher rates of calcifications, tissue congestion and cellular metaplasia were found in term vs. preterm placentas. Significantly increased rates of poor tissue vascularity, placental vascular occlusion and uteroplacental insufficiency were demonstrated in preterm IUFD placentas. When comparing pathological findings in IUFD placentas delivered before and after 34 weeks' gestation, higher rates of abnormal cord insertion, calcifications, tissue congestion, infarcts and intravascular thrombi as well as poor tissue vascularity and placental vascular occlusion were demonstrated in IUFD placentas delivered before 34 weeks. Regardless of gestational age at the time of IUFD in more than 90% of placentas vascular wall thickening was found. A third of both term and preterm placentas demonstrated histological chorioamionitis.

Conclusions.?A vast majority of IUFD placentas reveal numerous pathological findings that reflect uteroplacental insufficiency and abnormal blood supply. Different characteristics were noted in term and preterm placentas of pregnancies complicated by IUFD. Better definition of causes and associated placental pathological findings of IUFD might aid clinicians in counseling such patients regarding the reason and risk of recurrence in subsequent pregnancies.     

Placental expression of syndecan 1 is diminished in preeclampsia

OBJECTIVE: Syndecan 1 is a cell surface heparan sulfate proteoglycan that binds growth factors and antithrombin III. The objective of this study was to examine whether placental expression of syndecan 1 in preeclampsia differs from that in normal pregnancy and whether gestational age and fetal growth affect syndecan 1 expression. STUDY DESIGN: An immunohistochemical analysis of 30 placentas of women with severe preeclampsia and 15 placentas of women without preeclampsia was performed with the monoclonal anti-syndecan 1 antibody B-B4. RESULTS: In 47% of preeclamptic placentas the immunoreactivity with antibody B-B4 was faint or absent, whereas 93% of the normal placentas exhibited strong immunoreactivity. The reduction in placental expression of syndecan 1 in preeclampsia was not associated with gestational age or impaired fetal growth. CONCLUSION: The expression of syndecan 1 on the chorionic villi is reduced in preeclampsia irrespective of gestational age or fetal growth.     

Elastic fibres in the human placenta

Recent studies described the presence of elastic fibres within stem villi of human term placenta. This particular study focuses on changes of the elastic fibre system in placental villous tree from placentas of different gestational ages. The presence of elastic fibres was researched by light and electron microscopy in first-, second-trimester and term human placentas. Light microscopic analysis revealed elastic fibres in the stroma of main stem villi and in large vessels present in the chorionic plate of term placentas. Transmission electron microscopy revealed a wide variation in microfibrillar component deposition in placentas from all the gestational ages studied. Although minimal amount of the microfibrillar component was observed only in some main stem villi of second-trimester placentas, abundant microfibrillar material was present in all types of placental villi in placental sections from term pregnancies. The amorphous component was only occasionally identified in sections from the chorionic plate of second trimester placentas. In ultra-thin sections from placental tissues from the 37th to the 42nd weeks of gestation, we can observe the amorphous component of the elastic fibres. Bundles of microfibrils with scanty participation of the amorphous component of the elastic fibres can be observed in stem villi. In mature intermediate villi, cells and their processes with distinct plasma membranes were seen close to some bundles of microfibrillar component, at times with small spots of the amorphous component. This study shows that elastic fibres of the villous stroma, are mainly composed of the microfibrillar component, while the amorphous component appears more frequently in advanced stages of villous differentiation of term placentas.     

Increased trophoblast inclusions in placentas from prematurely born infants: A potential marker of risk for preterm neurodevelopmental outcomes

Trophoblast inclusions (TIs) are placental abnormalities of the trophoblast bilayer. Present in 2–8% of full-term placentas, they are associated with poor neurodevelopment, including autism. Although previously unstudied, examination of chorionic villi from 108 preterm births revealed a ∼4 fold increase in the frequency of TIs (30.5%). Frequency of TIs was inversely related to gestational age (GA); 43% of placentas <30 weeks and 20% of placentas ≥32 weeks had TIs (χ2 = 4.41, p = 0.036). This increased prevalence in preterm infants suggests that TIs may indicate adverse intrauterine processes or undetected genetic abnormalities and could identify infants at risk for poor neurodevelopment.     

Surface area of chorionic villi of placentas: an index of intrauterine growth restriction of fetuses

Aim:  Histomorphometric studies of placentas from idiopathic intrauterine growth restricted (IUGR) fetuses as well as normal-weight (control) fetuses were performed to determine surface area of chorionic villi (mostly terminal and few intermediate) using stereological technique. The results were compared to determine the difference in the values of surface area of chorionic villi, and to establish any relationship between placental histomorphometric changes and IUGR.
Methods:  Placentas from fifty (50) full-term, uncomplicated deliveries were collected; twenty eight (28) of them were associated with IUGR babies and twenty two (22) were from normal-weight babies. Placental weights and volumes were measured. Pieces of placental tissues were formalin-fixed, processed and embedded in paraffin. Seven-micron sections were cut and stained with HE stain. Histomorphometric and stereological studies were performed.
Results:  IUGR placental weights and volumes were lower than those of controls. Surface areas of villi of IUGR placentas had a mean of 8.19 m² (SD ± 2.88). For control placentas, the mean was 10.02 m² (SD ± 1.83). The mean value of the surface area of villi of the IUGR group was significantly lower than that of the control group.
Conclusion:  These findings pointed to a defect in the normal interaction between trophoblast and maternal tissue, leading to a reduced surface area of villi. Because the surface area of the villi presents the interface between maternal and fetal circulation, its reduction might be the cause of idiopathic intrauterine growth restriction.     

Prenatal findings in congenital leukemia: a case report

We here describe a case of congenital leukemia that ended in intrauterine fetal demise at 30 weeks of gestation. Acute enlargement of the fetal trunk, elevated pulsatility index of the umbilical artery with concomitant decline of pulsatility index of the middle cerebral artery, pleural effusion, and polyhydramnios preceded the fetal death. Diagnosis of congenital myeloid leukemia was suggested by microscopic examination of the placental tissue, revealing immature myeloid precursors filling the lumina of fetal vessels in the umbilical cord and chorionic villi. Extensive vascular involvement of the placenta by leukemic cells was considered to be a primary cause of the fetal death.     

A comparison in concentration of heat shock proteins (HSP) 70 and 90 on chorionic villi of human placenta in normal pregnancies and in missed miscarriages

PURPOSE: To investigate the role of heat shock protein (HSP) on the chorionic villi of human placental cells and to compare the concentration of placental HSP70 & 90 in term deliveries and in missed miscarriages. MATERIALS AND METHODS: Fifty products of conception from women who experienced first trimester missed miscarriage and 50 placentas from women who gave birth at term were studied. An immunohistochemical investigation was carried out with which we marked the localization of heat shock proteins 70 and 90 on the syncytiotrophoblastic, cytotrophoblastic, stromal and blood vessel cells, using specific antibodies which can detect the presence of those proteins on light microscopy. We compared their expression with the normal placental tissue of term pregnancies and with material acquired from first trimester missed miscarriages. An indirect immunoperoxidase method was applied using polyclonal antibodies against HSP70 and HSP90 on formalin-fixed paraffin-embedded tissues. RESULTS: Expression of HSP90B was increased in chorionic villi of first trimester missed miscarriages concerning syncytiotrophoblasts, cytotrophoblasts, vessel and stroma cells compared to full-term placentas. There was a statistically significant increase of HSP90A expression in chorionic villi of first trimester missed miscarriages, concerning only the cytotrophoblast cells, compared to full-term placentas. Expression of HSP70 cognate protein was significantly increased in chorionic villi of first trimester missed miscarriages, concerning syncytiotrophoblastic cells only, compared to full-term placentas. Finally, HSP70 inducible protein was significantly increased in chorionic villi of first trimester missed miscarriages concerning syncytiotrophoblasts, cytotrophoblasts, vessel and stroma cells compared to full-term placentas. CONCLUSIONS: The results of the present study have sufficiently shown that there is an increase of HSP70 & 90 expression in chorionic villi of first trimester missed miscarriages compared to full-term placentas and this increase may have an important implication on the miscarriage process.     

Thrombophilia is not associated with an increase in placental abnormalities in women with intra-uterine fetal death

BACKGROUND: The aim of this study was to investigate whether women with thrombophilia and intrauterine fetal death have a higher incidence of placental lesions as compared with those without thrombophilia. METHOD: In a case-control study comprising 50 women with an obstetrical history of intrauterine fetal death, placental histology comparison was made between those with thrombophilia and those without thrombophilia. RESULTS: Of the women who had an intrauterine fetal death, eight (16%) had a thrombophilia factor. There were no differences in birth weight, gestational age and parity or in placental volume and weight between the eight women with and the 42 women without thrombophilia. There was no statistically significant difference between placentas of the women with and those without thrombophilia. CONCLUSION: In a group of women who had an obstetrical history of intrauterine fetal death, those with thrombophilia do not have a difference in placental histological lesions compared with the women without a thrombophilia factor. Future thrombophilia research should be focused on placental bed specimens.     

Stereological quantification of placental villus vascularization and its relation to umbilical artery Doppler flow in intrauterine growth restriction

The aim of this study was to investigate the changes in the number of vessels within tertiary stem villi and intermediate/terminal villi which may be responsible for the abnormalities in placental vascular resistance and Doppler velocity index values in growth-restricted fetuses. The placentas of 20 cases with intrauterine growth restriction and 30 cases which were appropriate for gestational age were studied. The umbilical artery resistance index, pulsatility index and systolic to diastolic ratio were measured in each case. The vessels were quantified by a stereological method described previously and vascular surface density and the volume portion of the villi were calculated. The placentas of preterm and term cases with intrauterine growth restriction displayed significant reductions in the vascular surface density of stem and intermediate/terminal villi and volume portion of intermediate/terminal villi stroma when compared with gestation-matched normally grown cases (p<0.05). There was no significant correlation between Doppler index values of the umbilical artery and the stereological parameters of the intermediate/terminal and stem villi in the intrauterine growth restriction group (p>0.05). Some of the pregnancies with intrauterine growth restriction (six patients) with normal Doppler flow velocity waveforms had reduced vascularization in the placentas, and these pregnancies were found to have no perinatal complications. We conclude that,although the placental villi show reduced vascularization in pregnancies with intrauterine growth restriction, the Doppler indices may be normal and this normal flow pattern is related to reduced complication rate.     

Mechanisms of pregnancy loss in antiphospholipid syndrome

Antiphospholipid antibodies are associated with intrauterine fetal growth retardation and fetal distress leading to premature birth or fetal death. These complications are caused by uteroplacental insufficiency that is the result of multiple placental thromboses, infarcts, and spiral artery vasculopathy, which are almost certainly provoked by the hypercoagulable state induced by aPL antibodies. Available data indicate that the thrombogenic function of aPL antibodies involves their general effect on platelets, endothelial cells, anticoagulant mechanisms, and fibrinolytic pathways, as well as their local effect on trophoblasts and villi cells, leading to reduction of annexin V (placental anticoagulant protein-I) production and inhibition of its anticoagulant function.     

孕中晚期双胎之一胎死宫内存活儿预后分析

目的:分析双胎之一胎死宫内(sIUFD)后存活儿的预后。方法:回顾分析2017年1月至2019年11月在郑州大学第三附属医院分娩的sIUFD病例58例,包括sIUFD发生孕周、胎死原因、不同孕周及不同绒毛膜性存活儿的新生儿结局及脑损伤情况,并随访其神经发育情况。结果:58例孕中晚期发生sIUFD的病例中单绒毛膜双羊膜囊双胎(MCDA)27例,双绒毛膜双羊膜囊双胎(DCDA)31例。死亡原因中脐带、胎盘异常占25.9%(15/58),胎儿发育异常占5.2%(3/58);存活儿的早产率为70.7%(41/58),其中最小孕周28+1周。与DCDA双胎组比较,MCDA双胎组分娩胎龄、出生体重、Apgar评分均较低。与孕中期比较,孕晚期发生sIUFD的早产率、MCDA双胎数及急诊剖宫产率更高,新生儿出生体重、Apgar评分更低。新生儿出生后头颅超声脑异常9例,其中新生儿脑损伤3例(5.2%,3/58),分别为2例脑软化,1例脑室内出血Ⅲ级。存活儿目前的存活率为91.4%(53/58),随访时间平均28个月,3例婴幼儿智能发育量表(CDCC)监测可疑。结论:绒毛膜性、死胎发生孕周、终止妊娠的孕周是影响妊娠结局的主要因素,需加强产前、产后神经影像学检查及远期标准化随访。     

Management of single fetal demise in a multiple gestation

Intrauterine fetal demise of 1 twin in a multiple gestation is a complex clinical situation. Chorionicity, gestational age at diagnosis, problems specific to the pregnancy, and the emotional needs of the patient can impact management. Strategies to optimize outcomes may include a multidisciplinary team approach and fetal surveillance. The following article reviews (1) adverse fetal and neonatal outcomes associated with intrauterine fetal demise of 1 twin, (2) the potential maternal impact, and (3) the strategies to possibly prevent poor outcomes. It is important to remember that even the most vigilant care may not avoid adverse sequelae in a portion of at-risk pregnancies.     

First-trimester maternal placental protein 13 levels in pregnancies resulting in adverse outcomes

BACKGROUND: In a previous study, reduced levels of maternal serum placental protein 13 (PP13) in the first trimester have been correlated with adverse pregnancy outcomes. The objective of this study was to compare first-trimester PP13 levels in control pregnancies with pregnancies resulting in one or more of the following adverse outcomes: intrauterine growth restriction (IUGR), small and very small (3rd, 5th, 10th centile) for gestational age (SGA), low (<1.5 and < 2.5 kg) birth weight (LBW), macrosomia (the > 90th centile), large birth weight (>4.5 kg), preterm (35-36 weeks) and very early (<34 weeks) delivery (PTD), and intrauterine fetal demise (IUFD). METHODS: Maternal serum samples from 1940, 11 to 14 weeks singleton pregnancies, were assayed for PP13 and the concentrations were corrected for gestational age, maternal weight, smoking status, and ethnic origin. A comparison of the levels of PP13 in 364 controls and 1576 adverse outcome categories was made. PP13 levels were expressed in terms of both concentration and multiple of medians (MoMs). RESULTS: Comparison of PP13 MoMs from SGA, PTD, and low birth weight samples with control pregnancy samples showed no statistically significant difference. In macrosomic pregnancies (>90th centile), levels of PP13 were significantly higher than controls (p = 0.0263) although the number of cases in this study was small. CONCLUSION: Decreased levels of PP13 were not significantly correlated with the studied adverse pregnancy outcomes of IUGR, PTD low birth weight, and IUFD. Further studies are required to evaluate if measurement of PP13 has any value in the early assessment of pregnancies.     

Morphology of the materno-fetal metabolic barrier in the human placenta]

On chorionic villi of normal human placentas obtained from different aged females morphological studies were made with a view to collecting new data on the molecular structure and material composition of the materno-fetal metabolism barrier. The basement membrane of the chorionic epithelium is characterized by a network of fine collagen filaments arranged parallel to the plane of the membrane and having diameters less than 200 A. Lying between the filament proteins are lipid molecules in the form of bimolecular lamellae, which with their longitudinal axes are oriented approximately vertical to the plane of the membrane and whose thickness is about 40 A. There are many bimolecular lipid layers. In addition, noncollagenic proteins and uronic-acid-free polysaccharides were also found in the epithelial basement membranes. The submicroscopic organization of the endothelial basement membrane of fetal capillaries is different from that of the epithelial basement membrane of chorionic villi. Whereas lipid components disposed vertically to the plane of the membrane and parallelly oriented protein filaments are also present, collagen seems to be nonexistent as is evident from polarization-optical results. Running parallel to the surface of villi and in the apical sections of the plasmodium are protein filaments which are arranged in the form of a network and probably have certain mechanical functions. The structure of the outer membrane is similar to that of the basement membranes because of the presence there in of oriented lipid inclusions. In the region of microvilli and in the outer zone of the plasmoditrophoblast of young placenta there has been found N-acetyl neuraminic acid. The so-called "placental fibrinoid" in the intervillous space is exclusively composed of fibrin. There are no additions of collagen to be found. Therefore, it appears unjustified to use the term "fibrinoid". Glycosaminoglycanes are present in the stroma of villi, and they are oriented in the direction of disposition of collagenous fibers. Their content in the stroma of villi decreases with the progress of gravidity. They are also involved in displacental material transport, although the degree of involvement decreases with the progress of gravidity. Functionally, they show what has been called a "molecular screening effect". The lipid-protein system of the epithelial basement membrane-together with the endothelial basement membrane of fetal vessels in the second half of gravidity-is the principal barrier to the passive passage there-through of substances.     

Velamentous cord insertion in dichorionic and monochorionic twin pregnancies – Does it make a difference?

ObjectiveTo estimate the prevalence of velamentous cord insertion (VCI) in dichorionic (DC) and monochorionic (MC) twins with and without twin-twin transfusion syndrome (TTTS), and to study the associated outcomes.MethodsWe recorded the type of umbilical cord insertion in all consecutive DC and MC placentas examined in two European tertiary medical centers. The association between VCI and perinatal outcomes was estimated and compared.ResultsA total of 1498 twin placentas were included in this study (DC placentas n = 550, MC placentas without TTTS n = 513 and MC placentas with TTTS n = 435). The prevalence of VCI in DC, MC without TTTS and MC with TTTS groups was 7.6%, 34.7% and 36.1%, respectively (P < 0.001). In MC twins (non-TTTS and TTTS groups), VCI was associated with severe birth weight discordance (odds ratio [OR] 4.76 95% CI 2.43, 10.47 and OR 4.52 95% CI 1.30, 28.59, respectively). In MC twins without TTTS, VCI was associated with small for gestational age (OR 1.66, 95% CI 1.12, 2.50). VCI was significantly associated with increased risk of intrauterine fetal demise in MC twins, and this effect was greater in the non-TTTS group (OR 2.71 95% CI 1.38, 5.47). These associations did not occur in DC group. Gestational age at birth was lower in the presence of VCI in the DC and MC twins without TTTS.ConclusionOur findings confirm that the prevalence of VCI is higher in MC twins than in DC twin pregnancies. VCI is an important indicator of adverse perinatal outcome, particularly in MC twins.     

Immunocytochemical staining patterns of placentas associated with hydrops fetalis

This study examined the morphology and immunocytochemical staining patterns of distribution of beta-human chorionic gonadotropin (beta-HCG), human placental lactogen (HPL), placental alkaline phosphatase (PLAP), and pregnancy-specific beta-1 glycoprotein (SP1) in 13 third-trimester placentas associated with hydrops fetalis and six normal control placentas matched for gestational age (+/- 2 weeks). Seven placentas were hydropic (540-1,080 g) and demonstrated histologic immaturity with large edematous chorionic villi showing few blood vessels, most of which contained immature hematopoietic elements. These placentas showed consistently increased staining for beta-HCG and decreased staining for PLAP when compared with control placentas, a pattern reminiscent of less mature placentas. HPL and SP1 staining were similar to those of controls. Six placentas were either sclerotic (four) or histologically unremarkable (two), and these did not differ in their immunocytochemical staining properties from control placentas. We conclude that third-trimester hydropic placentas, in addition to showing histologic immaturity, exhibit an immunocytochemical staining pattern associated with first-trimester placentas.     

Residual anastomoses after fetoscopic laser surgery in twin-to-twin transfusion syndrome: frequency, associated risks and outcome

Fetoscopic laser coagulation of placental vascular anastomoses is considered to be the treatment of choice in severe twin-to-twin transfusion syndrome. The aim of fetoscopic laser surgery is to separate completely the inter-twin placental circulation. Incomplete laser coagulation may result in residual vascular anastomoses. The incidence and clinical implications of residual anastomoses in twin-to-twin transfusion syndrome treated with fetoscopic laser surgery has not yet been studied. We examined all placentas treated with fetoscopic laser surgery and delivered at our center between June 2002 and December 2005 with vascular injection using colored dyes. Presence of residual anastomoses was studied in association with adverse outcome and inter-twin hemoglobin difference at birth. Adverse outcome was defined as fetal demise, neonatal death or severe cerebral injury. The relation between residual anastomoses and placental localization (anterior or posterior uterine wall) was evaluated. A total of 52 laser-treated placentas were studied. Residual anastomoses were detected in 33% (17/52) of placentas. Adverse outcome was similar in the groups with and without residual anastomoses, 18% (6/34) and 29% (20/70), respectively (p=0.23). Large inter-twin hemoglobin differences (>5g/dL) were found in 65% (11/17) of cases with residual anastomoses and 20% (7/35) of cases without residual anastomoses (p<0.01). Anterior placental localization was not associated with a more frequent presence of residual anastomoses. In conclusion, residual anastomoses at our institution are seen in one-third of monochorionic placentas treated with fetoscopic laser surgery. Although residual anastomoses in our study were not associated with adverse outcome, they were often associated with neonatal hematological complications.     

Placental Pathology in Patients Using Cocaine: An Observational Study

Objective: Although retroplacental hemorrhage is a major cause of fetal death, its etiology often remains obscure. In some reports, cocaine use by pregnant women has been associated with retroplacental hemorrhage and clinical abruptio placentae. This study was designed to assess the occurrence of chorionic villus hemorrhage, an entity shown recently to be associated with retroplacental hemorrhage, in the placentas of cocaine users.Methods: Twenty-nine placentas from cocaine users and 15 placentas from drug-free controls, as determined by questionnaire and urine toxicology screen, were examined prospectively, and pathological findings documented. The prevalence of retroplacental hemorrhage, chorionic villus hemorrhage, edema, chorioamnionitis, funisitis, infarction, fetal vessel thrombosis, and intervillus hemorrhage was examined in the two groups.Results: Chorioamnionitis was the most frequent finding in both groups (58% of cocaine users, 66% of controls). Edema of moderate severity or greater was found only in the cocaine-using group (17%). The prevalence of chorionic villus hemorrhage among women using cocaine also was 17%.Conclusion: Cocaine use during pregnancy may be associated with chorionic villus hemorrhage and villus edema, even in the absence of clinical abruptio placentae. The relationship between abnormal placental morphology and adverse perinatal outcomes remains to be determined.     

Pathologic features of placentas from singleton pregnancies obtained by in vitro fertilization and embryo transfer

Fifty placentas were collected at term from singleton pregnancies resulting from in vitro fertilization (IVF) and intrauterine embryo transfer. Their pathologic features were compared with those of a control group composed of 50 placentas obtained from spontaneous singleton pregnancies. The mean maternal age, mean gestational age, mean fetal weight, sex ratio, and rate of pregnancy complications did not differ. There was also no significant difference between the groups in the mean placental weight and in the incidence of placental pathologic lesions, including extended infarcts, massive perivillous fibrin depositions, chorioangiomas, and placental inflammatory lesions. The incidence of abnormal placental shapes was significantly (P less than .05) greater in the IVF group (22%) compared with the control group (6%). A significant (P less than .025) difference was observed between the groups in the distribution of umbilical cord insertions. The mean distance between the cord insertion and the closest placental margin was significantly (P less than .005) shorter in the group conceived by IVF (3.23 +/- 1.91 cm) than in the control group (4.54 +/- 2.42 cm). A relationship between these placental morphologic features and the superficial implantation and/or inadequate orientation of the blastocyst after IVF and intrauterine embryo transfer is proposed.     

Decreased first trimester PAPP-A is a predictor of adverse pregnancy outcome

OBJECTIVE: Low levels of maternal serum pregnancy associated plasma protein-A (PAPP-A) have been linked to chromosome anomalies such as trisomy 21, 13 and 18, triploidy and sex chromosome aneuploidy. Low levels of PAPP-A have also been implicated in spontaneous miscarriage. The purpose of this study was to evaluate whether low levels of first trimester PAPP-A are predictive of other adverse pregnancy outcomes. STUDY DESIGN: The study included patients with singleton pregnancies who underwent combined first trimester screening using nuchal translucency (NT) and maternal serum free beta-human chorionic gonadotrophin (free beta-hCG) and PAPP-A at 10-13 weeks' gestation. Patients with chromosome aberrations or fetal anomalies were excluded. Serum marker levels were expressed as gestational age-specific multiples of the median (MoMs). The incidences of various adverse pregnancy outcomes (spontaneous preterm labor, fetal growth restriction (FGR), proteinuric and non-proteinuric pregnancy induced hypertension (PIH), intrauterine fetal demise, oligohydramnios, spontaneous miscarriage and placental abruption) were evaluated, according to maternal PAPP-A MoM levels. RESULTS: Of the 1622 patients in the study, pregnancy complications were observed in 184 (11.3%). Patients with PAPP-A < or =0.25 MoM had significantly higher rates of FGR (RR = 3.12), proteinuric PIH (RR = 6.09), spontaneous miscarriage (RR = 8.76). No statistically significant differences were noted for other adverse outcomes evaluated Women with PAPP-A < or =0.50 MoM also had significantly higher rates of FGR (RR = 3.30) and spontaneous miscarriage (RR = 3.78). CONCLUSIONS: We conclude that decreased levels of first trimester maternal serum PAPP-A are predictive not only of chromosome anomalies but also of adverse pregnancy outcome.