Intracranial Hemorrhage In Premature Infants Research Articles

Impact of different angles of pulmonary surfactant administration on bronchopulmonaryplasia and intracranial hemorrhage in preterm infants: a prospective randomized controlled study

To investigate the effects of different angles of pulmonary surfactant (PS) administration on the incidence of bronchopulmonary dysplasia and intracranial hemorrhage in preterm infants. A prospective study was conducted on 146 preterm infants (gestational age <32 weeks) admitted to the Department of Neonatology, Provincial Hospital Affiliated to Anhui Medical University from January 2019 to May 2023. The infants were randomly assigned to different angles for injection of pulmonary surfactant groups: 0° group (34 cases), 30° group (36 cases), 45° group (38 cases), and 60° group (38 cases). Clinical indicators and outcomes were compared among the groups. The oxygenation index was lower in the 60° group compared with the other three groups, with shorter invasive ventilation time and oxygen use time, and a lower incidence of bronchopulmonary dysplasia than the other three groups (P<0.05). The incidence of intracranial hemorrhage was lower in the 60° group compared to the 0° group (P<0.05). The cure rate in the 60° group was higher than that in the 0° group and the 30° group (P<0.05). The clinical efficacy of injection of pulmonary surfactant at a 60° angle is higher than other angles, reducing the incidence of intracranial hemorrhage and bronchopulmonary dysplasia in preterm infants.

Effect of delayed cord clamping on cerebral hemodynamics in preterm infants

BackgroundUnstable cerebral hemodynamics is an important cause of intracranial hemorrhage in premature infants. The increased blood flow of delayed cord clamping (DCC) compared to immediate cord clamping (ICC) is equivalent to 1/3-1/4 of newborn blood volume. Our objective was to assess whether the increased blood flow causes fluctuations in cerebral blood flow and how. MethodsThis experiment was a prospective, observational study. Neonatologists selected preterm infants eligible for inclusion and exclusion, and divided them into DCC group and ICC group according to the way of umbilical cord ligation performed by obstetrics department, and matched them 1:1 according to gestational age. The peak systolic velocity （PSV) ，end diastolic velocity (EDV)，and resistance index (RI) of middle cerebral artery was measured by Mindray M9 color ultrasonic diagnostic instrument within 1 h, 24±1 h, 48±1 h, 72±1 h, respectively. ResultsThere was no significant difference in PSV, EDV and RI in middle cerebral artery between DCC group and ICC group (P > 0.05). There were no significant differences between groups and time (P > 0.05). The hemoglobin and hematocrit in DCC group were higher than those in ICC group within 2 h after birth (P < 0.05). (P > 0.05). ConclusionDCC can increase hemoglobin and hematocrit in preterm infants, but does not cause cerebral blood flow fluctuation within a certain range. DCC is a safe method of placental transfusion.

Neuroimaging of Germinal Matrix and Intraventricular Hemorrhage in Premature Infants.

Germinal matrix and intraventricular hemorrhage (GM-IVH) are the major causes of intracranial hemorrhage in premature infants. Cranial ultrasound (cUS) is the imaging modality of choice for diagnosing and classifying GM-IVH. Magnetic resonance imaging (MRI), usually performed at term-equivalent age, is more sensitive than cUS in identifying hemorrhage in the brain. Post-hemorrhagic ventricular dilatation is a significant complication of GM-IVH and correlates with adverse neurodevelopmental outcomes. In this review, we discuss the various imaging findings of GM-IVH in premature infants, focusing on the role of cUS and MRI.

Etiology and Prognosis of Intracranial Hemorrhage in Premature Infants, Cohort Research

Etiology and Prognosis of Intracranial Hemorrhage in Premature Infants, Cohort Research

Increased risk of intracranial hemorrhage in preterm infants with OPRM1 gene A118G polymorphism.

To investigate the relationship between the OPRM1 gene A118G polymorphism and intracranial hemorrhage (ICH) in premature infants and identify the relevant genes in disease occurrence. In the present case study analysis, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the genotype and allele frequencies of the OPRM1 gene All8G single nucleotide polymorphism (SNP) in a case group of premature infants with ICH (n=167) and a control group of premature infants (n=163) without ICH. In the case group, 73 (43.7%) wild type A118 homozygous (A/A), 82 (49.1%) mutant heterozygous (A/G), and 12 (7.2%) mutant G118 homozygous (G/G) individuals were observed. The frequencies of A and G alleles were 68.3% and 31.7% respectively. In the control group, 89 (54.6%) wild type A118 homozygous (A/A), 68 (41.7%) mutant heterozygous (A/G), and 6 (3.7%) mutant G118 homozygous (G/G) individuals were observed. The frequencies of A and G alleles were 75.5% and 24.5% respectively. There was no significant difference in the frequency distribution of the OPRM1 gene A118G polymorphism between the two groups (χ2=4.839, P=0.089). There was a significant difference in the positive rate of wild-type AA and mutant-type (A/G + G/G) between the two groups (χ2=3.913, P=0.048). Carrying the G allele of the individual was 1.5 times more frequent suffering from the risk of ICH than carrying the A allele [odds ratio (OR): 1.549; 95% confidence interval (CI): 1.003-2.391], indicating that the OPRM1 118G allele was positively correlated with ICH and can increase the risk of ICH occurrence. The OPRM1 gene A118G polymorphism is associated with ICH in premature infants. The OPRM1 gene A118G may play a critical role in the occurrence of ICH.

Investigation of in-patient neonatal death at 18 hospitals in Henan Province

Objective To investigate the situation and the causes of neonatal death in Henan Province. Methods This study retrospectively analyzed the clinical data of 277 neonates who died at 18 hospitals in Henan Province in 2017. Distribution and causes of neonatal deaths, differences between perinatal conditions of premature and term/post-term infants, causes of early (<7 d) and late (7-28 d) neonatal deaths and the differences in neonatal death cases between Maternal and Child Health Care Hospitals and General/Children's Hospitals were analyzed. We used t, rank-sum and Chi-square test (or corrected Chi-square test, or Fisher's exact test) for statistical analysis. Results (1) A total of 50 993 newborns were admitted to the 18 hospitals in 2017, 297 of which died with a mortality of 5.82‰. After excluding 20 cases with uncertain birth or maternal pregnancy history or clinical data, 277 cases with complete data were analyzed. Among them, 168 (60.6%) were preterm neonates and 109 (39.4%) were term/post-term ones. Early and late neonatal deaths accounted for 74.0% (205 cases) and 26.0% (72 cases), respectively. (2) The top five causes of neonatal deaths were infection (78 cases, 28.2%), asphyxia (54 cases, 19.5%), neonatal respiratory distress syndrome (NRDS, 33 cases, 11.9%), severe congenital malformations (26 cases, 9.4%) including cyanotic congenital heart diseases, digestive malformations, airway malformations and neural tube defects and pulmonary hemorrhage (23 cases, 8.3%). Among them, the top three causes of early neonatal deaths were asphyxia (48 cases, 23.4%), infection (43 cases, 21.0%) and NRDS (33 cases, 16.1%), while the main causes of late neonatal deaths were infection (35 cases, 48.6%), major congenital malformations (9 cases, 12.5%) and chromosome abnormities/inherited metabolic diseases (7 cases, 9.7%). (3) Maternal complications during pregnancy accounted for 79.1% (219 cases) and the predominant types were pregnancy-induced hypertension (43 cases, 19.6%), followed by infection (36 cases, 16.4%), placental-related conditions (32 cases, 14.6%), gestational diabetes mellitus (23 cases, 10.5%), hypothyroidism (20 cases, 9.1%), fetal distress (18, 8.2%), twin-twin transfusion syndrome (10 cases, 4.6%) and cholestasis syndrome (9 cases, 4.1%). (4) Compared with the term/post-term cases, the preterm cases had higher proportions of multiple births [27.4% (46/168) vs 6.4% (9/109), χ2=14.016, P<0.05], assisted reproduction [7.1% (12/168) vs 0.9% (1/109), χ2=4.421, P<0.05] and maternal hypertensive disorders of pregnancy [21.4% (36/168) vs 6.4% (7/109), χ2=11.353, P<0.05], infection [16.7% (28/168) vs 7.3% (8/109), χ2=4.295, P<0.05] and twin-to-twin transfusion syndrome [6.0% (10/168) vs 0.0% (0/109), χ2=6.707, P<0.05]. (5) Among all the early neonatal deaths, preterm cases had a higher incidence of NRDS than term/post-term neonates [20.3% (27/133) vs 8.3% (6/72), χ2=11.937, P<0.05], but lower incidence of meconium aspiration syndrome (MAS), severe congenital malformations and chromosome abnormalities/inherited metabolic diseases [0.8% (1/133) vs 5.6% (4/72), χ2=4.508; 3.8% (5/133) vs 16.7% (12/72), χ2=10.233; 1.5% (2/133) vs 6.9% (5/72), χ2=4.172; all P<0.05]. Among the late neonatal deaths, the incidence of severe intracranial hemorrhage in preterm infants was higher than that in term/post-term neonates [7.1% (3/42) vs 0.0% (0/30), χ2=2.205, P<0.05]. (6) Compared with the cases in General/Children's Hospitals, those in Maternal and Child Health Care Hospitals showed a higher proportion of preterm neonatal deaths [67.3% (105/156) vs 52.1% (63/121), χ2=6.010, P<0.05], younger gestational age [(32.8±5.3) weeks vs (34.6±4.9) weeks, t=3.072, P<0.05], lower birth weight [(2 132.6±1 014.5) g vs (2 409.4±987.3) g, t=2.513, P<0.05], and higher average age of death [M (P25-P75), 3 (1-8) d vs 2 (1-4) d, Z=3.710, P<0.05]. Conclusions Neonatal death occurs mainly within one week after birth in those with maternal complications. Late preterm deaths and term/post-term cases account for nearly half of total neonatal deaths. The causes of death for preterm and term/post-term newborns vary with postnatal age. Infection, asphyxia and severe congenital malformations are important causes of neonatal deaths. Key words: Infant mortality; Cause of death; Inpatients; Retrospective studies

Clinical effect of ibuprofen on preventing intracranial hemorrhage in premature infants and its influence on NT-proBNP and ET-1 level

Objective To investigate the clinical effect of ibuprofen on preventing intracranial hemorrhage in premature infants and its influence on the levels of NT-proBNP and ET-1. Methods From January 2016 to December 2017, 112 premature infants in Taizhou Hospital were selected as study objects after screening by inclusion and exclusion criteria.The infants were randomly divided into observation group and control group according to the digital table, with 56 cases in each group.The control group was treated with routine therapy, and the observation group was given ibuprofen prophylaxis.The incidence of intracranial hemorrhage, clinical index and serum NT-proBNP, ET-1 levels were compared between the two groups. Results There was significant difference in the incidence rate of intracranial hemorrhage between the observation group (17.86%) and the control group (30.36%)(χ2=12.472, P 0.05). There were no statistically significant differences in feeding intolerance and gastric hemorrhage between the two groups(all P>0.05). Conclusion The application of ibuprofen suspension can effectively prevent intracranial hemorrhage in premature infants, which is worthy of clinical use. Key words: Premature; Intracranial hemorrhage; Ibuprofen; NT-proBNP; ET-1

Early hypoxemia burden is strongly associated with severe intracranial hemorrhage in preterm infants.

Objectives:The objective of this study was to define the association between the burden of severe hypoxemia (SpO2≤70%) in the first week of life and development of severe ICH (grade III/IV) in preterm infants.Study Design:Infants born <32 weeks or weighing <1500g underwent prospective SpO2 recording from birth through 7d. Severe hypoxemia burden was calculated as the percentage of the error-corrected recording where SpO2≤70%. Binary logistic regression was used to model the relationship between hypoxemia burden and severe ICH.Results:A total of 163.3 million valid SpO2 data points were collected from 645 infants with mean EGA=27.7±2.6 weeks, BW=1005±291g; 38/645 (6%) developed severe ICH. There was a greater mean hypoxemia burden for infants with severe ICH (3%) compared to those without (0.1%) and remained significant when controlling for multiple confounding factors.Conclusion:The severe hypoxemia burden in the first week of life is strongly associated with severe ICH.

Avaliação do sistema nervoso auditivo central em neonatos com Hemorragia peri intraventricular

RESUMO Objetivo: verificar a ocorrência de Hemorragia peri intraventricular em recém-nascidos prematuros submetidos a cuidados intensivos neonatais, caracterizando a ocorrência de alteração auditiva central nessa população e sua variação em função do grau de hemorragia. Métodos: estudo longitudinal, retrospectivo. Dos 719 recém-nascidos prematuros, 46 (6,4%) apresentaram hemorragia peri-intraventricular. Foram selecionados 84 neonatos, distribuídos em Grupo Estudo formado por 42 com Hemorragia e Grupo Controle, com 42 sem Hemorragia Peri-intraventricular. Todos tiveram emissões otoacústicas evocadas por estímulo transiente presentes e foram submetidos à pesquisa do potencial evocado auditivo de tronco encefálico no período de internação e acompanhados durante dois anos, por meio de avaliação comportamental da audição. Resultados: houve maior ocorrência de alteração central no Grupo Estudo (33,4%) em relação ao Grupo Controle (4,8%), caracterizada pelo aumento de latência das ondas III e V e intervalo interpico I-V. Houve maior ocorrência de alteração auditiva central nos prematuros com hemorragia graus II, III e IV em relação ao grau I. Conclusão: A ocorrência de Hemorragia peri intraventricular foi de 6,4%. A ocorrência de alteração central foi de 33,4% e variou em função do grau da hemorragia: crianças com Hemorragia graus II, III e IV, apresentaram maior ocorrência de alteração central em relação às de grau I. No monitoramento audiológico, a alteração auditiva central manteve-se em 51,85% das crianças que já apresentavam tal alteração ao nascimento.

Statistical Analysis of Blood Cell Parameters in Premature Infants

&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;Analysis and discussion of the clinical statistics of the blood cell parameters in premature infants. &lt;strong&gt;Method: &lt;/strong&gt;From May 2008 to January 2015, 85 cases of premature infants were selected to analyze the relationship between blood cell parameters and birth weight, gestational age and the changes of blood cell parameters in premature infants with intracranial hemorrhage. &lt;strong&gt;Results: &lt;/strong&gt;Blood cell parameters PDW and PLT were decreased with the decrease of birth weight and gestational age. MPV increased with the decrease of birth weight and gestational age, the difference was statistically significant (&lt;em&gt;p &lt;/em&gt;&amp;lt; 0.05). Compared with the non-bleeding group, the intracranial hemorrhage in premature infants with PLT was significantly decreased, the difference was statistically significant &lt;em&gt;(p &lt;/em&gt;&amp;lt; 0.05), MPV and PDW were not statistically significant (&lt;em&gt;p &lt;/em&gt;&amp;gt; 0.05). &lt;strong&gt;Conclusion: &lt;/strong&gt;The blood cell parameters were correlated with the birth weight and gestational age, and the parameters of blood cells were closely related to the complications of premature infants and premature infants with intracranial hemorrhage.&lt;/p&gt;

Timing of cord clamping in very preterm infants: more evidence is needed

In December 2012, the American College of Obstetricians and Gynecologists published a Committee Opinion entitled "Timing of umbilical cord clamping after birth." It stated that "evidence exists to support delayed cord clamping in preterm infants, when feasible. The single most important benefit for preterm infants is the possibility for a nearly 50% reduction in IVH." However, the Committee Opinion added that the ideal timing of umbilical cord clamping has yet to be determined and recommended that large clinical trials be conducted in the most preterm infants. Published randomized controlled trials include <200 infants of <30 weeks' gestation, with assessments of neurodevelopmental outcome in less than one-half of the children. This is a major gap in the evidence. Without reliable data from randomized controlled trials that optimally include childhood follow-up evaluations, we will not know whether delayed cord clamping may do more overall harm than good. Ongoing trials of delayed cord clamping plan to report childhood outcomes in >2000 additional very preterm infants. Current recommendations may need to change when these results become available. Greater international collaboration could accelerate resolution of whether this promising intervention will improve disability-free survival in about 1 million infants who will be born very preterm globally each year.

Prevention at the Beginning of Life

The long-term prognosis of very preterm infants, particularly those with a birth weight of less than 1500 grams, is determined essentially by complications during postnatal intensive care. Many large studies have shown that high-grade intracranial hemorrhage in particular, whether with or without parenchymal involvement, limits these children’s long-term psychomotor prognosis (1). This is why discussion of the quality of treatment of preterm infants has focused on other quality indicators, particularly the intracranial hemorrhage rate, in addition to survival rates. Not long ago, this journal published an article on risk-adjusted analysis of the intracranial hemorrhage rate in preterm infants that not only showed how complicated it is to compare specialized facilities in terms of this quality indicator but also made plain the major variation in the incidence of intracranial hemorrhage in preterm infants (2). There are substantial differences in this parameter, in both Germany and other countries (3).

Overexpression of Vascular Endothelial Growth Factor in the Germinal Matrix Induces Neurovascular Proteases and Intraventricular Hemorrhage

Intracranial hemorrhage in preterm neonates may result in neonatal mortality and functional disabilities, but its pathogenic mechanisms are poorly defined and better therapies are needed. We used a tetracycline-regulated transgenic system to test whether the induction of vascular endothelial growth factor (VEGF) in the germinal matrix leads to intracranial hemorrhage. This genetic strategy initially induced a dense network of loosely adjoined endothelial cells and pericytes near lateral ventricles, similar to the immature vascular rete in human fetal brains. Yet, this rich vascular network transformed into low-vasculature patches correlated with hemorrhage and caspase-3 activation near birth. Gene expression and biochemical analyses suggested that downstream mediators of VEGF in this network include transcriptional factors ETS1 and HIF2α (hypoxia-inducible factor 2α), components of the PDGFβ (platelet-derived growth factor β) and TGFβ (transforming growth factor-β) receptor signaling pathways, matrix metalloproteinase-9 (MMP-9), and cathepsins. Prenatal administration of glucocorticoids markedly reduced mortality and cerebral hemorrhage in mutant animals, as in human neonates. This protective effect was not due to blocking vasculogenesis, but was instead associated with inhibition of neurovascular proteases, notably MMP-9, cathepsin B, and caspase-3. Collectively, these results support a causative role of VEGF in perinatal cerebral hemorrhage and implicate its downstream proteases as potential therapeutic targets.

Committee Opinion No. 543

The optimal timing for clamping the umbilical cord after birth has been a subject of controversy and debate. Although many randomized controlled trials in term and preterm infants have evaluated the benefits of delayed umbilical cord clamping versus immediate umbilical cord clamping, the ideal timing for cord clamping has yet to be established. Several systematic reviews have suggested that clamping the umbilical cord in all births should be delayed for at least 30-60 seconds, with the infant maintained at or below the level of the placenta because of the associated neonatal benefits, including increased blood volume, reduced need for blood transfusion, decreased incidence of intracranial hemorrhage in preterm infants, and lower frequency of iron deficiency anemia in term infants. Evidence exists to support delayed umbilical cord clamping in preterm infants, when feasible. The single most important clinical benefit for preterm infants is the possibility for a nearly 50% reduction in intraventricular hemorrhage. However, currently, evidence is insufficient to confirm or refute the potential for benefits from delayed umbilical cord clamping in term infants, especially in settings with rich resources.

Low-Voltage aEEG as Predictor of Intracranial Hemorrhage in Preterm Infants

The objectives of this prospective cohort study were to identify amplitude-integrated electroencephalography (aEEG) background patterns predictive of severe intracranial hemorrhage. Thirty ventilated preterm newborns weighing <1,000 g were assessed by an aEEG cerebral function monitor and ultrasound measurement of cerebral blood flow velocity at time of surfactant administration and tracheal suctioning simultaneously during first 48 hours of life. Birth weight was 624 ± 200 g (mean ± S.D.) and gestational age was 25 ± 2 weeks. Background electrical activity was predominantly discontinuous in 72% of infants. A sharp increase in electrical activity/burst density was observed during surfactant administration and tracheal suctioning in most infants, with a 33.5% increase in mean cerebral blood flow velocity. Burst suppression with low voltage was identified in 57% infants with severe intracranial hemorrhage, whereas no infant without hemorrhage exhibited this pattern (P = 0.014). We conclude that aEEG low-voltage burst suppression might have useful clinical applications with 100% positive predictive value for severe intracranial hemorrhage.

Intracranial hemorrhage in premature neonates treated with extracorporeal membrane oxygenation correlates with conceptional age

Objective To determine the effect of patient age on the risk of intracranial hemorrhage (ICH) in premature neonates treated with extracorporeal membrane oxygenation (ECMO). Study design This was a retrospective cohort study of neonates of <37 weeks' gestation treated with ECMO in the years 1992 through 2000 and reported to the Extracorporeal Life Support Organization Registry (n = 1524). The relation between ICH and patient age, defined as gestational age, postnatal age (PNA), and postconceptional age (PCA), was determined with the use of multiple logistic regression analysis. Results PNA was inversely correlated with ICH in the univariate analysis ( P = .01) but not in the multivariate analysis ( P = .36). PCA showed a strong univariate correlation with decreasing ICH: 26% of patients ≤32 weeks' PCA developed ICH as compared with 6% of patients with PCA of 38 weeks ( P = .004). Multiple logistic regression identified as independent predictors of ICH: PCA ( P = .005), sepsis ( P = .004), acidosis ( P = .0004), and treatment with sodium bicarbonate ( P = .002). Gestational age was correlated with ICH in the multivariate model only when PNA was included. Conclusions Postnatal age is not a strong independent predictor of ICH in premature neonates treated with ECMO. PCA is the best age-related predictor of ECMO-related ICH in premature infants.

HPA-1 carrier status and thrombocytopenia in preterm infants with a birth weight below 1500 grams.

In cohorts of infants with proven neonatal alloimmune thrombocytopenia (NAIT) an unusual high rate of preterm infants has been reported, raising the question of whether NAIT contributes to the high rate of intracranial hemorrhage in preterm infants. We genotyped the HPA-1-allele in a large cohort of term (n = 205) and very low birth weight infants (VLBW-infants, n = 299) with polymerase-chain-reaction and restriction enzyme digestion. HPA-1a/b is the only fetal HPA-1-genotype in which alloimmunization and NAIT could occur. Genotype distribution did not differ between term and VLBW-infants (p = 0.26). Furthermore, neither HPA-1a/b genotype nor platelet count at birth were of significant prognostic value in predicting subsequent intracranial haemorrhage or death in VLBW-infants (p = 0.93 and p = 0.19 respectively). Our data did not support the hypothesis that routine screening of preterm infants or their mothers for HPA-1-genotype is of additional value in the care of these infants.

Repeated prenatal corticosteroids reduce glial fibrillary acidic protein in the ovine central nervous system.

A single course of corticosteroid reduces intracranial hemorrhage in preterm infants. The mechanism of protection is unclear. Glial fibrillary acidic protein (GFAP), expressed by astrocytes, is regulated by glucosteroids and is an important component of the cells forming the blood brain barrier. We have evaluated the effect of prenatal corticosteroid upon ovine GFAP. Date-mated ewes were studied in two protocols and lambs delivered on day 125 or 145 (term = 150). In the maternal injection protocol (n = 36) ewes were administered saline, single or repeated injections of corticosteroid. In the fetal injection protocol (n = 48) direct ultrasound-guided fetal injections of saline, single or repeated corticosteroid were administered, and an additional control group did not receive fetal injections. Optic nerve GFAP immunohistochemistry was performed and quantified. At 125 days, repeated, but not single, administration of corticosteroid, by either maternal or fetal route, was associated with a significant reduction in GFAP (both p < 0.002); by 145 days, the deficit had recovered (both p > 0.05). The process of performing repeated fetal injections had an independent effect upon GFAP at 145 days (p = 0.002). Repeated administration of corticosteroid results in a reduction in GFAP in the developing ovine optic nerve, with recovery demonstrated by 145 days.

Cranial Ultrasonography

Cranial Ultrasonography

Significance of the plasminogen activator inhibitor of placental type (PAI-2) in pregnancy.

Marked changes in the hemostasis system, especially increases in PAI-2, are observed during pregnancy and at delivery. This inhibitor is produced by placental trophoblasts and by macrophages. PAI-2 occurs in two forms, a LMW and a HMW form. LMW PAI-2 is intracellular, HMW PAI-2 is secreted. PAI-2 inhibits both u-PA and two-chain t-PA. PAI-2 seems to be involved in the processes of invasion and remodeling of fetal and uterine tissues. It may protect against premature placental separation and secure hemostasis at parturition. Excess levels of PAI-2 in amniotic fluid may protect membranes from premature rupture. An imbalance between fibrinolytic activators and inhibitors may also be related to intracranial hemorrhage in premature infants. During preeclampsia t-PA and PAI-1 levels are markedly increased in plasma, and in cases of intrauterine growth retardation, u-PA and PAI-2 levels are decreased. While elevated PAI-1 concentrations might be helpful markers of severity of preeclampsia, decreased PAI-2 levels seem to indicate decreased placental function and intrauterine growth retardation.